FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Acharya, S Foletta, VC Lee, JW Rayborn, ME Rodriguez, IR Young, WS Hollyfield, JG AF Acharya, S Foletta, VC Lee, JW Rayborn, ME Rodriguez, IR Young, WS Hollyfield, JG TI SPACRCAN, a novel human interphotoreceptor matrix hyaluronan-binding proteoglycan synthesized by photoreceptors and pinealocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHONDROITIN SULFATE PROTEOGLYCAN; MACULAR DEGENERATION; HUMAN RETINA; IMMUNOCYTOCHEMICAL LOCALIZATION; SEQUENCE-ANALYSIS; CALCIUM; GLAND; PROTEINS; GLYCOPROTEIN; EXPRESSION AB The interphotoreceptor matrix is a unique extracellular complex occupying the interface between photoreceptors and the retinal pigment epithelium in the fundus of the eye. Because of the putative supportive role in photoreceptor maintenance, it is likely that constituent molecules play key roles in photoreceptor function and may be targets for inherited retinal disease. In this study we identify and characterize SPACRCAN, a novel chondroitin proteoglycan in this matrix. SPACRCAN was cloned from a human retinal cDNA library and the gene localized to chromosome 3q11.2. Analysis of SPACRCAN mRNA and protein revealed that SPACRCAN is expressed exclusively by photoreceptors and pinealocytes, SPACRCAN synthesized by photoreceptors is localized to the interphotoreceptor matrix where it surrounds both rods and cones, The functional protein contains 1160 amino acids with a large central mucin domain, three consensus sites for glycosaminoglycan attachment, two epidermal growth factor-like repeats, a putative hyaluronan-binding motif, and a potential transmembrane domain near the C-terminal, Lectin and Western blotting indicate an M-r around 400,000 before and 230,000 after chondroitinase ABC digestion. Removal of N- and O-linked oligosaccharides reduces the M-r to approximately 160,000, suggesting that approximately 60% of the mass of SPACRCAN is carbohydrate. Finally, we demonstrate that SPACRCAN binds hyaluronan and propose that associations between SPACRCAN and hyaluronan may be involved in organization of the insoluble interphotoreceptor matrix, particularly as SPACRCAN is the major proteoglycan present in this matrix. C1 Cleveland Clin Fdn, Cole Eye Inst, Cleveland, OH 44195 USA. NEI, NIH, Bethesda, MD 20892 USA. NIMH, NIH, Bethesda, MD 20892 USA. RP Hollyfield, JG (reprint author), Cleveland Clin Fdn, Cole Eye Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA. RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 FU NEI NIH HHS [EY 02362] NR 71 TC 38 Z9 41 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 10 PY 2000 VL 275 IS 10 BP 6945 EP 6955 DI 10.1074/jbc.275.10.6945 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 292RV UT WOS:000085809600036 PM 10702256 ER PT J AU Benbernou, N Muegge, K Durum, SK AF Benbernou, N Muegge, K Durum, SK TI Interleukin (IL)-7 induces rapid activation of Pyk2, which is bound to Janus kinase 1 and IL-7R alpha SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE KINASE; FOCAL ADHESION KINASE; RECEPTOR-GAMMA-CHAIN; N-TERMINAL KINASE; DEFECTIVE LYMPHOID DEVELOPMENT; MICE LACKING JAK3; DEFICIENT MICE; SIGNALING PATHWAY; COUPLED RECEPTORS; IL-7 RECEPTOR AB Interleukin-7 (IL-7) receptor signaling begins with activation of the Janus tyrosine kinases Jak1 and Jak3, which are associated with the receptor complex. To identify potential targets of these kinases, we examined Pyk2 (a member of the focal adhesion kinase family) using an IL-7-dependent murine thymocyte line, D1. We demonstrate that stimulation of D1 (or normal pro-T) cells by IL-7 rapidly increased tyrosine phosphorylation and enzymatic activity of Pyk2, with kinetics slightly lagging that of Jak1 and Jak3 phosphorylation. Conversely, IL-7 withdrawal resulted in a marked decrease of Pyk2 phosphorylation. Pyk2 was found to be physically associated with Jak1 prior to IL-7 stimulation and to increase its association with lL-7R alpha chain following IL-7 stimulation. Pyk2 appeared to be involved in cell survival, because antisense Pyk2 accelerated the cell death process. Activation of Pyk2 via the muscarinic and nicotinic receptors using carbachol or via intracellular Ca2+ rise using ionomycin/phorbol myristate acetate promoted survival in the absence of IL-7. These data support a role for Pyk2 in coupling Jak signaling to the trophic response. C1 NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr,NIH, Frederick, MD 21702 USA. NCI, Mol Immunoregulat Lab, NIH, Frederick, MD 21702 USA. RP Durum, SK (reprint author), NCI, Mol Immunoregulat Lab, NIH, Bldg 560,Rm 31-71, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 64 TC 30 Z9 30 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 10 PY 2000 VL 275 IS 10 BP 7060 EP 7065 DI 10.1074/jbc.275.10.7060 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 292RV UT WOS:000085809600051 PM 10702271 ER PT J AU Cissel, DS Beaven, MA AF Cissel, DS Beaven, MA TI Disruption of Raf-1/heat shock protein 90 complex and Raf signaling by dexamethasone in mast cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BASOPHILIC LEUKEMIA-CELLS; KAPPA-B ACTIVITY; FC-EPSILON-RI; NUCLEAR FACTOR; IGE RECEPTOR; KINASE; ACTIVATION; ALPHA; PATHWAY; HSP90 AB Antigen stimulation of mast cells via the IgE receptor, Fc epsilon RI, results in the recruitment of the cytosolic tyrosine kinase, Syk, and the activation of various signaling cascades. One of these, the extracellular signal-regulated kinase (ERK2) cascade, is inhibited by low concentrations of the immunosuppressant drug, dexamethasone, probably at a step prior to the activation of Raf-1 (Rider, L. G., Hirasawa, N., Santini, F., and Beaven, M. A. (1996) J. Immunol. 157, 2374-2380). We now show that treatment of cultured RBL-2H3 mast cells with nanomolar concentrations of dexamethasone causes dissociation of the Raf-1 heat shock protein 90 (Hsp90) complex. Raf-1 bereft of this protein fails to associate with the membrane or Ras in antigen-stimulated cells. Upstream events such as the Syk-dependent phosphorylation of Shc, the engagement of Shc with the adapter protein, Grb2, and the activation of Ras itself are unaffected. interestingly, the counterpart of Raf-1 in the c-Jun N-terminal kinase (JNK) cascade, MEKK-1 (mitogen-activated protein kinase/ERK kinase), is similarly associated with Hsp90 and this association as well as the activation of MEKK-1 are disrupted by dexamethasone treatment. Disruption of the ERK and JNK cascades at the level of Raf-1 and MEKK-1 could account for the inhibitory action of dexamethasone on the generation of inflammatory mediators in stimulated mast cells. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Beaven, MA (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10,Rm 8N109, Bethesda, MD 20892 USA. NR 37 TC 49 Z9 51 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 10 PY 2000 VL 275 IS 10 BP 7066 EP 7070 DI 10.1074/jbc.275.10.7066 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 292RV UT WOS:000085809600052 PM 10702272 ER PT J AU Wang, L Slayden, RA Barry, CE Liu, J AF Wang, L Slayden, RA Barry, CE Liu, J TI Cell wall structure of a mutant of Mycobacterium smegmatis defective in the biosynthesis of mycolic acids SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MASS-SPECTROMETRY; TUBERCULOSIS; ARABINOGALACTAN; IDENTIFICATION; COMPONENTS; RESISTANCE; FRAGMENTS; ENVELOPE; FLUIDITY; CHELONAE AB A mutant strain of Mycobacterium smegmatis defective in the biosynthesis of mycolic acids was recently isolated (Liu, J., and Nikaido, H. (1999) Proc. Natl. Acad. Sci. U. S. A. 96, 4011-4016), This mutant failed to synthesize full-length mycolic acids and accumulated a series of long chain beta-hydroxymeromycolates. In this work, we provide a detailed characterization of the localization of meromycolates and of the cell wall structure of the mutant. Thin layer chromatography showed that the insoluble cell wall matrix remaining after extraction with chloroform/methanol and SDS still contained a large portion of the total meromycolates. Matrix-assisted laser desorption/ionization and electrospray ionization mass spectroscopy analysis of fragments arising from Smith degradation of the insoluble cell wall matrix revealed that the meromycolates were covalently attached to arabinogalactan at the 5-OH positions of the terminal arabinofuranosyl residues. The arabinogalactan appeared to be normal in the mutant strain, as analyzed by NMR, Analysis of organic phase lipids showed that the mutant cell wall contained some of the extractable lipids but lacked glycopeptidolipids and lipooligosaccharides. Differential scanning calorimetry of the mutant cell wall failed to show the large cooperative thermal transitions typical of intact mycobacterial cell walls. Transmission electron microscopy showed that the mutant cell wall had an abnormal ultrastructure (without the electron-transparent zone associated with the asymmetric mycolate lipid layer). Taken together, these results demonstrate the importance of mycolic acids for the structural and functional integrity of the mycobacterial cell mall. The lack of highly organized lipid domains in the mutant cell wall explains the drug-sensitive and temperature-sensitive phenotypes of the mutant. C1 Univ Toronto, Dept Med Genet & Microbiol, Toronto, ON M5S 1A8, Canada. NIAID, TB Res Sect, Host Def Lab, NIH, Rockville, MD 20852 USA. RP Liu, J (reprint author), Univ Toronto, Dept Med Genet & Microbiol, 4382 Med Sci Bldg,1 Kings Coll Circle, Toronto, ON M5S 1A8, Canada. RI Barry, III, Clifton/H-3839-2012; Slayden, Richard/O-8626-2016; OI Slayden, Richard/0000-0001-6857-7277; Liu, Jun/0000-0002-0522-6733 FU Intramural NIH HHS [Z01 AI000783-11] NR 34 TC 38 Z9 39 U1 0 U2 7 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 10 PY 2000 VL 275 IS 10 BP 7224 EP 7229 DI 10.1074/jbc.275.10.7224 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 292RV UT WOS:000085809600072 PM 10702292 ER PT J AU Liu, XW Katagiri, Y Jiang, H Gong, LJ Guo, LY Shibutani, M Johnson, AC Guroff, G AF Liu, XW Katagiri, Y Jiang, H Gong, LJ Guo, LY Shibutani, M Johnson, AC Guroff, G TI Cloning and characterization of the promoter region of the rat epidermal growth factor receptor gene and its transcriptional regulation by nerve growth factor in BC12 cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PC12 CELLS; PHEOCHROMOCYTOMA CELLS; DOWN-REGULATION; RETINOIC ACID; SEQUENCE; EXPRESSION; ELEMENT; IDENTIFICATION; BINDING; ABSENCE AB Our previous studies have shown that treatment of PC12 cells with nerve growth factor (NGF) causes a profound down-regulation of the epidermal growth factor receptor (EGFR) mRNA and protein. Further, the NGF-induced down-regulation of the EGFR is under transcriptional control. To elucidate the molecular mechanism of this down-regulation we have cloned a 2.7-kilobase sequence from the promoter region of the rat EG;FR from a rat P1 library. Six transcriptional start sites were identified by 5'-rapid amplification of cDNA ends and primer extension. Sequence analysis showed a 62% overall homology with the human EGFR promoter region. To investigate its transcription, 1.1 kilobases of the 5'-flanking sequence were fused to a luciferase reporter gene. This sequence exhibited functional promoter activity in transient transfection experiments with PC12, C6, and CV-1 cells. Treatment of PC12 cells with NGF inhibited promoter activity. By transfection of promoter deletion constructs, a silencer element was found between nucleotides -260 and -181, and TCC repeat sequences appeared to be at least partially responsible for the down-regulation of the EGFR by NGF. Supportive evidence for the relevance of this sequence was obtained from gel mobility shift assays and by transfection of TCC mutation constructs. Our results demonstrate that TCC repeat sequences are required for the down-regulation of rat EGFR by NGF in PC12 cells and may lead to the identification of the NGF-responsive transcription factors. C1 NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NICHD, Growth Factors Sect, NIH, Bethesda, MD 20892 USA. NICHD, Dev & Mol Immun Lab, NIH, Bethesda, MD 20892 USA. RP Johnson, AC (reprint author), NCI, Mol Biol Lab, Div Basic Sci, NIH, Bldg 37,Rm 2D18, Bethesda, MD 20892 USA. RI Shibutani, Makoto/C-2510-2013 NR 34 TC 11 Z9 11 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 10 PY 2000 VL 275 IS 10 BP 7280 EP 7288 DI 10.1074/jbc.275.10.7280 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 292RV UT WOS:000085809600078 PM 10702298 ER PT J AU Tomizawa, M Kumaro, A Perrot, V Nakae, J Accili, D Rechler, MM AF Tomizawa, M Kumaro, A Perrot, V Nakae, J Accili, D Rechler, MM TI Insulin inhibits the activation of transcription by a C-terminal fragment of the forkhead transcription factor FKHR - A mechanism for insulin inhibition of insulin-like growth factor-binding protein-1 transcription SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RAT HEPATOMA-CELLS; PAX3-FKHR FUSION PROTEIN; CAENORHABDITIS-ELEGANS; GENE-EXPRESSION; ALVEOLAR RHABDOMYOSARCOMA; RESPONSE SEQUENCE; KINASE-B; PROMOTER ACTIVITY; MAMMALIAN-CELLS; MESSENGER-RNA AB The forkhead rhabdomyosarcoma transcription factor (FKHR) is a promising candidate to be the transcription factor that binds to the insulin response element of the insulin-like growth factor-binding protein-1 (IGFBP-1) promoter and mediates insulin inhibition of IGFBP-1 promoter activity. Cotransfection of mouse FKHR increased IGFBP-1 promoter activity 2-3-fold in H4IIE rat hepatoma cells; insulin inhibited FKHR-stimulated promoter activity similar to 70%. A C-terminal fragment of mouse FKHR (residues 208-652) that contains the transcription activation domain fused to a Gal4 DNA binding domain potently stimulated Gal4 promoter activity. Insulin inhibited FKHR fragment-stimulated promoter activity by similar to 70%. Inhibition was abolished by coincubation with the phosphatidylinositol-3 kinase inhibitor, LY294002. The FKHR 208-652 fragment contains two consensus sites for phosphorylation by protein kinase B (PKB)/Akt, Ser-253 and Ser-316. Neither site is required for insulin inhibition of promoter activity stimulated by the FKHR fragment, and overexpression of Akt does not inhibit FKHR fragment-stimulated Gal4 promoter activity. These results suggest that insulin- and phosphatidylinositol-3 kinase-dependent phosphorylation of another site in the fragment by a kinase different from PKB/Akt inhibits transcription activation by the fragment. Phosphorylation of this site also may be involved in insulin inhibition of transcription activation by full-length FKHR, but only after phosphorylation of Ser-253 by PKB/Akt. C1 NIDDK, Growth & Dev Sect, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Rechler, MM (reprint author), NIDDK, Growth & Dev Sect, Clin Endocrinol Branch, NIH, Bldg 10 Rm 8D12, Bethesda, MD 20892 USA. NR 62 TC 60 Z9 61 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 10 PY 2000 VL 275 IS 10 BP 7289 EP 7295 DI 10.1074/jbc.275.10.7289 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 292RV UT WOS:000085809600079 PM 10702299 ER PT J AU Pedram, A Razandi, M Kehrl, J Levin, ER AF Pedram, A Razandi, M Kehrl, J Levin, ER TI Natriuretic peptides inhibit G protein activation - Mediation through cross-talk between cyclic GMP-dependent protein kinase and regulators of G protein-signaling proteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HETEROTRIMERIC G-PROTEINS; HAMSTER OVARY CELLS; RGS PROTEINS; ASTROCYTE PROLIFERATION; PHYSIOLOGICAL-ROLE; COUPLED RECEPTORS; ALPHA-SUBUNITS; FAMILY; PATHWAYS; CGMP AB Atrial natriuretic peptide (ANP) inhibits the proliferation of many cells, in part through interfering with signal transduction enacted by G protein-coupled growth factor receptors. Signaling interactions between ANP and the G protein-coupled growth factor receptor ligand, endothelin-3 (ET-3), regulate astrocyte proliferation at a very proximal but undefined point. Here, we find that ANP inhibits the ability of ET-3 to activate G alpha(q), and G alpha(i) in these cells. ANP stimulated the translocation of endogenous regulators of G protein-signaling (RGS) proteins 3 and 4 from the cytosol to the cell membrane, and enhanced their association with G alpha(q) and G alpha(i). ANP effects were significantly blocked by HS-142-1, an inhibitor of guanylate cyclase activation, or by ET-3, KT5823, an inhibitor of cyclic GRIP-dependent protein kinase (PKG) reversed the RGS translocation induced by ANP; conversely, expression of an active catalytic subunit of PKG-I, or 8-bromo-cyclic GMP stimulated RGS translocation, ANP caused the phosphorylation of both RGS proteins in a PKG-dependent fashion, and the expressed PKG tin the absence of ANP) also stimulated RGS phosphorylation. A novel cross-talk between PKG and RGS proteins is stimulated by ANP and leads to the increased translocation and association of RGS proteins with G alpha. The rapid inactivation of G proteins provides a mechanism by which ANP inhibits downstream signaling to the cell proliferation program. C1 Long Beach VA Med Ctr, Med Serv 111I, Div Endocrinol, Long Beach, CA 90822 USA. Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA. Univ Calif Irvine, Dept Pharmacol, Irvine, CA 92717 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Levin, ER (reprint author), Long Beach VA Med Ctr, Med Serv 111I, Div Endocrinol, 5901 E 7th St, Long Beach, CA 90822 USA. RI Levin, Ellis/J-5402-2013; OI Kehrl, John/0000-0002-6526-159X FU NINDS NIH HHS [NS-30521] NR 46 TC 48 Z9 55 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 10 PY 2000 VL 275 IS 10 BP 7365 EP 7372 DI 10.1074/jbc.275.10.7365 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 292RV UT WOS:000085809600089 PM 10702309 ER PT J AU Shlyakhtenko, LS Hsieh, P Grigoriev, M Potaman, VN Sinden, RR Lyubchenko, YL AF Shlyakhtenko, LS Hsieh, P Grigoriev, M Potaman, VN Sinden, RR Lyubchenko, YL TI A cruciform structural transition provides a molecular switch for chromosome structure and dynamics SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE cruciform conformation; Holliday junctions; DNA supercoiling; site-specific recombination; atomic force microscopy ID HOLLIDAY JUNCTION COMPLEX; ATOMIC-FORCE MICROSCOPY; CRYSTAL-STRUCTURE; RELATIVE ORIENTATION; SUPERCOILED DNA; TN3 RESOLVASE; PROTEIN RUVA; RECOMBINATION; SEGMENTS; BINDING AB The interaction between specific sites along a DNA molecule is often crucial for the regulation of genetic processes. However, mechanisms regulating the interaction of specific sites are unknown. We have used atomic force microscopy to demonstrate that the structural transition between cruciform conformations can act as a molecular switch to facilitate or prevent communication between distant regions in DNA. Cruciform structures exist in vivo and they are critically involved in the initiation of replication and the regulation of gene expression in different organisms. Therefore, structural transitions of the cruciform may play a key role in these processes. (C) 2000 Academic Press. C1 Arizona State Univ, Dept Microbiol, Tempe, AZ 85287 USA. NIH, Bethesda, MD 20892 USA. Texas A&M Univ, Inst Biosci & Technol, Houston, TX 77030 USA. RP Lyubchenko, YL (reprint author), Arizona State Univ, Dept Microbiol, Tempe, AZ 85287 USA. FU NIGMS NIH HHS [GM 54991] NR 36 TC 55 Z9 58 U1 0 U2 1 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 10 PY 2000 VL 296 IS 5 BP 1169 EP 1173 DI 10.1006/jmbi.2000.3542 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 292BL UT WOS:000085774200001 PM 10698623 ER PT J AU Panchenko, AR Marchler-Bauer, A Bryant, SH AF Panchenko, AR Marchler-Bauer, A Bryant, SH TI Combination of threading potentials and sequence profiles improves fold recognition SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE protein evolution; fold recognition; threading; sequence profiles ID PROTEIN FOLDS; ALIGNMENT; DATABASE; PREDICTION; MODELS; IDENTIFICATION; EVOLUTION; ACCURACY; MATRICES; SUCCESS AB Using a benchmark set of structurally similar proteins, we conduct a series of threading experiments intended to identify a scoring function with an optimal combination of contact-potential and sequence-profile terms. The benchmark set is selected to include many medium-difficulty fold recognition targets, where sequence similarity is undetectable by BLAST but structural similarity is extensive. The contact potential is based on the log-odds of non-local contacts involving different amino acid pairs, in native as opposed to randomly compacted structures. The sequence profile term is that used in PSI-BLAST. We find that combination of these terms significantly improves the success rate of fold recognition over use of either term alone, with respect to both recognition sensitivity and the accuracy of threading models. Improvement is greatest for targets between 10 % and 20 % sequence identity and 60 % to 80 % superimposable residues, where the number of models crossing critical accuracy and significance thresholds more than doubles. We suggest that these improvements account for the successful performance of the combined scoring function at CASP3. We discuss possible explanations as to why sequence-profile and contact-potential terms appear complementary. C1 Natl Ctr Biotechnol Informat, Computat Biol Branch, NIH, Bethesda, MD 20894 USA. RP Bryant, SH (reprint author), Natl Ctr Biotechnol Informat, Computat Biol Branch, NIH, Bldg 38A,Room 8N805, Bethesda, MD 20894 USA. RI Marchler-Bauer, Aron/A-9681-2009 NR 56 TC 91 Z9 93 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 10 PY 2000 VL 296 IS 5 BP 1319 EP 1331 DI 10.1006/jmbi.2000.3541 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 292BL UT WOS:000085774200014 PM 10698636 ER PT J AU Rosenberg, LE Schechter, AN AF Rosenberg, LE Schechter, AN TI Gene therapist, heal thyself SO SCIENCE LA English DT Editorial Material C1 Princeton Univ, Princeton, NJ 08544 USA. NIH, Bethesda, MD 20892 USA. RP Rosenberg, LE (reprint author), Princeton Univ, Princeton, NJ 08544 USA. NR 0 TC 18 Z9 18 U1 0 U2 2 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 10 PY 2000 VL 287 IS 5459 BP 1751 EP 1751 DI 10.1126/science.287.5459.1751 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 292BY UT WOS:000085775300015 PM 10755924 ER PT J AU Nandanan, E Jang, SY Moro, S Kim, HO Siddiqui, MA Russ, P Marquez, VE Busson, R Herdewijn, P Harden, TK Boyer, JL Jacobson, KA AF Nandanan, E Jang, SY Moro, S Kim, HO Siddiqui, MA Russ, P Marquez, VE Busson, R Herdewijn, P Harden, TK Boyer, JL Jacobson, KA TI Synthesis, biological activity, and molecular modeling of ribose-modified deoxyadenosine bisphosphate analogues as P2Y(1) receptor ligands SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CONFORMATIONAL-ANALYSIS; PHOSPHOLIPASE-C; BICYCLO<3.1.0>HEXANE TEMPLATE; P-2Y-PURINOCEPTOR AGONISTS; SELECTIVE ANTAGONIST; PURINERGIC RECEPTOR; POTENT ANTAGONISTS; MEDIATED RESPONSES; SUGAR RING; NUCLEOSIDES AB The structure-activity relationships of adenosine-3',5'-bisphosphates as P2Y(1) receptor antagonists have been explored, revealing the potency-enhancing effects of the NG-methyl group and the ability to substitute the ribose moiety (Nandanan et al. J. Med. Chem. 1999, 42, 1625-1638). We have introduced constrained carbocyclic rings (to explore the role of sugar puckering), non-glycosyl bonds to the adenine moiety, and a phosphate group shift. The biological activity of each analogue at P2Y(1) receptors was characterized by measuring its capacity to stimulate phospholipase C in turkey erythrocyte membranes (agonist effect) and to inhibit its stimulation elicited by 30 nM 2-methylthioadenosine-5'-diphosphate (antagonist effect). Addition of the N-6-methyl group in several cases converted pure agonists to antagonists. A carbocyclic N-6-methyl-2'-deoxyadenosine bisphosphate analogue was a pure P2Y(1) receptor antagonist and equipotent to the ribose analogue (MRS 2179). In the series of ring-constrained methanocarba derivatives where a fused cyclopropane moiety constrained the pseudosugar ring of the nucleoside to either a Northern (N) or Southern (S) conformation, as defined in the pseudorotational cycle, the 6-NH2 (N)-analogue was a pure agonist of EC50 155 nM and 86-fold more potent than the corresponding (S)-isomer. The 2-chloro-N-6-methyl-(N)-methanocarba analogue was an antagonist of IC50 51.6 nM. Thus, the ribose ring (N)-conformation appeared to be favored in recognition at P2Y(1) receptors. A cyclobutyl analogue was an antagonist with IC50 of 805 nM, while morpholine ring-containing analogues were nearly inactive. Anhydrohexitol ring-modified bisphosphate derivatives displayed micromolar potency as agonists (6-NH2) or antagonists (N-6-methyl). A molecular model of the energy-minimized structures of the potent antagonists suggested that the two phosphate groups may occupy common regions. The (N)- and (S)-methanocarba agonist analogues were docked into the putative binding site of the previously reported P2Y(1) receptor model. C1 NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. NCI, Med Chem Lab, Bethesda, MD 20892 USA. Katholieke Univ Leuven, Rega Inst Med Res, Lab Pharmaceut Chem, B-3000 Louvain, Belgium. Univ Padua, Dept Pharmaceut Sci, Mol Modeling Sect, I-35131 Padua, Italy. Yonsei Univ, Coll Med, Seoul, South Korea. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, NIH, LBC, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA. RI Moro, Stefano/A-2979-2012; Jacobson, Kenneth/A-1530-2009; Erathodiyil, Nandanan/A-8333-2010 OI Moro, Stefano/0000-0002-7514-3802; Jacobson, Kenneth/0000-0001-8104-1493; FU NHLBI NIH HHS [HL54889]; NIGMS NIH HHS [GM 38213] NR 54 TC 112 Z9 112 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAR 9 PY 2000 VL 43 IS 5 BP 829 EP 842 DI 10.1021/jm990249v PG 14 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 292QD UT WOS:000085805800010 PM 10715151 ER PT J AU Boyer, FE Prasad, JVNV Domagala, JM Ellsworth, EL Gajda, C Hagen, SE Markoski, LJ Tait, BD Lunney, EA Palovsky, A Ferguson, D Graham, N Holler, T Hupe, D Nouhan, C Tummino, PJ Urumov, A Zeikus, E Zeikus, G Gracheck, SJ Sanders, JM VanderRoest, S Brodfuehrer, J Iyer, K Sinz, M Gulnik, SV Erickson, JW AF Boyer, FE Prasad, JVNV Domagala, JM Ellsworth, EL Gajda, C Hagen, SE Markoski, LJ Tait, BD Lunney, EA Palovsky, A Ferguson, D Graham, N Holler, T Hupe, D Nouhan, C Tummino, PJ Urumov, A Zeikus, E Zeikus, G Gracheck, SJ Sanders, JM VanderRoest, S Brodfuehrer, J Iyer, K Sinz, M Gulnik, SV Erickson, JW TI 5,6-dihydropyran-2-ones possessing various sulfonyl functionalities: Potent nonpeptidic inhibitors of HIV protease SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ANTIVIRAL ACTIVITY; BINDING; MODE; 5,6-DIHYDRO-4-HYDROXY-2-PYRONES; PNU-140690; DESIGN AB On the basis of previous SAR findings and molecular modeling studies, a series of compounds were synthesized which possessed various sulfonyl moieties substituted at the 4-position of the C-3 phenyl ring substituent of the dihydropyran-2-one ring system. The sulfonyl substituents were added in an attempt to fill the additional S-3' pocket and thereby produce increasingly potent inhibitors of the target enzyme. Racemic and enantiomerically resolved varieties of selected compounds were synthesized. All analogues in the study displayed decent binding affinity to HIV protease, and several compounds were shown to possess very good antiviral efficacy and safety margins. X-ray crystallographic structures confirmed that the sulfonamide and sulfonate moieties were filling the S3' pocket of the enzyme. However, the additional substituent did not provide improved enzymatic inhibitory or antiviral activity as compared to the resolved unsubstituted aniline. The addition of the sulfonyl moiety substitution does not appear to provide favorable pharamacokinectic parameters. Selected inhibitors were tested for antiviral activity in clinical isolates and exhibited similar antiviral activity against all of the HIV-1 strains tested as they did against the wild-type HIV-1, In addition, the inhibitors exhibited good antiviral efficacies against HIV-1 strains that displayed resistance to the currently marketed protease inhibitors. C1 Parke Davis Pharmaceut Res, Dept Chem, Ann Arbor, MI 48105 USA. Parke Davis Pharmaceut Res, Dept Biochem, Ann Arbor, MI 48105 USA. Parke Davis Pharmaceut Res, Dept Infect Dis, Ann Arbor, MI 48105 USA. Parke Davis Pharmaceut Res, Dept PDM, Ann Arbor, MI 48105 USA. NCI, Frederick Canc Res & Dev Ctr, Struct Biochem Program, PRI Dyncorp, Frederick, MD 21702 USA. RP Boyer, FE (reprint author), Parke Davis Pharmaceut Res, Dept Chem, 2800 Plymouth Rd, Ann Arbor, MI 48105 USA. RI ID, IMCACAT/D-5867-2014 NR 31 TC 43 Z9 46 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAR 9 PY 2000 VL 43 IS 5 BP 843 EP 858 DI 10.1021/jm990281p PG 16 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 292QD UT WOS:000085805800011 PM 10715152 ER PT J AU Gao, Y Luo, J Yao, ZJ Guo, RB Zou, H Kelley, J Voigt, JH Yang, DJ Burke, TR AF Gao, Y Luo, J Yao, ZJ Guo, RB Zou, H Kelley, J Voigt, JH Yang, DJ Burke, TR TI Inhibition of Grb2 SH2 domain binding by non-phosphate-containing ligands. 2. 4-(2-malollyl)phenylalanine as a potent phosphotyrosyl mimetic SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID STRUCTURE-BASED DESIGN; SOLID-PHASE SYNTHESIS; PEPTIDE LIGANDS; L-O-(2-MALONYL)TYROSINE; SPECIFICITY; AFFINITY; RECEPTOR AB Nonhydrolyzable phosphotyrosyl (pTyr) mimetics serve as important components of many competitive Grb2 SH2 domain inhibitors. To date, the most potent of these inhibitors have relied on phosphonate-based structures to replace the 4-phosphoryl group of the parent pTyr residue. Reported herein is the design and evaluation of a new pTyr mimetic, p-malonylphenylalanine (Pmf), which does not contain phosphorus yet, in Grb2 SH2 domain binding systems, approaches the potency of phosphonate-based pTyr mimetics. When incorporated into high affinity Grb2 SH2 domain-directed platforms, Pmf is 15-20 times more potent than the closely related previously reported pTyr mimetic, O-malonyltyrosine (OMT). Pmf-containing inhibitors show inhibition constants as low as 8 nM in extracellular Grb2 binding assays and in whole cell systems, effective blockade of both endogenous Grb2 binding to cognate erbB-2, and downstream MAP kinase activation. Evidence is provided that use of an N-alpha-oxalyl auxiliary enhances effectiveness of Pmf and other inhibitors in both extracellular and intracellular contexts. As one of the most potent Grb2 SH2 domain-directed pTyr mimetics yet disclosed, Pmf may potentially have utility in the design of new chemotherapeutics for the treatment of various proliferative diseases, including breast cancer. C1 NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Washington, DC 20007 USA. RP Burke, TR (reprint author), NCI, Med Chem Lab, Div Basic Sci, NIH, Bldg 37,Room 5C06, Bethesda, MD 20892 USA. RI Burke, Terrence/N-2601-2014; Yao, Zhu-Jun/E-7635-2015 NR 41 TC 62 Z9 63 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAR 9 PY 2000 VL 43 IS 5 BP 911 EP 920 DI 10.1021/jm9904248 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 292QD UT WOS:000085805800016 PM 10715157 ER PT J AU Nacro, K Bienfait, B Lee, J Han, KC Kang, JH Benzaria, S Lewin, NE Bhattacharyya, DK Blumberg, PM Marquez, VE AF Nacro, K Bienfait, B Lee, J Han, KC Kang, JH Benzaria, S Lewin, NE Bhattacharyya, DK Blumberg, PM Marquez, VE TI Conformationally constrained analogues of diacylglycerol (DAG). 16. How much structural complexity is necessary for recognition and high binding affinity to protein kinase C? SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; 5-DISUBSTITUTED TETRAHYDRO-2-FURANONE TEMPLATE; NATIONAL-CANCER-INSTITUTE; PHORBOL ESTER; BIOLOGICAL EVALUATION; BRYOSTATIN ANALOGS; TUMOR PROMOTERS; FACTOR RECEPTOR; DRUG DISCOVERY; LIGANDS AB The design of potent protein kinase C (PK-C) Ligands with low nanomolar binding affinities was accomplished by the combined use of pharmacophore- and receptor-guided approaches based on the structure of the physiological enzyme activator, diacylglycerol (DAG). Earlier use of the former approach, which was based on the structural equivalence of DAG and phorbol ester pharmacophores, identified a fixed template for the construction of a semirigid "recognition domain" that contained the three principal pharmacophores of DAG constrained into a lactone ring (DAG-lactones). In the present work, the pharmacophore-guided approach was refined to a higher level based on the X-ray structure of the C1b domain of PK-C delta complexed with phorbol-13-O-acetate. A systematic search that involved modifying the DAG-lactone template with a combination of linear or branched acyl and alpha-alkylidene chains, which functioned as variable hydrophobic "affinity domains", helped identify compounds that optimized hydrophobic contacts with a group of conserved hydrophobic amino acids located on the top half of the C1 domain where the phorbol binds. The hydrophilic/hydrophobic balance of the molecules was estimated by the octanol/water partition coefficients (log P) calculated according to a fragment-based approach. The presence of branched alpha-alkylidene or acyl chains was of critical importance to reach low nanomolar binding affinities for PK-C. These branched chains appear to facilitate important van der Waals contacts with hydrophobic segments of the protein and help promote the activation of PK-C through critical membrane interactions. Molecular modeling of these DAG-lactones into an empty C1b domain using the program AutoDock 2.4 suggests the existence of competing binding modes (sn-1 and sn-2) depending on which carbonyl is directly involved in binding to the protein. Inhibition of epidermal growth factor (EGF) binding, an indirect PK-C mediated response, was realized with some DAG-lactones at a dose 10-fold higher than with the standard phorbol-12,13-dibutyrate (PDBU). Through the National Cancer Institute (NCI) 60-cell line in vitro screen, DAG-lactone 31 was identified as a very selective and potent antitumor agent. The NCI's computerized, pattern-recognition program COMPARE, which analyzes the degree of similarity of mean-graph profiles produced by the screen, corroborated our principles of drug design by matching the profile of compound 31 with that of the nontumor-promoting antitumor phorbol ester, prostratin. The structural simplicity and the degree of potency achieved with some of the DAG-lactones described here should dispel the myth that chemical complexity and pharmacological activity go hand in hand. Even as a racemate, DAG-lactone 31 showed low namomolar binding affinity for PK-C and displayed selective antitumor activity at equivalent nanomolar levels. Our present approach should facilitate the generation of multiple libraries of structurally similar DAG-lactones to help exploit molecular diversity for PK-C and other high-affinity receptors for DAG and the phorbol esters. The success of this work suggests that substantially simpler, high-affinity structures could be identified to function as surrogates of other complex natural products. C1 NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Seoul Natl Univ, Coll Pharm, Med Chem Lab, Seoul 151742, South Korea. RP Marquez, VE (reprint author), NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NR 58 TC 65 Z9 65 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAR 9 PY 2000 VL 43 IS 5 BP 921 EP 944 DI 10.1021/jm9904607 PG 24 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 292QD UT WOS:000085805800017 PM 10715158 ER PT J AU Thompson, PM Giedd, JN Woods, RP MacDonald, D Evans, AC Toga, AW AF Thompson, PM Giedd, JN Woods, RP MacDonald, D Evans, AC Toga, AW TI Growth patterns in the developing brain detected by using continuum mechanical tensor maps SO NATURE LA English DT Article ID ALZHEIMERS-DISEASE; IMAGES AB The dynamic nature of growth and degenerative disease processes requires the design of sensitive strategies to detect, track and quantify structural change in the brain in its full spatial and temporal complexity(1). Although volumes of brain substructures are known to change during development(2), detailed maps of these dynamic growth processes have been unavailable. Here we report the creation of spatially complex, four-dimensional quantitative maps of growth patterns in the developing human brain, detected using a tensor mapping strategy with greater spatial detail and sensitivity than previously obtainable. By repeatedly scanning children (aged 3-15 years) across time spans of up to four years, a rostro-caudal wave of growth was detected at the corpus callosum, a fibre system that relays information between brain hemispheres. Peak growth rates, in fibres innervating association and language cortices, were attenuated after puberty, and contrasted sharply with a severe, spatially localized loss of subcortical grey matter. Conversely, at ages 3-6 years, the fastest growth rates occurred in frontal networks that regulate the planning of new actions. Local rates, profiles, and principal directions of growth were visualized in each individual child. C1 Univ Calif Los Angeles, Sch Med, Div Brain Mapping, Dept Neurol,Lab Neuroimaging, Los Angeles, CA 90095 USA. NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. McGill Univ, Montreal Neurol Inst, Montreal, PQ H3A 2B4, Canada. RP Thompson, PM (reprint author), Univ Calif Los Angeles, Sch Med, Div Brain Mapping, Dept Neurol,Lab Neuroimaging, 710 Westwood Plaza, Los Angeles, CA 90095 USA. EM thompson@loni.ucla.edu RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 18 TC 546 Z9 552 U1 2 U2 20 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 9 PY 2000 VL 404 IS 6774 BP 190 EP 193 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 293UC UT WOS:000085870900053 PM 10724172 ER PT J AU Lee, JS Collins, KM Brown, AL Lee, CH Chung, JH AF Lee, JS Collins, KM Brown, AL Lee, CH Chung, JH TI hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response SO NATURE LA English DT Article ID CELL-CYCLE; OVARIAN-CANCER; S-PHASE; SACCHAROMYCES-CEREVISIAE; PROTEIN-KINASE; GENE; TRANSCRIPTION; BREAST; YEAST; ATM AB Mutations in the BRCA1 (ref. 1) tumour suppressor gene are found in almost all of the families with inherited breast and ovarian cancers and about half of the families with only breast cancer(2,3). Although the biochemical function of BRCA1 is not well understood, it is important for DNA damage repair(4-7) and cell-cycle checkpoints(8-10). BRCA1 exists in nuclear foci but is hyperphosphorylated and disperses after DNA damage(11,12). It is not known whether BRCA1 phosphorylation and dispersion and its function in DNA damage response are related. In yeast the DNA damage response and the replication-block checkpoint are mediated partly through the Cds1 kinase family(13-20). Here we report that the human Cds1 kinase (hCds1/Chk2)(21-23) regulates BRCA1 function after DNA damage by phosphorylating serine 988 of BRCA1. We show that hCds1 and BRCA1 interact and colocalize within discrete nuclear foci but separate after gamma irradiation. Phosphorylation of BRCA1 at serine 988 is required for the release of BRCA1 from hCds1. This phosphorylation is also important for the ability of BRCA1 to restore survival after DNA damage in the BRCA1-mutated cell line HCC1937. C1 NHLBI, Lab Mol Hematol, NIH, Bethesda, MD 20892 USA. RP Chung, JH (reprint author), NHLBI, Lab Mol Hematol, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 29 TC 398 Z9 410 U1 3 U2 17 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 9 PY 2000 VL 404 IS 6774 BP 201 EP 204 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 293UC UT WOS:000085870900056 PM 10724175 ER PT J AU Rubinstein, YR Driggers, PH Ogryzko, VV Thornton, AM Ozato, K Pontzer, CH AF Rubinstein, YR Driggers, PH Ogryzko, VV Thornton, AM Ozato, K Pontzer, CH TI An IFN regulatory factor-2 DNA-binding domain dominant negative mutant exhibits altered cell growth and gene expression SO ONCOGENE LA English DT Article DE interferon; interferon regulatory factor; cell growth ID FACTOR-I IRF-1; TRANSCRIPTION FACTOR; PROTEIN-KINASE; INTERFERON SYSTEM; CYCLIN KINASES; INHIBITOR P21; DIFFERENTIATION; INDUCTION; ARREST; TRANSFORMATION AB In order to study interferon regulatory factor (IRF) family mediation of cell growth regulation, we established U937 cell lines stably transfected with a truncated form of IRF-2 lacking the transcriptional repressor domain. The truncated IRF-2 contained the DNA binding domain (DBD) and bound the ISRE, Phenotypically, the IRF-2 DBD transfectants exhibited reduced cell growth, altered morphology and increased cell death, Consistent with alterations in growth characteristics, the IRF-2 DBD transfectants constitutively expressed higher levels of the cyclin dependent kinase inhibitor p21(WAF1/Cip1) than did control clones. The level of p21(WAF1/Cip1) expression was positively correlated with the level of DBD expressed, as well as with the level of growth inhibition in these clones, DBD expression also correlated with expression of other members of the growth regulatory complex, cyclin dependent kinase 2 and cyclin A, but not proliferating cell nuclear antigen. These results imply active repression by IRF-2 to keep p21(WAF1/Cip1) transcriptionally silent. C1 Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Pontzer, CH (reprint author), Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. RI Ogryzko, Vasily/M-6665-2015 OI Ogryzko, Vasily/0000-0002-8548-1389 NR 36 TC 7 Z9 7 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 9 PY 2000 VL 19 IS 11 BP 1411 EP 1418 DI 10.1038/sj.onc.1203435 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 295AD UT WOS:000085942700006 PM 10723132 ER PT J AU Ren, SR Smith, MJ Louro, ID McKie-Bell, P Bani, MR Wagner, M Zochodne, B Redden, DT Grizzle, WE Wang, ND Smith, DI Herbst, RA Bardenheuer, W Opalka, B Schutte, J Trent, JM Ben-David, Y Ruppert, JM AF Ren, SR Smith, MJ Louro, ID McKie-Bell, P Bani, MR Wagner, M Zochodne, B Redden, DT Grizzle, WE Wang, ND Smith, DI Herbst, RA Bardenheuer, W Opalka, B Schutte, J Trent, JM Ben-David, Y Ruppert, JM TI The p44(S10) locus, encoding a subunit of the proteasome regulatory particle, is amplified during progression of cutaneous malignant melanoma SO ONCOGENE LA English DT Article DE proteasome; regulatory particle; p44(S10); gene amplification; melanoma ID COMPARATIVE GENOMIC HYBRIDIZATION; GENE AMPLIFICATION; BREAST-CANCER; CELL-LINES; DNA; COMPLEX; DEGRADATION AB Gene amplification is frequently present in human tumors, although specific target genes relevant to many amplified loci remain unidentified. An expression cloning assay enabled identification of a candidate oncogene derived from human chromosome 3p14.1, The cDNA retrieved from morphologically transformed cells contained the full-length protein coding region and detected an abundant transcript in the same cells. Sequence analysis revealed identity with the wild-type sequence of p44(S10), a highly conserved subunit of the 26S proteasome that exhibits similarity to the Arabidopsis fus6/cop11 family of signaling molecules. p44(S10) gene copy number and mRNA expression were increased in association with segmental 1.8-11-fold chromosomal gains in cutaneous malignant melanoma cell lines (5/13; 40%) and tumors (2/40; 5%), and in breast cancer MCF-7 cells. Likewise, malignant progression of human radial growth phase WM35 melanoma cells was associated with amplification and increased expression of endogenous p44(S10), and increased expression of p44(S10) was sufficient to induce proliferation of WM35 cells in vivo. The results demonstrate segmental copy number gains within chromosome 3p in cutaneous malignant melanoma and suggest that deregulation of a proteasome regulatory particle subunit may contribute to the malignant phenotype. C1 Univ Alabama, Dept Biochem & Mol Genet, Birmingham, AL USA. Univ Alabama, Dept Med, Div Hematol Oncol, Birmingham, AL USA. Univ Alabama, Ctr Comprehens Canc, Birmingham, AL USA. Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada. Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Mayo Clin & Mayo Fdn, Dept Lab Med & Pathol, Rochester, MN 55905 USA. Hannover Med Sch, Dept Dermatol, D-30449 Hannover, Germany. Univ Essen Gesamthsch, Sch Med, Dept Med Oncol Canc Res, W German Canc Ctr Essen, D-45122 Essen, Germany. Natl Human Genome Res Inst, NIH, Bethesda, MD USA. RP Ruppert, JM (reprint author), Room 570 WTI,1824 6th Ave S, Birmingham, AL 35294 USA. FU NCI NIH HHS [CA48031, R29CA65686] NR 31 TC 21 Z9 22 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 9 PY 2000 VL 19 IS 11 BP 1419 EP 1427 DI 10.1038/sj.onc.1203462 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 295AD UT WOS:000085942700007 PM 10723133 ER PT J AU Weinrich, M Stuart, M AF Weinrich, M Stuart, M TI Provision of methadone treatment in primary care medical practices - Review of the Scottish experience and implications for US policy SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID GENERAL-PRACTITIONERS; MAINTENANCE TREATMENT; OUTCOMES AB Context Under new proposed regulations, US physicians outside of traditional methadone clinics could prescribe methadone to patients with opioid dependence. No large-scale evaluations of US programs in which methadone maintenance is provided by primary care physicians are available, but primary care physicians in Scotland have participated in such programs on a large scale. Objective To review the history, operation, and outcome data on the efficacy and safety of 2 Scottish primary care-based opioid agonist treatment programs to derive lessons for the US context. Design and Setting Naturalistic study of programs in Edinburgh and Glasgow, Scotland, with data obtained through site visits and interviews conducted in 1996 and 1998, as well as from published reports and retrospective analysis of electronic databases. Main Outcome Measures Proportions of injection drug users who were enrolled in the methadone maintenance programs, average methadone doses in the pro grams, and methadone-related deaths. Results A total of 60% to 80% of injection drug users in Edinburgh and 41% to 73% of those in Glasgow were enrolled in methadone maintenance in 1998-1999, Dose levels are consistent with US recommendations (for Edinburgh in 1998, 61 mg; for Glasgow in 1994-1996, 54 mg). The Glasgow program required supervised consumption of methadone in community pharmacies for the first year and experienced significantly fewer methadone-related deaths than Edinburgh in 1997 (17 vs 30 deaths; P<.0001). Programs in both Edinburgh and Glasgow provided support to primary care physicians and achieved levels of general practitioner participation of 59% (1998) and 30% (1999), respectively. Conclusions The Scottish experience indicates that prescription of methadone in office-based settings can expand access to an important treatment modality. Primary care physicians safely prescribed methadone for maintenance treatment when provided with adequate support. Diversion of methadone was minimized by requiring supervised consumption in community pharmacies. C1 Univ Maryland, Dept Neurol, Baltimore, MD 21201 USA. Univ Maryland Baltimore Cty, Dept Sociol & Anthropol, Baltimore, MD 21228 USA. RP Weinrich, M (reprint author), NICHHD, Natl Ctr Med Rehabil Res, NIH, 6100 Execut Blvd,Room 2A03,MSC 7510, Bethesda, MD 20892 USA. NR 54 TC 47 Z9 48 U1 0 U2 2 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 8 PY 2000 VL 283 IS 10 BP 1343 EP 1348 DI 10.1001/jama.283.10.1343 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 289ND UT WOS:000085628100035 PM 10714738 ER PT J AU Venable, RM Brooks, BR Pastor, RW AF Venable, RM Brooks, BR Pastor, RW TI Molecular dynamics simulations of gel (L-beta I) phase lipid bilayers in constant pressure and constant surface area ensembles SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID COMPUTER-SIMULATION; DIPALMITOYLPHOSPHATIDYLCHOLINE BILAYER; LIQUID/LIQUID INTERFACES; PHOSPHOLIPID-BILAYER; BOUNDARY-CONDITIONS; FLUID MEMBRANES; TENSION; PHOSPHATIDYLCHOLINE; TRANSITION; DISORDER AB The results of a series of molecular dynamics simulations of the gel state of a dipalmitoylphosphatidylcholine bilayer at 293 K are described. The simulations, ranging from 40 ps to 2.5 ns, show clearly that: a flexible cell geometry is essential during equilibration; Ewald summation of electrostatics is superior to spherical cutoff methods; water exchange with the carbonyl group of chain 2 takes place on the ns time scale, while there is almost no hydration of chain 1. There is overall good agreement (D-spacing, chain tilt, fraction gauche, and area compressibility modulus) with experiment, though the surface area per lipid is slightly underestimated. The randomization of torsion 1 of chain 2 from exclusively gauche minus (as specified in the initial condition modeled from the crystal structure of a related lipid) to a mixture of g+/g- over the course of approximately 2 ns is a critical feature of the study. The torsional equilibration proceeded steadily when simulating at constant surface tension, but was effectively quenched by simulation at constant area. The associated presence of conformational degeneracy of this torsion, and conformational disorder in the upper region of chain 2, is most likely associated with the seemingly anomalous infrared (IR) results for gauche bonds in the upper region of the chains. It may also be a characteristic of the gel phase, and be related to the long time required for the gel to subgel transition. [S0021-9606(00)50210-4]. C1 US FDA, Phys Lab, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. NHLBI, Computat Biophys Sect, Biophys Chem Lab, Bethesda, MD 20892 USA. RP Venable, RM (reprint author), US FDA, Phys Lab, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. NR 44 TC 76 Z9 76 U1 0 U2 9 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD MAR 8 PY 2000 VL 112 IS 10 BP 4822 EP 4832 DI 10.1063/1.481085 PG 11 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 288LG UT WOS:000085563800043 ER PT J AU Delaglio, F Kontaxis, G Bax, A AF Delaglio, F Kontaxis, G Bax, A TI Protein structure determination using molecular fragment replacement and NMR dipolar couplings SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID LIQUID-CRYSTALLINE MEDIUM; HUMAN UBIQUITIN; HETERONUCLEAR NMR; CHEMICAL-SHIFTS; MACROMOLECULES; RESOLUTION; RELAXATION; H-1-NMR; ANGLES; PHASE C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Bax, A (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. NR 27 TC 198 Z9 200 U1 1 U2 11 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 8 PY 2000 VL 122 IS 9 BP 2142 EP 2143 DI 10.1021/ja993603n PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 294ME UT WOS:000085914400045 ER PT J AU Wlodawer, A Gustchina, A AF Wlodawer, A Gustchina, A TI Structural and biochemical studies of retroviral proteases SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY LA English DT Review DE retrovirus; aspartic protease; AIDS; protein structure; enzyme kinetics ID HUMAN-IMMUNODEFICIENCY-VIRUS; ROUS-SARCOMA VIRUS; SUBSTRATE-BINDING POCKETS; SYNTHETIC HIV-1 PROTEASE; TYPE-1 PROTEASE; CRYSTAL-STRUCTURE; 3-DIMENSIONAL STRUCTURE; ASPARTIC PROTEINASES; ANEMIA VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS-1 PROTEASE AB Retroviral proteases form a unique subclass of the family of aspartic proteases. These homodimeric enzymes from a number of viral sources have by now been extensively characterized, both structurally and biochemically. The importance of such knowledge to the development of new drugs against AIDS has been, to a large extent, the driving force behind this progress. High-resolution structures are now available for enzymes from human immunodeficiency virus types 1 and 2. simian immunodeficiency virus. feline immunodeficiency virus, Rous sarcoma virus. and equine infectious anemia virus. In this review. structural and biochemical data for retroviral protrases are compared in order to analyze the similarities and differences between the enzymes from different sources and to enhance our understanding of their propel-ties. (C) 2000 Elsevier Science B.V. All rights reserved. C1 NCI, Frederick Canc Res & Dev Ctr, Program Struct Biol, Macromol Crystallog Lab, Frederick, MD 21702 USA. RP Wlodawer, A (reprint author), NCI, Frederick Canc Res & Dev Ctr, Program Struct Biol, Macromol Crystallog Lab, Frederick, MD 21702 USA. EM wlodawer@ncifcrf.gov NR 107 TC 141 Z9 144 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4838 J9 BBA-PROTEIN STRUCT M JI Biochim. Biophys. Acta-Protein Struct. Molec. Enzym. PD MAR 7 PY 2000 VL 1477 IS 1-2 BP 16 EP 34 DI 10.1016/S0167-4838(99)00267-8 PG 19 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 295ZL UT WOS:000085998500004 PM 10708846 ER PT J AU McDermott, MM Fried, L Simonsick, E Ling, S Guralnik, JM AF McDermott, MM Fried, L Simonsick, E Ling, S Guralnik, JM TI Asymptomatic peripheral arterial disease is independently associated with impaired lower extremity functioning - The Women's Health and Aging Study SO CIRCULATION LA English DT Article DE arteries; aging; peripheral vascular disease ID CARDIOVASCULAR HEALTH; PRESSURE INDEX; DISABILITY; MORTALITY; AGE AB Background-We report the implications of asymptomatic lower extremity peripheral arterial disease (PAD) for lower extremity functioning among participants in the Women's Health and Aging Study, an observational study of disabled women greater than or equal to 65 years of age living in and around Baltimore. Methods and Results-The ankle brachial index (ABI) and measures of upper and lower extremity functioning were measured among study participants. Of 933 women with ABI less than or equal to 1.50, 328 (35%) had an ABI <0.90, consistent with PAD. Sixty-three percent of PAD participants had no exertional leg pain. Among participants without exertional leg pain, lower ABI levels were associated with slower walking velocity, poorer standing balance score, slower time to arise 5 times consecutively from a seated position, and fewer blocks walked per week, adjusting for age, sex, race, cigarette smoking, and comorbidities, ABI was not associated independently with measures of upper extremity functioning. Conclusions-Asymptomatic PAD is common and is independently associated with impaired lower extremity functioning. In addition to preventing cardiovascular morbidity and death, further study is warranted to identify effective interventions to improve functioning among the growing number of men and women with asymptomatic PAD. C1 Northwestern Univ, Sch Med, Chicago, IL 60611 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. NIA, Epidemiol Biometry & Demog Program, Bethesda, MD 20892 USA. RP McDermott, MM (reprint author), 675 N St Clair,Suite 18-200, Chicago, IL 60611 USA. FU NIA NIH HHS [N01-AG-1-2112] NR 19 TC 126 Z9 133 U1 0 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 7 PY 2000 VL 101 IS 9 BP 1007 EP 1012 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 291RV UT WOS:000085750600012 PM 10704168 ER PT J AU Guttmacher, AE Callahan, JR AF Guttmacher, AE Callahan, JR TI Did Robert Louis Stevenson have hereditary hemorrhagic telangiectasia? SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Biographical-Item DE hereditary hemorrhagic telangiectasia; Robert Louis Stevenson AB Chronic illness played a major role in the life and literary success of Robert Louis Stevenson. However, the exact nature of his chronic illness remains unclear. It is possible that Stevenson had hereditary hemorrhagic telangiectasia (Osler-Rendu-Weber Syndrome). This would explain his chronic respiratory complaints, recurrent episodes of pulmonary hemorrhage, and his death, at age 44 years, of probable cerebral hemorrhage. It would also explain his mother's hitherto unreported but apparent stroke, at age 38 years. Further support for this hypothesis might come from new details about the health of Stevenson and his relatives or from molecular analysis of tissue specimens remaining from. him. (C) 2000 Wiley-Liss, Inc. C1 Univ Vermont, Coll Med, Dept Pediat, Burlington, VT USA. Univ Vermont, Coll Med, Dept Med, Burlington, VT USA. RP Guttmacher, AE (reprint author), Natl Human Genome Res Inst, 31 Ctr Dr,MSC 2152,Bldg 31,Room 4B09, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAR 6 PY 2000 VL 91 IS 1 BP 62 EP 65 DI 10.1002/(SICI)1096-8628(20000306)91:1<62::AID-AJMG11>3.0.CO;2-3 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 288UN UT WOS:000085583000011 PM 10751091 ER PT J AU Ta, LE Dionne, RA Friction, JR Hodges, JS Kajander, KC AF Ta, LE Dionne, RA Friction, JR Hodges, JS Kajander, KC TI SYM-2081 a kainate receptor antagonist reduces allodynia and hyperalgesia in a freeze injury model of neuropathic pain SO BRAIN RESEARCH LA English DT Review DE rat; neuropathic pain; fentanyl; excitatory amino acid; kainate receptor ID EXCITATORY AMINO-ACIDS; SPINOTHALAMIC TRACT NEURONS; CENTRAL NERVOUS-SYSTEM; DORSAL-ROOT GANGLION; EXPERIMENTAL PERIPHERAL NEUROPATHY; SUBSTANCE-P; SPINAL-CORD; SCIATIC-NERVE; RAT MODEL; CENTRAL SENSITIZATION AB Cold-freeze injury at -4 degrees C to the rat sciatic nerve produces mechanical allodynia and thermal hyperalgesia [M.A. Kleive, P.S. Jungbluth, J.A. Uhlenkamp, K.C. Kajander, Cold injury to rat sciatic nerve induces thermal hyperalgesia or analgesia, gth World Congress on Pain, Vancouver, BC, Canada, August 1996 (Abstract).]. The NMDA receptor, an excitatory amino acid (EAA) receptor, appears to be involved in the development of allodynia and hyperalgesia following nerve injury, The role, if any, of the kainate receptor, another EAA receptor, remains unknown. In the current study, we evaluated a whether (2S,4R)-4-methylglutamic acid (SYM-2081), a recently developed kainate receptor antagonist, attenuates increased responsiveness following cold injury to the sciatic nerve. During baseline testing, Sprague-Dawley rats were evaluated for frequency of withdrawal from van Frey filaments and latency of withdrawal from a radiant thermal source. Animals were then anesthetized, the left sciatic nerve was exposed, and the nerve was cooled to -4 degrees C for 15 min (n = 24). For control rats (n = 24), all procedures were identical except that the nerve was maintained at 37 degrees C. Testing resumed on the third day following surgery. On the fifth post-operative day, SYM-2081 (150 or 100 mg/kg), fentanyl citrate (0.04 mg/kg) or vehicle was injected intraperitoneally. Injury to the rat sciatic nerve induced a significant increase in withdrawal frequency and a significant decrease in withdrawal latency (ANOVA, p < 0.05). SYM-2081 and fentanyl significantly reduced these responses (p < 0.05). These results suggest that kainate and opioid receptors are involved in the mechanical allodynia and thermal hyperalgesia that develop following cold injury to the sciatic nerve. (C) 2000 Published by Elsevier Science B.V. All rights reserved. C1 Natl Inst Dent & Craniofacial Res, Pain & Neurosensory Mechanisms Branch, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Dept Diagnost & Surg Sci, Minneapolis, MN 55455 USA. Univ Minnesota, Oral Hlth Clin Res Ctr, Minneapolis, MN 55455 USA. Univ Minnesota, Div Biostat, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Oral Sci, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Cell Biol, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Neuroanat, Minneapolis, MN 55455 USA. Univ Minnesota, Grad Program Neurosci, Minneapolis, MN 55455 USA. RP Ta, LE (reprint author), Natl Inst Dent & Craniofacial Res, Pain & Neurosensory Mechanisms Branch, NIH, 10 Ctr Dr,Bldg 10,Room 1N-103, Bethesda, MD 20892 USA. FU NIDCR NIH HHS [P30-DEO9737]; NINDS NIH HHS [R01-NS33908, R43-NS35827] NR 112 TC 28 Z9 28 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 6 PY 2000 VL 858 IS 1 BP 106 EP 120 DI 10.1016/S0006-8993(99)02437-3 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 289TU UT WOS:000085638700015 PM 10700603 ER PT J AU Pankov, R Cukierman, E Katz, BZ Matsumoto, K Lin, DC Lin, S Hahn, C Yamada, KM AF Pankov, R Cukierman, E Katz, BZ Matsumoto, K Lin, DC Lin, S Hahn, C Yamada, KM TI Integrin dynamics and matrix assembly: Tensin-dependent translocation of alpha(5)beta(1) integrins promotes early fibronectin fibrillogenesis SO JOURNAL OF CELL BIOLOGY LA English DT Article DE fibronectin; integrin; tensin; vitronectin; extracellular matrix ID CELL-ADHESION; CULTURED FIBROBLASTS; SELF-ASSOCIATION; BINDING-SITE; RECEPTOR; ACTIN; IDENTIFICATION; LOCALIZATION; MIGRATION; POLYMERIZATION AB Fibronectin matrix assembly is a multistep, integrin-dependent process,To investigate the role of integrin dynamics in fibronectin fibrillogenesis, we developed an antibody-chasing technique for simultaneous tracking of two integrin populations by different antibodies. We established that whereas the vitronectin receptor alpha(v)beta(3) remains within focal contacts, the fibronectin receptor alpha(5)beta(1) translocates from focal contacts into and along extracellular matrix (ECM) contacts. This escalator-like translocation occurs relative to the focal contacts at 6.5 +/- 0.7 mu m/h and is independent of cell migration. It is induced by ligation of alpha(5)beta(1) integrins and depends on interactions with a functional actin cytoskeleton and vitronectin receptor ligation. During cell spreading, translocation of ligand-occupied alpha(5)beta(1) integrins away from focal contacts and along bundles of actin filaments generates ECM contacts. Tensin is a primary cytoskeletal component of these ECM contacts, and a novel dominant-negative inhibitor of tensin blocked ECM contact formation, integrin translocation, and fibronectin fibrillogenesis without affecting focal contacts. We propose that translocating alpha(5)beta(1) integrins induce initial fibronectin fibrillogenesis by transmitting cytoskeleton-generated tension to extracellular fibronectin molecules. Blocking this integrin translocation by a variety of treatments prevents the formation of ECM contacts and fibronectin fibrillogenesis. These studies identify a localized, directional, integrin translocation mechanism for matrix assembly. C1 Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92697 USA. RP Yamada, KM (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bldg 30,Room 421,30 convent Dr MSC 4370, Bethesda, MD 20892 USA. RI Pankov, Roumen/B-3284-2014 OI Pankov, Roumen/0000-0002-3157-3659 NR 54 TC 277 Z9 283 U1 1 U2 18 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAR 6 PY 2000 VL 148 IS 5 BP 1075 EP 1090 DI 10.1083/jcb.148.5.1075 PG 16 WC Cell Biology SC Cell Biology GA 292CC UT WOS:000085775700022 PM 10704455 ER PT J AU Nishikomori, R Ehrhardt, RO Strober, W AF Nishikomori, R Ehrhardt, RO Strober, W TI T helper type 2 cell differentiation occurs in the presence of interleukin 12 receptor beta 2 chain expression and signaling SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE cytokine; interleukin 4; reversibility; signal transducer and activator of transcription 4 T helper type 1 ID INTERFERON-GAMMA PRODUCTION; IFN-GAMMA; TH2 CELLS; CYTOKINE RESPONSES; LEISHMANIA-MAJOR; TRANSGENIC MICE; BALB/C MICE; IL-4 GENE; C-MAF; STAT6 AB The differentiation of CD4(+) T cells into T helper type 1 (Th1) cells is driven by interleukin (IL)-12 through the IL-12 receptor beta 2 (IL-12R beta 2) chain, whereas differentiation into Th2 cells is driven by IL-4, which downregulates IL-12R beta 2 chain. We reexamined such differentiation using IL-12R beta 2 chain transgenic mice. We found that CD4(+) T cells from such mice were able to differentiate into Th2 cells when primed with IL-4 or IL-4 plus IL-12. In the latter case, the presence of IL-4 suppressed interferon (IFN)-gamma production 10-100-fold compared with cells cultured in IL-12 alone. Finally, in studies of the ability of IL-12 to convert Th2 cells bearing a competent IL-12R to the Th1 cells, we showed that: (a) T cells bearing the IL-12R beta 2 chain transgene and primed under Th2 conditions could not be converted to Th1 cells by repeated restimulation under Th1 conditions; and (b) established Th2 clones transfected with the IL-12R beta 2 chain construct continued to produce IL-4 when cultured with IL-12. These studies show that IL-4-driven Th2 differentiation can occur in the presence of persistent IL-12 signaling and that IL-4 inhibits IFN-gamma production under these circumstances. They also show that established Th2 cells cannot be converted to Th1 cells via IL-12 signaling. C1 NIAID, Mucosal Immun Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. Prot Design Labs Inc, Fremont, CA 94555 USA. RP Strober, W (reprint author), NIAID, Mucosal Immun Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NR 49 TC 53 Z9 53 U1 0 U2 0 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 6 PY 2000 VL 191 IS 5 BP 847 EP 858 DI 10.1084/jem.191.5.847 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 292RZ UT WOS:000085810000011 PM 10704465 ER PT J AU Chang, YC Wickes, BL Miller, GF Penoyer, LA Kwon-Chung, KJ AF Chang, YC Wickes, BL Miller, GF Penoyer, LA Kwon-Chung, KJ TI Cryptococcus neoformans STE12 alpha regulates virulence but is not essential for mating SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE haploid fruiting; mating assay; STE12; cotransformation; virulence factor ID YEAST STE12 PROTEIN; CELL-TYPE; FILAMENTOUS GROWTH; CANDIDA-ALBICANS; GENE; ALPHA; COMPLEMENTATION; TRANSFORMATION; FILOBASIDIELLA; IDENTIFICATION AB The Cryptococcus neoformans STE12 alpha gene, a homologue of Saccharomyces cerevisiae STE12, exists only in mating type (MAT)alpha cells. In S. cerevisiae, STE12 was required for mating and filament formation. In C. neoformans, haploid fruiting on filament agar required STE12 alpha. The ability to form hyphae, however, was not affected by deletion of STE12 alpha when convergently growing MATa strains were present. Furthermore, ste12 alpha disruptants were fertile when mated with MATa strains, albeit with reduced mating frequency. Most importantly, the virulence of a ste12 alpha disruptant of serotype D strain was significantly reduced in a mouse model. When the ste12 alpha locus was reconstituted with the wild-type allele by cotransformation, virulence was restored. Histopathological analysis demonstrated a reduction in capsular size of yeast cells, less severe cystic lesions, and stronger immune responses in meninges of mice mice infected with ste12 alpha cells than those of mice infected with STE12 alpha cells. Using reporter gene constructs, we found that STE12 alpha controls the expression of several phenotypes known to be involved in virulence, such as capsule and melanin production. These results demonstrate a clear molecular link between mating type and virulence in C. neoformans. C1 NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NIH, Vet Resources Program, Off Director, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Dept Microbiol, San Antonio, TX 78284 USA. RP NIAID, Clin Invest Lab, NIH, Bldg 10,Rm 11C304, Bethesda, MD 20892 USA. EM June-Kwon-Chung@nih.gov FU NIAID NIH HHS [R29 AI043522, R29AI43522-01] NR 46 TC 109 Z9 111 U1 1 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0022-1007 EI 1540-9538 J9 J EXP MED JI J. Exp. Med. PD MAR 6 PY 2000 VL 191 IS 5 BP 871 EP 881 DI 10.1084/jem.191.5.871 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 292RZ UT WOS:000085810000013 PM 10704467 ER PT J AU Gonzalez, IM Karron, RA Eichelberger, M Walsh, EE Delagarza, VW Bennett, R Chanock, RM Murphy, BR Clements-Mann, ML Falsey, AR AF Gonzalez, IM Karron, RA Eichelberger, M Walsh, EE Delagarza, VW Bennett, R Chanock, RM Murphy, BR Clements-Mann, ML Falsey, AR TI Evaluation of the live attenuated cpts 248/404 RSV vaccine in combination with a subunit RSV vaccine (PFP-2) in healthy young and older adults SO VACCINE LA English DT Article DE respiratory syncytial virus vaccines; adults; elderly ID RESPIRATORY SYNCYTIAL VIRUS; INFLUENZA-A INFECTIONS; FUSION PROTEIN VACCINE; CHRONICALLY ILL; SEROPOSITIVE CHILDREN; PROTECTIVE EFFICACY; CYSTIC-FIBROSIS; IMMUNOGENICITY; SAFETY; PNEUMONIA AB The safety and immunogenicity of the live attenuated cold-passaged, temperature-sensitive (cpts) 248/404 respiratory syncytial Virus (RSV) A2 and the RSV A2 purified F glycoprotein (PFP-2) vaccine candidates were evaluated in a placebo-controlled trial in 60 healthy young adults and 60 healthy elderly subjects using simultaneous and sequential (cpts 248/404 followed by PFP-2) vaccination schedules. Both vaccines were well tolerated. The cpts 248/404 vaccine was moderately infectious in both young and old volunteers, but was highly restricted in replication in those who were infected. After both vaccines, RSV neutralizing antibody (neut Ab) titers increased fourfold in 22% of young subjects and in 16% of elderly subjects. Of those with low levels of RSV neut Ab (titer <9), 10/12 (83% of) young subjects and six/eight (75% of) elderly subjects had a greater than or equal to four fold rise in neut Ab titer, Young and elderly subjects immunized simultaneously had similar serum IgG and IgA postimmunization titers to RSV F (IgG, 16.4 vs 16.2, IgA 11.6 vs 12.5, respectively) as did those who were immunized sequentially (IgG 17.4 vs 17.0, IgA 13.0 vs 13.5). In both age groups, sequential immunization elicited higher postimmunization RSV F IgG and IgA titers than simultaneous immunization. Further studies that combine the PFP-2 subunit vaccine with a less attenuated RSV vaccine should be performed. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Int Hlth, Div Dis Control, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. Rochester Gen Hosp, Infect Dis Unit, Rochester, NY 14621 USA. Univ Rochester, Sch Med & Dent, Rochester, NY 14621 USA. Johns Hopkins Univ, Sch Med, Dept Geriatr, Baltimore, MD 21224 USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Karron, RA (reprint author), Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Int Hlth, Div Dis Control, Baltimore, MD 21205 USA. FU NIAID NIH HHS [AI-000030, AI-000087]; PHS HHS [N01-A0-62712] NR 48 TC 47 Z9 48 U1 2 U2 4 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 6 PY 2000 VL 18 IS 17 BP 1763 EP 1772 DI 10.1016/S0264-410X(99)00527-7 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 294EN UT WOS:000085898500006 PM 10699324 ER PT J AU Lappalainen, I Giliani, S Franceschini, R Bonnefoy, JY Duckett, C Notarangelo, LD Vihinen, M AF Lappalainen, I Giliani, S Franceschini, R Bonnefoy, JY Duckett, C Notarangelo, LD Vihinen, M TI Structural basis for SH2D1A mutations in X-linked lymphoproliferative disease SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID GROWTH-FACTOR RECEPTORS; CRYSTAL-STRUCTURE; SIGNAL-TRANSDUCTION; ENCODING GENE; HIGH-AFFINITY; SH3 DOMAINS; SRC; BINDING; PROTEIN; PEPTIDE AB X-linked lymphoproliferative disease (XLP) is a rare and severe immune deficiency, characterized by abnormal immune responses to the Epstein-Barr virus. Recently, the gene responsible for XLP, SH2D1A, has been identified and shown to code for a small cytoplasmic protein with an SH2 domain that interacts with SLAM and 2B4, two receptorial molecules involved in signal transduction in T and NK cells, respectively. A variety of SH2D1A gene mutations have been reported thus far in XLP males. Here we describe a single-strand conformation polymorphism assay for mutation analysis in XLP. Four novel patients with SH2D1A. mutations are described. These mutants, and the others previously reported in the literature, have been included in a Registry (SH2D1Abase) that is fully accessible on the World Wide Web. A three-dimensional model of the SH2 domain of the SH2D1A protein has been developed, based on homology with other SH2 domains. The structural consequences of disease-causing SH2D1A mutations are discussed. (C) 2000 Academic Press. C1 Univ Tampere, Inst Med Technol, FIN-33014 Tampere, Finland. Tampere Univ Hosp, FIN-33520 Tampere, Finland. Univ Helsinki, Dept Biosci, Div Biochem, FIN-00014 Helsinki, Finland. Univ Brescia, Spedali Civili, Pediat Clin, Lab Med Mol Angelo Nocivelli, Brescia, Italy. Ctr Immunol Pierre Fabre 5, F-74164 St Julien en Genevois, France. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Lappalainen, I (reprint author), Univ Tampere, Inst Med Technol, FIN-33014 Tampere, Finland. RI Vihinen, Mauno/A-8452-2012; Notarangelo, Luigi/F-9718-2016 OI Vihinen, Mauno/0000-0002-9614-7976; Notarangelo, Luigi/0000-0002-8335-0262 FU Telethon [E.0668] NR 56 TC 22 Z9 24 U1 0 U2 0 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 2000 VL 269 IS 1 BP 124 EP 130 DI 10.1006/bbrc.2000.2146 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 294PA UT WOS:000085918600022 PM 10694488 ER PT J AU de Koning-Ward, TF Fidock, DA Thathy, V Menard, R van Spaendonk, RML Waters, AP Janse, CJ AF de Koning-Ward, TF Fidock, DA Thathy, V Menard, R van Spaendonk, RML Waters, AP Janse, CJ TI The selectable marker human dihydrofolate reductase enables sequential genetic manipulation of the Plasmodium berghei genome SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE human DHFR; circumsporozoite protein; Plasmodium berghei; selection marker; transfection ID MALARIA PARASITES; BLOOD STAGES; ANTIMALARIAL ACTIVITY; FALCIPARUM; EXPRESSION; WR99210; PROTEIN; TRANSFORMATION; TRANSFECTION; SPOROZOITES AB Genetic transformation of malaria parasites has been limited by the number of selectable markers available. For the rodent malaria parasite. Plasmodium berghei, only a single selection marker has been at hand, utilising the dihydrofolate reductase-thymidylate synthase gene from either P. berghei or Toxoplasma gondii to confer resistance to the anti-malarial drug pyrimethamine. Here we report the use of the human dihydrofolate reductase (hDHFR) gene as a new selectable marker, which confers resistance to the antifolate inhibitor WR99210 upon both pyrimethamine sensitive and resistant isolates of P. berghei. Transfection with circular constructs containing the hDHFR gene resulted in the generation of highly resistant parasites containing multiple copies of episomally-maintained plasmids. These parasites showed around a 1000-fold increase in resistance to WR99210 compared to the parental parasites. We were also able to generate and select transgenic parasites harbouring only a single copy of hDHFR targeted into their genome, despite the fact that these parasites showed only a fivefold increase in resistance to WR99210 compared to the parental parasites. Importantly, and for the first time with malaria parasites, the hDHFR gene could be used in conjunction with the existing pyrimethamine selectable markers. This was demonstrated by reintroducing the circumsporozoite (CS) gene into transgenic CS-knockout mutant parasites that contained the P. berghei DHFR-TS selectable marker. The development of hDHFR as a second selectable marker will greatly expand the use of transformation technology in Plasmodium, enabling more extensive genetic manipulation and thus facilitating more comprehensive studies on the biology of the malaria parasite. (C) 1000 Published by Elsevier Science B.V. All rights reserved. C1 Leiden Univ, Med Ctr, Dept Parasitol, NL-2300 RC Leiden, Netherlands. NIAID, Malaria Genet Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NYU Med Ctr, Dept Pathol, Michael Heidelberger Div Immunol, New York, NY 10016 USA. RP Waters, AP (reprint author), Leiden Univ, Med Ctr, Dept Parasitol, Postbox 9600, NL-2300 RC Leiden, Netherlands. RI Waters, Andy/C-9377-2009; OI Waters, Andy/0000-0001-8900-2982; Fidock, David/0000-0001-6753-8938 NR 34 TC 58 Z9 61 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD MAR 5 PY 2000 VL 106 IS 2 BP 199 EP 212 DI 10.1016/S0166-6851(99)00189-9 PG 14 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 293ZC UT WOS:000085884300001 PM 10699250 ER PT J AU Elmendorf, HG Singer, SM Nash, TE AF Elmendorf, HG Singer, SM Nash, TE TI Targeting of proteins to the nuclei of Giardia lamblia SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article ID PHYLOGENETIC PLACE; LACKING PROTOZOAN; T-ANTIGEN; SEQUENCE; DNA; EUKARYOTE; TRANSPORT; LOCATION; CYSTS; RNA C1 NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Elmendorf, HG (reprint author), Georgetown Univ, Dept Biol, Washington, DC 20057 USA. NR 19 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD MAR 5 PY 2000 VL 106 IS 2 BP 315 EP 319 DI 10.1016/S0166-6851(99)00219-4 PG 5 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 293ZC UT WOS:000085884300013 PM 10699262 ER PT J AU Dignam, JJ Fisher, B AF Dignam, JJ Fisher, B TI Occurrence of stroke with tamoxifen in NSABP B-24 SO LANCET LA English DT Letter ID BREAST-CANCER; ADJUVANT C1 NASBP Biostat Ctr, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15213 USA. RP Fisher, B (reprint author), NASBP Biostat Ctr, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15213 USA. NR 3 TC 23 Z9 24 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAR 4 PY 2000 VL 355 IS 9206 BP 848 EP 849 DI 10.1016/S0140-6736(05)72466-1 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 291YG UT WOS:000085766900058 PM 10711957 ER PT J AU Zou, ZQ Gao, CL Nagaich, AK Connell, T Saito, S Moul, JW Seth, P Appella, E Srivastava, S AF Zou, ZQ Gao, CL Nagaich, AK Connell, T Saito, S Moul, JW Seth, P Appella, E Srivastava, S TI p53 regulates the expression of the tumor suppressor gene maspin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BREAST-CANCER CELLS; WILD-TYPE P53; PLASMINOGEN-ACTIVATOR; APOPTOSIS; GROWTH; TRANSCRIPTION; ANGIOGENESIS; CARCINOMA; ARREST; CYCLE AB Maspin has been shown to inhibit tumor cell invasion and metastasis in breast tumor cells. Maspin expression was detected in normal breast and prostate epithelial cells, whereas tumor cells exhibited reduced or no expression. However, the regulatory mechanism of maspin expression remains unknown. We report here a rapid and robust induction of maspin expression in prostate cancer cells (LNCaP, DU145, and PC3) and breast tumor cells (MCF7) following wild type p53 expression from an adenovirus p53 expression vector (AdWTp53). p53 activates the maspin promoter by binding directly to the p53 consensus-binding site present in the maspin promoter. DNA-damaging agents and cytotoxic drugs induced endogenous maspin expression in cells containing the wild type p53, Maspin expression was refractory to the DNA-damaging agents in cells containing mutant p53, These results, combined with recent studies of the tumor metastasis suppressor gene KAI1 and plasminogen activator inhibitor 1 (PAI1), define a new category of molecular targets of p53 that have the potential to negatively regulate tumor invasion and/or metastasis. C1 Uniformed Serv Univ Hlth Sci, Dept Surg, Ctr Prostate Dis Res, Bethesda, MD 20814 USA. Walter Reed Army Med Ctr, Dept Surg, Urol Serv, Washington, DC 20307 USA. NCI, Med Breast Canc Sect, Med Branch, NIH, Bethesda, MD 20892 USA. NIH, Cell Biol Lab, Bethesda, MD 20892 USA. RP Zou, ZQ (reprint author), Uniformed Serv Univ Hlth Sci, Dept Surg, Ctr Prostate Dis Res, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. NR 19 TC 214 Z9 227 U1 0 U2 7 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 3 PY 2000 VL 275 IS 9 BP 6051 EP 6054 DI 10.1074/jbc.275.9.6051 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 290AP UT WOS:000085654400002 PM 10692390 ER PT J AU Zhu, DM Tekle, E Huang, CY Chock, PB AF Zhu, DM Tekle, E Huang, CY Chock, PB TI Inositol tetrakisphosphate as a frequency regulator in calcium oscillations in HeLa cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PAROTID ACINAR-CELLS; POSITIVE FEEDBACK; GENE-EXPRESSION; RAT HEPATOCYTES; 1,4,5-TRISPHOSPHATE; 1,3,4,5-TETRAKISPHOSPHATE; PHOSPHORYLATION; TRISPHOSPHATE; MECHANISM; RECEPTOR AB Cellular signaling mediated by inositol (1,4,5)trisphosphate (Ins(1,4,5)P-3) results in oscillatory intracellular calcium (Ca2+) release. Because the amplitude of the Ca2+ spikes is relatively invariant, the extent of the agonist-mediated effects must reside in their ability to regulate the oscillating frequency. Using electroporation techniques, we show that Ins(1,4,5)P-3, Ins(1,3,4,5)P-4, and Ins(1,3,4,6)P-4 cause a rapid intracellular Ca2+ release in resting HeLa cells and a transient increase in the frequency of ongoing Ca2+ oscillations stimulated by histamine. Two poorly metabolizable analogs of Ins(1,4,5)P-3, Ins(2,4,5)P-3, and 2,3-dideoxy-Ins(1,4,5)P-3, gave a single Ca2+ spike and failed to alter the frequency of ongoing oscillations. Complete inhibition of Ins (1,4,5)P-3 3-kinase (IP3K) by either adriamycin or its specific antibody blocked Ca2+ oscillations. Partial inhibition of IP3K causes a significant reduction in frequency. Taken together, our results indicate that Ins(1,3,4,5)P-4 is the frequency regulator in vivo, and IP3K, which phosphorylates Ins(1,4,5)P-3 to Ins(1,3,4,5)P-4, plays a major regulatory role in intracellular Ca2+ oscillations. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Chock, PB (reprint author), NHLBI, Biochem Lab, NIH, Bldg 3,Rm 204,3 Ctr Dr,MSC-0342, Bethesda, MD 20892 USA. NR 34 TC 23 Z9 23 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 3 PY 2000 VL 275 IS 9 BP 6063 EP 6066 DI 10.1074/jbc.275.9.6063 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 290AP UT WOS:000085654400005 PM 10692393 ER PT J AU Schang, LM Hwang, GJH Dynlacht, BD Speicher, DW Bantly, A Schaffer, PA Shilatifard, A Ge, H Shiekhattar, R AF Schang, LM Hwang, GJH Dynlacht, BD Speicher, DW Bantly, A Schaffer, PA Shilatifard, A Ge, H Shiekhattar, R TI Human PC4 is a substrate-specific inhibitor of RNA polymerase II phosphorylation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CDK-ACTIVATING KINASE; C-TERMINAL DOMAIN; TRANSCRIPTION FACTOR TFIIH; CYCLIN-DEPENDENT KINASES; PROTEIN-KINASE; CATALYTIC SUBUNIT; COACTIVATOR PC4; DNA; REPAIR; SUPPRESSION AB The activity of cyclin-dependent protein kinases (cdks) is physiologically regulated by phosphorylation, association with the specific cyclin subunits, and repression by specific cdh. inhibitors. All three physiological regulatory mechanisms are specific for one or more cdks, but none is known to be substrate specific. In contrast, synthetic cdk peptide inhibitors that specifically inhibit cdk phosphorylation of only some substrates, "aptamers," have been described, Here, we show that PC4, a naturally occurring transcriptional coactivator, competitively inhibits cdk-1, -2, and -7-mediated phosphorylation of the largest subunit of RNA polymerase I (RNAPII), but it does not inhibit phosphorylation of other substrates of the same kinases, Interestingly, the phosphorylated form of PC4 is devoid of kinase inhibitory activity. We also show that wild-type PC4 but not the kinase inhibitory-deficient mutant of PC4 represses transcription in vivo. Our results point to a novel role for PC4 as a specific inhibitor of RNAPII phosphorylation. C1 Wistar Inst, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. NICHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02558 USA. St Louis Univ, Sch Med, Dept Biochem & Mol Biol, St Louis, MO 63104 USA. RP Shiekhattar, R (reprint author), Wistar Inst, 3601 Spruce St, Philadelphia, PA 19104 USA. NR 38 TC 18 Z9 19 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 3 PY 2000 VL 275 IS 9 BP 6071 EP 6074 DI 10.1074/jbc.275.9.6071 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 290AP UT WOS:000085654400007 PM 10692395 ER PT J AU Shirakawa, H Landsman, D Postnikov, YV Bustin, M AF Shirakawa, H Landsman, D Postnikov, YV Bustin, M TI NBP-45, a novel nucleosomal binding protein with a tissue-specific and developmentally regulated expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHROMOSOMAL-PROTEINS; CHROMATIN; TRANSCRIPTION; DOMAIN; HMG-17; ACTIVATION; DNA; ENHANCEMENT; REGION; CORES AB Here we characterize a novel murine nuclear protein, which we named NBP-45, that is related to the ubiquitous nuclear proteins HMG-14/-17, binds specifically to nucleosome core particles, and can function as a transcriptional activator. NBP-45 mRNA is expressed at low levels and in variable amounts in all mouse tissues tested but is especially abundant in RNA extracted from 7-day-old mouse embryos, suggesting that it functions in early embryonic development, NBP-45 is composed of 406 amino acids and is encoded by a single size transcript. The region spanning the N-terminal 85 amino acids contains three segments that are highly homologous to functionally important domains in the HMG-14/-17 protein family: the nuclear localization signal, the nucleosome binding domain, and the chromatin unfolding domain. The protein region spanning the C-terminal 321 amino acids has a 42% content of negatively charged residues. The first 23 amino acids contain a region necessary for nuclear entry of the protein, the region spanning residues 12-40 is the main nucleosomal binding domain of the protein, and the negatively charged, C-terminal domain is necessary for transcription activation. The functional domains of NBP-45 are indicative of a nuclear protein that binds to nucleosomes, thereby creating a chromatin region of high local negative charge. Our studies establish the nucleosomal binding domain as a protein motif that is present in other than just the ubiquitous HMG-14/-17 proteins. We suggest that the nucleosomal binding domain motif is a protein module that facilitates binding to nucleosomes in chromatin. C1 NCI, Prot Sect, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Bustin, M (reprint author), NCI, Prot Sect, Div Basic Sci, NIH, Bldg 37,Rm 3D-12, Bethesda, MD 20892 USA. RI Landsman, David/C-5923-2009; Shirakawa, Hitoshi/D-1406-2009; Bustin, Michael/G-6155-2015; OI Landsman, David/0000-0002-9819-6675 NR 37 TC 40 Z9 41 U1 1 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 3 PY 2000 VL 275 IS 9 BP 6368 EP 6374 DI 10.1074/jbc.275.9.6368 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 290AP UT WOS:000085654400049 PM 10692437 ER PT J AU Poulin, B Sekiya, F Rhee, SG AF Poulin, B Sekiya, F Rhee, SG TI Differential roles of the Src homology 2 domains of phospholipase C-gamma l (PLC-gamma l) in platelet-derived growth factor-induced activation of PLC-gamma l in intact cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE KINASE SUBSTRATE; SH2 DOMAINS; FACTOR RECEPTOR; ANTIGEN RECEPTOR; BINDING-SITE; C-GAMMA-1; ASSOCIATION; PHOSPHORYLATION; SPECIFICITY; STIMULATION AB Upon stimulation of cells with platelet-derived growth factor (PDGF), phospholipase C-gamma 1 (PLC-gamma 1) binds to the tyrosine-phosphorylated PDGF receptor through one or both of its Src homology 2 (SH2) domains, is phosphorylated by the receptor kinase, and is thereby activated to hydrolyze phosphatidylinositol 4,5-bisphosphate, Association of PLC-gamma 1 with the insoluble subcellular fraction is also enhanced in PDGF-stimulated cells. The individual roles of the two SH2 domains of PLC-gamma 1 in mediating the interaction between the enzyme and the PDGF receptor have now been investigated by functionally disabling each domain. A critical Arg residue in each SH2 domain was mutated to Ala, Both wild-type and mutant PLC-gamma 1 proteins were transiently expressed in a PLC-gamma 1-deficient fibroblast cell line, and these transfected cells were stimulated with PDGF, The mutant protein in which the COOH-terminal SH2 domain was disabled bound to the PDGF receptor. Accordingly, it was phosphorylated by the receptor, catalyzed the production of inositol phosphates, and mobilized intracellular calcium to extents similar to (but slightly less than) those observed with the wild-type enzyme. In contrast, the mutant in which the NH2-terminal SH2 domain was impaired did not bind to the PDGF receptor and consequently was neither phosphorylated nor activated. These results suggest that the NH2-terminal SH2 domain, but not the COOH-terminal SH2 domain, of PLC-gamma 1 is required for PDGF-induced activation of PLC-gamma 1, Functional impairment of the SH2 domains did not affect the PDGF-induced redistribution of PLC-gamma 1, suggesting that recruitment of PLC-gamma 1 to the particulate fraction does not involve the SH2 domains. C1 NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. RP Rhee, SG (reprint author), NHLBI, Lab Cell Signaling, NIH, Bldg 3,Rm 122, Bethesda, MD 20892 USA. NR 40 TC 26 Z9 26 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 3 PY 2000 VL 275 IS 9 BP 6411 EP 6416 DI 10.1074/jbc.275.9.6411 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 290AP UT WOS:000085654400055 PM 10692443 ER PT J AU Kireeva, ML Komissarova, N Waugh, DS Kashlev, M AF Kireeva, ML Komissarova, N Waugh, DS Kashlev, M TI The 8-nucleotide-long RNA : DNA hybrid is a primary stability determinant of the RNA polymerase II elongation complex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; 3-DIMENSIONAL STRUCTURE; TRANSCRIPTIONAL ARREST; SOLUTION CONFORMATION; TERNARY COMPLEXES; NASCENT RNA; INITIATION; INVITRO; SITE; PURIFICATION AB The sliding clamp model of transcription processivity, based on extensive studies of Escherichia coli RNA polymerase, suggests that formation of a stable elongation complex requires two distinct nucleic acid components: an 8-9-nt transcript-template hybrid, and a DNA duplex immediately downstream from the hybrid. Here, we address the minimal composition of the processive elongation complex in the eukaryotes by developing a method for promoter-independent assembly of functional elongation complex of S. cerevisiae RNA polymerase II from synthetic DNA and RNA oligonucleotides, me show that only one of the nucleic acid components, the 8-nt RNA: DNA hybrid, is necessary for the formation of a stable elongation complex with RNA polymerase II. The double-strand DNA upstream and downstream of the hybrid does not affect stability of the elongation complex. This finding reveals a significant difference in processivity determinants of RNA polymerase II and E. coli RNA polymerase. In addition, using the imperfect RNA:DNA hybrid disturbed by the mismatches in the RNA, we show that nontemplate DNA strand may reduce the elongation complex stability via the reduction of the RNA:DNA hybrid length. The structure of a "minimal stable" elongation complex suggests a key role of the RNA:DNA hybrid in RNA polymerase II processivity. C1 NCI, Adv Biosci Labs Inc, Basic Res Program, Frederick Canc Res & Dev Ctr,NIH, Frederick, MD 21702 USA. RP NCI, Adv Biosci Labs Inc, Basic Res Program, Frederick Canc Res & Dev Ctr,NIH, Bldg 539,Room 222, Frederick, MD 21702 USA. EM mkashlev@mail.ncifcrf.gov NR 47 TC 141 Z9 141 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 3 PY 2000 VL 275 IS 9 BP 6530 EP 6536 DI 10.1074/jbc.275.9.6530 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 290AP UT WOS:000085654400070 PM 10692458 ER PT J AU Majidi, M Gutkind, JS Lichy, JH AF Majidi, M Gutkind, JS Lichy, JH TI Deletion of the COOH terminus converts the ST5 p70 protein from an inhibitor of RAS signaling to an activator with transforming activity in NIH-3T3 cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHATIDYLINOSITOL 3-KINASE; HUMAN CHROMOSOME-11; FACTOR RECEPTOR; SH3 DOMAINS; IDENTIFICATION; KINASE; BINDING; GENE; MAP AB Expression of the human protein ST5-p70 correlates with reduced tumorigenic phenotype in mammalian cells, reverts their transformed phenotype, and restores their contact-dependent growth, Furthermore, expression of p70 in COS-7 cells suppresses activation of mitogen activated protein kinase MAPK/ERK2 by the largest ST5 product, p126, in response to epidermal growth factor stimulation. Here we show that deletions of the COOH-terminal region of p70 transform NIH3T3 cells and induce their anchorage-independent growth. Analysis of signaling leading to MAPK/ERK2 stimulation revealed that in COS-7 cells, expression of either p70-Delta C1 or p70-Delta C2 markedly enhanced ERK2 activity in a growth factor-independent manner. Whereas wild-type p70 slightly inhibited ERK2 activation by RAS and MEK2, co-expression or p70-Delta C1 or p70-Delta C2 with either protein stimulated ERK2 cooperatively. This activity was completely blocked by the dominant negative mutants RAS17N: or MEKAA suggesting that p70 functions upstream of RAS. Unlike wild-type p70, expression of p70-Delta C1 or p70-Delta C2 mutant did not interfere with the ability of ST5-p126 to stimulate ERK2. Taken together, the data suggest that the COOH-terminal tail, residues 489-609, contains some of the critical determinants for the function of p70, Loss of this region converts the protein from an inhibitor to a constitutive activator of the RAS-ERK2 pathway. C1 Armed Forces Inst Pathol, Dept Cellular Pathol, Washington, DC 20306 USA. NIDCR, NIH, Bethesda, MD 20892 USA. RP Majidi, M (reprint author), Armed Forces Inst Pathol, Dept Cellular Pathol, Washington, DC 20306 USA. RI Gutkind, J. Silvio/A-1053-2009 FU NCI NIH HHS [R01-CA64114] NR 28 TC 16 Z9 18 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 3 PY 2000 VL 275 IS 9 BP 6560 EP 6565 DI 10.1074/jbc.275.9.6560 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 290AP UT WOS:000085654400074 PM 10692462 ER PT J AU Ma, BY Nussinov, R AF Ma, BY Nussinov, R TI Molecular dynamics simulations of a beta-hairpin fragment of protein G: Balance between side-chain and backbone forces SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE protein folding; side-chain interaction; hydrogen bonding; hydrophobic interactions; beta-peptide; beta-hairpin ID TRANSITION-STATE; PEPTIDES; DOMAIN; MODEL; TURNS; FOLD AB How is the native structure encoded in the amino acid sequence? For the traditional backbone centric view, the dominant forces are hydrogen bonds (backbone) and phi-psi propensity. The role of hydrophobicity is nonspecific. For the side-chain centric view, the dominant force of protein folding is hydrophobicity. In order to understand the balance between backbone and side-chain forces, we have studied the contributions of three components of a beta-hairpin peptide: turn, backbone hydrogen bonding and side-chain interactions, of a 16-residue fragment of protein G. The peptide folds rapidly and cooperatively to a conformation with a defined secondary structure and a packed hydrophobic cluster of aromatic side-chains. Our strategy is to observe the structural stability of the beta-hairpin under systematic perturbations of the turn region, backbone hydrogen bonds and the hydrophobic core formed by the side-chains, respectively. Ln our molecular dynamics simulations, the peptides are solvated. with explicit water molecules, and an all-atom force field (CFF91) is used. Starting from the original peptide (G41EWTYDDATKTFTVTE56), we carried out the following MD simulations. (1) unfolding at 350 K; (2) forcing the distance between the C-alpha atoms of ASP47 and LYS50 to be 8 Angstrom; (3) deleting two turn residues (Ala48 and Thr49) to form a beta-sheet complex of two short peptides, GEWTYDD and KTFTVTE; (4) four hydrophobic residues (W43, Y45, F52 and T53) are replaced by a glycine residue step-by-step; and (5) most importantly, four amide hydrogen atoms (T44, D46, T53, and T55, which are crucial for backbone hydrogen bonding), are substituted by fluorine atoms. The fluorination not only makes it impossible to form attractive hydrogen bonding between the two beta-hairpin strands, but also introduces a repulsive force between the two strands due to the negative charges on the fluorine and oxygen atoms. Throughout all simulations, we observe that backbone hydrogen bonds are very sensitive to the perturbations and are easily broken. Ln contrast, the hydrophobic core survives most perturbations. In the decisive test of fluorination, the fluorinated peptide remains folded under our simulation conditions (5 ns, 278 K). Hydrophobic interactions keep the peptide folded, even with a repulsive force between the beta-strands. Thus, our results strongly support a side-chain centric view for protein folding. (C) 2000 Academic Press. C1 NCI, FCRDC, Intramural Res Support Program, SAIC,Lab Expt & Computat Biol, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Fac Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, FCRDC, Intramural Res Support Program, SAIC,Lab Expt & Computat Biol, Bldg 469,Rm 151, Frederick, MD 21702 USA. RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU NCI NIH HHS [N01-CO-56000] NR 35 TC 106 Z9 106 U1 0 U2 2 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 3 PY 2000 VL 296 IS 4 BP 1091 EP 1104 DI 10.1006/jmbi.2000.3518 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 291NG UT WOS:000085742500013 PM 10686106 ER PT J AU Zeiger, E AF Zeiger, E TI Death and antimutagenicity SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Editorial Material C1 NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Zeiger, E (reprint author), NIEHS, Environm Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD MAR 3 PY 2000 VL 466 IS 1 BP 125 EP 127 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 296AU UT WOS:000086001500016 PM 10798932 ER PT J AU Zhang, L Chang, YH Barker, JL Hu, Q Zhang, L Maric, D Li, BS Rubinow, DR AF Zhang, L Chang, YH Barker, JL Hu, Q Zhang, L Maric, D Li, BS Rubinow, DR TI Testosterone and estrogen affect neuronal differentiation but not proliferation in early embryonic cortex of the rat: the possible roles of androgen and estrogen receptors SO NEUROSCIENCE LETTERS LA English DT Article DE testosterone; estrogen; sexual dimorphism; cortex; differentiation; proliferation ID EXPRESSION; BRAIN; ESTRADIOL; NUCLEUS; CULTURE; CELLS; SEX AB We examined the effect of testosterone (T) and 17 beta-estradiol (E) on differentiation and proliferation of cultured neurons from the cortex of 14-day-rat embryos (E14) using immunocytochemistry. We found that the cultures receiving E had significantly more neurons with longer neurites than the control cultures, while both fewer and less differentiated neurons were seen after 24 h of incubation with T. However, neither T nor E changed the number of cells positive for BrdU, a proliferation marker. We also found that the androgen receptor (AR) was markedly expressed in the neurons, whereas the expression of estrogen receptor (ERalpha) was barely detectable. These results suggest that E and T differ in effect on differentiation, while neither affect proliferation in early developmental cortex. Furthermore, since the AR is expressed in the cortical neurons by E14, the inhibitory effect of T on differentiation may be receptor-mediated, while the stimulatory effects of estrogen in the cortex do not appear to involve nuclear ERalpha at this developmental stage. Published by Elsevier Science Ireland Ltd. C1 NIMH, Behav Endocrinol Branch 2C02, NIH, Bethesda, MD 20892 USA. NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. NINDS, Synapt Funct Unit, NIH, Bethesda, MD 20892 USA. NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Zhang, L (reprint author), NIMH, Behav Endocrinol Branch 2C02, NIH, Bldg 36,9000 Rockville Pike, Bethesda, MD 20892 USA. EM zhangl@codon.nih.gov NR 16 TC 35 Z9 36 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD MAR 3 PY 2000 VL 281 IS 1 BP 57 EP 60 DI 10.1016/S0304-3940(99)00942-8 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 292BA UT WOS:000085773200015 PM 10686415 ER PT J AU Fujinaga, M Cherney, MM Tarasova, NI Bartlett, PA Hanson, JE James, MNG AF Fujinaga, M Cherney, MM Tarasova, NI Bartlett, PA Hanson, JE James, MNG TI Structural study of the complex between human pepsin and a phosphorus-containing peptidic transition-state analog SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID ACTIVE-CENTER GEOMETRIES; BARRIER HYDROGEN-BONDS; CRYSTALLOGRAPHIC ANALYSIS; ASPARTIC PROTEINASES; MOLECULAR-STRUCTURES; CATALYTIC MECHANISM; CRYSTAL-STRUCTURE; SERINE PROTEASES; X-RAY; RESOLUTION AB The refined crystal structure of the complex between human pepsin and a synthetic phosphonate inhibitor, Iva-Val-Val-Leu(P)-(O)Phe-Ala-Ala-OMe [Iva = isovaleryl, Leu(P) = the phosphinic acid analog of L-leucine, (O)Phe = L-3-phenyllactic acid, OMe = methyl ester], is presented. The structure was refined using diffraction data between 30 and 1.9 Angstrom resolution to a final R factor (Sigma \ \F(o)\ - \F(c)\ \/ Sigma \F(o)\, where \F(o)\ and \F(c)\ are the observed and calculated structure-factor amplitudes, respectively) of 20.0%. The interactions of the inhibitor with the enzyme show the locations of the binding sites on the enzyme from S4 to S3'. Modeling of the inhibitor binding to porcine pepsin shows very similar binding sires, except at S4. Comparison of the complex structure with the structures of related inhibitors bound to penicillopepsin helps to rationalize the observed differences in the binding constants. The convergence of reaction mechanisms and geometries in different families of proteinases is also discussed. C1 Univ Alberta, Dept Biochem, Med Res Council Canada, Grp Prot Struct & Funct, Edmonton, AB T6G 2H7, Canada. NCI, Mol Aspects Drug Design Sect, ABL Basic Res Program, FCDRC, Frederick, MD 21702 USA. Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA. RP James, MNG (reprint author), Univ Alberta, Dept Biochem, Med Res Council Canada, Grp Prot Struct & Funct, Edmonton, AB T6G 2H7, Canada. EM michael.james@ualberta.ca FU NCI NIH HHS [CA-22747, N01-CO-46000] NR 37 TC 23 Z9 23 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD MAR PY 2000 VL 56 BP 272 EP 279 DI 10.1107/S0907444999016376 PN 3 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 295CZ UT WOS:000085950300003 PM 10713513 ER PT J AU Dufour, MC AF Dufour, MC TI Summation of US-Japan workshop SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Editorial Material C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NIAAA, Rockville, MD 20852 USA. RP Dufour, MC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAR PY 2000 VL 24 IS 3 BP 395 EP 395 PG 1 WC Substance Abuse SC Substance Abuse GA 298FE UT WOS:000086128000027 ER PT J AU Vasan, RS Levy, D Larson, MG Benjamin, EJ AF Vasan, RS Levy, D Larson, MG Benjamin, EJ TI Interpretation of echocardiographic measurements: A call for standardization SO AMERICAN HEART JOURNAL LA English DT Review ID LEFT-VENTRICULAR MASS; TWO-DIMENSIONAL ECHOCARDIOGRAPHY; BODY-SURFACE AREA; APPROVED RECOMMENDATION 1987; NUTRITION EXAMINATION SURVEY; BLOOD-PRESSURE; APPARENTLY HEALTHY; ADULT-POPULATION; REFERENCE VALUES; GENDER DIFFERENCES AB Background Although echocardiography is used extensively in clinical medicine, guidelines for quantitative interpretation of echocardiographic measurements are unavailable. The goals of this investigation were to provide an overview of scientific standards for formulating reference values, with clinical chemistry used as a model, to evaluate published echocardiographic reference limits, to survey clinical echocardiography laboratories regarding their interpretation of echocardiographic measurements, and to provide recommendations for improving the interpretation and reporting of echocardiographic measurements. Methods and Results We reviewed the original reports of the international Federation of Clinical Chemistry on guidelines for formulating reference valves. We obtained published reports on echocardiographic reference limits through searches of electronic databases supplemented by a manual search of relevant bibliographies. We also surveyed echocardiographic laboratories in 35 adult acute-care hospitals in Eastern Massachusetts. Studies on echocardiographic reference values were evaluated with the use of guidelines from clinical chemistry. Responses from the 29 participating echocardiographic laboratories were evaluated for their practice of quantitative echocardiographic interpretation. There is considerable heterogeneity in the echocardiographic reference values available in the literature. There is also a lack of agreement in the literature and among echocardiographers regarding the partitioning of reference values (by sex, ethnicity, or age), the anthropometric measure to be used for indexation, and the choice of cut-points for categorizing values within the abnormal range. Conclusions We advocate that echocardiographic reference limits be standardized and a consensus generated regarding the partitioning of reference limits and the indexation of echocardiographic measurements, Such measures can aid in quantitative echocardiographic interpretation and render the results more scientific and consistent. C1 Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA 01702 USA. Beth Israel Hosp, Div Cardiol, Boston, MA 02215 USA. Beth Israel Hosp, Div Clin Epidemiol, Boston, MA 02215 USA. Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02215 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, NHLBI, 5 Thurber St, Framingham, MA 01702 USA. OI Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [N0I-HC-38038]; NINDS NIH HHS [R0I-NS-17950] NR 106 TC 45 Z9 47 U1 0 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAR PY 2000 VL 139 IS 3 BP 412 EP 422 DI 10.1067/mhj.2000.101777 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 291WJ UT WOS:000085761900009 PM 10689255 ER PT J AU Carmelli, D Fabsitz, RR Swan, GE Reed, T Miller, B Wolf, PA AF Carmelli, D Fabsitz, RR Swan, GE Reed, T Miller, B Wolf, PA TI Contribution of genetic and environmental influences to ankle-brachial blood pressure index in the NHLBI twin study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE aging; blood pressure; genetics; twins ID PERIPHERAL ARTERIAL-DISEASE; RISK-FACTORS; CARDIOVASCULAR-DISEASE; GENERAL-POPULATION; CIGARETTE-SMOKING; HEART-DISEASE; ATHEROSCLEROSIS; CONCORDANCE; PREVALENCE; AGE AB The ankle-brachial index (ABI) is widely used in the clinical diagnosis of peripheral arterial disease. The contributions of genetic and environmental influences to normal and abnormal ABI values are unknown. In this study, the authors used available data on 94 monozygotic pairs and 90 dizygotic pairs of elderly, White, male twins examined in 1995-1997 to investigate the contributions of genetic and environmental influences to normative ABI values. Within-twin-pair correlations for normative ABI values were statistically significant, and the correlation in monozygotic twin pairs was significantly greater than that in dizygotic pairs. Structural equation modeling of the variance-covariance matrices of monozygotic and dizygotic twins indicated that 48% of the observed variability in ABI values could be attributed to additive genetic effects. In contrast, concordance rates for low ABI values (ABI less than or equal to 0.9) for both monozygotic and dizygotic twins were significantly greater than would be expected by chance alone, but within-pair monozygotic similarity was not significantly greater than dizygotic similarity A matched-cotwin analysis in 21 pairs that were discordant for low ABI values found that twins with low ABI values were physically less active and more likely to be persistent smokers than their normal-control brothers. These findings reinforce the role of individual health practices (e.g,, physical activity, smoking) in the manifestation of peripheral arterial disease among subjects matched for age, genetics. and early shared environ ment. C1 SRI Int, Hlth Sci Ctr, Menlo Park, CA 94025 USA. NHLBI, Washington, DC USA. Indiana Univ, Sch Med, Dept Med Genet, Indianapolis, IN 46202 USA. Univ Calif San Francisco, Mt Zion Hosp, Dept Neurol, Med Ctr, San Francisco, CA 94143 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. RP Carmelli, D (reprint author), SRI Int, Hlth Sci Ctr, 333 Ravenswood Ave, Menlo Park, CA 94025 USA. FU NHLBI NIH HHS [HL51429] NR 30 TC 36 Z9 37 U1 0 U2 1 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 2000 VL 151 IS 5 BP 452 EP 458 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 289ZX UT WOS:000085652800004 PM 10707913 ER PT J AU Nelson, JJ Liao, DP Sharrett, AR Folsom, AR Chambless, LE Shahar, E Szklo, M Eckfeldt, J Heiss, G AF Nelson, JJ Liao, DP Sharrett, AR Folsom, AR Chambless, LE Shahar, E Szklo, M Eckfeldt, J Heiss, G TI Serum albumin level as a predictor of incident coronary heart disease - The Atherosclerosis Risk in Communities (ARIC) study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE coronary disease; incidence; mortality; risk factors; serum albumin; smoking ID CARDIOVASCULAR-DISEASE; MORTALITY; ASSOCIATION; MICROALBUMINURIA; ATHEROGENESIS; INFLAMMATION; FIBRINOGEN; STROKE; CANCER; INJURY AB Various studies have reported an inverse association between serum albumin level and incident coronary heart disease (CHD), though biologic mechanisms have not been established. The authors examined the association between serum albumin level and CHD in the Atherosclerosis Risk in Communities cohort, comprising 14,506 White and African-American middle-aged men and women. The mean albumin level in this population was 3.9 g/dl (standard deviation 0.3). During 5.2 years of follow-up, 470 incident CHD events occurred. The hazard ratio for incident CHD associated with a 1-standard deviation decrease in serum albumin level was 1.26 (95% confidence interval (Cl): 1.15, 1.38) after adjustment for age, gender, and ethnicity and 1.18 (95% Cl: 1.07, 1.30) after additional adjustment for covariates related to CHD. Hazard ratios were similar across gender and ethnic groups. However, there was statistically significant effect modification by smoking status, with hazard ratios of 1.01 (95% Cl: 0.84, 1.22) among never smokers, 1.09 (95% Cl: 0.92, 1.30) among former smokers, and 1.35 (95% Cl: 1.17, 1.54) among current smokers. Further adjustment for factors related to renal disease, nutrition, platelet aggregation, inflammation, use of angiotensin-converting enzyme inhibitors, and hemostasis factors attenuated the albumin-CHD relation only slightly. In this study, serum albumin was inversely associated with incident CHD at the baseline examination in current smokers but not in never or former smokers. Albumin level may be a marker of susceptibility to the inflammatory response that results from smoking. C1 Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27514 USA. NHLBI, Bethesda, MD 20892 USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC 27514 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Univ Minnesota, Sch Med, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. RP Heiss, G (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27514 USA. FU NHLBI NIH HHS [N01-HC-55018, N01-HC-55015, N01-HC-55016] NR 51 TC 47 Z9 48 U1 0 U2 2 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 2000 VL 151 IS 5 BP 468 EP 477 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 289ZX UT WOS:000085652800006 PM 10707915 ER PT J AU Chambless, LE Folsom, AR Clegg, LX Sharrett, AR Shahar, E Nieto, FJ Rosamond, WD Evans, G AF Chambless, LE Folsom, AR Clegg, LX Sharrett, AR Shahar, E Nieto, FJ Rosamond, WD Evans, G TI Carotid wall thickness is predictive of incident clinical stroke - The Atherosclerosis Risk in Communities (ARIC) Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE carotid arteries; cerebrovascular disorders; incidence; risk factors; ultrasonography ID INTIMA-MEDIA THICKNESS; CORONARY HEART-DISEASE; B-MODE ULTRASOUND; IMPROVED LIPOLYTIC EFFICIENCY; ARTERIAL-WALL; ENZYMATIC DETERMINATION; CARDIOVASCULAR-DISEASE; CIGARETTE-SMOKING; PHYSICAL-ACTIVITY; SHORT-TERM AB Few studies have determined whether carotid artery intima-media thickness (IMT) is associated prospectively with risk of first ischemic stroke. In the Atherosclerosis Risk in Communities Study, carotid IMT, an index of generalized atherosclerosis, was defined as the mean of IMT measured by B-mode ultrasonography at six sites of the carotid arteries. The authors assessed the relation of mean IMT to stroke incidence over 6-9 years' followup (1987-1995) among 7,865 women and 6,349 men aged 45-64 years without prior stroke at baseline in four US communities. There were 90 incident ischemic stroke events for women and 109 for men. In sex-specific Cox proportional hazards models adjusting only for age, race, and community, the hazard rate ratios comparing extreme mean IMT values (greater than or equal to 1 mm) to values less than 0.6 mm were 8.5 for women (95% confidence interval: 3.5, 20.7) and 3.6 for men (95% confidence interval: 1.5, 9.2). The relation was graded, and models with cubic splines indicated significant nonlinearity, with hazards increasing more rapidly at lower IMTs than at higher IMTs. Thus, models using linear IMT values substantially underestimate the strength of the association at lower IMTs, The strength of the association was reduced by the inclusion of putative stroke risk factors, but it remained elevated at higher IMTs. Hence, mean carotid IMT is a noninvasive predictor of future ischemic stroke incidence. C1 Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC 27514 USA. Univ N Carolina, Sch Publ Hlth, Div Epidemiol, Chapel Hill, NC 27514 USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. NCI, Bethesda, MD 20892 USA. NHLBI, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Div Epidemiol, Baltimore, MD USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth, Winston Salem, NC USA. RP Chambless, LE (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC 27514 USA. FU NHLBI NIH HHS [N01-HC-55015, N01-HC-55016, N01-HC-55018] NR 59 TC 430 Z9 468 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAR 1 PY 2000 VL 151 IS 5 BP 478 EP 487 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 289ZX UT WOS:000085652800007 PM 10707916 ER PT J AU Kleinerman, RA Kaune, WT Hatch, EE Wacholder, S Linet, MS Robison, LL Niwa, S Tarone, RE AF Kleinerman, RA Kaune, WT Hatch, EE Wacholder, S Linet, MS Robison, LL Niwa, S Tarone, RE TI Are children living near high-voltage power lines at increased risk of acute lymphoblastic leukemia? SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE child; electric wiring; electromagnetic fields; environmental exposure; leukemia; lymphocytic; acute ID MAGNETIC-FIELDS; RESIDENTIAL EXPOSURE; CHILDHOOD LEUKEMIA; CANCER AB In the National Cancer Institute/Children's Cancer Group case-control study of childhood acute lymphoblastic leukemia (1989-1993), living in a home with a high-voltage wire code was not associated with disease risk. To further investigate risk near power lines, the authors analyzed distance to transmission and three-phase primary distribution lines within 40 m of homes and created an exposure index of distance and strength of multiple power lines (408 case-control pairs). Neither distance nor exposure index was related to risk of childhood acute lymphoblastic leukemia, although both were associated with in-home magnetic field measurements. Residence near high-voltage lines did not increase risk. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM Factors, Richland, WA USA. Univ Minnesota, Div Pediat Epidemiol & Clin Res, Minneapolis, MN USA. Westat Inc, Rockville, MD USA. RP Kleinerman, RA (reprint author), NCI, Div Canc Epidemiol & Genet, EPS 7044,6120 Execut Blvd, Bethesda, MD 20892 USA. OI Kleinerman, Ruth/0000-0001-7415-2478 NR 18 TC 25 Z9 26 U1 0 U2 2 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 2000 VL 151 IS 5 BP 512 EP 515 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 289ZX UT WOS:000085652800011 PM 10707920 ER PT J AU Lautenberger, JA Stephens, JC O'Brien, SJ Smith, MW AF Lautenberger, JA Stephens, JC O'Brien, SJ Smith, MW TI Significant admixture linkage disequilibrium across 30 cM around the FY locus in African Americans SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; DUFFY-NEGATIVE INDIVIDUALS; ADMIXED POPULATIONS; HUMAN GENOME; LENGTH-POLYMORPHISM; CHEMOKINE RECEPTOR; ETHNIC-DIFFERENCES; PLASMODIUM-VIVAX; HOMOSEXUAL MEN; MAPPING GENES AB Scientists, to understand the importance of allelic polymorphisms on phenotypes that are quantitative and environmentally interacting, are now turning to population-association screens, especially in instances in which pedigree analysis is difficult. Because association screens require linkage disequilibrium between markers and disease loci, maximizing the degree of linkage disequilibrium increases the chances of discovering functional gene-marker associations. One theoretically valid approach-mapping by admixture linkage disequilibrium (MALD), using recently admired African Americans-is empirically evaluated here by measurement of marker associations with 15 short tandem repeats (STRs) and an insertion/deletion polymorphism of the AT3 locus in a 70-cM segment at 1q22-23, around the FY (Duffy) locus. The FY polymorphism ( - 46T->C) disrupts the GATA promoter motif, specifically blocking FY erythroid expression and has a nearly fixed allele-frequency difference between European Americans and native Africans that is likely a consequence of a selective advantage of EY - / - in malaria infections. Analysis of linkage disequilibrium around the EY gene has indicated that there is strong and consistent linkage disequilibrium between EY and three nanking loci (D1S303, SPTA1, and D1S484) spanning 8 cM. We observed significant linkage-disequilibrium signals over a 30-cM region from -4.4 to 16.3 cM (from D1S2777 to D1S196) for STRs and at 26.4 cM (AT3), which provided quantitative estimates of centimorgan limits, by MALD assessment in African American population-association analyses, of 5-10 cM. C1 NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, Sci Applicat Int Corp Frederick, Frederick, MD 21702 USA. NCI, Lab Genomic Divers, Frederick, MD 21701 USA. RP Smith, MW (reprint author), NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, Sci Applicat Int Corp Frederick, POB B, Frederick, MD 21702 USA. RI Smith, Michael/B-5341-2012 FU NCI NIH HHS [N01-CO-56000] NR 50 TC 76 Z9 80 U1 0 U2 0 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 2000 VL 66 IS 3 BP 969 EP 978 DI 10.1086/302820 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 337QM UT WOS:000088373200019 PM 10712211 ER PT J AU Ho, GYF Bailey-Wilson, JE AF Ho, GYF Bailey-Wilson, JE TI The transmission/disequilibrium test for linkage on the X chromosome SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article AB The transmission/disequilibrium test (TDT), which detects linkage between a marker and disease loci in the presence of linkage disequilibrium, was introduced by Spielman et al. The original TDT requires families in which the genotypes ate known for both parents and for at least one affected offspring, and this limits its applicability to diseases with late onset. The sib-TDT, or S-TDT which utilizes families with affected and unaffected siblings, was introduced as an alternative method, by Spielman and Ewens, and the TDT and S-TDT can be combined in an overall test (i.e., a combined-TDT, or C-TDT). The TDT statistics described so far are for autosomal chromosomes. We have extended these TDT methods to test for linkage between S-linked markers and diseases that affect either males only or both sexes. For diseases of late onset, when parental genotypes are often unavailable, the X-linkage C-TDT may allow for more power than is provided by the X-linknge TDT alone. C1 Natl Ctr Human Genome Res, Inherited Dis Res Branch, NIH, Baltimore, MD 21224 USA. Albert Einstein Coll Med, Dept Epidemiol & Social Med, New York, NY USA. RP Bailey-Wilson, JE (reprint author), Natl Ctr Human Genome Res, Inherited Dis Res Branch, NIH, 333 Cassell Dr,Suite 2000, Baltimore, MD 21224 USA. OI Bailey-Wilson, Joan/0000-0002-9153-2920 NR 3 TC 14 Z9 14 U1 0 U2 0 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 2000 VL 66 IS 3 BP 1158 EP 1160 DI 10.1086/302822 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 337QM UT WOS:000088373200036 PM 10712228 ER PT J AU Kronenberg, F Rich, SS Sholinsky, P Arnett, DK Province, ME Myers, RH Eckfeldt, JH Williams, RR Hunt, SC AF Kronenberg, F Rich, SS Sholinsky, P Arnett, DK Province, ME Myers, RH Eckfeldt, JH Williams, RR Hunt, SC TI Insulin and hypertension in the NHLBI Family Heart Study - A sibpair approach to a controversial issue SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE insulin; hypertension; body mass index; obesity; sibpair study ID BLOOD-PRESSURE LEVELS; NERVOUS-SYSTEM ACTIVITY; MIDDLE-AGED MEN; RISK-FACTORS; GLUCOSE-INTOLERANCE; FASTING INSULIN; CARDIOVASCULAR RISK; RESISTANCE SYNDROME; METABOLIC SYNDROME; SERUM-INSULIN AB The association between insulin and hypertension remains equivocal. We therefore investigated insulin levels in 3037 normotensive and 1067 hypertensive subjects from the National Heart, Lung and Blood Institute (NHLBI) Family Heart Study (FHS) by two different approaches. First, we compared insulin levels between normotensive and 275 untreated hypertensive subjects. Insulin levels unadjusted as well as adjusted for age, sex, and center were significantly higher in hypertensives. After adjustment for body mass index (BMI), insulin remained significantly higher only in the diastolic hypertensive group (mean +/- SD 77.0 +/- 36.7 pmol/L, P < .01) but not in the isolated systolic hypertensive group (67.0 +/- 38.2 pmol/L) when compared to normotensives (63.2 +/- 29.1 pmol/L). A sibpair analysis was then used that compared the intra-sibpair differences in insulin concentrations to the intra-sibpair differences in blood pressure (BP) levels. This approach was intended to control for the effects of genetic and residual shared environmental variance upon insulin levels. The intra-sibpair difference in insulin concentrations between concordant (diastolic and systolic Delta BP < 5 mm Hg) and discordant sibpairs (diastolic and systolic Delta BP > 15 and > 20 mm Hg, respectively) was no longer significantly different when adjusted for BMI (2.7 v 5.9 pmol/L for diastolic and -1.7 v -1.8 pmol/L for systolic BP). Even the random selection of one sibpair from each of the 326 families independently of insulin and BP levels did not result in a significant correlation between the intra-sibpair differences in insulin and BP. Using an insulin resistance index instead of insulin did not change our findings. Our investigation in the FHS sample of families suggests that there is only a small, if any, influence of insulin levels on BP after adjustment for obesity-related sources of variation. Am J Hypertens 2000;13:240-250 (C) 2000 American Journal of Hypertension Ltd. C1 Univ Utah, Salt Lake City, UT USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27103 USA. NHLBI, Dept Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. Washington Univ, Div Biostat, St Louis, MO USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Fairview Univ Med Ctr, Dept Lab Med & Pathol, Minneapolis, MN USA. RP Kronenberg, F (reprint author), Univ Innsbruck, Inst Med Biol & Human Genet, Schopfstr 41, A-6020 Innsbruck, Austria. EM Florian.Kronenberg@uibk.ac.at RI Kronenberg, Florian/B-1736-2008 OI Kronenberg, Florian/0000-0003-2229-1120 FU NHLBI NIH HHS [UO1-HL-56563, UO1-HL-56564, UO1-HL-56565] NR 57 TC 5 Z9 5 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD MAR PY 2000 VL 13 IS 3 BP 240 EP 250 DI 10.1016/S0895-7061(99)00177-6 PG 11 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 300WZ UT WOS:000086277900004 PM 10777027 ER PT J AU Gennaro, V Finkelstein, MM Ceppi, M Fontana, V Montanaro, F Perrotta, A Puntoni, R Silvano, S AF Gennaro, V Finkelstein, MM Ceppi, M Fontana, V Montanaro, F Perrotta, A Puntoni, R Silvano, S TI Mesothelioma and lung tumors attributable to asbestos among petroleum workers SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE maintenance workers; occupational epidemiology; refinery workers; oil refinery; lung cancer; mesothelioma; pleural tumor; mortality; smoking; asbestos ID CANCER-CAUSING PROPERTIES; OIL REFINERY WORKERS; PLEURAL MESOTHELIOMA; MORTALITY; EMPLOYEES; INDUSTRY; EXPOSURE; SMOKING; PLANT; CHEMICALS AB Background Asbestos exposure has been definitively found to be associated with both mesothelioma and lung cancer. Nevertheless, in the overall population of oil refinery workers potentially exposed to asbestos, many studies clearly show a definitely increased risk of mesothelioma, but no proven excess of lung cancer after comparison to the general population. Through the presentation of new data and the re-appraisal of two recent and independent epidemiological studies conducted in Liguria, Italy, and Ontario, Canada, we attempt to shed light on this apparently paradoxical finding. Methods Lung cancer mortality was studied among maintenance workers exposed to asbestos, and among two other subgroups of refinery employees: blue collar and white collar workers. The comparison with blue collar workers was performed in order to take into account the role of healthy worker effect smoking habit, and the socioeconomic level. The comparison with white collar workers was performed to control for other occupational lung carcinogens. Results and Conclusions Results reveal a consistency between the two studies and show that 96-100% of the mesotheliomas and 42-49% of the lung tumors arising among maintenance workers were attributable to asbestos exposure. Our new analysis, estimating two cases of asbestos-related lung cancer for each case of mesothelioma, confirms published findings on the magnitude of asbestos-related tumors in oil refineries. (C) 2000 Wiley-Liss, Inc. C1 Natl Canc Inst, I-16132 Genoa, Italy. Ontario Minist Labor, Toronto, ON, Canada. Occupat Hyg & Safety Dpt, La Spezia, Italy. RP Gennaro, V (reprint author), Natl Canc Inst, Largo Rosanna Benzi 10, I-16132 Genoa, Italy. OI Montanaro, Fabio/0000-0002-1609-2216 NR 39 TC 30 Z9 30 U1 1 U2 2 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 2000 VL 37 IS 3 BP 275 EP 282 DI 10.1002/(SICI)1097-0274(200003)37:3<275::AID-AJIM5>3.0.CO;2-I PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 280ZP UT WOS:000085133900005 PM 10642417 ER PT J AU Shrivastav, S Cusumano, A Kanno, Y Chen, G Bryant, JL Kopp, JB AF Shrivastav, S Cusumano, A Kanno, Y Chen, G Bryant, JL Kopp, JB TI Role of T lymphocytes in renal disease in HIV-transgenic mice SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE human immunodeficiency virus type 1 (HIV-1); focal segmental glomerulosclerosis (FSGS); CD4 lymphocytes; macrophages ID HUMAN-IMMUNODEFICIENCY-VIRUS; TROPICAL SPASTIC PARAPARESIS; ACCESSORY PROTEINS; NEPHROPATHY; GLOMERULOSCLEROSIS; KIDNEY; GENES; NEF AB The pathogenesis of human immunodeficiency virus (HIV) associated focal segmental glomerulosclerosis (FSGS) has remained obscure. It has been proposed that renal parenchymal cells may be infected with HIV-1, If such infection occurs, the target cells would be expected to express viral proteins and thus could be targets for cytotoxic T lymphocytes. We previously described mice transgenic for a gag-pol-deleted HIV-1 genome that developed FSGS. In the present study, we tested the requirement for functional T cells in the evolution of renal disease in this model, We bred the HIV-transgenic mice (T26) with athymic nude mice to produce athymic T26 mice. We confirmed by flow cytometry of peripheral blood, thymus, lymph node, and spleen that the athymic T26 mice lacked mature T cells. The athymic T26 mice developed renal disease characterized by FSGS, tubular atrophy and dilatation, and interstitial infiltrate that was qualitatively identical to that seen in the parental T26 mice. Quantitative assessment of the athymic T26 mouse kidneys showed that glomerulosclerosis, tubular injury, and interstitial infiltrate were less severe compared with the parental T26 mouse kidneys, Although T26 mouse kidneys had a mixed cellular infiltrate composed of CD4 cells, CD8 cells, and macrophages, interstitial infiltrates within the athymic T26 mouse kidneys included macrophages but lacked both CD4 and CD8 cells. The renal expression of the HIV transgene was 1.7-fold greater in T26 mice compared with athymic T26 mice. We conclude that mature T cells are not absolutely required for the development of HIV-associated nephropathy in transgenic mice but that, in their absence, renal disease is significantly milder. These data suggest that T-cell-mediated cytotoxicity directed against renal cells expressing virally encoded proteins is not an essential feature of renal pathogenesis in this model. (C) 2000 by the National Kidney Foundation, Inc. C1 NIDDKD, Kidney Dis Sect, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. NIDR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. Ctr Med Educ & Clin Invest, Nephrol Sect, Buenos Aires, DF, Argentina. RP Kopp, JB (reprint author), NIDDKD, Kidney Dis Sect, Metab Dis Branch, NIH, 10-3N16, Bethesda, MD 20892 USA. OI Kopp, Jeffrey/0000-0001-9052-186X NR 28 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAR PY 2000 VL 35 IS 3 BP 408 EP 417 DI 10.1016/S0272-6386(00)70193-4 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 288UQ UT WOS:000085583200006 PM 10692266 ER PT J AU Goldenberg, RL Andrews, WW Mercer, BM Moawad, AH Meis, PJ Iams, JD Das, A Caritis, SN Roberts, JM Miodovnik, M Menard, K Thurnau, G Dombrowski, MP McNellis, D AF Goldenberg, RL Andrews, WW Mercer, BM Moawad, AH Meis, PJ Iams, JD Das, A Caritis, SN Roberts, JM Miodovnik, M Menard, K Thurnau, G Dombrowski, MP McNellis, D CA Natl Inst Child Hlth Human Dev Mat TI The Preterm Prediction Study: Granulocyte colony-stimulating factor and spontaneous preterm birth SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE cytokines; granulocyte colony-stimulating factor; preterm birth ID HISTOLOGIC CHORIOAMNIONITIS; BACTERIAL VAGINOSIS; FETAL FIBRONECTIN; INFECTION; DELIVERY; PREGNANCY; CYTOKINES; LABOR; RISK AB OBJECTIVE: Granulocyte colony-stimulating factor is elevated in the amniotic fluid and plasma of women with chorioamnionitis and active preterm labor. We investigated the relationship between plasma granulocyte colony-stimulating factor and subsequent spontaneous preterm birth in pregnant women without symptoms. STUDY DESIGN: We performed a nested case-control study involving 194 women who had a singleton spontaneous preterm birth and 194 matched term control subjects from the patient pool (n = 2929) enrolled in the Preterm Prediction Study. Plasma collected at 24 and 28 weeks' gestation was analyzed for granulocyte colony-stimulating factor, and the results were compared with subsequent spontaneous preterm birth. RESULTS: Compared with term control subjects, women who were delivered of their infants spontaneously at <28 weeks' gestation had increased mean granulocyte colony-stimulating factor values at 24 weeks' gestation (84.7 +/- 38.4 vs 67.7 +/- 28.6 pg/mL; P=.049), and women who were delivered of their infants at <32 weeks' gestation had increased mean plasma granulocyte colony-stimulating factor Values at 28 weeks' gestation (80.4 +/- 24.1 vs 55.9 +/- 16.5 pg/mL; P =.001). At 24 weeks' gestation a granulocyte colony-stimulating factor value >75th percentile in control subjects (approximately 80 pg/mL) was found in 48.9% (23/47) of all women delivered of their infants at <32 weeks' gestation versus 14.9% (7/47) of the term control subjects (adjusted odds ratio. 6.2; 95% confidence interval, 1.8-20.8). At 28 weeks' gestation a granulocyte colony-stimulating factor value >75th percentile was found in 36.8% (7/19) of women delivered of their infants at <32 weeks' gestation versus 5.3% (1/19) of term control subjects (adjusted odds ratio, 25.7; 95% confidence interval, 1.5-470.4). When measured at 24 or 28 weeks' gestation, granulocyte colony-stimulating factor did not predict spontaneous preterm birth at 32 to 34 weeks' gestation or at 35 to 36 weeks' gestation. CONCLUSION: In pregnant women without symptoms at 24 and 28 weeks' gestation, elevated plasma granulocyte colony-stimulating factor levels are associated with subsequent early (32 weeks' gestation) spontaneous preterm birth, especially within the next 4 weeks, but not with late spontaneous preterm birth. These data provide further evidence that early spontaneous preterm birth is associated with an inflammatory process that is identifiable by the presence of a cytokine in maternal plasma several weeks before the early spontaneous preterm birth; however, later spontaneous preterm birth is not associated with this process. C1 Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. NICHHD, Dept Obstet & Gynecol, Bethesda, MD 20892 USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48202 USA. Univ Oklahoma, Dept Obstet & Gynecol, Norman, OK 73019 USA. Med Univ S Carolina, Dept Obstet & Gynecol, Charleston, SC 29425 USA. Univ Cincinnati, Dept Obstet & Gynecol, Cincinnati, OH USA. Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. Univ Tennessee, Dept Obstet & Gynecol, Knoxville, TN 37996 USA. Wake Forest Univ, Dept Obstet & Gynecol, Winston Salem, NC 27109 USA. Univ Pittsburgh, Magee Womens Ctr, Dept Obstet & Gynecol, Pittsburgh, PA USA. George Washington Univ, Ctr Biostat, Dept Obstet & Gynecol, Washington, DC 20052 USA. RP Goldenberg, RL (reprint author), Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. OI caritis, steve/0000-0002-2169-0712 FU NICHD NIH HHS [HD21434, HD21410, HD21414] NR 25 TC 55 Z9 57 U1 0 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAR PY 2000 VL 182 IS 3 BP 625 EP 630 DI 10.1067/mob.2000.104210 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 300BJ UT WOS:000086232700026 PM 10739519 ER PT J AU Goldenherg, RL Andrews, WW Guerrant, RL Newman, M Mercer, B Iams, J Meis, P Moawad, A Das, A VanDorsten, JP Caritis, SN Thurnau, G Bottoms, S Miodovnik, M McNellis, D Roberts, JM AF Goldenherg, RL Andrews, WW Guerrant, RL Newman, M Mercer, B Iams, J Meis, P Moawad, A Das, A VanDorsten, JP Caritis, SN Thurnau, G Bottoms, S Miodovnik, M McNellis, D Roberts, JM CA Natl Inst Child Hlth Human Dev Mat TI The Preterm Prediction Study: Cervical lactoferrin concentration, other markers of lower genital tract infection, and preterm birth SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE bacterial vaginosis; interleukin 6; lactoferrin; prematurity; sialidase ID BACTERIAL VAGINOSIS; FETAL FIBRONECTIN; METRONIDAZOLE; DELIVERY; INTERLEUKIN-6; WOMEN AB OBJECTIVE: This study was undertaken to determine the relationship among cervical lactoferrin concentration, other cervical markers potentially related to infection, and spontaneous preterm birth. STUDY DESIGN: Cervical lactoferrin concentrations obtained at 22 to 24 weeks' gestation among 121 women who had a spontaneous preterm birth <35 weeks' gestation were compared with cervical lactoferrin concentrations among 121 women matched for race, parity, and center who were delivered at greater than or equal to 37 weeks' gestation. Results were compared against levels of cervical interleukin 6, fetal fibronectin, and sialidase, against cervical length according to ultrasonography, and according to the bacterial vaginosis Gram stain score. RESULTS: Cervical lactoferrin concentrations ranged from not measurable (19% of the concentrations were below the threshold for this assay) to a titer of greater than or equal to 1:64. There was no significant difference in the overall distributions of lactoferrin concentrations between the case patients and control subjects (P=.18). Only when the highest titers of lactoferrin were considered were there more women in the spontaneous preterm birth group (6/121 vs 0/121; P=.03). According to Spearman correlation analyses the cervical lactoferrin concentrations were strongly related to interleukin 6 concentration (r=.51; P=.0001), sialidase activity (r=.38; P=.0001), and bacterial vaginosis (r=.38; P=.0001), were weakly related to fetal fibronectin (r=.16, P=.01), and were not related to cervical length. With the 90th percentile (a dilution of 1:32) used as a cutoff to establish a dichotomous variable, lactoferrin concentration had the following odds ratios and 95% confidence intervals for associations with other potential markers of infection: bacterial vaginosis odds ratio, 4.8 (95% confidence interval, 2.2-10.3); interleukin 6 concentration odds ratio, 2.8 (95% confidence interval, 1.2-6.5); sialidase activity odds ratio, 5.5 (95% confidence interval, 2.2-13.7); fetal fibronectin concentration odds ratio, 0.6 (95% confidence interval, 0.2-2.0); chlamydiosis odds ratio, 2.3 (95% confidence interval, 0.8-6.9); and short cervix odds ratio, 0.5 (95% confidence interval. 0.2-1.4). CONCLUSIONS: Lactoferrin found in the cervix correlated well with other markers of lower genital tract infection. High lactoferrin levels were associated with spontaneous preterm birth but had a very low predictive sensitivity. C1 Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. Univ Virginia, Div Geog Med, Charlottesville, VA USA. Univ Tennessee, Dept Obstet & Gynecol, Memphis, TN 38103 USA. Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. Wake Forest Univ, Dept Obstet & Gynecol, Winston Salem, NC 27103 USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. George Washington Univ, Ctr Biostat, Washington, DC USA. Med Univ S Carolina, Dept Obstet & Gynecol, Charleston, SC 29425 USA. Univ Pittsburgh, Magee Womens Ctr, Dept Obstet & Gynecol, Pittsburgh, PA USA. Univ Oklahoma, Dept Obstet & Gynecol, Oklahoma City, OK 73190 USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. NICHHD, Dept Obstet & Gynecol, Bethesda, MD 20892 USA. Univ Cincinnati, Dept Obstet & Gynecol, Cincinnati, OH USA. RP Goldenherg, RL (reprint author), Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. OI caritis, steve/0000-0002-2169-0712 FU NICHD NIH HHS [HD21414, HD21434, HD21410] NR 25 TC 29 Z9 30 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAR PY 2000 VL 182 IS 3 BP 631 EP 635 DI 10.1067/mob.2000.104211 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 300BJ UT WOS:000086232700027 PM 10739520 ER PT J AU Goldenberg, RL Iams, JD Das, A Mercer, BM Meis, PJ Moawad, AH Miodovnik, M VanDorsten, JP Caritis, SN Thurnau, GR Dombrowski, MP Roberts, JM McNellis, D AF Goldenberg, RL Iams, JD Das, A Mercer, BM Meis, PJ Moawad, AH Miodovnik, M VanDorsten, JP Caritis, SN Thurnau, GR Dombrowski, MP Roberts, JM McNellis, D CA Natl Inst Child Hlth Human Dev Mat TI The Preterm Prediction Study: Sequential cervical length and fetal fibronectin testing for the prediction of spontaneous preterm birth SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE cervical ultrasonography; fetal fibronectin; preterm birth ID BACTERIAL VAGINOSIS; RISK-FACTORS; DELIVERY AB OBJECTIVES: This study was undertaken to further elucidate the pathogenesis of preterm birth by means of traditional risk factors and new markers for preterm birth derived from the Preterm Prediction Study. STUDY DESIGN: A total of 3076 women (2929 with singleton gestations and 147 with twin pregnancies) were categorized according to the presence of risk factors including black race, low body mass index, the presence of bacterial vaginosis, and previous preterm birth. At 24 and 28 weeks' gestation cervical length was measured and categorized as short (less than or equal to 25 mm) or normal (>25 mm). Vaginal and cervical fetal fibronectin concentrations were measured at 24, 26, 28, and 30 weeks' gestation and results were categorized as positive (greater than or equal to 50 ng/mL) or negative (<50 ng/mL). RESULTS: At 24 to 26 weeks' gestation women with each of the risk factors were more likely to have positive fibronectin test results or to have a short cervix. Among women with negative fetal fibronectin results at 24 to 26 weeks' gestation those with a short cervix were more likely to have positive fetal fibronectin results at 28 to 30 weeks' gestation, and among those with normal cervical length those women who had positive fetal fibronectin results were more likely to have a short cervix at later evaluation. Most women who had positive fetal fibronectin results at 24 to 26 weeks' gestation had negative results at 28 to 30 weeks' gestation, whereas most but not all women who had a short cervix at 24 to 26 weeks' gestation still had a short cervix at 28 to 30 weeks' gestation. In each period women with both a positive fetal fibronectin result and a short cervix were at substantially increased risk of spontaneous preterm birth; women with either marker alone had intermediate and approximately equal risks of spontaneous preterm birth, and women without either marker had a low risk of spontaneous preterm birth. CONCLUSION: Regardless of other risk factors, a short cervix predicts a subsequent positive fetal fibronectin result, and a positive fetal fibronectin result predicts subsequent cervical shortening. These data do not support a single sequence of events leading to spontaneous preterm birth. C1 Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. Univ Cincinnati, Dept Obstet & Gynecol, Cincinnati, OH USA. George Washington Univ, Ctr Biostat, Washington, DC 20052 USA. NICHHD, Dept Obstet & Gynecol, Bethesda, MD 20892 USA. Univ Tennessee, Dept Obstet & Gynecol, Memphis, TN 38103 USA. Wake Forest Univ, Dept Obstet & Gynecol, Winston Salem, NC 27109 USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. Med Univ S Carolina, Dept Obstet & Gynecol, Charleston, SC 29425 USA. Univ Pittsburgh, Magee Womens Ctr, Dept Obstet & Gynecol, Pittsburgh, PA USA. Univ Oklahoma, Dept Obstet & Gynecol, Oklahoma City, OK USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. RP Goldenberg, RL (reprint author), Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. OI caritis, steve/0000-0002-2169-0712 FU NICHD NIH HHS [HD21410, HD21414, HD21434] NR 12 TC 65 Z9 65 U1 1 U2 6 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAR PY 2000 VL 182 IS 3 BP 636 EP 643 DI 10.1067/mob.2000.104212 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 300BJ UT WOS:000086232700028 PM 10739521 ER PT J AU Shen, DF Fardeau, C Roberge, FG LeHoang, P Chan, CC AF Shen, DF Fardeau, C Roberge, FG LeHoang, P Chan, CC TI Rearrangement of immunoglobulin gene in metastatic Waldenstrom macroglobulinemia to the vitreous SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB PURPOSE: To report metastatic Waldenstrom macroglobulinemia cells with immunoglobulin heavy chain gene rearrangement in the vitreous and the blood. METHODS: A 58-year-old man with Waldenstrom macroglobulinemia developed bilateral vitreous, Diagnostic vitrectomy was performed on the left eye. The vitreous cells and the peripheral blood lymphocytes were analyzed using microdissection and polymerase chain reaction amplification. RESULTS: Vitrectomy specimen of the left eye contained a few degenerated cells. Molecular analysis showed immunoglobulin heavy chain gene rearrangement at the third complementary determining region of the vitreal infiltrating cells and peripheral blood lymphocytes. CONCLUSIONS: Waldenstrom macroglobulinemia rarely metastasizes to the vitreous. Molecular detection of the immunoglobulin heavy chain gene third complementary determining region rearrangement is helpful in the diagnosis of the malignancy. Microdissection combined with polymerase chain reaction is a useful and innovative tool for molecular pathological investigation. (C) 2000 by Elsevier Science Inc. All rights reserved. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. Hop La Pitie Salpetriere, Dept Ophthalmol, Paris, France. RP Chan, CC (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Rm 10N103,10 Ctr Dr, Bethesda, MD 20892 USA. NR 5 TC 5 Z9 5 U1 0 U2 0 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 2000 VL 129 IS 3 BP 395 EP 396 DI 10.1016/S0002-9394(99)00383-9 PG 2 WC Ophthalmology SC Ophthalmology GA 292QX UT WOS:000085807500028 PM 10704566 ER PT J AU Hoang, AT Huang, JP Rudra-Ganguly, N Zheng, JP Powell, WC Rabindran, SK Wu, C Roy-Burman, P AF Hoang, AT Huang, JP Rudra-Ganguly, N Zheng, JP Powell, WC Rabindran, SK Wu, C Roy-Burman, P TI A novel association between the human heat shock transcription factor 1 (HSF1) and prostate adenocarcinoma SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID BREAST-CANCER; PROTEIN HSP27; CELL-LINES; MULTIDRUG-RESISTANCE; EXPRESSION; CARCINOMA; GENE; GROWTH; APOPTOSIS; STRESS AB A search for differentially expressed genes in a pair of nonmetastatic (PC-3) versus metastatic variant (PC-3M) human prostate carcinoma cell lines led to identification of the human heat shock factor (HSF1) as an overexpressed gene product in PC-3M tells. Analysis of primary prostate cancer specimens indicated that HSF1 is generally up-regulated in most of the malignant prostate epithelial cells relative to the normal prostate cells. Among the known effecters of HSF1 action, constitutive levels of HSP70 and HSP90 are not significantly altered by the naturally elevated expression of HSF1 as in PC-SM cells or by transduced overexpression of HSF1 in PC-3 cells. The basal levels of HSP27 in both cases are, however, consistently increased by two- to threefold. With respect to response to heat shock, high basal concentration of HSP90 is not further enhanced in these cells, and HSP70 is up-regulated irrespective of HSF1 level Heat shock, however, causes an increase in HSP27 when HSF1 is up-regulated, except when the expression of HSF1 is already too high. These results document for the first time that HSF1 is overexpressed in human prostate cancer cells, at least one consequence of which in the prostate cancer cell. lines tested is stimulation of both basal and stress-induced expression of HSP27, an important factor in cell growth, differentiation, or apoptosis. C1 Univ So Calif, Sch Med, Dept Pathol, Los Angeles, CA 90033 USA. Univ So Calif, Sch Med, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USA. Wyeth Ayerst Res, Pearl River, NY USA. NCI, NIH, Bethesda, MD 20892 USA. RP Roy-Burman, P (reprint author), Univ So Calif, Sch Med, Dept Pathol, 2011 Zonal Ave, Los Angeles, CA 90033 USA. FU NCI NIH HHS [CA59705, R01 CA059705, T32 CA009320, T32-CA09320]; NIAID NIH HHS [T32 AI007078, T32-AI07078] NR 44 TC 89 Z9 106 U1 2 U2 5 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 2000 VL 156 IS 3 BP 857 EP 864 DI 10.1016/S0002-9440(10)64954-1 PG 8 WC Pathology SC Pathology GA 290XF UT WOS:000085702600016 PM 10702402 ER PT J AU Kono, H Enomoto, N Connor, HD Wheeler, MD Bradford, BU Rivera, CA Kadiiska, MB Mason, RP Thurman, RG AF Kono, H Enomoto, N Connor, HD Wheeler, MD Bradford, BU Rivera, CA Kadiiska, MB Mason, RP Thurman, RG TI Medium-chain triglycerides inhibit free radical formation and TNF-alpha production in rats given enteral ethanol SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE tumor necrosis factor-alpha; intracellular calcium; free radicals; alcohol ID ALCOHOLIC LIVER-DISEASE; SATURATED FATTY-ACIDS; NECROSIS-FACTOR ALFA; KUPFFER CELLS; DIETARY-FAT; CALCIUM; EXPOSURE; INFUSION; FIBROSIS; PATHOGENESIS AB This study determined whether free radical formation by the liver, tumor necrosis factor (TNF)-alpha production by isolated Kupffer cells, and plasma endotoxin are affected by dietary saturated fat. Rats were fed enteral ethanol and corn oil (E-CO) or medium-chain triglycerides (E-MCT) and control rats received corn oil (C-CO) or medium-chain triglycerides (C-MCT) for 2 wk. E-CO rats developed moderate fatty infiltration and slight inflammation; however, E-MCT prevented liver injury. Serum aspartate aminotransferase levels, gut permeability, and plasma endotoxin doubled with E-CO but were blunted similar to 50% with E-MCT. In Kupffer cells from E-CO rats, intracellular calcium was elevated by lipopolysaccharide (LPS) in a dose-dependent manner. In cells from E-MCT rats, increases were blunted by similar to 40-50% at all concentrations of LPS. The LPS-induced increase in TNF-alpha production by Kupffer cells was dose dependent and was blunted by 40% by MCT. E-CO increased radical adducts and was reduced similar to 50% by MCT. MCT prevent early alcohol-induced liver injury, in part, by inhibition of free radical formation and TNF-alpha production by inhibition of endotoxin-mediated activation of Kupffer cells. C1 Univ N Carolina, Dept Pharmacol, Hepatobiol & Toxicol Lab, Chapel Hill, NC 27599 USA. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Bradford, BU (reprint author), Univ N Carolina, Dept Pharmacol, Hepatobiol & Toxicol Lab, CB 7365,Mary Ellen Jones Bldg, Chapel Hill, NC 27599 USA. NR 50 TC 39 Z9 43 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD MAR PY 2000 VL 278 IS 3 BP G467 EP G476 PG 10 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 292BZ UT WOS:000085775400016 PM 10712267 ER PT J AU Lee, S Yu, H Wing, Y Chan, C Lee, AM Lee, DTS Chen, CN Lin, KM Weiss, MG AF Lee, S Yu, H Wing, Y Chan, C Lee, AM Lee, DTS Chen, CN Lin, KM Weiss, MG TI Psychiatric morbidity and illness experience of primary care patients with chronic fatigue in Hong Kong SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID NEURASTHENIA AB Objective: The authors' goal was to examine the prevalence and experience of psychiatric morbidity among primary care patients with chronic fatigue in Hong Kong. Method: One hundred adult patients with medically unexplained fatigue for 6 or more months were assessed with the Explanatory Model Interview Catalogue, psychopathological rating scales, and an enhanced version of the Structured Clinical Interview for DSM-III-R. Results: The lifetime prevalence of DSM-III-R depressive and anxiety disorders was 54%. Current depressive and anxiety disorders were identified in 28 patients, who exhibited more psychopathology and functional impairment than other patients. Thirty-three patients had somatoform pain disorder, and 30 had undifferentiated somatoform disorder, but most of them could also be diagnosed as having shenjing shuairuo (weakness of nerves) and, to a lesser extent, ICD-10 neurasthenia. Chronic fatigue syndrome diagnosed according to the 1988 Centers for Disease Control criteria was rare (3%) and atypical. Generally, patients mentioned fatigue if asked, but pains (36%), insomnia (20%), and worries (13%) were the most troublesome symptoms. Most patients attributed illness onset to psychosocial sources. Conclusions: Psychiatric morbidity was common among primary care patients with chronic fatigue. Subthreshold psychiatric morbidity was very common and was more validly represented by the disease construct of shenjing shuairuo or neurasthenia than somatoform disorder. C1 Chinese Univ Hong Kong, Dept Community & Family Med, Hong Kong, Hong Kong, Peoples R China. Chinese Univ Hong Kong, Dept Psychol, Hong Kong, Hong Kong, Peoples R China. Harbor UCLA Med Ctr, NIMH, Res Ctr Psychobiol Ethn, Torrance, CA 90509 USA. Swiss Trop Inst, Dept Publ Hlth & Epidemiol, CH-4002 Basel, Switzerland. RP Lee, S (reprint author), Prince Wales Hosp, Dept Psychiat, 11-F, Hong Kong, Hong Kong, Peoples R China. RI Lee, Sing/O-2136-2015 FU NIMH NIH HHS [MH-47193] NR 18 TC 36 Z9 36 U1 2 U2 6 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 2000 VL 157 IS 3 BP 380 EP 384 DI 10.1176/appi.ajp.157.3.380 PG 5 WC Psychiatry SC Psychiatry GA 291JP UT WOS:000085731200010 PM 10698813 ER PT J AU Lindley, AA Gray, RH Herman, AA Becker, S AF Lindley, AA Gray, RH Herman, AA Becker, S TI Maternal cigarette smoking during pregnancy and infant ponderal index at birth in the Swedish Medical Birth Register, 1991-1992 SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID INTRAUTERINE GROWTH-RETARDATION; FULL-TERM INFANTS; FETAL GROWTH; BODY PROPORTIONALITY; POSTNATAL-GROWTH; RETARDED INFANTS; GESTATIONAL-AGE; RISK-FACTORS; WEIGHT; DETERMINANTS AB Maternal smoking during pregnancy reduces mean birthweight(1-4) and increases the risk of small-for-gestational-age infants.(4-8) The ponderal index is a measure of birthweight in relation to crown-heel length and is used to classify "symmetric" growth retardation (with normal ponderal index) and "asymmetric" growth retardation (with low ponderal index). Asymmetric infants are thinner and have less birthweight per centimeter of length than symmetrical infants. Intrauterine growth-retarded infants with symmetric body proportions have higher rates of neonatal complications(9,10) and higher rates of hospitalization in the first year of life than asymmetric infants,(11) and they lag behind asymmetric infants in later physical growth.(12-15) Earlier studies of the effect of maternal smoking on infant ponderal index reported no statistically significant effect,(1,2,16,17) but one investigation reported a reduction in ponderal index among the infants of smokers.(18) Recognizing that ponderal index is strongly correlated with the degree of birthweight reduction,(19) the present study is the first to control for both gestational age and birthweight. C1 NIH, Natl Ctr Child Hlth & Human Dev, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA. Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. Natl Sch Publ Hlth, Medunsa, South Africa. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Populat & Family Hlth Sci, Baltimore, MD USA. RP Lindley, AA (reprint author), 23514 Beachwood Blvd, Beachwood, OH 44122 USA. NR 29 TC 22 Z9 25 U1 0 U2 0 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 2000 VL 90 IS 3 BP 420 EP 423 DI 10.2105/AJPH.90.3.420 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 287GM UT WOS:000085498200017 PM 10705863 ER PT J AU Schluchter, MD Stoller, JK Barker, AF Buist, AS Crystal, RG Donohoe, JF Fallat, RJ Turino, GM Vreim, CE Wu, MC AF Schluchter, MD Stoller, JK Barker, AF Buist, AS Crystal, RG Donohoe, JF Fallat, RJ Turino, GM Vreim, CE Wu, MC CA Alpha 1-Antitrypsin Deficiency Reg TI Feasibility of a clinical trial of augmentation therapy for alpha(1)-antitrypsin deficiency SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID ALPHA-1-ANTITRYPSIN DEFICIENCY; REPLACEMENT THERAPY; ALVEOLAR STRUCTURES; EMPHYSEMA; EFFICACY; REGISTRY; DECLINE; DISEASE AB We examined the feasibility of a randomized clinical trial of intravenous augmentation therapy for individuals with alpha 1-antitrypsin (alpha 1AT) deficiency, basing calculations on newly available data obtained from the NHLBI Registry of Patients with Severe Deficiency of Alpha 1-Antitrypsin. Using rate of FEV1 decline as the primary outcome and adjusting for noncompliance, a study of subjects with Stage II chronic obstructive pulmonary disease (COPD) (initial FEV1 35 to 49% predicted) with biannual spirometry measures obtained over 4 yr of follow-up would require 147 subjects per treatment arm to detect a difference in FEV1 decline of 23 ml/yr (i,e., a 28% reduction), the difference observed in the NHLBI Registry (1-sided test, alpha = 0.05, 90% power). To detect a 40% reduction in mortality in a 5-year study of subjects with baseline FEV1 35 to 49% predicted, recruited over the first 2 yr and then followed an additional 3 yr, 342 subjects per treatment arm would be needed. Though significant impediments to carrying out a clinical trial exist, including the cost of such a trial and the potential difficulties in recruiting patients for a placebo-controlled trial, we recommend a randomized controlled trial as the best method to evaluate the efficacy of intravenous augmentation therapy and of possible future treatments. C1 Cleveland Clin Fdn, Dept Biostat & Epidemiol, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Pulm & Crit Care Med, Cleveland, OH 44195 USA. Oregon Hlth Sci Univ, Dept Pulm & Crit Care Med, Portland, OR 97201 USA. Cornell Univ, New York Hosp, Div Pulm & Crit Care Med, New York, NY USA. Univ N Carolina, Dept Med, Div Pulm, Chapel Hill, NC USA. Calif Pacific Med Ctr, Div Pulm, San Francisco, CA USA. Columbia Univ, Dept Med, New York, NY USA. NHLBI, Div Lung Dis, NIH, Bethesda, MD 20892 USA. NHLBI, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. RP Schluchter, MD (reprint author), Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Div Clin Epidemiol, 11100 Euclid Ave, Cleveland, OH 44106 USA. FU NHLBI NIH HHS [N01-HR-86036] NR 23 TC 26 Z9 26 U1 0 U2 4 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 2000 VL 161 IS 3 BP 796 EP 801 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 295YN UT WOS:000085996400022 PM 10712324 ER PT J AU Matsui, K Takeda, K Yu, ZX Valencia, J Travis, WD Moss, J Ferrans, VJ AF Matsui, K Takeda, K Yu, ZX Valencia, J Travis, WD Moss, J Ferrans, VJ TI Downregulation of estrogen and progesterone receptors in the abnormal smooth muscle cells in pulmonary lymphangioleiomyomatosis following therapy - An immunohistochemical study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID UTERINE CERVICAL FIBROBLASTS; STEROID-RECEPTORS; MATRIX METALLOPROTEINASE; TISSUE INHIBITOR; GELATINASE-B; HORMONAL-REGULATION; GENE-EXPRESSION; BREAST-CANCER; LYMPHANGIOMYOMATOSIS; LUNG AB Immunohistochemical and confocal microscopic studies were made on lung tissue from 10 women with lymphangioleiomyomatosis (LAM) to evaluate the distribution of estrogen receptors (ER) and progesterone receptors (PR) in the abnormal smooth muscle cells (LAM cells) that characterize this disorder. PR and ER were localized mainly in the nuclei of large, epithelioid LAM cells, in five patients in whom tissues were obtained before treatment. However, the reaction for PR and ER was essentially negative in similarly processed tissues from five patients studied after receiving hormonal therapy (progesterone and tamoxifen). In the untreated group, staining for ER and PR colocalized with that for HMB-45, but not with that for membrane type-1 matrix metalloproteinase (MT-1-MMP), which we have shown to be localized in proliferating LAM cells. These observations demonstrate that PR and ER are selectively expressed in a subpopulation of LAM cells that are larger in size, have a limited ability to proliferate, and do not produce MT-1-MMP, the enzyme that activates MMP-2 (which is secreted by LAM cells and is capable of lysing elastin and collagens), ER and PR in LAM cells appear to be downregulated by hormonal therapy. C1 NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, Washington, DC USA. RP Ferrans, VJ (reprint author), NHLBI, Pathol Sect, NIH, Bldg 10,Room 2N240,10 Ctr Dr,MSC 1518, Bethesda, MD 20892 USA. NR 31 TC 75 Z9 80 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 2000 VL 161 IS 3 BP 1002 EP 1009 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 295YN UT WOS:000085996400053 PM 10712355 ER PT J AU Jones, DW Sempos, CT Thom, TJ Harrington, AM Taylor, HA Fletcher, BW Mehrotra, BD Wyatt, SB Davis, CE AF Jones, DW Sempos, CT Thom, TJ Harrington, AM Taylor, HA Fletcher, BW Mehrotra, BD Wyatt, SB Davis, CE TI Rising levels of cardiovascular mortality in Mississippi, 1979-1995 SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE Mississippi; mortality; cardiovascular; trends; United States ID BLOOD-PRESSURE; SOCIOECONOMIC-STATUS; UNITED-STATES; HEART-DISEASE; RISK-FACTORS; HYPERTENSION; BLACKS AB Background: Cardiovascular disease rates are improving in the United States, but not for certain subgroups, especially some African Americans. The objective of the study is to assess current levers and trends in cardiovascular disease mortality in Mississippi. Methods: Mortality statistics from the U.S. vital statistics system for the period 1979-95 were used. Comparison of age-adjusted mortality rates in Mississippi with the other states for the year 1995 and with the nation as a whole over the period of 1979-95 was performed. Results: Mississippians had the highest age-adjusted cardiovascular disease morality rates in the nation in 1995. Overall, the cardiovascular rates in Mississippi were 37% higher than for the U.S. African American men and women from Mississippi had especially high cardiovascular mortality rates, approximately 50% and 70% higher than their white counterparts, respectively. The higher burden of cardiovascular disease in African Americans from Mississippi was especially marked in the younger age groups. Since about 1984-85, cardiovascular mortality rates in Mississippi have been increasing for African Americans, whereas nationally they have been decreasing. In contrast, cardiovascular mortality rates for whites in Mississippi have been declining, but at a much slower rate than seen nationally. The wide divergence in trends for African American and white men and women over that period in Mississippi has lead to an estimated 19,400 excess cardiovascular deaths. Virtually identical trends were found for heart disease. Conclusions: Cardiovascular diseases are a major public health problem in Mississippi that is especially severe in African American residents, and the problem is growing worse each year. It is important to identify the determinants of and solutions for this enormous public health problem in Mississippi. C1 Univ Mississippi, Ctr Med, Div Hypertens, Jackson, MS 39216 USA. NIH, Off Res Minor Hlth, Bethesda, MD 20892 USA. NHLBI, Epidemiol & Biometry Program, Bethesda, MD 20892 USA. George Washington Univ, Sch Publ Hlth & Hlth Sci, St Louis, MO USA. Jackson State Univ, Jackson, MS 39217 USA. Tougaloo Coll, Dept Chem, Jackson, MS USA. Univ N Carolina, Dept Biostat, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA. RP Jones, DW (reprint author), Univ Mississippi, Ctr Med, Div Hypertens, 2500 N State St, Jackson, MS 39216 USA. NR 24 TC 19 Z9 19 U1 1 U2 3 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 2000 VL 319 IS 3 BP 131 EP 137 DI 10.1097/00000441-200003000-00001 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 295YT UT WOS:000085996800001 PM 10746822 ER PT J AU Sipe, JD AF Sipe, JD TI Serum amyloid A: from fibril to function. Current status SO AMYLOID-INTERNATIONAL JOURNAL OF EXPERIMENTAL AND CLINICAL INVESTIGATION LA English DT Article DE AA; SAA; amyloid fibril; acute phase reactant; high density lipoprotein; lipid synthesis; cholesterol transport; cholesterol metabolism ID ACUTE-PHASE RESPONSE; A SAA; ACUTE-INFLAMMATION; SMOOTH-MUSCLE; CHOLESTEROL; EXPRESSION; CELLS; GENE; MECHANISMS; MOUSE C1 NIH, Ctr Sci Review, Bethesda, MD 20892 USA. RP Sipe, JD (reprint author), NIH, Ctr Sci Review, 6701 Rockledge Dr, Bethesda, MD 20892 USA. NR 23 TC 22 Z9 23 U1 0 U2 2 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 2000 VL 7 IS 1 BP 10 EP 12 DI 10.3109/13506120009146815 PG 3 WC Biochemistry & Molecular Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; General & Internal Medicine; Research & Experimental Medicine GA 315NT UT WOS:000087120400003 PM 10842696 ER PT J AU Towler, EM Wilson, LK Zhou, YC Ma, TS Fisher, RJ AF Towler, EM Wilson, LK Zhou, YC Ma, TS Fisher, RJ TI A complete system for identifying inhibitors of creatine kinase B SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID BROAD-SPECTRUM; SOLID TUMORS; LUNG-CANCER; SERUM; CELLS; GROWTH AB We have developed a complete system for discovery of lead compounds as inhibitors of creatine kinase B. In this article, we describe production and purification of the recombinant protein, conditions and features of an optimized high-throughput screening assay, and results of our implementation of the system using a diverse compound library. (C) 2000 Academic Press. C1 NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick, MD 21702 USA. Methodist Hosp, Houston, TX 77030 USA. Baylor Coll Med, Vet Adm Med Ctr, Houston, TX 77030 USA. RP Towler, EM (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick, MD 21702 USA. RI Fisher, Robert/B-1431-2009 FU NCI NIH HHS [N01-CO-56000] NR 24 TC 2 Z9 3 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD MAR 1 PY 2000 VL 279 IS 1 BP 96 EP 99 DI 10.1006/abio.1999.4449 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 292BX UT WOS:000085775200013 PM 10683236 ER PT J AU Handa, A Kashimura, T Takeuchi, S Yamamoto, A Murohashi, I Bessho, M Hirashima, K AF Handa, A Kashimura, T Takeuchi, S Yamamoto, A Murohashi, I Bessho, M Hirashima, K TI Expression of functional granulocyte colony-stimulating factor receptors on human B-lymphocytic leukemia cells SO ANNALS OF HEMATOLOGY LA English DT Article DE G-CSF; G-CSF receptor; B-lymphocytic leukemia ID ACUTE LYMPHOBLASTIC-LEUKEMIA; FACTOR G-CSF; PROLIFERATIVE RESPONSE; CD34 EXPRESSION; DIFFERENTIATION; CHEMOTHERAPY; TRANSLOCATIONS; INTERLEUKIN-3; APOPTOSIS; LYMPHOMA AB We analyzed the expression of cell surface antigens and granulocyte colony-stimulating factor (G-CSF) receptors using flow cytometry, the expression of G-CSF mRNA receptor, using reverse transcription (RT)-PCR, and tested the effect of G-CSF on leukemia colony formation. A total of 14 lymphocytic leukemia patients were examined, seven with acute lymphocytic leukemia (ALL), two with adult T-cell leukemia (ATL), two with B-chronic lymphocytic leukemia (CLL), two with chronic myelocytic leukemia in lymphoid blastic crisis (CML-LBC), and one with plasma cell leukemia (PCL). The presence of G-CSF receptors was demonstrated in 4/14 (29%) patients, two with ALL, one with CLL, and one with CML-LBC, and was associated with stimulation of leukemia clonogenic cell growth by G-CSF. In addition, all four positive leukemia cell types expressed typical B-cell antigens, Our results indicated that G-CSF receptors are expressed on some portion of B-lymphoid leukemia and that their receptors are functional as growth stimulators. C1 Saitama Med Sch, Dept Internal Med 1, Moroyama, Saitama 3500451, Japan. RP Handa, A (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10 Rm 7C 218,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 34 TC 5 Z9 6 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0939-5555 J9 ANN HEMATOL JI Ann. Hematol. PD MAR PY 2000 VL 79 IS 3 BP 127 EP 131 DI 10.1007/s002770050567 PG 5 WC Hematology SC Hematology GA 307JD UT WOS:000086649400005 PM 10803934 ER PT J AU Soldan, SS Leist, TP Juhng, KN McFarland, HF Jacobson, S AF Soldan, SS Leist, TP Juhng, KN McFarland, HF Jacobson, S TI Increased lymphoproliferative response to human herpesvirus type 6A variant in multiple sclerosis patients SO ANNALS OF NEUROLOGY LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; POLYMERASE CHAIN-REACTION; EPSTEIN-BARR-VIRUS; T-CELL MEMORY; NERVOUS-SYSTEM; DISEASE; BLOOD; HUMAN-HERPESVIRUS-6; INFECTION; REACTIVATION AB Several reports have suggested an association of human herpesvirus 6 (HHV-6) and multiple sclerosis (MS) based on immunohistochemical demonstration of HHV-6 antigens in inflammatory lesions, detection of increased HHV-6 specific serum antibody titers, and amplification of HHV-6 DNA from sera and cerebrospinaf fluid of IMS patients but not in controls. Characterization of the cellular immune response of MS patients to HHV-6 may further clarify the role of HHV-6 in MS and provide insight into the pathogenesis of this immune-mediated disease. We have compared lymphoproliferative responses to HHV-6A (U1102)-, HHV-6B (Z29)-, and HHV-7 (H7SB)-infected cell lysates in healthy controls and patients with MS. Most healthy controls (71%) proliferated to HHV-6B lysate, and fewer (33%) responded to the HHV-6A lysate. In contrast, 67% of MS patients had a lymphoproliferative response to HHV-6A, which is a significant increase in comparison with healthy controls. A similar frequency of lymphoproliferative response (78%) to HHV-6B was demonstrated in MS patients. Lymphoproliferation to HHV-7 lysate was demonstrated in 23% of healthy controls and 28% of MS patients. These results indicate that the lymphoproliferative response to the HHV-6A variant, which was recently reported to have greater neurotropism, is increased in MS patients. C1 NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. George Washington Univ, Dept Genet, Inst Biomed Sci, Washington, DC USA. RP Jacobson, S (reprint author), NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, 9000 Rockville Pike,Bldg 10,Room 5B-16, Bethesda, MD 20892 USA. NR 47 TC 74 Z9 75 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAR PY 2000 VL 47 IS 3 BP 306 EP 313 DI 10.1002/1531-8249(200003)47:3<306::AID-ANA5>3.0.CO;2-A PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 291JV UT WOS:000085731700005 PM 10716249 ER PT J AU Bara-Jimenez, W Shelton, P Sanger, TD Hallett, M AF Bara-Jimenez, W Shelton, P Sanger, TD Hallett, M TI Sensory discrimination capabilities in patients with focal hand dystonia SO ANNALS OF NEUROLOGY LA English DT Article ID TEMPORAL DISCRIMINATION; BASAL GANGLIA; WRITERS CRAMP; REPRESENTATION; INHIBITION AB To explore the concept that dystonia may result from dysfunction of the sensory system, 14 patients with focal hand dystonia were tested during two somatosensory discrimination tasks. Compared with controls, patients had a higher threshold in a task involving discrimination of two electric stimuli closely related temporally, an abnormality that correlated with the degree of severity of dystonia. There was no significant difference in a single-touch, gross localization task. The possible relevance of these findings to the pathogenesis of dystonia is discussed. C1 NINDS, NIH, Human Motor Control Sect, Med Neurol Branch, Bethesda, MD 20892 USA. Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. RP Hallett, M (reprint author), NINDS, NIH, Human Motor Control Sect, Med Neurol Branch, Bldg 10,Room 5N226,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. NR 20 TC 43 Z9 45 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD MAR PY 2000 VL 47 IS 3 BP 377 EP 380 DI 10.1002/1531-8249(200003)47:3<377::AID-ANA16>3.0.CO;2-2 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 291JV UT WOS:000085731700016 ER PT J AU Casamassimi, A De Luca, A Agrawal, S Stromberg, K Salomon, DS Normanno, N AF Casamassimi, A De Luca, A Agrawal, S Stromberg, K Salomon, DS Normanno, N TI EGF-related antisense oligonucleotides inhibit the proliferation of human ovarian carcinoma cells SO ANNALS OF ONCOLOGY LA English DT Article DE antisense oligonucleotides; EGF-related peptides; ovarian carcinoma ID GROWTH-FACTOR RECEPTOR; DIFFERENTIAL IMMUNOHISTOCHEMICAL DETECTION; MAMMARY EPITHELIAL-CELLS; FACTOR-RELATED PROTEINS; FACTOR-ALPHA; COLORECTAL TUMORS; SUPERGENE FAMILY; MESSENGER-RNA; CANCER CELLS; AMPHIREGULIN AB Background: The epidermal growth factor (EGF)-like peptides CRIPTO (CR), amphiregulin (AR) and transforming growth factor alpha (TGF alpha) are expressed in human ovarian carcinomas. Materials and methods: The expression of AR, CR and TGF alpha in ovarian carcinoma cell lines was assessed by immunocytochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). The antiproliferative effects of antisense phosphorothioate oligodeoxynucleotides (AS S-Oligos) directed against either AR, CR or TGF alpha was evaluated by using a clonogenic assay. Results: A majority of the ovarian carcinoma cell lines was found to express TGF alpha, AR and CR mRNAs and proteins. AS S-Oligos directed against either AR, CR or TGF alpha were able to inhibit the anchorage-independent growth of NIH:OVCAR3 and NIH:OVCAR8 cells in a dose dependent manner. A 30%-50% growth inhibition was observed at a 2 mu M concentration of the AS S-Oligos. Treatment of these cells with combinations of EGF-related AS S-Oligos resulted in a more significant growth inhibition when compared to treatment with a single AS S-oligo. A 60%-75% growth inhibition was observed using combinations of AR, CR and TGF alpha AS S-oligos at a total concentration of 2 mu M. An additive growth-inhibitory effect occurred when ovarian carcinoma cells were exposed to the AS S-Oligos after treatment with either paclitaxel or cis-platinum. Conclusions: These data suggest that EGF-related peptides function as autocrine growth factors in ovarian carcinoma cells, and that they might represent targets for experimental therapy of ovarian carcinoma. C1 ITN Fdn Pascale, Novel Therapeut Approaches Sect, I-80131 Naples, Italy. Hybridon Inc, Cambridge, MA USA. NCI, Tumor Growth Factor Sect, LTIB, NIH, Bethesda, MD 20892 USA. US FDA, DCB, CBER, Bethesda, MD 20014 USA. RP Normanno, N (reprint author), ITN Fdn Pascale, Novel Therapeut Approaches Sect, I-80131 Naples, Italy. RI De Luca, Antonella/J-8737-2016 OI De Luca, Antonella/0000-0001-5762-447X NR 29 TC 23 Z9 24 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAR PY 2000 VL 11 IS 3 BP 319 EP 325 DI 10.1023/A:1008350811639 PG 7 WC Oncology SC Oncology GA 297UE UT WOS:000086100400018 PM 10811499 ER PT J AU Li, QD Yu, JJ Mu, CJ Yunmbam, MK Slavsky, D Cross, CL Bostick-Bruton, F Reed, E AF Li, QD Yu, JJ Mu, CJ Yunmbam, MK Slavsky, D Cross, CL Bostick-Bruton, F Reed, E TI Association between the level of ERCC-1 expression and the repair of cisplatin-induced DNA damage in human ovarian cancer cells SO ANTICANCER RESEARCH LA English DT Article DE cisplatin; ovarian cancer; ERCC-1; platinum-DNA adduct; nucleotide excision repair ID NUCLEOTIDE EXCISION-REPAIR; MESSENGER-RNA EXPRESSION; INTERSTRAND CROSS-LINKS; CARCINOMA CELLS; COMPLEMENTATION GROUP-1; ESCHERICHIA-COLI; GENE-EXPRESSION; MAMMALIAN-CELLS; RESISTANCE; LINES AB Nucleotide excision repair (NER) is responsible for the repair of platinum-DNA lesions. ERCC-1 is a critical gene within the NER pathway, and cells without a functional ERCC-1 do not repair cisplatin-caused DNA damage. The present study was therefore designed to evaluate the relationship between the expression of ERCC-1 and the repair of cisplatin-induced DNA adducts in human ovarian cancer cells in vitro. One hour exposure of MCAS cells to cisplatin yielded an approximately two-fold increment in the levels of ERCC-1 mRNA and ERCC-1 protein, as determined respectively, by Northern and Western blottings. In addition nuclear run-on assay showed that ERCC-1 gene transcription rate was increased to about the same extent as steady-state ERCC-1 mRNA and protein, in response to cisplatin treatment. However; the levels of ERCC-1 mRNA, ERCC-1 protein, and ERCC-1 transcript in MCAS cells are twofold lower. than those in A2780/CP70 cells, as previously reported. Furthermore, the repair of cispIatin-DNA adducts in MCAS cells, as measured,by atomic absorption spectrometry, is also nearly two-fold less than that in A2780/CP70 cells, indicating a strong association between the level of ERCC-1 expression and the activity of excision repair in these two human ovarian tumor cell lines. These results suggest that ERCC-1 may be a useful marker to monitor, the repair of platinum-DNA damage in tumor cells, and further highlight that potential pharmacological approaches which specifically inhibit ERCC-1 expression may increase cellular sensitivity to cisplatin. C1 NCI, Med Ovarian Canc Serv, Med Branch,Dev Therapeut Dept, Div Clin Sci,NIH, Bethesda, MD 20892 USA. RP Reed, E (reprint author), NCI, Med Ovarian Canc Serv, Med Branch,Dev Therapeut Dept, Div Clin Sci,NIH, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 68 TC 119 Z9 122 U1 0 U2 5 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 2000 VL 20 IS 2A BP 645 EP 652 PG 8 WC Oncology SC Oncology GA 309JL UT WOS:000086764700001 PM 10810335 ER PT J AU Lee-Huang, S Huang, PL Sun, YT Chen, HC Kung, HF Huang, PL Murphy, WJ AF Lee-Huang, S Huang, PL Sun, YT Chen, HC Kung, HF Huang, PL Murphy, WJ TI Inhibition of MDA-MB-231 human breast tumor xenografts and HER2 expression by anti-tumor agents GAP31 and MAP30 SO ANTICANCER RESEARCH LA English DT Article DE breast carcinoma; anti-tumor; xenograft; in vitro ID GROWTH-FACTOR RECEPTOR; CANCER; AMPLIFICATION; RESISTANCE; GAP-31; MAP-30; DNA AB GAP31 (Gelonium protein of 31 kDa) and MAP30 (Momordica protein of 30 kDa) are agents isolated from the medicinal plants Gelonium multiflorum and Momordica charantia, respectively. The current study was conducted to investigate the efficacy of GAP31 and MAP30 on estrogen-independent and highly metastatic human breast tumor MDA-MB-231 both in vitro and in vivo. The effect of these agents on the expression of breast tumor antigen HER2 (also known as neu or as c-erbB 2) was also examined. Treatment of MDA-MB-231 breast cancer cells with GAP31 and MAP30 resulted in inhibition of cancer cell proliferation as well as inhibition of the expression of HER2 gene in vitro. When MDA-MB-231 human breast cancer cells were transferred into SCID mice, the mice developed extensive metastases and all mice succumbed to tumor by day 46. Treatment of the human breast cancer bearing SCID mice with GAP32 or MAP30 at 10 mu g/injection EOD for 10 injections resulted in significant increases in survival, with 20-25% of the mice remaining tumor free for 96 days. Thus antitumor agents GAP31 and MAP30 are effective against human br east cancer MDA-MB-231 in vitro and in vivo. There agents may therefore be of potential therapeutic use against breast carcinomas. C1 NCI, Frederick Canc Res & Dev Ctr, SAIC, Frederick, MD 21702 USA. NYU, Sch Med, Dept Biochem, New York, NY 10016 USA. NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Biochem Physiol, Frederick, MD 21701 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Murphy, WJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC, Bldg 567,Room 210, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000]; NIAID NIH HHS [R01 AI31343] NR 30 TC 43 Z9 59 U1 0 U2 6 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 2000 VL 20 IS 2A BP 653 EP 659 PG 7 WC Oncology SC Oncology GA 309JL UT WOS:000086764700002 PM 10810336 ER PT J AU Hall, LM Krauthauser, CM Wexler, RS Hollingshead, MG Slee, AM Kerr, JS AF Hall, LM Krauthauser, CM Wexler, RS Hollingshead, MG Slee, AM Kerr, JS TI The hollow fiber assay: Continued characterization with novel approaches SO ANTICANCER RESEARCH LA English DT Article DE hollow fiber; cell density; racemic flavopiridol; Western blot analysis; xenograft ID TUMOR-CELLS; IN-VIVO; SENSITIVITY AB The hollow fiber assay, a unique in vivo model, permits the simultaneous evaluation of compound efficacy against multiple cell lines in two physiological compartments This assay has been used to characterize in vivo activity of cytotoxic compounds. The purpose of the present study was to characterize and optimize this assay for compounds with a defined mechanism of action, specifically cell cycle inhibition. Two human tumor cell lines and one normal human cell line were loaded into polyvinylidene fluoride hollow fibers at two or more cell concentrations and grown in mice for 3-10 days. The data demonstrate the importance of characterizing the initial loading density of various cell lines in the evaluation of compounds. All studies were performed with cells in the linear part of the cell growth curves. Initial loading densities of 1-2 x 10(4) cells/fiber gave the greatest opportunity for growth in the three human cell lines tested (HCT116 colon carcinoma, NCI-H460 non-small cell carcinoma, and AG 1523 normal fibroblast). Utilizing the MTT assay, standard curves were constructed to correlate the fnal number of cells with optical density (OD) readings at 540nm in. order to calculate cell numbers in the fibers. Insights into the mechanism of action of cisplatin have been gained using Western blot analysis of the cell cycle markers PCNA (a protein present throughout the cell cycle) and Rb (a protein that acts as a tumor suppressor gene product) from the hollow fiber cells. In cisplatin-treated NCI-H460 cells both PCNA and Rb phosphorylation decreased, suggesting the arrest of the cells prior to the S phase. Standard therapeutic agents, cisplatin, racemic flavopiridol, cyclophosphamide and mitomycin C, were evaluated independently in the hollow fiber assay and the xenograft model. The data demonstrate that compounds active in the hollow fiber assay are also active in the xenograft. C1 Dupont Merck Pharmaceut Co, Expt Stn, Wilmington, DE 19880 USA. NCI, Frederick Canc Res & Dev Ctr, DCTD, Dev Therapeut Program,Biol Testing Branch, Frederick, MD 21707 USA. RP Hall, LM (reprint author), Dupont Merck Pharmaceut Co, Expt Stn, E400-5233,Route 141 Henry Clay Rd,POB 80400, Wilmington, DE 19880 USA. NR 13 TC 40 Z9 42 U1 0 U2 3 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 2000 VL 20 IS 2A BP 903 EP 911 PG 9 WC Oncology SC Oncology GA 309JL UT WOS:000086764700041 PM 10810375 ER PT J AU Landry, ML Stanat, S Biron, K Brambilla, D Britt, W Jokela, J Chou, SW Drew, WL Erice, A Gilliam, B Lurain, N Manischewitz, J Miner, R Nokta, M Reichelderfer, P Spector, S Weinberg, A Yen-Lieberman, B Crumpacker, C AF Landry, ML Stanat, S Biron, K Brambilla, D Britt, W Jokela, J Chou, SW Drew, WL Erice, A Gilliam, B Lurain, N Manischewitz, J Miner, R Nokta, M Reichelderfer, P Spector, S Weinberg, A Yen-Lieberman, B Crumpacker, C CA AIDS Clin Trials Grp CMV Resistance Working Grp TI A standardized plaque reduction assay for determination of drug susceptibilities of cytomegalovirus clinical isolates SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID IMMUNOCOMPROMISED PATIENTS; GANCICLOVIR; RESISTANT; FOSCARNET; VIRUS; UL97; AIDS AB Twelve laboratories collaborated in formulating and testing a standardized plaque reduction assay for cyto megalovirus (CMV) cell-associated clinical isolates, Four characterized and plaque-purified CMV strains, as well as six coded clinical isolates obtained after antiviral therapy, were distributed and tested. Good agreement was obtained for four of the clinical isolates, but a broad distribution of results was obtained for two Isolates. Analysis of these results indicates the problems associated,vith clinical isolates, including the large genetic variability and the highly cell-associated phenotype. This collaborative effort, by addressing these problems, represents a significant step toward the development of a standardized assay. C1 Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06520 USA. Glaxo Wellcome, Res Triangle Pk, NC USA. New England Res Inst, Watertown, MA 02172 USA. Univ Alabama, Birmingham, AL USA. Univ Oregon, Portland, OR USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Minnesota, Minneapolis, MN USA. Univ N Carolina, Chapel Hill, NC USA. Rush Med Coll, Chicago, IL 60612 USA. US FDA, Bethesda, MD 20014 USA. NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. Univ Texas, Galveston, TX 77555 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Harvard Univ, Boston, MA 02115 USA. RP Landry, ML (reprint author), Yale Univ, Sch Med, Dept Lab Med, 333 Cedar St, New Haven, CT 06520 USA. FU NIAID NIH HHS [U01 AI038858, AI32766, AI38858, AI41690] NR 13 TC 77 Z9 80 U1 1 U2 1 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 2000 VL 44 IS 3 BP 688 EP 692 DI 10.1128/AAC.44.3.688-692.2000 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 285QF UT WOS:000085399200034 PM 10681339 ER PT J AU Stone, DL Carey, WF Christodoulou, J Sillence, D Nelson, P Callahan, M Tayebi, N Sidransky, E AF Stone, DL Carey, WF Christodoulou, J Sillence, D Nelson, P Callahan, M Tayebi, N Sidransky, E TI Type 2 Gaucher disease: the collodion baby phenotype revisited SO ARCHIVES OF DISEASE IN CHILDHOOD LA English DT Article DE congenital ichthyosis; glucocerebrosidase deficiency; genotype; Gaucher disease ID GLUCOCEREBROSIDASE GENE; CONGENITAL ICHTHYOSIS; TARGETED DISRUPTION; MOUSE MODEL; MUTATIONS; DELETION; NEONATE; FETUS AB The association of Gaucher disease, the inherited deficiency of lysosomal glucocerebrosidase (EC 3.2.1.45), and congenital ichthyosis was first noted a decade ago. Subsequently, a null allele type 2 Gaucher mouse was generated that also exhibited ichthyotic skin, confirming that the skin disorder and enzyme deficiency were directly related. This paper details the clinical and molecular characterisation of 6 cases of type 2 Gaucher disease presenting with the collodion baby phenotype. The identified mutant glucocerebrosidase alleles include two novel mutations (S196P and R131L) and two rare point mutations (R120W and R257Q), as well as alleles resulting from recombination with the nearby glucocerebrosidase pseudogene. There is significant genotypic heterogeneity in this rare subset of patients with type 2 Gaucher disease. Gaucher disease should be considered in the differential diagnosis of congenital ichthyosis in the newborn period. C1 NIMH, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. Womens & Childrens Hosp, Dept Chem Pathol, N Adelaide, SA, Australia. Royal Alexandra Hosp Children, Western Sydney Genet Program, Westmead, NSW, Australia. Univ Sydney, Dept Paediat & Child Hlth, Sydney, NSW, Australia. RP Sidransky, E (reprint author), NIMH, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. RI Christodoulou, John/E-5866-2015 NR 24 TC 31 Z9 31 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-9888 J9 ARCH DIS CHILD JI Arch. Dis. Child. PD MAR PY 2000 VL 82 IS 2 SI SI BP F163 EP F166 DI 10.1136/fn.82.2.F163 PG 4 WC Pediatrics SC Pediatrics GA 291CM UT WOS:000085716200015 PM 10685993 ER PT J AU Regier, DA AF Regier, DA TI Community diagnosis counts SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Editorial Material ID INTERVIEW SCHEDULE; DISORDERS; VALIDITY; HISTORY C1 NIMH, Bethesda, MD 20892 USA. RP Regier, DA (reprint author), NIMH, 31 Ctr Dr,Suite 4A52, Bethesda, MD 20892 USA. NR 20 TC 15 Z9 15 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAR PY 2000 VL 57 IS 3 BP 223 EP 224 DI 10.1001/archpsyc.57.3.223 PG 2 WC Psychiatry SC Psychiatry GA 291JM UT WOS:000085731000003 PM 10711907 ER PT J AU Dugi, KA Amar, MJA Haudenschild, CC Shamburek, RD Bensadoun, A Hoyt, RF Fruchart-Najib, J Madj, Z Brewer, HB Santamarina-Fojo, S AF Dugi, KA Amar, MJA Haudenschild, CC Shamburek, RD Bensadoun, A Hoyt, RF Fruchart-Najib, J Madj, Z Brewer, HB Santamarina-Fojo, S TI In vivo evidence for both lipolytic and nonlipolytic function of hepatic lipase in the metabolism of HDL SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE hepatic lipase; HDL metabolism; lipolysis; nonlipolytic function ID HIGH-DENSITY-LIPOPROTEIN; RECEPTOR-RELATED PROTEIN; HUMAN ADENOVIRUS TYPE-5; TRIGLYCERIDE LIPASE; RAT-LIVER; CHOLESTERYL ESTER; TRANSGENIC MICE; PLASMA-LIPOPROTEINS; FIREFLY LUCIFERASE; SELECTIVE UPTAKE AB To investigate the in vivo role that hepatic lipase (HL) plays in HDL metabolism independently of its lipolytic function, recombinant adenovirus (rAdV) expressing native HL, catalytically inactive HL (HL-145G), and luciferase control was injected in HL-deficient mice. At day 4 after infusion of 2x10(8) plaque-forming units of rHL-AdV and rHL-145G-AdV, similar plasma concentrations were detected in postheparin plasma (HL=8.4+/-0.8 mu g/mL and HL-145G= 8.3+018 mu g/mL). Mice expressing HL had significant reductions of cholesterol (- 76%), phospholipids (PL; -68%), HDL cholesterol (-79%), apolipoprotein (apo) A-I (-45%), and apoA-II (-59%; P<0.05 for all), whereas mice expressing HL-145G decreased their cholesterol (-49%), PL (-40%), HDL cholesterol (-42%), and apoA-II (-89%; P<0.005 for all) but had no changes in apoA-I. The plasma kinetics of I-125-labeled apoA-I HDL, I-131-labeled apoA-II HDL, and [H-3]cholesteryl ester (CE) HDL revealed that compared with mice expressing luciferase control (fractional catabolic rate [FCR] in d(-1): apoA-I HDL=1.3+0.1; apoA-II HDL=2.1+/-0; CE HDL=4.1+/-0.7), both HL and HL-145G enhanced the plasma clearance of CEs and apoA-II present in HDL (apoA-II HDL=5.6+/-0.5 and 4.4+/-0.2; CE HDL=9.3+/-0.0 and 8.3+/-1.1, respectively), whereas the clearance of apoA-I HDL was enhanced in mice expressing HL (FCR=4.6+/-0.3) but not HL-145G (FCR=1.4+/-0.4). These combined findings demonstrate that both lipolytic and nonlipolytic functions of HL are important for HDL metabolism in vivo. Our study provides, for the first time, in vivo evidence for a role of HL in HDL metabolism independent of lipolysis and provides new insights into the role of HL in facilitating distinct metabolic pathways involved in the catabolism of apoA-I- versus apoA-II-containing HDL. C1 NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Lab Anim Med & Surg, NIH, Bethesda, MD 20892 USA. Cornell Univ, Ithaca, NY 14853 USA. Inst Pasteur, Fac Pharm, U325, INSERM, Lille, France. RP Santamarina-Fojo, S (reprint author), NHLBI, Mol Dis Branch, NIH, Bldg 10,Room 7N115,10 Ctr Dr,MSC 1666, Bethesda, MD 20892 USA. NR 55 TC 48 Z9 49 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 2000 VL 20 IS 3 BP 793 EP 800 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 293CN UT WOS:000085834100026 PM 10712405 ER PT J AU Couture, P Otvos, JD Cupples, LA Lahoz, C Wilson, PWF Schaefer, EJ Ordovas, JM AF Couture, P Otvos, JD Cupples, LA Lahoz, C Wilson, PWF Schaefer, EJ Ordovas, JM TI Association of the C-514T polymorphism in the hepatic lipase gene with variations in lipoprotein subclass profiles - The Framingham Offspring Study SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE hepatic lipase; HDL; gene polymorphisms; lipoprotein particle size ID HIGH-DENSITY-LIPOPROTEIN; CORONARY-ARTERY DISEASE; POSTHEPARIN PLASMA LIPASES; ISCHEMIC-HEART-DISEASE; HDL CHOLESTEROL LEVELS; TRIGLYCERIDE LIPASE; SUBFRACTION DISTRIBUTION; APOLIPOPROTEIN-B; PARTICLE-SIZE; MEN AB Hepatic lipase is involved in the metabolism of several lipoproteins and has a key role in reverse cholesterol transport. A common C-to-T substitution at position -514 of the hepatic lipase promoter has been associated with variations in plasma high density lipoprotein cholesterol (HDL-C) levels and hepatic lipase activity. The aim of the current study was to investigate the association of this polymorphism to lipoprotein levels in a population-based sample of 1314 male and 1353 female Framingham Offspring Study participants. In men and women, carriers of the -514T allele had higher HDL-C and apolipoprotein A-I (apoAI) concentrations compared with noncarriers. The higher HDL-C levels associated with the -514T allele was due to an increase in the HDL2-C subfraction, and this association was stronger in women compared with men (P=0.0043 versus 0.0517). To gain further understanding about the metabolic basis of these effects, HDL and low density lipoprotein (LDL) subclass profiles were measured by using automated nuclear magnetic resonance spectroscopy and gradient gel electrophoresis, respectively. The association of the -514T allele with higher HDL-C levels seen in men and women was primarily due to significant increases in the large HDL subfractions (size range 8.8 to 13.0 nm). In contrast, there was no relationship between the hepatic lipase polymorphism at position -514 and the LDL particle size distribution after adjustment for familial relationships, age, body mass index, smoking, alcohol intake, use of beta-blockers, apoE genotype, and menopausal status and estrogen therapy in women. Moreover, multiple regression analyses suggested that the C-514T polymorphism contributed significantly to the variability of HDL particle size in men and women (P<0.04). Thus, our results show that the C-514T polymorphism in the hepatic lipase gene is associated with significant variations in the lipoprotein profile in men and women. C1 Tufts Univ, USDA, Human Nutr Res Ctr Aging, Lipid Metab Lab, Boston, MA 02111 USA. N Carolina State Univ, Dept Biochem, Raleigh, NC 27695 USA. Boston Univ, Sch Publ Hlth, Framingham, MA USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Ordovas, JM (reprint author), Tufts Univ, USDA, Human Nutr Res Ctr Aging, Lipid Metab Lab, 711 Washington St, Boston, MA 02111 USA. OI Ordovas, Jose/0000-0002-7581-5680 FU NHLBI NIH HHS [HL35243, HL54776]; PHS HHS [N01-38038] NR 65 TC 86 Z9 97 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 2000 VL 20 IS 3 BP 815 EP 822 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 293CN UT WOS:000085834100029 PM 10712408 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 ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE diabetes; atherosclerosis; subclinical disease; stroke; heart attack ID CORONARY HEART-DISEASE; AVERAGE CHOLESTEROL LEVELS; MYOCARDIAL-INFARCTION; OLDER ADULTS; HEALTH; ATHEROSCLEROSIS; PREVALENCE; GLUCOSE; EVENTS; PRAVASTATIN AB Previously diagnosed diabetes mellitus, newly diagnosed diabetes mellitus, and impaired glucose tolerance are important determinants of the risk of clinical cardiovascular disease (CVD). We have evaluated the relation of patients with subclinical CVD, diabetes, and impaired glucose tolerance and "normal" subjects and the risk of clinical CVD in the Cardiovascular Health Study. Diabetes (1343), impaired glucose tolerance (1433), and normal (2421) were defined by World Health Organization criteria at baseline in 1989 to 1990. The average follow-up was 6.4 years (mean age 73 years). Diabetics had a higher prevalence of clinical and subclinical CVD at baseline. Compared with diabetes in the absence of subclinical disease, the presence of subclinical CVD and diabetes was associated with significant increased adjusted relative risk of death (1.5, CI 0.93 to 2.41), relative risk of incident coronary heart disease (1.99, CI 1.25 to 3.19), and incident myocardial infarction (1.93, CI 0.96 to 3.91). The risk of clinical events was greater for participants with a history of diabetes compared with newly diagnosed diabetics at baseline. Compared with nondiabetic nonhypertensive subjects without subclinical disease, patients with a combination of diabetes, hypertension, and subclinical disease had a 12-fold increased risk of stroke. Fasting blood glucose levels were a weak predictor of incident coronary heart disease as were most other risk factors. Subclinical CVD was the primary determinant of clinical CVD among diabetics in the Cardiovascular Health Study. C1 Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. CHS Coordinating Ctr, Seattle, WA USA. Kaiser Permanente Georgia, Tucker, GA USA. Johns Hopkins Radiol, Neuroradiol Div, Baltimore, MD USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Tufts New England Med Ctr, Dept Radiol, Boston, MA USA. RP Kuller, LH (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Room A527,130 DeSoto St, Pittsburgh, PA 15261 USA. FU NHLBI NIH HHS [HC-85082] NR 43 TC 109 Z9 120 U1 0 U2 2 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 2000 VL 20 IS 3 BP 823 EP 829 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 293CN UT WOS:000085834100030 PM 10712409 ER PT J AU Howard, BV Robbins, DC Sievers, ML Lee, ET Rhoades, D Devereux, RB Cowan, LD Gray, RS Welty, TK Go, OT Howard, WJ AF Howard, BV Robbins, DC Sievers, ML Lee, ET Rhoades, D Devereux, RB Cowan, LD Gray, RS Welty, TK Go, OT Howard, WJ TI LDL cholesterol as a strong predictor of coronary heart disease in diabetic individuals with insulin resistance and low LDL - The Strong Heart Study SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE low density lipoprotein cholesterol; coronary heart disease; diabetes mellitus; insulin resistance; Indians, North American ID CARDIOVASCULAR-DISEASE; RISK-FACTORS; AMERICAN-INDIANS; MYOCARDIAL-INFARCTION; US POPULATION; MORTALITY; MELLITUS; WOMEN; MEN; LIPOPROTEINS AB Diabetes has been shown to increase the risk of coronary heart disease in ail populations studied. However, there is a lack of information on the relative importance of diabetes-associated risk factors for cardiovascular disease (CVD), especially the role of lipid levels, because low density lipoprotein (LDL) cholesterol often is not elevated in diabetic individuals. The objective of this analysis was to evaluate CVD risk factors, in a large cohort of diabetic individuals and to compare the importance of dyslipidemia (ie, elevated triglycerides and low levels of high density lipoprotein [HDL] cholesterol) and LDL cholesterol in determining CVD risk in diabetic individuals. The Strong Heart Study assesses coronary heart disease and its risk factors in American Indians in Arizona, Oklahoma, and South/North Dakota. The baseline clinical examinations (July 1989 to January 1992) consisted of a personal interview, physical examination, and drawing of blood samples for 4549 study participants (2034 with diabetes), 45 to 74 years of age. Follow-up averaged 4.8 years. Fatal and nonfatal CVD events were confirmed by standardized record review. Participants with diabetes, compared with those with normal glucose tolerance, had lower LDL cholesterol levels bur significantly elevated triglyceride levels, lower HDL cholesterol levels, and smaller LDL particle size. Significant independent predictors of CVD in those with diabetes included age, albuminuria, LDL cholesterol, HDL cholesterol (inverse), fibrinogen, and.. percent body fat (inverse). A 10-mg/dL increase in LDL cholesterol was associated with a 12% increase in CVD risk. Thus, even at concentrations well below the National Cholesterol Education Program target of 130 mg/dL, LDL cholesterol is a strong independent predictor of coronary heart disease in individuals with diabetes, even when components of diabetic dyslipidemia are present. These results support recent recommendations for aggressive control of LDL cholesterol in diabetic individuals, with a target level of <100 mg/dL. C1 MedStar Res Inst, Washington, DC 20010 USA. Washington Hosp Ctr, Washington, DC 20010 USA. Univ Oklahoma, Hlth Sci Ctr, Ctr Amer Indian Hlth Res, Oklahoma City, OK USA. Univ Oklahoma, Dept Biostat & Epidemiol, Oklahoma City, OK USA. Cornell Univ, Coll Med, Ithaca, NY USA. St Johns Hosp, W Lothian NHS Trust, Howden, Scotland. Univ Colorado, Hlth Sci Ctr, Nat Elder Res Ctr, Boulder, CO 80309 USA. Aberdeen Area Tribal Chairmens Hlth Board, Rapid City, SD USA. NIH, Phoenix, AZ USA. RP Howard, BV (reprint author), MedStar Res Inst, 108 Irving St NW, Washington, DC 20010 USA. FU NHLBI NIH HHS [UL01-HL-41654, U01-HL-41642, U01-HL-41652] NR 43 TC 126 Z9 139 U1 1 U2 13 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 2000 VL 20 IS 3 BP 830 EP 835 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 293CN UT WOS:000085834100031 PM 10712410 ER PT J AU Meischke, H Sellers, DE Robbins, ML Goff, DC Daya, MR Meshack, A Taylor, J Zapka, J Hand, MM AF Meischke, H Sellers, DE Robbins, ML Goff, DC Daya, MR Meshack, A Taylor, J Zapka, J Hand, MM TI Factors that influence personal perceptions of the risk of an acute myocardial infarction SO BEHAVIORAL MEDICINE LA English DT Article DE acute myocardial infarction; misconceptions; risk perceptions ID EMERGENCY MEDICAL-SERVICES; HEART-ATTACK SYMPTOMS; RAPID-EARLY-ACTION; CORONARY-TREATMENT; DISEASE; PREDICTORS; PREVENTION; KNOWLEDGE; DESIGN; HEALTH AB Personal risk perceptions of acute myocardial infarction (AMI) affect people's preventive health behaviors as well as their beliefs during a heart attack episode. The authors investigated factors that are associated with personal risk perceptions of having an AMI. A random-digit-dial survey was conducted among 1294 respondents, aged 18 years or older, in 20 communities across the nation as part of the Rapid Early Action for Coronary Treatment (REACT) trial. Results of two mixed-model linear regression analyses suggested that worse perceived general health, more risk factors, and greater knowledge were associated with greater perception of AMI risk. The results also showed that women who answered, incorrectly, that heart disease is not the most common cause of death for women in the United States reported significantly lower risk perceptions that women who answered this question correctly. The findings in this study suggest that interventions need to target specific mis-conceptions regarding AMI risk. C1 Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Educ Dev Ctr, Newton, MA USA. Univ Rhode Isl, Canc Prevent Res Ctr, Kingston, RI 02881 USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Univ Texas, Hlth Sci Ctr, Sch Publ Hlth, Houston, TX USA. Mississippi Univ Women, Columbus, MS USA. Univ Massachusetts, Dept Med, Div Prevent & Behav Med, Worcester, MA 01605 USA. NHLBI, Natl Heart Attack Alert Program, NIH, Bethesda, MD 20892 USA. RP Meischke, H (reprint author), Univ Washington, Dept Hlth Serv, Box 357660, Seattle, WA 98195 USA. NR 31 TC 30 Z9 31 U1 0 U2 1 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 USA SN 0896-4289 J9 BEHAV MED JI Behav. Med. PD SPR PY 2000 VL 26 IS 1 BP 4 EP 13 PG 10 WC Behavioral Sciences; Psychiatry SC Behavioral Sciences; Psychiatry GA 345WJ UT WOS:000088837900001 PM 10971879 ER PT J AU Martin, L Rosen, LN Durand, DB Knudson, KH Stretch, RH AF Martin, L Rosen, LN Durand, DB Knudson, KH Stretch, RH TI Psychological and physical health effects of sexual assaults and nonsexual traumas among male and female United States Army soldiers SO BEHAVIORAL MEDICINE LA English DT Article DE mental health; military; physical health; sexual assault; traumatic experiences ID POSTTRAUMATIC-STRESS-DISORDER; VIETNAM VETERANS; CHILDHOOD ABUSE; MENTAL-HEALTH; US ARMY; CRIMINAL VICTIMIZATION; NATIONAL SAMPLE; DESERT-STORM; PREVALENCE; SYMPTOMS AB Lifetime trauma history was assessed in a health study of active duty United States Army soldiers. Five hundred fifty-five male and 573 female soldiers in the sample were asked whether they had ever experienced 14 different potentially traumatic experiences, including sexual assaults, violent stressors to self, land terrifying events that occurred to others and were secondarily traumatic through exposure by gaining information or as a witness to the event. Most soldiers had experienced multiple traumas, and premilitary exposure to events was much more common than exposure to Events after entering the military: Global measures of current psychological distress and physical health symptoms were predicted by the lifetime number of sexual assaults and traumas to self: Social support from military unit leaders moderated the relationship between accumulated exposure to traumas and both health measures, whereas unit cohesion was directly associated with fever mental health problems. C1 Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Natl Inst Justice, Washington, DC USA. Walter Reed Army Inst Res, Washington, DC USA. NIH, Rockville, MD USA. RP Rosen, LN (reprint author), Univ Maryland, Sch Med, Baltimore, MD 21201 USA. EM rosenl@ujp.usdoj.gov NR 60 TC 48 Z9 48 U1 1 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0896-4289 EI 1940-4026 J9 BEHAV MED JI Behav. Med. PD SPR PY 2000 VL 26 IS 1 BP 23 EP 33 PG 11 WC Behavioral Sciences; Psychiatry SC Behavioral Sciences; Psychiatry GA 345WJ UT WOS:000088837900003 PM 10971881 ER PT J AU McCowan, B Newman, JD AF McCowan, B Newman, JD TI The role of learning in chuck call recognition by squirrel monkeys (Saimiri sciureus) SO BEHAVIOUR LA English DT Article ID VERVET MONKEYS; ALARM CALLS; VOCALIZATIONS; JAPANESE; BEHAVIOR; TAMARINS; MACAQUES; ONTOGENY; FUSCATA AB This study explored the role of learning in the development of chuck call recognition in squirrel monkeys. We experimentally exposed subjects of four different age classes, under controlled conditions, to the chuck calls of genetically unrelated individuals of different social affinities. Using playback experimentation, we tested the hypothesis that subjects at different developmental stages respond preferentially to the chuck calls of genetically unrelated familiar social group companions when compared to those of unfamiliar individuals from outside of the social group. Results demonstrated that adults vocally respond preferentially to the chuck calls of familiar social group members. Subadults behaviorally respond preferentially to the chuck calls of close social associates within their social groups. Juveniles behaviorally responded more strongly to the playback of chuck calls arising from individuals within their colony when compared to the playback of 'silence.' Infants did not behaviorally or vocally respond preferentially to the chuck calls of close social associates or other social group members. These results demonstrate that learning plays a role in chuck call recognition in squirrel monkeys and may suggest that infants,gradually learn to acoustically recognize social companions within their group. C1 Univ Calif Davis, Calif Reg Primate Res Ctr, Davis, CA 95616 USA. NICHD, Comparat Ethol Lab, NIH, Anim Ctr, Poolesville, MD 20837 USA. RP McCowan, B (reprint author), Univ Calif Davis, Vet Med Teaching & Res Ctr, 18830 Rd 112, Tulare, CA 93274 USA. NR 42 TC 10 Z9 10 U1 0 U2 6 PU BRILL ACADEMIC PUBLISHERS PI LEIDEN PA PLANTIJNSTRAAT 2, P O BOX 9000, 2300 PA LEIDEN, NETHERLANDS SN 0005-7959 J9 BEHAVIOUR JI Behaviour PD MAR PY 2000 VL 137 BP 279 EP 300 DI 10.1163/156853900502088 PN 3 PG 22 WC Behavioral Sciences; Zoology SC Behavioral Sciences; Zoology GA 305FM UT WOS:000086528800002 ER PT J AU Davis, DA Newcomb, FM Moskovitz, J Wingfield, PT Stahl, SJ Kaufman, J Fales, HM Levine, RL Yarchoan, R AF Davis, DA Newcomb, FM Moskovitz, J Wingfield, PT Stahl, SJ Kaufman, J Fales, HM Levine, RL Yarchoan, R TI HIV-2 protease is inactivated after oxidation at the dimer interface and activity can be partly restored with methionine sulphoxide reductase SO BIOCHEMICAL JOURNAL LA English DT Article DE polyprotein processing; redox regulation; retroviruses; thioredoxin; viral maturation ID HUMAN IMMUNODEFICIENCY VIRUS-1; SULFOXIDE RESIDUES; S-THIOLATION; THIOLTRANSFERASE GLUTAREDOXIN; RESPIRATORY BURST; PROTEINS; BIOCHEMISTRY; DISULFIDES AB Human immunodeficiency viruses encode a homodimeric protease that is essential for the production of infectious virus. Previous studies have shown that HIV-1 protease is susceptible to oxidative inactivation at the dimer interface at Cys-95, a process that can be reversed both chemically and enzymically, Here we demonstrate a related yet distinct mechanism of reversible inactivation of the HIV-2 protease. Exposure of the HIV-2 protease to H2O2 resulted in conversion of the two methionine residues (Met-76 and Met-95) to methionine sulphoxide as determined by amino acid analysis and mass spectrometry. This oxidation completely inactivated protease activity. However, the activity could be restored (up to 40%) after exposure of the oxidized protease to methionine sulphoxide reductase, This treatment resulted in the reduction of methionine sulphoxide 95 but not methionine sulphoxide 76 to methionine, as determined by peptide mapping/mass spectrometry. We also found that exposure of immature HIV-2 particles to H2O2 led to the inhibition of polyprotein processing in maturing virus particles comparable to that demonstrated for HIV-1 particles. Thus oxidative inactivation of the HIV protease in vitro and in maturing viral particles is not restricted to the type 1 proteases, These studies indicate that two distinct retroviral proteases are susceptible to inactivation after a very minor modification at residue 95 of the dimer interface and suggest that the dimer interface might be a viable target for the development of novel protease inhibitors. C1 NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NIAMSD, Prot Express Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Davis, DA (reprint author), NCI, HIV & AIDS Malignancy Branch, NIH, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Levine, Rodney/D-9885-2011 NR 30 TC 45 Z9 47 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 2000 VL 346 BP 305 EP 311 DI 10.1042/0264-6021:3460305 PN 2 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 295PP UT WOS:000085977300008 PM 10677347 ER PT J AU Landstrom, TR Mei, J Karlsson, M Manganiello, V Degerman, E AF Landstrom, TR Mei, J Karlsson, M Manganiello, V Degerman, E TI Down-regulation of cyclic-nucleotide phosphodiesterase 3B in 3T3-L1 adipocytes induced by tumour necrosis factor alpha and cAMP SO BIOCHEMICAL JOURNAL LA English DT Article DE diabetes; gene expression; insulin; lipolysis; protein kinase A ID HORMONE-SENSITIVE LIPASE; DEPENDENT PROTEIN-KINASE; AMP PHOSPHODIESTERASE; GENE-EXPRESSION; RAT ADIPOCYTES; INSULIN-RESISTANCE; ADIPOSE-TISSUE; THYROID-HORMONE; IN-VITRO; PHOSPHORYLATION AB We have used murine 3T3-L1 cells, which differentiate in culture and acquire morphological and biochemical features of mature adipocytes, as a model for studying the expression of cyclic-nucleotide phosphodiesterase (PDE) 3B activity, protein and mRNA during differentiation and during long-term treatment of the cells with tumour necrosis factor alpha (TNF-alpha), a cytokine associated with insulin resistance, and a cAMP analogue, N(6),2'-O-dibutyryl cAMP (dbcAMP). PDE3B activity, protein and mRNA could be detected 4 days after the initiation of differentiation of 3T3-L1 preadipocytes. Treatment of 3T3-L1 adipocytes with 10 ng/ml TNF-alpha for 24 h produced a maximal (50%) decrease in PDE3B activity, protein and mRNA, which was well correlated with both activation of protein kinase A (PKA) and stimulation of lipolysis, presumably reflecting an increase in intracellular cAMP concentration. To investigate the effect of cAMP on PDE3B we treated 3T3-L1 adipocytes with dbcAMP. After 4 h with 0.5 mM dbcAMP, PDE3B activity was decreased by 80%, which was also correlated with a decrease in PDE3B protein and mRNA. This effect was abolished in the presence of N-[2-(bromocinnamylamino)ethyl]-5-isoquinoline sulphonamide] (H-89), a specific PKA inhibitor. We conclude that the lipolytic effect of TNF-alpha involves the down-regulation of PDE3B, which is associated with increased activation of PKA, presumably owing to increased levels of cAMP. In addition, the PKA activation induced by dbcAMP resulted in the downregulation of PDE3B. These results, which suggest that PDE3B is a novel target for long-term regulation by TNF-alpha and cAMP, could contribute to the understanding of the mechanisms of insulin resistance. C1 Lund Univ, Dept Cell & Mol Biol, Sect Mol Signalling, S-22100 Lund, Sweden. NHLBI, Sect Biochem Physiol, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Landstrom, TR (reprint author), Lund Univ, Dept Cell & Mol Biol, Sect Mol Signalling, POB 94, S-22100 Lund, Sweden. EM tova.rahn_landstrom@medkem.lu.se NR 49 TC 48 Z9 48 U1 0 U2 0 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAR 1 PY 2000 VL 346 BP 337 EP 343 PN 2 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 295PP UT WOS:000085977300012 ER PT J AU Bhagwat, SV Boyd, MR Ravindranath, V AF Bhagwat, SV Boyd, MR Ravindranath, V TI Multiple forms of cytochrome P450 and associated monooxygenase activities in human brain mitochondria SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE human; brain; mitochondria; cytochrome P450; drug metabolism; monooxygenases ID O-DEETHYLASE ACTIVITY; SUBCELLULAR-DISTRIBUTION; XENOBIOTIC METABOLISM; HUMAN PLACENTA; RAT-LIVER; SYSTEM; PURIFICATION; AFLATOXIN-B1; ACTIVATION; MICROSOMES AB We have investigated cytochrome P450 (P450) and associated monooxygenase activities in human brain mitochondria isolated from eight regions of four human brain samples obtained at autopsy. P450-associated monooxygenase activities including aminopyrine N-demethylase (APD), 7-ethoxycoumarin O-deethylase (ECD), p-nitrophenol hydroxylase (PNPH), and N-nitrosodimethylamine N-demethylase (ND-MAD) were detectable in the mitochondria from human brain regions. Immunoblot experiments using antisera to purified rat liver microsomal P450, namely P4502B1/2, P4501A1/2,and P4502E1, revealed immunoreactive bands in isolated mitochondria from different regions of thr human brain. The antibody to P4502B1/2 and P4501A1/2 inhibited the human brain mitochondrial APD and ECD activities, respectively. The addition of antiserum to microsomal NADPH cytochrome P450 reductase did not affect the mitochondrial P450-associated monooxygenase activities, although it completely inhibited the corresponding activities in brain microsomes. Overall, the present study demonstrates, in human brain mitochondria, the presence of multiple forms of P450 belonging to the 1A, 2B, and 2E subfamilies that are involved in xenobiotic metabolism (C) 2000 Elsevier Science Inc. C1 Natl Inst Mental Hlth & Neurosci, Dept Neurochem, Bangalore 560029, Karnataka, India. NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program, NIH, Frederick, MD 21702 USA. RP Ravindranath, V (reprint author), Natl Inst Mental Hlth & Neurosci, Dept Neurochem, Hosur Rd, Bangalore 560029, Karnataka, India. FU NIMH NIH HHS [MH55494] NR 36 TC 39 Z9 41 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD MAR 1 PY 2000 VL 59 IS 5 BP 573 EP 582 DI 10.1016/S0006-2952(99)00362-7 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 276VT UT WOS:000084899600013 PM 10660123 ER PT J AU Khosraviani, M Blake, RC AF Khosraviani, M Blake, RC TI Binding properties of a monoclonal antibody directed toward lead-chelate complexes SO BIOCONJUGATE CHEMISTRY LA English DT Article ID METAL-ION; DTPA; INDIUM; EXPOSURE; SITE; IMMUNOASSAY; LIBRARIES; DESIGN; ELISA; TUMOR AB A monoclonal antibody (2C12) that recognizes a Pb(II)-cyclohexyldiethylenetriamine pentaacetic acid complex was produced by the injection of BALB/c mice with a Pb(II)-chelate complex covalently coupled to a carrier protein. The ability of purified antibody to interact with a variety of metal-free chelators and metal-chelate complexes was assessed by measuring equilibrium dissociation constants. The antibody bound to metal-free trans-cyclohexyldiethylenetriamine pentaacetic acid (CHXDTPA) with an equilibrium dissociation constant of 2.3 x 10(-7) M. Addition of Pb(II) increased the affinity of the antibody for the complex by 25-fold; Pb(II) was the only metal. cation (of 15 different di-, tri-, and hexavalent metals tested) that increased the affinity of the antibody for CHXDTPA. The increased affinity was due primarily to an increase in the association rate constant. The antibody also had the ability to interact with ethylenediamine tetraacetic acid (EDTA), diethylenetriamine pentaacetic acid (DTPA), and structurally related derivatives, but with affinities from 50- to 10000-fold less than that determined for CHXDTPA. Addition of metals to EDTA-based chelators reduced the affinity of the antibody for these ligands. However, when DTPA was used as the chelator, addition of Pb(IT) increased the affinity of the antibody for the complex by 200-fold. The sensitivity of prototype immunoassays for Pb(II) could be modulated by changing the structure of the immobilized metal-chelate complex and/or the soluble chelator used to complex Pb(II) in the test solution. C1 Tulane Univ, Sch Med, Dept Ophthalmol, New Orleans, LA 70112 USA. Xavier Univ, Dept Basic Pharmaceut Sci, New Orleans, LA 70125 USA. NCI, Radioimmune & Inorgan Chem Sect, NIH, Bethesda, MD 20892 USA. Xavier Ctr Bioenvironm Res, New Orleans, LA 70112 USA. RP Blake, RC (reprint author), Tulane Univ, Sch Med, Dept Ophthalmol, 1430 Tulane Ave, New Orleans, LA 70112 USA. EM dblake@tmcpop.tmc.tulane.edu NR 37 TC 59 Z9 69 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD MAR-APR PY 2000 VL 11 IS 2 BP 267 EP 277 DI 10.1021/bc9901548 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 296KK UT WOS:000086023400017 PM 10725104 ER PT J AU Suzuki, M Youle, RJ AF Suzuki, M Youle, RJ TI New magic bullets against cancer SO BIOFUTUR LA French DT Article ID RIBONUCLEASE; PROTEIN; SUPERFAMILY; INHIBITION; TUMORS C1 NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Suzuki, M (reprint author), NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NR 19 TC 0 Z9 0 U1 0 U2 1 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0294-3506 J9 BIOFUTUR JI Biofutur PD MAR PY 2000 VL 2000 IS 198 BP 34 EP 37 PG 4 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 301DW UT WOS:000086294000008 ER PT J AU Cuthbert, BN Schupp, HT Bradley, MM Birbaumer, N Lang, PJ AF Cuthbert, BN Schupp, HT Bradley, MM Birbaumer, N Lang, PJ TI Brain potentials in affective picture processing: covariation with autonomic arousal and affective report SO BIOLOGICAL PSYCHOLOGY LA English DT Article DE emotion; attention; arousal; event-related potentials; slow potentials ID STARTLE REFLEX; EMOTION; STIMULI; REFLECTIONS; ATTENTION; ATTITUDES; COMPONENT; RESOURCES; RESPONSES; CONTEXT AB Emotionally arousing picture stimuli evoked scalp-recorded event-related potentials. A late, slow positive voltage change was observed, which was significantly larger for affective than neutral stimuli. This positive shift began 200-300 ms after picture onset: reached its maximum amplitude approximate to 1 s after picture onset, and was sustained for most of a 6-s picture presentation period. The positive increase was not related to local probability of content type, but was accentuated for pictures that prompted increased autonomic responses and reports of greater affective arousal (e.g. erotic or violent content). These results suggest that the late positive wave indicates a selective processing of emotional stimuli, reflecting the activation of motivational systems in the brain. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Univ Florida, NIMH, Ctr Study Emot & Attent, Gainesville, FL 32610 USA. RP Lang, PJ (reprint author), Univ Florida, NIMH, Ctr Study Emot & Attent, Box 100165 HSC, Gainesville, FL 32610 USA. FU NIMH NIH HHS [MH37757, MH43975, MH52384] NR 46 TC 751 Z9 774 U1 12 U2 79 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD MAR PY 2000 VL 52 IS 2 BP 95 EP 111 DI 10.1016/S0301-0511(99)00044-7 PG 17 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 294NZ UT WOS:000085918500001 PM 10699350 ER PT J AU Kilburn, BA Wang, J Duniec-Dmuchkowski, ZM Leach, RE Romero, R Armant, DR AF Kilburn, BA Wang, J Duniec-Dmuchkowski, ZM Leach, RE Romero, R Armant, DR TI Extracellular matrix composition and hypoxia regulate the expression of HLA-G and integrins in a human trophoblast cell line SO BIOLOGY OF REPRODUCTION LA English DT Article ID CYTOTROPHOBLAST DIFFERENTIATION; INVASION; IMPLANTATION; INVITRO; PLACENTA; RECEPTOR; PATHWAY; INVIVO AB During human placentation, extravillous cytotrophoblast cells emerge from chorionic villi contacting the decidua to invade the uterine wall. When isolated from first-trimester placentae, cytotrophoblast cells undergo step-wise differentiation in vitro that recapitulates the phenotypic heterogeneity observed in vivo. We examined a cell line, HTR-8/SVneo, that has been established from human first-trimester cytotrophoblast to determine whether these cells possess some of the unique cytotrophoblast characteristics that have been described previously. Exposure during serum-free culture to hypoxic conditions (2% oxygen concentration) increased HTR-8/SVneo cell proliferation and reduced invasion of a three-dimensional basement membrane (Matrigel), During culture on surfaces coated with individual extracellular matrix proteins, HTR-8/SVneo cells expressed cytokeratin but not the trophoblast-specific major histocompatibility protein, HLA-G. However, HLA-G expression was induced in HTR-8/SVneo cells that contacted Matrigel, Expression of the alpha 5 integrin subunit was relatively unaffected by matrix composition, whereas alpha 1 was up-regulated and alpha 6 was down-regulated after transferring cells to Matrigel. Hypoxia increased alpha 6 and decreased both alpha 1 and HLA-G expression on Matrigel, HTR-8/SVneo cells retain several important characteristics associated with primary cultures of first-trimester human cytotrophoblast cells, including their altered behavior in response to a changing maternal environment. C1 Wayne State Univ, Sch Med, Dept Obstet & Gynecol, CS Mott Ctr Human Growth & Dev, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Anat & Cell Biol, CS Mott Ctr Human Growth & Dev, Detroit, MI 48201 USA. NICHHD, Perinatol Res Branch, NIH, Bethesda, MD 20892 USA. RP Armant, DR (reprint author), Wayne State Univ, Sch Med, Dept Obstet & Gynecol, CS Mott Ctr Human Growth & Dev, 275 E Hancock Ave, Detroit, MI 48201 USA. OI Armant, D. Randall/0000-0001-5904-9325 FU NIAAA NIH HHS [AA12057]; NICHD NIH HHS [HD36764] NR 30 TC 120 Z9 127 U1 0 U2 2 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 2000 VL 62 IS 3 BP 739 EP 747 DI 10.1095/biolreprod62.3.739 PG 9 WC Reproductive Biology SC Reproductive Biology GA 287XV UT WOS:000085533500032 PM 10684818 ER PT J AU Horkay, F Tasaki, I Basser, PJ AF Horkay, F Tasaki, I Basser, PJ TI Osmotic swelling of polyacrylate hydrogels in physiological salt solutions SO BIOMACROMOLECULES LA English DT Article ID DISCONTINUOUS VOLUME TRANSITIONS; WEAKLY CHARGED POLYELECTROLYTES; POLYMER GELS; PHASE-TRANSITION; IONIC GELS; ACTION-POTENTIALS; SCATTERING; THERMODYNAMICS; NETWORKS; BEHAVIOR AB The swelling behavior of fully neutralized sodium polyacrylate gels was investigated in aqueous solutions of alkali metal (LiCl, NaCl, KCl, CsCl) and alkaline earth metal salts (CaCl2, SrCl2, BaCl2). The total salt concentration and the ratio of monovalent to divalent cations were varied in the biologically significant range. It is found that the concentrations of both monovalent and divalent cations vary continuously and smoothly in the gel despite the abrupt change in the gel volume. The individual elastic, mixing, and ionic contributions to the free energy of the gel were separately determined as a function of the degree of network swelling to elucidate the thermodynamics of swelling. Shear modulus measurements performed at different Ca2+ concentrations suggest that Ca2+ does not form stable cross-links between the polymer chains, At low and moderate swelling ratios the concentration dependence of the shear modulus follows a power law behavior, G proportional to phi". with n = 0.34 +/- 0.03. At high swelling degrees, however, the shear modulus increases with increasing swelling. The value of the Flory-Huggins interaction parameter, chi, determined from osmotic swelling pressure and shear modulus measurements, strongly depends on the ionic composition of the equilibrium solution and increases with increasing Ca2+ concentration. C1 NICHD, Sect Tissue Biophys & Biomimet, NIH, Bethesda, MD 20892 USA. RP Horkay, F (reprint author), NICHD, Sect Tissue Biophys & Biomimet, NIH, 13 South Dr, Bethesda, MD 20892 USA. RI Basser, Peter/H-5477-2011 NR 39 TC 162 Z9 163 U1 4 U2 39 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1525-7797 J9 BIOMACROMOLECULES JI Biomacromolecules PD SPR PY 2000 VL 1 IS 1 BP 84 EP 90 DI 10.1021/bm9905031 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Organic; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA 433ER UT WOS:000168746700012 PM 11709847 ER PT J AU Fears, TR Gail, MH AF Fears, TR Gail, MH TI Analysis of a two-stage case-control study with cluster sampling of controls: Application to nonmelanoma skin cancer SO BIOMETRICS LA English DT Article DE case-control study; population-based case-control study; pseudolikelihood; skin cancer; survey sampling; two-phase case-control study; ultraviolet radiation ID 2-STAGE CASE-CONTROL; ULTRAVIOLET-RADIATION; LOGISTIC-REGRESSION; EXPOSURE AB We present a pseudolikelihood approach for analyzing a two-stage population-based case control study with cluster sampling of controls. These methods were developed to analyze data from a study of nonmelanoma skin cancer (NMSC). This study was designed to evaluate the role of ultraviolet radiation (UVB) on NMSC risk while adjusting for age group, which is known for all subjects, and for other individual-level factors, such as susceptibility to sunburn, which are known only for participants in the case-control study. The methods presented yield estimates of relative and absolute risk, with standard errors, while accounting naturally for the two-stage sampling of the cohort and cluster sampling of controls. C1 NCI, Biostat Branch, Bethesda, MD 20892 USA. RP Fears, TR (reprint author), NCI, Biostat Branch, Execut Plaza S,Room 8040,6120 Execut Blvd,MSC 724, Bethesda, MD 20892 USA. NR 19 TC 4 Z9 4 U1 0 U2 0 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 2000 VL 56 IS 1 BP 190 EP 198 DI 10.1111/j.0006-341X.2000.00190.x PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 297CU UT WOS:000086064600025 PM 10783795 ER PT J AU Thall, PF Simon, RM Shen, Y AF Thall, PF Simon, RM Shen, Y TI Approximate Bayesian evaluation of multiple treatment effects SO BIOMETRICS LA English DT Article DE Bayesian inference; categorical data; clinical trials; multivariate failure times; survival analysis ID SUBSET ANALYSIS; CLINICAL-TRIAL; MODELS; CANCER AB We propose an approximate Bayesian method for comparing an experimental treatment to a control based on a randomized clinical trial with multivariate patient outcomes. Overall treatment effect is characterized by a vector of parameters corresponding to effects on the individual patient outcomes. We partition the parameter space into four sets where, respectively, the experimental treatment is superior to the control, the control is superior to the experimental, the two treatments are equivalent, and the treatment effects are discordant. We compute posterior probabilities of the parameter sets by treating an estimator of the parameter vector like a random variable in the Bayesian paradigm. The approximation may be used in any setting where a consistent, asymptotically normal estimator of the parameter vector is available. The method is illustrated by application to a breast cancer data set consisting of multiple time-to-event outcomes with covariates and to count data arising from a cross-classification of response, infection, and treatment in an acute leukemia trial. C1 Univ Texas, MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. NCI, Biometr Res Branch, Rockville, MD 20852 USA. RP Thall, PF (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Biostat, Box 237,1515 Holcombe Blvd, Houston, TX 77030 USA. OI Shen, Yu/0000-0002-3899-7868 NR 14 TC 6 Z9 6 U1 0 U2 0 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 2000 VL 56 IS 1 BP 213 EP 219 DI 10.1111/j.0006-341X.2000.00213.x PG 7 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 297CU UT WOS:000086064600028 PM 10783798 ER PT J AU Izmirlian, G Brock, D Ferrucci, L Phillips, C AF Izmirlian, G Brock, D Ferrucci, L Phillips, C TI Active life expectancy from annual follow-up data with missing responses SO BIOMETRICS LA English DT Article DE active life expectancy; aging; disability; Markov model; mortality AB Active life expectancy (ALE) at a given age is defined as the expected remaining years free of disability. In this study three categories of health status are defined according to the ability to perform activities of daily living independently. Several studies have used increment-decrement life tables to estimate ALE, without error analysis, from only a baseline and one follow-up interview. The present work conducts an individual-level covariate analysis using a three-state Markov chain model fur multiple follow-up data. Using a logistic link, the model estimates single-year transition probabilities among states of health, accounting for missing interviews. This approach has the advantages of smoothing subsequent estimates and increased power by using all follow-ups. We compute ALE and total life expectancy from these estimated single-year transition probabilities. Variance estimates are computed using the delta method. Data from the Iowa Established Population for the Epidemiologic Study of the Elderly are used to test the effects of smoking on ALE on all 5-year age groups past 65 years, controlling for sex and education. C1 NIA, Epidemiol Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. INRCA, Dept Geriatr, Osped I Fraticini, Florence, Italy. RP Izmirlian, G (reprint author), NIA, Epidemiol Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. NR 12 TC 15 Z9 15 U1 0 U2 0 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 2000 VL 56 IS 1 BP 244 EP 248 DI 10.1111/j.0006-341X.2000.00244.x PG 5 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 297CU UT WOS:000086064600032 PM 10783802 ER PT J AU Dunson, DB Weinberg, CR AF Dunson, DB Weinberg, CR TI Modeling human fertility in the presence of measurement error SO BIOMETRICS LA English DT Article DE Bayesian hierarchical model; conception; fecundability; latent variables; mixture model; ovulation ID BASAL BODY-TEMPERATURE; CONCEPTION; OVULATION; PROBABILITY; PREGNANCY; SURVIVAL; SEX; INTERCOURSE; VARIABLES; POTENCY AB The probability of conception in a given menstrual cycle is closely related to the timing of intercourse relative to ovulation. Although commonly used markers of time of ovulation are known to be error Drone, most fertility models assume the day of ovulation is measured without error. We develop a mixture model that allows the day to be misspecified. We assume that the measurement errors are i.i.d. across menstrual cycles. Heterogeneity among couples in the per cycle likelihood of conception is accounted for using a beta mixture model. Bayesian estimation is straightforward using Markov chain Monte Carlo techniques. The methods are applied to a prospective study of couples at risk of pregnancy. In the absence of validation data or multiple independent markers of ovulation, the identifiability of the measurement error distribution depends on the assumed model. Thus, the results: of studies relating the timing of intercourse to the probability of conception should be interpreted cautiously. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Dunson, DB (reprint author), NIEHS, Biostat Branch, MD A3-03,POB 12233, Res Triangle Pk, NC 27709 USA. NR 26 TC 19 Z9 19 U1 0 U2 5 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 2000 VL 56 IS 1 BP 288 EP 292 DI 10.1111/j.0006-341X.2000.00288.x PG 5 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 297CU UT WOS:000086064600038 PM 10783808 ER PT J AU Jin, AJ Nossal, R AF Jin, AJ Nossal, R TI Rigidity of triskelion arms and clathrin nets SO BIOPHYSICAL JOURNAL LA English DT Article ID COATED PIT FORMATION; CONFORMATIONAL CHANGE; ELECTRON-MICROSCOPY; VESICLE FORMATION; PROTEINS; ACTIN; DISSOCIATION; CAVEOLAE; DYNAMICS; POLYMER AB Statistical analysis is applied to a set of electron micrographic images (Kocsis, E,, B. L. Trus, C, J. Steer, M. E, Bisher, and A, C. Steven. 1991. J. Struct. Biol. 107:6-14), from which quantitative measures are obtained to support the notion that the three arms of a triskelion have statistically identical properties and exhibit independent structural fluctuations. additionally, a study of local contour fluctuations, which indicates that the elastic properties of a triskelion arm are approximately constant over the entire arm length, is used along with a small deformation statistical mechanics theory to derive an:effective, average flexural rigidity for the arms. This result is used to estimate the bending energy necessary to deform a clathrin patch, and comparison is made with the deformation energy of an equivalent area of non-clathrin-coated membrane. We estimate that the rigidity of the clathrin lattice is at least comparable to that of a typical membrane. Hence, the natural curvature of a clathrin cage can stabilize, and perhaps propel, the formation of intracellular coated vesicles. C1 NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. NIAMSD, Phys Biol Lab, NIH, Bethesda, MD 20892 USA. RP Nossal, R (reprint author), NICHHD, Lab Integrat & Med Biophys, NIH, Bldg 12A,Rm 2041, Bethesda, MD 20892 USA. EM rjn@helix.nih.gov OI Jin, Albert/0000-0003-3826-1081 NR 53 TC 28 Z9 28 U1 0 U2 4 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 2000 VL 78 IS 3 BP 1183 EP 1194 PG 12 WC Biophysics SC Biophysics GA 290VD UT WOS:000085697800010 PM 10692308 ER PT J AU Schuck, P AF Schuck, P TI Size-distribution analysis of macromolecules by sedimentation velocity ultracentrifugation and Lamm equation modeling SO BIOPHYSICAL JOURNAL LA English DT Article ID FREDHOLM INTEGRAL-EQUATIONS; INTERACTING PARTICLES; GENERALIZED SYSTEMS; 1ST KIND; REGULARIZATION; SOLUTES AB A new method for the size-distribution analysis of polymers by sedimentation velocity analytical ultracentrifugation is described. It exploits the ability of Lamm equation modeling to discriminate between the spreading of the sedimentation boundary arising from sample heterogeneity and from diffusion. Finite element solutions of the Lamm equation for a large number of discrete noninteracting species are combined with maximum entropy regularization to represent a continuous size-distribution. As in the program CONTIN, the parameter governing the regularization constraint is adjusted by variance analysis to a predefined confidence level. Estimates of the partial specific volume and the frictional ratio of the macromolecules are used to calculate the diffusion coefficients, resulting in relatively high-resolution sedimentation coefficient distributions c(s) or molar mass distributions c(M). It can be applied to interference optical data that exhibit systematic noise components, and it does not require solution or solvent plateaus to be established. More details on the size-distribution can be obtained than from van Holde-Weischet analysis. The sensitivity to the values of the regularization parameter and to the shape parameters is explored with the help of simulated sedimentation data of discrete and continuous model size distributions, and by applications to experimental data of continuous and discrete protein mixtures. C1 NIH, Mol Interact Resource Bioengn & Phys Sci Program, ORS, Bethesda, MD 20892 USA. RP Schuck, P (reprint author), NIH, Mol Interact Resource Bioengn & Phys Sci Program, ORS, Bldg 13,Rm 3N17,13 S Dr, Bethesda, MD 20892 USA. OI Schuck, Peter/0000-0002-8859-6966 NR 61 TC 1975 Z9 1986 U1 25 U2 152 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 2000 VL 78 IS 3 BP 1606 EP 1619 PG 14 WC Biophysics SC Biophysics GA 290VD UT WOS:000085697800047 PM 10692345 ER PT J AU Xiang, CC Chen, YD AF Xiang, CC Chen, YD TI cDNA microarray technology and its applications SO BIOTECHNOLOGY ADVANCES LA English DT Review DE cDNA microarray; technology; RNA expression assay technique ID GENE-EXPRESSION PATTERNS; SERIAL ANALYSIS; GENOME ANALYSIS; DNA MICROARRAY; HYBRIDIZATION; IDENTIFICATION; ARRAYS; SYSTEM; SCALE AB The cDNA microarray is the most powerful tool for studying gene expression in many different organisms. It has been successfully applied to the simultaneous expression of many thousands of genes and to large-scale gene discovery, as well as polymorphism screening and mapping of genomic DNA clones. It is a high throughput, highly parallel RNA expression assay technique that permits quantitative analysis of RNAs transcribed from both known and unknown genes. This technique provides diagnostic fingerprints by comparing gene expression patterns in normal and pathological cells, and because it can simultaneously track expression levels of many genes, it provides a source of operational context for inference and predication about complex cell control systems. This review describes this recently developed cDNA microarray technology and its application to gene discovery and expression, and to diagnostics for certain diseases, (C) 2000 Published by Elsevier Science Inc. All rights reserved. C1 USA, Med Res Inst Infect Dis, Dept Mol Virol, Div Virol, Frederick, MD 21702 USA. Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. RP Xiang, CC (reprint author), Univ Calif Los Angeles, Microarray Core Facil, Room 5554,Gonda Ctr,695 Young Dr S, Los Angeles, CA 90095 USA. NR 23 TC 43 Z9 55 U1 1 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0734-9750 J9 BIOTECHNOL ADV JI Biotechnol. Adv. PD MAR PY 2000 VL 18 IS 1 BP 35 EP 46 DI 10.1016/S0734-9750(99)00035-X PG 12 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 304XL UT WOS:000086509300003 PM 14538118 ER PT J AU Kovanen, PE Junttila, I Takaluoma, K Saharinen, P Valmu, L Li, WQ Silvennoinen, O AF Kovanen, PE Junttila, I Takaluoma, K Saharinen, P Valmu, L Li, WQ Silvennoinen, O TI Regulation of Jak2 tyrosine kinase by protein kinase C during macrophage differentiation of IL-3-dependent myeloid progenitor cells SO BLOOD LA English DT Article ID HL-60 LEUKEMIA-CELLS; SIGNAL-TRANSDUCTION; TRANSCRIPTION FACTOR; HEMATOPOIETIC-CELLS; CYTOKINE RECEPTORS; PHORBOL ESTERS; GROWTH-FACTOR; CYCLE ARREST; ACTIVATION; EXPRESSION AB Differentiation of macrophages from myeloid progenitor cells depends on a discrete balance between cell growth, survival, and differentiation signals. Interleukin-8 (IL-3) supports the growth and survival of myeloid progenitor cells through the activation of Jak2 tyrosine kinase, and macrophage differentiation has been shown to be regulated by protein kinase C (PKC). During terminal differentiation of macrophages, the cells lose their mitogenic response to IL-3 and undergo growth arrest, but the underlying signaling mechanisms have remained elusive. Here we show that in IL-3-dependent 32D myeloid progenitor cells, the differentiation-inducing PKC isoforms PKC-(C) 2000 by The American Society of Hematology alpha and PKC-delta specifically caused rapid inhibition of IL-3-induced tyrosine phosphorylation. The target for this inhibition was Jak2, and the activation of PKC by 12-O-tetradecanoyl-phorbol-13-acetate treatment also abrogated Ii-a-induced tyrosine phosphorylation of Jak2 in Ba/F3 cells, The mechanism of this regulation was investigated in 32D and COS7 cells, and the inhibition of Jak2 required catalytic activity of PKC-delta and involved the phosphorylation of Jak2 on serine and threonine residues by the associated PKC-delta, Furthermore, PKC-delta inhibited the in vitro catalytic activity of Jak2, indicating that Jak2 was a direct target for PKC-delta In 32D cells, the inhibition of Jak2 either by PKC-delta, tyrosine kinase inhibitor AG490, or IL-3 deprivation caused a similar growth arrest. Reversal of PKC-delta-mediated inhibition by the overexpression of Jak2 promoted apoptosis in differentiating 32D cells. These results demonstrate a PKC-mediated negative regulatory mechanism of cytokine signaling and Jak2, and they suggest that it serves to integrate growth-promoting and differentiation signals during macrophage differentiation. (C) 2000 by The American Society of Hematology. C1 Tampere Univ, Inst Med Technol, Lab Mol Immunol, FIN-33101 Tampere, Finland. Tampere Univ Hosp, Dept Clin Microbiol, Tampere, Finland. Haartman Inst, Dept Virol, Helsinki, Finland. Univ Helsinki, Dept Biosci, Helsinki, Finland. NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. RP Silvennoinen, O (reprint author), Tampere Univ, Inst Med Technol, Lab Mol Immunol, Lenkkeilijankatu 6, FIN-33101 Tampere, Finland. RI Saharinen, Pipsa/C-9601-2016 OI Saharinen, Pipsa/0000-0003-2652-0584 NR 50 TC 33 Z9 33 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 2000 VL 95 IS 5 BP 1626 EP 1632 PG 7 WC Hematology SC Hematology GA 288LR UT WOS:000085564700014 PM 10688817 ER PT J AU Pinto, LA Blazevic, V Shearer, GM Patterson, BK Dolan, MJ AF Pinto, LA Blazevic, V Shearer, GM Patterson, BK Dolan, MJ TI Alloantigen-induced anti-HIV activity occurs prior to reverse transcription and can be generated by leukocytes from HIV-infected individuals SO BLOOD LA English DT Letter ID CELLS; CD28 C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Northwestern Univ, Childrens Mem Hosp, Sch Med, Lab Viral Pathogenesis, Chicago, IL 60614 USA. Wilford Hall USAF Med Ctr, Infect Dis Serv, Lackland AFB, TX 78236 USA. RP Pinto, LA (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 9 TC 18 Z9 19 U1 0 U2 0 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 2000 VL 95 IS 5 BP 1875 EP 1876 PG 2 WC Hematology SC Hematology GA 288LR UT WOS:000085564700049 PM 10744387 ER PT J AU Sloand, E Maciejewski, J Dunn, D Moss, J Young, N AF Sloand, E Maciejewski, J Dunn, D Moss, J Young, N TI Response: Strong evidence for correction of the PNH defect SO BLOOD LA English DT Letter ID COMPLEMENT REGULATORY PROTEIN; ACCELERATING FACTOR DAF; PHOSPHOLIPASE-C; MEMBRANE C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Sloand, E (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 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 2000 VL 95 IS 5 BP 1877 EP 1878 PG 2 WC Hematology SC Hematology GA 288LR UT WOS:000085564700051 ER PT J AU Gadian, DG Aicardi, J Watkins, KE Porter, DA Mishkin, M Vargha-Khadem, F AF Gadian, DG Aicardi, J Watkins, KE Porter, DA Mishkin, M Vargha-Khadem, F TI Developmental amnesia associated with early hypoxic-ischaemic injury SO BRAIN LA English DT Article DE episodic memory; perinatal; hypoxic-ischaemic injury; hippocampus; magnetic resonance imaging ID MAGNETIC-RESONANCE SPECTROSCOPY; TEMPORAL-LOBE EPILEPSY; ISCHEMIC ENCEPHALOPATHY; HIPPOCAMPAL PATHOLOGY; CEREBRAL-PALSY; MEMORY; ASPHYXIA; CA1 AB We recently reported on three young patients with severe impairments:of episodic memory resulting from brain injury sustained early in life. These findings have led us to hypothesize that such impairments might be a previously unrecognized consequence of perinatal hypoxic-ischaemic injury. Neuropsychological and quantitative magnetic resonance investigations were carried out on five young patients, all of whom had suffered hypoxic-ischaemic episodes at or shortly after birth. All five patients showed severe impairments of episodic memory (memory for events), with relative preservation of semantic memory (memory for facts). However, none had any of the major neurological deficits that are typically associated with hypoxic-ischaemic injury, and all attended mainstream schools. Quantitative magnetic resonance investigations revealed severe bilateral hippocampal atrophy in all cases. As a group, the patients also showed bilateral reductions in grey matter in the regions of the putamen and the ventral part of the thalamus, On the basis of their clinical histories and the pattern of magnetic resonance findings, we attribute the patients' pathology and associated memory:impairments primarily to hypoxic-ischaemic episodes sustained very early in life. We suggest that the degree of hypoxia-ischaemia was sufficient to produce selective damage to particularly vulnerable regions of the brain, notably the hippocampi, but was not sufficient to result in the more severe neurological and cognitive deficits that can follow hypoxic-ischaemic injury. The impairments in episodic memory may be difficult to recognize, particularly in early childhood, but this developmental amnesia can have debilitating consequences, both at home and at school, and may preclude independent life in adulthood. C1 UCL, Inst Child Hlth, Radop & Phys Unit, London WC1N 1EH, England. Inst Child Hlth, Neurosci Unit, London, England. Inst Child Hlth, Cognit Neurosci Unit, London, England. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Gadian, DG (reprint author), UCL, Inst Child Hlth, Radop & Phys Unit, 30 Guilford St, London WC1N 1EH, England. EM dgadian@ich.ucl.ac.uk RI Gadian, David/C-4961-2008; Vargha-Khadem, Faraneh/C-2558-2008; Watkins, Kate/A-6559-2012; OI Watkins, Kate/0000-0002-2621-482X NR 33 TC 208 Z9 208 U1 2 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD MAR PY 2000 VL 123 BP 499 EP 507 DI 10.1093/brain/123.3.499 PN 3 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 293DV UT WOS:000085837000006 PM 10686173 ER PT J AU Stefan, K Kunesch, E Cohen, LG Benecke, R Classen, J AF Stefan, K Kunesch, E Cohen, LG Benecke, R Classen, J TI Induction of plasticity in the human motor cortex by paired associative stimulation SO BRAIN LA English DT Article DE plasticity; motor cortex; transcranial magnetic stimulation ID LONG-TERM POTENTIATION; TRANSCRANIAL MAGNETIC STIMULATION; ADULT SQUIRREL-MONKEYS; ISCHEMIC NERVE BLOCK; LASTING POTENTIATION; VISUAL-CORTEX; MOVEMENT REPRESENTATIONS; HORIZONTAL CONNECTIONS; SYNAPTIC TRANSMISSION; CORTICAL PLASTICITY AB Current models of motor cortical plasticity, developed in studies on experimental animals, emphasize the importance of the conjoint activity of somatosensory afferents and intrinsic motor cortical circuits, The hypothesis that an enduring change in excitability in the cortical output circuitry can be induced in the human motor cortex by a paired-stimulation protocol was tested, Low-frequency median nerve stimulation was paired with transcranial magnetic stimulation (TMS) over the optimal cranial site for stimulating the abductor pollicis brevis muscle (APB), This protocol induced an increase in the amplitudes of the motor evoked potentials (MEPs) in the resting APE as well as a prolongation of the silent period measured in the precontracted APE following TMS; amplitudes of MEPs measured in voluntary contraction remained unchanged. Experiments testing the excitability of spinal motoneurons using F-wave studies and electrical stimulation of the brainstem suggested that the site of the plastic changes was within the motor cortex, The increases in resting amplitudes and silent period duration were conditionally dependent on the timing between the afferent and the magnetic stimulation in that they were present when events elicited by afferent and magnetic stimulation were synchronous at the level of the motor cortex. Plasticity induced by paired stimulation evolved rapidly (within 30 min), was persistent (minimum duration 30-60 min) yet reversible, and was topographically specific, This combination of features and the similarity to properties of induced enduring changes in synaptic efficacy, as elucidated in animal studies, leads us to propose that the induced plasticity may represent a signature of associative long-term potentiation of cortical synapses or closely related neuronal mechanisms in the human cortex. C1 Univ Rostock, Neurol Klin, D-18055 Rostock, Germany. NINDS, Human Cort Physiol Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Classen, J (reprint author), Univ Rostock, Neurol Klin, Gehlsheimer Str 20, D-18055 Rostock, Germany. NR 68 TC 684 Z9 699 U1 5 U2 28 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD MAR PY 2000 VL 123 BP 572 EP 584 DI 10.1093/brain/123.3.572 PN 3 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 293DV UT WOS:000085837000012 PM 10686179 ER PT J AU Gerring, J Brady, K Chen, A Quinn, C Herskovits, E Bandeen-Roche, K Denckla, MB Bryan, RN AF Gerring, J Brady, K Chen, A Quinn, C Herskovits, E Bandeen-Roche, K Denckla, MB Bryan, RN TI Neuroimaging variables related to development of Secondary Attention Deficit Hyperactivity Disorder after closed head injury in children and adolescents SO BRAIN INJURY LA English DT Article ID TRAUMATIC BRAIN INJURY; INFARCTION; ADHD; RISK AB Objective: To characterize children who develop Secondary Attention Deficit Hyperactivity Disorder (S-ADHD) after severe and moderate closed head injury (CHI) according to neuroimaging variables. Method: Ninety-nine children fi-om 4-19 years who suffered severe and moderate CHI were prospectively followed for a year after injury. Premorbid psychiatric status was determined by administration to the parent of a structured psychiatric interview. This interview was readministered 1 year after injury to determine the presence of post-dosed head injury S-ADHD. An MRI was performed 3 months after injury to define lesion locations and volumes. Results: A set of multiple logistic regression models determined that the odds of developing S-ADHD were 3.64 times higher among children with thalamus injury, and 3.15 times higher among children with basal ganglia injury. There was no significant difference in lesion volumes in any of the locations of interest between the group who developed S-ADHD and the group who did not develop S-ADHD. Conclusion: The data support an association between S-ADHD and injury in either or both the thalamus and basal ganglia, but they do not definitively demonstrate whether injury in either structure has an effect on S-ADHD in the absence of injury in the other. C1 Kennedy Krieger Res Inst, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Johns Hopkins Sch Publ Hlth, Baltimore, MD USA. NIH, Bethesda, MD 20892 USA. RP Gerring, J (reprint author), Kennedy Krieger Res Inst, 707 N Broadway, Baltimore, MD 21205 USA. RI Bryan, R. Nick/P-1661-2014 FU NCRR NIH HHS [MO-RR00052]; NIMH NIH HHS [K20 MH-00997] NR 30 TC 45 Z9 45 U1 1 U2 3 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 0269-9052 J9 BRAIN INJURY JI Brain Inj. PD MAR PY 2000 VL 14 IS 3 BP 205 EP 218 PG 14 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 294EE UT WOS:000085897700001 PM 10759038 ER PT J AU Heyliger, SO Ni, Q Rothman, RB AF Heyliger, SO Ni, Q Rothman, RB TI Resolution of two [(35)S]GTP-gamma-S binding sites and their response to chronic morphine treatment: A binding surface analysis SO BRAIN RESEARCH BULLETIN LA English DT Article DE opioid receptors; G-proteins; tolerance; dependence ID MU-OPIOID RECEPTOR; NEUROBLASTOMA SH-SY5Y CELLS; GUINEA-PIG BRAIN; G-PROTEINS; RAT-BRAIN; INDUCED DESENSITIZATION; DOWN-REGULATION; HIGH-AFFINITY; TOLERANCE; ACTIVATION AB The mechanisms by which prolonged exposure to morphine leads to tolerance are not fully understood. We investigated the effects of etorphine (ET) on [(35)S]guanosine 5'-(thio)-triphosphate ([(35)S]GTP-gamma-S) binding in brains of rats made tolerant to morphine via the implantation of morphine (or placebo) pellets. Binding surface analysis was used to characterize the interactions of ET, Gpp(Np)H and GTP-gamma-S with sites labeled by [(35)S]GTP-gamma-S. Data sets were fitted to one- and two-site binding models using the nonlinear least squares curve fitting program MLAB-PC (Civilized Software, Bethesda, MD, USA). Two binding sites were readily resolved. Chronic morphine significantly increased the B(max) and K(d) of the high affinity binding site, ET stimulated [(35)S]GTP-gamma-S binding in placebo membranes via an increase in the B(max) of the high affinity binding site. In contrast, ET stimulated [(35)S]GTP-gamma-S in chronic morphine membranes via a large decrease in the K(d) of the high affinity site. These results suggest that chronic morphine treatment alters the mechanism by which ET stimulates [(35)S]GTP-gamma-S binding to G-proteins. Since proper G-protein/receptor coupling increases [(35)S]GTP-gamma-S binding via an increase in B(max) values, these results suggest that opioid receptors in chronic morphine membranes are not normally coupled to G-proteins. These findings corroborate earlier studies that reported changes in G-protein function in morphine tolerant animals. published by Elsevier Science Inc. C1 Natl Inst Drug Abuse, Clin Psychopharmacol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Rothman, RB (reprint author), Natl Inst Drug Abuse, Clin Psychopharmacol Sect, Intramural Res Program, NIH, POB 5180,5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM rrothman@inra.nida.nih.gov NR 36 TC 6 Z9 7 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD MAR 1 PY 2000 VL 51 IS 4 BP 357 EP 362 DI 10.1016/S0361-9230(99)00261-0 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 289TW UT WOS:000085638900010 PM 10704787 ER PT J AU Nicolson, R Lenane, M Hamburger, SD Fernandez, T Bedwell, J Rapoport, JL AF Nicolson, R Lenane, M Hamburger, SD Fernandez, T Bedwell, J Rapoport, JL TI Lessons from childhood-onset schizophrenia SO BRAIN RESEARCH REVIEWS LA English DT Article; Proceedings Paper CT Nobel Symposium 111: Schizophrenia - Pathophysiological Mechanisms CY OCT 01-03, 1998 CL KAROLINSKA INST, STOCKHOLM, SWEDEN SP Nobel Fdn HO KAROLINSKA INST DE childhood-onset schizophrenia; risk factors; genetic vulnerability ID SEX-CHROMOSOME ANOMALIES; OBSTETRIC COMPLICATIONS; ROSCOMMON FAMILY; FOLLOW-UP; EYE-TRACKING; PREMORBID ADJUSTMENT; BIRTH COHORT; DSM-III; RELATIVES; AGE AB Childhood-onset schizophrenia (with an onset of psychosis by age 12) is a rare and severe form of the disorder which is clinically and neurobiologically continuous with the adult-onset disorder. Very early onset diseases provide an opportunity to look for more salient or striking risk or etiologic factors in a possibly more homogenous patient population. For the 47 patients with very early onset schizophrenia studied to date, there were more severe premorbid neurodevelopmental abnormalities, more cytogenetic anomalies, and potentially greater family histories of schizophrenia and associated spectrum disorders than later onset cases. There was no evidence for relatively increased obstetrical complications or environmental stress. These data, while preliminary, suggest a very early age of onset of schizophrenia may be secondary to greater genetic vulnerability. It is anticipated that future genetic studies of these patients may provide important etiologic information. (C) 2000 Published by Elsevier Science B.V. All rights reserved. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Rapoport, JL (reprint author), NIMH, Child Psychiat Branch, 10 Ctr Dr MSC 1600, Bethesda, MD 20892 USA. RI Nicolson, Robert/E-4797-2011; Fernandez, Thomas/D-4295-2009 OI Fernandez, Thomas/0000-0003-0830-022X NR 92 TC 51 Z9 51 U1 5 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0173 J9 BRAIN RES REV JI Brain Res. Rev. PD MAR PY 2000 VL 31 IS 2-3 BP 147 EP 156 DI 10.1016/S0165-0173(99)00032-6 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 298GA UT WOS:000086129900007 PM 10719143 ER PT J AU Christov, K Shilkaitis, A Green, A Mehta, RG Grubbs, C Kelloff, G Lubet, R AF Christov, K Shilkaitis, A Green, A Mehta, RG Grubbs, C Kelloff, G Lubet, R TI Cellular responses of mammary carcinomas to aromatase inhibitors: Effects of vorozole SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE vorozole; aromatase inhibitors; mammary tumors; apoptosis ID BREAST-CANCER PATIENTS; NUDE-MOUSE MODEL; ESTROGEN BIOSYNTHESIS; POSTMENOPAUSAL WOMEN; APOPTOSIS; ENDOCRINE; RAT; TAMOXIFEN; DEATH; TUMORIGENESIS AB Vorozole (Vz) is a competitive non-steroidal inhibitor of aromatase, which has been used to treat breast cancer in postmenopausal women and in various chemoprevention pre-clinical studies. Recently, we assessed the inhibitory effect of Vz on Mnu-induced mammary carcinogenesis (Lubet et al., 1994), as well as on the progression of mammary tumors (Lubet et al., 1998). In this study we evaluated the effects of Vz on tumor growth, serum estradiol, cell proliferation, apoptotic and non-apoptotic cell death to determine whether any of these 'surrogate' markers might reflect the efficacy of various doses of Vz. Vz at doses of 2.5 (Hi), 0.32 (Md), and 0.08 (Lo) mg/kg body weight induced complete (100%), 60%, and 20% regression of mammary tumors, respectively. Vz at Hi and Md doses caused a decrease in serum estradiol within the first two days of treatment, and the estradiol values remained low with additional treatment for 4 and 10 days. When Vz was administered to animals bearing palpable tumors a time and dose-dependent decrease in the proliferating cells (BrdU-LI) was observed. The percentage of apoptotic cells (Al) sharply increased 2 days after initiation of Vz treatment and then decreased followed by an increase in non-apoptotic dead cells. Interestingly even the Lo dose of Vz, which was only moderately effective in suppressing tumor growth, decreased cell proliferation and increased cell death in the peripheral tumor areas at 4 and 10 days after initiation of treatment. The time- and dose-dependent alterations in various cell parameters suggest two different phases of Vz-induced cellular responses: (1) an early phase (2-4 days of treatment) with a sharp increase in apoptotic cells and decrease in proliferating cells, and (2) a later phase (10 days) with disintegration of tumor parenchyma, increase in non-apoptotic dead cells, and decrease in apoptotic cells. The dose-dependent decrease in proliferating cells and increase in apoptotic and non-apoptotic cell death in Vz-treated animals suggest that these biomarkers might be used as potential surrogate endpoints for efficacy in breast cancer chemoprevention and therapy studies with aromatase inhibitors. C1 Univ Illinois, Dept Surg Oncol, Chicago, IL 60612 USA. Univ Alabama, Chemoprevent Ctr, Birmingham, AL USA. NCI, Chemoprevent Branch, Bethesda, MD 20892 USA. RP Christov, K (reprint author), Univ Illinois, Dept Surg Oncol, 840 S Wood St,M-C 820, Chicago, IL 60612 USA. FU NCI NIH HHS [N0 1-CN-55179-MAO] NR 37 TC 21 Z9 21 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD MAR PY 2000 VL 60 IS 2 BP 117 EP 128 DI 10.1023/A:1006384026252 PG 12 WC Oncology SC Oncology GA 312PB UT WOS:000086950700003 PM 10845274 ER PT J AU Hajeer, AH Lear, JT Ollier, WER Naves, M Worthington, J Bell, DA Smith, AG Bowers, WP Jones, PW Strange, RC Fryer, AA AF Hajeer, AH Lear, JT Ollier, WER Naves, M Worthington, J Bell, DA Smith, AG Bowers, WP Jones, PW Strange, RC Fryer, AA TI Preliminary evidence of an association of tumour necrosis factor microsatellites with increased risk of multiple basal cell carcinomas SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article DE basal cell carcinoma; genetic susceptibility; haplotypes; microsatellites; polymorphism; tumour necrosis factor ID SYSTEMIC LUPUS-ERYTHEMATOSUS; FACTOR-ALPHA; POLYMORPHISMS; CANCER; LIGHT AB Tumour necrosis factor alpha (TNF-alpha) appears important in ultraviolet-induced immunosuppression, suggesting that it is a susceptibility candidate for cutaneous basal cell carcinoma (BCC), We now describe data on the association between TNF microsatellite polymorphisms, first on susceptibility in 202 controls and 133 cases each having two to 30 BCCs, and secondly, within the cases, on BCC numbers. The data show that the proportions of individuals with TNF a1- and a7-containing genotypes were significantly different (P = 0.0271, P = 0.0393, respectively) between cases and controls, Secondly, within the cases, TNF alleles d4 (P = 0.023) and d6 (P = 0.006) alone, and the TNF a2-b4-d5 haplotype (P = 0.007), were significantly associated with the number of BCC lesions, These preliminary data provide the first evidence that TNF microsatellite polymorphism may influence the pathogenesis of multiple BCC. C1 Univ Keele, N Staffordshire Hosp, Postgrad Med Sch, Ctr Cell & Mol Med,Cent Pathol Lab, Stoke On Trent, Staffs, England. Univ Manchester, ARC, Epidemiol Res Unit, Manchester, Lancs, England. N Staffordshire Hosp, Dept Dermatol, Stoke On Trent, Staffs, England. NIEHS, Biochem Risk Anal Lab, Res Triangle Pk, NC 27709 USA. Royal Cornwall Hosp, Dept Dermatol, Truro, Cornwall, England. Keele Univ, Dept Math, Keele, Staffs, England. RP Fryer, AA (reprint author), Univ Keele, N Staffordshire Hosp, Postgrad Med Sch, Ctr Cell & Mol Med,Cent Pathol Lab, Stoke On Trent, Staffs, England. RI Worthington, Jane/M-9770-2014; Naves Diaz, Manuel/O-5100-2014; lear, john/I-5465-2015; OI Worthington, Jane/0000-0003-0544-042X; lear, john/0000-0002-2969-9922; Hajeer, Ali/0000-0003-2727-9964 NR 17 TC 31 Z9 33 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD MAR PY 2000 VL 142 IS 3 BP 441 EP 445 DI 10.1046/j.1365-2133.2000.03353.x PG 5 WC Dermatology SC Dermatology GA 296GP UT WOS:000086016300007 PM 10735947 ER PT J AU Ravussin, E Bogardus, C AF Ravussin, E Bogardus, C TI Energy balance and weight regulation: genetics versus environment SO BRITISH JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Symposium on Diet and the Metabolic Syndrome CY AUG 26-28, 1999 CL YSTAD, SWEDEN SP Swedish Nutrit Fdn, Swedish Soc Med DE energy balance; weight regulation; obesity; genetics; environment; energy metabolism ID BODY-MASS INDEX; AUTOSOMAL GENOMIC SCAN; TWINS REARED APART; HUMAN OBESITY; PIMA-INDIANS; METABOLIC PREDICTORS; UNITED-STATES; GAIN; FAT; LOCUS AB The prevalence of obesity is reaching epidemic proportions in many industrialized countries. There is growing evidence that, even if the trigger of this epidemic is found in changes in the environment, genes are interacting with the environment to cause weight gain. Studies of twins reared apart indicate that approximately two-thirds of the variability in BMI is attributed to genetic factors. From prospective studies in Pima Indians we can ascribe 12 % of the variability in BMI to metabolic rate, 5 % to fat oxidation, and another probable 10 % to the level of spontaneous physical activity. These data indicate that at least 40 % of the variability in BMI is related to genetic factors involved in the regulation of food intake and/or volitional activity. This indicates that the most likely successful therapy for obesity may target pathways of the regulation of food intake. Similarly, an environment favouring engagement in physical activity should be promoted. C1 NIDDK, Eli Lilly & Co, Clin Diabet & Nutr Sect, Phoenix, AZ 85016 USA. RP Ravussin, E (reprint author), NIDDK, Eli Lilly & Co, Clin Diabet & Nutr Sect, Phoenix, AZ 85016 USA. NR 30 TC 73 Z9 74 U1 1 U2 4 PU C A B INTERNATIONAL PI WALLINGFORD PA C/O PUBLISHING DIVISION, WALLINGFORD OX10 8DE, OXON, ENGLAND SN 0007-1145 J9 BRIT J NUTR JI Br. J. Nutr. PD MAR PY 2000 VL 83 SU 1 BP S17 EP S20 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 321NN UT WOS:000087461700004 PM 10889787 ER PT J AU Song, LS Ren, GJ Chen, ZL Chen, ZH Zhou, ZN Cheng, HP AF Song, LS Ren, GJ Chen, ZL Chen, ZH Zhou, ZN Cheng, HP TI Electrophysiological effects of protopine in cardiac myocytes: inhibition of multiple cation channel currents SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE protopine; herb medicine; antiarrhythmia; ionic currents; action potential; heart ID VENTRICULAR MYOCYTES; CORYDALIS TUBERS; CALCIUM AB 1 Protopine (Pro) from Corydalis tubers has been shown to have multiple actions on cardiovascular system, including anti-arrhythmic, anti-hypertensive and negative inotropic effects. Although it was thought that Pro exerts its actions through blocking Ca2+ currents, the electrophysiological profile of Pro is unclear. The aim of this study is to elucidate the ionic mechanisms of Pro effects in the heart. 2 In single isolated Ventricular myocytes from guinea-pig, extracellular application of Pro markedly and reversibly abbreviates action potential duration, and decreases the rate of upstroke (dV/dt)(max), amplitude and overshoot of action potential in a dose-dependent manner. Additionally, it produces a slight, but significant hyperpolarization of the resting membrane potential. 3 Pro at 25, 50 and 100 mu M reduces L-type Ca2+ current (I-Ca,I-L) amplitude to 89.1, 61.9 and 45.8% of control, respectively, and significantly slows the decay kinetics of ICa,L at higher concentration. The steady state inactivation of I-Ca,I-L is Shifted negatively by 5.9-7.0 mV (at 50-100 mu M Pro), whereas the voltage-dependent activation of I-Ca,I-L remains unchanged. In contrast, Pro at 100 mu M has no evident effects on T-type Ca2+ current (I-Ca,I-T). 4 In the presence of Pro, both the inward rectifier (I-Kl) and delayed rectifier (I-K) potassium currents are variably inhibited, depending on Pro concentrations. 5 Sodium current (I-Na), recorded in low [Na+](o) (40 mM) solution, is more potently suppressed by Pro. At 25 mu M, Pro significantly attenuated I-Na at most of the test voltages (-60- + 40 mV, with a 53% reduction at -30 mV. 6 Thus, Pro is not a selective Ca2+ channel antagonist. Rather, it acts as a promiscuous inhibitor of cation channel currents including I-Ca,I-L, I-K, I-Kl as well as I-Na. These findings may provide some mechanistic explanations for the therapeutic actions of Pro in the heart. C1 NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Kunming Med Coll, Affiliated Hosp 1, Dept Cardiol, Kunming 650032, Yunnan, Peoples R China. Yunnan Pharmacol Labs Nat Prod, Kunming 650031, Yunnan, Peoples R China. Chinese Acad Sci, Shanghai Inst Physiol, Shanghai 200031, Peoples R China. RP Song, LS (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Song, Long-Sheng/D-5899-2012 NR 22 TC 29 Z9 31 U1 0 U2 3 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 2000 VL 129 IS 5 BP 893 EP 900 DI 10.1038/sj.bjp.0703132 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 291BX UT WOS:000085714400011 PM 10696087 ER PT J AU Sherman, CD Portier, CJ AF Sherman, CD Portier, CJ TI Calculation of the cumulative distribution function of the time to a small observable tumor SO BULLETIN OF MATHEMATICAL BIOLOGY LA English DT Article ID 2-STAGE MODEL; QUANTITATIVE-ANALYSIS; CARCINOGENESIS; NUMBER; SIZE; HEPATOCARCINOGENESIS; LESIONS; CLONES; FOCI AB Multistage mathematical models of carcinogenesis (when applied to tumor incidence data) have historically assumed that the growth kinetics of cells in the malignant state are disregarded and the formation of a single malignant cell is equated with the emergence of a detectable tumor. The justification of this simplification is, from a mathematical point of view, to make the estimation of turner incidence rates tractable. However, analytical forms are not mandatory in the estimation of tumor incidence rates. Portier et al.(1996b. Math. Biosci. 135, 129-146) have demonstrated the utility of the Kolmogorov backward equations in numerically calculating tumor incidence. By extending their results, the cumulative distribution function of the time to a small observable tumor may be numerically obtained. (C) 2000 Society for Mathematical Biology. C1 San Francisco State Univ, Dept Math, San Francisco, CA 94132 USA. NIEHS, Lab Computat Biol & Risk Assessment, Res Triangle Pk, NC 27709 USA. RP Sherman, CD (reprint author), San Francisco State Univ, Dept Math, 1600 Holloway Ave, San Francisco, CA 94132 USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 22 TC 10 Z9 10 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0092-8240 J9 B MATH BIOL JI Bull. Math. Biol. PD MAR PY 2000 VL 62 IS 2 BP 229 EP 240 DI 10.1006/bulm.1999.0148 PG 12 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 287XN UT WOS:000085532900002 PM 10824428 ER PT J AU Meldrum, ML AF Meldrum, ML TI On the pill: A social history of oral contraceptives, 1950-1970. SO BULLETIN OF THE HISTORY OF MEDICINE LA English DT Book Review C1 NIH, Bethesda, MD 20892 USA. RP Meldrum, ML (reprint author), NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4319 USA SN 0007-5140 J9 B HIST MED JI Bull. Hist. Med. PD SPR PY 2000 VL 74 IS 1 BP 206 EP 206 PG 1 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA 293NM UT WOS:000085859100045 ER PT J AU Mertineit, C Samlalsingh-Parker, J Glibetic, M Ricard, G Noya, JD Aranda, JV AF Mertineit, C Samlalsingh-Parker, J Glibetic, M Ricard, G Noya, JD Aranda, JV TI Nitric oxide, prostaglandins, and impaired cerebral blood flow autoregulation in group B streptococcal neonatal meningitis SO CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY LA English DT Article DE cerebrovascular autoregulation; group B Streptococcus; neonatal meningitis; anti-inflammatory agents; prostanoids; nitric oxide synthase; gene expression; nitric oxide ID CEREBROVASCULAR AUTOREGULATION; PNEUMOCOCCAL MENINGITIS; BACTERIAL-MENINGITIS; NEWBORN PIGLET; SYNTHASE GENE; BRAIN EDEMA; INDOMETHACIN; HYPERTENSION; INFLAMMATION; THROMBOXANE AB Impaired autoregulation of cerebral blood flow (CBF) contributes to CNS damage during neonatal meningitis. We tested (i) the hypothesis that cerebrovascular autoregulation is impaired during early onset group B streptococcal (GBS) meningitis, (ii) whether this impairment is regulated by vasoactive mediators such as prostaglandins and (or) nitric oxide (NO), and (iii) whether this impairment is preventable by specific and (or) nonspecific inhibitors: dexamethasone, ibuprofen, and N omega-nitro-L-arginine, a NO inhibitor. Sterile saline or 10(9) colony-forming units (cfu) of heat-killed GBS was injected into the cerebral ventricle of newborn piglets. CBF autoregulation was determined by altering cerebral perfusion pressure (CPP) with balloon-tipped catheters placed in the aorta. GBS produced a narrow range of CBF autoregulation due to an impairment at the upper limit of CPP. We report that in vivo in the early stages (first 2 h) of induced GBS inflammation (i) GBS impairs the upper limit of cerebrovascular autoregulation; (ii) ibuprofen, dexamethasone, and N omega-nitro-L-arginine not only prevent this GBS-induced autoregulatory impairment but improve the range of cerebrovascular autoregulation; (iii) these autoregulatory changes do not involve circulating cerebral prostanoids; and (iv) the observed changes correlate with the induction of NO synthase gene expression. Thus, acute early onset GBS-induced impairment of the upper limit of CBF autoregulation can be correlated with increases of NO synthase production, suggesting that NO is a vasoactive mediator of CBF. C1 McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ, Canada. McGill Univ, Dept Pediat, Montreal, PQ H3A 2T5, Canada. McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Ctr Perinatal Res & Dev Pharmacol, Montreal, PQ H3T 1E2, Canada. Wayne State Univ, Childrens Hosp Michigan, Div Clin Pharmacol, Detroit, MI USA. RP Aranda, JV (reprint author), NICHD, NIH, Pediat Pharmacol Res Unit Network, Childrens Hosp Michigan, 3901 Beaubien Blvd, Detroit, MI 48201 USA. NR 39 TC 7 Z9 7 U1 0 U2 1 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA, ONTARIO K1A 0R6, CANADA SN 0008-4212 J9 CAN J PHYSIOL PHARM JI Can. J. Physiol. Pharmacol. PD MAR PY 2000 VL 78 IS 3 BP 217 EP 227 DI 10.1139/cjpp-78-3-217 PG 11 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA 285ME UT WOS:000085392200004 PM 10721813 ER PT J AU Schlemper, RJ Dawsey, SM Itabashi, M Iwashita, A Kato, Y Koike, M Lewin, KJ Riddell, RH Shimoda, T Sipponen, P Stolte, M Watanabe, H AF Schlemper, RJ Dawsey, SM Itabashi, M Iwashita, A Kato, Y Koike, M Lewin, KJ Riddell, RH Shimoda, T Sipponen, P Stolte, M Watanabe, H TI Differences in diagnostic criteria for esophageal squamous cell carcinoma between Japanese and Western pathologists SO CANCER LA English DT Article; Proceedings Paper CT 11th World Congress of Gastroenterology CY SEP 05-13, 1998 CL VIENNA, AUSTRIA DE diagnosis; esophagus; squamous cell carcinoma; Japan; Western countries ID ENDOSCOPIC TREATMENT; CANCER; LINXIAN; MUCOSA; CHINA; RISK AB BACKGROUND. Large discrepancies have been found between Western and Japanese pathologists in the diagnosis of adenoma/dysplasia versus carcinoma for gastric and colorectal glandular lesions. It is important to determine whether similar differences exist in the diagnosis of esophageal squamous lesions. METHODS. Eleven expert gastrointestinal patholagists from Japan, North America, and Europe individually reviewed a set of microscopic slides containing 21 sections of biopsies and corresponding endoscopic mucosal resection specimens from Japanese patients with superficial esophageal squamous neoplastic lesions. The pathologists indicated the pathologic findings on which they based each diagnosis. RESULTS. Invasion was the most important diagnostic criterion of carcinoma for the Western pathologists whereas nuclear and structural features were more important far the Japanese pathologists. For two sections showing low grade dysplasia according to most Western pathologists, the Japanese pathologists diagnosed suspected carcinoma in one case and definite carcinoma in the other. For nine sections with high grade dysplasia according to the Western pathologists, the Japanese pathologists diagnosed suspected carcinoma in two cases and definite carcinoma in seven cases. For six sections with suspected carcinoma according to most Western pathalogists, the Japanese pathologists diagnosed suspected carcinoma in one case and definite carcinoma in five cases. Four sections showed definite carcinoma according to both the Western and Japanese pathologists. Thus, there was agreement among the Western and Japanese pathologists for only 5 of the 21 sections (kappa value, 0.04). However, when high grade dysplasia, noninvasive carcinoma, and suspected carcinoma were grouped together, the agreement was excellent (19 of the 21 sections; kappa value, 0.75). CONCLUSIONS. In Japan, esophageal squamous cell carcinoma is diagnosed mainly based on nuclear criteria, even in cases judged to be noninvasive low grade dysplasia in the West. This difference in diagnostic practice may contribute to the relatively high incidence rate and good prognosis of superficial esophageal carcinoma in Japan. To improve the comparability of research data, the authors recommend that high grade dysplasia, noninvasive carcinoma, and suspected carcinoma be grouped together into one category of "noninvasive high grade neoplasia." (C) 2000 American Cancer Society. C1 Fukuoka Univ, Sch Med, Dept Internal Med, Jonan Ku, Fukuoka 8140180, Japan. Natl Canc Inst, Canc Prevent Studies Branch, Bethesda, MD USA. Ibaraki Prefectural Cent Hosp, Dept Pathol, Tomobe, Japan. Fukuoka Univ, Chikushi Hosp, Dept Pathol, Fukuoka 81401, Japan. Inst Canc, Dept Pathol, Tokyo, Japan. Tokyo Metropolitan Komagome Hosp, Dept Pathol, Tokyo, Japan. Univ Calif Los Angeles, Ctr Hlth Sci, Dept Pathol, Los Angeles, CA 90024 USA. McMaster Univ, Med Ctr, Dept Pathol, Hamilton, ON L8N 3Z5, Canada. Natl Canc Ctr Hosp, Clin Lab Div, Tokyo, Japan. Jorvi Hosp, Dept Pathol, SF-02740 Espoo, Finland. Inst Pathol, Klinikum Bayreuth, Bayreuth, Germany. Niigata Univ, Sch Med, Dept Pathol 1, Niigata, Japan. RP Schlemper, RJ (reprint author), Fukuoka Univ, Sch Med, Dept Internal Med, Jonan Ku, 7-45-1 Nanakuma, Fukuoka 8140180, Japan. RI Riddell, Robert/J-5557-2016 NR 33 TC 65 Z9 66 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 0008-543X J9 CANCER JI Cancer PD MAR 1 PY 2000 VL 88 IS 5 BP 996 EP 1006 DI 10.1002/(SICI)1097-0142(20000301)88:5<996::AID-CNCR8>3.0.CO;2-Q PG 11 WC Oncology SC Oncology GA 291PT UT WOS:000085745800008 PM 10699887 ER PT J AU Hunter, CP AF Hunter, CP TI Epidemiology, stage at diagnosis, and tumor biology of breast carcinoma in multiracial and multiethnic populations SO CANCER LA English DT Article; Proceedings Paper CT National Action Plan on Breast Cancer Workshop on Multicultural Aspects of Breast Cancer Etiology CY MAR 17-19, 1999 CL WASHINGTON, D.C. ID NON-HISPANIC WHITE; CANCER SURVIVAL; SOCIOECONOMIC-STATUS; RACIAL-DIFFERENCES; SOCIAL-CLASS; NEW-MEXICO; WOMEN; RACE; AGE; MAMMOGRAPHY AB All women, regardless of their racial or ethnic origin or heritage, are at risk of developing breast cancer. Variations in breast carcinoma incidence rates among multicultural populations suggest that etiologic factors differ in their biologic expression and impact on disease outcome. Key among those factors that affect breast carcinoma development are the roles of genetics and the environment, the reproductive experience;Ind the effects of endogenous and exogenous hormones in women, the change in immune status and host vulnerability, and the biologic determinants of breast carcinoma. Cultural dynamics, sociodemographic differences, and behavioral characteristics across population subgroups modulate how biologic disease is expressed among different races and ethnic groups. These interactions contribute to the observed variations in breast carcinoma incidence, mortality, and survival. Stage, a measure of disease status, is used to assess prognosis, plan treatment, and evaluate outcome. Numerous studies have reported a more advanced stage of breast carcinoma at diagnosis in racial/ethnic subgroups, especially among women from African American, Hispanic, American Indian, and native Hawaiian cultures. Factors associated with advanced stage at diagnosis in multicultural populations range from changes in the basic biological characteristics at the molecular and cellular level, to more complex behavioral attributes unique to a particular multicultural population, to societal issues--such as access to care and socioeconomic conditions--all of which impact on the health measure called "stage at diagnosis." Rapid advancements in knowledge of cancer biology and of genetic markers and tumor products are providing new mechanisms for identifying etiologic pathways that can be utilized for better screening, detection, treatment and monitoring of disease. Further studies are needed that evaluate the biologic and molecular alterations in tumor development, progression, and response to therapy. Public health attention needs to be directed toward the societal influences that impact breast carcinoma development, as well as;augmenting recognition of the need for culturally appropriate, broad-based behavioral changes at the community level. In addition, continued efforts are needed to ensure the inclusion of multicultural population subgroups and minority investigators in all aspects of research--basic, clinical and applied. (C) 2000 American Cancer Society. C1 Natl Inst Hlth, Off Res Womens Hlth, Bethesda, MD 20892 USA. RP Hunter, CP (reprint author), Natl Inst Hlth, Off Res Womens Hlth, Bethesda, MD 20892 USA. NR 37 TC 84 Z9 84 U1 2 U2 3 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 2000 VL 88 IS 5 SU S BP 1193 EP 1202 DI 10.1002/(SICI)1097-0142(20000301)88:5+<1193::AID-CNCR3>3.0.CO;2-D PG 10 WC Oncology SC Oncology GA 292MW UT WOS:000085799600003 PM 10705354 ER PT J AU Johnson-Thompson, MC Guthrie, J AF Johnson-Thompson, MC Guthrie, J TI Ongoing research to identify environmental risk factors in breast carcinoma SO CANCER LA English DT Article; Proceedings Paper CT National Action Plan on Breast Cancer Workshop on Multicultural Aspects of Breast Cancer Etiology CY MAR 17-19, 1999 CL WASHINGTON, D.C. DE polymorphisms; polychlorinated biphenyls; dieldrin; organochlorines; electric and magnetic fields (EMF); environment; breast carcinoma ID CANCER MORTALITY; UNITED-STATES; PROGRAMS; EXPOSURE AB Environmental exposures, timing and duration of exposure, and one's genetic susceptibility all contribute to breast carcinoma and its progression. The purpose of this article was to identify known and suspected environmental causes of breast carcinoma, identify some Environmental risk factors that may represent significant risk factors for certain groups, and describe current studies, supported by the National institutes of Health/National Institute of Environmental Health Sciences, that clarify how environmental factors contribute to the development of breast carcinoma. Known and suspected environmental risk factors include organochlorine pesticides and other synthetic chemicals, hormonal factors (including exogenous endocrine disrupters), diet, tobacco and alcohol use, radiation, and magnetic fields. In at least 50% of breast carcinoma cases, none of the known risk factors apply. It is likely that an environmental component accounts for much of the unknown 50% of risk. Knowing the environment al factors For breast carcinoma development is an area that should be investigated intensely because it offers our best hope for prevention. Understanding why African-American women have a more aggressive form of breast carcinoma, whether they receive adequate follow-up treatment, and how these Factors contribute to increased mortality rates requires further exploration. Data that demonstrate the lower incidence rate of breast carcinoma in Asian women, the relation to low far diets and diets high in phytoestrogens, and how this might serve as a model for all women should be investigated. Finally, differences in behavioral and cultural attitudes, ethnicity, economic status, and life-style influences among different groups of women require further study to determine how these factors contribute to enhancing or reducing breast carcinoma risk. (C) 2000 American Cancer Society. C1 NIEHS, Off Deputy Director, Res Triangle Pk, NC 27709 USA. RP Johnson-Thompson, MC (reprint author), NIEHS, Off Deputy Director, POB 12233,111 Alexander Dr,MD B209, Res Triangle Pk, NC 27709 USA. NR 19 TC 44 Z9 45 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 0008-543X J9 CANCER JI Cancer PD MAR 1 PY 2000 VL 88 IS 5 SU S BP 1224 EP 1229 DI 10.1002/(SICI)1097-0142(20000301)88:5+<1224::AID-CNCR8>3.0.CO;2-H PG 6 WC Oncology SC Oncology GA 292MW UT WOS:000085799600008 PM 10705359 ER PT J AU Albanes, D Malila, N Taylor, PR Huttunen, JK Virtamo, J Edwards, BK Rautalahti, M Hartman, AM Barrett, MJ Pietinen, P Hartman, TJ Sipponen, P Lewin, K Teerenhovi, L Hietanen, P Tangrea, JA Virtanen, M Heinonen, OP AF Albanes, D Malila, N Taylor, PR Huttunen, JK Virtamo, J Edwards, BK Rautalahti, M Hartman, AM Barrett, MJ Pietinen, P Hartman, TJ Sipponen, P Lewin, K Teerenhovi, L Hietanen, P Tangrea, JA Virtanen, M Heinonen, OP TI Effects of supplemental alpha-tocopherol and beta-carotene on colorectal cancer: results from a controlled trial (Finland) SO CANCER CAUSES & CONTROL LA English DT Article DE alpha-tocopherol; beta-carotene; chemoprevention; colorectal cancer; micronutrients; trial; vitamin E ID KINASE-C ACTIVITY; SERUM VITAMIN-E; COLON-CANCER; ANTIOXIDANT VITAMINS; CELL-PROLIFERATION; CARDIOVASCULAR-DISEASE; RANDOMIZED TRIAL; RISK; PREVENTION; ADENOMAS AB Background: Some epidemiological investigations suggest that higher intake or biochemical status of vitamin E and beta-carotene might be associated with reduced risk of colorectal cancer. Methods: We tested the effects of alpha-tocopherol and beta-carotene supplementation on the incidence of colorectal cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a double-blind, placebo-controlled trial among 29,133 50-69-year-old male cigarette smokers. Participants were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), both agents, or a placebo daily for 5-8 years. Incident colorectal cancers (n = 135) were identified through the nationwide cancer registry, and 99% were histologically confirmed. Intervention effects were evaluated using survival analysis and proportional hazards models. Results: Colorectal cancer incidence was somewhat lower in the alpha-tocopherol arm compared to the no alpha-tocopherol arm, but this finding was not statistically significant (relative risk (RR) = 0.78, 95% confidence interval (CI) 0.55-1.09; log-rank test p = 0.15). beta-Carotene had no effect on colorectal cancer incidence (RR = 1.05, 95% CI 0.75-1.47; log-rank test p = 0.78). There was no interaction between the two substances. Conclusion: Our study found no evidence of a beneficial or harmful effect for beta-carotene in colorectal cancer in older male smokers, but does provide suggestive evidence that vitamin E supplementation may have had a modest preventive effect. The latter finding is in accord with previous research linking higher vitamin E status to reduced colorectal cancer risk. C1 NCI, Div Clin Sci, NIH, Bethesda, MD 20892 USA. Natl Publ Hlth Inst, Helsinki, Finland. NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. Informat Management Serv Inc, Silver Spring, MD USA. Jorvi Hosp, Dept Pathol, SF-02740 Espoo, Finland. Univ Calif Los Angeles, Sch Med, Dept Pathol, Los Angeles, CA 90024 USA. Univ Helsinki, Cent Hosp, Dept Publ Hlth, Helsinki, Finland. RP NCI, Div Clin Sci, NIH, 6006 Execut Blvd,Suite 321,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Albanes, Demetrius/B-9749-2015 FU NCI NIH HHS [N01-CN-45165] NR 48 TC 114 Z9 115 U1 0 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 EI 1573-7225 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAR PY 2000 VL 11 IS 3 BP 197 EP 205 DI 10.1023/A:1008936214087 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 292KV UT WOS:000085794000001 PM 10782653 ER PT J AU Farrow, DC Vaughan, TL Sweeney, C Gammon, MD Chow, WH Risch, HA Stanford, JL Hansten, PD Mayne, ST Schoenberg, JB Rotterdam, H Ahsan, H West, AB Dubrow, R Fraumeni, JF Blot, WJ AF Farrow, DC Vaughan, TL Sweeney, C Gammon, MD Chow, WH Risch, HA Stanford, JL Hansten, PD Mayne, ST Schoenberg, JB Rotterdam, H Ahsan, H West, AB Dubrow, R Fraumeni, JF Blot, WJ TI Gastroesophageal reflux disease, use of H-2 receptor antagonists, and risk of esophageal and gastric cancer SO CANCER CAUSES & CONTROL LA English DT Article DE esophageal neoplasms; gastric neoplasms; gastroesophageal reflux disease; H-2 receptor antagonists ID HISTAMINE-2-RECEPTOR ANTAGONISTS; RISING INCIDENCE; UNITED-STATES; ADENOCARCINOMA; CARDIA; CIMETIDINE; ALCOHOL; TOBACCO; DRUGS; CARCINOMA AB Objective: The incidence of esophageal adenocarcinoma has risen rapidly in the past two decades, for unknown reasons. The goal of this analysis was to determine whether gastroesophageal reflux disease (GERD) or the medications used to treat it are associated with an increased risk of esophageal or gastric cancer, using data from a large population-based case-control study. Methods: Cases were aged 30-79 years, newly diagnosed with esophageal adenocarcinoma (n = 293), esophageal squamous cell carcinoma (n = 221), gastric cardia adenocarcinoma (n = 261), or non-cardia gastric adenocarcinoma (n = 368) in three areas with population-based tumor registries. Controls (n = 695) were chosen by random digit dialing and from Health Care Financing Administration rosters. Data were collected using an in-person structured interview. Results: History of gastric ulcer was associated with an increased risk of non-cardia gastric adenocarcinoma (OR 2.1, 95% CI 1.4-3.2). Risk of esophageal adenocarcinoma increased with frequency of GERD symptoms; the odds ratio in those reporting daily symptoms was 5.5 (95% CI 3.2-9.3). Ever having used H-2 blockers was unassociated with esophageal adenocarcinoma risk (OR 0.9, 95% CI 0.5-1.5). The odds ratio was 1.3 (95% CI 0.6-2.8) in long-term (4 or more years) users, but increased to 2.1 (95% CI 0.8-5.6) when use in the 5 years prior to the interview was disregarded. Risk was also modestly increased among users of antacids. Neither GERD symptoms nor use of H-2 blockers or antacids was associated with risk of the other three tumor types. Conclusions: Individuals with long-standing GERD are at increased risk of esophageal adenocarcinoma, whether or not the symptoms are treated with H-2 blockers or antacids. C1 Univ Washington, Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98109 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98109 USA. Columbia Univ, Joseph L Mailman Sch Publ Hlth, Div Epidemiol, New York, NY USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. Univ Washington, Dept Pharm, Seattle, WA 98195 USA. New Jersey Dept Hlth & Senior Serv, Off Canc Epidemiol, Trenton, NJ USA. Columbia Univ, Coll Phys & Surg, Dept Pathol, New York, NY USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA. Int Epidemiol Inst, Rockville, MD USA. RP Farrow, DC (reprint author), Univ Washington, Fred Hutchinson Canc Res Ctr, Program Epidemiol, 1100 Fairview Ave N,POB 19024,MP-474, Seattle, WA 98109 USA. OI Sweeney, Carol/0000-0003-1113-7160 FU NCI NIH HHS [5U01-CA57923, U01-CA57949, U01-CA57983] NR 21 TC 138 Z9 140 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAR PY 2000 VL 11 IS 3 BP 231 EP 238 DI 10.1023/A:1008913828105 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 292KV UT WOS:000085794000005 PM 10782657 ER PT J AU Rimer, BK AF Rimer, BK TI Cancer control research 2001 SO CANCER CAUSES & CONTROL LA English DT Article DE evidence; prevention and control; risk communication; screening trends; tailored ID PRIMARY-CARE SETTINGS; PERSONALIZED FEEDBACK; TAILORED FEEDBACK; SMOKING CESSATION; RANDOMIZED TRIAL; BREAST-CANCER; MAMMOGRAPHY; MESSAGES; SMOKERS; IMPACT AB Objectives: Major societal changes, including the changing demographics of US society and the genetics and communications revolutions, are providing new opportunities to control cancer both in the United States and around the world. This article examines the implications of these trends and other issues in the context of cancer control research. A seven-item strategy for cancer control research is proposed. Results: Epidemiology, statistics, genetics, and bio-behavioral research are central disciplines for cancer control research. The identification of particular at-risk populations is increasingly possible. Cancer control research must focus on increasing fundamental knowledge in order to accelerate improvements in cancer prevention and early detection. Cancer control research also must be used to conduct trials of new cancer detection methods, overcome differential participation in cancer screening, develop evidence-based strategies to improve decision-making, and develop evidence-based cancer communications. A comprehensive cancer surveillance system is the foundation for cancer control research. Cancer control research must aim to reduce cancer risk, incidence, and mortality, and improve quality of life. These are important challenges for the new millennium. C1 NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Rimer, BK (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Blvd,Room 242, Bethesda, MD 20892 USA. FU NCI NIH HHS [5U19-CA-72099-03, R01-CA-55917] NR 97 TC 6 Z9 6 U1 7 U2 7 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAR PY 2000 VL 11 IS 3 BP 257 EP 270 DI 10.1023/A:1008953206396 PG 14 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 292KV UT WOS:000085794000008 PM 10782660 ER PT J AU Marcus, PM Newman, B Millikan, RC Moorman, PG Baird, DD Qaqish, B AF Marcus, PM Newman, B Millikan, RC Moorman, PG Baird, DD Qaqish, B TI The associations of adolescent cigarette smoking, alcoholic beverage consumption, environmental tobacco smoke, and ionizing radiation with subsequent breast cancer risk (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE adolescence; alcohol drinking; breast neoplasms; risk factors; smoking ID YOUNG-WOMEN; IRRADIATION; AGE AB Objectives: Studies of breast cancer among survivors of the World War II atomic bomb blasts over Japan suggest that the adolescent breast may be particularly sensitive to carcinogenic insult. To further explore that possibility we examined the relationships of cigarette smoking, alcohol consumption, environmental tobacco smoke (ETS) exposure, and medical treatment with ionizing radiation during adolescence with subsequent breast cancer risk. Methods: Data from the Carolina Breast Cancer Study, a population-based, case-control study of breast cancer in North Carolina women aged 20-74 years (864 cases, 790 controls), were analyzed. Results: A modest increase in breast cancer risk was suggested for women who began to smoke cigarettes between the ages of 10 and 14 years (OR: 1.5, CI: 0.9-2.5), and for women exposed to ionizing radiation between ages 10 and 19 years to treat or monitor a medical condition (OR: 1.6, CI: 0.5-2.5). Neither exposure to ETS at home prior to age 18 years (OR: 1.1, CI: 0.9-1.3) nor initiation of alcoholic beverage consumption between ages 10 and 15 years (OR: 1.1, CI: 0.6-1.8) appeared to increase risk. Conclusions: Our results are consistent with previous evidence suggesting that some adolescent exposures could influence future breast cancer risk. C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. Queensland Univ Technol, Sch Publ Hlth, Kelvin Grove, Qld 4059, Australia. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Marcus, PM (reprint author), NCI, Div Canc Prevent, Execut Plaza N,Room 344,MSC 7354, Bethesda, MD 20892 USA. OI Baird, Donna/0000-0002-5544-2653 FU NCI NIH HHS [R25-CA57726, P50-CA58223, T32-CA09330] NR 43 TC 58 Z9 58 U1 1 U2 5 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAR PY 2000 VL 11 IS 3 BP 271 EP 278 DI 10.1023/A:1008911902994 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 292KV UT WOS:000085794000009 PM 10782661 ER PT J AU Hankey, BF Ries, A Kozavy, CL Feuer, EJ Merrill, RM Clegg, LX Edwards, BK AF Hankey, BF Ries, A Kozavy, CL Feuer, EJ Merrill, RM Clegg, LX Edwards, BK TI Partitioning linear trends in age-adjusted rates (vol 11, pg 31, 2000) SO CANCER CAUSES & CONTROL LA English DT Correction C1 NCI, Canc Stat Branch, Bethesda, MD 20892 USA. RP Hankey, BF (reprint author), NCI, Canc Stat Branch, Execut Plaza N,Room 343J,6130 Execut Blvd,MSC 735, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAR PY 2000 VL 11 IS 3 BP 288 EP 288 DI 10.1023/A:1008917616318 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 292KV UT WOS:000085794000012 ER PT J AU Warren, KE Patel, MC McCully, CM Montuenga, LM Balis, FM AF Warren, KE Patel, MC McCully, CM Montuenga, LM Balis, FM TI Effect of P-glycoprotein modulation with cyclosporin A on cerebrospinal fluid penetration of doxorubicin in non-human primates SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE multidrug resistance; P-glycoprotein; doxorubicin; cyclosporin A; blood-brain barrier ID MULTIDRUG-RESISTANCE; DRUG-RESISTANCE; NORMAL-TISSUES; BRAIN; GENE; ETOPOSIDE; PHARMACOKINETICS; VINBLASTINE; ANTIBODY; CELLS AB Purpose: P-glycoprotein (Pgp) is a transmembrane drug efflux pump that is expressed in multidrug resistant cancer cells and in a variety of normal tissues, including brain capillary endothelial cells which comprise the blood-brain barrier. We studied the effects of the Pgp inhibitor, cyclosporin A (CsA), on the cerebrospinal fluid (CSF) penetration of the Pgp substrate, doxorubicin, in non-human primates. Methods: The animals received doxorubicin alone (2.0 mg/kg i.v. over 60 min) or doxorubicin (1 mg/kg i.v. over 60 min) and CsA (loading dose 4.0 mg/kg i.v. over 2 h, followed by continuous infusion of 12 mg/kg per day over 48 h). Plasma and CSF were collected over 48 h and the doxorubicin concentration was measured by reverse-phase high-pressure liquid chromatography (HPLC) with fluorescence detection (detection limit 5 nM). A two-compartment model was fitted to the plasma concentration-time data. Results: Pgp was demonstrated to be present in the epithelium of the choroid plexus by immunohistochemical methods, indicating that CSF drug penetration could be used as a surrogate for blood-brain barrier penetration. Steady state whole blood CsA concentrations, which were measured with a fluorescence-polarization immunoassay (TDX) that detects both CsA and its metabolites, ranged from 551-1315 mu g/l at 24 h. The clearance of doxorubicin in four animals was reduced by 34%, 38%, 45% and 49% when given with CsA. The doxorubicin concentration in the CSF was <5 nM in all animals, both after doxorubicin alone and doxorubicin with CsA. Conclusions: The Pgp inhibitor, CsA, at a concentration that alters systemic clearance of doxorubicin, does not appear to significantly increase the CSF penetration of doxorubicin. C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. NCI, Med Branch, Bethesda, MD 20892 USA. RP Warren, KE (reprint author), NCI, Pediat Oncol Branch, Bldg 10,Rm 13N240,10 Ctr Dr, Bethesda, MD 20892 USA. NR 31 TC 26 Z9 26 U1 2 U2 5 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAR PY 2000 VL 45 IS 3 BP 207 EP 212 DI 10.1007/s002800050031 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 285RD UT WOS:000085401300004 PM 10663638 ER PT J AU Balis, FM Blaney, SM McCully, CL Bacher, JD Murphy, RF Poplack, DG AF Balis, FM Blaney, SM McCully, CL Bacher, JD Murphy, RF Poplack, DG TI Methotrexate distribution within the subarachnoid space after intraventricular and intravenous administration SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE methotrexate; cerebrospinal fluid; intrathecal; pharmacokinetics ID CENTRAL-NERVOUS-SYSTEM; CEREBROSPINAL-FLUID; RHESUS-MONKEYS; PHARMACOKINETICS; PHARMACOLOGY; CHEMOTHERAPY; RESERVOIR; LEUKEMIA AB Purpose: Intrathecal methotrexate achieves high concentrations in cerebrospinal fluid (CSF), but drug distribution throughout the subarachnoid space after an intralumbar dose is limited. The objective of this study was to quantify methotrexate distribution in CSF after intraventricular and intravenous administration and to identify factors that influence CSF distribution. Methods: Nonhuman primates (Macaca mulatta) with permanently implanted catheters in the lateral and fourth ventricles received methotrexate by bolus injection (0.5 mg) and infusion (0.05 to 0.5 mg/day over 24 to 168 h) into the lateral ventricle, as well as intravenous infusions. CSF was sampled from the lumbar space, fourth ventricle and the subarachnoid space at the vertex. Methotrexate in CSF and plasma was measured with the dihydrofolate reductase inhibition assay. Results: After bolus intraventricular injection, methotrexate exposure in lumbar CSF ranged from 11% to 69% of that achieved in the fourth ventricle. During continuous intraventricular infusions, methotrexate steady-state concentrations (C-ss) in lumbar CSF and CSF from the vertex were only 20% to 25% of the ventricular CSF C-ss. The dose, duration of infusion, and infusate volume did not influence drug distribution to the lumbar CSF, but probenicid increased the lumbar to ventricular C-ss ratio, suggesting the involvement of a probenicid-sensitive transport pump in the efflux of MTX from the CSF. During the intravenous infusions, the ventricular methotrexate C-ss was lower than the lumbar C-ss and the C-ss in CSF from the vertex. Conclusion: Methotrexate CSF distribution after intraventricular injection was uneven, and at steady-state CSF methotrexate concentrations were lower at sites that were more distant from the injection site. C1 NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NIH, Vet Resources Program, Bethesda, MD 20892 USA. RP Balis, FM (reprint author), NCI, Pediat Oncol Branch, NIH, Bldg 10,Rm 13N240,10 Ctr Dr,MSC 1928, Bethesda, MD 20892 USA. NR 21 TC 25 Z9 27 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAR PY 2000 VL 45 IS 3 BP 259 EP 264 DI 10.1007/s002800050038 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 285RD UT WOS:000085401300011 PM 10663645 ER PT J AU Pennello, G Devesa, S Gail, M AF Pennello, G Devesa, S Gail, M TI Association of surface ultraviolet B radiation levels with melanoma and nonmelanoma skin cancer in United States blacks SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CUTANEOUS MALIGNANT-MELANOMA; SUN EXPOSURE; CARCINOMA; WHITES AB Ultraviolet B (UVB) radiation exposure increases the risk of skin cancer in whites. Motivated by indications that United States geographic variation of relative skin cancer risk in blacks approaches that in whites, we used Poisson regression to estimate the risk of skin cancer in blacks as a function of average annual surface-levels of UVB radiation, measured by Robertson-Berger meters. United States data were used on deaths in 506 state economic areas, 1970-1994, and on incident cases in the nine areas of the Surveillance, Epidemiology, and End Results Program, 1973-1994, For black males, the age-adjusted relative risk of mortality for a 50% increase in UVB radiation was significantly above one for malignant melanoma, 1970-1994 (1.16; 95% confidence interval, 1.02-1.32) and nearly so for nonmelanoma skin cancer, 1970-1981 (1.18; 95% confidence interval, 1.00-1.39), for which the time period was chosen to avoid AIDS-related deaths from Kaposi's sarcoma. However, for black females, the relative risk of mortality was not significantly elevated for either skin cancer, and, for both black males and females, the relative risk of incidence was not significantly elevated for melanoma in the period 1973-1994. Incidence data on nonmelanoma skin cancer were not available. Although the public health implication is uncertain because of the much lower absolute risk of skin cancer in blacks compared with whites, the findings suggest that sunlight exposure increases skin cancer risk in blacks. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Pennello, G (reprint author), US FDA, Ctr Devices & Radiol Hlth, OSB DBS HFZ-542,1350 Piccard Dr, Rockville, MD 20850 USA. NR 36 TC 26 Z9 26 U1 0 U2 1 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 2000 VL 9 IS 3 BP 291 EP 297 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 295TG UT WOS:000085983500008 PM 10750668 ER PT J AU Hoque, ATMS Liu, XB Kagami, H Swaim, WD Wellner, RB O'Connell, BC Ambudkar, IS Baum, BJ AF Hoque, ATMS Liu, XB Kagami, H Swaim, WD Wellner, RB O'Connell, BC Ambudkar, IS Baum, BJ TI Construction and function of a recombinant adenovirus encoding a human aquaporin 1-green fluorescent protein fusion product SO CANCER GENE THERAPY LA English DT Article DE gene transfer; salivary gland; radiation damage; water channel; green fluorescent protein; fusion protein ID RECTAL GLAND TUBULES; RAT SALIVARY-GLANDS; IN-VITRO; MEMBRANE CAPACITANCE; SQUALUS-ACANTHIAS; FLUID MOVEMENT; WATER CHANNEL; GENE-THERAPY; LIVING CELLS; EXPRESSION AB Transfer of the human aquaporin 1 (hAQP1) gene provides a novel way to potentially correct the severe salivary hypofunction associated with therapeutic radiation for head and neck cancer. To facilitate the study of individual cells transduced with this gene, we have designed a fusion product of the hAQP1 and jellyfish green fluorescent protein (GFP) cDNAs. An expression plasmid, pACCMVhAQP1GFP, and a recombinant adenovirus, AdhAQP1GFP, encoding this fusion product were constructed. Both the recombinant plasmid and virus directed the expression of the encoded, 55-kDa fusion protein (hAQP1GFP), which was detected in the plasma membranes of several epithelial cell lines (293, SMIE, and A5). hAQP1 GFP was functionally active and facilitated fluid movement across a polarized salivary epithelial cell monolayer (similar to 5-fold noninfected controls) in response to an osmotic gradient. In response to a hypotonic challenge, individual epithelial cells expressing the fusion protein exhibited significantly more capacitance (used herein as an indicator of cell swelling) than control cells. Conversely, in response to a hypertonic challenge, individual infected cells shrunk more rapidly (similar to 2- to 3-fold) and to a greater extent than control cells. We conclude that AdhAQP1GFP is a useful experimental tool to identify and study individual cells expressing a water channel transgene. C1 Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Baum, BJ (reprint author), Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, Bldg 10,Room 1N113,10 Ctr Dr,MSC 1190, Bethesda, MD 20892 USA. OI O'Connell, Brian/0000-0003-4529-7664 NR 32 TC 9 Z9 12 U1 1 U2 1 PU STOCKTON PRESS PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD MAR PY 2000 VL 7 IS 3 BP 476 EP 485 DI 10.1038/sj.cgt.7700146 PG 10 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 302BP UT WOS:000086345300014 PM 10766354 ER PT J AU Dudley, ME Ngo, LT Westwood, J Wunderlich, JR Rosenberg, SA AF Dudley, ME Ngo, LT Westwood, J Wunderlich, JR Rosenberg, SA TI T-cell clones from melanoma patients immunized against an anchor-modified gp100 peptide display discordant effector phenotypes SO CANCER JOURNAL LA English DT Article DE cytotoxic T lymphocyte; immunotherapy-adoptive; epitopes-therapeutic use; melanoma ID TUMOR-INFILTRATING LYMPHOCYTES; ANTIGEN GP100; IN-VITRO; ADOPTIVE IMMUNOTHERAPY; METASTATIC MELANOMA; MULTIPLE EPITOPES; IDENTIFICATION; CTL; INTERLEUKIN-2; RECOGNITION AB PURPOSE The modified peptide epitope gp100:209-217 (210M), referred to as g209-2M, of the gp100 melanocyte differentiation protein, when administered to melanoma patients by subcutaneous injection in incomplete Freund's adjuvant, is capable of generating HLA-A2-restricted CD8(+) lymphocytes that specifically recognize the native gp100:209-217 (g209) pep tide as well as gp100-expressing tumor cells. To evaluate the suitability of cloned lymphocytes from immunized patients for use in adoptive transfer therapy protocols, the functional and phenotypic variation of individual CD8(+) T cell clones comprising the antitumor immune response was evaluated METHODS T-cell clones from melanoma patients who received g209-2M immunization were isolated and expanded, and their specific antitumor functional phenotypes were characterized RESULTS g209-specific CD8(+) lymphocytes that specifically recognized gp100-expressing tumor cells were readily obtained from g209-2M-immunized patients. There was substantial variation in the absolute levels of cytokine secretion and target cell lysis by g209-specific clones from each patient Furthermore, individual clones demonstrated discordant secretion of different proinflammatory cytokines These clonal phenotypes were stable, even after large expansions in cell number. DISCUSSION These results indicate that g209-2M peptide immunization of melanoma patients leads to a functionally diverse population of T cells, many of which are capable of expansion at vivo to cell numbers appropriate fbr adoptive immunotherapy. However, the selection of a particular antigen-specific T-cell clone for treatment should be based on multiple functional criteria. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Dudley, ME (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B-46,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 24 TC 36 Z9 37 U1 0 U2 0 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PONE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. Sci. Am. PD MAR-APR PY 2000 VL 6 IS 2 BP 69 EP 77 PG 9 WC Oncology SC Oncology GA 342YZ UT WOS:000088676100007 PM 11069222 ER PT J AU Joshi, BH Plautz, GE Puri, RK AF Joshi, BH Plautz, GE Puri, RK TI Interleukin-13 receptor alpha chain: A novel tumor-associated transmembrane protein in primary explants of human malignant gliomas SO CANCER RESEARCH LA English DT Article ID PSEUDOMONAS EXOTOXIN; SIGNAL-TRANSDUCTION; CHIMERIC PROTEIN; IL-13 RECEPTOR; CARCINOMA-CELLS; CANCER-CELLS; EGF RECEPTOR; BRAIN-TUMORS; TOXIN; LINES AB Human malignant glioma cell lines express high levels of interleukin-13 receptor (IL-13R), However, the subunit structure of this receptor in primary brain tumor cells is not known. Herein, we examined the subunit composition of IL-13R by analyzing the expression of four different putative subunits of IL-13R complex in 25 primary explants of malignant brain tumors. Reverse transcription-PCR (RT-PCR) of RNA from these tumor cells, normal astrocytes, and normal brain tissue showed that transcripts of IL-13R alpha chain were present in greater abundance in malignant glioma cells compared with normal astrocytes or normal brain tissues. The transcripts for two other chains (e.g., IL-13R alpha' and IL-4R beta), on the other hand, yielded similar PCR positivity in brain tumors as well as in normal samples, whereas transcripts for gamma c chain were absent in all brain tumor cells and normal tissues. The specificity of RT-PCR products for these genes was confirmed by oligo liquid hybridization analysis using a radiolabeled sequence-specific internal probe. Indirect immunofluorescence studies for different receptor chains confirmed the RT-PCR results and demonstrated a striking difference in the level of expression of IL-13R alpha protein between normal astrocytes and malignant astrocytoma cells. These studies establish the IL-13R alpha subunit as a novel tumor-specific protein that may be useful as a tumor marker, a target for cytotoxin/immunotoxin, or alternatively, a tumor-associated antigen for active, specific immunotherapy. C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Surg Res Ctr, Cleveland, OH 44195 USA. RP Puri, RK (reprint author), NIH Bldg 29B,Room 2NN10,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 26 TC 131 Z9 145 U1 0 U2 3 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 2000 VL 60 IS 5 BP 1168 EP 1172 PG 5 WC Oncology SC Oncology GA 293RA UT WOS:000085865700005 PM 10728667 ER PT J AU Feldman, AL Libutti, SK AF Feldman, AL Libutti, SK TI Correspondence re: Q-R. Chen et al., liposomes complexed to plasmids encoding angiostatin and endostatin inhibit breast cancer in nude mice. Cancer Res., 59 : 3308-3312, 1999. SO CANCER RESEARCH LA English DT Letter ID GENE-THERAPY; TUMOR C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Libutti, SK (reprint author), NCI, Surg Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RI Feldman, Andrew/D-5028-2012 NR 6 TC 6 Z9 6 U1 0 U2 0 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 2000 VL 60 IS 5 BP 1463 EP 1463 PG 1 WC Oncology SC Oncology GA 293RA UT WOS:000085865700052 PM 10728714 ER PT J AU Qasba, PK AF Qasba, PK TI Involvement of sugars in protein-protein interactions SO CARBOHYDRATE POLYMERS LA English DT Article; Proceedings Paper CT 6th Biennial Frontiers in Carbohydrate Research Conference CY MAY 12-13, 1999 CL PURDUE UNIV, W LAFAYETTE, INDIANA SP Whistler Ctr Carbohydrate Res HO PURDUE UNIV DE glycosaminoglycans; alpha-lactalbumin; GalNAc residue ID FIBROBLAST GROWTH-FACTOR; ASPARAGINE-LINKED OLIGOSACCHARIDES; MOLECULAR-DYNAMICS SIMULATIONS; LYSOSOMAL-ENZYME PHOSPHORYLATION; MANNOSE-BINDING PROTEIN; WHEAT-GERM-AGGLUTININ; ALPHA-D-MANNOSIDASE; RAT-LIVER; RECOGNITION DETERMINANTS; ENDOPLASMIC-RETICULUM AB In a cell there is an intricate machinery involved in the biosynthesis of complex oligosaccharides of glycoproteins, glycolipids, and proteoglycans. These oligosaccharides play important roles in several biological processes, including the folding and transport of glycoproteins across cellular compartments. Defective glycan synthesis has been shown to have serious pathological consequences and result in several human diseases. The oligosaccharide moieties bind to cellular proteins with high specificity and modulate the homo- and heterodimerization of glycoproteins. Owing to the conformational flexibility of oligosaccharides, the torsional angles of a disaccharide unit, particularly around the 1-6-linkage, adjust in such a way that the side groups of the oligosaccharides orient themselves in a manner that promotes favorable interactions with the binding residues of the protein. Branched oligosaccharides cross-link proteins and generate infinite networks of protein-carbohydrate complexes, resulting in the modulation of various cell responses. Glycosaminoglycans, the oligosaccharide moieties of proteoglycans, bind growth factors with a high degree of specificity and induce interactions with growth factor receptors, thereby regulating their biological activity. Using an experimental model system to study the sugar mediated protein-protein interactions, we are investigating the sugar ligand-dependent interactions between or-Lactalbumin (alpha-LA) and beta-1,4-galactosyltransferase (beta 4Gal-T). Also, using a molecular modeling method, we are investigating the heparin dependent dimerization of fibroblast growth factor and growth factor receptor. Our results, together with studies from various other laboratories, support the hypothesis that in the oligosaccharide induced recognition process, sugars accelerate the assembly of the complex by positioning and orienting the molecules in an optimal fashion that brings about specific protein-protein or protein-carbohydrate interactions. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 NCI, Frederick Canc Res & Dev Ctr, Struct Glycobiol Sect, Lab Expt & Computat Biol, Frederick, MD 21702 USA. RP Qasba, PK (reprint author), NCI, Frederick Canc Res & Dev Ctr, Struct Glycobiol Sect, Lab Expt & Computat Biol, POB B,Bldg 469,Room 221, Frederick, MD 21702 USA. NR 62 TC 27 Z9 28 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0144-8617 J9 CARBOHYD POLYM JI Carbohydr. Polym. PD MAR PY 2000 VL 41 IS 3 BP 293 EP 309 DI 10.1016/S0144-8617(99)00148-4 PG 17 WC Chemistry, Applied; Chemistry, Organic; Polymer Science SC Chemistry; Polymer Science GA 264DJ UT WOS:000084164800009 ER PT J AU Yuspa, SH AF Yuspa, SH TI Overview of carcinogenesis: past, present and future SO CARCINOGENESIS LA English DT Editorial Material AB In the foregoing articles, the editors of Carcinogenesis have identified the major themes of current carcinogenesis research and assembled an outstanding group of authors to review these areas. I have been asked to provide a historical overview of past accomplishments and describe how these contributed to the broader efforts to overcome the burden of human cancer. My assignment also included a look into the future. As scientists me formulate hypotheses that attempt to predict the future. Occasionally we are successful, The pioneers of carcinogenesis research were remarkably successful in predicting the future. Armed with primitive technology relative to today, these scientists studied the biology of carcinogenesis and conceptualized a framework for cancer pathogenesis that virtually everyone working in cancer research follows today. The current generation has been charged with filling in the details, In the details lay the future. Together with past accomplishments, these emerging details form a remarkable picture of progress in understanding and application, creating realistic and imminent promise to achieve victory in the fight against cancer. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. RP Yuspa, SH (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 22 Z9 23 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAR PY 2000 VL 21 IS 3 BP 341 EP 344 PG 4 WC Oncology SC Oncology GA 294XA UT WOS:000085934700002 PM 10688853 ER PT J AU Poirier, MC Santella, RM Weston, A AF Poirier, MC Santella, RM Weston, A TI Carcinogen macromolecular adducts and their measurement SO CARCINOGENESIS LA English DT Article ID HYDROCARBON-DNA ADDUCTS; WHITE BLOOD-CELLS; LUNG-CANCER; HEPATOCELLULAR-CARCINOMA; CHEMICAL CARCINOGENS; HEMOGLOBIN ADDUCTS; AFLATOXIN EXPOSURE; METABOLIC-ACTIVATION; AROMATIC-AMINES; PROTEIN ADDUCTS AB Damage to DNA induced by carcinogenic chemicals reflects exposure and is directly related to tumor formation, whereas modification of protein provides relatively precise dosimetry for stable adducts of proteins with a known half-life. Sophisticated methods for the detection and quantitation of DNA and protein adducts have been developed during the last similar to 25 years. For DNA adducts the most widely used methods include electrochemical detection, mass spectrometry, fluorescence and phosphorescence spectroscopy, immunoassays and immunohistochemistry and (32)P-post-labeling. Detection limits for quantitative assays are typically in the range of 1 adduct in 10(7) or 10(9) nucleotides. However, accelerator mass spectrometry, which is highly sophisticated but less accessible, has a detection limit of similar to 1 adduct in 10(12) nucleotides, Methods for the determination of protein adducts include immunoassay and a variety of elegant high-resolution mass spectrometry approaches. The detection limit of similar to 0.1 fmol for protein adducts, is based primarily on method specificity and the availability of large quantities of sample material. Using these highly sensitive methods a major achievement has been the biomonitoring of chemically exposed human populations. Validation of macromolecular adduct formation in humans has been predicated on studies in animal models. Adduct formation in humans appears to be indicative of molecular dosimetry and suggestive of increased human cancer risk. However, despite the large body of literature documenting DNA and protein adduct molecular dosimetry for many carcinogen exposures, the relationship between adduct formation and human cancer risk has been defined for only a few carcinogens. Thus, elucidation of this association remains a compelling challenge. For the future, integration of DNA and protein adduct measurements together with documentation of correlative and subsequent events, and host susceptibility factors, within the context of valid molecular epidemiologic study designs, will further our understanding of human disease mechanisms. C1 NCI, Carcinogen DNA Interact Sect, LCCTP,Div Basic Sci, NIH, Bethesda, MD 20892 USA. Columbia Univ, Joseph L Mailman Sch Publ Hlth, New York, NY 10032 USA. NIOSH, Mol Carcinogenesis Team, TMBB, Hlth Effects Lab Div,CDC, Morgantown, WV 26505 USA. RP Poirier, MC (reprint author), NCI, Carcinogen DNA Interact Sect, LCCTP,Div Basic Sci, NIH, Bldg 37,Room 2A05,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. EM poirierm@exchange.nih.gov NR 84 TC 137 Z9 144 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAR PY 2000 VL 21 IS 3 BP 353 EP 359 DI 10.1093/carcin/21.3.353 PG 7 WC Oncology SC Oncology GA 294XA UT WOS:000085934700004 PM 10688855 ER PT J AU Balmain, A Harris, CC AF Balmain, A Harris, CC TI Carcinogenesis in mouse and human cells: parallels and paradoxes SO CARCINOGENESIS LA English DT Review ID SKIN TUMOR PROGRESSION; BETA-CATENIN; RAS GENE; P53 GENE; HA-RAS; TRANSGENIC MICE; CHEMICAL CARCINOGENESIS; SUPPRESSOR GENES; HIGH-FREQUENCY; HUMAN CANCER AB It has been known since the last century that genetic changes are important in carcinogenesis [Boveri,T. (1914) Zur Frage der Erstehung Maligner Tumoren. Gustav Fischer, Jena]. Observations of tumor cells growing in tissue culture led to the prediction, even before the true nature of the genetic material was known, that alterations at the chromosomal level were critically involved in the process of neoplastic development. The past 20 gears have seen the transition of carcinogenesis studies from the purely observational to the molecular genetic level. Although much more needs to be done, it is nevertheless gratifying to be able to piece together the sequence of events from carcinogen exposure, metabolism of the carcinogen to the activated form, formation of specific carcinogen-DNA adducts, misrepair leading to the fixation of mutations in particular target genes, and the resulting selective outgrowth of neoplastic cells. The nature of manly of these steps has been clarified only in the relatively recent past, and only for a small number of specific target genes, but the fact that we can say with confidence that such processes occur and are causal changes in tumorigenesis represents a tremendous advance over the situation pertaining 20 years ago. The purpose of this review is to summarize the advances over this time period in our understanding of some of the genetic alterations that contribute to neoplasia, with particular emphasis on chemical carcinogenesis in rodents and the parallels with transformation of human cells. C1 Univ Calif San Francisco, Ctr Canc, San Francisco, CA 94115 USA. NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Balmain, A (reprint author), Univ Calif San Francisco, Ctr Canc, 2340 Sutter St, San Francisco, CA 94115 USA. EM abalmain@cc.ucsf.edu NR 99 TC 80 Z9 83 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAR PY 2000 VL 21 IS 3 BP 371 EP 377 DI 10.1093/carcin/21.3.371 PG 7 WC Oncology SC Oncology GA 294XA UT WOS:000085934700006 PM 10688857 ER PT J AU Zhou, YF Shou, M Harrell, RF Yu, ZX Unger, EF Epstein, SE AF Zhou, YF Shou, M Harrell, RF Yu, ZX Unger, EF Epstein, SE TI Chronic non-vascular cytomegalovirus infection: effects on the neointimal response to experimental vascular injury SO CARDIOVASCULAR RESEARCH LA English DT Article DE arteries; angioplasty; cytokines; infection/inflammation; restenosis ID SCAVENGER RECEPTOR; ATHEROSCLEROSIS; PROLIFERATION; EXPRESSION; RESTENOSIS; KINETICS; GROWTH; CELLS AB Objective: Epidemiologic and mechanistic evidence implicates a role for cytomegalovirus (CMV) in atherogenesis. Recently, we demonstrated that CMV has the capacity to causally contribute to atherogenesis; acute infection of rats with rat CMV(RCMV) 1 day after carotid artery injury increased neointimal accumulation. Importantly, in the injured vessel infectious virus could not be detected and viral genome was present only transiently, suggesting that additional mechanisms play a role in the virus-induced exacerbation of the vascular injury response other than the changes caused by direct infection of vessel wall cells. The present investigation was designed to determine whether chronic persistent RCMV infection, more relevant to the clinical situation, also exacerbates the response to injury and, if so, whether similar mechanisms are operative. Methods: Sixty 3-week-old male Spraque-Dawley rats received an i.p. injection of either 10(6) TCID50 RCMV (Priscott strain) or normal saline. The left carotid artery was balloon-injured 3 months after infection. Rats were killed 6 weeks later. This model produces persistent infection, as demonstrated by presence of infectious virus in the salivary glands at time of sacrifice. Results: The neointima to media (N/M) ratio of the injured vessel was 41% greater in the RCMV-infected than in control rats (1.40+/-0.48 vs. 0.99+/-0.45; P=0.003). The aorta never contained infectious RCMV, and exhibited RCMV DNA, detected by PCR, only transiently. The persistent infection of non-vascular tissues was associated with increased serum levels of IL-2, IL-4 and IFN-gamma. Conclusions: CMV infection of young rats causes persistent infection of non-vascular tissues and increased cytokine levels. The neointimal response to subsequent vascular injury is increased, despite absence of virus from the vessel wall. These findings, as in acute infection following vascular injury, suggest that inflammatory and immune responses to chronic persistent CMV infection contribute to an exaggerated response to vascular injury. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Washington Hosp Ctr, Vasc Biol Lab, Cardiovasc Res Inst, Washington, DC 20010 USA. Univ Calif Los Angeles, Sch Med, Dept Cardiovasc Surg, Los Angeles, CA 90024 USA. NHLBI, Pathol Branch, NIH, Bethesda, MD 20895 USA. US FDA, Rockville, MD 20852 USA. RP Zhou, YF (reprint author), Washington Hosp Ctr, Vasc Biol Lab, Cardiovasc Res Inst, GHRB-217,108 Irving St, Washington, DC 20010 USA. NR 24 TC 15 Z9 18 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD MAR PY 2000 VL 45 IS 4 BP 1019 EP 1025 DI 10.1016/S0008-6363(99)00394-6 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 288MN UT WOS:000085566800025 PM 10728428 ER PT J AU Ribeiro, CMP McKay, RR Hosoki, E Bird, GS Putney, JW AF Ribeiro, CMP McKay, RR Hosoki, E Bird, GS Putney, JW TI Effects of elevated cytoplasmic calcium and protein kinase C on endoplasmic reticulum structure and function in HEK293 cells SO CELL CALCIUM LA English DT Article ID ENTRY AB In human embryonic kidney (HEK) cells stably transfected with green fluorescent protein targeted to the endoplasmic reticulum (ER), elevation of intracellular Ca2+ ([Ca2+](i)) altered ER morphology, making it appear punctate. Electron microscopy revealed that these punctate structures represented circular and branched rearrangements of the endoplasmic reticulum, but did not involve obvious swelling or pathological fragmentation. Activation of protein kinase C with phorbol 12-myristate 13-acetate (PMA), prevented the effects of ionomycin on ER structure without affecting the elevation of [Ca2+](i). These results suggest that protein kinase C activation alters cytoplasmic or ER components underlying the effects of high [Ca2+](i) on ER structure. Treatment of HEK cells with PMA also reduced the size of the thapsigargin-sensitive Ca2+ pool and inhibited Ca2+ entry in response to thapsigargin. Thus, protein kinase C activation has multiple actions on the calcium storage and signalling function of the endoplasmic reticulum in HEK cells: (1) reduced intracellular Ca2+ storage capacity, (2) inhibition of capacitative Ca2+ entry, and (3) protection of the endoplasmic reticulum against the effects of high [Ca2+](i). (C) 2000 Harcourt Publishers Ltd. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Putney, JW (reprint author), NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RI Ribeiro, Carla Maria/A-6955-2009 NR 11 TC 51 Z9 51 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 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD MAR PY 2000 VL 27 IS 3 BP 175 EP 185 DI 10.1054/ceca.2000.0108 PG 11 WC Cell Biology SC Cell Biology GA 304VG UT WOS:000086504400005 PM 11007130 ER PT J AU Giampietri, C Levrero, M Felici, A D'Alessio, A Capogrossi, MC Gaetano, C AF Giampietri, C Levrero, M Felici, A D'Alessio, A Capogrossi, MC Gaetano, C TI E1A stimulates FGF-2 release promoting differentiation of primary endothelial cells SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE angiogenesis; E1A; FGF-2; matrix metalloproteinase; endothelial cell; differentiation ID FIBROBLAST GROWTH-FACTOR; SECRETORY SIGNAL SEQUENCE; LARGE T-ANTIGEN; ADENOVIRUS E1A; TUMOR ANGIOGENESIS; MOLECULAR-CLONING; FACTOR RECEPTOR; DNA-SYNTHESIS; PROTEIN; GENE AB Basic Fibroblast Growth Factor (FGF-2) is a growth and survival factor and represents one of the most potent differentiation agents of vascular system, In the present study we describe that adenoviral oncoprotein E1A regulates FGF-2 production and determines the acquisition of a pro-angiogenic phenotype in primary bovine aortic endothelial cells (BAEC). Following their transfection, wild type E1A proteins 12S and 13S (wtE1A) stimulated BAEC to differentiate on reconstituted basement membrane matrix (Matrigel). This outcome was paralleled by invasion and migration enhancement in wtE1A-transfected cells. This stimulating effect was absent with the E1A mutant dl646N. Accordingly, zymography and RT - PCR analyses showed that matrix metalloproteinase-9 protein- and mRNA-levels increased following wtE1A transfection. Interestingly, wtE1A-transfected BAEC showed FGF-2mRNA-and protein-levels higher than controls. Further, FGF-2 neutralization reduced the amount of MMP-9 released in the supernatant of E1A-transfected cells and strongly inhibited BAEC differentiation, thus suggesting that wtE1A activates BAEC by a mechanism, at least partially, dependent on a FGF-2 autocrine/paracrine loop. C1 Ist Ricovero & Cura Caratiere Sci, Ist Dermopat Immacolata, Lab Patol Vascolare, I-00167 Rome, Italy. Univ Rome La Sapienza, Fdn Andrea Cesalpino, Lab Espress Gen, I-00161 Rome, Italy. Univ Cagliari, Ist Med Interna, I-09124 Cagliari, Italy. Univ Rome La Sapienza, Dipartimento Istol & Embriol Med, I-00161 Rome, Italy. NCI, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. RP Gaetano, C (reprint author), Ist Ricovero & Cura Caratiere Sci, Ist Dermopat Immacolata, Lab Patol Vascolare, Via Monti di Creta 104, I-00167 Rome, Italy. OI Gaetano, Carlo/0000-0002-5238-1832 NR 78 TC 9 Z9 10 U1 1 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD MAR PY 2000 VL 7 IS 3 BP 292 EP 301 DI 10.1038/sj.cdd.4400654 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 293KN UT WOS:000085850900006 PM 10745274 ER PT J AU Herrera, AH Elzey, B Law, DJ Horowits, R AF Herrera, AH Elzey, B Law, DJ Horowits, R TI Terminal regions of mouse nebulin: Sequence analysis and complementary localization with N-RAP SO CELL MOTILITY AND THE CYTOSKELETON LA English DT Article DE skeletal muscle; myotendinous junction; mouse ID SKELETAL-MUSCLE SARCOMERE; THIN-FILAMENTS; IMMUNOELECTRON MICROSCOPY; MONOCLONAL-ANTIBODIES; CONNECTIN TITIN; STRIATED-MUSCLE; ACTIN-FILAMENTS; POINTED ENDS; Z-LINE; PROTEIN AB The regions of mouse nebulin extending from the ends of the super repeats to the C-terminus and N-terminus were cloned and sequenced. Comparison of the mouse sequence with the previously published human sequence shows that the terminal regions of nebulin are highly conserved. The four phosphorylation motifs and SH3 domain found at the C-terminus of mouse nebulin are identical to those found in human nebulin, with the exception of four conservative substitutions. The modules linking this C-terminal region to the super repeats have deletions relative to both fetal and adult human nebulins that correspond to integral numbers of modules, making the mouse C-terminal simple repeat region among the shortest observed to date. The N-terminal region and the C-terminal modules were expressed in Escherichia coli and used for antibody production. Immunofluorescent labeling of these regions of nebulin in isolated myofibrils demonstrates that they are located near the center of the sarcomere and near the Z-line, respectively. Immunogold labeling with antibodies raised against the N-terminal nebulin sequence localizes this region in the A-band near the tips of the thin filaments. Nebulin localization is complementary to that of N-RAP, another muscle-specific protein containing nebulin-like super repeats; nebulin is exclusively found in the sarcomeres, while N-RAP is confined to the terminal bundles of actin filaments at the myotendinous junction. (dagger)Published 2000 Wiley-Liss, Inc. C1 NIAMSD, NIH, Phys Biol Lab, Bethesda, MD 20892 USA. Univ Missouri, Div Cell Biol & Biophys, Kansas City, MO 64110 USA. RP Horowits, R (reprint author), NIAMSD, NIH, Phys Biol Lab, Bldg 6,Room 408,MSC 2751, Bethesda, MD 20892 USA. NR 34 TC 20 Z9 20 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0886-1544 J9 CELL MOTIL CYTOSKEL JI Cell Motil. Cytoskeleton PD MAR PY 2000 VL 45 IS 3 BP 211 EP 222 DI 10.1002/(SICI)1097-0169(200003)45:3<211::AID-CM4>3.0.CO;2-Y PG 12 WC Cell Biology SC Cell Biology GA 290LP UT WOS:000085678000004 PM 10706776 ER PT J AU Dai, R Pincus, MR Friedman, FK AF Dai, R Pincus, MR Friedman, FK TI Molecular modeling of mammalian cytochrome P450s SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE cytochrome P450; molecular modeling; protein structure; drug metabolism ID SITE-DIRECTED MUTAGENESIS; PROTEIN SECONDARY STRUCTURE; CRYSTAL-STRUCTURE; ACTIVE-SITE; SUBSTRATE-SPECIFICITY; PHARMACOPHORE MODEL; MEMBRANE TOPOLOGY; MICROSOMAL P450S; DRUG-METABOLISM; AMINO-ACID AB The cytochrome P450s are a superfamily of hemoprotein enzymes responsible for the metabolism of a wide variety of xenobiotic and endogenous compounds. The individual P450s exhibit unique substrate specificity and stereoselectivity profiles which reflect corresponding differences in primary sequence and tertiary structure. In the absence of an experimental structure, models for mammalian P450s have been generated by their homology with bacterial P450s of known structure. The rather low sequence identity between target and template proteins renders P450 modeling a challenging task. However, the substrate recognition properties of several P450s are consistent with recently developed working models. This review summarizes the major concepts and current approaches of molecular modeling of P450s. C1 NCI, Mol Carcinogenesis Lab, Bethesda, MD 20892 USA. Vet Adm Med Ctr, Dept Pathol & Lab Med, Brooklyn, NY 11209 USA. SUNY Hlth Sci Ctr, Dept Pathol, New York, NY 11239 USA. RP Friedman, FK (reprint author), NCI, Mol Carcinogenesis Lab, Bldg 37 Room 3E-24, Bethesda, MD 20892 USA. RI Friedman, Fred/D-4208-2016 NR 63 TC 27 Z9 28 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 2000 VL 57 IS 3 BP 487 EP 499 DI 10.1007/PL00000709 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 308JZ UT WOS:000086708800013 PM 10823248 ER PT J AU London, ED Ernst, M Grant, S Bonson, K Weinstein, A AF London, ED Ernst, M Grant, S Bonson, K Weinstein, A TI Orbitofrontal cortex and human drug abuse: Functional imaging SO CEREBRAL CORTEX LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; CEREBRAL GLUCOSE-UTILIZATION; POSITRON EMISSION TOMOGRAPHY; MEDIAL PREFRONTAL CORTEX; OLD-WORLD MONKEY; HUMAN BRAIN; MACAQUE MONKEYS; RHESUS-MONKEY; COCAINE; CYTOARCHITECTURE AB The orbitofrontal cortex (OFC) plays a central role in human behavior. Anatomically connected with association areas of all sensory modalities, limbic structures. prefrontal cortical regions that mediate executive function and subcortical nuclei, this brain region can serve to integrate the physical and emotional attributes of a stimulus-object and establish a motivational value based on estimation of potential reward. To the extent that addictive disorders reflect a dysregulation of the ability to evaluate potential reward against harm from drug self-administration. it would be anticipated that substance abuse disorder might reflect dysfunction of the OFC. With the application of brain imaging techniques to the study of human substance abuse, evidence has been obtained that activity in the OFC and its connections plays a role in several components of the maladaptive behavior of substance abuse, including expectancy, craving and impaired decision making. C1 NIDA, Brain Imaging Ctr, Baltimore, MD 21224 USA. RP London, ED (reprint author), NIDA, Brain Imaging Ctr, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 59 TC 226 Z9 235 U1 5 U2 19 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD MAR PY 2000 VL 10 IS 3 BP 334 EP 342 DI 10.1093/cercor/10.3.334 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 293QZ UT WOS:000085865600013 PM 10731228 ER PT J AU Vollmer, WM Enright, PL Pedula, KL Speizer, F Kuller, LH Kiley, J Weinmann, GG AF Vollmer, WM Enright, PL Pedula, KL Speizer, F Kuller, LH Kiley, J Weinmann, GG TI Race and gender differences in the effects of smoking on lung function SO CHEST LA English DT Article DE gender; lung function; race; smoking ID FORCED EXPIRATORY VOLUME; PULMONARY-FUNCTION; RISK FACTOR; RESPIRATORY SYMPTOMS; VENTILATORY FUNCTION; CIGARETTE-SMOKING; REFERENCE VALUES; ONE 2ND; DECLINE; DISEASE AB Study objective: To assess the extent to which the relationship between smoking and lung function in adults varies by gender and race/ethnicity. Design: A random-effects metaregression analysis to synthesize results from common cross-sectional regression models fit to participants in each of 10 gender-race strata in each of eight large population-based observational studies or clinical trials. Setting: Source data collected as part of the most recently completed examination cycle for each of the participating studies. Participants: Participants ranged in age from 30 to 85 years, although the age, race, gender, and general health characteristics of each of the populations varied greatly, Interventions: Most of the studies were observational in nature, although some did involve lifestyle interventions. All treatment assignments were ignored in the analysis. Measurements and results: All studies measured lung function using standardized methods,vith centrally trained and certified technicians. Study findings confirm statistically significant, dose-related smoking effects in all race-gender groups studied. Significant gender differences in the effects of cigarette smoking were seen only for blacks; black men who smoked had greater smoking-related declines in FEV, than did black women. This effect was present in only one of two smoking models, however. Significant racial differences in the effects of smoking were seen only for men, with Asian/Pacific Islanders having smaller smoking-related declines than white men in both models. Conclusions: In summary, this analysis generally failed to support the hypothesis of widespread differences in the effects of cigarette smoking on lung function between gender or racial subgroups. C1 Ctr Hlth Res, Portland, OR 97227 USA. Univ Arizona, Resp Sci Ctr, Tucson, AZ USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Pittsburgh, Pittsburgh, PA USA. NHLBI, Div Lung Dis, NIH, Bethesda, MD 20892 USA. RP Vollmer, WM (reprint author), Ctr Hlth Res, 3800 N Kaiser Ctr Dr, Portland, OR 97227 USA. NR 37 TC 38 Z9 39 U1 0 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAR PY 2000 VL 117 IS 3 BP 764 EP 772 DI 10.1378/chest.117.3.764 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 293YZ UT WOS:000085884000027 PM 10713004 ER PT J AU Bornstein, MH Suess, PE AF Bornstein, MH Suess, PE TI Physiological self-regulation and information processing in infancy: Cardiac vagal tone and habituation SO CHILD DEVELOPMENT LA English DT Article ID INDIVIDUAL-DIFFERENCES; VISUAL HABITUATION; RECOGNITION MEMORY; LATER IQ; ATTENTION; PERFORMANCE; STABILITY; BEHAVIOR; PRETERM; SKILLS AB This study investigates the role of physiological self-regulation (cardiac vagal tone) in information processing (habituation) in 81 infants. Nucleus ambiguus vagal tone (V-na, a measure of respiratory sinus arrhythmia) was used to index cardiac vagal tone. Physiological self-regulation was operationalized as the change in V-na from a baseline period of measurement to habituation. Decreases in V-na consistently related to habituation efficiency, operationalized as accumulated looking time (ALT) in all infants twice at 2 months and twice at 5 months; however, this relation was accounted for by infants who met an habituation criterion on each task. Among habituators, shorter lookers also had greater V-na suppression during habituation. Within-age and between-age suppression of vagal tone predicted ALT, but ALT did not predict suppression of vagal tone. Physiological self-regulation provided by the vagal system appears to play a role in information processing in infancy as indexed by habituation. C1 NICHHD, Bethesda, MD 20892 USA. RP Bornstein, MH (reprint author), NICHHD, 6705 Rockledge Dr,Suite 8030, Bethesda, MD 20892 USA. NR 49 TC 71 Z9 71 U1 3 U2 17 PU BLACKWELL PUBLISHERS PI MALDEN PA 350 MAIN STREET, STE 6, MALDEN, MA 02148 USA SN 0009-3920 J9 CHILD DEV JI Child Dev. PD MAR-APR PY 2000 VL 71 IS 2 BP 273 EP 287 DI 10.1111/1467-8624.00143 PG 15 WC Psychology, Educational; Psychology, Developmental SC Psychology GA 307ZJ UT WOS:000086683800001 PM 10834463 ER PT J AU Wu, YY Hruszkewycz, AM Delgado, RM Yang, A Vortmeyer, AO Moon, YW Weil, RJ Zhuang, ZP Remaley, AT AF Wu, YY Hruszkewycz, AM Delgado, RM Yang, A Vortmeyer, AO Moon, YW Weil, RJ Zhuang, ZP Remaley, AT TI Limitations on the quantitative determination of telomerase activity by the electrophoretic and ELISA based TRAP assays SO CLINICA CHIMICA ACTA LA English DT Article DE telomere; ELISA; telomerase ID IMMORTAL CELLS; CANCER; EXPRESSION; TUMORS; DNA AB Telomerase is a promising new tumor marker and can be detected using the TRAP (Telomeric Repeat Amplification Protocol) method. To address factors affecting its quantitative determination, we evaluated two commercial TRAP assays, an electrophoretic and an ELISA assay formats, using cultured cells and human tumor samples. We found that both TRAP assays had a limited linearity from 250 to 5000 tumor cells, with a similar intra-assay variation. The quantification of TRAP products was affected by high cell number in sample, the presence of non-tumor cells, and interfering substances in patient specimens. Because both assays have different limitations, determination of telomerase by a combined use of the two may provide more accurate information on the telomerase activity in a specimen. Extracts of specimens should also be tested at several concentrations to insure that the result is not being falsely decreased by an inhibitor. The quantitative results for telomerase activity by the TRAP assays, however, should be interpreted cautiously. Published by Elsevier Science B.V. C1 CC NIH, Dept Clin Pathol, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Remaley, AT (reprint author), CC NIH, Dept Clin Pathol, Bldg 10,Room 2C 407, Bethesda, MD 20892 USA. NR 16 TC 57 Z9 59 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD MAR PY 2000 VL 293 IS 1-2 BP 199 EP 212 DI 10.1016/S0009-8981(99)00238-7 PG 14 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 292DU UT WOS:000085779500015 PM 10699434 ER PT J AU Wu, YY Delgado, R Costello, R Sunderland, T Dukoff, R Csako, G AF Wu, YY Delgado, R Costello, R Sunderland, T Dukoff, R Csako, G TI Quantitative assessment of apolipoprotein E genotypes by image analysis of PCR-RFLP fragments SO CLINICA CHIMICA ACTA LA English DT Article DE Alzheimer disease; Apolipoprotein E; electrophoresis; genotyping; polymerase chain reaction (PCR); restriction fragment length polymorphism (RFLP) ID POLYMERASE CHAIN-REACTION; RESTRICTION; AMPLIFICATION; POLYMORPHISM; DISEASE; BIOLOGY; ALLELE; RISK AB Apolipoprotein E (APOE) genotyping usually involves polymerase chain reaction (PCR) and assessment of restriction fragment length polymorphism (RFLP) by gel electrophoresis. We made determination of HhaI restriction endonuclease digestive patterns more objective and improved diagnostic accuracy with a quantitative approach using sensitive DNA stain (SYBR Green) and image analysis of gel patterns. For distinguishing true and partially-digested restriction fragments, band ratios were calculated for the staining intensity of gel patterns from 116 sample runs of 63 human blood specimens. Each of these specimens was independently genotyped for APOE by at least two (and most of them by three) different PCR-RFLP methods. Based on the distribution of band ratios, decision levels were established and used for developing a program for computer-aided interpretation of APOE genotypes (Microsoft Excel software). Appropriateness of the decision levels for band ratios was validated by APOE genotyping of additional 61 specimens. The approach described here is applicable to a variety of other molecular diagnostic techniques that are based on PCR-RFLP or sequence-specific signal amplifications. Published by Elsevier Science B.V. C1 Warren G Magnuson Clin Ctr, Dept Clin Pathol, NIH, Bethesda, MD 20892 USA. NIMH, Geriatr Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP Csako, G (reprint author), Warren G Magnuson Clin Ctr, Dept Clin Pathol, NIH, Bethesda, MD 20892 USA. NR 21 TC 13 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD MAR PY 2000 VL 293 IS 1-2 BP 213 EP 221 DI 10.1016/S0009-8981(99)00237-5 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 292DU UT WOS:000085779500016 PM 10699435 ER PT J AU Park, SH Gray, WC Hernandez, I Jacobs, M Ord, RA Sutharalingam, M Smith, RG Van Echo, DA Wu, SL Conley, BA AF Park, SH Gray, WC Hernandez, I Jacobs, M Ord, RA Sutharalingam, M Smith, RG Van Echo, DA Wu, SL Conley, BA TI Phase I trial of all-trans retinoic acid in patients with treated head and neck squamous carcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; CELL CARCINOMA; CANCER; PHARMACOKINETICS; CHEMOPREVENTION; ISOTRETINOIN; TUMORS AB Although retinoids show promise for prevention of second primary upper aerodigestive tract tumors, the optimum retinoid, dose, and schedule are unknown, All-trans retinoic acid (ATRA) has greater affinity for retinoic acid receptors and may be more active than other retinoids but has a shorter plasma half life and may up-regulate its own metabolism, We defined the maximum long-term tolerable dose, dosing frequency, pharmacokinetics, and toxicity of ATRA in patients with treated squamous cell carcinoma of the head and neck (SCCHN), Twenty-one patients were randomized to 45, 90, or 150 mg/m(2) ATRA either once daily, or as divided doses every 8 h, for 1 year. Pharmacokinetics were assessed periodically, Fourteen men and seven women with previous SCCHN of initial stage I-IV were treated. Grade greater than or equal to 3 toxicities (reversible) included headache and hypertriglyceridemia in 5 and 6 patients each, mucositis in 2 patients, and hyperbilirubinemia, elevated alkaline phosphatase, colitis, lipasemia, xerostomia, eczema, and arthritis in 1 patient each, The 150-mg/m(2) dose was not tolerable. Doses were reduced for grade greater than or equal to 3 toxicity in seven of eight patients at 90 mg/m2 daily. Three of nine patients at 45 mg/m(2)/day required dose reduction, two at the once-daily dose. Day 1 ATRA area under the plasma concentration versus time curve (AUC) increased with dose, and after 1-2 months of continued dosing, the AUC declined in 7 of 13 patients (54%) studied. ATRA AUC did not correlate with toxicity severity or frequency. Fifteen mg/m2/day every 8 h is a tolerable dose for 1 year in patients with treated SCCHN, ATRA pharmacokinetics did not correlate with toxicity. C1 Univ Maryland, Sch Med, Dept Med, Div Hematol Oncol, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Radiat Oncol, Baltimore, MD 21201 USA. Univ Maryland, Sch Dent, Program Oncol, Baltimore, MD 21201 USA. Univ Maryland, Sch Dent, Div Dev Therapeut, Program Oncol, Baltimore, MD 21201 USA. Univ Maryland, Sch Dent, Dept Oral & Maxillofacial Surg, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Surg, Div Otolaryngol Head & Neck Surg, Baltimore, MD 21201 USA. Baltimore Vet Adm Med Ctr, Dept Med, Div Hematol Oncol, Baltimore, MD 21201 USA. RP Conley, BA (reprint author), NCI, Canc Diag Program, Diagnost Res Branch, Room 700,Execut Plaza N,6130 Execut Blvd, Rockville, MD 20852 USA. EM conleyb@mail.nih.gov FU NCI NIH HHS [U-01-CA-69854] NR 19 TC 21 Z9 21 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR PY 2000 VL 6 IS 3 BP 847 EP 854 PG 8 WC Oncology SC Oncology GA 294KF UT WOS:000085909900014 PM 10741706 ER PT J AU Eura, M Chikamatsu, K Katsura, F Obata, A Sobao, Y Takiguchi, M Song, YS Appella, E Whiteside, TL DeLeo, AB AF Eura, M Chikamatsu, K Katsura, F Obata, A Sobao, Y Takiguchi, M Song, YS Appella, E Whiteside, TL DeLeo, AB TI A wild-type sequence p53 peptide presented by HLA-A24 induces cytotoxic T lymphocytes that recognize squamous cell carcinomas of the head and neck SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR-ANTIGENS; IDENTIFICATION; MUTANT; GENERATION; PROTEASOME; MOLECULES; EPITOPES; PROTEINS; ALLELES AB Evidence has accumulated indicating that HLA-A2-restricted CTLs specific for human wild-type sequence p53 epitopes lyse tumor cells expressing mutant p53, To explore the possibility that wild-type sequence p53 peptides could also be used in vaccines for patients expressing HLA-A24 antigen, another frequent HLA class I allele, we investigated the induction of RLA-A24-restricted p53-specific CTLs from the peripheral blood lymphocytes of normal donors. Of six p53-derived peptides possessing an HLA-A24 binding moth, the p53 peptide 125-134 (p53(125-134)) was found to have a high binding capacity and induced peptide-specific CTLs from peripheral blood mononuclear cells, using peptide-pulsed autologous dendritic cells and subsequent cultivation with cytokines interleukin 2 and interleukin 7, Bulk CTL populations lysed peptide-pulsed HLA-A24(+) targets as well as HLA-A24(+) squamous cell carcinoma of the head and neck (SCCHN) cell lines, However, IFN-gamma pretreatment of HLA-A24(+) SCCHN cell lines was necessary for lysis, suggesting that a ligand density higher than that normally expressed by tumor cells is required for these CTLs to mediate lysis, Moreover, a cloned CTL, designated TH#99, isolated from the bulk population by limiting dilution, lysed HLA-A24(+) SCCHN targets more efficiently than the bulk CTL population, Lysis was inhibited by anti-HLA class I monoclonal antibody but not by anti-HLA-DR monoclonal antibody. These results indicate that HLA-A24-restricted CTLs recognizing the wild-type sequence p53(125-134) can be generated using autologous dendritic cells from precursors present in peripheral blood lymphocytes obtained from normal HLA-A24(+) donors. This finding suggests that vaccine strategies targeting wild-type sequence p53 epitopes can be extended to a wider range of cancer patients. C1 Kumamoto Univ, Sch Med, Dept Otolaryngol, Kumamoto 8608556, Japan. Kumamoto Univ, Sch Med, Div Viral Immunol, Kumamoto 8608556, Japan. Kumamoto Univ, Sch Med, AIDS Res Ctr, Kumamoto 8608556, Japan. NCI, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Inst Canc, Div Basic Res, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Otolaryngol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15213 USA. RP Eura, M (reprint author), Kumamoto Univ, Sch Med, Dept Otolaryngol, 1-1-1 Honjo, Kumamoto 8608556, Japan. RI Takiguchi, Masafumi/E-7468-2013 NR 37 TC 36 Z9 36 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 2000 VL 6 IS 3 BP 979 EP 986 PG 8 WC Oncology SC Oncology GA 294KF UT WOS:000085909900032 PM 10741724 ER PT J AU Shin, JA Kim, SH Kim, UK Chae, JJ Choe, SJ Namkoong, Y Kim, HS Park, YB Lee, CC AF Shin, JA Kim, SH Kim, UK Chae, JJ Choe, SJ Namkoong, Y Kim, HS Park, YB Lee, CC TI Identification of four novel mutations of the low-density lipoprotein receptor gene in Korean patients with familial hypercholesterolemia SO CLINICAL GENETICS LA English DT Article DE familial hypercholesterolemia; low-density lipoprotein receptor gene; point mutation; single-strand conformation polymorphism ID LDL-RECEPTOR; MOLECULAR-GENETICS; POPULATION; SEQUENCE; PROTEIN; SITE; DNA AB To obtain insight into the genetic variation of the low-density lipoprotein (LDL) receptor gene in Korean patients with familial hypercholesterolemia (FH), we used single-strand conformation polymorphism to screen all 18 exons and a promotor of the LDL receptor gene in 20 unrelated Korean FH patients. Four novel point mutations were detected in 5 FH patients and were characterized by sequence analysis. Of them, one is a nonsense mutation, a Glu --> Stop (CAG --> TAG) at codon 161, and results in a large deletion. The other three, which were a Ala --> Glu (GCG --> GAG) mutation at signal peptide, Cys --> Tyr (TGC --> TAC) at codon 210, and Pro --> Leu (CTG --> CCG) at codon 584, were novel missense mutations, which modified the highly conserved region of the LDL receptor gene. All these mutations were absent in normolipidemic controls and were associated in heterozygote carriers with clinical signs of FH. Identification of these novel mutations provides another example of the molecular heterogeneity of the LDL receptor gene mutations causing FH. C1 Seoul Natl Univ, Dept Mol Biol, Seoul, South Korea. Seoul Natl Univ, Dept Biol, Seoul, South Korea. Seoul Natl Univ, SRC Cell Differentiat, Seoul, South Korea. NIAMSD, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea. Kangnung Natl Univ, Dept Biol, Kangnung, South Korea. RP Lee, CC (reprint author), Seoul Natl Univ, Coll Nat Sci, Dept Biol, Seoul 151742, South Korea. NR 21 TC 6 Z9 8 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD MAR PY 2000 VL 57 IS 3 BP 225 EP 229 DI 10.1034/j.1399-0004.2000.570309.x PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 299TA UT WOS:000086212900011 PM 10782930 ER PT J AU Fukui, M Whittlesey, K Metcalfe, DD Dastych, J AF Fukui, M Whittlesey, K Metcalfe, DD Dastych, J TI Human mast cells express the hyaluronic-acid-binding isoform of CD44 and adhere to hyaluronic acid SO CLINICAL IMMUNOLOGY LA English DT Article DE mast cell; CD44; hyaluronic acid ID FUNCTIONAL-CHARACTERIZATION; VARIANT ISOFORMS; RECEPTOR CD44; SERUM LEVELS; HUMAN SKIN; METASTASIS; ANTIBODIES; CANCER; FORMS; MECHANISM AB CD44 is expressed in various isoforms on multiple cell lineages including those of hematopoietic origin and is believed in part to mediate cell adhesion to hyaluronic acid. Elevated levels of soluble CD44 (sCD44) have been identified in the serum of some patients with specific neoplasms. We thus sought to determine whether human mast cells express functional CD44 and whether sCD44 might be associated with systemic mast cell disease. Using a standard assay, CD34(+)-derived cultured human mast cells were first demonstrated to adhere to hyaluronic-acid-coated surfaces. Human mast cells were then found by flow cytometry to express CD44S, but not the v5, v6, v7, and v8 isoforms, and to shed CD44S following activation induced by PMA or aggregation of Fc epsilon RI. However, CD44S was not found to be consistently elevated in serum obtained from patients with mastocytosis or individuals experiencing anaphylaxis, Thus, human cultured mast cells express and shed CD44S, which appears to mediate the attachment of these cells to hyaluronic acid. (C) 2000 Academic Press. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. Int Inst Mol & Cell Biol, Lab Mol Immunol, Warsaw, Poland. RP Fukui, M (reprint author), NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NR 36 TC 16 Z9 16 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 2000 VL 94 IS 3 BP 173 EP 178 DI 10.1006/clim.1999.4830 PG 6 WC Immunology SC Immunology GA 294TW UT WOS:000085927300003 PM 10692236 ER PT J AU Marra, CM Boutin, P McArthur, JC Hurwitz, S Simpson, G Haslett, PAJ van der Horst, C Nevin, T Hook, EW AF Marra, CM Boutin, P McArthur, JC Hurwitz, S Simpson, G Haslett, PAJ van der Horst, C Nevin, T Hook, EW CA AIDS Clin Trials Grp 145 Team TI A pilot study evaluating ceftriaxone and penicillin G as treatment agents for neurosyphilis in human immunodeficiency virus-infected individuals SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 51st Annual Meeting of the American-Academy-of-Neurology CY APR 17-24, 1999 CL TORONTO, CANADA SP Amer Acad Neurol ID SYPHILIS; THERAPY; TYPE-1; SERUM AB To compare intravenous (iv) ceftriaxone and penicillin G as therapy for neurosyphilis, blood and CSF were collected before and 14-26 weeks after therapy from 30 subjects infected with human immunodeficiency virus (HIV)-1 who had (1) rapid plasma reagin (RPR) test titers greater than or equal to 1:16, (2) reactive serum treponemal tests, and (3) either reactive CSF-Venereal Disease Research Laboratory (VDRL) tests or; CSF abnormalities: (a) CSF WBC values greater than or equal to 20/mu L or (b) CSF protein values greater than or equal to 50 mg/dL. At baseline, more ceftriaxone recipients had skin symptoms and signs (6 [43%] of 14 vs. 1 [6%] of 16; P = .03), and more penicillin recipients had a history of neurosyphilis (7 [44%] of 16 vs. 1 [7%] of 14; P = .04), There was no difference in the proportion of subjects in each group whose CSF measures improved. Significantly more ceftriaxone recipients had a decline in serum RPR titers (8 [80%] of 10 vs. 2 [13%] of 15; P = .003), even after controlling for baseline RPR titer, skin symptoms and signs, or prior neurosyphilis were controlled for, Differences in the 2 groups limit comparisons between them. However, iv ceftriaxone may be an alternative to penicillin for treatment of HIV-infected patients with neurosyphilis and concomitant early syphilis. C1 Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Div Infect Dis, Seattle, WA 98195 USA. Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harbor UCLA Med Ctr, Dept Med, Los Angeles, CA USA. NYU, Dept Med, New York, NY 10016 USA. Univ N Carolina, Dept Med, Div Infect Dis, Chapel Hill, NC 27515 USA. NIAID, Adult ACTG Operat Ctr, Bethesda, MD 20892 USA. Univ Alabama, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA. RP Marra, CM (reprint author), Univ Washington, Harborview Med Ctr, Dept Neurol, 325 9Th Ave,Box 359775, Seattle, WA 98104 USA. FU NIAID NIH HHS [AI27664]; NINDS NIH HHS [NS34235] NR 19 TC 64 Z9 74 U1 0 U2 3 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 2000 VL 30 IS 3 BP 540 EP 544 DI 10.1086/313725 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 302BR UT WOS:000086345500026 PM 10722441 ER PT J AU Handa, A Jubran, RF Dickstein, B Boylan, A Luban, NLC Young, NS Brown, KE AF Handa, A Jubran, RF Dickstein, B Boylan, A Luban, NLC Young, NS Brown, KE TI GB virus C/Hepatitis G virus infection is frequent in American children and young adults SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HEPATITIS-G-VIRUS; BLOOD-DONORS; C-VIRUS; PREVALENCE; TRANSMISSION; DISEASE; AGENT AB The novel flavivirus GB virus C/hepatitis G virus (GBV-C/HGV) has been detected in similar to\2% of blood donors in the United States, and neutralizing antibody to the envelope protein (E2), a marker of previous infection with GBV-C/HGV, is present in similar to 9% of donors, The rate of GBV-C/HGV infection among American children is unknown. To determine whether viral infection might occur during childhood, 160 serum specimens (obtained from blood bank samples) from children and young adults with no history of transfusion were tested. Viral RNA and antibody to E2 were detected in 6.3% and 9.4% of subjects, respectively. Evidence of previous or current infection (viremia and/or antibody to E2) was detected in 13.8% of subjects, indicating that GBV-C/HGV infection appears to be common among American children and young adults, even in the absence of blood transfusion. C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Hematol Oncol, Washington, DC 20010 USA. Childrens Natl Med Ctr, Dept Lab Med, Washington, DC 20010 USA. RP Handa, A (reprint author), NIH, Bldg 10,Room 7C218,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 18 TC 9 Z9 10 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 2000 VL 30 IS 3 BP 569 EP 571 DI 10.1086/313702 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 302BR UT WOS:000086345500029 PM 10722444 ER PT J AU Pinn, VW AF Pinn, VW TI Agenda for women's health research - Improving women's musculoskeletal health SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article AB Increased attention and resources focused on women's health during the past decade have resulted in new offices, policies, and programs of the Federal government. The Office of Research on Women's Health, established by the National Institutes of Health in 1990, is a focal point for all National Institutes of Health-supported efforts to improve women's health through biomedical and behavioral research. The Office of Research on Women's Health ensures women's appropriate inclusion in research studies supported by the National Institutes of Health. Through the development of a comprehensive agenda for research on women's health, the Office of Research on Women's Health encourages the consideration of gender issues and gender differences in health and disease in research sponsored by the National Institutes of Health. The importance of research to study and improve women's musculoskeletal health has become increasingly recognized. Clinicians, researchers, and representatives of professional and advocacy organizations concerned with women's musculoskeletal health participated in the development of the initial research agenda on women's health in 1991 and participated in the meetings to update and revise the agenda in 1996 and 1997, As a result of meetings convened to review and revise the agenda on women's health for the twenty-first century, many recommendations for additional research on women's musculoskeletal health have been developed and now are being implemented across the National Institutes of Health. C1 Off Res Womens Hlth, NIH, Bethesda, MD 20892 USA. RP Pinn, VW (reprint author), Off Res Womens Hlth, NIH, 1 Ctr Dr,Bldg 1,Room 201, Bethesda, MD 20892 USA. NR 19 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD MAR PY 2000 IS 372 BP 9 EP 16 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 293QK UT WOS:000085864200003 PM 10738410 ER PT J AU Spyker, DA Harvey, ED Harvey, BE Harvey, AM Rumack, BH Peck, CC Atkinson, AJ Woosley, RL Abernethy, DR Cantilena, LR AF Spyker, DA Harvey, ED Harvey, BE Harvey, AM Rumack, BH Peck, CC Atkinson, AJ Woosley, RL Abernethy, DR Cantilena, LR TI Assessment and reporting of clinical pharmacology information in drug labeling - Commentary SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material C1 Purdue Pharma LP, Norwalk, CT 06850 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Rocky Mt Poison & Drug Ctr, Denver, CO USA. Georgetown Univ, Washington, DC USA. NIH, Ctr Clin, Bethesda, MD USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Spyker, DA (reprint author), Purdue Pharma LP, 100 Connecticut Ave, Norwalk, CT 06850 USA. NR 3 TC 16 Z9 16 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 2000 VL 67 IS 3 BP 196 EP 200 DI 10.1067/mcp.2000.104737 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 296LT UT WOS:000086026400002 PM 10741621 ER PT J AU Kavcic, V Krar, FJ Doty, RW AF Kavcic, V Krar, FJ Doty, RW TI Temporal cost of switching between kinds of visual stimuli in a memory task SO COGNITIVE BRAIN RESEARCH LA English DT Article DE human memory; visual stimuli; switching; asymmetry; reaction time; inertia ID RECOGNITION; PERFORMANCE AB These experiments measured the extra time required to respond when the type of stimulus was changed from one trial to the next. Heretofore, switching costs have been measured for a change in task, but we wished to isolate the cost of changing the sensorial component per se and its necessary analytical processing, as distinct from changing the question being posed or the type of response to be given. Thus, the task was identical throughout the experiments: continuous recognition in a single, 240-trial session, in which the subject was required to distinguish initial from repeat appearances of a stimulus, the single repetition of each stimulus occurring after 1-31 intervening trials. There were two categories of 200-ms stimuli, linguistic (words and non-words) and images (multiple-colored or gray scale panels, human faces, or butterflies); and two conditions of switching, predictable (alternating on each trial) or unpredictable, in which the switch occurred after three to eight trials of one kind. In the majority of cases, there was a robust switching cost, from 24 to 92 ms. The similarity of costs in the predictable and unpredictable modes suggests that this cost is derived at least as much from terminating the modus operandi for the preceding type of stimulus as from a reconfiguration of processing for the new type of stimulus. In the switch between words and images, the costs were "paradoxical" (asymmetrical), in that the switching from an image to a word was more costly than the reverse, that is, changing from the more to the less difficult required the greater time. This, too, is compatible with the idea that termination of the previous mode of processing is a major component of the cost. Thus, in contemplating the neuronal/cognitive events underlying visual memory, consideration must be given to the inertia of pre-existing linkages. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ Rochester, Sch Med & Dent, Dept Neurobiol & Anat, Med Ctr, Rochester, NY 14642 USA. NIMH, NIH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Doty, RW (reprint author), Univ Rochester, Sch Med & Dent, Dept Neurobiol & Anat, Med Ctr, Box 603, Rochester, NY 14642 USA. NR 13 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0926-6410 J9 COGNITIVE BRAIN RES JI Cognit. Brain Res. PD MAR PY 2000 VL 9 IS 2 BP 199 EP 203 DI 10.1016/S0926-6410(99)00059-2 PG 5 WC Computer Science, Artificial Intelligence; Neurosciences; Neuroimaging SC Computer Science; Neurosciences & Neurology GA 299JR UT WOS:000086195800009 ER PT J AU Magruder, KM Calderone, GE AF Magruder, KM Calderone, GE TI Public health consequences of different thresholds for the diagnosis of mental disorders SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID NATIONAL-COMORBIDITY-SURVEY; UNITED-STATES; DEPRESSION; PREVALENCE AB The acceptance of subthreshold disorders in psychiatry is a controversial topic with multiple implications for public health policy. Using subthreshold depression as an example, we provide documentation based on data from epidemiologic and clinical studies suggesting that subthreshold conditions are not uncommon, there is significant associated disability (with significant societal costs), and the course of illness often leads to the development of the full-blown disorder, The potential societal benefits of developing and testing low-cost, low-risk, and nontraditional treatments are considered. The recommendations are to match treatment intensity and cost with severity level in a staged approach. Copyright (C) 2000 by W.B. Saunders Company. C1 Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. NIMH, Rockville, MD 20857 USA. RP Magruder, KM (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 67 President St,PO 250861, Charleston, SC 29425 USA. NR 6 TC 34 Z9 35 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 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD MAR-APR PY 2000 VL 41 IS 2 SU 1 BP 14 EP 18 DI 10.1016/S0010-440X(00)80003-6 PG 5 WC Psychiatry SC Psychiatry GA 293LT UT WOS:000085853800003 PM 10746899 ER PT J AU Fekete, JM Norcross, JL Newman, JD AF Fekete, JM Norcross, JL Newman, JD TI Artificial turf foraging boards as environmental enrichment for pair-housed female squirrel monkeys SO CONTEMPORARY TOPICS IN LABORATORY ANIMAL SCIENCE LA English DT Article ID NONHUMAN-PRIMATES; RHESUS-MONKEYS; BEHAVIOR; DEVICE AB We investigated the use of artificial turf foraging boards to determine if providing captive squirrel monkeys an opportunity for semi-natural foraging behavior would 1) alter the monkeys' time budget to better approximate that seen in wild populations, 2) reduce the stereotypic, self-injurious, and aggressive behavior occasionally seen in captive squirrel monkeys, and 3)provide sustained enrichment. Five groups of pair-housed female squirrel monkeys were videotaped the week prior to, the week following, and for 2 weeks during the enrichment phase, when treat-enhanced boards were provided for 2 h daily, During the first 30 min of daily enrichment, inactivity declined 35.3%, locomotion increased 3.8%, and board-related behaviors occupied 36.3% of the activity budget; these changes were not evident after 1.5 h, Stereotypic behavior (pacing, headswinging, tailchewing) and aggression were not altered by the foraging opportunity, The foraging board retained the interest of the subjects across 2 weeks in the same daily pattern. Use of the foraging board altered the squirrel monkeys' time budget to become more like activity patterns seen in wild populations. C1 NICHHD, Comparat Ethol Lab, Poolesville, MD 20837 USA. RP Fekete, JM (reprint author), NICHHD, Comparat Ethol Lab, POB 529, Poolesville, MD 20837 USA. NR 34 TC 8 Z9 8 U1 0 U2 8 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1060-0558 J9 CONTEMP TOP LAB ANIM JI Contemp. Top. Lab. Anim. Sci. PD MAR PY 2000 VL 39 IS 2 BP 22 EP 26 PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 304CC UT WOS:000086464200004 PM 11487235 ER PT J AU Chen, PH Miller, GF Powell, DA AF Chen, PH Miller, GF Powell, DA TI Colitis in a female tamarin (Saguinus mystax) SO CONTEMPORARY TOPICS IN LABORATORY ANIMAL SCIENCE LA English DT Article AB An adult wild-caught female tamarin (Saguinus mystax) housed in a biomedical research facility was found moribund and extremely dehydrated, with severe diarrhea. She initially responded to supportive therapy but died 3 days later. Necropsy findings included hyperemia of the colonic mucosa, mesenteric lymphadenopathy, acanthocephalid parasites (Prosthenorchis elegans) embedded in the mucosa of the terminal ileum and cecum, and free filarid nematodes (Dipetalonema sp,) in the abdominal cavity, Campylobacter sp, was recovered from the colon, With the exception of changes associated with the parasites, significant histologic changes were limited to the colon. Changes consistent with acute enteric viral infection were found against a background of chronic inflammation. Enterocytes were variably hypertrophied, degenerate, and attenuated. Numerous epithelial syncytial cells were present, and some affected cells (uni- as well as multinucleated) contained intranuclear inclusions. Lymphoid follicles were mildly depleted and contained rare syncytia, Measles (Morbillivirus) infection was confirmed by using immunohistochemistry, reverse transcriptase polymerase chain reaction, and Southern blot analysis. In contrast to the cutaneous rash, respiratory involvement, and low mortality characteristic of Old World monkeys with measles, severe diarrhea with high mortality occurs in New World monkeys with this disease, In addition, our case differs from previous reports of measles in New World monkeys in that syncytial cell formation apparently was limited to the colon of our animal. C1 NIH, Vet Resources Program, Off Director, Bethesda, MD 20892 USA. RP Chen, PH (reprint author), NIH, Vet Resources Program, Off Director, Bldg 10, Bethesda, MD 20892 USA. NR 11 TC 6 Z9 6 U1 0 U2 2 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1060-0558 J9 CONTEMP TOP LAB ANIM JI Contemp. Top. Lab. Anim. Sci. PD MAR PY 2000 VL 39 IS 2 BP 47 EP 49 PG 3 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 304CC UT WOS:000086464200010 PM 11487241 ER PT J AU Slonim, AD Patel, KM Ruttimann, UE Pollack, MM AF Slonim, AD Patel, KM Ruttimann, UE Pollack, MM TI The impact of prematurity: A perspective of pediatric intensive care units SO CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the Pediatric-Academic-Societies CY MAY 02-06, 1997 CL WASHINGTON, D.C. SP Pediat Acad Soc DE outcomes; prematurity; resource utilization; pediatric intensive care unit; cost; consumption; PRISM III; severity of illness; neonatology; gestational age ID LOW-BIRTH-WEIGHT; BRONCHOPULMONARY DYSPLASIA; INFANTS; AGE; MORTALITY; HEALTH; MORBIDITY; CHILDREN; BORN AB Objective: To evaluate the relative resource use of pediatric intensive care unit (PICU) patients who had been born prematurely. Design: Nonconcurrent cohort study. Setting: Consecutive admissions to 16 voluntary PICUs, Patients: A total of 431 formerly premature patients (FPP) and 5,319 nonpremature patients. Interventions: None Methods: Patients with a history of prematurity and a prematurity-related complication or an anatomical deformity were compared for demographic and resource requirements to a group of nonpremature patients by a bivariable logistic regression analysis that controlled for age as a co-morbid factor. Results: Compared with other patients, FPP were younger (34.9 +/- 2.2 months vs. 72.4 +/- 1.0 months; p < .001), readmitted to the PICU more often during the same hospitalization (11.1% vs. 5.5%; p < .001), used more chronic technologies (ventilators, gastrostomy tubes, tracheostomy tubes, and parenteral nutrition; 30.3% vs. 5.6%; p < .001), and had longer lengths of stay (5.98 +/- 0.59 days vs. 3.56 +/- 0.12 days; p = .004). FPP had significantly higher use of ventilators (45.5% vs. 35.0%; p < .007) and lower use of arterial catheters (27.8% vs. 35.9%, p = .006) and central venous catheters (16.9% vs. 20.9%, p = .026) than nonprematures. The need for other PICU resources, including vasopressors, were similar. Conclusions: FPP used more chronic and acute care resources than patients who were not prematurely born. Continued improvements in neonatal care will influence change in many aspects of the health care system. This will also affect the delivery of care to the current patient base of the PICU. C1 Warren G Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. NIAID, NIH, Washington, DC USA. George Washington Univ, Sch Med, Dept Pediat, Washington, DC 20052 USA. George Washington Univ, Sch Med, Dept Anesthesiol, Washington, DC 20052 USA. Childrens Natl Med Ctr, Childrens Res Inst, Dept Crit Care Med, Washington, DC 20010 USA. Childrens Natl Med Ctr, Childrens Res Inst, Ctr Hlth Serv & Clin Res, Washington, DC 20010 USA. RP Slonim, AD (reprint author), Warren G Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. NR 22 TC 12 Z9 12 U1 0 U2 1 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 2000 VL 28 IS 3 BP 848 EP 853 DI 10.1097/00003246-200003000-00040 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 296XF UT WOS:000086051500040 PM 10752841 ER PT J AU Slonim, AD Ognibene, FP AF Slonim, AD Ognibene, FP TI Sedation of children by adult intensivists - Reply SO CRITICAL CARE MEDICINE LA English DT Letter ID PEDIATRIC PROCEDURES; KETAMINE; MIDAZOLAM C1 NIH, Bethesda, MD 20892 USA. RP Slonim, AD (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 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 2000 VL 28 IS 3 BP 910 EP 910 DI 10.1097/00003246-200003000-00069 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 296XF UT WOS:000086051500069 ER PT J AU Balow, JE Austin, HA AF Balow, JE Austin, HA TI Progress in the treatment of proliferative lupus nephritis SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review ID STEM-CELL TRANSPLANTATION; AUTOIMMUNE-DISEASE; MYCOPHENOLATE MOFETIL; CONTROLLED TRIAL; MURINE LUPUS; CD40 LIGAND; T-CELLS; CYCLOPHOSPHAMIDE THERAPY; PULSE CYCLOPHOSPHAMIDE; GLOMERULAR-DISEASE AB Lupus nephritis is often well developed at the time of diagnosis. High-dose corticosteroids are universally accepted as the initial approach to the control of severe inflammation in the kidney. Long-term disease control and the minimization of iatrogenic risk usually require adjunctive therapies that target the more fundamental immunoregulatory disturbances of lymphoid cells. Of the available cytotoxic drugs, cyclophosphamide is currently among the most effective, although it cannot be considered ideal in terms of efficacy or toxicity. New prospects for the treatment of proliferative lupus nephritis include novel immunosuppressive agents (e,g, mycophenolate, cyclosporine, fludarabine), combination chemotherapy (e.g. cyclophosphamide plus fludarabine), and sequential chemotherapy (e.g, cyclophosphamide-azathioprine), immunological reconstitution using intensive cytoreductive chemotherapy (with or without stem cell rescue), co-stimulatory molecule inhibition (e.g. humanized anti-CD154 monoclonal antibody, CTLA4-Ig). Gene therapy remains an attractive prospect, but its feasibility clearly depends on the further definition of lupus-promoting genes and the availability of methods to establish stable expression of disease-corrective genes in the appropriate lymphoid cells. Curr Opin Nephrol Hypertens 9:107-115. (C) 2000 Lippincott Williams & Wilkins. C1 NIDDK, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. RP Balow, JE (reprint author), NIDDK, Kidney Dis Sect, NIH, Bldg 10,Room 9N-222, Bethesda, MD 20892 USA. NR 83 TC 16 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD MAR PY 2000 VL 9 IS 2 BP 107 EP 115 DI 10.1097/00041552-200003000-00003 PG 9 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 289PD UT WOS:000085630400003 PM 10757214 ER PT J AU Kimmel, PL AF Kimmel, PL TI The nephropathies of HIV infection: pathogenesis and treatment SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; THROMBOTIC MICROANGIOPATHY; TRANSGENIC MICE; EXPRESSION; PROGNOSIS; APOPTOSIS; KIDNEY; CELLS AB Several different renal syndromes have been reported in patients with HIV infection. Patient characteristics and a syndrome approach may help the clinician formulate a tentative diagnosis, but a renal biopsy is necessary to make a firm diagnosis in patients with chronic renal disease in the setting of HIV infection. The pathogenesis of the HIV nephropathies can teach us much about the pathophysiology of common renal problems such as IgA nephropathy, immune complex glomerulonephritis, focal segmental glomerulosclerosis, and diabetic renal disease. HIV-associated renal disease may be the result of the interaction of the expression of specific HIV genes in patients with distinct genetic susceptibilities to disease in particular environments. New treatment approaches have provided hope for patients with classic HIV-associated nephropathy. Curr Opin Nephrol Hypertens 9:117-122. (C) 2000 Lippincott Williams & Wilkins. C1 George Washington Univ, Med Ctr, Dept Med, Div Renal Dis & Hypertens, Washington, DC 20037 USA. NIDDKD, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. RP Kimmel, PL (reprint author), George Washington Univ, Med Ctr, Dept Med, Div Renal Dis & Hypertens, 2150 Penn Ave NW, Washington, DC 20037 USA. NR 34 TC 27 Z9 28 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD MAR PY 2000 VL 9 IS 2 BP 117 EP 122 DI 10.1097/00041552-200003000-00004 PG 6 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 289PD UT WOS:000085630400004 PM 10757215 ER PT J AU Fenton, WS AF Fenton, WS TI Community interventions SO CURRENT OPINION IN PSYCHIATRY LA English DT Article ID MENTAL-HEALTH-SERVICES; CASE-MANAGEMENT; SCHIZOPHRENIA; CARE; THERAPY; GUIDELINES; DEPRESSION; DISORDERS; ILLNESS; AGENCY AB Once confined to institutions, most patients with severe mental illness are now treated in the community. Intervention research has provided rigorous demonstration of the effectiveness of targeted psychosocial treatment and support strategies to address problems including substance abuse, homelessness, unemployment, and medication non-compliance. Regrettably, routine care is influenced little by effective treatments developed in the laboratory. Curr Opin Psychiatry 13:189-194. (C) 2000 Lippincott Williams & Wilkins. C1 NIMH, Div Mental Disorders Behav Res & AIDS, Bethesda, MD 20892 USA. RP Fenton, WS (reprint author), NIMH, Div Mental Disorders Behav Res & AIDS, Room 6216, Bethesda, MD 20892 USA. NR 48 TC 3 Z9 3 U1 10 U2 11 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 2000 VL 13 IS 2 BP 189 EP 194 DI 10.1097/00001504-200003000-00009 PG 6 WC Psychiatry SC Psychiatry GA 296UE UT WOS:000086044100009 ER PT J AU Weinstein, JN Buolamwini, JK AF Weinstein, JN Buolamwini, JK TI Molecular targets in cancer drug discovery: Cell-based profiling SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review ID DIFFERENTIAL CYTOTOXICITY DATA; ELLIPTICINE ANALOGS; LINES; INSTITUTE; SCREEN; MECHANISM; PANELS; PHARMACOLOGY; FEASIBILITY; PATTERNS AB The phrase "molecular target-based drug discovery" usually implies an in vitro biochemical assay or battery of assays. One portion of the U.S. National Cancer Institute's drug discovery program, to the contrary, examines molecular targets for cancer therapy in a cell-based format. That approach has a number of significant limitations, but it has produced databases of significant utility on the activities and structures of tested compounds, as well as on molecular characteristics of the cell types used for testing. C1 NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. Univ Mississippi, Sch Pharm, Dept Med Chem, University, MS 38677 USA. Univ Mississippi, Sch Pharm, Pharmaceut Sci Res Inst, University, MS 38677 USA. RP Weinstein, JN (reprint author), NCI, Mol Pharmacol Lab, NIH, Bldg 37,Rm 5D-02,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 43 TC 17 Z9 18 U1 2 U2 6 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD MAR PY 2000 VL 6 IS 4 BP 473 EP 483 DI 10.2174/1381612003400894 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 305XX UT WOS:000086568000007 PM 10788592 ER PT J AU Barchi, JJ AF Barchi, JJ TI Emerging roles of carbohydrates and glycomimetics in anticancer drug design SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review ID N-ACETYLGLUCOSAMINYLTRANSFERASE-V; ASN-LINKED OLIGOSACCHARIDES; COLON CANCER-CELLS; LEWIS-X ANALOGS; PROSTATE-CANCER; GLYCOSYLATION INHIBITORS; TRISACCHARIDE INHIBITORS; COMBINATORIAL LIBRARIES; MUCIN GLYCOSYLATION; INDUCE ANTIBODIES AB Tumorigenesis is accompanied by marked changes in the expression and presentation of various macromolecules at the cell surface. These tumor-associated adjustments result from the differential expression of genes coding for the production or post-translational modifications of these macromolecules during transformation to a particular tumor phenotype. In turn, tumor cells acquire distinct biophysical properties which set them apart from their normal counterparts. Alterations of carbohydrate structures and their organization on the surface of neoplastic cells is a hallmark of the tumorigenic and, most notably, the metastatic phenotype, Carbohydrate-protein and carbohydrate-carbohydrate interactions are critical events in the progression, dissemination and invasion of cancer cells. Many cell-cell contacts and subsequent remodeling of the tumor microenvironment are mediated by cell-surface glycans. The discovery of agents that modulate these interactions or interfere with the processing of tumor associated oligosaccharides is a fervent area of research today. This review will highlight the current status of the use of carbohydrate-based compounds that are being evaluated as potential anticancer therapeutics. In addition, the use of structures based on glycopeptides and carbohydrate mimetics will also be discussed. C1 NCI, NIH, Med Chem Lab, Div Basic Sci, Bethesda, MD 20892 USA. RP Barchi, JJ (reprint author), NCI, NIH, Med Chem Lab, Div Basic Sci, 37 Convent Dr MSC4255,Bldg 37,Rm 5C02, Bethesda, MD 20892 USA. RI Barchi Jr., Joseph/N-3784-2014 NR 124 TC 52 Z9 52 U1 1 U2 10 PU BENTHAM SCIENCE PUBL BV PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD MAR PY 2000 VL 6 IS 4 BP 485 EP 501 DI 10.2174/1381612003400876 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 305XX UT WOS:000086568000008 PM 10788593 ER PT J AU Weinstein, M Yang, X Deng, CX AF Weinstein, M Yang, X Deng, CX TI Functions of mammalian Smad genes as revealed by targeted gene disruption in mice SO CYTOKINE & GROWTH FACTOR REVIEWS LA English DT Review DE Smads; embryo; angiogenesis; immunity; cancer ID GROWTH-FACTOR-BETA; TUMOR-SUPPRESSOR GENE; MAD-RELATED PROTEIN; EARLY MOUSE EMBRYO; TGF-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1; JUVENILE POLYPOSIS; SIGNAL-TRANSDUCTION; CHROMOSOME 18Q21.1; MESODERM INDUCTION AB The Smad genes are the intracellular mediators of TGF-beta signals. Targeted mutagenesis in mice has yielded valuable new insights into the functions of this important gene family. These experiments have shown that Smad2 and Smad4 are needed for gastrulation, Smad5 for angiogenesis, and Smad3 for establishment of the mucosal immune response and proper development of the skeleton. In addition, these experiments have shown us the importance of gene dosage in this family, as several of its members yielded haploinsufficiency phenotypes, These include gastrulation and craniofacial defects for Smad2, accelerated wound healing for Smad3, and the incidence of gastric cancer for Smad4. Combinatorial genetics has also revealed functions of Smads in left/right isomerism and liver development. Published by Elsevier Science Ltd. C1 NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Deng, CX (reprint author), NIDDKD, Genet Dev & Dis Branch, NIH, 10-9N105,10 Ctr Dr, Bethesda, MD 20892 USA. RI deng, chuxia/N-6713-2016 NR 75 TC 129 Z9 141 U1 1 U2 3 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-JUN PY 2000 VL 11 IS 1-2 BP 49 EP 58 DI 10.1016/S1359-6101(99)00028-3 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 325ZM UT WOS:000087707200006 PM 10708952 ER PT J AU Wahl, SM Orenstein, JM Chen, WJ AF Wahl, SM Orenstein, JM Chen, WJ TI TGF-beta influences the life and death decisions of T lymphocytes SO CYTOKINE & GROWTH FACTOR REVIEWS LA English DT Review DE TGF-beta; T lymphocytes; apoptosis; inflammation; thymus ID GROWTH-FACTOR-BETA; CELL-DEATH; TGF-BETA-1-DEFICIENT MICE; INFLAMMATORY RESPONSE; APOPTOSIS; ACTIVATION; FACTOR-BETA-1; MITOCHONDRIA; EXPRESSION; PEPTIDES AB TGF-beta is a powerful mediator of immune cell phenotype and function. In TGF-beta 1 homozygous null mice, aberrant regulation of the immune response culminates in lethal cardiopulmonary inflammation. In dissecting the underlying mechanisms leading to the attack of self, a role for TGF-beta 1 in controlling apoptosis and T cell selection patterns was uncovered. Increased levels of apoptosis and TCR mediated cell death disrupted normal negative and positive T cell selection in the thymus. Moreover, in peripheral T cell populations, increased T lymphocyte death was associated with increased expression of apoptosis-inducing receptors, Persistent activation of T cells engendered unchecked apoptosis which, rather than reducing, further exacerbated, tissue inflammation due to the absence of TGF-beta 1 TGF-beta 1 normally generated by macrophages during clearance of apoptotic cells contributes to dampening of inflammatory sequelae associated with phagocytosis. Collectively, these data demonstrate a pivotal role for TGF-beta in multiple stages of T cell apoptosis, selection, activation and clearance. Published by Elsevier Science Ltd. C1 Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. George Washington Univ, Med Ctr, Dept Pathol, Washington, DC 20037 USA. RP Wahl, SM (reprint author), Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, 30 Convent Dr,MSC 4352, Bethesda, MD 20892 USA. NR 51 TC 53 Z9 55 U1 0 U2 0 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-JUN PY 2000 VL 11 IS 1-2 BP 71 EP 79 DI 10.1016/S1359-6101(99)00030-1 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 325ZM UT WOS:000087707200008 PM 10708954 ER PT J AU Letterio, JJ AF Letterio, JJ TI Murine models define the role of TGF-beta as a master regulator of immune cell function SO CYTOKINE & GROWTH FACTOR REVIEWS LA English DT Review DE transforming growth factor-beta (TGF-beta); Smad; immune cell; mice ID TRANSFORMING-GROWTH-FACTOR; GROWTH-FACTOR-BETA-1 NULL MICE; COLONY-STIMULATING FACTOR; TARGETED DISRUPTION; KNOCKOUT MICE; HEMATOPOIETIC PROGENITORS; HUMAN-LYMPHOCYTES; LANGERHANS CELLS; DENDRITIC CELLS; MUTANT MICE AB Many members of transforming growth factor-beta (TGF-beta) superfamily, including not only TGF-beta, but also the activins, and bone morphogenetic proteins (BMPs), have been demonstrated to affect the development and function of immune cells. From the proliferation and differentiation of pluripotent stem cells, to the activation and migration of mature lymphoid and myeloid lineages, the TGF-beta s have been recognized for their ability to modulate the manner in which such cells respond to stimuli in their environment. Recent studies involving disruption of this pathway in genetically engineered mice now emphasize the importance of this activity and validate functional models predicted by in vitro studies. Phenotypic differences between mice harboring mutations in the TGF-beta 1 ligand and the TGF-beta receptor-activated signaling intermediate Smad3 are presented and serve to highlight the valuable role of these in vivo genetic tests of function. (C) 2000 Published by Elsevier Science Ltd. All rights reserved. C1 NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. RP Letterio, JJ (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bldg 41,Roo C629,41 Lib Dr, Bethesda, MD 20892 USA. NR 53 TC 55 Z9 57 U1 0 U2 0 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-JUN PY 2000 VL 11 IS 1-2 BP 81 EP 87 DI 10.1016/S1359-6101(99)00031-3 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 325ZM UT WOS:000087707200009 PM 10708955 ER PT J AU Ashcroft, GS Roberts, AB AF Ashcroft, GS Roberts, AB TI Loss of Smad3 modulates wound healing SO CYTOKINE & GROWTH FACTOR REVIEWS LA English DT Review DE SMAD; TGF-beta signaling; wound healing; inflammation ID GROWTH-FACTOR-BETA; ACUTE CUTANEOUS WOUNDS; TGF-BETA; TRANSCRIPTIONAL ACTIVATION; TARGETED DISRUPTION; EPITHELIAL-CELLS; HEALTHY HUMANS; SKIN; PROTEINS; EXPRESSION AB TGF-beta plays a central and critical role in tissue repair. The recent identification of TGF-beta signal transduction pathways involving Smad proteins has now made it possible to explore their contribution to the activities of TGF-beta in vivo. Both Smad3 and its closely related homolog Smad2 act as latent nuclear transcriptional activators and mediate intracellular signaling by TGF-beta s and activin, each of which regulates cellular functions pivotal to cutaneous wound healing. Mice null for Smad3 (Smad3(ex8/ex8)) survive into adulthood and show accelerated cutaneous wound healing characterized by an increased rate of re-epithalialization and a reduced local inflammatory infiltrate. These data implicate Smad3 in specific pathways of tissue repair and suggest that it could be a target for the development of therapeutic strategies to modulate wound healing. Published by Elsevier Science Ltd. C1 NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. RP Roberts, AB (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. NR 52 TC 58 Z9 64 U1 0 U2 3 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-JUN PY 2000 VL 11 IS 1-2 BP 125 EP 131 DI 10.1016/S1359-6101(99)00036-2 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 325ZM UT WOS:000087707200014 PM 10708960 ER PT J AU Kim, SJ Im, YH Markowitz, SD Bang, YJ AF Kim, SJ Im, YH Markowitz, SD Bang, YJ TI Molecular mechanisms of inactivation of TGF-beta receptors during carcinogenesis SO CYTOKINE & GROWTH FACTOR REVIEWS LA English DT Review DE TGF-beta; receptors; tumor suppressor; transcriptional regulation; DNA methylation ID GROWTH-FACTOR-BETA; HUMAN GASTRIC-CANCER; NONPOLYPOSIS COLORECTAL-CANCER; II GENE MUTATION; INSTABILITY-ASSOCIATED MUTATIONS; EWINGS-SARCOMA TRANSLOCATION; TUMOR-SUPPRESSOR GENE; ETS DOMAIN PROTEIN; CELL LUNG-CANCER; MICROSATELLITE INSTABILITY AB Signals from the TGF-beta s are mediated by the TGF-beta receptors and their substrates, the Smad proteins. Inactivation of either of the two transmembrane serine/threonine kinases called the TGF-beta type I and type II receptors is now known to underlie a wide variety of human pathologies including, especially carcinogenesis. Numerous studies have now demonstrated that the TGF-beta receptor complex and its downstream signaling intermediates constitute a tumor suppressor pathway. We review here a specific pathway of mutational inactivation of the TGF-beta type II receptor resulting from microsatellite instability and demonstrate that, by contrast. the most common mechanism of loss of expression of the TGF-beta type II receptor involves transcriptional repression. This provides a new target for therapeutic intervention. Published by Elsevier Science Ltd. C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. Univ Hosp Cleveland, Ireland Canc Ctr, Cleveland, OH 44122 USA. Univ Hosp Cleveland, Dept Med, Cleveland, OH 44122 USA. Case Western Reserve Univ, Cleveland, OH 44122 USA. Seoul Natl Univ, Coll Med, Canc Res Ctr, Seoul, South Korea. RP Kim, SJ (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. RI Bang, Yung Jue/J-2759-2012 NR 102 TC 140 Z9 157 U1 1 U2 12 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-JUN PY 2000 VL 11 IS 1-2 BP 159 EP 168 DI 10.1016/S1359-6101(99)00039-8 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 325ZM UT WOS:000087707200017 PM 10708963 ER PT J AU Lindsay, RS Dabelea, D Roumain, J Hanson, RL Bennett, PH Knowler, WC AF Lindsay, RS Dabelea, D Roumain, J Hanson, RL Bennett, PH Knowler, WC TI Type 2 diabetes and low birth weight - The role of paternal inheritance in the association of low birth weight and diabetes SO DIABETES LA English DT Article ID MELLITUS AB Lower birth weight is associated with an increased occurrence of type 2 diabetes in later life. Whether this relationship is explained by environmental or genetic factors is unknown. We have examined the potential for genetic influences by determining whether parental diabetes is associated with lower birth weight in 1,608 children of known birth weight and gestational age born between 1941 and 1993 in the Gila River Indian Community in Arizona. The previously described relationships of maternal diabetes to increased birth weight and offspring diabetes were observed. In contrast to this we have determined novel relationships between low birth weight and paternal diabetes, The offspring of diabetic fathers were, on average, 78 g lighter than the offspring of nondiabetic fathers. For fathers, lower birth weight in their offspring was associated with an increased risk of later diabetes, i.e., fathers of offspring in the lowest quintile of birth weight, who were not diabetic at the time of birth of their child, had a 1.8-fold increased risk of developing diabetes later in life (95% CI 1.2-2.7; P = 0.004). For children, lower birth weight predicted diabetes in the offspring if paternal but not maternal diabetes was present, but it was not associated with higher plasma glucose if neither parent had diabetes. We conclude that the risk of diabetes associated with low birth weight is strongly related to the development of paternal diabetes, suggesting a genetic link between lower birth weight and later diabetes. C1 NIDDKD, NIH, Phoenix, AZ 85014 USA. RP Lindsay, RS (reprint author), NIDDKD, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 11 TC 113 Z9 118 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAR PY 2000 VL 49 IS 3 BP 445 EP 449 DI 10.2337/diabetes.49.3.445 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 290AU UT WOS:000085654800018 PM 10868967 ER PT J AU Baier, LJ Permana, PA Traurig, M Dobberfuhl, A Wiedrich, C Sutherland, J Thuillez, P Luczy-Bachman, G Hara, M Horikawa, Y Hinokio, Y Hanson, RL Bogardus, C AF Baier, LJ Permana, PA Traurig, M Dobberfuhl, A Wiedrich, C Sutherland, J Thuillez, P Luczy-Bachman, G Hara, M Horikawa, Y Hinokio, Y Hanson, RL Bogardus, C TI Mutations in the genes for hepatocyte nuclear factor (HNF)-1 alpha,-4 alpha,-1 beta, and-3 beta; the dimerization cofactor of HNF-1; and insulin promoter factor 1 are not common causes of early-onset type 2 diabetes in pima Indians SO DIABETES CARE LA English DT Article ID FACTOR-1-ALPHA GENE; JAPANESE SUBJECTS; YOUNG; NIDDM; MODY; PREVALENCE; IPF1 AB OBJECTIVE - Maturity-onset diabetes of the young (MODY) is a genetically heterogeneous subtype of type 2 diabetes characterized by an early age at onset and autosomal dominant inheritance. MODI( can result from heterozygous mutations in at least five genes. The purpose of this study was to determine whether alterations in known MODY genes and two MODY candidate genes contribute to the development of early-onset ripe 2 diabetes in Pima Indians. RESEARCH DESIGN AND METHODS - The coding regions of the known MODY genes hepatocyte nuclear factor (HNF)-1 alpha, HNF-4 alpha, HNF-1 beta, and insulin promoter factor 1 and the coding regions of two MODY candidate genes, HNF-3 beta and the dimerization cofactor of HNF-1, were sequenced in genomic DNA from Pima Indians. The primary "affected" study population consisted of 46 Pima Indians whose age at onset of type 2 diabetes was less than or equal to 20 years. DNA sequence variants identified in the affected group were then analyzed in a group of 80 "unaffected" Pima Indians who were at least 40 years old and had normal glucose tolerance. RESULTS - A total of Il polymorphisms were detected in these genes. However, none of the polymorphisms differed in frequency among Pima Indians with an early age at onset of diabetes compared with older Pima Indians with normal glucose tolerance. CONCLUSIONS - Mutations in these known MODY or MODE candidate genes are not a common cause of early-onset diabetes ill Pima Indians. C1 NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85016 USA. Univ Chicago, Howard Hughes Med Inst, Chicago, IL 60637 USA. Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA. RP Baier, LJ (reprint author), NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, 4212 N 16Th St, Phoenix, AZ 85016 USA. RI Dobberfuhl, Angela/C-9450-2012; Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 20 TC 11 Z9 12 U1 0 U2 0 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 2000 VL 23 IS 3 BP 302 EP 304 DI 10.2337/diacare.23.3.302 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 289GA UT WOS:000085611100008 PM 10868855 ER PT J AU Limburg, PJ Ahlquist, DA Gilbert, JA Harrington, JJ Klee, GG Roche, PC AF Limburg, PJ Ahlquist, DA Gilbert, JA Harrington, JJ Klee, GG Roche, PC TI Immunodiscrimination of colorectal neoplasia using MUC1 antibodies: Discrepant findings in tissue versus stool SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE colorectal neoplasms; stool tests; MUC1; mucins ID OCCULT-BLOOD-TEST; FLEXIBLE SIGMOIDOSCOPY; GENE-EXPRESSION; CANCER; CARCINOMA; HEMOCCULT; COLON; SURVEILLANCE; SENSITIVITY; COLONOSCOPY AB Colorectal tumor-associated antigens are attractive targets for novel stool-screening assays. MUC1, a glycoprotein antigen, is aberrantly expressed in transformed colorectal mucosa and represents a candidate fecal biomarker. In this study, tissue staining and stool testing were performed to further clarify the discriminant potential of MUC1 in markedly different biologic media. One anti-MUC1 monoclonal antibody (MA5) was used for immunohistochemistry and two commercially available MUC1 assay kits (ELSA-CA 15-3 and Truquant BR) were used for stool detection. On tissue staining, MUC1 expression was strong in 40/40 (100%) adenocarcinomas, moderate in 42/55 (76%) adenomas, faint in 8/28 (29%) juxtatu-moral mucose specimens, and absent in 15/15 (0%) nonadjacent mucosa specimens. Conversely MUC1 levels in stool testing did not differ between colorectal cancer cases (N = 14) and controls (N = 14). Based on these results, MUC1 appears to be a functional tumor biomarker in colorectal tissue but not in stool. Bacterial metabolism within stool may unmask the core antigen of MUC1 and account for this discordance in immunoreactivity. C1 Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN 55905 USA. Mayo Clin, Dept Lab Med, Rochester, MN 55905 USA. NCI, Div Canc Prevent, Off Prevent Oncol, NIH, Bethesda, MD 20892 USA. RP Ahlquist, DA (reprint author), Mayo Clin, Div Gastroenterol & Hepatol, 200 1st St SW, Rochester, MN 55905 USA. FU NCI NIH HHS [CA 71680] NR 33 TC 8 Z9 11 U1 0 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD MAR PY 2000 VL 45 IS 3 BP 494 EP 499 DI 10.1023/A:1005484921740 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 298RU UT WOS:000086153600008 PM 10749323 ER PT J AU Carmona, GN Jufer, RA Goldberg, SR Gorelick, DA Greig, NH Yu, QS Cone, EJ Schindler, CW AF Carmona, GN Jufer, RA Goldberg, SR Gorelick, DA Greig, NH Yu, QS Cone, EJ Schindler, CW TI Butyrylcholinesterase accelerates cocaine metabolism: In vitro and in vivo effects in nonhuman primates and humans SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID PLASMA CHOLINESTERASE ACTIVITY; TOXICITY; CARBOXYLESTERASE; COMPLICATIONS; PURIFICATION; COCAETHYLENE; CATALYZES; MICE AB Butyrylcholinesterase (BChE) is known to metabolize cocaine in humans. In the present study, three different experiments were performed to determine whether the addition of horse serum-derived BChE would accelerate the metabolism of cocaine. In the first experiment, the addition of BChE to squirrel monkey plasma in vitro reduced the half-life of cocaine by over 80%, decreased the production of the metabolic product benzoylecgonine, and increased ecgonine methyl ester formation. The effect of BChE on cocaine metabolism was reversed by a specific BChE inhibitor. In the second, in vivo, experiment, exogenously administered BChE reduced peak cocaine concentrations when given to anesthetized squirrel monkeys. Finally, incubation of cocaine with added BChE in human plasma in vitro resulted in a decrease in cocaine half-life similar to that observed with squirrel monkey plasma. The magnitude of the decrease in cocaine half-life was proportional to the amount of added BChE. Together, these results indicate that exogenously administered BChE can accelerate cocaine metabolism in such a way as to potentially lessen the behavioral and toxic effects of cocaine. Therefore, BChE may be useful as a treatment for cocaine addiction and toxicity. C1 NIDA, Behav Neurosci Branch, Preclin Pharmacol Sect, Intramural Res Program,NIH, Baltimore, MD 21224 USA. NIDA, Chem & Drug Metab Sect, NIH, Baltimore, MD 21224 USA. NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. RP Carmona, GN (reprint author), NIDA, Behav Neurosci Branch, Preclin Pharmacol Sect, Intramural Res Program,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 21 TC 34 Z9 34 U1 0 U2 7 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD MAR PY 2000 VL 28 IS 3 BP 367 EP 371 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 285PA UT WOS:000085396400019 PM 10681384 ER PT J AU Chrambach, A Chrambach, A Brining, SK AF Chrambach, A Chrambach, A Brining, SK TI Gel electrophoretic distinction between Congo Red nonreactive beta-amyloid (1-42) and beta-amyloid (1-40) SO ELECTROPHORESIS LA English DT Article DE beta-amyloid; surface net charge; Congo Red binding ID ALZHEIMERS-DISEASE; A-BETA-42(43); PROTEIN AB Congo-Red nonreactive beta-amyloid (1-42) exibits in gel electrophoresis (pH 8.82, 0.01 hn ionic strength, 2 degrees C) a surface charge density larger than that of the corresponding peptide of length (1-40), and a size indistinguishable from that of (1-40). C1 NICHHD, Macromol Anal Sect, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Chrambach, A (reprint author), NICHHD, Macromol Anal Sect, Lab Cellular & Mol Biophys, NIH, Bldg 10,Rm 9D50, Bethesda, MD 20892 USA. EM acc@cu.nih.gov NR 9 TC 2 Z9 2 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD MAR PY 2000 VL 21 IS 4 BP 760 EP 761 DI 10.1002/(SICI)1522-2683(20000301)21:4<760::AID-ELPS760>3.0.CO;2-5 PG 2 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 292DT UT WOS:000085779400012 PM 10733218 ER PT J AU Gombocz, E Chrambach, A Yefimov, S Yergey, AL AF Gombocz, E Chrambach, A Yefimov, S Yergey, AL TI Electroelution of nonfluorescent stacked proteins detected by fluorescence optics from gel electrophoretic bands for transfer into mass spectrometry SO ELECTROPHORESIS LA English DT Article DE stacked nonfluorescent protein; mass spectrometry; fluorescence scanning; cascade blue; electroelution ID POLYMER-SOLUTION; SDS-PROTEIN; APPARATUS; SEPARATION; RECOVERY AB The extreme accuracy of spectrometrically determined masses of proteins has opened the possibility to identify proteins separated as gel electrophoretic bands in the absence of specific immunologic ways of identification. For the purpose of protein transfer from gel electrophoretic bands to mass spectrometer, electroelution from the intact get has advantages, in particular when apparatus with capacity for fluorescent scanning allows one to direct the electroelution cell over the band under computer control. To avoid fluorescent labeling of the protein which is incompatible with mass spectrometric identification, it is proposed to selectively stack the unlabeled protein and detect it by comigrating tracking dye prior to electroelution. The feasibility of the approach is exemplified in case of a single protein, but still remains to be demonstrated in conjunction with the selective stacking or unstacking of a single protein from a mixture of several proteins. C1 NICHD, Sect Macromol Anal, NIH, Bethesda, MD 20892 USA. NICHD, Sect Mass Spectrometry & Metab, NIH, Bethesda, MD 20892 USA. NICHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Chrambach, A (reprint author), NICHD, Sect Macromol Anal, NIH, Bldg 10,Rm 9D50, Bethesda, MD 20892 USA. NR 18 TC 5 Z9 5 U1 0 U2 1 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 2000 VL 21 IS 5 BP 846 EP 849 DI 10.1002/(SICI)1522-2683(20000301)21:5<846::AID-ELPS846>3.0.CO;2-L PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 300ND UT WOS:000086258300004 PM 10768768 ER PT J AU Celli, S Marto, JA Falchetto, R Shabanowitz, J Valdivia, LA Fung, JJ Hunt, DF Kelly, RH AF Celli, S Marto, JA Falchetto, R Shabanowitz, J Valdivia, LA Fung, JJ Hunt, DF Kelly, RH TI Serum protein immunogenicity: Implications for liver xenografting SO ELECTROPHORESIS LA English DT Article; Proceedings Paper CT Meeting of the American-Electrophoresis-Society CY AUG 08-10, 1999 CL BETHESDA, MARYLAND SP Amer Electrophoresis Soc DE liver xenografting; serum proteins; immunogenicity; immunoelectrophoresis ID RECEPTOR-RELATED PROTEIN; DENSITY-LIPOPROTEIN-RECEPTOR; ALPHA-TRYPSIN INHIBITOR; AMINO-ACID-SEQUENCES; TANDEM MASS-SPECTRA; ANTIGEN DELIVERY; ALPHA(2)-MACROGLOBULIN RECEPTOR; PEPTIDE VACCINE; BINDING; RAT AB The objectives of this study were threefold: (i) assess immunogenicity of donor plasma proteins following hepatic xenotransplantation, (ii) identify potential immunogens, and (iii) consider the implications of antibody formation against these plasma proteins in xenograft survival. We studied liver and heart xenografts in a concordant combination, hamster to rat. All grafts were examined at necropsy for evidence of rat immunoglobulin G (IgG) deposition. Cardiac xenografts were placed in recipients who had, or had tin G (IgG) deposition. Cardiac xenografts were placed In recipients who naa, or naa not, been sensitized with hamster serum. Hepatic xenografts were placed in naive recipients to see if antibodies to hamster serum proteins could be eluted from the Department of Chemistry, rejecting organ. Sera of immunized rats were examined for the presence of anti-hamster antibodies by immunoelectrophoresis and by Western blotting following sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) separation of hamster serum. Antibodies in sera of immunized rats were compared with those eluted from rejecting livers. Candidate antigens were identified by tandem mass spectrometry, sequence analysis, and reference to protein databases. Results showed that sera of immunized rats recognized a minimum of four different antigens in hamster serum by immunoelectrophoresis, and a minimum of seven by the more sensitive SDS-PAGE Western blot. IgG eluted from rejecting livers bound three of seven candidate antigens recognized by sera of the immunized animals. Sequence analysis searches revealed proteinase inhibitors in each of the three SDS-PAGE bands common to the above samples. All of these candidate proteinase inhibitor immunogens share a common catabolic fate, uptake via the lipoprotein-related protein (LRP/alpha 2-macroglobulin receptor CD91). Sensitization to hamster serum proteins hastened cardiac xenograft rejection in 30-50% of recipients (depending on sensitization protocol). Vascular deposition of rat IgG occurred in all rejecting xenografts. Antibody binding to proteinase inhibitors could disturb their functional activity and contribute to the pathogenesis of delayed xenograft rejection. C1 Univ Pittsburgh, Dept Surg, Transplant Inst, Pittsburgh, PA 15260 USA. Univ Virginia, Dept Chem, Charlottesville, VA 22903 USA. Univ Pittsburgh, Sch Med, Dept Pathol, Div Clin Immunopathol, Pittsburgh, PA 15260 USA. RP Celli, S (reprint author), NIAID, Lab Cellular & Mol Immunol, NIH, Bldg 4,Room 111, Bethesda, MD 20892 USA. RI Fung, John/A-2679-2012; Hunt, Donald/I-6936-2012; Celli, Susanna/M-7138-2014 OI Hunt, Donald/0000-0003-2815-6368; NR 38 TC 1 Z9 1 U1 0 U2 1 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 2000 VL 21 IS 5 BP 965 EP 975 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 300ND UT WOS:000086258300020 PM 10768783 ER PT J AU St'astna, M Radko, SP Chrambach, A AF St'astna, M Radko, SP Chrambach, A TI Separation efficiency in protein zone electrophoresis performed in capillaries of different diameters SO ELECTROPHORESIS LA English DT Article; Proceedings Paper CT Meeting of the American-Electrophoresis-Society CY AUG 08-10, 1999 CL BETHESDA, MARYLAND SP Amer Electrophoresis Soc DE capillary diameter; separation efficiency; proteins; capillary zone electrophoresis ID WALL ADSORPTION; TEMPERATURE-GRADIENTS; POLYMER; LENGTH AB R-phycoerythrin (PHYCO, M-r 240 000), glucose-6-phosphate dehydrogenase (GPD, M-r 104 000) and two charge isomers of recombinant green fluorescent protein (GFP-1 and GFP-2, M-r 27 000) were subjected to capillary zone electrophoresis (CZE) In capillaries of 50, 100 and 150 mu m inner diameter at various sample concentrations, electric field strengths, and lengths of the initial zone with the purpose of testing the hypothesis that protein - capillary wall interactions rather than thermal effects are predominantly responsible for the peak spreading of proteins in CZE. The efficiency of CZE was expressed in terms of the number of theoretical plates, N, or the plate height corrected by subtracting the contribution from initial zone length, H'. The latter has the advantage of solely reflecting contributions to the separation efficiency arising from intracolumn peak spreading in capillaries of different diameters. The separation efficiency measured varied widely, by two orders of magnitude, for these proteins under identical conditions, with GPD exhibiting the highest and PHYCO the lowest values of N. H' was found to be independent of sample concentrations within the concentration ranges studied, 1-100 mu g/mL for PHYCO and 100-1000 mu g/mL for GPD, while exhibiting a decrease with sample concentration for GFP, especially in 150 mu m diameter capillaries, within the concentration range 1-100 mu g/mL. H' was also found to be independent of electric field strength up to 300-400 V/cm for PHYCO and GFP. In all experiments, the CZE of proteins in 100 mu m diameter capillaries provided a higher or, at least, equal efficiency, compared to that in 50 or 150 mu m diameter capillaries. It may be concluded that the protein - capillary wall interactions and protein microheterogeneity are the dominant sources of peak spreading and their specific combinations are thought to be responsible for the wide variation in separation efficiency between proteins in CZE observed under identical conditions. C1 NICHHD, Sect Macromol Anal, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Chrambach, A (reprint author), NICHHD, Sect Macromol Anal, Lab Cellular & Mol Biophys, NIH, Bldg 10,Rm 9D50, Bethesda, MD 20892 USA. RI Stastna, Miroslava/G-9266-2014 NR 27 TC 7 Z9 7 U1 1 U2 7 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 2000 VL 21 IS 5 BP 985 EP 992 DI 10.1002/(SICI)1522-2683(20000301)21:5<985::AID-ELPS985>3.0.CO;2-5 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 300ND UT WOS:000086258300022 PM 10768785 ER PT J AU Xiao, H Palhan, V Yang, YL Roeder, RG AF Xiao, H Palhan, V Yang, YL Roeder, RG TI TIP30 has an intrinsic kinase activity required for up-regulation of a subset of apoptotic genes SO EMBO JOURNAL LA English DT Article DE apoptosis; metastasis suppressor; SCLC; Tat; transcription ID RNA-POLYMERASE-II; CARBOXYL-TERMINAL DOMAIN; MYC-INDUCED APOPTOSIS; CELL LUNG-CARCINOMA; WILD-TYPE P53; HIV-1 TAT; P-TEFB; COMPLEX-FORMATION; IN-VITRO; TRANSCRIPTION C1 Rockefeller Univ, Biochem & Mol Biol Lab, New York, NY 10021 USA. NCI, Lab Immune Cell Biol, Bethesda, MD 20892 USA. RP Roeder, RG (reprint author), Rockefeller Univ, Biochem & Mol Biol Lab, New York, NY 10021 USA. FU NIAID NIH HHS [AI37327] NR 46 TC 70 Z9 86 U1 0 U2 3 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 2000 VL 19 IS 5 BP 956 EP 963 DI 10.1093/emboj/19.5.956 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 291RJ UT WOS:000085749600017 PM 10698937 ER PT J AU Nakae, J Barr, V Accili, D AF Nakae, J Barr, V Accili, D TI Differential regulation of gene expression by insulin and IGF-1 receptors correlates with phosphorylation of a single amino acid residue in the forkhead transcription factor FKHR SO EMBO JOURNAL LA English DT Article DE gene expression; hepatocyte; insulin; kinase; phosphorylation ID PROTEIN-KINASE-B; CAENORHABDITIS-ELEGANS; SER/THR KINASE; ACTIVATION; SIGNALS; DAF-16; HOMOLOGY; PDK1; HEAD; AKT AB The transcription factor FKHR is inhibited by phosphorylation in response to insulin and IGF-1 through Akt kinase. Here we show that FKHR phosphorylation in hepatocytes conforms to a hierarchical pattern in which phosphorylation of the Akt site at S-253, in the forkhead DNA binding domain, is a prerequisite for the phosphorylation of two additional potential Akt sites, T-24 and S-316. Using insulin receptor-deficient hepatocytes, we show that T-24 fails to be phosphorylated by IGF-1 receptors, suggesting that this residue is targeted by a kinase specifically activated by insulin receptors, Lack of T-24 phosphorylation is associated with the failure of IGF-1 to induce nuclear export of FKHR, and to inhibit expression of a reporter gene under the transcriptional control of the IGF binding protein-1 insulin response element. We propose that site-specific phosphorylation of FKHR is one of the mechanisms by which insulin and IGF-I receptors exert different effects on gene expression. C1 Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP Accili, D (reprint author), Columbia Univ Coll Phys & Surg, Dept Med, 630 W 168 St, New York, NY 10032 USA. NR 37 TC 201 Z9 202 U1 0 U2 4 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 2000 VL 19 IS 5 BP 989 EP 996 DI 10.1093/emboj/19.5.989 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 291RJ UT WOS:000085749600020 PM 10698940 ER PT J AU He, LS Liu, JH Collins, I Sanford, S O'Connell, B Benham, CJ Levens, D AF He, LS Liu, JH Collins, I Sanford, S O'Connell, B Benham, CJ Levens, D TI Loss of FBP function arrests cellular proliferation and extinguishes c-myc expression SO EMBO JOURNAL LA English DT Article DE cell growth; c-myc; far upstream element; FUSE-binding protein ID RNA-POLYMERASE-II; GREEN FLUORESCENT PROTEIN; FAR UPSTREAM ELEMENT; IN-VIVO; DUPLEX DESTABILIZATION; ADENOVIRUS VECTORS; SUPERHELICAL DNA; MAMMALIAN-CELLS; K-PROTEIN; BINDING AB The c-myc regulatory region includes binding sites for a large set of transcription factors, The present studies demonstrate that in the absence of FBP [far upstream element (FUSE)-binding protein], which binds to the single-stranded FUSE, the remainder of the set fails to sustain endogenous c-myc expression. A dominant-negative FBP DNA-binding domain lacking effector activity or an antisense FBP RNA, expressed via replication-defective adenovirus vectors, arrested cellular proliferation and extinguished native c-myc transcription from the P1 and P2 promoters. The dominant-negative FBP initially augmented the single-stranded character of FUSE: however once c-myc expression was abolished, melting at FUSE could no longer be supported. In contrast, with antisense FBP RNA, the single-stranded character of FUSE decreased monotonically as the transcription of endogenous c-myc declined, Because transcription is the major source of super-coiling in vivo, we propose that by binding torsionally strained DNA, FBP measures promoter activity directly. we also show that FUSE is predicted to behave as a torsion-regulated switch poised to regulate c-myc and to confer a higher order regulation on a large repertoire of factors. C1 NCI, DCS, Pathol Lab, Bethesda, MD 20892 USA. NIDCR, Therapy & Therapeut Branch, Bethesda, MD 20892 USA. Mt Sinai Sch Med, Dept Biomath Sci, New York, NY 10029 USA. RP Levens, D (reprint author), NCI, DCS, Pathol Lab, Bldg 10,Room 2N105, Bethesda, MD 20892 USA. RI Levens, David/C-9216-2009; Benham, Craig/G-1512-2013; OI Levens, David/0000-0002-7616-922X; O'Connell, Brian/0000-0003-4529-7664 NR 53 TC 102 Z9 106 U1 0 U2 3 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 2000 VL 19 IS 5 BP 1034 EP 1044 DI 10.1093/emboj/19.5.1034 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 291RJ UT WOS:000085749600024 PM 10698944 ER PT J AU Levine, OS Liu, G Garman, RL Dowell, SF Yu, SG Yang, YH AF Levine, OS Liu, G Garman, RL Dowell, SF Yu, SG Yang, YH TI Haemophilus influenzae type b and Streptococcus pneumoniae as causes of pneumonia among children in Beijing, China SO EMERGING INFECTIOUS DISEASES LA English DT Article ID HONG-KONG; CONJUGATE VACCINES; YOUNG-CHILDREN; CARRIAGE; INFECTIONS; MENINGITIS; IMPLEMENTATION; DISEASES; INFANTS; BURDEN AB To determine if Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae could be identified more often from the nasopharynx of patients-with pneumonia than from control patients, we obtained nasopharyngeal swab specimens from 96 patients with chest x-ray-confirmed pneumonia and 214 age-matched control patients with diarrhea or dermatitis from the outpatient department at Beijing Children's Hospital. Pneumonia patients were more likely to be colonized with Hib and S. pneumoniae than control patients, even after the data were adjusted for possible confounding factors such as day-care attendance, the presence of other children in the household, and recent antibiotic use. In China, where blood cultures from pneumonia patients are rarely positive, the results of these nasopharyngeal cultures provide supporting evidence for the role of Hib and S. pneumoniae as causes of childhood pneumonia. C1 Ctr Dis Control & Prevent, Atlanta, GA USA. Capital Univ Med Sci, Beijing Childrens Hosp, Beijing, Peoples R China. Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. RP Levine, OS (reprint author), NIAID, Div Microbiol & Infect Dis, Resp Dis Branch, 6700-B Rockledge Dr,Room 3133, Bethesda, MD 20892 USA. NR 25 TC 22 Z9 25 U1 0 U2 1 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 2000 VL 6 IS 2 BP 165 EP 170 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 308AZ UT WOS:000086687500009 PM 10756150 ER PT J AU Jeong, KH Jacobson, L Pacak, K Widmaier, EP Goldstein, DS Majzoub, JA AF Jeong, KH Jacobson, L Pacak, K Widmaier, EP Goldstein, DS Majzoub, JA TI Impaired basal and restraint-induced epinephrine secretion in corticotropin-releasing hormone-deficient mice SO ENDOCRINOLOGY LA English DT Article ID PHENYLETHANOLAMINE-N-METHYLTRANSFERASE; TYROSINE-HYDROXYLASE GENE; CATECHOLAMINE-SYNTHESIZING ENZYMES; SYMPATHETIC NERVOUS-SYSTEM; TISSUE-SPECIFIC EXPRESSION; RAT ADRENAL-MEDULLA; IMMOBILIZATION STRESS; MESSENGER-RNA; PARAVENTRICULAR NUCLEUS; CONSCIOUS RATS AB CRH is thought to play a role in responses of the adrenocortical and adrenomedullary systems during stress. To investigate the role of CRH in stress-induced secretions of corticosterone and epinephrine, we subjected wild-type (WT) and CRH-deficient (knockout, KO) mice to restraint, and analyzed plasma corticosterone, plasma catecholamines, and adrenal phenylethanolamine N-methyltransferase (PNMT) gene expression and activity before and during 3 h of restraint. Plasma corticosterone increased over 40-fold in WT mice, but minimally in CRH KO mice. Adrenal corticosterone content tended to increase in CRH KO mice, although to levels 5-fold lower than that in WT mice. CRH KO mice had significantly lower plasma epinephrine and higher norepinephrine than WT mice at baseline, and delayed epinephrine secretion during restraint. Adrenal PNMT messenger RNA content in CRH KO mice tended to be lower than that in WT mice, though the degree of induction was similar in both genotypes. PNMT enzyme activity was significantly lower in CRH KO mice. Pharmacological adrenalectomy abolished restraint-induced corticosterone secretion and PNMT gene expression in WT mice, consistent with an absolute requirement of glucocorticoids for PNMT gene expression. We conclude that glucocorticoid insufficiency in CRH KO mice leads to decreased basal and restraint-induced plasma epinephrine and adrenal PNMT gene expression and enzyme activity. C1 Harvard Univ, Sch Med, Div Endocrinol, Childrens Hosp, Boston, MA 02115 USA. NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. Boston Univ, Dept Biol, Boston, MA 02215 USA. RP Majzoub, JA (reprint author), Harvard Univ, Sch Med, Div Endocrinol, Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. EM majzoub@a1.tch.harvard.edu NR 58 TC 62 Z9 62 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 2000 VL 141 IS 3 BP 1142 EP 1150 DI 10.1210/en.141.3.1142 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 337WH UT WOS:000088385700034 PM 10698191 ER PT J AU Krsmanovic, LZ Martinez-Fuentes, AJ Arora, KK Mores, N Tomic, M Stojilkovic, SS Catt, KJ AF Krsmanovic, LZ Martinez-Fuentes, AJ Arora, KK Mores, N Tomic, M Stojilkovic, SS Catt, KJ TI Local regulation of gonadotroph function by pituitary gonadotropin-releasing hormone SO ENDOCRINOLOGY LA English DT Article ID INDUCED CALCIUM OSCILLATIONS; MESSENGER RIBONUCLEIC-ACIDS; RAT ANTERIOR-PITUITARY; HYPOTHALAMIC NEURONS; PULSE-GENERATOR; RHESUS-MONKEY; AUTOCRINE REGULATION; GNRH; EXPRESSION; RECEPTORS AB Cultured rat pituitary cells and immortalized pituitary gonadotrophs (alpha T3-1 cells) express specific messenger RNA transcripts for GnRH and exhibit positive immunostaining for the GnRH peptide. Each cell type released GnRH during both static culture and perifusion, albeit in lesser amounts than cultured hypothalamic cells and GT1-7 neurons. In perifused pituitary cells, exposure to a GnRH agonist stimulated the release of GnRH as well as LH. In contrast, treatment with a GnRH receptor antagonist or with GnRH antiserum decreased basal LH release. In pituitary cell cultures, a small proportion of gonadotrophs exhibited high amplitude and low frequency baseline Ca2+ oscillations in the absence of GnRH stimulation. Such spontaneous oscillations were comparable to those induced by pico-molar concentrations of GnRH and could be abolished by treatment with a GnRH antagonist. These in vitro findings indicate that locally produced GnRH causes low level activation of pituitary GnRH receptors, induces spontaneous intracellular Ca2+ oscillations, and contributes to basal LH secretion in cultured pituitary cells. In vivo, such autocrine or paracrine actions of pituitary-derived GnRH could provide a mechanism for the maintenance of optimal responsiveness of the gonadotrophs to pulses of GnRH arising in the hypothalamus. The presence and actions of GnRH in the anterior pituitary gland, the major site of expression of GnRH receptors, suggest that local regulatory effects of the neuropeptide could supplement the primary hypothalamic mechanism for the control of episodic gonadotropin secretion. C1 NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Catt, KJ (reprint author), NICHHD, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Room 6A-36, Bethesda, MD 20892 USA. EM catt@helix.nih.gov RI Tomic, Melanija/C-3371-2016; OI MORES, Nadia/0000-0002-4197-0914 NR 38 TC 30 Z9 33 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 2000 VL 141 IS 3 BP 1187 EP 1195 DI 10.1210/en.141.3.1187 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 337WH UT WOS:000088385700039 PM 10698196 ER PT J AU Mahato, D Goulding, EH Korach, KS Eddy, EM AF Mahato, D Goulding, EH Korach, KS Eddy, EM TI Spermatogenic cells do not require estrogen receptor-alpha for development or function SO ENDOCRINOLOGY LA English DT Article ID MESSENGER-RIBONUCLEIC-ACID; REPRODUCTIVE-TRACT; WILD-TYPE; BETA EXPRESSION; MICE LACKING; ER-ALPHA; MOUSE; TRANSPLANTATION; TESTIS; AROMATASE AB Estrogen receptors alpha (ER alpha) and beta (ER beta) are ligand-dependent transcription factors and members of the nuclear hormone receptor superfamily encoded by separate genes. Male mice homozygous for a mutation in the gene encoding ER alpha are infertile. To determine whether germ cells or somatic cells require ER alpha, germ cells were transplanted from donor males homozygous for the mutation (ER alpha(-/-)) to testes of wild-type (ER alpha(+/+)) recipient mice depleted of germ cells. The recipients served as "surrogate fathers" for the infertile ER alpha(-/-) males. When mated to wild-type females, the recipients sired offspring heterozygous for the mutation (ER alpha(+/-)) and carrying the coat-color marker of the ER alpha(-/-) donor mice. These studies show that male germ cells do not require ER alpha for development or to function in fertilization, and imply that male ER alpha(-/-) mice are infertile due to disruption of estrogen action within somatic cells of the male reproductive system. C1 NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Mahato, D (reprint author), NIEHS, Reprod & Dev Toxicol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM mahato@niehs.nih.gov OI Korach, Kenneth/0000-0002-7765-418X NR 32 TC 92 Z9 103 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 2000 VL 141 IS 3 BP 1273 EP 1276 DI 10.1210/en.141.3.1273 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 337WH UT WOS:000088385700049 PM 10698205 ER PT J AU Stratakis, CA Chrousos, GP AF Stratakis, CA Chrousos, GP TI Adrenal cancer SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Article ID HUMAN ADRENOCORTICAL NEOPLASMS; FAMILIAL ADENOMATOUS POLYPOSIS; PRECLINICAL CUSHINGS-SYNDROME; BECKWITH-WIEDEMANN SYNDROME; CARCINOMA CELL-LINE; P53 MUTATIONS; CORTICAL CARCINOMA; ONCOGENIC MUTATIONS; RECEPTOR GENE; NO EVIDENCE AB Adrenal cancer is a rare neoplasm. Up to 1 in 1500 adrenal incidentalomas, however, may hide a carcinoma, which, if diagnosed late or left untreated, is associated with significant morbidity and mortality. Despite extensive investigation of the molecular mechanisms involved in adrenal carcinogenesis and significant improvements in diagnostic imaging, efforts to cure advanced adrenal cancer remain largely unsuccessful. This article reviews the recent advances in molecular understanding, clinical diagnosis, and treatment of adrenal cancer. C1 Georgetown Univ, Sch Med, Dept Pediat, Div Pediat Endocrinol, Washington, DC 20007 USA. Georgetown Univ, Sch Med, Dept Pediat, Dept Genet, Washington, DC 20007 USA. NICHHD, Unit Genet & Endocrinol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIH, Interinst Pediat Endocrinol Training Program, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), NICHD, Unit Genet & Endocrinol, SPE, DEB,NIH, Bldg 10,Room 10N262,10 Ctr Dr MSC1862, Bethesda, MD 20892 USA. NR 82 TC 16 Z9 18 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 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD MAR PY 2000 VL 29 IS 1 BP 15 EP + DI 10.1016/S0889-8529(05)70113-4 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 292WR UT WOS:000085818700003 PM 10732261 ER PT J AU Goehl, TJ AF Goehl, TJ TI Reviews in environmental health, 2000 SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Goehl, TJ (reprint author), Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 2000 VL 108 SU 1 BP 3 EP 4 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 293MA UT WOS:000085854600002 PM 10698718 ER PT J AU Hoppin, JA Aro, A Hu, H Ryan, PB AF Hoppin, JA Aro, A Hu, H Ryan, PB TI Measurement variability associated with KXRF bone lead measurement in young adults SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE bone; cadavers; K X-ray fluorescence (KXRF); lead; young adults ID X-RAY-FLUORESCENCE; IN-VIVO; CHILDHOOD; EXPOSURE; TEENAGERS; CHILDREN; SKELETON AB In vivo bone lead measurement using K X-ray fluorescence (KXRF) has been used to estimate long-term lead exposure, especially in adults. Relatively few studies have been conducted on young subjects with this technique. To explore the measurement variability of KXRF bone lead measurements in young subjects, the tibiae of two male cadavers from Boston, Massachusetts, 17 and 20 years of age, were obtained for repeated bone lead measurements. Bone lead concentrations were measured using a grid of nine locations, 1 cm apart, centered at the midpoint of the tibia. Each location was sampled using five 60-min measurements. Measured concentrations ranged from < 0 to 11.8 mu g Pb/g bone mineral across a tibia with mean concentrations for the midpoint locations of 0.8 mu g Pb/g bone mineral SD = 2.5 and 2.0 mu g Pb/g bone mineral (SD = 1.9) for the left and right legs of the younger subject and 3.6 mu g Pb/g bone mineral (SD = 2.6) and 6.0 mu g Pb/g bone mineral (SD = 3.3) for the left and right legs of the older subject. Although bone lead concentrations did not vary significantly by measurement location in an individual leg, reported measurement uncertainty increased significantly at locations that were 1 cm from the center of the tibia horizontally (p < 0.0001). Symmetry in bone lead concentration between legs was observed for the 17-year-old subject. Potential asymmetry between the left and right legs was suggested for the 20-year-old subject (p = 0.06). These data describe the degree of variability that may be associated with bone lead measurements of young subjects with low bone lead concentrations using a standard spot-source KXRF instrument. Because of the importance of conducting additional research on adolescent lead toxicity, further improvements to the precision of KXRF measurement are needed. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA USA. RP Hoppin, JA (reprint author), NIEHS, Epidemiol Branch, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. EM hoppin1@niehs.nih.gov RI Ryan, P. Barry/A-7662-2009; OI Hu, Howard/0000-0002-3676-2707 NR 24 TC 0 Z9 0 U1 0 U2 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 2000 VL 108 IS 3 BP 239 EP 242 DI 10.2307/3454440 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 296NX UT WOS:000086031400033 ER PT J AU Gnagy, S Ming, EE Devesa, SS Hartge, P Whittemore, AS AF Gnagy, S Ming, EE Devesa, SS Hartge, P Whittemore, AS TI Declining ovarian cancer rates in US women in relation to parity and oral contraceptive use SO EPIDEMIOLOGY LA English DT Article DE oral contraceptive use; ovarian neoplasms; parity; time trends; menopause ID UNITED-STATES; TRENDS AB Ovarian cancer incidence and mortality rates have declined among U.S. women age 35-59 years during the period 1970-1995. Epidemiologic studies have shown that ovarian cancer risk decreases with increasing parity and increasing duration of oral contraceptive use. During this period, parity has declined while oral contraceptive use has increased. We compared temporal trends in observed ovarian cancer incidence rates with rates predicted by changes in parity and duration of oral contraceptive use to determine whether the changes in these characteristics could explain the declining rates in younger women. In addition, we wished to examine whether oral contraceptive use continues to be protective to postmenopausal women. To predict changes in rates between 1970 and 1995, we assumed that increases in parity and duration of oral contraceptive use induce proportional decreases in incidence rates. We found that the rates predicted by these assumptions agreed well with observed rates in young women (age 30-49) but were substantially lower than observed rates in older women (age 50-64). The data indicate that the relative decrease in incidence rates due to the protective effect of oral contraceptive use declines with age. C1 Stanford Univ, Med Ctr, Sch Med, Div Epidemiol,Dept Hlth Res & Policy, Stanford, CA 94305 USA. NCI, Epidemiol & Biostat Program, Div Canc Etiol, Rockville, MD USA. RP Whittemore, AS (reprint author), Stanford Univ, Med Ctr, Sch Med, Div Epidemiol,Dept Hlth Res & Policy, Redwood Bldg,Room T204, Stanford, CA 94305 USA. FU NCI NIH HHS [R35-CA47448] NR 13 TC 42 Z9 45 U1 2 U2 5 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 2000 VL 11 IS 2 BP 102 EP 105 DI 10.1097/00001648-200003000-00004 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 286WW UT WOS:000085472700004 PM 11021604 ER PT J AU Tarone, RE Chu, KC Brawley, OW AF Tarone, RE Chu, KC Brawley, OW TI Implications of stage-specific survival rates in assessing recent declines in prostate cancer mortality rates SO EPIDEMIOLOGY LA English DT Article DE mortality; prostate neoplasms; survival; time trends; tumor staging; race ID UNITED-STATES; TRENDS; CARCINOMA; EPIDEMIOLOGY AB It has been noted that the most important evidence for a benefit of early detection of prostate cancer using prostate specific antigen (PSA) testing would be a decline in prostate cancer mortality rates to levels below those existing before diagnostic use of PSA testing. We document a decrease in U.S. prostate cancer mortality rates in white men less than 85 years of age to levels below those existing in 1986, the year use of PSA testing was approved. In fact, for men 60-79 yeats of age, prostate cancer mortality rates were lower in 1997 than in any year since 1950. Although it has been argued that the decrease in prostate cancer mortality rates began too soon to be explained by PSA testing, stage-specific survival rates indicate that a rapid decrease in mortality may be explained by the large number of high-grade prostate cancers detected before metastasis. If recent decreases in U.S. prostate cancer mortality rates are due to early detection using PSA testing, randomized clinical trials investigating PSA testing will show early evidence of a mortality benefit. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Off Special Populat Res, Bethesda, MD 20892 USA. RP Tarone, RE (reprint author), NCI, Div Canc Epidemiol & Genet, EPS 8022, Bethesda, MD 20892 USA. NR 16 TC 90 Z9 91 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 2000 VL 11 IS 2 BP 167 EP 170 DI 10.1097/00001648-200003000-00014 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 286WW UT WOS:000085472700014 PM 11021614 ER PT J AU Hatch, EE Kleinerman, RA Linet, MS Tarone, RE Kaune, WT Auvinen, A Baris, D Robison, LL Wacholder, S AF Hatch, EE Kleinerman, RA Linet, MS Tarone, RE Kaune, WT Auvinen, A Baris, D Robison, LL Wacholder, S TI Do confounding or selection factors of residential wiring codes and magnetic fields distort findings of electromagnetic fields studies? SO EPIDEMIOLOGY LA English DT Article DE selection bias; confounding; magnetic fields; wire codes; childhood leukemia; case-control studies ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CHILDHOOD-CANCER; WIRE CODES; EXPOSURE; NONRESPONDENTS; RESPONDENTS; ASSOCIATION AB In contrast with several previous studies, our recent large case-control study found little association between childhood acute lymphoblastic leukemia (ALL) and electric-power-line wire codes. Here we examine internal evidence from our study to assess the possibility that selection bias and/or confounding may have affected the findings. We compared the relation between childhood ALL and wire codes and direct measurements of magnetic fields in subjects who participated in all phases of the study with the relation in all subjects, including those who declined to allow access inside the home. We found that the odds ratio for ALL among those living in homes with very high current configurations increased by 23% when 107 "partial participants" were excluded. We found similar, but slightly smaller, increases in the odds ratios when we performed the same comparisons using direct measurements of magnetic fields, excluding subjects who allowed only a measurement outside the front door. "Partial participants" tended to be characterized by lower socioeconomic status than subjects who participated fully, suggesting possible selection bias. We also examined the relation between a large number of potential confounding variables and both proxy and direct measurements of magnetic fields. Univariate adjustment for individual variables changed the odds ratio for ALL by less than 8%, while simultaneous adjustment for several factors reduced the estimate by a maximum of 15%. We conclude that while confounding alone is unlikely to be an important source of bias in our own and previous studies of magnetic fields, selection bias may be more of a concern, particularly in light of the generally low response rates among controls in case-control studies. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM Factors, Richland, WA USA. Univ Minnesota, Div Pediat Epidemiol & Clin Res, Minneapolis, MN USA. RP Hatch, EE (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Bethesda, MD 20892 USA. OI Kleinerman, Ruth/0000-0001-7415-2478; Auvinen, Anssi/0000-0003-1125-4818 FU NCI NIH HHS [R01-CA4805, U10-CA13539] NR 20 TC 45 Z9 46 U1 0 U2 3 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 2000 VL 11 IS 2 BP 189 EP 198 DI 10.1097/00001648-200003000-00019 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 286WW UT WOS:000085472700019 PM 11021619 ER PT J AU Harty, TP Rogawski, MA AF Harty, TP Rogawski, MA TI Felbamate block of recombinant N-methyl-D-aspartate receptors: selectivity for the NR2B subunit SO EPILEPSY RESEARCH LA English DT Article DE felbamate; NMDA receptor; NR2 subunit; voltage-clamp recording ID NMDA RECEPTORS; RAT-BRAIN; IN-VITRO; ANTICONVULSANT; ANTAGONIST; GLYCINE; HALOPERIDOL; POTENT; ACID; SENSITIVITY AB The anticonvulsant felbamate blocks N-methyl-D-asparate (NMDA) receptors but fails to exhibit the neurobehavioral toxicity characteristic of other NMDA receptor antagonists. To investigate the possibility that felbamate's favorable toxicity profile could be related to NMDA receptor subtype selectivity, we examined the specificity of felbamate block of recombinant NMDA. receptors composed of the NR1a subunit and various NR2 subunits. Felbamate produced a rapid, concentration-dependent block of currents evoked by 50 mu M NMDA and 10 mu M glycine in human embryonic kidney 293 cells expressing the rat NR1a subunit, and either the NR2A, NR2B or NR2C subunits; the IC50 values for block were 2.6, 0.52 and 2.4 mM, respectively (holding potential, - 60 mV). The Hill coefficient values were < 1 and, in kinetic analyses, onset and recovery from block were well fit by double exponential functions, indicating binding to more than one blocking site on the NMDA receptor channel complex. The higher affinity of felbamate block of NMDA receptors containing the NR2B subunit could be accounted for by more rapid association and slower dissociation from these sites. We conclude that felbamate exhibits modest selectivity for NMDA receptors composed of NR1a/NR2B subunits. This selectivity could, in part, account for the more favorable clinical profile of felbamate in comparison with NMDA receptor antagonists that do not show subunit selectivity. (C) 2000 Elsevier Science B.V. All rights reserved. C1 NINDS, Neuronal Excitabil Sect, Epilepsy Res Branch, NIH, Bethesda, MD 20892 USA. RP Rogawski, MA (reprint author), NINDS, Neuronal Excitabil Sect, Epilepsy Res Branch, NIH, Bldg 10,Room 5N-250,10 Ctr Dr,MSC 1408, Bethesda, MD 20892 USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 38 TC 55 Z9 56 U1 0 U2 1 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 2000 VL 39 IS 1 BP 47 EP 55 DI 10.1016/S0920-1211(99)00108-4 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 281WC UT WOS:000085183600006 PM 10690753 ER PT J AU Avliyakulov, NK Lukes, J Kajava, AV Liedberg, B Lundstrom, I Svensson, SPS AF Avliyakulov, NK Lukes, J Kajava, AV Liedberg, B Lundstrom, I Svensson, SPS TI Suramin blocks nucleotide triphosphate binding to ribosomal protein L3 from Trypanoplasma borreli SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE nucleotide triphosphate; Kinetoplastida; ribosome; L3 protein; suramin ID ESCHERICHIA-COLI; TRYPANOSOMA-BRUCEI; ELONGATION-FACTORS; EF-G; RNA; SITE; TRANSLATION; GENERATION; SUBUNIT; ATPASE AB Ribosomal protein L3 (L3) has been demonstrated to participate in formation of the peptidyltransferase center and is essential for its catalytic activity. In the present study we show that L3 is able to bind nucleotide triphosphates with high and specific affinity in vitro. L3 was serendipitously identified by screening of a genomic phage library from a primitive kinetoplastid flagellate Trypanoplasma borreli with the ATPase domain of the topoisomerase II gene as a probe. The cloned gene was overexpressed and purified as a his-tag fusion protein in E. coli. Radioligand binding experiments, using [gamma-S-35]ATP, showed that L3 is able to bind ATP but also GTP and UTP with similar high affinity (IC50 50-100 nm), while it has no ATPase activity. Furthermore, we showed that L3 has more than 500-fold higher affinity for nucleotide triphosphates compared to the corresponding nucleotide monophosphates and diphosphates. Molecular genetic and biochemical analyses allowed us to localize the NTP binding domain of L3 to the N-terminal 296 residues. Suramin, a polysulfonated naphthylamine derivative of urea, known for its chemotherapeutic effects completely inhibited the binding of [gamma-S-35]ATP at subclinical levels. Results obtained with surface plasmon resonance technology showed that suramin both forms weak multimolecular complexes with L3 and binds strongly to L3 in nearly stoichiometric amounts. C1 Linkoping Univ, Fac Hlth Sci, Dept Pharmacol, SE-58185 Linkoping, Sweden. Linkoping Univ, Dept Appl Phys, SE-58185 Linkoping, Sweden. Acad Sci Czech Republ, Inst Parasitol, CR-37005 Ceske Budejovice, Czech Republic. Univ S Bohemia, Fac Biol, Ceske Budejovice, Czech Republic. NIH, Ctr Mol Modeling, CIT, Bethesda, MD 20892 USA. RP Svensson, SPS (reprint author), Linkoping Univ, Fac Hlth Sci, Dept Pharmacol, SE-58185 Linkoping, Sweden. RI Lukes, Julius/H-6760-2012; Kajava, Andrey/E-1107-2014; Liedberg, Bo/N-6093-2014 OI Lukes, Julius/0000-0002-0578-6618; Kajava, Andrey/0000-0002-2342-6886; NR 50 TC 6 Z9 6 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD MAR PY 2000 VL 267 IS 6 BP 1723 EP 1731 DI 10.1046/j.1432-1327.2000.01169.x PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 299TB UT WOS:000086213000022 PM 10712604 ER PT J AU Giuliani, C Napolitano, G Mastino, A Di Vincenzo, S D'Agostini, C Grelli, S Bucci, I Singer, DS Kohn, LD Monaco, F Garaci, E Favalli, C AF Giuliani, C Napolitano, G Mastino, A Di Vincenzo, S D'Agostini, C Grelli, S Bucci, I Singer, DS Kohn, LD Monaco, F Garaci, E Favalli, C TI Thymosin-alpha 1 regulates MHC class I expression in FRTL-5 cells at transcriptional level SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE MHC class I; thymic factor; NF-kappa B; immunomodulators; gene regulation ID INTERLEUKIN-2 RECEPTOR EXPRESSION; LEWIS LUNG-CARCINOMA; CHRONIC HEPATITIS-B; NF-KAPPA-B; GENE-EXPRESSION; LYMPHOBLASTOID INTERFERON; THYMIC HORMONES; ENHANCER-A; MODULATION; CYCLOPHOSPHAMIDE AB In this study we examined the effect of the synthetic peptide thymosin-alpha 1 (T alpha 1) on MHC class I expression in FRTL-5 cells. Treatment with T alpha 1 increased expression of MHC class I surface molecules and mRNA, which reached its peak (153 +/- 8% of the control value) after 12 h. Chloramphenicol acetyltransferase (CAT) analysis, following transfection with a plasmid containing the regulatory sequence of MHC class I (or its deletion derivatives) with the CAT reporter gene, and electrophoretic mobility shift assay experiments demonstrated that the action of T alpha 1 was at the transcriptional level, and its mechanism of action is likely due to increased binding between the complex p50/fra-2 and the enhancer A sequence of the 5' flanking region of a swine class 1 gene (PD1). An increase in the expression of MHC class 1 surface molecules was also observed by flow cytometry in murine and human tumor cell lines and in primary cultures of human macrophages, This study shows for the first time an effect of T alpha 1 on the regulation of gene expression at the molecular level, and may further contribute to explaining the results obtained using T alpha 1 in the control of infectious diseases and tumor growth. C1 Univ Roma Tor Vergata, Dept Expt Med & Biochem Sci, I-00133 Rome, Italy. Univ Chieti, Chair Endocrinol, Chieti, Italy. Univ Messina, Fac Sci, Inst Microbiol, Messina, Italy. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Favalli, C (reprint author), Univ Roma Tor Vergata, Dept Expt Med & Biochem Sci, Via Tor Vergata 135, I-00133 Rome, Italy. RI Mastino, Antonio/A-4686-2008 NR 29 TC 54 Z9 68 U1 0 U2 2 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 2000 VL 30 IS 3 BP 778 EP 786 DI 10.1002/1521-4141(200003)30:3<778::AID-IMMU778>3.3.CO;2-9 PG 9 WC Immunology SC Immunology GA 292DV UT WOS:000085779600007 PM 10741392 ER PT J AU Juhaszova, M Church, P Blaustein, MP Stanley, EF AF Juhaszova, M Church, P Blaustein, MP Stanley, EF TI Location of calcium transporters at presynaptic terminals SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE chick; immunocytochemistry; Na+/Ca2+ exchanger; plasma membrane ATP-driven Ca2+ pump; transmitter release site ID SQUID GIANT SYNAPSE; PLASMA-MEMBRANE; TRANSMITTER RELEASE; ACETYLCHOLINE-RELEASE; NA+-CA2+ EXCHANGER; NA+/CA2+ EXCHANGER; KINETIC-PROPERTIES; CA2+ TRANSPORT; SMOOTH-MUSCLE; VESICLES AB The plasma membrane ATP-driven Ca2+ pump (PMCA) and the Na+/Ca2+ exchanger (NCX) are the major means of Ca2+ extrusion at presynaptic nerve terminals, but little is know about the location of these transporters relative to the major sites of Ca2+ influx, the transmitter release sites. We used immunocytochemistry to identify these transport proteins in a calyx-type presynaptic nerve terminal from the ciliary ganglion of the chick. The PMCA clusters were localized to the transmitter release sites, as identified by staining for the secretory vesicle-specific protein synaptotagmin I. This colocalization was not due to the presence of the pump on the secretory vesicle itself because membrane fractionation of chick brain synaptosomes demonstrated comigration of the pump with surface membrane and not vesicle markers. In contrast, the NCX did not colocalize with synaptotagmin but tended to be located at nonsynaptic regions of the terminal. The PMCA location, near the transmitter release sites, suggests that it plays a role in priming the release site by maintaining a low free Ca2+ level, facilitating the dissociation of the ion from its binding sites. The PMCA may also replenish external Ca2+ in the synaptic cleft following periods of synaptic activity. In contrast, the NCX location suggests a role in the rapid emptying of cytoplasmic Ca2+ uptake organelles which serve as the main line of defence against high free Ca2+. C1 Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. NINDS, Synapt Mech Sect, Bethesda, MD 20892 USA. RP Blaustein, MP (reprint author), Univ Maryland, Sch Med, Dept Physiol, 655 W Baltimore St, Baltimore, MD 21201 USA. FU NINDS NIH HHS [NS16106] NR 56 TC 67 Z9 68 U1 0 U2 0 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 2000 VL 12 IS 3 BP 839 EP 846 DI 10.1046/j.1460-9568.2000.00974.x PG 8 WC Neurosciences SC Neurosciences & Neurology GA 300NH UT WOS:000086258700007 PM 10762313 ER PT J AU Arking, R Burde, V Graves, K Hari, R Feldman, E Zeevi, A Soliman, S Saraiya, A Buck, S Vettraino, J Sathrasala, K Wehr, N Levine, RL AF Arking, R Burde, V Graves, K Hari, R Feldman, E Zeevi, A Soliman, S Saraiya, A Buck, S Vettraino, J Sathrasala, K Wehr, N Levine, RL TI Forward and reverse selection for longevity in Drosophila is characterized by alteration of antioxidant gene expression and oxidative damage patterns SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE longevity; gene expression; Drosophila; antioxidant genes; oxidative damage; catalase; CuZnSOD; MnSOD; selection ID LONG-LIVED STRAIN; EXTENDED LONGEVITY; LIFE-SPAN; SUPEROXIDE-DISMUTASE; STRESS RESISTANCE; MELANOGASTER; PROTEIN; OVEREXPRESSION; HYPOTHESIS; SENESCENCE AB Patterns of antioxidant gene expression and of oxidative damage were measured throughout the adult life span of a selected long-lived strain (La) of Drosophila melanogaster and compared to that of their normal-lived progenitor strain (Ra). Extended longevity in the La strain is correlated with enhanced antioxidant defense system gene expression, accumulation of CuZnSOD protein, and an increase in ADS enzyme activities. Extended longevity is strongly associated with a significantly increased resistance to oxidative stress. Reverse-selecting this long-lived strain for shortened longevity (RevLa strain) yields a significant decrease in longevity accompanied by reversion to normal levels of its antioxidant defense system gene expression patterns and antioxidant enzyme patterns. The significant effects of forward and reverse selection in these strains seem limited to the ADS enzymes; 11 other enzymes with primarily metabolic functions show no obvious effect of selection on their activity levels whereas six other enzymes postulated to play a role in flux control may actually be involved in NADPH reoxidation and thus support the enhanced activities of the ADS enzymes. Thus, alterations in the longevity of these Drosophila strains are directly correlated with corresponding alterations in; 1) the mRNA levels of certain antioxidant defense system genes; 2) the protein level of at least one antioxidant defense system gene; 3) the activity levels of the corresponding antioxidant defense system enzymes, and 4) the ability of the organism to resist the histological damage arising from oxidative stress. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Wayne State Univ, Dept Biol Sci, Detroit, MI 48202 USA. NHLBI, Biochem Lab, Bethesda, MD 20892 USA. RP Arking, R (reprint author), Wayne State Univ, Dept Biol Sci, Detroit, MI 48202 USA. RI Levine, Rodney/D-9885-2011 NR 50 TC 82 Z9 84 U1 0 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD MAR PY 2000 VL 35 IS 2 BP 167 EP 185 DI 10.1016/S0531-5565(99)00094-7 PG 19 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 305EG UT WOS:000086526000005 PM 10767577 ER PT J AU Dayan, M Segal, R Globerson, A Habut, B Shearer, GM Mozes, E AF Dayan, M Segal, R Globerson, A Habut, B Shearer, GM Mozes, E TI Effect of aging on cytokine production in normal and experimental systemic lupus erythematosus-afflicted mice SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE experimental systemic lupus erythematosus (SLE); aging; cytokine profile ID AGE-RELATED-CHANGES; ANTI-DNA IDIOTYPE; T-LYMPHOCYTES; INDUCTION; SEX; MANIFESTATIONS; INVOLVEMENT; DISEASE; CELLS; SLE AB Aging mice of strains susceptible to the induction of experimental systemic lupus erythematosus (SLE) develop a milder disease than young animals. To find out whether the decrease in susceptibility to disease is due to age-associated changes in cytokine profile, we first examined the secretion of cytokines by healthy mice aged 2-15 months. A gradual age-related decline in the levels of interleukin (IL)-2 and interferon (IFN) gamma, and an increase in IL-4, IL-10, IL-1, and tumor necrosis factor (TNF) alpha were observed. Experimental SLE was induced in 2- and 10-month-old mice by immunization with the monoclonal anti-DNA antibody bearing the 16/6 Id. Early increased production of pro-inflammatory cytokines (TNF alpha and IL-l), followed by a peak of the Th1-type cytokines (IL-2, IFN gamma) were observed in young mice. The Th2-type cytokines (IL-4, IL-10) peaked later. In contrast, only a mild increase in all of the above cytokines was determined in 10-month immunized mice. It thus appears that the decline in susceptibility to SLE induction in older mice may be related to changes in the capacity to produce cytokines. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel. Shmuel Harofeh Geriatr Ctr, Beer Yaakov, Israel. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Segal, R (reprint author), Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel. NR 27 TC 24 Z9 25 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD MAR PY 2000 VL 35 IS 2 BP 225 EP 236 DI 10.1016/S0531-5565(00)00076-0 PG 12 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 305EG UT WOS:000086526000009 PM 10767581 ER PT J AU Aguilera, G Rabadan-Diehl, C AF Aguilera, G Rabadan-Diehl, C TI Regulation of vasopressin V-1b receptors in the anterior pituitary gland of the rat SO EXPERIMENTAL PHYSIOLOGY LA English DT Article; Proceedings Paper CT 1999 World Congress on Neurohypophysial Hormones CY 1999 CL EDINBURGH, SCOTLAND SP British Neuroendocrine Grp, Physiol Soc, Soc Endocrinol, Blackwell Sci Ltd, Ferring Pharmaceut, Glenkinchie Distillery, Organon, Parke Davis, Smithkline Beecham ID MESSENGER-RIBONUCLEIC-ACID; CHROMOSOMAL LOCALIZATION; ARGININE VASOPRESSIN; MOLECULAR-CLONING; CHRONIC STRESS; EXPRESSION; GENE; SECRETION; ADRENOCORTICOTROPIN; GLUCOCORTICOIDS AB Vasopressin secreted by parvocellular neurones of the hypothalamic paraventricular nucleus modulates pituitary adrenocorticotrophic hormone (ACTH) secretion by acting upon vasopressin V-1b type receptors in the pituitary corticotroph coupled to phospholipase C. Regulation of V-1b receptors contributes to the adaptation of the hypothalamic-pituitary-adrenal (HPA) axis to stress, as evidenced by the correlation between vasopressin receptor number and pituitary ACTH responsiveness. V-1b receptor upregulation during chronic stress is associated with elevated circulating glucocorticoids and vasopressin expression in parvocellular neurones, suggesting that these factors control V-1b receptor expression. Removal of circulating glucocorticoids by adrenalectomy causes sustained vasopressin receptor downregulation, but reduces V-1b receptor mRNA only transiently. The latter effect is not mediated by increased corticotrophin-releasing hormone (CRH) and vasopressin release, since it is not prevented by lesions of the hypothalamic paraventricular nucleus. Adrenalectomy causes sustained V-1b receptor loss in Brattleboro rats, which lack hypothalamic vasopressin, suggesting that vasopressin mediates V-1b receptor mRNA recovery. Exogenous glucocorticoid administration downregulates pituitary vasopressin binding but increases V-1b receptor mRNA and facilitates coupling of the receptor to phospholipase C, effects which may contribute to the refractoriness of vasopressin actions to glucocorticoid feedback. The lack of parallelism between changes in pituitary vasopressin binding and V-1b receptor mRNA levels during manipulation of the HPA axis indicates that V-1b receptor content depends on post-transcriptional mechanisms rather than steady-state V-1b receptor mRNA levels. These studies suggest that interaction between glucocorticoids and vasopressin plays an important role in regulating V-1b receptor mRNA expression during alterations of the HPA axis. In addition, the recent characterization of a major part of the V-1b receptor gene provides a basis for studying the molecular mechanisms regulating the V-1b receptor. C1 NICHHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Aguilera, G (reprint author), NICHHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NR 47 TC 20 Z9 20 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0958-0670 J9 EXP PHYSIOL JI Exp. Physiol. PD MAR PY 2000 VL 85 SI SI BP 19S EP 26S DI 10.1111/j.1469-445X.2000.tb00004.x PG 8 WC Physiology SC Physiology GA 306CY UT WOS:000086580000004 PM 10795903 ER PT J AU Ristori, G Salvetti, M Pesole, G Attimonelli, M Buttinelli, C Martin, R Riccio, P AF Ristori, G Salvetti, M Pesole, G Attimonelli, M Buttinelli, C Martin, R Riccio, P TI Compositional bias and mimicry toward the nonself proteome in immunodominant T cell epitopes of self and nonself antigens SO FASEB JOURNAL LA English DT Article DE T lymphocytes; tolerance; molecular mimicry; immunogenicity; vaccine design ID MYELIN BASIC-PROTEIN; MAJOR HISTOCOMPATIBILITY COMPLEX; C VIRUS-ANTIGENS; MULTIPLE-SCLEROSIS; MOLECULAR MIMICRY; POSITIVE SELECTION; INNATE IMMUNITY; CYTOCHROME-C; RECOGNITION; SEQUENCE AB We investigated whether and how molecular mimicry affects the shaping of the helper T cell repertoire. We implemented an algorithm that measures the probability of mimicry between epitopes of known immunogenicity and self or nonself proteomes. This algorithm yields 'similarity profiles', which represent the probability of matching between all contiguous overlapping peptides of the antigen under examination and those in the proteome(s) considered. Similarity profiles between helper T cell epitopes (of self or microbial antigens and allergens) and human or microbial SWISSPROT collections were produced. For each antigen, both collections yielded largely overlapping profiles, demonstrating that self-nonself discrimination does not rely on qualitative features that distinguish human from microbial peptides. However, epitopes whose probability of mimicry with self or nonself prevails are, respectively, tolerated or immunodominant and coexist within the same (auto-)antigen regardless of its self/nonself nature. Epitopes ton self and nonself antigens) can cross-stimulate T cells at increasing potency as their similarity with nonself augments. Mimicry, rather than complicating self-nonself discrimination, assists in the shaping of the immune repertoire and helps define the defensive or autoreactive potential of a T cell. Being a predictor of epitope immunogenicity, it bears relevance to vaccine design. C1 Univ La Sapienza, Dipartimento Sci Neurol, I-00185 Rome, Italy. Univ Basilicata, Dipartimento Biol DBAF, I-85100 Potenza, Italy. Univ Bari, Dip Biochim & Biol Mol, Bari, Italy. NINCDS, Cellular Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Salvetti, M (reprint author), Univ La Sapienza, Dipartimento Sci Neurol, V Univ 30, I-00185 Rome, Italy. RI Pesole, Graziano/C-1408-2009; Pesole, Graziano/E-9051-2014 OI Pesole, Graziano/0000-0003-3663-0859; Pesole, Graziano/0000-0003-3663-0859 NR 48 TC 18 Z9 18 U1 1 U2 2 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 2000 VL 14 IS 3 BP 431 EP 438 PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 291TJ UT WOS:000085751900001 PM 10698957 ER PT J AU Damjanovski, S Puzianowska-Kuznicka, M Ishuzuya-Oka, A Shi, YB AF Damjanovski, S Puzianowska-Kuznicka, M Ishuzuya-Oka, A Shi, YB TI Differential regulation of three thyroid hormone-responsive matrix metalloproteinase genes implicates distinct functions during frog embryogenesis SO FASEB JOURNAL LA English DT Article DE apoptosis; extracellular matrix; Xenopus laevis; morphogenesis; organogenesis ID EXTRACELLULAR-MATRIX; TRANSCRIPTIONAL ACTIVATION; XENOPUS-LAEVIS; CELL-DEATH; EXPRESSION; TAIL; METAMORPHOSIS; APOPTOSIS; MORPHOGENESIS; HYBRIDIZATION AB Matrix metalloproteinases (MMPs) are a family of Zn2+-dependent extracellular proteases capable of degrading various proteinaceous components of the extracellular matrix (ECM), They are expressed in developmental and pathological processes such as postlactation mammary gland involution and tumor metastasis, Relatively few studies have been carried out to investigate the function of MMPs during embryogenesis and postembryonic organ development. Using Xenopus development as a model system, we and others have previously isolated three MMP gems as thyroid hormone response genes, They have distinct temporal and organ-specific regulations during thyroid hormone-dependent metamorphosis, We demonstrate here that three MMPs-stromelysin-3 (ST3), collagenases-3 (Col3), and collagenases-4 (Col4)-also have distinct spatial and temporal expression profiles during embryogenesis, Consistent with earlier suggestions that ST3 is a direct thyroid hormone response gem whereas Col3 and Col4 are not, we show that precocious overexpression of thyroid hormone receptors in the presence of thyroid hormone lead to increased expression of ST3, but not Col3, Furthermore, our whole-mount in situ hybridizations reveal a tight but distinct association of individual MMPs with tissue remodeling in different regions of the animal during embryogenesis, These results suggest that ST3 is likely to play a role in ECM remodeling that facilitate apoptotic tissue remodeling or resorption, whereas Col3 and Col4 appear to participate in connective tissue degradation during development. C1 NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. Dokkyo Univ, Sch Med, Dept Histol & Neurobiol, Mibu, Tochigi 32102, Japan. RP Shi, YB (reprint author), NICHHD, Mol Embryol Lab, NIH, Bldg 18T,Rm 106, Bethesda, MD 20892 USA. RI Damjanovski, Sashko/N-8728-2015 NR 47 TC 31 Z9 31 U1 2 U2 6 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 2000 VL 14 IS 3 BP 503 EP 510 PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 291TJ UT WOS:000085751900009 PM 10698965 ER PT J AU Raviv, Y Puri, A Blumenthal, R AF Raviv, Y Puri, A Blumenthal, R TI P-glycoprotein-overexpressing multidrug-resistant cells are resistant to infection by enveloped viruses that enter via the plasma membrane SO FASEB JOURNAL LA English DT Article DE viral invasion; membrane fusion; photosensitized labeling; hydrophobic labeling ID VESICULAR STOMATITIS-VIRUS; BIOLOGICAL-MEMBRANES; CONFORMATIONAL-CHANGES; FUSION ACTIVITY; TRANSPORTER; PEPTIDES; HEMAGGLUTININ; FLUORESCENCE; PROTEINS AB The multidrug resistance gene product P-glycoprotein confers drug resistance to tumor cells by acting as a transporter that blocks: the entry into the cell of a great variety of drugs and hydrophobic pep tides. In this study we find that in drug-resistant cells, the insertion of the influenza virus fusion protein (hemagglutinin-2) into the plasma membrane is blocked and that the fusion of the viral envelope with the plasma membrane of these cells is impaired. Multidrug-resistant cells display significant resistance to infection by envelope viruses that invade cells by fusion with the plasma membrane, but not to infection by pH-dependent viruses that penetrate cells by fusion with endocytic vesicles, These observations suggest that multidrug resistance phenomena may protect cells from infection by a large group of disease-causing viruses that includes human immunodeficiency virus, herpes simplex virus, and some cancer-inducing retroviruses. C1 NCI, Intramural Res Support Program, SAIC Frederick,Lab Expt & Computat Biol, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Raviv, Y (reprint author), NCI, Intramural Res Support Program, SAIC Frederick,Lab Expt & Computat Biol, Frederick Canc Res & Dev Ctr, Bldg 469,Room 211, Frederick, MD 21702 USA. FU PHS HHS [N01-56000] NR 24 TC 20 Z9 20 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 PY 2000 VL 14 IS 3 BP 511 EP 515 PG 5 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 291TJ UT WOS:000085751900010 PM 10698966 ER PT J AU Lee, CGL Ramachandra, M Jeang, KT Martin, MA Pastan, I Gottesman, MM AF Lee, CGL Ramachandra, M Jeang, KT Martin, MA Pastan, I Gottesman, MM TI Effect of ABC transporters on HIV-1 infection: inhibition of virus production by the MDR1 transporter SO FASEB JOURNAL LA English DT Article DE ABC transporters; acquired immunodeficiency syndrome; AIDS; P-glycoprotein; virus entry ID BICISTRONIC EXPRESSION SYSTEM; MULTIDRUG TRANSPORTER; P-GLYCOPROTEIN; SALMONELLA-TYPHIMURIUM; OLIGOPEPTIDE PERMEASE; HYDROPHOBIC PEPTIDES; PROTEASE INHIBITORS; MAMMALIAN-CELLS; GENE; BINDING AB (3)The MDR1 multidrug transporter P-gp (P-glycoprotein) is an efflux pump that extrudes diverse hydrophobic drugs and peptides from cells. Since the entry of HIV-1 into cells involves an initial interaction of the viral gp41 hydrophobic peptide with the plasma membrane, a potential effect of P-gp on HIV-1 infectivity was explored. Virus production was greatly decreased when P-gp was overexpressed at the surface of a continuous CD4(+) human T-leukemic cell line (12D7) infected with HIV-1(NL4-3) a T-tropic molecular clone of HIV-1. P-gp overexpression did not significantly alter the surface expression or distribution of either the HIV-1 receptor CD4 or the coreceptor CXCR4. Reduction of HIV-1 infectivity in P-gp-expressing cells occurred both during the fusion of viral and plasma membranes and at subsequent step(s) in the HIV-1 life cycle. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 1A09,37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 28 TC 54 Z9 55 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 2000 VL 14 IS 3 BP 516 EP 522 PG 7 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 291TJ UT WOS:000085751900011 PM 10698967 ER PT J AU Gunther, MR Sturgeon, BE Mason, RP AF Gunther, MR Sturgeon, BE Mason, RP TI A long-lived tyrosyl radical from the reaction between horse metmyoglobin and hydrogen peroxide SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE myoglobin; electron spin resonance; spin trapping; tyrosine; free radicals ID ELECTRON-SPIN-RESONANCE; PHOTOSYSTEM-II; RIBONUCLEOTIDE REDUCTASE; MYOGLOBIN; SPECTROSCOPY; TRYPTOPHAN; OXIDATION; SPECTRUM; TRAP AB The reaction between metmyoglobin (metMb) and hydrogen peroxide has been known since the 1950s to produce globin-centered free radicals. The direct electron spin resonance spectrum of a solution of horse metMb and hydrogen peroxide at room temperature consists of a multilined signal that decays in minutes at room temperature. Comparison of the direct ESR spectra obtained from the system under N-2- and O-2-saturated conditions demonstrates the presence of a peroxyl radical, identified by its g-value of 2.014. Computer simulations of the spectra recorded 3 s after the mixture of metMb and H2O2 were calculated using hyperfine coupling constants of alpha(H2,6) = 1.3 G and alpha(H3,5) = 7.0 G for the ring and alpha(beta)(H1) = 16.7 G and alpha(beta)(H2) = 14.2 G for the methylene protons, and are consistent with a highly constrained, conformationally unstable tyrosyl radical. Spectra obtained at later time points contained a mixture of the 3 s signal and another signal that was insufficiently resolved for simulation. Efficient spin trapping with 3,5-dibromo-4-nitrosobenzenesulfonic acid was observed only when the spin trap was present at the time of H2O2 addition. Spin trapping experiments with either 5,5-dimethyl-1-pyrroline N-oxide (DMPO) or perdeuterated 2-methyl-2-nitrosopropane (MNP-d(9)), which have been shown to trap tyrosyl radicals, were nearly equally effective when the spin trap was added before or 10 min after the addition of H2O2. The superhyperfine structure of the ESR spectra obtained from Pronase-treated MNP-d(9)/.metMb confirmed the assignment to a tyrosyl radical. Delayed spin trapping experiments with site-directed mutant myoglobins in which either Tyr-103 or Tyr-146 was replaced by phenylalanine indicated that radical adduct formation with either DMPO or MNP-d(9) requires the presence of Tyr-103 at all time points, implicating that residue as the radical site. (C) 2000 Elsevier Science Inc. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Gunther, MR (reprint author), W Virginia Univ, Dept Biochem, POB 9142, Morgantown, WV 26506 USA. NR 29 TC 64 Z9 65 U1 0 U2 11 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 1 PY 2000 VL 28 IS 5 BP 709 EP 719 DI 10.1016/S0891-5849(00)00164-7 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 301EE UT WOS:000086295000007 PM 10754266 ER PT J AU Komarov, AM Wink, DA Feelisch, M Schmidt, HHHW AF Komarov, AM Wink, DA Feelisch, M Schmidt, HHHW TI Electron-paramagnetic resonance spectroscopy using N-methyl-D-glucamine dithiocarbamate iron cannot discriminate between nitric oxide and nitroxyl: Implications for the detection of reaction products for nitric oxide synthase SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE nitric oxide; nitroxyl; EPR; nitric oxide synthase; superoxide dismutase; free radical ID SUPEROXIDE-DISMUTASE; CENTER-DOT; GENERATION; COMPLEX AB Purified neuronal nitric oxide synthase (NOS) does not produce nitric oxide (NO) unless high concentrations of superoxide dismutase (SOD) are added, suggesting that nitroxyl (NO(-)) or a related molecule is the principal reaction product of NOS, which is SOD-dependently converted to NO. This hypothesis was questioned by experiments using electron paramagnetic resonance spectroscopy and iron N-methyl-D-glucamine dithiocarbamate (Fe-MGD) as a trap for NO. Although NOS and the NO donor S-nitroso-N-acetyl-penicillamine produced an electron paramagnetic resonance signal, the NO- donor, Angeli's salt (AS) did not. AS is a labile compound that rapidly hydrolyzes to nitrite, and important positive control experiments showing that AS was intact were lacking. On reinvestigating this crucial experiment, we find identical MGD(2)-Fe-NO complexes both from S-nitroso-N-acetyl-penicillamine and AS but not from nitrite. Moreover, the yield of MGD(2)-Fe-NO complex from AS was stoichiometric even in the absence of SOD. Thus, MGD(2)-Fe directly detects NO(-), and any conclusions drawn from MGD(2)-Fe-NO complexes with respect to the nature of the primary NOS product (NO, NO(-), or a related N-oxide) are invalid. Thus, NOS may form NO(-) or related N-oxides instead of NO. (C) 2000 Elsevier Science Inc. C1 Univ Wurzburg, Dept Pharmacol & Toxicol, Wurzburg, Germany. George Washington Univ, Med Ctr, Dept Physiol & Expt Med, Washington, DC 20037 USA. NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. UCL, Wolfson Inst Biomed Res, London, England. RP Schmidt, HHHW (reprint author), Univ Giessen, Rudolf Buchheim Inst Pharmakol, Frankfurter Str 107, D-35392 Giessen, Germany. EM harald.schmidt@pharma.med.uni-giessen.de RI Schmidt, Harald H. H. W./B-1549-2008; Feelisch, Martin/C-3042-2008 OI Schmidt, Harald H. H. W./0000-0003-0419-5549; Feelisch, Martin/0000-0003-2320-1158 NR 17 TC 33 Z9 35 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD MAR 1 PY 2000 VL 28 IS 5 BP 739 EP 742 DI 10.1016/S0891-5849(00)00156-8 PG 4 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 301EE UT WOS:000086295000010 PM 10754269 ER PT J AU Cardozo-Pelaez, F Brooks, PJ Stedeford, T Song, SJ Sanchez-Ramos, J AF Cardozo-Pelaez, F Brooks, PJ Stedeford, T Song, SJ Sanchez-Ramos, J TI DNA damage, repair, and antioxidant systems in brain regions: A correlative study SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE DNA damage; DNA repair; 8-hydroxy-2 '-deoxyguanosine; brain regions; oxyradicals; antioxidants; free radicals ID OXIDATIVE DAMAGE; PARKINSONS-DISEASE; PROTEIN OXIDATION; LIPID-PEROXIDATION; ALZHEIMERS-DISEASE; SUBSTANTIA-NIGRA; AGE; MITOCHONDRIA; CLONING; MOUSE AB 8-Hydroxy-2'-deoxyguanosine (oxo(8)dG) has been used as a marker of free radical damage to DNA and has been shown to accumulate during aging. Oxidative stress affects some brain regions more than others as demonstrated by regional differences in steady state oxo(8)dG levels in mouse brain. In our study, we have shown that regions such as the midbrain, caudate putamen, and hippocampus show high levels of oxo(8)dG in total DNA, although regions such as the cerebellum, cortex, and pens and medulla have lower levels. These regional differences in basal levels of DNA damage inversely correlate with the regional capacity to remove oxo(8)dG from DNA. Additionally, the activities of antioxidant enzymes (Cu/Zn superoxide dismutase, mitochondrial superoxide dismutase, and glutathione peroxidase) and the levels of the endogenous antioxidant glutathione are not predictors of the degree of free radical induced damage to DNA in different brain regions. Although each brain region has significant differences in antioxidant defenses, the capacity to excise the oxidized base from DNA seems to be the major determinant of the steady state levels of oxo(8)dG in each brain region. C1 Univ S Florida, Dept Neurol, Tampa, FL 33620 USA. Univ S Florida, James Haley Vet Affairs Res Serv, Tampa, FL 33620 USA. Univ S Florida, Coll Publ Hlth, Tampa, FL 33620 USA. NIAAA, NIH, Rockville, MD 20852 USA. RP Sanchez-Ramos, J (reprint author), Univ S Florida, Dept Neurol, MDC 55,12901 Bruce B Downs Blvd, Tampa, FL 33620 USA. RI Sanchez-Ramos, Juan/A-1188-2009 OI Sanchez-Ramos, Juan/0000-0002-3391-7857 NR 42 TC 98 Z9 100 U1 0 U2 2 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 1 PY 2000 VL 28 IS 5 BP 779 EP 785 DI 10.1016/S0891-5849(00)00172-6 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 301EE UT WOS:000086295000015 PM 10754274 ER PT J AU Salzer, R Steiner, G Mantsch, HH Mansfield, J Lewis, EN AF Salzer, R Steiner, G Mantsch, HH Mansfield, J Lewis, EN TI Infrared and Raman imaging of biological and biomimetic samples SO FRESENIUS JOURNAL OF ANALYTICAL CHEMISTRY LA English DT Review ID NEAR-IR SPECTROSCOPY; HUMAN BREAST-TISSUE; FT-IR; SECONDARY STRUCTURE; COMPONENT ANALYSIS; TUNABLE FILTER; SYSTEMS; SPECTRA; SPECTROMETER; MICROSCOPY AB Established methods for imaging of biological or biomimetic samples, such as fluorescence and optical microscopy, magnetic resonance imaging (MRI), X-ray tomography or positron emission tomography (PET) are currently complemented by infrared (both near-IR and mid-IR) as well as Raman spectroscopic imaging, whether it be on a microscopic or macroscopic scale. These vibrational spectroscopic techniques provide a wealth of information without a priori knowledge of either the spectral data or the composition of the sample. Infrared radiation does not harm the organism, no electric potential needs to be applied, and the measurements are not influenced by electromagnetic fields, in addition, no extrinsic labeling or staining, which may perturb the system under investigation, has to be added. The immense volume of information contained in spectroscopic images requires multivariate analysis methodologies in order to effectively mine the chemical and spatial information contained within the data as well as to analyze a time-series of images in order to reveal the origin of a chemical or biochemical process. The promise and limitations of this new analytical tool are surveyed in this review. C1 Tech Univ Dresden, Inst Analyt Chem, D-01062 Dresden, Germany. Natl Res Council Canada, Inst Biodiagnost, Winnipeg, MB R3B 1Y6, Canada. NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Tech Univ Dresden, Inst Analyt Chem, D-01062 Dresden, Germany. RI huang, hongqi/N-1473-2014 NR 54 TC 70 Z9 73 U1 2 U2 23 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0937-0633 J9 FRESEN J ANAL CHEM JI Fresenius J. Anal. Chem. PD MAR-APR PY 2000 VL 366 IS 6-7 BP 712 EP 726 DI 10.1007/s002160051565 PG 15 WC Chemistry, Analytical SC Chemistry GA 307PG UT WOS:000086661300020 PM 11225782 ER PT J AU Nanni, L Schelper, RL Muenke, M AF Nanni, L Schelper, RL Muenke, M TI Molecular genetics of holoprosencephaly SO FRONTIERS IN BIOSCIENCE LA English DT Article DE holoprosencephaly; forebrain development; Sonic Hedgehog; ZIC2; SIX3; nodal; TGIF; review ID LEMLI-OPITZ-SYNDROME; SONIC-HEDGEHOG GENE; MURINE HOMEOBOX GENE; CRITICAL REGION; RETINOIC ACID; FOREBRAIN DEVELOPMENT; REDUCTASE GENE; NEURAL-TUBE; MUTATIONS; DROSOPHILA AB Holoprosencephaly (HPE) is a common developmental defect of the human forebrain and midface. Pathological studies have identified different categories of severity of the brain and craniofacial malformations observed in HPE, although the variable clinical spectrum of HPE extends in unbroken sequence from alobar HPE and cyclopia to clinically unaffected carriers in familial HPE. The etiology of HPE is extremely heterogeneous including both environmental and genetic causes. Here we focus on molecular aspects of HPE in light of the recent identification of some of the genes causing human HPE and other candidate genes involved in forebrain development, through different approaches, such as positional cloning and functional cloning, based on animal models. These approaches will aid in the identification of additional genes involved in HPE and in a better understanding of the molecular genetics of brain development. C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. SUNY Hlth Sci Ctr, Dept Pathol, Syracuse, NY 13210 USA. RP Muenke, M (reprint author), NHGRI, Med Genet Branch, NIH, 10 Ctr Dr,MSC 1852,Bldg 10,10C101, Bethesda, MD 20892 USA. FU NICHD NIH HHS [HD29862, HD28732] NR 83 TC 14 Z9 14 U1 0 U2 1 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD MAR 1 PY 2000 VL 5 BP D334 EP D342 DI 10.2741/Nanni PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 343KT UT WOS:000088702100006 PM 10704430 ER PT J AU Stratakis, CA AF Stratakis, CA TI Genetics of Carney complex and related familial lentiginoses, and other multiple tumor syndromes SO FRONTIERS IN BIOSCIENCE LA English DT Review DE lentigenes; myxoma; Carney complex; multiple endocrine neoplasia; Peutz-Jeghers syndrome; Ruvalcaba-Myhre-Smith syndrome; LEOPARD syndrome; arterial dissections; genetics; review ID PEUTZ-JEGHERS-SYNDROME; SPOTTY SKIN PIGMENTATION; ADRENOCORTICAL NODULAR DYSPLASIA; LAUGIER-HUNZIKER SYNDROME; AU-LAIT SPOTS; ENDOCRINE OVERACTIVITY; CARDIAC MYXOMA; POLYPOSIS SYNDROMES; LEOPARD-SYNDROME; CUSHING SYNDROME AB Carney complex is a multiple endocrine neoplasia (MEN) syndrome that affects the adrenal cortex, the pituitary and thyroid glands, and the gonads. The complex is also associated with skin and mucosa pigmentation abnormalities and myxoid and other neoplasms of mesenchymal and neural crest origin. Thus, this syndrome also belongs to another group of genetic disorders, the lentiginoses(or lentig (e) under bar noses), which include the Peutz-Jeghers, LEOPARD, arterial dissections and lentiginosis, and Laugier-Hunziker syndromes, Cowden disease and Ruvalcaba-Myhre-Smith (Bannayan-Zonana) syndrome and the centrofacial, benign patterned and segmental lentiginoses, all of which can be associated with a variety of developmental defects. The inheritance of Carney complex, just like that of the other MENs and the lentiginoses, is autosomal dominant. Genetic loci or genes have been identified for Carney complex, Peutz-Jeghers and Ruvalcaba-Myhre-Smith syndromes, but not for other lentiginoses. Elucidation of the molecular defects responsible for these disorders is expected to shed light on aspects of early neural crest differentiation, the regulation of pigmentation, the development of autonomous endocrine function, and endocrine and nonendocrine tumorigenesis. C1 NICHHD, Unit Genet & Endocrinol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), NICHHD, Unit Genet & Endocrinol, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. NR 128 TC 24 Z9 26 U1 0 U2 0 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD MAR 1 PY 2000 VL 5 BP D353 EP D366 DI 10.2741/Stratakis PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 343KT UT WOS:000088702100008 PM 10704431 ER PT J AU Wu, SM Leschek, EW Rennert, OM Chan, WY AF Wu, SM Leschek, EW Rennert, OM Chan, WY TI Luteinizing hormone receptor mutations in disorders of sexual development and cancer SO FRONTIERS IN BIOSCIENCE LA English DT Article DE molecular endocrinology; luteinizing hormone receptor; activating; familial male-limited precocious puberty; inactivating; Leydig cell hypoplasia; male pseudohermaphroditism; amenorrhea; review ID LIMITED PRECOCIOUS PUBERTY; LEYDIG-CELL HYPOPLASIA; CONSTITUTIVELY ACTIVATING MUTATION; HUMAN LUTROPIN/CHORIOGONADOTROPIN RECEPTOR; HORMONE/CHORIONIC GONADOTROPIN RECEPTOR; PROTEIN-COUPLED RECEPTORS; 2 DIFFERENT PHENOTYPES; EXTRACELLULAR DOMAIN; CHORIOGONADOTROPIN RECEPTOR; MALE PSEUDOHERMAPHRODITISM AB Human male sexual development is regulated by chorionic gonadotropin (CG) and luteinizing hormone (LH). Aberrant sexual development caused by both activating and inactivating mutations of the human luteinizing hormone receptor (LHR) have been described. All known activating mutations of the LHR are missense mutations caused by single base substitution. The most common activating mutation is the replacement of Asp-578 by Gly due to the substitution of A by G at nucleotide position 1733. All activating mutations are present in exon 11 which encodes the transmembrane domain of the receptor. Constitutive activity of the LHR causes LH releasing hormone-independent precocious puberty in boys and the autosomal dominant disorder familial male-limited precocious puberty (FMPP). Both germline and somatic activating mutations of the LHR have been found in patients with testicular tumors. Activating mutations have no effect on females. The molecular genetics of the inactivating mutations of the LHR are more variable and include single base substitution, partial gene deletion, and insertion. These mutations are not localized and are present in both the extracellular and transmembrane domain of the receptor. Inactivation of the LHR gives rise to the autosomal recessive disorder Leydig cell hypoplasia (LCH) and male hypogonadism or male pseudohermaphroditism. Severity of the clinical phenotype in LCH patients correlates with the amount of residual activity of the mutated receptor. Females are less affected by inactivating mutation of the LHR. Symptoms caused by homozygous inactivating mutation of the LHR include polycystic ovaries and primary amenorrhea. C1 Georgetown Univ, Childrens Med Ctr, Dept Pediat, Washington, DC 20007 USA. Georgetown Univ, Childrens Med Ctr, Dept Cell Biol, Washington, DC 20007 USA. Georgetown Univ, Childrens Med Ctr, Dept Biochem, Washington, DC 20007 USA. Georgetown Univ, Childrens Med Ctr, Dept Mol Biol, Washington, DC 20007 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Ctr Res Mothers & Children, 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. NR 87 TC 26 Z9 28 U1 0 U2 1 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD MAR 1 PY 2000 VL 5 BP D343 EP D352 DI 10.2741/Wu PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 343KT UT WOS:000088702100007 PM 10704433 ER PT J AU Wahlfors, JJ Zullo, SA Loimas, S Nelson, DM Morgan, RA AF Wahlfors, JJ Zullo, SA Loimas, S Nelson, DM Morgan, RA TI Evaluation of recombinant alphaviruses as vectors in gene therapy SO GENE THERAPY LA English DT Article DE alphavirus; Sindbis virus; Semliki Forest virus; gene transfer vector ID SEMLIKI-FOREST-VIRUS; SINDBIS VIRUS; EXPRESSION VECTORS; CELL-LINES; RNA; PROTEIN; SYSTEM; DNA; EFFICIENCY; ADENOVIRUS AB Alphavirus vectors based on Sindbis virus and Semliki Forest virus (SFV) were characterized as potential gene transfer vectors. Initial studies were performed using vectors engineered to transfer either lacZ or green fluorescent protein (GFP). High levels of gene transfer were achieved in human primary fibroblasts, BHK and 293T cells, with low levels of transduction observed in more than 20 other target cells. Alphavirus-based expression was generally very high, but transient in every cell type. Replication-competent alphavirus was never detected in SFV preparations but could be produced by Sindbis-based vectors at a frequency of up to 3 x 10(-3) infectious units per mi. We constructed a human clotting factor IX (hFIX) cDNA-containing Sindbis virus and compared it with hFIX cDNA-harboring adenoviral and retroviral vectors. In most cases, hFIX levels obtained with Sindbis vector were initially at least an order of magnitude higher than those obtained with other viral vectors. These data demonstrate that alphavirus vectors compare favorably with adenovirus vectors as systems to promote high-level transient gene expression and should be considered as an alternative vector for gene transfer and potential gene therapy studies. C1 NIH, Clin Gene Therapy Branch, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. Univ Kuopio, AI Virtanen Inst, FIN-70211 Kuopio, Finland. George Washington Univ, Grad Program Genet, Washington, DC USA. RP Morgan, RA (reprint author), NIH, Clin Gene Therapy Branch, Natl Human Genome Res Inst, 10 Ctr Dr,Bldg 10,Rm 10C103, Bethesda, MD 20892 USA. NR 36 TC 32 Z9 35 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD MAR PY 2000 VL 7 IS 6 BP 472 EP 480 DI 10.1038/sj.gt.3301122 PG 9 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 292GH UT WOS:000085785500004 PM 10757020 ER PT J AU Schlessinger, D AF Schlessinger, D TI Alleles and aging: The effects of different forms of genes on aging and longevity SO GENERATIONS-JOURNAL OF THE AMERICAN SOCIETY ON AGING LA English DT Article ID LIFE-SPAN; EPSILON-4; MICE C1 NIA, Intramural Res Program, Baltimore, MD 21224 USA. RP Schlessinger, D (reprint author), NIA, Intramural Res Program, Baltimore, MD 21224 USA. NR 22 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC AGING PI SAN FRANCISCO PA 833 MARKET ST, STE 511, SAN FRANCISCO, CA 94103-1824 USA SN 0738-7806 J9 GENERATIONS JI Generations-J. Am. Soc. Aging PD SPR PY 2000 VL 24 IS 1 BP 36 EP 42 PG 7 WC Gerontology SC Geriatrics & Gerontology GA 320GG UT WOS:000087393000008 ER PT J AU Warner, HR Hodes, RJ AF Warner, HR Hodes, RJ TI Hype, hope, and reality - Telomere length, telomerase, and aging SO GENERATIONS-JOURNAL OF THE AMERICAN SOCIETY ON AGING LA English DT Article ID HUMAN FIBROBLASTS; CANCER; CELLS; MOUSE; END C1 NIA, Biol Aging Program, Bethesda, MD 20892 USA. RP Warner, HR (reprint author), NIA, Biol Aging Program, Bethesda, MD 20892 USA. NR 23 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC AGING PI SAN FRANCISCO PA 833 MARKET ST, STE 511, SAN FRANCISCO, CA 94103-1824 USA SN 0738-7806 J9 GENERATIONS JI Generations-J. Am. Soc. Aging PD SPR PY 2000 VL 24 IS 1 BP 48 EP 53 PG 6 WC Gerontology SC Geriatrics & Gerontology GA 320GG UT WOS:000087393000010 ER PT J AU Hu, N Roth, MJ Polymeropolous, M Tang, ZZ Emmert-Buck, MR Wang, QH Goldstein, AM Feng, SS Dawsey, SM Ding, T Zhuang, ZP Han, XY Ried, T Giffen, C Taylor, PR AF Hu, N Roth, MJ Polymeropolous, M Tang, ZZ Emmert-Buck, MR Wang, QH Goldstein, AM Feng, SS Dawsey, SM Ding, T Zhuang, ZP Han, XY Ried, T Giffen, C Taylor, PR TI Identification of novel regions of allelic loss from a genomewide scan of esophageal squamous-cell carcinoma in a high-risk Chinese population SO GENES CHROMOSOMES & CANCER LA English DT Article ID LASER CAPTURE MICRODISSECTION; GENETIC ALTERATIONS; SHANXI-PROVINCE; FHIT GENE; CANCER; P53; HETEROZYGOSITY; ALLELOTYPE; LOCALIZATION; HISTORY AB Esophageal cancer is one of the most common fatal cancers worldwide. Deletions of genomic regions are thought to be important in esophageal carcinogenesis. We conducted a genomewide scan for regions of allelic loss using microdissected DNA from II esophageal squamous-cell carcinoma patients with a family history of upper gastrointestinal tract cancer from a high-risk region in north central China. Allelic patterns of 366 fluorescently labeled microsatellite markers distributed at 10-cM intervals over the 22 autosomal chromosomes were examined. We identified 14 regions with very high frequency (greater than or equal to 75%) loss of heterozygosity (LOH), including broad regions encompassing whole chromosome arms (on 3p, 5q, 9p, 9q, and 13q), regions of intermediate size (on 2q, 4p, I Ip, and 15q), and more discrete regions identified by very high frequency LOH for a single marker (on 4q, 6q, 8p, 14q, and 17p). Among these 14 regions were 7 not previously described in esophageal squamous-cell carcinoma as having very high frequency LOH (on 2q, 4p, 4q, 6q, 8p, 14q, and 15q). The very high frequency LOH regions identified here may point to major susceptibility genes, including potential tumor suppressor genes and inherited gene loci, which will assist in understanding the molecular events involved in esophageal carcinogenesis and may help in the development of markers for genetic susceptibility testing and screening for the early detection of this cancer. Published 2000 Wiley-Liss, Inc. C1 NCI, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Bethesda, MD USA. Shanxi Canc Hosp, Taiyuan, Shanxi, Peoples R China. Informat Management Serv Inc, Silver Spring, MD USA. RP Taylor, PR (reprint author), 6006 Execut Blvd,Room 321, Bethesda, MD 20892 USA. NR 49 TC 78 Z9 88 U1 1 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD MAR PY 2000 VL 27 IS 3 BP 217 EP 228 DI 10.1002/(SICI)1098-2264(200003)27:3<217::AID-GCC1>3.0.CO;2-A PG 12 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 277PT UT WOS:000084942500001 PM 10679910 ER PT J AU Lastowski, K Makalowski, W AF Lastowski, K Makalowski, W TI Methodological function of hypotheses in science: Old ideas in new cloth SO GENOME RESEARCH LA English DT Editorial Material C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. Adam Mickiewicz Univ, Inst Philosophy, Poznan, Poland. RP Makalowski, W (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RI Makalowski, Wojciech/I-2843-2016 NR 6 TC 3 Z9 3 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 2000 VL 10 IS 3 BP 273 EP 274 DI 10.1101/gr.10.3.273 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 293TB UT WOS:000085868500002 PM 10720568 ER PT J AU Agarwala, R Applegate, DL Maglott, D Schuler, GD Schaffer, AA AF Agarwala, R Applegate, DL Maglott, D Schuler, GD Schaffer, AA TI A fast and scalable radiation hybrid map construction and integration strategy SO GENOME RESEARCH LA English DT Article ID HUMAN GENOME; STATISTICAL-METHODS; CHROMOSOMES; GENES AB This paper describes a fast and scalable strategy for constructing a radiation hybrid (RH) map from data on different RH panels. The maps on each panel are then integrated to produce a single RH map for the genome. Recurring problems in using maps from several sources are that the maps use different markers, the maps do not place the overlapping markers in same order, and the objective functions for map quality are incomparable. We use methods from combinatorial optimization to develop a strategy that addresses these issues. We show that by the standard objective functions of obligate chromosome breaks and maximum likelihood, software for the traveling salesman problem produces RH maps with better quality much more quickly than using software specifically tailored for RH mapping. We use known algorithms for the longest common subsequence problem as part of our map integration strategy. We demonstrate our methods by reconstructing and integrating maps for markers typed on the Genebridge 4 (GB4) and the Stanford G3 panels publicly available from the RH database. We compare map quality of our integrated map with published maps for GB4 panel and G3 panel by considering whether markers occur in the same order on a map and in DNA sequence contigs submitted to GenBank. We find that all of the maps are inconsistent with the sequence data for at least 50% of the contigs, but our integrated maps are more consistent. The map integration strategy not only scales to multiple RH maps but also to any maps that have comparable criteria for measuring map quality. Our software improves on current technology for doing RH mapping in areas of computation time and algorithms for considering a large number of markers for mapping. The essential impediments to producing dense high-quality RH maps are data quality and panel size, not computation. C1 NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Rice Univ, Dept Computat & Appl Math, Houston, TX 77005 USA. RP Schaffer, AA (reprint author), NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RI Schaffer, Alejandro/F-2902-2012 NR 33 TC 88 Z9 92 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 2000 VL 10 IS 3 BP 350 EP 364 DI 10.1101/gr.10.3.350 PG 15 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 293TB UT WOS:000085868500010 PM 10720576 ER PT J AU Mogayzel, PJ Ashlock, MA AF Mogayzel, PJ Ashlock, MA TI CFTR intron 1 increases luciferase expression driven by CFTR 5 '-flanking DNA in a yeast artificial chromosome SO GENOMICS LA English DT Article ID TRANSMEMBRANE CONDUCTANCE REGULATOR; CYSTIC-FIBROSIS GENE; TRANSGENIC MICE; PROMOTER REGION; CELLS; ELEMENT; IDENTIFICATION; INDUCTION; VECTOR; BASAL AB The DNA elements that account for the highly regulated expression of the cystic fibrosis transmembrane conductance regulator gene (CFTR) are poorly understood. The goal of this study was to assess the feasibility of using a yeast artificial chromosome (YAC)-based reporter gene construct to define these elements further. An similar to 350-kb YAC (y5'luc) was constructed by replacing CFTR with a luciferase reporter gene (luc). A second YAC (y5'lucI) was similarly constructed but included a putative positive regulatory element from CFTR intron I, Stable Chinese hamster ovary (CHO-K1) cell clones were derived using each YAC to assess the role that luc copy number and the presence of intron 1 played in luc expression. The CHO-K1 clonal cell lines demonstrated a wide range of luciferase activity. On average, this activity was significantly higher in clones derived from y5'lucI, After correcting for luc copy number, the presence of intron 1 was still associated with an increase in luciferase activity (P < 0.05), despite the fact that luciferase activity did not correlate with luc copy number in y5'luc-derived clones (r = -0.12), In contrast, the luciferase activity correlated well with luc copy number in the clones derived from y5'luc (r = 0.75), These data are consistent with a positive role for intron 1 in regulating CFTR expression, but suggest that copy number is not the only factor that determines expression levels, particularly when this element is present. This YAC-based reporter system will provide a unique strategy for further assessment of the cis-acting elements that control CFTR expression. (C) 2000 Academic Press. C1 Johns Hopkins Med Inst, Eudowoood Div Pediat Resp Sci, Baltimore, MD 21287 USA. Natl Human Genome Res Inst, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Mogayzel, PJ (reprint author), Johns Hopkins Hosp, Eudowood Div Pediat Resp Sci, 600 N Wolfe St,Pk 316, Baltimore, MD 21287 USA. NR 34 TC 11 Z9 11 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD MAR 1 PY 2000 VL 64 IS 2 BP 211 EP 215 DI 10.1006/geno.2000.6119 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 301LE UT WOS:000086311000010 PM 10729228 ER PT J AU Zunino, A Viaggi, S Ottaggio, L Fronza, G Schenone, A Roncella, S Abbondandolo, A AF Zunino, A Viaggi, S Ottaggio, L Fronza, G Schenone, A Roncella, S Abbondandolo, A TI Chromosomal aberrations evaluated by CGH, FISH and GTG-banding in a case of AIDS-related Burkitt's lymphoma SO HAEMATOLOGICA LA English DT Article DE CGH; FISH; Burkitt's lymphoma; AIDS; cytogenetics ID COMPARATIVE GENOMIC HYBRIDIZATION; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; COPY NUMBER CHANGES; ABNORMALITIES; LEUKEMIA; CELLS; EXPRESSION; APOPTOSIS; NONRANDOM; ANTIGEN AB Background and Objectives, We have previously reported on a complex chromosome rearrangement [der(17)] in a B-cell line, uno A, established from an _AIDS patient with Burkitt's lymphoma (BL), The aim of the present study was the definition of der(17) composition and the identification of complete or partial chromosome gains and losses In two cell clones (BRG A and BRG M) derived from this patient. Design and Methods, We applied comparative genome hybridization (CGH) to detect the DNA mis-representations in the genome of the two cell clones. Findings from CGH and banding analysis could then direct the choice of probes for chromosome painting experiments to elucidate der(17) composition. Results, CGH analysis identified gains of chromosomes 1q, 7q, 12q, 13q, 15q, 17p, 20p,q and losses of chromosomes 3p and 5q in BRG A and gain of chromosome 1q and loss in chromosome 6q In BRG M. Some of the detected alterations had already been described in lymphomas, while others appeared to be new. The combination of these techniques allowed a precise definition of der(17), composed by translocated regions from chromosomes 12 and 15, Interpretation and Conclusions, We demonstrated CGH to be a powerful tool In the Identification of recurrent chromosome aberrations In an AIDS-related at. and in ascertaining the origin of marker chromosomes. We were also able to identify a different pattern of aberrations and assess an independent sequence of events leading to the Ip gain In the two subclones. (C) 2000, Ferrata Storti Foundation. C1 Natl Canc Inst, Mutagenesis Lab, I-16132 Genoa, Italy. Univ Genoa, Dept Oncol Biol & Genet, Genoa, Italy. Natl Canc Inst, Biophys Lab, I-16132 Genoa, Italy. S Andrea Hosp, Anat Pathol Unit, La Spezia, Italy. Natl Canc Inst, Div Clin Immunol, I-16132 Genoa, Italy. RP Zunino, A (reprint author), Natl Canc Inst, Mutagenesis Lab, Largo Rosanna Benzi 10, I-16132 Genoa, Italy. NR 23 TC 8 Z9 8 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD MAR PY 2000 VL 85 IS 3 BP 250 EP 255 PG 6 WC Hematology SC Hematology GA 292FT UT WOS:000085784000007 PM 10702812 ER PT J AU Zubenko, GS Sunderland, T AF Zubenko, GS Sunderland, T TI Geriatric psychopharmacology: Why does age matter? SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review ID PSYCHOTROPIC-DRUG USE; BLOOD-BRAIN-BARRIER; INDUCED ORTHOSTATIC HYPOTENSION; POSITRON EMISSION TOMOGRAPHY; NURSING-HOME RESIDENTS; ELIMINATION HALF-LIFE; LEWY-BODY VARIANT; ALZHEIMERS-DISEASE; SENILE DEMENTIA; HIP FRACTURE AB Older adults respond less predictably than younger adults to most medications, typically requiring lower daily doses to achieve desired therapeutic effects and minimize adverse effects and toxicity. This unpredictability is particularly evident among the frail elderly, who are at the upper extreme of the life cycle and often suffer from central neurodegenerative disorders and/or a significant burden of comorbid medical problems. Yet this population has a burgeoning need for clinical services and in recent years has become an increasingly important focus of attention among practitioners. The goal of this review is to provide clinicians with a conceptual framework for understanding and responding to aging and age-related events that influence pharmacotherapeutics in older patients with behavioral disorders. Limitations and gaps in our knowledge base are also highlighted. The article includes a phenomenological overview of the aging process, a consideration of age-related factors that influence the pharmacokinetic and pharmacodynamic properties of psychotropic drugs, and suggested methods of enhancing medication compliance. C1 Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Carnegie Mellon Univ, Coll Sci, Dept Biol Sci, Pittsburgh, PA 15213 USA. NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. RP Zubenko, GS (reprint author), Western Psychiat Inst & Clin, E1230,3811 OHara St, Pittsburgh, PA 15213 USA. FU NIMH NIH HHS [MH43261, MH00540, MH/AG47346] NR 197 TC 15 Z9 15 U1 1 U2 5 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAR-APR PY 2000 VL 7 IS 6 BP 311 EP 333 DI 10.1093/hrp/7.6.311 PG 23 WC Psychiatry SC Psychiatry GA 294UP UT WOS:000085929000001 PM 10749389 ER PT J AU Murphy, EL Bryzman, SM Glynn, SA Ameti, DI Thomson, RA Williams, AE Nass, CC Ownby, HE Schreiber, GB Kong, FH Neal, KR Nemo, GJ AF Murphy, EL Bryzman, SM Glynn, SA Ameti, DI Thomson, RA Williams, AE Nass, CC Ownby, HE Schreiber, GB Kong, FH Neal, KR Nemo, GJ CA NHLBI Retrovirus Epidemiology Dono TI Risk factors for hepatitis C virus infection in United States blood donors SO HEPATOLOGY LA English DT Article ID SEXUALLY-TRANSMITTED DISEASES; LIVER-DISEASE; TRANSMISSION; PREVALENCE; ANTIBODIES; SEROPREVALENCE; JAPAN; SEROEPIDEMIOLOGY; POPULATION; MARYLAND AB Injection drug use (IDU) is a known risk factor for hepatitis C virus (HCV) infection, but the strength of other parenteral and sexual risk factors is unclear, In 1997, we performed a case-control study of 2,316 HCV-seropositive blood donors and 2,316 seronegative donors matched on age, sex, race/ethnicity, blood center, and first-time versus repeat-donor status. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Questionnaires were returned by 758 (33%) HCV+ and 1,039 (45%) control subjects (P = .001), The final multivariate model included only the following independent HCV risk factors: IDU (OR = 49.6; 95% CI: 20.3-121.1), blood transfusion in non-IDU (OR = 10.9; 95% CI, 6.5-18.2), sex with an IDU (OR = 6.3; 95% CI: 3.3-12.0), having been in jail more than 3 days (OR = 2.9; 95% CI: 1.3-6.6), religious scarification (OR = 2.8; 95% CI: 1.2-7.0), having been stuck or cut with a bloody object (OR = 2.1; 95% CI: 1.1-4.1), pierced ears or body parts (OR = 2.0; 95% CI: 1.1-3.7), and immunoglobulin injection (OR = 1.6; 95% CI: 1.0-2.6), Although drug inhalation and a high number of Lifetime sex partners were significantly more common among HCV seropositives, they were not associated with HCV after controlling for IDU and other risk factors. IDU, blood transfusion among non-IDU, and sex with an IDU are strong risk factors for HCV among United States blood donors, Weaker associations with incarceration, religious scarification, being stuck or cut with a bloody object, pierced ears or body parts, and immunoglobulin injection must be interpreted with caution. C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. E Bay Family Practice, Oakland, CA USA. Westat Inc, Rockville, MD USA. Amer Red Cross, Jerome H Holland Lab, Rockville, MD USA. Amer Red Cross, Blood Serv Chesapeake Reg, Baltimore, MD USA. Amer Red Cross, Blood Serv SE Michigan Reg, Detroit, MI USA. Univ Nottingham, Nottingham NG7 2RD, England. NHLBI, Bethesda, MD 20892 USA. RP Murphy, EL (reprint author), Univ Calif San Francisco, Box 0884, San Francisco, CA 94143 USA. FU NHLBI NIH HHS [N01-HB-47114, N01-HB-97077, N01-HB-97078] NR 39 TC 127 Z9 136 U1 1 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAR PY 2000 VL 31 IS 3 BP 756 EP 762 DI 10.1002/hep.510310329 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 289JY UT WOS:000085618500028 PM 10706569 ER PT J AU Taylor, JG Krause, B Shah, MJ Horwitz, B Mueller-Gaertner, HW AF Taylor, JG Krause, B Shah, MJ Horwitz, B Mueller-Gaertner, HW TI On the relation between brain images and brain neural networks SO HUMAN BRAIN MAPPING LA English DT Article DE fMRI; brain; PET; neural activity ID PHASE-LOCKING; BLOOD-FLOW; MODEL; CHAOS; FMRI; MAP AB The relationship between brain images observed by PET and fMRI and the underlying neural activity is analysed using recent results on the detailed nature of averaged and synchronised activity of coupled neural networks and on a simplifying model of the level of blood flow caused by neural activity. The conditions bn the coupled neural systems are specified that lead to structural equation models, giving support to analysis of the covariance structural equation modelling of brain imaging data. The relation between the resulting models and possible neural codes are analysed. Furthermore, a new form of structural equation model is derived, in which all neuronal activity arises as hidden variables. We discuss how the results of such analyses can be transported back to the domain of coupled temporally dynamic neural systems in the brain appropriate to EEG and MEG observations. (C) 2000 Wiley-Liss, Inc. C1 Kings Coll London, Dept Math, Strand, London WC2R 2LS, England. Res Ctr, Inst Med, Julich, Germany. Univ Dusseldorf, Dept Nucl Med, D-4000 Dusseldorf, Germany. Natl Inst Deafness & Other Commun Disorders, Voise Speech & Language Branch, NIH, Bethesda, MD USA. RP Taylor, JG (reprint author), Kings Coll London, Dept Math, Strand, London WC2R 2LS, England. NR 45 TC 21 Z9 22 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 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD MAR PY 2000 VL 9 IS 3 BP 165 EP 182 PG 18 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 290NP UT WOS:000085682500005 PM 10739367 ER PT J AU Ghanayem, BI Ward, SM Chanas, B Nyska, A AF Ghanayem, BI Ward, SM Chanas, B Nyska, A TI Comparison of the acute hematotoxicity of 2-butoxyethanol in male and female F344 rats SO HUMAN & EXPERIMENTAL TOXICOLOGY LA English DT Article DE 2-butoxyethanol; hematotoxicity; male and female F344 rats; erythrocytes morphology ID OCCUPATIONAL CHRONIC EXPOSURE; BUTOXYACETIC ACID; HEREDITARY SPHEROCYTOSIS; INHALED 2-BUTOXYETHANOL; HEMOLYTIC-ACTIVITY; ORGANIC-SOLVENTS; MAJOR METABOLITE; HUMANS; THROMBOSIS; DEFORMABILITY AB Administration of 2-butoxyethanol (BE) to rodents causes acute hemolytic anemia, and metabolic activation of BE to butoxyacetic acid (BAA) is required for the development of this effect. Recent studies have shown that female rats treated with BE exhibit a variety of histopathologic lesions that are absent in males and many of these lesions are attributed to the hemolytic effects of BE. Current studies were designed to compare the acute hematotoxicity of BE in male and female F344 rats. Rats were treated with 250 mg BE/kg body weight or water (control; 5 ml/kg) by gavage. At 4, 8, or 24 h after dosing, rats were anesthetized, blood was collected by cardiac puncture, and various blood parameters were measured. BE resulted in a time-dependent swelling of erythrocytes as evidenced by an early increase in hematocrit (Hct) and mean cell volume (MCV) in male rats. In contrast, increased Hct in female rats did not accompany an increase in MCV. It is likely that hemolysis was so severe at 4h that Hct exhibited a decline in female rats at that time point. Subsequently, red blood cell (RBCs), hemoglobin concentration (Hgb), and Hct declined as hemolysis progressed. However, the onset of BE-induced hemolysis was faster in female compared to male rats. These effects were also associated with a significant increase in the spleen weight to body weight ratio. Blood smears were also prepared and morphological changes evaluated by light microscopy included stomatocytosis, spherocytosis, and schistocytosis. Furthermore, aggregation of RBCs in female rats as evidenced by increased formation of rouleaux was observed at 24 h after BE administration. These effects were observed earlier and more frequently in female rats. No differences in the sensitivity of RBCs obtained from male and female rats and exposed to butoxyacetic acid (BAA) in vitro was observed as determined by measuring the packed cell volume. In conclusion, these data suggest that female rats are more sensitive to hemolysis and morphological alterations of erythrocytes induced by BE during the first 24 h after exposure compared to males. It is likely that the greater sensitivity of female rats to BE effects on RBCs may account for the reported development of thrombosis and tissue infarction in female rats. C1 NIEHS, NIH, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Ghanayem, BI (reprint author), NIEHS, NIH, Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. NR 30 TC 20 Z9 22 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0144-5952 J9 HUM EXP TOXICOL JI Hum. Exp. Toxicol. PD MAR PY 2000 VL 19 IS 3 BP 185 EP 192 DI 10.1191/096032700678827744 PG 8 WC Toxicology SC Toxicology GA 326PN UT WOS:000087744100005 PM 10889517 ER PT J AU Hafkemeyer, P Licht, T Pastan, I Gottesman, MM AF Hafkemeyer, P Licht, T Pastan, I Gottesman, MM TI Chemoprotection of hematopoietic cells by a mutant P-glycoprotein resistant to a potent chemosensitizer of multidrug-resistant cancers SO HUMAN GENE THERAPY LA English DT Article ID MULTIPLE-DRUG RESISTANCE; MURINE BONE-MARROW; HUMAN MDR1 GENE; PHASE-I TRIAL; STEM-CELLS; TRANSGENIC MICE; PRECURSOR CELLS; EXPRESSION; TRANSDUCTION; CHEMOTHERAPY AB Cancers are frequently chemoresistant because of overexpression of P-glycoprotein, Two different approaches to improve cancer treatment are currently being investigated in clinical trials: inhibition of P-glycoprotein function by reversing agents, and alleviation of leukocytopenia by MDR1 gene transfer to normal bone marrow of patients, We report here that retroviral vectors encoding a mutant P-glycoprotein (MDR1-F983A) protect hematopoietic cells from anticancer drugs even in the presence of trans-(E)-flupentixol, an inhibitor of P-glycoprotein, Transfer of either mutant or wild-type MDR1 to K562 erythroleukemia cells or primary murine bone marrow resulted in reduced accumulation of daunomycin and vinblastine because of increased drug efflux. trans-(E)-Flupentixol at concentrations up to 10 mu M failed to reverse drug efflux mediated by the product of the mutant MDR1 while wild-type P-glycoprotein was inhibited. In the presence of 2 mu M trans-(E)-flupentixol chemoresistance to daunomycin was circumvented only in K562 cells transduced with wild-type, but not with mutant, MDR1, Moreover, drug resistance of KB-8-5 epidermoid cancer cells, which express the wildtype MDR1 gene at levels comparable to clinical specimens from multidrug-resistant cancers, was fully overcome in the presence of trans-(E)-flupentixol. Vectors expressing mutant P-glycoprotein may help improve chemotherapy by allowing safe dose intensification under conditions in which multidrug-resistant cancers are rendered drug sensitive by reversing agents. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 1A09,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 54 TC 14 Z9 15 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 2000 VL 11 IS 4 BP 555 EP 565 DI 10.1089/10430340050015743 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 290CR UT WOS:000085659100005 PM 10724034 ER PT J AU Richard, G Brown, N Smith, LE Terrinoni, A Melino, G MacKie, RM Bale, SJ Uitto, J AF Richard, G Brown, N Smith, LE Terrinoni, A Melino, G MacKie, RM Bale, SJ Uitto, J TI The spectrum of mutations in erythrokeratodermias - novel and de novo mutations in GJB3 SO HUMAN GENETICS LA English DT Article ID GAP JUNCTION PROTEINS; MARIE-TOOTH-DISEASE; CORNIFIED CELL-ENVELOPE; INTERCELLULAR CHANNELS; MOLECULAR-CLONING; MISSENSE MUTATION; GENE; CONNEXIN; EXPRESSION; LORICRIN AB Intercellular channels in skin are a complex and functionally diverse system formed by at least eight connexins (Cx). Our recent molecular studies implicating Cx defects in inherited skin disorders emphasize the critical role of this signaling pathway in epidermal differentiation. Erythrokeratodermia variabilis (EKV) is an autosomal dominant genodermatosis with a striking phenotype characterized by the independent occurrence of transient localized erythema and hyperkeratosis. The disease maps to 1p34-p35, and recently we identified the causative gene GJB3 encoding Cx31. We have now investigated GJB3 in two families and three sporadic cases with EKV, and report three new heterozygous mutations. In a sporadic case, we detected a mutation leading to substitution of a conserved phenylalanine (F137L) in the third transmembrane domain, which likely interferes with the proper assembly or gating properties of connexons. In another family, all three affected individuals carried two distinct mutations on the same GJB3 allele. However, only a de novo heterozygous missense mutation replacing arginine 42 with proline (R42P) co-segregated with the disease, while a 12 bp deletion predicted to eliminate four amino acid residues in the variable carboxy terminal domain of Cx31 was also found in clinically unaffected relatives but not in 90 unaffected controls. Including the previously published mutations, in tote, five different missense mutations have now been detected in 6 out of 17 families investigated by our laboratory, all of which presumably affect the cytoplasmic amino terminal and transmembrane domains of Cx31. In contrast, two mutations linked to progressive high-tone hearing impairment were located in the second extracellular domain, suggesting that the character and position of Cx mutations determine their phenotypic expression in different tissues. However, the phenotypic spectrum of GJB3 mutations seems not to include progressive symmetric erythrokeratodermia, another dominant genodermatosis with overlapping features, since no mutations were found in six unrelated families tested. C1 Thomas Jefferson Univ, Jefferson Med Coll, Dept Dermatol & Cutaneous Biol, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Jefferson Inst Mol Med, Philadelphia, PA 19107 USA. NIAMSD, Genet Studies Sect, Lab Skin Biol, NIH, Bethesda, MD USA. Univ Roma Tor Vergata, Dept Expt Med, IDI, IRCCS,Lab Biochem, Rome, Italy. Univ Glasgow, Dept Dermatol, Glasgow G12 8QQ, Lanark, Scotland. RP Richard, G (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Dept Dermatol & Cutaneous Biol, 233 S 10th St,BLSB,Suite 409, Philadelphia, PA 19107 USA. RI TERRINONI, Alessandro/J-1533-2012 OI TERRINONI, Alessandro/0000-0002-7442-2252 FU NIAMS NIH HHS [P0I AR 38923] NR 42 TC 64 Z9 72 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 2000 VL 106 IS 3 BP 321 EP 329 DI 10.1007/s004390051045 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 307PE UT WOS:000086661100010 PM 10798362 ER PT J AU Huizing, M Anikster, Y Gahl, WA AF Huizing, M Anikster, Y Gahl, WA TI Characterization of a partial pseudogene homologous to the Hermansky-Pudlak syndrome gene HPS-1; relevance for mutation detection SO HUMAN GENETICS LA English DT Article AB The HPS-1 gene is the first gene found to be responsible for the autosomal recessive disorder Hermansky-Pudlak syndrome (HPS). HPS is characterized by oculocutaneous albinism, a platelet storage pool deficiency, and ceroid lipofuscinosis. The HPS-1 gene has been mapped to chromosome 10q23.1-23.3 and encodes a 79-kDa protein of unknown function with no homology to any known protein. A sequence database search has revealed that a portion of clone HS1119A7 shows high sequence similarity to HPS-1 cDNA. By performing sequence alignments and PCR amplification of cDNA from several human tissues, we have shown that part of this clone consists of an unprocessed partial HPS-1 pseudogene located on chromosome 22q12.2-12.3. The pseudogene contains several intact HPS-1 exons and shows 95% sequence homology to the HPS-1 cDNA. Exon 6 of the pseudogene has 100% sequence homology to exon 6 of HPS-1 itself. In the pseudogene, this exon is surrounded by portions of both its normal flanking introns. These data provide the first characterization of an HPS-1 pseudogene, called HPS1-psi 1. During amplification of exon 6 of the HPS-1 gDNA for mutation identification, the pseudogene might also be amplified, leading to a false positive for mutation. In addition, amplification of specific parts of the HPS-1 cDNA (e.g., exons 2-5) for mutation detection might lead to false positives for mutations, if the cDNA is contaminated with gDNA. This calls for caution when employing these screening approaches. C1 NICHHD, Sect Human Biochem Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Gahl, WA (reprint author), NICHHD, Sect Human Biochem Genet, Heritable Disorders Branch, NIH, 10 Ctr Dr,MSC 1830,Bldg 10,Room 9S-241, Bethesda, MD 20892 USA. NR 17 TC 5 Z9 6 U1 0 U2 0 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 2000 VL 106 IS 3 BP 370 EP 373 DI 10.1007/s004390051053 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 307PE UT WOS:000086661100018 PM 10798370 ER PT J AU Mandal, DM Wilson, AF Elston, RC Weissbecker, K Keats, BJ Bailey-Wilson, JE AF Mandal, DM Wilson, AF Elston, RC Weissbecker, K Keats, BJ Bailey-Wilson, JE TI Effects of misspecification of allele frequencies on the type I error rate of model-free linkage analysis SO HUMAN HEREDITY LA English DT Article DE quantitative trait; Haseman-Elston sib pair method; GASP software program; heterozygosity; computer simulation ID STRATEGIES AB Linkage analyses of simulated quantitative trait data were performed using the Haseman-Elston (H-E) sib pair regression test to investigate the effects of inaccurate allele frequency estimates on the type I error rates of this test. Computer simulations generating a quantitative trait in nuclear families were performed using GASP [1]. Assuming no linkage, several data sets were simulated; they differed in marker allele numbers and frequencies, number of sib pairs and number of sibships. Each set of simulated data was analyzed using (1) all parental marker data, (2) half of the parental marker data, and (3) no parental marker data, using both correct and incorrect allele frequencies in the latter 2 cases. The H-E sib pair linkage method was found to be robust to misspecification of marker allele frequencies regardless of the number of alleles, Copyright (C) 1999 S.Karger AG, Basel. C1 Natl Human Genome Res Inst, NIH, Triad Technol Ctr, Baltimore, MD 21224 USA. Louisiana State Univ, Med Ctr, Dept Med, Sect Genet & Geriatr, New Orleans, LA 70112 USA. Louisiana State Univ, Med Ctr, Dept Biometry & Genet, New Orleans, LA 70112 USA. Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. Tulane Univ, Med Ctr, Dept Psychiat & Neurol, Hayward Genet Program, New Orleans, LA USA. RP Bailey-Wilson, JE (reprint author), Natl Human Genome Res Inst, NIH, Triad Technol Ctr, Suite 2000,333 Cassell Dr, Baltimore, MD 21224 USA. RI Wilson, Alexander/C-2320-2009; OI Bailey-Wilson, Joan/0000-0002-9153-2920 FU NCRR NIH HHS [1P41RR03655]; NIGMS NIH HHS [GM283356] NR 13 TC 8 Z9 8 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PD MAR-APR PY 2000 VL 50 IS 2 BP 126 EP 132 DI 10.1159/000022900 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 262GC UT WOS:000084056600005 PM 10799971 ER PT J AU Fogt, F Urbanski, SJ Sanders, ME Furth, EE Zimmerman, RL Deren, JJ Noffsinger, AE Vortmeyer, AO Hartmann, CJ Odze, RL Brown, CA AF Fogt, F Urbanski, SJ Sanders, ME Furth, EE Zimmerman, RL Deren, JJ Noffsinger, AE Vortmeyer, AO Hartmann, CJ Odze, RL Brown, CA TI Distinction between dysplasia-associated lesion or mass (DALM) and adenoma in patients with ulcerative colitis SO HUMAN PATHOLOGY LA English DT Article DE dysplasia; ulcerative colitis; DALM; adenoma; microdissection; molecular pathology ID POLYPOID DYSPLASIA; COLONOSCOPY; DISEASE AB Polyps with epithelial dysplasia in ulcerative colitis (UC) represent either dysplasia-associated lesions or masses (DALMs) or sporadic adenomas. DALMs are frequently associated with associated carcinoma and are an indication for colectomy. Removal of the polyp is treatment of choice for sporadic adenomas. Differentiating between these 2 lesions is not always easy. The goal of this study was to distinguish DALMs from adenomas in patients with UC on a genetic basis. We evaluated genetic alterations in DALMs and compared them with a previously published set of dysplastic polyps in patients with UC that were considered adenomas for the following reasons: (1) polyps were located outside of current active disease; (2) polyps had histological features of sporadic adenomas; and (3) patients displayed a uneventful follow-up after polypectomy (UC-adenomas). In addition, adenomas not associated with UC were studied. Genetic alterations on chromosome 3p were assessed for the markers D3S1766, D3S2409, and D3S2387. LOH with or without microsatellite instability was found in 70%, 37%, and 57% of cases of DALM, respectively. In contrast, UC-adenomas lesions exhibited genetic alterations in 8.3%, 11.7%, and 15.3% for the respective markers. Spontaneous adenomas exhibited genetic alterations in 10.5%, 7.1%, and 0% of cases, which were not significantly different from the UC-adenoma results. These results indicate that UC-adenomas are genetically and biologically similar to sporadic adenomas and that UC-adenomas may biologically represent sporadic adenomas, supporting on a genetic basis the criteria chosen to diagnose adenomas in UC, Genetic markers on chromosome Sp may be useful in the differential diagnosis between PALM and UC-adenomas. Copyright (C) 2000 by W.B. Saunders Company. C1 Univ Penn, Presbyterian Med Ctr, Dept Pathol, Philadelphia, PA 19104 USA. Univ Penn, Presbyterian Med Ctr, Dept Gastroenterol, Philadelphia, PA 19104 USA. Univ Calgary, Dept Pathol, Calgary, AB, Canada. Brigham & Womens Hosp, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. Carolinas Med Ctr, Diagnost Labs, Charlotte, NC 28203 USA. RP Fogt, F (reprint author), Univ Penn, Presbyterian Med Ctr, Dept Pathol, 39th & Market St, Philadelphia, PA 19104 USA. NR 11 TC 41 Z9 40 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAR PY 2000 VL 31 IS 3 BP 288 EP 291 DI 10.1016/S0046-8177(00)80240-3 PG 4 WC Pathology SC Pathology GA 296QP UT WOS:000086035800004 PM 10746669 ER PT J AU Galateau-Salle, FB Luna, RE Horiba, K Sheppard, MN Hayashi, T Fleming, MV Colby, TV Bennett, W Harris, CC Stetler-Stevenson, WG Liotta, L Ferrans, VJ Travis, WD AF Galateau-Salle, FB Luna, RE Horiba, K Sheppard, MN Hayashi, T Fleming, MV Colby, TV Bennett, W Harris, CC Stetler-Stevenson, WG Liotta, L Ferrans, VJ Travis, WD TI Matrix metalloproteinases and tissue inhibitors of metalloproteinases in bronchial squamous preinvasive lesions SO HUMAN PATHOLOGY LA English DT Article DE lung; bronchus; squamous dysplasia; squamous metaplasia; basal cell hyperplasia; carcinoma in situ; metalloproteinase; tissue inhibitor of metalloproteinase; lung cancer ID CELL LUNG-CANCER; PRENEOPLASTIC LESIONS; BASEMENT-MEMBRANE; RESPIRATORY EPITHELIUM; EXTRACELLULAR-MATRIX; PROGELATINASE-A; TUMOR INVASION; CARCINOMA; EXPRESSION; METASTASIS AB Metalloproteinases and their inhibitors are known to play an important role in the extracellular matrix remodeling associated with preinvasive lesions and invasive carcinomas; however, little is known about their role in early lung carcinoma. Immunohistochemical studies were made of the reactivity of bronchial squamous preneoplastic lesions from cigarette smokers, including basal cell hyperplasia, squamous metaplasia, dysplasia, carcinoma in situ, and invasive squamous cell carcinoma for matrix metalloproteinases (MMPs), their tissue inhibitors (TIMPs), and type IV collagen in 13 patients. Staining for type IV collagen disclosed discontinuities in basement membranes from basal cell hyperplasia to dysplasia, progressing to destruction in carcinoma in situ and invasive carcinoma. Reactivity for MMP-9 was mild in basal cell hyperplasia and squamous metaplasia, increasing in carcinoma in situ and invasive carcinoma. In contrast, reactivity for MMP-1 was strong in basal fell hyperplasia and squamous metaplasia, decreasing in carcinoma in situ and invasive carcinoma. Some neoplastic cells in carcinoma in situ and invasive carcinoma were MMP-3 positive. Staining for MMP-2 and TIMP-1 was moderate to strong in all squamous preinvasive lesions. Confocal microscopy showed MMP-9-positive cells passing through fragmented basement membranes in which type IV collagen and MMP-9 were colocalized. Type IV collagen colocalized with MMP-2 in all lesions and with TIMP-1 in basal cell hyperplasia and squamous metaplasia. The inverse relationships between the reactivity for MMP-1 and MMP-9 with progression of bronchial squamous preinvasive lesions suggest important roles for these MMPs in basement membrane remodeling in these lesions. This is a US government work. There are no restrictions on its use. C1 Ctr Hop Reg & Univ Caen, Dept Pathol, Caen, France. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. Royal Brompton Hosp, Dept Histopathol, London SW3 6LY, England. Nagasaki Univ Hosp, Dept Pathol, Nagasaki, Japan. Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, Washington, DC 20306 USA. Mayo Clin, Dept Pathol, Scottsdale, AZ USA. NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Travis, WD (reprint author), Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, Washington, DC 20306 USA. RI Stetler-Stevenson, William/H-6956-2012; Galateau Salle, Francoise/J-1530-2015 OI Stetler-Stevenson, William/0000-0002-5500-5808; Galateau Salle, Francoise/0000-0003-3642-0165 NR 63 TC 35 Z9 39 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAR PY 2000 VL 31 IS 3 BP 296 EP 305 DI 10.1016/S0046-8177(00)80242-7 PG 10 WC Pathology SC Pathology GA 296QP UT WOS:000086035800006 PM 10746671 ER PT J AU Katoh, R Miyagi, E Nakamura, N Li, X Suzuki, K Kakudo, K Kobayashi, M Kawaoi, A AF Katoh, R Miyagi, E Nakamura, N Li, X Suzuki, K Kakudo, K Kobayashi, M Kawaoi, A TI Expression of thyroid transcription factor-1 (TTF-1) in human C cells and medullary thyroid carcinomas SO HUMAN PATHOLOGY LA English DT Article DE thyroid tumor; medullary carcinoma; thyroid transcription factor-1; TTF-1; immunohistochemistry; in situ hybridization ID FACTOR-I; THYROGLOBULIN PROMOTER; GENE-EXPRESSION; MIXED MEDULLARY; THYROPEROXIDASE; ANTIBODY; UPSTREAM; FEATURES; GLAND; BRAIN AB Thyroid transcription factor-1 (TTF-1) has been known to regulate the transcriptional activity of thyroid-specific genes in thyroid follicular cells. We recently identified TTF-1 mRNA expression in rat thyroid C cells. The current study was undertaken to elucidate how TTF-1 is expressed in human C cells and medullary thyroid carcinomas (MTCs), and how this expression influences the functions and clinical behavior of these cells. By immunohistochemistry, the nuclei of normal and hyperplastic C cells distinctively reacted with antibody against TTF-1, whereas the immunostaining intensity in C cells was rather weak and heterogeneous in comparison with that in follicular cells. Identical TTF-1 immunoreactivity was observed in all 15 MTC specimens examined. The reaction intensity did not depend on tumor patterns or cell features. In nonisotopic in situ hybridization, an antisense riboprobe clearly hybridized the cytoplasms of C cells and MTC cells, which concurrently showed immunohistochemical positivity for calcitonin. Northern blot analysis indicated a marked hybridization with TTF-1 mRNA of approximately 2.3 kb in an MTC specimen. Furthermore, the presence of TTF-1 mRNA was confirmed by reverse transcription polymerase chain reaction (RT-PCR) in the human MTC cell line, TT, Our results suggest that human thyroid C cells and MTC cells express TTF-1 in connection with their functional ability. Therefore, TTF-1 expression can be a functional marker not only for follicular cells and follicular cell tumors but also for C cells and medullary C cell carcinomas. Copyright (C) 2000 by W.B. Saunders Company. C1 Yamanashi Med Univ, Sch Med, Dept Pathol, Tamaho, Yamanashi 40938, Japan. NIDDK, Metab Dis Branch, Cell Regulat Sect, NIH, Bethesda, MD USA. Wakayama Med Coll, Dept Pathol, Wakayama 640, Japan. Tokyo Womens Med Coll, Dept Pathol, Tokyo 162, Japan. RP Katoh, R (reprint author), Yamanashi Med Univ, Sch Med, Dept Pathol, 1110 Shimokato, Tamaho, Yamanashi 40938, Japan. NR 27 TC 61 Z9 65 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 2000 VL 31 IS 3 BP 386 EP 393 DI 10.1016/S0046-8177(00)80255-5 PG 8 WC Pathology SC Pathology GA 296QP UT WOS:000086035800019 PM 10746684 ER PT J AU Culleton, B Levy, D AF Culleton, B Levy, D TI Much ado about nothing, or much to do about something? The continuing controversy over the role of uric acid in cardiovascular disease - Response SO HYPERTENSION LA English DT Letter ID CHRONIC HEART-FAILURE; RISK FACTOR; FOLLOW-UP; HYPERTENSION; HYPERURICEMIA C1 Univ Calgary, Div Nephrol, Calgary, AB, Canada. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Culleton, B (reprint author), Univ Calgary, Div Nephrol, Calgary, AB, Canada. NR 31 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAR PY 2000 VL 35 IS 3 BP E105 EP E108 PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 296GJ UT WOS:000086015800031 ER PT J AU Rengarajan, J Mittelstadt, PR Mages, HW Gerth, AJ Kroczek, RA Ashwell, JD Glimcher, LH AF Rengarajan, J Mittelstadt, PR Mages, HW Gerth, AJ Kroczek, RA Ashwell, JD Glimcher, LH TI Sequential involvement of NFAT and EGR transcription factors in fast regulation SO IMMUNITY LA English DT Article ID T-CELL ACTIVATION; CYCLOSPORINE-A; NUCLEAR FACTOR; LIGAND EXPRESSION; IMMUNE-RESPONSE; FAMILY MEMBERS; MICE LACKING; IL-4 GENE; PROMOTER; ELEMENT AB The critical function of NFAT proteins in maintaining lymphoid homeostasis was revealed in mice lacking both NFATp and NFAT4 (DKO). DKO mice exhibit increased lymphoproliferation, decreased activation-induced cell death, and impaired induction of Fast. The transcription factors Egr2 and Egr3 are potent activators of Fast expression. Here we find that Egr2 and Egr3 are NFAT target genes. Activation of Fast occurs via the NFAT-dependent induction of Egr3, as demonstrated by the ability of exogenously provided NFATp to restore Egr-dependent Fast promoter activity in DKO lymph node cells. Further, Egr3 expression is enriched in Th1 cells, suggesting a molecular basis for the known preferential expression of Fast in the Th1 versus Th2 subset. C1 Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. Robert Koch Inst, D-13353 Berlin, Germany. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Glimcher, LH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, 665 Huntington Ave, Boston, MA 02115 USA. FU NIA NIH HHS [AG37833]; NIAID NIH HHS [AI98005] NR 51 TC 126 Z9 128 U1 1 U2 1 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 2000 VL 12 IS 3 BP 293 EP 300 DI 10.1016/S1074-7613(00)80182-X PG 8 WC Immunology SC Immunology GA 301DC UT WOS:000086292100007 PM 10755616 ER PT J AU Teodori, L Tagliaferri, F Stipa, F Valente, MG Coletti, D Manganelli, A Guglielmi, M D'Angelo, LS Schafer, H Gohde, W AF Teodori, L Tagliaferri, F Stipa, F Valente, MG Coletti, D Manganelli, A Guglielmi, M D'Angelo, LS Schafer, H Gohde, W TI Selection, establishment and characterization of cell lines derived from a chemically-induced rat mammary heterogeneous tumor, by flow cytometry, transmission electron microscopy, and immunohistochemistry SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE flow cytometry; breast cancer; rat cell lines; DNA content; tumor heterogeneity ID BREAST-CANCER; CARCINOMA; METASTASES AB In order to isolate, characterize, and establish culture cell lines with different diagnostic and prognostic significance, derived from multiclonal neoplasms, a ductal infiltrating mammary tumor was induced in rats by 7,12-dimethyl-benz[a]anthracene. Clones with different DNA/protein content, being the DI of 1.16, 1.30, and 1.60, respectively, were observed in the primary tumor. Biparametric flow cytometry suggested that the clone at 1.30 is made up of two subpopulations with different protein and slightly different DNA contents. The culture, after a few passages, exhibited the presence of aneuploid cells and the absence of diploid components, demonstrating that only tumor cells survived. The limiting dilution method gave rise to four lines with DI of 1.16, 1.25, 1.30, and 1.50; a mean chromosome number of 45, 46, 47, and 88, respectively; and different morphological and ultrastructural features. These characteristics were stable during the experimental procedure, that is, for about 20 passages. Conversely, the detection of cytoskeletal proteins indicated that the tumor epithelial cells underwent early dedifferentiation into sarcoma-like cells showing markers of stromal cell type and thus exhibiting phenotypic instability in vitro, a feature reported in many advanced human breast cancers in vivo. In conclusion, this cellular model represents the in vivo situation and appears suitable for in vitro studies of tumor cell characteristics and might be used to predict clinical behavior. C1 ENEA, Sect Biol & Toxicol Sci, Rome, Italy. Univ Rome La Sapienza, Dept Surg, Rome, Italy. Univ Rome La Sapienza, Dept Histol & Med Embryol, Rome, Italy. Inst Chem Lagrange, Rome, Italy. NIH, Inst Gerontol, Baltimore, MD USA. Univ Cologne, Dept Surg, Cologne, Germany. Univ Munster, Inst Radiobiol, Munster, Germany. RP Teodori, L (reprint author), ENEA, Sect Biol & Toxicol Sci, Rome, Italy. NR 26 TC 5 Z9 5 U1 1 U2 2 PU SOC IN VITRO BIOLOGY PI LARGO PA 9315 LARGO DR WEST, STE 25, LARGO, MD 20774 USA SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD MAR PY 2000 VL 36 IS 3 BP 153 EP 162 PG 10 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 302HN UT WOS:000086359800003 PM 10777054 ER PT J AU Nasir, A Chaudhry, AZ Gillespie, J Kaiser, HE AF Nasir, A Chaudhry, AZ Gillespie, J Kaiser, HE TI Papillary microcarcinoma of the thyroid: A clinico-pathologic and prognostic review SO IN VIVO LA English DT Review DE papillary; microcarcinoma; thyroid; loss of heterozygosity; pathology; prognosis; therapy; review ID LYMPH-NODE METASTASIS; DISTANT METASTASES; CERVICAL LYMPHADENOPATHY; SURGICAL-TREATMENT; POTENTIAL PITFALL; CARCINOMA; CANCER; GLAND; AUTOPSY; DISEASE AB Papillary microcarcinoma (PMC) of the thyroid is the most common form of thyroid cancer, which usually remains clinically silent until its incidental histologic diagnosis in autopsy or surgical material. Autopsy incidence varies from 3%-36%. PMC may, however, present with clinical symptoms, the commonest of which is cervical lymphadenopathy with or without palpable thyroid nodules. Other reported presentations include cystic neck mass, pulmonary mass (es), metastases in the skull or vertebral column. The upper limit of size to define PMC is 10 mm in most studies but many studies include lesions up to 15 mm in diameter. Histologic variants include encapsulated and partially encapsulated papillary carcinoma, circumscribed microcarcinoma and occult sclerosing carcinoma. Younger age and size less than 10 mm (< 15 mm in other studies) are considered to be favorable prognostic factors. Size alone, however, cannot be regarded as a determinant of prognosis. Older age, larger tumor size, distant metastases, capsular invasion and multifocality indicate unfavorable prognosis. Loss of heterozygosity (LOH) is an infrequent finding, since small deletions may be missed by southern blot analysis. Activation of oncogenes ret and trk have been reported in papillary carcinoma. Some authors advocate conservative while others favor aggressive therapy including total thyroidectomy with or without Iodine (131)ablation. Additional investigative techniques are needed to identify the subset of PMC cases with a potential for aggressive clinical course, thereby targeting more aggressive therapy to an appropriate subset of tumors. C1 George Washington Univ, Sch Med & Hlth Sci, Dept Pathol, Washington, DC 20037 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. Univ Maryland, Dept Pathol, Baltimore, MD 21201 USA. Univ Vienna, Dept Gen & Expt Pathol, Vienna, Austria. Univ N Texas, Hlth Sci Ctr, Inst Canc Res, Ft Worth, TX USA. Int Soc Study Comparat Oncol Inc, Silver Spring, MD USA. Deutsch Gesell Vergleichende Onkol EV, Int Inst Anticanc Res, Kapandriti, Greece. RP Nasir, A (reprint author), George Washington Univ, Sch Med & Hlth Sci, Dept Pathol, 23rd & Eye St NW, Washington, DC 20037 USA. NR 101 TC 31 Z9 34 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 0258-851X J9 IN VIVO JI In Vivo PD MAR-APR PY 2000 VL 14 IS 2 BP 367 EP 376 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 316ZG UT WOS:000087197900010 PM 10836212 ER PT J AU Schwan, WR Huang, XZ Hu, L Kopecko, DJ AF Schwan, WR Huang, XZ Hu, L Kopecko, DJ TI Differential bacterial survival, replication, and apoptosis-inducing ability of Salmonella serovars within human and murine macrophages SO INFECTION AND IMMUNITY LA English DT Article ID INTRACELLULAR SURVIVAL; MOUSE MACROPHAGES; INNATE RESISTANCE; TYPHIMURIUM; STRAINS; TYPHI; MICE; PATHOGENICITY; PHAGOSOMES; EXPRESSION AB Salmonella serovars are associated with human diseases that range from mild gastroenteritis to host-disseminated enteric fever. Human infections by Salmonella enterica serovar Typhi can lead to typhoid fever, but this serovar does not typically cause disease in mice or other animals. In contrast, S. enterica serovar Typhimurium and S. enterica serovar Enteritidis, which are usually linked to localized gastroenteritis in humans and some animal species, elicit a systemic infection in mice. To better understand these observations, multiple strains of each of several chosen serovars of Salmonella were tested for the ability in the nonopsonized state to enter, survive. and replicate within human macrophage cells (U937 and elutriated primary cells) compared with murine macrophage cells (J774A.1 and primary peritoneal cells); in addition, death of the infected macrophages was monitored. The serovar Typhimurium strains all demonstrated enhanced survival within J774A.1 cells and murine peritoneal macrophages, compared with the significant, almost 100-fold declines in viable counts noted for serovar Typhi strains. Viable counts for serovar Enteritidis either matched the level of serovar Typhia (J774A.1 macrophages) or were comparable to counts for serovar Typhimurium (murine peritoneal macrophages), Apoptosis was significantly higher in J774A.1 cells infected with serovar Typhimurium strain LT2 compared to serovar Typhi strain Ty2, On the other hand, serovar Typhi survived at a level up to 100-fold higher in elutriated human macrophages and 2- to 3-fold higher in U937 cells compared to the serovar Typhimurium and Enteritidis strains tested, Despite the differential multiplication of serovar Typhi during infection of U937 cells, serovar Typhi caused significantly less apoptosis than infections with serovar Typhimurium. These observations indicate variability in intramacrophage survival and host cytotoxicity among the various serovars and are the first to show differences in the apoptotic response of distinct Salmonella serovars residing in human macrophage cells. These studies suggest that nonopsonized serovar Typhimurium enters, multiplies within, and causes considerable, acute death of macrophages, leading to a highly virulent infection in mice (resulting in death within 14 days). In striking contrast, nonopsonized serovar Typhi survives silently and chronically within human macrophages, causing little cell death, which allows for intrahost dissemination and typhoid fever (low host mortality). The type of disease associated with any particular serovar of Salmonella is linked to the ability of that serovar both to persist within and to elicit damage in a specific host's macrophage cells. C1 US FDA, Lab Enter & Sexually Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Univ Wisconsin, Dept Biol & Microbiol, La Crosse, WI 54601 USA. RP Kopecko, DJ (reprint author), US FDA, Lab Enter & Sexually Transmitted Dis, Ctr Biol Evaluat & Res, HFM440,NIH Campus,Bldg 29-420, Bethesda, MD 20892 USA. NR 33 TC 87 Z9 88 U1 0 U2 2 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 2000 VL 68 IS 3 BP 1005 EP 1013 DI 10.1128/IAI.68.3.1005-1013.2000 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 285UW UT WOS:000085407400001 PM 10678900 ER PT J AU Cooper, AM Segal, BH Frank, AA Holland, SM Orme, IM AF Cooper, AM Segal, BH Frank, AA Holland, SM Orme, IM TI Transient loss of resistance to pulmonary tuberculosis in p47phox(-/-) mice SO INFECTION AND IMMUNITY LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; NITRIC-OXIDE SYNTHASE; MYCOBACTERIUM-TUBERCULOSIS; MURINE MACROPHAGES; HYDROGEN-PEROXIDE; DISSEMINATED BCG; INFECTION; INACTIVATION; SUPEROXIDE; VIRULENCE AB Mycobacterium tuberculosis is an important respiratory pathogen the growth of which is controlled primarily by cytokine-activated macrophages. One of the principal mediators of this control is nitric oxide; however, superoxide has recently been shown to be protective in systemic mycobacterial infections. To determine whether superoxide is important in controlling M. tuberculosis during primary pulmonary infection, mice lacking the cytosolic p47(phox) gene (which is essential for effective superoxide production by the NADPH oxidase) were infected aerogenically. The lack of superoxide during an aerosol infection with M. tuberculosis resulted in a significant increase in bacterial growth over the early period of infection. Once antigen-specific gamma interferon-producing lymphocytes were detected in the draining lymph nodes, however, bacterial growth in the lung stopped. One interesting consequence of the lack of superoxide was an increase in neutrophilic infiltrates within the granuloma, This may be a consequence of increased tissue damage due to more rapid bacterial growth or may reflect a role for superoxide in controlling inflammation. C1 Colorado State Univ, Dept Microbiol, Ft Collins, CO 80523 USA. Colorado State Univ, Dept Pathol, Ft Collins, CO 80523 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Cooper, AM (reprint author), Colorado State Univ, Dept Microbiol, 200 W Lake, Ft Collins, CO 80523 USA. OI Cooper, Andrea/0000-0001-6050-3863 FU NIAID NIH HHS [AI40488, R01 AI040488, AI75320] NR 27 TC 108 Z9 113 U1 1 U2 2 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 2000 VL 68 IS 3 BP 1231 EP 1234 DI 10.1128/IAI.68.3.1231-1234.2000 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 285UW UT WOS:000085407400032 PM 10678931 ER PT J AU Egan, AF Blackman, MJ Kaslow, DC AF Egan, AF Blackman, MJ Kaslow, DC TI Vaccine efficacy of recombinant Plasmodium falciparum merozoite surface protein 1 in malaria-naive, -exposed, and/or -rechallenged Aotus vociferans monkeys SO INFECTION AND IMMUNITY LA English DT Article ID CARBOXYL-TERMINAL FRAGMENT; ERYTHROCYTE INVASION; ANTIBODIES; ANTIGEN; PARASITE; INHIBIT; IMMUNOGENICITY; TRANSMISSION; PRECURSOR; MORBIDITY AB Protection against a lethal challenge infection of Plasmodium falciparum was elicited in malaria-naive Aotus vociferans monkeys by vaccination with the C terminus 19-kDa protein of the major merozoite surface protein (MSP-1(19)) fused to tetanus toxoid universal T-cell epitopes P30 and P2. Three of four monkeys were protected against a 10(4)-parasite challenge. Four monkeys were challenged with 10(5) parasites; one seif cured the infection, two were protected against high parasitemia (<2%) but were treated for severe anemia (hematocrit of <25%), and the fourth was not protected. In this model system, anemia appears to be a manifestation of incomplete protection (prolonged low-level parasitemia). Enzyme-linked immunosorbent assay (ELISA) antibody titers correlated with protection. Antibodies from some protected monkeys inhibited secondary processing of MSP-1(42) to MSP-1(33) and MSP-1(19). To mimic the repeated reinfections seen in regions where malaria is endemic, a second malaria parasite challenge was administered 3 months later. All P30P2MSP-1(19)-vaccinated monkeys were protected; thus, a single challenge infection may underestimate vaccine efficacy. ELISA antibody titers correlated with protection against a second infection but had decreased compared to the first challenge. As most target populations for asexual blood-stage malaria vaccines will have been exposed to malaria parasites, a malaria parasite-exposed monkey was vaccinated with P30P2MSP-1(19). This monkey was completely protected, while a malaria parasite-naive P30P2MSP-1(19)-vaccinated monkey self-cured a low-grade parasitemia. Prior malaria parasite infection primed the production of anti-native MSP-1(19) antibodies, which were boosted by vaccination with recombinant P30P2MSP-1(19). Preliminary data suggest that immunogenicity studies of vaccines designed for malaria parasite-exposed populations should also be conducted in malaria parasite-exposed subjects. C1 NIAID, Malaria Vaccines Sect, NIH, Bethesda, MD 20892 USA. NIAID, Malaria Vaccine Dev Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Natl Inst Med Res, Div Parasitol, London NW7 1AA, England. RP Kaslow, DC (reprint author), Merck Res Labs, WP 16-225, W Point, PA 19486 USA. NR 27 TC 61 Z9 66 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 2000 VL 68 IS 3 BP 1418 EP 1427 DI 10.1128/IAI.68.3.1418-1427.2000 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 285UW UT WOS:000085407400056 PM 10678955 ER PT J AU Konadu, EY Lin, FYC Ho, VA Thuy, NTT Bay, PV Thanh, TC Khiem, HB Trach, DD Karpas, AB Li, J Bryla, DA Robbins, JB Szu, SC AF Konadu, EY Lin, FYC Ho, VA Thuy, NTT Bay, PV Thanh, TC Khiem, HB Trach, DD Karpas, AB Li, J Bryla, DA Robbins, JB Szu, SC TI Phase 1 and phase 2 studies of Salmonella enterica serovar Paratyphi A O-specific polysaccharide-tetanus toroid conjugates in adults, teenagers, and 2-to 4-year-old children in Vietnam SO INFECTION AND IMMUNITY LA English DT Article ID SICKLE-CELL-ANEMIA; INFLUENZAE TYPE-B; TYPHOID-FEVER; IMMUNOLOGICAL PROPERTIES; CAPSULAR POLYSACCHARIDE; RANDOMIZED TRIAL; SEROGROUP-A; MICE; VACCINE; ANTIBODIES AB Salmonella enterica serovar Paratyphi A O-specific polysaccharide (O-SP) was activated with 1-cyano-4-dimethylaminopyridinium tetrafluoroborate (CDAP) and bound to tetanus toxoid (TT) with adipic acid dihydrazide as a linker (SPA-TT1) or directly (SPA-TT2). In mice, these two conjugates elicited high levels of immunoglobulin G (IgG) anti-lipopolysaccharide (LPS) in serum with bactericidal activity (E. Konadu, J. Shiloach, D. A. Bryla, J. B. Robbins, and S. C. Szu, Infect. Immun. 64:2709-2715, 1996). The safety and immunogenicity of the two conjugates were then evaluated sequentially in Vietnamese adults, teenagers, and 2- to 4-year-old children. None of the vaccinees experienced significant side effects, and all had preexisting LPS antibodies. At 4 weeks after injection, there were significant increases of the geometric mean IgG and IgM anti-LPS levels in the adults and teenagers: both conjugates elicited a greater than fourfold rise in the IgG anti-LPS level in serum in greater than or equal to 80% of the volunteers. SPA-TT2, elicited slightly higher, though not statistically significantly, levels of IgG anti-LPS than did SPA-TT1 in these age groups. Accordingly, only SPA-TT2 was evaluated in the 2- to 4-year-old children. On a random basis, one or two injections were administered 6 weeks apart to the children. No significant side effects were observed, and the levels of preexisting anti-LPS in serum were similar in children of all ages. A significant rise in the IgG anti-LPS titer was elicited by the first injection (P = 0.0001); a second injection did not elicit a booster response. Representative sera from all groups had bactericidal activity that could be adsorbed by S. enterica serovar Paratyphi A LPS. C1 NICHHD, NIH, Bethesda, MD 20892 USA. Huu Nghi Hosp, Cao Lanh, Dong Thap, Vietnam. Inst Pasteur, Ho Chi Minh, Vietnam. Natl Inst Hyg & Epidemiol, Hanoi, Vietnam. RP Szu, SC (reprint author), NICHHD, NIH, Bldg 6,Room 424, Bethesda, MD 20892 USA. NR 66 TC 43 Z9 46 U1 0 U2 3 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 2000 VL 68 IS 3 BP 1529 EP 1534 DI 10.1128/IAI.68.3.1529-1534.2000 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 285UW UT WOS:000085407400071 PM 10678970 ER PT J AU Subramanian, G Koonin, EV Aravind, L AF Subramanian, G Koonin, EV Aravind, L TI Comparative genome analysis of the pathogenic spirochetes Borrelia burgdorferi and Treponema pallidum SO INFECTION AND IMMUNITY LA English DT Article ID BACTERIAL TRANSCRIPTION FACTOR; MULTIPLE SEQUENCE ALIGNMENTS; ESCHERICHIA-COLI; PROTEIN SEQUENCES; LYME-DISEASE; PSI-BLAST; DOMAINS; IDENTIFICATION; CLONING; SYSTEM AB A comparative analysis of the predicted protein sequences encoded in the complete genomes of Borrelia burgdorferi and Treponema pallidum provides a number of insights into evolutionary trends and adaptive strategies of the two spirochetes. A measure of orthologous relationships between gene sets, termed the orthology coefficient (OC), was developed. The overall OC value for the gene sets of the two spirochetes is about 0,43, which means that less than one-half of the genes show readily detectable orthologous relationships. This emphasizes significant divergence between the two spirochetes, apparently driven by different biological niches, Different functional categories of proteins as well as different protein families show a broad distribution of OC values, from near 1 (a perfect, one to-one correspondence) to near 0. The proteins involved in core biological functions, such as genome replication and expression, typically show high OC values. In contrast, marked variability is seen among proteins that are involved in specific processes, such as nutrient transport, metabolism, gene-specific transcription regulation, signal transduction, and host response. Differences in the gene complements encoded in the two spirochete genomes suggest active adaptive evolution for their distinct niches. Comparative analysis of the spirochete genomes produced evidence of gene exchanges with other bacteria, archaea, and eukaryotic hosts that seem to have occurred at different points in the evolution of the spirochetes. Examples are presented of the use of sequence profile analysis to predict proteins that are likely to play a role in pathogenesis, including secreted proteins that contain specific protein-protein interaction domains, such as von Willebrand A, YWTD, TPR, and PR1, some of which hitherto have been reported only in eukaryotes, We tentatively reconstruct the likely evolutionary process that has led to the divergence of the two spirochete lineages; this reconstruction seems to point to an ancestral state resembling the symbiotic spirochetes found in insect guts. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. NR 83 TC 52 Z9 55 U1 2 U2 3 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 2000 VL 68 IS 3 BP 1633 EP 1648 DI 10.1128/IAI.68.3.1633-1648.2000 PG 16 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 285UW UT WOS:000085407400084 PM 10678983 ER PT J AU Kojima, H Toda, M Sitkovsky, MV AF Kojima, H Toda, M Sitkovsky, MV TI Comparison of Fas- versus perforin-mediated pathways of cytotoxicity in TCR- and Thy-1-activated murine T cells SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE cytotoxic T lymphocyte; Fas ligand; perforin; retargeting; TCR; Thy-1 ID TOXIC LYMPHOCYTES-T; MONOCLONAL-ANTIBODY; LYMPHOKINE PRODUCTION; CANCER-IMMUNOTHERAPY; SIGNAL-TRANSDUCTION; RECEPTOR COMPLEX; CO-EXPRESSION; MICE LACKING; ACTIVATION; THY-1 AB T cell-mediated cytotoxicity can be triggered by cross-linking of TCR or Thy-1 surface proteins. While the TCR-triggered signaling initiates both perforin- and Fas ligand (FasL)-Fas-mediated mechanisms of cytotoxicity, it was not clear which mechanism was utilized by Thy-1-triggered signals and which pathway of cytotoxicity was triggered at low levels of antigen expression. It is shown that glycophosphatidylinositol-linked surface glycoprotein Thy-1 preferentially activates FasL-Fas- but not perforin-mediated cytotoxicity. This is explained by the lesser intensity of Thy-1-mediated signaling in T cells. The data suggest that Thy-1-triggered Fas-mediated cytotoxicity is completely dependent on cross-talk between Thy-1 and Ton signals since mutations in TCR-CD3 complex molecules or inhibition of tyrosine kinases or calcineurin abolished or strongly inhibited Thy-1-triggered FasL-Fas-mediated cytotoxicity. Lower concentrations of antigenic peptide or levels of cross-linking with anti-TCR-CDS mAb are required to trigger Fas-mediated than perforin-mediated cytotoxicity by different cytotoxic T lymphocyte (CTL) lines and clones, and it is shown that cross-linking of Thy-1 is much less efficient in triggering accumulation of second messengers (intracellular Ca2+) than cross-linking of TCR on CTL. Taken together, these data reflect the possibility of differential activation of FasL and/or perforin pathways of cytotoxicity depending on the nature of activating stimuli and surface receptor. C1 NIAID, Biochem & Immunopharmacol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. Keio Univ, Sch Med, Dept Physiol, Tokyo 1608582, Japan. RP Sitkovsky, MV (reprint author), NIAID, Biochem & Immunopharmacol Sect, Immunol Lab, NIH, Bldg 10-11N311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. RI Toda, Masahiro/L-2268-2013 NR 51 TC 16 Z9 16 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD MAR PY 2000 VL 12 IS 3 BP 365 EP 374 DI 10.1093/intimm/12.3.365 PG 10 WC Immunology SC Immunology GA 295RQ UT WOS:000085982000014 PM 10700471 ER PT J AU Hemmer, B Kondo, T Gran, B Pinilla, C Cortese, I Pascal, J Tzou, A McFarland, HF Houghten, R Martin, R AF Hemmer, B Kondo, T Gran, B Pinilla, C Cortese, I Pascal, J Tzou, A McFarland, HF Houghten, R Martin, R TI Minimal peptide length requirements for CD4(+) T cell clones - implications for molecular mimicry and T cell survival SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE autoimmunity; CD4(+) T cells; cross-reactivity; peptide combinatorial libraries; short antigenic peptides ID CLASS-II MOLECULES; ANTIGEN RECOGNITION; CROSS-REACTIVITY; STRUCTURAL BASIS; VIRAL PEPTIDES; LARGE NUMBERS; ALPHA-BETA; LIGANDS; RECEPTOR; SPECIFICITY AB CD4(+) T lymphocytes usually recognize peptides of 12-16 amino acids in the context of HLA class II molecules. We have recently used synthetic peptide combinatorial libraries to dissect in detail antigen recognition by autoreactive CD4(+) T cell clones (TCC). The results of these studies demonstrated that antigen recognition by T cells is highly degenerate and that many cross-reactive ligands can be defined, some of which much more potent than the selecting autoantigen. Based on these observations, we examined the response of a myelin basic protein-specific HLA class II-restricted CD4(+) TCC to truncation variants of optimal ligands, Surprisingly, pentapeptides, tetrapeptides and even tripeptides derived from different segments of the optimal ligands were recognized by the TCC, and some were even more potent than the selecting autoantigen. In addition, these peptides enhanced the survival of the TCC at low concentration. The relevance of this finding was supported by the generation of pentapeptide-specific CD4(+) TCC from peripheral blood lymphocytes. These observations not only change existing views on the length requirements for activation of CD4(+) HLA class Ii-restricted T cells, but also extend our knowledge about the flexibility of TCR recognition and the potential for cross-reactivity in the immune system. C1 NINDS, Cellular Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Torrey Pines Inst Mol Studies, San Diego, CA 92121 USA. Multiple Peptide Syst, San Diego, CA 92121 USA. RP Martin, R (reprint author), NINDS, Cellular Immunol Sect, Neuroimmunol Branch, NIH, Bldg 10,Room 5B-16,10 Ctr Dr,MSC 1400, Bethesda, MD 20892 USA. RI Gran, Bruno/A-2288-2013 OI Gran, Bruno/0000-0001-6384-2342 NR 43 TC 39 Z9 39 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD MAR PY 2000 VL 12 IS 3 BP 375 EP 383 DI 10.1093/intimm/12.3.375 PG 9 WC Immunology SC Immunology GA 295RQ UT WOS:000085982000015 PM 10700472 ER PT J AU Sharp, DS Burchfiel, CM Rodriguez, BL Sharrett, AR Sorlie, PD Marcovina, SM AF Sharp, DS Burchfiel, CM Rodriguez, BL Sharrett, AR Sorlie, PD Marcovina, SM TI Apolipoprotein A-1 predicts coronary heart disease only at low concentrations of high-density lipoprotein cholesterol: an epidemiological study of Japanese-Americans SO INTERNATIONAL JOURNAL OF CLINICAL & LABORATORY RESEARCH LA English DT Article DE apolipoprotein A-1; high-density lipoprotein-cholesterol; triglycerides; coronary arteriosclerosis; epidemiology ID A-I; ARTERY DISEASE; MYOCARDIAL-INFARCTION; PLASMA-LIPIDS; MEN; RISK; ATHEROSCLEROSIS; HAWAII; ACYLTRANSFERASE; TRIGLYCERIDE AB Conventional epidemiological and clinical studies of apolipoprotein A-1 and high-density lipoprotein-cholesterol have demonstrated, when examined jointly, that high-density lipoprotein is a better predictor of coronary heart disease. This strategy does not take into account known lipid metabolic relationships. A statistical approach that takes into account apoliprotein A-1 being a constituent of the high-density lipoprotein particle is more appropriate. Among 1,177 Japanese-American men of the Honolulu Heart Program cohort free of disease at baseline (1980-1982), 182 new coronary heart disease cases developed over a 12-year follow-up period. After removing the linear relationship with high-density lipoprotein-cholesterol, a relative measure of apoliprotein A-1 concentration was derived. Based on joint conditions of "low" and "high" relative apoliprotein h-l concentration and less than or equal to 40 and >40 mg/dl for the high-density lipoprotein-cholesterol distribution, four groupings were created. Among relative joint groupings of high/less than or equal to 40, low/less than or equal to 40, high/>40, and low/>40, respectively, the 12-year coronary heart disease incidence varied from 28.6, 18.2, 8.3, to 11.7 cases per 1,000 person-years. A test of statistical interaction was significant (P=0.028). Additional analyses revealed coronary heart disease cases were more likely among men with triglycerides >190 mg/dl. Observed patterns of relationships among relative apoliprotein A-1 level, high-density lipoprotein cholesterol, and triglycerides with incident coronary heart disease are consistent with patterns noted in clinical, laboratory, and transgenic animal research more capable of elucidating mechanisms of disease causation. This epidemiological study suggests similar mechanisms may be operating at a population level, and may contribute to the public health burden of coronary heart disease. C1 NHLBI, Epidemiol & Biometry Program, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Kuakini Med Ctr, Honolulu Heart Program, Honolulu, HI USA. Univ Hawaii Manoa, John A Burns Sch Med, Dept Med, Honolulu, HI 96822 USA. Univ Washington, NW Lipid Res Labs, Seattle, WA 98195 USA. RP Sharp, DS (reprint author), NIOSH, HELD BB, 1095 Willowdale Rd,MS 4020, Morgantown, WV 26505 USA. FU NHLBI NIH HHS [N01-HC-05102] NR 42 TC 12 Z9 12 U1 2 U2 5 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0940-5437 J9 INT J CLIN LAB RES JI Int. J. Clin. Lab. Res. PD MAR PY 2000 VL 30 IS 1 BP 39 EP 48 DI 10.1007/s005990070032 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 334WJ UT WOS:000088208400008 PM 10984131 ER PT J AU Egan, CA Meadows, KP Zone, JJ AF Egan, CA Meadows, KP Zone, JJ TI Plasmapheresis as a steroid saving procedure in bullous pemphigoid SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Article ID INTRAVENOUS GAMMA-GLOBULIN; BASEMENT-MEMBRANE; IMMUNOGLOBULIN; ANTIGEN; ANTIBODIES; DISEASE; BP180 AB Background Bullous pemphigoid is an immunobullous disease affecting predominantly older patients. In severe cases, high-dose corticosteroids and/or other immunosuppressants are often needed long term to control the disease. These can be associated with serious side-effects in this patient population. Objective To evaluate the benefit of plasmapheresis as a steroid saving agent in a cohort of 10 patients. Results Plasmapheresis was effective as a steroid saving therapy. All patients went into remission with a lower daily dosage of oral prednisone at 3 and 6 months postplasmapheresis. Two patients had side-effects from therapy that, while significant, did not interfere with long-term improvement in their disease. Eight patients had circulating immunoglobulin G (IgG) antibodies reactive with bullous pemphigoid antigen 1, and three of these had circulating antibodies reactive with bullous pemphigoid antigen 2 on Western immunoblot. Conclusions Plasmapheresis was an effective steroid sparing therapy in these patients. Due to its high cost and potential morbidity, plasmapheresis should not be recommended as routine therapy for bullous pemphigoid, but it is a useful adjunct in resistant cases. C1 Salt Lake City Vet Affairs Med Ctr, Dermatol Sect, Med Serv, Salt Lake City, UT USA. Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA. RP Egan, CA (reprint author), NCI, Dermatol Branch, NIH, Bldg 10,Room 12N238,10 Ctr Dr MSC 1908, Bethesda, MD 20892 USA. FU NIDDK NIH HHS [R01 DK50678-01A1] NR 24 TC 13 Z9 13 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD MAR PY 2000 VL 39 IS 3 BP 230 EP 235 DI 10.1046/j.1365-4362.2000.00876.x PG 6 WC Dermatology SC Dermatology GA 303PH UT WOS:000086430900018 PM 10759969 ER PT J AU Mohan, AK Degnan, D Feigley, CE Shy, CM Hornung, CA Mustafa, T Macera, CA AF Mohan, AK Degnan, D Feigley, CE Shy, CM Hornung, CA Mustafa, T Macera, CA TI Comparison of respiratory symptoms among community residents near waste disposal incinerators SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL HEALTH RESEARCH LA English DT Article DE incinerators; respiratory symptoms; hazardous waste ID HEALTH AB A previous survey found that residents near a hazardous waste incinerator reported more respiratory symptoms than residents of a nearby community. To explore the possibility that these findings might have been due to the use of a rural control site, far removed from urban pollution, we expanded the analysis to include reports of respiratory symptoms from residents of six additional communities. Residents of each of four study communities were exposed to the plumes of biomedical, municipal or hazardous waste combustors. For each study community, a comparison community was surveyed that was distant from major point sources of air pollution. Over 4200 respondents were queried by telephone about respiratory symptoms, smoking and other risk factors such as chemical exposures in the workplace and home, and provided a subjective assessment of air quality in their neighborhoods. Differences in symptom prevalence between each study community and its respective control community, as well as a combined control group, were explored, controlling for factors other than community exposure that may affect respiratory health. Results indicate a higher prevalence of all self-reported respiratory symptoms in one community near a hazardous waste incinerator compared with its control community. While this relationship persisted after controlling for perceived air quality and when compared with a combined control group, only respiratory symptoms of long duration remained significant. These results suggest that further examination of the respiratory health of residents living near this waste combustor source is warranted. C1 Univ S Carolina, Sch Publ Hlth, Columbia, SC 29208 USA. Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC 27599 USA. Univ S Carolina, Sch Med, Columbia, SC 29208 USA. RP Mohan, AK (reprint author), NCI, NIH, 6120 Execut Blvd,Room 7051, Rockville, MD 20852 USA. NR 14 TC 7 Z9 7 U1 0 U2 2 PU CARFAX PUBLISHING PI BASINGSTOKE PA RANKINE RD, BASINGSTOKE RG24 8PR, HANTS, ENGLAND SN 0960-3123 J9 INT J ENVIRON HEAL R JI Int. J. Environ. Health Res. PD MAR PY 2000 VL 10 IS 1 BP 63 EP 75 PG 13 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 302GV UT WOS:000086358100007 ER PT J AU Mariano, A Di Carlo, A Pastan, I Macchia, V AF Mariano, A Di Carlo, A Pastan, I Macchia, V TI Analysis of glycoproteins in cancers and normal tissues reactive with monoclonal antibodies B3 and B1 SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE monoclonal antibodies; Lewis(Y) carbohydrate antigens ID ANTIGENS; PROTEINS; TUMORS; BINDS AB In this study we show by immunoblotting that B1 and B3, two newly isolated monoclonal antibodies, react with a variety of glycoproteins with different molecular weights expressed in stomach, pancreas, colorectal and breast cancers. The pattern of reactivity differed among cancers arising in different tissues, although no correlation has been observed with the histopathological characteristics of the lesion analysed. MAb B3 and MAb B1, have a limited reactivity with peritumoral tissues, whereas react very strongly with metastatic lesion. Because of the limited reactivity of these antibodies with normal tissue, MAbs B3 and B1, armed with toxin in the form of recombinant immunotoxins, can be useful in treating certain kinds of cancer such as metastatic lesions. However, until current clinical trials are completed, we will not know if they will be helpful in cancer treatment. C1 Univ Naples Federico II, Dipartimento Biol & Patol Cellulare & Mol L Calif, I-80131 Naples, Italy. Univ Pisa, Dipartimento Patol Sperimentale Biotecnol Med Inf, I-56126 Pisa, Italy. NCI, Div Basic Sci, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Macchia, V (reprint author), Univ Naples Federico II, Dipartimento Biol & Patol Cellulare & Mol L Calif, Via S Pansini 5, I-80131 Naples, Italy. NR 13 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 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAR PY 2000 VL 16 IS 3 BP 549 EP 553 PG 5 WC Oncology SC Oncology GA 285TH UT WOS:000085403800016 PM 10675488 ER PT J AU Yu, JJ Lee, KB Mu, CJ Li, QD Abernathy, TV Bostick-Bruton, F Reed, E AF Yu, JJ Lee, KB Mu, CJ Li, QD Abernathy, TV Bostick-Bruton, F Reed, E TI Comparison of two human ovarian carcinoma cell lines (A2780/CP70 and MCAS) that are equally resistant to platinum, but differ at codon 118 of the ERCC1 gene SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE ERCC1; p53; DNA repair; cisplatin; ovarian cancer ID MESSENGER-RNA EXPRESSION; ACQUIRED CISPLATIN RESISTANCE; REPAIR EXCISION NUCLEASE; CANCER CELLS; DNA ADDUCT; TISSUES; P53; CHEMOTHERAPY; SENSITIVITY; MECHANISMS AB ERCC1 is an essential gene within the nucleotide excision repair process. We studied two human ovarian carcinoma cell lines for cisplatin resistance, which differed with respect to ERCC1. The A2780/CP70 cell line has been extensively studied previously, and has the wild-type ERCC1 sequence. The MCAS cell line has a recently described ERCC1 polymorphism at codon 118, which is associated with an approximate 50% reduction in codon usage. These cells did not differ with respect to p53 sequence nor p53 mRNA induction following cisplatin exposure. The induction of ERCC1 mRNA was markedly reduced in MCAS cells as compared to A2780/CP70 cells. At the IC50 cisplatin dose for each cell line, MCAS cells were less proficient at cisplatin-DNA adduct repair than A2780/CP70 cells. In absolute terms, A2780/CP70 cells repaired 3-fold as much adduct (2.7 pg/mu g DNA over 6 h vs 0.86 pg/mu g DNA); and when expressed in terms of the maximal DNA adduct load, A2780/CP70 cells repaired 50% more adduct than MCAS cells. MCAS cells had increased cytosolic inactivation of drug at the IC50 dose level, which has been previously suggested to be a compensatory cellular response for reduced DNA repair capacity. These data suggest the possibility that this specific ERCC1 polymorphism, may be associated with reduced DNA repair capacity in human ovarian cancer cells. This association may be effected through a reduction in peak production of ERCC1 mRNA, and a consequent reduction in the translation of ERCC1 mRNA into protein. C1 NCI, Med Ovarian Canc Sect, Dev Therapeut Dept, Med Branch,Div Clin Sci, Bethesda, MD 20892 USA. RP Reed, E (reprint author), NCI, Med Ovarian Canc Sect, Dev Therapeut Dept, Med Branch,Div Clin Sci, Bldg 10,Room 12N226, Bethesda, MD 20892 USA. NR 34 TC 134 Z9 145 U1 0 U2 2 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 2000 VL 16 IS 3 BP 555 EP 560 PG 6 WC Oncology SC Oncology GA 285TH UT WOS:000085403800017 PM 10675489 ER PT J AU Tawn, EJ Whitehouse, CA Holdsworth, D Morris, S Tarone, RE AF Tawn, EJ Whitehouse, CA Holdsworth, D Morris, S Tarone, RE TI Chromosome analysis of workers occupationally exposed to radiation at the Sellafield nuclear facility SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY LA English DT Article ID ATOMIC-BOMB SURVIVORS; HUMAN-LYMPHOCYTES; FOLLOW-UP; ABERRATIONS; FREQUENCY; EXPOSURES; DOSIMETRY; PLUTONIUM; SMOKING; CANCER AB Purpose: To investigate the relationship between stable chromosome aberration frequency in peripheral blood lymphocytes and occupational cumulative radiation exposure. Materials and methods: Cytogenetic analysis using G-banding was performed on peripheral blood lymphocyte cultures from 104 workers from the British Nuclear Fuels PLC facility at Sellafield, UK. The study group comprised 61 men with lifetime cumulative doses > 500 mSv, 39 men with minimal exposure (i.e. <50 mSv) who formed a control group and 4 men with intermediate doses. Results: The slope of the dose-response, adjusted for smoking status, for translocations and insertions was 0.55 +/- 0.31 x 10(-2)/cell/Sv. Consideration of chromosome breakpoints for all aberrations combined in the radiation workers revealed an excess in the C group chromosomes and a deficit in the F group chromosomes with breakpoints being concentrated in the terminal regions whereas the distribution in the control group did not deviate from expectation. Conclusions: The dose-response was not significantly different from the parallel FISH analysis (Tucker ct al. 1997) and confirms that chronic radiation exposure appears to be substantially less effective at inducing stable chromosome aberrations in comparison with acute exposure. C1 Westlakes Res Inst, Genet Unit, Moor Row CA24 3JY, Cumbria, England. British Nucl Fuels PLC, Dept Occupat Hlth, Seascale CA20 1PG, Cumbria, England. NCI, NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Tawn, EJ (reprint author), Westlakes Res Inst, Genet Unit, Westlakes Sci & Technol Pk, Moor Row CA24 3JY, Cumbria, England. NR 46 TC 14 Z9 15 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 0955-3002 J9 INT J RADIAT BIOL JI Int. J. Radiat. Biol. PD MAR PY 2000 VL 76 IS 3 BP 355 EP 365 PG 11 WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 294FV UT WOS:000085901600008 PM 10757315 ER PT J AU Karali, A Russell, P Stefani, FH Tamm, ER AF Karali, A Russell, P Stefani, FH Tamm, ER TI Localization of myocilin/trabecular meshwork-inducible glucocorticoid response protein in the human eye SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 09-14, 1999 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol, Natl Hlth Public Serv Award, Childern Hosp Res Fdn ID OPEN-ANGLE GLAUCOMA; TRABECULAR MESHWORK; CLINICAL-FEATURES; GENE; TIGR; MUTATION; IDENTIFICATION; OLFACTOMEDIN; EXPRESSION; CLONING AB PURPOSE. To study distribution and cellular localization of myocilin/trabecular meshwork-inducible glucocorticoid response protein (TIGR) in the human eye. METHODS. A peptide antibody against a portion of the myosin-like domain of myocilin/TIGR was developed. Different ocular tissues from three human donors were investigated by one- and two-dimensional gel electrophoresis and Western blot analysis. Immunohistochemistry was performed on 25 human eyes enucleated because of posterior choroidal melanoma and on 7 normal human donor eyes. RESULTS. By Western blot analysis, a band at approximately 57 kDa was visualized in cornea, trabecular meshwork, lamina cribrosa, optic nerve, retina, iris, ciliary body, and vitreous humor. By immunohistochemistry, immunoreactivity for myocilin/TIGR was observed in cells of the corneal epi- and endothelium and extracellularly in the corneal stroma and sclera. In the trabecular meshwork, cells of the uveal and corneoscleral meshwork were stained, as was the cribriform area directly adjacent to Schlemm's canal. Positive staining was seen in cells of the ciliary epithelium, ciliary muscle, lens epithelium, and in stromal and smooth muscle cells of the iris. Throughout the entire vitreous body, fine filamentous material was positively labeled. In the retina, staining was seen along the outer surface of rods and cones, in neurons of the inner and outer nuclear layer, and in the axons of optic nerve ganglion cells. Optic nerve axons were stained in the prelaminar, laminar, and postlaminar parts of the nerve. In the region of the lamina cribrosa, astrocytes in the glial columns and cribriform plates were positively labeled. CONCLUSIONS. Myocilin/TIGR is expressed in almost every ocular tissue. Depending on die respective tissue, it is observed extra- or intracellularly. The presence of myocilin/TIGR in optic nerve axons and lamina cribrosa astrocytes indicates that the trabecular meshwork might not be the only target of abnormal myocilin/TIGR in GLC1A-linked open-angle glaucoma. C1 Univ Erlangen Nurnberg, Dept Anat 2, D-91054 Erlangen, Germany. NEI, Lab Mechanisms Ocular Dis, NIH, Bethesda, MD 20892 USA. Univ Munich, Hosp Eye, D-8000 Munich, Germany. RP Tamm, ER (reprint author), Univ Erlangen Nurnberg, Dept Anat 2, Univ Str 19, D-91054 Erlangen, Germany. NR 37 TC 109 Z9 117 U1 0 U2 4 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR PY 2000 VL 41 IS 3 BP 729 EP 740 PG 12 WC Ophthalmology SC Ophthalmology GA 289KY UT WOS:000085621200017 PM 10711688 ER PT J AU Simonelli, F Testa, F de Crecchio, G Rinaldi, E Hutchinson, A Atkinson, A Dean, M D'Urso, M Allikmets, R AF Simonelli, F Testa, F de Crecchio, G Rinaldi, E Hutchinson, A Atkinson, A Dean, M D'Urso, M Allikmets, R TI New ABCR mutations and clinical phenotype in Italian patients with Stargardt disease SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; GENE ABCR; RETINITIS-PIGMENTOSA; PREVALENCE; DYSTROPHY AB PURPOSE. TO assess the mutation spectrum in the ABCR gene and clinical phenotypes in Italian families with autosomal recessive Stargardt disease (STGD1) and fundus flavimaculatus (FFM). METHODS. Eleven families from southern Italy, including 18 patients with diagnoses of STGD1, were clinically examined. Ophthalmologic examination included kinetic perimetry, electrophysiological studies, and fluorescein angiography. DNA samples of the affected individuals and their family members were analyzed for variants in all 50 exons of the ABCR gene by a combination of single-strand conformation polymorphism analysis and direct sequencing techniques. RESULTS. Ten ABCR variants were identified in IG (73%) of 22 mutant alleles of patients with STGD1. Five mutations of 10 that were found had not been previously described. The majority of variants represent missense amino acid substitutions, and all mutant alleles resegregate with the disease in the respective families. These ABCR variants were not detected in 170 unaffected control individuals (340 chromosomes) of Italian origin. Clinical evaluation of these families affected by STGD1 showed an unusually high frequency of early age-related macular degeneration (AMD) in parents of patients with STGD1 (8/22; 36%), consistent with the hypothesis that some heterozygous ABCR mutations enhance susceptibility to AMD. CONCLUSIONS. Patients from southern Italy with Stargardt disease show extensive allelic heterogeneity of the ABCR gene, concordant with previous observations in patients with STGD1 from different ethnic groups. Half the mutations identified in this study had not been previously described in patients with STGD1. Screening of increasingly large numbers of patients would help to determine whether this can be explained by ethnic differences, or is an indicator of extensive allelic heterogeneity of ABCR in STGD1 and other eye diseases. in 6 (55%) of 11 families, the first-degree relatives of patients with STGD1 were diagnosed with early AMD, supporting the previous observation that some STGD1 alleles are also associated with AMD. C1 Columbia Univ, Dept Ophthalmol, New York, NY 10032 USA. Columbia Univ, Dept Pathol, New York, NY 10032 USA. Univ Naples 2, Eye Clin, Naples, Italy. CNR, Int Inst Genet & Biophys, I-80125 Naples, Italy. Univ Naples Federico II, Eye Clin, Naples, Italy. NCI, Frederick Canc Res & Dev Ctr, Lab Gen Divers, Frederick, MD USA. RP Allikmets, R (reprint author), Columbia Univ, Dept Ophthalmol, 2nd Floor,630 W 168th St, New York, NY 10032 USA. RI Dean, Michael/G-8172-2012; Testa, Francesco/J-3185-2012; OI Dean, Michael/0000-0003-2234-0631; Simonelli, Francesca/0000-0001-8520-6769; Testa, Francesco/0000-0002-1482-1577 NR 23 TC 57 Z9 60 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR PY 2000 VL 41 IS 3 BP 892 EP 897 PG 6 WC Ophthalmology SC Ophthalmology GA 289KY UT WOS:000085621200039 PM 10711710 ER PT J AU Nussinov, R AF Nussinov, R TI Protein binding and protein folding SO ITALIAN JOURNAL OF BIOCHEMISTRY LA English DT Editorial Material C1 NCI, Lab Expt & Computat Biol, SAIC, FCRDC, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Fac Med, Sackler Inst Mol Med, Ramat Aviv, Israel. RP Nussinov, R (reprint author), NCI, Lab Expt & Computat Biol, SAIC, FCRDC, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMEDIA SRL PI MILAN PA VIA CARLO FARINI 70, 20159 MILAN, ITALY SN 0021-2938 J9 ITAL J BIOCHEM JI Ital. J. Biochem. PD MAR PY 2000 VL 49 IS 1 BP 1 EP 1 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 340LB UT WOS:000088533700001 ER PT J AU Pearson, GD Veille, JC Rahimtoola, S Hsia, J Oakley, CM Hosenpud, JD Ansari, A Baughman, KL AF Pearson, GD Veille, JC Rahimtoola, S Hsia, J Oakley, CM Hosenpud, JD Ansari, A Baughman, KL TI Peripartum cardiomyopathy - National Heart, Lung, and Blood Institute and Office of Rare Diseases (National Institutes of Health) workshop recommendations and review SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID LEFT-VENTRICULAR FUNCTION; ENDOMYOCARDIAL BIOPSY; MYOCARDITIS; PREGNANCY; FAILURE; CELLS; CARVEDILOL; AMLODIPINE; DIAGNOSIS; MORBIDITY AB Objective Peripartum cardiomyopathy (PPCM) is a rare life-threatening cardiomyopathy of unknown cause that occurs in the peripartum period in previously healthy women. In April 1997, the National Heart, Lung, and Blood Institute (NHLBI) and the Office of Rare Diseases of the National Institutes of Health (NIH) convened a Workshop on Peripartum Cardiomyopathy to foster a systematic review of information and to develop recommendations for research and education. Participants Fourteen workshop participants were selected by NHLBI staff and represented cardiovascular medicine, obstetrics, immunology, and pathology. A representative subgroup of 8 participants and NHLBI staff formed the writing group for this article and updated the literature on which the conclusions were based. The workshop was an open meeting, consistent with NIH policy. Evidence Data presented at the workshop were augmented by a MEDLINE search for English-language articles published from 1966 to July 1999, using the terms peripartum cardiomyopathy, cardiomyopathy, and pregnancy. Articles on the epidemiology, pathogenesis, pathophysiology, diagnosis, treatment, and prognosis of PPCM were included. Recommendation Process After discussion of data presented, workshop participants agreed on a standardized definition of PPCM, a general clinical approach, and the need for a registry to provide an infrastructure for future research. Conclusions Peripartum cardiomyopathy is a rare lethal disease about which little is known. Diagnosis is confined to a narrow period and requires echocardiographic evidence of left ventricular systolic dysfunction. Symptomatic patients should receive standard therapy for heart failure, managed by a multidisciplinary team. If subsequent pregnancies occur, they should be managed in collaboration with a high-risk perinatal center. Systematic data collection is required to answer important questions about incidence, treatment, and prognosis. C1 NHLBI, Div Heart & Vasc Dis, NIH, Bethesda, MD 20892 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Obstet & Gynecol, Winston Salem, NC 27103 USA. Univ So Calif, Div Cardiol, Los Angeles, CA USA. George Washington Univ, Sch Med & Hlth Sci, Div Cardiol, Washington, DC 20052 USA. Imperial Coll Med Sch, London, England. Med Coll Wisconsin, Div Cardiovasc Med, Milwaukee, WI 53226 USA. Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD USA. RP Pearson, GD (reprint author), NHLBI, Div Heart & Vasc Dis, NIH, 6701 Rockledge Dr,Room 9146,MSC 7940, Bethesda, MD 20892 USA. NR 43 TC 320 Z9 356 U1 1 U2 12 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 1 PY 2000 VL 283 IS 9 BP 1183 EP 1188 DI 10.1001/jama.283.9.1183 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 286BQ UT WOS:000085424100028 PM 10703781 ER PT J AU Wolmark, N Wieand, HS Hyams, DM Colangelo, L Dimitrov, NV Romond, EH Wexler, M Prager, D Cruz, AB Gordon, PH Petrelli, NJ Deutsch, M Mamounas, E Wickerham, DL Fisher, ER Rockette, H Fisher, B AF Wolmark, N Wieand, HS Hyams, DM Colangelo, L Dimitrov, NV Romond, EH Wexler, M Prager, D Cruz, AB Gordon, PH Petrelli, NJ Deutsch, M Mamounas, E Wickerham, DL Fisher, ER Rockette, H Fisher, B TI Randomized trial of postoperative adjuvant chemotherapy with or without radiotherapy for carcinoma of the rectum: National Surgical Adjuvant Breast and Bowel Project Protocol R-02 SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID REQUIRING PROLONGED OBSERVATION; RADIATION-THERAPY; CANCER; FLUOROURACIL; EXAMPLES; PATIENT; DESIGN AB Background: The conviction that postoperative radiotherapy and chemotherapy represent an acceptable standard of care for patients with Dukes' B (stage II) and Dukes' C (stage III) carcinoma of the rectum evolved in the absence of data from clinical trials designed to determine, whether the addition of radiotherapy results in improved disease-free survival and overall survival. This study was carried out to address this issue. An additional aim was to determine whether leucovorin (LV)-modulated 5-fluorouracil (5-FU) is superior to the combination of 5-FU, semustine, and vincristine (MOF) in men. Patients and Methods: Eligible patients (n = 694) with Dukes' B or C carcinoma of the rectum were enrolled in National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol R-02 from September 1987 through December 1992 and were followed. They were randomly assigned to receive either postoperative adjuvant chemotherapy alone (n = 348) or chemotherapy with postoperative radiotherapy (n = 346). All female patients (n = 287) received 5-FU plus LV chemotherapy; male patients received either MOF (n = 207) or 5-FU plus LV (n = 200), Primary analyses were carried out by use of a stratified log-rank statistic; P values are two-sided, Results: The average time on study for surviving patients is 93 months as of September 30, 1998. Postoperative radiotherapy resulted in no beneficial effect on disease-free survival (P = .90) or overall survival (P = .89), regardless of which chemotherapy was utilized, although it reduced the cumulative incidence of locoregional relapse from 13% to 8% at 5-year follow-up (P = .02). Male patients who received 5-FU plus LV demonstrated a statistically significant benefit in disease-free survival at 5 years compared with those who received MOF (55% versus 37%; P = .009) but not in 5-year overall survival (65% versus 62%; P = .17). Conclusions: The addition of postoperative radiation therapy to chemotherapy in Dukes' B and C rectal cancer did not alter the subsequent incidence of distant disease, although there was a reduction in locoregional relapse when compared with chemotherapy alone. C1 Natl Surg Adjuvant Breast & Bowel Project, Operat Ctr, Pittsburgh, PA 15212 USA. NSABP Biostat Ctr, Pittsburgh, PA USA. Desert Hosp, Ctr Comprehens Canc, Palm Springs, CA USA. Michigan State Univ, E Lansing, MI 48824 USA. Univ Kentucky, Lexington, KY 40506 USA. Royal Victoria Hosp, Montreal, ON, Canada. Lehigh Valley Med Ctr, Allentown, PA USA. Univ Texas San Antonio, San Antonio, TX 78285 USA. Sir Mortimer B Davis Jewish Hosp, Montreal, PQ H3T 1E2, Canada. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Mt Sinai Ctr Breast Hlth, Cleveland, OH USA. RP Wolmark, N (reprint author), Natl Surg Adjuvant Breast & Bowel Project, Operat Ctr, E Commons Profess Bldg,5th Floor, Pittsburgh, PA 15212 USA. FU NCI NIH HHS [CA37377, CA12027] NR 17 TC 321 Z9 336 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD MAR 1 PY 2000 VL 92 IS 5 BP 388 EP 396 DI 10.1093/jnci/92.5.388 PG 9 WC Oncology SC Oncology GA 287NK UT WOS:000085512000009 PM 10699069 ER PT J AU Engels, EA Eastman, H Ablashi, DV Wilks, RJ Braham, J Manns, A AF Engels, EA Eastman, H Ablashi, DV Wilks, RJ Braham, J Manns, A TI Persistent human herpesvirus 8 viremia associated with coinfection with human T-Cell lymphotropic virus type I and myelofibrosis SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Letter ID SARCOMA ASSOCIATED HERPESVIRUS; KAPOSIS-SARCOMA; INFECTION; BLOOD; HUMAN-HERPESVIRUS-8; PROGRESSION; ANTIBODIES; HIV C1 NCI, Rockville, MD USA. Adv Biotechnol Inc, Columbia, MD USA. Univ W Indies, Trop Metab Res Unit, Kingston 7, Jamaica. RP Engels, EA (reprint author), NCI, Rockville, MD USA. NR 16 TC 1 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD MAR 1 PY 2000 VL 23 IS 3 BP 283 EP 286 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 311KP UT WOS:000086883600013 PM 10839667 ER PT J AU Biggar, RJ Frisch, M Engels, E Goedert, JJ AF Biggar, RJ Frisch, M Engels, E Goedert, JJ TI The National AIDS-Cancer Match Registry(NACMR) SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract C1 NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. RI Frisch, Morten/E-9206-2016 OI Frisch, Morten/0000-0002-3864-8860 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 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD MAR 1 PY 2000 VL 23 IS 3 MA S3 BP A8 EP A8 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 311KP UT WOS:000086883600016 ER PT J AU Calista, D Landi, MT Landi, G AF Calista, D Landi, MT Landi, G TI Cutaneous malignant melanoma in five patients with HIV disease. SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract C1 M Bufalini Hosp, Dermatol Unit, Cesena, Italy. NCI, Genet Epidemiol Branch, NIH, Bethesda, MD 20892 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 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD MAR 1 PY 2000 VL 23 IS 3 MA 68 BP A31 EP A31 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 311KP UT WOS:000086883600106 ER PT J AU de Sanjose, S Bellas, C Marshall, V Santon, A Palacio, V Bosch, XF Whitby, D AF de Sanjose, S Bellas, C Marshall, V Santon, A Palacio, V Bosch, XF Whitby, D TI Herpes virus 8 infection among women with different sexual behavior SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract C1 Inst Catala Oncol, Serv Epidemiol, Lhospitalet De Llobregat, Spain. Inst Catala Oncol, Registre Canc, Lhospitalet De Llobregat, Spain. Hosp Ramon y Cajal, Serv Anat Patol, E-28034 Madrid, Spain. NCI, Viral Epidemiol Sect, AVP, FCRDC, Bethesda, MD 20892 USA. Hosp Monte Naranco, Oviedo, Spain. RI de Sanjose Llongueras, Silvia/H-6339-2014 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 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD MAR 1 PY 2000 VL 23 IS 3 MA 20 BP A19 EP A19 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 311KP UT WOS:000086883600059 ER PT J AU Engels, EA Sinclair, M Gastwirth, J Goebel, PB Stossel, A Biggar, R Goedert, J Whitby, D AF Engels, EA Sinclair, M Gastwirth, J Goebel, PB Stossel, A Biggar, R Goedert, J Whitby, D TI Performance of HHV-8 serological assays for testing sera from diverse populations SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract C1 NCI, SAIC Frederick, FCRDC, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 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 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD MAR 1 PY 2000 VL 23 IS 3 MA 84 BP A35 EP A35 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 311KP UT WOS:000086883600122 ER PT J AU Engels, EA Frisch, M Goedert, JJ Biggar, RJ AF Engels, EA Frisch, M Goedert, JJ Biggar, RJ TI Risk for hepatocellular carcinoma (HCC) and non-Hodgkin's lymphoma (NHL) among HIV-infected adults. SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract C1 NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. RI Frisch, Morten/E-9206-2016 OI Frisch, Morten/0000-0002-3864-8860 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 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD MAR 1 PY 2000 VL 23 IS 3 MA S4 BP A8 EP A8 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 311KP UT WOS:000086883600018 ER PT J AU Frisch, M Goedert, JJ Biggar, RJ AF Frisch, M Goedert, JJ Biggar, RJ TI Human papillomavirus-associated anogenital cancers in patients with HIV infection and AIDS SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract C1 NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. State Serum Inst, Danish Epidemiol Sci Ctr, Copenhagen, Denmark. RI Frisch, Morten/E-9206-2016 OI Frisch, Morten/0000-0002-3864-8860 NR 0 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD MAR 1 PY 2000 VL 23 IS 3 MA S5 BP A9 EP A9 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 311KP UT WOS:000086883600019 ER PT J AU Kang, E de Witte, M Malech, H Walker, R Morgan, R Little, RF Tisdale, JF AF Kang, E de Witte, M Malech, H Walker, R Morgan, R Little, RF Tisdale, JF TI Non-myeloablative allogeneic transplantation of genetically modified PBSCS for hematologic malignancies in HIV plus adults. SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NIAID, Bethesda, MD 20892 USA. NHGRI, Bethesda, MD USA. NIDDK, Bethesda, MD USA. NIH, Bethesda, MD 20892 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 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD MAR 1 PY 2000 VL 23 IS 3 MA 3 BP A15 EP A15 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 311KP UT WOS:000086883600042 ER PT J AU Kwak, LW AF Kwak, LW TI Translational development of vaccines against B-cell malignancies SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract C1 NCI, Dept Expt Transplantat & Immunol, Med Branch, Div Clin Sci, Bethesda, MD 20892 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 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD MAR 1 PY 2000 VL 23 IS 3 MA S13 BP A11 EP A11 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 311KP UT WOS:000086883600027 ER PT J AU Little, RF Pearson, D Gutierrez, M Steinberg, S Yarchoan, R Wilson, WH AF Little, RF Pearson, D Gutierrez, M Steinberg, S Yarchoan, R Wilson, WH TI Dose-adjusted EPOCH chemotherapy (CT) with suspension of antiretroviral therapy (ART) for HIV-associated non-Hodgkin's lymphoma (HIV-NHL) SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD MAR 1 PY 2000 VL 23 IS 3 MA S16 BP A11 EP A11 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 311KP UT WOS:000086883600030 ER PT J AU Mikovits, J Zhu, W Bagni, R Sausville, E Ruscetti, F Shoemaker, R AF Mikovits, J Zhu, W Bagni, R Sausville, E Ruscetti, F Shoemaker, R TI Characterization of hematopoietic progenitor cells following in vitro infection by Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8). SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract C1 SAIC Frederick, Lab Antiviral Drug Mechanisms, Frederick, MD USA. NCI, Dev Therapeut Program, DCTD, Frederick Canc & Dev Ctr, Frederick, MD 21701 USA. NCI, Lab Leukocyte Biol, DBS, Frederick Canc & Dev Ctr, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD MAR 1 PY 2000 VL 23 IS 3 MA 7 BP A16 EP A16 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 311KP UT WOS:000086883600046 ER PT J AU Naresh, KN Agarwal, B Nair, R Gopal, R Bhatia, K AF Naresh, KN Agarwal, B Nair, R Gopal, R Bhatia, K TI Lymphoid neoplasms in HIV positive individuals in India. SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract C1 Tata Mem Hosp, Bombay 400012, Maharashtra, India. NIH, Bethesda, MD 20892 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 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD MAR 1 PY 2000 VL 23 IS 3 MA 46 BP A26 EP A26 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 311KP UT WOS:000086883600085 ER PT J AU Pellett, PE Todd, D Sharma, UK Ablashi, D Dollard, SC Forghani, B Goedert, J Jenkins, FJ Lee, TH Neipel, F Whitby, D Nemo, G Busch, M AF Pellett, PE Todd, D Sharma, UK Ablashi, D Dollard, SC Forghani, B Goedert, J Jenkins, FJ Lee, TH Neipel, F Whitby, D Nemo, G Busch, M CA NHLBI REDS TI Multicenter comparison of HHV-8 serologic assays and assessment of HHV-8 seroprevalence in US blood donors SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract C1 CDC, Atlanta, GA 30333 USA. WESTAT Corp, Rockville, MD 20850 USA. ABI, Columbia, MD USA. Calif State Dept Hlth Serv, Berkeley, CA USA. NCI, NIH, Rockville, MD USA. NCI, NIH, Frederick, MD 21701 USA. Univ Pittsburgh, Pittsburgh, PA USA. Blood Ctr Pacific, San Francisco, CA USA. Univ Erlangen Nurnberg, Inst Virol, Erlangen, Germany. NHLBI, REDS, NIH, Bethesda, MD 20892 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 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD MAR 1 PY 2000 VL 23 IS 3 MA 86 BP A36 EP A36 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 311KP UT WOS:000086883600124 ER PT J AU Zoeteweij, JP Davis, D Rinderknecht, A Orenstein, JM Yarchoan, R Blauvelt, A AF Zoeteweij, JP Davis, D Rinderknecht, A Orenstein, JM Yarchoan, R Blauvelt, A TI Signal transduction pathways involved in reactivation of human herpesvirus 8 (HHV-8) in latently-infected cells: Evidence for distinct calcineurin- and protein kinase C-dependent pathways. SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. George Washington Univ, Dept Pathol, Washington, DC 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 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD MAR 1 PY 2000 VL 23 IS 3 MA 44 BP A25 EP A25 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 311KP UT WOS:000086883600082 ER PT J AU Welch, JE Brown, PL O'Brien, DA Magyar, PL Bunch, DO Mori, C Eddy, EM AF Welch, JE Brown, PL O'Brien, DA Magyar, PL Bunch, DO Mori, C Eddy, EM TI Human glyceraldehyde 3-phosphate dehydrogenase-2 gene is expressed specifically in spermatogenic cells SO JOURNAL OF ANDROLOGY LA English DT Article DE glycolysis; testis; spermatogenesis; flagellum ID MESSENGER-RIBONUCLEIC-ACID; TESTIS-SPECIFIC EXPRESSION; PORIN-BINDING DOMAIN; ALPHA-CHLOROHYDRIN; COMPLETE SEQUENCE; FIBROUS SHEATH; MOUSE; TRANSCRIPTS; PROTEIN; DNA AB Although the process of glycolysis is highly conserved in eukaryotes, several glycolytic enzymes have unique structural or functional features in spermatogenic cells. We previously identified and characterized the mouse complementary DNA (cDNA) and a gene for 1 of these enzymes, glyceraldehyde 3-phosphate dehydrogenase-s (Gapds). This gene is expressed only in spermatids. The enzyme appears to have an essential role in energy production required for fertilization, and it is reported to be susceptible to inhibition by certain environmental chemicals. We have now cloned and sequenced the cDNA for the human homologue of glyceraldehyde 3-phosphate dehydrogenase (GAPD2) and determined the structure of the gene. The messenger RNA (mRNA) was detected in testis, but not in 15 other human tissues analyzed by Northern blot technique. The deduced GAPD2 protein contains 408 amino acids and is 68% identical with somatic cell GAPD. GAPD2 has a 72-amino acid segment at the amino terminal end that is not present in somatic cell GAPD. This segment is proline-rich but contains smaller stretches of polyproline and is 30 amino acids shorter than the comparable segment of mouse GAPDS. The structure of the human GAPD2 gene was determined by polymerase chain reaction (PGR) to identify exon-intron junctions in a genomic clone and in total genomic DNA. The locations of these junctions in the GAPD2 gene corresponded precisely to those of the 11 exon-intron junctions in the mouse Gapds gene. Immunohistochemical studies found that GAPD2 is located in the principal piece of the flagellum of human spermatozoa, as are GAPDS in mouse and rat spermatozoa. GAPD2 extracted from human spermatozoa and analyzed by Western blot technique migrated with an apparent molecular weight of similar to 56 000, although the calculated molecular weight is 44 501. The conserved nature of the mouse, rat. and human enzymes suggests that they serve similar roles in these and other mammalian species. C1 NIEHS, Gamete Biol Sect, Lab Reprod & Dev Toxicol C4 01, NIH, Res Triangle Pk, NC 27709 USA. US EPA, Reprod Toxicol Div, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. Univ N Carolina, Dept Cell Biol & Anat, Chapel Hill, NC USA. Univ N Carolina, Dept Pediat, Chapel Hill, NC USA. Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC USA. Kyoto Univ, Fac Med, Dept Anat & Dev Biol, Kyoto, Japan. RP Eddy, EM (reprint author), NIEHS, Gamete Biol Sect, Lab Reprod & Dev Toxicol C4 01, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. FU NCI NIH HHS [CA16086]; NICHD NIH HHS [U54 HD035041, U54HD35041] NR 48 TC 89 Z9 96 U1 0 U2 1 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD MAR-APR PY 2000 VL 21 IS 2 BP 328 EP 338 PG 11 WC Andrology SC Endocrinology & Metabolism GA 288BA UT WOS:000085540900019 PM 10714828 ER PT J AU Earthman, CP Matthie, JR Reid, PM Harper, IT Ravussin, E Howell, WH AF Earthman, CP Matthie, JR Reid, PM Harper, IT Ravussin, E Howell, WH TI A comparison of bioimpedance methods for detection of body cell mass change in HIV infection SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE human immunodeficiency virus; acquired immunodeficiency syndrome; weight loss; extracellular water; intracellular water ID BIOELECTRICAL-IMPEDANCE ANALYSIS; EXTRACELLULAR WATER VOLUME; ALCOHOLIC HEPATITIS; HEMODIALYSIS-PATIENTS; MULTIFREQUENCY IMPEDANCE; NUTRITIONAL ASSESSMENT; PARENTERAL-NUTRITION; SURGICAL PATIENTS; CONTROLLED TRIAL; OXANDROLONE AB The maintenance of body cell mass (BCM) is critical for survival in human immunodeficiency virus (HIV) infection. Accuracy of bioimpedance for measuring change (Delta) in intracellular water (ICW), which defines BCM, is uncertain. To evaluate bioimpedance-estimated Delta BCM, the ICW of 21 weight-losing HIV patients was measured before and after anabolic steroid therapy by dilution (total body water by deuterium - extracellular water by bromide) and bioimpedance. Multiple-frequency modeling- and dilution-determined Delta ICW did not differ. The Delta ICW was predicted poorly by 50-kHz parallel reactance, 50-kHz impedance, and 200 - 5-kHz impedance. The Delta ICW predicted by 500 - 5-kHz impedance was closer to, but statistically different from, dilution-determined Delta ICW. However, the effect of random error on the measurement of systematic error in the 500 5-kHz method was 12-13% of the average measured Delta ICW; this was nearly twice the percent difference between obtained and threshold statistics. Although the 500 - 5-kHz method cannot be fully rejected, these results support the conclusion that only the multiple-frequency modeling approach accurately monitors Delta BCM in HIV infection. C1 Univ Arizona, Dept Nutr Sci, Tucson, AZ 85721 USA. Xitron Technol, Dept Med, San Diego, CA 92121 USA. NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. RP Howell, WH (reprint author), Virginia Tech, Dept Human Nutr Foods & Exercise, Blacksburg, VA 24061 USA. EM whhowell@ag.arizona.edu NR 62 TC 59 Z9 60 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD MAR PY 2000 VL 88 IS 3 BP 944 EP 956 PG 13 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 291NC UT WOS:000085742100019 PM 10710390 ER PT J AU Roth, SM Martel, GF Ivey, FM Lemmer, JT Metter, EJ Hurley, BF Rogers, MA AF Roth, SM Martel, GF Ivey, FM Lemmer, JT Metter, EJ Hurley, BF Rogers, MA TI High-volume, heavy-resistance strength training and muscle damage in young and older women SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE aging; gender; muscle injury; regeneration; resistance training ID HUMAN SKELETAL-MUSCLE; ULTRASTRUCTURAL-CHANGES; ECCENTRIC EXERCISE; ELDERLY MEN; ADAPTATIONS; RECOVERY; PEOPLE; SIZE AB To determine possible age differences in muscle damage response to strength training, ultrastructural muscle damage was assessed in seven 20- to 30-yr-old and six 65- to 75-yr-old previously sedentary women after heavy-resistance strength training (HRST). Subjects performed unilateral knee-extension exercise 3 days/wk for 9 wk. Bilateral muscle biopsies from the vastus lateralis were assessed for muscle damage via electron microscopy. HRST resulted in a 38 and 25% increase in strength in the young and older women, respectively (P < 0.05), but there were no between-group differences. In the young women, 2-4% of muscle fibers exhibited damage before and after training in both the trained and untrained legs (P = not significant). In contrast, muscle damage increased significantly after HRST, from 5 to 17% of fibers damaged (P < 0.01), in the older women in the trained leg compared with only 2 and 5% of fibers damaged in the untrained leg before and after training, respectively. The present results indicate that older women exhibit; higher levels of muscle damage after chronic HRST than do young women. C1 Univ Maryland, Coll Hlth & Human Performance, Dept Kinesiol, College Pk, MD 20742 USA. Univ Maryland Eastern Shore, Dept Phys Therapy, Princess Anne, MD 21853 USA. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Rogers, MA (reprint author), Univ Maryland, Coll Hlth & Human Performance, Dept Kinesiol, College Pk, MD 20742 USA. OI Roth, Stephen/0000-0002-7841-3695 FU NIA NIH HHS [1AG-42148, AG-00268] NR 31 TC 78 Z9 82 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD MAR PY 2000 VL 88 IS 3 BP 1112 EP 1118 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 291NC UT WOS:000085742100039 PM 10710410 ER PT J AU Hoare, SRJ Usdin, TB AF Hoare, SRJ Usdin, TB TI The discrepancy between the binding affinity of PTH (1-34) and RS 66271 is explained by interaction of the PTH/PTHrP receptor with G-protein SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Letter ID RS-66271; ANALOG; BONE C1 NIMH, Genet Lab, Bethesda, MD 20892 USA. RP Hoare, SRJ (reprint author), NIMH, Genet Lab, Bethesda, MD 20892 USA. NR 8 TC 5 Z9 5 U1 0 U2 2 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAR PY 2000 VL 15 IS 3 BP 605 EP 607 DI 10.1359/jbmr.2000.15.3.605 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 289FL UT WOS:000085609800026 PM 10750577 ER PT J AU Wang, J Lenardo, MJ AF Wang, J Lenardo, MJ TI Roles of caspases in apoptosis, development, and cytokine maturation revealed by homozygous gene deficiencies SO JOURNAL OF CELL SCIENCE LA English DT Editorial Material DE ced-3; genetic deficiency; homologous recombination; FAS/APO-1/CD95; knockout ID INTERLEUKIN-1-BETA CONVERTING-ENZYME; AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; FAS-MEDIATED APOPTOSIS; GAMMA-INDUCING FACTOR; CELL-DEATH; ICE/CED-3 PROTEASE; MICE DEFICIENT; GRANZYME-B; IN-VIVO; ACTIVATION AB Caspases are a group of cysteine proteases critical for apoptosis of eukaryotic cells. Deletion of genes that encode murine caspases suggests that caspases are involved not only in apoptosis but also in cytokine maturation and cell growth and differentiation. Among them, caspase-1 and caspase-11 are primarily Involved in the processing of proinflammatory cytokines, Caspase-3 and caspase-9 are essential for apoptosis during brain development, Caspase-8 is required for the development of heart muscle, cell proliferation in the hematopoietic lineage and death-receptor-mediated apoptosis. These studies suggest that caspases function in cell signaling events including apoptosis, cell growth and differentiation. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Lenardo, MJ (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. NR 42 TC 177 Z9 200 U1 1 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD MAR PY 2000 VL 113 IS 5 BP 753 EP 757 PG 5 WC Cell Biology SC Cell Biology GA 298RL UT WOS:000086152900003 PM 10671365 ER PT J AU Li, CJ Bogan, JA Natale, DA DePamphilis, ML AF Li, CJ Bogan, JA Natale, DA DePamphilis, ML TI Selective activation of pre-replication complexes in vitro at specific sites in mammalian nuclei SO JOURNAL OF CELL SCIENCE LA English DT Article DE DNA replication; Xenopus egg; hamster nucleus; eukaryotic replication origin; pre-replication complex ID ORIGIN RECOGNITION COMPLEX; XENOPUS EGG EXTRACT; CELL-FREE SYSTEM; DNA-REPLICATION; SIMIAN VIRUS-40; METAZOAN CHROMOSOMES; LICENSING SYSTEM; MIMOSINE ARRESTS; STRANDED-DNA; GENE DOMAIN AB As the first step in determining whether or not pre-replication complexes are assembled at specific sites along mammalian chromosomes, nuclei from G(1)-phase hamster cells were incubated briefly in Xenopus egg extract in order to initiate DNA replication. Most of the nascent DNA consisted of RNA-primed DNA chains 0.5 to 2 kb in length, and its origins in the DHFR gene region mere mapped using both the early labeled fragment assay and the nascent strand abundance assay. The results revealed three important features of mammalian replication origins. First, Xenopus egg extract can selectively activate the same origins of bi-directional replication (e.g. ori-beta and beta') that are used by hamster cells in vivo. Previous reports of a broad peak of nascent DNA centered at ori-beta/beta' appeared to result from the use of aphidicolin to synchronize nuclei and from prolonged exposure of nuclei to egg extracts. Second, these sites were not present until late G(1)-phase of the cell division cycle, and their appearance did not depend on the presence of Xenopus Ore proteins. Therefore, hamster pre-replication complexes appear to be assembled at specific chromosomal sites during G(1)-phase. Third, selective activation of ori-beta in late G(1)-nuclei depended on the ratio of Xenopus egg extract to nuclei, revealing that epigenetic parameters such as the ratio of initiation factors to DNA substrate could determine the number of origins activated. C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP DePamphilis, ML (reprint author), NICHHD, NIH, Bldg 6,Room 416, Bethesda, MD 20892 USA. NR 53 TC 33 Z9 33 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD MAR PY 2000 VL 113 IS 5 BP 887 EP 898 PG 12 WC Cell Biology SC Cell Biology GA 298RL UT WOS:000086152900016 PM 10671378 ER PT J AU Kim, JE Kim, EH Han, EH Park, RW Park, IH Jun, SH Kim, JC Young, MF Kim, IS AF Kim, JE Kim, EH Han, EH Park, RW Park, IH Jun, SH Kim, JC Young, MF Kim, IS TI A TGF-beta-inducible cell adhesion molecule, beta ig-h3, is downregulated in melorheostosis and involved in osteogenesis SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE melorheostosis; TGF-beta-induced gene product (beta ig-h3); osteoblast-specific factor 2; fibronectin; osteoblast differentiation ID GROWTH-FACTOR-BETA; CALVARIAL OSTEOBLAST DIFFERENTIATION; IN-VITRO; FIBRONECTIN; PROTEIN; CLONING; GENES; LINE AB Melorheostosis is a rare bone disease characterized by linear hyperostosis and associated soft tissue abnormalities. The skin overlying the involved bone lesion is often tense, shiny, erythematous, and scleodermatous. In order to look for genes differentially expressed between the normal and involved skin, we cultured skin fibroblasts from the skin lesions of several afflicted patients, and identified differentially expressed genes by reverse dot-blot hybridization. We found that the genes human TGF-beta-induced gene product (beta ig-h3), osteoblast-specific factor 2, osteonectin, fibronectin, and type I collagen were all downregulated in the affected skin fibroblasts, with beta ig-h3 the most significantly affected. The expression of beta ig-h3 was induced by TGF-beta in both affected and normal fibroblasts. in an effort to determine the mechanism of bone and skin abnormalities in melorheostosis, we made recombinant beta ig-h3. Both immobilized and soluble recombinant beta ig-h3 proteins with or without an RGD motif inhibited bone nodule formation of osteoblasts in vitro. Taken together, our results suggest that altered expression of several adhesion proteins may contribute to the development of hyperostosis and concomitant soft tissue abnormalities of melorheostosis, with beta ig-h3 in particular playing an important role in osteogenesis. (C) 2000 Wiley-Liss, Inc. C1 Kyungpook Natl Univ, Sch Med, Canc Res Inst, Jung Gu, Taegu 700422, South Korea. Kyungpook Natl Univ, Sch Med, Dept Biochem, Taegu 700422, South Korea. Kyungpook Natl Univ, Sch Med, Dept Orthoped Surg, Taegu 700422, South Korea. Kyungpook Natl Univ, Sch Med, Dept Surg, Taegu 700422, South Korea. Kyungpook Natl Univ, Sch Med, Dept Immunol, Taegu 700422, South Korea. NIDR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. RP Kim, IS (reprint author), Kyungpook Natl Univ, Sch Med, Canc Res Inst, Jung Gu, 101 Dongin Dong, Taegu 700422, South Korea. RI 김, 인산/I-8988-2014; Kim, In-San/D-3956-2017 NR 28 TC 85 Z9 89 U1 0 U2 3 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 PY 2000 VL 77 IS 2 BP 169 EP 178 DI 10.1002/(SICI)1097-4644(20000501)77:2<169::AID-JCB1>3.0.CO;2-L PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 297FD UT WOS:000086070500001 PM 10723084 ER PT J AU Wu, HB Kumar, A Tsai, WC Mascarenhas, D Healey, J Rechler, MM AF Wu, HB Kumar, A Tsai, WC Mascarenhas, D Healey, J Rechler, MM TI Characterization of the inhibition of DNA synthesis in proliferating mink lung epithelial cells by insulin-like growth factor binding protein-3 SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE IGF-1; Leu(60)-IGF-I; BrdU cell proliferation assay; covalent cross-linking; EGFs; type V TGF-beta receptor ID HUMAN-BREAST-CANCER; FACTOR-BETA-RECEPTOR; FACTOR-I; IGF-I; NUCLEAR TRANSPORT; V RECEPTOR; TGF-BETA; FIBROBLASTS; IGFBP-3; RAT AB insulin-like growth factor binding protein-3 (IGFBP-3) can inhibit cell growth by directly interacting with cells, as well as by forming complexes with IGF-I and ICF-II that prevent their growth-promoting activity. The present study examines the mechanism of inhibition of DNA synthesis by IGFBP-3 in CCL64 mink lung epithelial cells. DNA synthesis was measured by the incorporation of 5-bromo-2'-deoxyuridine, using an immunocolorimetric assay. Recombinant human IGFBP-3 (rh[N109D,N172D]IGFBP-3) inhibited DNA synthesis in proliferating and quiescent CCL64 cells. Inhibition was abolished by co-incubation of IGFBP-3 with a 20% molar excess of Leu(60)-IGF-I, a biologically inactive IGF-I analogue that binds to IGFBP-3 but not to IGF-I receptors. DNA synthesis was not inhibited by incubation with a preformed 1:1 molar complex of Leu(60)-IGF-I and IGFBP-3, indicating that only free IGFBP-3 inhibits CCL64 DNA synthesis. Inhibition by IGFBP-3 is not due to the formation of biologically inactive complexes with free ICF, since endogenous IGFs could not be detected in CCL64 conditioned media; any IGFs that might have been present could only have existed in inactive complexes, since endogenous IGFBPs were present in excess; and biologically active IGFs were not displaced from endogenous IGFBP complexes by Leu(60)-ICF-I. After incubation with CCL64 cells, I-125-IGFBP-3 was covalently cross-linked to a major similar to 400-kDa complex. This complex co-migrated with a complex formed after incubation with I-125-laleled transforming growth factor-beta (TGF-beta) that has been designated the type V TGF-beta receptor. I-125-ICFBP-3 binding to the similar to 400-kDa receptor was inhibited by co-incubation with unlabeled IGF-I or Leu(60)-ICF-I. The ability of Leu(60)-IGF-I to decrease both the inhibition of DNA synthesis by ICFBP-3 and IGFBP-3 binding to the similar to 400-kDa receptor is consistent with the hypothesis that the similar to 400-kDa IGFBP-3 receptor mediates the inhibition of CCL64 DNA synthesis by ICFBP-3. (C) 2000 Wiley-Liss, Inc. C1 NIDDK, Clin Endocrinol Branch, Growth & Dev Sect, NIH, Bethesda, MD 20892 USA. Celtrix Pharmaceut Inc, San Jose, CA 95110 USA. RP Rechler, MM (reprint author), NIH, Bldg 10,Room 8D12, Bethesda, MD 20892 USA. NR 41 TC 22 Z9 22 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 PY 2000 VL 77 IS 2 BP 288 EP 297 DI 10.1002/(SICI)1097-4644(20000501)77:2<288::AID-JCB11>3.0.CO;2-J PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 297FD UT WOS:000086070500011 PM 10723094 ER PT J AU Villevalois-Cam, L Tahiri, K Chauvet, G Desbuquois, B AF Villevalois-Cam, L Tahiri, K Chauvet, G Desbuquois, B TI Insulin-induced redistribution of the insulin-like growth factor II/mannose 6-phosphate receptor in intact rat liver SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE insulin; insulin-like growth factor II; insulin-like growth factor II/mannose 6-phosphate receptors; liver; Golgi apparatus; endosomes; plasma membrane ID FACTOR-II RECEPTOR; ADIPOCYTE CELL-SURFACE; TRANSFERRIN RECEPTORS; 3T3-L1 ADIPOCYTES; IGF-II; GLUCOSE TRANSPORTERS; BINDING-PROTEINS; PLASMA-MEMBRANE; HEPATOMA-CELLS; GOLGI ELEMENTS AB The ability of acute insulin treatment to elicit a redistribution of the liver Insulin-like growth factor-II/ mannose 6-phosphate (IGF-II/M6P) receptor has been studied in rats, using cell fractionation. Injection of insulin (0.4-50 mu g) led to a time- and dose-dependent decrease in IGF-II binding activity in Golgi-endosomal (GE) fractions, along with an increase in activity in the plasma membrane (PM) fraction; only receptor number was affected. Quantitative subfractionation of the microsomal fraction on sucrose density gradients showed that ICF-II binding activity distributed similarly to galactosyrtransferase (a Golgi marker), at slightly higher densities than in vivo internalized I-125-insulin, and at lower densities than 5' nucleotidase and alkaline phosphodiesterase (two plasma membrane markers). Insulin treatment led to a slight time-dependent and reversible shift of IGF-II binding activity toward higher densities. Subfractionation of the GE fraction on Percoll gradients showed that IGF-II binding activity was broadly distributed, with about 60% at low densities coinciding with galactosyltransferase and early internalized I-125-insulin and with 40% at high densities in the region of late internalized I-125-insulin. Insulin treatment caused a time-dependent and reversible shift of the distribution of IGF-II binding activity toward low densities. On SDS-PACE, the size of the affinity-labeled IGF-II/M6P receptor was comparable in GE and PM fractions (about 255 kDa), bur on Western blots receptor size was slightly lower in the latter (245 kDa) than in the former (255 kDa). insulin treatment did not affect the size, but modified the abundance of the IGF-II/M6P receptor in a manner similar to that of IGF-II binding. In vivo chloroquine treatment fully suppressed the changes in ICF-II binding activity in liver GE and PM fractions observed in insulin-treated rats. We conclude that insulin elicits a time-dependent and reversible redistribution of liver IGF-II receptors from Golgi elements and endosomes to the plasma membrane, presumably via early endosomes. (C) 2000 Wiley-Liss, Inc. C1 Hop Necker Enfants Malad, INSERM, U30, F-75015 Paris, France. RP Desbuquois, B (reprint author), NIH, Bldg 10,Room 8N246, Bethesda, MD 20892 USA. OI khadija, Tahiri/0000-0003-4065-524X NR 43 TC 4 Z9 4 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR PY 2000 VL 77 IS 2 BP 310 EP 322 DI 10.1002/(SICI)1097-4644(20000501)77:2<310::AID-JCB13>3.0.CO;2-4 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 297FD UT WOS:000086070500013 PM 10723096 ER PT J AU Ohnmacht, GA Marincola, FM AF Ohnmacht, GA Marincola, FM TI Heterogeneity in expression of human leukocyte antigens and melanoma-associated antigens in advanced melanoma SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Review ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-I ANTIGEN; MHC CLASS-I; TUMOR-INFILTRATING LYMPHOCYTES; MARKEDLY DECREASED EXPRESSION; CELL LUNG-CANCER; METASTATIC MELANOMA; GENE-EXPRESSION; DOWN-REGULATION; T-CELLS AB The study of tumor immunology has led to many innovative therapeutic strategies for the treatment of melanoma. The strategies are primarily dependent on melanoma-associated antigen peptide vaccination or T-cell-based therapy. These immunotherapies are totally reliant on proper copresentation of human leukocyte antigen class I molecules in sufficient quantity and the presence and availability of melanoma-associated antigenic peptides. Altered expression of either HLA class I molecules or melanoma antigens is known to occur. These defects lead to altered manufacture and copresentation of HLA class I molecules with melanoma-associated antigens to T-cells. Defects in any one combination can lead to loss of recognition of melanoma cells and their subsequent destruction by cytotoxic T-lymphocytes. Thus, these immunotherapy strategies can be thwarted by defects or heterogeneity of expression of human leukocyte antigen class I or of melanoma-associated antigens. Published 2000 Wiley-Liss, Inc. C1 NCI, Surg Branch, Bethesda, MD 20892 USA. NCI, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), NCI, Surg Branch, Bldg 10, Room 2B42, 10 Ctr Dr, Bethesda, MD 20892 USA. NR 96 TC 29 Z9 29 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 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD MAR PY 2000 VL 182 IS 3 BP 332 EP 338 DI 10.1002/(SICI)1097-4652(200003)182:3<332::AID-JCP3>3.0.CO;2-Z PG 7 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 278NA UT WOS:000084994800003 PM 10653599 ER PT J AU Kim, SN Kim, SG Park, SD Cho-Chung, YS Hong, SH AF Kim, SN Kim, SG Park, SD Cho-Chung, YS Hong, SH TI Participation of type II protein kinase A in the retinoic acid-induced growth inhibition of SH-SY5Y human neuroblastoma cells SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID BETA REGULATORY SUBUNIT; HUMAN NEURO-BLASTOMA; MOLECULAR-CLONING; HUMAN TESTIS; CYCLIC-AMP; RI-BETA; ADENOSINE-MONOPHOSPHATE; INDUCED DIFFERENTIATION; CATALYTIC SUBUNIT; RESPONSE ELEMENT AB To examine the role of protein kinase A (EC 2.7.1.37) isozymes in the retinoic acid-induced growth inhibition and neuronal differentiation, we investigated the changes of protein kinase A isozyme patterns in retinoic acid-treated SH-SY5Y human neuroblastoma cells. Retinoic acid induced growth inhibition and neuronal differentiation of SH-SY5Y cells in a dose- and time-dependent manner. Neuronal differentiation was evidenced by extensive neurite outgrowth, decrease of N-Myc oncoprotein, and increase of GAP-43 mRNA. Type II protein kinase A activity increased by 1.5-fold in differentiated SH-SY5Y cells by retinoic acid treatment. The increase of type II protein kinase A was due to the increase of RII beta and C alpha subunits. Since type II protein kinase A and RII beta have been known to play important role(s) in the growth inhibition and differentiation of cancer cells, we further investigated the role of the increased type II protein kinase A by overexpressing RII beta in SH-SY5Y cells. The growth of RII beta-overexpressing cells was slower than that of parental cells, being comparable to that of retinoic acid-treated cells. Retinoic acid treatment further increased the RII beta level and further inhibited the growth of RII beta-overexpressing cells, showing strong correlation between the level of RII beta and growth inhibition. However, RII beta-overexpressing cells did not show any sign of neuronal differentiation and responded to retinoic acid in the same way as parental cells. These data suggest that protein kinase A participates in the retinoic acid-induced growth inhibition through the up-regulation of RII beta/type II protein kinase A. (C) 2000 Wiley-Liss. Inc. C1 Seoul Natl Univ, Inst Mol Biol & Genet, Cell Biol Lab, Seoul 151742, South Korea. Seoul Natl Univ, Dept Biol Mol, Seoul 151, South Korea. Seoul Natl Univ, Res Ctr Cell Differat, Seoul 151, South Korea. NCI, Tumor Immunol & Biol Lab, Cellular Biochem Sect, Bethesda, MD 20892 USA. RP Hong, SH (reprint author), Seoul Natl Univ, Inst Mol Biol & Genet, Cell Biol Lab, Seoul 151742, South Korea. NR 47 TC 17 Z9 18 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD MAR PY 2000 VL 182 IS 3 BP 421 EP 428 DI 10.1002/(SICI)1097-4652(200003)182:3<421::AID-JCP13>3.0.CO;2-2 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 278NA UT WOS:000084994800013 PM 10653609 ER PT J AU Guo, ZH Kindy, MS Kruman, I Mattson, MP AF Guo, ZH Kindy, MS Kruman, I Mattson, MP TI ALS-linked Cu/Zn-SOD mutation impairs cerebral synaptic glucose and glutamate transport and exacerbates ischemic brain injury SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE amyotrophic lateral sclerosis; excitotoxicity; focal ischemia; lipid peroxidation; transgenic ID AMYOTROPHIC-LATERAL-SCLEROSIS; AMYLOID BETA-PEPTIDE; LIPID-PEROXIDATION PRODUCT; SUPEROXIDE-DISMUTASE MUTATION; CELL-DEATH; INCREASED 3-NITROTYROSINE; OXIDATIVE DAMAGE; TRANSGENIC MODEL; MOTOR-NEURONS; FAMILIAL ALS AB Although degeneration of lower motor neurons is the most striking abnormality in amyotrophic lateral sclerosis (ALS), more subtle alterations may occur in the brain. Mutations in copper/zinc superoxide dismutase (Cu/Zn-SOD) are responsible for some cases of inherited ALS, and expression of mutant Cu/Zn-SOD in transgenic mice results in progressive motor neuron loss and a clinical phenotype similar to that of ALS patients. It is now reported that Cu/Zn-SOD mutant mice exhibit increased vulnerability to focal ischemic brain injury after transient occlusion of the middle cerebral artery. Levels of glucose and glutamate transport in cerebral cortex synaptic terminals were markedly decreased, and levels of membrane lipid peroxidation were increased in Cu/Zn-SOD mutant mice compared to nontransgenic mice. These findings demonstrate that mutant Cu/Zn-SOD may endanger brain neurons by a mechanism involving impairment of glucose and glutamate transporters. Moreover, our data demonstrate a direct adverse effect of the mutant enzyme on synaptic function. C1 NIA, Neurosci Lab, Baltimore, MD 21224 USA. Vet Affairs Med Ctr, Lexington, KY USA. Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. Univ Kentucky, Dept Biochem, Lexington, KY 40536 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, GRC 4F01,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 41 TC 28 Z9 30 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAR PY 2000 VL 20 IS 3 BP 463 EP 468 PG 6 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 293AQ UT WOS:000085829700004 PM 10724110 ER PT J AU Shi, LM Fan, Y Lee, JK Waltham, M Andrews, DT Scherf, U Paull, KD Weinstein, JN AF Shi, LM Fan, Y Lee, JK Waltham, M Andrews, DT Scherf, U Paull, KD Weinstein, JN TI Mining and visualizing large anticancer drug discovery databases SO JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES LA English DT Article; Proceedings Paper CT 5th Interntional Conference on Chemical Structures CY JUN 02-06, 1999 CL NOORDWIJKERHOUT, NETHERLANDS ID TUMOR-CELL-LINES; GENETIC FUNCTION APPROXIMATION; AUTOMATED STRUCTURE EVALUATION; INFORMATION-SYSTEM; ARTIFICIAL-INTELLIGENCE; MOLECULAR PHARMACOLOGY; MULTIDRUG-RESISTANCE; ELLIPTICINE ANALOGS; HIV-1 INTEGRASE; 3D DATABASE AB In order to find more effective anticancer drugs, the U.S. National Cancer Institute (NCI) screens a large number of compounds in vitro against 60 human cancer cell lines from different organs of origin. About 70 000 compounds have been tested in the program since 1990, and each tested compound can be characterized by a vector (i.e., "fingerprint") of 60 anticancer activity, or -[log(GI(50))], values. GI(50) is the concentration required to inhibit cell growth by 50% compared with untreated controls. Although cell growth inhibitory activity for a single cell line is not very informative, activity patterns across the 60 cell lines can provide incisive information on the mechanisms of action of screened compounds and also on molecular targets and modulators of activity within the cancer cells. Various statistical and artificial intelligence methods, including principal component analysis, hierarchical cluster analysis,stepwise linear regression, multidimensional scaling, neural network modeling, and genetic function approximation, among others, can be used to analyze this large activity database. Mining the database can provide useful information: (a) for the development of anticancer drugs; (b) for a better understanding of the molecular pharmacology of cancer; and (c) for improvement of the drug discovery process. C1 NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Informat Technol Branch, Div Canc Treatment Diag & Ctr, NIH, Bethesda, MD 20892 USA. RP Shi, LM (reprint author), Amer Cyanamid Co, Quakerbridge & Clarksville Rd,POB 400, Princeton, NJ 08543 USA. RI Waltham, Mark/A-1728-2009 NR 69 TC 72 Z9 73 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0095-2338 J9 J CHEM INF COMP SCI JI J. Chem. Inf. Comput. Sci. PD MAR-APR PY 2000 VL 40 IS 2 BP 367 EP 379 DI 10.1021/ci990087b PG 13 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA 298PX UT WOS:000086149300024 PM 10761142 ER PT J AU Deuster, PA Petrides, JS Singh, A Chrousos, GP Poth, M AF Deuster, PA Petrides, JS Singh, A Chrousos, GP Poth, M TI Endocrine response to high-intensity exercise: Dose-dependent effects of dexamethasone SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PITUITARY-ADRENAL AXIS; CORTICOTROPIN-RELEASING HORMONE; DEHYDROEPIANDROSTERONE-SULFATE; CARDIOVASCULAR-DISEASE; TREADMILL EXERCISE; CORTISOL SECRETION; MARKED DIFFERENCES; STRESS; ADRENOCORTICOTROPIN; NEUROSTEROIDS AB We recently reported that in 30-50% of healthy men and women the release of ACTH and cortisol stimulated by exercise is not suppressed by prior administration of a 4-mg dose of dexamethasone (DEX). We now explore other potential differences between these subjects and those whose exercise response was suppressed by examining the effect of a smaller, l-mg, dose of DEX on exercise-stimulated ACTH and cortisol. Men (n = 15) and women (n = 9) were studied during three high intensity exercise tests: one after taking placebo, one after taking 1 mg DEX, and one after taking 4 mg DEX. Before participation, subjects underwent a test for classification as either a high (HR; n = 10) or low (LR; n = 14) reactor and a maximal exercise test to assess maximal aerobic capacity. Distinct dose-related reductions in plasma concentrations of ACTH, cortisol, and dehydroepiandrosterone (DHEA) were noted for Hn under the treatment conditions, whereas both doses of DEX blocked ACTH, cortisol, and DHEA release in LR. Furthermore, basal plasma cortisol, DHEA, and DHEA sulfate were significantly higher in HR compared to LR. Thus, there are inherent basal and stress-reactive differences in HR and LR, and these differences may be useful in constructing a model for the mechanisms and physiological regulation of hypothalamic-pituitary-adrenal axis activation, The question of whether these differences in reactivity of the ACTH-cortisol axis between the NR and LR groups have implications for individual short; term function or long term health remains to be answered. C1 Uniformed Serv Univ Hlth Sci, Dept Mil & Emergency Med, Bethesda, MD 20814 USA. NICHHD, Dev Endocrinol Branch, Bethesda, MD 20814 USA. RP Deuster, PA (reprint author), Uniformed Serv Univ Hlth Sci, Dept Mil & Emergency Med, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM pdeuster@usuhs.mil RI Deuster, Patricia/G-3838-2015 OI Deuster, Patricia/0000-0002-7895-0888 NR 45 TC 17 Z9 18 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2000 VL 85 IS 3 BP 1066 EP 1073 DI 10.1210/jc.85.3.1066 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 337WW UT WOS:000088387000027 PM 10720041 ER PT J AU Weyer, C Pratley, RE Salbe, AD Bogardus, C Ravussin, E Tataranni, PA AF Weyer, C Pratley, RE Salbe, AD Bogardus, C Ravussin, E Tataranni, PA TI Energy expenditure, fat oxidation, and body weight regulation: A study of metabolic adaptation to long-term weight change SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID X-RAY ABSORPTIOMETRY; OBESE WOMEN; FUEL UTILIZATION; OVERWEIGHT WOMEN; IDENTICAL-TWINS; GAIN; THERMOGENESIS; HUMANS; CARBOHYDRATE; DETERMINANTS AB Relatively low rates of energy expenditure and fat oxidation predict body weight gain. Weight gain, in turn, is associated with increases in energy expenditure and fat oxidation that may oppose further weight change. In response to experimental weight gain induced by overfeeding, increases in energy expenditure and fat oxidation are overcompensatory, i.e. greater than predicted for the change in body composition. To determine whether such metabolic adaptation occurs in response to spontaneous long term weight change, we conducted a longitudinal study in which 24-h energy expenditure (24-EE) and 24-h respiratory quotient (24-RQ; i.e. fat to carbohydrate oxidation) were repeatedly measured in 102 Pima Indians at baseline and after a mean follow-up of 3.6 +/- 2.7 yr, during which changes in body weight varied widely (-21 to +28 kg). We found that changes in 24-EE and 24-RQ in response to weight change were related to the amount of weight change, even after adjustment for body composition (partial r = 0.23 and -0.30, respectively; both P < 0.05). For a 15-kg weight gain, the increases in 24-EE (+244 Gal/day) and 24-h fat oxidation (+152 Gal/day) were 33 and 53 Gal/day greater than predicted from the cross-sectional relationship between both measures and body weight. Changes in 24-EE and 24-RQ varied substantially among individuals. Thus, on the average, spontaneous long term weight changes are accompanied by small metabolic adaptations in both energy expenditure and fat oxidation. The metabolic responses to weight changes are highly variable among individuals, however. C1 NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. RP Weyer, C (reprint author), NIDDKD, Clin Diabet & Nutr Sect, NIH, 4212 N 16th St,Room 5-41, Phoenix, AZ 85016 USA. EM cweyer@phx.niddk.nih.gov NR 55 TC 84 Z9 85 U1 0 U2 8 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 2000 VL 85 IS 3 BP 1087 EP 1094 DI 10.1210/jc.85.3.1087 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 337WW UT WOS:000088387000030 PM 10720044 ER PT J AU Merke, DP Keil, MF Jones, JV Fields, J Hill, S Cutler, GB AF Merke, DP Keil, MF Jones, JV Fields, J Hill, S Cutler, GB TI Flutamide, testolactone, and reduced hydrocortisone dose maintain normal growth velocity and bone maturation despite elevated androgen levels in children with congenital adrenal hyperplasia SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID 21-HYDROXYLASE DEFICIENCY; PRECOCIOUS PUBERTY; HEIGHT VELOCITY; CORTISOL; DISEASE; SPIRONOLACTONE; ADOLESCENCE; DESLORELIN; STANDARDS; GENOTYPE AB Treatment outcome in congenital adrenal hyperplasia is often suboptimal due to hyperandrogenism, treatment-induced hypercortisolism, or both. We previously reported better control of linear growth, weight gain, and bone maturation in a short term cross-over study of a new four-drug treatment regimen containing an antiandrogen (flutamide), an inhibitor of androgen to estrogen conversion (testolactone), reduced hydrocortisone dose, and fludrocortisone, compared to the effects of a control regimen of hydrocortisone and fludrocortisone. Twenty-eight children have completed 2 yr of follow-up in a subsequent long term randomized parallel study comparing these two treatment regimens. During 2 yr of therapy, compared to children receiving hydrocortisone, and fludrocortisone treatment, children receiving flutamide, testolactone, reduced hydrocortisone dose (average of 8.7 +/- 0.6 mg/m(2).day), and fludrocortisone had significantly (P less than or equal to 0.05) higher plasma 17-hydroxyprogesterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone levels. Despite elevated androgen levels, children receiving the new treatment regimen had normal linear growth rate (at 2 yr, 0.1 +/- 0.5 so units), and bone maturation (at 2 yr, 0.7 +/- 0.3 yr bone age/yr chronological age). No significant adverse effects were observed after 2 yr. We conclude that the regimen of flutamide, testolactone, reduced hydrocortisone dose, and fludrocortisone provides effective control of congenital adrenal hyperplasia with reduced risk of glucocorticoid excess. A long term study of this new regimen is ongoing. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Warren Grant Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Merke, DP (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. EM merked@mail.nih.gov NR 27 TC 72 Z9 77 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2000 VL 85 IS 3 BP 1114 EP 1120 DI 10.1210/jc.85.3.1114 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 337WW UT WOS:000088387000034 PM 10720048 ER PT J AU Vgontzas, AN Papanicolaou, DA Bixler, EO Hopper, K Lotsikas, A Lin, HM Kales, A Chrousos, GP AF Vgontzas, AN Papanicolaou, DA Bixler, EO Hopper, K Lotsikas, A Lin, HM Kales, A Chrousos, GP TI Sleep apnea and daytime sleepiness and fatigue: Relation to visceral obesity, insulin resistance, and hypercytokinemia SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID AIRWAY PRESSURE TREATMENT; BLOOD-PRESSURE; LEPTIN LEVELS; INTRACEREBROVENTRICULAR INJECTION; CYTOKINES; INTERLEUKIN-6; HUMANS; BODY; DISORDERS; PROFILES AB Sleep apnea and associated daytime sleepiness and fatigue are common manifestations of mainly obese middle-aged men. The onset of sleep apnea peaks in middle age, and its morbid and mortal sequelae include complications from accidents and cardiovascular events. The pathophysiology of sleep apnea remains obscure. The purpose of this study was to test three separate, albeit closely related, hypotheses. 1) Does sleep apnea contribute to the previously reported changes of plasma cytokine (tumor necrosis factor-alpha and interleukin-6) and leptin levels independently of obesity? 2) Among obese patients, is it generalized or visceral obesity that predisposes to sleep apnea? 3) Is apnea a factor independent from obesity in the development of insulin resistance? Obese middle-aged men with sleep apnea were first compared with nonapneic age- and body mass index (BMI)-matched obese and age-matched lean men. All subjects were monitored in the sleep laboratory for 4 consecutive nights. We obtained simultaneous indexes of sleep, sleep stages, and sleep apnea, including apnea/hypopnea index and percent minimum oxygen saturation. The sleep apneic men had higher plasma concentrations of the adipose tissue-derived hormone, leptin, and of the inflammatory, fatigue-causing, and insulin resistance-producing cytokines tumor necrosis factor-alpha and interleukin-6 than nonapneic obese men, who had intermediate values, or lean men, who had the lowest values. Because these findings suggested that sleep apneics might have a higher degree of insulin resistance than the BMT-matched controls, we studied groups of sleep-apneic obese and age- and BMI-matched nonapneic controls in whom we obtained computed tomographic scan measures of total, sc, and visceral abdominal fat, and additional biochemical indexes of insulin resistance, including fasting plasma glucose and insulin. The sleep apnea patients had a significantly greater amount of visceral fat compared to obese controls (<0.05) and indexes of sleep disordered breathing were positively correlated with visceral fat, but not with BMI or total or sc fat. Furthermore, the biochemical data confirmed a higher degree of insulin resistance in the group of apneics than in BMI-matched nonapneic controls. We conclude that there is a strong independent association among sleep apnea, visceral obesity, insulin resistance and hypercytokinemia, which may contribute to the pathological manifestations and somatic sequelae of this condition. C1 Penn State Univ, Dept Psychiat, Sleep Res & Treatment Ctr, Hershey, PA 17033 USA. Penn State Univ, Dept Radiol, Hershey, PA 17033 USA. Penn State Univ, Dept Hlth Evaluat Sci, Hershey, PA 17033 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Vgontzas, AN (reprint author), Penn State Univ, Dept Psychiat, Sleep Res & Treatment Ctr, 500 Univ Dr, Hershey, PA 17033 USA. EM axv3@psu.edu NR 31 TC 649 Z9 685 U1 3 U2 32 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 2000 VL 85 IS 3 BP 1151 EP 1158 DI 10.1210/jc.85.3.1151 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 337WW UT WOS:000088387000040 PM 10720054 ER PT J AU Papanicolaou, DA Vgontzas, AN AF Papanicolaou, DA Vgontzas, AN TI Editorial: Interleukin-6: The endocrine cytokine SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID POSTMENOPAUSAL WOMEN; DAYTIME SLEEPINESS; UNSTABLE ANGINA; ADIPOSE-TISSUE; BONE-MARROW; IN-VIVO; DISEASE; HUMANS; HYPOCHOLESTEROLEMIA; POPULATION C1 NICHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Penn State Univ, Coll Med, Dept Psychiat, Sleep Res & Treatment Ctr, Hershey, PA 17033 USA. RP Papanicolaou, DA (reprint author), NICHD, Pediat & Reprod Endocrinol Branch, NIH, Bldg 10,Room 9D42,10 Ctr Dr,MSC 1583, Bethesda, MD 20892 USA. EM papanicd@mail.nih.gov NR 30 TC 81 Z9 85 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 2000 VL 85 IS 3 BP 1331 EP 1333 DI 10.1210/jc.85.3.1331 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 337WW UT WOS:000088387000072 PM 10720086 ER PT J AU Koch, CA Pacak, K AF Koch, CA Pacak, K TI Intracranial arachnoid cysts SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Letter C1 NICHD, DEB, NIH, Bethesda, MD 20892 USA. RP Koch, CA (reprint author), NICHD, DEB, NIH, Bldg 10,Room 10N262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. RI Koch, Christian/A-4699-2008 OI Koch, Christian/0000-0003-3127-5739 NR 4 TC 0 Z9 0 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 2000 VL 85 IS 3 BP 1347 EP 1347 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 337WW UT WOS:000088387000080 PM 10720093 ER PT J AU Drapkin, PT O'Riordan, CR Yi, SM Chiorini, JA Cardella, J Zabner, J Welsh, MJ AF Drapkin, PT O'Riordan, CR Yi, SM Chiorini, JA Cardella, J Zabner, J Welsh, MJ TI Targeting the urokinase plasminogen activator receptor enhances gene transfer to human airway epithelia SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ADENOVIRUS VECTORS; CYSTIC-FIBROSIS; INHIBITOR COMPLEX; IN-VITRO; BINDING; EXPRESSION; CELLS; THERAPY; ENTRY; CARCINOMA AB Developing gene therapy for cystic fibrosis has been hindered by limited binding and endocytosis of vectors by human airway epithelia. Here we show that the apical membrane of airway epithelia express the urokinase plasminogen activator receptor (uPAR). Urokinase plasminogen activator (uPA), or a 7-residue peptide derived from this protein (u7-peptide), bound the receptor and stimulated apical endocytosis. Both ligands enhanced gene transfer by nonspecifically bound adenovirus and adenoassociated virus vectors and by a modified adenovirus vector that had been coupled to the u7-peptide. These data provide the first evidence that targeting an apical receptor can circumvent the two most important barriers to gene transfer in airway epithelia. Thus, the uPA/uPAR system may offer significant advantages for delivering genes and other pharmaceuticals to airway epithelia. C1 Univ Iowa, Coll Med, Program Gene Therapy, Iowa City, IA 52242 USA. Univ Iowa, Coll Med, Howard Hughes Med Inst, Iowa City, IA 52242 USA. Univ Iowa, Coll Med, Dept Physiol & Biophys, Iowa City, IA 52242 USA. Univ Iowa, Coll Med, Dept Internal Med, Iowa City, IA 52242 USA. Univ Iowa, Coll Med, Dept Otolaryngol, Iowa City, IA 52242 USA. Genzyme Corp, Framingham, MA 01701 USA. NIDCR, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. Toronto Hosp, Gen Div, Thorac Surg Res Lab, Toronto, ON M5G 1L7, Canada. RP Welsh, MJ (reprint author), Univ Iowa, Coll Med, Program Gene Therapy, Iowa City, IA 52242 USA. EM mjwelsh@blue.weeg.uiowa.edu NR 55 TC 45 Z9 47 U1 2 U2 4 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2000 VL 105 IS 5 BP 589 EP 596 DI 10.1172/JCI8858 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 291QD UT WOS:000085746800010 PM 10712430 ER PT J AU Yu, SH Gavrilova, O Chen, H Lee, R Liu, J Pacak, K Parlow, AF Quon, MJ Reitman, ML Weinstein, LS AF Yu, SH Gavrilova, O Chen, H Lee, R Liu, J Pacak, K Parlow, AF Quon, MJ Reitman, ML Weinstein, LS TI Paternal versus maternal transmission of a stimulatory G-protein alpha subunit knockout produces opposite effects on energy metabolism SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID BROWN ADIPOSE-TISSUE; HUMAN GNAS1 GENE; TARGETED DISRUPTION; PERINATAL LETHALITY; UNCOUPLING PROTEIN; ADENYLATE-CYCLASE; TRANSGENIC MICE; RECEPTOR; PSEUDOHYPOPARATHYROIDISM; LACKING AB Heterozygous disruption of Gnas, the gene encoding the stimulatory G-protein alpha subunit (G(s)alpha), leads to distinct phenotypes depending on whether the maternal (m-/+) or paternal (+/p-) allele is disrupted. G(s)alpha is imprinted, with the maternal allele preferentially expressed in adipose tissue. Hence, expression is decreased in m-/+ mice but normal in +/p- mice. M-/+ mice become obese, with increased lipid per cell in white and brown adipose tissue, whereas +/p- mice are thin, with decreased lipid in adipose tissue. These effects are not due to abnormalities in thyroid hormone status, food intake, or leptin secretion. +/p- mice are hypermetabolic at both ambient temperature (21 degrees C) and thermoneutrality (30 degrees C). In contrast, m-/+ mice are hypometabolic at ambient temperature and eumetabolic at thermoneutrality M-/+ and wild-type mice have similar dose-response curves for metabolic response to a beta(3)-adrenergic agonist, CL316243, indicating normal sensitivity of adipose tissue to sympathetic stimulation. Measurement of urinary catecholamines suggests that +/p- and m-/+ mice have increased and decreased activation of the sympathetic nervous system, respectively. This is to our knowledge the first animal model in which a single genetic defect leads to opposite effects on energy metabolism depending on parental inheritance. This probably results from deficiency of maternal- and paternal-specific Gnas gene products, respectively. C1 NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Harbor Med Ctr, Natl Hormone & Pituitary Program, Torrance, CA 90509 USA. NHLBI, Hypertens Endocrine Branch, NIH, Bethesda, MD 20892 USA. RP Weinstein, LS (reprint author), NIDDKD, Metab Dis Branch, NIH, Bldg 10 Room 8C101, Bethesda, MD 20892 USA. RI Quon, Michael/B-1970-2008; Reitman, Marc/B-4448-2013; OI Reitman, Marc/0000-0002-0426-9475; Quon, Michael/0000-0002-9601-9915 FU NIDDK NIH HHS [DK-9-2246] NR 62 TC 116 Z9 117 U1 1 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2000 VL 105 IS 5 BP 615 EP 623 DI 10.1172/JCI8437 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 291QD UT WOS:000085746800013 PM 10712433 ER PT J AU Uren, D Hwang, HK Hara, Y Takeda, K Kawamoto, S Tullio, AN Yu, ZX Ferrans, VJ Tresser, N Grinberg, A Preston, YA Adelstein, RS AF Uren, D Hwang, HK Hara, Y Takeda, K Kawamoto, S Tullio, AN Yu, ZX Ferrans, VJ Tresser, N Grinberg, A Preston, YA Adelstein, RS TI Gene dosage affects the cardiac and brain phenotype in nonmuscle myosin II-B-depleted mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HEAVY CHAIN-B; FAMILIAL HYPERTROPHIC CARDIOMYOPATHY; ISOFORMS; RECOMBINATION; MORPHOGENESIS; EXPRESSION; ANTIBODIES; MUTATIONS; REVEALS; CLONING AB Complete ablation of nonmuscle myosin heavy chain II-B (NMHC-B) in mice resulted in cardiac and brain defects that were lethal during embryonic development or on the day of birth. In this paper, we report on the generation of mice with decreased amounts of NMHC-B. First, we generated B-Delta I/B-Delta I mice by replacing a neural-specific alternative exon with the PGK-Neo cassette, This resulted in decreased amounts of NMHC-B in all tissues, including a decrease of 88% in the heart and 65% in the brain compared with B+/B+ tissues. B-Delta I/B-Delta I mice developed cardiac myocyte hypertrophy between 7 months and 11 months of age, at which time they reexpressed the cardiac beta-MHC. Serial sections of B-Delta I/B-Delta I brains showed abnormalities in neural cell migration and adhesion in the ventricular wall, Crossing B-Delta I/B-Delta I with B+/B- mice generated B-Delta I/B- mice, which showed a further decrease of approximately 55% in NMHC-B in the heart and brain compared with B-Delta I/B-Delta I mice. Five of 8 B-Delta I/B- mice were born with a membranous ventricular septal defect. Moreover, 5 of 5 B-Delta I/B- mice developed myocyte hypertrophy by 1 month; B-Delta I/B- mice also reexpressed the cardiac beta-MHC. More than 60% of B-Delta I/B- mice developed overt hydrocephalus and showed more severe defects in neural cell migration and adhesion than did B-Delta I/B-Delta I mice. These data on B-Delta I/B-Delta I and B-Delta I/B- mice demonstrate a gene dosage effect of the amount of NMHC-B on the severity and time of onset of the defects in the heart and brain. C1 NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. NINDS, Off Clin Director, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. RP Adelstein, RS (reprint author), NHLBI, Mol Cardiol Lab, NIH, Bldg 10,Room 8N202,10 Ctr Dr, Bethesda, MD 20892 USA. OI Adelstein, Robert/0000-0002-8683-2144 NR 32 TC 32 Z9 33 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2000 VL 105 IS 5 BP 663 EP 671 DI 10.1172/JCI8199 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 291QD UT WOS:000085746800018 PM 10712438 ER PT J AU Brewer, HB AF Brewer, HB TI The lipid-laden foam cell: an elusive target for therapeutic intervention SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID COA-CHOLESTEROL ACYLTRANSFERASE; ACYL-COENZYME-A; MACROPHAGES; EXPRESSION; CLONING; ENZYMES C1 NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. RP Brewer, HB (reprint author), NHLBI, Mol Dis Branch, NIH, Bldg 10,Room 7N115,10 Ctr Dr MSC 1666, Bethesda, MD 20892 USA. NR 15 TC 27 Z9 28 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2000 VL 105 IS 6 BP 703 EP 705 DI 10.1172/JCI9664 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 295NJ UT WOS:000085974500003 PM 10727436 ER PT J AU Cohen, OJ Fauci, AS AF Cohen, OJ Fauci, AS TI Benchmarks for antiretroviral therapy SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID HIV-1 INFECTION; LYMPHOID-TISSUE; LYMPHOCYTES; MORTALITY; AIDS C1 NIAID, Bethesda, MD 20892 USA. Dept Hlth & Human Serv, Henry J Kaiser Family Fdn Panel Clin Practices Tr, Washington, DC USA. RP Cohen, OJ (reprint author), NIAID, 31 Ctr Dr MSC 2520,Bldg 31,Room 7A05, Bethesda, MD 20892 USA. NR 25 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2000 VL 105 IS 6 BP 709 EP 710 DI 10.1172/JCI9590 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 295NJ UT WOS:000085974500005 PM 10727438 ER PT J AU Madico, G Quinn, TC Boman, J Gaydos, CA AF Madico, G Quinn, TC Boman, J Gaydos, CA TI Touchdown enzyme time release-PCR for detection and identification of Chlamydia trachomatis, C. pneumoniae, and C. psittaci using the 16S and 16S-23S spacer rRNA genes SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; RIBOSOMAL-RNA GENE; DNA AMPLIFICATION; REACTION ASSAY; ANTIGEN-DETECTION; URINE SPECIMENS; DIAGNOSIS; INFECTION; IMMUNOASSAY; MEN AB Three touchdown enzyme time release (TETR)-PCR assays were used to amplify different DNA sequences in the variable regions of the 16S and 16S-23S spacer rRNA genes specific for Chlamydia trachomatis, Chlamydia pneumoniae, and Chlamydia psittaci as improved tests for sensitive diagnosis and rapid species differentiation. The TETR-PCR protocol used 60 cycles of amplification, which provided improved analytical sensitivity (0.004 to 0.063 inclusion-forming unit of Chlamydia species per PCR). The sensitivity of TETR-PCR with primer set CTR 70-CTR 71 was 96.7%, and the specificity was 99.6%, compared to those of the AMPLICOR PCR for the detection of C. trachomatis in vaginal swab samples. TETR-PCR for C. pneumoniae with primer set CPN 90-CPN 91 was 90% sensitive and 93.3% specific compared with a nested PCR with primer set CP1/2-CPC/D for clinical respiratory samples. TETR-PCR for C. psittaci with primer set CPS 100-CPS 101 showed substantial agreement with cell culturing (kappa, 0.78) for animal tissue samples. Primer sets were then combined into a single multiplex TETR-PCR test. The respective 315-, 195-, and Ill-bp DNA target products were precisely amplified when DNA from each of the respective Chlamydia species or combinations of them was used. Multiplex chlamydia TETR-PCR correctly identified one strain of each of the 15 serovars of C. trachomatis, 22 isolates of C. pneumoniae, and 20 isolates of C. psittaci. The primer sets were specific for each species. No target products were amplified when DNA from C. pecorum or a variety of other microorganisms was tested for specificity. TETR-PCR with primers selected for specific sequences in the 16S and 16S-23S spacer rRNA genes is a valuable test that could be used either with individual primers or in a multiplex assay for the identification and differentiation of Chlamydia species from culture isolates or for the detection of chlamydiae in clinical samples. C1 Johns Hopkins Univ, Div Infect Dis, Baltimore, MD 21205 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Umea Univ, Umea, Sweden. RP Gaydos, CA (reprint author), Johns Hopkins Univ, Div Infect Dis, 1151 Ross Res Bldg,720 Rutland Ave, Baltimore, MD 21205 USA. RI Gaydos, Charlotte/E-9937-2010 NR 42 TC 121 Z9 128 U1 1 U2 6 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 2000 VL 38 IS 3 BP 1085 EP 1093 PG 9 WC Microbiology SC Microbiology GA 291ND UT WOS:000085742200025 PM 10699002 ER PT J AU Van der Pol, B Quinn, TC Gaydos, CA Crotchfelt, K Schachter, J Moncada, J Jungkind, D Martin, DH Turner, B Peyton, C Jones, RB AF Van der Pol, B Quinn, TC Gaydos, CA Crotchfelt, K Schachter, J Moncada, J Jungkind, D Martin, DH Turner, B Peyton, C Jones, RB TI Multicenter evaluation of the AMPLICOR and automated COBAS AMPLICOR CT/NG tests for detection of Chlamydia trachomatis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID LIGASE CHAIN-REACTION; FIRST-VOID URINE; TRANSCRIPTION-MEDIATED AMPLIFICATION; ROUTINE DIAGNOSTIC PCR; REACTION ASSAY; DNA AMPLIFICATION; NEISSERIA-GONORRHOEAE; WOMEN; SPECIMENS; INFECTION AB The fully automated COBAS AMPLICOR CT/NG and semiautomated AMPLICOR CT/NG tests were evaluated in a multicenter trial for the ability to detect Chlamydia trachomatis infections. Test performance compared to that of culture was evaluated for 2,236 matched endocervical swab and urine specimens obtained from women and for 1,940 matched urethral swab and urine specimens obtained from men. Culture-negative, PCR-positive specimens that tested positive in a direct fluorescent-antibody test or in a confirmatory PCR test for an alternative target sequence were resolved as true positives. The overall prevalences of chlamydia were 2.4% in women and 7.2% in men. The COBAS AMPLICOR and AMPLICOR formats yielded concordant results for 98.1% of the specimens. With the infected patient as the reference standard, the resolved sensitivities of COBAS AMPLICOR were 89.7% for endocervical swab specimens, 89.2% for female urine specimens, 88.6% for male urethral swab specimens, and 90.3% for male urine specimens. When results were analyzed as if only a single test had been performed on a single specimen type, the resolved sensitivity was always higher. The resolved specificities of PCR were 99.4% for endocervical swab specimens, 99.0% for female urine specimens, 98.7% for male urethral swab specimens, and 98.4% for male urine specimens. The internal control revealed that 2.4% of the specimens were inhibitory when initially tested. Nevertheless, valid results were obtained for 98.6% of the specimens because 59.1% of the inhibitory specimens were not inhibitory when a second aliquot was tested. The COBAS AMPLICOR and AMPLICOR CT/NG tests for C. trachomatis exhibited equally high sensitivity and specificity with both urogenital swab and urine specimens and thus are well suited for screening for C. trachomatis infection. C1 Univ Indianapolis, Sch Med, Indianapolis, IN 46227 USA. NIAID, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD 21204 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Thomas Jefferson Univ Hosp, Pittsburgh, PA 15260 USA. Louisiana State Univ, Baton Rouge, LA 70803 USA. City New Orleans Delgado Clin, New Orleans, LA 70101 USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. RP Van der Pol, B (reprint author), 545 N Barnhill 435, Indianapolis, IN 46202 USA. RI Gaydos, Charlotte/E-9937-2010 NR 36 TC 101 Z9 108 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 2000 VL 38 IS 3 BP 1105 EP 1112 PG 8 WC Microbiology SC Microbiology GA 291ND UT WOS:000085742200027 PM 10699004 ER PT J AU Warren, KE Frank, JA Black, FL Hill, RS Duyn, JH Aikin, AA Levis, BK Adamson, PC Balis, FM AF Warren, KE Frank, JA Black, FL Hill, RS Duyn, JH Aikin, AA Levis, BK Adamson, PC Balis, FM TI Proton magnetic resonance spectroscopic imaging in children with recurrent primary brain tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID H-1 MR SPECTROSCOPY; GRADE ASTROCYTOMAS; PROGNOSTIC FACTORS; METABOLITES; INVIVO; GLIOMAS; SPECTRA; CHOLINE AB Purpose: Proton magnetic resonance spectroscopic imaging (H-1-MRSI) is a noninvasive technique for spatial characterization of biochemical markers in tissues. We measured the relative tumor concentrations of these biochemical markers in children with recurrent brain tumors and evaluated their potential prognostic significance. Patients and Methods: H-1-MRSI was performed on 27 children with recurrent primary brain tumors referred to our institution for investigational drug trials, Diagnoses included high-grade glioma (n = 10), brainstem glioma (n = 7), medulloblastoma/peripheral neuroectodermal tumor (n = 6), ependymoma (n = 3), and pineal germinoma (n = 1). H-1-MRSI was performed on 1.5-T magnetic resonance imagers before treatment. The concentrations of choline (Cho) and N-acetyl-aspartate (NAA) in the tumor and normal brain were quantified using a multislice multivoxel method, and the maximum Cho:NAA ratio was determined for each patient's tumor. Results: The maximum Cho:NAA ratio ranged from 1.1 to 13.2 (median, 4.5); the Cho:NAA ratio in areas of normal-appearing brain tissue was less than 1.0, The maximum Cho:NAA ratio for each histologic subtype varied considerably; approximately equal numbers of patients within each tumor type had maximum Cho: NAA ratios above and below the median. Patients with a maximum Cho:NAA ratio greater than 4.5 had a median survival of 22 weeks, and all 13 patients died by 63 weeks. Patients with a Cho:NAA ratio less than or equal to 4.5 had a projected survival of more than 50% at 63 weeks. The difference was statistically significant (P = .0067, log-rank test). Conclusion: The maximum tumor Cho:NAA ratio seems to be predictive of outcome in children with recurrent primary brain tumors and should be evaluated as a prognostic indicator in newly diagnosed childhood brain tumors. J Clin Oncol 18:1020-1026, (C) 2000 by American Society of Clinical Oncology. C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. NINDS, Bethesda, MD 20892 USA. NIH, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. RP Warren, KE (reprint author), NCI, Pediat Oncol Branch, Bldg 10,Rm 13N240,10 Ctr Dr,MSC 1928, Bethesda, MD 20892 USA. RI Duyn, Jozef/F-2483-2010 NR 35 TC 60 Z9 61 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR PY 2000 VL 18 IS 5 BP 1020 EP 1026 PG 7 WC Oncology SC Oncology GA 288VW UT WOS:000085586000011 PM 10694552 ER PT J AU Fracasso, PM Westerveldt, P Fears, CA Rosen, DM Zuhowski, EG Cazenave, LA Litchman, M Egorin, MJ AF Fracasso, PM Westerveldt, P Fears, CA Rosen, DM Zuhowski, EG Cazenave, LA Litchman, M Egorin, MJ TI Phase I study of paclitaxel in combination with a multidrug resistance modulator, PSC 833 (valspodar), in refractory malignancies SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NONIMMUNOSUPPRESSIVE CYCLOSPORINE; SDZ PSC-833; CANCER; PHARMACOKINETICS; DOXORUBICIN; TRIAL; PHARMACODYNAMICS; ETOPOSIDE; SYSTEMS; TUMORS AB Purpose: To determine the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), and pharmacokinetics of paclitaxel when given with PSC 833 (valspodar) to patients with refractory solid tumors. Patients and Methods: Patients were initially treated with paclitaxel 175 mg/m(2) continuous intravenous infusion (CIVI) over 3 hours. Subsequently, 29 hours of treatment with CIVI PSC 833 was started 2 hours before paclitaxel treatment was initiated. In this combination, the starting dose of paclitaxel was 52.5 mg/m(2). Paclitaxel doses were escalated by 17.5 mg/m(2) increments for four subsequent cohorts. Each cohort consisted of three patients with the exception of the last cohort, which consisted of six patients. Data for the pharmacokinetics of paclitaxel with and without concurrent PSC 833 administration were obtained. Results: All 18 patients completed at least one course of concurrent treatment (median, two courses; range, one to six) and were evaluable for toxicity. The MTD for paclitaxel with PSC 833 was 122.5 mg/m(2). Neutropenia was the DLT, All patients had PSC 833 blood concentrations greater than 1,000 ng/mL before, during, and 24 hours after the paclitaxel infusion. PSC 833 produced small increases in the paclitaxel peak plasma concentrations and areas under the concentration-time curve, However, PSC 833 greatly prolonged the terminal phase of paclitaxel, resulting in plasma paclitaxel concentrations of more than 0.05 mu mol/L for much longer than expected, As a result, myelosuppression was comparable to that produced by full dose paclitaxel given without PSC 833, Of the 16 patients who were assessable for response, one patient experienced a partial response and an additional nine patients experienced disease stabilization after paclitaxel treatment alone. Conclusion: Treatment with paclitaxel 122.5 mg/m(2) as a 3-hour CIVI concurrent with a 29-hour CIVI of PSC 833 results in acceptable toxicity. The addition of PSC 833 alters the pharmacokinetics of paclitaxel, which explains the enhanced neutropenia experienced by patients treated with this drug combination. J Clin Oncol 18:1124-1134. (C) 2000 by American Society of Clinical Oncology. C1 Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. Univ Maryland, Sch Med, Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. NCI, Div Canc Treatment & Diag, Canc Therapy Evaluat Program, Bethesda, MD USA. Novartis Pharmaceut Corp, Hanover, NJ USA. RP Fracasso, PM (reprint author), Washington Univ, Sch Med, Dept Med, Box 8056,660 S Euclid Ave, St Louis, MO 63110 USA. FU NCRR NIH HHS [RR00036] NR 30 TC 52 Z9 53 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR PY 2000 VL 18 IS 5 BP 1124 EP 1134 PG 11 WC Oncology SC Oncology GA 288VW UT WOS:000085586000025 PM 10694566 ER PT J AU Andrawis, NS Battle, MM Klamerus, KJ Burghart, PH Neefe, L Weinryb, I Mayer, P Abernethy, DR AF Andrawis, NS Battle, MM Klamerus, KJ Burghart, PH Neefe, L Weinryb, I Mayer, P Abernethy, DR TI A pharmacokinetic and pharmacodynamic study of the potential drug interaction between tasosartan and atenolol in patients with stage 1 and 2 essential hypertension SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID CONGESTIVE-HEART-FAILURE; II ANTAGONIST LOSARTAN; PHARMACOLOGICAL PROPERTIES; RECEPTOR ANTAGONIST; DOUBLE-BLIND; ANGIOTENSIN; COMBINATION; THERAPIES; BLOCKADE; SYSTEM AB The primary objective of this study was to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of tasosartan and atenolol administered alone and concomitantly under steady-state conditions in 17 patients ages 18 to 65 years diagnosed with stage 2 to 2 essential hypertension. After a 3- to 14-day qualification period, all patients received placebo tasosartan on days -1 through 5 and 25 through 34, atenolol alone (50 mg) on days I through 5, atenolol(50mg) + tasosartan (50 mg) on days 6 through 19, and tasosartan (50 mg) alone on days 20 through 24. A PK and PD evaluation of atenolol alone was performed on study day 5. On study day 19, PK and PD of both tasosartan and atenolol were assessed. PK and PD evaluation for tasosartan alone was assessed on study day 24. The coadministration of atenolol + tasosartan did not affect the pharmacokinetics of tasosartan, its major metabolite (enoltasosartan), or atenolol when compared with tasosartan or atenolol administered separately For area under the change in diastolic blood pressure curve, the reduction was significantly greater after tasosartan + atenolol compared with that after atenolol alone (336 +/- 85 and 190 +/- 71 mmHg . 24 h; p < 0.05 for combination and atenolol alone, respectively mean +/- SEM). Combination therapy also caused a maximal reduction in diastolic blood pressure that is significantly more than with monotherapy with atenolol (-27 +/- 2 mmHg and -20 +/- 2 mmHg, respectively p < 0.05). The additive effects of tasosartan and atenolol in decreasing diastolic blood pressure may provide a rationale for combination antihypertensive therapy. (C) 2000 the American College of Clinical Pharmacology. C1 Georgetown Univ, Med Ctr, Dept Med, Div Clin Pharmacol, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Pharmacol, Div Clin Pharmacol, Washington, DC 20007 USA. RP Abernethy, DR (reprint author), NIA, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 34 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD MAR PY 2000 VL 40 IS 3 BP 231 EP 241 DI 10.1177/00912700022008892 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 286NF UT WOS:000085451500002 PM 10709151 ER PT J AU Daugherty, AL McKee, ML FitzGerald, DJ Mrsny, RJ AF Daugherty, AL McKee, ML FitzGerald, DJ Mrsny, RJ TI Epithelial application of Pseudomonas aeruginosa exotoxin A results in a selective targeting to cells in the liver, spleen and lymph node SO JOURNAL OF CONTROLLED RELEASE LA English DT Article; Proceedings Paper CT 9th International Symposium on Recent Advances in Drug Delivery Systems CY FEB 22-25, 1999 CL SALT LAKE CITY, UTAH DE mucosal immunization; Pseudomonas aeruginosa exotoxin A; cell targeting ID VACCINES AB Pseudomonas aeruginosa exotoxin A (PE) is a 67-kDa protein expressed under the selective pressure of a low iron environment. Previous studies using non-toxic PE chimeras containing a viral surface antigen, the V3 loop of MN gp120 from human immunodefiency virus type 1 (HIV-1), resulted in not only an effective mucosal immunization but also a striking systemic immune response following epithelial application, presently, we have examined the possibility that such a strong dual immune response was generated by the efficient targeting of critical cells of the immune system. Mice were dosed with 10 mu g of toxic PE or a non-toxic mutant of PE (ntPE) by intratracheal instillation. Examination of lung, liver and spleen tissues isolated 1, 8 and 12 h following intratracheal instillation with PE demonstrated specific cell damage in these tissues which was not observed in mice dosed with ntPE. Based upon the location and characteristics of observed responses, the cells targeted by PE appear to be involved in the antigen presentation arm of the immune response. Since ntPE chimeras with inserted peptide antigen epitopes from a wide variety of pathogens are easy to prepare and administer, these results support this approach fur mucosal immunization. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Genentech Inc, Dept Pharmaceut Res & Dev, Drug Delivery Biol Grp, S San Francisco, CA 94080 USA. NCI, Div Basic Sci, Mol Biol Lab, Biotherapy Sect, Bethesda, MD 20892 USA. RP Mrsny, RJ (reprint author), Genentech Inc, Dept Pharmaceut Res & Dev, Drug Delivery Biol Grp, MS 6,1 DNA Way, S San Francisco, CA 94080 USA. NR 10 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 J9 J CONTROL RELEASE JI J. Control. Release PD MAR 1 PY 2000 VL 65 IS 1-2 BP 297 EP 302 DI 10.1016/S0168-3659(99)00251-5 PG 6 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 294WP UT WOS:000085933700027 PM 10699289 ER PT J AU Wendel, T Curtis, R AF Wendel, T Curtis, R TI The heraldry of heroin: "Dope stamps" and the dynamics of drug markets in New York City SO JOURNAL OF DRUG ISSUES LA English DT Article ID EPIDEMIC C1 Natl Inst Drug Abuse, Heroin 21st Century Project, Bethesda, MD 20892 USA. Natl Inst Justice, Lower E Side Trafficking Study, Washington, DC 20531 USA. RP Wendel, T (reprint author), CUNY John Jay Coll Criminal Justice, New York, NY 10019 USA. NR 45 TC 21 Z9 21 U1 0 U2 0 PU J DRUG ISSUES INC PI TALLAHASSEE PA FLORIDA STATE UNIV, SCHOOL CRIMINOLOGY CRIMINAL JUSTICE, PO BOX 66696, TALLAHASSEE, FL 32313-6696 USA SN 0022-0426 J9 J DRUG ISSUES JI J. Drug Issues PD SPR PY 2000 VL 30 IS 2 BP 225 EP 259 PG 35 WC Substance Abuse SC Substance Abuse GA 330HK UT WOS:000087956600001 ER PT J AU Freedman, DM Cantor, KP Ward, MH Helzlsouer, KJ AF Freedman, DM Cantor, KP Ward, MH Helzlsouer, KJ TI A comparison of recent and long-term average measurements of nitrate in drinking water SO JOURNAL OF EXPOSURE ANALYSIS AND ENVIRONMENTAL EPIDEMIOLOGY LA English DT Article DE cancer; measurement; nitrate; non-Hodgkin's lymphoma; water ID NON-HODGKINS-LYMPHOMA; GASTRIC-CANCER; RISK; YORKSHIRE AB We evaluated the usefulness of a recent measure of drinking water nitrate as a predictor of long-term average nitrate exposure calculated from historic data. Exposure estimates were calculated for 214 study participants who used public water supplies between 1947 and 1980 in Minnesota. Long-term average nitrate was calculated by linking residential histories to historical nitrate data. For recent exposures, we averaged nitrate measurements in 1980, or the next closest year with measurements. The Spearman correlation coefficient for the relationship between the two measures was 0.54 (95% confidence interval [CI] =0.44-0.63). Agreement was highest among those residing 34 or more years in their town as of 1980 (r(a) =0.70; 95% CI =0.55-0.80). These findings suggest that taking into account the study participants' duration of residence may enhance the validity of using a recent measure as an indicator of past exposures. C1 NCI, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. RP Freedman, DM (reprint author), NCI, Radiat Epidemiol Branch, Room 7087,EPS 6120 Execut Blvd, Bethesda, MD 20892 USA. NR 13 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1053-4245 J9 J EXPO ANAL ENV EPID JI J. Expo. Anal. Environ. Epidemiol. PD MAR-APR PY 2000 VL 10 IS 2 BP 206 EP 209 DI 10.1038/sj.jea.7500083 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 330XR UT WOS:000087987200010 PM 10791601 ER PT J AU Tziraki, C Graubard, BI Manley, M Kosary, C Moler, JE Edwards, BK AF Tziraki, C Graubard, BI Manley, M Kosary, C Moler, JE Edwards, BK TI Effect of training on adoption of cancer prevention nutrition-related activities by primary care practices: Results of a randomized, controlled study SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE nutrition education; nutrition counseling; cancer prevention; primary care physicians ID COUNSELING PRACTICES; PHYSICIANS; EDUCATION; PROGRAM; ATTITUDES; CHOLESTEROL; MANAGEMENT; KNOWLEDGE; TRIAL; GUIDANCE AB OBJECTIVE: The National Cancer Institute (NCI) developed a manual to guide primary care practices in structuring their office environment and routine visits so as to enhance nutrition screening, advice/referral, and follow-up for cancer prevention. The adoption of the manual's recommendations by primary care practices was evaluated by examining two strategies: physician training on how to implement the manual's recommendations versus simple mailing of the manual. This article reports on the results of a randomized controlled trial to evaluate the effectiveness of these two strategies. DESIGN:A three-arm, randomized, controlled study. SETTING: Free-standing primary care physician practices in Pennsylvania and New Jersey. INTERVENTION: Each study practice was randomly assigned to one of three groups. The training group practices were invited to send one member from their practice of their choosing to a 3-hour "train-a-trainer" workshop, the manual-only-group practices were mailed the nutrition manual, and the control group practices received no intervention, For training group practices, training was provided in the four major components of the nutrition manual: how to organize the office environment to support cancer prevention nutrition-related activities; how to screen patient adherence to the NCI dietary guidelines; how to provide dietary advice/referral; and how to implement a patient follow-up system to support patients in making changes in their nutrition-related behaviors. MEASUREMENTS: The primary outcomes of the study were derived from two evaluation instruments. The observation instrument documented the tools and procedures recommended by the nutrition manual and adopted in patient charts and the office environment. The in-person structured interview evaluated the physician and staffs self-reported nutrition-related activities reflecting the nutrition manual's recommendations. Data from these two instruments were used to construct four adherence scores corresponding to the areas: office organization, nutrition screening, nutrition advice/referral, and patient follow-up. MAIN RESULTS: The adoption of the manual's recommendations was highest among the practices in the training group as reflected by their higher adherence scores. They organized their office (P = .005) and screened their patients regarding their eating habits (P = .046) significantly more closely to the recommendations of the nutrition manual than practices in the manual-only group. However, despite being the highest in compliance, the training group practices were only 54.9% adherent to the manual's recommendations regarding nutrition advice/referral, and 28.5% adherent to its recommendations on office organization, 23.5% adherent to its recommendations on nutrition screening, and 14.6% adherent to its patient follow-up recommendations. CONCLUSIONS: Primary care practices exposed to the nutrition manual in a training session adopted more of the manual's recommendations. Specifically, practices invited to training were more likely to perform nutrition screening and to structure their office environment to be conducive to providing nutrition-related services for cancer prevention. The impact of the training was moderate and not statistically significant for nutrition advice/referral or patient follow-up, which are important in achieving long-term dietary changes in patients. The overall low adherence scores to nutrition-related activities demonstrates that there is plenty of room for improvement among the practices in the training group. C1 NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Graubard, BI (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS-8024, Bethesda, MD 20892 USA. OI Moler, James/0000-0001-8738-6898 NR 36 TC 11 Z9 11 U1 1 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2000 VL 15 IS 3 BP 155 EP 162 DI 10.1046/j.1525-1497.2000.03409.x PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 292ZY UT WOS:000085828100002 PM 10718895 ER PT J AU Fauci, AS AF Fauci, AS TI Laudatio: In celebration of the 80th birthday of Maurice R. Hilleman, Ph.D. SO JOURNAL OF HUMAN VIROLOGY LA English DT Biographical-Item C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Fauci, AS (reprint author), NIAID, NIH, 31 Ctr Dr,Bldg 31 Room 7A-03, Bethesda, MD 20892 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 1090-9508 J9 J HUMAN VIROL JI J. Human Virol. PD MAR-APR PY 2000 VL 3 IS 2 BP 60 EP 62 PG 3 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA 317RK UT WOS:000087240600002 PM 10850890 ER PT J AU Zella, D Romerio, F Curreli, S Secchiero, P Cicala, C Zagury, D Gallo, RC AF Zella, D Romerio, F Curreli, S Secchiero, P Cicala, C Zagury, D Gallo, RC TI IFN-alpha 2b reduces IL-2 production and IL-2 receptor function in primary CD4(+) T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; NIH 3T3 CELLS; MAP KINASE; INTERFERON-ALPHA; SIGNALING PATHWAYS; GROWTH-FACTOR; IFN-ALPHA; PHOSPHORYLATION; GENE; PROLIFERATION AB Initially described as an antiviral cytokine, IFN-alpha has been subsequently shown to affect several cellular functions, including cellular differentiation and proliferation. For these reasons, IFN-alpha is currently used in clinical practice for the treatment of viral infections and malignancies. In this manuscript, we show two novel mechanisms concomitantly responsible for the antiproliferative effect of IFN-alpha. First, long-term treatment with IFN-alpha of primary CD4(+) T cells reduced surface expression of CD3 and CD28 These events resulted in decreased phosphorylation of the mitogen-activated extracellular signal-regulated activating kinase and its substrate extracellular signal-regulated kinase, leading to diminished production of IL-2. Second, IFN-alpha treatment of primary CD4(+) T cells reduced proliferative response to stimulation in the presence of exogenous IL-2 by markedly decreasing mRNA synthesis and surface expression of CD25 (alpha-chain), a critical component of the IL-2R complex. These results may be relevant for the antitumor effects of IFN-alpha and may help us to better understand its detrimental role in the inhibition of proliferation of the bulk of CD4(+) T cells (uninfected cells) in HIV-infected persons, who are known to overproduce IFN-alpha. C1 Univ Maryland, Inst Biotechnol, Inst Human Virol, Baltimore, MD 21201 USA. Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. Univ Ferrara, Human Anat Sect, Dept Morphol & Embryol, I-44100 Ferrara, Italy. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Inst Pierre & Marie Curie, Paris, France. RP Zella, D (reprint author), Univ Maryland, Inst Biotechnol, Inst Human Virol, 725 W Lombard St, Baltimore, MD 21201 USA. RI secchiero, paola/G-9689-2015 OI secchiero, paola/0000-0003-4101-7987 NR 70 TC 33 Z9 33 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 2000 VL 164 IS 5 BP 2296 EP 2302 PG 7 WC Immunology SC Immunology GA 286YU UT WOS:000085477100005 PM 10679063 ER PT J AU Yang, JC Perry-Lalley, D AF Yang, JC Perry-Lalley, D TI The envelope protein of an endogenous murine retrovirus is a tumor-associated T-cell antigen for multiple murine tumors SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE cytotoxic T lymphocyte; endogenous retrovirus; murine tumor; tumor antigen ID INFILTRATING LYMPHOCYTES; METASTATIC MELANOMA; REJECTION ANTIGEN; GENE; PEPTIDE; CLONING AB Recently, significant progress has been made in identifying specific tumor-associated antigens recognized by T cells and defining the specific peptide epitopes within these proteins that are processed and presented on class 1 major histocompatibility antigens. Most of these antigens have been identified in human melanoma, where many of them appear to be tissue-specific, nonmutated proteins expressed by melanoma and normal melanocytes but not by other tissues. There has been much less progress in identifying the tumor antigens on murine tumors that are recognized by T cells, and this has restricted the development of preclinical animal models for immunotherapy. The authors previously described a method for generating tumor-reactive T cells from murine tumors (tumor infiltrating lymphocytes) that are CD8(+) T cells recognizing autologous tumor and that can inhibit established tumor on adoptive transfer. Here the authors show that the envelope protein of an endogenous murine retrovirus of the AKV family, found in the germline of the C57BL/6 mouse, is recognized by tumor-infiltrating lymphocytes from two histologically different tumors syngeneic to that mouse strain. Furthermore, the authors identify the specific 9-amino acid peptide from the p15E transmembrane component of this envelope protein that is recognized in the context of major histocompatibility complex Kb, show that it is naturally presented and recognized on several other H-2(b) tumors, and that cytotoxic T lymphocytes specific for this epitope are therapeutic for these antigen-expressing tumors on adoptive transfer. C1 NCI, Surg Branch, Bethesda, MD 20892 USA. RP Yang, JC (reprint author), 2B-37,Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 16 TC 35 Z9 35 U1 0 U2 1 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-APR PY 2000 VL 23 IS 2 BP 177 EP 183 DI 10.1097/00002371-200003000-00001 PG 7 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 295EK UT WOS:000085953600001 PM 10746543 ER PT J AU Bettinotti, MP Norris, RD Hackett, JA Thompson, CO Simonis, TB Stroncek, D Marincola, FM AF Bettinotti, MP Norris, RD Hackett, JA Thompson, CO Simonis, TB Stroncek, D Marincola, FM TI Frequency of human leukocyte antigen-A 24 alleles in patients with melanoma determined by human leukocyte antigen-A sequence-based typing SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE HLA-A24; HLA-A class I typing; DNA sequencing; melanoma; immunotherapy; human clinical studies ID TUMOR-INFILTRATING LYMPHOCYTES; PEPTIDE-BASED IMMUNOTHERAPY; HLA-A2 SUBTYPES; EPITOPE; IDENTIFICATION; POLYMORPHISM; TYROSINASE; MART-1; CELLS AB The analysis of immune responses of patients with melanoma has led to the identification of melanoma-associated antigens targeted by T cells. Cytotoxic T lymphocytes recognize peptides from melanoma-associated antigens presented on the cancer cell surface in the context of HLA class I molecules. Immunodominant melanoma-associated antigen epitopes are being evaluated for their ability to immunize patients with advanced melanoma. However, these vaccination efforts are limited by the extensive polymorphism of the HLA class I heavy chain, which occurs in functional domains of the molecule. Patients with melanoma with the HLA-A-24 phenotype were recruited for vaccination with the peptide AFLPWHRLF from the melanoma-associated antigen tyrosinase. This peptide is recognized in association with HLA-A*2402. The HLA-A24 family includes at least 15 alleles whose frequency and ability to present the same peptide are unknown. The distribution of HLA-A24 alleles was studied in a melanoma population for the practical purpose of identifying patients suitable for vaccination with HLA-A*2402 epitopes. An HLA-A locus-specific polymerase chain reaction method followed by sequencing was developed to determine the HLA-A alleles in genomic DNA. HLA-A 24 was also typed in healthy persons of various ethnic backgrounds to further explore the HLA-A24 family. In white persons, the HLA-A*2402 allele was most common (in 85% of white persons and in 97% of the patients with melanoma). Fewer persons carried the HLA-A*2403 allele (13% in all samples, 3% in melanoma patients). Finally, two new alleles, HLA-A*2422 and HLA-A*24 null, were identified. These results suggest that vaccination with HLA-A*2402-associated epitopes has the potential for broad use in this patient population. C1 NCI, Surg Branch,HLA Lab, Dept Transfus Med,Clin Ctr, NIH, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), NCI, Surg Branch,HLA Lab, Dept Transfus Med,Clin Ctr, NIH, Bldg 10,Room 2B56, Bethesda, MD 20892 USA. NR 27 TC 7 Z9 7 U1 0 U2 1 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-APR PY 2000 VL 23 IS 2 BP 282 EP 287 DI 10.1097/00002371-200003000-00013 PG 6 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 295EK UT WOS:000085953600013 PM 10746555 ER PT J AU Domachowske, JB Bonville, CA Mortelliti, AJ Colella, CB Kim, U Rosenberg, HF AF Domachowske, JB Bonville, CA Mortelliti, AJ Colella, CB Kim, U Rosenberg, HF TI Respiratory syncytial virus infection induces expression of the anti-apoptosis gene IEX-1L in human respiratory epithelial cells SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Annual Meeting of the Pediatric-Academic-Societies CY MAY 01-04, 1999 CL SAN FRANCISCO, CALIFORNIA SP Pediat Acad Soc ID TUMOR-NECROSIS-FACTOR; DIFFERENTIAL DISPLAY; RECEPTOR; INTERLEUKIN-8 AB By means of differential display reverse-transcriptase polymerase chain reaction, increased expression of the mRNA encoding the anti-apoptosis gene IEX-IL was found in respiratory epithelial cells infected with respiratory syncytial virus (RSV). IEX-IL mRNA expression increased 5-7-fold in RSV-infected cells at 72 h after infection but remained unchanged in cells exposed to irradiated, replication-incompetent RSV, Because IEX-IL is reported to protect cells from apoptosis induced by tumor necrosis factor (TNF)-alpha, the effect of TNF-alpha on epithelial cell apoptosis in the context of RSV infection was determined. Epithelial cells were exposed to vehicle, RSV, or irradiated RSV for 72 h, and then TNF-alpha was added to appropriate cultures, Cytochemical staining of cellular DNA with 4,6-diamidino-2-phenylindole demonstrated TNF-alpha-induced apoptosis in 23.4% of control cells but only 5% of RSV-infected cells. These data show that RSV infection protects epithelial cells from TNF-alpha-induced apoptosis and that this effect is temporally associated with IEX-IL gene expression. C1 Upstate Med Univ, Dept Pediat, Div Infect Dis, Syracuse, NY 13210 USA. Upstate Med Univ, Dept Commun Sci, Syracuse, NY 13210 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Domachowske, JB (reprint author), Upstate Med Univ, Dept Pediat, Div Infect Dis, 750 E Adams St, Syracuse, NY 13210 USA. NR 26 TC 38 Z9 40 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 2000 VL 181 IS 3 BP 824 EP 830 DI 10.1086/315319 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 302BE UT WOS:000086344400002 PM 10720500 ER PT J AU Birx, DL Loomis-Price, LD Aronson, N Brundage, J Davis, C Deyton, L Garner, R Gordin, F Henry, D Holloway, W Kerkering, T Luskin-Hawk, R McNeil, J Michael, N Pierce, PF Poretz, D Ratto-Kim, S Renzullo, P Ruiz, N Sitz, K Smith, G Tacket, C Thompson, M Tramont, E Yangco, B Yarrish, R Redfield, RR AF Birx, DL Loomis-Price, LD Aronson, N Brundage, J Davis, C Deyton, L Garner, R Gordin, F Henry, D Holloway, W Kerkering, T Luskin-Hawk, R McNeil, J Michael, N Pierce, PF Poretz, D Ratto-Kim, S Renzullo, P Ruiz, N Sitz, K Smith, G Tacket, C Thompson, M Tramont, E Yangco, B Yarrish, R Redfield, RR CA rgp160 Phase II Vaccine Investigat TI Efficacy testing of recombinant human immunodeficiency virus (HIV) gp160 as a therapeutic vaccine in early-stage HIV-1-infected volunteers SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNE-RESPONSES; SEROPOSITIVE INDIVIDUALS; INFLUENZA VACCINATION; HUMORAL RESPONSES; DOUBLE-BLIND; INFECTION; IMMUNIZATION; AIDS; IMMUNOGENICITY; ENVELOPE AB A phase II efficacy trial was conducted with recombinant human immunodeficiency virus (HIV) type 1 envelope glycoprotein gp160 (rgp160) in 608 HIV-infected, asymptomatic volunteers with CD4(+) cell counts >400 cells/mm(3). During a 5-year study, volunteers received a 6-shot primary series of immunizations with either rgp160 or placebo over 6 months, followed by booster immunizations every 2 months. Repeated vaccination with rgp160 was safe and persistently immunogenic. Adequate follow-up and acquisition of endpoints allowed for definitive interpretation of the trial results, There was no evidence that rgp160 has efficacy as a therapeutic vaccine in early-stage HIV infection, as measured at primary endpoints (50% decline in CD4(+) cell count or disease progression to Waiter Reed stage 4, 5, or 6) or secondary endpoints. A transient improvement was seen in the secondary CD4 endpoint for the vaccination compared with the placebo arm, but this did not translate into improved clinical outcome. C1 Walter Reed Army Inst Res, Div Retrovirol, Rockville, MD 20850 USA. Henry M Jackson Fdn, Rockville, MD USA. NIAID, Bethesda, MD 20892 USA. Natl Naval Med Ctr, Bethesda, MD USA. Univ Maryland, Ctr Vaccine Dev, Baltimore, MD 21201 USA. Univ Maryland, Ctr Med Biotechnol, Baltimore, MD 21201 USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. VA Med Ctr, Washington Reg AIDS Program, Washington, DC USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Wilford Hall USAF Med Ctr, San Antonio, TX 78236 USA. Brooke Army Med Ctr, San Antonio, TX USA. William Beaumont Army Med Ctr, El Paso, TX 79920 USA. Darnall Army Community Hosp, Ft Hood, TX USA. Grad Hosp Philadelphia, Philadelphia, PA 19146 USA. Delaware CPCRA, Wilmington, DE USA. Richmond AIDS Consortium, Richmond, VA USA. Infect Dis Phys Inc, Annandale, VA USA. AIDS Res Alliance, Chicago, IL USA. Prot Sci Inc, Meriden, CT USA. AIDS Res Consortium, Atlanta, GA USA. Infect Dis Res Inst Inc, Tampa, FL USA. St Vincents Hosp & Med Ctr, New York, NY 10011 USA. RP Birx, DL (reprint author), Walter Reed Army Inst Res, Div Retrovirol, 13 Taft Ct,Suite 200, Rockville, MD 20850 USA. NR 51 TC 47 Z9 47 U1 1 U2 3 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 2000 VL 181 IS 3 BP 881 EP 889 DI 10.1086/315308 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 302BE UT WOS:000086344400010 PM 10720508 ER PT J AU Borkowsky, W Wara, D Fenton, T McNamara, J Kang, MH Mofenson, L McFarland, E Cunningham, C Duliege, AM Francis, D Bryson, Y Burchett, S Spector, SA Frenkel, LM Starr, S Van Dyke, R Jimenez, E AF Borkowsky, W Wara, D Fenton, T McNamara, J Kang, MH Mofenson, L McFarland, E Cunningham, C Duliege, AM Francis, D Bryson, Y Burchett, S Spector, SA Frenkel, LM Starr, S Van Dyke, R Jimenez, E CA AIDS Clin Trial Grp TI Lymphoproliferative responses to recombinant HIV-1 envelope antigens in neonates and infants receiving gp120 vaccines SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 5th Conference on Retroviruses and Opportunistic Infections CY FEB 01-05, 1998 CL CHICAGO, IL ID HUMAN-IMMUNODEFICIENCY-VIRUS; CELL-MEDIATED-IMMUNITY; COMPARATIVE SELECTIVITY; CORYNEBACTERIUM-PARVUM; BORDETELLA-PERTUSSIS; COMPLETE ADJUVANTS; MURAMYL DIPEPTIDE; INFECTED INFANTS; CHILDREN; VACCINATION AB Children of mothers infected with human immunodeficiency virus type 1 (HIV-1) were immunized at birth and at 1, 3, and 5 months with 1 of 3 doses of recombinant gp 120 vaccines prepared from SF-2 or MN strains of HIV-1. A total of 126 children were not infected; 21 received adjuvant only. Vaccine recipients developed lymphoproliferative responses on greater than or equal to 2 occasions, responding more often to homologous HIV-1 antigens than did adjuvant recipients (56% vs. 14%; P < .001). Responses were appreciated after 2 immunizations and were maintained for >84 weeks after the last immunization, hn accelerated immunization schedule(birth, 2 weeks, 2 months, and 5 months) with the lowest dose of the SF-2 vaccine produced responses in all 11 vaccinees by 4 weeks. Responses to heterologous envelope antigens were also detected. Immune responses to vaccination are achievable at an age when some infection (perinatal or breast milk exposure related) may be prevented. C1 NYU, Saul Krugman Div Infect Dis & Immun, Sch Med, Dept Pediat, New York, NY 10016 USA. SUNY, Dept Pediat, Syracuse, NY USA. Univ Calif San Francisco, Sch Med, Dept Pediat, San Francisco, CA 94143 USA. Chiron Corp, San Francisco, CA USA. VaxGen Corp, San Francisco, CA USA. Univ Calif San Diego, Sch Med, Dept Pediat, San Diego, CA 92103 USA. Univ Calif Los Angeles, Sch Med, Dept Pediat, Los Angeles, CA 90024 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. NIAID, NIH, Bethesda, MD 20892 USA. NICHHD, NIH, Bethesda, MD 20892 USA. Univ Colorado, Hlth Sci Ctr, Dept Pediat, Denver, CO 80262 USA. Childrens Hosp & Med Ctr, Seattle, WA 98105 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Tulane Univ, Sch Med, Dept Pediat, New Orleans, LA 70112 USA. San Juan City Hosp, Dept Pediat, San Juan, PR USA. RP Borkowsky, W (reprint author), NYU, Saul Krugman Div Infect Dis & Immun, Sch Med, Dept Pediat, 550 1St Ave, New York, NY 10016 USA. EM borkow01@mcgc16.med.nyu.edu OI Mofenson, Lynne/0000-0002-2818-9808 NR 17 TC 38 Z9 40 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR PY 2000 VL 181 IS 3 BP 890 EP 896 DI 10.1086/315298 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 302BE UT WOS:000086344400011 PM 10720509 ER PT J AU Goldstein, H Pettoello-Mantovani, M Bera, TK Pastan, IH Berger, EA AF Goldstein, H Pettoello-Mantovani, M Bera, TK Pastan, IH Berger, EA TI Chimeric toxins targeted to the human immunodeficiency virus type 1 envelope glycoprotein augment the in vivo activity of combination antiretroviral therapy in thy/liv-SCID-Hu mice SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Keystone Symposium on AIDS Pathogenesis CY JAN, 1999 CL KEYSTONE, COLORADO ID HIV-1 INFECTION; CD4-PSEUDOMONAS EXOTOXIN; PROLONGED SUPPRESSION; LYMPHOID-TISSUES; PLASMA VIREMIA; LOAD; IMMUNOTOXIN; REPLICATION; RESERVOIR; CELLS AB Highly active antiretroviral therapy (HAART), which combines multiple inhibitors of essential human immunodeficiency virus type 1 (HIV-1) enzymes, induces dramatic and sustained viral load reductions in many people infected with HIV-1, However, reservoirs of infected cells capable of producing replication-competent virus persist even after years of HAART, preventing elimination of infection. CD4-PE40 and 3B3(Fv)-PE38, chimeric toxins designed to target the HIV envelope (Env), represent a complementary class of agents that selectively kill productively infected cells. To investigate whether these Env-targeted toxins might serve as adjuncts to HAART for the elimination of infected cells, we tested their ability to augment HAART efficacy in vivo by using a thy/liv SCID-hu mouse model. CD4-PE40 and 3B3(Fv)-PE38 markedly enhanced the capacity of HAART to suppress acute HIV-1 infection and improved HAART-mediated viral load reduction in mice with established HIV-1 infection. These results represent the first demonstration of in vivo anti-HIV-1 efficacy for Env-targeted toxins and support their potential therapeutic utility in combination with HAART. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Goldstein, H (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Pediat, Chanin Bldg,Rm 601,1300 Morris Pk Ave, Bronx, NY 10461 USA. FU NCI NIH HHS [CA09173]; NINDS NIH HHS [NS39201]; PHS HHS [A1-27741] NR 32 TC 30 Z9 31 U1 0 U2 1 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 2000 VL 181 IS 3 BP 921 EP 926 DI 10.1086/315351 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 302BE UT WOS:000086344400015 PM 10720513 ER PT J AU Weissman, D Dybul, M Daucher, MB Davey, RT Walker, RE Kovacs, JA AF Weissman, D Dybul, M Daucher, MB Davey, RT Walker, RE Kovacs, JA TI Interleukin-2 up-regulates expression of the human immunodeficiency virus fusion coreceptor CCR5 by CD4(+) lymphocytes in vivo SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN T-LYMPHOCYTES; HIV REPLICATION; INFECTION; ENHANCEMENT; RESISTANCE; MECHANISMS; RESERVOIR; RECEPTOR; IL-15 AB Intermittent interleukin-2 (IL-2) therapy can substantially increase CD4(+) T cell counts of human immunodeficiency virus (HIV)-infected subjects. Administration of IL-2 led to transient up-regulation of CCR5 on CD4(+) T cells; up to 87% of CD4(+) cells expressed CCR5 after a 5-day cycle, with return to baseline levels within 2 weeks. Unlike in vitro studies, CCR5 was coexpressed with CD45RA and CXCR4 on CD4(+) T cells after IL-2 therapy. The observed increase in coreceptor expression was nor associated with detectable increases in viral replication. IL-2 therapy induced CCR5 expression in >90% of circulating memory CD4(+) T cells, determined to be a long-term reservoir of HIV, suggesting significant activation of these cells. These studies demonstrate that levels of expression of HIV coreceptors alone do not always correlate with HIV replication in vivo and that IL-2 therapy activates a majority of memory T cells in the circulation and likely throughout the immune system. C1 Univ Penn, Div Infect Dis, Philadelphia, PA 19104 USA. NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. Natl Inst Hlth, Ctr Clin, Dept Crit Care Med, Bethesda, MD USA. RP Weissman, D (reprint author), Univ Penn, Div Infect Dis, 536 Johnson Pavilion, Philadelphia, PA 19104 USA. NR 22 TC 37 Z9 37 U1 0 U2 1 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 2000 VL 181 IS 3 BP 933 EP 938 DI 10.1086/315303 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 302BE UT WOS:000086344400017 PM 10720515 ER PT J AU Inagaki, Y Myouga, F Kawabata, H Yamai, S Watanabe, H AF Inagaki, Y Myouga, F Kawabata, H Yamai, S Watanabe, H TI Genomic differences in Streptococcus pyogenes serotype M3 between recent isolates associated with toxic shock-like syndrome and past clinical isolates SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID GROUP-A STREPTOCOCCI; INVASIVE GROUP; SALMONELLA-TYPHIMURIUM; CHANGING EPIDEMIOLOGY; CHROMOSOMAL FRAGMENT; RHEUMATIC-FEVER; INFECTIONS; DNA; GENE; IDENTIFICATION AB Genomic differences among past Streptococcus pyogenes serotype M3 strains isolated in 1973 and before from patients with streptococcal pharyngitis, recent (1990s) serotype M3 clinical isolates from patients with pharyngitis, and recent M3 isolates from patients with toxic shock-like syndrome were investigated by restriction landmark genomic scanning and by modified random-amplified polymorphic DNA-polymerase chain reaction. Similar polymorphic DNA fragments were identified between the older M3 isolates and the recent isolates; also, the recent M3 clinical isolates from patients with pharyngitis were genetically indistinguishable, by the methods used, from the M3 isolates of patients with toxic shock-like syndrome. Although nucleotide sequences of these regions showed no apparent homology with known virulence factors, the DNA fragments could distinguish the recent M3 strains from the past strains. These results suggested that the recent strains have emerged because of genetic divergence. C1 NIAID, Dept Bacteriol, Shinjuku Ku, Tokyo 1628640, Japan. Natl Inst Basic Biol, Div Gene Express & Regulat 1, Okazaki, Aichi 444, Japan. Sci Univ Tokyo, Dept Biol Sci & Technol, Chiba, Japan. Kanagawa Prefectural Publ Hlth Lab, Dept Bacteriol & Pathol, Yokohama, Kanagawa, Japan. RP Watanabe, H (reprint author), NIAID, Dept Bacteriol, Shinjuku Ku, Tokyo 1628640, Japan. RI INAGAKI, Yoshishige/B-1458-2011 NR 39 TC 14 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 2000 VL 181 IS 3 BP 975 EP 983 DI 10.1086/315299 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 302BE UT WOS:000086344400022 PM 10720520 ER PT J AU Taranger, J Trollfors, B Lagergard, T Sundh, V Bryla, DA Schneerson, R Robbins, JB AF Taranger, J Trollfors, B Lagergard, T Sundh, V Bryla, DA Schneerson, R Robbins, JB TI Correlation between pertussis toxin IgG antibodies in postvaccination sera and subsequent protection against pertussis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID INFLUENZAE TYPE-B; BORDETELLA-PERTUSSIS; HOUSEHOLD EXPOSURE; WHOOPING-COUGH; TOXOID VACCINE; CAPSULAR POLYSACCHARIDE; EFFICACY; INFANTS; IMMUNIZATION; DIPHTHERIA AB All acellular pertussis vaccines contain pertussis toroid and induce protection against pertussis. This study investigated the relation between the postvaccination levels of pertussis toxin (PT) serum IgG and protection against pertussis. PT IgG was determined in sera obtained 21-77 days after the third vaccination from 813 children who received 3 doses of pertussis toroid. The children were followed for 21-33 months after vaccination for the occurrence of pertussis. Of the children, 126 were exposed to pertussis in their households. The median PT IgG concentration was 79 U/mL in those who developed severe pertussis (greater than or equal to 21 day of paroxysmal cough), 156 U/mL with mild pertussis (<21 days of paroxysmal cough), and 246 U/mL in those who did not develop pertussis (79 us. 246, P < .0001). Corresponding values in the 687 children with no household exposure were 99, 124, and 155 U/mL, respectively (99 vs. 155, P < .0001). Thus, there is a highly significant correlation between the level of vaccine-induced serum PT IgG and protection against pertussis. C1 Goteborg Primary Hlth Care Syst, Goteborg Pertussis Vaccine Study, Gothenburg, Sweden. Univ Gothenburg, Dept Med Microbiol & Immunol, Gothenburg, Sweden. NICHHD, NIH, Bethesda, MD 20892 USA. RP Taranger, J (reprint author), Goteborg Pertussis Vaccine Trial, St Paulig 6, S-41660 Gothenburg, Sweden. NR 31 TC 81 Z9 83 U1 0 U2 1 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 2000 VL 181 IS 3 BP 1010 EP 1013 DI 10.1086/315318 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 302BE UT WOS:000086344400026 PM 10720524 ER PT J AU Argaw, T Cohen, JI Klutch, M Lekstrom, K Yoshikawa, T Asano, Y Krause, PR AF Argaw, T Cohen, JI Klutch, M Lekstrom, K Yoshikawa, T Asano, Y Krause, PR TI Nucleotide sequences that distinguish Oka vaccine from parental Oka and other varicella-zoster virus isolates SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID POLYMERASE-CHAIN-REACTION; FRAGMENT-LENGTH-POLYMORPHISM; TRANSMISSION; STRAIN; IDENTIFICATION; CHILDREN; LEUKEMIA; VZV AB The sequences of similar to 34 Icb from the 3' end of the varicella-zoster virus (VZV) Oka vaccine strain and the previously sequenced Dumas strain were compared. Sequence differences were noted in the coding sequences of several VZV open reading frames (ORFs), including ORFs 48, 51, 52, 55, 56, 58, 59, 60, 62, 64, and 68, Tests based on differences in the ORF62 gene and in the ORF64 poly-A region successfully distinguished the Oka vaccine strain from its wild-type parent and from other Japanese and US clinical isolates. These changes remained stable after passage of the virus in humans. C1 US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Div Viral Prod, Bethesda, MD USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. Fujita Hlth Univ, Dept Pediat, Aichi, Japan. RP Krause, PR (reprint author), 29A-1C16,29 Lincoln Dr, Bethesda, MD 20892 USA. RI Asano, Yoshizo/F-6870-2012 NR 18 TC 47 Z9 66 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 2000 VL 181 IS 3 BP 1153 EP 1157 DI 10.1086/315335 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 302BE UT WOS:000086344400047 PM 10720545 ER PT J AU Habib, KE Rice, KC Chrousos, GP Gold, PW AF Habib, KE Rice, KC Chrousos, GP Gold, PW TI CRH-1 receptor antagonism exerts antidepressant- and anxiolytic-like effects in attenuating stress ulcerogenesis SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 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 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2000 VL 48 IS 2 MA 49 BP 190A EP 190A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 302CE UT WOS:000086346700061 ER PT J AU Turner, PL Masilamani, S Reyes, I Knepper, MA AF Turner, PL Masilamani, S Reyes, I Knepper, MA TI Inhibition of nitric oxide (NO) synthesis is associated with a selective increase in the renal abundance of the thiazide-sensitive NaCl cotransporter (TSC). SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 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 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2000 VL 48 IS 2 MA 131 BP 203A EP 203A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 302CE UT WOS:000086346700143 ER PT J AU Shah, FS Curr, K Hamburgh, M Parniak, M Mitsuya, H Prasad, VR AF Shah, FS Curr, K Hamburgh, M Parniak, M Mitsuya, H Prasad, VR TI Differential influence of nucleoside analog resistance mutations K65R and L74V on the overall mutation rate and error specificity of HIV-1 reverse transcriptase. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Montefiore, Childrens Hosp, Div Pediat Infect Dis, Bronx, NY USA. Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. McGill Univ, Montreal, PQ, Canada. NCI, Bethesda, MD 20892 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 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2000 VL 48 IS 2 MA 214 BP 221A EP 221A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 302CE UT WOS:000086346700227 ER PT J AU Blum, A Cannon, RO Costello, R Schenke, WH Csako, G AF Blum, A Cannon, RO Costello, R Schenke, WH Csako, G TI Endocrine and lipid effects of oral L-arginine treatment in healthy postmenopausal women SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID HORMONE-RELEASING HORMONE; NITRIC-OXIDE; ENDOTHELIAL-CELLS; DEFICIENT ADULTS; HEART-DISEASE; IN-VIVO; LIPOPROTEIN(A); INSULIN; VASODILATION; ESTROGEN AB As a substrate for nitric oxide synthesis, L-arginine may give the same protection as estrogen, but its other biologic effects may adversely affect atherogenesis. Therefore, possible endocrine and lipid effects of L-arginine were investigated in a double-blind, placebo-controlled, single crossover study. After randomization, oral L-arginine (9 g) or placebo was given daily for 1 month, with crossover to the alternate therapy after a 1-month washout period, to 10 postmenopausal women receiving no estrogen. Compared with placebo, L-arginine increased growth hormone (1.5 +/- 1.8 mg/L vs 0.6 +/- 0.6 mg/L, P = .04) but had no effect on insulin and catecholamines. Total cholesterol, triglyceride, apolipoprotein E, and low-, very-low-, and high-density lipoprotein cholesterol levels were also unaffected. Lipoprotein(a) measured by an immunoturbidimetric method was increased by L-arginine in 9 of 10 women relative to placebo (0.46 +/- 0.35 g/L vs 0.38 +/- 0.30 g/L, P = .053), and the changes in lipoprotein(a) levels significantly correlated with the relative increase in growth hormone (r = 0.85, P = .03). However, lipoprotein(a) measured by an enzyme-linked immunosorbent assay failed to demonstrate significant changes. Lack of an increase by L-arginine in lipoprotein(a) with a verifiable apolipoprotein(a) isoform-independent method, despite an increase in growth hormone, questions the validity of previous observations for growth hormone-induced increases in lipoprotein(a). The observed lack of effect on major endocrine hormones and lipid profile support the safety of oral L-arginine administration. C1 NIH, Dept Clin Pathol, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NHLBI, Cardiol Branch, Bethesda, MD 20892 USA. RP Csako, G (reprint author), NIH, Dept Clin Pathol, Ctr Clin, Bldg 10,Room 2C-407, Bethesda, MD 20892 USA. NR 38 TC 13 Z9 13 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD MAR PY 2000 VL 135 IS 3 BP 231 EP 237 DI 10.1067/mlc.2000.104909 PG 7 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA 290LD UT WOS:000085677000003 PM 10711861 ER PT J AU Sharp, RR Foster, M AF Sharp, RR Foster, M TI Involving study populations in the review of genetic research SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Article ID PARTICIPATORY RESEARCH; DISEASE PREVENTION; GENOME PROJECT; COMMUNITY; BIOETHICS; ETHICS; MODEL; RISKS; LEGAL AB Genetic research can present risks to all members of a study population, not just those who choose to participate in research. The authors suggest that community-based reviews of research Protocols can help identify and minimize stich research-related risks. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Univ Oklahoma, Norman, OK 73019 USA. RP Sharp, RR (reprint author), NIEHS, Res Triangle Pk, NC 27709 USA. FU NHGRI NIH HHS [HG010302] NR 48 TC 71 Z9 71 U1 0 U2 1 PU AMER SOC LAW MEDICINE ETHICS PI BOSTON PA 765 COMMONWEALTH AVE, 16TH FL, BOSTON, MA 02215 USA SN 0277-8459 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD SPR PY 2000 VL 28 IS 1 BP 41 EP + DI 10.1111/j.1748-720X.2000.tb00315.x PG 12 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA 384NJ UT WOS:000165951500005 PM 11067631 ER PT J AU Badolato, R Wang, JM Stornello, SL Ponzi, AN Duse, M Musso, T AF Badolato, R Wang, JM Stornello, SL Ponzi, AN Duse, M Musso, T TI Serum amyloid A is an activator of PMN antimicrobial functions: induction of degranulation, phagocytosis, and enhancement of anti-Candida activity SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE acute phase reactants; yeast; respiratory burst; flow cytometry ID HIGH-DENSITY LIPOPROTEINS; HUMAN-NEUTROPHILS; POLYMORPHONUCLEAR LEUKOCYTES; A SAA; RECEPTOR; PROTEIN; CELLS; EXPRESSION; CD11B/CD18; ADHESION AB Serum amyloid A (SAA) is a 12-kDa protein secreted in large amounts by liver cells during microbial infections or inflammatory diseases, We have recently reported that SAA induces chemotaxis of polymorphonuclear cells (PMN), monocytes, and T lymphocytes and stimulates their adhesion to endothelial monolayers. In this study, we investigated whether SAA regulates PMN antimicrobial activities. We found that recombinant SAA (rSAA), at concentrations comparable to serum levels attained during an acute phase response, is a potent activator of PMN. Stimulation of PMN by rSAA results in a rapid and transient increase of cytosolic calcium concentration and up-regulation of cell-surface expression of antigens involved in adhesion and microbial recognition such as CD11c and CD16. In addition, stimulation of PMN with rSAA increases secretion of lactoferrin, an antimicrobial protein that is contained in specific granules of PMN and enhances PMN phagocytic activity against heat-killed Candida albicans. Finally, activation of PMN with rSAA enhances their anti-Candida activity within 30 min of stimulation. These results suggest that SAA is involved in up-regulating PMN antimicrobial activities and that high circulating concentrations of SAA as seen in the acute phase response may constitute a potential host defense mechanism against fungal infections. C1 Univ Brescia, Pediat Clin, I-25121 Brescia, Italy. NCI, Mol Immunoregulat Lab, Div Basic Sci, FCRDC, Frederick, MD USA. Univ Turin, Dipartimento Sanita Pubbl & Microbiol, I-10124 Turin, Italy. RP Badolato, R (reprint author), Univ Brescia, Spedali Civili, Pediat Clin, I-25123 Brescia, Italy. RI Badolato, Raffaele/A-8081-2010 OI Badolato, Raffaele/0000-0001-7375-5410 NR 39 TC 64 Z9 64 U1 1 U2 6 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 2000 VL 67 IS 3 BP 381 EP 386 PG 6 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 330LY UT WOS:000087964600013 PM 10733099 ER PT J AU Tsunetsugu-Yokota, Y Kato, T Yasuda, S Matsuda, Z Suzuki, Y Koyanagi, Y Yamamoto, N Akagawa, K Cho, MW Takemori, T AF Tsunetsugu-Yokota, Y Kato, T Yasuda, S Matsuda, Z Suzuki, Y Koyanagi, Y Yamamoto, N Akagawa, K Cho, MW Takemori, T TI Transcriptional regulation of HIV-1 LTR during antigen-dependent activation of primary T cells by dendritic cells SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE antigen presentation; CD45RA(+) T; Sp1; NF-kappa B ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG TERMINAL REPEAT; NF-KAPPA-B; CREB-BINDING-PROTEIN; COSTIMULATORY SIGNALS; GENE-EXPRESSION; VIRAL GROWTH; TYPE-1; REPLICATION; INFECTION AB Numerous factors are known to bind human immunodeficiency virus (HIV) long terminal repeat (LTR) and activate viral transcription, but little is known as to how they function in naturally activated T cells and to what extent their binding is relevant to HIV replication in rico. To characterize the HIV LTR-binding factors responsible for antigen-dependent activation of HIV, we examined replication of LTR mutant viruses in CD4(+) T cells activated by different stimuli, NF-kappa B or Sp1 mutant virus replicated well in CD4(+) T cells activated by phorbol ester and calcium ionophore. When they were activated by antigen-pulsed dendritic cells, the replication of the Sp1-deleted virus was severely impaired in CD45RA(+), but not in CD45RO(+) T cell subsets that dominantly produce interleukin-2 (IL-2). Stimulation via CD3/CD28 induced a high level of IL-2 production in both T cell subsets, but Sp1-deleted virus poorly replicated in CD45RA(+) subset. The level of NF-kappa B and Sp1-binding factors did not differ between these subsets. Our results suggest that additional cofactors distinct from IL-2-inducing signaling molecules are important for LTR activation during antigen-dependent T cell activation. C1 Natl Inst Infect Dis, Dept Immunol, Tokyo, Japan. Natl Inst Infect Dis, AIDS Res Ctr, Tokyo, Japan. Tokyo Med Dent Sch, Dept Microbiol, Tokyo, Japan. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Tsunetsugu-Yokota, Y (reprint author), 1-23-1 Toyama Cho,Shinjuku Ku, Tokyo 1628640, Japan. RI Takemori, Toshitada/A-5909-2016 NR 34 TC 8 Z9 8 U1 0 U2 0 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 2000 VL 67 IS 3 BP 432 EP 440 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 330LY UT WOS:000087964600019 PM 10733105 ER PT J AU Ward, KM Aletras, AH Balaban, RS AF Ward, KM Aletras, AH Balaban, RS TI A new class of contrast agents for MRI based on proton chemical exchange dependent saturation transfer (CEST) SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE barbiturate; sugars; polymers; spin-lattice relaxation rate; amino acids; heterocyclic chemistry; indole ID MAGNETIZATION-TRANSFER; INVIVO; RATES; BRAIN; WATER AB It has been previously shown that intrinsic metabolites can be imaged based on their water proton exchange rates using saturation transfer techniques. The goal of this study was to identify an appropriate chemical exchange site that could be developed for use as an exogenous chemical exchange dependent saturation transfer (CEST) contrast agent under physiological conditions, These agents would function by reducing the water proton signal through a chemical exchange site on the agent via saturation transfer. The ideal chemical exchange site would have a large chemical shift from water, This permits a high exchange rate without approaching the fast exchange limit at physiological pH (6.5-7.6) and temperature (37 degrees C), as well as minimizing problems associated with magnetic field susceptibility. Numerous candidate chemicals (amino acids, sugars, nucleotides, heterocyclic ring chemicals) were evaluated in this preliminary study. Of these, barbituric acid and 5,6-dihydrouracil were more fully characterized with regard to pH, temperature, and concentration CEST effects. The best chemical exchange site found was the 5.33-ppm indole ring -NH site of 5-hydroxytryptophan, These data demonstrate that a CEST-based exogenous contrast agent for MRI is feasible. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Balaban, RS (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bldg 10,Room B1D-416, Bethesda, MD 20892 USA. RI Balaban, Robert/A-7459-2009; OI Balaban, Robert/0000-0003-4086-0948; Aletras, Anthony/0000-0002-3786-3817 NR 15 TC 531 Z9 540 U1 14 U2 107 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 2000 VL 143 IS 1 BP 79 EP 87 DI 10.1006/jmre.1999.1956 PG 9 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 294MG UT WOS:000085914600009 PM 10698648 ER PT J AU Kontaxis, G Clore, GM Bax, A AF Kontaxis, G Clore, GM Bax, A TI Evaluation of cross-correlation effects and measurement of one-bond couplings in proteins with short transverse relaxation times SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article ID CHEMICAL-SHIFT ANISOTROPY; LIQUID-CRYSTALLINE MEDIUM; DIPOLAR COUPLINGS; NMR-SPECTROSCOPY; SEQUENTIAL ASSIGNMENT; QUANTITATIVE MEASUREMENT; MULTIDIMENSIONAL NMR; LARGER PROTEINS; HUMAN UBIQUITIN; MACROMOLECULES AB Various strategies are described and compared for measurement of one-bond J(NH) and J(NC), splittings in larger proteins. In order to evaluate the inherent resolution obtainable in the various experiments, relaxation rates of N-15-H-1(N) coupled and heteronuclear decoupled resonances were measured at 600- and 800-MHz held strengths for both perdeuterated and protonated proteins. A comparison of decay rates for the two N-15-{H-N} doublet components shows average ratios of 4.8 and 3.5 at 800- and 600-MHz H-1 frequency, respectively, in the perdeuterated proteins, For the protonated proteins these ratios are 3.2 (800 MHz) and 2.4 (600 MHz). Relative to the regular HSQC experiment, the enhancement in TROSY N-15 resolution is 2.6 (perdeuterated; 800 MHz), 2.0 (perdeuterated; 600 MHz), 2.1 (protonated; 800 MHz), and 1.7 (protonated; 600 MHz). For the H-1 dimension, the upheld H-1(N)-{N-15} component on average relaxes slower than the downfield H-1(N)-{N-15} component by a factor of 1.8 (perdeuterated; 800 MHz) and 1.6 (perdeuterated; 600 MHz). The poor resolution for the upheld N-15-{H-1} doublet component in slowly tumbling proteins makes it advantageous to derive the J(NH) Splitting from the difference in frequency between the narrow downfield N-15 doublet component and either the H-1-decoupled N-15 resonance or the peak position in an experiment which J-scales the frequency of the upheld doublet component but maintains some of the advantages of the TROSY experiment. C1 NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Kontaxis, G (reprint author), NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 59 TC 104 Z9 105 U1 0 U2 13 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 2000 VL 143 IS 1 BP 184 EP 196 DI 10.1006/jmre.1999.1979 PG 13 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 294MG UT WOS:000085914600020 PM 10698659 ER PT J AU Huang, LM Huang, SY Chen, MY Chao, MF Lu, CY Tien, HF Lee, CY Jeang, KT AF Huang, LM Huang, SY Chen, MY Chao, MF Lu, CY Tien, HF Lee, CY Jeang, KT TI Geographical differences in human herpesvirus 8 seroepidemiology: A survey of 1,201 individuals in Asia SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE HHV8; antibody; sexually transmitted disease ID SARCOMA-ASSOCIATED HERPESVIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; KAPOSIS-SARCOMA; DNA-SEQUENCES; HUMAN-HERPESVIRUS-8 INFECTION; AIDS; PREVALENCE; ANTIBODIES; TRANSMISSION; POPULATION AB Since the discovery of human herpesvirus 8 (HHV8) as a contributory cause of Kaposis sarcoma, the clinical role of this virus has been actively investigated. An understanding of HHV8 seroepidemiology is critical for the study of its pathogenesis within a specific environment. A sere-survey is described in Taiwan of 1,201 individuals ranging in age from under 1 year to over 70. Indirect immunofluorescence assay was used to determine antibody titers against both latent and lytic antigens of HHV8. The results indicate that very few individuals (3-4%) were exposed to HHV8 before 10 years of age. Infection rate peaked (19.2%) between the ages of 21 to 40. Females showed a slightly higher seroprevalence for HHV8 than males, but the difference was not statistically significant. Pregnancy did not correlate with increased HHV8 infection rate nor with augmented HHV8 antibody titers. It is concluded that HHV8 in Taiwan is predominantly an infectious agent for adults. In this geographical locale, HHV8 is similar to herpes simplex virus type 2 in its likely transmission occurring presumptively through sexual routes. However, the study also indicates that a smaller portion of HHV8-transmission could occur through nonsexual contacts. J. Med. Virol. 60: 290-293, 2000. (C) 2000 Wiley-Liss, Inc. C1 Natl Taiwan Univ Hosp, Dept Pediat, Taipei, Taiwan. Natl Taiwan Univ Hosp, Dept Internal Med, Taipei, Taiwan. NIAID, Mol Microbiol Lab, Sect Mol Virol, Bethesda, MD 20892 USA. RP Huang, LM (reprint author), Natl Taiwan Univ Hosp, Dept Pediat, 7 Chung Shan S Rd, Taipei, Taiwan. RI Jeang, Kuan-Teh/A-2424-2008; OI TIEN, HWEI-FANG/0000-0002-1384-5593; LEE, CHIN-YUN/0000-0002-3938-377X; Huang, Li-Min/0000-0002-9291-260X; LU, CHUN-YI/0000-0002-5240-2808 NR 34 TC 29 Z9 36 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 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD MAR PY 2000 VL 60 IS 3 BP 290 EP 293 DI 10.1002/(SICI)1096-9071(200003)60:3<290::AID-JMV7>3.0.CO;2-G PG 4 WC Virology SC Virology GA 278VJ UT WOS:000085009400007 PM 10630961 ER PT J AU Bezrukov, SM AF Bezrukov, SM TI Ion channels as molecular Coulter counters to probe metabolite transport SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Review ID NUCLEAR-PORE COMPLEX; MITOCHONDRIAL OUTER-MEMBRANE; RESISTIVE PULSE TECHNIQUE; LIPID BILAYER-MEMBRANES; WATER-SOLUBLE POLYMERS; ESCHERICHIA-COLI; CONDUCTANCE FLUCTUATIONS; SUGAR-TRANSPORT; PHOSPHOLIPID-MEMBRANES; ALAMETHICIN CHANNELS C1 NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. St Petersburg Nucl Phys Inst, Gatchina 188350, Russia. RP Bezrukov, SM (reprint author), NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. NR 108 TC 131 Z9 134 U1 2 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-2631 EI 1432-1424 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD MAR 1 PY 2000 VL 174 IS 1 BP 1 EP 13 DI 10.1007/s002320001026 PG 13 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA 290KR UT WOS:000085675900001 PM 10741427 ER PT J AU Lackner, H Bahner, I Shigematsu, N Pannell, LK Mauger, AB AF Lackner, H Bahner, I Shigematsu, N Pannell, LK Mauger, AB TI Structures of five components of the actinomycin Z complex from Streptomyces fradiae, two of which contain 4-chlorothreonine SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID STEREOCHEMISTRY; SYRINGOMYCIN; DNA AB Structure elucidation of five components of the actinomycin Z complex (Z(1)-Z(5)) isolated from Streptomyces fradiae is described. The components were separated by Si gel column chromatography and TLC/PLC and analyzed by ESIMS, FABMS, LC-MS of derivatized hydrolysates, and 2D NMR techniques. This permitted determination of the complete structures of actinomycins Z(1)-Z(5). In Z(3) and Z(5), site 1 of the beta-depsipeptide is occupied by the rare 4-chloro-L-threonine, an amino acid not previously found in an actinomycin. The structural variants of the actinomycin Z complex have the molecular architecture typical of other actinomycins but possess greater structural diversity resulting from the presence of several highly unusual amino acids. Actinomycins Z(3) and Z(5), but not Z(1), were more potent than actinomycin D in cytotoxicity assays against three tumor cell lines. C1 NCI, Dev Therapeut Program, NIH, Bethesda, MD 20892 USA. NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. Univ Gottingen, Inst Organ Chem, D-37077 Gottingen, Germany. RP Mauger, AB (reprint author), NCI, Dev Therapeut Program, NIH, Bethesda, MD 20892 USA. RI Shigematsu, Naoyuki/B-9374-2014 NR 28 TC 15 Z9 17 U1 2 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD MAR PY 2000 VL 63 IS 3 BP 352 EP 356 DI 10.1021/np990416u PG 5 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 296ZB UT WOS:000086055700013 PM 10757717 ER PT J AU Hasan, CM Khan, S Jabbar, A Rashid, MA AF Hasan, CM Khan, S Jabbar, A Rashid, MA TI Nasimaluns A and B: neo-clerodane diterpenoids from Barringtonia racemosa SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID ACUTANGULA AB An ethanolic extract of the roots of Barringtonia racemosa afforded two novel neo-clerodane-type diterpenoids, methyl-15,16-epoxy-12-oxo-3,13(16),14-neo-clerodatrien-18,19-olide-17-carboxylate (nasimalun A, 1) and dimethyl-15,16-epoxy-3,13(16),14-neo-clerodatrien-17,18-dicarboxylate (17-carboxymethylhardwickiic acid methyl eater, nasimalun B, 2) by NMR and MS analyses and by comparison of their spectral data with related compounds. The relative stereochemistry of the asymmetric centers in 1 and 2 was determined by selective 1D NOESY experiments. C1 Univ Dhaka, Fac Pharm, Phytochem Res Lab, Dhaka 1000, Bangladesh. RP Rashid, MA (reprint author), NCI, SAIC Frederick, Frederick Canc Res & Dev Ctr, Bldg 560,Rm 32-63B,Post Box B, Frederick, MD 21702 USA. NR 14 TC 9 Z9 15 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD MAR PY 2000 VL 63 IS 3 BP 410 EP 411 DI 10.1021/np990488l PG 2 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 296ZB UT WOS:000086055700030 PM 10757734 ER PT J AU Meragelman, KM McKee, TC Boyd, MR AF Meragelman, KM McKee, TC Boyd, MR TI Siamenol, a new carbazole alkaloid from Murraya siamensis SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID AUSTRALIAN SOFT CORALS; ASPERGILLUS-TUBINGENSIS; LOBOPHYTUM; COUMARINS; SCLEROTIA AB A new carbazole alkaloid, siamenol (1), and two known alkaloids, mahanimbine (2) and mahanimbilol (3), have been isolated from the organic extract of Murraya siamensis. The novel compound exhibited HIV-inhibitory activity. C1 NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program, Div Canc Treatment & Diag,FCRDC, Frederick, MD 21702 USA. RP Boyd, MR (reprint author), NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program, Div Canc Treatment & Diag,FCRDC, Frederick, MD 21702 USA. NR 17 TC 61 Z9 63 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD MAR PY 2000 VL 63 IS 3 BP 427 EP 428 DI 10.1021/np990570g PG 2 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 296ZB UT WOS:000086055700036 PM 10757740 ER PT J AU Herman, D Opler, L Felix, A Valencia, E Wyatt, RJ Susser, E AF Herman, D Opler, L Felix, A Valencia, E Wyatt, RJ Susser, E TI A critical time intervention with mentally ill homeless men - Impact on psychiatric symptoms SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID CHRONIC-SCHIZOPHRENIA; HYPOFRONTALITY; HALOPERIDOL; INPATIENTS; TRIAL AB We describe the impact of a psychosocial intervention, critical time intervention (CTI), on the cardinal symptom dimensions of schizophrenia, namely negative, positive, and general psychopathology. Ninety-six men with schizophrenia and other psychotic disorders who were discharged from a homeless shelter were randomly assigned to receive either CTI or usual services only. CTI is a time-limited intervention designed to enhance continuity of care during the transition from institution to community. Symptom severity at baseline and at 6 months was assessed using the Positive and Negative Syndrome Scale. Using data on 76 subjects for whom we have complete symptom data, we assessed the impact of CTI on change in symptoms. The results suggest that CTI was associated with a statistically significant decrease in negative symptoms at the 6-month follow-up, reflecting modest clinical improvement. There was no significant effect on positive or general psychopathology symptoms. C1 Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. Albert Einstein Coll Med, Bronx, NY 10461 USA. New York State Off Mental Hlth, Albany, NY USA. Columbia Univ, Coll Phys & Surg, Columbia Presbyterian Med Ctr, New York, NY 10027 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10027 USA. Columbia Univ, Joseph L Mailman Sch Publ Hlth, New York, NY 10027 USA. Columbia Univ Coll Phys & Surg, NIMH, Neuropsychiat Branch, New York, NY 10032 USA. RP Herman, D (reprint author), Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, 100 Haven Ave,31F, New York, NY 10032 USA. FU NIMH NIH HHS [MH-01204, MH-48041] NR 16 TC 38 Z9 40 U1 0 U2 3 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 2000 VL 188 IS 3 BP 135 EP 140 DI 10.1097/00005053-200003000-00002 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 294QV UT WOS:000085922600002 PM 10749277 ER PT J AU Bisaglia, M Natalini, B Pellicciari, R Straface, E Malorni, W Monti, D Franceschi, C Schettini, G AF Bisaglia, M Natalini, B Pellicciari, R Straface, E Malorni, W Monti, D Franceschi, C Schettini, G TI C-3-fullero-tris-methanodicarboxylic acid protects cerebellar granule cells from apoptosis SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE apoptosis; cerebellar granule cells; fullerene derivative; reactive oxygen species ID NMDA RECEPTOR ACTIVATION; NEURONAL APOPTOSIS; OXIDATIVE STRESS; SUPEROXIDE-DISMUTASE; LIPID-PEROXIDATION; DNA FRAGMENTATION; NERVOUS-SYSTEM; DEATH; MECHANISMS; DEPOLARIZATION AB Buckminsterfullerenols were recently investigated for their protective properties in different models of acute and chronic neurodegeneration. We tested C-3-fullero-tris-methanodicarboxylic acid in our in vitro model of apoptotic neuronal death, which consists of shifting the culture K+ concentration from 25 to 5 mM for rat cerebellar granule cells. The impairment of mitochondrial respiratory function as well as chromatin derangement and fragmentation of DNA in apoptotic oligonucleosomes that occur in these conditions were protected by this compound in a concentration-dependent way. To assess whether antioxidant activity could account for the rescue of cerebellar granule cells from apoptosis, we tested the fullerene derivative under FeSO4-induced oxidative stress and found significant protection. Thus, we visualized membrane and cytoplasmic peroxides and reactive oxygen species and found a significant reduction of the species after 24 h in 5 mM K+ with the fullerene derivative. Such evidence suggests that this compound exerts a protective role in cerebellar granule cell apoptosis, likely reducing the oxidative stress. C1 Univ Perugia, Inst Chem & Technol Drugs, I-06100 Perugia, Italy. Ist Super Sanita, Dept Ultrastruct, I-00161 Rome, Italy. Univ Bologna, Dept Expt Pathol, Sect Microbiol & Virol, I-40126 Bologna, Italy. Univ Genoa, Natl Canc Inst, Unit Pharmacol & Neurosci, Genoa, Italy. Univ Genoa, Adv Biotechnol Ctr, Genoa, Italy. Univ Genoa, Dept Oncol, Genoa, Italy. RP Schettini, G (reprint author), Adv Biotechnol Ctr, Unit Pharmacol & Neurosci, Largo R Benzi 10, I-16132 Genoa, Italy. RI Monti, Daniela/G-9556-2012; Malorni, Walter/G-5874-2016 OI Monti, Daniela/0000-0001-8651-8123; NR 49 TC 75 Z9 77 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 2000 VL 74 IS 3 BP 1197 EP 1204 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 284ME UT WOS:000085335500034 PM 10693952 ER PT J AU Zhang, MF Chan, CC Vistica, B Hung, VV Wiggert, B Gery, I AF Zhang, MF Chan, CC Vistica, B Hung, VV Wiggert, B Gery, I TI Copolymer 1 inhibits experimental autoimmune uveoretinitis SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE Copolymer 1 (Cop 1); experimental autoimmune uveoretinitis (EAU) autoimmune disease; immunomodulation ID MYELIN BASIC-PROTEIN; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS; ANTERIOR UVEITIS; LEWIS RATS; CELLS; COP-1; MICE; SUPPRESSION; BINDING AB Copolymer 1 (Cop 1) inhibits experimental allergic encephalomyelitis induced by a variety of myelin proteins, but has been found ineffective so far in inhibiting other experimental autoimmune diseases such as diabetes or arthritis. Here, we report for the first time that Cop 1 inhibits the development of experimental autoimmune uveoretinitis, induced in mice by interphotoreceptor retinoid-binding protein (IRBP). Pooled data of three experiments showed that treatment with Cop 1, at 0.5 mg/mouse, reduced the disease severity by 53% (p = 0.0002). Cop 1 treatment also inhibited the proliferation and the production of cytokines by lymph node cells in response to IRBP and moderately reduced the antibody response to this antigen. The possible mechanisms of EAU inhibition by Cop 1 are discussed. (C) 2000 Elsevier Science B.V. All rights reserved. C1 NEI, NIH, Bethesda, MD 20892 USA. RP Gery, I (reprint author), NEI, NIH, Bethesda, MD 20892 USA. NR 25 TC 29 Z9 29 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD MAR 1 PY 2000 VL 103 IS 2 BP 189 EP 194 DI 10.1016/S0165-5728(99)00239-8 PG 6 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 285JL UT WOS:000085385900010 PM 10696914 ER PT J AU Barkmeier, JM Bielamowicz, S Takeda, N Ludlow, CL AF Barkmeier, JM Bielamowicz, S Takeda, N Ludlow, CL TI Modulation of laryngeal responses to superior laryngeal nerve stimulation by volitional swallowing in awake humans SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID LONG-LATENCY RESPONSES; BRAIN-STEM; MOTOR CORTEX; NEURONS; CAT; STROKE; INPUTS; ORGANIZATION; COORDINATION; DYSPHAGIA AB Laryngeal sensorimotor closure reflexes are important for the protection of the airway and prevent the entry of foreign substances into the trachea and lungs. The purpose of this study was to determine how such reflexes might be modulated during volitional swallowing in awake humans, when persons are at risk of entry of food or liquids into the airway. The frequency and the amplitude of laryngeal adductor responses evoked by electrical stimulation of the internal branch of the superior laryngeal nerve (ISLN) were studied during different phases of volitional swallowing. Subjects swallowed water on command while electrical stimuli were presented to the ISLN at various intervals from 500 ms to 5 s following the command. Laryngeal adductor responses to unilateral ISLN stimulation were recorded bilaterally in the thyroarytenoid muscles using hooked wire electrodes. Early ipsilateral R1 responses occurred at 17 ms, and later bilateral R2 began around 65 ms. The muscle responses to stimuli occurring during expiration without swallowing were quantified as control trials. Responses to stimulation presented before swallowing, during the swallow, within 3 s after swallowing, and between 3 and 5 s after a swallow were measured. The frequency and amplitude of three responses (ipsilateral RI and bilateral R2) relative to the control responses were compared across the different phases relative to the occurrence of swallowing. Results demonstrated that a reduction occurred in both the frequency and amplitude of the later bilateral R2 laryngeal responses to electrical stimulation for up to 3 s after swallowing (P = 0.005). The amplitude and frequency of ipsilateral R1 laryngeal responses, however, did not show a significant main effect following the swallow (P = 0.28), although there was a significant time by measure interaction (P = 0.006) related to reduced R1 response amplitude up to 3 s after swallowing (P = 0.021). Therefore, the more rapid and shorter unilateral R1 responses continued to provide some, albeit reduced, laryngeal protective functions after swallowing, whereas thr,later bilateral R2 responses were suppressed both in occurrence and amplitude for up to 3 s after swallowing. The results suggest that R2 laryngeal adductor responses are suppressed following swallowing when residues may remain in the laryngeal vestibule putting persons at increased risk for the entry of foreign substances into the airway. C1 Natl Inst Neurol Disorders & Stroke, Laryngeal & Speech Sect, Bethesda, MD 20892 USA. RP Barkmeier, JM (reprint author), Univ Arizona, Dept Speech & Hearing Sci, POB 210071, Tucson, AZ 85710 USA. OI Ludlow, Christy/0000-0002-2015-6171 NR 43 TC 21 Z9 22 U1 0 U2 1 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 2000 VL 83 IS 3 BP 1264 EP 1272 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 295DJ UT WOS:000085951200013 PM 10712454 ER PT J AU Liu, Z Richmond, BJ AF Liu, Z Richmond, BJ TI Response differences in monkey TE and perirhinal cortex: Stimulus association related to reward schedules SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID INFERIOR TEMPORAL CORTEX; VENTRAL STRIATUM; ENTORHINAL CORTEX; RHESUS-MONKEYS; PARAHIPPOCAMPAL CORTICES; INFEROTEMPORAL CORTEX; MACAQUE MONKEY; BEHAVING MONKEYS; VISUAL RESPONSES; DOPAMINE NEURONS AB Response differences in monkey TE and perirhinal cortex: stimulus association related to reward schedules. J. Neurophysiol. 83. 1677-1692, 2000. Anatomic and behavioral evidence shows that TE and perirhinal cortices are two directly connected but distinct inferior temporal areas. Despite this distinctness, physiological properties of neurons in these two areas generally have been similar with neurons in both areas showing selectivity for complex visual patterns and showing response modulations related to behavioral context in the sequential delayed match to-sample (DMS) trials, attention, and stimulus familiarity. Here we identify physiological differences in the neuronal activity of these two areas. We recorded single neurons from area TE and perirhinal cortex while the monkeys performed a simple behavioral task using randomly interleaved visually cued reward schedules of one, two, or three DMS trials. The monkeys used the cue's relation to the reward schedule (indicated by the brightness) to adjust their behavioral performance. They performed most quickly and most accurately in trials in which reward was immediately forthcoming and progressively less well as more intermediate trials remained. Thus the monkeys appeared more motivated as they progressed through the trial schedule. Neurons in both TE and perirhinal cortex responded to both the visual cues related to the reward schedules and the stimulus patterns used in the DMS trials. As expected, neurons in both areas showed response selectivity to the DMS patterns, and significant, but small, modulations related to the behavioral context in the DMS trial. However, TE and perirhinal neurons showed strikingly different response properties. The latency distribution of perirhinal responses was centered 66 ms later than the distribution of TE responses, a larger difference than the 10-15 ms usually found in sequentially connected visual cortical areas. In TE, cue-related responses were related to the cue's brightness. In perirhinal cortex, cue-related responses were related to the trial schedules independently of the cue's brightness. For example, some perirhinal neurons responded in the first trial of any reward schedule including the one trial schedule, whereas other neurons failed to respond in the first trial but respond in the last trial of any schedule. The majority of perirhinal neurons had more complicated relations to the schedule. The cue-related activity of TE neurons is interpreted most parsimoniously as a response to the stimulus brightness, whereas the cue-related activity of perirhinal neurons is interpreted most parsimoniously as carrying associative information about the animal's progress through the reward schedule. Perirhinal cortex may be part of a system gauging the relation between work schedules and rewards. C1 NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Richmond, BJ (reprint author), NIMH, Neuropsychol Lab, Bldg 9, Bethesda, MD 20892 USA. NR 67 TC 97 Z9 98 U1 3 U2 5 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 2000 VL 83 IS 3 BP 1677 EP 1692 PG 16 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 295DJ UT WOS:000085951200047 PM 10712488 ER PT J AU Ozaki, M Tohyama, K Kishida, H Buonanno, A Yano, R Hashikawa, T AF Ozaki, M Tohyama, K Kishida, H Buonanno, A Yano, R Hashikawa, T TI Roles of neuregulin in synaptogenesis between mossy fibers and cerebellar granule cells SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE neuregulin; NMDA receptor; synaptogenesis; cerebellar granule cell; mossy fiber ID EXPRESSION; GENE; RECEPTORS; LIGANDS; SUBUNIT; ERBB2; ARIA AB Neuregulins (NRGs), a large group of structurally related signaling proteins, are likely to have important roles in the development, maintenance and repair of the nervous system and other selected tissues. We have demonstrated, by using the major form of NRG cloned from the mouse cerebellum that both the soluble form and the membrane anchored form of NRG may serve different functions in synaptogenesis, The soluble form of NRG was produced by proteolytic cleavage of the membrane anchored form of NRG, The proteolytic cleavage was promoted by protein kinase activation. The cleaved form of NRG transsynaptically regulated the expression of the NMDA (N-methyl-D-aspartate) receptor subunit NR2C as neurally-derived factors, whereas the membrane anchored form of NRG showed a homophilic binding activity between NRG beta 1s, In adult mice the membrane anchored form of NRG was concentrated in neuro-terminals of both granule cells and pontocerebellar mossy fibers. The fact that NRG can be functionally viewed as cell recognition molecules as well as neurotrophic agents suggests new possibilities for the important class of molecules. J, Neurosci, Res. 59: 612-623, 2000, (C) 2000 Wiley-Liss, Inc. C1 Inst Phys & Chem Res, Brain Sci Inst, Lab Cellular Informat Proc, Wako, Saitama 3510198, Japan. Inst Phys & Chem Res, BSI, Lab Neural Architecture, Wako, Saitama 3510198, Japan. Iwate Med Univ, Ctr Electron Microscopy & Bioimaging Res, Morioka, Iwate, Japan. NICHD, NIH, Dev Neurobiol Lab, Bethesda, MD USA. RP Ozaki, M (reprint author), Inst Phys & Chem Res, Brain Sci Inst, Lab Cellular Informat Proc, Wako, Saitama 3510198, Japan. EM mozaki@postman.riken.go.jp NR 25 TC 41 Z9 42 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD MAR 1 PY 2000 VL 59 IS 5 BP 612 EP 623 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 290LE UT WOS:000085677100004 PM 10686589 ER PT J AU Watson, JC Stritakis, CA Bryant-Greenwood, PK Koch, CA Kirschner, LS Nguyen, T Carney, JA Oldfield, EH AF Watson, JC Stritakis, CA Bryant-Greenwood, PK Koch, CA Kirschner, LS Nguyen, T Carney, JA Oldfield, EH TI Neurosurgical implications of Carney complex SO JOURNAL OF NEUROSURGERY LA English DT Article DE Carney complex; pituitary adenoma; schwannoma; acromegaly; Cushing's syndrome ID SPOTTY SKIN PIGMENTATION; PSAMMOMATOUS MELANOTIC SCHWANNOMA; NODULAR ADRENOCORTICAL DISEASE; ENDOCRINE OVERACTIVITY; PITUITARY-ADENOMAS; CUTANEOUS MYXOMAS; SPECIAL ASSOCIATIONS; CUSHINGS-SYNDROME; CARDIAC MYXOMAS; ATRIAL-MYXOMA AB Object. The authors present their neurosurgical experience with Carney complex. Carney complex, characterized by spotty skin pigmentation, cardiac myxomas, primary pigmented nodular adrenocortical disease, pituitary tumors, and nerve sheath tumors (NSTs), is a recently described, rare, autosomal-dominant familial syndrome that is relatively unknown to neurosurgeons. Neurosurgery is required to treat pituitary adenomas and a rare NST, the psammomatous melanotic schwannoma (PMS), in patients with Carney complex. Cushing's syndrome, a common component of the complex, is caused by primary pigmented nodular adrenocortical disease and is not secondary to an adrenocorticotropic hormone-secreting pituitary adenoma. Methods. The authors reviewed 14 cases of Carney complex, five from the literature and nine from their own experience. Of the 14 pituitary adenomas recognized in association with Carney complex, 12 developed growth hormone (GH) hypersecretion (producing gigantism in two patients and acromegaly in 10), and results of immunohistochemical studies in one of the other two were positive for GH. The association of PMSs with Carney complex was established in 1990. Of the reported tumors. 28% were associated with spinal nerve sheaths. The spinal tumors occurred in adults (mean age 32 years, range 18-49 years) who presented with pain and radiculopathy. These NSTs may be malignant (10%) and, as with the cardiac myxomas, are associated with significant rates of morbidity and mortality. Conclusions. Because of the surgical comorbidity associated with cardiac myxoma and/or Cushing's syndrome, recognition of Carney complex has important implications for perisurgical patient management and family screening. Study of the genetics of Carney complex and of the biological abnormalities associated with the tumors may provide insight into the general pathobiological abnormalities associated with the tumors may provide insight into the general pathobiological features of pituitary adenomas and NSTs. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, Unit Genet Endocrinol, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Mayo Clin & Mayo Fdn, Dept Lab Med & Pathol, Rochester, MN 55905 USA. RP Oldfield, EH (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. RI Koch, Christian/A-4699-2008; OI Koch, Christian/0000-0003-3127-5739; Koch, Christian/0000-0003-0678-1242 NR 49 TC 39 Z9 41 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 2000 VL 92 IS 3 BP 413 EP 418 DI 10.3171/jns.2000.92.3.0413 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 285DX UT WOS:000085375400006 PM 10701527 ER PT J AU Dilsizian, V AF Dilsizian, V TI The role of myocardial perfusion imaging in vascular endothelial dysfunction SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Editorial Material ID CORONARY-ARTERY DISEASE; CHOLESTEROL-LOWERING THERAPY; ELEVATED GLUCOSE-LEVELS; NITRIC-OXIDE; DEPENDENT RELAXATION; RELAXING FACTOR; L-ARGININE; VASOMOTOR RESPONSE; ANGINA-PECTORIS; RISK-FACTORS C1 NIH, Bethesda, MD 20892 USA. RP Dilsizian, V (reprint author), NIH, 9000 Rockville Pike,Bldg 10,Room 7B-15, Bethesda, MD 20892 USA. NR 41 TC 15 Z9 15 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD MAR-APR PY 2000 VL 7 IS 2 BP 180 EP 184 DI 10.1016/S1071-3581(00)90042-4 PG 5 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 307JW UT WOS:000086651000015 PM 10796009 ER PT J AU Watabe, H Endres, CJ Breier, A Schmall, B Eckelman, WC Carson, RE AF Watabe, H Endres, CJ Breier, A Schmall, B Eckelman, WC Carson, RE TI Measurement of dopamine release with continuous infusion of [C-11]raclopride: Optimization and signal-to-noise considerations SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE [C-11]raclopride; bolus/infusion; amphetamine; noise; optimization ID POSITRON EMISSION TOMOGRAPHY; C-11 RACLOPRIDE BINDING; NONHUMAN-PRIMATES; PET; MICRODIALYSIS; SCHIZOPHRENIA; INVIVO; BOLUS AB PET studies with [C-11]raclopride provide an indirect measure of changes in synaptic dopamine. Previously, we used the bolus-plus-infusion (B/I) method to assess dopamine response from the percentage change in binding potential (Delta BP) before and after administration of amphetamine. The goal of this work is to optimize the measurement of changes in neurotransmitter with the B/I method by choosing the optimal timing for pre- and poststimulus scanning. Methods: Two sources of variability in Delta BP were considered: within-subject and between-subject noise. A noise model based on a phantom study and human data was used to evaluate the within-subject noise. For between-subject noise, simulated time-activity curves were generated from measured [C-11]raclopride input functions. Optimal timing to measure bBP was determined and applied to human data. Results: According to the simulation study, the optimal scan times for pre- and poststimulus scans were 39-50 and 58-100 min, respectively. The optimal timing resulted in a 28% noise reduction compared with the original timing. By applying the optimal timing to human studies, the statistical significance of the difference in Delta BP between patients with schizophrenia and healthy volunteers increased from P = 0.038 to 0.012. Conclusion: careful assessment of the sources of noise in receptor imaging studies can increase the sensitivity of the B/I method for the detection of biologic signals. C1 NIMH, PET Dept, Ctr Clin, NIH, Bethesda, MD 20892 USA. NIMH, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Carson, RE (reprint author), NIMH, PET Dept, Ctr Clin, NIH, Bldg 10,Rm 1C-401,10 Ctr Dr,MSC 1180, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 22 TC 81 Z9 82 U1 0 U2 0 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 2000 VL 41 IS 3 BP 522 EP 530 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 291GG UT WOS:000085725300026 PM 10716328 ER PT J AU Orecchia, R Infusini, E Sciutto, A Rapallo, A Di Vinci, A Nigro, S Geido, E Giaretti, W AF Orecchia, R Infusini, E Sciutto, A Rapallo, A Di Vinci, A Nigro, S Geido, E Giaretti, W TI Ki-ras activation in vitro affects GI and G2M cell-cycle transit times and apoptosis SO JOURNAL OF PATHOLOGY LA English DT Article DE Ki-ras activation; oncogenic signal; signal transduction; cell cycle; apoptosis; proliferative advantage; tumour progression ID FAS-MEDIATED APOPTOSIS; PROTEIN-KINASE-C; COLORECTAL ADENOMAS; GENOMIC INSTABILITY; DECREASED APOPTOSIS; ONCOGENIC RAS; NIH-3T3 CELLS; RESISTANCE; EXPRESSION; MUTATIONS AB Mutant ras genes occur frequently in human neoplasia and, in particular, in pancreatic, colorectal, and lung adenocarcinomas, Recent evidence suggests that G-->T and G-->C transversions of the Ki-ras gene in codon 12 may lead to biological effects in vitro and in vivo that may be associated with an abnormal cell cycle and increased tumour aggressiveness. The role of Ki-ras activation (a G-->C transversion in codon 12, arginine for glycine) in the cell cycle and apoptosis was investigated using control and permanently transfected NIH3T3 mouse fibroblasts. Flow cytometry was used to evaluate the G1-, S- and G2M-phase transit times, the potential doubling time, the growth fraction, and the cell loss factor during asynchronous exponential growth. Apoptosis was induced in both cell lines by absence of growth factors for an extended period of time (72 h) and quantitatively evaluated using the TUNEL method coupled with flow cytometry, It was found that codon 12 G-C Ki-ras transfected cells compared with controls, had a significant prolongation of G1 by about 50%, a reduction of the G2M transit time by 30%, and a decrease of the cell loss factor by about 90%. Apoptotic cells were about 10% in control and less than 0.5% in Ki-ras transfected cells after 72 h starvation-confluency. These data suggest that codon 12 G-->C Ki-ras activation in mouse NIH3T3 fibroblasts is associated with deregulation of checkpoint controls in the GI and G2M phases of the cell cycle and inhibition of apoptosis. It appears plausible that these cell mechanisms are related to a proliferative advantage and that they may also be important in the progression of human tumours characterized by specific Ki-ras mutations. Copyright (C) 2000 John Wiley & Sons, Ltd. C1 Natl Canc Inst, IST, Lab Biophys Cytometry, I-16132 Genoa, Italy. RP Giaretti, W (reprint author), Natl Canc Inst, IST, Lab Biophys Cytometry, Largo Rosanna Benzi 10, I-16132 Genoa, Italy. NR 44 TC 13 Z9 13 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD MAR PY 2000 VL 190 IS 4 BP 423 EP 429 PG 7 WC Oncology; Pathology SC Oncology; Pathology GA 294CW UT WOS:000085894300005 PM 10699990 ER PT J AU Rose, SR Baron, J Bernstein, D Yanovski, J Troendle, JF Leschek, E Chipman, J Cutler, GB AF Rose, SR Baron, J Bernstein, D Yanovski, J Troendle, JF Leschek, E Chipman, J Cutler, GB TI Suppression and recovery of GH secretion after GH injection in non-GH deficient short children SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM LA English DT Article DE growth disorders; IGF-I; somatotropin; growth hormone therapy ID GROWTH-HORMONE SECRETION; IDIOPATHIC SHORT STATURE; FACTOR-I; THERAPY; WITHDRAWAL AB Objective: To identify the effect of exogenous GH on endogenous GH secretion in 48 non-GH deficient short children participating in a placebo-controlled trial of GH therapy on final adult height. Design: Night GH secretion (mean of levels every 20 min from 20.00 to 08.00 h) was evaluated at baseline, 6 months before starting placebo or GH (somatotropin, 0.222 mg/kg/week, divided into 3 doses each week). At 6 months after starting injections, blood samples for GH were obtained hourly for 24 h after an injection, and every 20 min on each of the next two nights (with no additional placebo or GH injection). Results: IGF-I levels in the treatment group were elevated at 12 and 24 h but not at 36 h compared to the placebo group. Mean GH levels in the placebo group did not vary significantly among the four sampling periods. In the treatment group, the mean serum GH rose to a supraphysiological peak at an average time of 4 h after injection. Subsequently, mean GH level was significantly suppressed compared to placebo on the second night following GH injection, but returned to normal by the third night. Conclusion: After 6 months of a thrice weekly GH treatment regimen in non-GH deficient short children, endogenous GH secretion was reduced from 24 to 36 h after injection compared to placebo and returned to control levels by 48 to 60 h after injection. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. Univ Tennessee, Memphis, TN USA. RP Rose, SR (reprint author), 50 N Dunlap,4th Floor, Memphis, TN 38103 USA. NR 17 TC 5 Z9 5 U1 0 U2 1 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 PY 2000 VL 13 IS 3 BP 281 EP 288 PG 8 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 290WX UT WOS:000085701800007 PM 10714753 ER PT J AU Piedmont, RL McCrae, RR Riemann, R Angleitner, A AF Piedmont, RL McCrae, RR Riemann, R Angleitner, A TI On the invalidity of validity scales: Evidence from self-reports and observer ratings in volunteer samples SO JOURNAL OF PERSONALITY AND SOCIAL PSYCHOLOGY LA English DT Article ID NEO PERSONALITY-INVENTORY; SOCIAL DESIRABILITY SCALES; PIR FACET SCALES; MMPI-A; INDIVIDUAL-DIFFERENCES; SPOUSE RATINGS; K-CORRECTION; CONSCIENTIOUSNESS; AGREEABLENESS; CONSISTENCY AB Because of the potential for bias and error in questionnaire responding, many personality inventories include validity scales intended to correct biased scores or identify invalid protocols. The authors evaluated the utility of several types of validity scales in a volunteer sample of 72 men and 106 women who completed the Revised NEO Personality Inventory (NEO-PI-R; P. T. Costa Be R. R. McCrae, 1992) and the Multidimensional Personality Questionnaire (MPQ; A. Tellegen, 1978/1982) and were rated by 2 acquaintances on the observer form of the NEO-PI-R. Analyses indicated that the validity indexes lacked utility in this sample. A partial replication (N = 1,728) also failed to find consistent support for the use of validity scales. The authors illustrate the use of informant ratings in assessing protocol validity and argue that psychological assessors should limit their use of validity scales and seek instead to improve the quality of personality assessments. C1 Loyola Coll, Dept Pastoral Counseling, Columbia, MD 21045 USA. NIA, Personal Stress & Coping Sect, Gerontol Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Bielefeld, Dept Psychol, D-4800 Bielefeld, Germany. RP Piedmont, RL (reprint author), Loyola Coll, Dept Pastoral Counseling, 7135 Minstrel Way, Columbia, MD 21045 USA. NR 56 TC 139 Z9 139 U1 1 U2 10 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-3514 J9 J PERS SOC PSYCHOL JI J. Pers. Soc. Psychol. PD MAR PY 2000 VL 78 IS 3 BP 582 EP 593 DI 10.1037//0022-3514.78.3.582 PG 12 WC Psychology, Social SC Psychology GA 321ZN UT WOS:000087485400013 PM 10743882 ER PT J AU Vilner, BJ Bowen, WD AF Vilner, BJ Bowen, WD TI Modulation of cellular calcium by sigma-2 receptors: Release from intracellular stores in human SK-N-SH neuroblastoma cells SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID BIOLOGICAL EVALUATION; SELECTIVE LIGANDS; CARDIAC MYOCYTES; BINDING-SITES; AFFINITY; BRAIN; SUGGEST; REQUIREMENTS; HALOPERIDOL; APOPTOSIS AB Human SK-N-SH neuroblastoma cells expressed sigma-1 and sigma-2 receptors with similar pharmacological profiles to those of rodent-derived tissues, although sigma-2 receptors exhibited some affinity differences that might suggest heterogeneity or species differences. Structurally diverse sigma ligands produced two types of increases in intracellular (cytosolic) Ca2+ concentration ([Ca2+](i)) in these cells. CB-64D, CB-64L, JL-II-147, BD737, LR172, BD1008, haloperidol, reduced haloperidol, and ibogaine all produced an immediate, dose-dependent, and transient rise in [Ca2+](i). Sigma-inactive compounds structurally similar to the most active sigma ligands and ligands for several neurotransmitter receptors produced little or no effect. The high activity of CB-64D and ibogaine (sigma-2-selective ligands) compared with the low activity of (+)-pentazocine and other (+)-benzomorphans (sigma-1-selective ligands), in addition to enantioselectivity for CB-64D over CB-64L, strongly indicated mediation by sigma-2 receptors. The effect of CB-64D and BD737 was blocked by the sigma antagonists BD1047 and BD1063, further confirming specificity as a receptor-mediated event. The transient rise in [Ca2+](i) occurred in the absence of extracellular Ca2+ and was completely eliminated by pretreatment of cells with thapsigargin. Thus, sigma-2 receptors stimulate a transient release of Ca2+ from the endoplasmic reticulum. Prolonged exposure of cells to sigma-receptor ligands resulted in a latent and sustained rise in [Ca2+](i), with a pharmacological profile identical to that of the transient rise. This sustained rise in [Ca2+](i) was affected by neither the removal of extracellular Ca2+ nor thapsigargin pretreatment, suggesting latent sigma-2 receptor-induced release from thapsigargin-insensitive intracellular Ca2+ stores. Sigma-2 receptors may use Ca2+ signals in producing cellular effects. C1 NIDDK, Unit Receptor Biochem & Pharmacol, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Bowen, WD (reprint author), NIDDK, Unit Receptor Biochem & Pharmacol, Med Chem Lab, NIH, Bldg 8,Room B1-23,8 Ctr Dr MSC 0815, Bethesda, MD 20892 USA. NR 40 TC 113 Z9 121 U1 0 U2 7 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 2000 VL 292 IS 3 BP 900 EP 911 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 287RX UT WOS:000085520900011 PM 10688603 ER PT J AU Hunyady, B Palkovits, M Mezey, E AF Hunyady, B Palkovits, M Mezey, E TI Vesicular monoamine transporters in the rat stomach SO JOURNAL OF PHYSIOLOGY-PARIS LA English DT Article; Proceedings Paper CT 3rd International Symposium on Experimental and New Therapeutics Approaches to Ulcer Disease CY JUL 23-25, 1998 CL PECS, HUNGARY DE gastrointestinal system; stomach; rats; biogenic amines; histamine; serotonin; gastrin; enterochromaffin cell; enterochromaffin-like cell; gastric G cell; DOPA decarboxylase; histidine decarboxylase; vesicular monoamine transporter immunohistochemistry; in situ hybridization histochemistry ID ELECTRON-MICROSCOPIC IDENTIFICATION; ENDOCRINE-CELLS; HISTIDINE-DECARBOXYLASE; AMINE TRANSPORTERS; NERVOUS-SYSTEM; MAST-CELLS; EXPRESSION; HISTAMINE; DOPAMINE; LOCALIZATION AB Cellular distribution of vesicular monoamine transporters (VMATs), known to regulate vesicular storage and release of biogenic amines (i.e., catecholamines, serotonin, histamine, etc.), have been studied in the rat stomach using in situ hybridization histochemistry (ISHH) and immunohistochemical (IHC) techniques, S-35-UTP labeled riboprobes showed that mRNAs of both VMATs are expressed in the gastric mucosa. A combination of ISHH and MC verified that most of the parietal cells (among other epithelial cells) express mRNA of the peripheral type transporter (VMAT1) while enterochromaffin-like cells (ECL) of the fundic mucosa express mRNA of the central type (VMAT2). In addition, with double fluorescent IHC we detected VMAT1 protein in serotoninergic enterochromaffin cells (EC) of the stomach and in gastrin producing G cells of the antral mucosa. Similarly to the fundus, VMAT2 protein was present in ECL cells and in the enteric plexus. Surprisingly, serotonin- and/or histamine-containing cells in the connective tissue compartments of the stomach (i.e,, lamina propria and submucosa), immunoreactive for a mast cell specific antigen, displayed neither VMAT1 nor VMAT2 immunoreactivity. Distribution of VMATs in the rat stomach support our previous observations on aminergic properties of two important gastrointestinal (CT) epithelial cell populations primarily known for other specific secretory products, i.e. dopaminergic properties of acid producing parietal cells and histaminergic properties of gastrin producing G cells. These data emphasize the existence of a non-neuronal, intrinsic aminergic system in the GT tract. (C) 2000 Elsevier Science Ltd. Published by Editions scientifiques et medicales Elsevier SAS. C1 NINDS, Basic Neurosci Program, NIH, Bethesda, MD 20892 USA. NIMH, Genet Sect, NIH, Bethesda, MD 20892 USA. Med Univ Pecs, Dept Med 1, Pecs, Hungary. RP Mezey, E (reprint author), NINDS, Basic Neurosci Program, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 NR 37 TC 3 Z9 3 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0928-4257 J9 J PHYSIOLOGY-PARIS JI J. Physiol.-Paris PD MAR-APR PY 2000 VL 94 IS 2 BP 123 EP 130 DI 10.1016/S0928-4257(00)00152-2 PG 8 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 304TC UT WOS:000086499400008 PM 10791693 ER PT J AU Taaffe, DR Marcus, R AF Taaffe, DR Marcus, R TI Musculoskeletal health and the older adult SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE bone mass; exercise; muscle mass; muscle strength ID HUMAN GROWTH-HORMONE; BONE-MINERAL DENSITY; LUMBAR EXTENSION STRENGTH; POSTMENOPAUSAL ESTROGEN THERAPY; ISOMETRIC MUSCLE STRENGTH; ELDERLY WOMEN; REPLACEMENT THERAPY; RESISTANCE EXERCISE; BODY-COMPOSITION; SKELETAL-MUSCLE AB A decline in muscle mass and function, and in the mass and integrity of the skeletal system, are well-known consequences of aging. These changes impinge on the functional performance required for independent living and contribute to frailty and fracture risk. Resistance exercise has been shown to be an effective mode to circumvent age-related changes in the muscular system, although the benefit of exercise on bone mass in the aging skeleton is comparatively modest at best. This brief review highlights results from several studies that we have undertaken in older adults, examining aspects of the resistance training prescription as well as the potential beneficial role of hormones. What is common to all of these studies is the high degree of residual plasticity that remains in aging skeletal muscle. Risk factors for falls and fracture include reduced bone mass, muscle weakness, impaired balance, and lessened visual acuity. Among these, only muscle strength is reliably enhanced with resistance exercise, which may aid in reducing hip fracture risk as well as improving the ability to undertake daily activities and maintain independence. C1 Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Aging Study Unit, Palo Alto, CA 94304 USA. Stanford Univ, Dept Med, Stanford, CA 94305 USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. RP Marcus, R (reprint author), Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Aging Study Unit, GRECC 182-B,3801 Miranda Ave, Palo Alto, CA 94304 USA. NR 76 TC 31 Z9 32 U1 0 U2 1 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD MAR-APR PY 2000 VL 37 IS 2 BP 245 EP 254 PG 10 WC Rehabilitation SC Rehabilitation GA 380YN UT WOS:000165733400018 PM 10850831 ER PT J AU Troendle, JF AF Troendle, JF TI Stepwise normal theory multiple test procedures controlling the false discovery rate SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE false discovery rate; multiple testing; step-down; step-up; power AB The false discovery rate (FDR), or the expected proportion of falsely rejected null hypotheses to rejected null hypotheses, has recently been proposed as an error rate that multiple testing procedures should in certain circumstances control. So far, only a step-up procedure for independent test statistics has been created explicitly to control the FDR (Benjamini and Hochberg, 1995). In this paper, step-down and step-up procedures are described which asymptotically (as N -> infinity) control the FDR when the test statistics are the t statistics from consistent multivariate normal estimators of the tested parameters. Determination of the necessary critical constants for the normal theory procedures is achieved using numerical integration when the correlations are equal, or through simulation using the multivariate t distribution when the correlations are arbitrary. The critical constants of the normal theory procedures are compared to those of the Benjamini and Hochberg procedure under the normal assumption, and a large potential power increase is found. Simulation strongly supports the use of critical constants, obtained by an asymptotic argument, in small samples for as many as 30 tests. Adjusted FDR values can be found to quantify the evidence against a given hypothesis. (C) 2000 Published by Elsevier Science B.V. All rights reserved. C1 NICHHD, Biometry & Math Stat Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 12 TC 28 Z9 29 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD MAR 1 PY 2000 VL 84 IS 1-2 BP 139 EP 158 DI 10.1016/S0378-3758(99)00145-7 PG 20 WC Statistics & Probability SC Mathematics GA 278UA UT WOS:000085006300009 ER PT J AU Jensen, PS AF Jensen, PS TI Are stimulants overprescribed? Dr. Jensen replies SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Letter C1 NIMH, Off Director, Bethesda, MD 20892 USA. RP Jensen, PS (reprint author), Columbia Univ, New York State Psychiat Inst, Dept Child Psychiat, Ctr Advancement Child & Adolescent Mental Hlth, New York, NY 10027 USA. NR 9 TC 0 Z9 0 U1 2 U2 2 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 2000 VL 39 IS 3 BP 270 EP 271 DI 10.1097/00004583-200003000-00003 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 288TP UT WOS:000085580800003 ER PT J AU Dries, DL Exner, DV Domanski, MJ Greenberg, B Stevenson, LW AF Dries, DL Exner, DV Domanski, MJ Greenberg, B Stevenson, LW TI The prognostic implications of renal insufficiency in asymptomatic and symptomatic patients with left ventricular systolic dysfunction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID HEART-FAILURE; DIAGNOSIS; SURVIVAL AB OBJECTIVES The present analysis examines the prognostic implications of moderate renal insufficiency in patients with asymptomatic and symptomatic:left ventricular systolic dysfunction. BACKGROUND Chronic elevations in intracardiac filling pressures may lead to progressive ventricular dilation and heart failure progression. The ability to maintain fluid balance and prevent increased intracardiac filling pressures is critically dependent on the adequacy of renal function. METHODS This is a retrospective analysis of the Studies of Left Ventricular Dysfunction (SOLVD) Trials, in which moderate renal insufficiency is defined as a baseline creatinine clearance <60 ml/min, as estimated from the Cockroft-Gault equation. RESULTS In the SOLVD Prevention Trial, multivariate analyses demonstrated moderate renal insufficiency to be associated with an increased risk for all-cause mortality (Relative Risk [RR] 1.41; p = 0.001), largely explained by an increased risk for pump-failure death (RR 1.68; p = 0.007) and the combined end point death or hospitalization for heart failure (RR 1.33; p = 0.001). Likewise, in the Treatment Trial,multivariate analyses demonstrated moderate renal insufficiency to be associated with-an ir;creased risk for all-cause mortality (RR 1.41; p = 0.001), also largely explained by: an increased risk for pump-failure death (RR 1.49; p = 0.007) and the combined end point death or hospitalization for heart failure (RR 1.45; p = 0.001). CONCLUSIONS Even moderate degrees of renal insufficiency are; independently associated with an increased risk for all-cause mortality in patients with heart failure, largely explained by an increased risk of heart failure progression. These data suggest that, rather than simply being a marker of the severity of underlying disease, the adequacy of renal function may be a primary determinant of compensation in patients with heart failure, and therapy capable of improving renal function may delay disease progression. (C) 2000 by the American College of Cardiology. C1 Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA. NHLBI, Div Epidemiol & Clin Applicat, Clin Trials Res Grp, Bethesda, MD 20892 USA. Univ Calif San Diego, Div Cardiol, San Diego, CA 92103 USA. RP Dries, DL (reprint author), Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA. NR 12 TC 508 Z9 552 U1 0 U2 9 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 2000 VL 35 IS 3 BP 681 EP 689 DI 10.1016/S0735-1097(99)00608-7 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 292CD UT WOS:000085775800019 PM 10716471 ER PT J AU Baum, BJ Mooney, DJ AF Baum, BJ Mooney, DJ TI The impact of tissue engineering on dentistry SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID GENE-THERAPY; SALIVARY-GLANDS; CELLS; TRIAL AB Background. Tissue engineering is a novel and highly exciting field of research that aims to repair damaged tissues as well as create replacement (bioartificial) organs. Overview. The authors provide a general review of the principles underlying key tissue engineering strategies, as well as the typical components used. Several examples of preclinical and clinical progress are presented. These include passive approaches, such as dental implants, and inductive approaches that activate cells with specific molecular signals. Practice Implications. Tissue engineering will have a considerable effect on dental practice during the next 25 years. The greatest effects will likely be related to the repair and replacement of mineralized tissues, the promotion of oral wound healing and the use of gene transfer adjunctively. C1 NIDCR, GTTB, NIH, Bethesda, MD 20892 USA. Univ Michigan, Sch Dent, Ann Arbor, MI 48109 USA. RP Baum, BJ (reprint author), NIDCR, GTTB, NIH, Bldg 10,Room 1N113,MSC-1190, Bethesda, MD 20892 USA. NR 60 TC 40 Z9 43 U1 0 U2 2 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 2000 VL 131 IS 3 BP 309 EP 318 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 290KW UT WOS:000085676300014 PM 10715922 ER PT J AU Atkinson, JC O'Connell, A Aframian, D AF Atkinson, JC O'Connell, A Aframian, D TI Oral manisfestations of primary immunological diseases SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; CLASS-II DEFICIENCY; BONE-MARROW TRANSPLANTATION; DISCOID LUPUS-ERYTHEMATOSUS; IGA IMMUNE-RESPONSE; PRIMARY IMMUNODEFICIENCIES; OROFACIAL MANIFESTATIONS; DIGEORGE/VELOCARDIOFACIAL SYNDROME; PROTEIN-MALNUTRITION; PERIODONTAL STATUS AB Background. Primary immunodeficiencies have many oral manifestations. The clinical presentation of these diseases demonstrates the roles of different immune cells for the maintenance of oral health. Methods. The authors reviewed selected literature describing systemic and oral manifestations of the primary immunodeficiencies published between 1966 and 1999. Results. The authors found that oral candidiasis and herpetic infections are seen frequently in patients with T-cell deficiencies, while patients with B-cell deficiencies are most susceptible to bacterial infections. Periodontitis and oral candidiasis are found in some, but not all,: phagocyte deficiencies. Conclusions. These findings demonstrate that T cells, B cells and phagocytes all have roles in oral immunity. Clinical Implications. Acquired conditions that affect the immune system such as diabetes, alcoholism and acquired immunodeficiency syndrome, as well as certain medications, will affect oral defense mechanisms. The effects that acquired immunodeficiencies will have on oral health can be predicted from the oral manifestations of primary immunodeficiencies. C1 Natl Inst Dent & Craniofacial Res, NIH, Clin Res Core, Oral Med Training Program, Bethesda, MD 20892 USA. RP Atkinson, JC (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Clin Res Core, Oral Med Training Program, 10 Ctr Dr,Room 1N-113,MSC 1190, Bethesda, MD 20892 USA. OI O'Connell, Anne C/0000-0002-1495-3983 NR 90 TC 12 Z9 13 U1 0 U2 2 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 2000 VL 131 IS 3 BP 345 EP 356 PG 12 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 290KW UT WOS:000085676300018 PM 10715926 ER PT J AU Slavkin, HC AF Slavkin, HC TI The body's skin frontier and the challenges of wound healing: Keloids SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID GENE-EXPRESSION; TGF-BETA; FIBROBLASTS C1 Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. RP Slavkin, HC (reprint author), Natl Inst Dent & Craniofacial Res, 31 Ctr Dr,MSC 2290,Bldg 31,Room 2C39, Bethesda, MD 20892 USA. NR 26 TC 2 Z9 2 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 2000 VL 131 IS 3 BP 362 EP 365 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 290KW UT WOS:000085676300020 PM 10715928 ER PT J AU Jonnalagadda, SS Mitchell, DC Smiciklas-Wright, H Meaker, KB Van Heel, N Karmally, W Ershow, AG Kris-Etherton, PM AF Jonnalagadda, SS Mitchell, DC Smiciklas-Wright, H Meaker, KB Van Heel, N Karmally, W Ershow, AG Kris-Etherton, PM TI Accuracy of energy intake data estimated by a multiple-pass, 24-hour dietary recall technique SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID DOUBLY LABELED WATER; MAINTAIN BODY-WEIGHT; FOOD-INTAKE; FUNDAMENTAL PRINCIPLES; WOMEN; RECORDS; EXPENDITURE; OBESE; ADULTS; INTERVENTION AB Objective This study examined the accuracy of a multiple-pass, 24-hour dietary recall method for estimating energy intakes of men and women by comparing it with energy intake required for weight maintenance. Design Three-day, multiple-pass, 24-hour recalls were obtained on randomly selected days during a self-selected diet period when subjects were preparing their own meals and during a controlled diet period when all meals were provided by the study. During the dietary intervention, weight was maintained; body weight and dietary intake were monitored closely, thereby allowing estimation of the energy intake required for weight maintenance. Subjects/setting Seventy-eight men and women (22 to 67 years old) from the Dietary Effects on Lipoprotein and Thrombogenic Activity (DELTA) study participated in this study. All 24-hour recalls were collected using a computer-assisted, interactive, multiple-pass telephone interview technique. Energy requirements for each individual were determined by the energy content of the DELTA study foods provided to maintain weight. Statistical analysis Paired and independent t tests were conducted to examine differences among study variables. Agreement between recalled energy intake and weight maintenance energy intake was analyzed using the Bland-Altman technique, Results Compared with weight maintenance energy intake, during the self-selected diet period men and women underestimated energy intake by 11% and 13%, respectively. During the controlled diet period, men underestimated energy intake by 13%, whereas women overestimated energy by 1.3%. Applications/conclusions Men had a tendency to underestimate energy intake irrespective of the recording period. The accuracy of the recalled energy intake of women may be influenced by recording circumstances. Researchers should examine the factors influencing underreporting and overreporting by individuals and their impact on macronutrient and micronutrient intakes. Also, strategies need to be developed to minimize underreporting and overreporting. C1 Georgia State Univ, Dept Nutr, Atlanta, GA 30303 USA. Penn State Nutr Ctr, Diet Assessment Serv, University Pk, PA USA. Penn State Univ, Dept Nutr, University Pk, PA 16802 USA. US FDA, Div Reprod & Urol Prod, Rockville, MD 20857 USA. Penn State Univ, Dept Stat, University Pk, PA 16802 USA. Univ Minnesota, Div Epidemiol, Nutr Coordinating Ctr, Minneapolis, MN 55455 USA. Columbia Univ, Irving Ctr Clin Res, New York, NY USA. NHLBI, Div Heart & Vasc Dis, NIH, Bethesda, MD 20892 USA. RP Jonnalagadda, SS (reprint author), Georgia State Univ, Dept Nutr, Univ Plaza, Atlanta, GA 30303 USA. FU NHLBI NIH HHS [U01-HL49659] NR 51 TC 121 Z9 121 U1 0 U2 8 PU AMER DIETETIC ASSOC PI CHICAGO PA 120 S RIVERSIDE PLZ, STE 2000, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD MAR PY 2000 VL 100 IS 3 BP 303 EP 311 DI 10.1016/S0002-8223(00)00095-X PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 460MD UT WOS:000170310600010 PM 10719403 ER PT J AU Costello, RB Grumstrup-Scott, J AF Costello, RB Grumstrup-Scott, J TI Zinc: What role might supplements play? SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID DIETARY C1 NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Costello, RB (reprint author), NIH, Off Dietary Supplements, 31 Ctr Dr,Room 1B29,MSC 2086, Bethesda, MD 20892 USA. NR 15 TC 6 Z9 6 U1 0 U2 0 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD MAR PY 2000 VL 100 IS 3 BP 371 EP 375 DI 10.1016/S0002-8223(00)00113-9 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 460MD UT WOS:000170310600027 PM 10719417 ER PT J AU Shorr, RI Franse, LV Resnick, HE Di Bari, M Johnson, KC Pahor, M AF Shorr, RI Franse, LV Resnick, HE Di Bari, M Johnson, KC Pahor, M TI Glycemic control of older adults with type 2 diabetes: Findings from the Third National Health and Nutrition Examination Survey, 1988-1994 SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE age factors; diabetes mellitus; hypoglycemic agents; blood glucose; Hemoglobin A, glycosolated ID MORTALITY AB BACKGROUND: Although nearly half of all people who have diabetes are aged 65 or older, glycemic control of older adults with diabetes has nor been well described. METHODS: We conducted a cross-sectional study of 1,482 participants with self-reported type 2 diabetes in the Third National Health and Nutrition Examination Survey, 1988-1994 (NHANES III), a nationally representative sample of the US noninstitutionalized civilian population. Variables included in this analysis included age, sociodemographic factors, drug treatment, and level of glycemic control. RESULTS: The mean % (+/-SE) HbA(1c) was 7.78 +/- 0.21, 7.64 +/- 0.18, 7.71 +/- 0.14, and 7.27 +/- 0.14 in persons aged 20 to 54, 55 to 64, 65 to 74 and greater than or equal to 75 years, respectively. The mean mg/dL (+/-SE) fasting plasma glucose (FPG) was 175.9 +/- 7.6, 164.5 +/- 6.1, 183.3 +/- 5.3, and 158.5 +/- 5.5 in the four age groups and older, respectively. When controlling for race, gender, education, and duration of diabetes, age was not significantly associated with levels of HbA(1c) [P (trend) = 0.17] or FPG [P (trend) = 0.19]. Among NHANES III participants aged 65 or older, ADA guidelines for glycemic control (HbA(1c) < 7%) were achieved by 71%, 44%, and 27% of persons using no drug therapy, oral hypoglycemic agents, and insulin, respectively. CONCLUSIONS: Although many older adults with type 2 diabetes do not achieve targets for glucose control, there is no evidence to suggest that community-dwelling older adults with diabetes are treated less vigorously than younger persons with diabetes. C1 Univ Tennessee, Dept Prevent Med, Memphis, TN 38105 USA. Methodist Healthcare, Dept Med Educ, Memphis, TN USA. Vrije Univ Amsterdam, Inst Res Extramural Med, EMGO, Amsterdam, Netherlands. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Univ Florence, Dept Gerontol & Geriatr, Florence, Italy. Careggi Hosp, Florence, Italy. RP Shorr, RI (reprint author), Univ Tennessee, Dept Prevent Med, 66 N Pauline,Suite 633, Memphis, TN 38105 USA. RI DI BARI, MAURO/J-1524-2012 NR 18 TC 66 Z9 70 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2000 VL 48 IS 3 BP 264 EP 267 PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 294LB UT WOS:000085911800004 PM 10733051 ER PT J AU Moist, LM Port, FK Orzol, SM Young, EW Ostbye, T Wolfe, RA Hulbert-Shearon, T Jones, CA Bloembergen, WE AF Moist, LM Port, FK Orzol, SM Young, EW Ostbye, T Wolfe, RA Hulbert-Shearon, T Jones, CA Bloembergen, WE TI Predictors of loss of residual renal function among new dialysis patients SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID AMBULATORY PERITONEAL-DIALYSIS; CHRONIC-HEMODIALYSIS PATIENTS; CALCIUM-ANTAGONISTS; DISEASE; MORTALITY; PROGRESSION; HYPERTENSION; PRESERVATION; MAINTENANCE; INHIBITORS AB Residual renal function (RRF) in end-stage renal disease is clinically important as it contributes to adequacy of dialysis, quality of life, and mortality. This study was conducted to determine the predictors of RRF loss in a national random sample of patients initiating hemodialysis and peritoneal dialysis. The study controlled for baseline variables and included major predictors. The end point was loss of RRF, defined as a urine volume <200 ml/24 h at approximately 1 yr of follow-up. The adjusted odds ratios (AOR) and P values associated with each of the demographic, clinical, laboratory, and treatment parameters were estimated using an "adjusted" univariate analysis. Significant variables (P < 0.05) were included in a multivariate logistic regression model. Predictors of RRF loss were female gender (AOR = 1.45; P < 0.001), non-white race (AOR = 1.57; P = < 0.001), prior history of diabetes (AOR = 1.82; P = 0.006), prior history of congestive heart failure (AOR = 1.32; P = 0.03), and time to follow-up (AOR = 1.06 per month; P = 0.03). Patients treated with peritoneal dialysis had a 65% lower risk of RRF loss than those on hemodialysis (AOR = 0.35; P < 0.001). Higher serum calcium (AOR = 0.81 per mg/dl; P = 0.05), use of an angiotensin-converting enzyme inhibitor (AOR = 0.68; P < 0.001), and use of a calcium channel blocker (AOR = 0.77; P = 0.01) were independently associated with decreased risk of RRF loss. The observations of demographic groups at risk and potentially modifiable factors and therapies have generated testable hypotheses regarding therapies that may preserve RRF among end-stage renal disease patients. C1 Univ Western Ontario, Dept Med, London, ON, Canada. Univ Western Ontario, Dept Epidemiol, London, ON, Canada. Univ Western Ontario, Dept Biostat, London, ON, Canada. Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. Vet Adm Med Ctr, Ann Arbor, MI 48105 USA. NIDDKD, Program Epidemiol, Div Kidney Urol & Hematol Dis, Bethesda, MD 20892 USA. RP Moist, LM (reprint author), London Hlth Sci Ctr, SSC Campus,375 South St, London, ON N6A 4G5, Canada. NR 44 TC 287 Z9 299 U1 0 U2 2 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 2000 VL 11 IS 3 BP 556 EP 564 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 286WV UT WOS:000085472600019 PM 10703680 ER PT J AU Lenz, O Elliot, SJ Stetler-Stevenson, WG AF Lenz, O Elliot, SJ Stetler-Stevenson, WG TI Matrix metalloproteinases in renal development and disease SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Review ID MESSENGER-RNA EXPRESSION; HUMAN NEUTROPHIL COLLAGENASE; GROWTH-FACTOR-BETA; TISSUE INHIBITOR; DIABETIC NEPHROPATHY; MESANGIAL CELLS; IV COLLAGEN; TGF-BETA; GENE-EXPRESSION; IN-VITRO C1 NCI, Extracellular Matrix Pathol Sect, DCS, LP,DCBDC,NIC,NIH, Bethesda, MD 20892 USA. Univ Miami, Sch Med, Renal Cell Biol Lab, Miami, FL USA. RP Stetler-Stevenson, WG (reprint author), NCI, Extracellular Matrix Pathol Sect, DCS, LP,DCBDC,NIC,NIH, Bldg 10,Room 2A33,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Stetler-Stevenson, William/H-6956-2012; Lenz, Oliver/M-4672-2016 OI Stetler-Stevenson, William/0000-0002-5500-5808; Lenz, Oliver/0000-0003-2997-3976 NR 126 TC 172 Z9 187 U1 1 U2 5 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 2000 VL 11 IS 3 BP 574 EP 581 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 286WV UT WOS:000085472600021 PM 10703682 ER PT J AU Baker, SG AF Baker, SG TI Analyzing a randomized cancer prevention trial with a missing binary outcome, an auxiliary variable, and all-or-none compliance SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE finasteride; nonignorable missing data; Prostate Cancer Prevention Trial; randomized trials ID TO-TREAT ANALYSIS; CLINICAL-TRIALS; SURVIVAL-DATA; NONIGNORABLE NONRESPONSE; REGRESSION-ANALYSIS; COST-EFFECTIVENESS; SURROGATE; MODELS; SUBJECT; AIDS AB The Prostate Cancer Prevention Trial is a randomized chemoprevention trial designed to compare the effect of daily finasteride versus placebo on prostate cancer determined by biopsy. Investigators have scheduled a biopsy at the end of the trial in 7 years or following a positive prostate-specific antigen (PSA) on annual screening, The analysis will need to adjust for two likely complications. First, some subjects will not receive a biopsy, depending in part whether or not they had a positive PSA. The indicator of positive PSA is called an auxiliary variable, which is a variable observed after randomization and prior to outcome. Second, starting soon after randomization, some subjects randomized to finasteride will stop taking their tablets, and some Subjects randomized to placebo will obtain finasteride outside of the trial. This type of noncompliance is called all-or-none. To adjust for these complications, we formulate the appropriate likelihoods and obtain closed-form maximum likelihood estimates and variances. Without these adjustments, estimates may be biased, two-sided type I errors above nominal levels, and coverage of confidence intervals below nominal levels. C1 NCI, Div Canc Prevent, Biometry Res Grp, Bethesda, MD 20892 USA. RP Baker, SG (reprint author), NCI, Div Canc Prevent, Biometry Res Grp, Bethesda, MD 20892 USA. NR 29 TC 25 Z9 25 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD MAR PY 2000 VL 95 IS 449 BP 43 EP 50 DI 10.2307/2669521 PG 8 WC Statistics & Probability SC Mathematics GA 328HR UT WOS:000087845100005 ER PT J AU Buyske, S Fagerstrom, R Ying, ZL AF Buyske, S Fagerstrom, R Ying, ZL TI A class of weighted log-rank tests for survival data when the event is rare SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE cancer screening; censoring; G-rho family; peto-prentice test ID PROSTATE-CANCER AB In many epidemiological and medical follow-up studies, a majority of study subjects do not experience the event of interest during the follow-up period. An important example is the ongoing prostate, lung, colorectal, and ovarian cancer screening trial of the National Cancer Institute. In such a situation, the widely used G(rho) family of weighted log-rank statistics essentially reduces to the special case of the (unweighted) log-rank statistics. We propose a simple modification to the G(rho) family that adapts to survival data with rare events, a concept that we formulate in terms of a small number of events at the study endpoint relative to the sample size. The usual asymptotic properties, including convergence in distribution of the standardized statistics to the standard normal, are obtained under the rare event formulation. Semiparametric transformation models forming sequences of contiguous alternatives are considered and, for each rho, a specific such model is identified so that the corresponding modified G(rho) Statistic is asymptotically efficient. Simulation studies show that the proposed statistics do behave differently from the original G(rho) statistics when the event rate during the study period is low and the former could lead to a substantial efficiency gain over the latter. Extensions to the G(rho,gamma) family and to the regression problem are also given. C1 Rutgers State Univ, Dept Stat, Piscataway, NJ 08854 USA. NCI, Biometry Res Grp, Bethesda, MD 20892 USA. RP Buyske, S (reprint author), Rutgers State Univ, Dept Stat, Piscataway, NJ 08854 USA. RI Buyske, Steven/B-8130-2009; OI Buyske, Steven/0000-0001-8539-5416 NR 21 TC 11 Z9 11 U1 0 U2 4 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD MAR PY 2000 VL 95 IS 449 BP 249 EP 258 DI 10.2307/2669542 PG 10 WC Statistics & Probability SC Mathematics GA 328HR UT WOS:000087845100026 ER PT J AU Weinberg, CR Dunson, DB AF Weinberg, CR Dunson, DB TI Some issues in assessing human fertility SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article ID FECUNDABILITY; CONCEPTION; MODEL; DETERMINANTS; PROBABILITY; PREGNANCY; EVENT; CYCLE; TIME C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Weinberg, CR (reprint author), NIEHS, Biostat Branch, POB 12233, Res Triangle Pk, NC 27709 USA. NR 32 TC 12 Z9 12 U1 0 U2 2 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD MAR PY 2000 VL 95 IS 449 BP 300 EP 303 DI 10.2307/2669552 PG 4 WC Statistics & Probability SC Mathematics GA 328HR UT WOS:000087845100036 ER PT J AU Panlilio, LV Weiss, SJ Schindler, CW AF Panlilio, LV Weiss, SJ Schindler, CW TI Effects of compounding drug-related stimuli: Escalation of heroin self-administration SO JOURNAL OF THE EXPERIMENTAL ANALYSIS OF BEHAVIOR LA English DT Article DE self-administration; stimulus compounding; stimulus control; drug abuse; incentive-motivation; nose poke; rat ID APPETITIVE-AVERSIVE INTERACTIONS; INTRAVENOUS HEROIN; DISCRIMINATIVE STIMULI; COCAINE; RATS; REINFORCEMENT; OPERANT; ADDICTION; BEHAVIOR AB Previous experiments have demonstrated that presenting independently established discriminative stimuli in compound can substantially increase operant responding maintained by food reinforcement or shock avoidance. Recently, this phenomenon was also shown to occur with cocaine selfadministration. The present study further assessed the generality of these stimulus-compounding effects by systematically replicating them with heroin self-administration. Rats' nose-poke responses produced intravenous heroin (0.025 mg/kg per infusion) on a variable-ratio schedule when either a tone or a light was present. In the absence of these stimuli, responding was not reinforced. Once discriminative control by the tone and light had been established, the stimuli were presented in compound under extinction (with heroin discontinued) or maintenance conditions (with heroin available during test-stimulus presentations). In extinction, the tone-light compound increased responding approximately threefold compared to tone or light alone. Under maintenance conditions, compounding increased heroin intake approximately twofold. These effects closely matched those obtained earlier with cocaine. This consistency across pharmacological classes and across drug and nondrug reinforcers further confirms that (a) self-administered drugs support conditioning and learning in a manner similar to that supported by other reinforcers; and (b) multiple drug-related cues interact in lawful and predictable ways to affect drug seeking and consumption. C1 Natl Inst Drug Abuse, Intramural Res Program, Behav Neurosci Branch, Preclin Pharmacol Sect, Baltimore, MD 21224 USA. American Univ, Washington, DC 20016 USA. RP Panlilio, LV (reprint author), Natl Inst Drug Abuse, Intramural Res Program, Behav Neurosci Branch, Preclin Pharmacol Sect, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. FU NIDA NIH HHS [DA-08651-01A1] NR 43 TC 29 Z9 29 U1 1 U2 2 PU SOC EXP ANALYSIS BEHAVIOR INC PI BLOOMINGTON PA INDIANA UNIV DEPT PSYCHOLOGY, BLOOMINGTON, IN 47405 USA SN 0022-5002 J9 J EXP ANAL BEHAV JI J. Exp. Anal. Behav. PD MAR PY 2000 VL 73 IS 2 BP 211 EP 224 DI 10.1901/jeab.2000.73-211 PG 14 WC Psychology, Biological; Behavioral Sciences; Psychology, Experimental SC Psychology; Behavioral Sciences GA 305MF UT WOS:000086543300007 PM 10784010 ER PT J AU Senderowicz, AM Sausville, EA AF Senderowicz, AM Sausville, EA TI Preclinical and clinical development of cyclin-dependent kinase modulators SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID BREAST-CARCINOMA CELLS; FLAVOPIRIDOL INDUCES APOPTOSIS; HUMAN EPIDERMOID CARCINOMA; CARBOXY-TERMINAL DOMAIN; CDK-ACTIVATING KINASE; RNA-POLYMERASE-II; PROTEIN-KINASE; SELECTIVE INHIBITOR; CANCER-CELLS; IN-VITRO AB In the last decade, the discovery and cloning of the cyclin-dependent kinases (cdks), key regulators of cell cycle progression, have led to the identification of novel modulators of cdk activity. Initial experimental results demonstrated that these cdk modulators are able to block cell cycle progression, induce apoptotic cell death, promote differentiation inhibit angiogenesis, and modulate transcription. Alteration of cdk activity may occur indirectly by affecting upstream pathways that regulate cdk activity: or directly by targeting the cdk; holoenzyme. Two direct cdk modulators, flavopiridol and UCN-01, are showing promising results in early clinical trials, in which the drugs reach plasma concentrations that can alter cdk activity vitro. Although modulation of cdk activity is a well-grounded concept and new cdk modulators are being assessed for clinical testing, important scientific questions remain to be addressed. These questions include whether one or more cdks should be inhibited, how cdk inhibitors should be combined with other chemotherapy agents, and which cdk substrates should be used to assess the biologic effects of these drugs in patients. Thus, modulation of cdk activity is an attractive target for cancer chemotherapy, and several agents that modulate cdk activity are in or are approaching entry into clinical trials. C1 NCI, DTP Clin Trials Unit, Dev Therapeut Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Senderowicz, AM (reprint author), NIH, Bldg 10,Rm 6N113, Bethesda, MD 20892 USA. NR 134 TC 375 Z9 383 U1 0 U2 8 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR 1 PY 2000 VL 92 IS 5 BP 376 EP 387 DI 10.1093/jnci/92.5.376 PG 12 WC Oncology SC Oncology GA 287NK UT WOS:000085512000008 PM 10699068 ER PT J AU Bailey, EJ Erwin, DO Belin, P AF Bailey, EJ Erwin, DO Belin, P TI Using cultural beliefs and patterns to improve mammography utilization among African-American women: The Witness Project SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE cultural beliefs; breast cancer; mammography utilization; African Americans ID CARE-SEEKING BEHAVIOR; BREAST-CANCER; RACIAL-DIFFERENCES; SURVIVAL; RACE; BARRIERS; STAGE; DIAGNOSIS; TRENDS; AGE AB Breast cancer and early detection of the disease is a significant issue for all women. Moreover, the sociocultural implications in the differential mortality rates increased interest in possible barriers to screening practices. Recently, a number of studies have investigated African Americans' cultural beliefs associated with breast cancer. This study is based upon qualitative focus group data gathered from 1989 to 1991 and 1996. This article provides focus group data that informed ct culturally competent community-based cancer education program for African-American women-the Witness Project (R). Analyses of the qualitative data along with the quantitative outcome data revealed a direct relationship between cultural beliefs and patterns with mammography utilization. The once perceived cultural barriers can actually be applied as a cultural intervention strategy to improve breast cancer screening initiatives designed specifically for African-American women. C1 Univ Arkansas Med Sci, Arkansas Res Ctr, Dept Surg Oncol, Little Rock, AR 72205 USA. RP Bailey, EJ (reprint author), NCI, Comprehens Minor Biomed Branch, 6116 Execut Plaza Blvd, Bethesda, MD 20892 USA. NR 36 TC 67 Z9 67 U1 1 U2 2 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD MAR PY 2000 VL 92 IS 3 BP 136 EP 142 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 444BY UT WOS:000169379100010 PM 10745644 ER PT J AU Sher, L AF Sher, L TI The placebo effect and endogenous opioids SO JOURNAL OF THE ROYAL SOCIETY OF MEDICINE LA English DT Letter C1 NIMH, Bethesda, MD 20892 USA. RP Sher, L (reprint author), NIMH, Bldg 10,Room 3S-231,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1M 8AE, ENGLAND SN 0141-0768 J9 J ROY SOC MED JI J. R. Soc. Med. PD MAR PY 2000 VL 93 IS 3 BP 158 EP 158 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 293VV UT WOS:000085874900015 PM 10741321 ER PT J AU Enquist, EG Stratakis, CA Rushton, HG Walther, MM AF Enquist, EG Stratakis, CA Rushton, HG Walther, MM TI Laparoscopic diagnosis and clinical management of a solitary nonpalpable cryptorchid testicle in a postpubertal male SO JOURNAL OF UROLOGY LA English DT Article DE laparoscopy; cryptorchidism; testis C1 Natl Canc Inst, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, NIH, Bethesda, MD USA. Childrens Natl Med Ctr, Dept Pediat Urol, Washington, DC 20010 USA. RP Enquist, EG (reprint author), Natl Canc Inst, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NR 3 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAR PY 2000 VL 163 IS 3 BP 959 EP 960 DI 10.1016/S0022-5347(05)67863-9 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 282YX UT WOS:000085250300087 PM 10688031 ER PT J AU Blagosklonny, MV Dixon, SC Figg, WD AF Blagosklonny, MV Dixon, SC Figg, WD TI Efficacy of microtubule-active drugs followed by ketoconazole in human metastatic prostate cancer cell lines SO JOURNAL OF UROLOGY LA English DT Article DE prostate cancer; vinblastine; paclitaxel; ketoconazole ID IN-VITRO; PACLITAXEL TAXOL; PC-3; PHOSPHORYLATION; ESTRAMUSTINE; CHEMOTHERAPY; VINBLASTINE; APOPTOSIS; MUTATIONS; THERAPY AB Purpose: Once a relapse occurs following primary endocrine treatment, metastatic prostate cancer is one of the most therapy-resistant human neoplasms. Ketoconazole is used for complete androgen deprivation, and recent data suggest it has direct activity against prostate cancer cells. Materials and Methods: LNCaP, DU145, and PC3 cells, human prostate cancer cell lines, and HL60, a human leukemia cell line, were lysed and soluble proteins were harvested. Cells were plated in 96-well flat bottom plates and then exposed to the pharmacological agents, ketoconazole, vinblastine and paclitaxel. DNA synthesis was monitored by H-3-thymidine incorporation. Results: We demonstrate that ketoconazole exerts a cytostatic effect on a panel of human prostate cancer cell lines, with IC50 of 4 to 5 mu g./ml., 12 mu g./ml., and 25 mu g./ml. for LNCaP, PC3/PC3M, and DU145 cells, respectively. On the other hand, using microtubule-active drugs, vinblastine and paclitaxel, we found that PC3M and PC3 cells were more resistant than either DU145 or LNCaP cells. This resistance was associated with a lesser degree of Raf-1 and Bcl-2 phosphorylation following exposure to microtubule-active drugs. Combinations of microtubule-active drugs with ketoconazole were a beneficial treatment in DU145 cancer cells. Furthermore, ketoconazole blocked recovery of all the prostate cancer cell lines following 24 hours-pulse treatment with vinblastine. Conclusion: Pulse-administration of vinblastine followed by continuous administration of ketoconazole warrants investigation in the treatment of hormone-independent metastatic prostate cancer. C1 NCI, Div Clin Sci, Med Branch, NIH, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Div Clin Sci, Med Branch, NIH, 10 Ctr Dr,Bldg 10,Room 5A01, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 26 TC 26 Z9 26 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAR PY 2000 VL 163 IS 3 BP 1022 EP 1026 DI 10.1016/S0022-5347(05)67875-5 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 282YX UT WOS:000085250300098 PM 10688042 ER PT J AU Semba, CP Bakal, CW Calis, KA Grubbs, GE Hunter, DW Matalon, TAS Murphy, TP Stump, DC Thomas, S Warner, DL AF Semba, CP Bakal, CW Calis, KA Grubbs, GE Hunter, DW Matalon, TAS Murphy, TP Stump, DC Thomas, S Warner, DL CA Adivsory Panel Catheter Directed T TI Alteplase as an alternative to urokinase SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE alteplase; thrombolysis; tissue-type plasminogen activator; urokinase ID TISSUE-PLASMINOGEN-ACTIVATOR; DEEP-VEIN THROMBOSIS; CATHETER-DIRECTED THROMBOLYSIS; CENTRAL VENOUS CATHETERS; RT-PA; HEMODIALYSIS-PATIENTS; LOCAL THROMBOLYSIS; RANDOMIZED TRIAL; BYPASS GRAFTS; THERAPY C1 Stanford Univ, Med Ctr, Dept Intervent Radiol, Stanford, CA 94305 USA. Beth Israel Med Ctr, Dept Radiol, New York, NY 10003 USA. NIH, Bethesda, MD 20892 USA. Naples Cardiovasc Inst, Naples, FL USA. Fairview Univ, Ctr Med, Dept Radiol, Minneapolis, MN USA. New York Med Coll, Valhalla, NY 10595 USA. Rhode Isl Med Coll, Providence, RI USA. Genentech Inc, S San Francisco, CA 94080 USA. No Gen Hosp, Sheffield S5 7AU, S Yorkshire, England. Univ Illinois, Northbrook, IL USA. RP Semba, CP (reprint author), Stanford Univ, Med Ctr, Dept Intervent Radiol, H-3646, Stanford, CA 94305 USA. NR 42 TC 46 Z9 47 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD MAR PY 2000 VL 11 IS 3 BP 279 EP 287 DI 10.1016/S1051-0443(07)61418-3 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 294UE UT WOS:000085928100001 PM 10735420 ER PT J AU Dyer, NW Ching, B Bloom, ME AF Dyer, NW Ching, B Bloom, ME TI Nonsuppurative meningoencephalitis associated with Aleutian mink disease parvovirus infection in ranch mink SO JOURNAL OF VETERINARY DIAGNOSTIC INVESTIGATION LA English DT Article ID ACUTE INTERSTITIAL PNEUMONIA; MUSTELA-VISON; LESIONS; PATHOGENICITY; FERRETS; VIRUS; KITS AB Severe nonsuppurative meningoencephalitis associated with Aleutian mink disease parvovirus (ADV) infection was observed in adult ranch mink. Brain lesions included severe, locally extensive to coalescing lymphoplasmacytic meningoencephalitis with accompanying gliosis, satellitosis, and mild extension of inflammation into the leptomeninges. ADV was identified in mesenteric lymph node, spleen, brain, and liver of affected mink by polymerase chain reaction techniques. Sequences of the ADV isolate (TH5) revealed 2 unique residues in the region of the viral genome that determines pathogenicity. These findings suggest that certain strains of ADV may preferentially cause disease in the nervous system. ADV infection should be considered in the differential diagnosis of neurologic disorders in mink. C1 N Dakota State Univ, Vet Diagnost Lab, Fargo, ND 58105 USA. NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. RP Dyer, NW (reprint author), N Dakota State Univ, Vet Diagnost Lab, Fargo, ND 58105 USA. NR 24 TC 11 Z9 11 U1 0 U2 4 PU AMER ASSOC VETERINARY LABORATORY DIAGNOSTICIANS INC PI TURLOCK PA PO BOX 1522, TURLOCK, CA 95381 USA SN 1040-6387 J9 J VET DIAGN INVEST JI J. Vet. Diagn. Invest. PD MAR PY 2000 VL 12 IS 2 BP 159 EP 162 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA 297YH UT WOS:000086110300012 PM 10730948 ER PT J AU Zheng, ZM Baker, CC AF Zheng, ZM Baker, CC TI Parameters that affect in vitro splicing of bovine papillomavirus type 1 late pre-mRNAs SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE RNA splicing; papillomaviruses; gene expression; tumor viruses ID MESSENGER-RNA PRECURSORS; IMMUNODEFICIENCY-VIRUS TYPE-1; POLYMERASE; SUPPRESSOR; EXTRACTS; INVITRO; EXON AB During the course of study on regulated viral pre-mRNA splicing, an in vitro RNA splicing assay was developed to analyze how an exonic splicing enhancer stimulates splicing of bovine papillomavirus type 1 (BPV-1) late pre-mRNAs. The optimal concentration of HeLa nuclear extract (HNE) in a standard RNA splicing reaction depends on the individual substrate pre-mRNA. Splicing of a BPV-1 late pre-mRNA required 40% HNE and 2 h incubation at 30 degrees C. Higher HNE was detrimental to splicing and longer incubation times lead to RNA degradation. In the reaction containing 40% EDTA-treated HNE, 1.5-3.0 mM Mg2+ or 3 mM Mn2+, but not Co2+, were required to catalyze an efficient splicing reaction. Surprisingly, EDTA-untreated HNE in the absence of exogenous Mg2+ catalyzed very efficiently splicing of the RNA. Addition of Mg2+ from 0.1 to 0.5 mM, only enhanced slightly the splicing in EDTA-untreated HNE and excessive Mg2+ concentration (above 1.5 mM) in the reaction resulted in production of aberrant splicing products or intermediates. In contrast, addition of Mn2+ to EDTA-untreated HNE severely suppressed splicing. In addition, it was observed that the RNA transcribed from vector sequences downstream of the polylinker region of pSP72 vector, when connected to the 3' terminus of chimeric Drosophila doublesex-BPV-1 SE1 pre-mRNAs, suppressed dramatically splicing. RNA transcribed from the pSP72 polylinker region, when supplied in trans, also suppressed splicing. These results suggest that a DNA template used to make RNA transcripts should avoid these sequences as much as possible. Published by Elsevier Science B.V. C1 NCI, Basic Res Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Zheng, ZM (reprint author), NCI, Basic Res Lab, Div Basic Sci, NIH, Bldg 41,Rm D305, Bethesda, MD 20892 USA. NR 27 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD MAR PY 2000 VL 85 IS 1-2 BP 203 EP 214 DI 10.1016/S0166-0934(99)00172-X PG 12 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 290WY UT WOS:000085701900021 PM 10716353 ER PT J AU Sorensen, AB Lund, AH Ethelberg, S Copeland, NG Jenkins, NA Pedersen, FS AF Sorensen, AB Lund, AH Ethelberg, S Copeland, NG Jenkins, NA Pedersen, FS TI Sint1, a common integration site in SL3-3-induced T-cell lymphomas, harbors a putative proto-oncogene with homology to the septin gene family SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; MESSENGER-RNA DEGRADATION; RETROVIRAL INTEGRATION; CPG ISLANDS; LINKAGE MAP; C-MYC; MOUSE; PROVIRUSES; ACTIVATION; SEQUENCE AB The murine retrovirus SL3-3 is a potent inducer of T-cell lymphomas when inoculated into susceptible newborn mice. Previously, DNAs from twenty SL3-3-induced tumors were screened by PCR for provirus integration sites. Two out of 20 tumors demonstrated clonal provirus insertion into a common region. This region has now been isolated and characterized. The region, named SL3-3 integration site 1 (Sint1), maps to the distal end of mouse chromosome 11, corresponding to human chromosome 17q25, and may be identical to a mouse mammary tumor virus integration site in a T-cell lymphoma, Pad3. Two overlapping genomic lambda clones spanning about 35 kb were isolated and used as a starting point for a search for genes in the neighborhood of the virus integration sites. A genomic fragment was used as a hybridization probe to isolate a 3-kb cDNA clone, the expression of which was upregulated in one of two tumors harboring a provirus in Sint1, The cDNA clone is predicted to encode a protein which shows 97.0% identity to a human septin-like protein encoded by a gene which has been found as a fusion partner gene of MLL in an acute myeloid leukemia with a t(11;17)(q23;q25). Together these findings raise the possibility that a proto-oncogene belonging to the septin family, and located about 15 kb upstream of the provirus integration sites, is involved in murine leukemia virus-induced T-cell lymphomagenesis. C1 Univ Aarhus, Dept Mol & Struct Biol, DK-8000 Aarhus C, Denmark. Univ Aarhus, Dept Med Microbiol & Immunol, DK-8000 Aarhus, Denmark. NCI, Frederick Canc Res & Dev Ctr, Mammalian Genet Lab, ABL,Basic Res Program, Frederick, MD 21702 USA. RP Pedersen, FS (reprint author), Univ Aarhus, Dept Mol & Struct Biol, CF Mollers Alle,Bldg 130, DK-8000 Aarhus C, Denmark. RI Sorensen, Annette/B-6955-2008; Lund, Anders/F-4786-2014; OI Sorensen, Annette/0000-0002-2462-6281; Lund, Anders/0000-0002-7407-3398 NR 39 TC 32 Z9 34 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 2000 VL 74 IS 5 BP 2161 EP 2168 DI 10.1128/JVI.74.5.2161-2168.2000 PG 8 WC Virology SC Virology GA 283RT UT WOS:000085289900011 PM 10666245 ER PT J AU Waziri, A Soldan, SS Graf, MD Nagle, J Jacobson, S AF Waziri, A Soldan, SS Graf, MD Nagle, J Jacobson, S TI Characterization and sequencing of prototypic human T-lymphotropic virus type 1 (HTLV-1) from an HTLV-1/2 seroindeterminate patient SO JOURNAL OF VIROLOGY LA English DT Article ID CELL LEUKEMIA-VIRUS; SPASTIC PARAPARESIS; BLOOD-DONORS; I PROVIRUS; ANTIBODIES; PROTEASE; DNA AB Serological screening for human T-lymphotropic virus type 1 (HTLV-1) parallels the standard screening process for human immunodeficiency virus (HIV), in which samples found positive by enzyme-linked immunosorbent assay (ELISA) are confirmed with a modified Western blot procedure. There are a significant number of cases in which HTLV-1/2 ELISA-positive specimens demonstrate an incomplete banding pattern on this Western blot. Individuals providing these atypical antibody responses are categorized as seroindeterminate for HTLV-1/2. Although HTLV-1 genomic sequences are readily detectable in the peripheral blood lymphocytes (PBL) of seropositive individuals, previous studies have repeatedly demonstrated that PBL from the vast majority of HTLV-1/2 seroindeterminate individuals are PCR negative for HTLV-1, As a result, identification of the agent responsible for this indeterminate reactivity has been of interest. We have generated an HTLV-1-positive B-cell line (SI-1 B) from one of these seroindeterminate individuals. Previous screening for HTLV-1 in PBL from this patient had been routinely negative by primary PCR; however, HTLV-1 far had been periodically detected by nested PCR. DNA sequence data generated with genomic DNA from the SI-1 B cell line and HTLV-1-specific primers demonstrated the presence of a full-length viral genome with >97% homology to the Cosmopolitan form of HTLV-1. A 12-bp deletion was identified in the 3'-gag/5'-prot region, which would predict translation of altered or nonfunctional proteins from these genes. We propose that this HTLV-1/2-seroindeterminate patient is infected with a prototypic form of HTLV-1 at an extremely low viral load and that this finding may explain HTLV-1/2 seroindeterminate reactivity in at least a subset of these individuals. C1 NINDS, Viral Immunol Sect, Howard Hughes Med Inst, Res Scholars Program,NIH, Bethesda, MD 20892 USA. NINDS, Core DNA Sequencing Facil, Howard Hughes Med Inst, NIH,Res Scholars Program, Bethesda, MD 20892 USA. George Washington Univ, Inst Biomed Sci, Dept Genet, Washington, DC 20052 USA. RP Jacobson, S (reprint author), NINDS, Viral Immunol Sect, Howard Hughes Med Inst, Res Scholars Program,NIH, 9000 Rockville Pike,Room 5B-16, Bethesda, MD 20892 USA. FU NINDS NIH HHS [N01-NS-7-2372] NR 21 TC 18 Z9 19 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 2000 VL 74 IS 5 BP 2178 EP 2185 DI 10.1128/JVI.74.5.2178-2185.2000 PG 8 WC Virology SC Virology GA 283RT UT WOS:000085289900013 PM 10666247 ER PT J AU Betakova, T Moss, B AF Betakova, T Moss, B TI Disulfide bonds and membrane topology of the vaccinia virus A17L envelope protein SO JOURNAL OF VIROLOGY LA English DT Article ID INTERMEDIATE COMPARTMENT; ENDOPLASMIC-RETICULUM; VIRION MORPHOGENESIS; STAGE; GENE AB The envelope protein encoded by the vaccinia virus A17L open reading frame is essential for virion assembly. Our mutagenesis studies indicated that cysteines 101 and 121 form an intramolecular disulfide bond and that cysteine 178 forms an intermolecular disulfide linking two A17L molecules. This arrangement of disulfide bonds has important implications for the topology of the A17L protein and supports a two transmembrane model in which cysteines 101 and 121 are intraluminal and cysteine 178 is cytoplasmic. The structure of the A17L protein, however, was not dependent on these disulfide bonds, as a recombinant vaccinia virus with all three cysteine codons mutated to serines retained infectivity. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. Slovak Acad Sci, Inst Virol, Bratislava 84246, Slovakia. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 4 Ctr Dr,MSC 0445, Bethesda, MD 20892 USA. NR 27 TC 18 Z9 19 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 2000 VL 74 IS 5 BP 2438 EP 2442 DI 10.1128/JVI.74.5.2438-2442.2000 PG 5 WC Virology SC Virology GA 283RT UT WOS:000085289900042 PM 10666276 ER PT J AU Rajan, L Broussard, D Lozano, M Lee, CG Kozak, CA Dudley, JP AF Rajan, L Broussard, D Lozano, M Lee, CG Kozak, CA Dudley, JP TI The c-myc locus is a common integration site in type B retrovirus-induced T-cell lymphomas SO JOURNAL OF VIROLOGY LA English DT Article ID MAMMARY-TUMOR VIRUS; LONG TERMINAL REPEAT; MURINE LEUKEMIA-VIRUS; THYMIC LYMPHOMAS; INSERTIONAL MUTAGENESIS; TRANSGENIC MICE; REGION; PROVIRUSES; ACTIVATION; TRANSLOCATIONS AB Type B leukemogenic virus (TBLV) induces rapidly appearing T-cell leukemias. TBLV insertions near the c-myc gene were detectable in 2 of 30 tumors tested, whereas 80% of the tumors showed c-myc overexpression. TBLV insertions on chromosome 15 (including a newly identified locus, Pad7) may cause c-myc overexpression by cis-acting effects at a distance. C1 Univ Texas, Sect Mol Genet & Microbiol, Austin, TX 78705 USA. Univ Texas, Inst Mol & Cellular Biol, Austin, TX 78705 USA. NIAID, LMM, NIH, Bethesda, MD 20892 USA. RP Dudley, JP (reprint author), Univ Texas, Sect Mol Genet & Microbiol, 100 W 24th St, Austin, TX 78705 USA. FU NCI NIH HHS [CA34780] NR 38 TC 17 Z9 17 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 2000 VL 74 IS 5 BP 2466 EP 2471 DI 10.1128/JVI.74.5.2466-2471.2000 PG 6 WC Virology SC Virology GA 283RT UT WOS:000085289900048 PM 10666282 ER PT J AU Seth, A Ourmanov, I Schmitz, JE Kuroda, MJ Lifton, MA Nickerson, CE Wyatt, L Carroll, M Moss, B Venzon, D Letvin, NL Hirsch, VM AF Seth, A Ourmanov, I Schmitz, JE Kuroda, MJ Lifton, MA Nickerson, CE Wyatt, L Carroll, M Moss, B Venzon, D Letvin, NL Hirsch, VM TI Immunization with a modified vaccinia virus expressing simian immunodeficiency virus (SIV) Gag-Pol primes for an anamnestic Gag-specific cytotoxic T-lymphocyte response and is associated with reduction of viremia after SIV challenge SO JOURNAL OF VIROLOGY LA English DT Article ID RHESUS MACAQUES; VIRAL LOAD; PROTECTIVE EFFICACY; CYNOMOLGUS MONKEYS; ENVELOPE PROTEIN; IMMUNE-RESPONSES; TYPE-1 INFECTION; REPLICATION; ANKARA; PLASMA AB The immunogenicity and protective efficacy of a modified vaccinia virus Ankara (MVA) recombinant expressing the simian immunodeficiency virus (SIV) Gag-Pol proteins (MVA-gag-pol) was explored in rhesus monkeys expressing the major histocompatibility complex (MHC) class I allele, MamuA*01. Macaques received four sequential intramuscular immunizations with the MVA-gag-pol recombinant virus or nonrecombinant MVA as a control. Gag-specific cytotoxic T-lymphocyte (CTL) responses were detected in all MVA-gag-pol-immunized macaques by both functional assays and flow cytometric analyses of CD8(+) T cells that hound a specific MHC complex class I-peptide tetramer, with levels peaking after the second immunization. Following challenge with uncloned SIVsmE660, all macaques became infected; however, viral load set points were loner in MVA-gag-pol-immunized macaques than in the MVA-immunized control macaques. MVA-gag-pol-immunized macaques exhibited a rapid and substantial anamnestic CTL response specific for the p11C, C-M Gag epitope. The level at which CTL stabilized after resolution of primary viremia correlated inversely with plasma viral load set point (P = 0.03). Most importantly, the magnitude of reduction in viremia in the vaccinees was predicted by the magnitude of the vaccine-elicited CTL response prior to SIV challenge. C1 NIAID, Viral Dis Lab, NIH, Rockville, MD 20852 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02115 USA. NIAID, Mol Microbiol Lab, NIH, Rockville, MD 20852 USA. NCI, Div Clin Sci, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. RP Hirsch, VM (reprint author), NIAID, Viral Dis Lab, NIH, Twinbrook II Facil,12441 Parklawn Dr, Rockville, MD 20852 USA. RI Venzon, David/B-3078-2008 FU NIAID NIH HHS [AI-26507, AI-85343, P01 AI026507, U01 AI026507] NR 55 TC 123 Z9 123 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 2000 VL 74 IS 6 BP 2502 EP 2509 DI 10.1128/JVI.74.6.2502-2509.2000 PG 8 WC Virology SC Virology GA 286LH UT WOS:000085447100002 PM 10684264 ER PT J AU Lifson, JD Rossio, JL Arnaout, R Li, L Parks, TL Schneider, DK Kiser, RF Coalter, VJ Walsh, G Imming, RJ Fisher, B Flynn, BM Bischofberger, N Piatak, M Hirsch, VM Nowak, MA Wodarz, D AF Lifson, JD Rossio, JL Arnaout, R Li, L Parks, TL Schneider, DK Kiser, RF Coalter, VJ Walsh, G Imming, RJ Fisher, B Flynn, BM Bischofberger, N Piatak, M Hirsch, VM Nowak, MA Wodarz, D TI Containment of simian immunodeficiency virus infection: Cellular immune responses and protection from rechallenge following transient postinoculation antiretroviral treatment SO JOURNAL OF VIROLOGY LA English DT Article ID T-CELL; RHESUS MACAQUES; VIRAL LOAD; CD40 LIGAND; MEMORY; THERAPY; VIREMIA; REPLICATION; MICE; IMMUNIZATION AB To better understand the viral and host factors involved in the establishment of persistent productive infection by primate lentiviruses, we varied the time of initiation and duration of postinoculation antiretroviral treatment with tenofovir {9-[2-(R)-(phosphonomethoxy)propyl]adenine} while performing intensive virologic and immunologic monitoring in rhesus macaques, inoculated intravenously with simian immunodeficiency virus SIVsmE660. Postinoculation treatment did not block the initial infection, but we identified treatment regimens that prevented the establishment of persistent productive infection, as judged by the absence of measurable plasma viremia following drug discontinuation. While immune responses were heterogeneous, animals in which treatment resulted in prevention of persistent productive infection showed a higher frequency and higher levels of SIV-specific lymphocyte proliferative responses during the treatment period compared to control animals, despite the absence of either detectable plasma viremia or seroconversion. Animals protected front the initial establishment of persistent productive infection were also relatively or completely protected from subsequent homologous rechallenge. Even postinoculation treatment regimens that did not prevent establishment of persistent infection resulted in downmodulation of the level of plasma viremia following treatment cessation, compared to the viremia seen in untreated control animals, animals treated with regimens known to be ineffective, or the cumulative experience with the natural history of plasma viremia following infection with SIVsmE660. The results suggest that the host may be able to effectively control SIV infection if the initial exposure occurs under favorable conditions of low viral burden and in the absence of ongoing high level cytopathic infection of responding cells. These findings may be particularly important in relation to prospects for control of primate lentiviruses in the settings of both prophylactic and therapeutic vaccination for prevention of AIDS. C1 NCI, Retroviral Pathogenesis Lab, AIDS Vaccine Program, SAIC Frederick,Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Inst Adv Study, Program Theoret Biol, Princeton, NJ 08540 USA. NCI, Anim Sci Branch, Bethesda, MD 20892 USA. NIAID, Mol Microbiol Lab, Rockville, MD 20852 USA. RP Lifson, JD (reprint author), NCI, Retroviral Pathogenesis Lab, AIDS Vaccine Program, SAIC Frederick,Frederick Canc Res & Dev Ctr, Bldg 535,5th Floor, Frederick, MD 21702 USA. RI Nowak, Martin/A-6977-2008 FU NCI NIH HHS [N01-CO-56000] NR 59 TC 136 Z9 137 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 2000 VL 74 IS 6 BP 2584 EP 2593 DI 10.1128/JVI.74.6.2584-2593.2000 PG 10 WC Virology SC Virology GA 286LH UT WOS:000085447100010 PM 10684272 ER PT J AU Ourmanov, I Brown, CR Moss, B Carroll, M Wyatt, L Pletneva, L Goldstein, S Venzon, D Hirsch, VM AF Ourmanov, I Brown, CR Moss, B Carroll, M Wyatt, L Pletneva, L Goldstein, S Venzon, D Hirsch, VM TI Comparative efficacy of recombinant modified vaccinia virus Ankara expressing simian immunodeficiency virus (SIV) Gag-Pol and/or Env in macaques challenged with pathogenic SIV SO JOURNAL OF VIROLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; CYTOTOXIC T-LYMPHOCYTES; PROTECTIVE IMMUNITY; CYNOMOLGUS MONKEYS; ENVELOPE PROTEIN; ATTENUATED SIV; HIV; IMMUNIZATION; REPLICATION; INFECTION AB Prior studies demonstrated that immunization of macaques with simian immunodeficiency virus (SIV) Gag-Pol and Env recombinants of the attenuated poxvirus modified vaccinia virus Ankara (MVA) provided protection from high levels of viremia and AIDS following challenge with a pathogenic strain of SIV (V. M. Hirsch et al., J. Virol. 70:3741-3752, 1996), This MVA-SIV recombinant expressed relatively low levels of the Gag-Pol portion of the vaccine. To optimize protection, second-generation recombinant MVAs that expressed high levels of either Gag-Pol (MVA-gag-pol) or Env (MVA-env), alone or in combination (MVA-gag-pol-env), were generated. A cohort of 24 macaques was immunized with recombinant or nonrecombinant MVA (four groups of six animals) and was challenged with 50 times the dose at which 50% of macaques are infected with uncloned pathogenic SIVsmE660. Although all animals became infected postchallenge, plasma viremia was significantly reduced in animals that received the MVA-SN recombinant vaccines as compared with animals that received nonrecombinant MVA (P = 0.0011 by repeated-measures analysis of variance). The differences in the degree of virus suppression achieved by the three MVA-SIV vaccines were not significant. Most importantly, the reduction in levels of viremia resulted in a significant increase in median (P < 0.05 by Student's t test) and cumulative (P = 0.010 by log rank test) survival. These results suggest that recombinant MVA has considerable potential as a vaccine vector for human AIDS. C1 NIAID, Mol Microbiol Lab, Rockville, MD 20852 USA. NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. NCI, Data Management Sect, Bethesda, MD 20892 USA. RP Hirsch, VM (reprint author), NIAID, Mol Microbiol Lab, Twinbrook II Facil,12441 Parklawn Dr, Rockville, MD 20852 USA. RI Venzon, David/B-3078-2008 NR 75 TC 133 Z9 136 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 2000 VL 74 IS 6 BP 2740 EP 2751 DI 10.1128/JVI.74.6.2740-2751.2000 PG 12 WC Virology SC Virology GA 286LH UT WOS:000085447100028 PM 10684290 ER PT J AU Jobbagy, Z Garfield, S Baptiste, L Eiden, MV Anderson, WB AF Jobbagy, Z Garfield, S Baptiste, L Eiden, MV Anderson, WB TI Subcellular redistribution of Pit-2 P-i transporter/amphotropic leukemia virus (A-MuLV) receptor in A-MuLV-infected NIH 3T3 fibroblasts: Involvement in superinfection interference SO JOURNAL OF VIROLOGY LA English DT Article ID PROTEIN-KINASE-C; MURINE RETROVIRUSES; PHOSPHATE TRANSPORTER; CELLULAR RECEPTOR; HAMSTER-CELLS; EPSILON; CLONING; FAMILY; ENTRY AB Amphotropic murine leukemia virus (A-MuLV) utilizes the Pit-2 sodium-dependent phosphate transporter as a cell surface receptor to infect mammalian cells. Previous studies established that infection of cells with A-MuLV resulted in the specific down-modulation of phosphate uptake mediated by Pit-2 and in resistance to superinfection with A-MuLV, To study the mechanisms underlying these phenomena, we constructed plasmids capable of efficiently expressing epsilon epitope- and green fluorescent protein (GFP)-tagged human Pit-2 proteins in mammalian cells. Overexpression of epsilon-epitope-tagged Pit-2 transporters in NIH 3T3 cells resulted in a marked increase in sodium-dependent P-i uptake. This increase in P-i uptake was specifically blocked by A-MuLV infection but not by infection with ecotropic MuLV (E-MuLV) (which utilizes a cationic amino acid transporter, not Pit-2, as a cell surface receptor). These data, together with the finding that the tagged Pit-2 transporters retained their A-MuLV receptor function, indicate that the insertion of epitope tags does not affect either retrovirus receptor or P-i transporter function. The overexpressed epitope-tagged transporters were detected in cell lysates, by Western blot analysis using both epsilon-epitope- and GFP-specific antibodies as well as with Pit-2 antiserum. Both the epitope- and GFP-tagged transporters showed almost exclusive plasma membrane localization when expressed in NIH 3T3 cells, as determined by laser scanning confocal microscopy, Importantly, when NIH 3T3 cells expressing these proteins were productively infected with A-MuLV, the tagged transporters and receptors were no longer detected in the plasma membrane but rather were localized to a punctate structure within the cytosolic compartment distinct from Golgi, endoplasmic reticulum, endosomes, lysosomes, and mitochondria. The intracellular Pit-2 pool colocalized with the virus in A-MuLV-infected cells. A similar redistribution of the tagged Pit-2 proteins was not observed following infection with E-MuLV, indicating that the redistribution of Pit-2 is not directly attributable to general effects associated with retroviral infection but rather is a specific consequence of A-MuLV-Pit-2 interactions. C1 NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NIMH, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. RP Anderson, WB (reprint author), NCI, Cellular Oncol Lab, NIH, Bldg 37,Room 1E14,37 Convent Dr, Bethesda, MD 20892 USA. NR 30 TC 25 Z9 25 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 2000 VL 74 IS 6 BP 2847 EP 2854 DI 10.1128/JVI.74.6.2847-2854.2000 PG 8 WC Virology SC Virology GA 286LH UT WOS:000085447100039 PM 10684301 ER PT J AU Ono, A Orenstein, JM Freed, EO AF Ono, A Orenstein, JM Freed, EO TI Role of the gag matrix domain in targeting human immunodeficiency virus type 1 assembly SO JOURNAL OF VIROLOGY LA English DT Article ID AMINO-ACID SUBSTITUTION; VIRAL MEMBRANE-PROTEINS; TRANS GOLGI CISTERNAE; MURINE LEUKEMIA-VIRUS; INTRACELLULAR-TRANSPORT; ENVELOPE GLYCOPROTEIN; ENDOPLASMIC-RETICULUM; PLASMA-MEMBRANE; VESICULAR TRANSPORT; PARTICLE-PRODUCTION AB Human immunodeficiency virus type 1 (HIV-1) particle formation and the subsequent initiation of protease-mediated maturation occur predominantly on the plasma membrane. However, the mechanism by which HIV-1 assembly is targeted specifically to the plasma membrane versus intracellular membranes is largely unknown. Previously, we observed that mutations between residues 84 and 88 of the matrix (MA) domain of HIV-1 Gag cause a retargeting of virus particle formation to an intracellular site. In this study, we demonstrate that the mutant virus assembly occurs in the Golgi or in post-Golgi vesicles. These particles undergo core condensation in a protease-dependent manner, indicating that virus maturation can occur not only on the plasma membrane but also in the Golgi or post-Golgi vesicles. The intracellular assembly of mutant particles is dependent on Gag myristylation but is not influenced by p6(Gag) or envelope glycoprotein expression, Previous characterization of viral revertants suggested a functional relationship between the highly basic domain of MA (amino acids 17 to 31) and residues 84 to 88, We now demonstrate that mutations in the highly basic domain also retarget virus particle formation to the Golgi or post-Golgi vesicles. Although the basic domain has been implicated in Gag membrane binding, no correlation was observed between the impact of mutations on membrane binding and Gag targeting, indicating that these two functions of MA are genetically separable. Plasma membrane targeting of Gag proteins with mutations in either the basic domain or between residues 84 and 88 was rescued by coexpression with wild-type Gag; however, the two groups of MA mutants could not rescue each other. We propose that the highly basic domain of MA contains a major determinant of HIV-1 Gag plasma membrane targeting and that mutations between residues 84 and 88 disrupt plasma membrane targeting through an effect on the basic domain. C1 NIAID, NIH, Mol Microbiol Lab, Bethesda, MD 20892 USA. George Washington Univ, Med Ctr, Dept Pathol, Washington, DC 20037 USA. RP Freed, EO (reprint author), NIAID, NIH, Mol Microbiol Lab, Bldg 4,Rm 307,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 71 TC 166 Z9 172 U1 0 U2 3 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 2000 VL 74 IS 6 BP 2855 EP 2866 DI 10.1128/JVI.74.6.2855-2866.2000 PG 12 WC Virology SC Virology GA 286LH UT WOS:000085447100040 PM 10684302 ER PT J AU Akari, H Arold, S Fukumori, T Okazaki, T Strebel, K Adachi, A AF Akari, H Arold, S Fukumori, T Okazaki, T Strebel, K Adachi, A TI Nef-induced major histocompatibility complex class I down-regulation is functionally dissociated from its virion incorporation, enhancement of viral infectivity, and CD4 down-regulation SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG-TERM SURVIVOR; TYPE-1 NEF; HIV-1 NEF; N-TERMINUS; CELL-LINE; PROTEIN; GENE; GENERATION; PATHOGENICITY AB The N-terminal alpha-helix domain of the human immunodeficiency virus type 1 (HIV-1) Nef protein plays important roles in enhancement of viral infectivity, virion incorporation of Nef, and the down-regulation of major histocompatibility complex class I (MHC-I) expression on cell surfaces. In this study, we demonstrated that Met 20 in the alpha-helix domain was indispensable for the ability of Nef to modulate MHC-I expression but not for other events. We also showed that Met 20 was unnecessary for the down-regulation of CD4. These findings indicate that the region governing MHC-I down-regulation is proximate in the alpha-helix domain but is dissociated functionally from that determining enhancement of viral infectivity, virion incorporation of Nef, and CD4 down-regulation. C1 Univ Tokushima, Sch Med, Dept Virol, Tokushima 7708503, Japan. NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA. RP Akari, H (reprint author), Univ Tokushima, Sch Med, Dept Virol, 3 Kuramoto, Tokushima 7708503, Japan. EM akari@basic.med.tokushima-u.ac.jp NR 33 TC 93 Z9 94 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD MAR PY 2000 VL 74 IS 6 BP 2907 EP 2912 DI 10.1128/JVI.74.6.2907-2912.2000 PG 6 WC Virology SC Virology GA 286LH UT WOS:000085447100048 PM 10684310 ER PT J AU Davis, MD Wu, JW Owens, RA AF Davis, MD Wu, JW Owens, RA TI Mutational analysis of adeno-associated virus type 2 Rep68 protein endonuclease activity on partially single-stranded substrates SO JOURNAL OF VIROLOGY LA English DT Article ID SITE-SPECIFIC INTEGRATION; DNA HELICASE ACTIVITY; REPLICATION IN-VITRO; ADENOASSOCIATED VIRUS; TERMINAL REPEATS; VIRAL-DNA; WILD-TYPE; SEQUENCE REQUIREMENTS; DIRECTED MUTAGENESIS; COVALENT ATTACHMENT AB The endonuclease activity of the Rep68 and Rep78 proteins (Rep68/78) of adeno-associated virus type 2 (AAV) cuts at the terminal resolution site (trs) within the hairpin structure formed by the AAV inverted terminal repeats. Recent studies suggest that a DNA unwinding function of Rep68/78 may be required for endonuclease activity. We demonstrate that several mutant proteins which are endonuclease negative on a fully duplex hairpin substrate are endonuclease positive on a partially single-stranded hairpin substrate. Truncation analysis revealed that the endonuclease function is contained within the first 200 amino acids of Rep68/78. This endonucleolytic cleavage is believed to involve the covalent attachment of Rep68/78 to the trs via a phosphate-tyrosine linkage. A previous report (S. L. Walker, R. S. Wonderling, and R. A. Owens, J. Virol, 71:2722-2730, 1997) suggested that tyrosine 152 was part of the active site, We individually mutated each tyrosine within the first 200 amino acids of the Rep68 moiety of a maltose binding protein-Rep68/78 fusion protein to phenylalanine, Only mutation of tyrosine 156 resulted in a protein incapable of covalent attachment to a partially single-stranded hairpin substrate, suggesting that tyrosine 156 is part of the endonuclease active site. C1 NIDDKD, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. RP Owens, RA (reprint author), NIDDKD, Mol & Cellular Biol Lab, NIH, Bldg 8,Rm 310,8 Ctr Dr,MSC 0840, Bethesda, MD 20892 USA. NR 56 TC 32 Z9 32 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 2000 VL 74 IS 6 BP 2936 EP 2942 DI 10.1128/JVI.74.6.2936-2942.2000 PG 7 WC Virology SC Virology GA 286LH UT WOS:000085447100053 PM 10684315 ER PT J AU Ourmanov, I Bilska, M Hirsch, VM Montefiori, DC AF Ourmanov, I Bilska, M Hirsch, VM Montefiori, DC TI Recombinant modified vaccinia virus Ankara expressing the surface gp120 of simian immunodeficiency virus (SIV) primes for a rapid neutralizing antibody response to SIV infection in macaques SO JOURNAL OF VIROLOGY LA English DT Article ID NONNEUTRALIZING MONOCLONAL-ANTIBODIES; IMMUNE-RESPONSES; RHESUS-MONKEYS; PASSIVE-IMMUNIZATION; PROTECTIVE EFFICACY; SUBUNIT VACCINES; HIV-1 INFECTION; AIDS VACCINES; SCID MICE; TYPE-1 AB Neutralizing antibodies were assessed before and after intravenous challenge with pathogenic SIVsmE660 in rhesus macaques that had been immunized with recombinant modified vaccinia virus Ankara expressing one or more simian immunodeficiency virus gene products (MVA-SIV). Animals received either MVA-gag-pol, MVA-env, MVA-gag-pol-env, or nonrecombinant MVA. Although no animals were completely protected from infection with SIV, animals immunized with recombinant MVA-SIV vaccines had lower virus loads and prolonged survival relative to control animals that received nonrecombinant MVA (I. Ourmanov et al., J. Virol. 74:2740-2751, 2000), Titers of neutralizing antibodies measured with the vaccine strain SIVsmH-4 were low in the MVA-env and MVA-gag-pol-env groups of animals and were undetectable in the MMA-gag-pol and nonrecombinant MVA groups of animals on the day of challenge (4 weeks after final immunization). Titers of SIVsmH-4-neutralizing antibodies remained unchanged 1 week later but increased approximately 100-fold 2 weeks postchallenge in the MVA-env and MVA-gag-pol-env groups while the titers remained low or undetectable in the MVA-gag-pol and nonrecombinant MVA groups. This anamnestic neutralizing antibody response was also detected with T-cell-line-adapted stocks of SIVmac251 and SIV/DeltaB670 but not with SIVmac239, as this latter virus resisted neutralization. Most animals in each group had high titers of SIVsmH-4-neutralizing antibodies 8 weeks postchallenge. Titers of neutralizing antibodies were Low or undetectable until about 12 weeks of infection in all groups of animals and showed little or no evidence of an anamnestic response when measured with SIVsmE660, The results indicate that recombinant MVA is a promising vector to use to prime for an anamnestic neutralizing antibody response following infection with primate lentiviruses that cause AIDS. However, the Env component of the present vaccine needs improvement in order to target a broad spectrum of viral variants, including those that resemble primary isolates. C1 Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. NIAID, Mol Microbiol Lab, Rockville, MD 20852 USA. RP Montefiori, DC (reprint author), Duke Univ, Med Ctr, Dept Surg, Box 2926, Durham, NC 27710 USA. FU NIAID NIH HHS [AI-85343] NR 50 TC 49 Z9 50 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 2000 VL 74 IS 6 BP 2960 EP 2965 DI 10.1128/JVI.74.6.2960-2965.2000 PG 6 WC Virology SC Virology GA 286LH UT WOS:000085447100057 PM 10684319 ER PT J AU Dutta, C AF Dutta, C TI Commentary on "effects of strength training and detraining on muscle quality: Age and gender comparisons" SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material ID SKELETAL-MUSCLE; MEN; EXERCISE; WOMEN C1 NIA, Geriatr Program, Bethesda, MD 20892 USA. RP Dutta, C (reprint author), NIA, Geriatr Program, Suite 3-E327,Gateway Bldg,7201 Wisconsin, Bethesda, MD 20892 USA. NR 13 TC 3 Z9 3 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAR PY 2000 VL 55 IS 3 BP B158 EP B159 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 331XR UT WOS:000088044400007 ER PT J AU Hutter, D Yo, Y Chen, W Liu, PH Holbrook, NJ Roth, GS Liu, YS AF Hutter, D Yo, Y Chen, W Liu, PH Holbrook, NJ Roth, GS Liu, YS TI Age-related decline in Ras/ERK mitogen-activated protein kinase cascade is linked to a reduced association between Shc and EGF receptor SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID EPIDERMAL GROWTH-FACTOR; RIBOSOMAL S6 KINASE; SIGNAL-REGULATED KINASE; KAPPA-B-ALPHA; DNA-SYNTHESIS; TYROSINE KINASES; RAT HEPATOCYTES; MAP KINASE; IN-VITRO; C-FOS AB Numerous studies have demonstrated that the proliferative capacity of cells declines with age. Using rat primary hepatocytes as a model system, we recently demonstrated that this age-related decline in the proliferative response to mitogenic stimulation is associated with decreased activities of both extracellular signal-regulated kinase (ERK) and p70 S6 kinase (p70(S6k)). To unravel the molecular basis for age-related defects in the ERK pathway, we have now characterized the upstream signaling events that occur after epidermal growth factor (EGF) stimulation in young and aged hepatocytes. As previously noted for ERK, the activities of both MEK (the kinase immediately upstream of ERK) and pas following EGF stimulation were significantly lower in aged hepatocytes, An examination of the EGF receptor (EGFR) revealed a similar amount of EGFR in the two age groups. Likewise, EGFR and Shc, an adaptor protein that plays a crucial role in linking EGFR to Ras activation, underwent tyrosine phosphorylation to a similar degree in both young and aged hepatocytes. However, in aged cells Shc was unable to form stable complexes with EGFR after EGF stimulation. Our results suggest that a decrease in the association between Shc and EGFR in aged cells underlies the age-related declines in the ERK signaling cascade and in proliferative capacity. C1 NIA, Biol Chem Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. NIA, Cellular & Mol Biol Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Liu, YS (reprint author), NIA, Biol Chem Lab, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Liu, Yusen/E-3527-2011 NR 38 TC 34 Z9 37 U1 0 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAR PY 2000 VL 55 IS 3 BP B125 EP B134 PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 331XR UT WOS:000088044400002 PM 10795716 ER PT J AU Ingram, DK Long, JM AF Ingram, DK Long, JM TI Commentary on "age-dependent increase in infarct volume following photochemically induced cerebral infarction: Putative role of astroglia" SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material ID STEREOLOGICAL METHODS; TRANSECTION; INDUCTION; NEURONS; BRAIN C1 NIA, Neurosci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Ingram, DK (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAR PY 2000 VL 55 IS 3 BP B142 EP B143 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 331XR UT WOS:000088044400004 ER PT J AU Ivey, FM Tracy, BL Lemmer, JT NessAiver, M Metter, EJ Fozard, JL Hurley, BF AF Ivey, FM Tracy, BL Lemmer, JT NessAiver, M Metter, EJ Fozard, JL Hurley, BF TI Effects of strength training and detraining on muscle quality: Age and gender comparisons SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID CROSS-SECTIONAL AREA; OLDER MEN; SKELETAL-MUSCLE; HUMAN QUADRICEPS; HYPERTROPHY; YOUNG; ADAPTATIONS; MORPHOLOGY; TENSION; FLEXORS AB Maximal force production per unit of muscle mass (muscle quality, or MQ) has been used to describe the relative contribution of non-muscle-mass components to the changes in strength with age and strength training (ST). To compare the influence of age and gender on MQ response to ST and detraining, 11 young men (20-30 years), nine young women (20-30 years), 11 older men (65-75 years), and 11 older women (65-75 years), were assessed for quadriceps MQ at baseline, after 9 weeks of ST, and after 31 weeks of detraining. MQ was calculated by dividing quadriceps one repetition maximum (1RM) strength by quadriceps muscle volume determined by magnetic resonance imaging. All groups demonstrated significant increases in 1RM strength and muscle volume after training (all p < .05). All groups also increased their MQ with training (all p < .01), but the gain in hla was significantly greater in young women than in the other three groups (p < .05). After 31 weeks of detraining, MQ values remained significantly elevated above baseline levels in all groups (p < .05), except the older women. These results indicate that factors other than muscle mass contribute to strength gains with ST in young and older men and women, but those other factors may account for a higher portion of the strength gains in young women. These factors continue to maintain strength levels above baseline for up to 31 weeks after cessation of training in young men and women, and in older men. C1 Univ Maryland, Dept Kinesiol, College Pk, MD 20742 USA. Univ Maryland, Sch Med, Baltimore VA Med Ctr, Baltimore, MD 21201 USA. Univ Colorado, Dept Kinesiol & Appl Physiol, Boulder, CO 80309 USA. Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Medford, MA 02155 USA. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. Morton Plant Mease Hlth Care, Florida Geriatr Res Program, Clearwater, FL USA. RP Hurley, BF (reprint author), Univ Maryland, Dept Kinesiol, College Pk, MD 20742 USA. RI Fozard, James Leonard/B-3660-2009 FU NIA NIH HHS [1-AG-4-2148] NR 28 TC 91 Z9 94 U1 0 U2 10 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAR PY 2000 VL 55 IS 3 BP B152 EP B157 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 331XR UT WOS:000088044400006 PM 10795719 ER PT J AU Miller, RA Nadon, NL AF Miller, RA Nadon, NL TI Principles of animal use for gerontological research SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID AGING RESEARCH; MODELS; MICE AB This essay presents some practical advice and suggestions for those who wish to use mice and rats in experiments on the biology of aging. Ten principles set forth guidance on choice of ages, choice of stocks, the importance of specific pathogen-free status, the uses of necropsy data, the dangers of pooling samples from different individuals, planning ahead for loss of aged mice to death and disease, the use of cost-adjusted power calculations, and the dangers of inferring causal associations from correlated age effects. C1 Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Geriatr Ctr, Ann Arbor, MI 48109 USA. Ann Arbor VA Med Ctr, Inst Gerontol, Ann Arbor, MI USA. NIA, Bethesda, MD 20892 USA. RP Miller, RA (reprint author), Univ Michigan, Geriatr Ctr, CCGCB, Room 5316, Ann Arbor, MI 48109 USA. FU NIA NIH HHS [AG08808, AG13283] NR 10 TC 75 Z9 76 U1 0 U2 4 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAR PY 2000 VL 55 IS 3 BP B117 EP B123 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 331XR UT WOS:000088044400001 PM 10795715 ER PT J AU Rantanen, T Harris, T Leveille, SG Visser, M Foley, D Masaki, K Guralnik, JM AF Rantanen, T Harris, T Leveille, SG Visser, M Foley, D Masaki, K Guralnik, JM TI Muscle strength and body mass index as long-term predictors of mortality in initially healthy men SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID JAPANESE-AMERICAN MEN; PHYSICAL-ACTIVITY; GRIP STRENGTH; WOMEN; AGE; OSTEOARTHRITIS; WEAKNESS; DISEASE; FITNESS; PEOPLE AB Background. Muscle weakness, low body weight, and chronic diseases are often observed in the same people: however, the association of muscle strength with mortality, independent of disease status and body weight, has nor been elucidated. The: aim was to assess hand grip strength as a predictor of all-cause mortality within different levels of body mass index (BMI) in initially disease-free men. Methods. Mortality was followed prospectively over 30 years. Maximal hand grip strength tests and BMI assessments were done at baseline in 1965 to 1970. The participants were 6040 healthy men aged 45 to 68 years at baseline living on Oahu, Hawaii. Results, The death rates per 1000 person years were 24.6 in those with BMI <20, 18.5 in the middle BMI category, and 18.0 in those with BMI greater than or equal to 25. For grip strength tertiles, the mortality rates were 24.8 in the lowest, 18.5 in the middle, and 14.0 in the highest third. In Cox regression models, within each tertile of grip strength, BMI showed only minimal effect on mortality. In contrast, in each category of BMI there was a gradient of decreasing mortality risk with increasing grip strength. Among those with BMI <20, the adjusted relative risks (RRs) of mortality over 30 years were 1.36 (95% confidence interval 1.14-1.63) for those in the lowest third of strength at baseline, 1.27 (1.02-1.58) in the middle, and 0.92 (0.66-1.29) in the highest third. Correspondingly, for those with BMI 20-24.99, the RRs of death were 1.25 (1.08-1.45), 1.14 (1.00-1.32), and 1.0 (reference) in the fewest, middle, and highest third of grip strength, respectively. In those with BMI greater than or equal to 25, the RRs were 1.39 (1.16-1.65) in the lowest, 1.27(1.08-1.49) in the middle, and 1.14 (0.98-1.32) in the highest third of grip strength. Models were adjusted for age, education, occupation, smoking. physical activity, and body height. Conclusions. In healthy middle-aged men, long-term mortality risk was associated with grip strength at baseline. independent of BMI. The possible interpretation of the finding is that early life influences on muscle strength may have long-term implications for mortality. Additionally, higher strength itself may provide greater physiologic and functional reserve that protects against mortality. C1 Univ Jyvaskyla, Dept Hlth Sci, SF-40351 Jyvaskyla, Finland. NIA, Epidemiol Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. Vrije Univ Amsterdam, Fac Med, Inst Res Extramural Med, Amsterdam, Netherlands. Kuakini Med Ctr, Honolulu Asia Aging Study, Honolulu Heart Program, Honolulu, HI USA. RP Rantanen, T (reprint author), Univ Jyvaskyla, Dept Hlth Sci, POB 35, SF-40351 Jyvaskyla, Finland. RI Rantanen, Taina/O-6579-2016 OI Rantanen, Taina/0000-0002-1604-1945 NR 43 TC 239 Z9 243 U1 6 U2 18 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAR PY 2000 VL 55 IS 3 BP M168 EP M173 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 331XR UT WOS:000088044400019 PM 10795731 ER PT J AU Chevalier, RL Goyal, S Kim, A Chang, AY Landau, D LeRoith, D AF Chevalier, RL Goyal, S Kim, A Chang, AY Landau, D LeRoith, D TI Renal tubulointerstitial injury from ureteral obstruction in the neonatal rat is attenuated by IGF-1 SO KIDNEY INTERNATIONAL LA English DT Article DE development; unilateral ureteral obstruction; insulin-like growth factor-1; apoptosis; congenital obstructive nephropathy ID GROWTH-FACTOR-I; RECEPTOR GENE-EXPRESSION; MESSENGER-RNA; EXPERIMENTAL HYDRONEPHROSIS; ACCELERATES RECOVERY; DEVELOPING KIDNEY; COLLECTING DUCT; APOPTOSIS; FAILURE; NEPHRECTOMY AB Background. The administration of insulin-like growth factor-1 (IGF-1) has been shown to ameliorate the renal injury resulting from ischemic acute renal failure. As there are a number of similarities between acute renal failure and obstructive nephropathy, we examined the effects of IGF-1 on the renal cellular response to unilateral ureteral obstruction (UUO) in the neonatal rat. Methods. Forty-five rats were subjected to UUO or sham operation within the first 48 hours of life and received IGF-1 (2 mg/kg/day) or saline for the following three or seven days, after which kidneys were removed for study by morphometry and immunohistochemistry. To determine the effects of UUO on endogenous expression of IGF-1 and its receptor, six additional rats were subjected to UUO or sham operation. and mRNA was measured by solution hybridization. Results. There was no effect of seven days of UUO on the renal expression of endogenous IGF-1 or its receptor. Moreover, seven days of exogenous IGF-1 did not improve the suppression of nephrogenesis, the delay in glomerular maturation, or the reduction in tubular proliferation induced by ipsilateral UUO. However. in the obstructed kidney, IGF-1 reduced tubular expression of vimentin. apoptosis, and tubular atrophy by 38 to 50% (P < 0.05). In addition. IGF-1 also decreased renal interstitial collagen deposition in the obstructed kidney by 44 % (P < 0.05). Following three days of UUO, the administration of IGF-1 also reduced tubular apoptosis (P < 0.05). bur did not alter tubular proliferation. Conclusions. IGF-1 has a profound salutary effect on the tubular and interstitial response to UUO in early development, without affecting glomerular injury or development. These results suggest that IGF-1 may have therapeutic potential in the management of congenital obstructive nephropathy. C1 Univ Virginia, Hlth Sci Ctr, Dept Pediat, Charlottesville, VA 22908 USA. Ben Gurion Univ Negev, IL-84105 Beer Sheva, Israel. NIDDK, Diabet Branch, NIH, Bethesda, MD USA. RP Chevalier, RL (reprint author), Univ Virginia, Hlth Sci Ctr, Dept Pediat, Box 386, Charlottesville, VA 22908 USA. OI Goyal, Sharad/0000-0002-6475-7411 FU NIDDK NIH HHS [DK44756, DK45179, DK52612] NR 52 TC 65 Z9 72 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAR PY 2000 VL 57 IS 3 BP 882 EP 890 DI 10.1046/j.1523-1755.2000.057003882.x PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 286TJ UT WOS:000085461500016 PM 10720941 ER PT J AU Ramsey, MJ DerSimonian, R Holtel, MR Burgess, LPA AF Ramsey, MJ DerSimonian, R Holtel, MR Burgess, LPA TI Corticosteroid treatment for idiopathic facial nerve paralysis: A meta-analysis SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Meeting of the Western Section of the American-Laryngological-Rhinological-and-Otological-Society CY JAN 08-10, 1999 CL DENVER, COLORADO SP Amer Laryngol Rhinol & Otol Soc, W Sect DE meta; analysis; corticosteroids; idiopathic facial nerve paralysis; Bell's palsy ID BELLS-PALSY; CLINICAL-TRIALS; DOUBLE-BLIND; STEROIDS; PREDNISONE; PROGNOSIS; ACYCLOVIR; ROCHESTER; MINNESOTA; THERAPY AB Objective: A meta-analysis was designed to evaluate facial recovery in patients with complete idiopathic facial nerve paralysis (IFNP) by comparing outcomes of those treated with corticosteroid therapy with outcomes of those treated with placebo or no treatment. Study Design: Meta-analysis of prospective trials evaluating corticosteroid therapy for idiopathic facial nerve paralysis. Methods: A protocol was followed outlining methods for trial selection, data extraction, and statistical analysis. A MEDLINE search of the English language literature was performed to identify clinical trials evaluating steroid treatment of IFNP, Three independent observers used an eight-point analysis to determine inclusion criteria. Data analysis was limited to individuals with clinically complete IFNP. The endpoints measured were clinically complete or incomplete facial motor recovery. Effect magnitude and significance were evaluated by calculating the rate difference and Fisher's Exact Test P value. Pooled analysis was performed with a random effects model. Results: Forty-seven trials were identified. Of those, 27 were prospective and 20 retrospective. Three prospective trials met the inclusion criteria. Tests of heterogeneity indicate the trial with the smallest sample size (RD = -0.19; 95% CI, -0.58-0.20), to be an outlier. It was excluded from the final analysis, Analyses of data from the remaining two studies indicate corticosteroid treatment improves complete facial motor recovery for individuals with complete IFNP, Rate difference demonstrates a 17% (99% CI, 0.01-0.32) improvement in clinically complete recovery for the treatment group based on the random effects model. Conclusions: Corticosteroid treatment provides a clinically and statistically significant improvement in recovery of function in complete IFNP. C1 Tripler Army Med Ctr, Div Otolaryngol Head & Neck Surg, MCHK DSH, Honolulu, HI 96859 USA. NIH, Bethesda, MD 20892 USA. RP Ramsey, MJ (reprint author), Tripler Army Med Ctr, Div Otolaryngol Head & Neck Surg, MCHK DSH, 1 Jarrett White Rd, Honolulu, HI 96859 USA. NR 57 TC 53 Z9 58 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD MAR PY 2000 VL 110 IS 3 BP 335 EP 341 DI 10.1097/00005537-200003000-00001 PN 1 PG 7 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 291QR UT WOS:000085748000001 PM 10718415 ER PT J AU Athanasiou, M Mavrothalassitis, G Sun-Hoffman, L Blair, DG AF Athanasiou, M Mavrothalassitis, G Sun-Hoffman, L Blair, DG TI FLI-1 is a suppressor of erythroid differentiation in human hematopoietic cells SO LEUKEMIA LA English DT Article DE ETS transcription factors; FLI-1; erythroid differentiation; GATA-1; GATA-1 promoter; K562 ID TRANSCRIPTION FACTOR GATA-1; MURINE LEUKEMIA-VIRUS; GENE-EXPRESSION; ETS FAMILY; ERYTHROLEUKEMIA-CELLS; PUTATIVE ONCOGENE; LINE K562; HEL CELLS; PROLIFERATION; BINDING AB The FLI-1 oncogene, a member of the ETS family of transcription factors, is associated with both normal and abnormal hematopoietic cell growth and lineage-specific differentiation. We have previously shown that overexpression of FLI-1 in pluripotent human hematopoietic cells leads to the induction of a megakaryocytic phenotype. In this report we show that FLI-1 also acts as an inhibitor of erythroid differentiation. Following the induction of erythroid differentiation, pluripotent cells express reduced levels of FLI-1, In contrast, when FLI-1 is overexpressed in these cells, the levels of erythroid markers are reduced. The ability of FLI-1 overexpressing cells to respond to erythroid-specific inducers such as hemin and Ara-C is also inhibited, and the uninduced cells show a reduced level of the erythroid-associated GATA-1 transcription factor mRNA. Furthermore, expression of a GATA-1 promoter-driven reporter construct in K562 cells is inhibited by co-transfection with a construct expressing FLI-1, Our results support the hypothesis that FLI-1 can act both positively and negatively in the regulation of hematopoietic cell differentiation, and that inhibition of GATA-1 expression may contribute to FLI-1-mediated inhibition of erythroid differentiation. C1 NCI, Basic Res Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Intramural Res Support Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Univ Crete, Sch Med, Heraklion, Crete, Greece. Univ Crete, IMBB FORTH, Heraklion, Crete, Greece. RP Blair, DG (reprint author), NCI, Basic Res Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, POB B,Bldg 469,Rm 102, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 52 TC 56 Z9 58 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAR PY 2000 VL 14 IS 3 BP 439 EP 445 DI 10.1038/sj.leu.2401689 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 291QW UT WOS:000085748400015 PM 10720139 ER PT J AU Zwiebel, JA AF Zwiebel, JA TI New agents for acute myelogenous leukemia SO LEUKEMIA LA English DT Article; Proceedings Paper CT Meeting on Acute Leukemia Forum'99: Advances and Controversies in the Therapy of Acute Myeloid Leukemia CY APR 16, 1999 CL SAN FRANCISCO, CALIFORNIA DE histone acetylation; angiogenesis; fenretinide; leukemia; protein kinase ID ACUTE PROMYELOCYTIC LEUKEMIA; HISTONE DEACETYLASE COMPLEX; ACUTE MYELOID-LEUKEMIA; PLZF-RAR-ALPHA; RETINOIC ACID; TUMOR ANGIOGENESIS; FUSION PARTNER; GROWTH-FACTOR; REPRESSION; PROTEIN AB New agents for the treatment of acute myelogenous leukemia are discussed that reflect different treatment mechanisms. These include histone acetylation, angiogenesis inhibition, protein kinase inhibitors, and a novel retinoid. Efficacy and safety in phase I and phase II trials reviewed, as well as the problems involved in crossing over from treatment of solid tumors to blood disorders. C1 NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diagnosis, Bethesda, MD 20892 USA. RP Zwiebel, JA (reprint author), NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diagnosis, EPN 715,6130 Execut Blvd, Bethesda, MD 20892 USA. NR 24 TC 12 Z9 14 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAR PY 2000 VL 14 IS 3 BP 488 EP 490 DI 10.1038/sj.leu.2401662 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA 291QW UT WOS:000085748400024 PM 10720147 ER PT J AU Nicot, C Mahieux, R Opavsky, R Wolff, L Brady, JN Boxer, L Franchini, G AF Nicot, C Mahieux, R Opavsky, R Wolff, L Brady, JN Boxer, L Franchini, G TI Repression of the human c-Myb promoter by Tax in HTLV-I transformed cells SO LEUKEMIA LA English DT Meeting Abstract C1 NIH, Div Basic Sci, Basic Res Lab, Bethesda, MD 20892 USA. NIH, Div Basic Sci, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. NIH, Div Basic Sci, Cellular Oncol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAR PY 2000 VL 14 IS 3 MA 8 BP 537 EP 537 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA 291QW UT WOS:000085748400047 ER PT J AU Iha, H Kasai, T Kibler, KV Jeang, KT AF Iha, H Kasai, T Kibler, KV Jeang, KT TI Pleiotropic effect of HTLV-1 Tax on multiple cellular processes: Aneuploidy, DNA damage and transcription SO LEUKEMIA LA English DT Meeting Abstract C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 3 TC 0 Z9 0 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAR PY 2000 VL 14 IS 3 MA 9 BP 538 EP 538 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA 291QW UT WOS:000085748400048 ER PT J AU Mahieux, R Pise-Masison, CA Lambert, PF Nicot, C De Marchis, L Gessain, A Green, P Hall, WW Brady, JN AF Mahieux, R Pise-Masison, CA Lambert, PF Nicot, C De Marchis, L Gessain, A Green, P Hall, WW Brady, JN TI Analysis of p53 inactivation in HTLV-1 and HTLV-2 infected cells SO LEUKEMIA LA English DT Meeting Abstract C1 NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. Inst Pasteur, Unite Oncol Virale, F-75724 Paris, France. Ohio State Univ, Dept Vet Biosci, Columbus, OH 43210 USA. Ohio State Univ, Dept Mol Virol, Columbus, OH 43210 USA. Univ Coll Dublin, Dept Microbiol, Dublin 2, Ireland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAR PY 2000 VL 14 IS 3 MA 14 BP 541 EP 541 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA 291QW UT WOS:000085748400053 ER PT J AU Pise-Masison, CA Mahieux, R Jiang, H Radonovich, M Brady, JN AF Pise-Masison, CA Mahieux, R Jiang, H Radonovich, M Brady, JN TI The NF-kappa B pathway is important for HTLV-I Tax inactivation of p53 in lymphocytes SO LEUKEMIA LA English DT Meeting Abstract C1 NCI, Virus Tumor Biol Sect, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAR PY 2000 VL 14 IS 3 MA 13 BP 541 EP 541 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA 291QW UT WOS:000085748400052 ER PT J AU Zhou, Y Chun, ACS Wong, CM Kung, HF Jeang, KT Jin, DY AF Zhou, Y Chun, ACS Wong, CM Kung, HF Jeang, KT Jin, DY TI Novel cellular proteins targeted by HTLV-1 Tax SO LEUKEMIA LA English DT Meeting Abstract C1 Univ Hong Kong, Inst Mol Biol, Hong Kong, Hong Kong, Peoples R China. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAR PY 2000 VL 14 IS 3 MA 16 BP 543 EP 543 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA 291QW UT WOS:000085748400055 ER PT J AU Takemoto, S Taguchi, H Casareto, L Mulloy, JC Franchini, G AF Takemoto, S Taguchi, H Casareto, L Mulloy, JC Franchini, G TI STAT5 activation downstream of the IL-4 receptor in ATLL cells SO LEUKEMIA LA English DT Meeting Abstract C1 NCI, Basic Res Lab, Div Basic Sci, Bethesda, MD 20892 USA. Kochi Med Sch, Dept Internal Med 3, Kochi, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAR PY 2000 VL 14 IS 3 MA 19 BP 545 EP 545 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA 291QW UT WOS:000085748400058 ER PT J AU Kubota, R Nagai, M Osame, M Jacobson, S AF Kubota, R Nagai, M Osame, M Jacobson, S TI Differentiated HTLV-I Tax-specific CD8+cells correlate with the proviral load in HAM/TSP patients SO LEUKEMIA LA English DT Meeting Abstract C1 NINDS, Viral Immunol Sect, NIB, NIH, Bethesda, MD 20892 USA. Kagoshima Univ, Sch Med, Dept Internal Med 3, Kagoshima 8908520, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAR PY 2000 VL 14 IS 3 MA 21 BP 546 EP 546 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA 291QW UT WOS:000085748400060 ER PT J AU Albertini, RJ Sullivan, L Judice, S Ardell, S Jacobson, S Allegretta, M AF Albertini, RJ Sullivan, L Judice, S Ardell, S Jacobson, S Allegretta, M TI A test for HTLV-1-mediated in vivo T-cell expansion SO LEUKEMIA LA English DT Meeting Abstract C1 Univ Vermont, Genet Toxicol Lab, Burlington, VT USA. NIH, Bethesda, MD 20892 USA. BioMosaics Inc, Charlotte, VT USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAR PY 2000 VL 14 IS 3 MA 23 BP 548 EP 548 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA 291QW UT WOS:000085748400062 ER PT J AU Azimi, N Mariner, J Jacobson, S Waldmann, TA AF Azimi, N Mariner, J Jacobson, S Waldmann, TA TI IL-15 contributes to the spontaneous proliferation of HAM/TSP PBMC SO LEUKEMIA LA English DT Meeting Abstract C1 NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NINDS, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAR PY 2000 VL 14 IS 3 MA 28 BP 553 EP 553 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA 291QW UT WOS:000085748400067 ER PT J AU Derse, D Shuh, M Hill, S Lloyd, P Morse, B Heidecker, G AF Derse, D Shuh, M Hill, S Lloyd, P Morse, B Heidecker, G TI Viral genetic determinants of HTLV-I infectivity and replication SO LEUKEMIA LA English DT Meeting Abstract C1 NCI, Basic Res Lab, Div Basic Sci, Frederick, MD 21701 USA. NCI, IRSP SAIC Frederick, FCRDC, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAR PY 2000 VL 14 IS 3 MA 29 BP 554 EP 554 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA 291QW UT WOS:000085748400068 ER PT J AU Ciminale, V Zotti, L D'Agostino, DM Ferro, T Casareto, L Franchini, G Torrisi, MR Bernardi, P Chieco-Bianchi, L AF Ciminale, V Zotti, L D'Agostino, DM Ferro, T Casareto, L Franchini, G Torrisi, MR Bernardi, P Chieco-Bianchi, L TI Mitochondrial protein encoded in the X-II ORF of HTLV-I SO LEUKEMIA LA English DT Meeting Abstract C1 Univ Padua, Dept Oncol & Surg Sci, I-35100 Padua, Italy. Univ Padua, Dept Biomed Sci, I-35100 Padua, Italy. NCI, Basic Res Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Univ Rome, Dept Expt Med & Pathol, Rome, Italy. RI Bernardi, Paolo/C-3656-2008 OI Bernardi, Paolo/0000-0001-9187-3736 NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAR PY 2000 VL 14 IS 3 MA 31 BP 556 EP 556 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA 291QW UT WOS:000085748400070 ER PT J AU Hou, XH Foley, S Cueto, M Robinson, MA AF Hou, XH Foley, S Cueto, M Robinson, MA TI Cellular proteins that interact with HTLV-I p13 SO LEUKEMIA LA English DT Meeting Abstract C1 NIAID, Immunogenet Lab, Twinbrook 2 Facil, NIH, Rockville, MD 20852 USA. Novartis Inst Biomed Res, Biomol Struct & Comp CTA, Summit, NJ 07901 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAR PY 2000 VL 14 IS 3 MA 32 BP 556 EP 556 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA 291QW UT WOS:000085748400071 ER PT J AU Mulloy, JC Trovato, R Fu, KS Fullen, J Leonard, WJ Franchini, G AF Mulloy, JC Trovato, R Fu, KS Fullen, J Leonard, WJ Franchini, G TI The HTLV-1 p12(I) protein enhances Jak/STAT activation through the interleukin-2 receptor SO LEUKEMIA LA English DT Meeting Abstract C1 NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAR PY 2000 VL 14 IS 3 MA 33 BP 557 EP 557 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA 291QW UT WOS:000085748400072 ER PT J AU Johnson, JM Fullen, J Casareto, L Mulloy, JC Franchini, G AF Johnson, JM Fullen, J Casareto, L Mulloy, JC Franchini, G TI p12(I) may contribute to HTLV-1 escape from immune detection SO LEUKEMIA LA English DT Meeting Abstract C1 NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAR PY 2000 VL 14 IS 3 MA 34 BP 558 EP 558 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA 291QW UT WOS:000085748400073 ER PT J AU Xie, XY Sorbara, L Kreitman, RJ Fukushima, PI Kingma, DW Stetler-Stevenson, M AF Xie, XY Sorbara, L Kreitman, RJ Fukushima, PI Kingma, DW Stetler-Stevenson, M TI Development of lymphoproliferative disorder of granular lymphocytes in association with hairy cell leukemia SO LEUKEMIA & LYMPHOMA LA English DT Article DE lymphoproliferative disorder; large granular lymphocytes; in association; hairy cell leukemia; HCL; LGL ID NATURAL-KILLER-CELLS; PERIPHERAL-BLOOD; EXPRESSION; DISEASES; GENES AB Lymphoproliferative disorder of granular lymphocytes (LDGL) is a low grade T-cell disease characterized by clonal expansion of large granular lymphocytes of either T cell or natural killer (NK) cell lineage that express the cytotoxic T-cell/NK cell antigens CD16, CD56 and/or CD57. LDGL has been described in association with other malignancies, leading to theories of a common abnormal stem cell as well as development of the LDGL as an immune response to a primary tumor, We have studied 32 patients with hairy cell leukemia (HCL). In 15 patients (47%) we detected an increase in cells expressing cytotoxic T-cell/NK cell antigens, In 10(31%) patients these cells were of T cell lineage, while 5 patients (16%) had increased NK-cells. T cell clonality was detected by PCR in all cases with increased cytotoxic T-cells in which adequate DNA was obtained from peripheral blood. Since in 2 patients the LDGL was not present at diagnosis but developed during follow up, our data suggests that clonal LDGL may develop in response to the HCL. The significance of LDGL in the setting of HCL and flow cytometric evaluation of HCL versus LDGL will be discussed. C1 NCI, NIH, Pathol Lab, Div Clin Sci, Bethesda, MD 20892 USA. RP Stetler-Stevenson, M (reprint author), NCI, NIH, Pathol Lab, Div Clin Sci, Bldg 10,Room 2N-108, Bethesda, MD 20892 USA. NR 27 TC 13 Z9 13 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD MAR PY 2000 VL 37 IS 1-2 BP 97 EP 104 DI 10.3109/10428190009057632 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 290YV UT WOS:000085706200008 PM 10721773 ER PT J AU Corn, M AF Corn, M TI Biomedical computing: Territorial expansion for informatics SO M D COMPUTING LA English DT Editorial Material C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Corn, M (reprint author), Natl Lib Med, Bethesda, MD 20894 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0724-6811 J9 M D COMPUT JI M D Comput. PD MAR-APR PY 2000 VL 17 IS 2 BP 22 EP 26 PG 5 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA 300RM UT WOS:000086266000004 PM 10778294 ER PT J AU McCray, AT AF McCray, AT TI Improving access to healthcare information: The Lister Hill National Center for Biomedical Communications SO M D COMPUTING LA English DT Editorial Material ID WORLD-WIDE-WEB; IMAGES C1 Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20209 USA. RP Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20209 USA. NR 25 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-6811 J9 M D COMPUT JI M D Comput. PD MAR-APR PY 2000 VL 17 IS 2 BP 29 EP 34 PG 6 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA 300RM UT WOS:000086266000006 PM 10778296 ER PT J AU Afeworki, M van Dam, GM Devasahayam, N Murugesan, R Cook, J Coffin, D A-Larsen, JHA Mitchell, JB Subramanian, S Krishna, MC AF Afeworki, M van Dam, GM Devasahayam, N Murugesan, R Cook, J Coffin, D A-Larsen, JHA Mitchell, JB Subramanian, S Krishna, MC TI Three-dimensional whole body imaging of spin probes in mice by time-domain radiofrequency electron paramagnetic resonance SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE EPR imaging; in vivo EPR; free radicals; pulsed EPR; time-domain EPR ID MAGNETIC-RESONANCE; FREE-RADICALS; EPR; SPECTROSCOPY; ESR AB Imaging of stable paramagnetic spin probes in phantom objects and in vivo was evaluated using a RF time domain EPR spectrometer/imager operating at 300 MHz. Projections were collected using static magnetic field gradients and images were reconstructed using filtered back-projection techniques. Results from phantom objects containing approximately 10(17) spins of stable paramagnetic probes with single narrow EPR spectra provide three-dimensional spatial images with resolution better than 2 mm, When the spin probe was administered to mice, the spin probe accumulation was temporally observed in the thoracic, abdominal, and pelvic regions. A three-dimensional image (from 144 projections) from a live mouse was collected in 5 min. Using fiducial markers, the spin probe accumulation in organs such as liver, kidney, and bladder could be observed. Differences in the oxygen status between liver and kidney were observed from the EPR images from mice administered with spin probe, by treating the time-domain responses with convolution difference approach, prior to image reconstruction. The results from these studies suggest that, with the use of stable paramagnetic spin probes and time-domain RF EPR, it is possible to perform in vivo imaging on animals and also obtain important spatially resolved physiologic information. Published 2000 Wiley-Liss, Inc.(dagger). C1 NCI, Radiat Biol Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. Nyoomed Innovat AB, Malmo, Sweden. Univ Groningen Hosp, Dept Surg, Groningen, Netherlands. Madurai Kamaraj Univ, Sch Chem, Madurai 625021, Tamil Nadu, India. RP Krishna, MC (reprint author), NCI, Radiat Biol Branch, Div Clin Sci, NIH, Bldg 10,Room B3-B69, Bethesda, MD 20892 USA. RI Ardenkjar-Larsen, Jan Henrik/B-5765-2017 OI Ardenkjar-Larsen, Jan Henrik/0000-0001-6167-6926 NR 29 TC 47 Z9 49 U1 1 U2 6 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 2000 VL 43 IS 3 BP 375 EP 382 DI 10.1002/(SICI)1522-2594(200003)43:3<375::AID-MRM9>3.0.CO;2-G PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 288JF UT WOS:000085559100009 PM 10725880 ER PT J AU Frankfater, C Maus, E Gaal, K Segade, F Copeland, NG Gilbert, DJ Jenkins, NA Shipley, JM AF Frankfater, C Maus, E Gaal, K Segade, F Copeland, NG Gilbert, DJ Jenkins, NA Shipley, JM TI Organization of the mouse microfibril-associated glycoprotein-2 (MAGP-2) gene SO MAMMALIAN GENOME LA English DT Article ID ELASTIN-ASSOCIATED MICROFIBRILS; FIBRILLIN-CONTAINING MICROFIBRILS; EXTRACELLULAR MICROFIBRILS; DEVELOPMENTAL EXPRESSION; COMPONENT; REGION; INITIATOR; PROTEINS; ANTIGEN AB A 1.4-kb EST clone encoding mouse microfibril-associated glycoprotein-2 (MAGP-2), identified by its similarity with the reported human cDNA, was used to screen a mouse 129 genomic bacterial artificial chromosome (BAC) library. The mouse gene contains 10 exons spanning 16 kb, located on the distal region of Chromosome (Chr) 6. The exons range in size from 24 to 963 bp, with the ATG located in exon 2. The tenth and largest exon contains 817 bp of 3' untranslated sequence, including a B2 repetitive element. Northern analysis demonstrates abundant expression of MAGP-2 mRNA in skeletal muscle, lung, and heart. Sequence analysis of additional cDNA clones suggests that the two mRNA forms of MAGP-2 in the mouse arise from alternative polyadenylation site usage. The promoter does not contain an obvious TATA box, and the sequence surrounding the start site does not conform to the consensus for an initiator promoter element. Additionally, the mouse promoter contains 22 copies of a CT dinucleotide repeat sequence located similar to 155 bp 5' to exon 1. C1 Washington Univ, Sch Med, Barnes Jewish Hosp, Dept Med,Div Pulm & Crit Care Med, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Cell Biol, St Louis, MO 63110 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. RP Shipley, JM (reprint author), Washington Univ, Sch Med, Barnes Jewish Hosp, Dept Med,Div Pulm & Crit Care Med, 216 S Kingshighway Blvd, St Louis, MO 63110 USA. NR 20 TC 9 Z9 10 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD MAR PY 2000 VL 11 IS 3 BP 191 EP 195 DI 10.1007/s003350010036 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 305CE UT WOS:000086520600002 PM 10723723 ER PT J AU Sandvik, SLH Bilski, P Pakulski, JD Chignell, CF Coffin, RB AF Sandvik, SLH Bilski, P Pakulski, JD Chignell, CF Coffin, RB TI Photogeneration of singlet oxygen and free radicals in dissolved organic matter isolated from the Mississippi and Atchafalaya River plumes SO MARINE CHEMISTRY LA English DT Article DE dissolved organic matter; singlet oxygen; EPR; ultrafiltration; photochemistry; coastal waters ID NATURAL-WATERS; HUMIC SUBSTANCES; FULVIC-ACID; FLUORESCENCE PROPERTIES; PHOTOCHEMICAL FORMATION; OPTICAL-ABSORPTION; YELLOW SUBSTANCE; QUANTUM YIELDS; SURFACE WATERS; CARBON-CYCLE AB The photoreactivity to UV light of ultrafiltered dissolved organic matter (DOM) collected during cruises along salinity transects in the Mississippi and Atchafalaya River plumes was examined by measuring photogenerated free radicals and singlet molecular oxygen (O-1(2)) photosensitization. Singlet oxygen was detected by its infrared phosphorescence at 1270 nm using both steady-state and time-resolved techniques. The O-1(2) quantum yields were corrected for self-quenching of O-1(2) by the DOM substrates. Photogenerated free radicals were monitored dy electron paramagnetic resonance (EPR). Two size fractions of the dissolved organic matter were examined: material retained with a 3 kDa cut-off filter and material retained with a 1 kDa cut-off filter. The highest O-1(2) quantum yields were found in the lower molecular mass material. Then was little change in the O-1(2) quantum yields with increasing salinity, indicating that the photosensitizing ability of the estuarine DOM does not decrease as terrestrial DOM is transported to sea and mixes with marine DOM. In contrast to O-1(2) formation, the steady-state levels of photoproduced free radicals did not significantly differ between high and low molecular mass DOM, and the levels were substantially higher in riverine DOM than along plume salinity transects. This rapid transition in free radical level suggests that terrestrially-derived DOM experiences significant changes in this aspect of its photoreactivity in low (< 10 ppt) salinity waters. Published by Elsevier Science B.V. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. USN, Res Lab, EQSS, Washington, DC 20375 USA. RP Sandvik, SLH (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233,MD F0-06, Res Triangle Pk, NC 27709 USA. NR 57 TC 57 Z9 59 U1 1 U2 28 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4203 J9 MAR CHEM JI Mar. Chem. PD MAR PY 2000 VL 69 IS 1-2 BP 139 EP 152 DI 10.1016/S0304-4203(99)00101-2 PG 14 WC Chemistry, Multidisciplinary; Oceanography SC Chemistry; Oceanography GA 297GB UT WOS:000086072800011 ER PT J AU Wojnowski, L Stancato, LF Larner, AC Rapp, UR Zimmer, A AF Wojnowski, L Stancato, LF Larner, AC Rapp, UR Zimmer, A TI Overlapping and specific functions of Braf and Craf-1 proto-oncogenes during mouse embryogenesis SO MECHANISMS OF DEVELOPMENT LA English DT Article DE Braf; Craf-1; proto-oncogenes; embryogenesis ID SIGNAL-TRANSDUCTION PATHWAY; B-RAF; DIFFERENTIAL REGULATION; A-RAF; GENE-EXPRESSION; KINASE CASCADE; GROWTH-FACTOR; CELLS; ACTIVATION; MICE AB The three mammalian Raf serine/threonine protein kinases mediate the transduction of proliferative and differentiative signals from cell surface receptors to the nucleus. In vertebrates, Raf signaling has been implicated in the progression of mouse embryos through the two-cell stage and in the induction of posterior mesoderm. However, mouse embryos mutant for each of the Raf genes exhibit no developmental defects before mid-gestation. Here we describe the phenotype of mouse mutants with different combinations of mutant Craf-1 and Braf alleles. Our results show that Raf signaling is indeed indispensable for normal development beyond the blastocyst stage. However, due to a significant redundancy between Craf-1 and Braf, either gene is sufficient for normal development until mid-gestation. The molecular and developmental mechanisms for this redundancy were investigated by monitoring the expression of Raf genes throughout embryogenesis and by biochemical studies in mutant cell lines. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Epidauros Biotechnol Ag, D-82347 Bernried, Germany. NIMH, Genet Lab, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Bethesda, MD 20892 USA. Univ Wurzburg, Inst Med Strahlenkunde & Zellforsch, Wurzburg, Germany. RP Wojnowski, L (reprint author), Epidauros Biotechnol Ag, Neuland 1, D-82347 Bernried, Germany. RI Zimmer, Andreas/B-8357-2009 NR 33 TC 78 Z9 81 U1 0 U2 4 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 1 PY 2000 VL 91 IS 1-2 BP 97 EP 104 DI 10.1016/S0925-4773(99)00276-2 PG 8 WC Developmental Biology SC Developmental Biology GA 298NR UT WOS:000086146500010 PM 10704835 ER PT J AU Beanan, MJ Feledy, JA Sargent, TD AF Beanan, MJ Feledy, JA Sargent, TD TI Regulation of early expression of Dlx3, a Xenopus anti-neural factor, by beta-catenin signaling SO MECHANISMS OF DEVELOPMENT LA English DT Article DE early expression; Dlx3; Xenopus anti-neural factor; beta-catenin signaling ID SPEMANN ORGANIZER; LAEVIS EMBRYOS; MOLECULAR MECHANISM; EQUATORIAL REGION; CORTICAL ROTATION; AXIS FORMATION; INDUCTION; GENE; SIAMOIS; LITHIUM AB The ectoderm of the pre-gastrula Xenopus embryo has previously been shown to be at least partially patterned along the dorsal-ventral axis. The early expression of the anti-neural homeodomain gene D1x3 is localized to the ventral ectoderm by a mechanism that occurs prior to gastrulation and is independent of the Spemann organizer. The repression of D1x3 is mediated by signaling though beta-catenin, but is probably not dependent on the induction of the Xnr3 or chordin genes by beta-catenin. We propose a model in which this early regulation of D1x3 accounts for the pro-neural bias of dorsal ectoderm. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Sargent, TD (reprint author), NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. NR 43 TC 21 Z9 21 U1 3 U2 4 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 1 PY 2000 VL 91 IS 1-2 BP 227 EP 235 DI 10.1016/S0925-4773(99)00303-2 PG 9 WC Developmental Biology SC Developmental Biology GA 298NR UT WOS:000086146500022 PM 10704847 ER PT J AU Cope, JU Tsokos, M Helman, LJ Gridley, G Tucker, MA AF Cope, JU Tsokos, M Helman, LJ Gridley, G Tucker, MA TI Inguinal hernia in patients with Ewing sarcoma: A clue to etiology SO MEDICAL AND PEDIATRIC ONCOLOGY LA English DT Article DE inguinal hernia; Ewing sarcoma; etiology; congenital anomaly ID SOFT-TISSUE SARCOMAS; TESTICULAR DESCENT; CHILDHOOD-CANCER; BONE; CRYPTORCHIDISM; CHILDREN; RISK AB Background. Various congenital anomalies have been associated with childhood cancer, but as yet no anomaly has been consistently found with Ewing sarcoma (ES). Recently a large case-control study of ES patients reported a greater number of hernias in both cases and their sibling controls than in population controls. Most of these hernias were inguinal. Because these anomalies were also reported previously in two case series, we looked for inguinal hernias in a different population of ES patients. Procedure. We abstracted medical records for 306 pathologically confirmed ES/primitive neuroectodermal tumor (PNET) patients seen at NIH between 1960 and 1992. Epidemiological data on demographics and medical conditions were analyzed. The frequency of anomalies was compared to expected rates to calculate relative risk and confidence intervals. Results. Anomalies were present in 67 (22%) cases. A particular anomaly, inguinal hernia, was reported for 13 (5%) NIH cases. Compared to population estimates for white children, the relative risk of inguinal hernia among white NIH cases was 13.3 (95% CI 3.60-34.1) for females and 6.67 (95% Cl 2.67-13.7) for males. Conclusions. The findings of inguinal hernias in some patients with ES suggest that a disruption in normal embryological development occurred. This may provide an important clue to the etiology of ES. We hypothesize that these hernias may relate to an in utero exposure or indicate an underlying genetic disorder. Future studies should carefully evaluate ES families for genetic disease and explore environmental factors. Med. Pediatr. Oncol. 34:195-199, 2000. Published 2000 Wiley-Liss, Inc. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Dept Pathol, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Cope, JU (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS Room 7007, Bethesda, MD 20892 USA. NR 24 TC 10 Z9 11 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0098-1532 J9 MED PEDIATR ONCOL JI Med. Pediatr. Oncol. PD MAR PY 2000 VL 34 IS 3 BP 195 EP 199 DI 10.1002/(SICI)1096-911X(200003)34:3<195::AID-MPO6>3.0.CO;2-B PG 5 WC Oncology; Pediatrics SC Oncology; Pediatrics GA 289XA UT WOS:000085646200006 PM 10696126 ER PT J AU Lipschultz, CA Li, YL Smith-Gill, S AF Lipschultz, CA Li, YL Smith-Gill, S TI Experimental design for analysis of complex kinetics using surface plasmon resonance SO METHODS-A COMPANION TO METHODS IN ENZYMOLOGY LA English DT Article ID PROTEIN-PROTEIN INTERACTIONS; SITE-DIRECTED MUTAGENESIS; TRANSFER-RNA SYNTHETASE; MACROMOLECULAR INTERACTIONS; MONOCLONAL-ANTIBODIES; BINDING AFFINITIES; ANTIGEN; LYSOZYME; BIOSENSORS; IMMOBILIZATION AB Using BIAcore surface plasmon resonance technology, we found that the real-time association kinetics of Fabs specific for hen egg-white lysozyme did not conform to a 1:1. Langmuir association model. Heterogeneity of the components is not the source of the complex kinetics. Informed by independent structural data suggesting conformational flexibility differences among these antibodies, we chose global mathematical analysis based on a two-phase model, consistent with the encounter-docking view of protein-protein associations. Experimental association times (T-a) from 2 to 250 min revealed that initial dissociation rates decreased with increasing T-a, confirming a multiphasic association. The relationship between observed dissociation rate and T-a is characteristic of each antibody-antigen complex. We define a new parameter, T-50, the time at which the encounter and final complexes are of equimolar concentration. The observed T-50 is a function of analyte concentration and the encounter and docking rate constants. Simulations showed that when the ligand is saturated at high analyte concentrations, T-50 reaches a minimum value, T-50(MIN), which can be used to compare antigen-antibody complexes. For high-affinity complexes with rapid rearrangement to a stable complex, T-50(MIN) approaches T-1/2 of the rearrangement forward rate constant, We conclude that experiments with a range of T-a are essential to assess the nature of the kinetics, regardless of whether a two-state or 1:1 model is applicable. We suggest this strategy because each T-a potentially reveals a different distribution of molecular states; for two-step analysis, a range of T-a that brackets T-50 is optimal. C1 NCI, Basic Res Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr,NIH, Frederick, MD 21702 USA. RP Lipschultz, CA (reprint author), NCI, Basic Res Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr,NIH, Frederick, MD 21702 USA. NR 45 TC 68 Z9 70 U1 1 U2 18 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD MAR PY 2000 VL 20 IS 3 BP 310 EP 318 DI 10.1006/meth.1999.0924 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 292KR UT WOS:000085793700005 PM 10694453 ER PT J AU Potapova, O Gorospe, M Dougherty, RH Dean, NM Gaarde, WA Holbrook, NJ AF Potapova, O Gorospe, M Dougherty, RH Dean, NM Gaarde, WA Holbrook, NJ TI Inhibition of c-Jun N-terminal kinase 2 expression suppresses growth and induces apoptosis of human tumor cells in a p53-dependent manner SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PROTEIN-KINASE; ACTIVATION DOMAIN; UV-LIGHT; HA-RAS; P53; JNK; TRANSFORMATION; DIFFERENTIATION; PHOSPHORYLATION; UBIQUITINATION AB c-Jun N-terminal kinase (JNK) plays a critical role in coordinating the cellular response to stress and has been implicated in regulating cell growth and transformation. To investigate the growth-regulatory functions of JNK1 and JNK2, we used specific antisense oligonucleotides (AS) to inhibit their expression. A survey of several human tumor cell lines revealed that JNKAS treatment markedly inhibited the growth of cells with mutant p53 status but not that of cells with normal p53 function, To further examine the influence of p53 on cell sensitivity to JNKAS treatment, we compared the responsiveness of RKO, MCF-7, and HCT116 cells with normal p53 function to that of RKO E6, MCF-7 E6, and HCT116 p53(-/-), which were rendered p53 deficient by different methods. Inhibition of JNK2 (and to a lesser extent JNK1) expression dramatically reduced the growth of p53-deficient cells but not that of their normal counterparts. JNK2AS-induced growth inhibition was correlated with significant apoptosis, JNK2AS treatment induced the expression of the cyclin-dependent kinase inhibitor p21(Cip1/Waf1) in parental MCF-7, RKO, and HCT116 cells but not in the p53-deficient derivatives. That p21(Cip1/Waf1) expression contributes to the survival of JNK2AS-treated cells was supported by additional experiments demonstrating that p21(Cip1/Waf1) deficiency in HCT116 cells also results in heightened sensitivity to JNKAS treatment. Our results indicate that perturbation of JNK2 expression adversely affects the growth of otherwise nonstressed cells, p53 and its downstream effector p21(Cip1/Waf1) important in counteracting these detrimental effects and promoting cell survival. C1 NIA, Cell Stress & Aging Sect, Biol Chem Lab, GRC,NIH, Baltimore, MD 21224 USA. ISIS Pharmaceut, Carlsbad, CA 92008 USA. RP Holbrook, NJ (reprint author), NIA, Cell Stress & Aging Sect, Biol Chem Lab, GRC,NIH, 5600 Nathan Shock Dr,Box 12, Baltimore, MD 21224 USA. NR 44 TC 105 Z9 105 U1 0 U2 2 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 2000 VL 20 IS 5 BP 1713 EP 1722 DI 10.1128/MCB.20.5.1713-1722.2000 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 284PY UT WOS:000085342200025 PM 10669748 ER PT J AU Chiariello, M Marinissen, MJ Gutkind, JS AF Chiariello, M Marinissen, MJ Gutkind, JS TI Multiple mitogen-activated protein kinase signaling pathways connect the Cot oncoprotein to the c-jun promoter and to cellular transformation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR MEF2C; TRANSDUCTION PATHWAY; GENE-EXPRESSION; T-CELLS; COUPLED RECEPTORS; GROWTH-FACTORS; NUCLEAR FACTOR; 3T3 CELLS; FOS GENE; ONCOGENE AB The serine/threonine kinase Cot is a member of the mitogen-activated protein kinase (MAPK) kinase kinase family implicated in cellular transformation. Enhanced expression of this protein has been shown to activate both the MAPK and the c-Jun N-terminal kinase (JNK) pathways and to stimulate the nuclear factor of activated T cells and NF-kappa B-dependent transcription. However, the nature of the normal functions of the Cot protein and the molecular mechanisms responsible for its oncogenic potential are still largely unknown. Here, we show that overexpression of the cot proto-oncogene is sufficient to stimulate the expression of c-jun and that, in turn, the activity of c-Jun is required for Cot-induced transformation. These observations prompted us to explore the molecular events by which Cot regulates c-jun expression. We found that Cot potently stimulates the activity of the c-jun promoter utilizing JNK-dependent and -independent pathways, the latter involving two novel members of the MAPK family, p38 gamma (ERK6) and ERK5. Molecularly, this activity was found to be dependent on the ability of Cot to activate, in vivo, members of each class of the MAPK kinase superfamily, including MEK, SEK, MKK6, and MEK5. Furthermore, the use of dominant interfering molecules revealed that Cot requires JNK, p38s, and ERK5 to stimulate the c-jun promoter fully and to induce neoplastic transformation. These findings indicate that Got represents the first example of a serine/threonine kinase acting simultaneously on all known MAPK cascades. Moreover, these observations strongly suggest that the transforming ability of Cot results from the coordinated activation of these pathways, which ultimately converge on the regulation of the expression and activity of the product of the c-jun proto-oncogene. C1 Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Gutkind, JS (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, 9000 Rockville Pike, Bldg 30,Room 211, Bethesda, MD 20892 USA. RI Gutkind, J. Silvio/A-1053-2009; Chiariello, Mario/O-3642-2014 OI Chiariello, Mario/0000-0001-8434-5177 NR 75 TC 155 Z9 162 U1 1 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 2000 VL 20 IS 5 BP 1747 EP 1758 DI 10.1128/MCB.20.5.1747-1758.2000 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 284PY UT WOS:000085342200028 PM 10669751 ER PT J AU Jiang, H Lu, HX Schiltz, RL Pise-Masison, CA Ogryzko, VV Hakatani, Y Brady, JN AF Jiang, H Lu, HX Schiltz, RL Pise-Masison, CA Ogryzko, VV Hakatani, Y Brady, JN TI PCAF interacts with tax and stimulates tax transactivation in a histone acetyltransferase-independent manner (vol 19, pg 8136, 1999) SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Correction C1 NCI, Virus Tumor Biol Sect, Lab Receptor Biol & Gene Express, Div Basic Sci,NIH, Bethesda, MD 20892 USA. NICHHD, NIH, Bethesda, MD 20892 USA. George Washington Univ, GWIBS, Grad Program Genet, Washington, DC 20037 USA. RP Jiang, H (reprint author), NCI, Virus Tumor Biol Sect, Lab Receptor Biol & Gene Express, Div Basic Sci,NIH, Bethesda, MD 20892 USA. NR 1 TC 2 Z9 2 U1 0 U2 0 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 2000 VL 20 IS 5 BP 1897 EP 1897 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 284PY UT WOS:000085342200042 ER PT J AU Schmidt, M Nazarov, V Stevens, L Watson, R Wolff, L AF Schmidt, M Nazarov, V Stevens, L Watson, R Wolff, L TI Regulation of the resident chromosomal copy of c-myc by c-Myb is involved in myeloid leukemogenesis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HUMAN HEMATOPOIETIC-CELLS; MACROPHAGE TUMORS INVIVO; RECEPTOR FUSION PROTEIN; BINDING-SITES; GEL-ELECTROPHORESIS; GENE-EXPRESSION; RAPID INDUCTION; MESSENGER-RNA; TARGET GENES; BALB/C MICE AB c-myb is a frequent target of retroviral insertional mutagenesis in murine leukemia virus-induced myeloid leukemia. Induction of the leukemogenic phenotype is generally associated with inappropriate expression of this transcriptional regulator. Despite intensive investigations, the target genes of c-myb that are specifically involved in development of these myeloid lineage neoplasms are still unknown. In vitro assays have indicated that c-myc may be a target gene of c-Myb; however, regulation of the resident chromosomal gene has not yet been demonstrated. To address this question further, we analyzed the expression of c-myc in a myeloblastic cell line, M1, expressing a conditionally active c-Myb-estrogen receptor fusion protein (MybER), Activation of MybER both prevented the growth arrest induced by interleukin-6 (IL-6) and rapidly restored c-myc expression in nearly terminal differentiated cells that had been exposed to IL-6 for 3 days. Restoration occurred in the presence of a protein synthesis inhibitor but not after a transcriptional block, indicating that c-myc is a direct, transcriptionally regulated target of c-Myb. c-myc is a major target that transduces Myb's proliferative signal, as shown by the ability of a c-Myc-estrogen receptor fusion protein alone to also reverse growth arrest in this system. To investigate the possibility that this regulatory connection contributes to Myb's oncogenicity, we expressed a dominant negative Myb in the myeloid leukemic cell line RI-4-11, In this cell line, c-myb is activated by insertional mutagenesis and cannot be effectively down regulated by cytokine. Myb's ability to regulate c-myc's expression was also demonstrated in these cells, showing a mechanism through which the protooncogene c-myb can exert its oncogenic potential in myeloid lineage hematopoietic cells. C1 NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. NCI, Genet Lab, Bethesda, MD 20892 USA. St Marks Hosp, Imperial Coll Sch Med, Ludwig Inst Canc Res, London EC1V 2PS, England. RP Wolff, L (reprint author), NCI, Cellular Oncol Lab, Bldg 37,Rm 2D11,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 76 TC 53 Z9 54 U1 0 U2 2 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 2000 VL 20 IS 6 BP 1970 EP 1981 DI 10.1128/MCB.20.6.1970-1981.2000 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 288CX UT WOS:000085545200007 PM 10688644 ER PT J AU Otsuka, T Jakubczak, J Vieira, W Bottaro, DP Breckenridge, D Larochelle, WJ Merlino, G AF Otsuka, T Jakubczak, J Vieira, W Bottaro, DP Breckenridge, D Larochelle, WJ Merlino, G TI Disassociation of met-mediated biological responses in vivo: the natural hepatocyte growth factor/scatter factor splice variant NK2 antagonizes growth but facilitates metastasis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID FACTOR SCATTER FACTOR; PAPILLARY RENAL CARCINOMAS; C-MET; TYROSINE KINASE; TRANSGENIC MICE; PROTOONCOGENE PRODUCT; EPITHELIAL-CELLS; FACTOR-RECEPTOR; PHOSPHATIDYLINOSITOL 3-KINASE; ABNORMAL-DEVELOPMENT AB Hepatocyte growth factor/scatter factor (HGF/SF) stimulates numerous cellular activities capable of contributing to the metastatic phenotype, including growth, motility, invasiveness, and morphogenetic transformation. When inappropriately expressed in vivo, an HGF/SF transgene induces numerous hyperplastic and neoplastic lesions. NK1 and NK2 are natural splice variants of HGF/SF; all interact with a common receptor, Met. Although both agonistic and antagonistic properties have been ascribed to each isoform in vitro, NK1 retains the full spectrum of HGF/SF-like activities when expressed as a transgene in vivo. Here we report that transgenic mice broadly expressing NK2 exhibit none of the phenotypes characteristic of HGF/SF or NK1 transgenic mice. Instead, when coexpressed in NK2-HGF/SF bitransgenic mice, NK2 antagonizes the pathological consequences of HGF/SF and discourages the subcutaneous growth of transplanted Met-containing melanoma cells. Remarkably, the metastatic efficiency of these same melanoma cells is dramatically enhanced in NK2 transgenic host mice relative to wild-type recipients, rivaling levels achieved in HGF/SF and NK1 transgenic hosts. Considered in conjunction with reports that in vitro NK2 induces scatter, but not other activities, these data strongly suggest that cellular motility is a critical determinant of metastasis. Moreover, our results demonstrate how alternatively structured ligands can be exploited in vivo to functionally dissociate Met-mediated activities and their downstream pathways. C1 NCI, Mol Genet Sect, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Merlino, G (reprint author), NCI, Mol Genet Sect, Mol Biol Lab, NIH, Bldg 37,Room 2E24, Bethesda, MD 20892 USA. RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 NR 74 TC 48 Z9 50 U1 0 U2 2 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 2000 VL 20 IS 6 BP 2055 EP 2065 DI 10.1128/MCB.20.6.2055-2065.2000 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 288CX UT WOS:000085545200015 PM 10688652 ER PT J AU Danilkovitch, A Donley, S Skeel, A Leonard, EJ AF Danilkovitch, A Donley, S Skeel, A Leonard, EJ TI Two independent signaling pathways mediate the antiapoptotic action of macrophage-stimulating protein on epithelial cells SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID FOCAL ADHESION KINASE; GROWTH-FACTOR-I; CYCLE PROGRESSION; TYROSINE KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; EXTRACELLULAR-MATRIX; INHIBITS APOPTOSIS; SURVIVAL SIGNALS; GENE-PRODUCT; TUMOR-CELLS AB In addition to its effects on macrophage function, macrophage-stimulating protein (MSP) is a growth and motility factor for epithelial cells. The growth and survival of epithelial cells generally require two signals, one generated by interaction with extracellular matrix via integrins, the other initiated by a growth factor. Therefore we investigated the effect of MSP on epithelial cell survival. Survival of epithelial cells cultured overnight in serum-free medium was promoted by adhesion, which activated both the phosphatidylinositol 3'-kinase (PI3-K)/AKT and mitogen-activated protein kinase (MAPK) pathways, operating independently of one another. The number of apoptotic cells resulting from inhibition of either pathway alone was approximately doubled by simultaneous inhibition of both pathways. This shows that each pathway made a partial contribution to the prevention of apoptosis. In the presence of an inhibitor of either pathway, MSP increased the activity of the other pathway so that the single uninhibited pathway alone was sufficient to prevent apoptosis, In contrast to the results with adherent cells, although MSP also prevented apoptosis of cells in suspension (anoikis), its effect was mediated only by the PI3-K/AKT pathway. Despite activation of MAPK by MSP, anoikis was not prevented in suspended cells with a blocked PI3-K/AKT pathway. Thus, activation of MAPK alone is not sufficient to mediate MSP antiapoptotic effects. Cell adhesion generates an additional signal, which is essential for MSP to use MAPK in an antiapoptotic pathway. This may involve translocation of MSP-activated MAPK from the cytoplasm into the nucleus, which occurs only in adherent cells. Our results suggest that there is cross talk between cell matrix adhesion and growth factors in the regulation of cell survival via the MAPK pathway. Growth factors induce MAPK activation, and adhesion mediates MAPK translocation from the cytoplasm into the nucleus. C1 NCI, Immunopathol Sect, Immunobiol Lab, FCRDC, Frederick, MD 21702 USA. RP Danilkovitch, A (reprint author), NCI, Immunopathol Sect, Immunobiol Lab, FCRDC, Bldg 560,Rm 12-46, Frederick, MD 21702 USA. NR 90 TC 88 Z9 90 U1 0 U2 0 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 2000 VL 20 IS 6 BP 2218 EP 2227 DI 10.1128/MCB.20.6.2218-2227.2000 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 288CX UT WOS:000085545200031 PM 10688668 ER PT J AU Katz, BZ Zamir, E Bershadsky, A Kam, Z Yamada, KM Geiger, B AF Katz, BZ Zamir, E Bershadsky, A Kam, Z Yamada, KM Geiger, B TI Physical state of the extracellular matrix regulates the structure and molecular composition of cell-matrix adhesions SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID FOCAL ADHESIONS; CULTURED FIBROBLASTS; SIGNAL-TRANSDUCTION; TYROSINE PHOSPHORYLATION; INTERFERENCE REFLECTION; MONOCLONAL-ANTIBODY; INTEGRIN FUNCTION; ALPHA-ACTININ; BINDING-SITE; FIBRONECTIN AB This study establishes that the physical state of the extracellular matrix can regulate integrin-mediated cytoskeletal assembly and tyrosine phosphorylation to generate two distinct types of cell-matrix adhesions. In primary fibroblasts, alpha(5)beta(1) integrin associates mainly with fibronectin fibrils and forms adhesions structurally distinct from focal contacts, independent of actomyosin-mediated cell contractility. These "fibrillar adhesions" are enriched in tensin, but contain low levels of the typical focal contact components paxillin, vinculin, and tyrosine-phosphorylated proteins. However, when the fibronectin is covalently linked to the substrate, alpha(5)beta(1) integrin forms highly tyrosine-phosphorylated, "classical" focal contacts containing high levels of paxillin and vinculin. These experiments indicate that the physical state of the matrix, not just its molecular composition, is a critical factor in defining cytoskeletal organization and phosphorylation at adhesion sites. We propose that molecular organization of adhesion sites is controlled by at least two mechanisms: 1) specific integrins associate with their ligands in transmembrane complexes with appropriate cytoplasmic anchor proteins (e.g., fibronectin-alpha(5)beta(1) integrin-tensin complexes), and 2) physical properties (e.g., rigidity) of the extracellular matrix regulate local tension at adhesion sites and activate local tyrosine phosphorylation, recruiting a variety of plaque molecules to these sites. These mechanisms generate structurally and functionally distinct types of matrix adhesions in fibroblasts. C1 Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. Natl Inst Craniofacial & Dent Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD USA. RP Geiger, B (reprint author), Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. EM benny.geiger@weizmann.ac.il OI Yamada, Kenneth/0000-0003-1512-6805 NR 53 TC 285 Z9 288 U1 1 U2 29 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAR PY 2000 VL 11 IS 3 BP 1047 EP 1060 PG 14 WC Cell Biology SC Cell Biology GA 294UV UT WOS:000085929500021 PM 10712519 ER PT J AU Emmert-Buck, MR Gillespie, JW Paweletz, CP Ornstein, DK Basrur, V Appella, E Wang, QH Huang, J Hu, N Taylor, P Petricoin, EF AF Emmert-Buck, MR Gillespie, JW Paweletz, CP Ornstein, DK Basrur, V Appella, E Wang, QH Huang, J Hu, N Taylor, P Petricoin, EF TI An approach to proteomic analysis of human tumors SO MOLECULAR CARCINOGENESIS LA English DT Article DE esophagus; neoplasia; microdissection; proteomics; two-dimensional electrophoresis ID MASS-SPECTROMETRIC IDENTIFICATION; LASER CAPTURE MICRODISSECTION; ANNEXIN-I; DIFFERENTIAL EXPRESSION; GEL-ELECTROPHORESIS; SAMPLE PREPARATION; COLORECTAL-CANCER; EPITHELIAL-CELLS; CARCINOMA; PROTEINS AB A strategy for proteomic analysis of microdissected cells derived from human tumor specimens is described and demonstrated by using esophageal cancer as an example. Normal squamous epithelium and corresponding tumor cells from two patients were procured by laser-capture microdissection and studied by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Fifty thousand cells resolved approximately 675 distinct proteins (or isoforms) with molecular weights ranging between 10 and 200 kDa and isoelectric points of pH 3-10. Comparison of the microdissected protein profiles showed a high degree of similarity between the matched normal-tumor samples (98% identical). However, 17 proteins showed tumor-specific alterations, including 10 that were uniquely present in the tumors and seven that were observed only in the normal epithelium. Two of the altered proteins were characterized by mass spectrometry and immunoblot analysis and were identified as cytokeratin 1 and annexin I. Acquisition of 2D-PAGE protein profiles, visualization of disregulated proteins, and subsequent determination of the identity of selected proteins through high-sensitivity MS-MS microsequencing are possible from microdissected cell populations. These separation and analytical techniques are uniquely capable of detecting tumor-specific alterations. Continued refinement of techniques and methodologies to determine the abundance and status of proteins in vivo holds great promise for future study of normal cells and associated neoplasms. Mol. Carcinog. 27:158-165, 2000. Published by Wiley-Liss Inc. C1 US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Tissue Proteom Unit, Bethesda, MD 20892 USA. NCI, Pathogenet Unit, Pathol Lab, Bethesda, MD 20892 USA. NCI, Canc Genome Anat Project, Off Director, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, Bethesda, MD 20892 USA. Shanxi Canc Hosp, Pathol Lab, Taiyuan, Peoples R China. NCI, Canc Prevent Studies Branch, Bethesda, MD 20892 USA. Georgetown Univ, Dept Chem, Washington, DC 20057 USA. RP Petricoin, EF (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Tissue Proteom Unit, Bethesda, MD 20892 USA. NR 36 TC 157 Z9 175 U1 0 U2 5 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 2000 VL 27 IS 3 BP 158 EP 165 DI 10.1002/(SICI)1098-2744(200003)27:3<158::AID-MC2>3.0.CO;2-2 PG 8 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 289WL UT WOS:000085644900002 PM 10708477 ER PT J AU Zhang, J Zhang, LX Meltzer, PS Barrett, JC Trent, JM AF Zhang, J Zhang, LX Meltzer, PS Barrett, JC Trent, JM TI Molecular cloning of human Hic-5, a potential regulator involved in signal transduction and cellular senescence SO MOLECULAR CARCINOGENESIS LA English DT Article DE Hic-5; p50; focal adhesion; senescence; 16p11 ID FOCAL ADHESION KINASE; HUMAN FIBROBLASTS; GENETIC-ANALYSIS; PROTEIN; PAXILLIN; IDENTIFICATION; BINDING; MOTIF; FIBRONECTIN; BREAKPOINT AB By using differential display, we cloned the human counterpart of the murine gene Hic-5 from senescent human keratinocytes. The full-length cDNA contained a short GC-stretch proceeding a consensus Kozak sequence followed by a single open reading frame of 1338 bp encoding a 461-amino acid protein with a predicted molecular weight of 50 kDa. The expression of this gene was prominent in cells of epithelial origin but low or absent in lymphoid tissues and hematopoietic cells. The deduced protein contained four LIM domains at the carboxyl-terminal end and four LD motifs at the amino-terminal half, sharing high similarities with the focal adhesion protein paxillin. Hic-5 may therefore function, like paxillin, as a potential adapter for the recruitment of structural and signaling molecules to certain subcellular sites or in focal adhesions. Isolation of the genomic sequence revealed that the gene covered a segment of 6 kb and spanned 11 exons from the translation initiation site ATG to the termination signal TGA. Fluorescent in situ hybridization by using a human Hic-5 specific probe localized the gene to human chromosome 16p11. Mol. Carcinog. 27:177-183, 2000. (C) 2000 Wiley-Liss, Inc. C1 Natl Human Genome Res Inst, Canc Genet Branch, NIH, Bethesda, MD USA. NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Zhang, J (reprint author), 5440 Nebraska Med Ctr, Omaha, NE 68198 USA. NR 27 TC 19 Z9 20 U1 1 U2 2 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 2000 VL 27 IS 3 BP 177 EP 183 DI 10.1002/(SICI)1098-2744(200003)27:3<177::AID-MC4>3.0.CO;2-S PG 7 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 289WL UT WOS:000085644900004 PM 10708479 ER PT J AU Lau, OD Kundu, TK Soccio, RE Ait-Si-Ali, S Khalil, EM Vassilev, A Wolffe, AP Nakatani, Y Roeder, RG Cole, PA AF Lau, OD Kundu, TK Soccio, RE Ait-Si-Ali, S Khalil, EM Vassilev, A Wolffe, AP Nakatani, Y Roeder, RG Cole, PA TI HATs off: Selective synthetic inhibitors of the histone acetyltransferases p300 and PCAF SO MOLECULAR CELL LA English DT Article ID GCN5-RELATED N-ACETYLTRANSFERASE; ACETYLATION; TRANSCRIPTION; BINDING; COACTIVATORS; CBP AB Histone acetyltransferases (HATs) play important roles in the regulation of gene expression. In this report, we describe the design, synthesis, and application of peptide CoA conjugates as selective HAT inhibitors for the transcriptional coactivators p300 and PCAF. Two inhibitors (Lys-CoA for p300 and H3-CoA-20 for PCAF) were found to be potent (IC50 approximate to 0.5 mu M) and selective (similar to 200-fold) in blocking p300 and PCAF HAT activities. These inhibitors were used to probe enzymatic and transcriptional features of HAT function in several assay systems. These compounds should be broadly useful as biological tools for evaluating the roles of HATs in transcriptional studies and may serve as lead agents for the development of novel antineoplastic therapeutics. C1 Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. Rockefeller Univ, Bioorgan Chem Lab, New York, NY 10021 USA. Rockefeller Univ, Biochem & Mol Biol Lab, New York, NY 10021 USA. NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Cole, PA (reprint author), Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. FU NCI NIH HHS [CA42567] NR 27 TC 237 Z9 243 U1 1 U2 16 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 2000 VL 5 IS 3 BP 589 EP 595 DI 10.1016/S1097-2765(00)80452-9 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 303ZG UT WOS:000086457600017 PM 10882143 ER PT J AU Robyr, D Wolffe, AP Wahli, W AF Robyr, D Wolffe, AP Wahli, W TI Nuclear hormone receptor coregulators in action: Diversity for shared tasks SO MOLECULAR ENDOCRINOLOGY LA English DT Review ID RETINOIC-ACID RECEPTOR; HUMAN ESTROGEN-RECEPTOR; DEPENDENT TRANSCRIPTIONAL ACTIVATION; LIGAND-INDEPENDENT RECRUITMENT; THYROID-HORMONE; STEROID-RECEPTORS; HISTONE DEACETYLASE; N-COR; SACCHAROMYCES-CEREVISIAE; CYCLIN D1 C1 Univ Lausanne, Inst Biol Anim, CH-1015 Lausanne, Switzerland. NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RP Wahli, W (reprint author), Univ Lausanne, Inst Biol Anim, Batiment Biol, CH-1015 Lausanne, Switzerland. EM walter.wahli@iba.unil.ch RI Wahli, Walter/B-1398-2009 OI Wahli, Walter/0000-0002-5966-9089 NR 146 TC 298 Z9 307 U1 0 U2 7 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAR PY 2000 VL 14 IS 3 BP 329 EP 347 DI 10.1210/me.14.3.329 PG 19 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 290MT UT WOS:000085680600001 PM 10707952 ER PT J AU Seagroves, TN Lydon, JP Hovey, RC Vonderhaar, BK Rosen, JM AF Seagroves, TN Lydon, JP Hovey, RC Vonderhaar, BK Rosen, JM TI C/EBP beta (CCAAT/enhancer binding protein) controls cell fate determination during mammary gland development SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID HUMAN BREAST-CANCER; PROGESTERONE-RECEPTOR; TRANSCRIPTIONAL ACTIVATOR; DUCTAL MORPHOGENESIS; IGF-II; MOUSE; EXPRESSION; DIFFERENTIATION; PROLIFERATION; MICE AB Deletion of the transcription factor CCAAT/enhancer binding protein (C/EBP)beta results in a severe inhibition of lobuloalveolar development in the mouse mammary gland. Because progesterone receptor (PR) is requisite for alveolar development, the expression of PR was investigated in C/EBP beta(-/-) mice. Unexpectedly, the number of PR-positive cells, as well as the levels of PR mRNA, were elevated 3-fold in the mammary glands of C/EBP beta(-/-) mice. Furthermore, in contrast to wild-type nulliparous mice, in which PR distribution shifted from a uniform to nonuniform pattern between 8-12 weeks of age, C/EBP beta(-/-) mice exhibited uniform PR distribution throughout all stages of mammary development analyzed. No change in C/EBP beta mRNA levels was observed in the mammary glands of PR-/- mice, suggesting that PR acts in a pathway either in parallel to or downstream of C/EBP beta. The overexpression and disrupted cellular distribution of PR in C/EBP beta(-/-) mice were coincident with a striking 10-fold decrease in cell proliferation after acute steroid hormone treatment, assayed by incorporation of bromodeoxyuridine. In wild-type mice, PR and bromodeoxyuridine-positive cells were adjacent to each other and rarely colocalized. No differences in the level or pattern of PR expression were observed in the uterus, suggesting that C/EBP beta influences PR in a mammary-specific fashion. Together, these data suggest that C/EBP beta may control cell fate decisions in the mammary gland through the appropriate temporal and spatial expression of molecular markers, such as PR, that induce the proliferation of alveolar progenitor cells via juxtacrine mechanisms. C1 Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA. NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. RP Rosen, JM (reprint author), Baylor Coll Med, Dept Cell Biol, M638A,1 Baylor Plaza, Houston, TX 77030 USA. EM jrosen@bcm.tmc.edu FU NCI NIH HHS [CA-16303, CA-77530-1] NR 34 TC 122 Z9 126 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAR PY 2000 VL 14 IS 3 BP 359 EP 368 DI 10.1210/me.14.3.359 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 290MT UT WOS:000085680600003 PM 10707954 ER PT J AU Moutsopoulos, NM Routsias, JG Vlachoyiannopoulos, PG Tzioufas, AG Moutsopoulos, HM AF Moutsopoulos, NM Routsias, JG Vlachoyiannopoulos, PG Tzioufas, AG Moutsopoulos, HM TI B-cell epitopes of intracellular autoantigens: Myth and reality SO MOLECULAR MEDICINE LA English DT Review ID SYSTEMIC LUPUS-ERYTHEMATOSUS; PRIMARY SJOGRENS-SYNDROME; VESICULAR STOMATITIS-VIRUS; DNA TOPOISOMERASE-I; EPSTEIN-BARR-VIRUS; RO/SS-A; HUMAN KERATINOCYTES; SS-A/RO; LA/SS-B; LA(SS-B) AUTOANTIGEN C1 Natl Inst Hlth, Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, Athens, Greece. Univ Athens, Sch Med, Dept Pathophysiol, GR-11527 Athens, Greece. RP Moutsopoulos, HM (reprint author), Natl Univ Athens, Sch Med, Dept Pathophysiol, 75 M Asias St, Athens 11527, Greece. NR 83 TC 20 Z9 20 U1 0 U2 1 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4319 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD MAR PY 2000 VL 6 IS 3 BP 141 EP 151 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 327MD UT WOS:000087796900001 PM 10965491 ER PT J AU Leland, P Taguchi, J Husain, SR Kreitman, RJ Pastan, I Puri, RK AF Leland, P Taguchi, J Husain, SR Kreitman, RJ Pastan, I Puri, RK TI Human breast carcinoma cells express type IIIL-4 receptors and are sensitive to antitumor activity of a chimeric IL-4-Pseudomonas exotoxin fusion protein in vitro and in vivo SO MOLECULAR MEDICINE LA English DT Article ID CIRCULARLY PERMUTED INTERLEUKIN-4; TUMOR-NECROSIS-FACTOR; COMMON GAMMA-CHAIN; PSEUDOMONAS EXOTOXIN; CANCER-CELLS; FUNCTIONAL COMPONENT; IL-2 RECEPTOR; IN-VIVO; KAPOSIS-SARCOMA; HUMAN-MELANOMA AB Background: Human breast carcinoma cell lines express high-affinity interleukin-4 receptors (IL-4R). We examined the expression and structure of these receptors on primary and cultured breast carcinoma cell lines and normal breast epithelial cells. We also tested the antitumor activity in vitro and in vivo of a fusion protein comprised of circular permuted IL-4 and truncated Pseudomonas exotoxin, termed IL-4(38-37)-PE38KDEL. Materials and Methods: Eight different primary cell cultures and cell lines of human breast carcinomas were examined for the expression of IL-4R by radiolabeled binding, reverse transcription polymerase chain reaction (RT-PCR) and Northern analyses, and subunit structure by crosslinking studies. The antitumor activity of IL-4 toxin was tested in vitro by cytotoxicity assays and in vivo in a xenograft model in immunodeficient animals. Results: I-125-IL-4 specifically bound to primary cell cultures and cell lines with a Iid ranging between 0.2 and 1 nM. Breast tumor cells were found to express IL-4R beta and IL-13R alpha' chains, but not IL-2R gamma(c) chain. These cells were highly sensitive to the cytotoxic effect of IL-4(38-37)-PE38KDEL. The IC,, (concentration inhibiting protein synthesis by 50%) ranged between approximately 0.005-1.5 nM. A normal breast epithelial cell culture was not sensitive to the cytotoxic activity of IL-4(38-37)PE38KDEL. MDA-MB231 human breast carcinoma cell line formed a rapidly growing tumor in nude mice. Intratumor and intraperitoneal administration of IL-4(38-37)-PE38KDEL caused a dose dependent regression of established tumors. A control toxin, anti-Tac(Fv)-PE38KDEL, targeted to the IL-2 receptor a chain did not cause regression of these tumors. Conclusions: These results suggest that IL-4(38-37)-PE38KDEL may be a useful agent for targeting of IL-4 receptor positive human breast carcinomas and further studies should be performed to explore fully its potential. C1 NIH, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,Food & Drug Adm, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, Div Canc Biol Diag & Ctr, NIH, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), NIH, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,Food & Drug Adm, Bethesda, MD 20892 USA. NR 50 TC 37 Z9 38 U1 0 U2 1 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4319 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD MAR PY 2000 VL 6 IS 3 BP 165 EP 178 PG 14 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 327MD UT WOS:000087796900003 PM 10965493 ER PT J AU Fernandez de Henestrosa, AR Ogi, T Aoyagi, S Chafin, D Hayes, JJ Ohmori, H Woodgate, R AF Fernandez de Henestrosa, AR Ogi, T Aoyagi, S Chafin, D Hayes, JJ Ohmori, H Woodgate, R TI Identification of additional genes belonging to the LexA regulon in Escherichia coli SO MOLECULAR MICROBIOLOGY LA English DT Article ID DNA POLYMERASE-II; NUCLEOTIDE-SEQUENCE; BINDING-SITES; LINKAGE MAP; EDITION 10; PROTEIN; K-12; REPRESSOR; CLEAVAGE; EXPRESSION AB Exposure of Escherichia coli to a variety of DNA-damaging agents results in the induction of the global 'SOS response'. Expression of many of the genes in the SOS regulon are controlled by the LexA protein. LexA acts as a transcriptional repressor of these unlinked genes by binding to specific sequences (LexA boxes) located within the promoter region of each LexA-regulated gene. Alignment of 20 LexA binding sites found in the E. coli chromosome reveals a consensus of 5'-TACTG(TA)(5)CAGTA-3'. DNA sequences that exhibit a close match to the consensus are said to have a low heterology index and bind LexA tightly, whereas those that are more diverged have a high heterology index and are not expected to bind LexA. By using this heterology index, together with other search criteria, such as the location of the putative LexA box relative to a gene or to promoter elements, we have performed computational searches of the entire E. coli genome to identify novel LexA-regulated genes. These searches identified a total of 69 potential LexA-regulated genes/operons with a heterology index of < 15 and included all previously characterized LexA-regulated genes. Probes were made to the remaining genes, and these were screened by Northern analysis for damage-inducible gene expression in a wild-type lexA(+) cell, constitutive expression in a lexA(Def) cell and basal expression in a non-inducible lexA(Ind(-)) cell. These experiments have allowed us to identify seven new LexA-regulated genes, thus bringing the present number of genes in the E. coli LexA regulon to 31. The potential function of each newly identified LexA-regulated gene is discussed. C1 NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. Kyoto Univ, Inst Virus Res, Sakyo Ku, Kyoto 6068507, Japan. Univ Rochester, Sch Med & Dent, Dept Biochem & Biophys, Rochester, NY 14642 USA. RP Woodgate, R (reprint author), NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bldg 6,Room 1A13,9000 Rockville Pike, Bethesda, MD 20892 USA. OI Ogi, Tomoo/0000-0002-5492-9072 FU NIGMS NIH HHS [GM52426] NR 44 TC 129 Z9 133 U1 1 U2 9 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 2000 VL 35 IS 6 BP 1560 EP 1572 DI 10.1046/j.1365-2958.2000.01826.x PG 13 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 296EY UT WOS:000086011100026 PM 10760155 ER PT J AU Gillette, WK Rhee, S Rosner, JL Martin, RG AF Gillette, WK Rhee, S Rosner, JL Martin, RG TI Structural homology between MarA of the AraC family of transcriptional activators and the integrase family of site-specific recombinases SO MOLECULAR MICROBIOLOGY LA English DT Letter ID SIMILARITIES C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Gillette, WK (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 16 TC 8 Z9 9 U1 0 U2 0 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 2000 VL 35 IS 6 BP 1582 EP 1583 DI 10.1046/j.1365-2958.2000.01803.x PG 2 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 296EY UT WOS:000086011100028 PM 10760157 ER PT J AU Verdier-Pinard, P Wang, ZQ Mohanakrishnan, AK Cushman, M Hamel, E AF Verdier-Pinard, P Wang, ZQ Mohanakrishnan, AK Cushman, M Hamel, E TI A steroid derivative with paclitaxel-like effects on tubulin polymerization SO MOLECULAR PHARMACOLOGY LA English DT Article ID ENDOGENOUS MAMMALIAN METABOLITE; MICROTUBULE-ASSOCIATED PROTEINS; COLCHICINE-BINDING-SITE; BETA-TUBULIN; MECHANISTIC BASIS; AMINO-ACIDS; TAXOL; 2-METHOXYESTRADIOL; ANALOGS; ESTRAMUSTINE AB The endogenous estrogen metabolite 2-methoxyestradiol has modest antimitotic activity that may result from a weak interaction at the colchicine binding site of tubulin, but it nevertheless has in vivo antitumor activity. Synthetic efforts to improve activity led to compounds that increased inhibitory effects on cell growth, tubulin polymerization, and binding of colchicine to tubulin. This earlier work was directed at modifications in the steroid A ring, which is probably analogous to the colchicine tropolonic C ring. One of the most active analogs prepared was 2-ethoxyestradiol (2EE). We report here that different modifications in the steroid B ring of 2EE yield compounds with two apparently distinct modes of action. Simple expansion of the B ring to seven members resulted in a compound comparable to 2EE in its ability to inhibit tubulin polymerization and colchicine binding to tubulin. Acetylation of the hydroxyl groups in this analog and in 2EE essentially abolished these inhibitory properties. The introduction of a ketone functionality at C6, together with acetylation of the hydroxyls at positions 3 and 17, produced a compound with activity similar to that of paclitaxel, in that the agent enhanced tubulin polymerization into polymers that were partially stable at 0 degrees C. The acetyl group at C17, but not that at C3, was essential for this paclitaxel-like activity. C1 NCI, Lab Drug Discovery Res & Dev,Dev Therapeut Progra, Div Canc Treatment & Diagnosis, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. Purdue Univ, Sch Pharm & Pharm Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. RP Hamel, E (reprint author), NCI, Lab Drug Discovery Res & Dev,Dev Therapeut Progra, Div Canc Treatment & Diagnosis, Frederick Canc Res & Dev Ctr, POB B,Bldg 469,Room 237, Ft Detrick, MD 21702 USA. NR 37 TC 36 Z9 36 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAR PY 2000 VL 57 IS 3 BP 568 EP 575 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 287TB UT WOS:000085521300019 PM 10692498 ER PT J AU Mukhin, AG Gundisch, D Horti, AG Koren, AO Tamagnan, G Kimes, AS Chambers, J Vaupel, DB King, SL Picciotto, MR Innis, RB London, ED AF Mukhin, AG Gundisch, D Horti, AG Koren, AO Tamagnan, G Kimes, AS Chambers, J Vaupel, DB King, SL Picciotto, MR Innis, RB London, ED TI 5-iodo-A-85380, an alpha 4 beta 2 subtype-selective ligand for nicotinic acetylcholine receptors SO MOLECULAR PHARMACOLOGY LA English DT Article ID IN-VIVO; HIGH-AFFINITY; RAT-BRAIN; CHOLINERGIC RECEPTORS; BINDING-SITES; RADIOIODINATED ANALOG; CHROMAFFIN CELLS; PC12 CELLS; EPIBATIDINE; EXPRESSION AB In an effort to develop selective radioligands for in vivo imaging of neuronal nicotinic acetylcholine receptors (nAChRs), we synthesized 5-iodo-3-(2(S)-azetidinylmethoxy)pyridine (5-iodo-A-85380) and labeled it with I-125 and I-123. Here we present the results of experiments characterizing this radioiodinated ligand in vitro. The affinity of 5-[I-125]iodo-A-85380 for alpha 4 beta 2 nAChRs in rat and human brain is defined by K-d values of 10 and 12 pM, respectively, similar to that of epibatidine (8 pM). In contrast to epibatidine, however, 5-iodo-A-85380 is more selective in binding to the alpha 4 beta 2 subtype than to other nAChR subtypes. In rat adrenal glands, 5-iodo-A-85380 binds to nAChRs containing alpha 3 and beta 4 subunits with 1/1000th the affinity of epibatidine, and exhibits 1/60th and 1/190th the affinity of epibatidine at alpha 7 and muscle-type nAChRs, respectively. Moreover, unlike epibatidine and cytisine, 5-[I-125]iodo-A-85380 shows no binding in any brain regions in mice homozygous for a mutation in the beta 2 subunit of nAChRs. Binding of 5-[I-125]iodo-A-85380 in rat brain is reversible, and is characterized by high specificity and a slow rate of dissociation of the receptor-ligand complex (t(1/2) for dissociation similar to 2 h). These properties, along with other features observed previously in in vivo experiments (low toxicity, rapid penetration of the blood-brain barrier, and a high ratio of specific to nonspecific binding), suggest that this compound, labeled with I-125 or I-123, is superior to other radioligands available for in vitro and in vivo studies of alpha 4 beta 2 nAChRs, respectively. C1 NIDA, Brain Imaging Ctr, Intramural Res Program, Baltimore, MD 21224 USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. RP London, ED (reprint author), NIDA, Brain Imaging Ctr, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Picciotto, Marina/F-8747-2012 OI Picciotto, Marina/0000-0002-4404-1280 FU NICHD NIH HHS [N01-HD-1-3138] NR 40 TC 149 Z9 150 U1 0 U2 6 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAR PY 2000 VL 57 IS 3 BP 642 EP 649 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 287TB UT WOS:000085521300028 PM 10692507 ER PT J AU Willenberg, HS Bornstein, SR Hiroi, N Path, G Goretzki, PE Scherbaum, WA Chrousos, GP AF Willenberg, HS Bornstein, SR Hiroi, N Path, G Goretzki, PE Scherbaum, WA Chrousos, GP TI Effects of a novel corticotropin-releasing-hormone receptor type I antagonist on human adrenal function SO MOLECULAR PSYCHIATRY LA English DT Article DE CRH; CRH-receptor antagonist; human; adrenal ID RAT-BRAIN; IMMUNOREACTIVE CORTICOTROPIN; INTRAADRENAL INTERACTIONS; ADRENOCORTICAL FUNCTION; CORTICAL-CELLS; MESSENGER-RNA; GLAND; EXPRESSION; SECRETION; PITUITARY AB Corticotropin-releasing hormone (CRH) is the principal regulator of the hypothalamic-pituitary-adrenal (HPA) axis and an activator of the sympathoadrenal (SA) and systemic sympathetic (SS) systems. Mental disorders, including major depression and, more recently, Alzheimer's disease have been associated with dysregulation of the HPA axis and the SA/SS systems. Treatment of rats or monkeys with the novel CRH receptor type 1 (CRH-R1) antagonist antalarmin inhibits the HPA and/or the SA/SS axes. This is the first study to examine the potential direct effect of antalarmin on human adrenal function. Adrenocortical and adrenomedullary cells were characterized by double-immunohistochemistry with anti-17 alpha hydroxylase (cortical cells) and anti-chromogranin A (chromaffin cells). Expression of CRH, ACTH, CRH type I and type II receptor mRNA were analyzed by reverse-transcription (RT) PCR, Human adrenal cortical and/or chromaffin cells in co-culture were incubated with CRH, antalarmin, and both CRH and antalarmin in vitro. Exposure of these cells to corticotropin or vehicle medium served as positive and negative controls, respectively. Cortical and chromaffin tissues were interwoven in the human adrenals, and both in site and in the co-culture system the endocrine cell types were in close cellular contact. ACTH, CRH, and CRH-R1 and CRH-R2 mRNAs were expressed in the human adrenal as determined by RT-PCR. CRH (10(-8) M) led to a moderate increase of cortisol release (145.7+/-20.0%) from cortical and chromaffin adrenal cells in co-culture. This effect corresponded to 41.8% of the maximal increase induced by ACTH (10(-8) M). The action of CRH was completely inhibited by antalarmin. CRH, ACTH, and both CRH-R1 and CRH-R2 mRNAs are expressed in the adult human adrenal gland, CRH stimulates cortisol production in cortical and chromaffin cell co-cultures. This effect is blocked by antalarmin, a selective CRH-R1 receptor antagonist, suggesting that CRH-R1 receptors are involved in an intraadrenal CRH/ACTH control system in humans. C1 NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Dusseldorf, Diabet Res Inst, D-4000 Dusseldorf, Germany. Univ Dusseldorf, Dept Surg, D-4000 Dusseldorf, Germany. RP Bornstein, SR (reprint author), NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NR 40 TC 45 Z9 46 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAR PY 2000 VL 5 IS 2 BP 137 EP 141 DI 10.1038/sj.mp.4000720 PG 5 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 307AF UT WOS:000086630600008 PM 10822340 ER PT J AU Yoshikawa, T Padigaru, M Karkera, JD Sharma, M Berrettini, WH Esterling, LE Detera-Wadleigh, SD AF Yoshikawa, T Padigaru, M Karkera, JD Sharma, M Berrettini, WH Esterling, LE Detera-Wadleigh, SD TI Genomic structure and novel variants of myo-inositol monophosphatase 2 (IMPA2) SO MOLECULAR PSYCHIATRY LA English DT Article DE bipolar affective disorder; chromosome 18; polymorphism; lithium; association ID MYOINOSITOL MONOPHOSPHATASE; BIPOLAR DISORDER; SUSCEPTIBILITY; TRANSCRIPTION; GENE; CHROMOSOME-18; PROMOTER; PROTEINS; LITHIUM; ILLNESS AB Recently, we cloned the human myo-inositol monophosphatase 2 (IMPA2) cDNA and established its map location to chromosome 18p11.2, a region previously implicated in bipolar disorder. Because the myo-inositol monophosphatase enzyme has been shown to be inhibited by lithium, an effective therapeutic agent for bipolar disorder, IMPA2 is a plausible positional and functional candidate gene. To permit comprehensive screening for variants we characterized the genomic structure and isolated the potential promoter of IMPA2 The gene was found to encode eight exons spanning similar to 27 kb, The proximal 1-kb 5' flanking region did not contain an obvious TATA box but multiple potential binding sites for Spl and consensus motifs for AP2 and other transcription factors were evident. Sequencing of the coding region and splice junctions in unrelated bipolar disorder patients detected novel variants. A missense mutation in exon 2, His76Tyr, was found in one patient. His76 is evolutionarily conserved and replacement with Tyr introduces a potential site for phosphorylation. The other polymorphisms included an Rsal polymorphism, IVS1-15G>A, and a T --> C silent mutation in the third nucleotide of codon 53 in exon 2. By Fisher's exact test the silent mutation showed a trend for association (P = 0.051) with bipolar disorder suggesting that further scrutiny of this gene is warranted. C1 NIMH, Unit Gene Mapping & Express, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. Univ Penn, Dept Psychiat, Ctr Neurobiol & Behav, Philadelphia, PA 19104 USA. RP Detera-Wadleigh, SD (reprint author), NIMH, Unit Gene Mapping & Express, Clin Neurosci Branch, NIH, Bldg 36,Rm 3D16, Bethesda, MD 20892 USA. NR 17 TC 41 Z9 44 U1 1 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAR PY 2000 VL 5 IS 2 BP 165 EP 171 DI 10.1038/sj.mp.4000688 PG 7 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 307AF UT WOS:000086630600012 PM 10822344 ER PT J AU Hu, S Brody, CL Fisher, C Gunzerath, L Nelson, ML Sabol, SZ Sirota, LA Marcus, SE Greenberg, BD Murphy, DL Hamer, DH AF Hu, S Brody, CL Fisher, C Gunzerath, L Nelson, ML Sabol, SZ Sirota, LA Marcus, SE Greenberg, BD Murphy, DL Hamer, DH TI Interaction between the serotonin transporter gene and neuroticism in cigarette smoking behavior SO MOLECULAR PSYCHIATRY LA English DT Article DE smoking; gene; polymorphism; serotonin transporter; personality; Neuroticism ID MAJOR DEPRESSION; NICOTINE DEPENDENCE; CESSATION TREATMENT; REGULATORY REGION; NUCLEUS-ACCUMBENS; HARM AVOIDANCE; YOUNG-ADULTS; POLYMORPHISM; PERSONALITY; ASSOCIATION AB Cigarette smoking behavior is influenced by both personality traits and inherited factors. Previous research showed that neuroticism-a broad personality domain that includes anxiety, depression, impulsiveness and vulnerability-increases the risk of being a smoker, primarily because of difficulty in quitting. Neuroticism has also been associated with the 5-HTTLPR, a functional polymorphism in the promoter for the serotonin transporter gene. We used population and family-based methods to analyze the joint effects of the 5-HTTLPR and neuroticism on smoking behavior in a population of 759 never, current, and former smokers, all members of sib-pairs, Our main finding is that smoking behavior is influenced by an interaction between neuroticism and 5-HTTLPR genotype. Specifically, neuroticism was positively correlated with current smoking and negatively associated with smoking cessation in individuals and siblings with poorly transcribed 5-HTTLPR-S genotypes, but not in those with the more highly expressed 5-HTTLPR-L genotype, Individuals with both a 5-HTTLPR-S genotype and a high level of neuroticism had the greatest difficulty in quitting smoking. These data, if replicated, suggest that smoking behavior is more strongly influenced by the combination of the serotonin transporter gene and neuroticism than by either factor alone, and that personality scores and 5-HTTLPR genotype may predict the clinical efficacy of certain smoking cessation drugs. C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NIDA, Oral Dis Prevent Risk Factors & Mol Epidemiol Bra, NIH, Bethesda, MD 20892 USA. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. RP Hamer, DH (reprint author), NCI, Biochem Lab, NIH, Bld 37,Rm 4A13,37 Convent Dr, Bethesda, MD 20892 USA. NR 46 TC 99 Z9 102 U1 2 U2 8 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAR PY 2000 VL 5 IS 2 BP 181 EP 188 DI 10.1038/sj.mp.4000690 PG 8 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 307AF UT WOS:000086630600014 PM 10822346 ER PT J AU Lerman, C Caporaso, NE Audrain, J Main, D Boyd, NR Shields, PG AF Lerman, C Caporaso, NE Audrain, J Main, D Boyd, NR Shields, PG TI Interacting effects of the serotonin transporter gene and neuroticism in smoking practices and nicotine dependence SO MOLECULAR PSYCHIATRY LA English DT Article DE smoking; genetics; serotonin ID FAGERSTROM TOLERANCE QUESTIONNAIRE; REGULATORY REGION; POLYMORPHISM; ANXIETY; ASSOCIATION; CESSATION AB Individual differences in propensity to nicotine dependence appear to be mediated, in part, by genetic factors.' The serotonin transporter gene has a functional polymorphism (5-HTTLPR) which modulates gene transcription and reuptake.(2,3) A possible role in nicotine dependence is suggested by a link between 5-HTTLPR and neuroticism,(4) a personality trait which has been related to smoking practices.(5) In a cross-sectional study of 185 smokers, we utilized multiple linear regression modeling to examine the interacting effects of the 5-HTTLPR and neuroticism on smoking practices and nicotine dependence. Genotype was classified according to the presence or absence of the short (s) allele vs the long (I) allele of 5-HTTLPR tie, s/s or s/l vs I/I). Models controlled for gender, age, race, and alcohol use. The 5-HTTLPR by neuroticism interaction effect was statistically significant in the models of nicotine intake (P = 0.05), nicotine dependence (P = 0.001), and smoking motivations (smoking to reduce negative mood (P = 0.01); smoking for stimulation (P = 0.01)), The results suggested that neuroticism was positively associated with these smoking practices among smokers with 5-HTTLPR S genotypes (s/s or s/l), but not among smokers with the L genotype (I/I), The 5-HTTLPR may modify the effects of neuroticism on smoking motivations and nicotine dependence. Assessment of 5-HTTLPR genotype and neuroticism may help to identify smokers who are more responsive to psychotropic medications, such as selective serotonin reuptake inhibitors (SSRIs), which are being used in smoking cessation treatment. C1 Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Washington, DC 20007 USA. NCI, Pharmacogenet Sect, Genet Epidemiol Branch, Bethesda, MD 20892 USA. Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19012 USA. NCI, Mol Epidemiol Sect, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Lerman, C (reprint author), Georgetown Univ, Med Ctr, Lombardi Canc Ctr, 2233 Wisconsin Ave NW,Suite 317, Washington, DC 20007 USA. RI Shields, Peter/I-1644-2012 FU NCI NIH HHS [CA63562] NR 30 TC 96 Z9 101 U1 3 U2 6 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAR PY 2000 VL 5 IS 2 BP 189 EP 192 DI 10.1038/sj.mp.4000672 PG 4 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 307AF UT WOS:000086630600015 PM 10822347 ER PT J AU Osher, Y Hamer, D Benjamin, J AF Osher, Y Hamer, D Benjamin, J TI Association and linkage of anxiety-related traits with a functional polymorphism of the serotonin transporter gene regulatory region in Israeli sibling pairs SO MOLECULAR PSYCHIATRY LA English DT Article DE neuroticism; harm avoidance; anxiety; genetics; serotonin transport ID PROMOTER POLYMORPHISM; PERSONALITY-TRAIT; PANIC DISORDER; HARM AVOIDANCE; POPULATION AB A functional polymorphism in the regulatory region of the serotonin transporter gene (5-HTTLPR) has been reported to be both associated and linked to anxiety-related personality measures, although other studies have not replicated these findings. The current study examines both association and linkage of the gene to two major anxiety-related personality measures, the harm avoidance scale on the Tridimensional Personality Questionnaire and the neuroticism scale of the NEO-PI-R, in a sample of 148 Israeli subjects comprising 74 same-sex sibling pairs. We replicated the reported association between the short allele and higher scores on the TPQ harm avoidance scale (P=0.03), including the subscale of shyness (P=0.02), and also found association in the same direction between the short allele and the NEO-PI-R neuroticism subscales of anxiety (P = 0.03) and depression (P = 0.04). Sib-pair linkage analysis, using the regression method, further supported a role of the 5-HTTLPR in anxiety-related personality traits. C1 Ben Gurion Univ Negev, Soroka Med Ctr, Dept Psychiat, IL-84101 Beer Sheva, Israel. Ben Gurion Univ Negev, Fac Hlth Sci, Beer Sheva Mental Hlth Ctr, Beer Sheva, Israel. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Benjamin, J (reprint author), Ben Gurion Univ Negev, Soroka Med Ctr, Dept Psychiat, POB 151, IL-84101 Beer Sheva, Israel. RI OSHER, YAMIMA/F-1359-2012 OI OSHER, YAMIMA/0000-0002-9635-7973 NR 21 TC 89 Z9 95 U1 4 U2 12 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAR PY 2000 VL 5 IS 2 BP 216 EP 219 DI 10.1038/sj.mp.4000660 PG 4 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 307AF UT WOS:000086630600021 PM 10822353 ER PT J AU Wu, T Kim, HJ Sellers, SE Meade, KE Agricola, BA Metzger, ME Kato, I Donahue, RE Dunbar, CE Tisdale, JF AF Wu, T Kim, HJ Sellers, SE Meade, KE Agricola, BA Metzger, ME Kato, I Donahue, RE Dunbar, CE Tisdale, JF TI Prolonged high-level detection of retrovirally marked hematopoietic cells in nonhuman primates after transduction of CD34(+) progenitors using clinically feasible methods SO MOLECULAR THERAPY LA English DT Article DE hematopoietic stem cell; retroviral; gene transfer; rhesus; in vivo; stroma; fibronectin; flt3; megakaryocyte growth and development factor; engraftment ID MEDIATED GENE-TRANSFER; BONE-MARROW CELLS; BLOOD STEM-CELLS; PERIPHERAL-BLOOD; IN-VITRO; AUTOLOGOUS TRANSPLANTATION; GROWTH-FACTORS; SELF-RENEWAL; CORD-BLOOD; ABILITY AB Low-level retroviral transduction and engraftment of hematopoietic long-term repopulating cells in large animals and humans remain primary obstacles to the successful application of hematopoietic stem cell (HSC) gene transfer in humans. Recent studies have reported improved efficiency by including stromal cells (STR), or the fibronectin fragment CH-296 (FN), and various cytokines such as flt3 ligand (FLT) during ex vivo culture and transduction in nonhuman primates. In this work, we extend our studies using the rhesus competitive repopulation model to further explore optimal and clinically feasible peripheral blood (PB) progenitor cell transduction methods. First, we compared transduction in the presence of either preformed autologous STR or immobilized FN. Long-term clinically relevant gene marking levels in multiple hematopoietic lineages from both conditions were demonstrated in vivo by semiquantitative PCR, colony PCR, and genomic Southern blotting, suggesting that FN could replace STR in ex vivo transduction protocols. Second, we compared transduction on FN in the presence of IL-3, IL-6, stem cell factor (SCF), and FLT (our best cytokine combination in prior studies) with a combination of megakaryocyte growth and development factor (MGDF), SCF, and FLT. Gene marking levels were equivalent in these animals, with no significant effect on retroviral gene transfer efficiency assessed in vivo by the replacement of IL-3 and IL-6 with MGDF. Our results indicate that SCF/G-CSF-mobilized PB CD34(+) cells are transduced with equivalent efficiency in the presence of either STR or FN, with stable long-term marking of multiple lineages at levels of 10-15% and transient marking as high as 54%. These results represent an advance in the field of HSC gene transfer using methods easily applied in the clinical setting. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. Takara Shuzo Co Ltd, Biotechnol Res Labs, Shiga 5202193, Japan. RP Dunbar, CE (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Room 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 37 TC 91 Z9 94 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAR PY 2000 VL 1 IS 3 BP 285 EP 293 DI 10.1006/mthe.2000.0034 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 366RR UT WOS:000090018800012 PM 10933944 ER PT J AU Hillman, CH Cuthbert, BN Cauraugh, J Schupp, HT Bradley, MM Lang, PJ AF Hillman, CH Cuthbert, BN Cauraugh, J Schupp, HT Bradley, MM Lang, PJ TI Psychophysiological responses of sport fans SO MOTIVATION AND EMOTION LA English DT Article; Proceedings Paper CT Annual Meeting of the North-American-Society-of-the-Psychology-of-Sport-and-Physical-Activity CY MAY 30, 1997 CL DENVER, COLORADO SP N Amer Soc Psychol Sport & Phys Activ ID STARTLE; EMOTION; PERCEPTION; PICTURES; REFLEX AB The present study investigated psychophysiological differences in identified sport fans within the context of the biphasic theory of emotion (P.J. Lang, 1985). Forty participants, grouped into three levels of identification with the local university athletic teams, viewed Jive pictures from each of two categories (team-relevant sport and team-irrelevant sport). Self-identified sport fans rated team-relevant pictures as more pleasant and arousing compared to team-irrelevant pictures. The P3 component of the event-related potential to an irrelevant startle probe was diminished and heart-rate deceleration was enhanced during team-relevant pictures as a function of fan identification level, suggesting that these pictures evoked a motivated attentional state. Neither probe-P3 nor heart rate differed for team-irrelevant pictures. Lastly, increased positivity for slow cortical potentials was evident for team-relevant compared to beam-irrelevant pictures, regardless of fan identification level. These results suggest the utility of psychophysiological measures in the study of sport fans, and for other positive emotions as well. C1 NIMH, Bethesda, MD 20892 USA. Univ Florida, Gainesville, FL 32611 USA. RP Cuthbert, BN (reprint author), NIMH, 6001 Execut Blvd,Room 6184,MSC 9625, Bethesda, MD 20892 USA. RI Hillman, Charles/A-4479-2009 NR 26 TC 12 Z9 12 U1 0 U2 3 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0146-7239 J9 MOTIV EMOTION JI Motiv. Emot. PD MAR PY 2000 VL 24 IS 1 BP 13 EP 28 DI 10.1023/A:1005535508771 PG 16 WC Psychology, Experimental; Psychology, Social SC Psychology GA 348TZ UT WOS:000089003700002 ER PT J AU Monti, P Inga, A Aprile, A Campomenosi, P Menichini, P Ottaggio, L Viaggi, S Ghigliotti, G Abbondandolo, A Fronza, G AF Monti, P Inga, A Aprile, A Campomenosi, P Menichini, P Ottaggio, L Viaggi, S Ghigliotti, G Abbondandolo, A Fronza, G TI p53 mutations experimentally induced by 8-methoxypsoralen plus UVA (PUVA) differ from those found in human skin cancers in PUVA-treated patients SO MUTAGENESIS LA English DT Article ID SQUAMOUS-CELL CARCINOMA; YEAST FUNCTIONAL ASSAY; CROSS-LINKABLE SITES; A RADIATION PUVA; MOLECULAR EPIDEMIOLOGY; ULTRAVIOLET-LIGHT; PSORALEN ADDUCTS; FOLLOW-UP; GENE; PSORIASIS AB 8-Methoxypsoralen (8-MOP) plus UVA irradiation (PUVA therapy) has been used for the treatment of psoriasis, PUVA therapy has been associated with an increased risk of developing skin squamous cell carcinoma (SCC), In order to determine the PUVA-induced p53 mutation spectrum, a yeast expression vector harbouring a human wild-type p53 cDNA was incubated with 8-MOP, and UVA irradiated in vitro. PUVA-damaged and undamaged DNA was transfected into a yeast strain containing the ADE2 gene regulated by a p53-responsive promoter, An 8-MOP concentration-dependent decrease in survival and increase in mutant frequency were observed. At a fixed 8-MOP concentration, survival decreased and mutant frequency increased as UVA irradiation increased. Eleven mutant clones contained 11 mutations: 10 were single base pair substitutions, the remaining one being a complex mutation. All eight T:A-targeted mutations were at 5'-TpA sites, hallmark mutations of PUVA mutagenesis, Through a rigorous statistical test, the PUVA-induced p53 mutation spectrum appears to differ significantly (P < 0.0002) from that observed in SCC in PUVA-treated patients, The present work demonstrates that a specific PUVA-induced mutational fingerprint could be obtained and recognized on human p53 cDNA, This result may suggest that PUVA therapy can be a risk factor for the development of SCC in psoriasis patients through a mechanism not involving the induction of p53 mutations. C1 Natl Canc Inst, Mutagenesis Lab, IST, I-16132 Genoa, Italy. Univ Genoa, Dept Oncol Biol & Genet, Genoa, Italy. Natl Canc Inst, Dermatol Unit, IST, I-16132 Genoa, Italy. RP Fronza, G (reprint author), Natl Canc Inst, Mutagenesis Lab, IST, Largo Rosanna Benzi 10, I-16132 Genoa, Italy. RI Campomenosi, Paola/C-9729-2011; OI Campomenosi, Paola/0000-0002-8853-1134 NR 51 TC 9 Z9 10 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD MAR PY 2000 VL 15 IS 2 BP 127 EP 132 DI 10.1093/mutage/15.2.127 PG 6 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 297GG UT WOS:000086073400006 PM 10719037 ER PT J AU Ton-That, TT Doron, D Pollard, BS Bacher, J Pollard, HB AF Ton-That, TT Doron, D Pollard, BS Bacher, J Pollard, HB TI In vivo bypass of hemophilia A coagulation defect by Factor XIIa implant SO NATURE BIOTECHNOLOGY LA English DT Article DE hemophilia A; hemophilia B; coagulation; calcium; factor VII; factor VIIa; factor VIII; factor IX; factor Xa; factor XIIa; phospholipids; bypass activity ID RECOMBINANT FACTOR-VIIA; EXTRINSIC PATHWAY INHIBITOR; ACTIVATED FACTOR-VII; HIGH-TITER INHIBITORS; ISLET TRANSPLANTATION; FACTOR-XA; MANAGEMENT; PATIENT; PURIFICATION; EXPERIENCE AB Hemophilia A and B coagulation defects, which are caused by deficiencies of Factor VIII and Factor IX, respectively, can be bypassed by administration of recombinant Factor VIIa. However, the short half-life of recombinant Factor VIIa in vivo negates its routine clinical use. We report here an in vivo method for the continuous generation of Factor VIIa. The method depends on the implantation of a porous chamber that contains Factor Xa or XIIa, and continuously generates Factor VIIa bypass activity from the subject's own Factor VII, which enters the chamber by diffusion. Once inside, the Factor VII is cleaved to Factor VIIa by the immobilized Factor Xa or XIIa. The newly created Factor VIIa diffuses out of the chamber and back into the circulation, where it can bypass the deficient Factors VIII or IX, and enable coagulation to occur. In vitro, this method generates sufficient Factor VIIa to substantially correct Factor VIII-deficient plasma when assessed by the classical aPTT coagulation assay. In vivo, a Factor XIIa peritoneal implant generates bypass activity for up to one month when tested in rhesus monkeys. Implantation of such a chamber in a patient with hemophilia A or B could eventually provide a Viable alternative to replacement therapies using exogenous coagulation factors. C1 Uniformed Serv Univ Hlth Sci, Sch Med, Dept Anat & Cell Biol, Bethesda, MD 20814 USA. NIDDKD, Cell Biol & Genet Lab, NIH, Bethesda, MD 20892 USA. NIH, Off Director, Bethesda, MD 20892 USA. NIH, Vet Resources Program, Natl Ctr Res Resources, Bethesda, MD 20892 USA. RP Pollard, HB (reprint author), Uniformed Serv Univ Hlth Sci, Sch Med, Dept Anat & Cell Biol, Bethesda, MD 20814 USA. NR 44 TC 10 Z9 10 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAR PY 2000 VL 18 IS 3 BP 289 EP 295 PG 7 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 292AC UT WOS:000085771100025 PM 10700143 ER PT J AU Cutrona, G Carpaneto, EM Ulivi, M Roncella, S Landt, O Ferrarini, M Boffa, LC AF Cutrona, G Carpaneto, EM Ulivi, M Roncella, S Landt, O Ferrarini, M Boffa, LC TI Effects in live cells of a c-myc anti-gene PNA linked to a nuclear localization signal SO NATURE BIOTECHNOLOGY LA English DT Article DE peptide nucleic acid (PNA); anti-gene; nuclear localization signal (NLS) peptide; c-myc; lymphomas ID LYMPHOMA CELLS; ACIDS PNA; PEPTIDE; DNA; STABILITY; INVASION; SEQUENCE; TRANSCRIPTION; LOCATION; BINDING AB Peptide nucleic acids (PNA) are synthetic homologs of nucleic acids in which the phosphate-sugar polynucleotide backbone is replaced by a flexible polyamide. In this study, a PNA construct was employed as an anti-gene agent in intact cells in culture. The cell lines studied were derived from Burkitt's lymphomas (BL) that presented a translocated and hyperexpressed c-myc oncogene. A 17-mer anti-myc PNA, complementary to a unique sequence located at the beginning of the second exon of the oncogene, and was covalently linked at its N terminus to a nuclear localization signal (NLS) (PNA-myc(wt)-NLS). When BL cells were exposed to PNA-myc(wt)-NLS, the anti-gene construct was localized predominantly in the cell nuclei and a rapid consequent downregulation of c-myc expression occurred. Under these conditions, both completion of a productive cell cycle and apoptosis were inhibited. C1 Natl Canc Inst, Serv Oncol Sperimentale, Genoa, Italy. Natl Canc Inst, Serv Immunol Clin, Genoa, Italy. Osped St Andrea, Serv Anat Patol, La Spezia, Italy. TIB MOLBIOL, D-10829 Berlin, Germany. Univ Genoa, Dipartimento Oncol Biol & Genet, Genoa, Italy. RP Boffa, LC (reprint author), Natl Canc Inst, Serv Oncol Sperimentale, Genoa, Italy. OI Ferrarini, Manlio/0000-0002-6154-2570; Cutrona, Giovanna/0000-0002-3335-1101 NR 31 TC 181 Z9 185 U1 3 U2 13 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAR PY 2000 VL 18 IS 3 BP 300 EP 303 PG 4 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 292AC UT WOS:000085771100027 PM 10700145 ER PT J AU Lohrum, MAE Ashcroft, M Kubbutat, MHG Vousden, KH AF Lohrum, MAE Ashcroft, M Kubbutat, MHG Vousden, KH TI Identification of a cryptic nucleolar-localization signal in MDM2 SO NATURE CELL BIOLOGY LA English DT Article ID TUMOR-SUPPRESSOR; P53; P14(ARF); PRODUCT; LOCUS; RB C1 NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Vousden, KH (reprint author), NCI, Frederick Canc Res & Dev Ctr, Room 22-96,W 17th St, Frederick, MD 21702 USA. NR 17 TC 149 Z9 150 U1 0 U2 6 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD MAR PY 2000 VL 2 IS 3 BP 179 EP 181 PG 3 WC Cell Biology SC Cell Biology GA 292AE UT WOS:000085771300019 PM 10707090 ER PT J AU Ross, DT Scherf, U Eisen, MB Perou, CM Rees, C Spellman, P Iyer, V Jeffrey, SS Van de Rijn, M Waltham, M Pergamenschikov, A Lee, JCE Lashkari, D Shalon, D Myers, TG Weinstein, JN Botstein, D Brown, PO AF Ross, DT Scherf, U Eisen, MB Perou, CM Rees, C Spellman, P Iyer, V Jeffrey, SS Van de Rijn, M Waltham, M Pergamenschikov, A Lee, JCE Lashkari, D Shalon, D Myers, TG Weinstein, JN Botstein, D Brown, PO TI Systematic variation in gene expression patterns in human cancer cell lines SO NATURE GENETICS LA English DT Article ID ANTICANCER DRUG SCREEN; MOLECULAR PHARMACOLOGY; EPITHELIAL-CELLS; BREAST; DIFFERENTIATION; ESTABLISHMENT; PROTEINS; ADHESION; DISPLAY; DISEASE AB We used cDNA microarrays to explore the variation in expression of approximately 8,000 unique genes among the 60 cell lines used in the National Cancer Institute's screen for anti-cancer drugs. Classification of the cell lines based solely on the observed patterns of gene expression revealed a correspondence to the ostensible origins of the tumours from which the cell lines were derived. The consistent relationship between the gene expression patterns and the tissue of origin allowed us to recognize outliers whose previous classification appeared incorrect. Specific features of the gene expression patterns appeared to be related to physiological properties of the cell lines, such as their doubling time in culture, drug metabolism or the interferon response. Comparison of gene expression patterns in the cell lines to those observed in normal breast tissue or in breast tumour specimens revealed features of the expression patterns in the tumours that had recognizable counterparts in specific cell lines, reflecting the tumour, stromal and inflammatory components of the tumour tissue. These results provided a novel molecular characterization of this important group of human cell lines and their relationships to tumours in vivo. C1 Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Surg, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Incyte Pharmaceut, Fremont, CA USA. Genometrix Inc, The Woodlands, TX USA. NCI, Informat Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diagnosis,NIH, Rockville, MD USA. Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA. RP Brown, PO (reprint author), Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA. RI Waltham, Mark/A-1728-2009; Bell, Tiffany/F-4403-2010; OI Eisen, Michael/0000-0002-7528-738X; Perou, Charles/0000-0001-9827-2247 FU NCI NIH HHS [CA 077097] NR 44 TC 1465 Z9 1511 U1 3 U2 60 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAR PY 2000 VL 24 IS 3 BP 227 EP 235 DI 10.1038/73432 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 288XW UT WOS:000085590600011 PM 10700174 ER PT J AU Scherf, U Ross, DT Waltham, M Smith, LH Lee, JK Tanabe, L Kohn, KW Reinhold, WC Myers, TG Andrews, DT Scudiero, DA Eisen, MB Sausville, EA Pommier, Y Botstein, D Brown, PO Weinstein, JN AF Scherf, U Ross, DT Waltham, M Smith, LH Lee, JK Tanabe, L Kohn, KW Reinhold, WC Myers, TG Andrews, DT Scudiero, DA Eisen, MB Sausville, EA Pommier, Y Botstein, D Brown, PO Weinstein, JN TI A gene expression database for the molecular pharmacology of cancer SO NATURE GENETICS LA English DT Article ID TUMOR-CELL-LINES; ANTICANCER DRUG SCREEN; DIHYDROPYRIMIDINE DEHYDROGENASE; ELLIPTICINE ANALOGS; CLUSTER-ANALYSIS; DNA MICROARRAY; L-ASPARAGINASE; INSTITUTE; PATTERNS; DISCOVERY AB We used cDNA microarrays to assess gene expression profiles in 60 human cancer cell lines used in a drug discovery screen by the National Cancer Institute. Using these data, we linked bioinformatics and chemoinformatics by correlating gene expression and drug activity patterns in the NCI60 lines. Clustering the cell lines on the basis of gene expression yielded relationships very different from those obtained by clustering the cell lines on the basis of their response to drugs. Gene-drug relationships for the clinical agents 5-fluorouracil and L-asparaginase exemplify how variations in the transcript levels of particular genes relate to mechanisms of drug sensitivity and resistance. This is the first study to integrate large databases on gene expression and molecular pharmacology. C1 NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. NCI, Informat Technol Branch,Dev Therapeut Program, Div Canc Treatment & Diagnosis, NIH, Bethesda, MD 20892 USA. NCI, SAIC, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. NCI, Off Associate Director, DTP,DCTD, NIH, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA. RP Weinstein, JN (reprint author), NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bldg 37-5D-02, Bethesda, MD 20892 USA. RI Waltham, Mark/A-1728-2009; Bell, Tiffany/F-4403-2010; OI Eisen, Michael/0000-0002-7528-738X FU NCI NIH HHS [CA77097] NR 46 TC 1001 Z9 1052 U1 4 U2 46 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAR PY 2000 VL 24 IS 3 BP 236 EP 244 DI 10.1038/73439 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 288XW UT WOS:000085590600012 PM 10700175 ER PT J AU Ruiz-Perez, VL Ide, SE Strom, TM Lorenz, B Wilson, D Woods, K King, L Francomano, C Freisinger, P Spranger, S Marino, B Dallapiccola, B Wright, M Meitinger, T Polymeropoulos, MH Goodship, J AF Ruiz-Perez, VL Ide, SE Strom, TM Lorenz, B Wilson, D Woods, K King, L Francomano, C Freisinger, P Spranger, S Marino, B Dallapiccola, B Wright, M Meitinger, T Polymeropoulos, MH Goodship, J TI Mutations in a new gene in Ellis-van Creveld syndrome and Weyers acrodental dysostosis SO NATURE GENETICS LA English DT Article ID REGION AB Ellis-van Creveld syndrome (EvC, MIM 225500) is an autosomal recessive skeletal dysplasia characterized by short limbs, short ribs, postaxial polydactyly and dysplastic nails and teeth(1,2). Congenital cardiac defects, most commonly a defect of primary atrial septation producing a common atrium, occur in 60% of affected individuals. The disease was mapped to chromosome 4p16 in nine Amish subpedigrees and single pedigrees from Mexico, Ecuador and Brazil(3). Weyers acrodental dysostosis (MIM 193530), an autosomal dominant disorder with a similar but milder phenotype, has been mapped in a single pedigree to an area including the EvC critical region(4). We have identified a new gene (EVC), encoding a 992-amino-acid protein, that is mutated in individuals with EvC. We identified a splice-donor change in an Amish pedigree and six truncating mutations and a single amino acid deletion in seven pedigrees. The heterozygous carriers of these mutations did not manifest features of EvC. We found two heterozygous missense mutations associated with a phenotype, one in a man with Weyers acrodental dysostosis and another in a father and his daughter, who both have the heart defect characteristic of EvC and polydactyly, but not short stature. We suggest that EvC and Weyers acrodental dysostosis are allelic: conditions. C1 Univ Newcastle Upon Tyne, Sch Biochem & Genet, Human Genet Unit, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. Novartis Pharmaceut Corp, Pharmacogenet Div, Gaithersburg, MD USA. Univ Munich, Klinikum Innenstadt, Abt Med Genet, D-8000 Munich, Germany. Natl Human Genome Res Inst, Med Genet Branch, NIH, Bethesda, MD USA. George Washington Univ, Grad Genet Program GWIBS, Washington, DC USA. Tech Univ Munich, Kinderklin, D-8000 Munich, Germany. Univ Bremen, Ctr Human Genet, Bremen, Germany. Osped Pediat Bambino Gesu, Rome, Italy. Univ La Sapienza, CSS Mendel Inst, Rome, Italy. RP Goodship, J (reprint author), Univ Newcastle Upon Tyne, Sch Biochem & Genet, Human Genet Unit, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. RI Wilson, David/A-6264-2010; Ruiz-Perez, Victor /K-6066-2014; Meitinger, Thomas/O-1318-2015; Dallapiccola, Bruno/K-8692-2016 OI Ruiz-Perez, Victor /0000-0003-0635-3619; Dallapiccola, Bruno/0000-0002-5031-1013 NR 15 TC 142 Z9 148 U1 0 U2 8 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAR PY 2000 VL 24 IS 3 BP 283 EP 286 DI 10.1038/73508 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 288XW UT WOS:000085590600021 PM 10700184 ER PT J AU Gessain, A Pecon-Slattery, J Meertens, L Mahieux, R AF Gessain, A Pecon-Slattery, J Meertens, L Mahieux, R TI Origins of HTLV-1 in South America SO NATURE MEDICINE LA English DT Letter C1 Inst Pasteur, Dept SIDA & Retrovirus, Unite Oncol Virale, F-75724 Paris 15, France. NCI, Lab Genom Divers, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Gessain, A (reprint author), Inst Pasteur, Dept SIDA & Retrovirus, Unite Oncol Virale, 25-28 Rue Dr Roux, F-75724 Paris 15, France. RI Meertens, Laurent/E-8043-2017 NR 0 TC 13 Z9 14 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAR PY 2000 VL 6 IS 3 BP 232 EP 232 DI 10.1038/73020 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 288TL UT WOS:000085580500002 PM 10700196 ER PT J AU Carter, R Mendis, KN Miller, LH Molineaux, L Saul, A AF Carter, R Mendis, KN Miller, LH Molineaux, L Saul, A TI Malaria transmission-blocking vaccines - how can their development be supported? SO NATURE MEDICINE LA English DT Editorial Material C1 Univ Edinburgh, Inst Cell Anim & Populat Biol, Edinburgh EH9 3JT, Midlothian, Scotland. WHO, Roll Back Malaria Project, CH-1211 Geneva 27, Switzerland. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. PO Royal Brisbane Hosp, Queensland Inst Med Res, Brisbane, Qld 4029, Australia. RP Carter, R (reprint author), Univ Edinburgh, Inst Cell Anim & Populat Biol, W Mains Rd, Edinburgh EH9 3JT, Midlothian, Scotland. RI Saul, Allan/I-6968-2013 OI Saul, Allan/0000-0003-0665-4091 NR 13 TC 85 Z9 86 U1 0 U2 6 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAR PY 2000 VL 6 IS 3 BP 241 EP 244 DI 10.1038/73062 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 288TL UT WOS:000085580500019 PM 10700212 ER PT J AU Wilson, SH Kunkel, TA AF Wilson, SH Kunkel, TA TI Passing the baton in base excision repair SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID DNA-POLYMERASE-BETA; HUMAN APURINIC ENDONUCLEASE; CRYSTAL-STRUCTURES; ABASIC SITES; LIGASE-III; PROTEIN; XRCC1; GLYCOSYLASE C1 NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Kunkel, TA (reprint author), NIEHS, Struct Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. NR 31 TC 239 Z9 241 U1 1 U2 2 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD MAR PY 2000 VL 7 IS 3 BP 176 EP 178 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 289YE UT WOS:000085648900005 PM 10700268 ER PT J AU Bernstein, HD AF Bernstein, HD TI A surprising function for SRP RNA? SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID SIGNAL RECOGNITION PARTICLE; ESCHERICHIA-COLI; ENDOPLASMIC-RETICULUM; MEMBRANE-PROTEINS; SEQUENCE BINDING; GTP HYDROLYSIS; DOMAIN; PEPTIDE; REGION; TRANSLOCATION C1 NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Bernstein, HD (reprint author), NIDDKD, Genet & Biochem Branch, NIH, Bldg 10,Room 9D-20,10 Ctr Dr, Bethesda, MD 20892 USA. NR 31 TC 7 Z9 7 U1 1 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD MAR PY 2000 VL 7 IS 3 BP 179 EP 181 DI 10.1038/73265 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 289YE UT WOS:000085648900006 PM 10700269 ER PT J AU Yang, F Forrer, P Dauter, Z Conway, JF Cheng, NQ Cerritelli, ME Steven, AC Pluckthun, A Wlodawer, A AF Yang, F Forrer, P Dauter, Z Conway, JF Cheng, NQ Cerritelli, ME Steven, AC Pluckthun, A Wlodawer, A TI Novel fold and capsid-binding properties of the lambda-phage display platform protein gpD SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID HERPES-SIMPLEX VIRUS; BACTERIOPHAGE-LAMBDA; RECOMBINANT BACULOVIRUSES; MACROMOLECULAR STRUCTURES; SURFACE LATTICE; SYSTEM; VP26; DIFFRACTION; REPLACEMENT; MATURATION AB The crystal structure of gpD, the capsid-stabilizing protein of bacteriophage lambda, was solved at 1.1 Angstrom resolution. Data were obtained from twinned crystals in space group PZ, and refined with anisotropic temperature factors to an R-factor of 0.098 (R-free = 0.132). GpD (109 residues) has a novel fold with an unusually low content of regular secondary structure. Noncrystallographic trimers with substantial intersubunit interfaces were observed. The C-termini are well ordered and located on one side of the trimer, relatively far from its three-fold axis. The N-termini are disordered up to Ser 15, which is close to the three-fold axis and on the same side as the C-termini. A density map of the icosahedral viral capsid at 15 Angstrom resolution, obtained by cryo-electron microscopy and image reconstruction, reveals gpD trimers, seemingly indistinguishable from the ones seen in the crystals, at all threefold sites. The map further reveals that the side of the trimer that binds to the capsid is the side on which both termini reside. Despite this orientation of the gpD trimer, fusion proteins connected by linker peptides to either terminus bind to the capsid, allowing protein and peptide display. C1 Univ Zurich, Inst Biochem, CH-8057 Zurich, Switzerland. NCI, Macromol Crystallog Lab, Program Struct Biol, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Brookhaven Natl Lab, NCI, FCRDC, Upton, NY 11973 USA. Brookhaven Natl Lab, NSLS, Upton, NY 11973 USA. NIAMSD, Struct Biol Lab, Bethesda, MD 20892 USA. RP Pluckthun, A (reprint author), Univ Zurich, Inst Biochem, Winterthurerstr 190, CH-8057 Zurich, Switzerland. RI Pluckthun, Andreas/C-2746-2009; Conway, James/A-2296-2010 OI Pluckthun, Andreas/0000-0003-4191-5306; Conway, James/0000-0002-6581-4748 NR 54 TC 108 Z9 114 U1 1 U2 7 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD MAR PY 2000 VL 7 IS 3 BP 230 EP 237 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 289YE UT WOS:000085648900020 PM 10700283 ER PT J AU Brambilla, R Cattabeni, F Ceruti, S Barbieri, D Franceschi, C Kim, YC Jacobson, KA Klotz, KN Lohse, MJ Abbracchio, MP AF Brambilla, R Cattabeni, F Ceruti, S Barbieri, D Franceschi, C Kim, YC Jacobson, KA Klotz, KN Lohse, MJ Abbracchio, MP TI Activation of the A(3) adenosine receptor affects cell cycle progression and cell growth SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Article DE adenosine; adenosine receptor; human A(3); CHO transfected cells; HEK293 transfected cells; cell growth modulation; cell cycle ID ANTAGONISTS; APOPTOSIS; AGONISTS; RAT; N-6-BENZYLADENOSINE-5'-URONAMIDES; 2-CHLORO-ADENOSINE; CLASSIFICATION; DERIVATIVES; HL-60 AB The A(3) adenosine receptor has been implicated in modulation of cell growth. As a first step to the characterization of the underlying mechanisms, we exposed Chinese hamster ovary (CHO) cells transfected with the human A(3) receptor (A(3)R-CHO) to selective A(3) receptor ligands. At micromolar concentrations, the A(3) agonists N-6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (IB-MECA) and its 2-chloro derivative Cl-IB-MECA reduced cell number, with no effects on either parental CHO cells (not expressing any adenosine receptor), or CHO cells transfected with the human A(1) receptor. Cl-IB-MECA also reduced cell number in the human HEK293 cell line transfected with the human A(3) receptor cDNA as opposed to the respective untransfected wild-type cells. In A(3)R-CHO, agonist-induced effects were antagonized by nanomolar concentrations of A(3) antagonists, including the triazoloquinazoline derivative MRS1220, the dihydropyridine derivative MRS 1191, and the triazolonaphthyridine derivative L-249,313, A(3) agonist-induced effects were not due to modulation of cell adhesion, nor to necrosis or apoptosis. Growth curves revealed highly impeded growth, and flow-cytometric analysis showed markedly reduced bromodeoxyuridine incorporation into nuclei. The effect on cell cycle was completely antagonized by MRS1191. Hence, activation of the human A(3) receptor in A(3)R-CHO results in markedly impaired cell cycle progression, suggesting an important role for this adenosine receptor subtype in cell cycle regulation and cell growth. C1 Univ Milan, Sch Pharm, Inst Pharmacol Sci, I-20133 Milan, Italy. Univ Modena, Dept Biomed Sci, Sect Gen Pathol, Modena, Italy. NIDDK, Bioorgan Chem Lab, Mol Recognit Sect, Bethesda, MD 20892 USA. Univ Wurzburg, Inst Pharmakol & Toxikol, D-97078 Wurzburg, Germany. RP Abbracchio, MP (reprint author), Univ Milan, Sch Pharm, Inst Pharmacol Sci, Via Balzaretti 9, I-20133 Milan, Italy. RI Ceruti, Stefania/A-6376-2008; Lohse, Martin/A-7160-2012; Jacobson, Kenneth/A-1530-2009; Abbracchio, Maria Pia/B-9342-2014; OI Ceruti, Stefania/0000-0003-1663-4211; Lohse, Martin/0000-0002-0599-3510; Jacobson, Kenneth/0000-0001-8104-1493; Abbracchio, Maria Pia/0000-0002-7833-3388; Klotz, Karl-Norbert/0000-0003-3553-3205 FU NIMH NIH HHS [01MH30003] NR 30 TC 76 Z9 76 U1 0 U2 5 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD MAR PY 2000 VL 361 IS 3 BP 225 EP 234 DI 10.1007/s002109900186 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 286VX UT WOS:000085470500001 PM 10731034 ER PT J AU Ajmani, RS Metter, EJ Jaykumar, R Ingram, DK Spangler, EL Abugo, OO Rifkind, JM AF Ajmani, RS Metter, EJ Jaykumar, R Ingram, DK Spangler, EL Abugo, OO Rifkind, JM TI Hemodynamic changes during aging associated with cerebral blood flow and impaired cognitive function SO NEUROBIOLOGY OF AGING LA English DT Article DE Alzheimer's disease; aging; oxidative stress; hemorheology; cerebral blood flow ID ALZHEIMERS-DISEASE; LIPID-PEROXIDATION; OXIDATIVE STRESS; CAROTID-ARTERY; RISK-FACTORS; BRAIN; AGE; PERFORMANCE; RAT AB This study investigates the age associated changes in hemorheological properties and cerebral blood flow. Partial correlations indicate that part of the age-dependent decrease in flow velocities can be attributed to a hemorheological decrement resulting in part from enhanced oxidative stress in the aged. A possible link with Alzheimer's pathology is suggested by the augmented hemorheological impairment resulting from in vitro incubation of red cells with amyloids. These results suggest that in aging, oxidative stress as well as amyloids may influence the fluid properties of blood, resulting in a potential decrement in blood Row and oxygen delivery to the brain. Animal intervention studies further demonstrate that altered hemorheological properties of blood can actually influence cognitive function. The relationships shown to exist between hemorheology, blood flow, amyloids, oxidative stress, and cognitive function suggest that these factors may be one of the mechanisms operating in the complex etiology of Alzheimer's disease. (C) 2000 Elsevier Science Inc. All rights reserved. C1 NIH, Gerontol Res Ctr, Baltimore, MD 21224 USA. NIH, Gerontol Res Ctr, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. NIH, Gerontol Res Ctr, Clin Invest Lab, Baltimore, MD 21224 USA. Cent Leather Res Inst, Chennai, India. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RP Rifkind, JM (reprint author), NIH, Gerontol Res Ctr, Room 4B09,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 37 TC 73 Z9 78 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAR-APR PY 2000 VL 21 IS 2 BP 257 EP 269 DI 10.1016/S0197-4580(00)00118-4 PG 13 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 328BY UT WOS:000087830000012 PM 10867210 ER PT J AU Maki, PM Resnick, SM AF Maki, PM Resnick, SM TI Longitudinal effects of estrogen replacement therapy on PET cerebral blood flow and cognition SO NEUROBIOLOGY OF AGING LA English DT Article DE estrogen; regional cerebral blood flow; memory; positron emission tomography; cognition; longitudinal ID POSITRON-EMISSION TOMOGRAPHY; HEALTHY POSTMENOPAUSAL WOMEN; ALZHEIMERS-DISEASE; OLDER WOMEN; GONADAL-STEROIDS; APOLIPOPROTEIN-E; MEMORY; RISK; ESTRADIOL; NEURONS AB Observational studies suggest that estrogen replacement therapy (ERT) may protect against age-related memory decline and lower the risk of Alzheimer's disease (AD). This study aimed to characterize the neural substrates of those effects by comparing 2-year longitudinal changes in regional cerebral blood flow (rCBF) in 12 ERT users and 16 nonusers. Positron emission tomography (PET) measurements of rCBF were obtained under three conditions: rest, and verbal and figural recognition memory tasks. Groups showed different patterns of change in rCBF over time in a number of brain areas. These group differences, for the most part, reflected regions of increased rCBF over time in users compared to nonusers. The greatest differences between ERT users and nonusers were in the hippocampus, parahippocampal gyrus, and temporal lobe, regions that form a memory circuit and that are sensitive to preclinical AD. Across a battery of standardized neuropsychological tests of memory, users obtained higher scores than did nonusers of comparable intellect. Group differences in longitudinal change in rCBF patterns may reflect one way through which hormones modulate brain activity and contribute to enhanced memory performance among ERT users. (C) 2000 Published by Elsevier Science Inc. All rights reserved. C1 NIA, Lab Personal & Cognit, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Maki, PM (reprint author), NIA, Lab Personal & Cognit, Gerontol Res Ctr, NIH, Box 3,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 54 TC 162 Z9 167 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAR-APR PY 2000 VL 21 IS 2 BP 373 EP 383 DI 10.1016/S0197-4580(00)00123-8 PG 11 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 328BY UT WOS:000087830000025 PM 10867223 ER PT J AU Berke, JD Hyman, SE AF Berke, JD Hyman, SE TI Addiction, dopamine, and the molecular mechanisms of memory SO NEURON LA English DT Review ID LONG-TERM POTENTIATION; IMMEDIATE-EARLY GENE; VENTRAL TEGMENTAL AREA; CONDITIONED PLACE PREFERENCE; RAT NUCLEUS-ACCUMBENS; C-FOS EXPRESSION; NEURONS IN-VIVO; PREPRODYNORPHIN MESSENGER-RNA; STRESS-INDUCED SENSITIZATION; LIMBIC-STRIATAL INTERACTIONS C1 NINDS, Sect Mol Plast, NIH, Bethesda, MD 20892 USA. NIMH, NIH, Bethesda, MD 20892 USA. RP Hyman, SE (reprint author), Boston Univ, Dept Psychol, Lab Cognit Neurobiol, 64 Cummington St, Boston, MA 02215 USA. NR 285 TC 759 Z9 810 U1 12 U2 96 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD MAR PY 2000 VL 25 IS 3 BP 515 EP 532 DI 10.1016/S0896-6273(00)81056-9 PG 18 WC Neurosciences SC Neurosciences & Neurology GA 301CY UT WOS:000086291700006 PM 10774721 ER PT J AU Zajicek, KB Price, CS Shoaf, SE Mehlman, PT Suomi, SJ Linnoila, M Higley, JD AF Zajicek, KB Price, CS Shoaf, SE Mehlman, PT Suomi, SJ Linnoila, M Higley, JD TI Seasonal variation in CSF5-HIAA concentrations in male rhesus macaques SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE seasonal variation; cerebrospinal fluid; 5-hydroxyindoleacetic acid; Macaca mulatta ID 5-HYDROXYINDOLEACETIC ACID CONCENTRATIONS; CEREBROSPINAL-FLUID MONOAMINE; DIMINISHED SOCIAL COMPETENCE; NONHUMAN PRIMATE MODEL; HEALTHY-VOLUNTEERS; AFFECTIVE-DISORDER; AMINE METABOLITES; VIOLENT OFFENDERS; FIRE SETTERS; BEHAVIOR AB Seasonal changes in cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) concentrations were assessed on multiple occasions in 103 free-ranging male rhesus macaques (macaca mulatta). At the time of sampling subjects ranged between the ages of 2 and 6 years. CSF samples were collected between the hours of 0900 and 1600 through the Fall, Winter, and Spring from 1990 through 1994. Data were analyzed in a general linear mixed model with random intercepts. Results indicated that CSF 5-HIAA concentrations decreased with age. CSF 5-HIAA concentrations were significantly increased in the Fall (October and November), which is the height of the breeding season, with no evidence of differences between Winter and Spring. There was also some evidence that the seasonal variation in CSF 5-HIAA concentrations was blunted in younger, more immature subjects. [Neuropsychopharmacology 22:240-250, 2000] Published by Elsevier Science Inc. C1 NICHHD, Comparat Ethol Lab, Poolesville, MD USA. NIAAA, Clin Studies Lab, Primate Unit, Poolesville, MD USA. Clin Studies Lab, Bethesda, MD USA. SUNY Stony Brook, Dept Anthropol, Stony Brook, NY 11794 USA. AGI Associates, Bethesda, MD USA. RP Higley, JD (reprint author), NIH Anim Ctr, POB 529,Bldg 112, Poolesville, MD 20837 USA. FU PHS HHS [223-89-1101] NR 50 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAR PY 2000 VL 22 IS 3 BP 240 EP 250 DI 10.1016/S0893-133X(99)00097-4 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 281ZT UT WOS:000085191900003 PM 10693151 ER PT J AU Ernst, M Zametkin, AJ Pascualvaca, D Matochik, JA Eisenhofer, G Murphy, DL Cohen, RM AF Ernst, M Zametkin, AJ Pascualvaca, D Matochik, JA Eisenhofer, G Murphy, DL Cohen, RM TI Adrenergic and noradrenergic plasma levels in Lesch-Nyhan disease SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE DHPG; epinephrine; Lesch-Nyhan disease; HPRT; self-injurious behaviour; aggression ID MONOAMINE-OXIDASE; AGGRESSIVE-BEHAVIOR; MOUSE MODEL; DOPAMINE; STRESS; NEUROTRANSMITTER; NOREPINEPHRINE; DEFICIENCY; ADAPTATION; RELEASE AB Noradrenergic dysfunction and abnormality in monoamine oxidase (MAO) enzyme activity have been reported previously in Lesch-Nyhan (LN) disease. This study examines peripheral indices of adrenergic, noradrenergic, and MAO function in children and young adults with LN disease (n = 11), and healthy subjects (n = 9). Blood samples, collected in identical conditions prior to a positron emission tomography (PET) study, were assayed for concentrations of epinephrine (EPI), norepinephrine (NE), and 3-methoxy-4-hydroxyphenylglycol (DHPG) (which results from the degradation of NE by monoamine oxidase type A [MAO-A]). The LN subjects had significantly higher EPI levels by 245% (p < .00) and lower DHPG levels by 42% (p <.00) compared to the control group. No group differences were noted in NE plasma levels. Cognitive function (IQ tested by Stanford Binet intelligence Scale) was associated with EPI in the LN group (r = 0.77, p = .009), but not in the control group. The abnormally high EPI plasma concentrations may indicate another biochemical dysfunction secondary to the absence of the HPRT enzyme in LN patients. such a biochemical deficit is likely to originate from the adrenal medulla, which is the primary site of EPI synthesis. The adrenal medulla may be directly affected by the absence of hypoxanthine guanine phosphoribosyl transferase (HPRT) enzyme, or may receive inappropriately high descending activation input from the brain. The abnormally low DHPG levels, in the context of normal NE levels, indicates low MAO activity, either as a primary deficit, or as secondary adaptive changes to spare NE levels that would otherwise be too low for adequate noradrenergic function. [Neuropsychopharmacology 22:320-326, 2000] Published by Elsevier Science Inc. C1 NIDA, Brain Imaging Ctr, Neuroimaging Branch, Baltimore, MD 21224 USA. NIMH, Cerebral Metab Lab, Bethesda, MD 20892 USA. NINDS, Psychol & Psychopathol Lab, Clin Neurosci Branch, Bethesda, MD 20892 USA. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Ernst, M (reprint author), NIDA, Brain Imaging Ctr, Neuroimaging Branch, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 38 TC 4 Z9 4 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAR PY 2000 VL 22 IS 3 BP 320 EP 326 DI 10.1016/S0893-133X(99)00119-0 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 281ZT UT WOS:000085191900012 PM 10693160 ER PT J AU Qureshi, NH Bankiewicz, KS Louis, DN Hochberg, FH Chiocca, EA Harsh, GR AF Qureshi, NH Bankiewicz, KS Louis, DN Hochberg, FH Chiocca, EA Harsh, GR TI Multicolumn infusion of gene therapy cells into human brain tumors: Technical report SO NEUROSURGERY LA English DT Article DE brain tumor; gene therapy; glioblastoma multiforme; malignant glioma; retroviral vectors; vector-producing cells ID IMPLANTATION AB OBJECTIVE: Effective gene therapy for brain tumors may require saturation of the tumors with tumoricidal doses of the therapeutic gene. Safe, precise, and efficient delivery of gene therapy vectors is required. Most reported cases of and published protocols for gene therapy for brain tumors involve freehand injection of retroviral vector-producing cells (VPCs) into the brain. Major disadvantages of this method include the inaccuracy of hand-guided needle placement and limited control of injection parameters. These factors can result in failure to deliver the viral vectors to specifically targeted sites within the brain, extensive tissue disruption resulting from excessively forceful injection, and reflux of the injectate along the needle tract. METHODS: We describe a novel stereotactic strategy for saturating tumor volumes with tumoricidal doses of gene therapy vectors and a new, more precise method of infusing VPCs. With our new instrument, the multicolumn stereotactic infusion system, needle placement is stereotactically guided and both VPC infusion and needle withdrawal are mechanically controlled. RESULTS: This technique, which has been used effectively for six patients, permits precise deposition of columns of VPCs throughout the targeted tumor volume. CONCLUSION: This technique should facilitate saturation of tumors with tumoricidal doses of gene therapy vectors and should improve the results of gene therapy protocols that rely on intraparenchymal injection for delivery. C1 Stanford Univ, Med Ctr, Stanford BrainTumor Ctr, Dept Neurosurg, Stanford, CA 94305 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Neurosurg, Mol Neurooncol Lab,Brain Tumor Ctr, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Pathol, Mol Neurooncol Lab,Brain Tumor Ctr, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Neurol, Mol Neurooncol Lab,Brain Tumor Ctr, Boston, MA USA. NINDS, Mol Therapeut Sect, Lab Mol Med & Neurosci, Bethesda, MD 20892 USA. RP Harsh, GR (reprint author), Stanford Univ, Med Ctr, Stanford BrainTumor Ctr, Dept Neurosurg, 300 Pasteur Dr,Edwards R227, Stanford, CA 94305 USA. FU NCI NIH HHS [CA62924] NR 9 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD MAR PY 2000 VL 46 IS 3 BP 663 EP 668 DI 10.1097/00006123-200003000-00027 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 290PH UT WOS:000085684200070 PM 10719863 ER PT J AU Worobec, AS Akin, C Scott, LM Metcalfe, DD AF Worobec, AS Akin, C Scott, LM Metcalfe, DD TI Mastocytosis complicating pregnancy SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID BLOOD MONONUCLEAR-CELLS; C-KIT; SYSTEMIC MASTOCYTOSIS; MANAGEMENT; MUTATION AB Objective: To review the experience of women who conceived after developing mastocytosis and who were observed at the National Institutes of Health. Methods: We reviewed our patient database for the years 1984-1998 to identify women with mastocytosis who had conceived. We then reviewed each woman's record, asked each woman to complete a questionnaire, and with permission wrote outside hospitals to obtain records of each labor and delivery. Results: We identified eight women who had become pregnant. These women delivered a total of 11 live infants. In approximately a third of the pregnancies, patients experienced:worsening of symptoms. They often used fewer medications during pregnancy because of safety concerns, and no greater incidence of adverse reactions was noted. Antihistamines were used most commonly, followed by oral prednisone. Medications used during delivery were well tolerated and included epidural analgesics. Neonates were generally healthy. None ito date have developed urticaria pigmentosa or systemic mastocytosis. Conclusion: A subset of women with mastocytosis might have had exacerbated mastocytosis during and after pregnancy, but labor and delivery progressed normally. Infants were born generally healthy and were without mastocytosis. Thus there appears to be no absolute contraindication to pregnancy for women with mastocytosis, although women should be aware that the choice to have a child is not without some added risk. (Obstet Gynecol 2000;95:391-5.). C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Worobec, AS (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C205,10 Ctr Dr,MSC 1881, Bethesda, MD 20892 USA. NR 14 TC 22 Z9 23 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAR PY 2000 VL 95 IS 3 BP 391 EP 395 DI 10.1016/S0029-7844(99)00591-8 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 287QM UT WOS:000085517300015 PM 10711550 ER PT J AU Baird, DD AF Baird, DD TI The great douching debate: To douche, or not to douche SO OBSTETRICS AND GYNECOLOGY LA English DT Letter ID INFECTION; RISK C1 Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Baird, DD (reprint author), Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. OI Baird, Donna/0000-0002-5544-2653 NR 6 TC 4 Z9 4 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAR PY 2000 VL 95 IS 3 BP 473 EP 473 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 287QM UT WOS:000085517300034 PM 10711568 ER PT J AU Cooke, KZ Fisher, AG Mayberry, W Oakley, F AF Cooke, KZ Fisher, AG Mayberry, W Oakley, F TI Differences in activities of daily living process skills of persons with and without Alzheimer's disease SO OCCUPATIONAL THERAPY JOURNAL OF RESEARCH LA English DT Article DE Alzheimer's disease; assessment; ADL; intervention ID CROSS-CULTURAL ASSESSMENT; FUNCTIONAL PERFORMANCE; MOTOR; DEMENTIA; SIGNS; HETEROGENEITY AB This study demonstrates a methodology for identifying differences in the experienced difficulty of activities of daily living (ADL) process actions of task performance between persons who have dementia of the Alzheimer type (DAT) and persons who are well. The information gathered indicates that persons with DAT have greater ADL deficits, hypothesized to be related to underlying declarative memory, and relatively intact ADL skills, hypothesized to be related to underlying procedural memory. C1 Boulder Manor Living Ctr, Longmont, CO USA. Colorado State Univ, Dept Occupat Therapy, Ft Collins, CO 80523 USA. NIH, Occupat Therapy Sect, Bethesda, MD 20892 USA. RP Cooke, KZ (reprint author), Boulder Manor Living Ctr, Longmont, CO USA. NR 65 TC 15 Z9 15 U1 2 U2 7 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0276-1599 J9 OCCUP THER J RES JI Occup. Ther. J. Res. PD SPR PY 2000 VL 20 IS 2 BP 87 EP 105 PG 19 WC Rehabilitation SC Rehabilitation GA 307DQ UT WOS:000086638300001 ER PT J AU Hsia, CC Nakashima, Y Thorgeirsson, SS Harris, CC Minemura, M Momosaki, S Wang, NJ Tabor, E AF Hsia, CC Nakashima, Y Thorgeirsson, SS Harris, CC Minemura, M Momosaki, S Wang, NJ Tabor, E TI Correlation of immunohistochemical staining and mutations of p53 in human hepatocellular carcinoma SO ONCOLOGY REPORTS LA English DT Article DE hepatocellular carcinoma; immunohistochemistry; mutation; p53; tumor suppressor gene ID GENE MUTATION; CANCER; OVEREXPRESSION; MARKER AB Mutations of the p53 tumor suppressor gene are common in hepatocellular carcinomas (HCCs). Detection of mutations by sequencing provides more information than immunohistochemical staining, but the equipment needed and the time required make it less practical for use in large-scale studies or in studies in developing countries. The degree of correlation between results obtained with these two methods has been studied in various tumors but has not been well-established in human HCCs. Paraffin sections of HCCs of 28 patients from Qidong, China were immunohistochemically stained using monoclonal antibody to p53. In addition, exons 5-8 of the p53 gene were sequenced in these HCCs. Of the 28 HCCs, nine had 0-9% of nuclei stained for p53, and 19 had 50-95% stained. Mutations in p53 exons 5-8 were found in 17/28 (61%) HCCs, including 15 at codon 249 (exon 7), one at codon 198 (exon 6), and one at codon 175 (exon 5). Among these 17 cases with p53 mutations, 16 cases (94%) had 50-95% of nuclei stained. Among 11 HCCs with no mutations by sequencing, 8 were also negative by immunohistochemistry (0-9% of nuclei stained) (73%) (the five HCCs with no staining whatsoever all had wild-type p53). Immunohistochemical staining to detect p53 mutations in human HCCs detected most mutations that were detected by sequencing (94% sensitivity, 73% specificity), and this method is therefore suitable when sequencing cannot be performed. C1 US FDA, CBER, Div Transfus Transmitted Dis, Rockville, MD 20852 USA. NCI, NIH, Bethesda, MD 20892 USA. Toyama Med & Pharmaceut Univ, Toyama, Japan. Qidong Liver Canc Inst, Qidong, Peoples R China. RP Tabor, E (reprint author), US FDA, CBER, Div Transfus Transmitted Dis, HFM-300,1401 Rockville Pike,Suite 400N, Rockville, MD 20852 USA. NR 15 TC 28 Z9 30 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD MAR-APR PY 2000 VL 7 IS 2 BP 353 EP 356 PG 4 WC Oncology SC Oncology GA 282AV UT WOS:000085194400025 PM 10671685 ER PT J AU Kitt, CA Gruber, K Davis, M Woolf, CJ Levine, JD AF Kitt, CA Gruber, K Davis, M Woolf, CJ Levine, JD TI Trigeminal neuralgia: opportunities for research and treatment SO PAIN LA English DT Review DE trigeminal neuralgia; epidemiology; diagnosis and assessment; etiology; treatment ID FACIAL-PAIN PATIENTS; NEUROVASCULAR COMPRESSION; DECOMPRESSION; FEATURES; BACLOFEN AB Trigeminal neuralgia was the focus of a recent workshop convened by the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute of Dental and Craniofacial Research (NIDCR). The workshop brought together basic scientists, clinicians, epidemiologists, and patient advocates. New research directions for epidemiology, diagnosis and assessment, pain mechanisms, and treatment were identified. (The workshop was held in Rockville MD on September 14, 1999, with financial support from NINDS, NIDCR, the NM Office of Rare Diseases, and the NM Pain Research Consortium.) (C) 2000 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved. C1 NINDS, Rockville, MD 20892 USA. NIDCR, Chron Dis Branch, Bethesda, MD 20892 USA. George Washington Univ, Sch Publ Hlth & Hlth Serv, Silver Spring, MD 20904 USA. Massachusetts Gen Hosp, Anesthesia Neural Plast Res Grp, Charlestown, MA 02129 USA. Univ Calif San Francisco, Div Neurosci, NIH, Pain Ctr, San Francisco, CA 94143 USA. RP Kitt, CA (reprint author), NINDS, 6001 Execut Blvd, Rockville, MD 20892 USA. NR 37 TC 72 Z9 84 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD MAR PY 2000 VL 85 IS 1-2 BP 3 EP 7 DI 10.1016/S0304-3959(99)00310-3 PG 5 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 289ZY UT WOS:000085652900002 PM 10692597 ER PT J AU Vargas, CM Macek, MD Marcus, SE AF Vargas, CM Macek, MD Marcus, SE TI Sociodemographic correlates of tooth pain among adults: United States, 1989 SO PAIN LA English DT Article; Proceedings Paper CT 125th Annual Meeting of the American-Public-Health-Association CY NOV 09-13, 1997 CL INDIANAPOLIS, INDIANA SP Amer Public Hlth Assoc, Natl Assoc Public Hlth Policy, APHA, Med Care Sect DE dental pain; NHIS; socioeconomic status; tooth pain; toothache ID QUALITY-OF-LIFE; OROFACIAL PAIN; ORAL HEALTH; PREVALENCE AB This study presents the sociodemographic distribution of tooth pain and the dental care utilization of affected individuals. Data for adults 20 years of age and over were derived from the 1989 National Health Interview Survey's supplements on dental health, orofacial pain, and health insurance (n = 33 073). Prevalence of tooth pain by socioeconomic status (SES) and adjusted odds ratios of reporting tooth pain in the past 6 months and of having no dental visits in the past year among persons reporting pain in the previous 6 months were computed taking into account the survey's complex sample design. Tooth pain in the past 6 months was reported by 14.5% (95% CI 14.0, 15.0) of adults aged 20-64 years and by 7.0% (95% CI 6.1, 7.9) of those 65 years and over. In the younger age group, tooth pain was more likely to be reported by those with low SES than it was by those with high SES; in the older age group, tooth pain was more likely reported by non-Hispanic blacks than it was by non-Hispanic whites or Hispanics. Of those reporting pain, younger and older non-Hispanic blacks and persons with lower educational attainment were more likely not to have a dental visit in the previous 12 months. Persons with low SES characteristics were more likely to report tooth pain and to endure their pain without the benefit of dental care while the pain was present. Published for the International Association for the Study of Pain by Elsevier Science B.V. C1 Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Off Anal Epidemiol & Hlth Promot, Hyattsville, MD 20782 USA. Univ Maryland, Baltimore Coll Dent Surg, Sch Dent, Dept Oral Hlth Care Delivery, Baltimore, MD 21201 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20894 USA. RP Vargas, CM (reprint author), Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Off Anal Epidemiol & Hlth Promot, 6525 Belcrest Rd,Room 730, Hyattsville, MD 20782 USA. NR 24 TC 53 Z9 56 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD MAR PY 2000 VL 85 IS 1-2 BP 87 EP 92 DI 10.1016/S0304-3959(99)00250-X PG 6 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 289ZY UT WOS:000085652900011 PM 10692606 ER PT J AU Bradshaw, H Miller, J Ling, QD Malsnee, K Ruda, MA AF Bradshaw, H Miller, J Ling, QD Malsnee, K Ruda, MA TI Sex differences and phases of the estrous cycle alter the response of spinal cord dynorphin neurons to peripheral inflammation and hyperalgesia SO PAIN LA English DT Article DE preprodynorphin; hormones; opioid; pain response ID ANALGESIC RESPONSE; MENSTRUAL-CYCLE; GENE-EXPRESSION; THERMAL PAIN; 17-BETA-ESTRADIOL; ANTINOCICEPTION; PREGNANCY; MODULATE; STRESS; WOMEN AB The neuromodulatory interactions of sex steroids with the opioid system may result in sex differences in pain and analgesia. Dynorphin is an endogenous kappa-opioid peptide that is upregulated in an animal model of peripheral inflammation and hyperalgesia and is possibly regulated by circulating levels of sex steroids. The present study compared behavioral responses of male, cycling female, and gonadectomized Sprague-Dawley rats in a model of persistent pain. Cycling female rats were behaviorally tested over a 14-day period, and their estrous cycles were monitored by daily vaginal smears. Thermal hyperalgesia was measured by paw withdrawal latencies taken prior to and 24-72 h after rats received a unilateral hindpaw injection of complete Freund's adjuvant (CFA). Prior to CFA administration, there was no significant difference in paw withdrawal latencies between male rats, cycling female rats, and ovariectomized female rats. Following CFA administration, female rats in proestrus exhibited significantly increased hyperalgesia compared with male rats, ovariectomized female rats, and female rats in other estrous stages (P less than or equal to 0.05). Levels of spinal preprodynorphin (PPD) mRNA induction in the L4-L5 segments were assessed by Northern blot analysis. PPD mRNA expression ipsilateral to the injected paw was significantly higher in female rats in diestrus (P less than or equal to 0.05) and proestrus (P less than or equal to 0.01) compared with rats in estrus and intact male rats. Ovariectomized rats had significantly higher levels of PPD mRNA expression compared with intact male rats (P less than or equal to 0.05). However, castrated male rats had significantly lower levels of PPD mRNA expression than intact male rats (P less than or equal to 0.05). PPD mRNA expression was not altered on the contralateral side of the spinal cord in any group. These results suggest a hormonal regulatory influence on the response of spinal cord dynorphin neurons to chronic inflammation and furthermore, that the association of the endocrine and opioid systems have the ability to influence an animal's sensitivity to pain. Published for the International Association for the Study of Pain by Elsevier Science B.V. C1 NIDCR, Pain & Neurosensory Mech Branch, NIH, Bethesda, MD 20892 USA. Florida State Univ, Neurosci Program, Tallahassee, FL 32306 USA. RP Ruda, MA (reprint author), NIDCR, Pain & Neurosensory Mech Branch, NIH, Bldg 49-1A11,49 Convent Dr, Bethesda, MD 20892 USA. RI Bradshaw, Heather/A-3333-2009 NR 32 TC 52 Z9 54 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD MAR PY 2000 VL 85 IS 1-2 BP 93 EP 99 DI 10.1016/S0304-3959(99)00253-5 PG 7 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 289ZY UT WOS:000085652900012 PM 10692607 ER PT J AU Adams, JH Wu, Y Fairfield, A AF Adams, JH Wu, Y Fairfield, A TI Malaria Research and Reference Reagent Resource Center SO PARASITOLOGY TODAY LA English DT News Item C1 Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA. Amer Type Culture Collect, Manassas, VA 20110 USA. NIAID, Int Programs Branch, Div Microbiol & Infect Dis, Bethesda, MD 20892 USA. RP Adams, JH (reprint author), Univ Notre Dame, Dept Biol Sci, POB 369, Notre Dame, IN 46556 USA. RI Adams, John/G-1800-2015 OI Adams, John/0000-0003-3707-7979 FU NIAID NIH HHS [R01 AI033656, R01 AI033656-06A2] NR 0 TC 12 Z9 13 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0169-4758 J9 PARASITOL TODAY JI Parasitol. Today PD MAR PY 2000 VL 16 IS 3 BP 89 EP 89 DI 10.1016/S0169-4758(99)01611-7 PG 1 WC Parasitology SC Parasitology GA 291BG UT WOS:000085712500002 PM 10689320 ER PT J AU Foster, CB Choi, EH Chanock, SJ AF Foster, CB Choi, EH Chanock, SJ TI Adenovirus and marrow transplantation in children SO PEDIATRIC PATHOLOGY & MOLECULAR MEDICINE LA English DT Article DE immunocompromised host; serotype; supportive care; viral infection ID INTRAVENOUS RIBAVIRIN THERAPY; SEVERE COMBINED IMMUNODEFICIENCY; INDUCED HEMORRHAGIC CYSTITIS; POLYMERASE CHAIN-REACTION; ACUTE RESPIRATORY-DISEASE; IN-SITU HYBRIDIZATION; VIRAL-INFECTIONS; IMMUNOCOMPROMISED PATIENTS; PULMONARY INFECTIONS; DIGEORGE-SYNDROME AB Adenovirus disease is a major cause of morbidity and mortality among recipients of marrow trans-plants. Recent advances have contributed to a finer understanding of the biological basis for viral persistence in the normal host as well as disseminated disease in the immunocompromised patient. However, these insights have not yielded new, effective therapeutic interventions. Currently, there are no proven antiviral therapies available for treating adenoviral disease. Anecdotal reports have indicated that combinations of ribavirin, intravenous immunoglobulin, and donor T cells are efficacious in cases with limited infection. We anticipate that the incidence of adenoviral infections in marrow transplant recipients will continue to increase because the pool of transplant recipients continues to enlarge and more immunosuppressive preparative regimens, including T-cell depletion, are more commonly used. This review summarizes the clinical manifestations of adenovirus in the bone marrow transplant population including such common complications as hemorrhagic cystitis and rarer manifestations of disseminated infection, such as nephritis, gastroenteritis, pneumonia, hepatitis, pancreatitis, and encephalitis. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Ctr Adv Technol,NIH, Gaithersburg, MD 20877 USA. RP Chanock, SJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Ctr Adv Technol,NIH, Gaithersburg, MD 20877 USA. NR 99 TC 0 Z9 0 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 1522-7952 J9 PEDIATR PATHOL MOL M JI Pediatr. Pathol. Mol. Med. PD MAR-JUN PY 2000 VL 19 IS 2-3 BP 97 EP 114 PG 18 WC Pathology; Pediatrics SC Pathology; Pediatrics GA 353FX UT WOS:000089265100002 ER PT J AU Cheng, TL Fields, CB Brenner, RA Wright, JL Lomax, T Scheidt, PC AF Cheng, TL Fields, CB Brenner, RA Wright, JL Lomax, T Scheidt, PC CA Dist Columbia Child Adolescent Inj TI Sports injuries: An important cause of morbidity in urban youth SO PEDIATRICS LA English DT Article DE sports injuries; surveillance; sports; adolescent injuries ID HIGH-SCHOOL; PREVENTION; CHILDREN AB Introduction. Sports injuries account for substantial morbidity and medical cost. To direct intervention, a population-based study of the causes and types of sports injuries was undertaken. Method. An injury surveillance system was established at all trauma center hospitals that treat residents 10 to 19 years old in the District of Columbia and the Chief Medical Examiner's Office. Medical record abstractions were completed for those seen in an emergency department, admitted to the hospital, or who died from injury June 1996 through June 1998. Findings. Seventeen percent (n = 2563) of all injuries occurred while participating in 1 of 6 sports (baseball/softball, basketball, biking, football, skating, and soccer) resulting in an event-based injury rate of 25.0 per 1000 adolescents or 25.0/1000 population year. Rates were higher in males for all sports. The most common mechanisms were falls (E880-888) and being struck by or against objects (E916-918). Hospitalization was required in 2% of visits and there were no deaths. Of those requiring hospitalization, 51% involved other persons, 12% were equipment-related, and 8% involved poor field/surface conditions. Of all baseball injuries, 55% involved ball or bat impact often of the head. Basketball injuries included several injuries from striking against the basketball pole or rim or being struck by a falling pole or backboard. Biking injuries requiring admission included 2 straddle injuries onto the bike center bar and collision with motor vehicles. Of all football injuries, 48 (7%) involved being struck by an opponent's helmet and 63 (9%) involved inappropriate field conditions including falls on or against concrete, glass, or fixed objects. In soccer there were 4 goal post injuries and a large proportion of intracranial injuries. There were 51 probable or clear assaults during sports and an additional 30 to 41 injuries from baseball bat assaults. Conclusions. Many sports including noncontact sports involved injuries of the head suggesting the need for improved head protection. Injuries involving collisions with others and assaults point to the need for supervision and enforcement of safety rules. The 16% of sports injury visits and 20% of hospitalizations related to equipment and environmental factors suggest that at least this proportion of injury may be amenable to preventive strategies. Design change may be warranted for prevention of equipment-related injuries. The many injuries involving inappropriate sports settings suggest the need for and use of available and safe locations for sports. C1 Childrens Natl Med Ctr, Dept Gen Pediat & Adolescent Med, Washington, DC 20010 USA. Childrens Res Inst, Washington, DC USA. George Washington Univ, Sch Med, Washington, DC USA. Childrens Natl Med Ctr, Dept Emergency Med, Washington, DC 20010 USA. NICHHD, Bethesda, MD 20892 USA. RP Cheng, TL (reprint author), Childrens Natl Med Ctr, Dept Gen Pediat, 111 Michigan Ave NW, Washington, DC 20010 USA. NR 13 TC 26 Z9 27 U1 0 U2 7 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAR PY 2000 VL 105 IS 3 BP art. no. EP e32 DI 10.1542/peds.105.3.e32 PG 6 WC Pediatrics SC Pediatrics GA 290MZ UT WOS:000085681100003 PM 10699134 ER PT J AU Nussenblatt, RB Gottesman, MM AF Nussenblatt, RB Gottesman, MM TI Organizer's introduction to the Symposium "Medical Research Ethics at the Millennium: What Have We Learned?" SO PERSPECTIVES IN BIOLOGY AND MEDICINE LA English DT Editorial Material C1 NEI, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. RP Nussenblatt, RB (reprint author), NEI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4319 USA SN 0031-5982 J9 PERSPECT BIOL MED JI Perspect. Biol. Med. PD SPR PY 2000 VL 43 IS 3 BP 305 EP 307 PG 3 WC History & Philosophy Of Science; Medicine, Research & Experimental SC History & Philosophy of Science; Research & Experimental Medicine GA 327LX UT WOS:000087796300002 ER PT J AU Bernardini, S Teti, A Marino, M Taranta, A Wetsel, WC Korach, KS Faraggiana, T Spera, G Migliaccio, S AF Bernardini, S Teti, A Marino, M Taranta, A Wetsel, WC Korach, KS Faraggiana, T Spera, G Migliaccio, S TI Modulation of steroid hormones responsiveness and differentiation events by specific protein kinase C isoforms in osteoblast-like cells in vitro SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Meeting Abstract C1 Univ Rome La Sapienza, Dept Histol & Medic Embryol, Rome, Italy. Univ Rome La Sapienza, Dept Expt Med, Rome, Italy. Univ Rome La Sapienza, Dept Med Physiopat, Rome, Italy. Univ Roma 3, Dept Biol, Rome, Italy. Univ Aquila, Dept Expt Med, I-67100 Laquila, Italy. NIEHS, RBS, LRDT, Res Triangle Pk, NC USA. Duke Univ, Dept Psychiat & Behav Sci, Durham, NC 27706 USA. Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD MAR PY 2000 VL 439 IS 5 MA 51 BP R267 EP R268 PG 2 WC Physiology SC Physiology GA 295KA UT WOS:000085964200074 ER PT J AU Marcus, PM Vineis, P Rothman, N AF Marcus, PM Vineis, P Rothman, N TI NAT2 slow acetylation and bladder cancer risk: a metaanalysis of 22 case-control studies conducted in the general population SO PHARMACOGENETICS LA English DT Article DE bladder neoplasms; arylamine n-acetyltransferase; meta analysis ID N-ACETYLTRANSFERASE POLYMORPHISM; CLINICAL-TRIALS; PHENOTYPE; GENOTYPE; CARCINOGENESIS; SMOKING; SUSCEPTIBILITY; DEBRISOQUINE; ASSOCIATION; HUMANS AB The NAT2 gene is involved in phase II detoxification of aromatic monoamines, a class of known bladder carcinogens. Certain allelic combinations result in the slow acetylation phenotype, which is thought to increase bladder cancer risk, We conducted a meta-analysis of all identifiable published case-control studies conducted in the general population that had examined the relationship of acetylation status and bladder cancer risk (22 studies, 2496 cases, 3340 controls). Using meta-analysis techniques that employed weighting based on individual-study variation, slow acetylators had an approximately 40% increase in risk compared with rapid acetylators [odds ratio (OR) 1.4, 95% confidence interval (CI) 1.2-1.6], Statistical tests indicated, however, that pooling of all studies, or of studies conducted in Caucasian populations, hid potentially important heterogeneity in the individual study results, and suggested that the relationship of NAT2 slow acetylation and bladder cancer risk might differ by geographical region. Studies conducted in Asia generated a summary OR of 2.1 (CI 1.2-3.8), in Europe, a summary OR of 1.4 (CI 1.2-1.6), and in the USA, a summary OR of 0.9 (CI 0.7-1.3). Among European studies, the relationship between NAT2 slow acetylation and bladder cancer risk did not differ by method used to assess acetylation status (older drug-based phenotyping methods: 10 studies, OR 1.5, CI 1.2-1.8; more recent NAT2 genotyping methods: four studies, OR 1.4, CI 1.1-1.7). Our results suggest that in most populations studied to date, NAT2 slow acetylation status is associated with a modest increase in bladder cancer risk. Pharmacogenetics 10:115-122 (C) 2000 Lippincott Williams & Wilkins. C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Turin, Turin, Italy. RP Marcus, PM (reprint author), NCI, Div Canc Prevent, 6130 Execut Blvd,Suite 344,Execut Plaza N,MSC 735, Bethesda, MD 20892 USA. NR 52 TC 102 Z9 105 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD MAR PY 2000 VL 10 IS 2 BP 115 EP 122 DI 10.1097/00008571-200003000-00003 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 298PN UT WOS:000086148500003 PM 10761999 ER PT J AU Murphy, PM Baggiolini, M Charo, IF Hebert, CA Horuk, R Matsushima, K Miller, LH Oppenheim, JJ Power, CA AF Murphy, PM Baggiolini, M Charo, IF Hebert, CA Horuk, R Matsushima, K Miller, LH Oppenheim, JJ Power, CA TI International union of pharmacology. XXII. Nomenclature for chemokine receptors SO PHARMACOLOGICAL REVIEWS LA English DT Review ID PROTEIN-COUPLED RECEPTOR; MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; MONOCYTE CHEMOATTRACTANT PROTEIN-1; SARCOMA-ASSOCIATED HERPESVIRUS; IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN INTERLEUKIN-8 RECEPTOR; HIGH-AFFINITY BINDING; HUMAN BETA-CHEMOKINE; NEUTROPHIL-ACTIVATING PEPTIDE-2; EOSINOPHIL EOTAXIN RECEPTOR AB Chemokine receptors comprise a large family of seven transmembrane domain G protein-coupled receptors differentially expressed in diverse cell types. Biological activities have been most clearly defined in leukocytes, where chemokines coordinate development, differentiation, anatomic distribution, trafficking, and effector functions and thereby regulate innate and adaptive immune responses. Pharmacological analysis of chemokine receptors is at an early stage of development. Disease indications have been established in human immunodeficiency virus/acquired immune deficiency syndrome and in Plasmodium vivax malaria, due to exploitation of CCR5 and Duffy, respectively, by the pathogen for cell entry. Additional indications are emerging among inflammatory and immunologically mediated diseases, but selection of targets in this area still remains somewhat speculative. Small molecule antagonists with nanomolar affinity have been reported for 7 of the 18 known chemokine receptors but have not yet been studied in clinical trials. Virally encoded chemokine receptors, as well as chemokine agonists and antagonists, and chemokine scavengers have been identified in medically important poxviruses and herpesviruses, again underscoring the importance of the chemokine system in microbial pathogenesis and possibly identifying specific strategies for modulating chemokine action therapeutically. The purpose of this review is to update current concepts of the biology and pharmacology of the chemokine system, to summarize key information about each chemokine receptor, and to describe a widely accepted receptor nomenclature system, ratified by the International Union of Pharmacology, that is facilitating clear communication in this area. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Univ Bern, Theodor Kocher Inst, Bern, Switzerland. Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, San Francisco, CA 94141 USA. Genentech Inc, S San Francisco, CA 94080 USA. Berlex Biosci, Dept Immunol, Richmond, CA USA. Univ Tokyo, Sch Med, Dept Mol Prevent Med, Bunkyo Ku, Tokyo 113, Japan. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Div Basic Sci, Frederick, MD 21702 USA. Serono Pharmaceut Res Inst, Geneva, Switzerland. RP Murphy, PM (reprint author), NIAID, Host Def Lab, NIH, Bldg 10,Room 11N113, Bethesda, MD 20892 USA. NR 422 TC 1349 Z9 1396 U1 1 U2 50 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0031-6997 J9 PHARMACOL REV JI Pharmacol. Rev. PD MAR PY 2000 VL 52 IS 1 BP 145 EP 176 PG 32 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 291FJ UT WOS:000085723200007 PM 10699158 ER PT J AU Heck, AM Yanovski, JA Calis, KA AF Heck, AM Yanovski, JA Calis, KA TI Orlistat, a new lipase inhibitor for the management of obesity SO PHARMACOTHERAPY LA English DT Review ID DIETARY-FAT ABSORPTION; HEALTHY-VOLUNTEERS; PANCREATIC LIPASE; UNITED-STATES; WEIGHT-LOSS; TETRAHYDROLIPSTATIN; PHARMACOKINETICS; RO-18-0647; PHARMACODYNAMICS; OVERWEIGHT AB Orlistat, a weight-loss agent with a novel mechanism of action, recently was approved by the Food and Drug Administration for the treatment of obesity It inhibits gastric and pancreatic lipases in the lumen of the gastrointestinal tract to decrease systemic absorption of dietary fat. In several trials lasting up to 2 years, orlistat was more effective than diet alone for weight reduction and maintenance of lost weight. Orlistat treatment also results in modest improvements in total cholesterol, low-density lipoprotein, blood pressure, and fasting glucose and insulin concentrations. The major adverse effects are gastrointestinal, usually occur early in therapy, and tend to decrease with continued treatment. Because orlistat may decrease the absorption of fat-soluble vitamins, a standard multiple-vitamin supplement is recommended daily during therapy to prevent abnormalities in vitamin serum concentrations. The potential for severe gastrointestinal discomfort and the modest degree of weight loss may limit the agent's clinical utility. Its longterm safety and effectiveness for weight maintenance, cost-effectiveness of treatment, and overall reduction in obesity-related morbidity and mortality remain to be determined. C1 Purdue Univ, Sch Pharm & Pharmacal Sci, Dept Pharm Practice, Indianapolis, IN USA. NICHHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Pharm, Drug Informat Serv, Bethesda, MD 20892 USA. RP Heck, AM (reprint author), Wishard Mem Hosp, Purdue Pharm Programs Off, D711 Myers Bldg,1001 W 10th St, Indianapolis, IN 46202 USA. NR 47 TC 102 Z9 108 U1 2 U2 23 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER BOX 806 171 HARRISON AVE, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD MAR PY 2000 VL 20 IS 3 BP 270 EP 279 DI 10.1592/phco.20.4.270.34882 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 291LM UT WOS:000085735700003 PM 10730683 ER PT J AU Riess, J Bicout, D Duguet, T Magyar, P AF Riess, J Bicout, D Duguet, T Magyar, P TI Hall plateau quantization due to hopping caused by electron-phonon interaction SO PHYSICA STATUS SOLIDI B-BASIC RESEARCH LA English DT Article; Proceedings Paper CT 8th International Conference on Hopping and Related Phenomena (HRP8) CY SEP 07-10, 1999 CL MURCIA, SPAIN SP Spanish Direc Gen Ensenanza Superior, Fdn Seneca, Univ Murcia ID SYSTEM AB We perform model calculations showing that electron-phonon interaction in the presence of a static substrate potential generates a hopping contribution to the Hall current which increases the width of the quantized Hall plateaus. This can explain why in typical quantum Hall systems the plateaus of sigma(xy) are slightly larger than those of the dissipative conductivity. Further, we show that in special situations even the entire width of the Hall plateau is due to this phonon induced hopping current. These results also show that absence of dissipation is not indispensable for the quantization of sigma(xy). C1 Univ Grenoble 1, Ctr Rech Tres Basses Temp, CNRS, F-38042 Grenoble 09, France. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Riess, J (reprint author), Univ Grenoble 1, Ctr Rech Tres Basses Temp, CNRS, BP 166, F-38042 Grenoble 09, France. NR 5 TC 0 Z9 0 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0370-1972 J9 PHYS STATUS SOLIDI B JI Phys. Status Solidi B-Basic Res. PD MAR PY 2000 VL 218 IS 1 BP 185 EP 188 DI 10.1002/(SICI)1521-3951(200003)218:1<185::AID-PSSB185>3.0.CO;2-K PG 4 WC Physics, Condensed Matter SC Physics GA 303PJ UT WOS:000086431000038 ER PT J AU Brinton, LA Brown, SL Colton, T Burich, MC Lubin, J AF Brinton, LA Brown, SL Colton, T Burich, MC Lubin, J TI Characteristics of a population of women with breast implants compared with women seeking other types of plastic surgery SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID RHEUMATOID-ARTHRITIS; AUGMENTATION MAMMAPLASTY; ORAL-CONTRACEPTIVES; LOS-ANGELES; FOLLOW-UP; CANCER; RISK AB Several previous studies have shown that breast implant patients demonstrate a number of differences compared with the general population. However, studies have not compared patients with breast implants with women receiving other types of plastic surgery, of interest because this latter group has been proposed as a comparison group for assessing the long-term health effects experienced by breast implant patients. Questionnaire data obtained from 7447 breast implant patients and 2203 patients with Other types plastic surgery were collected during the course of a retrospective cohort study, to determine whether implant patients demonstrate different characteristics compared with a more restricted group of patients. In contrast to previous investigations that compared implant patients with the general population, distinctive differences with respect to family income, number of pregnancies, alcohol consumption, cigarette smoking, or histories of previous gynecologic operations or operations for benign breast disease were not found. However, implant patients were significantly more likely than other plastic surgery patients to be white, have low levels of education, have early ages at first birth, be thin, and be screened frequently for breast disease. Furthermore, implant patients reported somewhat greater use of exogenous hormones and familial histories of rheumatoid arthritis. These results support the notion that other plastic surgery patients are a more appropriate comparison group than women in the general population for studies of the health effects of breast implants; however, there continue to be distinctive characteristics possessed by breast implant patients, which need to be taken into account in an assessment of what disease effects can be uniquely attributed to silicone breast implants. C1 NCI, Environm Epidemiol Branch, Bethesda, MD 20892 USA. US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Rockville, MD 20857 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. ABT Associates Inc, Cambridge, MA 02138 USA. NCI, Biostat Branch, Bethesda, MD 20892 USA. RP Brinton, LA (reprint author), NCI, Environm Epidemiol Branch, Execut Plaza S,Room 7068,6120 Execut Blvd,MSC 723, Bethesda, MD 20892 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 29 TC 43 Z9 44 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAR PY 2000 VL 105 IS 3 BP 919 EP 927 DI 10.1097/00006534-200003000-00014 PG 9 WC Surgery SC Surgery GA 292HB UT WOS:000085787600014 PM 10724251 ER PT J AU Szklo, M Chambless, LE Folsom, AR Gotto, A Nieto, FJ Patsch, W Shimakawa, T Sorlie, P Wijnberg, L AF Szklo, M Chambless, LE Folsom, AR Gotto, A Nieto, FJ Patsch, W Shimakawa, T Sorlie, P Wijnberg, L TI Trends in plasma cholesterol levels in the Atherosclerosis Risk in Communities (ARIC) study SO PREVENTIVE MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; CARDIOVASCULAR-DISEASE; SERUM-CHOLESTEROL; EDUCATIONAL-LEVEL; QUESTIONNAIRE; ADULTS; MORTALITY; SMOKING; LIPIDS; DIET AB Background. Data from the Atherosclerosis Risk in communities (ARIC) cohort study were examined both cross-sectionally and intraindividually to confirm recent findings from population-based studies showing a decline in total cholesterol CTC) levels in the United States. Methods, For the cross-sectional analysis, mean plasma TC levels from 15,792 participants aged 45-64 at baseline visit, and who were selected randomly from four U.S. communities, were examined for each year covered by the first cohort visit (1987, 1988, and 1989). Ninety-three percent of the cohort participants returned for the follow-up visit (1990, 1991, and 1992), and were included in the assessment of intraindividual TC trends. Results, Both mean TC and prevalence of hypercholesterolemia (defined as plasma cholesterol concentration greater than or equal to 240 mg/dl) consistently declined over the 3 years covered by visit 1 for all age-gender-race groups. For 1987, 1988, and 1989, mean TC values (mg/dl) were, respectively, 220.3, 216.7 and 214.1 (annual average change, -1.4%, P < 0.001). For these same years, hyper-cholesterolemia prevalence rates were 30.0, 27.8, and 25.3% (annual average change, -7.8%, P < 0.001). The mean plasma TC also decreased Within individuals between the two visits across race, gender, and age decade categories. With the exception of black men, this decline was more marked for older than younger subjects, but no consistent differences were seen between the racial groups. However, in whites, decreases were greater for men than for women. Expected results were seen when these changes were correlated with changes in cardiovascular risk factors between the two visits. Conclusion. The current study results are consistent with those of previous studies, and confirm the notion that preventive programs appear to be effective in reducing mean population TC levels. (C) 2000 American Health Foundation and Academic Press. C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. Cornell Univ, Coll Med, New York, NY 10021 USA. Landeskrankananstalten Salzburg, Dept Lab Med, Salzburg, Austria. NIH, Bethesda, MD 20892 USA. RP Szklo, M (reprint author), Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, 615 N Wolfe St, Baltimore, MD 21205 USA. NR 32 TC 16 Z9 19 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD MAR PY 2000 VL 30 IS 3 BP 252 EP 259 DI 10.1006/pmed.1999.0612 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 294QC UT WOS:000085921000010 PM 10684749 ER PT J AU Nephew, KP Osborne, E Lubet, RA Grubbs, CJ Khan, SA AF Nephew, KP Osborne, E Lubet, RA Grubbs, CJ Khan, SA TI Effects of oral administration of tamoxifen, toremifene, dehydroepiandrosterone, and vorozole on uterine histomorphology in the rat SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article ID AROMATASE INHIBITOR VOROZOLE; ADVANCED BREAST-CANCER; SPRAGUE-DAWLEY RATS; CELL-DEATH; POSTMENOPAUSAL PATIENTS; LUMINAL EPITHELIUM; UTERUS; PREVENTION; ESTROGENS; R-83842 AB Tamoxifen, toremifene, DHEA, and vorozole inhibit tumor growth in rodent mammary carcinoma models and are promising chemotherapeutic agents for use against breast cancer development. In the present study, the effect of these agents on uterine histomorphology following oral administration to mature ovary-intact rats (n = 380) was examined. Animals received diet only (control), tamoxifen (0.4 and 1 mg/kg of diet; 10 mg/kg BW by daily gavage), toremifene (3-30 mg/kg of diet), DHEA (24-2000 mg/kg of diet), or vorozole (0.08-1.25 mg/kg BW by daily gavage) for 28 days and were either sacrificed or returned to a basal diet and then sacrificed 21 days later. Treatment with toremifene (all doses) or tamoxifen (1 and 10 mg/kg) for 28 days produced a decrease (P < 0.05) in overall uterine size and myometrial thickness; however, uterine luminal and glandular epithelia cell height increased (P < 0.05) compared with control. These compartmentalized uterotrophic and antiestrogenic effects of toremifene and tamoxifen were still apparent after 21 days post-treatment. Administration of DHEA (2000 mg/kg of diet) for 28 days had dramatic uterotrophic effects, increasing (P < 0.05) overall uterine size and stimulating all three uterine compartments (epithelia, stroma, and myometrium), The other doses of DHEA, however, were not uterotrophic, Interestingly, after removal of DHEA from the diet, uterine weight and myometrial thickness decreased (P < 0.05), Vorozole (1.25 mg/kg) administration for 28 days had differential, compartmentalized uterine effects, producing an increase (P < 0.05) in epithelial cell height, a decrease(P < 0.05) in stromal size, but no change in myometrial thickness. After 21 days postadministration of vorozole, luminal epithelial cell height was increased (P < 0.05) compared with control. The data suggest that oral administration of tamoxifen, toremifene, DHEA, and vorozole results in differential, compartmentalized effects in the uterus that are highly dependent on treatment dose. The data may have implications for risk assessment of these agents prior to administration to healthy, cancer-free women. C1 Indiana Univ, Sch Med, Bloomington, IN 47405 USA. NCI, Div Canc Prevent, Chemoprevent Branch, Bethesda, MD 20892 USA. Univ Alabama, Chemoprevent Ctr, Birmingham, AL 35294 USA. Univ Cincinnati, Coll Med, Dept Cell Biol Neurobiol & Anat, Cincinnati, OH 45267 USA. RP Nephew, KP (reprint author), Indiana Univ, Sch Med, 302 Jordan Hall, Bloomington, IN 47405 USA. FU NCI NIH HHS [CA74748] NR 50 TC 20 Z9 21 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD MAR PY 2000 VL 223 IS 3 BP 288 EP 294 DI 10.1046/j.1525-1373.2000.22341.x PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 286TN UT WOS:000085461900011 PM 10719842 ER PT J AU Izevbigie, EB Bergen, WG AF Izevbigie, EB Bergen, WG TI beta-adrenergic agonist hyperplastic effect is associated with increased fibronectin gene expression and not mitogen-activated protein kinase modulation in C2C12 cells SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article ID FIBROBLAST GROWTH-FACTOR; MUSCLE SATELLITE CELLS; SKELETAL-MUSCLE; HEPARAN-SULFATE; FED RACTOPAMINE; ADIPOSE-TISSUE; MESSENGER-RNA; CYCLIC-AMP; RECEPTOR; PROLIFERATION AB beta-Adrenergic agonists (beta-AA) enhance protein accretion in skeletal muscles. This stimulation is characterized by increased protein synthesis, increased expression of myofibrillar protein genes and a depression in protein degradation in animals, and increased proliferation and DNA synthesis in muscle cells in vitro. The mechanism or signal path in muscle whereby beta-AA would elicit these physiological effects upon binding to the G protein-coupled beta-adrenergic receptor (beta-AR) is unclear. C2C12 myoblasts were used to determine beta-AR ligand binding characteristics, cyclic AMP synthesis in response to isoproterenol (ISO) stimulation, and effects of ISO on DNA synthesis, mitogen activated protein kinase (MAPK), and fibronectin (FN) gene expression. Results showed that C2C12 cells possess beta-AR which are specific, saturable, and of high affinity (K-d = 0.2 nM), Forskolin and ISO stimulated cAMP production by = 20-fold (P < 0.001) and 17-fold (P < 0,001), respectively. ISO and the cAMP analog, 8-bromo-cAMP (8-BC) stimulated DNA synthesis in proliferating cells by 150% (P < 0.05) and 200% (P < 0,01), respectively, without modulating MARK activity, whereas addition of fetal bovine serum to culture resulted in a 500% increase (P < 0.01) in DNA synthesis and MARK activation. DNA synthesis in C2C12 cells treated with ISO, 8 BC, or FBS was abolished in the presence of 25 mu M PD098059, an MAPK-kinase inhibitor, suggesting that an MARK-dependent pathway is likely involved in C2C12 proliferation. During cAMP elevating agent stimulation, basal MARK activity may be sufficient, in the presence of other putative signaling molecules, to support proliferation in these cells, ISO or 8-BC treatment increased FN mRNA by three- and seven-fold, respectively, in growing C2C12 cells implying a connection between increased DNA synthesis and FN gene expression. C1 Auburn Univ, Dept Anim & Dairy Sci, Regulatory Biol Program, Auburn, AL 36849 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Mol & Cellular Signaling Unit, NIH, Bethesda, MD 20892 USA. RP Auburn Univ, Dept Anim & Dairy Sci, Regulatory Biol Program, 216 Upchurch Hall, Auburn, AL 36849 USA. EM wbergen@acesag.auburn.edu NR 46 TC 7 Z9 7 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD MAR PY 2000 VL 223 IS 3 BP 302 EP 309 DI 10.1046/j.1525-1373.2000.22343.x PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 286TN UT WOS:000085461900013 PM 10719844 ER PT J AU Kumar, S Tsai, CJ Nussinov, R AF Kumar, S Tsai, CJ Nussinov, R TI Factors enhancing protein thermostability SO PROTEIN ENGINEERING LA English DT Article DE melting temperature; sequence; structure; thermophiles; thermostability ID ARCHAEON PYROCOCCUS-FURIOSUS; HYDROPHOBIC FOLDING UNITS; ION-PAIR NETWORKS; CRYSTAL-STRUCTURE; THERMAL-STABILITY; ALPHA-HELICES; GLUTAMATE-DEHYDROGENASE; GLOBULAR-PROTEINS; ESCHERICHIA-COLI; HYPERTHERMOPHILIC PROTEINS AB Several sequence and structural factors have been proposed to contribute toward greater stability of thermophilic proteins. Here we present a statistical examination of structural and sequence parameters in representatives of 18 nonredundant families of thermophilic and mesophilic proteins. Our aim was to look for systematic differences among thermophilic and mesophilic proteins across the families. We observe that both thermophilic and mesophilic proteins have similar hydrophobicities, compactness, oligomeric states, polar and non-polar contribution to surface areas, main-chain and side-chain hydrogen bonds. Insertions/deletions and proline substitutions do not show consistent trends between the thermophilic and mesophilic members of the families. On the other hand, salt bridges and side chain-side chain hydrogen bonds increase in the majority of the thermophilic proteins. Additionally, comparisons of the sequences of the thermophile-mesophile homologous protein pairs indicate that Arg and Tyr are significantly more frequent, while Cys and Ser are less frequent in thermophilic proteins, Thermophiles both have a larger fraction of their residues in the alpha-helical conformation, and they avoid Pro in their alpha-helices to a greater extent than the mesophiles, These results indicate that thermostable proteins adapt dual strategies to withstand high temperatures. Our intention has been to explore factors contributing to the stability of proteins from thermophiles with respect to the melting temperatures (T-m), the best descriptor of thermal stability. Unfortunately, T-m values are available only for a few proteins in our high resolution dataset, Currently, this limits our ability to examine correlations in a meaningful way. C1 NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Intramural Res Support Program, Bldg 469,Rm 151, Frederick, MD 21702 USA. FU NCI NIH HHS [N01CO56000] NR 60 TC 489 Z9 513 U1 10 U2 77 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD MAR PY 2000 VL 13 IS 3 BP 179 EP 191 DI 10.1093/protein/13.3.179 PG 13 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 314CL UT WOS:000087036600005 PM 10775659 ER PT J AU Boyington, JC Raiz, AN Brooks, AG Patamawenu, A Sun, PD AF Boyington, JC Raiz, AN Brooks, AG Patamawenu, A Sun, PD TI Reconstitution of bacterial expressed human CD94: The importance of the stem region for dimer formation SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article ID KILLER-CELL RECEPTORS; LY-49 MULTIGENE FAMILY; C-TYPE LECTINS; INHIBITORY RECEPTOR; HLA-E; MOLECULAR CHARACTERIZATION; MEMBRANE-PROTEINS; COMPLEX; RECOGNITION; CD94/NKG2A AB Human CD94 is a subunit of the disulfide-linked, heterodimeric natural killer (NK) cell surface receptor CD94/NKG2. This receptor, a member of the C-type lectin superfamily, participates in regulating NK cell directed lysis through interaction with the major histocompatibility antigen HLA-E. Two forms of CD94 were expressed using a bacterial expression system and refolded in vitro. One form, residues 34-179, designated S34, corresponds to the entire extracellular region of the receptor, including a 23-residue stem region, and the other, residues 51-179, designated E51, corresponds only to the putative carbohydrate recognition domain of the receptor. The refolded full-length S34 protein existed as a noncovalent dimer initially but formed an interchain disulfide bond upon storage for several months. In contrast, the stemless construct, E51, existed largely as a monomeric form. The stem region of S34, residues 34-56, is sensitive to proteolysis and its absence results in dissociation of the dimer. This suggests that the residues in the stem region of CD94 help to stabilize the dimeric conformation, (C) 2000 Academic Press. C1 NIAID, Struct Biol Sect, Off Sci Director, NIH, Rockville, MD 20852 USA. Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3052, Australia. RP Sun, PD (reprint author), NIAID, Struct Biol Sect, Off Sci Director, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. NR 27 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD MAR PY 2000 VL 18 IS 2 BP 235 EP 241 DI 10.1006/prep.1999.1188 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 291DW UT WOS:000085719700015 PM 10686155 ER PT J AU Bicout, DJ Szabo, A AF Bicout, DJ Szabo, A TI Entropic barriers, transition states, funnels, and exponential protein folding kinetics: A simple model SO PROTEIN SCIENCE LA English DT Article; Proceedings Paper CT Spring School on Self-Organization in Biological Systems CY MAY 24-29, 1998 CL ECOLE PHYS, LES HOUCHES, FRANCE HO ECOLE PHYS DE diffusion; exponential kinetics; free energy barriers; protein folding ID LANDSCAPE PERSPECTIVE; ENERGY LANDSCAPE; DYNAMICS; COORDINATE; MECHANISM; DIFFUSION; PATHWAYS; PARADOX; RATES AB This paper presents an analytically tractable model that captures the most elementary aspect of the protein folding problem, namely that both the energy and the entropy decrease as a protein folds. In this model, the system diffuses within a sphere in the presence of an attractive spherically symmetric potential. The native state is represented by a small sphere in the center, and the remaining space is identified with unfolded states. The folding temperature, the time-dependence of the populations, and the relaxation rate are calculated, and the folding dynamics is analyzed for both golf-course and funnel-like energy landscapes. This simple model allows us to illustrate a surprising number of concepts including entropic barriers, transition states, funnels, and the origin of single exponential relaxation kinetics. C1 Natl Inst Diabet & Kidney Dis, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Bicout, DJ (reprint author), Natl Inst Diabet & Kidney Dis, Phys Chem Lab, NIH, Bldg 5,Rm 136, Bethesda, MD 20892 USA. RI Szabo, Attila/H-3867-2012 NR 37 TC 70 Z9 71 U1 1 U2 10 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD MAR PY 2000 VL 9 IS 3 BP 452 EP 465 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 295XW UT WOS:000085994800003 PM 10752607 ER PT J AU Hochleitner, EO Borchers, C Parker, C Bienstock, RJ Tomer, KB AF Hochleitner, EO Borchers, C Parker, C Bienstock, RJ Tomer, KB TI Characterization of a discontinuous epitope of the human immunodeficiency virus (HIV) core protein p24 by epitope excision and differential chemical modification followed by mass spectrometric peptide mapping analysis SO PROTEIN SCIENCE LA English DT Article DE acetylation; differential chemical modification; discontinuous epitope; HIV-p24; mass spectrometry ID CAPSID PROTEIN; MOLECULAR CHARACTERIZATION; MONOCLONAL-ANTIBODY; SURFACE-TOPOLOGY; ANTIGEN; TYPE-1; GAG; COMPLEXES; RELEASE; BINDING AB A combination of epitope excision, epitope extraction, and differential chemical modification followed by mass spectrometric peptide mapping was used for the characterization of a discontinuous epitope that is recognized by the mouse anti-HIV-p24 monoclonal antibody 5E2.A3. In epitope excision, the protein is first bound to an immobilized antibody and then digested with proteolytic enzymes. In epitope extraction, the protein is first digested and subsequently allowed to react with the antibody. After epitope excision of the p24-5E2.A3 complex with endoproteinase Lys-C, a large fragment remained affinity bound corresponding to amino acids 1-158 of HIV-p24 (fragment 1-158). Further digestion, however, resulted in loss of affinity. Moreover, no affinity-bound fragments were observed after an epitope extraction experiment. These data from the epitope excision and extraction experiments suggest that the epitope is discontinuous. For the further characterization of the epitope, amino groups in the epitope-containing fragment were acetylated in both the affinity bound and free states followed by mass spectrometric analysis. Two successive acetylation reactions were performed: (1) the first used a low molar excess of acetic anhydride, and (2) the second, after separation from the antibody, a high molar excess of its hexadeuteroderivative. This isotopic labeling procedure, in combination with high resolution mass spectrometry, allowed the precise determination of relative reactivities of amino groups. In this study, no differences were observed in the ranking of the relative reactivities of five lysine residues. However, the N-terminal amino group was found to be part of the discontinuous epitope. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Tomer, KB (reprint author), NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RI Tomer, Kenneth/E-8018-2013 NR 31 TC 42 Z9 42 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD MAR PY 2000 VL 9 IS 3 BP 487 EP 496 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 295XW UT WOS:000085994800006 PM 10752610 ER PT J AU Kumar, S Ma, BY Tsai, CJ Nussinov, R AF Kumar, S Ma, BY Tsai, CJ Nussinov, R TI Electrostatic strengths of salt bridges in thermophilic and mesophilic glutamate dehydrogenase monomers SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE thermostability; salt bridge; melting temperature; electrostatics; glutamate dehydrogenase ID PROTEIN-PROTEIN INTERFACES; ION-PAIR NETWORKS; PYROCOCCUS-FURIOSUS; HIGH-TEMPERATURES; ACTIVE-SITE; STABILITY; BINDING; ENZYME; ENERGIES; COMPLEX AB Here we seek to understand the higher frequency of occurrence of salt bridges in proteins from thermophiles as compared to their mesophile homologs, me focus on glutamate dehydrogenase, owing to the availability of high resolution thermophilic (from Pyrococcus furiosus) and mesophilic (from Clostridium symbiosum) protein structures, the large protein size and the large difference in melting temperatures. We investigate the location, statistics and electrostatic strengths of salt bridges and of their networks within corresponding monomers of the thermophilic and mesophilic enzymes. We find that many of the extra salt bridges which are present in the thermophilic glutamate dehydrogenase monomer but absent in the mesophilic enzyme, form around the active site of the protein, Furthermore, salt bridges in the thermostable glutamate dehydrogenase cluster within the hydrophobic folding units of the monomer, rather than between them. Computation of the electrostatic contribution of salt bridge energies by solving the Poisson equation in a continuum solvent medium, shows that the salt bridges in Pyrococcus furiosus glutamate dehydrogenase are highly stabilizing, In contrast, the salt bridges in the mesophilic Clostridium symbiosum glutamate dehydrogenase are only marginally stabilizing. This is largely the outcome of the difference in the protein environment around the salt bridges in the two proteins. The presence of a larger number of charges, and hence, of salt bridges contributes to an electrostatically more favorable protein energy term. Our results indicate that salt bridges and their networks mag have an important role in resisting deformation/ unfolding of the protein structure at high temperatures, particularly in critical regions such as around the active site, Proteins 2000;38:368-383, Published 2000 Wiley-Liss, Inc.dagger. C1 NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr,Lab Expt & Computat, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr,Lab Expt & Computat, Bldg 469,Room 151, Frederick, MD 21702 USA. RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU NCI NIH HHS [N01-CO-56000] NR 47 TC 105 Z9 106 U1 0 U2 10 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-3585 J9 PROTEINS JI Proteins PD MAR 1 PY 2000 VL 38 IS 4 BP 368 EP 383 DI 10.1002/(SICI)1097-0134(20000301)38:4<368::AID-PROT3>3.0.CO;2-R PG 16 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 286WD UT WOS:000085471100003 PM 10707024 ER PT J AU O'Leary, KM AF O'Leary, KM TI Neuropsychological testing results SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID BORDERLINE PERSONALITY-DISORDER; DIALECTICAL BEHAVIOR-THERAPY; PICTURE ARRANGEMENT SUBTEST; OBJECT RELATIONS; SOCIAL COGNITION; MAJOR DEPRESSION; RORSCHACH TEST; DRUG-THERAPY; STORIES TOLD; MOOD-STATE AB Earlier clinical hypotheses regarding borderline personality disorder, based on projective psychological testing and intelligence tests, are examined. Recent findings of comparative deficits in this population in the domains of verbal and visual memory as well as visual perception are reviewed, together with clinical relevance. Efforts to examine the way individuals with this disorder process emotion-laden material are discussed, with suggestions for further research. C1 NIMH, Intramural Res Program, Off Clin Director, Bethesda, MD 20892 USA. RP O'Leary, KM (reprint author), NIMH, Intramural Res Program, Off Clin Director, Bldg 10,Room 3N218,10 Ctr Dr MSC 1274, Bethesda, MD 20892 USA. NR 87 TC 28 Z9 30 U1 1 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD MAR PY 2000 VL 23 IS 1 BP 41 EP + DI 10.1016/S0193-953X(05)70142-8 PG 21 WC Psychiatry SC Psychiatry GA 290MX UT WOS:000085680900005 PM 10729930 ER PT J AU Ungard, JT Beekman, M Gasior, M Carter, RB Dijkstra, D Witkin, JM AF Ungard, JT Beekman, M Gasior, M Carter, RB Dijkstra, D Witkin, JM TI Modification of behavioral effects of drugs in mice by neuroactive steroids SO PSYCHOPHARMACOLOGY LA English DT Article DE neuroactive steroids; pentylenetetrazol; bicuculline; picrotoxin; yohimbine; dizocilpine; cocaine; methamphetamine; locomotor activity; mice ID GAMMA-AMINOBUTYRIC-ACID; ANXIETY; ANTICONVULSANT; GANAXOLONE; RECEPTOR; PENTYLENETETRAZOL; NEUROSTEROIDS; DIAZEPAM AB Rationale: Neuroactive steroids represent a novel class of potential therapeutic agents (epilepsy, anxiety, migraine, drug dependence) thought to act through positive allosteric modulation of the GABA(A) receptor A synthetically derived neuroactive steroid, ganaxolone (3 alpha-hydroxy-3 beta-methyl-5 alpha-pregnan-20-one), is in phase-II clinical trials for epilepsy. Unlike traditional anticonvulsants such as diazepam and phenobarbital, ganaxolone shows equipotent suppression of both the seizure activity and the behavioral effects of pentylenetetrazol (PTZ) administration. Objectives: The present study explored possible reversal by ganaxolone and related neuroactive steroids of some behavioral effects of additional pharmacological challenges. Methods: Direct behavioral observation and photocell-counted locomotor activity of male, Swiss-Webster mice were made with various compounds alone and in conjunction with ganaxolone. Results: Ganaxolone both prevented and reversed PTZ-induced locomotor depression in mice. Further, ganaxolone reversed the locomotor depression induced by other convulsant/anxiogenic stimuli: bituculline, picrotoxin and, to a lesser extent, yohimbine. Ganaxolone failed to reverse the locomotor stimulation induced by cocaine, methamphetamine, dizocilpine, and phencyclidine. In addition to ganaxolone, the endogenous neuroactive steroids allopregnanolone and pregnanolone and the synthetic neuroactive steroid Co 2-1068 also reversed observed behaviors and locomotor depression induced by PTZ. Conclusions: The present findings support the unique pharmacological effects of neuroactive steroids as a novel class of positive allosteric modulators of GABA. C1 NIDA, Drug Dev Grp, Behav Neurosci Lab, Baltimore, MD 21224 USA. Univ Groningen, Ctr Pharm, Dept Med Chem, Groningen, Netherlands. Univ Calif Irvine, Dept Pharmacol, Irvine, CA 92717 USA. RP Witkin, JM (reprint author), NIDA, Drug Dev Grp, Behav Neurosci Lab, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 15 TC 12 Z9 13 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAR PY 2000 VL 148 IS 4 BP 336 EP 343 DI 10.1007/s002130050060 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 299BF UT WOS:000086175400002 PM 10928304 ER PT J AU Bradley, MM Lang, PJ AF Bradley, MM Lang, PJ TI Affective reactions to acoustic stimuli SO PSYCHOPHYSIOLOGY LA English DT Article DE emotion; sounds; memory; startle reflex; autonomic; facial EMG ID EMOTION; PERCEPTION; ATTENTION; PICTURES; STARTLE; REFLEX AB Emotional reactions to naturally occurring sounds (e.g., screams, erotica, bombs, etc.) were investigated in two studies. In Experiment 1, subjects rated the pleasure and arousal elicited when listening to each of 60 sounds, followed by an incidental free recall task. The shape of the two-dimensional affective space defined by the mean ratings for each secund was similar to that previously obtained for pictures, and, like memory for pictures, free recall was highest for emotionally arousing stimuli. In Experiment 2, autonomic and facial electromyographic (EMG) activity were recorded while a new group of subjects listened to the same set of sounds; the startle reflex was measured using visual probes. Listening to unpleasant sounds resulted in larger startle reflexes, more corrugator EMG activity, and larger heart rate deceleration compared with listening to pleasant sounds. Electrodermal reactions were larger for emotionally arousing than for neutral materials. Taken together, the data suggest that acoustic cues activate the appetitive and defensive motivational circuits underlying emotional expression in ways similar to pictures. C1 Univ Florida, NIMH, Ctr Study Emot & Attent, Gainesville, FL 32610 USA. RP Bradley, MM (reprint author), Univ Florida, NIMH, Ctr Study Emot & Attent, Box 100165 HSC, Gainesville, FL 32610 USA. FU NIMH NIH HHS [P50-MH52384, MH37757, MH43975] NR 39 TC 334 Z9 346 U1 5 U2 51 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD MAR PY 2000 VL 37 IS 2 BP 204 EP 215 DI 10.1017/S0048577200990012 PG 12 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 290ZY UT WOS:000085709100006 PM 10731770 ER PT J AU Schupp, HT Cuthbert, BN Bradley, MM Cacioppo, JT Ito, T Lang, PJ AF Schupp, HT Cuthbert, BN Bradley, MM Cacioppo, JT Ito, T Lang, PJ TI Affective picture processing: The late positive potential is modulated by motivational relevance SO PSYCHOPHYSIOLOGY LA English DT Article DE emotion; ERP; affective evaluation; late positive potential; slow wave; motivated attention ID BIOELECTRICAL ECHOES; ATTITUDES; CONTEXT; STIMULI; VARIES AB Recent studies have shown that the late positive component of the event-related-potential (ERP) is enhanced for emotional pictures, presented in an oddball paradigm, evaluated as distant from an established affective context. In other research, with context-free, random presentation, affectively intense pictures (pleasant and unpleasant) prompted similar enhanced ERP late positivity (compared with the neutral picture response). In an effort to reconcile interpretations of the late positive potential (LPP), ERPs to randomly ordered pictures were assessed, but using the faster presentation rate, brief exposure (1.5 s), and distinct sequences of six pictures, as in studies using an oddball based on evaluative distance. Again, results showed larger LPPs to pleasant and unpleasant pictures, compared with neutral pictures. Furthermore, affective pictures of high arousal elicited larger LPPs than less affectively intense pictures. The data support the view that late positivity to affective pictures is modulated both by their intrinsic motivational significance and the evaluative context of picture presentation. C1 Univ Florida, Ctr Study Emot & Attent, NIMH, Gainesville, FL 32610 USA. Univ Chicago, Dept Psychol, Chicago, IL 60637 USA. Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. RP Lang, PJ (reprint author), Univ Florida, Ctr Study Emot & Attent, NIMH, Box 100165 HSC, Gainesville, FL 32610 USA. FU NIMH NIH HHS [MH37757, MH43975, MH52384] NR 18 TC 553 Z9 580 U1 8 U2 58 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD MAR PY 2000 VL 37 IS 2 BP 257 EP 261 DI 10.1017/S0048577200001530 PG 5 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 290ZY UT WOS:000085709100012 PM 10731776 ER PT J AU Weidner, G Rice, T Knox, SS Ellison, RC Province, MA Rao, DC Higgins, MW AF Weidner, G Rice, T Knox, SS Ellison, RC Province, MA Rao, DC Higgins, MW TI Familial resemblance for hostility: The National Heart, Lung, and Blood Institute Family Heart Study SO PSYCHOSOMATIC MEDICINE LA English DT Article DE hostility; education; gender; familial aggregation ID RANDOMLY SELECTED FAMILIES; CORONARY-ARTERY DISEASE; MYOCARDIAL-INFARCTION; BODY-WEIGHT; A BEHAVIOR; MEN; AGE; WOMEN; TWINS; CHILDREN AB Objective: The purpose of this study was to examine whether several aspects of hostility as measured by the Cook-Medley Hostility Scale (ie, aggressive responding, hostile affect, cynicism, and overall hostility score) were determined in part by family factors (ie, genes and/of familial environments). Methods: Analyses were based on 680 European-American families (2525 individuals) from the NHLBI Family Heart Study (FHS), a population-based study of genetic and nongenetic determinants of CHD, atherosclerosis, and cardiovascular risk factors. The influence of family relationships, age, and education on the variation in each of the four hostility scores were estimated. Results: Significant familial resemblance in all hostility scores was found, accounting for 42% of the variance in total hostility, 30% in cynicism, 38% in aggressive responding, and 18% in hostile affect. Very little of this resemblance could be explained by similarities in education. Familial resemblance for cynicism was solely due to significant parent-offspring and sibling correlations (ie, no spouse resemblance), suggesting the possibility of genetic influences. Gender and generation differences were also evident in the familial correlations. Conclusions: Hostility aggregates in families. Both family environmental and genetic sources of resemblance are suggested for hostility. C1 NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Weidner, G (reprint author), SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA. RI Rice, Treva/D-1385-2009 FU NHLBI NIH HHS [N01-HC-2505, N01-HC-2506, N01-HC-25104] NR 36 TC 7 Z9 7 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD MAR-APR PY 2000 VL 62 IS 2 BP 197 EP 204 PG 8 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 301GJ UT WOS:000086302100006 PM 10772397 ER PT J AU Sherman, BF Bonanno, GA Wiener, LS Battles, HB AF Sherman, BF Bonanno, GA Wiener, LS Battles, HB TI When children tell their friends they have AIDS: Possible consequences for psychological well-being and disease progression SO PSYCHOSOMATIC MEDICINE LA English DT Article DE self-disclosure; behavior; self-concept; children; HIV; AIDS; disease progression ID IMMUNODEFICIENCY-VIRUS INFECTION; EMOTIONAL DISCLOSURE; HOMOSEXUAL IDENTITY; PHYSICAL HEALTH; GAY MEN; INHIBITION; CONCEAL; TRAUMAS; ILLNESS; STRESS AB Objective: Past research has demonstrated that self-disclosure of traumatic or secretive information produces observable health benefits. Self-disclosure has also been linked, albeit less consistently, to improved psychological health. The present study examined the physiological and psychological consequences of children's self-disclosure of their HIV/AIDS status to friends. Methods: Data were collected twice, one year apart, from 64 caregiver-child dyads in which all of the children were infected with HIV. Dependent variables included the child's CD4%, self-concept, and level of behavioral problems, Results: Children who had disclosed their HIV+ diagnosis to friends during the 1-year course of the study had a significantly larger increase in CD4% than children who had told their friends before the study or those children who had not yet disclosed their HIV+ diagnosis to friends. This effect remained significant when the child's age and level of medication (protease inhibitors) were statistically controlled. Self-disclosure to friends did not impact the child's behavior or self-concept. Conclusions: This is the first study to investigate the effect of self-disclosure in children. The results ware consistent with previous studies showing the positive health consequences of self-disclosure in adults, and suggest potentially important implications for professional and familial care givers of HIV/AIDS individuals. C1 Catholic Univ Amer, Washington, DC 20064 USA. NIH, Bethesda, MD 20892 USA. RP Bonanno, GA (reprint author), Columbia Univ, Coll Teachers, Dept Counseling & Clin Psychol, Box 218,525 W 120th St, New York, NY 10027 USA. NR 52 TC 47 Z9 48 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD MAR-APR PY 2000 VL 62 IS 2 BP 238 EP 247 PG 10 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 301GJ UT WOS:000086302100012 PM 10772404 ER PT J AU Costantini, M Mencaglia, E Giulio, PD Cortesi, E Roila, F Ballatori, E Tamburini, M Casali, P Licitra, L Candis, DD Massidda, B Luzzani, M Campora, E Placido, SD Palmeri, S Angela, PM Baracco, G Gareri, R Martignetti, A Ragosa, S Zoda, L Ionta, MT Bulletti, S Pastore, L AF Costantini, M Mencaglia, E Giulio, PD Cortesi, E Roila, F Ballatori, E Tamburini, M Casali, P Licitra, L Candis, DD Massidda, B Luzzani, M Campora, E Placido, SD Palmeri, S Angela, PM Baracco, G Gareri, R Martignetti, A Ragosa, S Zoda, L Ionta, MT Bulletti, S Pastore, L TI Cancer patients as 'experts' in defining quality of life domains. A multicentre survey by the Italian Group for the Evaluation of Outcomes in Oncology (IGEO) SO QUALITY OF LIFE RESEARCH LA English DT Article DE cancer; content analysis; quality of life ID OF-LIFE; BREAST-CANCER; THERAPY; ADJUSTMENT; VALIDATION; MASTECTOMY; MEDICINE AB Although the subjective nature of quality of life is generally accepted, less attention has been paid to the procedure of selecting domains to be explored with questionnaires. To explore what contributes to cancer patients' quality of life, a survey was conducted with the aim of identifying contents of quality of life using cancer patients as 'experts'. A questionnaire with open-ended items aimed at exploring the meaning of quality of life and at determining the contents of health and not health related quality of life, was submitted to a sample of cancer patients stratified by residence, cancer site and stage of disease. The 248 questionnaires received were transcribed and broken down into phrases to allow coding. A content analysis was performed, using as a conceptual framework, the domains identified by the Italian Society of Psycho-Oncology. Overall, 43 domains and a list of symptoms were identified. The two most frequently reported symptoms were pain (21.4% patients) and fatigue (14.1% patients). Social relationships and psychological domains were heavily represented. Twenty sub-domains related to the domain `psychological well-being'. This study suggests that information on the content of quality of life questionnaires to be submitted to people affected by a specific disease, should be derived by studying people suffering the specific disease. These results reinforce the criticism that available quality of life instruments are more likely to reflect the perspective of health professionals than patients. C1 Natl Canc Inst, Unit Clin Epidemiol & Trials, I-16132 Genoa, Italy. Ist Nazl Studio & Cura Tumori, Div Psychol, I-20133 Milan, Italy. Ist Ric Farmacol Mario Negri, Nursing Res Unit, Milan, Italy. Univ La Sapienza, Rome, Italy. Osped Policlin, Dept Med Oncol, Perugia, Italy. Univ Aquila, Dept Internal Med, Med Stat Unit, I-67100 Laquila, Italy. Ist Nazl Studio & Cura Tumori, Div Med Oncol, I-20133 Milan, Italy. Univ Cagliari, I-09124 Cagliari, Italy. Natl Canc Inst, Dept Pain Therapy & Palliat Care, Genoa, Italy. Natl Canc Inst, Dept Med Oncol 1, Naples, Italy. Univ Naples Federico II, Naples, Italy. Univ Palermo, I-90133 Palermo, Italy. Natl Canc Inst, Psychol Serv, Genoa, Italy. RP Costantini, M (reprint author), Natl Canc Inst, Unit Clin Epidemiol & Trials, L R Benzi 10, I-16132 Genoa, Italy. RI costantini, massimo/G-1443-2012; Licitra, Lisa/C-6271-2017; casali, Paolo Giovanni/D-1524-2017; OI Licitra, Lisa/0000-0003-0623-4118; casali, Paolo Giovanni/0000-0003-4056-8023; costantini, massimo/0000-0002-5293-7079 NR 36 TC 18 Z9 19 U1 1 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD MAR PY 2000 VL 9 IS 2 BP 151 EP 159 DI 10.1023/A:1008967104082 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 350PY UT WOS:000089111400003 PM 10983479 ER PT J AU Cameron, H AF Cameron, H TI Birth of neurons and demise of a dogma SO RECHERCHE LA French DT Article ID DENTATE GYRUS; ADULT NEUROGENESIS; PROLIFERATION; MEMORY; CELLS C1 NINDS, Inst Natl Accidents Cerebraux & Desordres Neurol, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Cameron, H (reprint author), NINDS, Inst Natl Accidents Cerebraux & Desordres Neurol, Mol Biol Lab, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU SOC ED SCIENTIFIQUES PI PARIS 06 PA 57 RUE DE SEINE, 75280 PARIS 06, FRANCE SN 0029-5671 J9 RECHERCHE JI Recherche PD MAR PY 2000 IS 329 BP 29 EP 35 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 289BT UT WOS:000085600000008 ER PT J AU Tully, DB Cox, VT Mumtaz, MM Davis, VL Chapin, RE AF Tully, DB Cox, VT Mumtaz, MM Davis, VL Chapin, RE TI Six high-priority organochlorine pesticides, either singly or in combination, are nonestrogenic in transfected HeLa cells SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE estrogen; endocrine disrupters; aldrin; dieldrin; endrin; 4 '-DDD; 4; 4 '-DDE; 4; 4 '-DDT ID CHLORINATED HYDROCARBON PESTICIDES; BREAST-CANCER CELLS; ESTROGEN-RECEPTOR; MEDIATED PROCESSES; YEAST; BINDING; PROTEIN; DDT; CHEMICALS; INDUCTION AB There have been increasing concerns that environmental chemicals may adversely affect the health of humans and wildlife by acting as endocrine modulators. These concerns have been augmented by the realization that human exposure occurs not just to single chemical agents, but typically to mixtures of chemicals that could exhibit estrogenic activity qualitatively and/or quantitatively different from that of individual components. To address these concerns, we have evaluated the ability of six organochlorine pesticides (4,4'-DDT, 4,4'-DDD, 4,4'-DDE, aldrin, dieldrin, or endrin, all classified high priority by ATSDR) to modulate transcriptional activation of an estrogen-responsive reporter gene in transfected HeLa cells. In these assays, HeLa cells cotransfected with an expression vector encoding estrogen receptor and an estrogen-responsive chloramphenicol acetyltransferase (CAT) reporter plasmid were exposed to these pesticides individually and in defined combinations. While estradiol consistently elicited 10- to 23-fold dose-dependent inductions in these assays, the six organochlorine pesticides showed no detectable dose-related response when tested individually. When tested in binary combinations, the pesticide mixtures showed no additional estrogenicity. Thus, the pesticides tested, singly or as mixtures, showed virtually no evidence of estrogenicity. Published by Elsevier Science. C1 NIEHS, Environm Toxicol Program, Toxicol Lab, Res Triangle Pk, NC 27709 USA. US Dept HHS, Publ Hlth Serv, Agcy Tox Substances & Dis Registry, Atlanta, GA USA. RP Tully, DB (reprint author), NIEHS, Environm Toxicol Program, Toxicol Lab, 111 TW Alexander Dr,Bldg 101,Room E-145, Res Triangle Pk, NC 27709 USA. OI Chapin, Robert/0000-0002-5997-1261 NR 33 TC 17 Z9 17 U1 0 U2 22 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD MAR-APR PY 2000 VL 14 IS 2 BP 95 EP 102 DI 10.1016/S0890-6238(00)00060-5 PG 8 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 320AC UT WOS:000087377900002 PM 10825672 ER PT J AU Jefferson, WN Padilla-Banks, E Newbold, RR AF Jefferson, WN Padilla-Banks, E Newbold, RR TI Lactoferrin is an estrogen responsive protein in the uterus of mice and rats SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE estrogens; environmental estrogens; uterotrophic bioassay; marker proteins; lactoferrin; complement C3 ID MOUSE UTERUS; REPRODUCTIVE-TRACT; EXPRESSION; RECEPTOR; GENE; PROGESTERONE; TISSUE; CYCLE; LACTOTRANSFERRIN; PURIFICATION AB To identify lactoferrin (LF) and determine its estrogen-responsiveness in the rat uterus, immature Sprague-Dawley rats were untreated or subcutaneously injected with 17 beta-estradiol (500 mu g/kg) for 3 days and uterine tissues collected. Outbred immature CD-1 mice, treated with 17 beta-estradiol, provided the positive control. By using a polyclonal antibody raised against mouse LF, minimal detectable protein was immunolocalized in uterine epithelial cells of untreated immature rats and mice. After estrogen treatment, LF was localized in all uterine epithelial cells of both species, although staining was more intense in mice than rats. In mice, LF was evenly distributed throughout the cytoplasm with intense staining in some cells, while in rats, it was seen mainly in the apical cytoplasm. For comparison to another well-known estrogen responsive protein in rats, complement C3 was immunolocalized within epithelial cells and it showed a different staining pattern than LF. Uterine tissue homogenates were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blots showed cross-reactivity with the mouse LF antibody. These findings indicate that LF is present in the rat uterus, and is induced by estrogens as reported in other species. Thus, LF is an important marker of estrogenic activity across species and will, therefore, have utility in screening for effects of environmental estrogenic compounds. Published by Elsevier Science Inc. C1 NIEHS, Div Intramural Res, Environm Toxicol Program,Dev Endocrinol Sect, Lab Toxicol,Reprod Toxicol Grp,NIH, Res Triangle Pk, NC 27709 USA. RP Newbold, RR (reprint author), NIEHS, Div Intramural Res, Environm Toxicol Program,Dev Endocrinol Sect, Lab Toxicol,Reprod Toxicol Grp,NIH, Res Triangle Pk, NC 27709 USA. NR 37 TC 19 Z9 19 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD MAR-APR PY 2000 VL 14 IS 2 BP 103 EP 110 DI 10.1016/S0890-6238(00)00061-7 PG 8 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 320AC UT WOS:000087377900003 PM 10825673 ER PT J AU Sarno, RJ Franklin, WL Prexl, WS AF Sarno, RJ Franklin, WL Prexl, WS TI Activity and population characteristics of Andean Condors in southern Chile SO REVISTA CHILENA DE HISTORIA NATURAL LA English DT Article DE Andean Condor; activity; Patagonia; sex ratio AB Data were collected on general activity patterns and population characteristics of free-ranging Andean Condors Vultur gryphus in Torres del Paine National Park, Chile from July 1992 to June 1994 during 3,680 h of observation. Seasonal differences were evident in relative abundance and activity patterns. The mean number of condors sighted, observation significantly higher in fall-winter than in spring-summer. There was a significant decrease from spring-summer to fall-winter in the percentage of observations during which we sighted solitary condors and a significant increase in the number of groups of condors. In addition, mean monthly maximum group size was significantly larger in fall-winter than spring-summer. The sex ratio (males:females) of juveniles was significantly skewed in favor of females, and that of adults was significantly skewed in favor of males. The significantly different adult:juvenile ratio of condors visiting the park could have resulted from differences in distribution and habitat use and/or low breeding rates. Differential juvenile mortality and dispersal could also have produced skewed age and sex ratios, but more research is needed. Condor activity seemed related to wind speed. The greatest proportion of condors was observed flying in calm and low winds and less frequently in moderate to very strong winds. Temperature seemed to have an important effect on aerial activity because the greatest proportion of condors was sighted flying and soaring on warm days. Temperature and wind speed were weakly correlated. C1 Iowa State Univ, Dept Anim Ecol, Ames, IA 50011 USA. RP Sarno, RJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Bldg 560,Room 11-84, Frederick, MD 21702 USA. NR 19 TC 19 Z9 20 U1 0 U2 8 PU SOCIEDAD BIOLGIA CHILE PI SANTIAGO PA CASILLA 16164, SANTIAGO 9, CHILE SN 0716-078X J9 REV CHIL HIST NAT JI Rev. Chil. Hist. Nat. PD MAR PY 2000 VL 73 IS 1 BP 3 EP 8 PG 6 WC Biodiversity Conservation; Ecology SC Biodiversity & Conservation; Environmental Sciences & Ecology GA 309MT UT WOS:000086772100001 ER PT J AU Pequegnat, W Fishbein, M Celentano, D Ehrhardt, A Garnett, G Holtgrave, D Jaccard, J Schachter, J Zenilman, J AF Pequegnat, W Fishbein, M Celentano, D Ehrhardt, A Garnett, G Holtgrave, D Jaccard, J Schachter, J Zenilman, J TI NIMH/APPC Workgroup on Behavioral and Biological Outcomes in HIV/STD Prevention Studies - A position statement SO SEXUALLY TRANSMITTED DISEASES LA English DT Article C1 NIMH, Off AIDS Res, NIH, Bethesda, MD 20814 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Columbia Univ, New York, NY 10027 USA. Univ Oxford, Oxford OX1 2JD, England. SUNY Albany, Albany, NY 12222 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Pequegnat, W (reprint author), NIMH, Off AIDS Res, NIH, 6001 Execut Blvd,Room 6,205,MSC 9,619, Bethesda, MD 20814 USA. RI Garnett, Geoffrey/A-9312-2008 NR 0 TC 94 Z9 96 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD MAR PY 2000 VL 27 IS 3 BP 127 EP 132 DI 10.1097/00007435-200003000-00001 PG 6 WC Infectious Diseases SC Infectious Diseases GA 290PN UT WOS:000085684700001 PM 10726643 ER PT J AU Yeo, AET Matsumoto, A Shih, JW Alter, HJ Goedert, JJ AF Yeo, AET Matsumoto, A Shih, JW Alter, HJ Goedert, JJ TI Prevalence of hepatitis G virus in patients with hemophilia and their steady female sexual partners SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID C VIRUS; TRANSMISSION; INFECTION; PROSTITUTES; DISEASE; AGENT; HCV AB Background: Hepatitis G virus (HGV), also known as GB virus C, is a newly discovered Flavivirus that is transmissible by blood transfusion and other possible routes. Objective: To study the risk of sexual transmission of HGV in female sexual partners of men with hemophilia (n = 161 couples). Methods: Blood samples obtained from 11 medical centers were analyzed for (1) HGV RNA by polymerase chain reaction; (2) antibodies to HGV by enzyme immunoassay; and (3) other viruses and T-cell counts by routine laboratory tests. Subjects completed a questionnaire that assessed sexual intercourse frequency, number of sexual partners, condom usage, sexually transmitted diseases, illicit drug usage, and needlestick or broken-glass injuries. Results: The HGV infection (RNA +/- antibody positive) prevalence was 48% among men and 21% among women. Prevalence of hepatitis C virus, hepatitis B virus, and HIV among men was 99%, 94%, and 86%, compared with 3%, 11%, and 12% among women, respectively. The odds ratio for HGV infection for women with an HGV-positive male sexual partner was 2.14 (P = 0.06) without adjustment, and 2.77 (P = 0.03) with adjustment for other variables, none of which were independently significant. Conclusion: These results suggest a low level of HGV sexual transmission. C1 NCI, Viral Epidemiol Branch, NIH, Rockville, MD USA. NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Goedert, JJ (reprint author), NCI, Viral Epidemiol Branch, NIH, 6120 Execut Blvd, Rockville, MD USA. NR 18 TC 12 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD MAR PY 2000 VL 27 IS 3 BP 178 EP 182 DI 10.1097/00007435-200003000-00012 PG 5 WC Infectious Diseases SC Infectious Diseases GA 290PN UT WOS:000085684700012 PM 10726654 ER PT J AU Sampei, K Goto, S Alkayed, NJ Crain, BJ Korach, KS Traystman, RJ Demas, GE Nelson, RJ Hurn, PD AF Sampei, K Goto, S Alkayed, NJ Crain, BJ Korach, KS Traystman, RJ Demas, GE Nelson, RJ Hurn, PD TI Stroke in estrogen receptor-alpha-deficient mice SO STROKE LA English DT Article DE estrogen; cerebral ischemia; gender; menopause; stroke ID CEREBRAL BLOOD-FLOW; CEREBROVASCULAR CO2 REACTIVITY; HORMONE REPLACEMENT THERAPY; MESSENGER-RIBONUCLEIC-ACID; NITRIC-OXIDE SYNTHASE; POSTMENOPAUSAL WOMEN; BCL-2 EXPRESSION; ARTERY OCCLUSION; VASCULAR INJURY; KNOCKOUT MOUSE AB Background and Purpose-Recent evidence suggests that endogenous estrogens or hormone replacement therapy can ameliorate brain damage from experimental stroke. Protective mechanisms involve enhanced cerebral vasodilation during ischemic stress as well as direct preservation of neuronal viability. We hypothesized that if the intracellular estrogen receptor subtype-alpha (ER alpha) is important to estrogen's signaling in the ischemic brain, then ER alpha-deficient (knockout) (ER alpha KO) female mice would sustain exaggerated cerebral infarction damage after middle cerebral artery occlusion, Methods-The histopathology of cresyl violet-stained tissues was evaluated after reversible middle cerebral artery occlusion (2 hours, followed by 22 hours of reperfusion) in ER alpha KO transgenic and wild-type (WT) mice (C57BL/6J background strain), End-ischemic cerebral blood flow mapping was obtained from additional female murine cohorts by using [C-14]iodoantipyrine autoradiography, Results-Total hemispheric tissue damage was not altered by ER alpha deficiency in female mice: 51.9+/-10.6 mm(3) in ER alpha KO versus 60.5+/-5.0 mm(3) in WT. Striatal infarction was equivalent, 12.2+/-1.7 mm(3) in ER alpha KO and 13.4+/-1.0 mm(3) in WT mice, but cortical infarction was paradoxically smaller relative to that of the WT (20.7+/-4.5 mm(3) in ER alpha KO versus 30.6+/-1.1 mm(3) in WT), Intraocclusion blood flow to the parietal cortex was higher in ER alpha KO than in WT mice, likely accounting for the reduced infarction in this anatomic area. There were no differences in stroke outcomes by region or genotype in male animals. Conclusions-Loss of ER alpha does not enhance tissue damage in the female animal, suggesting that estrogen inhibits brain injury by mechanisms that do not depend on activation of this receptor subtype. C1 Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21287 USA. Natl Inst Environm Hlth Sci, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC USA. Johns Hopkins Univ, Dept Psychol, Baltimore, MD 21218 USA. RP Hurn, PD (reprint author), Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, 600 N Wolfe St,Blalock 1404, Baltimore, MD 21287 USA. OI Korach, Kenneth/0000-0002-7765-418X FU NINDS NIH HHS [NS20020, NS33668]; NINR NIH HHS [NR03521] NR 52 TC 118 Z9 119 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2000 VL 31 IS 3 BP 738 EP 743 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 289HP UT WOS:000085614700028 PM 10700513 ER PT J AU Fenton, WS AF Fenton, WS TI Depression, suicide, and suicide prevention in schizophrenia SO SUICIDE AND LIFE-THREATENING BEHAVIOR LA English DT Article ID TERM FOLLOW-UP; RISK-FACTORS; AFFECTIVE-DISORDERS; NEGATIVE SYMPTOMS; CLOZAPINE TREATMENT; SPECTRUM DISORDERS; DEFICIT SYNDROME; NATURAL-HISTORY; MORTALITY; PREDICTION AB Suicide is the single largest cause of premature death among individuals with schizophrenia. Furthermore, epidemiological data indicate that nearly 80% of patients with the diagnosis of schizophrenia will experience a major depressive episode at some time during their lifetime. This report reviews recent findings relative to the risk of suicide in schizophrenia, including data from the Chestnut Lodge longitudinal study of schizophrenia subtypes and symptom domains. Paradoxically, those patients with schizophrenia who are most likely to recover or experience a good outcome are also those at greatest risk for suicide. The reduction of morbidity and mortality in schizophrenia should include depression and suicidality as targets for both psychopharmacological and psychosocial treatment. C1 NIH, Div Mental Disorders, Bethesda, MD 20892 USA. RP Fenton, WS (reprint author), NIMH, Ctr Neurosci, Room 6216-9621,6001 Execut Blvd, Bethesda, MD 20892 USA. NR 90 TC 106 Z9 110 U1 3 U2 9 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0363-0234 J9 SUICIDE LIFE-THREAT JI Suicide Life-Threat. Behav. PD SPR PY 2000 VL 30 IS 1 BP 34 EP 49 PG 16 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 303KK UT WOS:000086420900005 PM 10782717 ER PT J AU Rothman, RB Partilla, JS Baumann, MH Dersch, CM Carroll, FI Rice, KC AF Rothman, RB Partilla, JS Baumann, MH Dersch, CM Carroll, FI Rice, KC TI Neurochemical neutralization of methamphetamine with high-affinity nonselective inhibitors of biogenic amine transporters: A pharmacological strategy for treating stimulant abuse SO SYNAPSE LA English DT Article DE dopamine; serotonin; norepinephrine; transporters; methamphetamine; MDMA ID DOPAMINE; AMPHETAMINE; SEROTONIN; REUPTAKE; MONKEYS AB The abuse of methamphetamine (METH) and other amphetamine-like stimulants is a growing problem in the United States. METH is a substrate for the 12-transmembrane proteins which function as transporters for the biogenic amines dopamine (DA), serotonin (5-HT), and norepinephrine (NE). Increased release of CNS DA is thought to mediate the addictive effects of METH, whereas increased release of NE in both the peripheral and CNS is thought to mediate its cardiovascular effects. The neurotoxic effects of METH on both dopaminergic and serotonergic nerves requires the transport of METH into the nerve terminals. Thus, transport of METH into nerve terminals is the crucial first step in the production of METH-associated pharmacological and toxicological effects. A single molecular entity which would block the transport of METH at all three biogenic amine transporters might function to neurochemically neutralize METH. This agent would ideally be a high-affinity slowly dissociating agent at all three transporters, and also be amenable to formulation as a long-acting depot medication, such as has been accomplished with an analog of GBR12909. As a first step towards developing such an agent, we established an in vitro assay which selectively detects transporter substrates and used this assay to profile the ability of a lead compound, indatraline, to block the releasing effects of METH and MDMA at the DA, 5-HT, and NE transporters. The major finding reported here is that indatraline blocks the ability of METH and MDMA to release these neurotransmitters. (C) Published 2000 Wiley-Liss, Inc. C1 NIDA, Clin Psychopharmacol Sect, Intramural Res Program, DIR,NIH, Baltimore, MD 21224 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Rothman, RB (reprint author), NIDA, Clin Psychopharmacol Sect, Intramural Res Program, DIR,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 12 TC 58 Z9 61 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD MAR 1 PY 2000 VL 35 IS 3 BP 222 EP 227 DI 10.1002/(SICI)1098-2396(20000301)35:3<222::AID-SYN7>3.0.CO;2-K PG 6 WC Neurosciences SC Neurosciences & Neurology GA 277FR UT WOS:000084922500007 PM 10657029 ER PT J AU Cadet, JL Harrington, B Ordonez, S AF Cadet, JL Harrington, B Ordonez, S TI Bcl-2 overexpression attenuates dopamine-induced apoptosis in an immortalized neural cell line by suppressing the production of reactive oxygen species SO SYNAPSE LA English DT Article DE Parkinson's disease; neurodegenerative disease; dopamine; free radical production; catecholamines; apoptosis ID DEATH; NEUROTOXICITY; NEURONS AB Parkinson's disease is a neurodegenerative disease that is consequent to the loss of brain dopamine (DA) cells. These abnormalities are thought, in part, to be a manifestation of increased free radical production during the metabolism of catecholamines. The antiapoptic agent, bcl-2, has been shown to protect cells against the toxic effects of reactive oxygen species (ROS). Thus, we tested whether bcl-2 could attenuate the toxic effects of DA on immortalized neural cells. Our results show that DA caused dose-dependent cell death. The use of confocal microscopy and flow cytometry demonstrated that DA caused cell death through an apoptotic process. Moreover, DA caused a marked increase in ROS in these cells. Furthermore, overexpression of bcl-2 caused significant protection against DA-induced apoptosis. These results are discussed in terms of their support for a role of bcl-2 in the development of Parkinson's disease. (C) 2000 Wiley-Liss, Inc. C1 NIDA, Mol Neuropsychiat Sect, NIH, Intramural Res Program, Baltimore, MD 21224 USA. RP Cadet, JL (reprint author), NIDA, Mol Neuropsychiat Sect, NIH, Intramural Res Program, POB 5180, Baltimore, MD 21224 USA. NR 16 TC 21 Z9 22 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 0887-4476 J9 SYNAPSE JI Synapse PD MAR 1 PY 2000 VL 35 IS 3 BP 228 EP 233 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 277FR UT WOS:000084922500008 PM 10657030 ER PT J AU Sellitti, DF Dennison, D Akamizu, T Doi, SQ Kohn, LD Koshiyama, H AF Sellitti, DF Dennison, D Akamizu, T Doi, SQ Kohn, LD Koshiyama, H TI Thyrotropin regulation of cyclic adenosine monophosphate production in human coronary artery smooth muscle cells SO THYROID LA English DT Article ID RECEPTOR MESSENGER-RNA; GRAVES-DISEASE; FUNCTIONAL EXPRESSION; RAT PREADIPOCYTES; HEART-DISEASE; HYPOTHYROIDISM; CULTURE; CLONING; HEALTHY; RISK AB Thyroid disease has been associated with the occurrence of pathophysiologic changes in the vasculature that may result in part from altered serum thyroid hormone and serum lipid levels. Thyrotropin (TSH) levels are also altered in thyroid disease, but a direct effect of TSH on vascular smooth muscle has not previously been considered. In the present study, human coronary artery smooth muscle cells (CASMC) were induced into two morphologically distinct forms by culturing in either (1) growth factor supplemented, 0.5% serum medium (SmGM-3) or (2) basal medium (SmBM) plus 10% fetal bovine serum (FBS). Intracellular cyclic adenosine monophosphate (cAMP) accumulation was determined by radioimmunoassay after exposure to increasing doses of bovine TSH. Cells grown in SmBM/10% FBS for 3 days exhibited a dose-dependent increase in intracellular cAMP that reached a level 10 times higher than baseline at the highest dose examined (100 mIU/mL). In contrast, cells grown in SmGM-3 medium exhibited no change in intracellular cAMP on exposure to increasing TSII. Low serum (0.5% FBS) reduced the ability of TSH to stimulate cAMP above the control value in CASMC. Pretreatment of CASMC with either transforming growth factor-beta 1 (TGF-beta 1) or tumor necrosis factor-alpha (TNF-alpha) lowered basal levels of cAMP production, but did not inhibit the ability of TSH to stimulate cAMP production. Human, but not rat aortic smooth muscle cells in culture also responded to TSH with a significant increase in cAMP. The results of this study suggest that TSH may exert direct effects on vascular smooth muscle mediated by adenylate cyclase activation that could conceivably affect the progression of vascular disease associated with thyroid dysfunction. C1 Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA. Kyoto Univ, Dept Med & Clin Sci, Kyoto, Japan. NIDDKD, Cell Regulat Sect, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. Hyogo Prefectural Amagasaki Hosp, Div Endocrinol & Metab, Dept Internal Med, Amagasaki, Hyogo, Japan. RP Sellitti, DF (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med, Room A3060,4301 Jones Bridge Rd, Bethesda, MD 20814 USA. RI Koshiyama, Hiroyuki/H-3877-2011 NR 32 TC 34 Z9 35 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD MAR PY 2000 VL 10 IS 3 BP 219 EP 225 DI 10.1089/thy.2000.10.219 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 301TF UT WOS:000086325800004 PM 10779136 ER PT J AU Pistillo, MP Tazzari, PL Ellis, JH Ferrara, GB AF Pistillo, MP Tazzari, PL Ellis, JH Ferrara, GB TI Molecular characterization and applications of recombinant scFv antibodies to CD152 co-stimulatory molecule SO TISSUE ANTIGENS LA English DT Article DE CD152 co-stimulatory molecule; cytofluorimetry; ELISA; phage library; scFv antibodies; Western blot ID BY-PASSING IMMUNIZATION; T-CELLS; CD80 B7-1; CTLA-4; PHAGE; CD28; EXPRESSION; ACTIVATION; BINDING; LIBRARY AB Recombinant human monoclonal antibodies against CD152 have been generated by selecting a synthetic phage scFv library with purified CD152-Ig fusion protein. Sixteen scFv fragments were isolated which specifically react with CD152 by enzyme-linked immunoabsorbent assay (ELISA) and Western blot resulting in their clustering into two groups recognizing different antigenic determinants One group of scFvs (#3, #13, #40, #44, #47, #51, #57, #80 #83) recognized an epitope on CD152 dimer whereas another group (#15, #18, #31, #35, #54, #72, #81) recognized an epitope on both dimeric and monomeric CD152 molecule suggesting their possible use in understanding the subunit structure of CD152 which is still controversial. Sequencing of the VH genes revealed that all the scFvs belonged to the VH3 gene family but they were different in CDR3 length and composition. It was possible to correlate specific CDR3 sequences with reactivity of the two groups of scFvs Four scFvs #3, #40, #81 and #83, each representative of one specific CDR3, were selected for further analysis. Competition ELISA experiments showed that they recognize CD152 in its native configuration and bound to different epitopes from the CD80/CD86 interaction site. The scFvs were able to stain human T lymphocytes stimulated either with anti-CD3 and CD28 antibodies or PHA, PMA and ionomycin by cytofluorimetry suggesting that they can be useful reagents for monitoring the kinetics of surface-bound and intracellular CD152. C1 Ctr Biotecnol Avanzate, Immunogenet Lab, Natl Canc Inst, I-16132 Genoa, Italy. Policlin S Orsola Malpighi, Serv Transfus Med, Bologna, Italy. GlaxoWellcome Res & Dev, Immunopathol Unit, Stevenage, Herts, England. Univ Genoa, Dept Oncol Biol & Genet, Genoa, Italy. RP Pistillo, MP (reprint author), Ctr Biotecnol Avanzate, Immunogenet Lab, Natl Canc Inst, Largo Rosanna Benzi 10, I-16132 Genoa, Italy. NR 27 TC 11 Z9 11 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD MAR PY 2000 VL 55 IS 3 BP 229 EP 238 DI 10.1034/j.1399-0039.2000.550306.x PG 10 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 297TQ UT WOS:000086099100006 PM 10777098 ER PT J AU Pera, C Delfino, L Longo, A Pistillo, MP Ferrara, GB AF Pera, C Delfino, L Longo, A Pistillo, MP Ferrara, GB TI Novel associations among HLA-DQA1 and-DQB1 alleles, revealed by high-resolution sequence-based typing (SBT) SO TISSUE ANTIGENS LA English DT Article DE linkage disequilibrium; HLA-DQA1 and DQB1; PCR-SBT; PCR-SSP ID HLA; SUSCEPTIBILITY; DISEASE AB Althought it is a valuable tool for the identification of HLA alleles, sequence-based typing (SBT) presents difficulties when used to determine HLA-DQA1 and -DQB1 alleles Specifically, some HLA-DQA1 alleles have a three-base deletion at codon 56 of exon 2 that interferes with the sequencing read. Moreover, the frequently used primers for HLA-DQB1 may co-amplify the HLA-DQB2 pseudogene. To overcome these problems, we amplified DQA1 exon 2 using five group-specific polymerase chain reactions (PCRs) which allowed separation of deleted from non-deleted DQA1 alleles DQB1 exon 2 was amplified using two group-specific amplifications. To increase typing resolution, we also analyzed DQA1 exons 1, 3 and 4 and DQB1 exon 3 by PCR using sequence-specific primers (PCR-SSP) or SET analysis. Using this method we found some important associations between DQA1 and DQB1 alleles: DQA1*05011 and DQB1*0201, DQA1*0505 and DQB1*03011, DQA1*01021 and DQB1*06, DQA1*01022 and DQB1*0502. C1 Adv Biotechnol Ctr, Immunogenet Lab, Natl Canc Inst, I-16132 Genoa, Italy. Univ Genoa, Dept Oncol Biol & Genet, Genoa, Italy. RP Ferrara, GB (reprint author), Adv Biotechnol Ctr, Immunogenet Lab, Natl Canc Inst, Lgo R Benzi 10, I-16132 Genoa, Italy. NR 12 TC 23 Z9 24 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD MAR PY 2000 VL 55 IS 3 BP 275 EP 279 DI 10.1034/j.1399-0039.2000.550313.x PG 5 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 297TQ UT WOS:000086099100013 PM 10777105 ER PT J AU Chapman, S AF Chapman, S TI Banning smoking outdoors is seldom ethically justifiable SO TOBACCO CONTROL LA English DT Article ID RISK C1 Repace Assoc, Bowie, MD USA. NCI, Rockville, MD USA. NR 11 TC 25 Z9 25 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-4563 J9 TOB CONTROL JI Tob. Control PD MAR PY 2000 VL 9 IS 1 BP 95 EP 97 DI 10.1136/tc.9.1.95 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 291DG UT WOS:000085718400022 PM 10691763 ER PT J AU Bloch, M Shopland, DR AF Bloch, M Shopland, DR TI Outdoor smoking bans: more than meets the eye SO TOBACCO CONTROL LA English DT Article C1 NCI, Tobacco Control Res Branch, Rockville, MD 20852 USA. NCI, Smoking & Tobacco Control Program, Rockville, MD 20852 USA. RP Bloch, M (reprint author), NCI, Tobacco Control Res Branch, Rockville, MD 20852 USA. NR 2 TC 17 Z9 17 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-4563 J9 TOB CONTROL JI Tob. Control PD MAR PY 2000 VL 9 IS 1 BP 99 EP 99 DI 10.1136/tc.9.1.99 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 291DG UT WOS:000085718400024 PM 10691765 ER PT J AU Yoshida, A Newbold, RR Dixon, D AF Yoshida, A Newbold, RR Dixon, D TI Abnormal cell differentiation and p21 expression of endometrial epithelial cells following developmental exposure to diethylstilbestrol (DES) SO TOXICOLOGIC PATHOLOGY LA English DT Article DE neonatal mouse uterus; estrogen receptor; c-fos; lactoferrin; p21; p53; endocrine disrupters; environmental estrogens ID ESTROGEN-RECEPTOR; MOUSE UTERUS; C-FOS; GENITAL-TRACT; FEMALE MOUSE; RAT UTERUS; REPRODUCTIVE TRACTS; MICE; GROWTH; PROLIFERATION AB Gene expression relevant to abnormal cell differentiation and altered cell cycle in endometrial epithelial cells was investigated immunohistochemically in developing mouse uteri exposed neonatally to diethylstilbestrol (DES). Female CD-1 mice were given daily SC injections of 2 mu g of DES in corn oil or were given corn oil alone (control) at 1-5 days of age and euthanatized at 5, 6, 7, 8, 15, and 22 days of age. The endometrial epithelial cells of DES-treated mice at 5-8 days of age showed enhanced staining intensity for the estrogen receptor alpha (ER alpha), whereas the stromal cells showed decreased staining reaction; the epithelial cells showed that the protein encoded by the c-Sos proto-oncogene, which plays a key role in regulating diverse estrogen-related cellular differentiation patterns, was enhanced. These cells also showed increased expression of lactoferrin, a sensitive protein marker of estrogen exposure, although the staining intensity decreased after exposure ended. The stain for p21 protein, a mitotic inhibitor which suppresses cyclin-dependent kinase activity, showed frequent positively stained cells in DES-treated mice at 5-15 days of age, whereas no accumulation of p53 protein of either wild or mutant type was detected immunohistochemically in these cells. These results indicate that suppressed cell cycle activity of endometrial epithelial cells and abnormal estrogen-related differentiation at the developmental stage following neonatal DES exposure may be caused, in part, by transient altered expression of ER alpha and expression of the p21 gene, which appears to be induced by a p53-independent mechanism. C1 NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. RP Dixon, D (reprint author), NIEHS, Lab Expt Pathol, POB 12233,MD C2-09, Res Triangle Pk, NC 27709 USA. NR 35 TC 18 Z9 18 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI MT ROYAL PA 19 MANTUA RD, MT ROYAL, NJ 08061 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD MAR-APR PY 2000 VL 28 IS 2 BP 237 EP 245 DI 10.1177/019262330002800203 PG 9 WC Pathology; Toxicology SC Pathology; Toxicology GA 298NP UT WOS:000086146300003 PM 10805141 ER PT J AU Waalkes, MP Rehm, S Cherian, MG AF Waalkes, MP Rehm, S Cherian, MG TI Repeated cadmium exposures enhance the malignant progression of ensuing tumors in rats SO TOXICOLOGICAL SCIENCES LA English DT Article DE cadmium; carcinogenesis; rats; sarcoma; tumor progression; tumor invasion; tumor metastasis ID WISTAR CRL-(WI)BR RATS; DOSE-RESPONSE ANALYSIS; INJECTION SITE; IMMUNOHISTOCHEMICAL LOCALIZATION; MAGNESIUM ACETATES; METALLOTHIONEIN; CHLORIDE; CARCINOGENESIS; LIVER; APOPTOSIS AB Prior studies show that a single subcutaneous (sc) exposure to cadmium (Cd) will induce injection site sarcomas (ISS) in rats. These tumors, thought clearly malignant, do not often metastasize or invade subdermal muscle layers because of their location. Recent evidence indicates that when tumorigenic cells chronically exposed to Cd in vitro are inoculated into mice, tumor progression and invasiveness in the mice are enhanced. Thus, we studied the effects of repeated Cd exposures on tumor incidence, progression, and metastatic potential in rats. Wistar (WF) and Fischer (F344) rats (30 per group) were injected sc in the dorsal thoracic midline with CdCl2 once weekly for 18 weeks with doses of 0, 10, 20, or 30 mu mol Cd/kg. This resulted in total doses of 0, 180, 360, or 540 mu mol/kg. One other group of each strain received a low, loading dose of Cd (3 mu mol/kg) prior to 17 weekly injections of 30 mu mol/kg (total dose 513 mu mol/kg). Rats were observed for 2 years. Many F344 rats (57%) died within one week after the first injection of the highest dose, but WF rats were not affected. The low loading dose prevented acute lethality of the high dose in F344 rats. Surprisingly, latency (time to death by tumor) of ISS was the shortest in the groups given the low loading dose in both strains. ISS in these groups also showed the highest rate of metastasis and subdermal muscle layer invasion. Based on ISS incidence in the groups given the lowest total dose of Cd (180 mu moles/kg), F344 rats were more sensitive to tumor induction, showing an incidence of 37% compared to 3% in WF rats. On the other hand, Cd-induced ISS showed a higher overall metastatic rate in WF rats (18 metastatic ISS/68 total tumors in all treated groups; 27%) compared to F344 rats (6%). Immunohistochemically, the primary ISS showed high levels of metallothionein (MT), a cadmium-binding protein, while metastases were essentially devoid of MT. These results indicate that repeated Cd exposures more rapidly induce ISS. An initial low exposure to Cd further accelerates the appearance and enhances the metastatic potential and invasiveness of these tumors. The primary and metastatic ISS appear to have a differing phenotype, at least with regard to MT production. The association between multiple Cd exposures and enhanced metastatic potential of the ensuing tumors may have important implications in chronic exposures to Cd, or in cases of co-exposure of Cd with organic carcinogens, as in tobacco smoking. C1 NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC 27709 USA. Univ Western Ontario, Dept Pathol, London, ON N6A 5C1, Canada. RP Waalkes, MP (reprint author), NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, POB 12233,111 Alexander Dr,MD F0-09, Res Triangle Pk, NC 27709 USA. NR 40 TC 29 Z9 30 U1 2 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2000 VL 54 IS 1 BP 110 EP 120 DI 10.1093/toxsci/54.1.110 PG 11 WC Toxicology SC Toxicology GA 292MU UT WOS:000085799400013 PM 10746938 ER PT J AU Wang, W Wine, RN Chapin, RE AF Wang, W Wine, RN Chapin, RE TI Rat testicular Src: Normal distribution and involvement in ethylene glycol monomethyl ether-induced apoptosis SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID PROTEIN-TYROSINE KINASES; CALCIUM-CHANNEL BLOCKERS; EPIDERMAL GROWTH-FACTOR; IN-VITRO; SPERMATOCYTE APOPTOSIS; SIGNAL TRANSDUCTION; FOCAL ADHESION; ACTIVATION; EXPRESSION; TOXICITY AB Kinase activities were previously proposed to be central to germ cell apoptosis induced by ethylene glycol monomethyl ether (EGME) and its active metabolite methoxyacetic acid (MAA). We evaluated the role of tyrosine kinase pp60(c-src) in control and EGME-treated adult rat testis in vivo, as well as in vitro using cultured adult rat seminiferous tubules treated with MAA. In normal testicular tissue, immunoreactivity of Src was mostly detected in Sertoli cell cytoplasm and reached the maximum level around the lumen at spermiation. Src localization was confirmed by immunostaining of cocultures of Sertoli and germ cells and was further confirmed by electron microscopic observation that immunoreactivity was predominant in Sertoli cell cytoplasm as well as occasionally at the Sertoli/germ cell junctions. A single dose of 200 mg/kg EGME induced an increase of Src immunoexpression in both epithelium and interstitium in rat testis. Eight hours after treatment, an intensive immunostaining of Src began to be observed specifically in the cytoplasm of the dying spermatocytes. The apoptotic changes were replicated by exposure of 5 mM MAA in the adult rat seminiferous tubule culture model. Furthermore, spermatocyte degeneration was significantly prevented by cotreatment with 0.1 mu M geldanamycin, 10 mu M herbimycin A, or 10 mu M PP2, which are inhibitors of Src activity. These data collectively suggest that pp60(c-src) mediates Sertoli-germ cell interaction in physiological events, and may play an important role in EGME/MAA-induced germ cell apoptosis. C1 NIEHS, Natl Toxicol Program, Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP Chapin, RE (reprint author), NIEHS, Natl Toxicol Program, Toxicol Lab, Mail Drop B3-05,POB 12233, Res Triangle Pk, NC 27709 USA. OI Chapin, Robert/0000-0002-5997-1261 NR 44 TC 22 Z9 22 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAR 1 PY 2000 VL 163 IS 2 BP 125 EP 134 DI 10.1006/taap.1999.8870 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 295TB UT WOS:000085983000004 PM 10698670 ER PT J AU Aravind, L Koonin, EV AF Aravind, L Koonin, EV TI SAP - a putative DNA-binding motif involved in chromosomal organization SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID PROTEIN; TRANSCRIPTION; ELEMENTS; AFFINITY; DOMAIN; FINGER; FAMILY; GENE 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 Aravind, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. NR 20 TC 313 Z9 331 U1 2 U2 5 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD MAR PY 2000 VL 25 IS 3 BP 112 EP 114 DI 10.1016/S0968-0004(99)01537-6 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 292LZ UT WOS:000085797100006 PM 10694879 ER EF