FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Hesse, M Mitchison, NA AF Hesse, M Mitchison, NA TI Relapsing arthritis induced by cell transfer from collagen-immunised mice SO AUTOIMMUNITY LA English DT Article DE rheumatoid arthritis; autoimmunity; inflammation; in vivo animal models ID II COLLAGEN; ENCEPHALOMYELITIS; INTERLEUKIN-10 AB Collagen-induced arthritis is a well-established model of chronic inflammatory arthritis. We here introduce a development of this model which combines the benefits of adoptive transfer and sequential relapse, DBA/1 x B10.Q F1 hybrid mice were immunised with bovine type II collagen, and those which developed a sufficiently high level of arthritis served as donors of spleen cells transferred into BALB/c SCID hosts. After boosting with 500 mu g collagen, the development of host arthritis was monitored over a period of up to 256 days, during which up to three successive peaks were detected. In comparison with bovine collagen, mouse collagen used for boosting induced a lower initial peak but higher relapses, As expected, the transferred disease was more uniform than the freshly induced one. Previous information suggests that a shifting cytokine balance between protective and aggressive T cells may account for the relapse and remission. This study provides a model of relapsing polyarthritis, obtained with normal immunocytes boosted with a well-defined protein antigen in animals not themselves treated with adjuvant, As such it is relevant to the etiology of inflammatory arthritis in man, and, if further developed, could be of value for testing new therapeutic strategies. C1 Deutsch RheumaForsch Zentrum, D-10117 Berlin, Germany. RP Hesse, M (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 7,Rm 318, Bethesda, MD 20892 USA. NR 25 TC 4 Z9 4 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 0891-6934 J9 AUTOIMMUNITY JI Autoimmunity PY 2000 VL 32 IS 1 BP 27 EP 32 DI 10.3109/08916930008995984 PG 6 WC Immunology SC Immunology GA 340QJ UT WOS:000088545700003 PM 10958172 ER PT J AU Mahana, W Samaan, A Zhao, TM Kindt, TJ Simpson, RM AF Mahana, W Samaan, A Zhao, TM Kindt, TJ Simpson, RM TI Evidence for numeral and cellular reactivity against keratin and thyroglobulin in HTLV-I infected rabbits SO AUTOIMMUNITY LA English DT Article DE autoimmunity; injections; DNA; disease models; animal; abnormal host response ID VIRUS TYPE-I; AUTOIMMUNE-THYROIDITIS; HASHIMOTO THYROIDITIS; MYCOSIS-FUNGOIDES; ANTIBODIES; AUTOANTIBODIES; CARRIERS; LYMPHOMA; UVEITIS; CELLS AB Human T cell leukemia virus type T (HTLV-I) infection was initially associated with T cell leukemia and a progressive neurologic disease but has since been linked to an increasing number of autoimmune disorders, including Sjogren's syndrome, uveitis, and polyarthritis, A survey of serum samples from a rabbit model of HTLV-I infection revealed that all had antibodies against keratin and thyroglobulin, Sera from several infected rabbits also reacted with collagen, while antibody reactions with other autoantigens tested, including DNA, were rare and sporadic. In addition to antibodies, cellular reactivity to keratin, but not thyroglobulin, was demonstrated by cellular proliferation in presence of IL-2 and keratin, Expanded cell cultures were positive for T cell activation markers and CD8, Association of the auto-reactivity with HTLV-I infection rather than random anti-cellular responses was supported by the fact that no antikeratin or antithyroglobulin was seen in uninfected controls, including that inoculated with uninfected lymphocytes. Finding autoantibodies in rabbits infected using naked HTLV-I DNA clones provided further assurance that infection induced tbe autoimmune reactions detected. C1 NIAID, Immunogenet Lab, Twinbrook Facil, NIH, Rockville, MD 20852 USA. RP Simpson, RM (reprint author), NIAID, Immunogenet Lab, Twinbrook Facil, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. NR 40 TC 3 Z9 3 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 0891-6934 J9 AUTOIMMUNITY JI Autoimmunity PY 2000 VL 32 IS 1 BP 57 EP 65 DI 10.3109/08916930008995988 PG 9 WC Immunology SC Immunology GA 340QJ UT WOS:000088545700007 PM 10958176 ER PT J AU Read-Connole, EL AF Read-Connole, EL TI Mammalian and avian reovirus SO AVIAN AND POULTRY BIOLOGY REVIEWS LA English DT Article DE Mammalian and avian reovirus ID CENTRAL-NERVOUS-SYSTEM; PROTEIN-CODING ASSIGNMENT; RNA GENOME SEGMENTS; EXPERIMENTAL-INFECTION; ATTACHMENT PROTEIN; BOBWHITE QUAIL; STRAIN S1133; NITRIC-OXIDE; CHICKENS; IDENTIFICATION AB Avian reovirus is the cause of viral arthritis and is causally linked to disease syndromes, 'pale bird', 'helicopter disease', and 'chronic wasting disease', that produce stunted growth and development in many avian species. The diseases caused by avian reovirus are responsible for huge losses to the poultry industry despite vaccination. Mammalian strains of reovirus resemble avian reovirus at the molecular level, and also cause similar pathological effects. This review summarizes the current avian and mammalian reoviruses literature. C1 Univ Maryland, Cell & Mol Biol Program, College Pk, MD 20742 USA. Univ Maryland, Anim & Avian Sci Dept, College Pk, MD 20742 USA. RP NCI, HIV & AIDS Malignancy Branch, NIH, Bldg 10,12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM bconnole@box-b.nih.gov NR 83 TC 1 Z9 1 U1 1 U2 1 PU SCIENCE REVIEWS 2000 LTD PI ST ALBANS PA PO BOX 314, ST ALBANS AL1 4ZG, HERTS, ENGLAND SN 1470-2061 J9 AVIAN POULT BIOL REV JI Avian Poult. Biol. Rev. PY 2000 VL 11 IS 3 BP 123 EP 136 PG 14 WC Agriculture, Dairy & Animal Science SC Agriculture GA 361LY UT WOS:000089725600001 ER PT S AU Kenny, JJ Lustig, A Longo, DL AF Kenny, JJ Lustig, A Longo, DL BE Potter, M Melchers, F TI Positive selection of low affinity autoreactive B cells SO B 1 LYMPHOCYTES IN B CELL NEOPLASIA SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT 16th Workshop on the Mechanisms of B Cell Neoplasia CY OCT 28-29, 1999 CL NIH, NATL LIB MED, BETHESDA, MARYLAND SP NCI, Lab Genet, Div Basic Sci HO NIH, NATL LIB MED ID IMMUNE-DEFICIENT MICE; STREPTOCOCCUS-PNEUMONIAE; ESCAPE TOLERANCE; TRANSGENIC MICE; CHAIN GENE; ANTIBODIES; IDIOTYPE C1 NIA, B Cell Dev Sect, Immunol Lab, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA. RP Kenny, JJ (reprint author), NIA, B Cell Dev Sect, Immunol Lab, Gerontol Res Ctr,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 17 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-67567-1 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2000 VL 252 BP 39 EP 45 PG 7 WC Immunology; Microbiology SC Immunology; Microbiology GA BR65E UT WOS:000167097400005 PM 11125491 ER PT S AU Mage, RG Pospisil, R AF Mage, RG Pospisil, R BE Potter, M Melchers, F TI CD5 and other superantigens may select and maintain rabbit self-renewing B-lymphocytes and human B-CLL cells SO B 1 LYMPHOCYTES IN B CELL NEOPLASIA SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT 16th Workshop on the Mechanisms of B Cell Neoplasia CY OCT 28-29, 1999 CL NIH, NATL LIB MED, BETHESDA, MARYLAND SP NCI, Lab Genet, Div Basic Sci HO NIH, NATL LIB MED ID GENE CONVERSION-LIKE; H-MUTANT RABBITS; V-H; SOMATIC DIVERSIFICATION; IMMUNOGLOBULIN GENES; REGION SEQUENCES; GERMINAL-CENTERS; LYMPHOID ORGANS; ADULT-RABBITS; EXPRESSION C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. VIDIA, Prague 14200, Czech Republic. RP Mage, RG (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. RI Pospisil, Richard/B-7467-2012 NR 47 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-67567-1 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2000 VL 252 BP 87 EP 96 PG 10 WC Immunology; Microbiology SC Immunology; Microbiology GA BR65E UT WOS:000167097400010 PM 11125495 ER PT S AU Notkins, AL AF Notkins, AL BE Potter, M Melchers, F TI Polyreactive antibodies and polyreactive antigen-binding B (PAB) cells SO B 1 LYMPHOCYTES IN B CELL NEOPLASIA SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT 16th Workshop on the Mechanisms of B Cell Neoplasia CY OCT 28-29, 1999 CL NIH, NATL LIB MED, BETHESDA, MARYLAND SP NCI, Lab Genet, Div Basic Sci HO NIH, NATL LIB MED ID MONOREACTIVE HIGH-AFFINITY; MONOCLONAL AUTOANTIBODIES; RHEUMATOID-ARTHRITIS; NATURAL ANTIBODIES; ESCHERICHIA-COLI; T-CELLS; REPERTOIRE; LYMPHOCYTES; IGM; CIRCULATION C1 Natl Inst Dent & Craniofacial Res, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Notkins, AL (reprint author), Natl Inst Dent & Craniofacial Res, Expt Med Sect, Oral Infect & Immun Branch, NIH, 30 Convent Dr, Bethesda, MD 20892 USA. NR 32 TC 13 Z9 13 U1 1 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-67567-1 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2000 VL 252 BP 241 EP 249 PG 9 WC Immunology; Microbiology SC Immunology; Microbiology GA BR65E UT WOS:000167097400025 PM 11125481 ER PT S AU Potter, M Jones, G DuBois, W Williams, K Mushinski, E AF Potter, M Jones, G DuBois, W Williams, K Mushinski, E BE Potter, M Melchers, F TI Myeloma proteins that bind Hsp65 (GroEL) are polyreactive and are found in high incidence in pristane induced plasmacytomas SO B 1 LYMPHOCYTES IN B CELL NEOPLASIA SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT 16th Workshop on the Mechanisms of B Cell Neoplasia CY OCT 28-29, 1999 CL NIH, NATL LIB MED, BETHESDA, MARYLAND SP NCI, Lab Genet, Div Basic Sci HO NIH, NATL LIB MED ID HEAT-SHOCK PROTEINS; INDUCED ARTHRITIS; ANTIGEN-BINDING; B-CELLS; MICE; ANTIBODIES; AUTOANTIBODIES; CIRCULATION; EPITOPE; GENES AB The myeloma proteins produced by 44 plasmacytomas (PCTs) recently induced by pristane in BALB/cAnPt and closely related PCT susceptible congenic strains of mice were isolated chromatographically and screened against a panel of 10 protein, nucleic acid and lipid antigens. This sample was highly unusual because 82% of the proteins had IgG isotypes. Nine of the proteins bound to Hsp65 (GroEL), and all of these were polyreactaive. Twenty-one of the myeloma proteins were polyreactive and bound two or more antigens in the panel, and five were monoreactive. Thus, an antigen binding activity was determined for 59% of these myeloma proteins. C1 NCI, Genet Lab, NIH, Bethesda, MD 20892 USA. RP Potter, M (reprint author), NCI, Genet Lab, NIH, Bethesda, MD 20892 USA. NR 24 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-67567-1 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2000 VL 252 BP 265 EP 271 PG 7 WC Immunology; Microbiology SC Immunology; Microbiology GA BR65E UT WOS:000167097400027 PM 11125484 ER PT S AU Qi, CF Hori, M Taddesse-Heath, L Jenkins, NA Copeland, NG Shen, H Torrey, TA Hartley, JW Chattopadhyay, SK Fredrickson, TN Morse, HC AF Qi, CF Hori, M Taddesse-Heath, L Jenkins, NA Copeland, NG Shen, H Torrey, TA Hartley, JW Chattopadhyay, SK Fredrickson, TN Morse, HC BE Potter, M Melchers, F TI Diffuse large-cell and "true" histiocytic lymphomas of mice SO B 1 LYMPHOCYTES IN B CELL NEOPLASIA SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT 16th Workshop on the Mechanisms of B Cell Neoplasia CY OCT 28-29, 1999 CL NIH, NATL LIB MED, BETHESDA, MARYLAND SP NCI, Lab Genet, Div Basic Sci HO NIH, NATL LIB MED ID SOMATIC HYPERMUTATION; B-CELL; DISEASE; STRAINS; GENES C1 NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Mammalian Genet Lab, NIH, Frederick, MD 21701 USA. RP Qi, CF (reprint author), NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. OI Morse, Herbert/0000-0002-9331-3705 NR 17 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-67567-1 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2000 VL 252 BP 301 EP 305 PG 5 WC Immunology; Microbiology SC Immunology; Microbiology GA BR65E UT WOS:000167097400031 PM 11125488 ER PT S AU Potter, M Melchers, F AF Potter, M Melchers, F BE Potter, M Melchers, F TI Opinions on the nature of B-l cells and their relationship to B cell neoplasia SO B 1 LYMPHOCYTES IN B CELL NEOPLASIA SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT 16th Workshop on the Mechanisms of B Cell Neoplasia CY OCT 28-29, 1999 CL NIH, NATL LIB MED, BETHESDA, MARYLAND SP NCI, Lab Genet, Div Basic Sci HO NIH, NATL LIB MED ID CHRONIC LYMPHOCYTIC-LEUKEMIA; HEAVY-CHAIN CDR3; PERITONEAL-CAVITY; B-1 CELLS; AUTOANTIBODY PRODUCTION; NEGATIVE REGULATION; IMMUNE-RESPONSES; LYMPHOID-TISSUES; TRANSGENIC MICE; PEYERS-PATCHES C1 NCI, Genet Lab, NIH, Bethesda, MD 20892 USA. Basel Inst Immunol, Basel, Switzerland. RP Potter, M (reprint author), NCI, Genet Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. NR 90 TC 10 Z9 10 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-67567-1 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2000 VL 252 BP 307 EP 324 PG 18 WC Immunology; Microbiology SC Immunology; Microbiology GA BR65E UT WOS:000167097400032 PM 11125489 ER PT J AU Zheng, M Storz, G AF Zheng, M Storz, G TI Redox sensing by prokaryotic transcription factors SO BIOCHEMICAL PHARMACOLOGY LA English DT Article; Proceedings Paper CT Biochemical Pharmacology Symposium on Redox-Controlled Gene Regulation in Environmental Toxicity and Cancer CY JUN, 1999 CL OXFORD, ENGLAND DE OxyR; SoxR; disulfide bond; iron-sulfur cluster; oxidative stress ID DISULFIDE BOND FORMATION; DNA-BINDING ACTIVITY; COLI SOXR PROTEIN; ESCHERICHIA-COLI; OXIDATIVE STRESS; IN-VIVO; SALMONELLA-TYPHIMURIUM; HYDROGEN-PEROXIDE; 2FE-2S CENTERS; OXIDIZED FORM AB Prokaryotic cells employ redox-sensing transcription factors to detect elevated levels of reactive oxygen species and regulate expression of antioxidant genes. In Escherichia coli, two such transcription factors, OxyR and SoxR, have been well characterized. The OxyR protein contains a thiol-disulfide redox switch to sense hydrogen peroxide. The SoxR protein uses a 2Fe-2S cluster to sense superoxide generated by redox-cycling agents, as well as to sense nitric oxide. Both proteins are turned on and off with very fast kinetics (similar to minutes), allowing rapid cellular responses to oxidative stress. The mechanisms by which these and other prokaryotic proteins sense redox signals have provided useful paradigms for understanding redox signal transduction in eukaryotic cells. BIOCHEM PHARMACOL 59;1:1-6, 2000. (C) 1999 Elsevier Science Inc. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Zheng, M (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bldg 18T,Room 101, Bethesda, MD 20892 USA. OI Storz, Gisela/0000-0001-6698-1241 NR 27 TC 152 Z9 168 U1 2 U2 8 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 JAN 1 PY 2000 VL 59 IS 1 BP 1 EP 6 DI 10.1016/S0006-2952(99)00289-0 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 263JJ UT WOS:000084121300001 PM 10605928 ER PT J AU Sheikh, MS Hollander, MC Fornace, AJ AF Sheikh, MS Hollander, MC Fornace, AJ TI Role of Gadd45 in apoptosis SO BIOCHEMICAL PHARMACOLOGY LA English DT Article; Proceedings Paper CT Biochemical Pharmacology Symposium on Redox-Controlled Gene Regulation in Environmental Toxicity and Cancer CY JUN, 1999 CL OXFORD, ENGLAND DE Gadd45; p53; apoptosis; Brcal; MAP kinase; c-myc ID PROTEIN-KINASE CASCADES; DNA-DAMAGING AGENTS; CELL-CYCLE; GAMMA-RADIATION; ACTIVATION; STRESS; ARREST; GENE; P53; P21(WAF1/CIP1) AB gadd45 is a p53-regulated growth arrest and DNA-damage-inducible gene that is also regulated in a p53-independent manner. Whether Gadd45 plays a direct role in apoptosis remains unclear. Microinjection of the exogenous gadd45 expression vector into human fibroblasts has been shown to cause G(2) arrest hut not apoptosis. Recent studies suggest that Gadd45 may mediate genotoxic stress or Brca1-induced apoptosis via activation of c-Jun N-terminal kinase (JNK) and/or p38 mitogen-activated protein kinase (MAPK). Analyses of gadd45-deficient mice and cells have revealed that Gadd45 appears to exhibit pleiotropic effects, including cell cycle arrest at G(2)/M, DNA damage repair, and control of genomic stability, but is not required for radiation induced apoptosis. Furthermore, stress-induced activation of JNK and p38 MAPK is not altered in gadd45-deficient embryonic fibroblasts, suggesting that the lack of Gadd45 may not affect the JNK and p38 MAPK activity. Thus, although the evidence from gadd45-null cells suggests that Gadd45 probably does not play a direct role in genotoxic stress induced apoptosis, more in-depth studies are needed to firmly establish this contention. BIOCHEM PHARMACOL 59;1:43-45, 2000. (C) 1999 Elsevier Science Inc. C1 NCI, Gene Response Sect, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Sheikh, MS (reprint author), SUNY Hlth Sci Ctr, Dept Pharmacol, 750 E Adams St, Syracuse, NY 13210 USA. NR 37 TC 138 Z9 142 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JAN 1 PY 2000 VL 59 IS 1 BP 43 EP 45 DI 10.1016/S0006-2952(99)00291-9 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 263JJ UT WOS:000084121300006 PM 10605933 ER PT J AU Sohrab, MH Hasan, CM Rashid, MA AF Sohrab, MH Hasan, CM Rashid, MA TI Clausmarin-A from the leaves of Clausena heptaphylla SO BIOCHEMICAL SYSTEMATICS AND ECOLOGY LA English DT Article DE Clausena heptaphylla; rutaceae; coumarin; clausmarin A; chemotaxonomy ID CARBAZOLE C1 Univ Dhaka, Dept Pharm, Phytochem Res Lab, Dhaka 1000, Bangladesh. RP Rashid, MA (reprint author), SAIC Frederick, Natl Canc Inst, Frederick Canc Res & Dev Ctr, Bldg 560,Rm 32-63B,POB B, Frederick, MD 21702 USA. NR 13 TC 2 Z9 2 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0305-1978 J9 BIOCHEM SYST ECOL JI Biochem. Syst. Ecol. PD JAN PY 2000 VL 28 IS 1 BP 91 EP 93 DI 10.1016/S0305-1978(99)00035-6 PG 3 WC Biochemistry & Molecular Biology; Ecology; Evolutionary Biology SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology; Evolutionary Biology GA 239FR UT WOS:000082758600009 ER PT J AU Van Goor, F Krsmanovic, LZ Catt, KJ Stojilkovic, SS AF Van Goor, F Krsmanovic, LZ Catt, KJ Stojilkovic, SS TI Autocrine regulation of calcium influx and gonadotropin-releasing hormone secretion in hypothalamic neurons SO BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE LA English DT Article; Proceedings Paper CT 5th International Congress of Comparative Physiology and Biochemistry CY AUG 23-28, 1999 CL CALGARY, CANADA ID UNDERLYING PACEMAKER POTENTIALS; EMBRYONIC OLFACTORY PLACODE; GNRH NEURONS; SMALL-CONDUCTANCE; LOOP FEEDBACK; GT1-7 NEURONS; PREOPTIC AREA; RHESUS-MONKEY; K+ CHANNELS; RAT AB Gonadotropin-releasing hormone (GnRH) receptors are expressed in hypothalamic tissues from adult rats, cultured fetal hypothalamic cells, and immortalized GnRH-secreting neurons (GT1 cells). Their activation by GnRH agonists leads to an overall increase in the extracellular Ca2+-dependent pulsatile release of GnRH. Electrophysiological studies showed that GT1 cells exhibit spontaneous, extracellular Ca2+-dependent action potentials, and that their inward currents include Na+, T-type and L-type Ca2+ components. Several types of potassium channels, including apamin-sensitive Ca2+-controlled potassium (SK) channels, are also expressed in GT1 cells. Activation of GnRH receptors leads to biphasic changes in intracellular Ca2+ concentration ([Ca2+](i)), with an early and extracellular Ca2+-independent peak and a sustained and extracellular Ca2+-dependent plateau phase. During the peak [Ca2+](i) response, electrical activity is abolished due to transient hyperpolarization that is mediated by SK channels. This is followed by sustained depolarization and resumption of firing with increased spike frequency and duration. The agonist-induced depolarization and increased firing are independent of [Ca2+](i) and are not mediated by inhibition of K+ currents, but by facilitation of a voltage-insensitive and store depletion-activated Ca2+-conducting inward current. The dual control of pacemaker activity by SK and store depletion-activated Ca2+ channels facilitates voltage-gated Ca2+ influx at elevated [Ca2+](i) levels, but also protects cells from Ca2+ overload. This process accounts for the autoregulatory action of GnRH on its release from hypothalamic neurons. C1 NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Van Goor, F (reprint author), NICHHD, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Room 6A36,49 Convent Dr, Bethesda, MD 20892 USA. NR 50 TC 18 Z9 18 U1 0 U2 1 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA, ONTARIO K1A 0R6, CANADA SN 0829-8211 J9 BIOCHEM CELL BIOL JI Biochem. Cell Biol. PY 2000 VL 78 IS 3 BP 359 EP 370 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 338FV UT WOS:000088408600018 PM 10949086 ER PT J AU Stojilkovic, SS Tomic, M Van Goer, F Koshimizu, T AF Stojilkovic, SS Tomic, M Van Goer, F Koshimizu, T TI Expression of purinergic P2X(2) receptor-channels and their role in calcium signaling in pituitary cells SO BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE LA English DT Article; Proceedings Paper CT 5th International Congress of Comparative Physiology and Biochemistry CY AUG 23-28, 1999 CL CALGARY, CANADA DE ATP-gated channels; gonadotrophs; lactotrophs; somatotrophs ID GATED ION CHANNELS; EXTRACELLULAR ATP; SENSORY NEURONS; MESSENGER-RNA; P-2X RECEPTOR; RAT; DESENSITIZATION; ADENOSINE; LOCALIZATION; OSCILLATIONS AB Pituitary cells express purinergic receptor-channels (P2XR), the activation of which by ATP is associated with the facilitation of Ca2+ influx. Pharmacological, RT-PCR, and nucleotide sequence analyses confirm the presence of a wild type P2X(2a)R and a spliced isoform P2X(2b)R, which lacks a portion of carboxyl terminal amino acids. Wild type and spliced isoform receptors have a similar EC50 for ATP and time-course for activation, but the spliced isoform exhibits rapid and complete desensitization, whereas the wild type channel desensitizes slowly and incompletely. Deletion and insertion studies have revealed that a 6 residue sequence located in carboxyl tail (Arg(371)-Pro(376)) is required for sustained Ca2+ influx through wild type receptors. When co-expressed, the wild type and spliced channels form functional heteropolymeric channels. The patterns of Ca2+ signaling in the majority of pituitary cells expressing ATP-gated receptor-channels are highly comparable to those observed in cells co-transfected with P2X(2a)R and P2XR. ATP-induced [Ca2+](i) response in pituitary cells is partially inhibited by nifedipine, a blocker of voltage-gated L-type Ca2+ channels, suggesting that P2X(2)R not only drive Ca2+ into the cell, but also activate voltage-gated Ca2+ entry. Our results indicate that ATP represents a paracrine and (or) autocrine factor in the regulation of Ca2+ signaling, and that its actions are mediated in part by heteropolymeric P2X(2)R. C1 NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Stojilkovic, SS (reprint author), NICHHD, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Room 6A-36,40 Convent Dr, Bethesda, MD 20892 USA. RI Tomic, Melanija/C-3371-2016; OI Koshimizu, Taka-aki/0000-0001-5292-7535 NR 39 TC 9 Z9 9 U1 0 U2 0 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA, ONTARIO K1A 0R6, CANADA SN 0829-8211 J9 BIOCHEM CELL BIOL JI Biochem. Cell Biol. PY 2000 VL 78 IS 3 BP 393 EP 404 DI 10.1139/bcb-78-3-393 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 338FV UT WOS:000088408600020 PM 10949088 ER PT B AU Miles, EW Fan, YX Jhee, KH Ro, HS McPhie, P Rhee, S Davies, DR AF Miles, EW Fan, YX Jhee, KH Ro, HS McPhie, P Rhee, S Davies, DR BE Iriarte, A Kagan, HM MartinezCarrion, M TI Structure and function of tryptophan synthase SO BIOCHEMISTRY AND MOLECULAR BIOLOGY OF VITAMIN B6 AND PQQ-DEPENDENT PROTEINS LA English DT Proceedings Paper CT International Meeting on Biochemistry and Molecular Biology of Vitamin B6 and PQQ-Dependent Proteins CY OCT 31-NOV 05, 1999 CL SANTA FE, NM SP Int Union Biochem & Molec Biol, Bayer Corp Pharmaceut Div, Biomolec Instruments, Div Thermo Instrument Syst, Chiron Corp, Merck Sharp & Dhome Res Labs, Mitokor, Warner Lambert Corp, Parke Davis Pharmaceut Div, Univ Missouri, Sch Biol Sci ID ALPHA(2)BETA(2) COMPLEX; 3-DIMENSIONAL STRUCTURE; LIGANDS; PH AB Crystal structures of the tryptophan synthase alpha (2)beta (2) complex show binding sites in the beta subunit for pyridoxal phosphate, for substrates, and for a monovalent cation. Cations, including guanidine at low concentration, activate tryptophan synthase. Molecular modeling indicates that guanidine could bind to the cation site in the beta subunit. Our results demonstrate that the conformational states of the tryptophan synthase alpha (2)beta (2) complex are regulated by monovalent cations, chaotropic agents, pH, alpha subunit ligands, and temperature. C1 NIH, Bethesda, MD 20892 USA. RP Miles, EW (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 11 TC 1 Z9 1 U1 1 U2 1 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND BN 3-7643-6145-X PY 2000 BP 145 EP 150 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BR73F UT WOS:000167358600023 ER PT S AU Cragg, GM Boyd, MR Hallock, YF Newman, DJ Sausville, EA Wolpert, MK AF Cragg, GM Boyd, MR Hallock, YF Newman, DJ Sausville, EA Wolpert, MK BE Wrigley, S Hayes, MA Thomas, R Chrystal, EJT Nicholson, N TI Natural products drug discovery at the National Cancer Institute. Past achievements and new directions for the new millennium SO BIODIVERSITY: NEW LEADS FOR THE PHARMACEUTICAL AND AGROCHEMICAL INDUSTRIES SE Royal Society of Chemistry Special Publications LA English DT Proceedings Paper CT International Meeting on Biodiversity: A Source of New Leads for the Pharmaceutical and Agrochemical Industries CY SEP 05-08, 1999 CL UNIV ST ANDREWS, ST ANDREWS, SCOTLAND SP AstraZeneca Agrochem, Glaxo Wellcome Res & Dev, Smithkline Beecham HO UNIV ST ANDREWS ID ANTINEOPLASTIC AGENTS; POLYKETIDE SYNTHASES; MICROBIAL DIVERSITY; EXPLORATION; COMMUNITIES; ANTICANCER; INHIBITORS; MECHANISM; BINDING; VENTS C1 NCI, Frederick Canc Res & Dev Ctr, Div Canc Treatment & Diag, Dev Therapeut Program,Fairview Ctr, Frederick, MD 21701 USA. RP Cragg, GM (reprint author), NCI, Frederick Canc Res & Dev Ctr, Div Canc Treatment & Diag, Dev Therapeut Program,Fairview Ctr, POB B, Frederick, MD 21701 USA. NR 62 TC 1 Z9 1 U1 0 U2 0 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND SN 0260-6291 BN 0-85404-830-8 J9 ROY SOC CH PY 2000 IS 257 BP 22 EP 44 DI 10.1039/9781847550231-00022 PG 23 WC Biochemistry & Molecular Biology; Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Plant Sciences; Pharmacology & Pharmacy GA BR79D UT WOS:000167541500003 ER PT J AU DeGraba, TJ AF DeGraba, TJ TI Immunological aspects of acute stroke - Therapeutic implications SO BIODRUGS LA English DT Article ID CEREBRAL-ARTERY OCCLUSION; TUMOR-NECROSIS-FACTOR; ISCHEMIC CELL-DAMAGE; LEUKOCYTE ADHESION MOLECULES; POLYMORPHONUCLEAR LEUKOCYTES; REPERFUSION INJURY; ENDOTHELIAL-CELLS; HYPERTENSIVE RAT; BRAIN-DAMAGE; FACTOR-ALPHA AB Recent studies strongly suggest that cerebral ischaemia initiates a focal inflammatory response that results in significant secondary injury to brain tissue, thereby extending the ultimate size of a stroke. Factors involved in this cascade include the release of cytokines that cause a pro-inflammatory and prothrombotic state on cerebral vessel endothelium, the expression of leucocyte adhesion molecules, and the release of chemotactic factors allowing the migration of leucocytes into the area of injured brain tissue causing further damage. Animal studies have clearly demonstrated the detrimental effects of these inflammatory mediators in stroke models and additionally have shown dramatic reduction in infarct size using leucocyte adhesion modification and cytokine receptor blockade. The approach of modifying the effects of inflammatory cytokines and/or limiting leucocyte adhesion and migration into the region of injury holds great promise for identifying agents that will give significant neuronal protection following a stroke. C1 NINDS, Stroke Branch, Clin Stroke Res Unit, Bethesda, MD 20892 USA. RP DeGraba, TJ (reprint author), NINDS, Stroke Branch, Clin Stroke Res Unit, 36 Convent Dr,MSC 4128,Bldg 36,Room 4A-03, Bethesda, MD 20892 USA. NR 56 TC 0 Z9 0 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1173-8804 J9 BIODRUGS JI Biodrugs PD JAN PY 2000 VL 13 IS 1 BP 1 EP 8 DI 10.2165/00063030-200013010-00001 PG 8 WC Oncology; Immunology; Pharmacology & Pharmacy SC Oncology; Immunology; Pharmacology & Pharmacy GA 275RA UT WOS:000084832900001 PM 18034508 ER PT J AU Romano-Spica, V Mucci, N Ursini, CL Ianni, A Bhat, NK AF Romano-Spica, V Mucci, N Ursini, CL Ianni, A Bhat, NK TI Ets1 oncogene induction by ELF-modulated 50 MHz radiofrequency electromagnetic field SO BIOELECTROMAGNETICS LA English DT Article DE modulated RF fields; nonthermal effects; biological effects; ets gene; differential display; transcriptional regulation ID CALCIUM-ION EFFLUX; HUMAN PERIPHERAL LYMPHOCYTES; CENTRAL-NERVOUS-SYSTEM; PULSED MAGNETIC-FIELD; NEURO-BLASTOMA CELLS; VOLTAGE POWER-LINES; COLON-CANCER CELLS; LOW-FREQUENCY; BRAIN-TISSUE; LOW-LEVEL AB We have analyzed gene expression in hemopoietic and testicular cell types after their exposure to 50 MHz radiofrequency (RF) non-ionizing radiation modulated (80%) with a 16 Hz frequency. The exposure system generates a 0.2 mu T magnetic field parallel to the ground and a 60 V/m electric field orthogonal to the earth's magnetic field. Exposure conditions: were selected so as to interfere with the calcium ion flow. Under these electromagnetic field (EMF) conditions, we observed an overexpression of the ets1 mRNA in Jurkat T-lymphoblastoid and Leydig TM3 cell lines. This effect was observed only in the presence of the 16 Hz modulation, corresponding to the resonance frequency for calcium ion with a DC magnetic field of 45.7 mu T. We have also identified a putative candidate gene repressed after EMF exposure. The experimental model described in this paper may contribute to the understanding of the biological mechanisms involved in EMF effects. (C) 2000 Wiley-Liss, Inc. C1 Univ Cattolica Sacro Cuore, Inst Hyg & Publ Hlth, Fac Med, I-00168 Rome, Italy. ISPESL, Higher Inst Occupat Safety & Hlth, Dept Occupat Med, Monte Porzio Catone, Italy. Sci Applicat Int Corp Inc, Recombinant DNA Lab, Frederick Canc Res & Dev Ctr, Frederick, MD USA. RP Romano-Spica, V (reprint author), Univ Cattolica Sacro Cuore, Inst Hyg & Publ Hlth, Fac Med, LF Vito 1, I-00168 Rome, Italy. EM romanospica@caspur.it NR 83 TC 10 Z9 12 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0197-8462 J9 BIOELECTROMAGNETICS JI Bioelectromagnetics PD JAN PY 2000 VL 21 IS 1 BP 8 EP 18 DI 10.1002/(SICI)1521-186X(200001)21:1<8::AID-BEM3>3.0.CO;2-G PG 11 WC Biology; Biophysics SC Life Sciences & Biomedicine - Other Topics; Biophysics GA 275JY UT WOS:000084818100003 PM 10615087 ER PT J AU Schatzkin, A AF Schatzkin, A TI Going against the grain? Current status of the dietary fiber-colorectal cancer hypothesis SO BIOFACTORS LA English DT Article; Proceedings Paper CT 2nd International Conference on Food Factors (2nd ICoFF) CY DEC 12-17, 1999 CL KYOTO, JAPAN ID RANDOMIZED TRIAL; RISK; PREVENTION; COLON; FAT C1 NCI, Bethesda, MD 20892 USA. RP Schatzkin, A (reprint author), NCI, Bethesda, MD 20892 USA. NR 16 TC 5 Z9 6 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0951-6433 J9 BIOFACTORS JI Biofactors PY 2000 VL 12 IS 1-4 BP 305 EP 311 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 406XN UT WOS:000167241600045 PM 11216501 ER PT S AU Sternberg, EM AF Sternberg, EM BE Mayer, EA Saper, CB TI Interactions between the immune and neuroendocrine systems SO BIOLOGICAL BASIS FOR MIND BODY INTERACTIONS SE PROGRESS IN BRAIN RESEARCH LA English DT Article; Proceedings Paper CT Symposium on the Science and Practice of Mind/Body Interactions CY MAR 15-18, 1998 CL SEDONA, ARIZONA SP Procter & Gamble, Balm Fdn ID PITUITARY-ADRENAL AXIS; CORTICOTROPIN-RELEASING HORMONE; SYMPATHETIC NERVOUS-SYSTEM; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; INFLUENZA VIRAL-INFECTION; STRESS-INDUCED MODULATION; CHEMICAL SYMPATHECTOMY; BRAIN COMMUNICATION; SUBSTANCE-P; LEWIS RATS C1 NIMH, Reprod Neuroendocrine Immunol & Behav, NIH, Bethesda, MD 20892 USA. RP Sternberg, EM (reprint author), NIMH, Reprod Neuroendocrine Immunol & Behav, NIH, Bldg 10,Rm 2D-46,10 Ctr Dr,MSC 1284, Bethesda, MD 20892 USA. NR 47 TC 12 Z9 13 U1 1 U2 1 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 0-444-50049-9 J9 PROG BRAIN RES PY 2000 VL 122 BP 35 EP 42 PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA BP71A UT WOS:000085937700004 PM 10737049 ER PT S AU Janig, W Khasar, SG Levine, JD Miao, FJP AF Janig, W Khasar, SG Levine, JD Miao, FJP BE Mayer, EA Saper, CB TI The role of vagal visceral afferents in the control of nociception SO BIOLOGICAL BASIS FOR MIND BODY INTERACTIONS SE PROGRESS IN BRAIN RESEARCH LA English DT Article; Proceedings Paper CT Symposium on the Science and Practice of Mind/Body Interactions CY MAR 15-18, 1998 CL SEDONA, ARIZONA SP Procter & Gamble, Balm Fdn ID SYNOVIAL PLASMA EXTRAVASATION; SYMPATHETIC POSTGANGLIONIC NEURONS; RAT GASTROINTESTINAL-TRACT; TUMOR-NECROSIS-FACTOR; INDUCED HYPERALGESIA; SUBDIAPHRAGMATIC VAGOTOMY; MECHANICAL HYPERALGESIA; HEPATOPORTAL SYSTEM; BRAIN COMMUNICATION; ANESTHETIZED RAT C1 Univ Kiel, Inst Physiol, D-24098 Kiel, Germany. Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Oral Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Div Neurosci, Program Biomed Sci, San Francisco, CA 94143 USA. Univ Calif San Francisco, NIH, Pain Ctr, San Francisco, CA 94143 USA. RP Janig, W (reprint author), Univ Kiel, Inst Physiol, D-24098 Kiel, Germany. FU NIAMS NIH HHS [AR32634] NR 69 TC 46 Z9 48 U1 0 U2 4 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 0-444-50049-9 J9 PROG BRAIN RES PY 2000 VL 122 BP 273 EP 287 PG 15 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA BP71A UT WOS:000085937700020 PM 10737065 ER PT J AU Hyman, SE AF Hyman, SE TI The NIMH perspective: Next steps in schizophrenia research SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material C1 NIMH, Bethesda, MD 20892 USA. RP Hyman, SE (reprint author), NIMH, 31 Ctr Dr,Room 4A52, Bethesda, MD 20892 USA. NR 16 TC 21 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JAN 1 PY 2000 VL 47 IS 1 BP 1 EP 7 DI 10.1016/S0006-3223(99)00077-3 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 275RM UT WOS:000084834000001 PM 10650443 ER PT J AU Fenton, WS Hibbeln, J Knable, M AF Fenton, WS Hibbeln, J Knable, M TI Essential fatty acids, lipid membrane abnormalities, and the diagnosis and treatment of schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Review DE schizophrenia; membrane physiology; essential fatty acids; psychopharmacology; treatment; phospholipids ID MAGNETIC-RESONANCE SPECTROSCOPY; NIACIN CHALLENGE TEST; DOCOSAHEXAENOIC ACID; PHOSPHOLIPASE A(2); ERYTHROCYTE-MEMBRANES; SIGNAL-TRANSDUCTION; TARDIVE-DYSKINESIA; SKIN FIBROBLASTS; ARACHIDONIC-ACID; SEROTONINERGIC NEUROTRANSMISSION AB Recent research suggests that deficient uptake or excessive breakdown of membrane phospholipids may be associated with schizophrenia. We review available clinical research on abnormalities inn membrane fatty acid composition and metabolism in schizophrenia, and therapeutic trials of fatty acid in this disorder. All potentially, relevant English-language articles were identified from the medical and psychiatric literature with the aid of computer searches rising key words such as lipids, phospholipids, prostaglandins and schizophrenia. All studies which include human subjects are reviewed. Empirical studies related to membrane hypotheses of schizophrenia focus on: 1) assessment of prostaglandins (PGI and their essential fatty acid (EFA) precursors in the tissues of patients with schizophrenia; 2) evaluation of the niacin flush test as a possible diagnostic marker; 3) evaluation of phospholipase enzyme activity; 4) NMR spectroscopy studies of brain phospholipid metabolism, and 5) therapeutic trials of PG precursors for the treatment of schizophrenia. The most consistent clinical findings include red blood cell fatty acid membrane abnormalities, NMR spectroscopy evidence of increased phospholipid turnover and a therapeutic effect of omega-3 fatty acid supplementation of neuroleptic treatment in some schizophrenia patients, Studies of EFA metabolism have proved fruitful for generating and testing novel etiologic hypotheses and new therapeutic agents for schizophrenia. Greater attention to factors that influence tissue EFA levels such as diet, tobacco and alcohol al-e required to reconcile inconsistent findings. Treatment studies, although promising, require independent replication. (C) 1999 Society of Biological Psychiatry. C1 Stanley Treatment Programs, Rockville, MD USA. NIAAA, Rockville, MD 20852 USA. Stanley Fdn Res Program, Bethesda, MD USA. RP Fenton, WS (reprint author), 500 W Montgomery Ave, Rockville, MD 20850 USA. NR 119 TC 195 Z9 200 U1 3 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JAN 1 PY 2000 VL 47 IS 1 BP 8 EP 21 DI 10.1016/S0006-3223(99)00092-X PG 14 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 275RM UT WOS:000084834000002 PM 10650444 ER PT J AU Petrus, MJ Williams, JF Eckhaus, MA Gress, RE Fowler, DH AF Petrus, MJ Williams, JF Eckhaus, MA Gress, RE Fowler, DH TI An immunoablative regimen of fludarabine and cyclophosphamide prevents fully MHC-mismatched murine marrow graft rejection independent of GVHD SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE graft rejection; fludarabine; cyclophosphamide; allogeneic bone marrow transplantation ID TOTAL-BODY IRRADIATION; VERSUS-HOST DISEASE; CELL TRANSPLANTATION; LEUKEMIA-CELLS; MICE; MITOXANTRONE; MALIGNANCIES; ENGRAFTMENT; INHIBITOR; APOPTOSIS AB The prevention of graft rejection in the setting of nonmyeloablative transplant approaches might be mediated by chemotherapy-induced host immunoablation and by the graft-promoting effects of graft-versus-host disease (GVI-ID). To evaluate whether host immunoablation alone might allow for alloengraftment, we developed an F1-into-parent murine marrow rejection model using host preparative regimens of lethal total body irradiation (TBI; 950 cGy), sublethal irradiation (600 cGy), or combinations of fludarabine (Flu) and cyclophosphamide (Cy). A preparative regimen selectivity index (SI) was calculated to determine whether host lymphocytes were preferentially depleted relative to myeloid cells (SI = number of host myeloid/number host T lymphoid cells remaining after preparative regimen administration). Saline-treated recipients were assigned an SI value of 1.0. Recipients of lethal TBI had reduced myeloid cells relative to T cells (SI = 0.6). In contrast, all Flu/Cy regimens preferentially depleted host T cells: recipients of Flu (100 mg/kg per day)/Cy (50 mg/kg per day) for 10 days (SI = 28.1); recipients of Flu (100 mg/kg per day)/Cy (100 mg/kg per day) for 10 days (SI = 64.1); and recipients of Flu (100 mg/kg per day)/Cy (50 mg/kg per day) far 19 or 27 days (SI = 74.6). The 10-day regimen of Flu/Cy (50 mg/kg per day) did not severely reduce host T cell numbers, nor did it prevent F1 marrow rejection (<1% chimerism, n = 14). In contrast, the 10-day regimen of Flu/Cy (100 mg/kg per day) reduced T-cell numbers below that of lethal TBI recipients and prevented F1 marrow rejection (11.4% chimerism, n = 15); donor chimerism was predominant in lymphoid cells and was stable through day 240 post-BMT. Additionally, the 19- or 27-day regimen of Flu/Cy, which most selectively depleted host T cells, also prevented F1 marrow rejection (6.3% chimerism, n = 15). These results therefore demonstrate that optimized Flu-containing, immunoablative preparative regimens can prevent fully MHC-disparate marrow rejection independent of GVHD. C1 NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. NIH, Natl Ctr Res Resources, Bethesda, MD 20892 USA. RP Fowler, DH (reprint author), NCI, Med Oncol Branch, NIH, 9000 Rockville Pike,Bldg 10,Room 12N226, Bethesda, MD 20892 USA. NR 21 TC 31 Z9 33 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PY 2000 VL 6 IS 2A BP 182 EP 189 DI 10.1016/S1083-8791(00)70041-3 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 366UD UT WOS:000090022200003 PM 10816026 ER PT J AU Welniak, LA Blazar, BR Anver, MR Wiltrout, RH Murphy, WJ AF Welniak, LA Blazar, BR Anver, MR Wiltrout, RH Murphy, WJ TI Opposing roles of interferon-gamma on CD4(+) T cell-mediated graft-versus-host disease: Effects of conditioning SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE interferon-gamma; CD4(+) T lymphocytes; graft-versus-host disease; radiation; histocompatibility antigens class II ID BONE-MARROW TRANSPLANTATION; LARGE GRANULAR LYMPHOCYTES; TUMOR-NECROSIS-FACTOR; MONOCLONAL-ANTIBODY; IMMUNE INTERFERON; MICE; SUBSETS; CD4+; IMMUNODEFICIENCY; MACROPHAGES AB Although alloreactive T cells are required for the induction of graft-versus-host disease (GVHD), other factors can influence outcome in murine models of the disease. Lethal total body irradiation (TBI) conditioning regimens followed by reconstitution with allogeneic lymphohematopoietic cells results in the generation of donor anti-host cytotoxic T lymphocyte (CTL)-mediated solid organ (gut, liver, skin) destruction. In contrast, donor anti-host CTL-mediated hematopoietic failure is the primary cause of morbidity following sublethal TBI. To determine the role of interferon (IFN)-gamma in graft-versus-host reactions against hematopoietic and solid organ targets, we used IFN-gamma knockout mice as donors in both lethal TBI and bone marrow transplantation (BMT) rescue and sublethal TBI models. In this report, we show that CD4(+) T cells from IFN-gamma knockout (KO) mice resulted in accelerated GVHD after lethal TBI/BMT using a single major histocompatibility class Il mismatch model. In marked contrast, the use of these same IFN-gamma KO CD4(+) donor cells in combination with sublethal TBI significantly ameliorated GVHD-associated mortality. In these recipients, severe anemia, bone marrow aplasia, and intestinal lesions were observed in the presence but not the absence of donor-derived IFN-gamma. Administration of anti-IFN-gamma antibodies to sublethally irradiated recipients of wild-type donor cells confirmed the role of IFN-gamma depletion in CD4(+) T cell-mediated GVHD. In conclusion, the extent of conditioning markedly affects the role of IFN-gamma in GVHD lesions mediated by CD4(+) T cells. In models using sublethal TBI, the absence of IFN-gamma is protective from GVHD, whereas in lethal TBI situations, the loss is deleterious. C1 NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, IRSP, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Lab Leukocyte Biol, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Div Basic Sci, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Pathol & Histotechnol Lab, Frederick, MD 21702 USA. Univ Minnesota, Ctr Canc, Dept Bone Marrow Transplantat, Minneapolis, MN USA. RP Murphy, WJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, IRSP, Bldg 567,Rm 210, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000]; NHLBI NIH HHS [R01 HL63452]; NIAID NIH HHS [R01 AI34495] NR 29 TC 46 Z9 46 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PY 2000 VL 6 IS 6 BP 604 EP 612 DI 10.1016/S1083-8791(00)70025-5 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 378YU UT WOS:000165614400002 PM 11128810 ER PT S AU Saavedra, JE Hrabie, JA Keefer, LK AF Saavedra, JE Hrabie, JA Keefer, LK BE Moncada, S Gustafsson, LE Wiklund, NP Higgs, EA TI Nitric oxide-releasing derivatives of biomedically important substrates SO BIOLOGY OF NITRIC OXIDE, PT 7 SE PORTLAND PRESS PROCEEDINGS LA English DT Proceedings Paper CT 6th International Meeting on Biology of Nitric Oxide CY SEP 05-08, 1999 CL STOCKHOLM, SWEDEN ID CEREBRAL VASOSPASM; REVERSAL; DONORS C1 NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, SAIC Frederick, Frederick, MD 21702 USA. RP Saavedra, JE (reprint author), NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, SAIC Frederick, Frederick, MD 21702 USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 8 TC 0 Z9 0 U1 0 U2 0 PU PORTLAND PRESS LTD PI LONDON PA 59 PORTLAND PL, LONDON W1N 3AJ, ENGLAND SN 0966-4068 BN 1-85578-142-5 J9 PORTL PR P PY 2000 VL 16 BP 9 EP 9 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA BT52N UT WOS:000173244100009 ER PT J AU Tan, FI Lolait, SJ Brownstein, MJ Saito, N MacLeod, V Baeyens, DA Mayeux, PR Jones, SM Cornett, LE AF Tan, FI Lolait, SJ Brownstein, MJ Saito, N MacLeod, V Baeyens, DA Mayeux, PR Jones, SM Cornett, LE TI Molecular cloning and functional characterization of a vasotocin receptor subtype that is expressed in the shell gland and brain of the domestic chicken SO BIOLOGY OF REPRODUCTION LA English DT Article ID ARGININE VASOTOCIN; OXYTOCIN RECEPTOR; NEUROHYPOPHYSEAL HORMONES; ADRENERGIC-RECEPTOR; MATERNAL-BEHAVIOR; GALLUS-DOMESTICUS; PLASMA-LEVELS; GENE; OVIPOSITION; RAT AB In chickens, oviposition is correlated with increased plasma levels of the neurohypophysial hormone vasotocin, and vasotocin stimulates contraction of uterine strips in vitro. A gene encoding a vasotocin receptor subtype that we have designated the VT1 receptor was cloned from the domestic chicken. The open reading frame encodes a 370-amino acid polypeptide that displays seven segments of hydrophobic amino acids, typical of guanine nucleotide-protein-coupled receptors. Other structural features of the VT1 receptor include two potential N-linked glycosylation sites in the extracellular N-terminal region, a conserved aspartic acid in transmembrane domain 2 that is found in nearly all guanine nucleotide-protein-coupled receptors, and two potential protein kinase C phosphorylation sites in the third intracellular loop and C-terminal tail. Expressed VT1 receptors in COS7 cells bind neurohypophysial hormones with the following rank order of potency: vasotocin congruent to vasopressin > oxytocin congruent to mesotocin > isotocin. In addition, the expressed VT1 receptor mediates vasotocin-induced phosphatidylinositol turnover and Ca2+ mobilization. In the chicken, expression of VT1 receptor gene transcripts is limited to the shell gland (uterus) and the brain. Thus, the VT1 receptor that we have cloned may mediate contractions of the shell gland during oviposition and activate reproductive behaviors known to be stimulated by vasotocin in lower vertebrates. C1 Univ Arkansas Med Sci, Dept Phys & Biophys, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Pharmacol Toxicol, Little Rock, AR 72205 USA. Bristol Royal Infirm & Gen Hosp, Dept Med, Dorothy Crowfoot Hodgkin Labs, Bristol BS2 8HW, Avon, England. NIMH, Genet Lab, Bethesda, MD 20892 USA. Univ Arkansas, Dept Biol, Little Rock, AR 72202 USA. Nagoya Univ, Dept Anim Physiol, Nagoya, Aichi, Japan. RP Cornett, LE (reprint author), Univ Arkansas Med Sci, Dept Phys & Biophys, Slot 750,4301 W Markham St, Little Rock, AR 72205 USA. RI Brownstein, Michael/B-8609-2009 NR 47 TC 50 Z9 50 U1 5 U2 8 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 JAN PY 2000 VL 62 IS 1 BP 8 EP 15 DI 10.1095/biolreprod62.1.8 PG 8 WC Reproductive Biology SC Reproductive Biology GA 268EN UT WOS:000084401500002 PM 10611061 ER PT J AU Nalbant, D Johnson, HL Sterneck, E Johnson, PF Khan, SA Williams, SC AF Nalbant, D Johnson, HL Sterneck, E Johnson, PF Khan, SA Williams, SC TI C/EBP beta is important for steroid production in Leydig cells. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 Texas Tech Univ, Hlth Sci Ctr, Dept Cell Biol & Biochem, Lubbock, TX 79430 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. RI Johnson, Peter/A-1940-2012 OI Johnson, Peter/0000-0002-4145-4725 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2000 VL 62 SU 1 MA 57 BP 128 EP 128 PG 1 WC Reproductive Biology SC Reproductive Biology GA 328QV UT WOS:000087862300124 ER PT J AU Flaws, JA Furth, PA Hewitt, JA Hirshfield, AN AF Flaws, JA Furth, PA Hewitt, JA Hirshfield, AN TI Effect of Bcl-2 on the primordial follicle endowment. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 Univ Maryland, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. Univ Maryland, Dept Med, Baltimore, MD 21201 USA. Univ Maryland, Dept Physiol, Baltimore, MD 21201 USA. Univ Maryland, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. Univ Maryland, Dept Anat & Neurobiol, Baltimore, MD 21201 USA. Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA. NIAID, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2000 VL 62 SU 1 MA 220 BP 193 EP 193 PG 1 WC Reproductive Biology SC Reproductive Biology GA 328QV UT WOS:000087862300286 ER PT J AU Trewin, AL Dasmahapatra, A Wimpee, BAB Hutz, RJ AF Trewin, AL Dasmahapatra, A Wimpee, BAB Hutz, RJ TI Steady-state levels of aromatic hydrocarbon receptor (AhR) and ahr-nuclear translocator (ARNT) mRNAs in the rat ovary and liver are not estrous cycle-dependent. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 Univ Wisconsin, Dept Biol Sci, Milwaukee, WI 53201 USA. Univ Wisconsin, NIEHS, Marine & Freshwater Biomed Sci Ctr, Milwaukee, WI 53201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2000 VL 62 SU 1 MA 318 BP 232 EP 232 PG 1 WC Reproductive Biology SC Reproductive Biology GA 328QV UT WOS:000087862300384 ER PT J AU Hild, SA Reel, JR Attardi, BJ Blye, RP AF Hild, SA Reel, JR Attardi, BJ Blye, RP TI Age-dependent effects of CDB 4022 on testicular function and fertility in male rats. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 BIOQUAL Inc, Rockville, MD USA. NICHD, Contracept & Reprod Hlth Branch, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2000 VL 62 SU 1 MA 588 BP 337 EP 337 PG 1 WC Reproductive Biology SC Reproductive Biology GA 328QV UT WOS:000087862300651 ER PT J AU Ben-Yosef, T Benvenisty, N AF Ben-Yosef, T Benvenisty, N TI Hereditary cancer and developmental abnormalities SO BIOLOGY OF THE NEONATE LA English DT Review DE hereditary cancer; embryogenesis; development; tumor suppressor genes ID TUMOR-SUPPRESSOR GENE; DNA MISMATCH REPAIR; EMBRYONIC CELLULAR PROLIFERATION; DOMINANTLY INHERITED CANCER; DENYS-DRASH SYNDROME; EKER RAT MODEL; ATAXIA-TELANGIECTASIA; TARGETED DISRUPTION; FANCONI-ANEMIA; DEFICIENT MICE AB About 1% of all cancers are hereditary, caused by germline mutations in specific cancer-related genes. More than 25 different hereditary cancer syndromes are known, most of them involving mutations in tumor suppressor genes. These genes, which are related to cellular proliferation, might also be involved in differentiation. Hence, the phenotype of hereditary cancer syndromes might include developmental abnormalities, in addition to cancer predisposition, The information summarized here indicates that developmental phenotypes appear in both human patients and mouse models of the various hereditary cancer syndromes. These developmental abnormalities, wh ich involve a variety of tissues a nd organs, usually lead to embryonic malformation that prevents the birth of viable homozygous offspring, but can also be detected in heterozygotes. In some of the syndromes a correlation exists between tumor types and developmentally affected tissues. Comparison of mice and human phenotypes from both the cancer and the developmental aspects indicates that many of the mouse models mimic the human syndromes. Our analysis indicates that most tumor suppressor genes participate not only in the regulation of cell proliferation, but also in differentiation and embryogenesis. Copyright (C) 2000 S. Karger AG, Basel. C1 Hebrew Univ Jerusalem, Inst Life Sci, Dept Genet, IL-91904 Jerusalem, Israel. Natl Human Genome Res Inst, Med Genet Branch, NIH, Bethesda, MD USA. RP Benvenisty, N (reprint author), Hebrew Univ Jerusalem, Inst Life Sci, Dept Genet, IL-91904 Jerusalem, Israel. NR 90 TC 4 Z9 4 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0006-3126 J9 BIOL NEONATE JI Biol. Neonate PY 2000 VL 77 IS 1 BP 1 EP 11 DI 10.1159/000014188 PG 11 WC Pediatrics SC Pediatrics GA 267PY UT WOS:000084369500001 PM 10658824 ER PT S AU Varmus, H AF Varmus, H BE Downing, GJ TI Tools and technologies to enhance clinical research: public-private sector collaborations SO BIOMARKERS AND SURROGATE ENDPOINTS: CLINICAL RESEARCH AND APPLICATIONS SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT Conference on Biomarkers and Surrogate Endpoints: Clinical Research and Applications CY APR 15-16, 1999 CL BETHESDA, MD SP NIH, US FDA C1 NIH, Bethesda, MD 20892 USA. RP Varmus, H (reprint author), NIH, Bldg 10,Room 126,MSC 4135,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-50316-1 J9 INT CONGR SER PY 2000 VL 1205 BP XI EP XIV PG 4 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA BR67J UT WOS:000167122700001 ER PT S AU Kagan, JM AF Kagan, JM BE Downing, GJ TI Biomarkers for HIV/AIDS: challenges ahead SO BIOMARKERS AND SURROGATE ENDPOINTS: CLINICAL RESEARCH AND APPLICATIONS SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT Conference on Biomarkers and Surrogate Endpoints: Clinical Research and Applications CY APR 15-16, 1999 CL BETHESDA, MD SP NIH, US FDA C1 NIAID, Div Aids, Therapeut Res Program, Drug Dev & Clin Sci Branch,NIH, Bethesda, MD 20892 USA. RP Kagan, JM (reprint author), NIAID, Div Aids, Therapeut Res Program, Drug Dev & Clin Sci Branch,NIH, 6003 Execut Blvd,Room 2C23, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-50316-1 J9 INT CONGR SER PY 2000 VL 1205 BP 18 EP 22 PG 5 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA BR67J UT WOS:000167122700006 ER PT S AU Sunderland, T AF Sunderland, T BE Downing, GJ TI Prospective search for Alzheimer's disease (AD) biomarkers SO BIOMARKERS AND SURROGATE ENDPOINTS: CLINICAL RESEARCH AND APPLICATIONS SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT Conference on Biomarkers and Surrogate Endpoints: Clinical Research and Applications CY APR 15-16, 1999 CL BETHESDA, MD SP NIH, US FDA C1 NIMH, Geriatr Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP Sunderland, T (reprint author), NIMH, Geriatr Psychiat Branch, NIH, Bldg 10,Room 3N228,MSC 1275,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-50316-1 J9 INT CONGR SER PY 2000 VL 1205 BP 37 EP 40 PG 4 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA BR67J UT WOS:000167122700010 ER PT S AU Klausner, RD AF Klausner, RD BE Downing, GJ TI The early detection cancer research network SO BIOMARKERS AND SURROGATE ENDPOINTS: CLINICAL RESEARCH AND APPLICATIONS SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT Conference on Biomarkers and Surrogate Endpoints: Clinical Research and Applications CY APR 15-16, 1999 CL BETHESDA, MD SP NIH, US FDA C1 NCI, NIH, Bethesda, MD 20892 USA. RP Klausner, RD (reprint author), NCI, NIH, Bldg 31,Room 11A-48,MSC 2590,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-50316-1 J9 INT CONGR SER PY 2000 VL 1205 BP 43 EP 46 PG 4 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA BR67J UT WOS:000167122700012 ER PT S AU Shoulson, I Brady, L AF Shoulson, I Brady, L BE Downing, GJ TI Plenary session 3: Opportunities for developing biomarkers for central nervous system disorders - Introduction SO BIOMARKERS AND SURROGATE ENDPOINTS: CLINICAL RESEARCH AND APPLICATIONS SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT Conference on Biomarkers and Surrogate Endpoints: Clinical Research and Applications CY APR 15-16, 1999 CL BETHESDA, MD SP NIH, US FDA C1 NIMH, Preclin & Clin Therapeut Res Branch, NIH, Bethesda, MD 20892 USA. RP Shoulson, I (reprint author), NIMH, Preclin & Clin Therapeut Res Branch, NIH, 6001 Execut Blvd,Room 7185, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-50316-1 J9 INT CONGR SER JI Int. Congr. Ser. PY 2000 VL 1205 BP 47 EP 47 PG 1 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA BR67J UT WOS:000167122700013 ER PT S AU Fauci, AS AF Fauci, AS BE Downing, GJ TI Plenary session 4: Immune and inflammatory markers - Introduction and overview SO BIOMARKERS AND SURROGATE ENDPOINTS: CLINICAL RESEARCH AND APPLICATIONS SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT Conference on Biomarkers and Surrogate Endpoints: Clinical Research and Applications CY APR 15-16, 1999 CL BETHESDA, MD SP NIH, US FDA ID IMMUNODEFICIENCY VIRUS TYPE-1; HIV-1 INFECTION; LYMPHOCYTES; PLASMA C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Fauci, AS (reprint author), NIAID, NIH, Bldg 31,Room 7A-03,MSC 2520,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-50316-1 J9 INT CONGR SER PY 2000 VL 1205 BP 65 EP 68 PG 4 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA BR67J UT WOS:000167122700020 ER PT S AU Lipman, DJ AF Lipman, DJ BE Downing, GJ TI From ambiguities to insights SO BIOMARKERS AND SURROGATE ENDPOINTS: CLINICAL RESEARCH AND APPLICATIONS SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT Conference on Biomarkers and Surrogate Endpoints: Clinical Research and Applications CY APR 15-16, 1999 CL BETHESDA, MD SP NIH, US FDA C1 Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Lipman, DJ (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-50316-1 J9 INT CONGR SER PY 2000 VL 1205 BP 85 EP 88 PG 4 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA BR67J UT WOS:000167122700025 ER PT S AU London, ED Vocci, F AF London, ED Vocci, F BE Downing, GJ TI Neurosciences II: Biomarkers for alcohol and drug abuse SO BIOMARKERS AND SURROGATE ENDPOINTS: CLINICAL RESEARCH AND APPLICATIONS SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT Conference on Biomarkers and Surrogate Endpoints: Clinical Research and Applications CY APR 15-16, 1999 CL BETHESDA, MD SP NIH, US FDA ID CARBOHYDRATE-DEFICIENT TRANSFERRIN; COGNITIVE PERFORMANCE; NALTREXONE; SCOPOLAMINE; DRINKING; COCAINE; MARKERS; CONSUMPTION; ACTIVATION; INHIBITION C1 Natl Inst Drug Abuse, Lexington, KY 40583 USA. RP London, ED (reprint author), Natl Inst Drug Abuse, Lexington, KY 40583 USA. NR 41 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-50316-1 J9 INT CONGR SER PY 2000 VL 1205 BP 119 EP 131 PG 13 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA BR67J UT WOS:000167122700030 ER PT S AU Fischbach, GD Slavkin, H Kitt, CA AF Fischbach, GD Slavkin, H Kitt, CA BE Downing, GJ TI Neurosciences III: Biomarkers for pain assessment SO BIOMARKERS AND SURROGATE ENDPOINTS: CLINICAL RESEARCH AND APPLICATIONS SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT Conference on Biomarkers and Surrogate Endpoints: Clinical Research and Applications CY APR 15-16, 1999 CL BETHESDA, MD SP NIH, US FDA ID POSITRON EMISSION TOMOGRAPHY; NEUROPATHIC PAIN; POSTHERPETIC NEURALGIA; INFLAMMATORY PAIN; NERVE INJURY; HUMAN BRAIN; RAT; NOCICEPTORS; RECEPTOR; CHANNEL C1 Natl Inst Neurol Dis & Stroke, Bethesda, MD 20892 USA. RP Kitt, CA (reprint author), Natl Inst Neurol Dis & Stroke, Bethesda, MD 20892 USA. NR 28 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-50316-1 J9 INT CONGR SER PY 2000 VL 1205 BP 133 EP 140 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA BR67J UT WOS:000167122700031 ER PT S AU Piscitelli, SC Peck, CC AF Piscitelli, SC Peck, CC BE Downing, GJ TI Pharmacokinetic and pharmacodynamic methods in biomarker development and application SO BIOMARKERS AND SURROGATE ENDPOINTS: CLINICAL RESEARCH AND APPLICATIONS SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT Conference on Biomarkers and Surrogate Endpoints: Clinical Research and Applications CY APR 15-16, 1999 CL BETHESDA, MD SP NIH, US FDA ID BRAIN MAO-B; DOCETAXEL; THERAPY C1 NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Piscitelli, SC (reprint author), NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-50316-1 J9 INT CONGR SER PY 2000 VL 1205 BP 157 EP 164 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA BR67J UT WOS:000167122700033 ER PT S AU Sopko, G Friedman, L AF Sopko, G Friedman, L BE Downing, GJ TI Biomarkers in cardiovascular diseases SO BIOMARKERS AND SURROGATE ENDPOINTS: CLINICAL RESEARCH AND APPLICATIONS SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT Conference on Biomarkers and Surrogate Endpoints: Clinical Research and Applications CY APR 15-16, 1999 CL BETHESDA, MD SP NIH, US FDA C1 NHLBI, Bethesda, MD 20892 USA. RP Sopko, G (reprint author), NHLBI, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-50316-1 J9 INT CONGR SER PY 2000 VL 1205 BP 177 EP 178 PG 2 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA BR67J UT WOS:000167122700035 ER PT J AU Mowery, KA Schoenfisch, MH Saavedra, JE Keefer, LK Meyerhoff, ME AF Mowery, KA Schoenfisch, MH Saavedra, JE Keefer, LK Meyerhoff, ME TI Preparation and characterization of hydrophobic polymeric films that are thromboresistant via nitric oxide release SO BIOMATERIALS LA English DT Article DE nitric oxide; polymer materials; blood compatibility; biomaterial surfaces ID PERFORMANCE LIQUID-CHROMATOGRAPHY; PLATELET-AGGREGATION; IN-VIVO; 9-FLUORENYLMETHYL CHLOROFORMATE; PRECOLUMN DERIVATIZATION; VASCULAR ENDOTHELIUM; MEMBRANE-ELECTRODE; HEPARIN; SENSORS; BIOCOMPATIBILITY AB The preparation of hydrophobic polymer films (polyurethane and poly(vinyl chloride)) containing nitric oxide (NO)-releasing diazeniumdiolate functions is reported as a basis for improving the thromboresistivity of such polymeric materials for biomedical applications. Several different approaches for preparing NO-releasing polymer films are presented, including: (1) dispersion of diazeniumdiolate molecules within the polymer matrix; (2) covalent attachment of the diazeniumdiolate to the polymer backbone; and (3) ion-pairing of a diazeniumdiolated heparin species to form an organic soluble complex that can be blended into the polymer. Each approach is characterized in terms of NO release rates and in vitro biocompatibility. Results presented indicate that the polymer films prepared by each approach release NO for variable periods of time (10-72 h), although they differ in the mechanism, location and amount of NO released. In vitro platelet adhesion studies demonstrate that the localized NO release may prove to be an effective strategy for improving blood compatibility of polymer materials for a wide range of medical devices. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. RP Meyerhoff, ME (reprint author), Univ Michigan, Dept Chem, 930 N Univ Ave, Ann Arbor, MI 48109 USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU NCI NIH HHS [N01-CO-56000]; NIGMS NIH HHS [GM 56991] NR 58 TC 140 Z9 144 U1 1 U2 31 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD JAN PY 2000 VL 21 IS 1 BP 9 EP 21 DI 10.1016/S0142-9612(99)00127-1 PG 13 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 266FW UT WOS:000084290800003 PM 10619674 ER PT S AU Zuzak, KJ Schaeberle, MD Lewis, EN Levin, IW AF Zuzak, KJ Schaeberle, MD Lewis, EN Levin, IW BE MahadevanJansen, A Puppels, GJ TI Visible spectroscopic imaging studies of normal and ischemic dermal tissue SO BIOMEDICAL SPECTROSCOPY: VIBRATIONAL SPECTROSCOPY AND OTHER NOVEL TECHNIQUES SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Biomedical Spectroscopy - Vibrational Spectroscopy and Other Novel Techniques CY JAN 26-27, 2000 CL SAN JOSE, CA SP SPIE, Int Biomed Opt Soc DE hyperspectral imaging; liquid crystal tunable filter (LCTF); multivariate least squares analysis; oxyhemoglobin; ischemia; medical diagnostic ID MICROSCOPY; MICROCIRCULATION; OXYGENATION; CYTOCHROMES; MYOGLOBIN; HEART; STATE AB We describe a non-invasive, in vivo hyperspectral imaging method for visualizing the spatial distribution of dermal tissue oxygenation. Real-time images of the dermis are acquired both at multiple, contiguous wavelengths and at relatively narrow spectral bandwidths to generate a data cube consisting of one spectral and two spatial dimensions. For data collection, the sample area is illuminated by radiation, which is delivered by liquid light guides from a quartz tungsten halogen (QTH) source. Reflected light from the sample is first passed through a liquid crystal tunable filter (LCTF) and then imaged onto a silicon charged coupled device (CCD) detector. The subsequently digitized data are presented in terms of spectral images reflecting multivariate least squares analyses based upon linear combinations of oxy- and deoxyhemoglobin reference spectra. The generated gray scale images directly represent the varying spatial distributions of dermal tissue oxygenation. As an example, imaging data are obtained from normal tissue and induced ischemic tissue for which both the venous and arterial blood flow was artificially occluded. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Levin, IW (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. EM iwl@helix.nih.gov NR 21 TC 12 Z9 12 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3534-1 J9 PROC SPIE PY 2000 VL 3918 BP 17 EP 26 DI 10.1117/12.384958 PG 10 WC Medical Laboratory Technology; Spectroscopy SC Medical Laboratory Technology; Spectroscopy GA BQ31P UT WOS:000087915700003 ER PT S AU Chernomordik, V Hattery, DW Gandjbakhche, A Gannot, I Zaccanti, G AF Chernomordik, V Hattery, DW Gandjbakhche, A Gannot, I Zaccanti, G GP OSA OSA TI Analytical calculation of the mean time spent by photons inside an inclusion embedded in a highly scattering medium SO BIOMEDICAL TOPICAL MEETINGS, TECHNICAL DIGEST SE OSA TRENDS IN OPTICS AND PHOTONICS LA English DT Proceedings Paper CT Biomedical Topical Meeting CY APR 02-05, 2000 CL MIAMI BEACH, FL AB A random walk model is used to describe the mean flight time spent by photons inside an inclusion in a turbid medium. Good agreement has been found with Monte Carlo and experimental data. (C) 1999 Optical Society of America. C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP Chernomordik, V (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU OPTICAL SOC AMERICA PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-5695 BN 1-55752-632-X J9 OSA TRENDS OPT PHOTO PY 2000 VL 38 BP 75 EP 77 PG 3 WC Optics; Spectroscopy SC Optics; Spectroscopy GA BU51D UT WOS:000176203200021 ER PT S AU Hattery, DW Chernomordik, V Gandjbakhche, A Gannot, I Loew, M AF Hattery, DW Chernomordik, V Gandjbakhche, A Gannot, I Loew, M GP OSA OSA TI Quantifying fluorescent lifetime of deeply embedded sources in turbid media SO BIOMEDICAL TOPICAL MEETINGS, TECHNICAL DIGEST SE OSA TRENDS IN OPTICS AND PHOTONICS LA English DT Proceedings Paper CT Biomedical Topical Meeting CY APR 02-05, 2000 CL MIAMI BEACH, FL ID TISSUE AB We have developed and tested with numerical simulations a closed-form solution based on random walk theory for quantifying the lifetime of typical near infrared fluorophores embedded 5mm or greater in turbid media. (C) 1999 Optical Society of America. C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP Hattery, DW (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU OPTICAL SOC AMERICA PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-5695 BN 1-55752-632-X J9 OSA TRENDS OPT PHOTO PY 2000 VL 38 BP 281 EP 283 PG 3 WC Optics; Spectroscopy SC Optics; Spectroscopy GA BU51D UT WOS:000176203200084 ER PT S AU Kidder, LH Haka, AS Levin, IW Lewis, EN AF Kidder, LH Haka, AS Levin, IW Lewis, EN GP OSA OSA TI Advances in FT-IR spectroscopic imaging microscopy of biological tissue using infrared focal-plane array detectors SO BIOMEDICAL TOPICAL MEETINGS, TECHNICAL DIGEST SE OSA TRENDS IN OPTICS AND PHOTONICS LA English DT Proceedings Paper CT Biomedical Topical Meeting CY APR 02-05, 2000 CL MIAMI BEACH, FL ID TEMPOROMANDIBULAR-JOINT; BRAIN-TISSUE; SILICONE; MICROSPECTROSCOPY AB FF-IR spectroscopic imaging data can quantify the spatial variations in individual chemical or biochemical components. These changes can be correlated with diseased states in tissue biopsies. (C) 1999 Optical Society of America. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Kidder, LH (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU OPTICAL SOC AMERICA PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-5695 BN 1-55752-632-X J9 OSA TRENDS OPT PHOTO PY 2000 VL 38 BP 303 EP 305 PG 3 WC Optics; Spectroscopy SC Optics; Spectroscopy GA BU51D UT WOS:000176203200090 ER PT J AU Carroll, S Herrera, AH Horowits, R AF Carroll, S Herrera, AH Horowits, R TI Localization of N-RAP and of GFP-tagged N-RAP domains in cultured chick cardiomyocytes. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAMS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 107PLAT BP 19A EP 19A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779300109 ER PT J AU Ghosh, M Wang, Y Obungu, VH Beattie, DS AF Ghosh, M Wang, Y Obungu, VH Beattie, DS TI Mutations in the tether region of the iron-sulfur protein affect the activity of the cytochrome BC1 complex of yeast SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 W Virginia Univ, Morgantown, WV 26506 USA. NIH, Bethesda, MD 20892 USA. RI Ghosh, Mousumi/D-3180-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 147Plat BP 25A EP 25A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779300147 ER PT J AU Harvey, JJ Lee, PS Fucs, SF Knutson, JR Han, MK AF Harvey, JJ Lee, PS Fucs, SF Knutson, JR Han, MK TI Domain specific quenching of tryptophan fluorescence upon binding of mutant HIV-1 integrase to a 35 base pair synthetic substrate SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Washington, DC 20057 USA. Univ Wisconsin, Madison, WI 53706 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 171Pos BP 30A EP 30A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779300172 ER PT J AU Haliloglu, T Bahar, I Jernigan, RL AF Haliloglu, T Bahar, I Jernigan, RL TI Collective dynamics of class I MHC/peptide complexes and binding to T cell receptors SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Bogazici Univ, Ctr Polymer Res, Istanbul, Turkey. TUBITAK, Adv Polym Mat Res Ctr, Istanbul, Turkey. NCI, MSC 5677, NIH, Bethesda, MD 20892 USA. RI Jernigan, Robert/A-5421-2012 NR 3 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 196Pos BP 34A EP 34A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779300194 ER PT J AU Srinivasan, M Uehara, C Smith-Gill, S Willson, R AF Srinivasan, M Uehara, C Smith-Gill, S Willson, R TI Association energetics of cross-reactive specific antibodies SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Univ Houston, Houston, TX 77004 USA. NCI, Basic Res Lab, DBS, NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 221Pos BP 39A EP 39A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779300221 ER PT J AU Leikina, E LeDuc, DL Macosko, JC Epand, RF Epand, RM Shin, YK Chernomordik, LV AF Leikina, E LeDuc, DL Macosko, JC Epand, RF Epand, RM Shin, YK Chernomordik, LV TI FHA2: A minimal hemifusion machinery in hemagglutinin-mediated fusion? SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHD, LCMB, Bethesda, MD USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. McMaster Univ, Hamilton, ON, Canada. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 338Pos BP 58A EP 58A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779300334 ER PT J AU Markovic, I Leikina, E Chernomordik, LV AF Markovic, I Leikina, E Chernomordik, LV TI Cooperative activation of influenza virus hemagglutinin during viral entry SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHD, LCMB, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 340Pos BP 59A EP 59A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779300338 ER PT J AU Viard, M Ablan, S Lin, HMJ Hug, P Puri, A Blumenthal, R AF Viard, M Ablan, S Lin, HMJ Hug, P Puri, A Blumenthal, R TI Are "rafts" involved in HIV-1 entry? SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 344Pos BP 59A EP 59A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779300340 ER PT J AU Zhukovsky, M Bailey, A Leikina, E Chernomordik, L AF Zhukovsky, M Bailey, A Leikina, E Chernomordik, L TI The effects of liposome composition on cell-liposome fusion and protein inactivation in membrane fusion mediated by influenza hemagglutinin SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHD, LCMB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 342POS BP 59A EP 59A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779300339 ER PT J AU Niu, SL Mitchell, DC Litman, BJ AF Niu, SL Mitchell, DC Litman, BJ TI Dependence of G-protein binding by metarhodopsin II on bilayer lipid composition SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Rockville, MD 20852 USA. NIAAA, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 389Pos BP 67A EP 67A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779300386 ER PT J AU Spivak, CE Hayeslip, S AF Spivak, CE Hayeslip, S TI A fluorescent antagonist of the mu opioid receptor that labels internal receptors of living, stably transfected CHO cells. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIDA, Baltimore, MD 21224 USA. Univ Maryland, College Pk, MD 20742 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 388Pos BP 67A EP 67A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779300388 ER PT J AU Zhou, YY Zhang, SJ Lakatta, EG Xiao, RP AF Zhou, YY Zhang, SJ Lakatta, EG Xiao, RP TI Interaction between beta(2)-adrenergic receptor and G(i)-coupled receptor signaling in canine cardiomyocytes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 396Pos BP 68A EP 68A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779300395 ER PT J AU Haak, LL Smaili, SS Cheng, HP Russell, JT AF Haak, LL Smaili, SS Cheng, HP Russell, JT TI Mitochondrial uncouplers slow wave propagation in OP cells SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHD, NIH, LCMN, Bethesda, MD 20892 USA. NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 410Pos BP 70A EP 70A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779300408 ER PT J AU Territo, PR French, SA Balaban, RS AF Territo, PR French, SA Balaban, RS TI Rapid calcium activation of oxidative phosphorylation: The kinetics of mVO(2), NADH and light scattering in cardiac mitochondria. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 471Pos BP 81A EP 81A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779300468 ER PT J AU Tso, SC Xia, D Zhang, L Quinn, BN Deisenhofer, J Yu, L Yu, CA AF Tso, SC Xia, D Zhang, L Quinn, BN Deisenhofer, J Yu, L Yu, CA TI The location of the extramembrane domain of the iron-sulfur protein is the cytochrome bc(1) complex is redox state dependent. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. Oklahoma State Univ, Stillwater, OK 74078 USA. Howard Hughes Med Inst, Coconut Grove, FL 33133 USA. Univ Texas, SW Med Ctr, Dallas, TX 75235 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 484Pos BP 82A EP 82A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779300476 ER PT J AU Li-Smerin, Y Hackos, DH Swartz, KJ AF Li-Smerin, Y Hackos, DH Swartz, KJ TI Helical structure and packing orientation of the four transmembrane segments in the voltage-sensing domain of a K+ channel SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 574Pos BP 97A EP 97A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779300566 ER PT J AU Vinogradova, T Zhou, YY Cheng, H Yu, K Kuschel, BM Xiao, RP AF Vinogradova, T Zhou, YY Cheng, H Yu, K Kuschel, BM Xiao, RP TI Effects of Ca2+/calmodulin dependent protein kinase II on pacemaker activity in the sino-atrial node cells. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 582Pos BP 99A EP 99A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779300576 ER PT J AU Chen-Izu, Y Sham, JSK Lakatta, EG AF Chen-Izu, Y Sham, JSK Lakatta, EG TI Multiple conductance of L-type Ca2+ channels in rat ventricular myocyte SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Johns Hopkins Med Inst, Div Pulm Med, Baltimore, MD 21224 USA. NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 589Pos BP 100A EP 100A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779300583 ER PT J AU Minton, AP AF Minton, AP TI Effect of a concentrated "inert" macromolecular cosolute on the stability of a globular protein with respect to denaturation by heat and by chaotropes: A statistical-thermodynamical model SO BIOPHYSICAL JOURNAL LA English DT Article ID SELF-AVOIDING WALKS; EXCLUDED-VOLUME; ALPHA-LACTALBUMIN; DNA CONDENSATION; RIBONUCLEASE-A; MOLTEN GLOBULE; PRESSURE; CONSEQUENCES; EQUILIBRIUM; TEMPERATURE AB An equilibrium statistical-thermodynamic model for the effect of volume exclusion arising from high concentrations of stable macromolecules upon the stability of a trace globular protein with respect to denaturation by heat and by chaotropes is presented, The stable cosolute and the native form of the trace protein are modeled by effective hard spherical particles. The denatured state of the trace protein is represented as an ensemble of substates modeled by random coils having the same contour length but different rms end-to-end distances (i.e., different degrees of compaction). The excess or nonideal chemical potential of the native state and of each denatured substate is calculated as a function of the concentration of stable cosolute, leading to an estimate of the relative abundance of each state and substate, and the ensemble average free energy of the transition between native and denatured protein. The effect of the addition of stable cosolute upon the temperature of half-denaturation and upon the concentration of chaotrope required to half-denature the tracer at constant temperature is then estimated. At high cosolute concentration (>100 g/l) these effects are predicted to be large and readily measurable experimentally, provided that an experimental system exhibiting a fully reversible unfolding equilibrium at high total macromolecular concentration can be developed. C1 NIDDKD, Sect Phys Biochem, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Minton, AP (reprint author), NIDDKD, Sect Phys Biochem, Lab Biochem & Genet, NIH, Bldg 8,Rm 226, Bethesda, MD 20892 USA. NR 34 TC 149 Z9 149 U1 1 U2 15 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 BP 101 EP 109 PN 1 PG 9 WC Biophysics SC Biophysics GA 274NX UT WOS:000084772900010 PM 10620277 ER PT J AU Bradrick, TD West, FW Howell, EE AF Bradrick, TD West, FW Howell, EE TI Time-resolved fluorescence of wt R67 dihydrofolate reductase and its two single-tryptophan mutants. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NHLBI, NIH, Opt Spect Sect, Bethesda, MD 20892 USA. Univ Tennessee, Dept BCMB, Knoxville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 744Pos BP 126A EP 126A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779300737 ER PT J AU Shen, XH Knutson, J AF Shen, XH Knutson, J TI Femtosecond fluorescence spectroscopy or tryptophan measured by an upconversion technique SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 741Pos BP 126A EP 126A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779300733 ER PT J AU Tcherkasskaya, O Knutson, JR AF Tcherkasskaya, O Knutson, JR TI Decay-associated spectra and mutagenesis resolve tryptophan fluorescence in apomyoglobin. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI, NIH, LECB, Bethesda, MD 20892 USA. NHLBI, NIH, OSS, LBC, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 742Pos BP 126A EP 126A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779300736 ER PT J AU Watrob, HM Howard, KJ Le Grice, SFJ Barkley, MD AF Watrob, HM Howard, KJ Le Grice, SFJ Barkley, MD TI Probing HIV-1 reverse transcriptase using fluorescence spectroscopy SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Case Western Reserve Univ, Cleveland, OH 44106 USA. NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 743Pos BP 126A EP 126A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779300734 ER PT J AU Winterhalter, M Van Gelder, P Dumas, F Bezrukov, S AF Winterhalter, M Van Gelder, P Dumas, F Bezrukov, S TI Structure-function relationship of maltoporin from Escherichia coli SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 CNRS, IPBS, F-31077 Toulouse, France. Univ Basel, Biozentrum, Basel, Switzerland. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 808Plat BP 137A EP 137A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779300799 ER PT J AU Lippincott-Schwartz, J Presley, J Phair, R Hirschberg, K AF Lippincott-Schwartz, J Presley, J Phair, R Hirschberg, K TI Secretory protein trafficking in single live cells SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHD, Biol & Metab Branch, NIH, Bethesda, MD USA. Bioinformat Serv, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 812Symp BP 138A EP 138A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779300804 ER PT J AU Baker, BM Ding, YH Biddison, WE Wiley, DC AF Baker, BM Ding, YH Biddison, WE Wiley, DC TI Cavities and water in T-cell receptor specificity SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Cambridge, MA 02138 USA. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 854Plat BP 145A EP 145A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779300845 ER PT J AU Eisenberg, H Ghirlando, R Ebel, C AF Eisenberg, H Ghirlando, R Ebel, C TI Probing protein/sugar interactions. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Weizmann Inst Sci, IL-76100 Rehovot, Israel. NIH, Bethesda, MD 20892 USA. Inst Biol Struct, Grenoble, France. RI Ghirlando, Rodolfo/A-8880-2009 NR 0 TC 0 Z9 0 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 855Plat BP 145A EP 145A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779300848 ER PT J AU Kurokawa, J Soldatov, NM Adachi-Akahane, S Cleemann, L Morad, M AF Kurokawa, J Soldatov, NM Adachi-Akahane, S Cleemann, L Morad, M TI Regulation of Ca2+ sparks by carboxy-terminal tail of cardiac Ca2+ channel. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Georgetown Univ, Washington, DC 20057 USA. NIH, Bethesda, MD 20892 USA. Univ Tokyo, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 874Plat BP 149A EP 149A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779300867 ER PT J AU Rostovtseva, TK Liu, TT Colombini, M Parsegian, VA Bezrukov, SM AF Rostovtseva, TK Liu, TT Colombini, M Parsegian, VA Bezrukov, SM TI Allosterism without subunits: "Accelerated" titration of a monomeric ion channel. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Univ Maryland, College Pk, MD 20742 USA. RI Colombini, Marco/A-1540-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 889Pos BP 151A EP 151A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779300883 ER PT J AU Chik, JK Mizrahi, S Rau, DC Parsegian, A AF Chik, JK Mizrahi, S Rau, DC Parsegian, A TI Osmotic stress and Hofmeister solutes in hydroxypropylcellulose self-assembly SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 913Pos BP 155A EP 155A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779300907 ER PT J AU Parsegian, A Bezrukov, SM Rostovtseva, TK Rau, DC Sidorova, NY AF Parsegian, A Bezrukov, SM Rostovtseva, TK Rau, DC Sidorova, NY TI Hydration or dehydration, which is the more sensitive to osmotic stress? SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 914Pos BP 155A EP 155A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779300905 ER PT J AU Tekle, E Chock, BP AF Tekle, E Chock, BP TI Asymmetric distribution of electric-field induced membrane pores in DOPC vesicles. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1047Pos BP 178A EP 178A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301037 ER PT J AU Sukhareva, M Smith, S Barker, J AF Sukhareva, M Smith, S Barker, J TI Ryanodine receptors are clustered in neurites of cultured embryonic rat spinal and cortical neurons. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NINDS, NIH, Bethesda, MD 20817 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1102Pos BP 187A EP 187A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301094 ER PT J AU Durell, SR Bakker, EP Guy, HR AF Durell, SR Bakker, EP Guy, HR TI Does the KdpA subunit from the high affinity K+-translocating P-type KDP-ATPase have a structure similar to that of K+ channels? SO BIOPHYSICAL JOURNAL LA English DT Article ID POTASSIUM CHANNEL; TRANSPORT ATPASES; HKT1 AB Evidence is presented that the transmembrane KdpA subunit of the high affinity K+-translocating P-type Kdp-ATPase is evolutionarily derived from the superfamily of 2TM-type K+ channels in bacteria. This extends a previous study relating the K+ channels to the KtrAB, Trk, Trk1,2, and HKT1 K+ symporter superfamily of both prokaryotes and eukaryotes, Although the channels are formed by four single-MPM motif subunits, the transmembrane KdpA subunit and the transmembrane subunit of the symporter proteins are postulated to have four corresponding MPM motifs within a single sequence. Analysis of 17 KdpA sequences reveals a pattern of residue conservation similar to that of the symporters and channels, and consistent with the crystal structure of the KcsA K+ channel. In addition, the most highly conserved residues between the families, specifically the central glycines of the P2 segments, are those previously identified as crucial for the property of K+-selectivity that is common to each protein. This hypothesis is consistent with an experimental study of mutations that alter K+ binding affinity of the Kdp transporter. Although most of the results of a previous study of the transmembrane topology of KdpA are consistent with the 4-MPM model, the one deviation can be explained by a plausible change in the structure due to the experimental method. C1 NCI, Lab Expt & Computat Biol, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Univ Osnabruck, Abt Mikrobiol, D-49069 Osnabruck, Germany. RP Guy, HR (reprint author), NCI, Lab Expt & Computat Biol, Div Basic Sci, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 20 TC 52 Z9 53 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 BP 188 EP 199 PN 1 PG 12 WC Biophysics SC Biophysics GA 274NX UT WOS:000084772900018 PM 10620285 ER PT J AU Tomic, M Koshimizu, T Yuan, D Andric, SA Zivadinovic, D Stojilkovic, SS AF Tomic, M Koshimizu, T Yuan, D Andric, SA Zivadinovic, D Stojilkovic, SS TI Characterization of a plasma membrane calcium oscillator in rat pituitary somatotrophs SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1105Pos BP 188A EP 188A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301096 ER PT J AU Lockwich, TP Liu, XB Singh, B Ambudkar, I AF Lockwich, TP Liu, XB Singh, B Ambudkar, I TI Interaction of hTrp1 with lipid-raft domains in human submandibular gland cells: Implications in store-operated Ca2+ entry. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1134Pos BP 193A EP 193A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301128 ER PT J AU Basanez, G Zhang, J Chau, BN Frolov, VA Maksaev, GI Galanis, JD Hardwick, JM Zimmerberg, J AF Basanez, G Zhang, J Chau, BN Frolov, VA Maksaev, GI Galanis, JD Hardwick, JM Zimmerberg, J TI Caspase cleavage promotes Bcl-x(L)-dependent pore formation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHD, NIH, LCMB, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. RAS, Frumkin Inst Electrochem, Moscow, Russia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1146Pos BP 195A EP 195A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301140 ER PT J AU Gaal, M Kahr, H Pammer, P Gamsjager, R Forstner, G Kepplinger, KJF Groschner, K Abernethy, DR Soldatov, NM Romanin, C AF Gaal, M Kahr, H Pammer, P Gamsjager, R Forstner, G Kepplinger, KJF Groschner, K Abernethy, DR Soldatov, NM Romanin, C TI Interaction of calmodulin with the alpha 1C subunit in the Ca2+-dependent inactivation process. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Univ Linz, Inst Biophys, A-4040 Linz, Austria. Graz Univ, Inst Pharmacol & Toxicol, A-8010 Graz, Austria. Inst Aging, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1186Pos BP 201A EP 201A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301175 ER PT J AU Kepplinger, KJF Kahr, H Forstner, G Sonnleitner, M Schindler, H Schmidt, T Groschner, K Soldatov, NM Romanin, C AF Kepplinger, KJF Kahr, H Forstner, G Sonnleitner, M Schindler, H Schmidt, T Groschner, K Soldatov, NM Romanin, C TI A sequence in the carboxyl terminus of the alpha(1C) subunit critical for targeting, permeation, kinetics and run-down of class C-type Ca2+ channels. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Univ Linz, Inst Biophys, Linz, Austria. Graz Univ, Inst Pharmacol & Toxicol, A-8010 Graz, Austria. Inst Aging, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1187Pos BP 201A EP 201A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301178 ER PT J AU Stanley, EF Zheng, X Mirotznik, RR AF Stanley, EF Zheng, X Mirotznik, RR TI Inhibition of presynaptic calcium channels by pertussis toxin insensitive G-protein SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1265Pos BP 215A EP 215A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301257 ER PT J AU Bertram, R Sherman, A Kinard, TA Satin, LS AF Bertram, R Sherman, A Kinard, TA Satin, LS TI The phantom bursting model for pancreatic beta-cells SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Florida State Univ, Inst Mol Biophys, Tallahassee, FL 32306 USA. NIDDK, Math Res Branch, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1281Pos BP 218A EP 218A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301271 ER PT J AU Zhang, SJ Zhou, YY Xiao, RP Lakatta, EG AF Zhang, SJ Zhou, YY Xiao, RP Lakatta, EG TI Age-associated reduction in recovery of the equilibrium state of myocyte length during reduced interstimulus intervals at higher stimulation rates SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. NR 0 TC 3 Z9 3 U1 1 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1340Pos BP 227A EP 227A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301325 ER PT J AU Gu, J Xu, SG Yu, LPC AF Gu, J Xu, SG Yu, LPC TI Modeling the weakly attached cross-bridges in the A(.)M(.)ATP state SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1367Pos BP 231A EP 231A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301352 ER PT J AU Chen, Y Yan, B Chalovich, JM Brenner, B AF Chen, Y Yan, B Chalovich, JM Brenner, B TI A cooperative 2-state model for acto-myosin interactions (Hill et al. PNAS 77, 3186 (1980)) does predict an effect of Ca++ on the kinetics or binding of myosin S1 to regulated actin filaments SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIDDK, Math Res Branch, NIH, Bethesda, MD 20892 USA. E Carolina Univ, Sch Med, Greenville, NC USA. Hannover Med Sch, D-3000 Hannover, Germany. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1396Pos BP 236A EP 236A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301381 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 BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAMS, Natl Inst Hlth, Bethesda, MD 20892 USA. Univ Missouri, Div Cell Biol & Biophys, Kansas City, MO 64110 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1401POS BP 237A EP 237A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301384 ER PT J AU Xu, SG Gu, J Yu, LPC Lucaveche, C Reedy, M Gutierrez, G Wang, K AF Xu, SG Gu, J Yu, LPC Lucaveche, C Reedy, M Gutierrez, G Wang, K TI Structure of the wide Z band of the sonic muscle of type1 male midshipman fish SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1418Pos BP 240A EP 240A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301404 ER PT J AU Veigel, C Wang, F Bartoo, ML Hammer, J Sellers, JR Molloy, JE AF Veigel, C Wang, F Bartoo, ML Hammer, J Sellers, JR Molloy, JE TI Is one myosin V molecule sufficient for vesicular transport? SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Univ York, York YO10 5DD, N Yorkshire, England. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1430Pos BP 242A EP 242A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301415 ER PT J AU Trok, B Xu, S Yu, LC Barnett, VA AF Trok, B Xu, S Yu, LC Barnett, VA TI Temperature dependence of the conformation of myosin.ADP.V-1 permeablized rabbit psoas muscle fibers. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Univ Minnesota, Dept Physiol, Minneapolis, MN 55455 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1457Pos BP 246A EP 246A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301440 ER PT J AU Lewis, MK Adhikari, B Hsu, KB Chen, V Bass, AH Wang, K AF Lewis, MK Adhikari, B Hsu, KB Chen, V Bass, AH Wang, K TI Investigation of fish sonic muscle structure using dual-disk confocal fluorescence microscopy and 3D reconstruction SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Cornell Univ, Ithaca, NY 14853 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1471Pos BP 249A EP 249A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301456 ER PT J AU Hansen, PL Podgornik, R Parsegian, A AF Hansen, PL Podgornik, R Parsegian, A TI Dna as hollow charged cylinder SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1490Pos BP 252A EP 252A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301471 ER PT J AU Yan, B Chen, YD Miura, R AF Yan, B Chen, YD Miura, R TI Asymmetry and direction reversal in fluctuation-induced biased motion of particles in a periodic potential. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Univ British Columbia, Dept Math, Vancouver, BC, Canada. NIDDK, Math Res Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1497Pos BP 253A EP 253A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301480 ER PT J AU Demehin, AA Abugo, OO Kumar, RJ Rifkind, JM AF Demehin, AA Abugo, OO Kumar, RJ Rifkind, JM TI Quenching of eosin-5-maleimide by hemoglobin binding to band 3 SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Cent Leather Res Inst, Chennai, India. Univ Maryland, Sch Med, Ctr Fluorescence Spect, Baltimore, MD 21201 USA. NIA, Gerontol Res Ctr, Mol Dynam Sec, Lab Cell & Mol Biol, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1522Pos BP 257A EP 257A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301502 ER PT J AU Seheuss, V Lao, G Gerwin, CM Su, Q Rettig, J Sheng, ZH AF Seheuss, V Lao, G Gerwin, CM Su, Q Rettig, J Sheng, ZH TI Syntaphilin: A synaptic protein that controls assembly of the synaptic docking/fusion machinery SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Max Planck Inst, D-37077 Gottingen, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1534Pos BP 259A EP 259A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301516 ER PT J AU Hummer, G Garcia, AE Garde, S AF Hummer, G Garcia, AE Garde, S TI Molecular dynamics studies of helix formation in explicit solvent SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Rensselaer Polytech Inst, Troy, NY 12180 USA. Univ Calif Los Alamos Natl Lab, Los Alamos, NM 87545 USA. NIH, Bethesda, MD 20892 USA. RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1583Plat BP 268A EP 268A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301565 ER PT J AU Tcherkasskaya, O Gronenborn, AM AF Tcherkasskaya, O Gronenborn, AM TI Multisite fluorescence energy transfer for protein folding: Equilibrium unfolding of protein GB1 SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1585Plat BP 268A EP 268A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301566 ER PT J AU Durell, SR Guy, HR AF Durell, SR Guy, HR TI Structural models of the K(ir)2.1 channel SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1599Plat BP 270A EP 270A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301579 ER PT J AU Mayer, ML AF Mayer, ML TI Allosteric modulation and pore block in glutamate receptors SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHD, LCMN, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1622Symp BP 274A EP 274A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301600 ER PT J AU Gonzalez, A Shirokova, N Kirsch, WG Stem, MD Cheng, HP Pizarro, G Rios, E AF Gonzalez, A Shirokova, N Kirsch, WG Stem, MD Cheng, HP Pizarro, G Rios, E TI Ca release currents underlying local events produced by imperatoxin a in frog muscle. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Rush Univ, Chicago, IL 60612 USA. NIA, GRC, Baltimore, MD 21224 USA. Univ Republ, Montevideo, Uruguay. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1633Plat BP 276A EP 276A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301614 ER PT J AU Kirsch, WG Gonzalez, A Shirokova, N Pizarro, G Stern, MD Rios, E AF Kirsch, WG Gonzalez, A Shirokova, N Pizarro, G Stern, MD Rios, E TI The spark and the ember insights from interventions that interfere with CICR in skeletal muscle. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Rush Univ, Chicago, IL 60612 USA. Univ Republ, Montevideo, Uruguay. NIA, GRC, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1635Plat BP 276A EP 276A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301615 ER PT J AU Fronticelli, C Piro, C Karavitis, M Arosio, D Smith, SV Friedman, FK Brinigar, WS AF Fronticelli, C Piro, C Karavitis, M Arosio, D Smith, SV Friedman, FK Brinigar, WS TI Conformational and functional relevance of the COO- terminal residues in sperm whale myoglobin. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Johns Hopkins Univ, Baltimore, MD 21205 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. NCI, NIH, Bethesda, MD 20892 USA. Temple Univ, Philadelphia, PA 19122 USA. RI arosio, daniele/B-3160-2012; Friedman, Fred/D-4208-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1664Pos BP 281A EP 281A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301642 ER PT J AU Misra, S Hurley, JH AF Misra, S Hurley, JH TI Structure of the FYVE finger from Vps27p: A phosphatidylinositol 3-phosphate specific membrane targeting domain and PI-3 kinase effector SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1692Pos BP 286A EP 286A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301669 ER PT J AU Wojtuszewski, K Hawkins, MH Cole, JL AF Wojtuszewski, K Hawkins, MH Cole, JL TI HU-DNA complex formation studied by fluorescence anisotropy. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Wesleyan Univ, Middletown, CT 06549 USA. NCI, Pediat Branch, Bethesda, MD 20892 USA. Merck & Co Inc, Rahway, NJ 07065 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1756Pos BP 297A EP 297A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301736 ER PT J AU Fulor, E Lewis, MS Han, MK AF Fulor, E Lewis, MS Han, MK TI A thermodynamic analysis of the self-association of the DNA-binding protein Translin. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Georgetown Univ, Med Ctr, Washington, DC 20057 USA. NIH, ORS, BEPS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1761Pos BP 298A EP 298A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301739 ER PT J AU Gonzalez, M Weiler, S Ferretti, JA Ginsburg, A AF Gonzalez, M Weiler, S Ferretti, JA Ginsburg, A TI Ventral nervous system defective vnd/NK-2 homeodomain protein: Thermal unfolding and binding properties. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1763Pos BP 298A EP 298A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301740 ER PT J AU Sidorova, NY Rau, DC AF Sidorova, NY Rau, DC TI Self-footprint of the restriction endonuclease EcoRI. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1770Pos BP 299A EP 299A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301746 ER PT J AU Voloshchuk, N Hawkins, M Davenport, L AF Voloshchuk, N Hawkins, M Davenport, L TI The binding properties of HIV-1 integrase SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 CUNY Brooklyn Coll, Brooklyn, NY 11210 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1777Pos BP 300A EP 300A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301755 ER PT J AU Urbaneja, MA Casas-Finet, JR Ozarowski, A Maki, AH AF Urbaneja, MA Casas-Finet, JR Ozarowski, A Maki, AH TI A luminescence study of the binding of HIV-1 nucleocapsid protein NCP7 to stem-loop sequences SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, SAIC, Frederick, MD USA. Univ Calif Davis, Davis, CA 95616 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1778Pos BP 301A EP 301A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301756 ER PT J AU Tarasov, SG Casas-Finet, JR Cholody, WM Michejda, CJ AF Tarasov, SG Casas-Finet, JR Cholody, WM Michejda, CJ TI A steady-state and time-resolved fluorescence spectroscopy study of bisimidazoacridone-DNA interactions. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI, FCRDC, Frederick, MD USA. SAIC Frederick, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1800Pos BP 304A EP 304A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301776 ER PT J AU Hawkins, ME Balis, FM AF Hawkins, ME Balis, FM TI Fluorescence characterization of adenosine analogues, 4-amino-8-(2-deoxy-beta-D-ribofuranosyl)5'-O-dimethoxy-trityl-6-methyl-7 (8H)-pteridone (6MAP) and 4-amino-8-(2-deoxy-beta-D-ribofuranosyl)5'-O-dimethoxy-trityl-2,6-dimeth yl-7(8H)-pteridone (DMAP) SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1811Pos BP 306A EP 306A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301790 ER PT J AU Chen, YD AF Chen, YD TI Theoretical formalism for kinesin motility I. Bead movement powered by single one-headed kinesins SO BIOPHYSICAL JOURNAL LA English DT Article ID BROWNIAN PARTICLES; KINETIC MECHANISM; CRYSTAL-STRUCTURE; STOCHASTIC-MODEL; MOTOR PROTEIN; MOLECULES; TRANSPORT; DYNEIN; NCD; MICROTUBULES AB The directional movement on a microtubule of a plastic bead connected elastically to a single one-headed kinesin motor is studied theoretically. The kinesin motor can bind and unbind to periodic binding sites on the microtubule and undergo conformational changes while catalyzing the hydrolysis of ATP. An analytic formalism relating the dynamics of the bead and the ATP hydrolysis cycle of the motor is derived so that the calculation of the average velocity of the bead can be easily carried out. The formalism was applied to a simple three-state biochemical model to investigate how the velocity of the bead movement is affected by the external load, the diffusion coefficient of the bead, and the stiffness of the elastic element connecting the bead and the motor. The bead velocity was found to be critically dependent on the diffusion coefficient of the bead and the stiffness of the elastic element. A linear force-velocity relation was found for the model no matter whether the bead velocity was modulated by the diffusion coefficient of the bead or by the externally applied load. The formalism should be useful in modeling the mechanisms of chemimechanical coupling in kinesin motors based on in vitro motility data. C1 NIDDKD, Math Res Branch, NIH, Bethesda, MD 20892 USA. RP Chen, YD (reprint author), NIDDK, NIH, Math Res Branch, 9190 Rockville Pike,BSA Bldg,Suite 350, Bethesda, MD 20892 USA. NR 40 TC 15 Z9 15 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 BP 313 EP 321 PN 1 PG 9 WC Biophysics SC Biophysics GA 274NX UT WOS:000084772900028 PM 10620295 ER PT J AU Blank, PS Coorssen, JR Albertorio, F Zimmerberg, J AF Blank, PS Coorssen, JR Albertorio, F Zimmerberg, J TI Vesicle protein modification alters the rate and extent of calcium-triggered fusion SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1871Pos BP 316A EP 316A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301847 ER PT J AU Das, D Brooks, BR AF Das, D Brooks, BR TI Modeling the catalytic mechanism of Adenosine Kinase with QM/MM methods SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1969Pos BP 333A EP 333A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301946 ER PT J AU McQueen, PG di Francesco, V Garnier, J Munson, PJ AF McQueen, PG di Francesco, V Garnier, J Munson, PJ TI FORESST: Fold recognition from secondary structure. A web-based protein fold recognition system SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 1976Pos BP 334A EP 334A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779301953 ER PT J AU Malkov, D Bowie, D Mayer, ML AF Malkov, D Bowie, D Mayer, ML TI External divalent ions differentially block AMPA and kainate receptors SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHD, LCMN, NIH, Bethesda, MD 20892 USA. RI Mayer, Mark/H-5500-2013 NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2095Pos BP 355A EP 355A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302071 ER PT J AU Panchenko, V Mayer, ML AF Panchenko, V Mayer, ML TI Scanning mutagenesis of the pore region of GluR6. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHD, LCMN, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2098Pos BP 356A EP 356A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302078 ER PT J AU Courtemanche, M Guia, A Krummel, S Leblanc, N AF Courtemanche, M Guia, A Krummel, S Leblanc, N TI Modeling local interaction of K-Ca and Ca-L channels in coronary SMCs SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. NIA, LCS, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2130Pos BP 361A EP 361A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302107 ER PT J AU Tweedle, D Yang, HT Boheler, KR AF Tweedle, D Yang, HT Boheler, KR TI Temporal profile of ryanodine receptor gene expression and protein synthesis in mouse embryonic stem cell derived cardiac myocytes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2185Pos BP 370A EP 370A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302162 ER PT J AU Bernobich, E Davia, K Ranu, HK Terracciano, CMN MacLeod, KT Hajjar, RJ Harding, SE AF Bernobich, E Davia, K Ranu, HK Terracciano, CMN MacLeod, KT Hajjar, RJ Harding, SE TI Adenovirus-mediated Na/Ca exchanger overexpression depresses contractile function in adult rabbit cardiomyocytes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Univ London Imperial Coll Sci Technol & Med, Sch Med, London SW7 2AZ, England. NHLI, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Cardiovasc Res Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2199Pos BP 373A EP 373A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302178 ER PT J AU He, LP Soldatov, NM Cleemann, L Morad, M AF He, LP Soldatov, NM Cleemann, L Morad, M TI Molecular determinants of cAMP regulation of recombinant Na+-Ca2+ exchanger. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Georgetown Univ, Washington, DC 20007 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2201Pos BP 373A EP 373A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302179 ER PT J AU Forbes, JG Jin, AJ Wang, K AF Forbes, JG Jin, AJ Wang, K TI AFM investigation of native nebulin. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Univ Maryland, College Pk, MD 20742 USA. NIAMS, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2240Pos BP 380A EP 380A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302217 ER PT J AU Jin, AJ Forbes, JG Wang, K AF Jin, AJ Forbes, JG Wang, K TI Atomic force microscopy studies of a titin PEVK segment SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAMS, LPB, NIH, Bethesda, MD 20910 USA. Univ Maryland, College Pk, MD 20742 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2250Pos BP 381A EP 381A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302225 ER PT J AU Ebel, C Eisenberg, H Ghirlando, R AF Ebel, C Eisenberg, H Ghirlando, R TI Probing protein-sugar interactions SO BIOPHYSICAL JOURNAL LA English DT Article ID NUCLEOSOME CORE PARTICLE; PREFERENTIAL HYDRATION; ABSOLUTE INTERACTIONS; GUANIDINIUM CHLORIDE; NEUTRON-SCATTERING; AQUEOUS-SOLUTIONS; MUSCLE ALDOLASE; DETECT WATER; AMINO-ACID; X-RAY AB We have investigated the partial specific volumes (v) over bar(2) (ml/g), hydration, and cosolvent interactions of rabbit muscle aldolase by equilibrium sedimentation in the analytical ultracentrifuge and by direct density increment (partial derivative(rho)/partial derivative C-2)(mu) measurements over a range of sugar concentrations and temperature. In a series of sugars increasing in size, glucose, sucrose, raffinose, and alpha-cyclodextrin, (partial derivative(rho)/partial derivative C-2)(mu) decreases linearly with the solvent density rho(o). These sugar cosolvents do not interact with the protein; however, the interaction parameter B-1 (g water/g protein) mildly increases with increasing sugar size. The experimental B-1 values are smaller than values calculated by excluded volume (rolling ball) considerations. B-1 relates to hydration in this and in other instances studied. It decreases with increasing temperature, leading to an increase in (v) over bar(2) due to reduced water of hydration electrostriction. The density increments (partial derivative(rho)/partial derivative C-2)(mu) however, decrease in concave up form in the case of glycerol and in concave down form for trehalose, leading to more complex behavior in the case of carbohydrates playing a biological role as osmolytes and antifreeze agents. A critical discussion, based on the thermodynamics of multicomponent solutions, is presented. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. CNRS, CEA, Inst Biol Struct, F-38027 Grenoble 1, France. RP Eisenberg, H (reprint author), Weizmann Inst Sci, Dept Biol Struct, IL-76100 Rehovot, Israel. RI Ghirlando, Rodolfo/A-8880-2009 NR 69 TC 62 Z9 64 U1 3 U2 10 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 BP 385 EP 393 PN 1 PG 9 WC Biophysics SC Biophysics GA 274NX UT WOS:000084772900035 PM 10620302 ER PT J AU Garcia, AE Hummer, G AF Garcia, AE Hummer, G TI The kinetics of water penetration and escape in proteins SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Univ Calif Los Alamos Natl Lab, Los Alamos, NM 87545 USA. NIDDK, NIH, Bethesda, MD USA. RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2323Plat BP 394A EP 394A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302301 ER PT J AU Bennink, M Leuba, SH Leno, G AF Bennink, M Leuba, SH Leno, G TI Stretching single reconstituted lambda-DNA-chromatin fibers using optical tweezers. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Univ Twente, Dept Appl Phys, NL-7500 AE Enschede, Netherlands. NCI, NIH, Bethesda, MD 20892 USA. Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2328Plat BP 395A EP 395A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302304 ER PT J AU Schagina, LV Kaulin, YA Bezrukov, SM Takemoto, JY Malev, VV AF Schagina, LV Kaulin, YA Bezrukov, SM Takemoto, JY Malev, VV TI Spatial charge distribution effects in the conductance of syringomycin E ion channels. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 RAS, Inst Cytol, St Petersburg, Russia. Monell Chem Senses Ctr, Philadelphia, PA 19104 USA. NIH, Bethesda, MD 20892 USA. RAS, St Petersburg Nucl Phys Inst, Gatchina, Russia. Utah State Univ, Logan, UT 84322 USA. St Petersburg State Univ, Petergof, Russia. RI Takemoto, Jon/A-5309-2011 OI Takemoto, Jon/0000-0001-9919-9168 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2337Pat BP 396A EP 396A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302314 ER PT J AU Hackos, DH Swartz, KJ AF Hackos, DH Swartz, KJ TI Mutations of a conserved proline in the inner helix of the pore domain of the Shaker K+ channel with altered gating properties SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2349Plat BP 398A EP 398A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302326 ER PT J AU Swartz, KJ Li-Smerin, Y Hackos, D AF Swartz, KJ Li-Smerin, Y Hackos, D TI Tryptophan-scanning mutagenesis of the pore domain shell in the Shaker K+ channel SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2348Plat BP 398A EP 398A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302323 ER PT J AU Bezrukov, SM Rostovtseva, TK AF Bezrukov, SM Rostovtseva, TK TI The trimeric structure or OmpF bacterial porin channels probed by water-soluble polymers. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2387Pos BP 405A EP 405A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302361 ER PT J AU Kenworthy, AK Lippincott-Schwartz, J AF Kenworthy, AK Lippincott-Schwartz, J TI Protein and lipid diffusional mobility in Golgi membranes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHD, CBMB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2403Pos BP 408A EP 408A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302380 ER PT J AU Mitchell, DC Litman, BJ AF Mitchell, DC Litman, BJ TI Reduced water activity amplifies the poteniation of metarhodopsin II formation by ethanol. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAAA, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2420Pos BP 410A EP 410A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302394 ER PT J AU Polozova, A Litman, BJ AF Polozova, A Litman, BJ TI Acyl chain-based molecular sorting of lipids by a G-protein coupled receptor: Specific association of rhodopsin with polyunsaturated lipids. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAAA, NIH, Rockville, MD 20852 USA. RI Polozova, Alla/C-2395-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2419Pos BP 410A EP 410A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302391 ER PT J AU Polozov, IV Litman, BJ Gawrisch, K AF Polozov, IV Litman, BJ Gawrisch, K TI Deuterium-NMR studies of protein-lipid interactions - Rhodopsin's preference for polyunsaturated lipids. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAAA, Lab Membr Biochem Biophys, Rockville, MD 20852 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2432Pos BP 412A EP 412A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302406 ER PT J AU Safley, AM Polozov, IV Gawrisch, K AF Safley, AM Polozov, IV Gawrisch, K TI Order parameter profile of docosahexaenoic acid as determined from deuterium-NMR experiments. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2431Pos BP 412A EP 412A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302403 ER PT J AU Yau, WM Gawrisch, K AF Yau, WM Gawrisch, K TI Electric dipolar interactions between tryptophan and phospholipids SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAAA, NIH, Rockville, MD 20852 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2433Pos BP 413A EP 413A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302407 ER PT J AU McIntyre, JO Loeb-Hennard, C Tran, KY Goldthwaite, CA Kempner, ES AF McIntyre, JO Loeb-Hennard, C Tran, KY Goldthwaite, CA Kempner, ES TI Radiation target analysis of glutathione S-transferase (GST) and a novel fusion protein SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Vanderbilt Univ, Dept Mol Biol, Nashville, TN 37235 USA. NIAMS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2467Pos BP 418A EP 418A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302439 ER PT J AU Pummill, PE DeAngelis, PL Miller, JH Kempner, ES AF Pummill, PE DeAngelis, PL Miller, JH Kempner, ES TI Fusion proteins as internal standards for radiation inactivation target size analysis. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK 73104 USA. NIAMS, Phys Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2464Pos BP 418A EP 418A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302440 ER PT J AU Combs, CA Balaban, RS AF Combs, CA Balaban, RS TI Fluorescence recovery determination of enzyme activity topology (FRAT): Application to imaging dehydrogenase activity in living single cells. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2470Pos BP 419A EP 419A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302446 ER PT J AU Ginsburg, A Szczepanowski, RH Ruvinov, SB Nosworthy, NJ Sondej, M Peterkofsky, A AF Ginsburg, A Szczepanowski, RH Ruvinov, SB Nosworthy, NJ Sondej, M Peterkofsky, A TI Reversible, thermally induced domain unfolding in enzyme I of the E-coli PEP : sugar phosphotransferase system (PTS). SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2495Pos BP 423A EP 423A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302470 ER PT J AU Nussinov, R Kumar, S AF Nussinov, R Kumar, S TI Salt bridge stability in monomeric proteins SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 SAIC Frederick, IRSP, LECB, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, LECB, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2505Pos BP 425A EP 425A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302481 ER PT J AU Gallagher, SC Wang, X Gao, ZH Dyer, RB Trewhella, J Klee, CB AF Gallagher, SC Wang, X Gao, ZH Dyer, RB Trewhella, J Klee, CB TI Ca2+ binding to calcineurin B studied using site specific mutagenesis and fourier transform infrared spectroscopy. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Univ Calif Los Alamos Natl Lab, Los Alamos, NM 87545 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2572Pos BP 436A EP 436A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302545 ER PT J AU Gonzalez, A Pizarro, G Shirokova, N Kirsch, WG Rios, E Stern, MD AF Gonzalez, A Pizarro, G Shirokova, N Kirsch, WG Rios, E Stern, MD TI Local voltage-activated Ca release in frog skeletal muscle cells containing BAPTA. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Rush Univ, Chicago, IL 60612 USA. Univ Republ, Montevideo, Uruguay. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2580Pos BP 437A EP 437A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302554 ER PT J AU Gonzalez, A Kirsch, WG Shirokova, N Pizarro, G Brum, G Cheng, H Stern, MD Rios, E AF Gonzalez, A Kirsch, WG Shirokova, N Pizarro, G Brum, G Cheng, H Stern, MD Rios, E TI Rise times of ca sparks in skeletal muscle. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Rush Univ, Chicago, IL 60612 USA. Univ Republ, Montevideo, Uruguay. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2577Pos BP 437A EP 437A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302551 ER PT J AU Wang, SQ Song, LS Xu, L Meissner, G Lakatta, EG Rios, E Stern, MD Cheng, HP AF Wang, SQ Song, LS Xu, L Meissner, G Lakatta, EG Rios, E Stern, MD Cheng, HP TI Ca2+-driven irreversible gating of single ryanodine receptors reproduces the stereotyped duration of Ca2+ sparks SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIA, Lab Cardiovasc Sci, NIH, Baltimore, MD 21224 USA. Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC USA. Rush Univ, Dept Mol Biophys & Physiol, Chicago, IL 60612 USA. RI Song, Long-Sheng/D-5899-2012 NR 0 TC 1 Z9 1 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2578Pos BP 437A EP 437A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302553 ER PT J AU McEnery, MW Black, JL Dubel, SJ Sharp, AH Copeland, TD AF McEnery, MW Black, JL Dubel, SJ Sharp, AH Copeland, TD TI Epileptic and ataxic stargazer mice do not express the calcium channel gamma-2 subunit homolog (stargazin). SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Case Western Reserve Univ, Dept Physiol & Biophys, Cleveland, OH 44120 USA. Mayo Clin, Dept Psychiat & Psychol, Rochester, MN USA. NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2723Pos BP 462A EP 462A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302698 ER PT J AU Sukarev, S Durell, SR Guy, HR AF Sukarev, S Durell, SR Guy, HR TI Structural models of the gating mechanism of MscL channels. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Univ Maryland, College Pk, MD 20742 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2786Pos BP 473A EP 473A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302759 ER PT J AU Bose, S Dowd, JM Hendler, RW AF Bose, S Dowd, JM Hendler, RW TI Factors which control M-decay in the bacteriorhodopsin photocycle SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2797Pos BP 475A EP 475A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302770 ER PT J AU Hendler, RW Drachev, LA Bose, S Joshi, MK AF Hendler, RW Drachev, LA Bose, S Joshi, MK TI On the kinetics of voltage formation in purple membranes of Halobacterium salinarium SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2796Pos BP 475A EP 475A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302772 ER PT J AU Huster, D Feller, SE Arnold, K Gawrisch, K AF Huster, D Feller, SE Arnold, K Gawrisch, K TI Structure and dynamics of biomembranes - New insights from two-dimensional nuclear Overhauser enhancement spectroscopy SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Univ Leipzig, D-04103 Leipzig, Germany. Wabash Coll, Crawfordsville, IN 47933 USA. Natl Inst Hlth, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2000 VL 78 IS 1 MA 2839Pos BP 482A EP 482A PN 2 PG 1 WC Biophysics SC Biophysics GA 274RR UT WOS:000084779302812 ER PT J AU McCarthy, PK Huang, CH Levin, IW AF McCarthy, PK Huang, CH Levin, IW TI Raman spectroscopic study of polycrystalline mono- and polyunsaturated 1-eicosanoyl-d(39)-2-eicosenoyl-sn-glycero-3-phosphocholines: Bilayer lipid clustering and acyl chain order and disorder characteristics SO BIOPOLYMERS LA English DT Article DE lipid microdomains; Raman spectroscopy; polycrystalline sn-1 chain saturated and sn-2 chain mono- and polyunsaturated phosphatidylcholines ID MOLECULAR MECHANICS SIMULATIONS; VIBRATIONAL ASSIGNMENTS; GEL STATE; DOMAINS; MODEL; PHOSPHATIDYLCHOLINES; MEMBRANE; BEHAVIOR; SPECTRA; LONG AB Polycrystalline lipid samples of a series of mono- and polyunsaturated, double bond positional isomers of 1-eicosanoyl-d(39)-2-eicosenoyl-sn-glycero-3-phosphocholines [C(20-d(39)):C(20:1 Delta(j))PC, with j = 5, 8, 11, or 13; C(20-d(39)):C(20:2 Delta(11,14))PC; and C(20-d(39)):C(20:3 Delta(11,14,17))PC] were investigated using vibrational Raman spectroscopy to assess the acyl chain packing order-disorder characteristics and putative bilayer cluster formation of the isotopically differentiated acyl chains. Perdeuteration of specifically the saturated sn-1 acyl chains for these bilayer systems enables each chain's intra- and intermolecular conformational and organizational properties to be evaluated separately. Various saturated chain methylene CD2 and carbon-carbon (C-C) stretching mode peak height intensity ratios and line width parameters for the polycrystalline samples demonstrate a high degree of sn-1 chain order that is unaffected by either the double bond placement or number of unsaturated bonds within the sn-2 chain. In contrast, the unsaturated sn-2 chain spectral signatures reflect increasing acyl chain conformational disorder as either the cia double bond is generally repositioned toward the chain terminus or the number of double bonds increases from one to three, The lipid bilayer chain packing differences observed between the sn-1 and sn-2 chains of this series of monounsaturated and polyunsaturated 20 carbon chain lipids suggest the existence of laterally distributed microdomains predicated on the formation of highly ordered, saturated sn-1 chain clusters. (C) 2000 John Wiley & Sons, Inc. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Univ Virginia, Hlth Sci Ctr, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA. RP Levin, IW (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NR 21 TC 5 Z9 5 U1 0 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2000 VL 57 IS 1 BP 2 EP 10 DI 10.1002/(SICI)1097-0282(2000)57:1<2::AID-BIP2>3.0.CO;2-G PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 304DR UT WOS:000086468000001 PM 10679634 ER PT J AU Trinh, L Noronha, SB Fannon, M Shiloach, J AF Trinh, L Noronha, SB Fannon, M Shiloach, J TI Recovery of mouse endostatin produced by Pichia pastoris using expanded bed adsorption SO BIOSEPARATION LA English DT Article DE expanded bed adsorption; endostatin; Pichia pastoris ID ESCHERICHIA-COLI; TUMOR-GROWTH; ANGIOGENESIS; CHROMATOGRAPHY; PURIFICATION; EXPRESSION; CARCINOMA; INHIBITOR; DOMAIN; YEAST AB Endostatin, a 20 KDa fragment of collagen XVIII, was shown to have an inhibitory effect on angiogenesis and can potentially be used as a tumor growth suppressor. To obtain the amount needed for testing, the protein was successfully cloned and expressed in Pichia pastoris. At the end of the fermentation process, the concentration of the endostatin in the culture was 50 mg per liter, accompanied by 400 gr per liter (wet weight) of biomass. Before the protein can be captured and purified on a packed bed of heparin-Sepharose, the biomass must be removed. Because of the high biomass concentration, conventional biomass removal techniques like centrifugation or filtration are inefficient and cumbersome. Therefore, the expanded-bed adsorption technique was chosen as an alternative approach. An efficient procedure for the initial recovery and purification of the endostatin was developed. The process utilized a cation- exchanger resin instead of a heparin-based affinity resin, because its dynamic capacity was higher, even though it was affected by the high linear flow on the expanded bed. After adjusting the conductivity, pH and biomass concentration, the complete broth was pumped directly on the expanded-bed matrix (Streamline SP XL). Though the yields of protein are similar, the expanded-bed approach is superior to the packed-bed method for several reasons. The expanded-bed process was shorter (only 8 hours compared to 16 hours for the packed bed), it is cheaper, and the product has higher specific activity (29% compared with 18%). Endostatin produced by the expanded-bed adsorption method showed the expected bioactivity and is currently being tested for its potential as a tumor suppressor. C1 NIDDK, Biotechnol Unit, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. NR 20 TC 13 Z9 15 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-179X J9 BIOSEPARATION JI Bioseparation PY 2000 VL 9 IS 4 BP 223 EP 230 DI 10.1023/A:1008133914854 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 401JK UT WOS:000166924300004 PM 11321520 ER PT J AU Rogakou, EP Redon, C Boon, C Johnson, K Bonner, WM AF Rogakou, EP Redon, C Boon, C Johnson, K Bonner, WM TI Rapid histone extraction for electrophoretic analysis SO BIOTECHNIQUES LA English DT Article ID SULFATE POLYACRYLAMIDE GELS; ACID-UREA-TRITON C1 NCI, NIH, Bethesda, MD 20892 USA. RP Rogakou, EP (reprint author), NIH NCI Bldg 37,Rm 5D21,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 14 TC 13 Z9 13 U1 0 U2 2 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD JAN PY 2000 VL 28 IS 1 BP 38 EP + PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 273QE UT WOS:000084717700006 PM 10649766 ER PT J AU Shevchenko, YO Bale, SJ Compton, JG AF Shevchenko, YO Bale, SJ Compton, JG TI Mutation screening using automated bidirectional dideoxy fingerprinting SO BIOTECHNIQUES LA English DT Article ID DNA; POLYMORPHISMS; GENE; DDF AB The need continues to grow for mutation identification in genetic disease in both research and clinical settings. We have developed a rapid nonradioactive bidirectional dideoxy fingerprint mutation screening procedure that is performed using an automated DNA analyzer: This technique features standardized primers and easily interpreted results from separate, but simultaneously collected images for coding and noncoding strands. Another advantage is simplified mutation verification by sequencing using the same amplified DNA templates and also application to large multi-exon genes. We demonstrate the efficiency and reproducibility of the method in which we screen a DNA fragment encompassing exon 5 of the PTCH gene tin which mutations cause Gorlin Syndrome in a panel of 22 patients. C1 NIAMSD, Genet Studies Sect, NIH, Bethesda, MD 20892 USA. RP Compton, JG (reprint author), NIAMSD, Genet Studies Sect, NIH, 6 Ctr Dr MSC 2757, Bethesda, MD 20892 USA. NR 10 TC 14 Z9 14 U1 0 U2 2 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD JAN PY 2000 VL 28 IS 1 BP 134 EP 138 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 273QE UT WOS:000084717700024 PM 10649784 ER PT J AU Mantile, G Fuchs, C Cordella-Miele, E Peri, A Mukherjee, AB Miele, L AF Mantile, G Fuchs, C Cordella-Miele, E Peri, A Mukherjee, AB Miele, L TI Stable, long-term bacterial production of soluble, dimeric, disulfide-bonded protein pharmaceuticals without antibiotic selection SO BIOTECHNOLOGY PROGRESS LA English DT Article ID RANGE PLASMID RK2; RECOMBINANT HUMAN UTEROGLOBIN; SITE-SPECIFIC RECOMBINATION; CELL 10-KDA PROTEIN; ESCHERICHIA-COLI; PAR LOCUS; NUCLEOTIDE-SEQUENCE; PARTITION-FUNCTIONS; BACILLUS-SUBTILIS; VIRULENCE PLASMID AB Numerous biopharmaceuticals and other recombinant biotechnology products are made in prokaryotic hosts. However, bacterial production of native, biologically active eukaryotic proteins is rarely possible for disulfide-bonded and/or multisubunit proteins. We previously described the production of soluble, native disulfide-bonded dimeric proteins in the Escherichia coli cytoplasm (Miele et al., 1990; Mantile et al., 1993). Native, biologically active proteins with up to six disulfide bonds have been produced with our expression system (Garces et al., 1997). However, plasmid instability during induction limited its usefulness. We now report the stable, high-level expression of soluble, disulfide-bonded human uteroglobin without antibiotic selection. We designed a new vector containing a multifunctional stabilization region that confers complete plasmid stability and increased protein yields without copy number increases. Recombinant expression remains fully inducible after long-term continuous culture in nonselective liquid medium (at least 260 generations). This system may significantly expand the applications of bacterial expression to recombinant production of soluble, bioactive proteins for biochemical studies and biopharmaceutical/industrial purposes. As a result of the very broad activity spectrum of the stabilization region we selected, its use could be extended to bacterial hosts other than enterobacteria. C1 Loyola Univ, Med Ctr, Cardinal Bernardin Canc Ctr, Canc Immunol Program, Maywood, IL 60153 USA. NICHD, Sect Dev Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. US FDA, Cell Biol Lab, Div Monoclonal Antibodies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Miele, L (reprint author), Loyola Univ, Med Ctr, Cardinal Bernardin Canc Ctr, Canc Immunol Program, 2160 S 1st Ave,Room 204, Maywood, IL 60153 USA. NR 54 TC 6 Z9 6 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 8756-7938 J9 BIOTECHNOL PROGR JI Biotechnol. Prog. PD JAN-FEB PY 2000 VL 16 IS 1 BP 17 EP 25 DI 10.1021/bp990129g PG 9 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 282HT UT WOS:000085212900003 PM 10662484 ER PT J AU Wu, X Peters, JM Gonzalez, FJ Prasad, HS Rohrer, MD Gimble, JM AF Wu, X Peters, JM Gonzalez, FJ Prasad, HS Rohrer, MD Gimble, JM TI Frequency of stromal lineage colony forming units in bone marrow of peroxisome proliferator-activated receptor-alpha-null mice SO BONE LA English DT Article; Proceedings Paper CT 19th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 10-14, 1997 CL CINCINNATI, OHIO SP Amer Soc Bone & Mineral Res DE adipocyte; fibroblast; colony forming unit; peroxisome proliferator-activated receptor-alpha; osteoblast; stromal cell ID PPAR-ALPHA; GENE-EXPRESSION; OSTEOGENIC DIFFERENTIATION; DEFICIENT MICE; MURINE MODEL; CELL-TYPES; CFU-F; ADIPOGENESIS; INVITRO; GAMMA AB The bone marrow stroma, consisting of adipocytes, fibroblasts, and osteoblasts, develops from a multipotent mesenchymal progenitor. The recently described nuclear hormone receptors, known as peroxisome proliferator-activated receptors (PPARs), regulate transcription of genes involved in adipogenesis, Consistent with this is the observation that PPAR alpha-null mice exhibit greater extramedullary adipose stores compared with their wild-type controls. To determine if the status of the PPAR alpha protein also influenced bone marrow stromal cell differentiation, this study compared the frequency of colony forming units for bone marrow adipocytes (CFU-A), alkaline phosphatase-positive fibroblasts (CFU-F/ALP(+)), and osteoblasts (CFU-O) between wild-type and PPARa-null mice. The CFU frequencies for all lineages were not significantly different in either gender at age 3 weeks, independent of the PPAR alpha background. However, histologic analysis showed that the cross-sectional area of the femur in male PPAR alpha null mice was significantly greater than that of PPAR alpha-null female mice and of both wild-type genders. This was due to an increased marrow cavity space rather than an increased cortical bone area. In addition, while the percentage area of cortical bone occupied by lacunae was equivalent in the PPAR alpha and wild-type males, this value was significantly greater in PPAR alpha-null female mice compared with wild-type females, At age 3-6 months, no significant difference was observed in the CFU-A frequencies, based on either PPAR alpha status or gender. The wild-type male CFU-F/ALP(+) frequency was significantly greater than the CFU-F/ALP(+) in all other groups. Although the PPARa status had no influence on the CFU-O frequency, the number of CFU-O was greater in male than in female mice. Sequential incubation of stromal cells in either adipogenic- or osteoblastic-inducing media did not alter the number of CFU-A or CFU-O, These results indicate that the PPAR alpha-null genotype does not influence bone marrow stromal cell numbers. (C) 2000 by Elsevier Science Inc. All rights reserved. C1 Univ Oklahoma, Hlth Sci Ctr, Dept Surg, Oklahoma City, OK USA. Univ Oklahoma, Hlth Sci Ctr, Dept Oral Pathol, Oklahoma City, OK USA. Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA. Natl Canc Inst, NIH, Bethesda, MD USA. RP Gimble, JM (reprint author), Zen Bio Inc, 3200 Chapel Hill Nelson Blvd,Suite 102, Res Triangle Pk, NC 27709 USA. RI Peters, Jeffrey/D-8847-2011 FU NCI NIH HHS [CA50898] NR 53 TC 25 Z9 25 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 8756-3282 J9 BONE JI Bone PD JAN PY 2000 VL 26 IS 1 BP 21 EP 26 DI 10.1016/S8756-3282(99)00238-0 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 268CD UT WOS:000084396000004 PM 10617153 ER PT S AU Ohara, Y McCarron, RM Hoffman, TT Sugano, H Bembry, J Lenz, FA Spatz, M AF Ohara, Y McCarron, RM Hoffman, TT Sugano, H Bembry, J Lenz, FA Spatz, M BE Mendelow, AD Baethmann, A Czernick, Z Hoff, JT Ito, U James, HE Kuroiwa, T Marmarou, A Marshall, LF Reulen, HJ TI Adrenergic mediation of TNF alpha-stimulated ICAM-1 expression on human brain microvascular endothelial cells SO BRAIN EDEMA XI SE ACTA NEUROCHIRURGICA SUPPLEMENTA LA English DT Proceedings Paper CT 11th International Brain Oedema Symposium CY JUN 06-10, 1999 CL NEWCASTLE TYNE, ENGLAND DE ICAM-1; HBMEC; TNF alpha; adrenergic agents ID INTERCELLULAR-ADHESION MOLECULE-1; TUMOR-NECROSIS-FACTOR; PROTEIN-KINASE-C; INTERFERON-GAMMA; PERMEABILITY; SYSTEM AB Adrenergic innervation derived from locus ceruleus has been implicated in regulating BBB permeability and inflammatory responses associated with neurological disorders. This report demonstrates that adrenergic agents attenuate the tumor necrosis factor-alpha (TNF alpha)-induced expression of intercellular adhesion molecule-1 (ICAM-1) on cerebral microvascular endothelial cells (HBMEC) derived from human brains. HBMEC were incubated with isoproterenol (1-10 muM) alone or in the presence of propranolol (10 muM) for 30 min followed by the addition of various concentrations of TNFa. ICAM-1 expression on cultured HBMEC was dose-dependently upregulated by TNFa. Incubation with isoproterenol significantly reduced levels of ICAM-1 expression indicating the possible involvement of adrenergic agents on ICAM-1 expression. Treatment with propranolol (beta (1)/beta (2)-adrenergic antagonist) and butoxamine (beta (2)-adrenergic antagonist), but not atenolol (beta (1)-adrenergic antagonist) reversed this inhibitory effect. Isoproterenol also dose-dependently stimulated cAMP production (assayed by RIA) by HBMEC; propranolol treatment abolished this effect. These data show that the beta (2)-adrenergic receptor/cAMP pathway may be partly involved in TNF alpha -stimulated ICAM-1 expression and indicate the possible involvement of adrenergic mediation of capillary function including BBB integrity. C1 NIH, NINDS, Stroke Branch, Bethesda, MD 20892 USA. RP Spatz, M (reprint author), NIH, NINDS, Stroke Branch, Bldg 10,36 Convent Dr,MSC 4128, Bethesda, MD 20892 USA. NR 19 TC 9 Z9 9 U1 1 U2 2 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, A-1201 VIENNA, AUSTRIA SN 0065-1419 BN 3-211-83561-X J9 ACT NEUR S JI Acta Neurochir. Suppl. PY 2000 VL 76 BP 117 EP 120 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA BS52G UT WOS:000170202700024 PM 11449988 ER PT S AU Chen, Y McCarron, RM Azzam, N Bembry, J Reutzler, C Lenz, FA Spatz, M AF Chen, Y McCarron, RM Azzam, N Bembry, J Reutzler, C Lenz, FA Spatz, M BE Mendelow, AD Baethmann, A Czernick, Z Hoff, JT Ito, U James, HE Kuroiwa, T Marmarou, A Marshall, LF Reulen, HJ TI Endothelin-1 and nitric oxide affect human cerebromicrovascular endothelial responses and signal transduction SO BRAIN EDEMA XI SE ACTA NEUROCHIRURGICA SUPPLEMENTA LA English DT Proceedings Paper CT 11th International Brain Oedema Symposium CY JUN 06-10, 1999 CL NEWCASTLE TYNE, ENGLAND DE ET-1; NO; [Ca2+](i) mobilization; F-actin cytoskeleton ID HUMAN-NEUTROPHILS; CULTURED ASTROCYTES; ADP-RIBOSYLATION; ACTIN; INHIBITION; ASSOCIATION; BRAIN AB Endothelium. plays a central role in regulating the vascular tone, blood flow and blood brain barrier (BBB) permeability. The experiments presented here examine the mechanisms by which nitric oxide (NO) and endothelin-1 (ET-1) may be involved in these processes. The findings indicate that ET-l-stimulated [Ca2+](i) accumulation occurs through activation of ETA receptor. The capacity of NO to affect this response was indicated by results showing: 1) a two-fold increase in ET-1-stimulated [Ca2+](i) by L-NAME, the inhibitor of nitric oxide synthase, and 2) a dose-dependent decrease in [Ca2+](i) accumulation by pretreatment with Nor-1 (NO donor). Abrogation of this Nor-1 effect by ODQ (an inhibitor of guanylyl cyclase) or Rp-8-pCPT-cGMPS (an inhibitor of protein kinase G) and inhibition of ET-1 stimulated intracellular Ca2+ accumulation by 8-bromo-cGMP (a permeable, analog of cGMP) substantiate the involvement of inter-play between ET-1 and NO in [Ca2+](i) accumulation in HBMEC. ET-1 treatment also increased thickness of F-actin cytoskeletal filaments in HBMEC. This effect was attenuated by pretreatment with NO; NO also rarefied F-actin filaments in control cultures. The findings support a linkage between NO and ET-1 in regulating microvascular tone, microcirculation and BBB permeability and indicate a role for cGMP/cGMP protein kinase system and cytoskeletal changes in responses of HBMEC. C1 NIH, NINDS, Stroke Branch, Bethesda, MD 20892 USA. RP Spatz, M (reprint author), NIH, NINDS, Stroke Branch, Bldg 10,36 Convent Dr,MSC 4128, Bethesda, MD 20892 USA. NR 18 TC 14 Z9 14 U1 0 U2 0 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, A-1201 VIENNA, AUSTRIA SN 0065-1419 BN 3-211-83561-X J9 ACT NEUR S JI Acta Neurochir. Suppl. PY 2000 VL 76 BP 131 EP 135 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA BS52G UT WOS:000170202700027 PM 11449992 ER PT J AU del Zoppo, G Ginis, I Hallenbeck, JM Iadecola, C Wang, XK Feuerstein, GZ AF del Zoppo, G Ginis, I Hallenbeck, JM Iadecola, C Wang, XK Feuerstein, GZ TI Inflammation and stroke: Putative role for cytokines, adhesion molecules and iNOS in brain response to ischemia SO BRAIN PATHOLOGY LA English DT Article; Proceedings Paper CT 5th Altschul Symposium CY AUG 19-21, 1999 CL UNIV SASKATCHEWAN, SASKATOON, CANADA SP Hlth Canada, Div Adult Hlth, AstraZeneca, Univ Saskatchewan, Coll Med, DuPont Pharma, DuPont Pharmaceut Co, GlaxoWelcome Inc, Heart & Stroke Fdn, Hoffman La Roche Ltd, Merck Frosst Canada Inc, Hlth Canada, Lab Ctr Dis Control, Sanofi Canada Inc, Bristol Myers Squibb, Saskatchewan Nutraceut Networks, WHO HO UNIV SASKATCHEWAN ID TUMOR-NECROSIS-FACTOR; FOCAL CEREBRAL-ISCHEMIA; NITRIC-OXIDE SYNTHASE; INTERLEUKIN-1 RECEPTOR ANTAGONIST; ACTIVATED PROTEIN-KINASE; NF-KAPPA-B; TRANSIENT FOREBRAIN ISCHEMIA; MESSENGER-RNA EXPRESSION; CLOSED-HEAD INJURY; FACTOR-ALPHA AB Ischemic stroke is a leading cause of death and disability in developed countries, Yet, in spite of substantial research and development efforts, no specific therapy for stroke is available, Several mechnism for neuroprotection have been explored including ionchannels, excitatory amino acids and oxygen raicals yet none has culminated in an effective therapeutic effect, The review article on "inflammation and stroke" summarizes key data in support for the possibility that inflammatory cells and mediators are important contributing and confounding factors in ischemic brain injury. In particular, the role of cytokines, endothelial cells and leukocyte adhesion molecules, nitric oxide and cyclooxygenase (COX-2) products are discussed. Furthermore, the potential role for certain cytokines in modulation of brain vulnerability to ischemia is also reviewed,The data suggest that novel therapeutic strategies may evolve from detailed research on some specific inflammatory factors that act in spatial and temporal relationships with traditionally recognized neurotoxic factors, The dual nature of some mediators in reformatting of brain cells for resistance or sensitivity to injury demonstrate the delicate balance needed in interventions based on anti-inflammatory strategies. C1 DuPont Pharmaceut Co, Cardiovasc Dis Res, Expt Stn E400 3257, Wilmington, DE 19880 USA. Scripps Res Inst, La Jolla, CA USA. NIH, Bethesda, MD 20892 USA. Univ Minnesota, Dept Neurol, Minneapolis, MN 55455 USA. RP Feuerstein, GZ (reprint author), DuPont Pharmaceut Co, Cardiovasc Dis Res, Expt Stn E400 3257, Rt 141 & Henry Clay Rd, Wilmington, DE 19880 USA. FU NINDS NIH HHS [NS34179, NS35806] NR 163 TC 415 Z9 419 U1 3 U2 18 PU INT SOC NEUROPATHOLOGY PI PITTSBURGH PA 200 LOTHROP ST A506, PITTSBURGH, PA 15213 USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD JAN PY 2000 VL 10 IS 1 BP 95 EP 112 PG 18 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 276PV UT WOS:000084887300010 PM 10668900 ER PT J AU Hennighausen, L AF Hennighausen, L TI Mouse models for breast cancer SO BREAST CANCER RESEARCH LA English DT Review ID TRANSGENIC MICE; MAMMARY-GLAND; GENES C1 NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. RP Hennighausen, L (reprint author), NIDDKD, Lab Genet & Physiol, NIH, Bldg 8,Room 101, Bethesda, MD 20892 USA. NR 13 TC 27 Z9 28 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2000 VL 2 IS 1 BP 2 EP 7 DI 10.1186/bcr20 PG 6 WC Oncology SC Oncology GA 408PQ UT WOS:000167334900001 PM 11250684 ER PT J AU Liotta, LA Petricoin, EF AF Liotta, LA Petricoin, EF TI Beyond the genome to tissue proteomics SO BREAST CANCER RESEARCH LA English DT Review ID LASER CAPTURE MICRODISSECTION; CELLS C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Div Therapeut Prot, CBER, Food & Drug Adm,NIH, Bethesda, MD 20892 USA. RP Liotta, LA (reprint author), NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 10 TC 9 Z9 11 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2000 VL 2 IS 1 BP 13 EP 14 PG 2 WC Oncology SC Oncology GA 408PQ UT WOS:000167334900004 PM 11250687 ER PT J AU Liu, ET AF Liu, ET TI Breast cancer research: where we are and where we should go SO BREAST CANCER RESEARCH LA English DT Review C1 NCI, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Liu, ET (reprint author), NCI, Div Clin Sci, NIH, Bldg 31,Room 3A11, Bethesda, MD 20892 USA. NR 1 TC 4 Z9 4 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2000 VL 2 IS 2 BP 73 EP 76 DI 10.1186/bcr35 PG 4 WC Oncology SC Oncology GA 408PR UT WOS:000167335100001 PM 11250693 ER PT J AU Wakefield, LM Yang, YA Dukhanina, O AF Wakefield, LM Yang, YA Dukhanina, O TI Transforming growth factor-beta and breast cancer - Lessons learned from genetically altered mouse models SO BREAST CANCER RESEARCH LA English DT Review DE dominant-negative mutant receptors; mammary gland; transforming growth factor-beta; transgenic mice; tumor suppressor ID TGF-BETA; MAMMARY-GLAND; TARGETED DISRUPTION; II RECEPTOR; GROWTH-FACTOR-BETA-1 TRANSGENE; MICE; EXPRESSION; DIFFERENTIATION; TUMORIGENESIS; TGF-BETA-1 AB Transforming growth factor (TGF)-betas are plausible candidate tumor suppressors in the breast. They also have oncogenic activities under certain circumstances, however. Genetically altered mouse models provide powerful tools to analyze the complexities of TGF-beta action in the context of the whole animal. Overexpression of TGF-beta can suppress tumorigenesis in the mammary gland, raising the possibility that use of pharmacologic agents to enhance TGF-beta function locally might be an effective method for the chemoprevention of breast cancer. Conversely, loss of TGF-beta response increases spontaneous and induced tumorigenesis in the mammary gland. This confirms that endogenous TGF-betas have tumor suppressor activity in the mammary gland, and suggests that the loss of TGF-beta receptors seen in some human breast hyperplasias may play a causal role in tumor development. C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. RP Wakefield, LM (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Bldg 41,Room C629,41 Lib Dr MSC 5055, Bethesda, MD 20892 USA. NR 35 TC 36 Z9 36 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2000 VL 2 IS 2 BP 100 EP 106 DI 10.1186/bcr41 PG 7 WC Oncology SC Oncology GA 408PR UT WOS:000167335100007 PM 11250699 ER PT J AU Annab, LA Hawkins, RE Solomon, G Barrett, JC Afshari, CA AF Annab, LA Hawkins, RE Solomon, G Barrett, JC Afshari, CA TI Increased cell survival by inhibition of BRCA1 using an antisense approach in an estrogen responsive ovarian carcinoma cell line SO BREAST CANCER RESEARCH LA English DT Review DE antisense; BRCA1; cell death; estrogen; ovarian cancer; proliferation ID BREAST-CANCER PROGRESSION; SUPPRESSOR GENE BRCA1; TUMOR-SUPPRESSOR; TRANSCRIPTIONAL ACTIVATION; EPITHELIAL-CELLS; MEIOTIC CELLS; CORPUS-LUTEUM; UP-REGULATION; DNA-DAMAGE; EXPRESSION AB We tested the hypothesis that BRCA1 may play a role in the regulation of ovarian tumor cell death as well as the inhibition of ovarian cell proliferation. Introduction of BRCA1 antisense retroviral constructs into BG-1 estrogen-dependent ovarian adenocarcinoma cells resulted in reduced BRCA1 expression. BRCA1 antisense pooled populations and derived subclones were able to proliferate in monolayer culture without estrogen, whereas control cells began to die after 10 days of estrogen deprivation. In addition, both populations and subclones of BRCA1 antisense infected cells demonstrated a growth advantage in monolayer culture in the presence of estrogen and were able to proliferate in monolayer culture without estrogen, while control cells did not. Furthermore, clonal studies demonstrated that reduced levels of BRCA1 protein correlated with growth in soft agar and greater tumor formation in nude mice in the absence of estrogen. These data suggest that reduction of BRCA1 protein in BG-1 ovarian adenocarcinoma cells may have an effect on cell survival during estrogen deprivation both in vitro and in vivo. C1 NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Annab, LA (reprint author), NIEHS, Mol Carcinogenesis Lab, POB 12233,MD2-04, Res Triangle Pk, NC 27709 USA. NR 56 TC 14 Z9 15 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2000 VL 2 IS 2 BP 139 EP 148 DI 10.1186/bcr45 PG 10 WC Oncology SC Oncology GA 408PR UT WOS:000167335100011 PM 11056686 ER PT J AU Groner, B Hennighausen, L AF Groner, B Hennighausen, L TI Linear and cooperative signaling: roles for Stat proteins in the regulation of cell survival and apoptosis in the mammary epithelium SO BREAST CANCER RESEARCH LA English DT Review DE apoptosis; mammary gland; Stat3; tissue specific knock-out ID GLAND DEVELOPMENT; ACTIVATION; INVOLUTION; TRANSCRIPTION; PROLIFERATION; GROWTH; DEATH; MICE AB The mammary epithelium undergoes cyclical periods of cellular proliferation, differentiation and regression. These processes are under the control of the hormones secreted during pregnancy, lactation and involution. Signaling pathways have been identified that connect the hormonal stimuli with the transcription of genes responsible for the determination of the cellular fate. The kinetics of induction and deinduction have suggested that cytokine-activated Stat proteins play a crucial role. Stat5 is strongly activated towards the end of pregnancy, persists in an activated state during pregnancy and is rapidly inactivated after cessation of suckling. Stat3 activation is hardly detectable during lactation, but is strongly induced at the onset of involution. The phenotypes of mice in which these genes have been inactivated through homologous recombination corroborate some of the functional assignments deducted from the activation pattern. Stat3 activation seems to be a driving force in the induction of apoptosis early in the involution period. C1 Inst Biomed Res, D-60596 Frankfurt, Germany. NIH, Lab Genet & Physiol, Bethesda, MD 20892 USA. RP Groner, B (reprint author), Inst Biomed Res, George Speyer Haus,Paul Ehrich Str 42-44, D-60596 Frankfurt, Germany. NR 25 TC 30 Z9 30 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2000 VL 2 IS 3 BP 149 EP 153 DI 10.1186/bcr47 PG 5 WC Oncology SC Oncology GA 408QA UT WOS:000167338100001 PM 11250703 ER PT J AU Prime, W Sobel, ME Herrington, CS AF Prime, W Sobel, ME Herrington, CS TI Utilization of human tissue in breast cancer research SO BREAST CANCER RESEARCH LA English DT Review DE anonymized; coded; research; sample; tissue AB The use of human tissue, and material derived from such tissue, for research purposes is currently the subject of much debate. This debate needs to address several issues, including: the principle of abandonment; the distinction between identified and unidentified specimens; general versus specific informed consent; and, with the improvement in biotechnology and medical informatics, the design and security of research databases. The outcome of this debate will shape the way in which research studies using human biological materials are designed and executed. C1 Univ Liverpool, Royal Liverpool Univ Hosp, Canc Tissue Bank Res Ctr, Liverpool L69 3GA, Merseyside, England. NCI, Mol Pathol Sect, Bethesda, MD 20892 USA. RP Herrington, CS (reprint author), Univ Liverpool, Royal Liverpool Univ Hosp, Canc Tissue Bank Res Ctr, Duncan Bldg,Daulby St, Liverpool L69 3GA, Merseyside, England. OI Herrington, C Simon/0000-0001-9177-8165 NR 8 TC 6 Z9 6 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2000 VL 2 IS 4 BP 237 EP 240 DI 10.1186/bcr61 PG 4 WC Oncology SC Oncology GA 408QB UT WOS:000167338200001 PM 11250713 ER PT J AU Phillips, AC Vousden, KH AF Phillips, AC Vousden, KH TI Acetyltransferases and tumour suppression SO BREAST CANCER RESEARCH LA English DT Review DE acetylation; acetyltransferases; CBP; E1A; p300; tumour suppressors ID HISTONE ACETYLTRANSFERASES; CBP; P300; ACETYLATION; ACTIVATION; BINDING; PROTEIN; P53; COACTIVATORS AB The acetyltransferase p300 was first identified associated with the adenoviral transforming protein E1A, suggesting a potential role for p300 in the regulation of cell proliferation. Direct evidence demonstrating a role for p300 in human tumours was lacking until the recently publication by Gayther et al, which strongly supports a role for p300 as a tumour suppressor. The authors identify truncating mutations associated with the loss or mutation of the second allele in both tumour samples and cell lines, suggesting that loss of p300 may play a role in the development of a subset of human cancers. C1 NCI, Regulat Cell Growth Lab, FCRDC, Frederick, MD 21702 USA. RP Phillips, AC (reprint author), NCI, Regulat Cell Growth Lab, FCRDC, Bldg 560,Room 22-96,W 7th St, Frederick, MD 21702 USA. NR 24 TC 20 Z9 21 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2000 VL 2 IS 4 BP 244 EP 246 DI 10.1186/bcr63 PG 3 WC Oncology SC Oncology GA 408QB UT WOS:000167338200003 PM 11250715 ER PT J AU Couldrey, C Green, JE AF Couldrey, C Green, JE TI Metastases: the glycan connection SO BREAST CANCER RESEARCH LA English DT Review DE breast cancer; glycosylation; metastases; MGAT5; transgenic mouse model ID ASN-LINKED OLIGOSACCHARIDES; HUMAN-BREAST; N-ACETYLGLUCOSAMINYLTRANSFERASE; CANCER; ONCOGENE; EXPRESSION; CELLS; PROGRESSION; SURFACE AB An association between protein glycosylation and tumorigenesis has been recognized for over 10 years. Associations linking the importance of glycosylation events to tumor biology, especially the progression to metastatic disease, have been noted over many years, Recently, a mouse model in which beta1,6-N-acetylglucosaminyltransferase V (a rate-limiting enzyme in the N-glycan pathway) has been knocked out, was used to demonstrate the importance of glycosylation in tumor progression. By crossing mice lacking this enzyme with a transgenic mouse model of metastatic breast cancer, metastatic progression of the disease was dramatically reduced. These experiments provide in vivo evidence for the role of N-linked glycosylation in metastatic breast cancer and have significant implications for the development of new treatment strategies. C1 NCI, Lab Cell Regulat & Carcinogenesis, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Green, JE (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Div Basic Sci, NIH, Bldg 41,Room C629,41 Lib Dr, Bethesda, MD 20892 USA. NR 23 TC 61 Z9 64 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2000 VL 2 IS 5 BP 321 EP 323 DI 10.1186/bcr75 PG 3 WC Oncology SC Oncology GA 408QJ UT WOS:000167338900001 PM 11250723 ER PT J AU Hewitt, SC Couse, JF Korach, KS AF Hewitt, SC Couse, JF Korach, KS TI Estrogen receptor transcription and transactivation Estrogen receptor knockout mice: what their phenotypes reveal about mechanisms of estrogen action SO BREAST CANCER RESEARCH LA English DT Review DE estrogen receptor; estrogen receptor knockout; transgenic ID FOLLICLE-STIMULATING-HORMONE; EPIDERMAL GROWTH-FACTOR; VASCULAR INJURY RESPONSE; RAT GRANULOSA-CELLS; TARGETED DISRUPTION; SIGNALING PATHWAYS; OVARIAN FOLLICLES; DEFICIENT MICE; FSH-RECEPTORS; CROSS-TALK AB Natural, synthetic and environmental estrogens have numerous effects on the development and physiology of mammals. Estrogen is primarily known for its role in the development and functioning of the female reproductive system. However, roles for estrogen in male fertility, bone, the circulatory system and immune system have been established by clinical observations regarding sex differences in pathologies, as well as observations following menopause or castration. The primary mechanism of estrogen action is via binding and modulation of activity of the estrogen receptors (ERs), which are ligand-dependent nuclear transcription factors. ERs are found in highest levels in female tissues critical to reproduction, including the ovaries, uterus, cervix, mammary glands and pituitary gland. Since other affected tissues have extremely low levels of ER, indirect effects of estrogen, for example induction of pituitary hormones that affect the bone, have been proposed. The development of transgenic mouse models that lack either estrogen or ER have proven to be valuable tools in defining the mechanisms by which estrogen exerts its effects in various systems. The aim of this article is to review the mouse models with disrupted estrogen signaling and describe the associated phenotypes. C1 NIEHS, LRDT, NIH, Res Triangle Pk, NC 27709 USA. RP Korach, KS (reprint author), NIEHS, LRDT, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. OI Korach, Kenneth/0000-0002-7765-418X NR 43 TC 52 Z9 57 U1 2 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2000 VL 2 IS 5 BP 345 EP 352 PG 8 WC Oncology SC Oncology GA 408QJ UT WOS:000167338900005 ER PT J AU Steeg, PS AF Steeg, PS TI Molecular biology of breast cancer metastasis - 'Has it spread?': disarming one of the most terrifying questions SO BREAST CANCER RESEARCH LA English DT Review ID VASCULOGENIC MIMICRY; CELL-LINE; MODEL; PROTEIN C1 NCI, Womens Canc Sect, Pathol Lab, Div Clin Sci, Bethesda, MD 20892 USA. RP Steeg, PS (reprint author), NCI, Womens Canc Sect, Pathol Lab, Div Clin Sci, Bldg 10,Room 2A33, Bethesda, MD 20892 USA. NR 20 TC 8 Z9 8 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2000 VL 2 IS 6 BP 396 EP 399 DI 10.1186/bcr85 PG 4 WC Oncology SC Oncology GA 408TA UT WOS:000167342700003 PM 11250732 ER PT J AU Welch, DR Steeg, PS Rinker-Schaeffer, CW AF Welch, DR Steeg, PS Rinker-Schaeffer, CW TI Molecular biology of breast cancer metastasis - Genetic regulation of human breast carcinoma metastasis SO BREAST CANCER RESEARCH LA English DT Review DE BRMS1; E-cadherin; KAl1; KiSS1; MKK4; Nm23; metastasis; suppressor genes ID NUCLEOSIDE DIPHOSPHATE KINASE; HUMAN-CHROMOSOME 11; SUPPRESSOR GENE; E-CADHERIN; TUMOR-METASTASIS; PROSTATE-CANCER; MELANOMA-CELLS; BONE METASTASES; IN-VITRO; INVASIVE PHENOTYPE AB The present is an overview of recent data that describes the genetic underpinnings of the suppression of cancer metastasis. Despite the explosion of new information about the genetics of cancer, only six human genes have thus far been shown to suppress metastasis functionally. Not all have been shown to be functional in breast carcinoma. Several additional genes inhibit various steps of the metastatic cascade, but do not necessarily block metastasis when tested using in vivo assays. The implications of this are discussed. Two recently discovered metastasis suppressor genes block proliferation of tumor cells at a secondary site, offering a new target for therapeutic intervention. C1 Penn State Univ, Coll Med, Jake Gittlen Canc Res Inst, Hershey, PA 17033 USA. Univ Chicago, Prostate & Genitourinary Oncol Res Program, Urol Sect, Chicago, IL 60637 USA. NCI, Womens Canc Sect, Pathol Lab, Bethesda, MD 20892 USA. RP Welch, DR (reprint author), Penn State Univ, Coll Med, Jake Gittlen Canc Res Inst, Box H-059,500 Univ Dr, Hershey, PA 17033 USA. EM drw9@psu.edu RI Welch, Danny/B-7310-2009 OI Welch, Danny/0000-0002-1951-4947 FU NCI NIH HHS [P20 CA 66132, R01-CA62168, R29 CA69487] NR 93 TC 94 Z9 100 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2000 VL 2 IS 6 BP 408 EP 416 DI 10.1186/bcr87 PG 9 WC Oncology SC Oncology GA 408TA UT WOS:000167342700005 PM 11250734 ER PT J AU Zhou, Q Wulfkuhle, J Ouatas, T Fukushima, P Stetler-Stevenson, M Miller, FR Steeg, PS AF Zhou, Q Wulfkuhle, J Ouatas, T Fukushima, P Stetler-Stevenson, M Miller, FR Steeg, PS TI Cyclin D1 overexpression in a model of human breast premalignancy: preferential stimulation of anchorage-independent but not anchorage-dependent growth is associated with increased cdk2 activity SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE cyclin D1; premalignant disease progression anchorage-independent growth; MCF-10A cells ID EPITHELIAL-CELL LINE; CARCINOMA IN-SITU; ESTROGEN-RECEPTOR; GENE-EXPRESSION; CANCER RISK; ATYPICAL HYPERPLASIA; ECTOPIC EXPRESSION; E-CDK2 ACTIVATION; NIH3T3 CELLS; FOLLOW-UP AB Cyclin D1 is frequently overexpressed in human breast ductal carcinoma in situ (DCIS) specimens, which confer a high risk for the development of infiltrating ductal carcinoma. If causally involved in the genesis of human breast malignancy, cyclin D1 may represent an interesting target for chemopreventive approaches, as it sits at the junction of many growth factor and hormonal pathways. We have used the MCF-10A human breast cell line, derived from a mastectomy containing a low risk premalignant lesion, as a model system. Three cyclin D1 transfectants exhibited physiologically relevant levels of transgene overexpression, but no coordinate overexpression of other cell cycle related genes. Proliferation assays, flow cytometry, and cdk enzymatic assays of anchorage-dependent proliferation indicated only a minimal and transient effect of cyclin D1. In contrast, cyclin D1 overexpression significantly stimulated anchorage-independent colonization in soft agar or methylcellulose, accompanied by greater Gl-S progression. The cdk4 activity of the control- and cyclin D1 transfectants in colonization assays was comparable, but the cdk2 activity was higher in the latter. Injection of control- and cyclin D1 transfected MCF-10A cells in matrigel into nude mice failed to produce tumors within 1.5 years. The data suggest that cyclin D1 overexpression is an early feature of breast neoplastic progression, and can contribute to cancer development through the promotion of colonization. C1 NCI, Pathol Lab, Womens Canc Sect, Bethesda, MD 20892 USA. NCI, Pathol Lab, Flow Cytometry Unit, Div Clin Sci, Bethesda, MD 20892 USA. Wayne State Univ, Barbara Ann Karmanos Canc Inst, Breast Canc Program, Detroit, MI USA. RP Steeg, PS (reprint author), NCI, Pathol Lab, Womens Canc Sect, Bldg 10,Room 2A33, Bethesda, MD 20892 USA. NR 60 TC 23 Z9 23 U1 0 U2 1 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 JAN PY 2000 VL 59 IS 1 BP 27 EP 39 DI 10.1023/A:1006370603147 PG 13 WC Oncology SC Oncology GA 288DK UT WOS:000085546400003 PM 10752677 ER PT J AU Neglia, JP Linet, MS Shu, XO Severson, RK Potter, JD Mertens, AC Wen, W Kersey, JH Robison, LL AF Neglia, JP Linet, MS Shu, XO Severson, RK Potter, JD Mertens, AC Wen, W Kersey, JH Robison, LL TI Patterns of infection and day care utilization and risk of childhood acute lymphoblastic leukaemia SO BRITISH JOURNAL OF CANCER LA English DT Article DE childhood acute lymphoblastic leukaemia; infections; day care ID ACUTE-LEUKEMIA; MAGNETIC-FIELDS; CHILDREN; EXPOSURE; EPIDEMIOLOGY; ETIOLOGY; HISTORY; CANCER; AGE AB To investigate ii decreased exposure to common childhood infections is associated with risk of childhood acute lymphoblastic leukaemia (ALL) we conducted a case-control study of 1842 newly diagnosed and immunophenotypically defined cases of ALL under age 15, and 1986 matched controls in the US. Data regarding day care, sibship size and common childhood infections were obtained through parental interviews. Data were analysed stratified by leukaemia lineage and separately for 'common' childhood ALL (age 2-5 years, CD19, CD10-positive). Neither attendance at day care nor time at day care was associated with risk of ALL overall or 'common' ALL. Ear infections during infancy were less common among cases, with odds ratios of 0.86, 0.83, 0.71 and 0.69 for 1, 2-4, 5+ episodes, and continuous infections respectively (trend P = 0.026). No effect of sibship size or birth interval was seen. With one exception tear infections). these data do not support the hypothesis that a decrease in the occurrence of common childhood infection increases risk of ALL. (C) 2000 Cancer Research Campaign. C1 Univ Minnesota, Sch Med, Dept Pediat, Minneapolis, MN 55455 USA. Univ Minnesota, Sch Med, Dept Pediat, Lab Med & Pathol, Minneapolis, MN 55455 USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA. Univ S Carolina, Sch Med, Dept Pediat, Columbia, SC USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Karmanos Canc Inst, Detroit, MI USA. RP Neglia, JP (reprint author), Childrens Canc Grp, POB 60012, Arcadia, CA 91066 USA. OI Potter, John/0000-0001-5439-1500 FU NCI NIH HHS [CA 07036, CA 48051] NR 29 TC 60 Z9 60 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JAN PY 2000 VL 82 IS 1 BP 234 EP 240 PG 7 WC Oncology SC Oncology GA 267CA UT WOS:000084335900040 PM 10638995 ER PT J AU Kato, H Zhou, Y Asanoma, K Kondo, H Yoshikawa, Y Watanabe, K Matsuda, T Wake, N Barrett, JC AF Kato, H Zhou, Y Asanoma, K Kondo, H Yoshikawa, Y Watanabe, K Matsuda, T Wake, N Barrett, JC TI Suppressed tumorigenicity of human endometrial cancer cells by the restored expression of the DCC gene SO BRITISH JOURNAL OF CANCER LA English DT Article DE tumour suppression; tumour suppressor gene; DCC; endometrial carcinoma; apoptosis ID COLORECTAL CANCERS; CARCINOMAS; APOPTOSIS; HETEROZYGOSITY; CHROMOSOME-18; MUTATIONS; PHENOTYPE; RECEPTOR; ADHESION; PRODUCT AB To obtain functional evidence for DCC as a tumour suppressor associated with endometrial cancer, the human DCC cDNA encoding a complete open reading frame (ORF) was transfected into highly tumorigenic human endometrial carcinoma cells, HHUA and Ishikawa in which DCC expression was completely deleted. Reconstituted expression of DCC in HHUA had little effect on in vitro growth, but suppressed tumour formation in mice completely. The clones from Ishikawa had abundant DCC expression similar to that in normal endometrium. Their growth in vitro was suppressed and showed apoptotic phenotype. Lower levels of DCC expression in the prolonged passaged clones did not induce apoptosis, but still had the potential to suppress tumorigenicity. These observations imply a role of DCC in regulation of normal endometrial cell growth, and categorize DCC as the tumour suppressor gene for endometrial cancer. (C) 2000 Cancer Research Campaign. C1 Kyushu Univ, Med Inst Bioregulat, Dept Reprod Physiol & Endocrinol, Oita 8740838, Japan. Kyushu Univ, Med Inst Bioregulat, Dept Pathol, Oita 8740838, Japan. NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Kato, H (reprint author), Kyushu Univ, Med Inst Bioregulat, Dept Reprod Physiol & Endocrinol, Tsurumihara 4546, Oita 8740838, Japan. RI U-ID, Kyushu/C-5291-2016 NR 33 TC 23 Z9 28 U1 0 U2 3 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JAN PY 2000 VL 82 IS 2 BP 459 EP 466 DI 10.1054/bjoc.1999.0943 PG 8 WC Oncology SC Oncology GA 274QR UT WOS:000084777000033 PM 10646905 ER PT J AU Giri, N Kang, E Tisdale, JF Follman, D Rivera, M Schwartz, GN Kim, S Young, NS Rick, ME Dunbar, CE AF Giri, N Kang, E Tisdale, JF Follman, D Rivera, M Schwartz, GN Kim, S Young, NS Rick, ME Dunbar, CE TI Clinical and laboratory evidence for a trilineage haematopoietic defect in patients with refractory Diamond-Blackfan anaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE Diamond-Blackfan anaemia; neutropenia.; thrombocytopenia; bone marrow hypoplasia; long-term culture-initiating cell assay ID LONG-TERM CULTURE; RED-CELL APLASIA; HEMATOPOIETIC GROWTH-FACTORS; BONE-MARROW TRANSPLANTATION; LIMITING DILUTION; C-KIT; INITIATING CELLS; STEM-CELLS; ANEMIA; INTERLEUKIN-3 AB Diamond-Blackfan anaemia (DBA) is a constitutional pure red cell aplasia presenting in early childhood. In some patients, neutropenia and/or thrombocytopenia have also been observed during the course of the disease. We have followed 28 patients with steroid-refractory DBA for up to 13 years with serial peripheral blood counts and bone marrow (BM) aspirates and biopsies. In 21/28 (75%) patients, moderate to severe generalized BM hypoplasia developed, with overall cellularities ranging from 0% to 30%, Marrow hypoplasia correlated with the development of neutropenia (9/21: 43%) and/or thrombocytopenia (6/21; 29%) in many patients. No patient had either cytogenetic abnormalities or progressed to acute leukaemia, although one 13-year-old developed marked marrow fibrosis and trilineage dysplasia, We used the in vitro long-term culture-initiating cell (LTC-IC) assay to quantify multilineage, primitive haematopoietic progenitors in a representative subset of these patients. LTC-IC assays showed equivalent frequencies of cobblestone area forming cells (CAFCs) with a mean of 5.42/10(5) cells +/- 1.9 SD and 6.13/10(5) cells +/- 2.6 SD in nine patients and six normal controls respectively, The average clonogenic cell output per LTC-IC, however, was significantly lower in DBA patients (mean 2.16 +/- 1.2 SD vs. 7.36 +/- 2.7 SD in normal controls, P = 0.0008). Our results suggest that the underlying defect in patients with severe refractory DBA may not be limited to the erythroid lineage, as was evidenced by the development of pancytopenia, bone marrow hypoplasia and reduced clonogenic cell output in LTC-IC assays. C1 NIH, Ctr Clin, Hematol Serv, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NIDDK, Mol & Clin Haematol Branch, Bethesda, MD USA. NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Dunbar, CE (reprint author), NIH, Ctr Clin, Hematol Serv, Bldg 10,Room 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Brugnara, Carlo/A-8041-2010 OI Brugnara, Carlo/0000-0001-8192-8713 NR 42 TC 42 Z9 42 U1 0 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JAN PY 2000 VL 108 IS 1 BP 167 EP 175 PG 9 WC Hematology SC Hematology GA 286RL UT WOS:000085459200024 PM 10651740 ER PT J AU Gutmann, H Miller, DS Droulle, A Drewe, J Fahr, A Fricker, G AF Gutmann, H Miller, DS Droulle, A Drewe, J Fahr, A Fricker, G TI P-glycoprotein- and mrp2-mediated octreotide transport in renal proximal tubule SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE octreotide; p-glycoprotein (Pgp); multidrug resistance protein; multidrug resistance associated protein2 (mrp2); kidney; renal secretion; killifish; confocal microscopy; active transport ID ORGANIC ANION SECRETION; BLOOD-BRAIN-BARRIER; SOMATOSTATIN ANALOG; ENTERAL ABSORPTION; IN-VIVO; CYCLOSPORINE-A; OCTAPEPTIDE; PHARMACOKINETICS; EXCRETION; EFFLUX AB 1 Transepithelial transport of a fluorescent derivative of octreotide (NBD-octreotide) was studied in freshly isolated, functionally intact renal proximal tubules from killifish (Fundulus heteroclitus). 2 Drug accumulation in the tubular lumen was visualized by means of confocal microscopy and was measured by image analysis. Secretion of NBD-octreotide into the tubular lumen was demonstrated and exhibited the all characteristics of specific and energy-dependent transport. Steady slate luminal fluorescence averaged about five times cellular fluorescence and was reduced to cellular levels when metabolism was inhibited by NaCN. 3 NBD-octreotide secretion was inhibited in a concentration-dependent manner by unlabelled octreotide, verapamil and leukotriene C-4 (LTC4). Conversely, unlabelled octreotide reduced in a concentration dependent manner the p-glycoprotein (Pgp)-mediated secretion of a fluorescent cyclosporin A derivative (NBDL-CS) and the mrp2-mediated secretion of fluorescein methotrexate (FL-MTX). 4 This inhibition was not due to impaired metabolism or toxicity since octreotide had no influence on the active transport of fluorescein (FL), a substrate for the classical renal system. 5 The data are consistent with octreotide being transported across the brush border membrane of organic anion transport proximal kidney tubules by both Pgp and mrp2. C1 Univ Heidelberg, Inst Pharmaceut & Biopharm, D-69120 Heidelberg, Germany. Mt Desert Isl Biol Lab, Salsbury Cove, ME 04672 USA. Univ Basel Clin, Kantonsspital, Div Clin Pharmacol, Dept Internal Med, CH-4031 Basel, Switzerland. Univ Basel Clin, Kantonsspital, Res Dept, CH-4031 Basel, Switzerland. NIEHS, Res Triangle Pk, NC 27709 USA. Lycee Roosevelt, F-51100 Reims, France. Univ Marburg, Inst Pharmaceut & Biopharm, D-35032 Marburg, Germany. RP Fricker, G (reprint author), Univ Heidelberg, Inst Pharmaceut & Biopharm, Neuenheimer Feld 366, D-69120 Heidelberg, Germany. FU NIEHS NIH HHS [ES03828, P30 ES003828] NR 37 TC 27 Z9 29 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD JAN PY 2000 VL 129 IS 2 BP 251 EP 256 DI 10.1038/sj.bjp.0703003 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 279LV UT WOS:000085046000006 PM 10694230 ER PT J AU Miller, N Lacroix, EM Backus, JEB AF Miller, N Lacroix, EM Backus, JEB TI MEDLINEplus: building and maintaining the National Library of Medicine's consumer health Web service SO BULLETIN OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article AB MEDLINEplus is a Web-based consumer health information resource, made available by the National Library of Medicine (NLM). MEDLINEplus has been designed to provide consumers with a well-organized, selective Web site facilitating access to reliable full-text health information. In addition to full-text resources, MEDLINEplus directs consumers to dictionaries, organizations, directories, libraries, and clearinghouses for answers to health questions. For each health topic, MEDLINEplus includes a preformulated MEDLINE search created by librarians. The site has been designed to match consumer language to medical terminology. NLM has used advances in database and Web technologies to build and maintain MEDLINEplus, allowing health sciences librarians to contribute remotely to the resource. This article describes the development and implementation of MEDLINEplus, its supporting technology, and plans for future development. C1 Natl Lib Med, Publ Serv Div, Bethesda, MD 20894 USA. RP Miller, N (reprint author), Natl Lib Med, Publ Serv Div, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 8 TC 52 Z9 52 U1 0 U2 4 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 0025-7338 J9 B MED LIBR ASSOC JI Bull. Med. Libr. Assoc. PD JAN PY 2000 VL 88 IS 1 BP 11 EP 17 PG 7 WC Information Science & Library Science SC Information Science & Library Science GA 415LA UT WOS:000167721800002 PM 10658959 ER PT J AU Hussain, R Fikree, FF Berendes, HW AF Hussain, R Fikree, FF Berendes, HW TI The role of son preference in reproductive behaviour in Pakistan SO BULLETIN OF THE WORLD HEALTH ORGANIZATION LA English DT Article DE cohort studies; contraception; Pakistan; pregnancy, unwanted; sex; sex behaviour; socioeconomic factors ID SUBSEQUENT BEHAVIOR; RURAL BANGLADESH; FEMALE CHILDREN; INDIA; GENDER; FERTILITY; HEALTH; INTENTIONS; MORTALITY; RISK AB The sex of surviving children is an important determinant of reproductive behaviour in South Asia in general and Pakistan in particular. This cohort study evaluates the role of the sex of children on reproductive intentions and subsequent behaviour of women in urban slums of Karachi, Pakistan. The analysis is based on two rounds of surveys conducted in 1990-91 and 1995 of a cohort of married women aged 15-49 years. The results show that pregnancies became increasingly unwanted as the number of surviving sons increased. The sex of surviving children was strongly correlated with subsequent fertility and contraceptive behaviour. However, rather than an exclusive son preference, couples strove for one or more sons and at least one surviving daughter. The policy implications of the link between overt son preference and low status of women are discussed. C1 Univ New England, Sch Hlth, Armidale, NSW 2351, Australia. Populat Council, New York, NY 10021 USA. NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. RP Hussain, R (reprint author), Univ New England, Sch Hlth, Armidale, NSW 2351, Australia. FU NCI NIH HHS [SFCP08-024-N] NR 39 TC 29 Z9 30 U1 0 U2 5 PU WORLD HEALTH ORGANIZATION PI GENEVA 27 PA MARKETING AND DISSEMINATION, CH-1211 GENEVA 27, SWITZERLAND SN 0042-9686 J9 B WORLD HEALTH ORGAN JI Bull. World Health Organ. PY 2000 VL 78 IS 3 BP 379 EP 388 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 302CQ UT WOS:000086348000017 PM 10812738 ER PT J AU Hyman, SE AF Hyman, SE TI The genetics of mental illness: implications for practice SO BULLETIN OF THE WORLD HEALTH ORGANIZATION LA English DT Article DE mental disorders, genetics; neurosciences; mental disorders, drug therapy; genetic predisposition to disease; antipsychotic agents, therapeutic use ID SCHIZOPHRENIA; DEPRESSION; BRAIN; TWIN AB Many of the comfortable and relatively simple models of the nature of mental disorders, their causes and their neural substrates now appear quite frayed. Gone is the idea that symptom clusters, course of illness, family history and treatment response would coalesce in a simple way to yield valid diagnoses. Also too simple was the concept, born of early pharmacological successes, that abnormal levels of one or more neurotransmitters would satisfactorily explain the pathogenesis of depression or schizophrenia. Gone is the notion that there is a single gene that causes any menta I disorder or determines any behavioural variant. The concept of the causative gene has been replaced by that of genetic complexity, in which multiple genes act in concert with non-genetic factors to produce a risk of mental disorder. Discoveries in genetics and neuroscience can be expected to lead to better models that provide improved representation of the complexity of the brain and behaviour and the development of both. There are likely to be profound implications for clinical practice. The complex genetics of risk should reinvigorate research on the epidemiology and classification of mental disorders and explain the complex patterns of disease transmission within families. Knowledge of the timing of the the expression of risk genes during brain development and of their function should not only contribute to an understanding of gene action and the pathophysiology of disease but should also help to direct the search for modifiable environmental risk factors that convert risk into illness. The function of risk genes can only became comprehensible in the context of advances at the molecular, cellular and systems levels in neuroscience and the behavioural sciences. Genetics should yield new therapies aimed not just at symptoms but also at pathogenic processes, thus permitting the targeting of specific therapies to individual patients. C1 NIMH, Bethesda, MD 20892 USA. RP Hyman, SE (reprint author), NIMH, 6001 Execut Blvd,Room 8235,MSC 9669, Bethesda, MD 20892 USA. NR 27 TC 27 Z9 27 U1 0 U2 3 PU WORLD HEALTH ORGANIZATION PI GENEVA 27 PA MARKETING AND DISSEMINATION, CH-1211 GENEVA 27, SWITZERLAND SN 0042-9686 J9 B WORLD HEALTH ORGAN JI Bull. World Health Organ. PY 2000 VL 78 IS 4 BP 455 EP 463 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 318ZC UT WOS:000087313700007 PM 10885164 ER PT J AU Breman, JG AF Breman, JG TI Malaria control stymied in 2010, mastered in 2025 SO BULLETIN OF THE WORLD HEALTH ORGANIZATION LA English DT Editorial Material C1 NIH, Div Int Training & Res, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Breman, JG (reprint author), NIH, Div Int Training & Res, Fogarty Int Ctr, Bldg 31,Room B2C39,31 Ctr Dr,MSC 2220, Bethesda, MD 20892 USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU WORLD HEALTH ORGANIZATION PI GENEVA 27 PA MARKETING AND DISSEMINATION, CH-1211 GENEVA 27, SWITZERLAND SN 0042-9686 J9 B WORLD HEALTH ORGAN JI Bull. World Health Organ. PY 2000 VL 78 IS 12 BP 1450 EP 1452 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 393EH UT WOS:000166455900013 PM 11196493 ER PT J AU Dignam, JJ AF Dignam, JJ TI Differences in breast cancer prognosis among African-American and Caucasian women SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Article ID RANDOMIZED CLINICAL-TRIALS; BLACK-WHITE DIFFERENCES; UNITED-STATES; SOCIOECONOMIC-FACTORS; RACIAL-DIFFERENCES; STAGE-I; RADIATION-THERAPY; ADJUVANT BREAST; SURVIVAL; RACE AB This review explores factors potentially contributing to the disparity in survival after breast cancer between African-American and Caucasian women in the United States. A number of factors have been implicated as the cause of poorer survival for black women, including clinical and pathologic features of the disease that are indicative of poor prognosis, economic resource inequities, and differences in treatment access and efficacy. The latter is explored in detail using data from the National Surgical Adjuvant Breast and Bowel Project (NSABP), a nationwide multicenter clinical trials group for breast and colorectal cancers. Key studies into the disparity in breast cancer survival are reviewed according to proposed principal determinants of poorer outcome for black women. Results among black and white women participating in several randomized NSABP clinical trials are also presented. Primary endpoints in those studies were clinical and pathologic disease characteristics at study entry, time to disease progression or new cancers, and total survival time after breast cancer diagnosis and treatment. In most studies reported in the literature, the primary explanatory factor alone, such as stage of disease at diagnosis, did not fully account for differences in outcome between groups; when additional factors were taken into account, however, prognoses became more similar. Results from the NS-ABP clinical trials similarly indicated that when stage of disease and treatment were comparable, outcomes for blacks did not differ markedly from those of whites. In summary, black women, diagnosed at comparable disease stage as white women and treated appropriately, tend to experience similar breast cancer prognoses and survival. However, important clinical and pathologic disease characteristics may continue to place certain women at increased risk of poorer outcome, and warrant continued study. The opportunity for incresed clinical trial participation by black women is encouraged. C1 Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. NSABP, Pittsburgh, PA USA. RP Dignam, JJ (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. NR 61 TC 95 Z9 96 U1 3 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0007-9235 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD JAN-FEB PY 2000 VL 50 IS 1 BP 50 EP 64 DI 10.3322/canjclin.50.1.50 PG 15 WC Oncology SC Oncology GA 276DE UT WOS:000084859700007 PM 10735015 ER PT S AU Kohn, KW Pommier, Y AF Kohn, KW Pommier, Y BE Liehr, JG Giovanella, BC Verschaegen, CF TI Molecular and biological determinants of the cytotoxic actions of camptothecins - Perspective for the development of new topoisomerase I inhibitors SO CAMPTOTHECINS: UNFOLDING THEIR ANTICANER POTENTIAL SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on the Camptothecins - Unfolding their Anticancer Potential CY MAR 17-20, 2000 CL ARLINGTON, VIRGINIA SP New York Acad Sci, Pharmacia & Upjohn ID RING-MODIFIED CAMPTOTHECIN; DEPENDENT PROTEIN-KINASE; MEDIATED DNA CLEAVAGE; CELL-CYCLE; ANTITUMOR-ACTIVITY; HUMAN P53; DAMAGE; REPLICATION; COMPLEXES; DERIVATIVES AB Camptothecin, originally discovered in 1957 as an antitumor activity in plant extracts, has recently become one of the most promising leads to new anticancer drugs. After lingering for many years, interest in camptothecin was revitalized in 1985 upon discovery of its specific action on topoisomerase I. Detailed elucidation of action mechanisms at the molecular, cellular, and pharmacologic levels has made camptothecin and its congeners perhaps the best understood among clinical anticancer drugs. Promising chemical variants of camptothecin, and recently other chemical categories of topoisomerase I-targeted drugs, provide unusually rich opportunities for rational drug selection and design. This is made possible by current concepts based, for the most part, on a sound experimental foundation, which points the way towards optimally effective therapy. C1 NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Kohn, KW (reprint author), NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NR 57 TC 61 Z9 66 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-291-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 922 BP 11 EP 26 PG 16 WC Oncology; Multidisciplinary Sciences SC Oncology; Science & Technology - Other Topics GA BT10N UT WOS:000171966000002 PM 11193886 ER PT S AU Takimoto, CH Thomas, R AF Takimoto, CH Thomas, R BE Liehr, JG Giovanella, BC Verschaegen, CF TI The clinical development of 9-aminocamptothecin SO CAMPTOTHECINS: UNFOLDING THEIR ANTICANER POTENTIAL SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on the Camptothecins - Unfolding their Anticancer Potential CY MAR 17-20, 2000 CL ARLINGTON, VIRGINIA SP New York Acad Sci, Pharmacia & Upjohn ID COLLOIDAL DISPERSION FORMULATION; TOPOISOMERASE-I INHIBITOR; PERFORMANCE LIQUID-CHROMATOGRAPHY; METASTATIC COLORECTAL-CARCINOMA; CONTINUOUS INTRAVENOUS-INFUSION; ADULT CANCER-PATIENTS; PHASE-I; CAMPTOTHECIN DERIVATIVES; SOLID TUMORS; ORAL 9-AMINOCAMPTOTHECIN AB 9-Aminocamptothecin (9-AC) is a topoisomerase I-targeting agent first synthesized by Wani and Wall in 1986. Because of its potent in vitro effects and promising preclinical activity in colorectal cancer animal models, it was designated a high-priority compound for further drug development by the NCI. In 1993, 9-AC first entered clinical trials as a 72-hour intravenous (i.v.) infusion. Predictable myelosuppression was the major dose-limiting toxicity, and pharmacokinetic studies showed a relatively short plasma half-life and unstable lactone ring. Unfortunately, phase II studies using this schedule showed minimal or no activity in tumors such as colorectal and lung cancer. Modest activity was observed in ovarian cancer and in refractory lymphomas. Efforts to improve systemic drug exposure by utilizing alternative schedules of administration of 9-AC such as prolonged, continuous intravenous infusions have also been tested. However, phase II studies of 120-hour weekly infusions of 9-AC have not shown improved activity against solid tumors such as colorectal cancer. More recently, a daily times 5 days i.v. administration schedule has been tested. Currently, further development of intravenously administered 9-AC for the treatment of colorectal cancer is not promising. Thus, topotecan and irinotecan remain the only two successfully developed topoisomerase I-targeting drugs in the United States. This experience with 9-AC raises important questions regarding how to best select new topoisomerase I-targeting drugs for future clinical development. C1 NCI, Div Clin Sci, Med Branch, Dev Therapeut Dept, Bethesda, MD 20889 USA. RP Takimoto, CH (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Med Oncol, 7703 Floyd Curl Dr,MSC 7884, San Antonio, TX 78229 USA. NR 64 TC 16 Z9 18 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-291-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 922 BP 224 EP 236 PG 13 WC Oncology; Multidisciplinary Sciences SC Oncology; Science & Technology - Other Topics GA BT10N UT WOS:000171966000022 PM 11193898 ER PT J AU Brown, MR Kohn, EC Hutter, RVP AF Brown, MR Kohn, EC Hutter, RVP TI The new millennium - Applying novel technology to the study of the cancer cell in situ SO CANCER LA English DT Reprint ID PROSTATIC INTRAEPITHELIAL NEOPLASIA; MICRODISSECTION; CONSTRUCTION C1 NCI, Pathol Lab, Bethesda, MD 20892 USA. St Barnabas Med Ctr, Dept Pathol, Livingston, NJ USA. RP Kohn, EC (reprint author), NCI, Pathol Lab, Bldg 10,Room 2A33,10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. NR 20 TC 6 Z9 6 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD JAN 1 PY 2000 VL 88 IS 1 BP 2 EP 5 DI 10.1002/(SICI)1097-0142(20000101)88:1<2::AID-CNCR2>3.0.CO;2-K PG 4 WC Oncology SC Oncology GA 270YW UT WOS:000084565600002 PM 10618599 ER PT J AU Anderson, WF Reeves, JE Elias, A Berkel, HJ AF Anderson, WF Reeves, JE Elias, A Berkel, HJ TI Outcome of patients with metastatic breast carcinoma treated at a private medical oncology clinic SO CANCER LA English DT Article DE metastatic breast carcinoma; chemotherapy; endocrine therapy; patient selection bias; generalizability ID HIGH-DOSE CHEMOTHERAPY; PROGENITOR-CELL SUPPORT; LONG-TERM SURVIVAL; ADJUVANT CHEMOTHERAPY; PROGNOSTIC FACTORS; CANCER INCIDENCE; DRUG-THERAPY; STAGE-II; TRIALS; RISK AB BACKGROUND. Metastatic breast carcinoma usually is fatal. The median survival after recurrence is 2 years. Five-year survival after recurrence is approximately 10-20%. Although encouraging data have been reported from clinical trials, two issues confound the translation of clinical research to the general medical community: patient selection bias and the absence of untreated controls. Therefore, the authors examined their community-based metastatic breast carcinoma patients, comparing their results with reports from clinical trials and with untreated historic controls. METHODS. This was a nonconcurrent cohort study of 407 community-based metastatic breast carcinoma patients treated at the authors' private medical oncology clinic in northeast Louisiana. Prognostic variables were correlated with survival time. RESULTS, The median age of the patients at the time of diagnosis of breast carcinoma was 61 years. The median age at the time of first recurrence was 65 years. The median overall survival and median survival after recurrence were 4.5 years and 20.1 months, respectively. The 5-year and 10-year survival rates were 17% and 2.5%, respectively. CONCLUSIONS. Although clinical trial participants and the authors' private practice cohort are incommensurable, outcomes in these disparate groups were similar but, unfortunately, not much different from those of untreated historic controls. Cancer 2000;88:95-107. (C) 2000 American Cancer Society. C1 NCI, Div Canc Prevent, Prevent Oncol Branch, Bethesda, MD 20892 USA. Canc Care Associates, Oklahoma City, OK USA. Glenwood Reg Med Ctr, Dept Pathol, W Monroe, LA USA. Louisiana State Univ, Med Ctr, Feist Weiller Canc Ctr, Sect Canc Control & Prevent, Shreveport, LA USA. RP Anderson, WF (reprint author), NCI, Div Canc Prevent, Prevent Oncol Branch, Execut Plaza S,Suite T41,6120 Execut Blvd,MSC 710, Bethesda, MD 20892 USA. NR 75 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD JAN 1 PY 2000 VL 88 IS 1 BP 95 EP 107 DI 10.1002/(SICI)1097-0142(20000101)88:1<95::AID-CNCR14>3.0.CO;2-P PG 13 WC Oncology SC Oncology GA 270YW UT WOS:000084565600014 PM 10618611 ER PT J AU Fisher, ER AF Fisher, ER TI Pathologic findings from the National Surgical Adjuvant Breast Project (NSABP) eight-year update of protocol B-17 - Reply SO CANCER LA English DT Letter C1 Allegheny Gen Hosp, Continuing Care Ctr, Natl Surg Adjuvant Breast & Bowel Project, Headquarters Pathol, Pittsburgh, PA 15212 USA. RP Fisher, ER (reprint author), Allegheny Gen Hosp, Continuing Care Ctr, Natl Surg Adjuvant Breast & Bowel Project, Headquarters Pathol, Pittsburgh, PA 15212 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD JAN 1 PY 2000 VL 88 IS 1 BP 243 EP 244 DI 10.1002/(SICI)1097-0142(20000101)88:1<243::AID-CNCR36>3.0.CO;2-E PG 2 WC Oncology SC Oncology GA 270YW UT WOS:000084565600036 ER PT J AU Hankey, BF Ries, LA Kosary, CL Feuer, EJ Merrill, RM Clegg, LX Edwards, BK AF Hankey, BF Ries, LA Kosary, CL Feuer, EJ Merrill, RM Clegg, LX Edwards, BK TI Partitioning linear trends in age-adjusted rates SO CANCER CAUSES & CONTROL LA English DT Article DE age-adjusted rates; cancer mortality; linear models; regression analysis; surveillance AB Objective: Surveillance of chronic diseases includes monitoring trends in age-adjusted rates in the general population. Statistics that are calculated to describe and compare trends include the annual percent change and the percent change for a specified time period. However, it is also of interest to determine the contribution specific diseases make to an overall trend in order to better understand the impact of interventions and changes in the prevalence of risk factors. The objective here is to provide a method for partitioning a linear trend in age-adjusted rates into disease-specific components. Methods: The method presented is based on linear regression. The decreasing trend in age-adjusted cancer mortality rates for the total United States during the period 1991-96 is analyzed to illustrate the method. Results: Trends in mortality for cancers of the colon/rectum, breast, lung/bronchus, and prostate are found to be responsible for 75% of the decreasing trend in cancer mortality. Conclusions: It is possible to partition an overall trend in age-adjusted rates under the assumption that it and the trends for all mutually exclusive and exhaustive subgroups of interest are linear. C1 NCI, Canc Stat Branch, Canc Surveillance Res Program, Div Canc Control & Populat Sci,EPN, Bethesda, MD 20892 USA. NCI, Appl Res Branch, Canc Surveillance Res Program, Div Canc Control & Populat Sci,EPN, Bethesda, MD 20892 USA. Brigham Young Univ, Dept Hlth Sci, Provo, UT 84602 USA. RP Edwards, BK (reprint author), NCI, Canc Stat Branch, Canc Surveillance Res Program, Div Canc Control & Populat Sci,EPN, Room 343,6130 Execut Blvd, Bethesda, MD 20892 USA. NR 3 TC 25 Z9 27 U1 1 U2 1 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 JAN PY 2000 VL 11 IS 1 BP 31 EP 35 DI 10.1023/A:1008953201688 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 257ZW UT WOS:000083814400004 PM 10680727 ER PT J AU Kokkinakis, DM Moschel, RC Pegg, AE Schold, SC AF Kokkinakis, DM Moschel, RC Pegg, AE Schold, SC TI Potentiation of BCNU antitumor efficacy by 9-substituted O-6-benzylguanines. Effect of metabolism SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE carmustine; O-6-benzyl-2 '-deoxyguanosine; O-6-benzylguanosine; O-6-benzyl-9-cyanomethylguanine; O-6-methylguanine-DNA methyltransferase ID HUMAN O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; HUMAN TUMOR-CELLS; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; DNA METHYLTRANSFERASE; ALKYLATING-AGENTS; DEPLETION; DERIVATIVES; XENOGRAFTS; RATS; 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA AB Purpose: O-6-Benzylguanine (BG), an O-6-methylguanine-DNA methyltransferase (MGMT) inactivator, potentiates the efficacy of 1,3-bis(2-chloroethyl)-1-nitro-sourea (BCNU) and of other DNA chloroethylating and methylating anticancer drugs and is currently undergoing clinical trials. O(6-)Benzyl-2'-deoxyguanosine (dBG), a less effective MGMT inactivator than BG in vitro, is at least as effective as BG in combination with BCNU against tumor xenografts in athymic mice. In order to identify the mechanism of dBG activation in in vivo systems we tested the metabolism, ability to inactivate MGMT, and efficacy to potentiate BCNU in vivo of two additional 9-substituted derivatives of BG, namely O-6-benzyl-9-cyanomethylguanine (CMBG) and O-6-benzylguanosine (BGS). Methods: Metabolism and disposition of these drugs was examined in athymic mice and Sprague-Dawley rats. MGMT suppression was determined in human medulloblastoma (Daoy) tumor xenografts in athymic mice following treatment with BGS, dBG, and CMBG and was compared with the loss of resistance to BCNU as determined by tumor growth delays. Results: Growth delays at 25 mg/m(2) BCNU and 133 mg/m(2) BG or equimolar doses of CMBG, BGS or dBG were 23.0, 2.5, 21.3 days, and 30.4 days, respectively. The above differences did not correlate with the ED(50)s Of 0.2, 13, 11 mu M, and 2 mu M determined for the above compounds, respectively, in cell free extracts. Differences in the efficacies of the 9-substituted compounds did correlate, however, with the extent of their metabolic conversion to BG. The maximum concentrations of BG in blood achieved after the administration of equimolar (250 mu mol/kg) doses of CMBG, BGS and dBG were 10, 30 mu M, and 55 mu M, respectively. Although such levels were lower than those achieved in circulation by administration of an equimolar amount of BC, BG levels persisted longer following treatments with BGS or dBG than after treatment with BG itself. Formation of BG was required for continuous and prolonged (>16 h) suppression of MGMT activity to non-detectable levels (< 5 fmol/mg protein). Conclusion: Metabolism of BGS and dBG to BG explains the unexpected high efficacy of these compounds in potentiating the antitumor activity of BCNU in the athymic mouse model. The faster and more effective suppression of tumor MGMT by dBG and its greater efficacy, as compared with BGS, also correlates with a more rapid accumulation of BG in blood after dBG than after BGS administration, which results in faster and complete suppression of MGMT in Daoy xenografts. Thus, metabolism of dBG and BGS to BG appears to be the determining factor for continuous and prolonged suppression of MGMT activity, and that near complete suppression of such activity during and following BCNU administration is required for the higher efficacy of treatments. Similarly, the failure of CMBG to suppress tumor MGMT to the same extent as BGS, in spite of their similar ED50 values, could be attributed to the metabolism of this compound mainly by pathways other than conversion to BG. C1 Univ Texas, SW Med Ctr, Dept Neurosurg, Dallas, TX 75235 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Cellular & Mol Physiol, Hershey, PA 17033 USA. Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Pharmacol, Hershey, PA 17033 USA. Duke Univ, Med Ctr, Div Neurol, Durham, NC 27710 USA. RP Kokkinakis, DM (reprint author), Univ Texas, SW Med Ctr, Dept Neurosurg, 5323 Harry Hines Blvd, Dallas, TX 75235 USA. FU NCI NIH HHS [CA 57725, CA78561] NR 22 TC 14 Z9 14 U1 0 U2 0 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 JAN PY 2000 VL 45 IS 1 BP 69 EP 77 DI 10.1007/PL00006746 PG 9 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 269FJ UT WOS:000084465800012 PM 10647505 ER PT J AU Huang, WY Newman, B Millikan, RC Conway, K Hulka, BS Schell, MJ Liu, ET AF Huang, WY Newman, B Millikan, RC Conway, K Hulka, BS Schell, MJ Liu, ET TI Risk of breast cancer according to the status of HER-2/neu oncogene amplification SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID POLYMERASE CHAIN-REACTION; GROWTH-FACTOR RECEPTOR; REPRODUCTIVE FACTORS; GENE AMPLIFICATION; MOLECULAR-BIOLOGY; PROTEIN; EXPRESSION; C-ERBB-2; OVEREXPRESSION; EPIDEMIOLOGY AB We examined risk factors for breast cancer after subdividing cases based on the presence of HER-2/neu oncogene amplification in their tumors. Data were from the Carolina Breast Cancer Study, a population-based, case-control study of 577 invasive breast cancer patients, diagnosed during 1993-1996 and ages 20-74 years, and 790 controls frequency-matched on race and age. Information on breast cancer risk factors was obtained from structured personal interviews. About 20% of paraffin-embedded tissues from the breast cancers of cases were identified as positive for HER-2/neu amplification (HER-2/neu+) by differential PCR, Early age at menarche, higher waist:hip ratio, and family history of breast or ovarian cancer were associated with elevated odds ratios (ORs) for both HER-2/neu+ and HER-2/neu- breast cancers. Breastfeeding for at least 1 year was inversely associated with HER-2/neu+ breast cancer [OR, 0.3; 95% confidence interval (CI), 0.1-0.7] more so than HER-2/neu- breast cancer (OR, 0.8; 95% CI, 0.5-1.2). Most of the remaining risk factors had ORs around 1.0 for both HER-2/neu+ and HER-2/neu- breast cancers, although a few exhibited possible associations with one disease subtype in analyses stratified by menopausal status. These study results suggest that most recognized breast cancer risk factors do not operate through HER-2/neu amplification in breast carcinogenesis. Differential effects of long-term breastfeeding by HER-2/neu amplification status have been observed in earlier studies and are provocative; however, the direction and magnitude of the associations have not been consistent. C1 Univ N Carolina, Lineberger Comprehens Canc Ctr, Carolina Breast Canc Study, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA. Galxo Wellcome Res & Dev, Worldwide Epidemiol, Res Triangle Pk, NC 27709 USA. Queensland Univ Technol, Sch Publ Hlth, Kelvin Grove 4059, Australia. NCI, NIH, Div Clin Sci, Bethesda, MD 20892 USA. RP Huang, WY (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Carolina Breast Canc Study, Chapel Hill, NC 27599 USA. RI Liu, Edison/C-4141-2008 FU NCI NIH HHS [P50-CA 58223] NR 42 TC 22 Z9 24 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2000 VL 9 IS 1 BP 65 EP 71 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 279QJ UT WOS:000085056400007 PM 10667465 ER PT J AU Falk, RT Rossi, SC Fears, TR Sepkovic, DW Migella, A Adlercreutz, H Donaldson, J Bradlow, HL Ziegler, RG AF Falk, RT Rossi, SC Fears, TR Sepkovic, DW Migella, A Adlercreutz, H Donaldson, J Bradlow, HL Ziegler, RG TI A new ELISA kit for measuring urinary 2-hydroxyestrone, 16 alpha-hydroxyestrone, and their ratio: Reproducibility, validity, and assay performance after freeze-thaw cycling and preservation by boric acid SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BREAST-CANCER RISK; ESTROGEN METABOLITES; WOMEN; ESTRADIOL; PROFILE; DIET AB There is considerable controversy regarding the role of estrogen metabolites in breast cancer risk, fueled in part by the development of a rapid ELISA that is suitable for large scale investigations, An earlier version of the ELISA could detect values of the 2-hydroxyestrone (2-OHE1) and 16 alpha-hydroxyestrone (16 alpha-OHE1) metabolites as tow as 2 ng/ml and produce consistent results in premenopausal urines, However, reproducibility was problematic in postmenopausal urines where concentrations of these compounds are much lower. In response to our concern, a new ELISA was developed with a sensitivity of 0.625 ng/ml, which we evaluated using the same pre- and postmenopausal urine samples analyzed in the earlier ELISA. In this report, we present findings on the new kit with regard to reproducibility of the 2-OHE1 and 16 alpha-OHE1 measurements, comparability of results with gas chromatography-mass spectroscopy values, and with regard to the stability of the metabolites after repeated freeze-thaw cycles and after preservation by boric acid, For the most part, we found the new ELISA to be reproducible, with assay coefficients of variation ranging from 10 to 20%, and intraclass correlation coefficients (ICCs) ranging from 80 to 95% in both the pre- and postmenopausal urines. ELISA results for 16 alpha-OHE1 differed from 1 day (i.e., batch) to the next, and the absolute values of the metabolites obtained by the ELISA were consistently lower than but well correlated with those obtained by gas chromatography-mass spectroscopy, Values of the 2-OHE1:16 alpha-OHE1 ratio also differed between the methods, but because the range of values was not large, the magnitude of these differences was not as great. For the ratio, the correlation between methods was excellent, and the ICCs were high for both groups of women, After preservation by boric acid, values of the ratio varied according to acid concentration but not in a linear fashion. Ratio values were similar in urine samples exposed to four different freeze-thaw cycle treatments, although values for all treatments were consistently lower in one batch. Because batch-to-batch variability was not negligible, it is advisable that matched cases and controls be analyzed in the same batch. Provided this is done, the relatively low assay coefficient of variation and high ICC demonstrate that the new ELISA kit can reliably measure the 2OHE(1):16 alpha-OHE1 ratio and detect small case-control differences in large population-based studies, where rapid and relatively easy laboratory methods are critical. C1 NCI, Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Off Sci Policy, Bethesda, MD 20892 USA. Stang Canc Res Lab, New York, NY 10021 USA. Univ Helsinki, Folkhalsan Res Ctr, FIN-00014 Helsinki, Finland. Univ Helsinki, Dept Clin Chem, FIN-00014 Helsinki, Finland. RP Falk, RT (reprint author), NCI, Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,MSC 7234, Bethesda, MD 20892 USA. NR 21 TC 44 Z9 45 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 JAN PY 2000 VL 9 IS 1 BP 81 EP 87 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 279QJ UT WOS:000085056400009 PM 10667467 ER PT J AU Ziogas, A Gildea, M Cohen, P Bringman, D Taylor, TH Seminara, D Barker, D Casey, G Haile, R Liao, SY Thomas, D Noble, B Kurosaki, T Anton-Culver, H AF Ziogas, A Gildea, M Cohen, P Bringman, D Taylor, TH Seminara, D Barker, D Casey, G Haile, R Liao, SY Thomas, D Noble, B Kurosaki, T Anton-Culver, H TI Cancer risk estimates for family members of a population-based family registry for breast and ovarian cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENETIC EPIDEMIOLOGY; IN-SITU; HISTORY; AGE; BRCA1; MUTATIONS; CARCINOMA; WOMEN; ONSET; IDENTIFICATION AB Population-based breast and ovarian cancer family registries can facilitate studies to evaluate genetic and environmental factors in the etiology of these malignancies. The purpose of this study is to describe what is, as far as we know, the first population-based breast and ovarian cancer family registry and to estimate breast and ovarian cancer risk in relatives of breast and ovarian cancer probands, Population-based consecutive incident cases of breast and ovarian cancer were invited to participate in the University of California, Irvine breast and ovarian family registry. In this study, we report data on 1567 breast cancer and 328 ovarian cancer probands, The operational components of this family registry include enrollment of probands, family history interviewing, confidentiality, pathology, verification and review, biospecimen bank, statistical/genetic analysis, and special studies on positional cloning of known genes. All of the components are tracked through the University of California, Irvine Genetic Research Information System. In non-Hispanic-white breast cancer probands, relative risk (RR) of breast cancer in mothers and sisters is significantly elevated [RR = 1.7 and 95% confidence interval (CI) = 1.4-2.0 and RR = 2.8 and 95% CI = 2.3-3.3, respectively]. In families of ovarian cancer probands, mothers are at increased risk of ovarian cancer (RR = 4.6; 95% CI, 2.1-8.7), RR of breast cancer in mothers of Hispanic breast cancer probands is significantly elevated (RR = 4.9; 95% CI, 2.6-8.5). No elevation of breast or ovarian cancer risk was observed among relatives of Asian probands, In general, there is a decrease in RR among mothers and sisters with increase in age of onset of probands, In second-degree relatives and first cousins, the breast cancer hazards ratios increase with increase in the number of affected first-degree relatives and decrease with increase in age at onset of the proband. C1 Univ Calif Irvine, Dept Med, Div Epidemiol, Irvine, CA 92697 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ Utah, Dept Physiol, Salt Lake City, UT 84108 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ So Calif, Dept Prevent Med, Los Angeles, CA 90033 USA. RP Anton-Culver, H (reprint author), Univ Calif Irvine, Dept Med, Div Epidemiol, 224 Irvine Hall, Irvine, CA 92697 USA. FU NCI NIH HHS [CA-58860] NR 45 TC 50 Z9 53 U1 1 U2 2 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 JAN PY 2000 VL 9 IS 1 BP 103 EP 111 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 279QJ UT WOS:000085056400012 PM 10667470 ER PT J AU Seth, P AF Seth, P TI Pre-clinical studies with tumor suppressor genes SO CANCER GENE THERAPY SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article ID WILD-TYPE P53; BREAST-CANCER CELLS; KINASE INHIBITOR P27(KIP1); CYCLE ARREST; LUNG-CANCER; IN-VIVO; THERAPY; APOPTOSIS; PROTEIN; GROWTH C1 NCI, Med Breast Canc Sect, Med Branch, NIH, Bethesda, MD 20892 USA. RP Seth, P (reprint author), NCI, Med Breast Canc Sect, Med Branch, NIH, Bldg 10,Room 12 N226, Bethesda, MD 20892 USA. NR 52 TC 2 Z9 2 U1 0 U2 0 PU KLUWER ACADEMIC / PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2000 VL 465 BP 183 EP 192 PG 10 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA BQ12U UT WOS:000087237400017 PM 10810626 ER PT J AU Campbell, I Moyana, T Carlsen, S Zheng, CY Xiang, J AF Campbell, I Moyana, T Carlsen, S Zheng, CY Xiang, J TI Adenoviral transfer of xenogeneic MHC class I gene results in loss of tumorigenicity and inhibition of tumor growth SO CANCER GENE THERAPY LA English DT Article DE xenogeneic major histocompatibility complex class I; allogeneic major histocompatibility complex class I; gene therapy; recombinant adenovirus ID HISTOCOMPATIBILITY COMPLEX GENE; T-CELL RESPONSE; LUNG-CARCINOMA; H-2KB GENE; EXPRESSION; ANTIGEN; REJECTION; IMMUNITY; CANCER; IMMUNOTHERAPY AB The immune system confers protection against a variety of pathogens and contributes to the destruction of neoplastic cells. Foreign major histocompatibility complex (MHC) protein serves as a potent stimulus to the immune system. In this report, a mouse H-2K(b) gene was introduced into two poorly immunogenic tumor cell lines, a mouse colonic carcinoma cell line, MCA-26 (H-2 K-d), and a rat mammalian carcinoma cell line, LN-4, in an effort to stimulate tumor rejection. Our results showed that the expression of xenogeneic MHC class I antigen completely abolished the LN-4 tumorigenicity in rats, whereas the expression of allogeneic MHC class I antigen only partially reduced the MCA-26 tumorigenicity in mice. Rats with tumor regression of LN-4/H-2K(b) developed a T helper type 1-dominant response, whereas rats with LN-4 tumor growth developed a T helper type 2-dominant response. The immunized rats that experienced LN-4/H-2Kb tumor regression further developed protective immunity against a subsequent challenge of LN-4 cells. This protective immunity was mediated by the LN-4 tumor-specific cellular immune response against both the transduced and the parental LN-4 cells. Recombinant adenoviral vectors are highly efficient at in vitro and in vivo gene delivery. The LN4 cells transfected with the recombinant adenovirus AdV-H-2K(b) in vitro expressed the cell surface H-2K(b) molecule by fluorescence-activated cell sorter analysis. Adenovirus-mediated H-2K(b) gene transfer in vivo can further significantly inhibit pre-established LN-4 tumors. Those rats with complete tumor regression further developed protective immunity against the subsequent challenge of a parental LN-4 tumor. Therefore, our study indicates that the adenovirus-mediated transfer of xenogeneic MHC class I gene may be an effective alternative to the current protocol of cancer gene therapy in which the allogeneic MHC class I gene is used. C1 Univ Saskatchewan, Saskatoon Canc Ctr, Coll Med, Dept Microbiol, Saskatoon, SK S7N 4H4, Canada. Univ Saskatchewan, Saskatoon Canc Ctr, Coll Med, Dept Oncol, Saskatoon, SK S7N 4H4, Canada. Univ Saskatchewan, Saskatoon Canc Ctr, Coll Med, Dept Pathol, Saskatoon, SK S7N 4H4, Canada. NIDR, Gene Therapy Branch, NIH, Bethesda, MD 20892 USA. RP Xiang, J (reprint author), Univ Saskatchewan, Saskatoon Canc Ctr, Coll Med, Dept Microbiol, 20 Campus Dr, Saskatoon, SK S7N 4H4, Canada. NR 34 TC 6 Z9 6 U1 0 U2 0 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 JAN PY 2000 VL 7 IS 1 BP 37 EP 44 DI 10.1038/sj.cgt.7700116 PG 8 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 285RH UT WOS:000085401500005 PM 10678354 ER PT J AU Puhlmann, M Brown, CK Gnant, M Huang, J Libutti, SK Alexander, HR Bartlett, DL AF Puhlmann, M Brown, CK Gnant, M Huang, J Libutti, SK Alexander, HR Bartlett, DL TI Vaccinia as a vector for tumor-directed gene therapy: Biodistribution of a thymidine kinase-deleted mutant SO CANCER GENE THERAPY LA English DT Article; Proceedings Paper CT 88th Annual Meeting of the American-Association-for-Cancer-Research CY APR 12-16, 1997 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Canc Res DE vaccinia; gene therapy; biodistribution; luciferase; thymidine kinase ID IN-VITRO; VIRUS; EXPRESSION; PROMOTERS; PROTEINS AB Tumor-directed gene therapy, such as "suicide gene" therapy, requires high levels of gene expression in a high percentage of tumor cells in vivo to be effective. Current vector strategies have been ineffective in achieving these goals. This report introduces the attenuated (thymidine kinase (TK)-negative) replication-competent vaccinia virus (VV) as a potential vector for tumor-directed gene therapy by studying the biodistribution of VV in animal tumor models. A TK-deleted recombinant VV (Western Reserve strain) expressing luciferase on a synthetic promoter was constructed. Luciferase activity was measured in vitro after transduction of a variety of human and murine tumor cell lines and in vivo after intraperitoneal (i.p.) delivery in C57BL/6 mice with 7-day i.p, rumors (10(6) MC-38 cells). Three other in vivo tumor models were examined for tumor-specific gene expression after intravenous delivery of VV (human melanoma in nude mice, adenocarcinoma liver metastasis in immunocompetent mice, and subcutaneous sarcoma in the rail. In addition, a replication-incompetent vaccinia (1 mu g of psoralen and ultraviolet light, 365 nm, 4 minutes) was tested in vitro and in vivo and compared with active virus. Luciferase activity in i.p, tumors at 4 days after i.p. injection of VV was >7000-fold higher than lung, >3000-fold higher than liver, and >250-fold higher than ovary. In addition, intravenous injection of VV resulted in markedly higher tumor luciferase activity compared with any other organ in every model tested (up to 188,000-fold higher than liver and 77,000-fold higher than lung). Inactivation of the virus resulted in negligible gene expression in viva In summary, VV has a high transduction efficiency in tumor cells with high levels of gene expression. The results suggest a selective in vivo replication of TK-deleted VV in tumor cells. Replication competent, TK-deleted VV appears to be an ideal vector for testing the in vivo delivery of toxic genes to tumor cells. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Bartlett, DL (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B17,10 Ctr Dr, Bethesda, MD 20892 USA. OI Gnant, Michael/0000-0003-1002-2118 NR 18 TC 96 Z9 101 U1 0 U2 5 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 JAN PY 2000 VL 7 IS 1 BP 66 EP 73 DI 10.1038/sj.cgt.7700075 PG 8 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 285RH UT WOS:000085401500009 PM 10678358 ER PT J AU Yerushalmi, N Brinkmann, U Brinkmann, E Pai, L Pastan, I AF Yerushalmi, N Brinkmann, U Brinkmann, E Pai, L Pastan, I TI Attenuating the growth of tumors by intratumoral administration of DNA encoding Pseudomonas exotoxin via cationic liposomes SO CANCER GENE THERAPY LA English DT Article DE cationic lipids; transfection; cancer therapy ID MEDIATED GENE-TRANSFER; IN-VIVO; BREAST-CANCER; NUDE-MICE; THERAPY; CELLS; INHIBITION; EFFICIENCY; COMPLEXES; DELIVERY AB A gene therapy approach was taken to inhibit tumor growth by transfecting tumor cells with a plasmid encoding a truncated but active form of Pseudomonas exotoxin A (PE), using cationic lipids as the transfection reagent. Cells transfected with this plasmid express PE intracellularly and undergo apoptosis, Transfection was optimized in vitro using two cationic lipids, DOGS and DOSPER. A ratio of between 1:4 and 1:10 (wt/wt) was found to be optimal for DOSPER, and the ratio 1:4 was used for the in vivo study when a smaller injection volume was desired. Estimating the activity of the PE-encoding plasmid was done both directly, by counting cells in vitro after transfection, and by using a cytotoxicity assay, and indirectly, by cotransfecting the plasmid with a plasmid carrying a reporter beta-galactosidase gene and observing a reduction in beta-galactosidase activity with increasing amounts of the PE-encoding plasmid. The cotransfection method was found to be very sensitive, and showed transfection of cells even with 1-2 ng of the PE-encoding plasmid per 10(5) cells. Complexes of the PE-encoding plasmid together with cationic lipid were injected into tumor xenografts in athymic nude mice. The tumor growth of transfected tumors was attenuated compared with control untreated tumors or tumors transfected with a nontoxin-expressing vector. These results indicate the potential of such a treatment for attenuating solid tumor growth in vivo. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37,Room 4E16,37 Convent Dr,MSC4255, Bethesda, MD 20892 USA. NR 20 TC 17 Z9 18 U1 1 U2 3 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 JAN PY 2000 VL 7 IS 1 BP 91 EP 96 DI 10.1038/sj.cgt.7700115 PG 6 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 285RH UT WOS:000085401500012 PM 10678361 ER PT J AU Pincus, MR Brandt-Rauf, PW Michl, J Carty, RP Friedman, FK AF Pincus, MR Brandt-Rauf, PW Michl, J Carty, RP Friedman, FK TI ras-p21-induced cell transformation: Unique signal transduction pathways and implications for the design of new chemotherapeutic agents SO CANCER INVESTIGATION LA English DT Review ID ONCOGENIC RAS-P21 PROTEIN; ENCODED P21 PROTEIN; N-TERMINAL KINASE; OOCYTE MATURATION; XENOPUS OOCYTES; BINDING DOMAIN; 3-DIMENSIONAL STRUCTURES; RAS FARNESYLATION; GENE-EXPRESSION; DNA-SYNTHESIS C1 VA Med Ctr, Dept Pathol & Lab Med, Brooklyn, NY 11209 USA. SUNY Hlth Sci Ctr, Dept Pathol, Brooklyn, NY 11203 USA. Columbia Univ, Coll Phys & Surg, Dept Environm Sci, New York, NY USA. NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Pincus, MR (reprint author), VA Med Ctr, Dept Pathol & Lab Med, 800 Poly Pl, Brooklyn, NY 11209 USA. RI Friedman, Fred/D-4208-2016 FU NCI NIH HHS [CA 69243, R01 CA 42500] NR 56 TC 28 Z9 28 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2000 VL 18 IS 1 BP 39 EP 50 DI 10.3109/07357900009023061 PG 12 WC Oncology SC Oncology GA 281DD UT WOS:000085142100007 PM 10701366 ER PT J AU Hartge, P AF Hartge, P TI Hair dyes, cancer, and epidemiology SO CANCER INVESTIGATION LA English DT Editorial Material C1 NCI, Bethesda, MD 20892 USA. RP Hartge, P (reprint author), NCI, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2000 VL 18 IS 4 BP 408 EP 408 DI 10.3109/07357900009012186 PG 1 WC Oncology SC Oncology GA 305PK UT WOS:000086549300016 PM 10808379 ER PT J AU Sparber, A Jonas, W White, J Derenzo, E Johnson, E Bergerson, S AF Sparber, A Jonas, W White, J Derenzo, E Johnson, E Bergerson, S TI Cancer clinical trials and subject use of natural herbal products SO CANCER INVESTIGATION LA English DT Review ID MEDICINE; COMPLEMENTARY C1 NIH, Dept Nursing, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Family Practice, Bethesda, MD 20814 USA. NCI, Off Canc Complementary & Alternat Med, Bethesda, MD 20892 USA. Derenzo & Associates, Rockville, MD USA. NIH, Dept Nutr, Bethesda, MD 20892 USA. RP Sparber, A (reprint author), NIH, Dept Nursing, Bldg 10,Room 7D55, Bethesda, MD 20892 USA. NR 10 TC 7 Z9 7 U1 1 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2000 VL 18 IS 5 BP 436 EP 439 DI 10.3109/07357900009032815 PG 4 WC Oncology SC Oncology GA 315WJ UT WOS:000087135700005 PM 10834028 ER PT J AU Montuenga, LM Mulshine, JL AF Montuenga, LM Mulshine, JL TI New molecular strategies for early lung cancer detection SO CANCER INVESTIGATION LA English DT Article ID K-RAS ONCOGENE; RETINOBLASTOMA SUSCEPTIBILITY GENE; NUCLEAR RIBONUCLEOPROTEIN A2/B1; PREINVASIVE BRONCHIAL LESIONS; GROWTH-FACTOR RECEPTOR; 13-CIS-RETINOIC ACID; ABERRANT METHYLATION; SCREENING TOOLS; FORMER SMOKERS; EXPRESSION C1 Univ Navarra, Sch Med, Dept Histol & Pathol, E-31080 Pamplona, Spain. NCI, Intervent Sect, Med Branch, NIH, Bethesda, MD 20892 USA. RP Mulshine, JL (reprint author), Dept Cell & Canc Biol, Bldg 10,Room 12N226,10 Ctr Dr,MSC 1906, Bethesda, MD 20892 USA. NR 65 TC 6 Z9 6 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2000 VL 18 IS 6 BP 555 EP 563 DI 10.3109/07357900009012195 PG 9 WC Oncology SC Oncology GA 336DD UT WOS:000088285900008 PM 10923104 ER PT J AU Bishop, PC Rao, VK Wilson, WH AF Bishop, PC Rao, VK Wilson, WH TI Burkitt's lymphoma: Molecular pathogenesis and treatment SO CANCER INVESTIGATION LA English DT Article ID NONCLEAVED-CELL LYMPHOMA; NON-HODGKINS-LYMPHOMA; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; NATIONAL-CANCER-INSTITUTE; TUMOR-SUPPRESSOR GENE; CENTER B-CELLS; C-MYC; ANTICANCER AGENTS; RANDOMIZED TRIAL; VIRUS INFECTION C1 NCI, Div Clin Sci, Med Branch, Bethesda, MD 20892 USA. RP Wilson, WH (reprint author), NCI, Div Clin Sci, Med Branch, Bld 10-12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 66 TC 33 Z9 35 U1 0 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2000 VL 18 IS 6 BP 574 EP 583 DI 10.3109/07357900009012197 PG 10 WC Oncology SC Oncology GA 336DD UT WOS:000088285900010 PM 10923106 ER PT J AU Salomon, DS AF Salomon, DS TI Cell-cell and cell-extracellular matrix adhesion molecules communicate with growth factor receptors: An interactive signaling web SO CANCER INVESTIGATION LA English DT Editorial Material ID INTEGRIN-LINKED KINASE; GLYCOGEN-SYNTHASE KINASE-3; BETA-CATENIN; E-CADHERIN; SURVIVAL; CANCER; GENE C1 NCI, Tumor Growth Factor Sect, Lab Tumor Immunol & Biol, Div Basic Sci,NIH, Bethesda, MD 20892 USA. RP Salomon, DS (reprint author), NCI, Tumor Growth Factor Sect, Lab Tumor Immunol & Biol, Div Basic Sci,NIH, Bethesda, MD 20892 USA. NR 18 TC 2 Z9 3 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2000 VL 18 IS 6 BP 591 EP 593 DI 10.3109/07357900009012199 PG 3 WC Oncology SC Oncology GA 336DD UT WOS:000088285900012 PM 10923108 ER PT J AU Arun, B Curti, BD Longo, DL Stevens, D Alvord, WG Gause, BL Watson, T Kopp, WC Janik, JE AF Arun, B Curti, BD Longo, DL Stevens, D Alvord, WG Gause, BL Watson, T Kopp, WC Janik, JE TI Elevations in serum soluble interleukin-2 receptor levels predict relapse in patients with hairy cell leukemia SO CANCER JOURNAL FROM SCIENTIFIC AMERICAN LA English DT Article DE follow-up study; disease progression; lymphoproliferative malignancy; neutropenia; human ID TERM FOLLOW-UP; ALPHA-INTERFERON; 2-CHLORODEOXYADENOSINE; PENTOSTATIN; REMISSION AB PURPOSE Interferon-alfa, 2'-deoxycoformycin, and 2-chlorodeoxy-adenosine (2-CdA) are effective in the management of patients with hairy cell leukemia These agents produce remissions in most patients, but relapses occur with ail three drugs. The optimal means to follow patients for relapse after treatment has not been determined a METHODS We retrospectively examined serial serum soluble interleukin-2 receptor levels (sIL-2R) and absolute granulocyte counts in eight patients with relapsed hairy cell leukemia. All were treated with 2-CdA at the time of relapse. Serum samples were available at 3- to 6-month intervals from 5 to 9 years before relapse and 2-CdA treatment. RESULTS sIL-2R levels increase only in patients who go on to relapse. sIL-2R levels doubled a mean of 17.1 months (range, 4-36 months) before absolute granulocyte count decreased by 50%, DISCUSSION Demonstration of a rising serum sIL-2R level in patients with hairy cell leukemia identified those,vith an increased risk of relapse who need more frequent observation than patients who maintain a stable sIL-2R level. Early intervention may ameliorate the toxicity of salvage therapy because disease-related neutropenia may be anticipated. C1 NIA, NIH, Gerontol Res Ctr, Baltimore, MD 21224 USA. Georgetown Univ, Vincent T Lombardi Canc Res Ctr, Washington, DC USA. NCI, Clin Res Branch, Biol Response Modifiers Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. NCI, Clin Serv Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. NCI, Data Management Serv Inc, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Longo, DL (reprint author), NIA, NIH, Gerontol Res Ctr, Box 9,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 16 TC 8 Z9 9 U1 0 U2 1 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 USA SN 1081-4442 J9 CANCER J SCI AM JI Cancer J. Sci. Am. PD JAN-FEB PY 2000 VL 6 IS 1 BP 21 EP 24 PG 4 WC Oncology SC Oncology GA 281NA UT WOS:000085166100004 PM 10696734 ER PT S AU Hursting, SD AF Hursting, SD BE Mason, J Nitenberg, G TI Nutritional modulation of the carcinogenesis process: Targets and examples SO CANCER & NUTRITION PREVENTION AND TREATMENT SE NESTLE NUTRITION WORKSHOP SERIES: CLINICAL & PERFORMANCE PROGRAM LA English DT Proceedings Paper CT 4th Nestle Nutrition Workshop CY OCT 31-NOV 04, 1999 CL KUALA LUMPUR, MALAYSIA ID SKIN TUMOR PROMOTION; DIETARY RESTRICTION; CALORIE RESTRICTION; BENZOPYRENE-INDUCED NEOPLASIA; ARYLALKYL ISOTHIOCYANATES; SPONTANEOUS TUMORIGENESIS; CANCER CHEMOPREVENTION; ORGANOSULFUR COMPOUNDS; DIALLYL SULFIDE; TRANSGENIC MICE C1 NCI, NIH, Div Canc Prevent, Bethesda, MD 20892 USA. RP Hursting, SD (reprint author), NCI, NIH, Div Canc Prevent, 6130 Execut Blvd,Suite T-41, Bethesda, MD 20892 USA. NR 99 TC 1 Z9 1 U1 0 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1422-7584 BN 3-8055-7081-3 J9 NES NUTR WS PY 2000 VL 4 BP 1 EP 21 PG 21 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA BS72H UT WOS:000170993300002 PM 11490567 ER PT S AU Albanes, D AF Albanes, D BE Mason, J Nitenberg, G TI Prostate cancer: Epidemiology and prevention SO CANCER & NUTRITION PREVENTION AND TREATMENT SE NESTLE NUTRITION WORKSHOP SERIES: CLINICAL & PERFORMANCE PROGRAM LA English DT Proceedings Paper CT 4th Nestle Nutrition Workshop CY OCT 31-NOV 04, 1999 CL KUALA LUMPUR, MALAYSIA ID VITAMIN-D METABOLITES; UNITED-STATES; BETA-CAROTENE; FOLLOW-UP; ALPHA-TOCOPHEROL; BODY-SIZE; CARDIOVASCULAR-DISEASE; SUBSEQUENT DEVELOPMENT; CONTROLLED TRIAL; FATTY-ACIDS C1 NCI, Canc Prevent Studies Branch, Bethesda, MD 20892 USA. RP Albanes, D (reprint author), NCI, Canc Prevent Studies Branch, 6006 Execut Blvd,Suite 321, Bethesda, MD 20892 USA. RI Albanes, Demetrius/B-9749-2015 NR 45 TC 1 Z9 1 U1 0 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1422-7584 BN 3-8055-7081-3 J9 NES NUTR WS PY 2000 VL 4 BP 55 EP 65 PG 11 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA BS72H UT WOS:000170993300005 PM 11490582 ER PT J AU Richardson, MA White, JD AF Richardson, MA White, JD TI Complementary/alternative medicine and cancer research - A national initiative SO CANCER PRACTICE LA English DT Article ID ALTERNATIVE MEDICINE; UNITED-STATES; THERAPIES; PREVALENCE; SCIENCE; TRENDS C1 Univ Texas, Sch Publ Hlth, Ctr Alternat Med Res, Houston, TX USA. NCI, Off Canc Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Richardson, MA (reprint author), Univ Texas, Sch Publ Hlth, Ctr Alternat Med Res, Houston, TX USA. FU NCI NIH HHS [5 U24 CA66826-03] NR 32 TC 11 Z9 11 U1 2 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1065-4704 J9 CANCER PRACT JI Cancer Pract. PD JAN-FEB PY 2000 VL 8 IS 1 BP 45 EP 48 DI 10.1046/j.1523-5394.2000.81010.x PG 4 WC Oncology; Health Care Sciences & Services; Nursing SC Oncology; Health Care Sciences & Services; Nursing GA 278LL UT WOS:000084991200012 PM 10732539 ER PT J AU Salnikow, K Blagosklonny, MV Ryan, H Johnson, R Costa, M AF Salnikow, K Blagosklonny, MV Ryan, H Johnson, R Costa, M TI Carcinogenic nickel induces genes involved with hypoxic stress SO CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; MESSENGER-RNA STABILITY; INDUCIBLE FACTOR-1; ERYTHROPOIETIN GENE; TRANSFORMED CELLS; PROTEIN; EXPRESSION; INDUCTION; WORKERS AB Carcinogenic nickel compounds alter the program of gene expression in normal cells and induce a pattern of gene expression similar to that found in nickel-induced cancers, Here we have demonstrated that nickel exposure induced hypoxic signaling pathways by inducing hypoxia-inducible transcription factor-1 (HIF-1), which mediated the induction of genes required by cells to survive hypoxia. We also show that a new gene, Cap43, is dependent upon HIF-1 because only HIF-1-proficient cells induced Cap43 when exposed to either hypoxia or nickel. We also show that glyceraldehyde-3-phosphate dehydrogenase, a gene induced by hypoxia through HIF-1, was similar to Cap43 in that it required HIF-1-proficient cells to be induced by either nickel or hypoxia, These data demonstrate that nickel exposure turns on signaling for hypoxic stress, which may be important in its carcinogenesis. C1 NYU, Sch Med, Nelson Inst Environm Med, New York, NY 10016 USA. NYU, Sch Med, Kaplan Comprehens Canc Ctr, New York, NY 10016 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Biol, Ctr Mol Genet, La Jolla, CA 92093 USA. RP Salnikow, K (reprint author), NYU, Sch Med, Dept Environm Med, 550 1st Ave, New York, NY 10016 USA. RI costa, max/H-1754-2012; OI Johnson, Randall/0000-0002-4084-6639 FU NCI NIH HHS [CA13687]; NIEHS NIH HHS [ES00260, ES05512] NR 28 TC 126 Z9 136 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 JAN 1 PY 2000 VL 60 IS 1 BP 38 EP 41 PG 4 WC Oncology SC Oncology GA 274KL UT WOS:000084765000009 PM 10646848 ER PT J AU Leitner, WW Ying, H Driver, DA Dubensky, TW Restifo, NP AF Leitner, WW Ying, H Driver, DA Dubensky, TW Restifo, NP TI Enhancement of tumor-specific immune response with plasmid DNA replicon vectors SO CANCER RESEARCH LA English DT Article ID VIVO GENE-TRANSFER; APOPTOTIC CELLS; VIRUS; VACCINES; ANTIGEN; IMMUNIZATION; EXPRESSION; PATHWAY AB To enhance the immunogenicity of nucleic acid vaccines, we used plasmid DNA vectors that contained replicons derived from the prototype alphavirus, Sindbis, and another alphavirus, Semliki Forest virus. When transfected into cells or injected directly into animal muscle, these plasmids launch a self-replicating RNA vector (replicon) which in turn directs the expression of a model tumor antigen. Immunization with plasmid DNA replicons elicited immune responses at doses 100 to 1000-fold lower than conventional DNA plasmids and effectively treated mice bearing an experimental tumor expressing the model antigen. Significantly, replicon-based DNA plasmids did not produce a greater quantity of antigen; instead, antigen production differed qualitatively. Plasmid DNA replicons mediated antigen production that was homogeneous in all transfected cells and associated with the apoptotic death of the host cells. Because of their safety and efficacy,:plasmid DNA replicons may be useful in the development of recombinant vaccines for infectious diseases and cancer. C1 NCI, NIH, Bethesda, MD 20892 USA. Chiron Corp, Ctr Gene Therapy, Emeryville, CA 94608 USA. RP Leitner, WW (reprint author), NCI, NIH, Bldg 10,Room 2B46, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008; Leitner, Wolfgang/F-5741-2011; OI Leitner, Wolfgang/0000-0003-3125-5922; Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 24 TC 132 Z9 159 U1 0 U2 1 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 JAN 1 PY 2000 VL 60 IS 1 BP 51 EP 55 PG 5 WC Oncology SC Oncology GA 274KL UT WOS:000084765000012 PM 10646851 ER PT J AU Goebel, SU Vortmeyer, AO Zhuang, ZP Serrano, J Jensen, RT Lubensky, IA AF Goebel, SU Vortmeyer, AO Zhuang, ZP Serrano, J Jensen, RT Lubensky, IA TI Identical clonality of sporadic gastrinomas at multiple sites SO CANCER RESEARCH LA English DT Article ID ALLELIC DELETIONS; CHROMOSOME 11Q13; MEN1; GENE; TUMORS AB Gastrinomas are neuroendocrine neoplasms that occur sporadically and in patients with multiple endocrine neoplasia type 1 (MEN1), In MEN1, multiple gastrinomas have been shown to arise by independent clonal events (Debelenko, et al,, Cancer Res., 57: 2238-2243, 1997). The purpose of the present study was to analyze clonality in 20 sporadic gastrinomas from eight patients in whom the tumor was present in at least two separate sites. A combination of methods was used to assess clonality, including MEN1 gene mutation analysis, loss of heterozygosity analysis of the MEN1 locus, and analysis of X-chromosome inactivation at the human androgen receptor locus (human androgen receptor analysis). In three patients, a semantic MEN1 gene mutation was detected in the tumor. Identical mutations were found in other tumors at different sites within the same patients. Human androgen receptor analysis in three informative patients and loss of heterozygosity analysis in five patients revealed identical clonal patterns in the tumors from multiple sites in each patient, We conclude that sporadic gastrinomas at multiple sites are monoclonal and that MEN1 gene alterations in gastrinomas occur before the development of tumor metastases. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Lubensky, IA (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2A33,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 19 TC 12 Z9 12 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 JAN 1 PY 2000 VL 60 IS 1 BP 60 EP 63 PG 4 WC Oncology SC Oncology GA 274KL UT WOS:000084765000014 PM 10646853 ER PT J AU Bernhard, EJ Mitchell, JB Deen, D Cardell, M Rosenthal, DI Brown, JM AF Bernhard, EJ Mitchell, JB Deen, D Cardell, M Rosenthal, DI Brown, JM TI Re-evaluating gadolinium(III) texaphyrin as a radiosensitizing agent SO CANCER RESEARCH LA English DT Article ID TUMOR AB Gadolinium(III) texaphyrin (Gd-tex) was recently proposed as a radiosensitizing agent that combines preferential tumor uptake with detection of drug localization by magnetic resonance imaging (S. W, Young el al,, Proc, Natl, Acad, Sci, USA, 93: 6610-6615, 1996), In view of the initial report on this compound, four radiobiology laboratories undertook independent efforts to further study radiosensitization by Gd-tex, In addition to repeating the previously reported studies on Gd-tex in HT-29 cells, we tested five other human tumor cell lines (U-87 MG, U251-NCI, SW480, A549, and MCF-7), These studies included a Gd tex treatment period of 24 h before irradiation (as in the original publication), with concentrations of Gd-tex ranging from 20-500 mu M. In neither the HT-29 cells nor any of the other five human cell lines did we see radiation sensitization by Gd-tex, Two cell lines (MCF-7 and U-87 MG) were further tested for radiosensitization by Gd-tex under hypoxic conditions. No radiosensitization was observed in either case. Finally, the radiation response of two tumor lines were assessed in vivo. Neither HT-29 xenografts in severe combined immunodeficient (SCID) mice nor RIF-1 tumors growing in C3H mice demonstrated radiosensitization after Gd-tex treatment before single or fractionated doses of radiation. Our results raise questions about the efficacy of Gd-tex as a radiosensitizing agent. C1 Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. NCI, Radiat Biol Branch, Div Clin Sci, Bethesda, MD 20892 USA. Univ Calif San Francisco, Brain Tumor Res Ctr, San Francisco, CA 94143 USA. Stanford Univ, Sch Med, Dept Radiat Oncol, Stanford, CA 94305 USA. RP Bernhard, EJ (reprint author), Univ Penn, Dept Radiat Oncol, 185 john Morgan Bldg, Philadelphia, PA 19104 USA. FU NCI NIH HHS [CA73820, CA-15201] NR 15 TC 37 Z9 37 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 JAN 1 PY 2000 VL 60 IS 1 BP 86 EP 91 PG 6 WC Oncology SC Oncology GA 274KL UT WOS:000084765000019 PM 10646858 ER PT J AU Hayes, RB Zhang, L Yin, S Swenberg, JA Xi, L Wiencke, J Bechtold, WE Yao, M Rothman, N Haas, R O'Neill, JP Zhang, D Wiemels, J Dosemeci, M Li, G Smith, MT AF Hayes, RB Zhang, L Yin, S Swenberg, JA Xi, L Wiencke, J Bechtold, WE Yao, M Rothman, N Haas, R O'Neill, JP Zhang, D Wiemels, J Dosemeci, M Li, G Smith, MT TI Genotoxic markers among butadiene polymer workers in China SO CARCINOGENESIS LA English DT Article ID CULTURED HUMAN-LYMPHOCYTES; SISTER-CHROMATID EXCHANGE; SYNTHETIC RUBBER WORKERS; OCCUPATIONAL EXPOSURE; CHROMOSOMAL-ABERRATIONS; INHALATION EXPOSURE; SPECIES-DIFFERENCES; 1,3-BUTADIENE; INDUCTION; METABOLITES AB While 1,3-butadiene is carcinogenic in rodents, cancer causation in humans is less certain. We examined a spectrum of genotoxic outcomes in 41 butadiene polymer production workers and 38 non-exposed controls, in China, to explore the role of butadiene in human carcinogenesis. Because in vitro studies suggest that genetic polymorphisms in glutathione S-transferase enzymes influence genotoxic effects of butadiene, we also related genotoxicity to genetic polymorphisms in GSTT1 and GSTM1. Among butadiene-exposed workers, median air exposure was 2 p.p.m. (6 h time-weighted average), due largely to intermittent high level exposures. Compared with unexposed subjects, butadiene-exposed workers had greater levels of hemoglobin N-(2,3,4-trihydroxybutyl)valine (THBVal) adducts (P < 0.0001) and adduct levels tended to correlate, among butadiene-exposed workers, with air measures (P = 0.03). Butadiene-exposed workers did not differ, however, from unexposed workers with respect to frequency of uninduced or diepoxybutane-induced sister chromatid exchanges, aneuploidy as measured by fluorescence in situ hybridization of chromosomes 1, 7, 8 and 12, glycophorin A variants or lymphocyte hprt somatic mutation. Also among the exposed, greater THBVal levels were not associated with increases in uninduced sister chromatid exchanges, aneuploidy, glycophorin A or hprt mutations. Butadiene-exposed workers had greater lymphocyte (P = 0.002) and platelet counts (P = 0.07) and lymphocytes as a percentage of white blood cells were moderately correlated with greater THBVal levels (Spearman's phi = 0.32, P = 0.07). Among butadiene-exposed workers, neither GSTM1 nor GSTT1 genotype status predicted urinary mercapturic acid butanediol formation, THBVal adducts, uninduced sister chromatid exchanges, aneuploidy or mutations in the glycophorin A or hprt genes. Overall, the study demonstrated exposure to butadiene in these workers, by a variety of short-term and long-term measures, but did not show specific genotoxic effects, at the chromosomal or gene levels, related to that exposure. C1 NCI, Occupat Studies Branch, Bethesda, MD 20892 USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. Chinese Acad Prevent Med, Beijing, Peoples R China. Univ N Carolina, Sch Publ Hlth & Med, Chapel Hill, NC USA. Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. Inhalat Toxicol Res Inst, Albuquerque, NM 87185 USA. Calif State Dept Hlth, Berkeley, CA USA. Univ Vermont, Genet Lab, Burlington, VT USA. Yanshan Petrochem Prod Corp, Inst Occupat Med, Yanshan, Peoples R China. RP Hayes, RB (reprint author), NCI, Occupat Studies Branch, Bethesda, MD 20892 USA. EM hayesr@exchange.nih.gov NR 59 TC 62 Z9 64 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2000 VL 21 IS 1 BP 55 EP 62 DI 10.1093/carcin/21.1.55 PG 8 WC Oncology SC Oncology GA 277YF UT WOS:000084960600009 PM 10607734 ER PT J AU Steele, VE Kelloff, GJ Balentine, D Boone, CW Mehta, R Bagheri, D Sigman, CC Zhu, SY Sharma, S AF Steele, VE Kelloff, GJ Balentine, D Boone, CW Mehta, R Bagheri, D Sigman, CC Zhu, SY Sharma, S TI Comparative chemopreventive mechanisms of green tea, black tea and selected polyphenol extracts measured by in vitro bioassays SO CARCINOGENESIS LA English DT Article ID TRACHEAL EPITHELIAL-CELLS; PHASE-II ENZYMES; (-)-EPIGALLOCATECHIN GALLATE; LIPID-PEROXIDATION; TUMOR INITIATION; CANCER CHEMOPREVENTION; N-NITROSODIETHYLAMINE; CAMELLIA-SINENSIS; MOUSE SKIN; A/J MICE AB Black tea extracts (hot aqueous, polyphenols and theaflavins) and green tea extracts (hot aqueous, polyphenols, epicatechin, epicatechin gallate, epigallocatechin and epigallocatechin gallate) were tested in nine standardized cell culture assays for comparative cancer chemopreventive properties. Most black and green tea extracts strongly inhibited neoplastic transformation in mouse mammary organ cultures, rat tracheal epithelial cells and human lung tumor epithelial cells. Nearly all tea fractions strongly inhibited benzo[a]pyrene adduct formation with human DNA. Induction of phase II enzymes, glutathione-S-transferase and quinone reductase, were enhanced by nearly all tea fractions, while glutathione was induced by only a few fractions. Ornithine decarboxylase activity was inhibited by nearly all the green tea fractions, but none of the black tea fractions. 12-O-tetradecanoylphorbol-13-acetate-induced free radicals were inhibited by most tea fractions, These results provide strong evidence of both anti-mutagenic, anti-proliferative and anti-neoplastic activities for both black and green tea extracts. Such anticancer mechanisms may well be responsible for the cancer preventive efficacies seen in both experimental and human studies. C1 NCI, Chemoprevent Branch, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. Mantech Environm Technol Inc, Res Triangle Pk, NC 27709 USA. Univ Illinois, Chicago, IL 60612 USA. CCS Associates, Mt View, CA 94043 USA. Thomas J Lipton Co, Englewood Cliffs, NJ 07632 USA. RP Steele, VE (reprint author), NCI, Chemoprevent Branch, Div Canc Prevent, NIH, EPN Room 201,MSC 7322,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 63 TC 122 Z9 130 U1 2 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2000 VL 21 IS 1 BP 63 EP 67 DI 10.1093/carcin/21.1.63 PG 5 WC Oncology SC Oncology GA 277YF UT WOS:000084960600010 PM 10607735 ER PT J AU Lantry, LE Zhang, ZQ Yao, RS Crist, KA Wang, Y Ohkanda, J Hamilton, AD Sebti, SM Lubet, RA You, M AF Lantry, LE Zhang, ZQ Yao, RS Crist, KA Wang, Y Ohkanda, J Hamilton, AD Sebti, SM Lubet, RA You, M TI Effect of farnesyltransferase inhibitor FTI-276 on established lung adenomas from A/J mice induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone SO CARCINOGENESIS LA English DT Article ID GERANYLGERANYLTRANSFERASE-I INHIBITOR; FARNESYL-PROTEIN TRANSFERASE; TUMOR-CELL LINES; K-RAS; SELECTIVE-INHIBITION; ONCOGENIC RAS; N-RAS; CANCER; CAAX; PRENYLATION AB The Ras protein undergoes a series of post-translational modifications at the C-terminal CAAX motif, which culminates with the anchoring of p21 Ras to the plasma membrane where it relays growth regulatory signals from receptor tyrosine kinases to various pathways of cell signal transduction, FTI-276 is a CAAX peptidomimetic of the carboxyl terminal of Ras proteins. Pharmacokinetic analysis of FTI-276 in A/J mice with a time-release pellet system showed a dose of 50 mg/kg body wt achieved an average serum level of 1.68 mu g/ml for up to 30 days following implantation, In the present study, 4 week old A/J mice were initiated with a single dose of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (100 mg/kg), and monitored for 18 weeks, Mice were grouped for daily delivery (time-release pellet) of 50 mg/kg of FTI-276 for 30 days (n = 12) and the control group (n = 12), Analysis of tumors from time-release pellet treated animals showed a 60% reduction in tumor multiplicity and a 42% reduction in tumor incidence. Moreover, FTI-276 treatment resulted in a significant reduction in tumor volume (similar to 58%), Mutation analysis of the lung tumors from both treatment groups revealed that most of the tumors harbored mutations in the codon 12 of K-ras and there is no significant difference in the incidence and types of mutations between tumors from the treated and control animals. This is the first demonstration of chemotherapeutic efficacy of a synthetic CAAX peptidomimetie farnesyltransferase inhibitor in a primary lung tumor model. C1 Med Coll Ohio, Dept Pathol, Toledo, OH 43699 USA. Med Coll Ohio, Dept Surg, Toledo, OH 43699 USA. Yale Univ, Dept Chem, New Haven, CT 06511 USA. Univ S Florida, H Lee Moffitt Comprehens Canc Ctr, Tampa, FL 33647 USA. NCI, Chemoprevent Branch, Bethesda, MD 20892 USA. Univ S Florida, Dept Biochem & Mol Biol, Inst Res, Tampa, FL 33647 USA. RP You, M (reprint author), Med Coll Ohio, Dept Pathol, POB 10008, Toledo, OH 43699 USA. FU NCI NIH HHS [CA58554, CN-55184] NR 33 TC 37 Z9 37 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2000 VL 21 IS 1 BP 113 EP 116 DI 10.1093/carcin/21.1.113 PG 4 WC Oncology SC Oncology GA 277YF UT WOS:000084960600017 PM 10607742 ER PT S AU Ackerman, MJ Yoo, T Jenkins, D AF Ackerman, MJ Yoo, T Jenkins, D BE Lemke, HU Vannier, MW Inamura, K Farman, AG Doi, K TI The visible human project: From data to knowledge SO CARS 2000: COMPUTER ASSISTED RADIOLOGY AND SURGERY SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 14th International Congress and Exhibition on Computer Assisted Radiology and Surgery (CARS 2000) CY JUN 28-JUL 01, 2000 CL SAN FRANCISCO, CA AB The U.S. National Library of Medicine, in partnership with the U.S. National Institute for Dental and Craniofacial Research, the U.S. National Eye Institute, the U.S. National Science Foundation, the U.S. National Institute for Deafness and Other Communication Disorders, and the U.S. National Cancer Institute, have begun a three prong effort within the Visible Human Project to address: the creation of a new, online, digital, head-and-neck atlas; the development of a tool kit of computational programs capable of automatically performing many of the basic data handling functions required for using Visible Human data in applications; and the improved resolution of future Visible Human data sets through the reduction of the anatomical artifacts introduced by the methods used to stabilize and section the anatomical materials and the introduction of staining and wide-spectrum methods for increasing tissue contrast. C1 US Natl Lib Med, Off High Performance Comp & Commun, Bethesda, MD 20894 USA. RP Ackerman, MJ (reprint author), US Natl Lib Med, Off High Performance Comp & Commun, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 4 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-50536-9 J9 INT CONGR SER PY 2000 VL 1214 BP 11 EP 16 PG 6 WC Computer Science, Interdisciplinary Applications; Radiology, Nuclear Medicine & Medical Imaging; Surgery SC Computer Science; Radiology, Nuclear Medicine & Medical Imaging; Surgery GA BR11B UT WOS:000165685600002 ER PT S AU Summers, RM Pusanik, LM Malley, JD Reed, JE Johnson, CD AF Summers, RM Pusanik, LM Malley, JD Reed, JE Johnson, CD BE Lemke, HU Vannier, MW Inamura, K Farman, AG Doi, K TI Method of labeling colonic polyps at CT colonography using computer-assisted detection SO CARS 2000: COMPUTER ASSISTED RADIOLOGY AND SURGERY SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 14th International Congress and Exhibition on Computer Assisted Radiology and Surgery (CARS 2000) CY JUN 28-JUL 01, 2000 CL SAN FRANCISCO, CA DE CT colonography; visualization; colon cancer; computer-assisted diagnosis ID VIRTUAL BRONCHOSCOPY; COLORECTAL POLYPS; COLONOSCOPY; DISPLAY AB A display method for computer-assisted diagnosis using CT colonography is described and demonstrated. The method highlights voxels on the CT scan corresponding to sites of possible polyps. A physician can rapidly review CT images labeled in this manner. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bldg 10, Bethesda, MD 20892 USA. EM rms@nih.gov NR 16 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-50536-9 J9 INT CONGR SER JI Int. Congr. Ser. PY 2000 VL 1214 BP 785 EP 789 PG 5 WC Computer Science, Interdisciplinary Applications; Radiology, Nuclear Medicine & Medical Imaging; Surgery SC Computer Science; Radiology, Nuclear Medicine & Medical Imaging; Surgery GA BR11B UT WOS:000165685600132 ER PT J AU Kohn, KW Andoh, T AF Kohn, KW Andoh, T TI Symposium: Downstream from Topoisomerase-DNA Lesions - Life-or-death consequences for the cell SO CELL BIOCHEMISTRY AND BIOPHYSICS LA English DT Editorial Material ID DAMAGE; EXPRESSION; LINES; P53 C1 NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Soka Univ, Fac Engn, Hachioji, Tokyo 1920003, Japan. RP Kohn, KW (reprint author), NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1085-9195 J9 CELL BIOCHEM BIOPHYS JI Cell Biochem. Biophys. PY 2000 VL 33 IS 2 BP 171 EP 173 DI 10.1385/CBB:33:2:171 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 397MY UT WOS:000166700500004 PM 11325036 ER PT J AU Kohn, KW Shao, RG Pommier, Y AF Kohn, KW Shao, RG Pommier, Y TI How do drug-induced topoisomerase I-DNA lesions signal to the molecular interaction network that regulates cell cycle checkpoints, DNA replication, and DNA repair? SO CELL BIOCHEMISTRY AND BIOPHYSICS LA English DT Article; Proceedings Paper CT 9th Conference on DNA Topoisomerases in Therapy CY OCT, 1998 CL NEW YORK, NEW YORK ID DEPENDENT PROTEIN-KINASE; SINGLE-STRANDED-DNA; COMPLEX-FORMATION; CYTO-TOXICITY; P34 SUBUNIT; BINDING; P53; PHOSPHORYLATION; CAMPTOTHECIN; KU AB Recent results suggest that potentially lethal DNA lesions may result when replication forks encounter trapped topoisomerase-DNA complexes or some other types of DNA damage. Such events produce what are called replication-encounter lesions. These lesions have the characteristic that they may allow single stranded DNA-associated replication protein A (RPA) to become juxtaposed to dsDNA end-associated DNA-protein kinase. Our results suggest that DNA-protein kinases may then hyperphosphorylate the RPA2 subunit. We discuss a possible pathway by which hyperphosphorylation of RPA2 could lead to the release of active p53. This could constitute a pathway for signaling the presence of replication-encounter lesions to the p53-dependent cell cycle arrest and/or apoptosis initiator systems. C1 NCI, Mol Pharmacol Lab, Div Basic Sci, Bethesda, MD 20892 USA. RP Kohn, KW (reprint author), NCI, Mol Pharmacol Lab, Div Basic Sci, Bethesda, MD 20892 USA. NR 26 TC 26 Z9 26 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1085-9195 J9 CELL BIOCHEM BIOPHYS JI Cell Biochem. Biophys. PY 2000 VL 33 IS 2 BP 175 EP 180 DI 10.1385/CBB:33:2:175 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 397MY UT WOS:000166700500005 PM 11325037 ER PT J AU Lee, SJ Choi, SA Cho, CK Kim, TH Jeong, KS Yoo, SY Lee, YS AF Lee, SJ Choi, SA Cho, CK Kim, TH Jeong, KS Yoo, SY Lee, YS TI Adaptive response is differently induced depending on the sensitivity to radiation-induced cell death in mouse epidermal cells SO CELL BIOLOGY AND TOXICOLOGY LA English DT Article DE adaptive response; normal cells; neoplastic cells; protein kinase C; cell death ID PROTEIN-KINASE-C; IONIZING-RADIATION; HUMAN-LYMPHOCYTES; X-RAYS; APOPTOSIS; INDUCTION; TRANSFORMATION; IRRADIATION; ACTIVATION; LINES AB We investigated the relationship between induction of radio-adaptive response and cell death in mouse normal and neoplastic epidermal cells. Mouse normal primary keratinocytes (PK), cancer-prone cells [v-ras(Ha)-transfected mouse keratinocytes (ras-PK), and line 308 cells (mouse skin papilloma cells which have activated ras(Ha) gene with A-to-T transversion at codon 61) were primed with a low dose of gamma-rays (0.01 Gy), and were challenged with a high dose (4 Gy) after a 4 or 7 h interval. The induction of cell death in PK was 2-10 times higher and was also more rapid in PK than in ras-PK or 308 cells. Low-dose pretreatment with a 4 h interval decreased cell death, and this adaptive response was prominent in PK, whereas it was less obvious in the cases of ras-PK and 308 cells. The response of each protein kinase C (PKC) isozymes to high-dose radiation, especially PKC alpha, PKC delta, PKC epsilon, and PKC eta, were different between the normal and ras oncogene-activated neoplastic keratinocytes; translocation of these isozymes to membrane occurred more rapidly in normal than in neoplastic cells. Furthermore, low-dose pretreatment did not induce the translocation of PKC delta in PK significantly more than in ras-PK and 308. Thus, the difference in the induction of radio-adaptive responses between mouse normal and neoplastic epidermal cells reflects difference in the rapidity of cell death, and responsiveness of PKC may affect this adaptive response. C1 Korea Canc Ctr Hosp, Lab Radiat Effect, Seoul 139706, South Korea. NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Lee, SJ (reprint author), Korea Canc Ctr Hosp, Lab Radiat Effect, 215-4 Gongneung Dong, Seoul 139706, South Korea. NR 23 TC 16 Z9 16 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0742-2091 J9 CELL BIOL TOXICOL JI Cell Biol. Toxicol. PY 2000 VL 16 IS 3 BP 175 EP 184 DI 10.1023/A:1007658905639 PG 10 WC Cell Biology; Toxicology SC Cell Biology; Toxicology GA 351BE UT WOS:000089135500004 PM 11032361 ER PT J AU Hongpaisan, J AF Hongpaisan, J TI Inhibition of proliferation of contaminating fibroblasts by D-valine in cultures of smooth muscle cells from human myometrium SO CELL BIOLOGY INTERNATIONAL LA English DT Article DE X-ray microanalysis; diffusible elements; ion transport; smooth muscle; myometrium; cell culture; oxytocin; fura-2; calcium; fibroblast ID X-RAY-MICROANALYSIS; INTRACELLULAR CALCIUM; OXYTOCIN; CONTRACTION; PROTEINS AB Replacement of L-valine with D-valine in a standard culture medium can selectively inhibit fibroblast proliferation. The aim of the present study was to investigate whether human myometrial cells cultured with D-valine instead of L-valine can survive and express their characteristics. Cultured cells (95-98%) maintain expression of the intermediate filament desmin, which is the specific marker for mature muscle cells. By transmission electron microscopy, the cells showed the general morphology of smooth muscle cells in culture. Oxytocin in serum-free culture medium at 37 degrees C (5 min) caused a concentration-dependent increase in cellular Na and total Ca, and a decrease in K content as determined by X-ray microanalysis. The percentage of cells cultured with D-valine responding to oxytocin stimulation was larger than that of cells cultured with L-valine, suggesting less contamination of smooth muscle cells by fibroblasts in the presence of D-valine. As shown by measurements with fura-2, D-valine-cultured cells retained the characteristic increase in intracellular free Ca2+ ions after oxytocin stimulation. (C) 2000 Academic Press. C1 Univ Uppsala, Dept Med Cell Biol, Sect Human Anat, S-75123 Uppsala, Sweden. RP Hongpaisan, J (reprint author), NINDS, Neurobiol Lab, NIH, Bldg 36,Rm 2A-21, Bethesda, MD 20892 USA. NR 21 TC 11 Z9 12 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1065-6995 J9 CELL BIOL INT JI Cell Biol. Int. PY 2000 VL 24 IS 1 BP 1 EP 7 DI 10.1006/cbir.1999.0448 PG 7 WC Cell Biology SC Cell Biology GA 307AU UT WOS:000086631900001 PM 10826768 ER PT J AU Larisch-Bloch, S Danielpour, D Roche, NS Lotan, R Hsing, AY Kerner, H Hajouj, T Lechleider, RJ Roberts, AB AF Larisch-Bloch, S Danielpour, D Roche, NS Lotan, R Hsing, AY Kerner, H Hajouj, T Lechleider, RJ Roberts, AB TI Selective loss of the transforming growth factor-beta apoptotic signaling pathway in mutant NRP-154 rat prostatic epithelial cells SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID STAUROSPORINE-INDUCED APOPTOSIS; BREAST-CANCER CELLS; RECEPTOR-TYPE-II; BCL-X-L; HIPPOCAMPAL-NEURONS; DOWN-REGULATION; SMAD PROTEINS; DPC4 GENE; INDUCTION; EXPRESSION AB Retroviral insertional mutagenesis was used to select mutant NRP-154 rat prostate carcinoma cells resistant to transforming growth factor (TGF)-beta-induced cell death. Similar to the parental cells, a mutant clone, M-NRP1, expressed TGF-beta receptors and was still responsive to induction both of direct target genes by TGF-beta and of apoptosis by staurosporine or okadaic acid. In contrast, indicators of cell growth, strongly suppressed by TGF-beta in the parental cells, were unaffected in M-NRP1 cells. M-NRP1 cells overexpress the antiapoptotic protein, Bcl-xL, and show dysregulated expression and localization of a protein related to a novel human septin, ARTS (designation of apoptotic response to TGF-beta signals), cloned by homology to an exonic sequence flanked by the viral long terminal repeats in M-NRP1 cells and shown to make cells competent to undergo apoptosis in response to TGF-beta, We propose that ARTS might operate within the same apoptotic pathway as Bcl-xL and that M-NRP1 cells could serve as a useful model for characterization of this pathway. C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA. Rambam Med Ctr, Dept Pathol, IL-31096 Haifa, Israel. RP Roberts, AB (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Bldg 41,Room C629,41 Lib Dr,MSC 5055, Bethesda, MD 20892 USA. FU NCI NIH HHS [P30CA43703] NR 68 TC 25 Z9 25 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD JAN PY 2000 VL 11 IS 1 BP 1 EP 10 PG 10 WC Cell Biology SC Cell Biology GA 281KX UT WOS:000085160000001 PM 10672898 ER PT S AU Steinbrecher, A Reinhold, D Quigley, L Gado, A Tresser, N Izikson, L Born, I Faust, J Neubert, K Martin, R Ansorge, S Brocke, S AF Steinbrecher, A Reinhold, D Quigley, L Gado, A Tresser, N Izikson, L Born, I Faust, J Neubert, K Martin, R Ansorge, S Brocke, S BE Langner, J Ansorge, S TI Dipeptidyl peptidase IV in inflammatory CNS disease SO CELLULAR PEPTIDASES IN IMMUNE FUNCTIONS AND DISEASES 2 SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT International Conference on Cellular Peptidases in Immune Functions and Diseases II CY SEP 12-14, 1999 CL MAGDEBURG, GERMANY SP Deutsch Forschungsgemeinsch, Minist Kultur Landes Sachsen Anhalt, Otto VonGuericke Univ Magdeburg, Martin Luther Univ Halle Wittenberg, Becton Dickinson GmbH Heidelberg, Biochrom Beteilig GmbH & Co Centeon Liederbach, Karl Roth GmbH & Co KG, NEN Life Sci Prod GmbH, R & D Syst, Roche Diagnost GmbH DE experimental autoimmune encephalomyelitis; dipeptidyl peptidase IV (DP IV, CD26); inhibitors; autoimmune disease; T cell ID MYELIN BASIC-PROTEIN; CHEMOKINE REGULATION; HUMAN-LYMPHOCYTES; T-CELLS; INHIBITORS; CD26; AUTOIMMUNITY; PROLIFERATION; ANTIBODIES; ACTIVATION AB Current pathogenic concepts of inflammatory demyelinating disorders such as multiple sclerosis (MS) are based on the hypothesis that a T cell-mediated autoimmune response is involved in the disease process. One of the primary goals in the in the development of immotherapies for autoimmune diseases has been to achieve inactivation of disease-inducing lymphocytes either by direct inhibition or suppression through regulatory cells and/or cytokines. The CD26 antigen is identical with the cell surface ectopeptidase dipeptidyl peptidase IV (DP TV, EC 3.4.14.5) which is involved in regulating T cell activation and growth. Activated T cells, including those specific for myelin antigens, express high levels of CD26/DP IV. In vitro, reversible DP IV inhibitors suppress T cell proliferation and pro-inflammatory cytokine production in response to myelin antigens. Further studies will evaluate the role of DP IV inhibition in T cell-mediated inflammatory disease of the central nervous system. C1 NINDS, NIH, Bethesda, MD 20892 USA. RP Steinbrecher, A (reprint author), NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 17 TC 9 Z9 9 U1 0 U2 0 PU KLUWER ACADEMIC / PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-46383-0 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2000 VL 477 BP 145 EP 153 PG 9 WC Cell Biology; Immunology; Medicine, Research & Experimental SC Cell Biology; Immunology; Research & Experimental Medicine GA BQ32C UT WOS:000087923000016 PM 10849741 ER PT J AU Burg, MB AF Burg, MB TI Macromolecular crowding as a cell volume sensor SO CELLULAR PHYSIOLOGY AND BIOCHEMISTRY LA English DT Article DE macromolecular crowding; cell volume regulation; water activity ID CYTOSOLIC PROTEIN-CONCENTRATION; DOG RED-CELLS; ESCHERICHIA-COLI; CYTOPLASM; CONSEQUENCES; DIFFUSION; SIGNAL; MODEL AB The non-ideal properties of solutions containing high concentrations of macromolecules can result in enormous increases in the activity of the individual macromolecules. There is considerable evidence that macromolecular crowding and confinement not only occur in cells, but that these are major determinants of the activity of the proteins and other intracellular macromolecules. This concept has important implications for cell volume regulation because, under crowded conditions, relatively small changes in concentration, consequent to alterations of water content, lead to large changes in macromolecular activity which could provide a mechanism by which cells sense changes in their volume. This brief review considers 1) direct demonstrations that introducing a high concentration of appropriate macromolecules into cells in vitro produced volume regulatory changes, 2) the physical chemical principles involved in the effects of crowding of macromolecules on their activity, 3) estimates of the actual intracellular activity of macromolecules, 4) a proposed model of how changes in macromolecular crowding could signal volume regulation in cells, and 5) brief consideration of the complexities introduced by interactions between macromolecules, water and cosolutes. Conclusions: The hypothesis that macromolecular crowding provides a mechanism by which cells sense changes in their volume is plausible and is supported by striking observations in red blood cell ghosts and perfused barnacle muscle cells. However, the signaling molecules involved have not been identified, the proposed model is not fully consistent with the experiments, experimental verification in intact cells is lacking, and numerous alternative or additional mechanisms are not excluded. Copyright (C) 2000 S. Karger AG, Basel. C1 NHLBI, Bethesda, MD 20892 USA. RP Burg, MB (reprint author), NIH, Bldg 10,Room 6N260, Bethesda, MD 20892 USA. NR 19 TC 54 Z9 55 U1 0 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-8987 J9 CELL PHYSIOL BIOCHEM JI Cell. Physiol. Biochem. PY 2000 VL 10 IS 5-6 BP 251 EP 256 DI 10.1159/000016371 PG 6 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 392FJ UT WOS:000166400200002 PM 11125203 ER PT J AU Guo, ZH Mattson, MP AF Guo, ZH Mattson, MP TI Neurotrophic factors protect cortical synaptic terminals against amyloid- and oxidative stress-induced impairment of glucose transport, glutamate transport and mitochondrial function SO CEREBRAL CORTEX LA English DT Article ID FIBROBLAST GROWTH-FACTOR; LONG-TERM POTENTIATION; MANGANESE SUPEROXIDE-DISMUTASE; MEMBRANE LIPID-PEROXIDATION; FOCAL CEREBRAL-ISCHEMIA; HIPPOCAMPAL-NEURONS; BETA-PEPTIDE; CALCIUM HOMEOSTASIS; RAT-BRAIN; FACTOR RECEPTOR AB Previous studies have shown that several different neurotrophic factors can prevent death of cortical and hippocampal neurons induced by excitotoxic and oxidative insults in cell culture and in vivo. Because neuronal degeneration may be initiated by alterations occurring in synaptic compartments in disorders ranging from Alzheimer's disease to stroke, we tested the hypothesis that neurotrophic factors can exert direct protective actions at the level of the synapse. We now report that a nine amino acid bioactive fragment of activity-dependent neurotrophic factor (ADNF-9) enhances basal glucose and glutamate transport, and attenuates oxidative impairment of glucose and glutamate transport induced by amyloid beta-peptide and Fe2+, in neocortical synaptosomes. Preservation of transporter function required only short-term (1-2 h) pretreatments. Basic fibroblast growth factor (bFGF) was also effective in suppressing oxidative impairment of synaptic transporter functions, while nerve growth factor (NGF) was less effective. Additional analyses showed that ADNF-9, hFGF and NGF suppress oxidative stress and mitochondrial dysfunction induced by amyloid P-peptide and Fe2+ in synaptosomes. Our data suggest that ADNF-9 can act locally in synaptic compartments to suppress oxidative stress and preserve function of glucose and glutamate transporters. Such synapto-protective actions suggest roles for activity-dependent trophic signaling in preventing degeneration of neuronal circuits, and indicate possible therapeutic applications of agents that stimulate local synaptic (transcription-independent) neurotrophic factor signaling pathways. C1 Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. Univ Kentucky, Dept Anat & Neurobiol, Lexington, KY 40536 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 FU NIA NIH HHS [AG05144, AG14554]; NINDS NIH HHS [NS35253] NR 79 TC 83 Z9 84 U1 1 U2 1 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 JAN PY 2000 VL 10 IS 1 BP 50 EP 57 DI 10.1093/cercor/10.1.50 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 269ZM UT WOS:000084510700006 PM 10639395 ER PT J AU Fettes, KJ Howard, N Hickman, DT Adah, SA Player, MR Torrence, PF Micklefield, J AF Fettes, KJ Howard, N Hickman, DT Adah, SA Player, MR Torrence, PF Micklefield, J TI Replacement of the phosphodiester linkage in DNA with sulfamide and 3 '-N-sulfamate groups SO CHEMICAL COMMUNICATIONS LA English DT Article ID OLIGONUCLEOTIDES; DUPLEX; INHIBITORS AB Replacing phosphodiester linkages in DNA with neutral 3'-N-sulfamate groups has little effect on the binding affinity for complementary DNA or RNA, whereas incorporation of sulfamide groups into DNA results in considerable destabilisation of isosequential duplexes. C1 UMIST, Dept Chem, Manchester M60 1QD, Lancs, England. Univ London Birkbeck Coll, Dept Chem, London WC1H 0PP, England. NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. No Arizona Univ, Dept Chem, Flagstaff, AZ 86011 USA. RP Micklefield, J (reprint author), UMIST, Dept Chem, Faraday Bldg,POB 88, Manchester M60 1QD, Lancs, England. RI Micklefield, Jason/I-8502-2016 OI Micklefield, Jason/0000-0001-8951-4873 NR 12 TC 11 Z9 11 U1 0 U2 6 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD,, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1359-7345 J9 CHEM COMMUN JI Chem. Commun. PY 2000 IS 9 BP 765 EP 766 DI 10.1039/b001586p PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 309QH UT WOS:000086779800018 ER PT J AU Takeuchi, Y Kirihara, K Kirk, KL Shibata, N AF Takeuchi, Y Kirihara, K Kirk, KL Shibata, N TI Synthesis of carbonyl-bridged peptides containing an alpha-fluoroglycine residue SO CHEMICAL COMMUNICATIONS LA English DT Article ID CHEMISTRY; ACIDS AB Gabriel reaction of hydantoins with bromofluoroacetate provides a general method for the synthesis of carbonyl-bridged peptides containing an alpha-fluoroglycine residue. C1 Toyama Med & Pharmaceut Univ, Fac Pharmaceut Sci, Toyama 9300194, Japan. NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Takeuchi, Y (reprint author), Toyama Med & Pharmaceut Univ, Fac Pharmaceut Sci, Sugitani 2630, Toyama 9300194, Japan. EM takeuchi@ms.toyama-u.ac.jp NR 11 TC 12 Z9 12 U1 1 U2 4 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1359-7345 J9 CHEM COMMUN JI Chem. Commun. PY 2000 IS 9 BP 785 EP 786 DI 10.1039/b001265n PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 309QH UT WOS:000086779800028 ER PT J AU Brantly, M Avila, NA Shotelersuk, V Lucero, C Huizing, M Gahl, WA AF Brantly, M Avila, NA Shotelersuk, V Lucero, C Huizing, M Gahl, WA TI Pulmonary function and high-resolution CT findings in patients with an inherited form of pulmonary fibrosis, Hermansky-Pudlak syndrome, due to mutations in HPS-1 SO CHEST LA English DT Article DE albinism; CT scans; pulmonary fibrosis; pulmonary function tests ID PALE EAR EP; GRANULOMATOUS COLITIS; LOCUS HETEROGENEITY; GENE; MOUSE; ALBINISM; DISEASE; MODELS AB Objective: To describe and correlate pulmonary function and high-resolution CT (HRCT) scan scores in individuals with a high risk for development of pulmonary fibrosis, ie, Hermansky-Pudlak syndrome (HPS) patients with mutations in the HPS-I gene. Design: Cross-sectional analysis of consecutive, eligible patients. Patients: Thirty-eight HPS inpatients at the National Institutes of Health Clinical Center with HPS-1 mutations. Results: Thirty-seven patients were Puerto Rican and exhibited the typical 16-base pair (bp) duplication in exon 15 of HPS-1. One non-Puerto Rican was homozygous for a different mutation (intervening sequence 17 -2 A --> C) previously reported in the HPS-1 gene; he died at age 35 of pulmonary insufficiency. For the 23 patients who had pulmonary symptoms, the mean age of onset was 35 years. For all 38 patients (mean age, 37 +/- 2 years), the mean FVC was 71% of predicted; the mean FEV1, 76%; mean total lung capacity (TLC), 72%; mean vital capacity (VC), 68%; and mean diffusing capacity of the lung for carbon monoxide (DLCO), 72%. When patients were grouped according to the extent of their reduction in FVC, the other four pulmonary function parameters followed the FVC. Seventeen patients had abnormal chest radiographs, and 31 (82%) had abnormal HRCT scans of the chest, for which a scoring system of 0 (normal) to 3 (severe fibrosis) is presented. The mean +/- SEM HRCT score for 38 patients was 1.30 +/- 0.17. HRCT scores correlated inversely with FVC and DLCO. Conclusions: Mutations in the HPS-1 gene, whether or not they involve the typical 16-bp duplication seen in Puerto Rican patients, are associated with fatal pulmonary fibrosis. In affected patients, the FVC, FEV1, TLC, VC, and DLCO fall in concert, and this functional deficit correlates with HRCT scan evidence of progression of interstitial lung disease. C1 NHLBI, Clin Studies Sect, Pulm Crit Care Med Branch, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NICHHD, Sect Human Biochem Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Gahl, WA (reprint author), NICHD, NIH, 10 Ctr Dr,MSC 1830,Bldg 10,Room 9S-241, Bethesda, MD 20892 USA. NR 36 TC 87 Z9 89 U1 1 U2 3 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JAN PY 2000 VL 117 IS 1 BP 129 EP 136 DI 10.1378/chest.117.1.129 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 274PN UT WOS:000084774400025 PM 10631210 ER PT J AU McDougle, CJ Scahill, L McCracken, JT Aman, MG Tierney, E Arnold, LE Freeman, BJ Martin, A McGough, JJ Cronin, P Posey, DJ Riddle, MA Ritz, L Swiezy, NB Vitiello, B Volkmar, FR Votolato, NA Walson, P AF McDougle, CJ Scahill, L McCracken, JT Aman, MG Tierney, E Arnold, LE Freeman, BJ Martin, A McGough, JJ Cronin, P Posey, DJ Riddle, MA Ritz, L Swiezy, NB Vitiello, B Volkmar, FR Votolato, NA Walson, P TI Research Units on Pediatric Psychopharmacology (RUPP) autism network - Background and rationale for an initial controlled study of risperidone SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID PERVASIVE DEVELOPMENTAL DISORDERS; OBSESSIVE-COMPULSIVE DISORDER; DOUBLE-BLIND; MENTAL-RETARDATION; ATYPICAL ANTIPSYCHOTICS; FENFLURAMINE TREATMENT; BEHAVIORAL SYMPTOMS; TARDIVE-DYSKINESIA; INFANTILE-AUTISM; BLOOD SEROTONIN AB This article reviews the background and rationale for the choice of the atypical antipsychotic agent risperidone as the first drug to be studied by the RUPP Autism Network. Risperidone has potent effects on serotonin and dopamine neuronal systems, which have been implicated in the pathophysiology of autism. Unlike typical antipsychotics, such as haloperidol and pimozide, which have been shown to be effective for reducing many of the maladaptive behaviors associated with autism, the unique ratio of serotonin to dopamine receptor blockade for risperidone seems to produce a lower risk of acute and chronic extrapyramidial side effects and enhanced efficacy for the negative symptoms of autism. Indirect clinical and preclinical evidence supporting the use of risperidone to treat impaired social behavior, interfering repetitive phenomena and aggressions as targets of pharmacotherapy for patients with autism are reviewed. The safety and tolerability of risperidone also are summarized. C1 Indiana Univ, Sch Med, Indianapolis, IN USA. Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT 06520 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Ohio State Univ, Columbus, OH 43210 USA. Kennedy Kreiger Inst, Baltimore, MD USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NIMH, Bethesda, MD 20892 USA. RP McDougle, CJ (reprint author), Indiana Univ, James Whitcomb Riley Hosp Children, Sch Med, Dept Psychiat, 702 Barnhill Dr,Room 3701, Indianapolis, IN 46202 USA. OI Scahill, Lawrence/0000-0001-5073-1707 NR 92 TC 76 Z9 77 U1 5 U2 11 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD JAN PY 2000 VL 9 IS 1 BP 201 EP + PG 25 WC Psychiatry SC Psychiatry GA 281AU UT WOS:000085136600012 PM 10674197 ER PT J AU Cabrera, NJ Tamisk-LeMonda, CS Bradley, RH Hofferth, S Lamb, ME AF Cabrera, NJ Tamisk-LeMonda, CS Bradley, RH Hofferth, S Lamb, ME TI Fatherhood in the twenty-first century SO CHILD DEVELOPMENT LA English DT Article ID PATERNAL INVOLVEMENT; CHILDRENS BEHAVIOR; PARENTS; SUPPORT; IMPACT; FAMILY; SOCIALIZATION; SCHEDULES; DIVORCE; GENDER AB The twentieth century has been characterized by four important social trends that have fundamentally changed the social cultural context in which children develop: women's increased labor force participation, increased absence of nonresidential fathers in the lives of their children, increased involvement of fathers in intact families, and increased cultural diversity in the U.S.. In this essay, we discuss how these trends are changing the nature of father involvement and family life, and in turn affecting children's and fathers' developmental trajectories. WE end with an eye toward the twenty-first century by examining how the children of today will construct their expectations about the roles of fathers and mothers as they become the parents of tomorrow. This life-span approach to fatherhood considers the broader sociohistorical context in which fatherhood develops, and emphasizes the urgent need to consider mothers, fathers, and family structure in future research as we seek to understand and model the effects of parenting on children's development. C1 NICHHD, Populat Res Ctr, DBSB, Bethesda, MD 20892 USA. NYU, New York, NY 10012 USA. Univ Arkansas, Little Rock, AR 72204 USA. Univ Michigan, Inst Social Res, Ann Arbor, MI 48109 USA. RP Cabrera, NJ (reprint author), NICHHD, Populat Res Ctr, DBSB, 6100 Execut Blvd,Room 3B07, Bethesda, MD 20892 USA. NR 91 TC 384 Z9 404 U1 13 U2 98 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 JAN-FEB PY 2000 VL 71 IS 1 BP 127 EP 136 DI 10.1111/1467-8624.00126 PG 10 WC Psychology, Educational; Psychology, Developmental SC Psychology GA 416EM UT WOS:000167767400015 PM 10836566 ER PT J AU Deng, YJ Notkins, AL AF Deng, YJ Notkins, AL TI Molecular determinants of polyreactive antibody binding: HCDR3 and cyclic peptides SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE polyreactive antibody; Fab fragment; baculovirus expression system; site-directed mutagenesis ID COMPLEMENTARITY-DETERMINING REGION; B-CELL REPERTOIRE; HEAVY-CHAIN CDR3; ANTIGEN-BINDING; RHEUMATOID FACTORS; HIGH-AFFINITY; MONOCLONAL AUTOANTIBODIES; MONOREACTIVE ANTIBODIES; NATURAL AUTOANTIBODY; SYNTHETIC PEPTIDE AB Human monoclonal antibody 63 (mAb63) is an IgM/lambda polyreactive antibody that binds to multiple self and non-self antigens. The molecular basis of polyreactivity is still unclear. The present study was initiated to prepare a recombinant Fab of mAb63 and use it to study the determinants involved in polyreactivity. The baculovirus system was employed to express large amounts of mAb63 Fab in Sf9 cells. Our experiments showed that infected Sf9 cells secreted a soluble 50-kD Fab heterodimer that bound to multiple self and non-self antigens. The antigen-binding activity of mAb63 Fab was inhibited by both homologous and heterologous antigens. To study in more detail the molecular determinants involved in polyreactivity, the heavy chain complementarity-determining region 3 (HCDR3), which is known to play a key role in the binding of monoreactive antibodies to antigens, was subjected to site-directed mutagenesis. A single substitution, alanine for arginine, at position 100A resulted in complete loss of antigen-binding activity. The 19 amino acids comprising the HCDR3 of mAb63 were then synthesized and a cyclic peptide prepared. The cyclic peptide showed the same antigen-binding pattern as the parental mAb63 and the recombinant mAb63 Fab. A five amino acid motif (RFLEW), present in the HCDR3 of mAb63, was found by searching the GenBank in three of 50 other human polyreactive antibodies, but in none of nearly 2500 human antibodies thought to be monoreactive. It is concluded that HCDR3 plays a major role in polyreactivity and that in some cases cyclic peptides comprising the HCDR3, by themselves, may be polyreactive. C1 NIDR, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Deng, YJ (reprint author), NIDR, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bldg 30,Room 112,30 Convent Dr,MSC 4322, Bethesda, MD 20892 USA. NR 50 TC 16 Z9 17 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD JAN PY 2000 VL 119 IS 1 BP 69 EP 76 DI 10.1046/j.1365-2249.2000.01096.x PG 8 WC Immunology SC Immunology GA 271ZG UT WOS:000084625100010 PM 10606966 ER PT J AU Zhu, MZ Marshall, J Cole, D Schlom, J Tsang, KY AF Zhu, MZ Marshall, J Cole, D Schlom, J Tsang, KY TI Specific cytolytic T-cell responses to human CEA from patients immunized with recombinant avipox-CEA vaccine SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; HUMAN CARCINOEMBRYONIC ANTIGEN; CANARYPOX-RABIES RECOMBINANT; DENDRITIC CELLS; IN-VITRO; VIRUS; PEPTIDE; RECOGNITION; EXPRESSION; IDENTIFICATION AB Avipox viruses are replication-defective members of the poxvirus family. Avipox-derived vectors such as ALVAC (canarypox) and fowlpox have the ability to infect mammalian cells, including human cells, but do not replicate. The first clinical trial of an avipox recombinant vaccine for patients with advanced carcinomas has recently been conducted using the ALVAC vector and the human carcinoembryonic antigen (CEA) transgene (designated ALVAC-CEA; J.L. Marshall et al., J. Clin. Oncol., 17: 332-337, 1999), The T-cell responses elicited by patients before and after vaccination with the ALVAC-CEA recombinants are characterized in this report. Pre- and postvaccination peripheral blood mononuclear cells (PMBCs) of the eight patients positive for HLA-class I A2 allele, were incubated with the HLA-AZ-CEA peptide CAP-1 and interleukin 2, In no cases using prevaccination PMBCs could cultures be established that had the ability to lyse C1R-A2 target cells pulsed with the CAP-1 peptide. However, T-cell cultures from seven of eight of these same patients, obtained from PBMCs after ALVAC-CEA vaccination, were shown to lyse C1R-A2 cells only when pulsed with CAP-I, Moreover, all seven of these T-cell cultures were shown to lyse allogeneic human carcinoma cell lines (SW1463 and SW480) that were both A2(+) and expressed CEA; an allogeneic tumor cell line (LS174T) expressing CEA that was negative for A2 expression was not lysed. HLA-A2(+) and CEA(+) autologous tumor cells were also capable of being lysed by CEA-specific T cells from this patient. Analysis of this CTL line also revealed the expression of several homing and adhesion-associated molecules. Fluorescence-activated cell sorter analysis of the T-cell lines established from patients after ALVAC-CEA vaccination revealed that most were CD8(+)/CD4(-), but many also had a CD8(+)/CD4(+) component. Analyses of T-cell receptor V beta usage of several of the CEA specific CTL lines showed a relatively diverse V beta pattern. These studies demonstrate for the first time the ability to vaccinate cancer patients with an avipox recombinant and derive T cells that are capable of lysing allogeneic and autologous tumor cells in a MHC-restricted manner. These studies thus form the rationale to use such replication-deficient recombinant vaccines in future cancer vaccine trials. C1 NCI, NIH, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Div Med Oncol, Washington, DC 20007 USA. Med Univ S Carolina, Dept Surg, Charleston, SC 29425 USA. RP Schlom, J (reprint author), NCI, NIH, Tumor Immunol & Biol Lab, 10 Ctr Dr,Bldg 10,Room 8B07, Bethesda, MD 20892 USA. NR 50 TC 93 Z9 100 U1 1 U2 3 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 JAN PY 2000 VL 6 IS 1 BP 24 EP 33 PG 10 WC Oncology SC Oncology GA 276YP UT WOS:000084906200004 PM 10656428 ER PT J AU van Stolk, R Stoner, G Hayton, WL Chan, K DeYoung, B Kresty, L Kemmenoe, BH Elson, P Rybicki, L Church, J Provencher, K McLain, D Hawk, E Fryer, B Kelloff, G Ganapathi, R Budd, GT AF van Stolk, R Stoner, G Hayton, WL Chan, K DeYoung, B Kresty, L Kemmenoe, BH Elson, P Rybicki, L Church, J Provencher, K McLain, D Hawk, E Fryer, B Kelloff, G Ganapathi, R Budd, GT TI Phase I trial of exisulind (sulindac sulfone, FGN-1) as a chemopreventive agent in patients with familial adenomatous polyposis SO CLINICAL CANCER RESEARCH LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUG; COLORECTAL-CANCER; MAMMARY CARCINOGENESIS; MURINE MODEL; CELL-DEATH; METABOLITE; INHIBITION; APOPTOSIS; CYCLOOXYGENASE; EXPRESSION AB Exisulind (sulindac sulfone; FGN-1), a metabolite of sulindac without known effects on prostaglandin synthesis, can promote apoptosis and inhibit tumorigenesis in preclinical systems. We performed a Phase I trial of this compound in patients with familial adenomatous polyposis (FAP) to examine the tolerability and safety of this drug in the cancer chemoprevention setting. Six patients each were treated with exisulind at doses of 200, 300, and 400 mg p.o. twice a day. Reversible hepatic dysfunction was noted in four of six patients treated at the 400-mg p.o., twice-a-day dose level, but in only one to two of six patients treated at each of the lower dose levels. The serum half-life of exisulind was 6-9 h; little drug accumulation was noted over time. A nonsignificant trend toward increased apoptosis in polyps was noted at the maximum tolerated dose, but no decrease in polyp numbers or significant effects on cellular proliferation was noted. After treatment, polyps tended to display a "halo" appearance grossly and mucinous differentiation histologically, The maximum safe dose of exisulind is 300 mg p.o. twice a day in patients with subtotal colectomies. Reversible hepatic dysfunction limits further dose escalation. A decrease in polyp numbers could not be demonstrated, but the trend toward increased apoptosis at the MTD and the observation of mucinous change histologically suggest that further investigation of drugs of this class might be warranted. C1 Cleveland Clin Fdn, Taussig Canc Ctr, Dept Gastroenterol, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Biostat & Epidemiol, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Colorectal Surg, Cleveland, OH 44195 USA. Ohio State Univ, Coll Med, Columbus, OH 43210 USA. Ohio State Univ, Coll Publ Hlth, Columbus, OH 43210 USA. Ohio State Univ, Coll Pharm, Columbus, OH 43210 USA. NCI, Bethesda, MD 20892 USA. RP Budd, GT (reprint author), Cleveland Clin Fdn, Taussig Canc Ctr, Dept Gastroenterol, Desk T-40,9500 Euclid Ave, Cleveland, OH 44195 USA. FU PHS HHS [N01-55119] NR 30 TC 72 Z9 73 U1 0 U2 0 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 JAN PY 2000 VL 6 IS 1 BP 78 EP 89 PG 12 WC Oncology SC Oncology GA 276YP UT WOS:000084906200011 PM 10656435 ER PT J AU Li, YW Bhuiyan, M Alhasan, S Senderowicz, AM Sarkar, FH AF Li, YW Bhuiyan, M Alhasan, S Senderowicz, AM Sarkar, FH TI Induction of apoptosis and inhibition of c-erbB-2 in breast cancer cells by flavopiridol SO CLINICAL CANCER RESEARCH LA English DT Article ID DEPENDENT KINASE INHIBITOR; HUMAN LUNG; DRUG FLAVOPIRIDOL; CARCINOMA CELLS; OVEREXPRESSION; LEUKEMIA; METASTASIS; NSC-649890; ACTIVATION; L86-8275 AB Flavopiridol is a flavone that inhibits several cyclin-dependent kinases and exhibits potent growth-inhibitory activity against a number of human tumor cell lines, both in vitro and when grown as xenografts in mice. It is presently being investigated as a novel antineoplastic agent in the primary screen conducted by the Developmental Therapeutics Program, National Cancer Institute. Because breast cancer is the most common cancer and second leading cause of cancer-related deaths in women in the United States, we investigated whether flavopiridol could be an effective agent against a series of isogenic breast cancer cell lines having different levels of erbB-2 expression and differential invasion and metastatic characteristics. Flavopiridol was found to inhibit the growth of MDA-MB-435 (parental) and 435.eB (stable transfectants) cells that were established by transfecting c-erbB-2 cDNA into, MDA-MB-435. Induction of apoptosis was also observed in these cell lines when treated with flavopiridol, as measured by DNA laddering, PARP, and CPP32 cleavages. We also found modest up-regulation of fax and down-regulation of Bcl-2, but there was a significant down-regulation of c-erbB-2 in flavopiridol-treated cells. Gelatin zymography showed that flavopiridol inhibits the secretion of matrix metalloproteinase (MMP; MMPs 2 and 9) in the breast cancer cells and that the inhibition of c-erbB-2 and MMPs may be responsible for the inhibition of cell invasion observed in flavopiridol-treated cells. Collectively, these molecular effects of flavopiridol, however, were found to be independent of c-erbB-2 overexpression, suggesting that flavopiridol may be effective in all breast cancer, From these results, we conclude that flavopiridol inhibits the growth of MDA-MB-435 breast cancer cells, induces apoptosis, regulates the expression of genes, and inhibits invasion and, thus, may inhibit metastasis of breast cancer cells. These findings suggest that flavopiridol may be an effective chemotherapeutic or preventive agent against breast cancer. C1 Wayne State Univ, Sch Med, Dept Pathol, Karmanos Canc Inst, Detroit, MI 48201 USA. NCI, Dev Therapeut Program, Bethesda, MD 20892 USA. RP Sarkar, FH (reprint author), Wayne State Univ, Sch Med, Dept Pathol, Karmanos Canc Inst, 9374 Scott Hall,540 E Canfield Ave, Detroit, MI 48201 USA. NR 30 TC 38 Z9 41 U1 0 U2 1 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 JAN PY 2000 VL 6 IS 1 BP 223 EP 229 PG 7 WC Oncology SC Oncology GA 276YP UT WOS:000084906200029 PM 10656453 ER PT J AU Svingen, PA Tefferi, A Kottke, TJ Kaur, G Narayanan, VL Sausville, EA Kaufmann, SH AF Svingen, PA Tefferi, A Kottke, TJ Kaur, G Narayanan, VL Sausville, EA Kaufmann, SH TI Effect of the bcr/abl kinase inhibitors AG957 and NSC 680410 on chronic myelogenous leukemia cells in vitro SO CLINICAL CANCER RESEARCH LA English DT Article ID ABL TYROSINE KINASE; DRUG-INDUCED APOPTOSIS; APO-1/FAS RECEPTOR/LIGAND SYSTEM; CHEMOTHERAPY-INDUCED APOPTOSIS; TOPOISOMERASE-II LEVELS; BCR-ABL; PHILADELPHIA-CHROMOSOME; POSITIVE CELLS; BONE-MARROW; K562 CELLS AB The tyrphostin AG957 (NSC 654705) inhibits p210(bcr/abl), the transforming kinase responsible for most eases of chronic myelogenous leukemia (CML), The present studies were performed to determine the fate of AG957-treated cells and assess the selectivity of AG957 for CML myeloid progenitors, When K562 cells (derived from a patient with blast crisis CML) were treated with AG957, dose- and time-dependent p210(ber/abl) down-regulation was followed by mitochondrial release of cytochrome c, activation of caspase-9 and caspase-3, and apoptotic morphological changes. These apoptotic changes were inhibited by transfection with cDNA encoding dominant negative caspase-9 but not dominant-negative FADD or blocking anti-Fas antibodies, In additional experiments, a 24-h AG957 exposure caused dose-dependent inhibition of K562 colony formation in soft agar. To extend these studies to clinical samples of CML, peripheral blood mononuclear cells from 10 chronic phase CML patients and normal controls were assayed for the growth of hematopoietic colonies in vitro in the presence of increasing concentrations of AG957. These assays demonstrated selectivity of AG957 for CML progenitors, with median IC(50)s (CML versus normal) of 7.3 versus >20 mu M AG957 in granulocyte colony-forming cells (P < 0.001), 5.3 versus >20 mu M in granulocyte/macrophage colony-forming cells (P < 0.05), and 15.5 versus >20 mu M in erythroid colony-forming cells (P > 0.05). The adamantyl ester of AG957 (NSC 680410) down-regulated p210(bcr/abl) in K562 cells and inhibited granulocyte colony formation in CML specimens at lower concentrations; without enhanced toxicity in normal progenitors. These observations not only demonstrate that AG957-induced p210(bcr/abl) down-regulation is followed by activation of the cytochrome c/Apaf-1/caspase-9 pathway but also indicate that this class of kinase inhibitor exhibits selectivity worthy of further evaluation. C1 Mayo Clin, Div Oncol Res, Dept Oncol, Rochester, MN 55905 USA. Mayo Clin, Dept Internal Med, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Mayo Med Sch, Dept Pharmacol, Rochester, MN 55905 USA. NCI, Dev Therapeut Program, Div Canc Treatment & Diagnost, Bethesda, MD 20892 USA. RP Kaufmann, SH (reprint author), Mayo Clin, Div Oncol Res, Dept Oncol, Guggenheim 1342,200 1st St SW, Rochester, MN 55905 USA. FU NCI NIH HHS [U01 CA69912, R01 CA69008] NR 91 TC 67 Z9 69 U1 0 U2 0 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 JAN PY 2000 VL 6 IS 1 BP 237 EP 249 PG 13 WC Oncology SC Oncology GA 276YP UT WOS:000084906200031 PM 10656455 ER PT J AU Levy, R Davis, TA AF Levy, R Davis, TA TI Correspondence re: T. Davis et al, therapy of B-cell lymphoma with anti-CD20 antibodies can result in loss of CD20 antigen expression. Clin. Cancer Res., 5 : 611-615, 1999. Reply SO CLINICAL CANCER RESEARCH LA English DT Letter C1 Stanford Univ, Sch Med, Div Oncol M211, Stanford, CA 94305 USA. NCI, NIH, Rockville, MD 20852 USA. RP Levy, R (reprint author), Stanford Univ, Sch Med, Div Oncol M211, 300 Pasteur Dr, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2000 VL 6 IS 1 BP 318 EP 318 PG 1 WC Oncology SC Oncology GA 276YP UT WOS:000084906200042 ER PT J AU Yuan, CC Peterson, RJ Wang, CD Goodsaid, F Waters, DJ AF Yuan, CC Peterson, RJ Wang, CD Goodsaid, F Waters, DJ TI 5 ' nuclease assays for the loci CCR5-+/Delta 32, CCR2-V64I, and SDFI-G80IA related to pathogenesis of AIDS SO CLINICAL CHEMISTRY LA English DT Article ID MOLECULAR BEACONS; GENETIC INFORMATION; DISEASE PROGRESSION; HIV-1 INFECTION; HUMAN DNA; ALLELE; GENOME; POLYMORPHISMS; HYBRIDIZATION; RESTRICTION AB Background: Variations within the human genome play important roles in human disease. To study variations related to susceptibility to AIDS, we have developed 5' nuclease assays that eliminate post-PCR molecular biology steps. Methods: TaqMan assays based on the 5' nuclease activity of Tag polymerase and fluorescent resonance energy transfer were developed to score alleles at the biallelic loci CCR5-+/Delta 32, CCR2-V641 and SDF1-G801A. For each assay, 72 samples were analyzed. Data collection and analysis were performed on the Prism 7700 Sequence Detection System. For comparison with gel electrophoresis methods, each locus was also scored on a subset of 24 samples, using restriction enzymes or single-strand conformational polymorphism (SSCP). Results: Clear allelic discrimination was obtained on each of the 72 samples for all three TaqMan assays. The TaqMan scores for the subset of 24 samples were concordant with the restriction enzyme and SSCP scores. Conclusions: Because of its simplicity, speed, and potential for automation and miniaturization, TaqMan is an excellent candidate for investigation of genetic variation in clinical, research, and forensic settings. (C) 2000 American Association for Clinical Chemistry. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Gen Divers, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, AIDS Vaccine Program, Frederick, MD 21702 USA. PE Appl Biosyst, Foster City, CA 94404 USA. RP Waters, DJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Gen Divers, Frederick, MD 21702 USA. FU NCI NIH HHS [N01CO56000] NR 28 TC 8 Z9 8 U1 0 U2 2 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JAN PY 2000 VL 46 IS 1 BP 24 EP 30 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 274YR UT WOS:000084793100004 PM 10620568 ER PT J AU Liu, YQ Kyle, E Lieberman, R Crowell, J Kelloff, G Bergan, RC AF Liu, YQ Kyle, E Lieberman, R Crowell, J Kelloff, G Bergan, RC TI Focal adhesion kinase (FAK) phosphorylation is not required for genistein-induced FAK-beta-1-integrin complex formation SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE focal adhesion kinase; prostate cancer; genistein; integrin; cell adhesion; tyrosine kinase inhibitor ID PROTEIN-TYROSINE KINASE; PROSTATE-CANCER CELLS; SIGNAL-TRANSDUCTION; PP125(FAK); EXPRESSION; TUMOR; FIBRONECTIN; DOMAIN; ASSOCIATION; INHIBITION AB It has previously been shown that changes in the activity of focal adhesion kinase (FAK), and its binding to beta -1-integrin, accompany genistein-induced adhesion of prostate cells. Consumption of genistein world wide is associated with a lower incidence of metastatic prostate cancer. Early human clinical trials of genistein are under way to evaluate genistein's potential causal role in this regard. Though an important cell adhesion-associated signaling molecule, FAK's role in regulating prostate cell adhesion was not clear. Elucidation of this process would provide important information relating to both biology and potential clinical endpoints. It was hypothesized that FAK activation and complex formation are temporally related in prostate cells, and can thus be separated. Significant activation of FAK was demonstrated when cells adhered to fibronectin, as compared to poly-l-lysine, thus demonstrating that beta -1-integrin plays a significant role in activating FAK. Neither FAK activation, nor FAK-integrin complex formation, required beta -1-integrin ligand. However, disruption of the cellular cytoskeleton by cytochalasin D prevented FAK activation, but did not block genistein-induced complex formation. In the face of a disrupted cytoskeleton, signaling through FAK could not be restored through either integrin cross linking, or re-establishment of tensile forces via attachment to solid matrix. These studies demonstrate that FAK-beta -1-integrin complex formation does not require FAK activation, suggesting that it is an early event in prostate cell adhesion. An intact cytoskeleton is necessary for FAK activation. The functional importance of beta -1-integrin in prostate cells is demonstrated. Current findings support plans to test genistein in prostate cancer. C1 Northwestern Univ, Sch Med, Dept Med, Div Hematol Oncol, Chicago, IL 60611 USA. Northwestern Univ, Robert H Lurie Canc Ctr, Chicago, IL 60611 USA. NCI, Bethesda, MD 20892 USA. RP Bergan, RC (reprint author), Northwestern Univ, Sch Med, Dept Med, Div Hematol Oncol, Olson 8524,710 N Fairbanks, Chicago, IL 60611 USA. NR 41 TC 28 Z9 28 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PY 2000 VL 18 IS 3 BP 203 EP 212 DI 10.1023/A:1006729106034 PG 10 WC Oncology SC Oncology GA 409JV UT WOS:000167381300001 PM 11315093 ER PT J AU Khanna, C Prehn, J Yeung, C Caylor, J Tsokos, M Helman, L AF Khanna, C Prehn, J Yeung, C Caylor, J Tsokos, M Helman, L TI An orthotopic model of murine osteosarcoma with clonally related variants differing in pulmonary metastatic potential SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE cancer; model; murine; orthotopic; osteosarcoma; spontaneous pulmonary metastasis ID NUDE-MICE; IN-VITRO; VASCULOGENIC MIMICRY; CANCER METASTASIS; CARCINOMA-CELLS; TISSUE; TUMORS; VIVO; LUNG; MICROENVIRONMENT AB To provide an investigative tool for the study of osteosarcoma (OSA) biology we have developed a syngeneic (balb/c) murine model of OSA, using cell lines derived from a spontaneously occurring murine OSA (Schmidt et al. Differentiation 1988; 39: 151-60). This model is characterized by orthotopic primary tumor growth, a period of minimal residual disease, spontaneous pulmonary metastasis, and clonally related variants (K7M2 and K12) that differ in pulmonary metastatic potential. Primary tumor and pulmonary metastasis histology was consistent with OSA in human patients. Expression of bone sialoprotein, biglyan, decorrin, and osteopontin was suggestive of bone lineage cells. The development and use of a more aggressive OSA cell line (K7M2) resulted in spontaneous metastasis to the lungs in over 90% of mice, whereas metastases were seen in only 33% of mice when a less aggressive OSA cell line (K12; Schmidt et al. Differentiation 1988; 39: 151-60) was used. Death from metastasis occurred at a median of 76 days using K7M2 whereas no median was achieved after 140 days using K12. Angiogenic potential, characterized by CD31 and factor VIII staining of primary tumors and pulmonary metastases, was greater in the K7M2 model compared to the K12 model. No significant differences in the in vitro or in vivo expression of angiogenesis associated genes (flt1, flt4, TIE1, TIE2, and VEGF) was found between K7M2 and K12. This well characterized and relevant model of OSA will be a valuable resource to improve our understanding of the biology and treatment of metastasis in OSA. C1 NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Khanna, C (reprint author), NCI, Pediat Oncol Branch, NIH, 10-13N240,10 Ctr Dr, Bethesda, MD 20892 USA. NR 41 TC 108 Z9 117 U1 1 U2 7 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PY 2000 VL 18 IS 3 BP 261 EP 271 DI 10.1023/A:1006767007547 PG 11 WC Oncology SC Oncology GA 409JV UT WOS:000167381300008 PM 11315100 ER PT J AU Graybill, JR Sobel, J Saag, M van der Horst, C Powderly, W Cloud, G Riser, L Hamill, R Dismukes, W AF Graybill, JR Sobel, J Saag, M van der Horst, C Powderly, W Cloud, G Riser, L Hamill, R Dismukes, W CA NIAID Mycoses Study Grp AIDS Cooperative Treatment Grp TI Diagnosis and management of increased intracranial pressure in patients with AIDS and cryptococcal meningitis SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; TUBERCULOUS MENINGITIS; AMPHOTERICIN-B; CEREBROSPINAL-FLUID; ITRACONAZOLE; FLUCONAZOLE; THERAPY; TISSUE AB This study was undertaken to characterize the laboratory and clinical course of patients with AIDS and cryptococcal meningitis who had normal or elevated cerebrospinal fluid (CSF) pressure. Data were obtained retrospectively from a randomized multicenter quasifactorial phase III study comparing amphotericin B with or without flucytosine in primary treatment of cryptococcal meningitis. CSF pressure was measured before treatment and at 2 weeks. Repeated lumbar punctures were done to drain CSF and to reduce pressure, Patients with the highest baseline opening pressures (greater than or equal to 250 mm H2O) were distinguished by higher titers of cryptococcal capsular polysaccharide antigen in CSF; more frequently positive India ink smears of CSF; and more frequent headache, meningismus, papilledema, hearing loss, and pathological reflexes. After receiving antifungal therapy, those patients whose CSF pressure was reduced by >10 mm or did not change had more frequent clinical response at 2 weeks than did those whose pressure increased >10 mm (P <.001), Patients with pretreatment opening pressure greater than or equal to 250 mm H2O had increased short-term survival compared with those with higher pressure, We recommend that opening pressures greater than or equal to 250 mm H2O be treated with large-volume CSF drainage. C1 Audie L Murphy Mem Vet Hosp Div, S Texas Vet Hlth Care Syst, Infect Dis Sect 111F, San Antonio, TX 78284 USA. Houston Vet Adm Hosp, Houston, TX USA. Wayne State Univ, Detroit, MI USA. Univ Alabama Birmingham, Birmingham, AL USA. Univ N Carolina, Chapel Hill, NC USA. Washington Univ, St Louis, MO USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Audie L Murphy Mem Vet Hosp Div, S Texas Vet Hlth Care Syst, Infect Dis Sect 111F, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. EM graybill@uthscsa.edu FU NIAID NIH HHS [AI-65296, AI-15082] NR 32 TC 202 Z9 219 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN PY 2000 VL 30 IS 1 BP 47 EP 54 DI 10.1086/313603 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 278TJ UT WOS:000085004800011 PM 10619732 ER PT J AU Sata, F Sapone, A Elizondo, G Stocker, P Miller, VP Zheng, W Raunio, H Crespi, CL Gonzalez, FJ AF Sata, F Sapone, A Elizondo, G Stocker, P Miller, VP Zheng, W Raunio, H Crespi, CL Gonzalez, FJ TI CYP3A4 allelic variants with amino acid substitutions in exons 7 and 12: Evidence for an allelic variant with altered catalytic activity SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID HUMAN LIVER-MICROSOMES; NIFEDIPINE OXIDASE; GENETIC-POLYMORPHISM; NUCLEAR RECEPTOR; CYTOCHROME-P450; BACULOVIRUS; EXPRESSION; METABOLISM; OXIDATION; STEREOSELECTIVITY AB Objective: To determine the existence of mutant and variant C Y P3A4 alleles in three racial groups and to assess functions of the variant alleles by complementary deoxyribonucleic acid (cDNA) expression, Methods: A bacterial artificial chromosome that contains the complete C Y P3A4 gene: was isolated and the exons and surrounding introns were directly sequenced to develop primers to polymerase chain reaction (PCR) amplify and sequence the gene from lymphocyte DNA. DNA samples from Chinese, black, and white subjects were screened. Mutating the affected amino acid in the wild-type cDNA and expressing the variant enzyme with use of the baculovirus system was used to functionally evaluate the variant allele having a missense mutation, Results: To investigate the existence of mutant and variant C Y P3A4 alleles in humans, all 13 exons and the 5'-flanking region of the human C Y P3A4 gene in three racial groups were sequenced and four alleles were identified. An A-->G point mutation in the 5'-flanking region of the human C Y P3A4 gene, designated C Y P3A4*1B, was found in the three different racial groups, The frequency of this allele in a white population was 4.2%, whereas it was 66.7% in black subjects. The C Y P3A4*1B allele was not found in Chinese subjects. A second variant allele, designated C Y P3A4*2 having a Ser222Pro change, was found at a frequency of 2.7% in the white population and was absent in the black: subjects and Chinese subjects analyzed. Baculovirus-directed cDNA expression revealed that the C Y P3A4*2 P450 had a lower intrinsic clearance for the C Y P3A4 substrate nifedipine compared with the wild-type: enzyme but was not significantly different from the wild-type enzyme for testosterone 6 beta-hydroxylation. Another rare allele, designated C Y P3A4*3, was found in a single Chinese subject who had a Met445Thr change in the conserved heme-binding region of the P450. Conclusions: These are the fu st examples of potential function polymorphisms resulting from missense mutations in the C Y P3A4 gene, The C Y P3A4*2 allele was found to encode a P450 with substrate-dependent altered kinetics compared with the wild-type P450. C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. Gentest Corp, Woburn, MA USA. Univ S Carolina, Sch Publ Hlth, Columbia, SC 29208 USA. Univ Oulu, Dept Pharmacol & Toxicol, Oulu, Finland. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, NIH, Bldg 37,Room 3E24, Bethesda, MD 20892 USA. RI Sapone, Andrea/E-6704-2013; OI Sapone, Andrea/0000-0001-8496-6977 NR 38 TC 238 Z9 258 U1 0 U2 3 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 JAN PY 2000 VL 67 IS 1 BP 48 EP 56 DI 10.1067/mcp.2000.104391 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 280DP UT WOS:000085087200007 PM 10668853 ER PT S AU Wise, RA AF Wise, RA BE Uylings, HBM VanEden, CG DeBruin, JPC Feenstra, MGP Pennartz, CMA TI Interactions between medial prefrontal cortex and meso-limbic components of brain reward circuitry SO COGNITION, EMOTION AND AUTONOMIC RESPONSES: THE INTEGRATIVE ROLE OF THE PREFRONTAL CORTEX AND LIMBIC STRUCTURES SE Progress in Brain Research LA English DT Review CT 21st International Summer School of Brain Research CY AUG 23-27, 1999 CL ROYAL NETHERLANDS ACAD SCI, AMSTERDAM, NETHERLANDS SP Pfizer bv, VanDenHouten Fdn, N V Organon, Antec Leyden, Grat Sch Neurosci Amsterdam, Inst Rech Pierre Fabre, Janssen Res Fdn, Merck Res Lab USA, Noldus Informat Technol bv, Novartis Pharma AG, Switzerland, Philips Med Syst, Sanofi Rech, Solvay Pharmaceut, Stichting Het Remmert Adriaan Laan Fonds, Synthelabo Rech, Yamanouchi Europe B V HO ROYAL NETHERLANDS ACAD SCI ID VENTRAL TEGMENTAL AREA; CAT CAUDATE-NUCLEUS; INVIVO PRESYNAPTIC CONTROL; METABOTROPIC GLUTAMATE RECEPTORS; INCREASES DOPAMINE RELEASE; EXCITATORY AMINO-ACIDS; IN-VIVO MICRODIALYSIS; FREELY MOVING RATS; METHYL-D-ASPARTATE; ELECTRICAL-STIMULATION C1 NIDA, Intramural Res Program, Baltimore, MD 21224 USA. RP Wise, RA (reprint author), NIDA, Intramural Res Program, POB 5180, Baltimore, MD 21224 USA. EM rwise@intra.nida.nih.gov RI Wise, Roy/A-6465-2012 NR 58 TC 13 Z9 13 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 0-444-50332-3 J9 PROG BRAIN RES JI Prog. Brain Res. PY 2000 VL 126 BP 255 EP 262 PG 8 WC Neurosciences SC Neurosciences & Neurology GA BS30A UT WOS:000169388500016 PM 11105651 ER PT J AU Goodman, MF Woodgate, R AF Goodman, MF Woodgate, R TI The biochemical basis and in vivo regulation of SOS-induced mutagenesis promoted by Escherichia coli DNA polymerase V (UmuD ' C-2) SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT Cold Spring Harbor Symposium on Quantitative Biology CY 2000 CL NEW YORK, NEW YORK SP Amgen Inc, Aventis Pharma AG, BASF Biores Corp, BioVentures Inc, Bristol Myers Squibb Co, Chiron Corp, Chugai Res Inst Molec Med Inc, Diagnost Prod Corp, DuPont Pharmaceut Co, Forest Labs, Genentech Inc, Genetics Inst, Glaxo Wellcome Inc, Hoffmann La Roche Inc, Johnson & Johnson, Kyowa Hakko Kogyo Co Ltd, Eli Lilly & Co, Merck Res Labs, New England BioLabs Inc, Novartis Pharma Res, OSI Pharmaceut Inc, Pall Corp, Palmetto Partners Ltd, Parke Davis Pharmaceut Res, PE Biosystem, Pfizer Inc, Pharmacia & Upjohn Inc, Res Genetics Inc, Shering Plough Corp, SmithKline Beecham Pharmaceut, AstraZeneca ID SINGLE-STRANDED-DNA; CONSTITUTIVE EXPRESSION; XERODERMA-PIGMENTOSUM; INDUCIBLE MUTAGENESIS; ACCESSORY PROTEINS; ULTRAVIOLET-LIGHT; III HOLOENZYME; RECA PROTEIN; POL-II; DAMAGE C1 Univ So Calif, Hedco Mol Biol Lab, Dept Biol Sci & Chem, Los Angeles, CA 90089 USA. NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. RP Goodman, MF (reprint author), Univ So Calif, Hedco Mol Biol Lab, Dept Biol Sci & Chem, Los Angeles, CA 90089 USA. FU NIGMS NIH HHS [GM-42554, GM-21422] NR 71 TC 17 Z9 18 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 2000 VL 65 BP 31 EP 40 DI 10.1101/sqb.2000.65.31 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 449GW UT WOS:000169676800005 PM 12760018 ER PT J AU Gerlach, VL Feaver, WJ Fischhaber, PL Richardson, JA Aravind, L Koonin, EV Bebenek, K Kunkel, TA Friedberg, EC AF Gerlach, VL Feaver, WJ Fischhaber, PL Richardson, JA Aravind, L Koonin, EV Bebenek, K Kunkel, TA Friedberg, EC TI Human DNA polymerase kappa: A novel DNA polymerase of unknown biological function encoded by the DINB1 gene SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT Cold Spring Harbor Symposium on Quantitative Biology CY 2000 CL NEW YORK, NEW YORK SP Amgen Inc, Aventis Pharma AG, BASF Biores Corp, BioVentures Inc, Bristol Myers Squibb Co, Chiron Corp, Chugai Res Inst Molec Med Inc, Diagnost Prod Corp, DuPont Pharmaceut Co, Forest Labs, Genentech Inc, Genetics Inst, Glaxo Wellcome Inc, Hoffmann La Roche Inc, Johnson & Johnson, Kyowa Hakko Kogyo Co Ltd, Eli Lilly & Co, Merck Res Labs, New England BioLabs Inc, Novartis Pharma Res, OSI Pharmaceut Inc, Pall Corp, Palmetto Partners Ltd, Parke Davis Pharmaceut Res, PE Biosystem, Pfizer Inc, Pharmacia & Upjohn Inc, Res Genetics Inc, Shering Plough Corp, SmithKline Beecham Pharmaceut, AstraZeneca ID ACUTE MYELOGENOUS LEUKEMIA; ESCHERICHIA-COLI DINB; XERODERMA-PIGMENTOSUM; MOUSE HOMOLOGS; THYMINE DIMER; PROTEIN; MUTAGENESIS; ETA; BYPASS; UMUC C1 Univ Texas, SW Med Ctr, Dept Pathol, Lab Mol Pathol, Dallas, TX 75390 USA. Texas A&M Univ, Dept Biol, College Stn, TX USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Gerlach, VL (reprint author), Univ Texas, SW Med Ctr, Dept Pathol, Lab Mol Pathol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. FU NCI NIH HHS [CA-75733, CA-83314, CA-69029] NR 44 TC 11 Z9 11 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 2000 VL 65 BP 41 EP 49 DI 10.1101/sqb.2000.65.41 PG 9 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 449GW UT WOS:000169676800006 PM 12760019 ER PT J AU Bebenek, K Kunkel, TA AF Bebenek, K Kunkel, TA TI Streisinger revisited: DNA synthesis errors mediated by substrate misalignments SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT Cold Spring Harbor Symposium on Quantitative Biology CY 2000 CL NEW YORK, NEW YORK SP Amgen Inc, Aventis Pharma AG, BASF Biores Corp, BioVentures Inc, Bristol Myers Squibb Co, Chiron Corp, Chugai Res Inst Molec Med Inc, Diagnost Prod Corp, DuPont Pharmaceut Co, Forest Labs, Genentech Inc, Genetics Inst, Glaxo Wellcome Inc, Hoffmann La Roche Inc, Johnson & Johnson, Kyowa Hakko Kogyo Co Ltd, Eli Lilly & Co, Merck Res Labs, New England BioLabs Inc, Novartis Pharma Res, OSI Pharmaceut Inc, Pall Corp, Palmetto Partners Ltd, Parke Davis Pharmaceut Res, PE Biosystem, Pfizer Inc, Pharmacia & Upjohn Inc, Res Genetics Inc, Shering Plough Corp, SmithKline Beecham Pharmaceut, AstraZeneca ID POLYMERASE-III HOLOENZYME; ESCHERICHIA-COLI; BASE SUBSTITUTION; MISMATCH REPAIR; MUTATIONAL SPECIFICITY; FRAMESHIFT FIDELITY; NUCLEOTIDE MISINCORPORATION; TRANSIENT MISALIGNMENT; REVERSE-TRANSCRIPTASE; REPLICATION FIDELITY C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Bebenek, K (reprint author), NIEHS, Mol Genet Lab, POB 12233, Res Triangle Pk, NC 27709 USA. NR 53 TC 55 Z9 56 U1 0 U2 5 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 2000 VL 65 BP 81 EP 91 DI 10.1101/sqb.2000.65.81 PG 11 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 449GW UT WOS:000169676800010 PM 12760023 ER PT J AU Wilson, SH Sobol, RW Beard, WA Horton, JK Prasad, R Berg, BJV AF Wilson, SH Sobol, RW Beard, WA Horton, JK Prasad, R Berg, BJV TI DNA polymerase beta and mammalian base excision repair SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT Cold Spring Harbor Symposium on Quantitative Biology CY 2000 CL NEW YORK, NEW YORK SP Amgen Inc, Aventis Pharma AG, BASF Biores Corp, BioVentures Inc, Bristol Myers Squibb Co, Chiron Corp, Chugai Res Inst Molec Med Inc, Diagnost Prod Corp, DuPont Pharmaceut Co, Forest Labs, Genentech Inc, Genetics Inst, Glaxo Wellcome Inc, Hoffmann La Roche Inc, Johnson & Johnson, Kyowa Hakko Kogyo Co Ltd, Eli Lilly & Co, Merck Res Labs, New England BioLabs Inc, Novartis Pharma Res, OSI Pharmaceut Inc, Pall Corp, Palmetto Partners Ltd, Parke Davis Pharmaceut Res, PE Biosystem, Pfizer Inc, Pharmacia & Upjohn Inc, Res Genetics Inc, Shering Plough Corp, SmithKline Beecham Pharmaceut, AstraZeneca ID 5'-TERMINAL DEOXYRIBOSE-PHOSPHATE; DEOXYRIBOPHOSPHODIESTERASE DRPASE ACTIVITY; ANTIGEN-DEPENDENT REPAIR; CHAIN-REACTION ASSAY; CANCER CELL-LINES; BIG BLUE(R) RAT2; METHYL METHANESULFONATE; COMET-ASSAY; ESCHERICHIA-COLI; NUCLEOTIDE INCORPORATION C1 NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RI Sobol, Robert/E-4125-2013 OI Sobol, Robert/0000-0001-7385-3563 NR 97 TC 31 Z9 32 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 2000 VL 65 BP 143 EP 155 DI 10.1101/sqb.2000.65.143 PG 13 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 449GW UT WOS:000169676800016 PM 12760029 ER PT J AU Yang, W Junop, MS Ban, C Obmolova, G Hsieh, P AF Yang, W Junop, MS Ban, C Obmolova, G Hsieh, P TI DNA mismatch repair: From structure to mechanism SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT Cold Spring Harbor Symposium on Quantitative Biology CY 2000 CL NEW YORK, NEW YORK SP Amgen Inc, Aventis Pharma AG, BASF Biores Corp, BioVentures Inc, Bristol Myers Squibb Co, Chiron Corp, Chugai Res Inst Molec Med Inc, Diagnost Prod Corp, DuPont Pharmaceut Co, Forest Labs, Genentech Inc, Genetics Inst, Glaxo Wellcome Inc, Hoffmann La Roche Inc, Johnson & Johnson, Kyowa Hakko Kogyo Co Ltd, Eli Lilly & Co, Merck Res Labs, New England BioLabs Inc, Novartis Pharma Res, OSI Pharmaceut Inc, Pall Corp, Palmetto Partners Ltd, Parke Davis Pharmaceut Res, PE Biosystem, Pfizer Inc, Pharmacia & Upjohn Inc, Res Genetics Inc, Shering Plough Corp, SmithKline Beecham Pharmaceut, AstraZeneca ID ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; ATP-HYDROLYSIS; HETERODUPLEX DNA; MOLECULAR SWITCH; SLIDING CLAMP; HMUTS-ALPHA; RECOGNITION; BINDING; PROTEIN C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Yang, W (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RI Yang, Wei/D-4926-2011; Ban, Changill/F-5426-2013; Junop, Murray/E-4160-2015 OI Yang, Wei/0000-0002-3591-2195; Junop, Murray/0000-0001-6676-5717 NR 47 TC 23 Z9 25 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 2000 VL 65 BP 225 EP 232 DI 10.1101/sqb.2000.65.225 PG 8 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 449GW UT WOS:000169676800023 PM 12760036 ER PT J AU Lee, JS Collins, K Brown, A Lee, CH Chung, JH AF Lee, JS Collins, K Brown, A Lee, CH Chung, JH TI The function of BRCA1 in DNA damage response SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT Cold Spring Harbor Symposium on Quantitative Biology CY 2000 CL NEW YORK, NEW YORK SP Amgen Inc, Aventis Pharma AG, BASF Biores Corp, BioVentures Inc, Bristol Myers Squibb Co, Chiron Corp, Chugai Res Inst Molec Med Inc, Diagnost Prod Corp, DuPont Pharmaceut Co, Forest Labs, Genentech Inc, Genetics Inst, Glaxo Wellcome Inc, Hoffmann La Roche Inc, Johnson & Johnson, Kyowa Hakko Kogyo Co Ltd, Eli Lilly & Co, Merck Res Labs, New England BioLabs Inc, Novartis Pharma Res, OSI Pharmaceut Inc, Pall Corp, Palmetto Partners Ltd, Parke Davis Pharmaceut Res, PE Biosystem, Pfizer Inc, Pharmacia & Upjohn Inc, Res Genetics Inc, Shering Plough Corp, SmithKline Beecham Pharmaceut, AstraZeneca ID EARLY EMBRYONIC LETHALITY; MAMMARY EPITHELIAL-CELLS; OVARIAN-CANCER; ATAXIA-TELANGIECTASIA; S-PHASE; HUMAN BREAST; SCHIZOSACCHAROMYCES-POMBE; SACCHAROMYCES-CEREVISIAE; NUCLEAR PHOSPHOPROTEIN; CYCLE REGULATION C1 NHLBI, Lab Mol Hematol, NIH, Bethesda, MD 20892 USA. RP Lee, JS (reprint author), NHLBI, Lab Mol Hematol, NIH, Bethesda, MD 20892 USA. NR 81 TC 1 Z9 1 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 2000 VL 65 BP 547 EP 552 DI 10.1101/sqb.2000.65.547 PG 6 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 449GW UT WOS:000169676800059 PM 12760072 ER PT S AU Sausville, EA Johnson, J Alley, M Zaharevitz, D Senderowicz, AM AF Sausville, EA Johnson, J Alley, M Zaharevitz, D Senderowicz, AM BE Hanski, C Scherubl, H Mann, B TI Inhibition of CDKs as a therapeutic modality SO COLORECTAL CANCER: NEW ASPECTS OF MOLECULAR BIOLOGY AND IMMUNOLOGY AND THEIR CLINICAL APPLICATIONS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Colorectal Cancer - New Aspects of Molecular Biology, Immunology and Clinical Applications CY OCT 08-09, 1999 CL BERLIN, GERMANY ID CYCLIN-DEPENDENT KINASES; BREAST-CARCINOMA CELLS; FLAVOPIRIDOL INDUCES APOPTOSIS; ACTIVITY IN-VIVO; ANTITUMOR-ACTIVITY; HUMAN CANCER; SELECTIVE INHIBITOR; POTENT INHIBITOR; G(1) ARREST; GROWTH AB Altered cell cycle control has emerged as a recurring theme in neoplasia. Strategies that would return toward normal the altered cell cycle control present in tumor cells have appeal as novel approaches to cancer treatment. Cyclin-dependent kinases (CDKs) control the progression through the cell cycle, operating at the transition from the G(2) to M and G(1) to S phases, and progression through S. CDKs are regulated by a complex set of mechanisms, including the presence of activating cyclins, regulatory phosphorylations, and endogenous CDK inhibitors at "checkpoints." This overview focuses on progress in defining compounds that can antagonize directly the action of CDKs. These have emerged as various types of ATP site-directed inhibitors, including flavopiridol, N-substituted adenine derivatives, the natural product butyrolactone, staurosporine derivatives, and, more recently, the synthetic paullones. Paullones appear to be of interest in that one of the most active members of the class, 9-nitropaullone (alsterpaullone), requires relatively brief periods of exposure to living cells in order to effect lasting effects on cellular and proliferative potential. Two of these compounds, flavopiridol and UCN-01 (7-hydroxy-staurosporine), have entered early clinical trials and achieved concentrations that might potentially modulate CDK function. In the case of UCN-01, unexpected human plasma protein binding might prevent direct inhibition of CDKs but allow drug concentrations to be achieved that indirectly affect CDKs by checkpoint abrogation. Further studies with CDK inhibitors should define the expected end point of CDK inhibition more clearly in preclinical models and clinical systems, including cytostasis, apoptosis, or differentiation. C1 NCI, Dev Therapeut Program, Div Canc Treatment & Diag, Rockville, MD 20852 USA. RP Sausville, EA (reprint author), NCI, Dev Therapeut Program, Div Canc Treatment & Diag, 6130 Execut Blvd,Suite 843, Rockville, MD 20852 USA. NR 63 TC 77 Z9 79 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-277-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 910 BP 207 EP 222 PG 16 WC Oncology; Gastroenterology & Hepatology; Medicine, Research & Experimental; Multidisciplinary Sciences SC Oncology; Gastroenterology & Hepatology; Research & Experimental Medicine; Science & Technology - Other Topics GA BQ73F UT WOS:000089326500015 PM 10911915 ER PT J AU Wu, CO Yu, KF Yuan, WS AF Wu, CO Yu, KF Yuan, WS TI Large sample properties and confidence bands for component-wise varying-coefficient regression with longitudinal dependent variable SO COMMUNICATIONS IN STATISTICS-THEORY AND METHODS LA English DT Article DE bandwidth; component-wise smoothing; growth curve; kernel estimation; longitudinal study ID CORRELATED ERRORS; LINEAR-MODELS; CURVES AB Longitudinal studies with repeatedly measured dependent variable (out-come) and time-invariant covariates are common in biomedical and epidemiological studies. A useful statistical tool to evaluate the effects of covariates on the outcome variable over time is the varying-coefficient regression, which considers a linear relationship between the covariates and the outcome at a specific time point but assumes the linear coefficients to be smooth curves over time. In order to provide adequate smoothing for each coefficient curve, Wu and Chiang (1999) proposed a class of component-wise kernel estimators and determined the large sample convergence rates and some of the constant tcr;Ils of the mean squared errors of their estimators. In this paper we calculate the explicit large sample mean squared errors, including the convergence rates and all the constant terms, and the asymptotic distributions of the kernel estimators of Wu and Chiang (1999). These asymptotic distributions are used to construct point-wise confidence intervals and Bonferroni-type confidence bands for the coefficient curves. Through a Monte Carlo simulation, we show that our confidence regions have adequate coverage probabilities. Applying our procedures to a NIH fetal growth study, we show that our procedures are useful to determine the effects of maternal height, cigarette smelting and alcohol consumption on the growth of fetal abdominal circumference over time during pregnancy. C1 Johns Hopkins Univ, Dept Math Sci, Baltimore, MD 21218 USA. NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. NR 30 TC 1 Z9 1 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0361-0926 J9 COMMUN STAT-THEOR M JI Commun. Stat.-Theory Methods PY 2000 VL 29 IS 5-6 BP 1017 EP 1037 DI 10.1080/03610920008832530 PG 21 WC Statistics & Probability SC Mathematics GA 308RV UT WOS:000086727400009 ER PT J AU Han, L Wang, KQ Cheng, YR Du, ZY Rosenthal, NE Primeau, F AF Han, L Wang, KQ Cheng, YR Du, ZY Rosenthal, NE Primeau, F TI Summer and winter patterns of seasonality in Chinese college students: A replication SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID AFFECTIVE-DISORDER; MOOD; PREVALENCE; BEHAVIOR; DEPRESSION AB The goal of this study is to replicate an earlier epidemiological finding of seasonal changes in mood and behavior among Chinese medical students using an independent study population. Three hundred nineteen college students were surveyed with a Chinese version of the Seasonal Pattern Assessment Questionnaire (SPAQ) and the Beck Depression Inventory (BDI) in Jining, China, during March of 1996. The frequency of seasonal patterns and prevalence rates of seasonal affective disorder (SAD) were estimated and compared with data from the medical student survey conducted in the same city. The mean Global Seasonality Score (GSS) of this college student sample was 9.9 +/- 4.9; 84% of the subjects reported some problems with the changing seasons. Summer difficulties were more prevalent than winter difficulties by a ratio of 1.9 to 1 (38.9% v 20.1%). The estimated rates of summer SAD and subsyndromal-SAD (s-SAD) were 7.5% and 11.9%, respectively, as compared with the corresponding winter figures of 5.6% and 6.3%. In addition, the prevalence estimates of winter pattern or winter SADs were higher in males than in females, but the corresponding summer figures showed no gender difference. Compared with the data from the medical student survey, this college student sample had a higher GSS (P < .01) but comparable summer to winter and female to male ratios for the prevalence of SADs (P < .05). These results replicate our previous findings that seasonal problems are common in China, but the predominant problems are summer difficulties rather than winter difficulties, and there is no female preponderance in the prevalence estimates of such problems. Both findings stand in contrast to most Western studies but are consistent with the only other published study performed in the Orient. Copyright (C) 2000 by W.B. Saunders Company. C1 NIMH, Clin Psychobiol Branch, Bethesda, MD 20892 USA. Jining Med Coll, Jining, Peoples R China. Affiliated Psychiat Hosp, Jining, Peoples R China. RP Han, L (reprint author), McGill Univ, St Marys Hosp Ctr, Dept Psychiat, 3830 Lacome Ave, Montreal, PQ H3T 1M5, Canada. NR 18 TC 15 Z9 15 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD JAN-FEB PY 2000 VL 41 IS 1 BP 57 EP 62 DI 10.1016/S0010-440X(00)90132-9 PG 6 WC Psychiatry SC Psychiatry GA 274ZA UT WOS:000084793900009 PM 10646620 ER PT J AU Wilbur, WJ Neuwald, AF AF Wilbur, WJ Neuwald, AF TI A theory of information with special application to search problems SO COMPUTERS & CHEMISTRY LA English DT Article DE information theory; confirmatory information; protein tertiary structure; protein secondary structure; solvent accessibility; alignment profile ID PROTEIN FOLD RECOGNITION; STRUCTURE PREDICTION; SEQUENCE AB Classical information theory concerns itself with communication through a noisy channel and how much one can infer about the channel input from a knowledge of the channel output. Because the channel is noisy the input and output are only related statistically and the rate of information transmission is a statistical concept with little meaning for the individual symbol used in transmission. Here we develop a more intuitive notion of information that is concerned with asking the right questions-that is, with finding those questions whose answer conveys the most information. We call this confirmatory information. In the first part of the paper we develop the general theory, show how it relates to classical information theory, and how in the special case of search problems it allows us to quantify the efficacy of information transmission regarding individual events. That is, confirmatory information measures how well a search for items having certain observable properties retrieves items having some unobserved property of interest. Thus confirmatory information facilitates a useful analysis of search problems and contrasts with classical information theory, which quantifies the efficiency of information transmission but is indifferent to the nature of the particular information being transmitted. The last part of the paper presents several examples where confirmatory information is used to quantify protein structural properties in a search setting. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Natl Lib Med, Bethesda, MD 20894 USA. Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. RP Wilbur, WJ (reprint author), Natl Lib Med, Bldge 38A,Room 8S806,8600 Rockville Pike, Bethesda, MD 20894 USA. FU NLM NIH HHS [R01 LM006747] NR 19 TC 3 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0097-8485 J9 COMPUT CHEM JI Comput. Chem. PD JAN PY 2000 VL 24 IS 1 BP 33 EP 42 DI 10.1016/S0097-8485(99)00045-5 PG 10 WC Chemistry, Multidisciplinary; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA 269QB UT WOS:000084488100004 PM 10642878 ER PT J AU Wan, HH Wootton, JC AF Wan, HH Wootton, JC TI A global compositional complexity measure for biological sequences: AT-rich and GC-rich genomes encode less complex proteins SO COMPUTERS & CHEMISTRY LA English DT Article DE biological sequences; AT-rich; CC-rich ID DIRECTIONAL MUTATION PRESSURE; AMINO-ACID-SEQUENCES; NUCLEOTIDE-SEQUENCES; EVOLUTIONARY DISTANCES; MOLECULAR EVOLUTION; LOCAL COMPLEXITY; DNA-SEQUENCES; CODON USAGE; G+C-CONTENT; SUBSTITUTIONS AB Different local regions of natural amino acid or nucleotide sequences show remarkable heterogeneity in residue composition, reflecting diversity in evolutionary history and physicochemical constraints. Compositional complexity measures are helpful for describing and understanding this variegation. Motivated by same open problems in comparative genomics and protein folding, we have developed a new 'global' compositional complexity measure, G(1), which overcomes a crucial limitation of earlier methods. The 'local' measures used in previous research resemble entropy functions and are inherently dependent on an underlying probability distribution. Local measures cannot rigorously compare complexity across sequences of substantially different size, because real sequences show very irregular heterogeneity and do not have the necessary ergodicity in scaling and asymptotic properties. G(1) is a member of a new class of scale-independent, distribution-independent complexity functions. For a sequence S of length L on an N-letter alphabet, G(1) is derived from ratios in the integer partition lattice, P({L,N}) of L with N parts, where the elements of P({L,N}) are the state vectors of S, (n(1), n(2), n(N)), ranked by an order principle. We present theorems and proofs relating to the metric properties of G(1) and its relationship to other state-vector-dependent compositional complexity functions, together with a fully-efficient O(L) algorithm to compute G(1). The distributions of G(1) were calculated for the entire sets of translated proteins encoded by extensively sequenced genomes. The results establish the existence of a clear evolutionary principle, common to bacteria, archaea and eukaryotes, that the proteins encoded by more extreme AT-rich and GC-rich genomes have generally lower compositional complexity than those of more typical organisms. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Wan, HH (reprint author), NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,8th Floor,8600 Rockville Pike, Bethesda, MD 20894 USA. EM hwan@nih.gov; woot-ton@ncbi.nlm.nih.gov NR 92 TC 37 Z9 38 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0097-8485 J9 COMPUT CHEM JI Comput. Chem. PD JAN PY 2000 VL 24 IS 1 BP 71 EP 94 DI 10.1016/S0097-8485(99)00048-0 PG 24 WC Chemistry, Multidisciplinary; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA 269QB UT WOS:000084488100007 PM 10642881 ER PT J AU Wurthner, JU Mukhopadhyay, AK Peimann, CJ AF Wurthner, JU Mukhopadhyay, AK Peimann, CJ TI A cellular automaton model of cellular signal transduction SO COMPUTERS IN BIOLOGY AND MEDICINE LA English DT Article DE cellular automata; desensitization; mouse Leydig cells; signal transduction; simulation ID MOUSE LEYDIG-CELLS; ADENYLATE-CYCLASE; SIMULATION; SYSTEMS; CAMP; HCG AB On the basis of cellular automata models, a software specifically tailored to model biochemical reactions involved in cellular signal transduction was implemented on a personal computer. Recent data regarding desensitization processes in mouse Leydig cells are used to simulate the underlying reactions of signal transduction. Pretreatment of real Leydig cells with different molecules results in a modification of the signal transduction cascade leading to a diminished response of the cells during subsequent stimulations, The model is capable of simulating the complex behavior of this intracellular second messenger production in a qualitative and semi-quantitative way. The results indicate that quantitative simulations on a molecular level will be possible once appropriate computer hardware is available, The simulations and results of the cellular automaton presented are easily described and comprehended, which make it a useful tool that will facilitate research in cellular signal transduction and other fields covering complex reaction networks, (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Univ Hamburg, Inst Hormone & Fertil Res, D-22529 Hamburg, Germany. Univ Hamburg, Inst Comp Sci Med, D-20246 Hamburg, Germany. RP Wurthner, JU (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Bldg 41,Rm C629,41 Lib Dr, Bethesda, MD 20982 USA. NR 17 TC 15 Z9 15 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0010-4825 J9 COMPUT BIOL MED JI Comput. Biol. Med. PD JAN PY 2000 VL 30 IS 1 BP 1 EP 21 DI 10.1016/S0010-4825(99)00020-7 PG 21 WC Biology; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Computer Science; Engineering; Mathematical & Computational Biology GA 285QM UT WOS:000085399800001 PM 10695812 ER PT S AU Bailey, JJ Berson, AS Handelsman, H AF Bailey, JJ Berson, AS Handelsman, H GP IEEE IEEE TI Dysrhythmia hazard after hospitalization for myocardial infarction: Prognosis by ejection fraction compared with signal-averaged ECG SO COMPUTERS IN CARDIOLOGY 2000, VOL 27 SE COMPUTERS IN CARDIOLOGY LA English DT Proceedings Paper CT 27th Annual Meeting of Computers in Cardiology CY SEP 24-27, 2000 CL CAMBRIDGE, MA SP European Soc Cardiol, Hlth Sci & Technol, Harvard MIT Div ID COST-EFFECTIVENESS; SURVIVORS; DEATH AB We retrieved reports of left ventricular ejection fraction (LVEF) and signal-averaged ECGs (SAECG) used to predict risk of a dysrhythmic event. From each report the number of cases with and without events was extracted to establish accurate values for true positive rate (tpr=sensitivity) and false positive rate (fpr=1 minus specificity). For all the LVEF reports these values were collected and tpr values were plotted vs fpr. The (fpr,tpr) data were summarized by a meta ROC graph using the method of Moses and Shapiro.. A composite weighted mean value and 95% confidence interval were also derived. A summary meta-ROC curve for the SAECG reports was similarly obtained., Meta-ROC analysis of multiple reports better summarizes the performances of different prognostic methods, and allows the effect of combining tests for a larger population to be simulated. C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Bailey, JJ (reprint author), NHLBI, NIH, Bethesda, MD 20892 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0276-6574 BN 0-7803-6557-7 J9 COMPUT CARDIOL PY 2000 VL 27 BP 765 EP 768 DI 10.1109/CIC.2000.898637 PG 4 WC Cardiac & Cardiovascular Systems; Computer Science, Interdisciplinary Applications; Engineering, Biomedical SC Cardiovascular System & Cardiology; Computer Science; Engineering GA BR66S UT WOS:000167110800197 ER PT J AU Xiang, BS AF Xiang, BS TI Coherence-transfer table: A convenient method for deriving coherence-transfer pathways of an NMR pulse sequence. II. Coherence-transfer table in I+, I-, and I-z system SO CONCEPTS IN MAGNETIC RESONANCE LA English DT Article DE spectroscopy; magnetic resonance; nuclear magnetic resonance; coherence-transfer pathway; coherence-transfer table ID FIELD GRADIENTS; SPECTROSCOPY; HAMILTONIANS; SELECTION; FORMALISM AB A convenient method for deriving coherence-transfer pathways in a table format, called a coherence-transfer table, using the shift operator basis l(+), l(-), and l(z) has been developed. This method can be used for analyzing various nuclear magnetic resonance (NMR) pulse sequences. The coherence-transfer table is constructed by using some fairly simple rules. Coherence-transfer pathways, coherence-level pathways, and NMR signals of an NMR pulse sequence can be found easily from the table. (C) 2000 John Wiley & Sons, inc. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Xiang, BS (reprint author), Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY 14853 USA. NR 20 TC 4 Z9 4 U1 0 U2 6 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1043-7347 J9 CONCEPT MAGNETIC RES JI Concepts Magn. Resonance PY 2000 VL 12 IS 1 BP 43 EP 53 DI 10.1002/(SICI)1099-0534(2000)12:1<43::AID-CMR5>3.0.CO;2-G PG 11 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Chemistry; Physics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 267DY UT WOS:000084342700005 ER PT J AU Pelupessy, P Chiarparin, E AF Pelupessy, P Chiarparin, E TI Hartmann-Hahn polarization transfer in liquids: An ideal tool for selective experiments SO CONCEPTS IN MAGNETIC RESONANCE LA English DT Article DE heteronuclear cross-polarization; selective experiments; Hartmann-Hahn ID J-CROSS-POLARIZATION; PULSED-FIELD GRADIENTS; MAGNETIC-RESONANCE; COUPLING-CONSTANTS; COHERENCE-TRANSFER; HETERONUCLEAR; NMR; HOMONUCLEAR; SPECTROSCOPY; SPECTRA AB Cross-polarization using continuous-wave spin-locking fields has never become routine in liquid-state nuclear magnetic resonance. Efficiency of cross-polarization tends to be strongly attenuated if radio-frequency (RF) fields are not perfectly homogeneous. It has recently been demonstrated that imperfections in RF-fields have little effect on efficiency of polarization transfer, provided that RF-amplitudes are comparable to magnitudes of heteronuclear scalar coupling constants, rendering this method ideal for selective experiments. The technique can be exploited for the excitation of nuclei with a low gyromagnetic factor like (13C) and N-15, as well as of nuclei with a high gyromagnetic factor like H-1. Several useful applications are discussed. (C) 2000 John Wiley & Sons, Inc. Concepts Magn Reson 12: 103-124, 2000. C1 Univ Lausanne, Chim Sect, BCH, CH-1015 Lausanne, Switzerland. RP Pelupessy, P (reprint author), NIDDKD, Labs Chem Phys, NIH, Bldg 5, Bethesda, MD 20892 USA. NR 30 TC 41 Z9 41 U1 1 U2 14 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1043-7347 J9 CONCEPT MAGNETIC RES JI Concepts Magn. Resonance PY 2000 VL 12 IS 3 BP 103 EP 124 DI 10.1002/(SICI)1099-0534(2000)12:3<103::AID-CMR1>3.0.CO;2-# PG 22 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Chemistry; Physics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 305XV UT WOS:000086567800001 ER PT B AU Kruth, HS Zhang, WY Ishii, I AF Kruth, HS Zhang, WY Ishii, I BE Lewis, BS Halon, DA Flugelman, MY Touboul, P TI Patocytosis: A novel endocytic pathway for macrophage uptake of LDL SO CORONARY ARTERY DISEASE: PREVENTION TO INTERVENTION LA English DT Proceedings Paper CT 3rd International Congress on Coronary Artery Disease CY OCT 02-05, 2000 CL LYON, FRANCE ID LOW-DENSITY-LIPOPROTEIN; SURFACE-CONNECTED COMPARTMENTS; HUMAN MONOCYTE-MACROPHAGES; FOAM-CELL-FORMATION; LIPID-ACCUMULATION; AGGREGATION; RECEPTOR; INTIMA AB Blood low density lipoproteins (LDL) carry cholesterol into blood vessel walls where the cholesterol can accumulate causing atherosclerotic plaques, the cause of most heart attacks and strokes. LDL is susceptible to aggregate and this promotes LDL retention within the vessel wall. Accumulation of LDL in the vessel wall attracts scavenger cells such as macrophages. Under some conditions macrophages take up LDL, degrade it, and store LDL's cholesterol in lipid droplets. Our research has focused on a novel macrophage endocytic pathway that results in a different fate for LDL cholesterol within macrophages. Incubation of aggregated low density lipoproteins (AgLDL) and other small hydrophobic particles with macrophages leads to their accumulation within a large cytoplasmic labyrinth of surface-connected compartments (SCC) by a process we have named patocytosis. In contrast to rapid and complete degradation of LDL that enters macrophages by coated-pit type endocytosis, most AgLDL that enters macrophages by patocytosis is not degraded. Interestingly, macrophages can reverse LDL aggregation when AgLDL is taken up by patocytosis, Macrophages disaggregate and release AgLDL from SCC when the macrophages are exposed to plasminogen in serum. Macrophages convert inactive serum plasminogen to the active protease, plasmin. This plasmin partially degrades the accumulated AgLDL causing it to disaggregate and release from macrophage SCC. Because aggregation of LDL contributes to its retention in atherosclerotic plaques, macrophage reversal of LDL aggregation should facilitate removal of LDL from atherosclerotic plaques. C1 NHLBI, Sect Expt Atherosclerosis, NIH, Bethesda, MD 20892 USA. RP Kruth, HS (reprint author), NHLBI, Sect Expt Atherosclerosis, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 88-323-0101-6 PY 2000 BP 3 EP 11 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA BR10J UT WOS:000165663200001 ER PT J AU Frattali, CM Sonies, BC AF Frattali, CM Sonies, BC TI Speech and swallowing disturbances in corticobasal degeneration SO CORTICOBASAL DEGENERATION AND RELATED DISORDERS SE ADVANCES IN NEUROLOGY LA English DT Article ID BASAL GANGLIONIC DEGENERATION C1 NIH, Dept Rehabil Med, Speech & Language Pathol Sect, Bethesda, MD 20892 USA. RP Frattali, CM (reprint author), NIH, Dept Rehabil Med, Speech & Language Pathol Sect, Bethesda, MD 20892 USA. NR 23 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0091-3952 J9 ADV NEUROL JI Adv.Neurol. PY 2000 VL 82 BP 153 EP 160 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BP34T UT WOS:000084759000015 PM 10624479 ER PT J AU Overwijk, WW Restifo, NP AF Overwijk, WW Restifo, NP TI Autoimmunity and the immunotherapy of cancer: Targeting the "self" to destroy the "other" SO CRITICAL REVIEWS IN IMMUNOLOGY LA English DT Review DE melanocyte differentiation antigen; gp100; TRP-1; vitiligo; autoimmune disease; melanoma; melanosome; vaccine; T lymphocyte ID MHC CLASS-II; CYTOTOXIC T-LYMPHOCYTES; TUMOR-INFILTRATING LYMPHOCYTES; TYROSINASE-RELATED PROTEIN-2; CHEDIAK-HIGASHI-SYNDROME; B-LYMPHOBLASTOID-CELLS; BROWN LOCUS PROTEIN; EYED DILUTION LOCUS; IMMUNE-RESPONSE; METASTATIC MELANOMA AB It is increasingly clear that immunity to "self''-antigens may result in tumor destruction in mouse and man. But which antigens should be targeted with therapeutic cancer vaccines? In the case of melanoma, recognition of melanocyte differentiation antigens (MDA) can be associated with autoimmune depigmentation (vitiligo). We propose that intersection of protein transport to melanosomes and endosomes allows for the loading of MDA-derived peptides on MHC class II molecules, resulting in the activation of MDA-specific CD4(+) "helper" T cells that aid the induction of melanoma-specific CD8(+) T cells. Thus, the immunogenicity of MDA may be a consequence of their unique cell biology. Studies of MDA-based vaccines can provide new insight into the development of more effective cancer vaccines. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Overwijk, WW (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B42, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [NIH0010139353, Z01 BC010763-01, Z99 TW999999] NR 126 TC 50 Z9 50 U1 0 U2 0 PU BEGELL HOUSE INC PI NEW YORK PA 79 MADISON AVE, SUITE 1205, NEW YORK, NY 10016-7892 USA SN 1040-8401 J9 CRIT REV IMMUNOL JI Crit. Rev. Immunol. PY 2000 VL 20 IS 6 BP 433 EP 450 PG 18 WC Immunology SC Immunology GA 436MC UT WOS:000168938800001 PM 11396680 ER PT J AU Elvevag, B Goldberg, TE AF Elvevag, B Goldberg, TE TI Cognitive impairment in schizophrenia is the core of the disorder SO CRITICAL REVIEWS IN NEUROBIOLOGY LA English DT Review DE cognitive dysfunction; attention; working memory; episodic memory; semantic memory ID MONOZYGOTIC TWINS DISCORDANT; CARD SORTING TEST; SCHIZOTYPAL PERSONALITY-DISORDER; MILDLY DISTURBED SCHIZOPHRENICS; VISUOSPATIAL WORKING-MEMORY; FIRST-EPISODE SCHIZOPHRENIA; CONTINUOUS PERFORMANCE-TEST; TEMPORAL-LOBE EPILEPSY; NEUROPSYCHOLOGICAL DEFICITS; THOUGHT-DISORDER AB Patients with schizophrenia exhibit an exceedingly wide range of symptoms from a variety of domains. The cardinal features are abnormal ideas (such as delusions); abnormal perceptions (such as hallucinations); formal thought disorder (as evidenced by disorganized speech); motor, volitional, and behavioral disorders; and emotional disorders (such as affective flattening or inappropriateness). In addition to these diverse, and sometimes bizarre symptoms, it has become increasingly apparent that the disorder is, to variable degrees, accompanied by a broad spectrum of cognitive impairments. This review addresses the question of whether the cognitive deficits seen in schizophrenic patients are the core features of the disorder. In other words, we explore whether schizophrenia is best characterized by symptoms or cognitive deficits (we suggest the latter) and moreover, whether there is a specific cognitive deficit profile that may assist in diagnosis. First, we discuss what the cognitive deficits are. Then we address in turn the reality, frequency, predictive validity, specificity, course and susceptibility to neuroleptic effects of these cognitive impairments. In brief, we argue that various cognitive deficits are enduring features of the schizophrenia illness, that they are not state-related and are not specific to subtypes of the illness, and, more specifically, that working memory and attention are characteristically impaired in patients with schizophrenia, irrespective of their level of intelligence. Last, we conclude that problems in these cognitive domains are at the very core of the dysfunction in this disease. C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Goldberg, TE (reprint author), NIMH, Clin Brain Disorders Branch, NIH, Bldg 10,Room 4S235, Bethesda, MD 20892 USA. NR 211 TC 449 Z9 455 U1 11 U2 78 PU BEGELL HOUSE INC PI REDDING PA 50 CROSS HIGHWAY, REDDING, CT 06896 USA SN 0892-0915 J9 CRIT REV NEUROBIOL JI Crit. Rev. Neurobiol. PY 2000 VL 14 IS 1 BP 1 EP 21 PG 21 WC Neurosciences SC Neurosciences & Neurology GA 406ZB UT WOS:000167245800001 PM 11253953 ER PT J AU FitzGerald, D Mrsny, RJ AF FitzGerald, D Mrsny, RJ TI New approaches to antigen delivery SO CRITICAL REVIEWS IN THERAPEUTIC DRUG CARRIER SYSTEMS LA English DT Review DE vaccination; tolerization; mucosal immunity; antigen delivery ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEAT-LABILE ENTEROTOXIN; COLONY-STIMULATING FACTOR; TOXIN-B-SUBUNIT; CELLULAR IMMUNE-RESPONSES; MARGINAL ZONE MACROPHAGES; HERPES-SIMPLEX VIRUS; CYTOTOXIC T-CELLS; COMPLEX CLASS-I; MAJOR HISTOCOMPATIBILITY MOLECULES AB An improved understanding of immunologic events associated with immunization, the identification of promising new antigens, and an increased capacity to generate these antigens through chemical and biotechnology methods have led to many new vaccine opportunities. Inappropriate antigen exposure, however, can result in unwanted outcomes, such as incomplete protection, allergic reactions, autoimmunity, infection, or even tolerization. Thus, proper antigen delivery is critical for achieving the desired outcome. A number of vaccination approaches have now been described with varied degrees of success. The relative success of these approaches can be correlated with antigen delivery to specific presentation cells and stimulation of the immune system at sites where protective immunity is most appropriate. In addition, a greater understanding of mechanisms involving cells and effector molecules in the events of immunity may allow for improved possibilities for initiating, augmenting, and maintaining the response to a delivered antigen. This review provides insights into the various strategies currently being explored to optimize antigen delivery and the immune response to that antigen. C1 NCI, Bethesda, MD 20892 USA. Genentech Inc, S San Francisco, CA 94080 USA. RP Mrsny, RJ (reprint author), NCI, Bethesda, MD 20892 USA. NR 447 TC 9 Z9 9 U1 0 U2 0 PU BEGELL HOUSE INC PI NEW YORK PA 79 MADISON AVE, SUITE 1205, NEW YORK, NY 10016-7892 USA SN 0743-4863 J9 CRIT REV THER DRUG JI Crit. Rev. Ther. Drug Carr. Syst. PY 2000 VL 17 IS 3 BP 165 EP 248 PG 84 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 323UB UT WOS:000087582400001 PM 10868289 ER PT J AU Hayakawa, Y Kirk, KL Kimoto, H AF Hayakawa, Y Kirk, KL Kimoto, H TI Crystal and molecular structure of 6-methyl-2-(trifluoromethyl)-(6H)-imidazo[1,2-c]pyrimidin-5-one SO CRYSTAL RESEARCH AND TECHNOLOGY LA English DT Article DE crystal structure; imidazo[1,2-c]pyrimidine; trifluoromethyl; cycloaddition; cytosine; bromoacetoxime AB The title compound (C8H6F3N3O) crystallizes as colorless plates, triclinic, a = 10.916(2) Angstrom, b = 11.140(1) Angstrom, c = 8.368(1) Angstrom, a = 95.938(9)degrees, beta = 105.24(1)degrees, gamma = 64.843(9)degrees, V = 888.6(2) Angstrom(3), Z = 4, D-calc = 1.623g/cm(3), space group P (1) over bar. The structure was solved by direct methods and refined by the full-matrix least-squares method (R-w = 0.047). C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Natl Ind Res Inst Nagoya, Dept Chem, Kita Ku, Nagoya, Aichi 4628510, Japan. RP Kirk, KL (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 6 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 0232-1300 J9 CRYST RES TECHNOL JI Cryst. Res. Technol. PY 2000 VL 35 IS 3 BP 343 EP 348 DI 10.1002/1521-4079(200003)35:3<343::AID-CRAT343>3.0.CO;2-L PG 6 WC Crystallography SC Crystallography GA 303YH UT WOS:000086455100013 ER PT J AU Buggage, RR Chan, CC Matteson, DM Reed, GF Whitcup, SM AF Buggage, RR Chan, CC Matteson, DM Reed, GF Whitcup, SM TI Apoptosis in cytomegalovirus retinitis associated with AIDS SO CURRENT EYE RESEARCH LA English DT Article DE cytomegalovirus; retinitis; apoptosis; AIDS; in situ hybridization ID FAS LIGAND; MURINE CYTOMEGALOVIRUS; CELLS; INFECTION; CYTOKINES; UVEITIS AB Purpose. To determine the role of apoptosis in the pathogenesis of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome. Methods. Forty-three eyes from patients with cytomegalovirus retinitis treated before the introduction of highly active antiretroviral therapy were examined by routine histopathology and in situ techniques to detect apoptosis (TUNEL assay). Apoptosis was graded on a scale from 0 to 3+ by quantitating the number of TUNEL positive cells per case using a standard grading procedure. Statistical analysis describing the association between apoptosis grade and the proportions of eyes with active CMV infection, with choroidal inflammation and treated with the sustained-release intravitreal ganciclovir implant was performed using the Armitage procedure. Results. Apoptosis in both CMV infected and uninfected retinal cells was detected in 28 of 41 eyes (68%); 13 (45%) with active and 15 (55%) with inactive cytomegalovirus retinitis. The degree of apoptosis was mild (1+) in 14 eyes, moderate (2+) in 6 eyes and severe (3+) in 8 eyes. Apoptosis was not identified in two eyes without CMVR. An increase in apoptosis grade was positively associated with active CMVR (p = 0.014). There was no significant association between apoptosis and choroidal inflammation. The presence and the severity of apoptosis was less in eyes treated with the sustained-release intravitreal ganciclovir implant compared to those treated with systemic anti-viral therapy, however, the difference was not statistically significant. Conclusions. Apoptosis contributes to retinal cell loss in eyes with cytomegalovirus retinitis associated with AIDS but did not correlate with the progressive loss of retinal cell function in patients with treated, inactive CMVR. C1 NEI, NIH, Bethesda, MD 20892 USA. RP Buggage, RR (reprint author), NEI, NIH, 10 Ctr Dr,Bldg 10,Room 10 N112, Bethesda, MD 20892 USA. NR 18 TC 12 Z9 16 U1 0 U2 0 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PY 2000 VL 21 IS 3 BP 721 EP 729 DI 10.1076/0271-3683(200009)21:3;1-R;FT721 PG 9 WC Ophthalmology SC Ophthalmology GA 375QL UT WOS:000165412700006 PM 11120560 ER PT J AU Zhang, MF Hung, L Gery, I AF Zhang, MF Hung, L Gery, I TI Vasoactive intestinal peptide (VIP) exacerbates endotoxin-induced uveitis (EIU) in mice SO CURRENT EYE RESEARCH LA English DT Article DE vasoactive intestinal peptide (VIP); endotoxin induced uveitis (EIU); endotoxemia; cytokines ID TNF-ALPHA; IN-VITRO; RAT; MACROPHAGES; CYTOKINES; VIVO AB Purpose. We have previously shown that inhibition of the proinflammatory cytokine tumor necrosis factor- (TNF)-alpha exacerbates the inflammatory process of EIU. To further examine this paradoxic phenomenon, we investigated here the effect on EIU of VIP, a neuropeptide that inhibits TNF-alpha production. Methods. VIP was injected concurrently with endotoxin at doses that induce EIU or lethality in mice. Severity of EIU was measured by counting infiltrating cells in eye sections, at 1 or 5 days post endotoxin injection. Survival of mice was monitored periodically, while serum levels of TNF-alpha, interleukin-(IL)-1 beta and IL-10 were determined by caputure ELISA. Results. Treatment with VIP exacerbated EIU but provided partial protection from the lethal endotoxin effect. VIP treatment also reduced serum levels of TNF-alpha and IL-1 beta, but increased levels of IL-10. Conclusion. This study further established the paradoxical observation that EIU is exacerbated by lowering the levels of circulating pro-inflammatory cytokines, in particular TNF-alpha. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Zhang, MF (reprint author), 10 Ctr Dr,Bldg 10,Rm 10N208, Bethesda, MD 20892 USA. NR 21 TC 4 Z9 4 U1 0 U2 0 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PY 2000 VL 21 IS 6 BP 913 EP 917 DI 10.1076/ceyr.21.6.913.6986 PG 5 WC Ophthalmology SC Ophthalmology GA 412RX UT WOS:000167569100001 PM 11262614 ER PT J AU Foster, CB Chanock, SJ AF Foster, CB Chanock, SJ TI Mining variations in genes of innate and phagocytic immunity: current status and future prospects SO CURRENT OPINION IN HEMATOLOGY LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; SINGLE-NUCLEOTIDE POLYMORPHISMS; MANNOSE-BINDING LECTIN; HUMAN-GENOME-PROJECT; FC-GAMMA-RIIIA; CYSTIC-FIBROSIS; HIV-1 INFECTION; LUNG-DISEASE; SUSCEPTIBILITY; PROGRESSION AB The large number of sequence variations in human genes reflects the diversity of human populations and the response to prior environmental and pathogen challenges. Currently, major efforts are under way to identify and catalog single-nucleotide polymorphisms for use in genetic studies designed to explore the contribution of common variants to both disease susceptibility and interindividual differences in outcomes. So far, the most productive approach has been to search with candidate genes for which there is a scientific rationale (eg, prior data on the biologic implications of one or more variant alleles), Recently, there has been an explosion in the number of genetic association studies seeking to correlate one or more well-defined outcomes with variant alleles. These studies provide a foundation for identifying and applying genetic risk factors to clinical medicine. However, a number of challenges must be met before widespread use in clinical medicine can be undertaken. These include more efficient bioinformatics, basic insights into the significance of the variant alleles, ethical issues, and the availability of cost-effective, high-throughput platforms for genotype analysis. (C) 2000 Lippincott Williams & Wilkins, Inc. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Chanock, SJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Ctr Adv Technol, 8717 Grovemont Circle, Gaithersburg, MD 20877 USA. NR 63 TC 13 Z9 13 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD JAN PY 2000 VL 7 IS 1 BP 9 EP 15 DI 10.1097/00062752-200001000-00003 PG 7 WC Hematology SC Hematology GA 379YQ UT WOS:000165671100003 PM 10608498 ER PT J AU Cotch, MF AF Cotch, MF TI The socioeconomic impact of vasculitis SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review ID SYSTEMIC VASCULITIS; DAMAGE INDEX; GRANULOMATOSIS; CLASSIFICATION; EPIDEMIOLOGY AB Information detailing the socioeconomic impact of the vasculitides on society has been difficult to obtain. Recent published studies provide preliminary information suggesting that the impact of systemic vasculitis may be significant and far greater than previously anticipated, A rough estimate of expenditures for vasculitis-related hospitalizations for polyarteritis nodosa, hypersensitivity vasculitis, Wegener's granulomatosis, giant cell arteritis and Takayasu's arteritis in the US amounted to $150 million per year. Costs associated with outpatient care, disability, and death were not calculated, A more comprehensive investigation into the economic and social burden of these conditions is necessary. Aspects to consider include quantifying the incidence and prevalence of disease, estimating the direct, indirect, and intangible costs of care, assessing longterm clinical outcomes, and measuring quality of life from the patient perspective. (C) 2000 Lippincott Williams & Wilkins, Inc. C1 NEI, NIH, Bethesda, MD 20892 USA. RP Cotch, MF (reprint author), NEI, NIH, 6160 Execut Blvd,Suite 350,MSC 7164, Bethesda, MD 20892 USA. OI Cotch, Mary Frances/0000-0002-2046-4350 FU Intramural NIH HHS [Z99 EY999999] NR 16 TC 16 Z9 17 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI CURR. OPIN. RHEUMATOL. PD JAN PY 2000 VL 12 IS 1 BP 20 EP 23 DI 10.1097/00002281-200001000-00004 PG 4 WC Rheumatology SC Rheumatology GA 304CR UT WOS:000086465600004 PM 10647950 ER PT J AU Shetty, HU Huang, W AF Shetty, HU Huang, W TI Measurement of myo-inositol in biological systems by mass spectrometric and in vivo H-1 magnetic resonance spectroscopic techniques SO CURRENT ORGANIC CHEMISTRY LA English DT Article ID LOCALIZED PROTON SPECTROSCOPY; PROBABLE ALZHEIMER-DISEASE; HUMAN-BRAIN INVIVO; CEREBROSPINAL-FLUID; METABOLITE CONCENTRATIONS; ABSOLUTE QUANTITATION; GAS-CHROMATOGRAPHY; MULTIPLE-SCLEROSIS; MYOINOSITOL UPTAKE; LIPID MYOINOSITOL AB Cells utilize myo-inositol for osmoregulation and phosphatidylinositol signaling. Mass spectrometric and in vivo magnetic resonance spectroscopic techniques have been complementarily used in our laboratories to investigate brain myo-inositol metabolism. Mass spectrometric quantitation methods are surveyed focusing primarily on derivatization reactions, gas chromatographic separation and detection of ions. Monitoring of the m/z 373 fragment ion generated from acetate derivative provides precise quantitation of myo-inositol in biological matrices. The technique and its clinical applications are discussed. Measurement of myo-inositol transport using a stable isotope technique is illustrated for cultured neurons. In addition, the possible use of the technique in probing phosphatidylinositol turnover is discussed. An in vivo H-1 magnetic resonance spectroscopic technique is described for measuring the absolute concentration of myo-inositol in human brain. Magnetic resonance spectroscopy with short echo-time enables detection of the resonance peak of myo-inositol (3.56 ppm) when the water resonance peak is suppressed by narrow band radio-frequency pulses. The review focuses on an external reference method involving collection of data from the human subject and the phantom containing aqueous myo-inositol standard solution in the same scanning session. The method takes into account differences in longitudinal and transverse relaxation time constants of myo-inositol between brain tissue and aqueous solution. Application of the technique is illustrated by measuring brain myo-inositol in Down syndrome adults and Alzheimer disease patients. Advantages and limitations of this noninvasive technique in monitoring metabolic processes are discussed. C1 NIA, Sect Brain Physiol & Metab, NIH, Bethesda, MD 20892 USA. SUNY Stony Brook, Dept Radiol, Stony Brook, NY 11794 USA. RP Shetty, HU (reprint author), NIA, Sect Brain Physiol & Metab, NIH, Bldg 10,Room 6C 103,10 Ctr Dr,Msc 1582, Bethesda, MD 20892 USA. NR 94 TC 3 Z9 3 U1 0 U2 1 PU BENTHAM SCIENCE PUBL BV PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1385-2728 J9 CURR ORG CHEM JI Curr. Org. Chem. PD JAN PY 2000 VL 4 IS 1 BP 1 EP 17 DI 10.2174/1385272003376382 PG 17 WC Chemistry, Organic SC Chemistry GA 287VZ UT WOS:000085528500002 ER PT J AU Sweitzer, TD Love, DC Hanover, JA AF Sweitzer, TD Love, DC Hanover, JA TI Regulation of nuclear import and export SO CURRENT TOPICS IN CELLULAR REGULATION, VOL 36 SE CURRENT TOPICS IN CELLULAR REGULATION LA English DT Review ID PORE-TARGETING COMPLEX; PROTEIN IMPORT; HNRNP A1; NUCLEOCYTOPLASMIC TRANSPORT; TETRATRICOPEPTIDE REPEATS; GLCNAC TRANSFERASE; BINDING-PROTEIN; KINASE KINASE; IN-VITRO; SIGNAL C1 NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. RP Sweitzer, TD (reprint author), NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. NR 65 TC 15 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0070-2137 J9 CURR TOP CELL REGUL PY 2000 VL 36 BP 77 EP 94 PG 18 WC Cell Biology; Physiology SC Cell Biology; Physiology GA BQ27H UT WOS:000087771600003 PM 10842747 ER PT J AU Pant, HC Veeranna Grant, P AF Pant, HC Veeranna Grant, P TI Regulation of axonal neurofilament phosphorylation SO CURRENT TOPICS IN CELLULAR REGULATION, VOL 36 SE CURRENT TOPICS IN CELLULAR REGULATION LA English DT Review ID CYCLIN-DEPENDENT KINASE-5; NEURONAL INTERMEDIATE FILAMENTS; GLYCOGEN-SYNTHASE KINASE-3; PROTEIN-KINASE; TAIL DOMAIN; CDC2-LIKE KINASE; ALZHEIMERS-DISEASE; SQUID AXOPLASM; BOVINE BRAIN; SPINAL-CORD C1 NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Pant, HC (reprint author), NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. NR 82 TC 26 Z9 26 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0070-2137 J9 CURR TOP CELL REGUL PY 2000 VL 36 BP 133 EP 150 PG 20 WC Cell Biology; Physiology SC Cell Biology; Physiology GA BQ27H UT WOS:000087771600006 PM 10842750 ER PT J AU Aramburu, J Rao, A Klee, CB AF Aramburu, J Rao, A Klee, CB TI Calcineurin: From structure to function SO CURRENT TOPICS IN CELLULAR REGULATION, VOL 36 SE CURRENT TOPICS IN CELLULAR REGULATION LA English DT Review ID DEPENDENT PROTEIN PHOSPHATASE; NF-KAPPA-B; ACTIVATED T-CELLS; TRANSCRIPTION FACTOR NFAT1; LONG-TERM DEPRESSION; VACUOLAR H+-ATPASE; IMMUNOPHILIN-IMMUNOSUPPRESSANT COMPLEXES; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; SIGNAL-TRANSDUCTION PATHWAY; CYCLOPHILIN-CYCLOSPORINE-A C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. Univ Pompeu Fabra, Fac Ciencies Salut Vida, Barcelona 08002, Spain. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Aramburu, J (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RI Aramburu, J/G-8991-2014 OI Aramburu, J/0000-0001-9279-9523 NR 352 TC 203 Z9 212 U1 1 U2 11 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0070-2137 J9 CURR TOP CELL REGUL PY 2000 VL 36 BP 237 EP 295 PG 59 WC Cell Biology; Physiology SC Cell Biology; Physiology GA BQ27H UT WOS:000087771600011 PM 10842755 ER PT J AU Boyd, MT Zimonjic, DB Popescu, NC Athwal, R Haines, DS AF Boyd, MT Zimonjic, DB Popescu, NC Athwal, R Haines, DS TI Assignment of the MDM2 binding protein gene (MTBP) to human chromosome band 8q24 by in situ hybridization SO CYTOGENETICS AND CELL GENETICS LA English DT Article C1 Med Coll Penn & Hahnemann Univ, Ctr Canc, Philadelphia, PA USA. NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. Temple Univ, Fels Inst, Philadelphia, PA 19122 USA. RP Boyd, MT (reprint author), Univ Liverpool, Dept Surg, Daulby St,5th Floor UCD, Liverpool L69 3GA, Merseyside, England. RI Boyd, Mark/I-6792-2012 OI Boyd, Mark/0000-0002-2336-2106 NR 4 TC 4 Z9 4 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 2000 VL 90 IS 1-2 BP 64 EP 65 DI 10.1159/000015663 PG 2 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 363BA UT WOS:000089812800010 PM 11060448 ER PT J AU Kleiter, N Artner, I Copeland, NG Gilbert, DJ Jenkins, NA Kratochwil, K AF Kleiter, N Artner, I Copeland, NG Gilbert, DJ Jenkins, NA Kratochwil, K TI Genomic organization and chromosome location of the murine Rpl23 gene SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID RIBOSOMAL-PROTEIN GENES; MOUSE; REGION; MAP; SEQUENCES AB The mouse gene coding for ribosomal protein L23 (Rpl23) has been fully sequenced, including 580 bp of the 5' upstream region. The 5-kb gene comprises 5 exons and contains an unusually long (3,153 bp) third intron. The gene was mapped to the distal region of mouse chromosome 11, homologous to human chromosome 17q21 --> q22. Copyright (C) 2000 S. Karger AG, Basel. C1 Austrian Acad Sci, Inst Mol Biol, A-5020 Salzburg, Austria. NCI, Mouse Canc Genet Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Kratochwil, K (reprint author), Austrian Acad Sci, Inst Mol Biol, Billrothstr 11, A-5020 Salzburg, Austria. NR 20 TC 2 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 2000 VL 90 IS 3-4 BP 227 EP 230 DI 10.1159/000056774 PG 4 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 388BU UT WOS:000166158200003 PM 11124519 ER PT J AU Doyle, JL DeSilva, U Miller, W Green, ED AF Doyle, JL DeSilva, U Miller, W Green, ED TI Divergent human and mouse orthologs of a novel gene (WBSCR15/Wbscr15) reside within the genomic interval commonly deleted in Williams syndrome SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; BEUREN-SYNDROME; 7Q11.23; REGION; PREDICTION; SEQUENCES; DATABASE; DISORDER; PROTEINS; PROGRAM AB Williams syndrome (WS) is a contiguous gene deletion disorder resulting in complex and intriguing clinical features. Detailed molecular characterization studies of the genomic segment on human chromosome 7q11.23 commonly deleted in WS have uncovered numerous genes, each of which is being actively studied for its possible role in the etiology of the syndrome. Our efforts have focused on the comparative mapping and sequencing of the WS region in human and mouse. In previous studies, we uncovered important differences in the long-range organization of these human and mouse genomic regions; in particular, the notable absence of large duplicated blocks of DNA in mouse that are present in human. Aided by available genomic sequence data, we have used a combination of gene-prediction programs and cDNA isolation to identify the human and mouse orthologs of a novel gene (WBSCR15 and Wbscr15, respectively) residing within the genomic segment commonly deleted in WS. Unlike the flanking genes, which are closely related in human and mouse, WBSCR15 and Wbscr15 are strikingly different with respect to their cDNA and corresponding protein sequences as well as tissue-expression pattern. Neither the WBSCR15- nor Wbscr15-encoded amino acid sequence shows a statistically significant similarity to any characterized protein. These findings reveal another interesting evolutionary difference between the human and mouse WS regions and provide an additional candidate gene to evaluate with respect to its possible role in the pathogenesis of WS. Copyright (C) 2000 S. Karger AG, Basel. C1 NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. Penn State Univ, Dept Comp Sci & Engn, University Pk, PA 16802 USA. RP Green, ED (reprint author), NHGRI, Genome Technol Branch, NIH, 49 Convent Dr,Bldg 49,Room 2A08, Bethesda, MD 20892 USA. FU NLM NIH HHS [LM05110] NR 30 TC 11 Z9 14 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 2000 VL 90 IS 3-4 BP 285 EP 290 DI 10.1159/000056790 PG 6 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 388BU UT WOS:000166158200019 PM 11124535 ER PT J AU Loh, ED Broussard, SR Liu, Q Copeland, NG Gilbert, DJ Jenkins, NA Kolakowski, LF AF Loh, ED Broussard, SR Liu, Q Copeland, NG Gilbert, DJ Jenkins, NA Kolakowski, LF TI Chromosomal localization of GPR48, a novel glycoprotein hormone receptor like GPCR, in human and mouse with radiation hybrid and interspecific backcross mapping SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID ORGANIZATION; GENE AB We report the chromosomal localization in both mouse and human of a novel G-protein-coupled receptor, GPR48, which resembles glycoprotein hormone receptors, that may be implicated in Wilms tumor deletion syndromes such as WAGR. This receptor forms a novel sub-family of glycoprotein hormone-like GPCRs. We have mapped this receptor to human chromosome 11p14 --> p13 by several approaches, including radiation hybrid and interspecific backcross mapping, and show that GPR48 is close to BDNF. This data differs from the recently published mapping of LGR4 (5q34 --> q35.1) (Hsu et al., 1998). Additionally, we show that Gpr48 and Bdnfare tightly linked on mouse chromosome 2, in a region with conserved synteny to human 11p14 --> p13. Copyright(C)2000S.KargerAG.Basel. C1 Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA. Merck Res Labs, Dept Human Genet, W Point, PA USA. NCI, Mouse Canc Genet Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Kolakowski, LF (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pharmacol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NHLBI NIH HHS [5T32-HL07446-19] NR 10 TC 16 Z9 20 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 2000 VL 89 IS 1-2 BP 2 EP 5 DI 10.1159/000015576 PG 4 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 332WD UT WOS:000088096600002 PM 10894923 ER PT J AU Baek, JY Jun, DY Taub, D Kim, YH AF Baek, JY Jun, DY Taub, D Kim, YH TI Assignment of human 3-phosphoglycerate dehydrogenase (PHGDH) to human chromosome band 1p12 by fluorescence in situ hybridization SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID SERINE C1 Kyungpook Natl Univ, Coll Nat Sci, Dept Microbiol, Taegu 702701, South Korea. NIA, Immunol Lab, Ctr Gerontol Res, NIH, Baltimore, MD 21224 USA. RP Kim, YH (reprint author), Kyungpook Natl Univ, Coll Nat Sci, Dept Microbiol, Taegu 702701, South Korea. NR 4 TC 2 Z9 2 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 2000 VL 89 IS 1-2 BP 6 EP 7 DI 10.1159/000015577 PG 2 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 332WD UT WOS:000088096600003 PM 10894924 ER PT J AU Jeong, KS Song, BJ Keck-Waggoner, CL Huh, CG Popescu, NC AF Jeong, KS Song, BJ Keck-Waggoner, CL Huh, CG Popescu, NC TI Assignment of the mitochondrial aldehyde dehydrogenase gene (Aldh2) to mouse chromosome 5 by fluorescence in situ hybridization SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID LOCALIZATION; CLONING; LIVER; RAT C1 NIAAA, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Song, BJ (reprint author), NIAAA, Lab Membrane Biochem & Biophys, NIH, Pk 5 Bldg,Rm 425,12420 Parklawn Dr, Rockville, MD 20852 USA. NR 10 TC 0 Z9 0 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 2000 VL 89 IS 1-2 BP 54 EP 55 DI 10.1159/000015563 PG 2 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 332WD UT WOS:000088096600016 PM 10894937 ER PT J AU Topol, LZ Modi, WS Koochekpour, S Blair, DG AF Topol, LZ Modi, WS Koochekpour, S Blair, DG TI DRM/GREMLIN (CKTSF1B1) maps to human chromosome 15 and is highly expressed in adult and fetal brain SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID BONE MORPHOGENETIC PROTEINS; COMPARATIVE GENOMIC HYBRIDIZATION; TUMOR-SUPPRESSOR GENE; PROGENITOR CELLS; GROWTH-FACTORS; CANCER; DIFFERENTIATION; SUPERFAMILY; REGION; LINES AB We have mapped and characterized the human homolog of Drm/Gremlin (CKTFS1B1), a member of a family of BMP antagonists that have been linked to both developmental and transformation-related functions. By screening a human cDNA library, we isolated a 3.3-kb cDNA containing the 552-bp region encoding the human DRM protein. CKTFS1B1 was localized on human chromosome 15q13 --> q15 by somatic cell hybrid analysis and, more precisely, using radiation hybrids, to a region of markers linked to SGNE1, secretory granule neuroendocrine protein 1 and RYR3, the ryanodyne receptor 3. Northern blot analysis showed the presence of a single DRM-specific mRNA expressed ill different human tissues, including brain, ovary, intestine and colon. In the brain, DRM expression is associated with the region localized around the internal capsule in the large subcortical nuclei. DRM appears to be predominantly expressed in normal cells and tissues, including normal neurons, astrocytes and fibroblasts. Interestingly, we detected DRM expression in normal cells obtained from several patients, but not in tumor cell lines established from the same patients. The data suggest that down-regulation of DRM is associated with tumor progression, and support the hypothesis that human DRM may play an important role during both neuroembryological development and carcinogenesis. Copyright(C)2000S.KargerAG,Basel. C1 NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. NCI, Basic Res Lab, Frederick, MD 21701 USA. NCI, ABL, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Blair, DG (reprint author), NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, POB B,Bldg 469,Rm 102, Ft Detrick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 30 TC 40 Z9 44 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 2000 VL 89 IS 1-2 BP 79 EP 84 DI 10.1159/000015568 PG 6 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 332WD UT WOS:000088096600021 PM 10894942 ER PT J AU Kaye, FJ Shows, TB AF Kaye, FJ Shows, TB TI Assignment of Ubiquilin2 (UBQLN2) to human chromosome Xp11.23 -> p11.1 by GeneBridge radiation hybrids SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID PROTEIN C1 Natl Naval Med Ctr, Bethesda, MD 20889 USA. NCI, Med Branch, Bethesda, MD 20892 USA. Roswell Pk Canc Inst, Dept Canc Genet, Buffalo, NY 14263 USA. RP Kaye, FJ (reprint author), Natl Naval Med Ctr, Bldg 8,Rm 5101, Bethesda, MD 20889 USA. RI kaye, frederic/E-2437-2011 FU NCI NIH HHS [CA63333]; NHGRI NIH HHS [HG0697] NR 7 TC 5 Z9 5 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 2000 VL 89 IS 1-2 BP 116 EP 117 DI 10.1159/000015588 PG 2 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 332WD UT WOS:000088096600030 PM 10894951 ER PT J AU Lemmer, ER Welch, JL Tsai, T Keck-Waggoner, CL Huh, CG Zimonjic, DB Popeseu, NC Thorgeirsson, SS AF Lemmer, ER Welch, JL Tsai, T Keck-Waggoner, CL Huh, CG Zimonjic, DB Popeseu, NC Thorgeirsson, SS TI Genomic structure and chromosome location of the mouse RelA p65 gene (Rela) SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID NF-KAPPA-B; HYBRIDIZATION; LOCALIZATION; IMBALANCES; SUBUNIT AB The RelA (p65) subunit of transcription factor NF-kappa B plays a critical role in development, and rela(-/-) knockout mice die in utero from massive liver apoptosis. Only partial sequences of the mouse XL la gene are available. We have determined the genomic structure of mouse Rela and promoter, and have mapped the gene to chromosome 19B1-3. Copyright (C) 2000 S. Karger AG. Basel. C1 NCI, Expt Carcinogenesis Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Div Basic Sci, NIH, 37 Convent Dr MSC 4255,Bldg 37,Room 3C28, Bethesda, MD 20892 USA. NR 14 TC 2 Z9 2 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 2000 VL 89 IS 1-2 BP 129 EP 132 DI 10.1159/000015591 PG 4 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 332WD UT WOS:000088096600033 PM 10894954 ER PT J AU Roessler, E Du, Y Glinka, A Dutra, A Niehrs, C Muenke, M AF Roessler, E Du, Y Glinka, A Dutra, A Niehrs, C Muenke, M TI The genomic structure, chromosome location, and analysis of the human DKK1 head inducer gene as a candidate for holoprosencephaly SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID ANTERIOR PRIMITIVE ENDODERM; ORGANIZER; INDUCTION; HYBRIDIZATION; XENOPUS; PLATE AB Holoprosencephaly (HPE) is the most common developmental defect of the brain and face in humans. Here we report the analysis of the human ortholog of dkk-1 as a candidate gene for HPE. We determined the genomic structure of the human gene DKK1 and mapped it to chromosome 10q11.2. Functional analysis of four missense mutations identified in HPE patients revealed preserved activity in head induction assays in frogs suggesting a limited role for this gene in HPE pathogenesis, Copyright (C) 2000 S. Karger AG, Basel. C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Dept Genet, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Dept Neurol, Philadelphia, PA 19104 USA. Deutsch Krebsforschungszentrum, Div Mol Embryol, Heidelberg, Germany. NHGRI, Med Genet Branch, Cytogenet & Confocal Microscopy Core, Bethesda, MD 20892 USA. RP Muenke, M (reprint author), NHGRI, Med Genet Branch, NIH, Bld 10,10C101, Bethesda, MD 20892 USA. FU NICHD NIH HHS [HD29862, HD28732] NR 18 TC 16 Z9 18 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 2000 VL 89 IS 3-4 BP 220 EP 224 DI 10.1159/000015618 PG 5 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 346ZK UT WOS:000088901600025 PM 10965128 ER PT J AU Gu, Z Gilbert, DJ Valentine, VA Jenkins, NA Copeland, NG Zambetti, GP AF Gu, Z Gilbert, DJ Valentine, VA Jenkins, NA Copeland, NG Zambetti, GP TI The p53-inducible gene EI24/PIG8 localizes to human chromosome 11q23 and the proximal region of mouse chromosome 9 SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID P53; APOPTOSIS AB Activation of the p53 tumor suppressor leads to either a cell cycle arrest or to apoptosis and the factors that influence these responses are poorly understood. It is clear, however, that p53 regulates these processes by inducing a series of downstream target genes. One recently identified p53-target gene, EI24 (alias PIG8), induces apoptosis when ectopically expressed. To better understand the biological properties of EI24 and its potential relevance to disease, in particular cancer, we determined the chromosomal location and pattern of gene expression of EI24. EI24 is widely expressed in adult tissues and throughout mouse embryogenesis. The genomic locus of EI24 was mapped to the proximal region of mouse chromosome 9 and human chromosome 11q23-->q24, a region frequently altered in human cancers. These results suggest that EI24 may play an important role in the p53 tumor suppressor pathway. Copyright (C) 2000 S. Karger AG, Basel. C1 St Jude Childrens Res Hosp, Dept Biochem, Memphis, TN 38105 USA. St Jude Childrens Res Hosp, Dept Tumor Cell Biol, Memphis, TN 38105 USA. Univ Tennessee, Dept Biochem, Memphis, TN USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD USA. RP Zambetti, GP (reprint author), St Jude Childrens Res Hosp, Dept Biochem, 332 N Lauderdale St, Memphis, TN 38105 USA. FU NCI NIH HHS [CA63230, CA21765] NR 10 TC 10 Z9 10 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 2000 VL 89 IS 3-4 BP 230 EP 233 DI 10.1159/000015620 PG 4 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 346ZK UT WOS:000088901600027 PM 10965130 ER PT J AU Zhang, Q Topol, LZ Athanasiou, M Copeland, NG Gilbert, DJ Jenkins, NA Blair, DG AF Zhang, Q Topol, LZ Athanasiou, M Copeland, NG Gilbert, DJ Jenkins, NA Blair, DG TI Cloning of the murine Drm gene (Cktsf1b1)and characterization of its oncogene suppressible promoter SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID NUCLEAR FACTOR-I; THYMIDINE KINASE PROMOTER; G1/S PHASE; MOUSE CHROMOSOME-2; BINDING-ACTIVITY; LINKAGE MAP; CELL-LINE; EXPRESSION; CERBERUS; PROTEIN AB The Drm gene, first identified in rat cells in our laboratory, appears to play a significant role in early embryo patterning and limb bud development. We have now isolated mouse Drm (mDrm) cDNA as well as genomic DNA clones and have mapped the Drm gene (Cktsf1b1) to murine chromosome 2. Cktsf1b1 is regulated in a tissue specific fashion and is expressed only in nontransformed mouse cells or primary fibroblasts in culture, but not in established transformed or tumor-derived mouse cell lines. The major transcription start sites map to within 69 bp upstream of the initiating ATG, A promoter was contained in the -214 to +1 bp 5' flanking region, and promoter/reporter constructs showed 10-fold higher activity than control in REF-1 (rat), A31 (mouse) and CHO (hamster) cells. The region contains a TATA sequence and multiple potential transcription factor binding sites. Promoter activity was dose-dependently inhibited by cotransfection with either ras or mos oncogenes, but oncogene inhibition was reversed and the overall activity increased when cells were treated with the MAP kinase kinase (MKK) inhibitor PD98059. An NF-1 and Yi-like site, identified in the minimal promoter region, showed different mobility shift patterns when normal and transformed cell nuclear extracts are compared, Mutation of the NF-1 site reduced Cktsf1b1 promoter activity 25%, while mutation of the Yi-like site destroyed all the activity, Our results indicate that the expression of Cktsf1b1, a gene associated with early development and cell transformation, is sensitive to MKK levels and may be regulated via multiple transcription factor complexes. Copyright (C) 2000 S. Karger AG, Basel. C1 NCI, Basic Res Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Intramural Res Support Program, Frederick, MD USA. NCI, Mammalian Genet Lab, Frederick, MD 21701 USA. RP Blair, DG (reprint author), NCI, Basic Res Lab, POB B, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 37 TC 3 Z9 4 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 2000 VL 89 IS 3-4 BP 242 EP + DI 10.1159/000015625 PG 11 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 346ZK UT WOS:000088901600032 PM 10965135 ER PT J AU Adams, DJ van der Weyden, L Kovacic, A Lovicu, F Copeland, NG Gilbert, DJ Jenkins, NA Ioannou, PA Morris, BJ AF Adams, DJ van der Weyden, L Kovacic, A Lovicu, F Copeland, NG Gilbert, DJ Jenkins, NA Ioannou, PA Morris, BJ TI Chromosome localization and characterization of the mouse and human zinc finger protein 265 gene SO CYTOGENETICS AND CELL GENETICS LA English DT Article; Proceedings Paper CT 9th International Workshop on the Identification of Transcribed Sequences (TS 99) CY OCT 28-31, 1999 CL WASHINGTON, D.C. SP US DOE ID RENIN MESSENGER-RNA; EXPRESSION; LINKAGE AB The chromosome location and pattern of expression of the gene encoding the zinc finger protein 265 (alias "Zis") in human (ZNF265) and mouse (Zfp265) was determined. By interspecific backcross analysis, we mapped Zfp265 to mouse chromosome 3q. ZNF265 was localized to human chromosome 1p31 by fluorescence in situ hybridization. Since discovery of Zfp265 (in rat) came from studies of changes in renin expression in kidney cell lines, we examined the cell specificity of expression in kidney and also determined hybridization of cDNA with RNA in other tissues. We Found that expression was not confined to renin mRNA-containing cells but was ubiquitous. Moreover, the fact that highly conserved homologs of ZNF265p exist in lower organisms (e.g., C4SR in Xenopus), suggests that this protein may have a generalized role in posttranscriptional mechanisms in various cell types and species, Copyright (C) 2000 S. Karger AG, Basel. C1 Univ Sydney, Dept Physiol, Gene Lab, Sydney, NSW 2006, Australia. Univ Sydney, Inst Biomed Res F13, Sydney, NSW 2006, Australia. SE Area Labs Serv, Dept Haematol, Cytogenet & Mol Genet Unit, Randwick, NSW, Australia. NCI, Frederick Canc Res & Dev Ctr, Mammalian Genet Lab, ABL Basic Res Program, Frederick, MD 21702 USA. Royal Childrens Hosp, Murdoch Inst, Melbourne, Vic, Australia. Univ Sydney, Dept Anat & Histol, Sydney, NSW 2006, Australia. RP Morris, BJ (reprint author), Univ Sydney, Dept Physiol, Gene Lab, Bldg F13, Sydney, NSW 2006, Australia. NR 18 TC 12 Z9 15 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 2000 VL 88 IS 1-2 BP 68 EP 73 DI 10.1159/000015487 PG 6 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 303VJ UT WOS:000086445300014 PM 10773668 ER PT J AU Sanders, S Keck-Waggoner, CL Zimonjic, DB Popescu, NC Thorgeirsson, SS AF Sanders, S Keck-Waggoner, CL Zimonjic, DB Popescu, NC Thorgeirsson, SS TI Assignment of WDR7 (alias TRAG, TGF-beta resistance associated gene) to orthologous regions of human chromosome 18q21.1 -> q22 and mouse chromosome 18D.1-E.3 by fluorescence in situ hybridization SO CYTOGENETICS AND CELL GENETICS LA English DT Article; Proceedings Paper CT 4th International Chromosome 6 Workshop CY JUN 10-12, 1999 CL CAMBRIDGE, ENGLAND C1 NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, NIH, Bldg 37,Room 3C28,37 Convent Dr,MSC4255, Bethesda, MD 20892 USA. NR 8 TC 4 Z9 4 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 2000 VL 88 IS 3-4 BP 324 EP 325 DI 10.1159/000015520 PG 2 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 319PV UT WOS:000087351100041 PM 10828621 ER PT B AU Strober, W Fuss, I Kitani, A AF Strober, W Fuss, I Kitani, A BE Andus, T Rogler, G Schlottmann, K Frick, E Adler, G Zeitz, M Schmiegel, W Scholmerich, J TI Counter-regulation in the mucosal immune system and the mechanism of mucosal inflammation SO CYTOKINES AND CELL HOMEOSTASIS IN THE GASTROINTESTINAL TRACT SE FALK SYMPOSIUM LA English DT Proceedings Paper CT Falk Symposium on Cytokines and Cell Homeostasis in the Gastrointestinal Tract CY SEP 16-18, 1999 CL REGENSBURG, GERMANY SP Falk Fdn ID CD4(+) T-CELLS; GROWTH-FACTOR-BETA; ALPHA MUTANT MICE; BOWEL-DISEASE; INTERLEUKIN-10-DEFICIENT MICE; COLONIC INFLAMMATION; EXPERIMENTAL COLITIS; IL-2-DEFICIENT MICE; ORAL TOLERANCE; RESPONSES C1 NIAID, Mucosal Immun Sect, Bethesda, MD 20892 USA. RP Strober, W (reprint author), NIAID, Mucosal Immun Sect, 10 Ctr Dr,MSC 1890, Bethesda, MD 20892 USA. RI Rogler, Gerhard/O-5308-2015 OI Rogler, Gerhard/0000-0002-1733-9188 NR 34 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-8758-9 J9 FALK SYMP PY 2000 VL 113 BP 3 EP 12 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BS12A UT WOS:000168726200001 ER PT J AU Husebekk, A Fellowes, V Read, EJ Williams, J Petrus, MJ Gress, RE Fowler, DH AF Husebekk, A Fellowes, V Read, EJ Williams, J Petrus, MJ Gress, RE Fowler, DH TI Selection and expansion of T cells from untreated patients with CLL: source of cells for immune reconstitution? SO CYTOTHERAPY LA English DT Article DE CLL; negative selection; T cell expansion; cell processing ID CHRONIC-LYMPHOCYTIC-LEUKEMIA; B-CELL; FLUDARABINE; COSTIMULATION; REGENERATION; DISEASE AB Background Lymphocyte-derived malignancies can be treated with combinations of drugs that efficiently eradicate normal and malignant lymphocytes. Lack of T lymphocytes after treatment of B lymphocyte CLL (B-CLL) makes the patients susceptible to serious infections and may limit the benefit of the therapy. The aim of the study was to purify and culture-expand normal T lymphocytes from B-CLL patients prior to therapy. These cells could be frozen and given to the patients in the period post-chemotherapy. Methods T lymphocyte were isolated from the mononuclear cell apheresis products from five patients with previously untreated B-CLL. The apheresis products were red-cell depleted by density gradient centrifugation. B-lymphocyte purging was performed by incubating with MAbs to four different B-cell epitopes, followed by magnetic-bead depletion. One round of negative selection removed >90% of the B lymphocytes. The T-lymphocyte enriched cell suspension was cultured for 10/11 days in the presence of IL-2 and the anti-T cell receptor Ab OKT3. In addition, in some cultures anti-CD22 ricin immunotoxin was added. Results T cells from CLL patients expanded 4.7-21-fold over a 10/11 days culture interval. After culture, CLL cells could no longer be identified by flow cytometric evaluation. The cultured T lymphocytes were predominately CD8+, and were capable of lysing autologous CLL cells through a fas-dependent mechanism. Discussion Selection and expansion of T lymphocytes by this method may represent a strategy for enhancing immunity in the lymphocytic period following CLL treatment. C1 NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Husebekk, A (reprint author), Univ Tromso Hosp, Dept Immunol & Transfus Med, N-9038 Tromso, Norway. NR 24 TC 5 Z9 6 U1 0 U2 1 PU ISIS MEDICAL MEDIA LTD PI OXFORD PA 59 ST ALDATES, OXFORD OX1 1ST, ENGLAND SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PY 2000 VL 2 IS 3 BP 187 EP 193 DI 10.1080/146532400539143 PG 7 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 332LR UT WOS:000088076200003 PM 12042041 ER PT J AU Kaufman, J Charney, D AF Kaufman, J Charney, D TI Comorbidity of mood and anxiety disorders SO DEPRESSION AND ANXIETY LA English DT Review DE depression; anxiety disorders; comorbidity ID POSTTRAUMATIC-STRESS-DISORDER; CORTICOTROPIN-RELEASING FACTOR; EPIDEMIOLOGIC CATCHMENT-AREA; CROSS-NATIONAL EPIDEMIOLOGY; EARLY SEPARATION ANXIETY; PANIC DISORDER; SOCIAL PHOBIA; GENERALIZED ANXIETY; MAJOR DEPRESSION; FAMILY AB This article reviews data on the prevalence of panic, social phobia, generalized anxiety, and posttraumatic stress disorder and research documenting the comorbidity of these disorders with major depression (MDD). These anxiety disorders al-e frequently comorbid with MDD, and 50%-60% of individuals with MDD report a lifetime history of one ol more of these anxiety disorders. The anxiety disorders are also highly correlated with one another and approximately one-quarter to one-half of individuals with each of the anxiety disorders report a lifetime history of an alcohol or substance use disorder: Anxiety, disorders rarely, exist in isolation, with sever-al studies reporting that over 90% of individuals with anxiety disorders have a lifetime history of other psychiatric problems. Implications for research are discussed, including the potential benefit of using combined categorical and dimensional rating scale approaches iii future genetic, biochemical, neuroimaging, and treatment studies. The clinical implications of the findings al-e also discussed, and the results of recent clinical trials summarized. Available data suggests selective serotonin reuptake inhibitors are the first-line pharmacological treatment for these disorders, and that newer serotonin ann norepinephrine reuptake inhibitors show significant promise, especially for comorbid cases. Comorbidity among depression? and anxiety disorders is associated with greater symptom severity, and a considerably higher incidence of suicidality. Increased public awareness about these disorders and the availability, of effective treatments is sorely needed. Published 2000 Wiley-Liss, Inc. C1 Yale Univ, Dept Psychiat, New Haven, CT 06511 USA. NIMH, Bethesda, MD 20892 USA. RP Kaufman, J (reprint author), Yale Univ, Dept Psychiat, Towers Suite 2H,100 York St, New Haven, CT 06511 USA. NR 81 TC 160 Z9 163 U1 13 U2 55 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2000 VL 12 SU 1 BP 69 EP 76 DI 10.1002/1520-6394(2000)12:1+<69::AID-DA9>3.0.CO;2-K PG 8 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 373CC UT WOS:000165269900009 PM 11098417 ER PT J AU Wassermann, EM AF Wassermann, EM TI Side effects of repetitive transcranial magnetic stimulation SO DEPRESSION AND ANXIETY LA English DT Article DE safety; risk; seizure; stimulation parameters ID LONG-TERM POTENTIATION; PREFRONTAL CORTEX; ELECTRICAL-STIMULATION; MOTOR CORTEX; SAFETY; EPILEPSY; SEIZURES; DEPRESSION; INDUCTION; RATS AB The side effects of repetitive transcranial magnetic stimulation are largely unexplored and the limits of safe exposure have not been determined except as regards the acute production of seizures. Although tissue damage is unlikely, however, cognitive and other adverse effects have been observed and the possibility of unintended long-term changes in brain function are theoretically possible. Published 2000 Wiley-Liss, Inc. C1 NINDS, Brain Stimulat Unit, NIH, Bethesda, MD 20892 USA. RP Wassermann, EM (reprint author), NINDS, Brain Stimulat Unit, NIH, 10 Ctr Dr MSC 1428, Bethesda, MD 20892 USA. NR 42 TC 17 Z9 17 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 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2000 VL 12 IS 3 BP 124 EP 129 DI 10.1002/1520-6394(2000)12:3<124::AID-DA3>3.0.CO;2-E PG 6 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 379MA UT WOS:000165644800003 PM 11126186 ER PT J AU Rodebaugh, TL Chambless, DL Terrill, DR Floyd, M Uhde, T AF Rodebaugh, TL Chambless, DL Terrill, DR Floyd, M Uhde, T TI Convergent, discriminant, and criterion-related validity of the Social Phobia and Anxiety Inventory SO DEPRESSION AND ANXIETY LA English DT Article DE social phobia; assessment; Social Phobia and Anxiety Inventory; psychometrics ID PRIVATE SELF-CONSCIOUSNESS; COGNITIVE ASSESSMENT; CONCURRENT VALIDITY; ADJUSTMENT; VALIDATION AB The psychometric properties of the Social Phobia Anxiety Inventory (SPAI) were assessed in a sample of participants who either had a primary diagnosis of social phobia or were normal volunteers. Positive evidence was obtained on the SPAI's concurrent and predictive convergent validity: it teas significantly correlated with other measures of social anxiety obtained from self-report questionnaires of social impairment and with behavioral assessment measures administered im conjunction with a conversation role-play, including measures of negative thinking, subjective anxiety, and self-perceived skill and apparent nervousness. Discriminant validity was demonstrated by the SPAI's significantly stronger relationship with public than private self-consciousness. There was no overlap in SPAI scores ipl the normal volunteer and socially phobic groups, demonstrating criterion-related validity (C) 2000 Wiley-Liss, Inc. C1 Univ N Carolina, Dept Psychol, Chapel Hill, NC 27599 USA. American Univ, Washington, DC 20016 USA. NIMH, Bethesda, MD 20892 USA. RP Chambless, DL (reprint author), Univ N Carolina, Dept Psychol, CB 3270, Chapel Hill, NC 27599 USA. NR 27 TC 7 Z9 9 U1 15 U2 17 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PY 2000 VL 11 IS 1 BP 10 EP 14 DI 10.1002/(SICI)1520-6394(2000)11:1<10::AID-DA2>3.0.CO;2-3 PG 5 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 290AX UT WOS:000085655100002 PM 10723630 ER PT J AU Munksgaard, L Frisch, M Melbye, M Hjalgrim, H AF Munksgaard, L Frisch, M Melbye, M Hjalgrim, H TI Incidence patterns of Lyme disease and cutaneous B-cell non-Hodgkin's lymphoma in the United States SO DERMATOLOGY LA English DT Article DE Lyme disease; cutaneous B-cell lymphoma; geographic correlation ID BORRELIA-BURGDORFERI; INFECTION AB Background: Several reports have suggested a link between infection with Borrelia burgdorferi (the spirochete causing Lyme disease) and development of cutaneous B-cell non-Hodgkin's lymphoma (CBCL). Methods: We did a correlation analysis of CBCL and Lyme disease using data from the Surveillance, Epidemiology and End Results program and from the Centers for Disease Central and Prevention. Results: We could not demonstrate a geographic correlation between incidence rates of Lyme disease and CBCL. Conclusion: This observation suggests that infection with B. burgdorferi is not a major risk factor for CBCL in the USA. Copyright (C) 2000 S. Karger AG, Basel. C1 Statens Serum Inst, Danish Epidemiol Sci Ctr, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Munksgaard, L (reprint author), Statens Serum Inst, Danish Epidemiol Sci Ctr, Dept Epidemiol Res, 5 Artillerivej, DK-2300 Copenhagen, Denmark. RI Frisch, Morten/E-9206-2016 OI Frisch, Morten/0000-0002-3864-8860 NR 13 TC 11 Z9 12 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-8665 J9 DERMATOLOGY JI Dermatology PY 2000 VL 201 IS 4 BP 351 EP 352 DI 10.1159/000051553 PG 2 WC Dermatology SC Dermatology GA 387YK UT WOS:000166150500015 PM 11146349 ER PT J AU Malkova, L Bachevalier, J Webster, M Mishkin, M AF Malkova, L Bachevalier, J Webster, M Mishkin, M TI Effects of neonatal inferior prefrontal and medial temporal lesions on learning the rule for delayed nonmatching-to-sample SO DEVELOPMENTAL NEUROPSYCHOLOGY LA English DT Article ID LASTING MEMORY IMPAIRMENT; RHESUS-MONKEYS; INFANT MONKEYS; RECOGNITION MEMORY; HIPPOCAMPAL-FORMATION; VISUAL RECOGNITION; PERIRHINAL CORTEX; MACAQUE MONKEYS; AFFERENT INPUT; FRONTAL-CORTEX AB The ability of rhesus monkeys to master the rule for delayed nonmatching-to-sample (DNMS) has a protracted ontogenetic development, reaching adult levels of proficiency around 4 to 5 years of age (Bachevalier, 1990). To test the possibility that this slow development could be due, at least in part, to immaturity of the prefrontal component of a temporo-prefrontal circuit important for DNMS rule learning (Kowalska, Bachevalier, & Mishkin, 1991; Weinstein, Saunders, & Mishkin, 1988), monkeys with neonatal lesions of the inferior prefrontal convexity were compared on DNMS with both normal controls and animals given neonatal lesions of the medial temporal lobe. Consistent with our previous results (Bachevalier & Mishkin, 1994; Malkova, Mishkin, & Bachevalier, 1995), the neonatal medial temporal lesions led to marked impairment in rule learning (as well as in recognition memory with long delays and list lengths) at both 3 months and 2 years of age. By contrast, the neonatal inferior convexity lesions yielded no impairment in rule-learning at 3 months and only a mild impairment at 2 years, a finding that also contrasts sharply with the marked effects of the same lesion made in adulthood. This pattern of sparing closely resembles the one found earlier after neonatal lesions to the cortical visual area TE (Bachevalier & Mishkin, 1994; Malkova et al., 1995). The functional sparing at 3 months probably reflects the fact that the temporo-prefrontal circuit is nonfunctional at this early age, resulting in a total dependency on medial temporal contributions to rule learning. With further development, however, this circuit begins to provide a supplementary route for learning. C1 NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Bachevalier, J (reprint author), Univ Texas, Hlth Sci Ctr, Dept Neurobiol & Anat, 6431 Fannin St, Houston, TX 77030 USA. FU NICHD NIH HHS [HD 35471]; NIMH NIH HHS [NIMH 58846, R01 MH058846] NR 51 TC 20 Z9 21 U1 0 U2 2 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 8756-5641 J9 DEV NEUROPSYCHOL JI Dev. Neuropsychol. PY 2000 VL 18 IS 3 BP 399 EP 421 DI 10.1207/S1532694207Malkova PG 23 WC Psychology, Developmental; Psychology; Psychology, Experimental SC Psychology GA 432UW UT WOS:000168714900007 PM 11385832 ER PT J AU Schatz, J Craft, S Koby, M DeBaun, MR AF Schatz, J Craft, S Koby, M DeBaun, MR TI A lesion analysis of visual orienting performance in children with cerebral vascular injury SO DEVELOPMENTAL NEUROPSYCHOLOGY LA English DT Article ID EARLY INFANCY; ATTENTION; DEFICITS; STROKE AB Anterior brain insults during development have been shown to result in visual orienting deficits; however, the type of orienting deficit has varied across studies. Performance on an orienting task was examined in relation to the location and volume of injury on magnetic resonance exams in 15 children with cerebral infarction and 32 control children. Contralateral lesions including the parietal lobe were associated with larger validity effects, suggesting difficulties disengaging attention. A similar trend was found for the middle-frontal gyrus. Basal ganglia injury contralateral to a given hemifield was associated with less facilitation of attention. Lesion volume in each hemisphere did not show a significant relation with contralateral validity effects. The data suggest that variability in the type of visual orienting deficits shown in prior studies of children with anterior brain insults may be related in part to the specific location of lesions within the frontal lobe. C1 Univ S Carolina, Dept Psychol, Columbia, SC 29208 USA. Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Natl Inst Hlth, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. RP Schatz, J (reprint author), Univ S Carolina, Dept Psychol, Columbia, SC 29208 USA. NR 23 TC 8 Z9 8 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 8756-5641 J9 DEV NEUROPSYCHOL JI Dev. Neuropsychol. PY 2000 VL 17 IS 1 BP 49 EP 61 DI 10.1207/S15326942DN1701_03 PG 13 WC Psychology, Developmental; Psychology; Psychology, Experimental SC Psychology GA 337CN UT WOS:000088340000003 PM 10916574 ER PT J AU Bornstein, MH Suess, PE AF Bornstein, MH Suess, PE TI Child and mother cardiac vagal tone: Continuity, stability, and concordance across the first 5 years SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article ID HEART-RATE-VARIABILITY; SUSTAINED ATTENTION; INFANTS; AGE; SIMILARITIES AB In this prospective longitudinal study, vagal tone and heart period were measured at 2 months and at 5 years in children and their mothers to evaluate the development of vagal regulation at rest and during an environmental task. Child baseline vagal tone and heart period were discontinuous; mother baseline vagal tone was discontinuous, but heart period was continuous. Group mean baseline-to-task change in vagal tone and heart period were continuous in both children and mothers. Children reached adult levels of baseline vagal tone by 5 years and did not differ from their mothers in baseline-to-task change in vagal tone or heart period. Baseline vagal tone tended to be stable, but baseline heart period and baseline-to-task change in vagal tone and heart period were unstable in children; both were stable in mothers. Baseline-to-task change in vagal tone showed consistent child-mother concordance. These findings contribute to understanding psychophysiological development, especially the ontogenesis of the vagal system and its regulatory capacity. C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP Bornstein, MH (reprint author), NICHHD, NIH, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. NR 47 TC 102 Z9 103 U1 1 U2 12 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD JAN PY 2000 VL 36 IS 1 BP 54 EP 65 DI 10.1037/0012-1649.36.1.54 PG 12 WC Psychology, Developmental SC Psychology GA 275CR UT WOS:000084802300005 PM 10645744 ER PT B AU Radke-Yarrow, M AF Radke-Yarrow, M BE Bergman, LR Cairns, RB Nilsson, LG Nystedt, L TI Real and statistical parents and children: The varied discoveries of research SO DEVELOPMENTAL SCIENCE AND THE HOLISTIC APPROACH LA English DT Proceedings Paper CT Symposium on Developmental Science and the Holistic Approach CY MAY, 1997 CL SWEDEN SP Bank Sweden, Tercentenary Fdn, Swedish Council Planning & Coordinat Res ID PSYCHOPATHOLOGY C1 NIMH, Bethesda, MD 20892 USA. RP Radke-Yarrow, M (reprint author), NIMH, Bethesda, MD 20892 USA. NR 20 TC 0 Z9 0 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC PUBL PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430 USA BN 0-8058-3374-9 PY 2000 BP 165 EP 175 PG 11 WC Psychology SC Psychology GA BP67U UT WOS:000085841100011 ER PT J AU Shuldiner, AR Nguyen, W Kao, WHL Beamer, BA Andersen, RE Pratley, R Brancati, FL AF Shuldiner, AR Nguyen, W Kao, WHL Beamer, BA Andersen, RE Pratley, R Brancati, FL TI Pro115GIn peroxisome proliferator-activated receptor-gamma and obesity SO DIABETES CARE LA English DT Letter C1 Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Epidemiol, Baltimore, MD USA. NIDDKD, NIH, Phoenix, AZ USA. RP Shuldiner, AR (reprint author), Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, 725 W Lombard St,Room S-422, Baltimore, MD 21201 USA. FU NIDDK NIH HHS [R01 DK-49692] NR 4 TC 8 Z9 8 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 JAN PY 2000 VL 23 IS 1 BP 126 EP 127 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 268ZL UT WOS:000084450900026 PM 10857984 ER PT J AU Gavin, JR Abrahamson, MJ Blonde, L Celebi, D Donovan, DS Kanzer-Lewis, G Kuschner, PR Mulcahy, K Reasner, CA Rodbard, H Zimmerman, B AF Gavin, JR Abrahamson, MJ Blonde, L Celebi, D Donovan, DS Kanzer-Lewis, G Kuschner, PR Mulcahy, K Reasner, CA Rodbard, H Zimmerman, B TI New treatment paradigm for managing outcomes in type 2 diabetes SO DIABETES EDUCATOR LA English DT Article ID METFORMIN; MELLITUS; ADULTS AB Diabetes education is at the core of quality diabetes care. Like other chronic diseases, diabetes requires many difficult lifestyle adaptations. The role of the diabetes educator is to help individuals with type 2 diabetes and those who are at risk for diabetes make these adaptations through Diabetes Self-Management Education (DSME) and care management. This is a complex role with varied responsibilities. DSME is an interactive, collaborative, ongoing process involving the person with diabetes and the diabetes educator Diabetes educators need the skill and experience necessary to promote effective self-management in the person with diabetes. Self-management skills lead to appropriate behavior changes and improved adherence to medication and blood glucose monitoring. These and other self care behaviors help delay and/or prevent chronic complications associated with diabetes. Many new treatments for diabetes have been introduced in the past several years; however; diabetes management is still frequently not aggressive enough to meet the ADA treatment goals designed to prevent the onset and progression of complications.(1) All too often, the clinical diagnosis of type 2 diabetes is made 9 to 12 years after the onset of the disease.(1) Indeed, by the time diabetes is diagnosed, 15% to 20% of patients have developed retinopathy and 5% to 10% have proteinuria.(1) It is now known that the atherogenic pattern of risk factors associated with insulin resistance has been found even before the onset of type 2 diabetes, underscoring the need for early diagnosis and treatment.(2) An estimated 16 million people in the United States are affected by diabetes.(3) This chronic disease accounts for $100 billion in health cave costs per year causes a widespread decline in patients' quality of life, and leads to high rates of disability, disease-related complications, and death.(4-7) To address these concerns, a multidisciplinary panel of leading US diabetes experts convened to review the traditional approach to diabetes treatment and to suggest a new treatment paradigm that provides earlier diagnosis and more effective management of the patient with diabetes. C1 NIH, Res Scholars Program, HHM1, Chevy Chase, MD 20815 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Joslin Clin, Boston, MA 02215 USA. Alton Ochsner Med Fdn & Ochsner Clin, Dept Internal Med, Cardiol Sect, New Orleans, LA 70121 USA. Columbia Univ, Columbia Presbyterian Med Ctr, Coll Phys & Surg, Diabetes Management Serv, New York, NY 10032 USA. GKL Associates, Pomona, NY USA. Amer Assoc Diabet Educ, Chicago, IL 60603 USA. Univ Calif Irvine, Irvine Med Ctr, Osteoporosis Diagnost Ctr, Long Beach, CA USA. Inova Diabetes Ctr, Fairfax, VA USA. Univ Texas, Hlth Sci Ctr, Texas Diabetes Inst, San Antonio, TX USA. Amer Assoc Clin Endocrinologists, Rockville, MD USA. Mayo Clin & Mayo Grad Sch Med, Rochester, MN 55901 USA. RP Gavin, JR (reprint author), NIH, Res Scholars Program, HHM1, Chevy Chase, MD 20815 USA. NR 15 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC DIABETES EDUCATORS PI CHICAGO PA STE 1240, 444 NORTH MICHIGAN AVE, CHICAGO, IL 60611-3901 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PY 2000 SU S BP 2 EP 6 PG 7 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 358BW UT WOS:000089538200001 ER PT J AU Weyer, C Hanson, K Bogardus, C Pratley, RE AF Weyer, C Hanson, K Bogardus, C Pratley, RE TI Long-term changes in insulin action and insulin secretion associated with gain, loss, regain and maintenance of body weight SO DIABETOLOGIA LA English DT Article DE weight loss; weight gain; weight regain; weight maintenance; weight cycling; insulin resistance; acute insulin response; disposition index; glucose clamp; obesity ID DEPENDENT DIABETES-MELLITUS; IMPAIRED GLUCOSE-TOLERANCE; SEVERELY OBESE SUBJECTS; X-RAY ABSORPTIOMETRY; FAT DISTRIBUTION; VISCERAL FAT; PIMA-INDIANS; RISK-FACTORS; SENSITIVITY; WOMEN AB Aims/hypothesis. We aimed to quantify changes in insulin action and insulin secretion associated with long-term gain, loss, regain, and maintenance of body weight in subjects with normal (NGT) or impaired (IGT) glucose tolerance. Methods. Insulin action (hyperinsulinaemic clamp) and insulin secretion (intravenous glucose challenge) were measured longitudinally in 209 Pima Indians [body weight 94.4 +/- 22.8 kg (means +/- SD) 89 women/120 men, 151 NGT/58 IGT], who either lost (n = 110) or gained (n = 99) weight (-23% to +29%) over 2.6 +/- 2.0 years. Insulin action and insulin secretion were reassessed on a third occasion in 33 subjects who lost at least 5% body weight over 1.5 +/- 0.8 years and then either regained or maintained weight over the subsequent 1.8 +/- 1.1 years. Results. There was a linear negative relation between changes in body weight and changes in insulin-stimulated glucose disposal in subjects with normal glucose tolerance (r = -0.51, p < 0.0001) and impaired glucose tolerance (r = -0.54, p < 0.0001). In contrast. changes in the acute insulin response were positively related to weight changes in subjects with normal glucose tolerance (r = +0.26, p < 0.005) but negatively in those with impaired glucose tolerance (r = -0.51, p < 0.0001). Improvements in insulin action after an average of 10% weight loss were lost with weight regain but largely preserved with weight maintenance. Conclusion/interpretation. Improvements in insulin action are proportional to the amount of weight loss, similar in magnitude to the impairment in insulin action with weight gain, preserved with long-term weight maintenance and similar between subjects with normal and with impaired glucose tolerance. Weight gain could, however, have more detrimental effects in people with impaired glucose tolerance, in whom insulin secretion decreases rather than increases to compensate for the decreased insulin action. 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,Rm 5-41, Phoenix, AZ 85016 USA. NR 49 TC 54 Z9 57 U1 1 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JAN PY 2000 VL 43 IS 1 BP 36 EP 46 DI 10.1007/s001250050005 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 277MU UT WOS:000084938000005 PM 10663214 ER PT J AU Filie, AC Copeland, C Wilder, AM Abati, A AF Filie, AC Copeland, C Wilder, AM Abati, A TI Individual specimen triage of effusion samples: An improvement in the standard of practice, or a waste of resources? SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article DE triage; effusion; diagnosis; turnaround time ID FINE-NEEDLE ASPIRATION AB The standard of practice in cytopathology does not include an individual specimen triage (IST) for sample optimization, but rather prescribes a uniform procedure, e.g., for smears, cell blocks, and cytospins. IST requires additional resources. We sought to evaluate whether IST would result in enhanced diagnostic accuracy and specimen turnaround time in effusions. In order to evaluate the efficacy of IST, 50 effusion samples (31 pleural, 16 peritoneal, and 3 pericardial), each with a minimum volume of 50 ml, were utilized. Each sample was prepared via IST to include at least two initial prepared Diff-Quik-stained cytospins on which the IST was based as well as a standard cytopreparation protocol for nontriaged samples (NTS) which was limited to 3 smears (2 Papanicolaou-stained, and 1 Diff-Quik-stained) and a hematoxylin-eosin (H&E)-stained cell block section. All triaged and NTS were reviewed retrospectively to determine if IST offered any advantages over the standard cytopreparation protocol for effusion samples Each was evaluated for diagnostic concordance, turnaround time for final diagnosis, and optimal preparation In 46 cases, diagnoses in IST and NTS were 100% concordant. Four cases showed minor discrepancies between the original and rite NTS diagnoses. In general, the discordant cases were due to sparse cellularity in a specimen composed largely of blood. There was no difference in turnaround time for final diagnosis. Based on a review, of all samples, the combination of cell block preparation and cytospins (stained with Diff-Quik and Papanicolaou stains) were considered optimal for microscopic evaluation. IST offers no practical advantage over the NTS standard specimen preparation in relation to the accuracy of final diagnosis or turnaround time. The lysing of grossly bloody fluids with subsequent preparation of cytospins yielded superior preparations for microscopic evaluation over NTS The standard preparation of effusion samples should include the preparation of a cell block, and cytospins stained with Diff-Quik and Papanicolaou stains for optimal microscopic evaluation. Diagn. Cytopathol. 2000,22:7-10. (C) 2000 Wiley-Liss, Inc. C1 NCI, Cytopathol Sect, Pathol Lab, Bethesda, MD 20892 USA. RP Filie, AC (reprint author), NCI, Cytopathol Sect, Pathol Lab, 10 Ctr Dr Bldg,10 R2A19, Bethesda, MD 20892 USA. NR 5 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD JAN PY 2000 VL 22 IS 1 BP 7 EP 10 DI 10.1002/(SICI)1097-0339(200001)22:1<7::AID-DC3>3.0.CO;2-U PG 4 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 269MU UT WOS:000084482800003 PM 10613964 ER PT J AU Robertson, KD AF Robertson, KD TI The role of DNA methylation in modulating Epstein-Barr virus gene expression SO DNA METHYLATION AND CANCER SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID TRANSCRIPTIONAL INITIATION SITE; LATENT MEMBRANE-PROTEIN; BAMHI C-PROMOTER; CPG METHYLATION; CYTOSINE METHYLATION; BURKITT-LYMPHOMA; BINDING-PROTEIN; RECOMBINANT VACCINIA; DENOVO METHYLATION; NUCLEAR ANTIGEN-2 C1 NIH, LME, VICHD, Bethesda, MD 20892 USA. RP Robertson, KD (reprint author), NIH, LME, VICHD, Bldy 18T,Rm 106,18 Lib Dr, Bethesda, MD 20892 USA. NR 77 TC 19 Z9 19 U1 1 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2000 VL 249 BP 21 EP 34 PG 14 WC Immunology; Microbiology SC Immunology; Microbiology GA BQ31E UT WOS:000087897100002 PM 10802936 ER PT J AU Luhn, K Makalowski, W Brosius, J AF Luhn, K Makalowski, W Brosius, J TI A tRNA pseudogene in the archaeon Methanococcus jannaschii SO DNA SEQUENCE LA English DT Article DE archaea; Methanococcus jannaschii; tRNA(Ser-UCR) pseudogene ID TRANSFER-RNA; SEQUENCE; GENOME; GENE; BACTERIA AB While searching the first completely sequenced genome of the archaeon Methanococcus jannaschii for a small RNA gene, we discovered a 5' truncated gene of a transfer RNA (tRNA(Ser-UCR)) at position 334,431 - 334,486; including the CCA-end that exactly matched the 3' terminal domain of the annotated M. jannaschii tRNA(Ser-UCR) gene located at position 303,992 - 304,081. This truncated tRNA gene covering 56 nucleotides (about 2/3) of the genuine tRNA represents, to the best of our knowledge, the first described tRNA pseudogene in the archaeal domain. C1 Univ Munster, Inst Expt Pathol Mol Neurobiol, D-48149 Munster, Germany. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Brosius, J (reprint author), Univ Munster, Inst Expt Pathol, Von Esmarch Str 56, D-48149 Munster, Germany. RI Brosius, Jurgen/F-5029-2016; Makalowski, Wojciech/I-2843-2016 OI Brosius, Jurgen/0000-0003-1650-2059; NR 11 TC 1 Z9 1 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1042-5179 J9 DNA SEQUENCE JI DNA Seq. PY 2000 VL 11 IS 1-2 BP 97 EP + PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 345EP UT WOS:000088802700012 PM 10902915 ER PT J AU Chase, D Golden, A Heidecker, G Ferris, DK AF Chase, D Golden, A Heidecker, G Ferris, DK TI Caenorhabditis elegans contains a third Polo-like kinase gene SO DNA SEQUENCE LA English DT Article DE Polo-like kinase; polo-box; cell cycle; C. elegans ID SACCHAROMYCES-CEREVISIAE CDC5; ANAPHASE-PROMOTING COMPLEX; CELL-CYCLE REGULATION; PROTEIN-KINASE; DROSOPHILA POLO; MITOSIS; PLK; IDENTIFICATION; LOCALIZATION; CLONING AB The Polo family of serine/ threonine kinases have been implicated in cell cycle control in a number of diverse organisms. Their localization and biochemical activity suggest that they play an important role in centrosome maturation, G2-to-M phase progression, the promotion of anaphase, and cytokinesis. The Polo family of kinases is distinct from other serine/threonine kinases in that they all contain a polo-box sequence motif in their non-catalytic C-terminal domain. Recently, it was reported that two Polo-related kinases, Plc1 and Plc2, are present in C. elegans. Plc2 has diverged from Plc1 with poor homology within the polo-box sequence and only had 40% amino acid identity with Plc1. We report here the full-length cDNA sequence of another Polo-related kinase from C. elegans. The predicted protein product has greater than 70% amino acid identity with PLK-1/Plc1, and has a highly conserved polo-box domain. C1 NCI, NIA, FCRF, Frederick, MD 21702 USA. NCI, FCRF, SAIC, Frederick, MD 21702 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. NIDDKD, LBG, Bethesda, MD 20892 USA. RP Ferris, DK (reprint author), NCI, NIA, FCRF, Frederick, MD 21702 USA. FU NCI NIH HHS [N01CO56000] NR 31 TC 14 Z9 19 U1 0 U2 2 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1042-5179 J9 DNA SEQUENCE JI DNA Seq. PY 2000 VL 11 IS 3-4 BP 327 EP 334 DI 10.3109/10425170009033251 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 373QP UT WOS:000165300600022 PM 11092748 ER PT S AU Hauser, SE Le, DX Thoma, GR AF Hauser, SE Le, DX Thoma, GR BE Lopresti, DP Zhou, J TI Automated zone correction in bitmapped document images SO DOCUMENT RECOGNITION AND RETRIEVAL VII SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT 7th Annual Document Recognition and Retrieval Conference CY JAN 26-27, 2000 CL SAN JOSE, CA SP SPIE, Soc Imaging Sci & Technol DE document image analysis; page segmentation ID TECHNICAL JOURNALS; DECOMPOSITION; SYSTEM AB The optical character recognition system (OCR) selected by the National Library of Medicine (NLM) as part of its system for automating the production of MEDLINE(R) records frequently segments the scanned page images into zones which are inappropriate for NLM's application. Software has been created in-house to correct the zones using character coordinate and character attribute information provided as part of the OCR output data. The software correctly delineates over 97% of the zones of interest tested to date. C1 Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20209 USA. RP Hauser, SE (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20209 USA. NR 13 TC 2 Z9 2 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3585-6 J9 P SOC PHOTO-OPT INS PY 2000 VL 3967 BP 248 EP 258 PG 11 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Optics SC Computer Science; Optics GA BP40C UT WOS:000085028100027 ER PT J AU Kohn, MC AF Kohn, MC TI Effects of TCDD on thyroid hormone homeostasis in the rat SO DRUG AND CHEMICAL TOXICOLOGY LA English DT Article; Proceedings Paper CT Tri-Service/EPA/ATSDR Toxicology Conference on Topics in Toxicology and Risk Assessment CY APR 12-15, 1999 CL WRIGHT-PATTERSON AF BASE, OHIO SP ManTech Environm Technol Inc, Naval Res Ctr Detachment, USA Ctr Hlth Promot & Prevet Med, Div Toxicol Agcy Tox Subst & Dis Registry, US EPA, Natl Res Council & Natl Acad Sci ID DOSE-RESPONSE RELATIONSHIPS; CELL-PROLIFERATION; CANCER MORTALITY; PARA-DIOXINS; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; THYROXINE; INDUCTION; GLAND; MODEL; CARCINOGENESIS AB A physiological dosimetric model was constructed to describe the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on circulating thyroid hormones in the rat and to test the hypothesis that these hormonal changes cause chronically elevated serum thyrotropin (thyroid stimulating hormone, TSH), which mediates growth promotion and may lead to thyroid tumors in TCDD-treated rats. The model included diffusion restricted distribution of TCDD among compartments for liver, kidney, white fat, slowly and rapidly perfused tissues, and the thyroxine-sensitive tissues brown fat, pituitary, and thyroid. Blood was distributed among major vessels and the capillary beds of the tissues. Metabolism of TCDD was limited to the liver. Secretion of 3,5,3'-triiodothyronine (T-3) and thyroxine (3,5,3',5'-tetraiodothyronine, T-4) from the thyroid was modeled as stimulated by circulating TSH, whose release from the pituitary was regulated by the hypothalamic peptides thyrotropin releasing hormone (activating) and somatostatin (inhibiting). Release of these peptides was represented as inhibited and activated, respectively, by circulating T-4. Binding proteins for T-3 and T-4 and metabolism of the hormones by deiodination were included in thyroxine-sensitive tissues. Induction of hepatic UDP-glucuronosyltransferase-1*6 (UGT), the enzyme which glucuronidates T-4, was modeled as induced by the complex formed between TCDD and the aryl hydrocarbon receptor. The computed extent of deiodination. primacy of the thyroid in generating T-3 from T-4, dependence of liver and kidney on locally produced T-3, and export of T-3 formed in the pituitary agreed with experimental observations. The model reproduced the observed decrease in circulating T-4 and elevated serum TSH following chronic administration of TCDD. The altered levels were attributed to the increased clearance of T-4 by the induced UGT and the consequent modification of feedback control of hormone releases. These results are consistent with the hypothesis of growth stimulation by elevated TSH, but measured values of this hormone in blood of rats vary over a large range, and the change induced by TCDD is often small. Measured UGT levels are less variable and the increase in this protein is much greater, suggesting that this response may be a more reliable biomarker for effects of TCDD on the thyroid. C1 NIEHS, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. RP Kohn, MC (reprint author), NIEHS, Lab Computat Biol & Risk Anal, POB 12233,Mail Drop A3-06, Res Triangle Pk, NC 27709 USA. NR 64 TC 24 Z9 25 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0148-0545 J9 DRUG CHEM TOXICOL JI Drug Chem. Toxicol. PY 2000 VL 23 IS 1 BP 259 EP 277 DI 10.1081/DCT-100100114 PG 19 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy; Toxicology SC Chemistry; Pharmacology & Pharmacy; Toxicology GA 292DD UT WOS:000085778100019 PM 10711401 ER PT J AU Guo, TL McCay, JA Brown, RD Musgrove, DL Butterworth, L Munson, AE Germolec, DR White, KL AF Guo, TL McCay, JA Brown, RD Musgrove, DL Butterworth, L Munson, AE Germolec, DR White, KL TI Glycidol modulation of the immune responses in female B6C3F1 mice SO DRUG AND CHEMICAL TOXICOLOGY LA English DT Article ID HOST-RESISTANCE; CELL-ACTIVITY; METASTASIS; INVITRO; RATS; CARCINOGENICITY; MUTAGENICITY; SUPPRESSION; LYMPHOCYTES; EXPOSURE AB The immunotoxic potential of glycidol was evaluated in female B6C3F1 mice using a battery of functional assays and three host resistance models. Glycidol was administered to the animals by oral gavage as a solution in sterile distilled water daily for 14 days at doses of 25, 125 and 250 mg/kg. In tier I, we observed that glycidol exposure produced a dose-related decrease in splenocyte IgM antibody-forming cell response to sheep red blood cells (sRBC); the spleen natural killer (NK) cell activity was also decreased. A decrease in B cell proliferative responses to anti-IgM F(ab')(2) and/or interleukin-4 (IL-4) was observed while the splenocyte proliferative responses to T cell mitogen ConA and B cell mitogen LPS were not affected. The splenocyte proliferative response to allogeneic cells as evaluated in the mixed leukocyte reaction (MLR) to DBA/2 spleen cells was not affected. In tier II, we found that exposure to glycidol decreased the number and percentage of B cells and the absolute number of CD4(+) T cells in the spleen while the number of total T cells, CD8(+) T cells and CD4(+) CD8(+) T cells was not affected. The cytotoxic T lymphocyte (CTL) response to mitomycin C-treated P815 mastocytoma was not affected; the cytotoxic activity of peritoneal macrophages was not suppressed. Moreover, the host resistance to Listeria monocytogenes was not affected although a slight increase in host resistance to Streptococcus pneumoniae was observed. However, exposure to glycidol decreased host resistance to the B16F10 melanoma tumor model with the maximal tumor formation in lung observed in the high dose group. Overall, these dada support the finding that glycidol is an immunosuppressive agent in female B6C3F1 mice. C1 Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP White, KL (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, POB 980613, Richmond, VA 23298 USA. FU NIEHS NIH HHS [ES 55094] NR 32 TC 18 Z9 21 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0148-0545 J9 DRUG CHEM TOXICOL JI Drug Chem. Toxicol. PY 2000 VL 23 IS 3 BP 433 EP 457 DI 10.1081/DCT-100100127 PG 25 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy; Toxicology SC Chemistry; Pharmacology & Pharmacy; Toxicology GA 346CB UT WOS:000088852000003 PM 10959546 ER PT J AU Paweletz, CP Gillespie, JW Ornstein, DK Simone, NL Brown, MR Cole, KA Wang, QH Huang, J Hu, N Yip, TT Rich, WE Kohn, EC Linehan, WM Weber, T Taylor, P Emmert-Buck, MR Liotta, LA Petricoin, EF AF Paweletz, CP Gillespie, JW Ornstein, DK Simone, NL Brown, MR Cole, KA Wang, QH Huang, J Hu, N Yip, TT Rich, WE Kohn, EC Linehan, WM Weber, T Taylor, P Emmert-Buck, MR Liotta, LA Petricoin, EF TI Rapid protein display profiling of cancer progression directly from human tissue using a protein biochip SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE SELDI; proteomics; biomarker; microdissection; laser; pharmacoproteomics; pharmacogenomics; mass spectrometry ID LASER-CAPTURE MICRODISSECTION; 2-DIMENSIONAL ELECTROPHORESIS; MOLECULAR ANALYSIS; SAMPLE PREPARATION AB The complicated, changing pattern of protein expression should contain important information about the pathologic process taking place in the cells of actual tissue. Utilization of this information for the selection of druggable targets could be possible if a means existed to rapidly analyze and display changes in protein expression in defined microscopic cellular subpopulations. As a demonstration of feasibility, we show the generation of sensitive, rapid, and reproducible molecular weight protein profiles of patient-matched normal, premalignant, malignant, and metastatic microdissected cell populations from stained human esophageal, prostate, breast, ovary, colon, and hepatic tissue sections through the application of an affinity-based biochip. Reproducible, discriminatory protein biomarker profiles can be obtained from as few as 25 cells in less than 5 min from dissection to the generation of the protein fingerprint. Furthermore, these protein pattern profiles reveal reproducible changes in expression as cells undergo malignant transformation, and are discriminatory for different tumor types. Consistent protein changes were identified in the microdissected cells from patient-matched tumor and normal epithelium from eight out of eight different malignant esophageal tissue sets and three out of three malignant prostate tissue sets. A means to rapidly generate a display of expressed proteins from microscopic cellular populations sampled from tissue could be an important enabling technology for pharmacoproteomics, molecular pathology, drug intervention strategies, therapeutic assessment of drug entities, disease diagnosis, toxicity, and gene therapy monitoring. Published 2000 Wiley-Liss, Inc.(+) C1 US FDA, Ctr Biol Evaluat & Res, Tissue Prote Unit, Div Cytokine Biol, Bethesda, MD 20892 USA. NCI, Canc Genome Anant Project, Off Director, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. NCI, Mol Signalling Unit, Bethesda, MD 20892 USA. NCI, Pathogenet Unit, Bethesda, MD 20892 USA. NCI, Canc Prevent Studies Branch, Bethesda, MD 20892 USA. Shanxi Canc Hosp, Pathol Lab, Taiyuan, Peoples R China. Ciphergen Biosyst Inc, Palo Alto, CA USA. Georgetown Univ, Dept Chem, Washington, DC 20057 USA. Roswell Pk Med Ctr, Buffalo, NY USA. RP Petricoin, EF (reprint author), US FDA, Ctr Biol Evaluat & Res, Tissue Prote Unit, Div Cytokine Biol, 8800 Rockville Pike,Bldg 29A, Bethesda, MD 20892 USA. RI Cole, Kristina/M-3922-2015 NR 15 TC 119 Z9 126 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 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD JAN PY 2000 VL 49 IS 1 BP 34 EP 42 DI 10.1002/(SICI)1098-2299(200001)49:1<34::AID-DDR6>3.0.CO;2-W PG 9 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 296JD UT WOS:000086020500006 ER PT J AU Hecht, SS Trushin, N Chhabra, SK Anderson, LM Nerurkar, PV AF Hecht, SS Trushin, N Chhabra, SK Anderson, LM Nerurkar, PV TI Metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone by cultured monkey lung explants SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID TOBACCO-SPECIFIC CARCINOGEN; CHEMICAL CARCINOGENESIS; N-NITROSAMINES; PHENETHYL ISOTHIOCYANATE; LIVER-MICROSOMES; PATAS MONKEY; RAT LUNG; URINE; N'-NITROSONORNICOTINE; TISSUE AB The metabolism of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was investigated in short-term cultures of monkey lung. Explants from the lungs of two patas monkeys (Erythrocebus patas) and one cynomolgus monkey (Macaca fascicularis) were incubated with 10 mu M [5-H-3]NNK and aliquots were analyzed for NNK metabolites by HPLC at various time points from 1 to 24 h. F344 rat lung tissue metabolism of NNK was assayed under the same conditions. Substantial amounts of metabolites from the alpha-hydroxylation metabolic activation pathway were detected in all cultures. In two of the monkey lung cultures, these metabolite levels were significantly higher than those formed by other pathways. All cultures also metabolized NNK by pyridine-N-oxidation and carbonyl reduction. The metabolism of NNK by cultured monkey lung was generally similar to that observed in rat lung, indicating that there are not major species differences between rodents and nonhuman primates in pulmonary metabolism of NNK. C1 Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA. NCI, Frederick, MD 21701 USA. Amer Hlth Fdn, Valhalla, NY 10595 USA. RP Hecht, SS (reprint author), Univ Minnesota, Ctr Canc, Box 806 Mayo,420 Delaware St SE, Minneapolis, MN 55455 USA. OI Hecht, Stephen/0000-0001-7228-1356 NR 26 TC 6 Z9 7 U1 0 U2 2 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 JAN PY 2000 VL 28 IS 1 BP 5 EP 9 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 271DU UT WOS:000084579600002 PM 10611133 ER PT J AU Rall, DP AF Rall, DP TI Laboratory animal tests and human cancer SO DRUG METABOLISM REVIEWS LA English DT Article; Proceedings Paper CT 1998 Arkansas Toxicology Symposium: Can Rodent Cancer Tests Predict for Human Cancers - Honoring Dr David P Rall CY NOV 12-13, 1998 CL LITTLE ROCK, ARKANSAS SP Dorothy Snider Fdn ID CHEMICALS; RISK AB The use of the results of laboratory animal tests to predict human cancer is effective in identifying potential human carcinogens before human exposure, permitting measures to be taken to prevent that exposure, a foolproof way to prevent human cancer. The purported, and highly publicized, faults of these tests, when examined critically, are shown not to be significant. Most chemicals are not carcinogenic; only about 1 in 10 are truly carcinogenic. The high doses used to maximize sensitivity do not produce false positives. All human carcinogens are carcinogenic in laboratory animals, and almost all animal carcinogens for which there is human exposure, when analyzed by epidemiological studies, show responses that are not statistically different. Most carcinogens are not banned, some are regulated, but many are not. The claimed costs of these health regulations are typically overestimated, and often greatly overestimated. Using the results of laboratory animal studies is good science and good public health. RP Rall, DP (reprint author), Care of Huff J, NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 23 TC 24 Z9 24 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2000 VL 32 IS 2 BP 119 EP 128 DI 10.1081/DMR-100100565 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 307QV UT WOS:000086665200002 PM 10774768 ER PT J AU Tomatis, L AF Tomatis, L TI Etiologic evidence and primary prevention of cancer SO DRUG METABOLISM REVIEWS LA English DT Article; Proceedings Paper CT 1998 Arkansas Toxicology Symposium: Can Rodent Cancer Tests Predict for Human Cancers - Honoring Dr David P Rall CY NOV 12-13, 1998 CL LITTLE ROCK, ARKANSAS SP Dorothy Snider Fdn ID ANIMALS; CHEMICALS AB For many decades, primary prevention of cancer was implemented on the basis of evidence for a causal relationship between exposure and human cancer that took into consideration biological plausibility, but did not depend on the degree of understanding of the underlying mechanisms. One of the credos of public health is that primary prevention can be implemented before reaching a complete understanding of mechanisms that could confirm/explain causality. Measures of primary prevention are taken on the basis of what is recognized as causative factors of human cancer. The most authoritative lists of recognized human carcinogens are those compiled from the evaluations of carcinogenic risk carried out by the International Agency for Research on Cancer (IARC) and the evaluations that the U.S. National Toxicology Program (NTP) publishes in its periodical Report on Carcinogens. Knowledge of mechanisms is accumulating at a fast pace, and although it has not yet led to the definition of an efficient strategy for primary prevention for the majority of cancer cases, it may drive the scientific establishment toward a high-risk approach to prevention. The most reasonable and socially acceptable development of primary prevention should be the blending of a population approach; that is, the shifting of the distribution of risk factors across an entire population in a favorable direction (e.g., a general decrease of the levels of exposure to environmental carcinogens) with the high-risk approach that will concern individuals with extreme values of genetically determined weaknesses in the interactions with the environment. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Tomatis, L (reprint author), Cave 25-R, I-34011 Trieste, Italy. NR 23 TC 6 Z9 6 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2000 VL 32 IS 2 BP 129 EP 137 DI 10.1081/DMR-100100566 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 307QV UT WOS:000086665200003 PM 10774769 ER PT J AU Barrett, JC AF Barrett, JC TI Molecular and environmental causes of cancer SO DRUG METABOLISM REVIEWS LA English DT Article; Proceedings Paper CT 1998 Arkansas Toxicology Symposium: Can Rodent Cancer Tests Predict for Human Cancers - Honoring Dr David P Rall CY NOV 12-13, 1998 CL LITTLE ROCK, ARKANSAS SP Dorothy Snider Fdn ID HAMSTER-EMBRYO CELLS; GROWTH-FACTOR-I; DIETHYLSTILBESTROL; TRANSFORMATION; EXPOSURE; MICE AB The multistep, clonal evolution model of cancer predicts fundamental mechanisms by which chemicals may influence the cancer process. These are illustrated by studies of the mechanisms of induction of carcinogenesis by estrogens and the inhibition of carcinogenesis by caloric restriction. C1 NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Barrett, JC (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 12 TC 2 Z9 2 U1 2 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2000 VL 32 IS 2 BP 139 EP 142 DI 10.1081/DMR-100100567 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 307QV UT WOS:000086665200004 PM 10774770 ER PT J AU Bucher, JR AF Bucher, JR TI Doses in rodent cancer studies: Sorting fact from fiction SO DRUG METABOLISM REVIEWS LA English DT Article; Proceedings Paper CT 1998 Arkansas Toxicology Symposium: Can Rodent Cancer Tests Predict for Human Cancers - Honoring Dr David P Rall CY NOV 12-13, 1998 CL LITTLE ROCK, ARKANSAS SP Dorothy Snider Fdn ID CELL-PROLIFERATION; HEPATOCARCINOGEN OXAZEPAM; CARCINOGENESIS; RISK; RESPONSES; PRIMIDONE; LIVER; MICE; RATS AB The belief that rodent cancer bioassays predict for human cancers is a fundamental public health precept based on sound biological principles. Nonetheless, it is appropriate to periodically debate this point as scientific understanding of cancer causation advances. This presentation addresses one of the many factors that determines the predictive value of rodent tumor bioassay results for human health: This is the issue of dose. Examination of several recent National Toxicology Program (NTP) studies demonstrates that the applied dose often far overestimates the actual effective dose, or maximum blood concentration attained in a rodent, when compared with similar relationships in humans. Further examination of the NTP database on rodent toxicity and carcinogenicity studies revealed summary information on factors that were pivotal in prechronic studies for selecting doses for chronic studies. Contrary to popular belief, target organ toxicity was a determining factor in only about,half of the studies. The typically minimal nature of the lesions which limit doses for chronic studies is described for several common target sites. Taken together, these facts paint a far different picture than the common public perception of the ''massive'' doses used in chronic rodent studies and suggest that, in some cases, dose limitations are actually so severe as to limit the sensitivity of a chronic bioassay to detect a carcinogenic effect. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Bucher, JR (reprint author), NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 29 TC 16 Z9 16 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2000 VL 32 IS 2 BP 153 EP 163 DI 10.1081/DMR-100100569 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 307QV UT WOS:000086665200006 PM 10774772 ER PT J AU Haseman, JK AF Haseman, JK TI Using the NTP database to assess the value of rodent carcinogenicity studies for determining human cancer risk SO DRUG METABOLISM REVIEWS LA English DT Article; Proceedings Paper CT 1998 Arkansas Toxicology Symposium: Can Rodent Cancer Tests Predict for Human Cancers - Honoring Dr David P Rall CY NOV 12-13, 1998 CL LITTLE ROCK, ARKANSAS SP Dorothy Snider Fdn ID LONG-TERM CARCINOGENICITY; BODY-WEIGHT; TUMOR-INCIDENCE; DIETARY RESTRICTION; FISCHER-344 RATS; B6C3F(1) MICE; F344 RATS; NEOPLASMS; CHEMICALS; SURVIVAL AB The large database of carcinogenicity results generated by the National Toxicology Program (NTP) provides a unique opportunity to critically evaluate important scientific issues such as (1) the frequency of positive outcomes, (2) the interspecies correlation in carcinogenic response between rats and mice, (3) the correlation between body weight and tumor incidence, (4) estimates of the false-positive and false-negative rates, and (5) the frequency of decreasing tumor incidences. Such database evaluations enable us to better understand the value and limitations of rodent carcinogenicity studies for determining human cancer risk. However, as the NTP database becomes increasingly accessible to the general scientific community, there is also increased opportunity for misuse of the database. This article reexamines and updates previous database evaluations, presents four scientific principles that should be employed by anyone attempting to use this database, and illustrates how failure to apply these principles can read to misleading results. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Haseman, JK (reprint author), NIEHS, Biostat Branch, Mail Drop A3-03,POB 12233, Res Triangle Pk, NC 27709 USA. NR 32 TC 16 Z9 17 U1 1 U2 4 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2000 VL 32 IS 2 BP 169 EP 186 DI 10.1081/DMR-100100570 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 307QV UT WOS:000086665200007 PM 10774773 ER PT J AU Melnick, RL Kohn, MC AF Melnick, RL Kohn, MC TI Dose-response analyses of experimental cancer data SO DRUG METABOLISM REVIEWS LA English DT Article; Proceedings Paper CT 1998 Arkansas Toxicology Symposium: Can Rodent Cancer Tests Predict for Human Cancers - Honoring Dr David P Rall CY NOV 12-13, 1998 CL LITTLE ROCK, ARKANSAS SP Dorothy Snider Fdn ID FEMALE B6C3F(1) MICE; INHALATION EXPOSURE; CELL-PROLIFERATION; DRINKING-WATER; AD-LIBITUM; F344 RATS; CORN-OIL; CARCINOGENICITY; 1,3-BUTADIENE; CHLOROFORM AB Dose-response analysis provides a powerful tool to determine causality from experimental cancer data, estimate low-dose risk, and evaluate mechanistic hypotheses. However, the interpretation of cancer dose-response data can be influenced by how the dose and response terms are characterized. Using the poly-3 quantal response method to adjust for the extensive and early development of lethal lymphomas in butadiene-exposed mice provided a means of obtaining a better representation of dose-response relationships for late-developing tumors induced by this chemical. Fitting a Weibull model to survival-adjusted tamer data for chloroprene and butadiene indicated similar carcinogenic potencies for these chemicals in mice. In conjunction with the rodent toxicity and carcinogenicity studies conducted by the National Toxicology Program, toxicokinetic studies are performed to characterize relationships between exposure and tissue concentrations of parent compound and metabolites. A. physiologically based pharmacokinetic model (PBPK) of butadiene dosimetry indicated that differences in carcinogenic response between rats and mice are not simply due to differences in tissue concentrations of epoxybutene, a mutagenic metabolic intermediate. Thus, factors beyond tissue dosimetry of this metabolite must be important in butadiene-induced carcinogenesis. A PBPK model far isoprene indicated that brood concentrations of isoprene epoxides are a better indicator of kidney cancer risk than are measurements of isoprene-exposure concentrations. An evaluation of dose response relationships for cytotoxicity, regenerative hyperplasia, and tumor induction by trihalomethanes indicates that for this family of chemicals, cell proliferation is not a reliable predictor of tumor response. C1 NIEHS, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. RP Melnick, RL (reprint author), NIEHS, Lab Computat Biol & Risk Anal, MD A3-06,POB 12233, Res Triangle Pk, NC 27709 USA. NR 24 TC 10 Z9 10 U1 1 U2 3 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2000 VL 32 IS 2 BP 193 EP 209 DI 10.1081/DMR-100100572 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 307QV UT WOS:000086665200009 PM 10774775 ER PT J AU Neckers, LM AF Neckers, LM TI Can the heat shock protein 90 inhibitor geldanamycin be designed to specifically inhibit HER-2 tyrosine kinase? SO DRUG RESISTANCE UPDATES LA English DT Review ID BREAST-CANCER; IN-VIVO; HSP90; BINDS; DEGRADATION; ANSAMYCINS; CHAPERONE; ONCOGENE; COMPLEX; FAMILY C1 NCI, Dept Cell & Canc Biol, Med Branch, Rockville, MD 20850 USA. RP Neckers, LM (reprint author), NCI, Dept Cell & Canc Biol, Med Branch, 9610 Med Ctr Dr,Suite 300, Rockville, MD 20850 USA. NR 22 TC 5 Z9 5 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1368-7646 J9 DRUG RESIST UPDATE JI Drug Resist. Update PY 2000 VL 3 IS 4 BP 203 EP 205 DI 10.1054/drup.2000.0149 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 354FN UT WOS:000089319300002 ER PT J AU Jarvinen, TAH Liu, ET AF Jarvinen, TAH Liu, ET TI Effects of HER-2/neu on chemosensitivity of tumor cells SO DRUG RESISTANCE UPDATES LA English DT Review ID TOPOISOMERASE-II-ALPHA; METASTATIC BREAST-CANCER; IN-SITU HYBRIDIZATION; GENE AMPLIFICATION; PREDICTIVE VALUE; ADJUVANT CHEMOTHERAPY; INTRINSIC CHEMORESISTANCE; MONOCLONAL-ANTIBODY; C-ERBB-2; P53 AB In solid tumors, such as breast and ovarian cancer, the predominant genetic mechanism for oncogene activation is through gene amplification. The HER-2 (also known as ErbB(2)/c-erbB2/HER-2/neu) oncogene is the most frequently amplified oncogene in breast cancer and its overexpression is associated with poor clinical outcome. In addition to its role in tumor progression, HER-2 has been implicated in altering tumor cell chemosensitivity to cytotoxic chemotherapy, particularly to anthracyclines. However, sophisticated in vitro studies have recently indicated that HER-2 may not have anything to do with the sensitivity of the cancer cells to cytotoxic drugs. Topoisomerase II alpha gene is a target gene for many cytotoxic drugs and is located just by the HER-2 at the 17q 12-q21. TopoII alpha amplification and deletion may account for both relative chemosensitivity and resistance to anthracycline-therapy depending on the specific genetic defect at the topoII alpha locus. Whereas HER-2 is an oncogene that dearly can drive tumor induction and growth, its function as a marker for chemoselection may be due to associated genetic changes in the topoII alpha gene. (C) 2000 Harcourt Publishers Ltd. C1 Univ Tampere, Inst Med Technol, FIN-33101 Tampere, Finland. Tampere Univ Hosp, Tampere, Finland. NCI, Div Clin Sci, Bethesda, MD 20892 USA. RP Jarvinen, TAH (reprint author), Univ Tampere, Inst Med Technol, POB 607, FIN-33101 Tampere, Finland. RI Liu, Edison/C-4141-2008 NR 50 TC 17 Z9 17 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1368-7646 J9 DRUG RESIST UPDATE JI Drug Resist. Update PY 2000 VL 3 IS 6 BP 319 EP 324 DI 10.1054/drup.2000.0166 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 397ER UT WOS:000166680800001 ER PT J AU Piscitelli, SC Bhat, N Pau, A AF Piscitelli, SC Bhat, N Pau, A TI A risk-benefit assessment of interleukin-2 as an adjunct to antiviral therapy in HIV infection SO DRUG SAFETY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; DOSE RECOMBINANT INTERLEUKIN-2; ACTIVE ANTIRETROVIRAL THERAPY; GLYCOL-MODIFIED INTERLEUKIN-2; NATURAL-KILLER-CELLS; CD4(+) T-CELLS; TYPE-1 INFECTION; CANCER-PATIENTS; INTRAVENOUS INTERLEUKIN-2; TNF-ALPHA AB Immunomodulation has become a major focus of HIV research in an effort to augment, boost or restore the patient's damaged immune system. Recombinant interleukin-2 is currently being studied in phase II/III trials in HIV-infected patients. Several clinical studies have demonstrated that intermittent regimens are associated with marked rises in CD4+ cell counts without an increase in viral load. Most of these studies employ 5 consecutive days of interleukin-2 therapy by continuous intravenous infusion or subcutaneous injection, repeated every 8 weeks. An alternative strategy is the daily administration of low doses of interleukin-2, but clinical experience with this regimen is limited. Interleukin-2 administration can adversely affect virtually every organ system, requiring aggressive supportive care. A variety of administration strategies and interventions are being evaluated to minimise toxicity. Currently, no clinical end-point data are available for interleukin-2 in HIV-infected patients. Until phase III studies are completed, interleukin-2 can be used in the research setting as an immunomodulator and adjunct to antiretroviral therapy. Its potential to activate latently infected cells and promote HIV eradication from reservoir sites is also an important area for further study. If clinical benefit can be demonstrated, interleukin-2 could be useful as an adjunct to antiretroviral therapy if adverse effects can be minimised and therapy can be given infrequently on an outpatient basis. C1 NIAID, Ctr Clin, Dept Pharm, NIH, Bethesda, MD 20892 USA. RP Piscitelli, SC (reprint author), NIAID, Ctr Clin, Dept Pharm, NIH, Bldg 10,Room 1N257, Bethesda, MD 20892 USA. NR 58 TC 9 Z9 9 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PD JAN PY 2000 VL 22 IS 1 BP 19 EP 31 DI 10.2165/00002018-200022010-00003 PG 13 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 275ZP UT WOS:000084851000003 PM 10647974 ER PT J AU Mason, RP Trumbore, MW Mason, PE AF Mason, RP Trumbore, MW Mason, PE TI Membrane biophysical interactions of amlodipine result in antioxidant properties SO DRUGS LA French DT Article ID CORONARY HEART-DISEASE; VITAMIN-E CONSUMPTION; CALCIUM-ANTAGONISTS; ATHEROSCLEROSIS; MORTALITY; FAILURE; RISK; MECHANISMS; NIFEDIPINE; PROBUCOL AB Objective: To assess the potential benefits of the antioxidant activity of certain pharmacological agents that may be beneficial in the treatment of cardiovascular disease, including coronary heart disease and heart failure, by reducing irreversible cell injury due to oxyradical damage. Methods: The antioxidant activities of representative calcium antagonists were examined and correlated with the molecular membrane interactions of the compounds, as measured by radioligand binding assays and high resolution differential scanning calorimetry. Results: The results of these experiments show a direct relationship between the antioxidant activities of the calcium antagonists and their affinity for the membrane lipid bilayer, as well as their ability to modulate membrane thermodynamic properties (amlodipine > verapamil much greater than diltiazem). The charged 1,4-dihydropyridine calcium antagonist amlodipine had the highest affinity for the membrane bilayer (K(p)10(4)) and produced the largest changes in membrane thermodynamic properties, including a reduction in the thermal phase transition temperature (-11%), enthalpy (-14%) and cooperative unit size (-59%), relative to control phosphatidylcholine liposomes. Conclusions: These findings indicate that lipophilic calcium antagonists inhibit lipid peroxidation in cellular membranes as a result of modulating physicochemical properties of the membrane lipid bilayer, independently of calcium channel inhibition. The antioxidant activity of highly lipophilic calcium antagonists, such as amlodipine, may contribute to new cytoprotective mechanisms of action in cardiovascular disease. C1 Med Coll Penn & Hahnemann Univ, Sch Med, Dept Med & Biochim, Inst Rech Cardiovasc & Pulm, Pittsburgh, PA USA. NCI, NIH, Bethesda, MD 20892 USA. RP Mason, RP (reprint author), Cardiovasc & Pulm Res Inst, 320 EN Ave 15 S Tower, Pittsburgh, PA 15212 USA. NR 31 TC 5 Z9 6 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PY 2000 VL 59 SI 2 BP 9 EP 16 DI 10.2165/00003495-200059992-00002 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 353LZ UT WOS:000089276900003 PM 11002854 ER PT J AU Kalil, N Cheson, BD AF Kalil, N Cheson, BD TI Management of chronic lymphocytic leukaemia SO DRUGS & AGING LA English DT Review ID AUTOIMMUNE HEMOLYTIC-ANEMIA; BONE-MARROW TRANSPLANTATION; RED-CELL APLASIA; PHASE-II TRIAL; NATIONAL-CANCER-INSTITUTE; NON-HODGKINS-LYMPHOMA; TUMOR LYSIS SYNDROME; TERM FOLLOW-UP; MULTIVARIATE SURVIVAL ANALYSIS; CHLORAMBUCIL PLUS PREDNISONE AB Chronic lymphocytic leukaemia (CLL) is the most common form of adult leukaemia in Western countries. The diagnosis requires mature-appearing lymphocytes in the peripheral blood to >5 x 10(9)/L. The immunophenotype typically includes B cell antigens CD19, CD20 and CD23, low expression of surface immunoglobulin and CD5+, with other T cell antigens absent. Bone marrow biopsy, although not required for diagnosis, must show at least 30% lymphocytes. Cytogenetic abnormalities are frequent in patients with CLL, and may be associated with poor prognosis. Clinically, most patients are asymptomatic at presentation, with incidental lymphadenopathy and/or hepatosplenomegaly in the routine physical examination. Infections by opportunistic pathogens are the major cause of death. Aggressive transformation occurs in 10% of patients with CLL, most commonly prolymphocytic leukaemia (PLL) and Richter's syndrome. PLL de novo must be differentiated from PLL of an aggressive transformation. The incidences of autoimmune diseases and solid or haemopoietic secondary malignancies are increased in patients with CLL. Clinical stags is the strongest prognostic factor in CLL. There is no indication for early intervention. The current recommendation to start treatment includes disease-related symptoms, massive and/or progressive hepatosplenomegaly or lymphadenopathy, increasing bone marrow failure, autoimmune disease, and recurrent infections. Alkylating agents (e.g. chlorambucil) and nucleoside analogues (e.g. fludarabine) are the most active agents for CLL. Fludarabine induces higher response rates, but no improvement in overall survival has been observed. Fludarabine is the drug of choice for the majority of patients with CLL. Chlorambucil may be helpful for elderly patients with poor performance, and for patients who do not tolerate fludarabine. No drug combination is better than single agents. For patients refractory to initial treatment, referral to a clinical trial is the best choice. Other salvage therapy includes retreatment with the same initial agent (chlorambucil or fludarabine) if initial response was observed, or fludarabine for patients refractory to chlorambucil. Promising new approaches include cycle-active agents, nelarabine, biological therapy such as anti-CD52 monoclonal antibody, bone marrow transplantation, including the use of submyeloablative preparative regimens ('minitransplant') to induce graft-versus-leukaemia effect, and gene therapy. Prophylactic antibacterials and intravenous immunoglobulin should not be used routinely during supportive care. Epoetin may be helpful for patients who have anaemia without obvious cause. Assessment of response to therapy in CLL has been updated by the National Cancer Institute Working Group, and these guidelines are used worldwide for clinical trials. C1 NCI, Bethesda, MD 20892 USA. RP Cheson, BD (reprint author), NCI, Execut Plaza N,Room 741, Bethesda, MD 20892 USA. NR 235 TC 32 Z9 32 U1 0 U2 1 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PD JAN PY 2000 VL 16 IS 1 BP 9 EP 27 DI 10.2165/00002512-200016010-00002 PG 19 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 275ZN UT WOS:000084850900002 PM 10733261 ER PT J AU Chrambach, A Radko, SP AF Chrambach, A Radko, SP TI Size-dependent retardation and resolution by electrophoresis of rigid, submicron-sized particles, using buffered solutions in presence of polymers: A review of recent work from the authors' laboratory SO ELECTROPHORESIS LA English DT Review DE capillary zone electrophoresis; submicron-sized particles; review ID MECHANISMS AB Capillary zone electrophoresis (CZE) was conducted in buffered solutions of polyacrylamide (PA) and polyethylene glycol (PEG) to find the degree and the manner in which separation and resolution of submicron-sized rigid spherical polystyrene sulfate and carboxylate particles were affected by the presence of those polymers. In resolving pairs of representative particles, maximal resolution was observed at or near the entanglement threshold concentration, c*, of the polymer. The value of that maximum represents a several-fold increase in resolution. Since c* can be calculated from intrinsic viscosity, and the latter from the molecular weight of the polymer (and some constants available in the literature), optimally resolving polymer conditions become predictable. The maximum can also be experimentally determined by measuring intrinsic viscosity and calculating c*, or by either systematically varying the concentration of a polymer of constant molecular weight or by varying the molecular weight of a polymer at constant concentration. An optimally resolving field strength is superimposed on the maximally resolving condition of polymer concentration and weight. C1 NICHHD, Lab Cellular & Mol Biophys, Macromol Anal Sect, NIH, Bethesda, MD 20892 USA. RP Chrambach, A (reprint author), NICHHD, Lab Cellular & Mol Biophys, Macromol Anal Sect, NIH, Bldg 10,Rm 9D50, Bethesda, MD 20892 USA. NR 14 TC 6 Z9 6 U1 1 U2 4 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 JAN PY 2000 VL 21 IS 2 BP 259 EP 265 DI 10.1002/(SICI)1522-2683(20000101)21:2<259::AID-ELPS259>3.0.CO;2-1 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 281RK UT WOS:000085174400002 PM 10674996 ER PT B AU Breman, JG AF Breman, JG BE Scheld, WM Craig, WA Hughes, JM TI Monkeypox: an emerging infection for humans? SO EMERGING INFECTIONS 4 LA English DT Proceedings Paper CT 39th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) CY SEP 26-29, 1999 CL SAN FRANCISCO, CA ID POLYMERASE-CHAIN-REACTION; VARIOLA-LIKE VIRUSES; SEROLOGICAL SURVEY; COWPOX VIRUS; ORTHOPOXVIRUS; DIFFERENTIATION; ZAIRE; DNA; SMALLPOX; MANAGEMENT C1 NIH, Div Int Training & Res, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Breman, JG (reprint author), NIH, Div Int Training & Res, Fogarty Int Ctr, Bethesda, MD 20892 USA. NR 88 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 1-55581-197-3 PY 2000 BP 45 EP 67 PG 23 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA BS08Q UT WOS:000168586400005 ER PT B AU Masur, H AF Masur, H BE Scheld, WM Craig, WA Hughes, JM TI Human immunodeficiency virus-related opportunistic infections in the era of highly active antiretroviral therapy SO EMERGING INFECTIONS 4 LA English DT Proceedings Paper CT 39th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) CY SEP 26-29, 1999 CL SAN FRANCISCO, CA ID PNEUMOCYSTIS-CARINII PNEUMONIA; CYTOMEGALOVIRUS RETINITIS; ACQUIRED-IMMUNODEFICIENCY; MAINTENANCE THERAPY; TRIMETHOPRIM-SULFAMETHOXAZOLE; DIHYDROPTEROATE SYNTHASE; GANCICLOVIR RESISTANCE; MYCOBACTERIUM-AVIUM; HIV-1 DISEASE; AIDS PATIENTS C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Masur, H (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. NR 50 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 1-55581-197-3 PY 2000 BP 165 EP 186 PG 22 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA BS08Q UT WOS:000168586400012 ER PT J AU Chrousos, GP AF Chrousos, GP TI The HPA axis and the stress response SO ENDOCRINE RESEARCH LA English DT Article; Proceedings Paper CT 9th Conference on the Adrenal Cortex CY JUN 17-20, 2000 CL UNIV TORONTO, ST MICHAELS COLL, TORONTO, CANADA SP Canadian Life Technologies Inc, Hoffman La Roche Ltd, Marcel Dekker Inc, Nikon, Qiagen Inc, Roche Diagnost, VWR Canlab HO UNIV TORONTO, ST MICHAELS COLL C1 NICHD, PREB, NIH, Bethesda, MD 20892 USA. RP Chrousos, GP (reprint author), NICHD, PREB, NIH, Bethesda, MD 20892 USA. NR 0 TC 21 Z9 22 U1 0 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0743-5800 J9 ENDOCR RES JI Endocr. Res. PY 2000 VL 26 IS 4 BP 513 EP 514 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 386MC UT WOS:000166064600005 PM 11196421 ER PT J AU Catt, KJ Reyes, AJO Zhang, M Smith, RD Hunyady, L AF Catt, KJ Reyes, AJO Zhang, M Smith, RD Hunyady, L TI Activation and phosphorylation of angiotensin AT(1) and AT(2) receptors SO ENDOCRINE RESEARCH LA English DT Article; Proceedings Paper CT 9th Conference on the Adrenal Cortex CY JUN 17-20, 2000 CL UNIV TORONTO, ST MICHAELS COLL, TORONTO, CANADA SP Canadian Life Technologies Inc, Hoffman La Roche Ltd, Marcel Dekker Inc, Nikon, Qiagen Inc, Roche Diagnost, VWR Canlab HO UNIV TORONTO, ST MICHAELS COLL C1 NIH, Endocrinol & Reprod Res Branch, Bethesda, MD 20892 USA. Semmelweis Univ, Sch Med, Dept Physiol, Budapest, Hungary. RP Catt, KJ (reprint author), NIH, Endocrinol & Reprod Res Branch, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0743-5800 J9 ENDOCR RES JI Endocr. Res. PY 2000 VL 26 IS 4 BP 559 EP 560 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 386MC UT WOS:000166064600013 PM 11196428 ER PT J AU Ehrhart-Bornstein, M Haidan, A Alesci, S Bornstein, SR AF Ehrhart-Bornstein, M Haidan, A Alesci, S Bornstein, SR TI Neurotransmitters and neuropeptides in the differential regulation of steroidogenesis in adrenocortical-chromaffin co-cultures SO ENDOCRINE RESEARCH LA English DT Article; Proceedings Paper CT 9th Conference on the Adrenal Cortex CY JUN 17-20, 2000 CL UNIV TORONTO, ST MICHAELS COLL, TORONTO, CANADA SP Canadian Life Technologies Inc, Hoffman La Roche Ltd, Marcel Dekker Inc, Nikon, Qiagen Inc, Roche Diagnost, VWR Canlab HO UNIV TORONTO, ST MICHAELS COLL ID ADRENAL-GLAND; CELLS; GALANIN AB Adrenocortical steroidogenesis is regulated in addition to a central regulation via the hypothalamus-pituitary-adrenal axis by intra-adrenal mechanisms involving the adrenal medulla. We could previously show that adrenocortical steroidogenesis is stimulated by co-culturing bovine adrenocortical cells with medullary chromaffin cells. This stimulation was due to soluble factors released from the chromaffin cells under basal, unstimulated conditions and involved the increased expression of P450 enzymes, StAR and de novo protein synthesis. In the present study we analyzed the differential regulation of the three cortical zones and characterized secretagogues involved in this stimulation. While cortisol and androstenedione release were increased 10 fold by incubation with chromaffin cell-conditioned medium, aldosterone secretion was not influenced. 80% of the stimulation proved to be due to adrenomedullary epinephrine, norepinephrine, ACTH, PACAP and PG-dependent mechanisms. Other adrenomedullary secretory products, serotonin, Met-enkephalin, Leu-enkephalin, galanin, CORP, substance P, VIP or NPY did not stimulate steroidogenesis in this system. Our data show that adrenomedullary cells differentially regulate the three adrenocortical zones. This stimulation predominantly depended on epinephrine, norepinephrine, PACAP, and ACTH released from the chromaffin cells and prostaglandin-dependent mechanisms such as interleukin-1. C1 NICHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Leipzig, Dept Internal Med 2, D-7010 Leipzig, Germany. RP Ehrhart-Bornstein, M (reprint author), NICHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NR 11 TC 25 Z9 25 U1 1 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0743-5800 J9 ENDOCR RES JI Endocr. Res. PY 2000 VL 26 IS 4 BP 833 EP 842 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 386MC UT WOS:000166064600049 PM 11196460 ER PT J AU Inadera, H Sekiya, T Yoshimura, T Matsushima, K AF Inadera, H Sekiya, T Yoshimura, T Matsushima, K TI Molecular analysis of the inhibition of monocyte chemoattractant protein-1 gene expression by estrogens and xenoestrogens in MCF-7 cells SO ENDOCRINOLOGY LA English DT Article ID NF-KAPPA-B; MESSENGER-RNA EXPRESSION; TUMOR-NECROSIS-FACTOR; BREAST-CANCER-CELLS; IN-VIVO; BISPHENOL-A; RECEPTOR; INDUCTION; MCP-1; TRANSCRIPTION AB Xenoestrogens (XEs) are a diverse group of chemicals that mimic estrogenic actions and may have adverse effects on human health. The influence of these compounds on cytokine production or immune system function remains unclear. In this study we have examined the effects of 17 beta-estradiol (E-2) and XEs on chemoattractant cytokine (chemokine) production and analyzed the molecular mechanism. Monocyte chemoattractant protein-1 (MCP-1), also termed monocyte chemotactic and activating factor, is a member of the chemokine family and attracts mainly blood monocytes. Human mammary tumor cell Line MCF-7 cells produce a large quantity of MCP-1 in response to interleukin-1 alpha (IL-1 alpha). Addition of E-2 to MCF-7 cells inhibited MCP-1 production in a dose-dependent manner. XEs, bisphenol A, and NP also inhibited MCP-1 production, although the potency was 3-4 orders of magnitude lower than that of E-2. E-2, bisphenol A, and NP inhibited MCP-1 messenger RNA expression in MCF-7 cells. Two closely located nuclear factor-kappa B sites, Al and A2, have been identified in the promoter of the human MCP-1 gene. A luciferase construct containing this enhancer region (pGLM-ENH) was activated by IL-la, and a mutation at either the Al or A2 site resulted in a loss of IL-la responsiveness. Treatment with E-2 or XEs decreased the IL-la-inducible pGLM-ENH luciferase activity significantly. In an electrophoretic mobility shift assay and supershift analysis, we found that treatment with E-2 or XEs diminished the IL-1 alpha-induced complex formation with both Al and A2 probes, which was identified immunochemically to consist of nuclear factor-kappa B, p50, and p65. The IL-1 alpha-induced p50/c-Rel complex to the A2 probe was also, to a lesser extent, decreased by E-2 or XE treatment. The effects of E-2 and XEs on the expression of MCP-1 seem to be much more dramatic than the effects of these agents on the promoters used in the luciferase assay, suggesting the involvement of an additional site(s) of the promoter region of the MCP-1 gene or posttranscriptional regulation of MCP-1 gene expression by E-2 and XEs. This work represents the first report describing possible regulation of immune system function by XEs through inhibiting chemokine production. C1 Univ Tokyo, Sch Med, Dept Mol Prevent Med, Bunkyo Ku, Tokyo 1130033, Japan. NCI, Immunopathol Sect, Mol Immunoregulat Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Matsushima, K (reprint author), Univ Tokyo, Sch Med, Dept Mol Prevent Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan. EM koujim@m.u-tokyo.ac.jp NR 45 TC 53 Z9 55 U1 1 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2000 VL 141 IS 1 BP 50 EP 59 DI 10.1210/en.141.1.50 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 267AJ UT WOS:000084332200007 PM 10614622 ER PT J AU De Luca, F Uyeda, JA Mericq, V Mancilla, EE Yanovski, JA Barnes, KM Zile, MH Baron, J AF De Luca, F Uyeda, JA Mericq, V Mancilla, EE Yanovski, JA Barnes, KM Zile, MH Baron, J TI Retinoic acid is a potent regulator of growth plate chondrogenesis SO ENDOCRINOLOGY LA English DT Article ID LONGITUDINAL BONE-GROWTH; VITAMIN-A-DEFICIENCY; MONOCLONAL-ANTIBODY; HORMONE-SECRETION; CHONDROCYTES; EPIPHYSEAL; RECEPTORS; CELLS; PROLIFERATION; CLOSURE AB Vitamin A deficiency and excess both cause abnormalities in mammalian longitudinal bone growth. Because all-trans retinoic acid (RA) is synthesized from vitamin A, we hypothesized that RA regulates growth plate chondrogenesis. Consistent with this hypothesis, a single oral dose of RA reduced the height of the rat proximal tibial growth plate. To determine whether RA acts directly on growth plate, fetal rat metatarsal bones were cultured in the presence of RA. In this system, RA inhibited longitudinal bone growth by three mechanisms: 1) decreased chondrocyte proliferation, (assessed by H-3-thymidine incorporation), particularly in the proliferative zone of the growth plate; 2) decreased matrix synthesis (assessed by (SO4)-S-35 incorporation into glycosaminoglycans); and 3) decreased cell hypertrophy (determined histologically). The growth-inhibiting effects of RA were completely reversed by a retinoic acid receptor (RAR) antagonist. In the absence of exogenous RA, this antagonist accelerated bone growth, as did an RA-specific neutralizing antibody, suggesting that endogenous RA negatively regulates growth plate chondrogenesis. We conclude that RA, acting through RARs, negatively regulates longitudinal bone growth by inhibiting growth plate chondrocyte proliferation, chondrocyte hypertrophy, and matrix synthesis. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Michigan State Univ, Dept Food Sci & Human Nutr, E Lansing, MI 48824 USA. RP De Luca, F (reprint author), Univ Maryland, Sch Med, Dept Pediat, 22 S Greene St,Room N5E13, Baltimore, MD 21201 USA. EM fdeluca@peds.umaryland.edu RI Mericq, Veronica/F-3927-2010 NR 42 TC 46 Z9 48 U1 0 U2 3 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 JAN PY 2000 VL 141 IS 1 BP 346 EP 353 DI 10.1210/en.141.1.346 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 267AJ UT WOS:000084332200042 PM 10614657 ER PT J AU Martinez, A Kapas, S Miller, MJ Ward, Y Cuttitta, F AF Martinez, A Kapas, S Miller, MJ Ward, Y Cuttitta, F TI Coexpression of receptors for adrenomedullin, calcitonin gene-related peptide, and amylin in pancreatic beta-cells SO ENDOCRINOLOGY LA English DT Article ID ISLET AMYLOID POLYPEPTIDE; INSULIN-SECRETION; RAT ADRENOMEDULLIN; HYPOTENSIVE PEPTIDE; MOLECULAR-CLONING; EXPRESSION; INHIBITION; LOCALIZATION; PRECURSOR; BINDING AB Three receptors have been characterized by their ability to bind adrenomedullin (AM): L1, RDC1, and CRLR. Immunohistochemical analysis and RT-PCR showed that all three receptors are expressed by the insulin-producing cells of the islets of Langerhans. RDC1 and CRLR in the presence of particular modifying proteins can also bind calcitonin gene-related peptide (CGRP). Such data suggest that the inhibitory effect caused by both AM and CGRP on insulin secretion is mediated by a direct interaction with the beta-cell. We also identified receptors for amylin, the third member of the AM peptide family, in mouse insulin-secreting cells. The beta-cells located closer to the periphery of the islets had a stronger immunoreactivity for the AM/ CGRP receptors. This observation could be related to a paracrine mechanism, given the proximity of AM- and CGRP-secreting cells (F and delta-cells, respectively), which are located at the periphery of the islets. Interestingly, the smooth muscle cells in the pancreatic vasculature expressed only RDC1, which is in agreement with physiological data showing that AM functions in the cardiovascular system are mainly mediated through a CGRP1 receptor. These data further implicate AM and the other components of its peptide family as important regulators of insulin release. C1 NCI, NIH, Dept Cell & Canc Biol, Bethesda, MD 20892 USA. St Bartholomews & Royal London Sch Med & Dent, Mol Signaling Grp, Clin Sci Res Ctr, London E1 2AT, England. RP Martinez, A (reprint author), NCI, NIH, Dept Cell & Canc Biol, Bldg 10,Room 13N262,9000 Rockville Pike, Bethesda, MD 20892 USA. EM martineza@bprb.nci.nih.gov RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 32 TC 56 Z9 62 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2000 VL 141 IS 1 BP 406 EP 411 DI 10.1210/en.141.1.406 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 267AJ UT WOS:000084332200048 PM 10614663 ER PT J AU Kasik, J Muglia, L Stephan, DA Menon, RK AF Kasik, J Muglia, L Stephan, DA Menon, RK TI Identification, chromosomal mapping, and partial characterization of mouse Insl6: A new member of the insulin family SO ENDOCRINOLOGY LA English DT Article ID GROWTH-FACTORS; RELAXIN; GENE; SUPERFAMILY; CLONING AB A new member of the mouse insulin family, Insl6, was identified from mouse expressed sequence tags through the use of bioinformatics. A full length cDNA was sequenced and predicts a protein of 191 amino acids. The protein contains a signal peptide and has A and B peptides as well as a connecting peptide consistent with the contention that it is a member of the insulin family. Northern analysis demonstrates that the primary site of expression is the testis, but message is also found in the kidney, small bowel, heart, brain and thymus. The gene was mapped to mouse chromosome 19 by radiation hybrid mapping. The chromosomal location and primary structure of this protein suggest a functional relationship to relaxin and relaxin-related proteins. C1 Univ Pittsburgh, Sch Med, Dept Pediat, Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. NIH, NHGRI, Bethesda, MD 20892 USA. RP Menon, RK (reprint author), Univ Pittsburgh, Sch Med, Dept Pediat, Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. EM menonr@chplink.chp.edu NR 15 TC 27 Z9 28 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 JAN PY 2000 VL 141 IS 1 BP 458 EP 461 DI 10.1210/en.141.1.458 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 267AJ UT WOS:000084332200056 PM 10614671 ER PT J AU de Boer, JG Holcroft, J Cunningham, ML Glickman, BW AF de Boer, JG Holcroft, J Cunningham, ML Glickman, BW TI Tris(2,3-dibromopropyl)phosphate causes a gradient of mutations in the cortex and outer and inner medullas of the kidney of lacl transgenic rats SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE mutation; kidney; Big Blue ratsmts; tris(2,3-dibromopropyl)phosphate; tissue specificity ID FLAME-RETARDANT; REACTIVE METABOLITE; COVALENT BINDING; DNA DAMAGE; MUTAGENICITY; PHOSPHATE; LIVER; MICE; 1,2-DIBROMO-3-CHLOROPROPANE; 2-BROMOACROLEIN AB Tris(2,3-dibromopropyl) phosphate (TDBP) is a kidney carcinogen in rats in which exposure results in tumors specifically in the outer medulla. We have previously shown that TDBP induces mutation in the rat kidney. Here we demonstrate that TDBP induces mutation in the kidney of the F344 Big Blue lacl transgenic rat in a gradient with the highest induction (6.4-fold) in the cortex and lowest induction (2.2-fold) in the inner medulla, when given at 2000 ppm in the feed for 45 days. Similar results were obtained at 100 ppm, although the gradient effect was less pronounced. Because exposure to TDBP results in increased cell proliferation in the outer medulla, our results suggest that tissue-specific targeting of TDBP-induced kidney tumors reflects the combination of cell proliferation and mutation induction. This is also the First known case when transgenic animals have been used to study mutation at the suborgan revel. (C) 2000 Wiley-Liss, Inc. C1 Univ Victoria, Ctr Environm Hlth, Victoria, BC V8W 3N5, Canada. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP de Boer, JG (reprint author), Univ Victoria, Ctr Environm Hlth, POB 3020, Victoria, BC V8W 3N5, Canada. NR 29 TC 2 Z9 2 U1 2 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2000 VL 36 IS 1 BP 1 EP 4 DI 10.1002/1098-2280(2000)36:1<1::AID-EM1>3.0.CO;2-B PG 4 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 339LG UT WOS:000088478100001 PM 10918353 ER PT J AU Witt, KL Knapton, A Wehr, CM Hook, GJ Mirsalis, J Shelby, MD MacGregor, JT AF Witt, KL Knapton, A Wehr, CM Hook, GJ Mirsalis, J Shelby, MD MacGregor, JT TI Micronucleated erythrocyte frequency in peripheral blood of B6C3F(1) mice from short-term, prechronic, and chronic studies of the NTP carcinogenesis bioassay program SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE micronucleus assay; normochromatic erythrocytes; polychromatic erythrocytes; genetic damage; B6C3F(1) mice; chemical exposures ID FISCHER 344 RATS; INDUCTION; TOXICITY; 1,3-BUTADIENE; PERSISTENCE; INHALATION; EXPOSURES; PROTOCOL; BENZENE; DAMAGE AB The mouse peripheral blood micronucleus (MN) test was performed on samples collected from 20 short-term, 67 subchronic, and 5 chronic toxicity and carcinogenicity studies conducted by the National Toxicology Program (NTP). Data are presented for studies not previously published. Aspects of protocol that distinguish this test from conventional short-term bone marrow MN tests are duration of exposure, and absence of repeat tests and concurrent positive controls. Furthermore, in contrast to short-term bone marrow MN tests where scoring is limited to polychromatic erythrocytes (PCE), longer term studies using peripheral blood may evaluate MN in both, or either, the normochromatic (NCE) or PCE populations. The incidence of MN-PCE provides on index of damage induced within 72 hr of sampling, whereas the incidence of MN in the NCE population at steady state provides an index of average damage during the 30-day period preceding sampling. The mouse peripheral blood MN test has been proposed as a useful adjunct to rodent toxicity tests and has been effectively incorporated as a routine part of overall toxicity testing by the NTP. Data derived From peripheral blood MN analyses of dosed animals provide a useful indication of the in vivo potential for induced genetic damage and supply an important piece of evidence to be considered in the overall assessment of toxicity and health risk of a particular chemical. Although results indicate that the test has low sensitivity for prediction of carcinogenicity, a convincingly positive result in this assay appears to be highly predictive of rodent carcinogenicity. (C) 2000 Wiley-Liss, Inc. C1 ILS Inc, Res Triangle Pk, NC 27709 USA. US FDA, Laurel, MD USA. USDA, Western Reg Res Ctr, Albany, CA 94710 USA. NIEHS, Res Triangle Pk, NC 27709 USA. SRI Int, Menlo Park, CA 94025 USA. RP Witt, KL (reprint author), ILS Inc, POB 13501, Res Triangle Pk, NC 27709 USA. NR 45 TC 54 Z9 56 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2000 VL 36 IS 3 BP 163 EP 194 DI 10.1002/1098-2280(2000)36:3<163::AID-EM1>3.0.CO;2-P PG 32 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 369HJ UT WOS:000165059600001 PM 11044899 ER PT J AU Zeiger, E AF Zeiger, E TI Commentary - An interesting state of affairs in genetic toxicology SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Editorial Material ID CHEMICALS; CARCINOGENICITY; GUIDELINES; ASSAYS; TESTS C1 NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Zeiger, E (reprint author), OECD, Environm Hlth & Safety Div, 2 Rue Andre Pascal, F-75775 Paris 16, France. NR 30 TC 9 Z9 9 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2000 VL 35 IS 2 BP 82 EP 85 DI 10.1002/(SICI)1098-2280(2000)35:2<82::AID-EM2>3.0.CO;2-I PG 4 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 297RY UT WOS:000086097500002 PM 10712741 ER PT J AU Gocke, E Muller, L Guzzie, PJ Brendler-Schwaab, S Bulera, S Chignell, CF Henderson, LM Jacobs, A Murli, H Snyder, RD Tanaka, N AF Gocke, E Muller, L Guzzie, PJ Brendler-Schwaab, S Bulera, S Chignell, CF Henderson, LM Jacobs, A Murli, H Snyder, RD Tanaka, N TI Considerations on photochemical genotoxicity: Report of the International Workshop on Genotoxicity Test Procedures Working Group SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Editorial Material DE photochemical genotoxicity; UV radiation; V79 cells; dose-response curve ID PHOTOMUTAGENESIS TEST DEVELOPMENT; DNA-DAMAGE; CHROMOSOMAL ABERRATION; SUNSCREEN COMPOUNDS; GENE CONVERSION; VISIBLE-LIGHT; CHO CELLS; ASSAY; 8-METHOXYPSORALEN; CHLORPROMAZINE AB Recent toxicological observations have caused concern regarding the need to test, For example, pharmaceuticals and cosmetic products For photochemical genotoxicity. The objective of this report is to give assistance on how to adapt existing test methods to investigate the potential of light-absorbing compounds to induce genotoxic effects on photoactivation. In general, the Organization For Economic Co-Operation & Economic Development (OECD) draft guideline on in vitro phototoxicity testing served as a basis for consideration. Concomitant exposure of the cells to the test compound and solar simulated light was considered appropriate as the initial, basic test condition. Optimization of the exposure scheme, e.g., a change of the irradiation spectrum, might be indicated depending on the initial test results. Selection of test compound concentrations should be based on results obtained with the dark version of the respective test system but might have to be modified if phototoxic effects are observed. Selection of the irradiation dose has to be performed individually For each test system based on dose-effect studies. The irradiation should induce per se a small, reproducible toxic or genotoxic effect. The report includes a specification of necessary controls, discusses Factors that might have an impact on the irradiation characteristics, and gives a rationale for the omission of an external metabolic activation system. It also addresses the question that physicochemical and pharmacokinetic properties might trigger the need to test cc chemical For photochemical genotoxicity. Relevant experimental observations are presented to back up the recommendations. The working group did not reach a consensus as to whether a single, adequately perfomed in vitro test for clastogenicity would be sufficient to exclude a photogenotoxic liability or whether a test battery including a gene mutation assay would be needed for product safety testing regarding photochemical genotoxicity. (C) 2000 Wiley-Liss, Inc. C1 F Hoffmann La Roche & Co Ltd, PRNS, CH-4070 Basel, Switzerland. BfaRM, Berlin, Germany. Pfizer Inc, Groton, CT 06340 USA. Bayer AG, D-5600 Wuppertal, Germany. Parke Davis Pharmaceut Res, Ann Arbor, MI USA. NIEHS, LPC, Res Triangle Pk, NC 27709 USA. US FDA, Rockville, MD 20857 USA. Covance Labs Inc, Vienna, Austria. Dupont Merck Pharmaceut Co, Newark, DE USA. Hatano Res Inst, Kanagawa, Japan. RP Gocke, E (reprint author), F Hoffmann La Roche & Co Ltd, PRNS, Bldg 73-215, CH-4070 Basel, Switzerland. NR 27 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2000 VL 35 IS 3 BP 173 EP 184 DI 10.1002/(SICI)1098-2280(2000)35:3<173::AID-EM4>3.0.CO;2-E PG 12 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 300ZF UT WOS:000086283100004 PM 10737952 ER PT J AU Phillips, DH Farmer, PB Beland, FA Nath, RG Poirier, MC Reddy, MV Turteltaub, KW AF Phillips, DH Farmer, PB Beland, FA Nath, RG Poirier, MC Reddy, MV Turteltaub, KW TI Methods of DNA adduct determination and their application to testing compounds for genotoxicity SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article; Proceedings Paper CT International Workshop on Genotoxicity Test Procedures CY MAR 25-26, 1999 CL WASHINGTON, D.C. DE DNA adducts; genotoxicity; radioactivity; (32)P-postlabeling; immunoassay; mass spectrometry; endogenous DNA damage ID CHROMATOGRAPHY MASS-SPECTROMETRY; LIQUID-CHROMATOGRAPHY; RISK ASSESSMENT; IN-VITRO; 1,N-2-PROPANODEOXYGUANOSINE ADDUCTS; P-32-POSTLABELING ASSAY; QUANTITATIVE-ANALYSIS; ALKALINE-HYDROLYSIS; CARCINOGEN EXPOSURE; LIPID-PEROXIDATION AB At the International Workshop on Genotoxicity Test Procedures (IWGTP) held in Washington, DC (March 25-26, 1999), a working group considered the uses of DNA adduct determination methods For testing compounds for genotoxicity. When a drug or chemical displays an unusual or inconsistent combination of positive and negative results in in vitro and in vivo genotoxicity assays and/or in carcinogenicity experiments, investigations into whether or not DNA adducts are formed may be helpful in assessing whether or not the test compound is a genotoxin. DNA adduct determinations can be carried out using radiolabeled compounds and measuring radioactive decay (scintillation counting) or isotope ratios (accelerator mass spectrometry) in the isolated DNA. With unlabeled compounds adducts may be measured by (32)p-post-labeling analysis of the DNA, or by physicochemical methods including moss spectrometry, fluorescence spectroscopy, or electrochemical detection, or by immunochemical methods. Each of these approaches has different strengths and limitations, influenced by sensitivity, cost, time, and interpretation of results. The design of DNA binding studies needs to be on a case-by-case basis, depending on the compound's profile of activity. DNA purity becomes increasingly important the more sensitive, and less chemically specific, the assay. While there may be adduct levels at which there is no observable biological effect, there are at present insufficient data on which to set a threshold level For biological significance. (C) 2000 Wiley-Liss, Inc. C1 Inst Canc Res, Haddow Labs, Sutton SM2 5NG, Surrey, England. Univ Leicester, MRC, Toxicol Unit, Leicester, Leics, England. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NCI, Bethesda, MD 20892 USA. Covance Labs Inc, Genet & Cellular Toxicol, Vienna, VA USA. Merck Res Labs, West Point, PA USA. Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, Livermore, CA USA. RP Phillips, DH (reprint author), Inst Canc Res, Haddow Labs, Cotswold Rd, Sutton SM2 5NG, Surrey, England. EM davidp@icr.ac.uk NR 98 TC 91 Z9 98 U1 0 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2000 VL 35 IS 3 BP 222 EP 233 DI 10.1002/(SICI)1098-2280(2000)35:3<222::AID-EM9>3.0.CO;2-E PG 12 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 300ZF UT WOS:000086283100009 PM 10737957 ER PT J AU Heddle, JA Dean, S Nohmi, T Boerrigter, M Casciano, D Douglas, GR Glickman, BW Gorelick, NJ Mirsalis, JC Martus, HJ Skopek, TR Thybaud, V Tindall, KR Yajima, N AF Heddle, JA Dean, S Nohmi, T Boerrigter, M Casciano, D Douglas, GR Glickman, BW Gorelick, NJ Mirsalis, JC Martus, HJ Skopek, TR Thybaud, V Tindall, KR Yajima, N TI In vivo transgenic mutation assays SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article; Proceedings Paper CT International Workshop on Genotoxicity Test Procedures CY MAR 25-26, 1999 CL WASHINGTON, D.C. DE transgenic mutation assays; Muta (TM) Mouse; BigBlue (R) mouse/rat; lacl; lacZ ID ENDOGENOUS HPRT GENE; BLUE(TM) B6C3F1 MICE; IN-VIVO; MOUSE MODEL; STATISTICAL-ANALYSIS; SOMATIC MUTATIONS; LACI TRANSGENE; MUTAGENICITY; LYMPHOCYTES; ACCUMULATION AB Transgenic rodent gene mutation models provide quick and statistically reliable assays for mutations in the DNA From any tissue. For regulatory applications, assays should be based on neutral genes, be generally available in several laboratories, and be readily transferable. Five or Fewer repeated treatments are inadequate to conclude that a compound is negative but more than 90 daily treatments may risk complications. A sampling time of 35 days is suitable for most tissues and chemicals, while shorter sampling times might be appropriate for highly proliferative tissues. For phage-based assays, 5 to 10 animals per group should be analyzed, assuming a spontaneous mutant frequency (MF) of similar to 3 x 10(-5) mutants/locus and 125,000-300,000 plaque or colony forming units (PFU or CFU) per tissue. Data should be generated For two dose groups but three should be treated, at the maximum tolerated dose (MTD), two-thirds the MTD, and one-third the MTD. Concurrent positive control animals are only necessary during validation, but positive control DNA must be included in each plating. Tissues should be processed and analyzed in a block design and the total number of PFUs or CFUs and the MF for each tissue and animal reported. Sequencing data would not normally be required but might provide useful additional information in specific circumstances. Statistical tests used should consider the animal as the experimental unit. Nonparametric statistical tests are recommended. A positive result is a statistically significant dose-response and/or statistically significant increase in any dose group compared to concurrent negative controls using an appropriate statistical model. A negative result is statistically nonsignificant with all mean MF within two standard deviations of the control. (C) 2000 Wiley-Liss, Inc. C1 York Univ, Dept Biol, Toronto, ON M3J 1P3, Canada. Res Toxicol Ctr, Rome, Italy. Natl Inst Hlth Sci, Div Genet & Mutagenesis, Tokyo 158, Japan. Leven Inc, Bogart, GA 30622 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Hlth Canada, Ctr Environm Hlth, Mutagenesis Sect, Ottawa, ON K1A 0L2, Canada. Univ Victoria, Ctr Environm Hlth, Victoria, BC, Canada. Procter & Gamble Co, Ivorydale Tech Ctr, Cincinnati, OH 45217 USA. SRI Int, Toxicol Lab, Menlo Park, CA 94025 USA. Novartis Pharma AG, PCS Tox Path, Genet & Expt Toxicol, Basel, Switzerland. Merck Res Labs, W Point, PA USA. Rhone Poulenc Rorer, Nonclin Safety Assessment, Vitry Sur Seine, France. NIEHS, Mol Mutagenesis Grp, Lab Environm Carcinogenesis & Mutagenesis, Res Triangle Pk, NC 27709 USA. Snow Brand Milk Prod Co Ltd, Res Inst Life Sci, Ishibashi, Tochigi, Japan. RP Heddle, JA (reprint author), York Univ, Dept Biol, Room 247,Farquaharson Life Sci Bldg,4700 Keele St, Toronto, ON M3J 1P3, Canada. NR 48 TC 72 Z9 73 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2000 VL 35 IS 3 BP 253 EP 259 DI 10.1002/(SICI)1098-2280(2000)35:3<253::AID-EM11>3.0.CO;2-J PG 7 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 300ZF UT WOS:000086283100011 PM 10737959 ER PT B AU Ward, MH Nuckols, JR Weigel, SJ Miller, RS Maxwell, SK AF Ward, MH Nuckols, JR Weigel, SJ Miller, RS Maxwell, SK BE Raynal, JA Nuckols, JR Reyes, R Ward, M TI Estimating environmental exposure to agricultural pesticides using remote sensing and a geographic information system SO ENVIRONMENTAL ENGINEERING AND HEALTH SCIENCES LA English DT Proceedings Paper CT International Symposium on Environmental Engineering and Health Sciences: A Joint Effort for the XXIst Century CY OCT 26-30, 1998 CL CHOLULA, MEXICO SP US DHHS, Agcy Tox Subst Dis Registry, NCI, Occupat Epidemiol Brach, NIEHS, Superfund Bas Res Program, Pan Amer Hlth Org, Univ Amer Puebla, World Meteorol Org ID CANCER; CHILDREN; RISK AB Satellite imagery data has been used to map land cover in various applications. We used historical Farm Service Agency records as a source of ground truth data to classify a late summer 1984 satellite image into crop species in a three county area in south central Nebraska, USA. Probabilities were calculated for pesticide use by crop from pesticide use databases. The area of primary drift affected by pesticide applications using a ground boom sprayer was estimated using a computer model and was mapped in a geographic information system (GIS). Residences from a population-based case-control study of non-Hodgkin's lymphoma (NHL) were overlaid on the map and classified as to whether they were located within a township boundary (community) or not (rural). Corn, soybeans, sorghum, and alfalfa were the major crops grown in the study area. Eighty-five percent of residences could be located and of these, 22 percent had at least one of the four major crops within 500 meters of the residence. Five hundred meters is a conservative distance for drift effects from pesticides applied in agriculture. The estimates of potential pesticide exposure based on proximity of crop fields to the residence were compared to the estimates that included areas affected by primary drift. We found that only considering the proximity to crop fields underestimates the amount of potential pesticide exposure for most individuals. Further, our results demonstrate that this method for exposure assessment is feasible, and that indirect exposure to residences in agricultural production regions is likely to occur. This study demonstrates that engineering technology can be used to develop new methods of exposure assessment for environmental epidemiology studies. This method may prove to be a useful addition to questionnaire and other methods of pesticide exposure assessment in health studies. C1 NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Ward, MH (reprint author), NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NR 30 TC 0 Z9 0 U1 1 U2 6 PU WATER RESOURCES PUBLICATIONS PI LITTLETON PA P O BOX 2841, LITTLETON, CO 80161 USA BN 1-887201-17-3 PY 2000 BP 125 EP 144 PG 20 WC Engineering, Environmental; Public, Environmental & Occupational Health SC Engineering; Public, Environmental & Occupational Health GA BR19D UT WOS:000165838100011 ER PT J AU Cocco, P Kazerouni, N Zahm, SH AF Cocco, P Kazerouni, N Zahm, SH TI Cancer mortality and environmental exposure to DDE in the United States SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE breast cancer; cancer of the corpus uteri; DDE; DDT; environment; epidemiology; liver cancer; multiple myeloma; non-Hodgkin lymphoma; pancreatic cancer ID NON-HODGKINS-LYMPHOMA; BREAST-CANCER; ORGANOCHLORINE COMPOUNDS; RISK; RESIDUES; TISSUE AB To explore the role of DDE, the major and most persistent DDT derivative, in cancer etiology, we examined the association of the 1968 adipose DDE levels of population samples from 22 U.S. states with age-adjusted mortality rates between 1975 and 1994 for multiple myeloma; non-Hodgkin lymphoma (NHL); and cancer of the breast, corpus uteri, liver, and pancreas. Separate analyses were conducted by gender and race. Covariates in the regression models included average per-capita income, percent metropolitan residents, and the population density. Liver cancer mortality increased significantly with adipose DDE levels in both sexes among whites, but not among African Americans. No association was observed for pancreatic cancer and multiple myeloma. Breast cancer mortality was inversely correlated with adipose DDE levels among both white and African American women. Significant inverse correlations were also observed for uterine cancer among white women, whereas no association was observed for African Americans and for NHL among whites (men and women) and African American women. The results for pancreatic cancer, multiple myeloma, NHL, breast cancer, and uterine cancer did not support the hypothesis of an association with past adipose levels of the DDT derivative DDE. The multivariate analysis confirmed most findings. The association between liver cancer and DDE observed among whites, particularly in view of the occurrence of hepatic neoplasms in laboratory animals exposed to DDT, warrants further investigation. C1 Univ Cagliari, Inst Occupat Med, I-09124 Cagliari, Italy. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD USA. RP Cocco, P (reprint author), Univ Cagliari, Inst Occupat Med, Via San Giorgio 12, I-09124 Cagliari, Italy. RI Zahm, Shelia/B-5025-2015 NR 25 TC 59 Z9 61 U1 1 U2 7 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 JAN PY 2000 VL 108 IS 1 BP 1 EP 4 DI 10.2307/3454288 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 273XP UT WOS:000084734900018 PM 10620518 ER PT J AU Ward, MH Nuckols, JR Weigel, SJ Maxwell, SK Cantor, KP Miller, RS AF Ward, MH Nuckols, JR Weigel, SJ Maxwell, SK Cantor, KP Miller, RS TI Identifying populations potentially exposed to agricultural pesticides using remote sensing and a geographic information system SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE agriculture; epidemiology; exposure assessment; geographic information systems; pesticides; remote sensing ID RISK-FACTORS; CANCER; DEPOSITION; FAMILIES; CHILDREN; WORKERS AB pesticides used in agriculture may cause adverse health effects among the population living near agricultural areas. However, identifying the populations most likely to be exposed is difficult. We conducted a feasibility study to determine whether satellite imagery could be used to reconstruct historical crop patterns. We used historical Farm Service Agency records as a source of ground reference data to classify a late summer 1984 satellite image into crop species in a three-county area in south central Nebraska. Residences from a population-based epidemiologic study of non-Hodgkin lymphoma were located on the crop maps using a geographic information system (GIS). Corn, soybeans, sorghum, and alfalfa were the major crops grown in the study area. Eighty-five percent of residences could be located, and of these 22% had one of the four major crops within 500 m of the residence, an intermediate distance for the range of drift effects from pesticides applied in agriculture. We determined the proximity of residences to specific crop species and calculated crop-specific probabilities of pesticide use based on available data. This feasibility study demonstrated that remote sensing data and historical records on crop location can be used to create historical crop maps. The crop pesticides that were likely to have been applied can be estimated when information about crop-specific pesticide use is available. Using a GIS, zones of potential exposure to agricultural pesticides and proximity measures can be determined for residences in a study. C1 Colorado State Univ, Environm Hlth Adv Syst Lab, Dept Environm Hlth, Ft Collins, CO 80523 USA. NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Raytheon Co, EROS Data Ctr, Sioux Falls, SD USA. RP Nuckols, JR (reprint author), Colorado State Univ, Environm Hlth Adv Syst Lab, Dept Environm Hlth, 147 Environm Hlth Bldg, Ft Collins, CO 80523 USA. RI Miller, Ryan/G-6356-2010; OI Miller, Ryan/0000-0003-3892-0251 FU NCI NIH HHS [N02-CP-71100] NR 40 TC 73 Z9 77 U1 2 U2 19 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 JAN PY 2000 VL 108 IS 1 BP 5 EP 12 DI 10.2307/3454289 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 273XP UT WOS:000084734900019 PM 10622770 ER PT J AU Burkhart, JG Ankley, G Bell, H Carpenter, H Fort, D Gardiner, D Gardner, H Hale, R Helgen, JC Jepson, P Johnson, D Lannoo, M Lee, D Lary, J Levey, R Magner, J Meteyer, C Shelby, MD Lucier, G AF Burkhart, JG Ankley, G Bell, H Carpenter, H Fort, D Gardiner, D Gardner, H Hale, R Helgen, JC Jepson, P Johnson, D Lannoo, M Lee, D Lary, J Levey, R Magner, J Meteyer, C Shelby, MD Lucier, G TI Strategies for assessing the implications of malformed frogs for environmental health SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE amphibian malformation; environmental health ID ULTRAVIOLET-RADIATION; RETINOIC ACID; HOMEOTIC TRANSFORMATION; AMPHIBIAN POPULATIONS; THYROID-HORMONE; HYLA-REGILLA; LIMBS; RECEPTORS; SURVIVAL; TOXICITY AB The recent increase in the incidence of deformities among natural frog populations has raised concern about the state of the environment and the possible impact of unidentified causative agents on the health of wildlife and human populations. An open workshop on Strategies for Assessing the Implications of Malformed Frogs for Environmental Health was convened on 4-5 December 1997 at the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina. The purpose of the workshop was to share information among a multidisciplinary group with scientific interest and responsibility for human and environmental health at the federal and state level. Discussions highlighted possible causes and recent findings directly related to frog deformities and provided insight into problems and strategies applicable to continuing investigation in several areas. Possible causes of the deformities were evaluated in terms of diagnostics performed on field amphibians, biologic mechanisms that can lead to the types of malformations observed, and parallel laboratory and field studies. Hydrogeochemistry must be more integrated into environmental toxicology because of the pivotal role of the aquatic environment and the importance of faces and transport relative to any potential exposure. There is no indication of whether there may be a human health factor associated with the deformities. However, the possibility that causal agents may be waterborne indicates a need to identify the relevant factors and establish the relationship between environmental and human health in terms of hazard assessment. C1 NIEHS, Res Triangle Pk, NC 27709 USA. US EPA, Mid Continent Ecol Div, Duluth, MN 55804 USA. US EPA, Off Sci & Technol, Off Water, Washington, DC 20460 USA. Minnesota Dept Hlth, St Paul, MN USA. Stover Grp, Stillwater, OK USA. Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92717 USA. Colorado State Univ, USA, Ctr Environm Hlth Res, Ctr Environm Toxicol & Technol, Ft Collins, CO 80523 USA. Coll William & Mary, Virginia Inst Marine Sci, Gloucester Point, VA 23062 USA. Minnesota Pollut Control Agcy, St Paul, MN USA. Oregon State Univ, Corvallis, OR 97331 USA. No Prairie Ctr, Jamestown, ND USA. Ball State Univ, Muncie Ctr Med Educ, Muncie, IN 47306 USA. AECL, Chalk River, ON, Canada. US Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. Vermont Dept Environm Conservat, Ra LaRosa Environm Lab, Waterbury, VT USA. US Fish & Wildlife Serv, Natl Wildlife Hlth Res Ctr, Madison, WI 53711 USA. RP Burkhart, JG (reprint author), NIEHS, MD C1-08,Box 12233, Res Triangle Pk, NC 27709 USA. RI Jepson, Paul/E-8669-2011 OI Jepson, Paul/0000-0003-3419-4715 NR 32 TC 53 Z9 62 U1 1 U2 6 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 JAN PY 2000 VL 108 IS 1 BP 83 EP 90 DI 10.2307/3454299 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 273XP UT WOS:000084734900029 PM 10620528 ER PT J AU Linet, MS AF Linet, MS TI Evolution of cancer epidemiology SO EPIDEMIOLOGIC REVIEWS LA English DT Review ID NON-HODGKINS-LYMPHOMA; ATOMIC-BOMB SURVIVORS; BREAST-CANCER; LUNG-CANCER; CHILDHOOD LEUKEMIA; HEPATOCELLULAR-CARCINOMA; PROSTATE-CANCER; UNITED-STATES; SUN EXPOSURE; IN-UTERO C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Linet, MS (reprint author), NCI, Div Canc Epidemiol & Genet, MSC 7238,Execut Plaza S,Room 7054,6120 Execut Blv, Bethesda, MD 20892 USA. NR 191 TC 12 Z9 13 U1 4 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0193-936X J9 EPIDEMIOL REV JI Epidemiol. Rev. PY 2000 VL 22 IS 1 BP 35 EP 56 PG 22 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 340WZ UT WOS:000088560400008 PM 10939006 ER PT J AU Brown, LM AF Brown, LM TI Helicobacter pylori: Epidemiology and routes of transmission SO EPIDEMIOLOGIC REVIEWS LA English DT Review ID TO-PERSON TRANSMISSION; UPPER GASTROINTESTINAL ENDOSCOPY; GASTROESOPHAGEAL REFLUX DISEASE; PRECANCEROUS GASTRIC-LESIONS; UNIDENTIFIED CURVED BACILLI; HOUSEFLIES MUSCA-DOMESTICA; CORONARY HEART-DISEASE; PEPTIC-ULCER DISEASE; HEPATITIS-A VIRUS; ORAL-ORAL ROUTE C1 NCI, Biostat Branch, Div Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Brown, LM (reprint author), NCI, Biostat Branch, Div Epidemiol & Genet, NIH, Execut Plaza S,Room 8026,MSC 7244, Bethesda, MD 20892 USA. NR 203 TC 406 Z9 439 U1 2 U2 59 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0193-936X J9 EPIDEMIOL REV JI Epidemiol. Rev. PY 2000 VL 22 IS 2 BP 283 EP 297 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 395GT UT WOS:000166573100009 PM 11218379 ER PT J AU Longnecker, MP Michalek, JE AF Longnecker, MP Michalek, JE TI Serum dioxin level in relation to diabetes mellitus among Air Force Veterans with background levels of exposure SO EPIDEMIOLOGY LA English DT Article DE dioxin; diabetes mellitus; glucose metabolism; environmental exposures; insulin levels; body mass; gender; occupations ID GLUCOSE TRANSPORTING ACTIVITY; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TCDD; WORKERS; RATS; TOXICITY; VIETNAM; TISSUE; WEIGHT AB Data from several epidemiologic studies suggest that exposure to unusually high amounts of dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin) increases the risk of diabetes mellitus, and experimental data suggest that the mechanism for this is decreased cellular glucose uptake. To investigate the dose-response relation more closely, we examined the association of serum dioxin level with prevalence of diabetes mellitus and with levels of serum insulin and glucose among 1,197 veterans in the Air Force Health Study who never had contact with dioxin-contaminated herbicides and whose serum dioxin level was within the range of background exposure typically seen in the United States (less than or equal to 10 ng/kg lipid). Compared with those whose serum dioxin level was in the first quartile (<2.8 ng/kg lipid), the multivariate adjusted odds of diabetes among those in the highest quartile (greater than or equal to 5.2 ng/kg lipid) was 1.71 (95% confidence interval = 1.00-2.91). The association was slightly attenuated after adjustment for serum triglycerides. Whether adjustment for serum triglycerides was appropriate, however, cannot be determined with available data. The association of background-level dioxin exposure with the prevalence of diabetes in these data may well be due to reasons other than causality, although a causal contribution cannot be wholly dismissed. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. USAF, Res Lab, Brooks AFB, TX USA. RP Longnecker, MP (reprint author), NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. OI Longnecker, Matthew/0000-0001-6073-5322 NR 35 TC 94 Z9 95 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JAN PY 2000 VL 11 IS 1 BP 44 EP 48 DI 10.1097/00001648-200001000-00010 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 266TH UT WOS:000084316000010 PM 10615842 ER PT J AU Clay, JR AF Clay, JR TI Determining K+ channel activation curves from K+ channel currents SO EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS LA English DT Article DE potassium channels; current-voltage relations; Xenopus oocytes; HEK-293 cells ID SQUID GIANT-AXON; POTASSIUM CHANNELS; GATING CURRENTS; SODIUM-CHANNELS; SINGLE-CHANNEL; HEART-CELLS; VOLTAGE; BLOCK AB Potassium ion channels are generally believed to have current-voltage (IV) relations which are linearly related to driving force (V - E-K), where V is membrane potential and E-K is the potassium ion equilibrium potential. Consequently, activation curves for K+ channels have often been measured by normalizing voltage-clamp families of macroscopic K+ currents with (V - E-K), where V is the potential of each successive step in the voltage clamp sequence. However, the IV relation for many types of K+ channels actually has a non-linear dependence upon driving force which is well described by the Goldman-Hodgkin-Katz relation. When the GHK dependence on (V - E-K) is used in the normalization procedure, a very different voltage dependence of the activation curve is obtained which may more accurately reflect this feature of channel gating. Novel insights into the voltage dependence of the rapidly inactivating I-A channels Kv1.4 and Kv4.2 have been obtained when this procedure was applied to recently published results. C1 NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Clay, JR (reprint author), NINDS, Neurophysiol Lab, NIH, Bldg 36,Rm 2C02, Bethesda, MD 20892 USA. NR 18 TC 19 Z9 19 U1 1 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0175-7571 J9 EUR BIOPHYS J BIOPHY JI Eur. Biophys. J. Biophys. Lett. PY 2000 VL 29 IS 7 BP 555 EP 557 DI 10.1007/s002490000091 PG 3 WC Biophysics SC Biophysics GA 387YT UT WOS:000166151200013 PM 11156298 ER PT J AU Fisher, B AF Fisher, B TI Tamoxifen for the prevention of breast cancer - Pro SO EUROPEAN JOURNAL OF CANCER LA English DT Editorial Material ID SURGICAL-ADJUVANT-BREAST; RECEPTOR-POSITIVE TUMORS; TRIAL; CHEMOTHERAPY C1 Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15212 USA. RP Fisher, B (reprint author), Natl Surg Adjuvant Breast & Bowel Project, E Commons Profess Bldg,4 Allegheny Ct,Suite 602, Pittsburgh, PA 15212 USA. FU NCI NIH HHS [U10-CA-69974, U10-CA-37377] NR 17 TC 25 Z9 26 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JAN PY 2000 VL 36 IS 2 BP 142 EP 145 DI 10.1016/S0959-8049(99)00269-5 PG 4 WC Oncology SC Oncology GA 288ED UT WOS:000085548400010 PM 10741272 ER PT J AU Trimble, EL AF Trimble, EL TI Saving the lymph nodes SO EUROPEAN JOURNAL OF GYNAECOLOGICAL ONCOLOGY LA English DT Article ID ENDOMETRIAL CANCER; VULVAR CANCER; LYMPHADENECTOMY; CARCINOMA; PATTERNS; WOMEN C1 NCI, Bethesda, MD 20892 USA. RP Trimble, EL (reprint author), NCI, 6130 Excut Blvd Suite 741,MSC 7436, Bethesda, MD 20892 USA. NR 16 TC 1 Z9 1 U1 0 U2 0 PU S O G CANADA INC PI MONTREAL PA 1 PLACE VILLE MARIE, MONTREAL, QB 3900, CANADA SN 0392-2936 J9 EUR J GYNAECOL ONCOL JI Eur. J. Gynaecol. Oncol. PY 2000 VL 21 IS 1 BP 13 EP 16 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 282RQ UT WOS:000085232600002 PM 10726611 ER PT J AU Tewari, KS Disaia, PJ AF Tewari, KS Disaia, PJ TI On the evolution of a successful treatment program for a solid tumor system SO EUROPEAN JOURNAL OF GYNAECOLOGICAL ONCOLOGY LA English DT Review ID GERM-CELL TUMORS; ENDODERMAL SINUS TUMOR; GYNECOLOGIC-ONCOLOGY-GROUP; BLEOMYCIN COMBINATION CHEMOTHERAPY; PATHOLOGIC ANALYSIS; IMMATURE TERATOMA; TESTICULAR CANCER; OVARIAN-CANCER; CISPLATIN; VINBLASTINE C1 Univ Calif Irvine, Med Ctr, Chao Family NCI Designated Comprehens Canc Ctr, Div Gynecol Oncol, Orange, CA 92868 USA. RP Disaia, PJ (reprint author), Univ Calif Irvine, Med Ctr, Chao Family NCI Designated Comprehens Canc Ctr, Div Gynecol Oncol, 101 City Dr, Orange, CA 92868 USA. NR 104 TC 1 Z9 1 U1 0 U2 1 PU I R O G CANADA, INC PI MONTREAL PA 4900 COTE ST-LUC, APT#212, MONTREAL, QUEBEC H3W 2H3, CANADA SN 0392-2936 J9 EUR J GYNAECOL ONCOL JI Eur. J. Gynaecol. Oncol. PY 2000 VL 21 IS 4 BP 339 EP 347 PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 362RL UT WOS:000089792000004 PM 11055479 ER PT J AU Cocco, L Rhee, SG Gilmour, RS Manzoli, FA AF Cocco, L Rhee, SG Gilmour, RS Manzoli, FA TI Inositide-specific phospholipase C signalling in the nucleus SO EUROPEAN JOURNAL OF HISTOCHEMISTRY LA English DT Article; Proceedings Paper CT 28th National Congress of the Italian-Society-for-Histochemistry CY JUN 02-04, 1999 CL CAMERINO, ITALY SP Italian Soc Histochem ID PROTEIN-KINASE-C; SWISS 3T3 CELLS; GROWTH-FACTOR-I; FRIEND-CELLS; ERYTHROLEUKEMIA-CELLS; DNA-SYNTHESIS; LIPID CYCLE; S-PHASE; IGF-I; DIFFERENTIATION C1 Univ Bologna, Inst Human Anat, I-40126 Bologna, Italy. NHLB, Cell Signalling Lab, NIH, Bethesda, MD 20892 USA. Fac Med, Dept Mol Med, Auckland, New Zealand. RP Cocco, L (reprint author), Univ Bologna, Inst Human Anat, Via Irnerio 48, I-40126 Bologna, Italy. NR 44 TC 11 Z9 11 U1 0 U2 0 PU LUIGI PONZIO E FIGLIO PI PAVIA PA VIA D DA CATALOGNA 1/3, 27100 PAVIA, ITALY SN 1121-760X J9 EUR J HISTOCHEM JI Eur. J. Histochem. PY 2000 VL 44 IS 1 BP 45 EP 50 PG 6 WC Cell Biology SC Cell Biology GA 293RJ UT WOS:000085866600004 PM 10868292 ER PT J AU Wang, J Lobito, AA Shen, F Hornung, F Winoto, A Lenardo, MJ AF Wang, J Lobito, AA Shen, F Hornung, F Winoto, A Lenardo, MJ TI Inhibition of Fas-mediated apoptosis by the B cell antigen receptor through c-FLIP SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE apoptosis; c-FLIP; B lymphocyte ID DOMAIN-CONTAINING PROTEIN; MATURE T-LYMPHOCYTES; DEATH DOMAIN; SIGNALING COMPLEX; CASPASE HOMOLOG; IN-VIVO; INTERACTS; CD40; EXPRESSION; FADD AB Cross-linking of the B cell antigen receptor (BCR) induces resistance to Fas (APO-1/CD95)-dependent apoptosis and thereby regulates one mechanism of B cell selection during antigen stimulation. To investigate the molecular mechanism by which BCR signaling regulates the Fas pathway, we examined the expression of constituents of the death inducing signaling complex (DISC), including Fas, FADD, caspase-8 and cellular FLICE-inhibitory protein (c-FLIP). No significant changes in the cellular levels of Fas, FADD or caspase-8 were observed after BCR cross-linking. By contrast, the long isoform of c-FLIP (c-FLIPL) was significantly up-regulated by BCR cross-linking in primary B cells and in two B cell lines, A20 and WEHI-279. Moreover, transfection of c-FLIPL into A20 cells inhibited Fas-dependent apoptosis and suppressed recruitment of caspase-8 to the DISC. BCR cross-linking or FLIP overexpression also protects B cells from TRAIL-induced apoptosis. Thus, BCR signaling up-regulates c-FLIPL and suppresses the Fas- and TRAIL-receptor apoptosis pathways which could be important for tolerance and selection of antigen-specific B cells. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. RP Lenardo, MJ (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. NR 47 TC 110 Z9 115 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JAN PY 2000 VL 30 IS 1 BP 155 EP 163 DI 10.1002/1521-4141(200001)30:1<155::AID-IMMU155>3.0.CO;2-X PG 9 WC Immunology SC Immunology GA 271KM UT WOS:000084592800017 PM 10602037 ER PT J AU Xu, H Wawrousek, EF Redmond, TM Nickerson, JM Wiggert, B Chan, CC Caspi, RR AF Xu, H Wawrousek, EF Redmond, TM Nickerson, JM Wiggert, B Chan, CC Caspi, RR TI Transgenic expression of an immunologically privileged retinal antigen extraocularly enhances self tolerance and abrogates susceptibility to autoimmune uveitis SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE immune privilege; tolerance; uveitis; T cell; transgenic ID BINDING PROTEIN; T-CELLS; PERIPHERAL TOLERANCE; DISEASE; UVEORETINITIS; AUTOANTIGEN; THYMUS; MICE; IRBP; PROLIFERATION AB Interphotoreceptor retinoid-binding protein (IRBP) is an immunologically privileged retinal antigen that can elicit experimental autoimmune uveitis (EAU). The nature and extent of tolerance to immunologically privileged self antigens is poorly understood. To investigate whether transgenic expression of IRBP extraocularly enhances tolerance and protects from EAU we prepared mice that express half of the mouse IRBP gene, containing a potent uveitogenic epitope (residues 161-180), under control of MHC class II promoter. Transgene mRNA was detectable in many tissues. Transgenic protein was undetectable by conventional assays, but was detected in thymic tissue by lymphocyte proliferation assay after induction of the promoter. Transgenic mice challenged with p161-180 did not develop EAU and had reduced immunological responses, but remained susceptible to EAU induced by whole IRBP, that contains additional uveitogenic epitopes. Disease was also induced by wild type T cells specific to p161-180. Thus, extraocular expression of a privileged retinal antigen enhances self tolerance, supporting the notion that sequestration contributes to immune privilege. Exceedingly low levels of transgene expression result in tolerance that is both profound and epitope specific, implying anergy or deletion of the endogenous uveitogenic repertoire. The same level of expression is, however, insufficient to tolerize wild-type effector T cells in the periphery. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. Emory Univ, Dept Ophthalmol, Atlanta, GA 30322 USA. RP Caspi, RR (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N222, Bethesda, MD 20892 USA. RI Wawrousek, Eric/A-4547-2008; OI Redmond, T. Michael/0000-0002-1813-5291 NR 28 TC 37 Z9 38 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JAN PY 2000 VL 30 IS 1 BP 272 EP 278 DI 10.1002/1521-4141(200001)30:1<272::AID-IMMU272>3.3.CO;2-O PG 7 WC Immunology SC Immunology GA 271KM UT WOS:000084592800030 PM 10602050 ER PT J AU Moron-Concepcion, JA Rocha, B Wise, R Hope, BT AF Moron-Concepcion, JA Rocha, B Wise, R Hope, BT TI Regional differences in dopamine uptake mechanisms: Evidence from DAT knock-out mice SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Meeting Abstract C1 NIDA, Behav Neurosci Branch, Baltimore, MD USA. RI Hope, Bruce/A-9223-2010 OI Hope, Bruce/0000-0001-5804-7061 NR 0 TC 1 Z9 1 U1 0 U2 3 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. PY 2000 VL 12 SU S BP 18 EP 18 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 335GW UT WOS:000088236600104 ER PT J AU Fields, RD AF Fields, RD TI Regulation of gene expression in neurons and glia by neuronal impulses SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Meeting Abstract C1 NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 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. PY 2000 VL 12 SU S BP 57 EP 57 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 335GW UT WOS:000088236600331 ER PT J AU Shaham, Y Erb, S Le, AD Stewart, J AF Shaham, Y Erb, S Le, AD Stewart, J TI The role of corticotropin-releasing factor (CRF) in stress-induced relapse to drug seeking SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Meeting Abstract C1 Concordia Univ, Montreal, PQ, Canada. NIDA, IRP, Baltimore, MD USA. CAMH, Toronto, ON, Canada. NR 0 TC 1 Z9 1 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. PY 2000 VL 12 SU S BP 100 EP 100 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 335GW UT WOS:000088236600573 ER PT J AU Allers, KA Baek, D Ghazi, L Walters, JR AF Allers, KA Baek, D Ghazi, L Walters, JR TI Multi-second oscillations in firing rates of rat subthalamic (STN) and globus pallidus (GP) neurons are correlated with bursts of 4-9 Hz cortical activity SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Meeting Abstract C1 NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 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. PY 2000 VL 12 SU S BP 134 EP 134 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 335GW UT WOS:000088236600771 ER PT J AU Holmes, A Holton, TR Liu, Z Dreiling, J Gleason, TC Sibley, DR Crawley, JN AF Holmes, A Holton, TR Liu, Z Dreiling, J Gleason, TC Sibley, DR Crawley, JN TI Attenuated responses to a D1/D5 agonist in dopamine D5 receptor knockout mice SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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. PY 2000 VL 12 SU S BP 172 EP 172 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 335GW UT WOS:000088236600990 ER PT J AU Pietrini, P Furey, ML Haxby, JV AF Pietrini, P Furey, ML Haxby, JV TI Effects of cholinergic enhancement on brain activity during working memory: PET and fMRI studies in human subjects. SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Meeting Abstract C1 Univ Pisa, Dept Human & Environm Sci, Pisa, Italy. NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. RI Furey, Maura/H-5273-2013 NR 0 TC 0 Z9 0 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. PY 2000 VL 12 SU S BP 176 EP 176 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 335GW UT WOS:000088236601012 ER PT J AU Wenthold, RJ Petralia, RS Zhao, HM Wang, YX Rubio, ME Ly, CD Roche, KW AF Wenthold, RJ Petralia, RS Zhao, HM Wang, YX Rubio, ME Ly, CD Roche, KW TI Targeting of receptors to Purkinje cell synapses SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Meeting Abstract C1 NIDCD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 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. PY 2000 VL 12 SU S BP 182 EP 182 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 335GW UT WOS:000088236601048 ER PT J AU Shalev, U Grimm, J Hope, B Morales, M Yap, J Highfield, D Shaham, Y AF Shalev, U Grimm, J Hope, B Morales, M Yap, J Highfield, D Shaham, Y TI Relapse to heroin, cocaine and sucrose seeking after different reward-free periods SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Meeting Abstract C1 NIDA, IRP, Behav Neurosci Branch, Baltimore, MD USA. RI Hope, Bruce/A-9223-2010 OI Hope, Bruce/0000-0001-5804-7061 NR 0 TC 0 Z9 0 U1 0 U2 2 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. PY 2000 VL 12 SU S BP 204 EP 204 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 335GW UT WOS:000088236601164 ER PT J AU Allen, SJ Smith, SKF Anderson, HA Yu, G Robertson, AGS Tyler, SJ Naylor, RL Mason, G Wilcock, GK Roche, PA Fraser, PE Dawbarn, D AF Allen, SJ Smith, SKF Anderson, HA Yu, G Robertson, AGS Tyler, SJ Naylor, RL Mason, G Wilcock, GK Roche, PA Fraser, PE Dawbarn, D TI Syntaxin 1A is a novel binding protein for presenilin-1 SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Meeting Abstract C1 Univ Bristol, Bristol BR1, Avon, England. Univ Toronto, Toronto, ON, Canada. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Bristol, Bristol BS8 1TH, Avon, England. NR 0 TC 0 Z9 0 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. PY 2000 VL 12 SU S BP 213 EP 213 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 335GW UT WOS:000088236601213 ER PT J AU Culmsee, C Monnig, J Kemp, BE Mattson, MP AF Culmsee, C Monnig, J Kemp, BE Mattson, MP TI AMP activated protein kinase protects hippocampal. neurons against metabolic, excitotoxic and oxidative insults SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Meeting Abstract C1 NIA, Neurosci Lab, Baltimore, MD USA. St Vincents Inst Med Res, Fitzroy, Vic 3065, Australia. RI Mattson, Mark/F-6038-2012; Kemp, Bruce/L-2633-2014 OI Kemp, Bruce/0000-0001-6735-5082 NR 0 TC 0 Z9 0 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. PY 2000 VL 12 SU S BP 231 EP 231 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 335GW UT WOS:000088236601323 ER PT J AU Lukaszewicz, A Savatier, P Cortay, V Seth, P Kennedy, H Dehay, C AF Lukaszewicz, A Savatier, P Cortay, V Seth, P Kennedy, H Dehay, C TI G1 phase regulation and differentiation of mouse cortical neuroblast SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Meeting Abstract C1 INSERM U371, F-69575 Bron, France. Ecole Normale Super Lyon, UMR5665, F-69364 Lyon, France. NCI, NIH, Bethesda, MD USA. RI Kennedy, Henry/B-9636-2013; SAVATIER, Pierre/J-4663-2014 OI Kennedy, Henry/0000-0002-2796-7663; NR 0 TC 0 Z9 0 U1 0 U2 2 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. PY 2000 VL 12 SU S BP 245 EP 245 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 335GW UT WOS:000088236601400 ER PT J AU Bron, R Klesse, LJ O'Bryan, J Shah, K Parada, LF Winter, J AF Bron, R Klesse, LJ O'Bryan, J Shah, K Parada, LF Winter, J TI Signal transduction pathways involved in growth factor-induced upregulation of nociceptive properties of dorsal root ganglion neurons SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Meeting Abstract C1 Novartis Inst Med Sci, London, England. UTSW, Dallas, TX USA. NIEH, Res Triangle Pk, NC USA. RI Parada, luis/B-9400-2014 NR 0 TC 0 Z9 0 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. PY 2000 VL 12 SU S BP 268 EP 268 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 335GW UT WOS:000088236601535 ER PT J AU Lanuza, MA Li, MX Jia, M Kim, S Davenport, R Dunlap, V Nelson, PG AF Lanuza, MA Li, MX Jia, M Kim, S Davenport, R Dunlap, V Nelson, PG TI Role of postsynaptic acetylcholine receptors in the synapse elimination at the neuromuscular junction in vitro SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Meeting Abstract C1 NICHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Biol, College Pk, MD 20742 USA. NR 0 TC 0 Z9 0 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. PY 2000 VL 12 SU S BP 277 EP 277 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 335GW UT WOS:000088236601589 ER PT J AU Garcia, N Lanuza, MA Alonso, I Santafe, M Diaz, J Nelson, PG Tomas, J AF Garcia, N Lanuza, MA Alonso, I Santafe, M Diaz, J Nelson, PG Tomas, J TI Effect of the protein kinase C activity on the acetylcholine receptor cluster maturation in the neuromuscular junctions of the neonatal rat SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Meeting Abstract C1 NICHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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. PY 2000 VL 12 SU S BP 280 EP 280 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 335GW UT WOS:000088236601603 ER PT J AU Dunnett, SB Brasted, PJ AF Dunnett, SB Brasted, PJ TI Functional reconstruction of the neostriatum by striatal transplants SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Cardiff Univ, Cardiff, S Glam, Wales. RI Dunnett, Stephen/A-5869-2010 OI Dunnett, Stephen/0000-0003-1826-1578 NR 0 TC 0 Z9 0 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. PY 2000 VL 12 SU S BP 292 EP 292 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 335GW UT WOS:000088236601673 ER PT J AU Shaham, Y Highfield, D Delfs, J Leung, S Stewart, J AF Shaham, Y Highfield, D Delfs, J Leung, S Stewart, J TI Clonidine blocks stress-induced reinstatement of heroin seeking in rats: an effect independent of locus coeruleus noradrenergic neurons SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE alpha-2 adrenergic receptors; clonidine; heroin self-administration; lateral tegmental noradrenergic nuclei; locus coeruleus; noradrenaline; reinstatement; relapse; stress; ST-91; ventral noradrenergic bundle ID CORTICOTROPIN-RELEASING FACTOR; OPIATE WITHDRAWAL; NORADRENALINE RELEASE; PREFRONTAL CORTEX; CERULEUS NEURONS; INDUCED RELAPSE; DRUG-SEEKING; BRAIN; BEHAVIOR; SYSTEM AB Using a reinstatement procedure, it has been shown that intermittent footshock stress reliably reinstates extinguished drug-taking behaviour in rats. Here we studied the role of noradrenaline (NE), one of the main brain neurotransmitters involved in responses to stress, in reinstatement of heroin seeking. We first determined the effect of clonidine, an alpha-2 adrenergic receptor agonist that decreases NE cell firing and release, on stress-induced reinstatement of heroin seeking. Rats were trained to self-administer heroin (0.1 mg/kg per infusion, IV, three 3-h sessions per day) for 9-10 days. Extinction sessions were given for up to II days during which saline was substituted for the drug. Tests for reinstatement were then conducted after exposure to intermittent footshock (5, 15 and 30 min, 0.5 mA). During testing, clonidine was injected systemically (10-40 mu g/kg, i.p.) or directly into the lateral or fourth ventricles (1-3 mu g) Clonidine (1-2 mu g per site) or its charged analogue, 2-[2,6-diethylphenylamino]-2-imidazole (ST-91, 0.5-1 mu g per site), was also injected bilaterally into the locus coeruleus (LC), the main noradrenergic cell group in the brain. Clonidine blocked stress-induced reinstatement of drug seeking when injected systemically or into the cerebral ventricles. In contrast, neither clonidine nor ST-91 consistently altered stress-induced reinstatement when injected into the locus coeruleus. We therefore studied the effect of lesions of the lateral tegmental NE neurons on stress-induced reinstatement. 6-Hydroxydopamine (6-OHDA) lesions performed after training for heroin self-administration had no effect on extinction of heroin-taking behaviour, but significantly attenuated reinstatement induced by intermittent footshock. These data suggest that: (i) clonidine prevents stress-induced relapse to heroin seeking by its action on neurons other than those of the locus coeruleus; and (ii) activation of the lateral tegmental NE neurons contributes to stress-induced reinstatement of heroin seeking. C1 NIDA, Behav Neurosci Branch, IRP, NIH, Baltimore, MD 21224 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Concordia Univ, Dept Psychol, CSBN, Montreal, PQ H3G 1M8, Canada. RP Shaham, Y (reprint author), Addict Res Fdn, Biobehav Res Dept, 33 Russell St, Toronto, ON M5S 2S1, Canada. RI shaham, yavin/G-1306-2014 NR 79 TC 131 Z9 139 U1 3 U2 4 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 JAN PY 2000 VL 12 IS 1 BP 292 EP 302 DI 10.1046/j.1460-9568.2000.00899.x PG 11 WC Neurosciences SC Neurosciences & Neurology GA 285AU UT WOS:000085366600031 PM 10651884 ER PT J AU Bateson, AN Tenn, CC Hope, BT Nakabeppu, Y AF Bateson, AN Tenn, CC Hope, BT Nakabeppu, Y TI A delayed but transient increase in striatal DeltaFosB and DeltaFosB-like proteins upon chronic diazepam treatment SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Meeting Abstract C1 Univ Alberta, Edmonton, AB T6G 2M7, Canada. NIDA, NIH, Baltimore, MD USA. Kyushu Univ, Fukuoka 812, Japan. RI Hope, Bruce/A-9223-2010; Nakabeppu, Yusaku/A-8902-2011 OI Hope, Bruce/0000-0001-5804-7061; NR 0 TC 0 Z9 0 U1 0 U2 1 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. PY 2000 VL 12 SU S BP 309 EP 309 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 335GW UT WOS:000088236601775 ER PT J AU Yu, ZY Liu, XH McCarron, RM AF Yu, ZY Liu, XH McCarron, RM TI Inhibition of apoptosis and nitric oxide synthase gene expression in rat cerebellar granule cells by 2-iodomelatonin SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Meeting Abstract C1 USN, Med Res Ctr, Bethesda, MD 20084 USA. NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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. PY 2000 VL 12 SU S BP 343 EP 343 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 335GW UT WOS:000088236601954 ER PT J AU Roche, KW Standley, S McCallum, J Ly, CD Wenthold, RJ AF Roche, KW Standley, S McCallum, J Ly, CD Wenthold, RJ TI Characterization of NMDA vs. AMPA receptor internalization SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Meeting Abstract C1 NIDCD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 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. PY 2000 VL 12 SU S BP 396 EP 396 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 335GW UT WOS:000088236602261 ER PT J AU De Leonibus, E Felici, A Oliverio, A Mele, A Pert, A AF De Leonibus, E Felici, A Oliverio, A Mele, A Pert, A TI Role of nucleus accumbens efferent pathways in the modulation of MK-801 induced locomotor activity. SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Meeting Abstract C1 Univ Rome La Sapienza, Dipartimento Genet & Biol Mol, I-00185 Rome, Italy. CNR, Ist Psicobiol & Psicofarmacol, I-00198 Rome, Italy. IRCCS, Rome, Italy. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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. PY 2000 VL 12 SU S BP 414 EP 414 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 335GW UT WOS:000088236602362 ER PT J AU Pietrobon, D Tottene, A Copeland, NG Jenkins, NA Fletcher, CF AF Pietrobon, D Tottene, A Copeland, NG Jenkins, NA Fletcher, CF TI Alpha1A-/- mice lacking P/Q-type voltage-dependent calcium channels: Phenotype and calcium-currents in cerebellar granule cells. SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Meeting Abstract C1 Univ Padua, Dept Biomed Sci, I-35100 Padua, Italy. NCI, Frederick Canc Res & Dev Ctr, Mammalian Genet Lab, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 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. PY 2000 VL 12 SU S BP 454 EP 454 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 335GW UT WOS:000088236602581 ER PT J AU Bichot, NP Thompson, KG Rao, SC Schall, JD AF Bichot, NP Thompson, KG Rao, SC Schall, JD TI Reliability of frontal eye field (FEF) neurons in signaling saccade targets during visual search SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Meeting Abstract C1 NIMH, NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Nashville, TN USA. NR 0 TC 0 Z9 0 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. PY 2000 VL 12 SU S BP 489 EP 489 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 335GW UT WOS:000088236602779 ER PT J AU Brown, MR Kohn, EC Hutter, RVP AF Brown, MR Kohn, EC Hutter, RVP TI The new millennium: applying novel technology to the study of the cancer cell in situ SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE LA English DT Article ID PROSTATIC INTRAEPITHELIAL NEOPLASIA; MICRODISSECTION; CONSTRUCTION C1 NCI, Pathol Lab, Bethesda, MD 20892 USA. St Barnabas Med Ctr, Dept Pathol, Livingston, NJ USA. RP Brown, MR (reprint author), NCI, Pathol Lab, Bldg 10,Room 2A33,10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6997 J9 EUR J NUCL MED JI Eur. J. Nucl. Med. PD JAN PY 2000 VL 27 IS 1 SU S BP S27 EP S30 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 273BH UT WOS:000084686500007 PM 10744468 ER PT J AU Vanhoenacker, FM De Beuckeleer, LH Van Hul, W Balemans, W Tan, GJ Hill, SC De Schepper, AM AF Vanhoenacker, FM De Beuckeleer, LH Van Hul, W Balemans, W Tan, GJ Hill, SC De Schepper, AM TI Sclerosing bone dysplasias: genetic and radioclinical features SO EUROPEAN RADIOLOGY LA English DT Review DE sclerosing bone dysplasia; bone sclerosis; bone osteochondrodysplasias ID CAMURATI-ENGELMANN-DISEASE; SPONASTRIME DYSPLASIA; CHROMOSOME 17Q12-Q21; DIAPHYSEAL DYSPLASIA; LOCALIZATION; MAPS AB Although knowledge of basic genetics in the field of sclerosing bone dysplasias is progressing, the radiologist still plays a pivotal role in the diagnosis of this relatively poorly understood group of disorders. Based on a target site approach, these anomalies are classified into three groups. Within each group, further differentiation can be made by distinctive clinical findings and by mode of inheritance: (a) dysplasias of endochondral bone formation: osteopetrosis (Albers-Schonberg disease), pycnodysostosis, enostosis, osteopoikilosis, osteopathia striata (Voorhoeve disease); (b) dysplasias of intramembranous bone formation: progressive diaphyseal dysplasia (Camurati-Engelmann disease) and variants, hyperotosis corticalis generalisata (Van Buchem disease) and variants; and (c) mixed sclerosing dysplasias: melorheostosis (Leri disease) and overlap syndromes. C1 Univ Antwerp Hosp, Dept Radiol, B-2650 Edegem, Belgium. Univ Antwerp, Dept Med Genet, B-2610 Antwerp, Belgium. Dr Janssen Ziekenhuis, Dept Radiol, NL-8303 BA Emmeloord, Netherlands. NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Vanhoenacker, FM (reprint author), Univ Antwerp Hosp, Dept Radiol, Wilrijkstr 10, B-2650 Edegem, Belgium. NR 28 TC 50 Z9 57 U1 0 U2 3 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PY 2000 VL 10 IS 9 BP 1423 EP 1433 DI 10.1007/s003300000495 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 352EG UT WOS:000089201100010 PM 10997431 ER PT J AU Choyke, PL AF Choyke, PL TI Acquired cystic kidney disease SO EUROPEAN RADIOLOGY LA English DT Review DE dialysis; acquired cystic kidney disease; renal cancer; screening; renal transplantation ID RENAL-CELL CARCINOMA; LONG-TERM DIALYSIS; TRANSPLANT RECIPIENTS; NATIVE KIDNEYS; HEMODIALYSIS; TUMORS; PERSPECTIVE; CT AB Acquired cystic kidney disease (ACKD), also known as acquired renal cystic disease (ARCD) occurs in patients who are on dialysis for end-stage renal disease. It is generally accepted that ACKD develops as a consequence of sustained uremia and can first manifest even before dialysis is initiated while the patient is still in chronic renal failure role of immune suppression, particularly in transplant recipients, in the development of ACKD, is still under investigation. The prevalence of ACKD directly related to the duration of dialysis and the risk of cancer is directly related to the presence of cysts. Herein we review the current understanding of the pathophysiology and imaging implications of ACKD. C1 NIH, Dept Radiol, Bethesda, MD 20892 USA. RP Choyke, PL (reprint author), NIH, Dept Radiol, Bldg 10,Room 1C660, Bethesda, MD 20892 USA. NR 33 TC 26 Z9 28 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PY 2000 VL 10 IS 11 BP 1716 EP 1721 DI 10.1007/s003300000601 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 370RZ UT WOS:000165137200007 PM 11097395 ER PT J AU Sullivan, DC AF Sullivan, DC TI NIH and cost-effectiveness studies for imaging SO EUROPEAN RADIOLOGY LA English DT Article; Proceedings Paper CT 3rd International Symposium on Strategic Studies in Radiology CY AUG 19-21, 1999 CL BERLIN, GERMANY ID AGE C1 NIH, Bethesda, MD 20892 USA. RP Sullivan, DC (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 4 TC 1 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PY 2000 VL 10 SU 3 BP S408 EP S410 DI 10.1007/PL00014108 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 336GR UT WOS:000088294000023 PM 11001461 ER PT S AU Chen, J Dagher, SM Fisher, CE Grunow, W Hattan, DG Kawamura, Y Knaap, AGAC Kuznesof, PM Larsen, JC Meyland, I Pascal, G Riordan, M Walker, R Wilson, JD Akkelidou, D Bellinger, DC Bolger, M Carrington, C Dewailly, E DiNovi, M Eriksen, GS Greig, J Hecker, EFF Herrman, JL Hotchkiss, JH Madsen, C Magos, LPA Mattia, A Moy, G Munro, IC Nishikawa, A Pennington, JA Petersen, B Renwick, AG Resnik, S Schlatter, J Sipes, GI Speijers, GJA Vavasour, E Verger, JP Vilu, R Wallin, H Weatherwax, J Whitehouse, DB AF Chen, J Dagher, SM Fisher, CE Grunow, W Hattan, DG Kawamura, Y Knaap, AGAC Kuznesof, PM Larsen, JC Meyland, I Pascal, G Riordan, M Walker, R Wilson, JD Akkelidou, D Bellinger, DC Bolger, M Carrington, C Dewailly, E DiNovi, M Eriksen, GS Greig, J Hecker, EFF Herrman, JL Hotchkiss, JH Madsen, C Magos, LPA Mattia, A Moy, G Munro, IC Nishikawa, A Pennington, JA Petersen, B Renwick, AG Resnik, S Schlatter, J Sipes, GI Speijers, GJA Vavasour, E Verger, JP Vilu, R Wallin, H Weatherwax, J Whitehouse, DB CA Joint FAO WHO Expert Committee Foo GP WHO WHO TI Evaluation of certain food additives and contaminants SO EVALUATION OF CERTAIN FOOD ADDITIVES AND CONTAMINANTS, 53RD REPORT SE WHO Technical Report Series LA English DT Article; Proceedings Paper CT 53rd Joint Meeting of the FAO/WHO on Food Additives CY JUN 01-10, 1999 CL ROME, ITALY SP FAO, WHO C1 Chinese Acad Prevent Med, Inst Nutr & Food Hyg, Beijing, Peoples R China. Food Regulatory Affairs, Bowden, Cheshire, England. FAO, Food & Nutr Div, Food Qual & Stand Serv, I-00100 Rome, Italy. Natl Food Adm Toxicol Lab, Helsinki, Finland. Tallinn Univ Technol, Dept Biochem, EE-200108 Tallinn, Estonia. Natl Ctr Study & Res Nutr & Food, Observ Food Consumpt, Paris, France. Hlth Canada, Chem Hlth Hazard Assessment Div, Bur Chem Safety, Food Directorate,Hlth Protect Branch, Ottawa, ON K1A 0L2, Canada. Natl Inst Publ Hlth & Environm Protect, Ctr Subst & Risk Assessment, NL-3720 BA Bilthoven, Netherlands. Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA. Univ Zurich, Inst Vet Pharmacol & Toxicol, Fed Off Publ Hlth, Zurich, Switzerland. Fac Exact & Nat Sci, Dept Ind, Buenos Aires, DF, Argentina. Univ Southampton, Clin Pharmacol Grp, Southampton, Hants, England. Novigen Sci Inc, Washington, DC USA. NIH, Div Nutr Res Coordinat, Bethesda, MD 20892 USA. Natl Inst Hlth Sci, Div Pathol, Biol Safety Res Ctr, Tokyo 158, Japan. CanTox Hlth Sci Int, Mississauga, ON, Canada. WHO, Programme Food Safety, CH-1211 Geneva, Switzerland. US FDA, Div Prod Policy, Off Premarket Approval, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. TNO BIBRA Int Ltd, Carshalton, Surrey, England. Minist Food Agr & Fisheries, Inst Food Safety & Toxicol, Danish Vet & Food Adm, Dept Biochem & Mol Toxicol, Soborg, Denmark. Cornell Univ, Dept Food Sci, Ithaca, NY 14853 USA. WHO, Int Programme Chem Safety, CH-1211 Geneva, Switzerland. Minist Agr Nat Management & Fisheries, Codex Comm Food Addit & Contaminants, Risk Subst & Nut Div, Dept Environm Qual & Hlth, The Hague, Netherlands. Dept Hlth, Joint Food Safety & Stand Grp, London SE1 6TE, England. Swedish Univ Agr Sci, Dept Anim Nutr & Management, S-75007 Uppsala, Sweden. US FDA, Div Prod Manufacture & Use, Off Premarket Approval, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Publ Hlth Ctr Quebec, Environm Hlth Serv, Beauport, PQ, Canada. US FDA, Contaminants Branch, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Harvard Univ, Sch Med, Childrens Hosp, Neuroepidemiol Unit, Boston, MA USA. Minist Hlth, State Gen Lab, Nicosia, Cyprus. Australia New Zealand Food Author, Canberra, ACT, Australia. Univ Surrey, Sch Biol Sci, Guildford GU2 5XH, Surrey, England. Minist Hlth, Food & Nutr Sect, Wellington, New Zealand. Natl Inst Agr Res, Sci Steering Comm European Union, Paris, France. Minist Food Agr & Fisheries, Inst Food Res & Nutr, Danish Vet & Food Adm, Soborg, Denmark. Natl Inst Hlth Sci, Div Food Addit, Tokyo 158, Japan. US FDA, Div Hlth Effects Evaluat, Off Premarket Approval, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Fed Int Hlth Protect Consumers & Vet Med, Food Toxicol Div, Berlin, Germany. Minsist Agr Fisheries & Food, Risk Anal & Int Coordinat Branch, London, England. Amer Univ Beirut, Dept Biol, Beirut, Lebanon. RP Chen, J (reprint author), Chinese Acad Prevent Med, Inst Nutr & Food Hyg, Beijing, Peoples R China. NR 191 TC 6 Z9 6 U1 1 U2 5 PU WORLD HEALTH ORGANIZATION PI GENEVA PA DISTRIBUTION & SALES SERVICE, 1211 27 GENEVA, SWITZERLAND SN 0512-3054 BN 92-4-120896-1 J9 WHO TECH REP SER JI WHO Tech. Rep. Ser. PY 2000 VL 896 BP 1 EP 128 PG 128 WC Chemistry, Applied; Food Science & Technology; Public, Environmental & Occupational Health; Toxicology SC Chemistry; Food Science & Technology; Public, Environmental & Occupational Health; Toxicology GA BS11W UT WOS:000168725000001 ER PT S CA Joint FAO WHO Expert Comm Food GP WHO TI Evaluation of certain veterinary drug residues in food - Introduction SO EVALUATION OF CERTAIN VETERINARY DRUG RESIDUES IN FOOD, 52ND REPORT SE WHO TECHNICAL REPORT SERIES LA English DT Article; Proceedings Paper CT 52nd Joint Meeting of the FAO/WHO Expert Committe on Food Additives CY FEB 02-11, 1999 CL FAO HEADQUARTERS, ROME, ITALY SP WHO HO FAO HEADQUARTERS ID INTESTINAL MICROFLORA; FLORA C1 Swedish Univ Agr Sci, Fac Vet Med, Dept Pharmacol & Toxicol, Uppsala, Sweden. Fed Inst Hlth Protect Consumers & Vet Med, Berlin, Germany. Univ Zimbabwe, Fac Vet Sci, Dept Preclin Vet Studies, Harare, Zimbabwe. Natl Ctr Vet & Food Studies, Natl Agcy Vet Med, Fougeres, France. Imperial Coll Sch Med, Div Med, Clin Pharmacol Sect, London, England. NIEHS, Res Triangle Pk, NC 27709 USA. USDA, Off Publ Hlth & Sci, Food Safety & Inspect Serv, Washington, DC 20250 USA. Sokoine Univ Agr, Dept Vet Physiol Biochem Pharmacol & Toxicol, Morogoro, Tanzania. Canadian Food Inspect Agcy, Hlth Anim Lab, Ctr Vet Drug Residues, Saskatoon, SK, Canada. US FDA, Off New Anim Drug Evaluat, Ctr Vet Med, Rockville, MD 20857 USA. Univ Nairobi, Coll Agr & Vet Sci, Fac Vet Med, Dept Publ Hlth Pharmacol & Toxicol, Kabete, Kenya. Univ Sao Paulo, Sch Vet Med, Dept Pathol, Appl Pharmacol & Toxicol Lab, Sao Paulo, Brazil. Vet Org Iran, Vet Diagnost Ctr, Pharmacokinet Unit, Tehran, Iran. Natl Inst Publ Hlth & Environm, Lab Residue Anal, NL-3720 BA Bilthoven, Netherlands. US FDA, Natl Ctr Toxicol Res, Div Microbiol & Chem, Jefferson, AR 72079 USA. Aviano Canc Ctr, Epidemiol Unit, I-33081 Aviano, Italy. WHO, Int Programme Chem Safety, CH-1211 Geneva, Switzerland. US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, Rockville, MD 20857 USA. US FDA, Ctr Vet Med, Rockville, MD 20857 USA. Int Agcy Res Canc, Unit Carcinogen Identificat & Evaluat, F-69372 Lyon, France. Natl Inst Hlth Sci, Biol Safety Res Ctr, Div Pathol, Sect 3, Tokyo 158, Japan. Inst Food Res, Dept Biochem, Norwich NR4 7UA, Norfolk, England. Danish Vet & Food Adm, Inst Food Safety & Toxicol, Soborg, Denmark. Natl Inst Publ Hlth & Environm, Ctr Subst & Risk Assessment, NL-3720 BA Bilthoven, Netherlands. Univ Guelph, Canadian Network Toxicol Ctr, Guelph, ON N1G 2W1, Canada. Minist Agr, Kimron Vet Inst, Natl Residue Lab, Bet Dagan, Israel. US FDA, Ctr Vet Med, Rockville, MD 20857 USA. Univ Leipzig, Fac Vet Med, Inst Pharmacol Pharm & Toxicol, D-7010 Leipzig, Germany. FAO, Food & Nutr Div, Food Qual & Stand Serv, Food Qual Liaison Grp, I-00100 Rome, Italy. US FDA, Ctr Vet Med, Residue Chem Team, Off New Anim Drug Evaluat, Rockville, MD 20857 USA. Natl Inst Vet Res, Dept Pharmacol & Toxicol, Pulawy, Poland. RP Swedish Univ Agr Sci, Fac Vet Med, Dept Pharmacol & Toxicol, Uppsala, Sweden. NR 24 TC 0 Z9 0 U1 1 U2 2 PU WORLD HEALTH ORGANIZATION PI GENEVA PA 1211 27 GENEVA, SWITZERLAND SN 0512-3054 BN 92-4-120893-7 J9 WHO TECH REP SER PY 2000 VL 893 BP 1 EP 89 PG 89 WC Chemistry, Applied; Food Science & Technology; Public, Environmental & Occupational Health; Toxicology SC Chemistry; Food Science & Technology; Public, Environmental & Occupational Health; Toxicology GA BS11V UT WOS:000168724800001 ER PT J AU Li, WH Boissinot, S Tan, Y Shyue, SK Hewett-Emmett, D AF Li, WH Boissinot, S Tan, Y Shyue, SK Hewett-Emmett, D TI Evolutionary genetics of primate color vision - Recent progress and potential limits to knowledge SO EVOLUTIONARY BIOLOGY, VOL 32 SE EVOLUTIONARY BIOLOGY LA English DT Review ID NEW-WORLD MONKEYS; GREEN OPSIN GENES; VISUAL PIGMENT GENES; MOLECULAR-GENETICS; HUMAN RED; SEQUENCE DIVERGENCE; ABSORPTION-SPECTRA; CONE PIGMENTS; LEMUR-CATTA; POLYMORPHISM C1 Univ Chicago, Dept Ecol & Evolut, Chicago, IL 60637 USA. NIDDK, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Texas, Ctr Human Genet, Houston, TX 77225 USA. Acad Sinica, Inst Biomed Sci, Taipei 11529, Taiwan. RP Li, WH (reprint author), Univ Chicago, Dept Ecol & Evolut, Chicago, IL 60637 USA. NR 55 TC 2 Z9 2 U1 1 U2 4 PU KLUWER ACADEMIC / PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0071-3260 J9 EVOL BIOL PY 2000 VL 32 BP 151 EP 178 PG 28 WC Genetics & Heredity SC Genetics & Heredity GA BR67V UT WOS:000167140700008 ER PT J AU Kotanen, PM Rosenthal, JP AF Kotanen, PM Rosenthal, JP TI Tolerating herbivory: does the plant care if the herbivore has a backbone? SO EVOLUTIONARY ECOLOGY LA English DT Article DE arthropod; compensation; damage; herbivory; insect; invertebrate; tolerance; vertebrate ID ARCTIC SALT-MARSH; ABOVEGROUND PRIMARY PRODUCTION; PUCCINELLIA-PHRYGANODES; RESOURCE AVAILABILITY; SHORTGRASS STEPPE; INSECT HERBIVORY; BUSH LUPINE; TOLERANCE; GRASS; OPTIMIZATION AB Differences in size-related ecology and behaviour between vertebrate and invertebrate herbivores lead to differences in the rates, tissue specificity, and spatial distribution of their damage, as well as in their indirect effects. As a result, many features of tolerance to herbivory by these groups also may differ. Tolerating vertebrate herbivory may demand the ability to tolerate sporadic non-specific impacts; this may be achieved by broad responses promoting regrowth and resource acquisition. In contrast, the diversity of different types of invertebrate damage seems likely to demand a correspondingly great variety of responses. These conclusions suggest that tolerance to invertebrates may involve a broader set of responses than tolerance to vertebrates; conversely, the greater specificity of these responses may make it more difficult for arthropod-tolerant plants to achieve cross-tolerance to other types of damage. C1 Univ Toronto, Dept Bot, Mississauga, ON L5L 1C6, Canada. NIH, Fogarty Int Ctr, Bethesda, MD USA. RP Kotanen, PM (reprint author), Univ Toronto, Dept Bot, Mississauga, ON L5L 1C6, Canada. OI Kotanen, Peter/0000-0002-7842-8715 NR 73 TC 22 Z9 23 U1 2 U2 20 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0269-7653 J9 EVOL ECOL JI Evol. Ecol. PY 2000 VL 14 IS 4-6 BP 537 EP 549 DI 10.1023/A:1010862201331 PG 13 WC Ecology; Evolutionary Biology; Genetics & Heredity SC Environmental Sciences & Ecology; Evolutionary Biology; Genetics & Heredity GA 448GT UT WOS:000169619700014 ER PT J AU Koch, CA Huang, SC Vortmeyer, AO Zhang, ZP Chrousos, GP Pacak, K AF Koch, CA Huang, SC Vortmeyer, AO Zhang, ZP Chrousos, GP Pacak, K TI A patient with MEN 2 and multiple mutations of RET in the germline SO EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES LA English DT Letter C1 NICHD, NIH, NINDS, Bethesda, MD 20892 USA. RP Koch, CA (reprint author), NICHD, NIH, NINDS, Bldg 10,Rm 9D42, Bethesda, MD 20892 USA. RI Koch, Christian/A-4699-2008 OI Koch, Christian/0000-0003-3127-5739 NR 3 TC 9 Z9 10 U1 0 U2 0 PU JOHANN AMBROSIUS BARTH VERLAG PI HEIDELBERG PA IM WEIHER 10, D-69121 HEIDELBERG, GERMANY SN 0947-7349 J9 EXP CLIN ENDOCR DIAB JI Exp. Clin. Endocrinol. Diabet. PY 2000 VL 108 IS 8 BP 493 EP 493 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 384HE UT WOS:000165936100001 PM 11149622 ER PT J AU Classen, J Steinfelder, B Liepert, J Stefan, K Celnik, P Cohen, LG Hess, A Kunesch, E Chen, R Benecke, R Hallett, M AF Classen, J Steinfelder, B Liepert, J Stefan, K Celnik, P Cohen, LG Hess, A Kunesch, E Chen, R Benecke, R Hallett, M TI Cutaneomotor integration in humans is somatotopically organized at various levels of the nervous system and is task dependent SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE somatotopy; input-output; inhibition; excitation; transcranial magnetic stimulation ID MAGNETIC BRAIN-STIMULATION; HUMAN MOTOR CORTEX; DORSAL INTEROSSEOUS MUSCLE; SILENT PERIOD; REFLEX RESPONSES; TRANSCRANIAL STIMULATION; ELECTRICAL-STIMULATION; SOMATOSENSORY CORTEX; OUTPUT NEURONS; HAND MUSCLE AB Integration of tactile afferent signals with motor commands is crucial for the performance of purposeful movements such as during manipulation of an object in the hand. To study the somatotopic organization of sensorimotor integration we applied electrical peripheral conditioning stimuli to a digit located near (homotopic stimulation) or distant from (heterotopic stimulation) relaxed or isometrically contracted intrinsic hand muscles at variable time intervals prior to transcranial magnetic stimulation (TMS). Cutaneous stimulation has previously been shown to modulate the amplitude of the motor evoked potential (MEP) and to shorten the duration of the silent period (SP) evoked by TMS. In relaxed target muscles the time-dependent modulation of TMS-evoked motor responses by homotopic conditioning stimulation differed from modulation by heterotopic stimulation. Similar differences in the modulation pattern evoked by homotopic and heterotopic conditioning stimulation were observed for two distinct target muscles of the hand (abductor digiti minimi, abductor pollicis brevis muscle). Differences in modulation were maximal when the conditioning stimulation was applied 25-30 ms and 150-200 ms prior to TMS. Comparison of the modulation of the amplitudes of MEPs evoked by transcranial electrical stimulation (TES) and the modulation of those evoked by TMS suggests that differences between homo-topic and heterotopic stimulation originate subcortically at 25- to 30-ms and, at least partially, cortically at 150-to 200-ms interstimulus intervals. In isometrically contracted intrinsic hand muscles the degree to which the SP was shortened reflected the location and the timing of the conditioning stimulus, Shortening was maximal when the conditioning stimulus was applied nearest to the contracted target muscle and 20 ms prior to the test stimulus. In contrast to the SP duration, the MEP size in voluntarily contracted target muscles was unaffected by the location of the conditioning stimulus. The somatotopic gradient of SP shortening was abolished when the two target muscles were simultaneously activated isometrically. Together, our findings suggest that somatotopy of input-output relationships is implemented at both a spinal and a cortical level in the human central nervous system and may also depend on the motor task involved. C1 Univ Rostock, Neurol Klin, Zentrum Nervenheilkunde, D-18147 Rostock, Germany. Univ Jena, Neurol Klin, Jena, Germany. NINDS, Med Neurol Branch, Human Cort Physiol Sect, Bethesda, MD 20892 USA. NINDS, Med Neurol Branch, Human Motor Control Sect, Bethesda, MD 20892 USA. RP Classen, J (reprint author), Univ Rostock, Neurol Klin, Zentrum Nervenheilkunde, Gehlsheimer Str 20, D-18147 Rostock, Germany. RI Chen, Robert/B-3899-2009 OI Chen, Robert/0000-0002-8371-8629 NR 57 TC 84 Z9 84 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD JAN PY 2000 VL 130 IS 1 BP 48 EP 59 DI 10.1007/s002210050005 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 269BQ UT WOS:000084456200005 PM 10638440 ER PT J AU Hain, TC Burnett, TA Kiran, S Larson, CR Singh, S Kenney, MK AF Hain, TC Burnett, TA Kiran, S Larson, CR Singh, S Kenney, MK TI Instructing subjects to make a voluntary response reveals the presence of two components to the audio-vocal reflex SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE pitch shift; vocalization; auditory feedback; voice fundamental frequency; audio-vocal reflex ID SPECIES-SPECIFIC VOCALIZATIONS; AUDITORY-CORTEX; SQUIRREL-MONKEY; PITCH; DISCRIMINATION; REPRESENTATION; POTENTIALS; DISCHARGE; FEEDBACK; MUSCLES AB Previous findings have shown that subjects respond to an alteration, or shift, of auditory feedback pitch with a change in voice fundamental frequency (F0). When pitch shifts exceeding 500 ms in duration were presented, subjects' averaged responses appeared to consist of both an early and a late component. The latency of the second response was long enough to be produced voluntarily. To test the hypothesis that there are two responses to pitch-shift stimuli and to clarify the role of intention, subjects were instructed to change their voice FO in the opposite direction of the pitch-shift stimulus, in the same direction, or not to respond at all. In a second group, subjects were tested under the above conditions as well as under instructions to raise voice FO or to lower FO as rapidly as possible upon hearing a pitch shift. Results showed that, when given instructions to produce a voluntary response, subjects made both an early vocal response (VR1) and a later vocal response (VR2), The second response, VR2, was almost always made in the instructed direction, whereas VR1 was often made incorrectly. The latency of VRI was reduced under instructions to respond to feedback pitch shifts by changing voice FO in the opposite direction, compared with that when told to ignore the pitch shifts. Latency and amplitude measures of VR2 differed under the various experimental conditions. These results demonstrate that there are two responses to pitch-shift stimuli. The first is relatively automatic but may be modulated by instructions to the participant. The second response is probably a voluntary one. C1 Northwestern Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Dept Neurol, Chicago, IL 60611 USA. Northwestern Univ, Dept Commun Sci & Disorders, Evanston, IL 60208 USA. Univ Cape Town Observ, Dept Logopaed, ZA-7925 Cape Town, South Africa. Natl Inst Hlth, Bethesda, MD USA. RP Hain, TC (reprint author), Northwestern Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, 675 N St Clair,15-200, Chicago, IL 60611 USA. RI Kiran, S/B-1892-2013 NR 26 TC 94 Z9 94 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD JAN PY 2000 VL 130 IS 2 BP 133 EP 141 DI 10.1007/s002219900237 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 275XN UT WOS:000084845600003 PM 10672466 ER PT J AU Lebedev, MA Wise, SP AF Lebedev, MA Wise, SP TI Oscillations in the premotor cortex: single-unit activity from awake, behaving monkeys SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE visually guided movement; motor cortex; sensorimotor cortex; rhythmicity; spike trains ID PRIMARY SOMATOSENSORY CORTEX; FIELD POTENTIAL OSCILLATIONS; SPONTANEOUS FIRING PATTERNS; CUED HAND MOVEMENTS; CAT VISUAL-CORTEX; NEURONAL-ACTIVITY; MOTOR CORTEX; SENSORIMOTOR CORTEX; RHESUS-MONKEYS; DEPENDENT MODULATION AB We examined single-unit activity in the dorsal premotor cortex for evidence of fast neuronal oscillations. Four rhesus monkeys performed a task in which visuospatial instruction stimuli indicated the direction of forelimb movement to be executed on each trial. After an instructed delay period of 1.5-3 s, movements to either the right or left of a central origin were triggered by a second visuospatial stimulus. From a database of 579 single units, 78 units (13%) contained periodic peaks in their autocorrelation histograms (ACHs), with oscillation frequencies typically 20-30 Hz (mean 27 Hz). An additional 26 units (5%) had oscillatory features that were identified in joint interspike-interval (ISI) plots. Three observations, taken together, suggest entrainment by rhythmic drive extrinsic to these neurons: shuffling ISIs attenuated ACH peaks, indicating a dependency on serial-order effects; oscillation frequency did not change during either increases or decreases in firing rate; and joint ISI plots contained features consistent with a rhythmicity interrupted by intervening discharges. In some cells, oscillations occurred for only one of the two directions of movement. During the delay period, such directional selectivity was observed in 37 units (60% of delay-period oscillators). For at least 17 of these units, we could exclude the possibility that oscillatory directional selectivity resulted from the difficulty in detecting oscillations due to low discharge rates (for one of the two movement directions). Directional selectivity in fast oscillations shows that they can reflect specific aspects of an intended action. C1 NIMH, Lab Syst Neurosci, NIH, Bethesda, MD 20892 USA. RP Lebedev, MA (reprint author), NIMH, Lab Syst Neurosci, NIH, 49 Convent Dr,Bldg 49,Room B1EE17,MSC 4401, Bethesda, MD 20892 USA. RI Lebedev, Mikhail/H-5066-2016 OI Lebedev, Mikhail/0000-0003-0355-8723 NR 79 TC 36 Z9 36 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD JAN PY 2000 VL 130 IS 2 BP 195 EP 215 DI 10.1007/s002210050022 PG 21 WC Neurosciences SC Neurosciences & Neurology GA 275XN UT WOS:000084845600010 PM 10672473 ER PT J AU Beason-Held, LL Purpura, KP Krasuski, JS Desmond, RE Mangot, DJ Daly, EM Optican, LM Rapoport, SI VanMeter, JW AF Beason-Held, LL Purpura, KP Krasuski, JS Desmond, RE Mangot, DJ Daly, EM Optican, LM Rapoport, SI VanMeter, JW TI Striate cortex in humans demonstrates the relationship between activation and variations in visual form SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE visual perception; object recognition; functional magnetic resonance imaging; neuroimaging; human ID TEXTURES; PERCEPTION; ELEMENTARY; STATISTICS; COMPONENTS; REGIONS; SYSTEM AB Electrophysiologic and functional imaging studies have shown that the visual cortex produces differential responses to the presence or absence of structure within visual textures. To further define and characterize regions involved in the analysis of form, functional magnetic resonance imaging (fMRI) was used to detect changes in activation during the viewing of four levels of isodipole textures. The texture levels systematically differed in the density of visual features such as extended contours and blocks of solid color present within the images. A linear relationship between activation level and density of structure was observed in the striate cortex of human subjects. This finding suggests that a special subpopulation of striate cortical neurons participates in the ability to extract and process structural continuity within visual stimuli. C1 NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, New York, NY USA. NEI, Sect Neural Modeling, NIH, Bethesda, MD USA. Sensor Syst, Sterling, VA USA. RP Beason-Held, LL (reprint author), NIA, Neurosci Lab, NIH, Bldg 10,Rm 6C414,9000 Rockvill Pike, Bethesda, MD 20892 USA. RI daly, eileen/B-6716-2011; OI Daly, Eileen/0000-0003-3625-3467 FU NINDS NIH HHS [NS 01677] NR 30 TC 12 Z9 12 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD JAN PY 2000 VL 130 IS 2 BP 221 EP 226 DI 10.1007/s002210050024 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 275XN UT WOS:000084845600012 PM 10672475 ER PT J AU Bratosiewicz, J Barcikowska, M Cervenakowa, L Brown, P Gajdusek, DC Liberski, PP AF Bratosiewicz, J Barcikowska, M Cervenakowa, L Brown, P Gajdusek, DC Liberski, PP TI A new point mutation of the PRNP gene in Gerstmann-Straussler-Scheinker case in Poland SO FOLIA NEUROPATHOLOGICA LA English DT Article; Proceedings Paper CT Annual Conference of Polish-Association-of-Neuropathologists CY MAY 20, 2000 CL WARSAW, POLAND DE Gerstmann-Straussler-Scheinker disease; new point mutation ID CREUTZFELDT-JAKOB-DISEASE AB We report here a case of Gerstmann-Straussler-Scheinker (GSS) disease wi th a new mutation at the codon 232 (Met to Thr) of the PRNP gene. This case was characterized by PrP-immunopositive kuru and multicentric plaques, these plaques were also seen in the cerebral cortex, hippocampus and in the deep subcortical nuclei. Diffuse PrP depositions were also detected. In the temporal cortex, a few plaques were immunopositive for both PIP and A beta; the latter was expressed at the periphery of the PrP-immunopositive cores. This mutation was absent from 40 healthy Polish controls and from 16 other Polish CTD cases, and we therefore believe that 232Thr is a new pathogenic mutation and not a benign polymorphism. C1 Med Acad Lodz, Lab Neuropathol & Electron Microscopy, Dept Biol Mol, PL-92216 Lodz, Poland. Polish Acad Sci, Med Res Ctr, Dept Neuropathol, Warsaw, Poland. NINDS, Cent Nervous Syst Studies Lab, NIH, Bethesda, MD 20892 USA. NR 5 TC 7 Z9 7 U1 1 U2 1 PU SEVERUS PUBLISHING HOUSE PI WARSAW PA UL CONRADA 4/146, 01-922 WARSAW, POLAND SN 0028-3894 J9 FOLIA NEUROPATHOL JI Folia Neuropathol. PY 2000 VL 38 IS 4 BP 164 EP 166 PG 3 WC Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 389TQ UT WOS:000166254300004 PM 11693719 ER PT J AU Suzuki, YJ Lorenzi, MV Shi, SS Day, RM Blumberg, JB AF Suzuki, YJ Lorenzi, MV Shi, SS Day, RM Blumberg, JB TI Homocysteine exerts cell type-specific inhibition of AP-1 transcription factor SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE AP-1; free radicals; gene expression; homocysteine; redox; signal transduction; thiols ID DNA-BINDING ACTIVITY; PLASMA HOMOCYSTEINE; VASCULAR-DISEASE; RISK FACTOR; REDOX REGULATION; PROTEIN; KINASE; IDENTIFICATION; GROWTH; HYPERHOMOCYSTEINEMIA AB Homocysteine (Hcy) exerts either promoting or suppressive effects on mitogenesis in a cell type-specific manner. Hey elicits proliferation of vascular smooth muscle cells, but is rather inhibitory to growth of endothelial cells and NIH/3T3 cells. In NIH/3T3 cells, we found that physiologically relevant concentrations (20-100 mu M) of Hcy inhibit the activity of activating protein-1 (AP-1) transcription factor, although it is capable of eliciting immediate-early signaling events. Hey induced p44/42 mitogen-activated protein kinase (MAPK) phosphorylation in control cells, but not in dominant negative p21(ras) transfected cells, indicating induction of the Ras-MAPK pathway. Hey also induced the activity of serum response factor and expression of c-fos and c-jun genes. Despite the activation of these upstream events, Hey potently inhibited AP-1 activity. Oxidized forms of Hey (Hcy thiolactone, homocystine) were less effective in affecting AP-1. Hey-mediated inhibition of AP-1 activity was not observed in A7r5 vascular smooth muscle cells. These results demonstrate that Hey exerts cell type- and redox-specific inhibition of AP-1 dependent biological events. (C) 2000 Elsevier Science Inc. C1 Tufts Univ, USDA, Human Nutr Res Ctr Aging, Antioxidants Res Lab, Boston, MA 02111 USA. Tufts Univ, Sch Nutr Sci & Policy, Cell & Mol Nutr Program, Boston, MA USA. NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Tufts Univ New England Med Ctr, Div Pulm & Crit Care, Boston, MA 02111 USA. RP Tufts Univ, USDA, Human Nutr Res Ctr Aging, Antioxidants Res Lab, 711 Washington St, Boston, MA 02111 USA. EM ysuzuki@hnrc.tufts.edu NR 31 TC 17 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD JAN PY 2000 VL 28 IS 1 BP 39 EP 45 DI 10.1016/S0891-5849(99)00200-2 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 276HL UT WOS:000084872000005 PM 10656289 ER PT J AU Alayash, AI AF Alayash, AI TI Hemoglobin-based blood substitutes and the hazards of blood radicals SO FREE RADICAL RESEARCH LA English DT Review DE hemoglobin; blood substitutes; free radicals ID CROSS-LINKED HEMOGLOBIN; CELL-FREE HEMOGLOBIN; NITRIC-OXIDE; OXYGEN CARRIERS; FERRYL INTERMEDIATE; HYDROGEN-PEROXIDE; MYOGLOBIN; PHARMACOLOGY; OXIDATION; EFFICACY AB Cell-free hemoglobins, chemically altered or genetically expressed in microbial host systems, have been developed as oxygen-carrying therapeutics. Site-directed modifications are introduced and serve to stabilize the protein molecules in a tetrameric and/or a polymeric functional form. Animal studies, as well as recent clinical studies, have suggested these proteins probably deliver oxygen to tissues. However, concerns still persist regarding the interference of hemoglobin and its oxidation products with the vascular redox balance, potentially impeding its clinical usefulness. This article reviews our current understanding of heme-mediated toxicities and some of the emerging protective strategies used to overcome hemoglobin side reactions. C1 US FDA, Ctr Biol Evaluat & Res, Lab Plasma Derivat, Bethesda, MD 20892 USA. RP Alayash, AI (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Plasma Derivat, Natl Inst Hlth Campus,Bldg 29,Rm 112,8800 Rockvil, Bethesda, MD 20892 USA. NR 42 TC 28 Z9 29 U1 0 U2 4 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1071-5762 J9 FREE RADICAL RES JI Free Radic. Res. PY 2000 VL 33 IS 4 BP 341 EP 348 DI 10.1080/10715760000300881 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 358PX UT WOS:000089567400001 PM 11022843 ER PT J AU Dumaswala, UJ Wilson, MJ Wu, YL Wykle, J Zhuo, L Douglass, LM Daleke, DL AF Dumaswala, UJ Wilson, MJ Wu, YL Wykle, J Zhuo, L Douglass, LM Daleke, DL TI Glutathione loading prevents free radical injury in red blood cells after storage SO FREE RADICAL RESEARCH LA English DT Article ID HUMAN-ERYTHROCYTES; PHOSPHOLIPID ASYMMETRY; HYDROGEN-PEROXIDE; SICKLE ERYTHROCYTES; MEMBRANE; PHOSPHATIDYLSERINE; OXIDATION; PROTEIN; IRON; TRANSPORT AB We have previously demonstrated that the loss of glutathione (GSH) and GSH-peroxidase (GSH-PX) in banked red blood cells (RBCs) is accompanied by oxidative modifications of lipids, proteins and loss of membrane integrity([1]). The objective of this study was to determine whether artificial increases in antioxidant (GSH) or antioxidant enzyme (catalase) content could protect membrane damage in the banked RBCs following an oxidant challenge. RBCs stored at 1-6 degreesC for 0, 42 and 84 days in a conventional additive solution (Adsol(R)) were subjected to oxidative stress using ferric/ascorbic acid (Fe/ASC) before and after enriching them with GSH or catalase using a hypotonic lysis-isoosmotic resealing procedure. This lysis-resealing procedure in the presence of GSH/catalase raised intracellular GSH and catalase concentrations 4-6 fold, yet produced only a small reduction in mean cell volume (MCV), mean cell hemoglobin (MCH) and mean cell hemoglobin concentrations (MCHC). Indicators of oxidative stress and membrane integrity were measured, including acetylcholinesterase (AChE) activity, GSH concentration, phosphatidylserine (PS) externalization (prothrombin-converting activity) and transmembrane lipid movements (C-14-lyso phosphatidylcholine flip-flop and PS transport). GSH-enrichment protected AChE activity in fresh (0 day) and stored (42 and 84 days) RBCs from Fe/ASC oxidation by 10, 23 and 26%, respectively, compared with not-enriched controls. Following oxidative stress, the rate of transbilayer lipid flip-flop did not increase in fresh cells, but increased 9.3 % in 42-day stored cells. Phosphatidylserine exposure, as measured by prothrombinase activity, increased 2.4-fold in fresh and 5.2-fold in 42-day stored cells exposed to Fe/ASC. Previous studies have shown that 42-day storage causes a moderate decrease in PS transport (similar to 50 %), whereas transport rates declined by up to 75 % in stored RBCs when challenged with Fe/ASC. GSH-enrichment prevented the increase in passive lipid flip-flop and the increase in prothrombinase activity, but offered no protection against oxidative damage of PS transport. In contrast to these effects, catalase-enrichment failed to protect GSH levels and AChE activity upon oxidative stress. Membrane protein thiol oxidation was assessed by labeling reactive protein thiols with 5-acetalamidofluorescein followed by immunoblotting with antifluorescein antibodies. Significant oxidation of membrane proteins was confirmed by a greater loss of thiols in stored RBCs than in fresh RBCs. These results demonstrate that it may be possible to prevent storage-mediated loss of AChE, increased lipid flip-flop, and increased PS exposure, by maintaining or increasing GSH levels of banked RBCs. C1 Univ Cincinnati, Med Ctr, Hoxworth Blood Ctr, Cincinnati, OH 45267 USA. Indiana Univ, Dept Biochem & Mol Biol, Bloomington, IN 47405 USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Dumaswala, UJ (reprint author), Univ Cincinnati, Med Ctr, Hoxworth Blood Ctr, POB 670055,3130 Highland Ave, Cincinnati, OH 45267 USA. FU NIGMS NIH HHS [GM47230] NR 44 TC 52 Z9 55 U1 0 U2 2 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1071-5762 J9 FREE RADICAL RES JI Free Radic. Res. PY 2000 VL 33 IS 5 BP 517 EP 529 DI 10.1080/10715760000301061 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 392ZB UT WOS:000166441800008 PM 11200085 ER PT J AU Chevion, M Berenshtein, E Stadtman, ER AF Chevion, M Berenshtein, E Stadtman, ER TI Human studies related to protein oxidation: Protein carbonyl content as a marker of damage SO FREE RADICAL RESEARCH LA English DT Article; Proceedings Paper CT Workshop on Markers of Oxidative Damage and Antioxidant Protection CY JUN 28-30, 1999 CL PRAGUE, CZECH REPUBLIC SP Int Life Sci Inst Europe DE protein carbonyl content; pentosidine; nitrotyrosine; o-tyrosine; dityrosine; diabetes; Alzheimer's disease; aging; man; review ID METHIONINE SULFOXIDE REDUCTASE; METAL-CATALYZED OXIDATION; NF-KAPPA-B; MITOCHONDRIAL DECAY; LIPID-PEROXIDATION; OXIDIZED PROTEINS; DIABETES-MELLITUS; ALZHEIMER-DISEASE; REDOX REGULATION; FREE-RADICALS AB Proteins constitute the major 'working force' for all forms of biological work. Their exact conformation and pattern of folding are tightly connected to their activity and function. Reactive oxygen and nitrogen species (ROS and RNS) are formed during normal metabolism and in higher fluxes under pathological conditions. They cause cellular damage, an important part of which is the oxidation of amino acid residues on proteins, forming protein carbonyls. Other direct modifications of protein side chains, such as o-tyrosine, chloro-, nitrotyrosine, and dityrosine, have been identified. In addition, carbohydrate and lipid derivatives can react with proteins Co form adducts that can be analyzed. Protein carbonyl content (PCC) is the most widely used marker of oxidative modification of proteins. There are several methodologies for the quantitation of PCC; in all of them 2,4-dinitrophenyl hydrazine is allowed to react with the protein carbonyls to form the corresponding hydrazone, which can be analyzed optically by radioactive counting or immunohistochemically. Using PCC as a marker, it could be demonstrated that oxidative damage to proteins correlates well with aging and the severity of some diseases. A critical evaluation of PCC and other markers of protein oxidation is presented, together with examples of protein oxidation in diabetes, neurodegenerative diseases, and aging. C1 Nestle Res Ctr, Mol Nutr Res Grp, CH-1000 Lausanne 26, Switzerland. Hebrew Univ Jerusalem, Dept Cellular Biochem, IL-91120 Jerusalem, Israel. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Chevion, M (reprint author), Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Cellular Biochem & Human Genet, POB 12272, IL-91120 Jerusalem, Israel. NR 71 TC 175 Z9 186 U1 3 U2 12 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1071-5762 J9 FREE RADICAL RES JI Free Radic. Res. PY 2000 VL 33 SU S BP S99 EP S108 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 390DD UT WOS:000166279600011 PM 11191280 ER PT J AU El-Osta, A Wolffe, AP AF El-Osta, A Wolffe, AP TI DNA methylation and histone deacetylation in the control of gene expression: Basic biochemistry to human development and disease SO GENE EXPRESSION LA English DT Review DE Rett syndrome; Fragile X syndrome; methyl-CpG binding proteins; DNA methyltransferase; histone deacetylase; chromatin remodeling; p16(INK4); 5-aza 2 ' deoxycytidine ID CPG-BINDING-PROTEIN; NEWLY REPLICATED CHROMATIN; NUCLEOSOME CORE PARTICLE; TRANSCRIPTION IN-VIVO; RETT-SYNDROME; MAMMALIAN DEVELOPMENT; DEPENDENT REPRESSION; CHROMOSOMAL PROTEIN; NEGATIVE REGULATOR; CRYSTAL-STRUCTURE AB DNA methylation is a major determinant in the epigenetic silencing of genes. The mechanisms underlying the targeting of DNA methylation and the subsequent repression of transcription are relevant to human development and disease, as well as for attempts at somatic gene therapy. The success of transgenic technologies in plants and animals is also compromised by DNA methylation-dependent silencing pathways. Recent biochemical experiments provide a mechanistic foundation for understanding the influence of DNA methylation on transcription. The DNA methyltransferase Dnmt1, and several methyl-CpG binding proteins, MeCP2, MBD2, and MBD3, all associate with histone deacetylase. These observations firmly connect DNA methylation with chromatin modifications. They also provide new pathways for the potential targeting of DNA methylation to repressive chromatin as well as the assembly of repressive chromatin on methylated DNA. Here we discuss the implications of the methylation-acetylation connection for human cancers and the developmental syndromes Fragile X and Rett, which involve a mistargeting of DNA methylation-dependent repression. C1 NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RP Wolffe, AP (reprint author), 501 Canal Blvd,Suite A100, Richmond, CA 94804 USA. NR 126 TC 94 Z9 98 U1 2 U2 10 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 1052-2166 J9 GENE EXPRESSION JI Gene Expr. PY 2000 VL 9 IS 1-2 BP 63 EP 75 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 374VZ UT WOS:000165366200006 PM 11097425 ER PT J AU Restifo, NP Ying, H Hwang, L Leitner, WW AF Restifo, NP Ying, H Hwang, L Leitner, WW TI The promise of nucleic acid vaccines SO GENE THERAPY LA English DT Review DE DNA vaccines; self-replicating vectors; dendritic cells; RNA vaccines; danger signals; apoptosis ID ESTABLISHED PULMONARY METASTASES; CYTOTOXIC T-LYMPHOCYTES; MARROW-DERIVED CELLS; DNA VACCINES; DENDRITIC CELLS; PLASMID DNA; IN-VIVO; ANTITUMOR IMMUNITY; IMMUNIZATION; ANTIGEN AB Establishing the effective use of 'naked' nucleic acids as vaccines would undoubtedly be one of the most important advances in the history of vaccinology. While nucleic acids show much promise for use as Vaccine vectors in experimental animals, not a single naked nucleic acid vector has been approved for use in humans, indeed, data from human clinical trials is scant: nucleic acid vaccines have not been clearly demonstrated to have any convincing efficacy in the prevention or treatment of infectious disease or cancer. Here we illustrate possible mechanisms underlying effective nucleic acid vaccination. we focus on progress that has been made in the improvement of their function. Additionally, we identify promising new strategies and try to forecast future developments that could lead to the real success of nucleic acid vaccines in the prevention and treatment of human disease. C1 NCI, Surg Branch, Bethesda, MD 20892 USA. RP Restifo, NP (reprint author), NCI, Surg Branch, Bldg 10,Room 2B42,10 Ctr Dr, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008; Leitner, Wolfgang/F-5741-2011; OI Leitner, Wolfgang/0000-0003-3125-5922; Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z99 CA999999, Z01 BC010763-01] NR 32 TC 60 Z9 62 U1 1 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD JAN PY 2000 VL 7 IS 2 BP 89 EP 92 DI 10.1038/sj.gt.3301117 PG 4 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 281DZ UT WOS:000085143800001 PM 10673713 ER PT B AU O'Brien, SJ Dean, M Smith, M Winkler, C Nelson, GW Martin, MP Carrington, M AF O'Brien, SJ Dean, M Smith, M Winkler, C Nelson, GW Martin, MP Carrington, M BE Boulyjenkov, V Berg, K Christen, Y TI The human genes that limit AIDS SO GENES AND RESISTANCE TO DISEASE LA English DT Proceedings Paper CT Joint WHO/Foundation IPSEN Meeting on Genes and Resistance to Disease CY FEB 07-08, 1999 CL VENICE, ITALY SP WHO, Fdn IPSEN ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-1 DISEASE PROGRESSION; CHEMOKINE RECEPTOR GENE; TYPE-1 INFECTION; HUMAN-GENOME; CCR5; RESISTANCE; LYMPHOCYTES; INDIVIDUALS; PHENOTYPE C1 NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Frederick, MD 21702 USA. RP O'Brien, SJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Bldg 560,Room 21-105, Frederick, MD 21702 USA. NR 52 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 3-540-66724-5 PY 2000 BP 9 EP 17 PG 9 WC Biochemistry & Molecular Biology; Infectious Diseases SC Biochemistry & Molecular Biology; Infectious Diseases GA BQ83L UT WOS:000089738900002 ER PT J AU Knutsen, T Rao, VK Ried, T Mickley, L Schneider, E Miyake, K Ghadimi, BM Padilla-Nash, H Pack, S Greenberger, L Cowan, K Dean, M Fojo, T Bates, S AF Knutsen, T Rao, VK Ried, T Mickley, L Schneider, E Miyake, K Ghadimi, BM Padilla-Nash, H Pack, S Greenberger, L Cowan, K Dean, M Fojo, T Bates, S TI Amplification of 4q21-q22 and the MXR gene in independently entry derived mitoxantrone-resistant cell lines SO GENES CHROMOSOMES & CANCER LA English DT Article ID BREAST-CANCER CELLS; DECREASED DRUG ACCUMULATION; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; OVEREXPRESSION; MECHANISM AB Molecular cytogenetic studies were conducted on three multidrug-resistant cancer sublines which are highly resistant to the chemotherapeutic agent mitoxantrone, an anthracenedione. The three independently selected sublines were derived by exposure to mitoxantrone or Adriamycin and do not overexpress MDR I or MRP. Two sublines, MCF-7 AdVp3000 and MCF-7 MX showed an amplification peak at 4q21-q22, as demonstrated by comparative genomic hybridization (CGH), while the third, SI-MI-80, did not. FISH using a whole chromosome 4 paint demonstrated multiple rearrangements involving chromosome 4 in MCF-7 AdVp3000 and MCF-7 MX, white SI-MI-80 contained only a simple reciprocal translocation. The parental cell lines had no chromosome 4 rearrangements and no copy number gain or amplification of chromosome 4. Spectral karyotyping (SKY) analysis revealed a balanced translocation, t(4;17)(q21-q22;p13) in SI-MI-80 and multiple clonal translocations involving chromosome 4 in MCF-7 AdVp3000 and MCF-7 MX A novel cDNA, designated MXR, which encodes an ABC half-transporter and is highly overexpressed in the three sublines, was localized to chromosome 4 by somatic cell hybrid analysis. Southern blot analysis demonstrated amplification of the MXR gene in MCF-7 AdVp3000 and MCF-7 MX, but not in SI-MI-80. FISH studies with a BAC probe for MXR localized the gene to 4q21-22 in the normal chromosome 4 and revealed in both MCF-7 AdVp3000 and MCF-7 MX amplification of MXR at one translocation juncture, shown by SKY to be t(4;5)(4qter-->4cen-->t4q21-22:: 5q13-->5qter) in MCF-7 AdVp3000 and t(6;4;6;3)(6pter-->6q15::4921-q22::hsr::bq?::3q?27-->3qter) in MCF MX; neither of the breakpoints in the partner chromosomes showed amplification by CGH. The data are consistent with the hypothesis of a transporter, presumably that encoded by the MXR gene, mediating mitoxantrone resistance. The MXR gene encodes a half-transporter and the absence of cytogenetic evidence of coamplification of other regions suggests that a partner may not be overexpressed, and instead the MXR half-transporter homodimerizes to mediate drug transport. Genes Chromosomes Cancer 27:110-116, 2000. Published 2000 Wiley-Liss, Inc dagger. C1 NCI, Med Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. Wadsworth Ctr, Albany, NY USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Wyeth Ayerst Res, Pearl River, NY USA. NCI, Lab Genom Divers, FCRDC, NIH, Frederick, MD 21701 USA. RP Knutsen, T (reprint author), NCI, Med Branch, Div Clin Sci, NIH, Bldg 10,Room 12N-226,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Dean, Michael/G-8172-2012; Pack, Svetlana/C-2020-2014 OI Dean, Michael/0000-0003-2234-0631; NR 25 TC 66 Z9 71 U1 1 U2 3 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 JAN PY 2000 VL 27 IS 1 BP 110 EP 116 DI 10.1002/(SICI)1098-2264(200001)27:1<110::AID-GCC14>3.0.CO;2-4 PG 7 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 260PV UT WOS:000083959800014 PM 10564593 ER PT J AU Chase, D Serafinas, C Ashcroft, N Kosinski, M Longo, D Ferris, DK Golden, A AF Chase, D Serafinas, C Ashcroft, N Kosinski, M Longo, D Ferris, DK Golden, A TI The Polo-like kinase PLK-1 is required for nuclear envelope breakdown and the completion of meiosis in Caenorhabditis elegans SO GENESIS LA English DT Article DE Polo-like kinase; meiosis; NEBD; C. elegans ID SACCHAROMYCES-CEREVISIAE CDC5; ANAPHASE-PROMOTING COMPLEX; XENOPUS EGG EXTRACTS; CELL-DIVISION-CYCLE; PROTEIN-KINASE; C-ELEGANS; DROSOPHILA POLO; SPINDLE POLES; M-PHASE; GENE AB The Polo-like kinases are key regulatory molecules required during the cell cycle for the successful completion of mitosis, We have cloned a C. elegans homolog of the Drosophila melanogaster polo gene (designated plk-1 for C, elegans polo-like kinase-l) and present the subcellular localization of the PLK-1 protein during the meiotic and mitotic cell cycles in C, elegans oocytes and embryos, respectively. Disruption of PLK-1 expression by RNA-mediated interference (RNAi) disrupts normal oocyte and embryonic development. Inspection of oocytes revealed a defect in nuclear envelope breakdown (NEBD) before ovulation. This defect in NEED was also observed in oocytes that were depleted of the cyclin-dependent kinase NCC-1 (C. elegans homolog of Cdc2), The plk-1 RNAI oocytes were fertilized; however the resulting embryos were unable to separate their meiotic chromosomes or form and extrude polar bodies. These defects led to embryonic arrest as single cells. Published 2000 Wiley-Liss, Inc.(dagger) C1 NCI, Frederick Canc Res Facil, SAIC, Frederick, MD 21701 USA. NCI, NIA, FCRF, Frederick, MD 21702 USA. NCI, Lab Leukocyte BIol, FCRF, Frederick, MD 21702 USA. NCI, Dev Signal Transduct Grp, Gene Regulat & Chromosome Biol Lab, FCRF, Frederick, MD 21702 USA. NIA, Baltimore, MD 21224 USA. RP NCI, Frederick Canc Res Facil, SAIC, Frederick, MD 21701 USA. EM Ferris@mail.ncifcrf.gov FU NCI NIH HHS [N01CO56000] NR 49 TC 80 Z9 92 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-954X EI 1526-968X J9 GENESIS JI Genesis PD JAN PY 2000 VL 26 IS 1 BP 26 EP 41 DI 10.1002/(SICI)1526-968X(200001)26:1<26::AID-GENE6>3.0.CO;2-O PG 16 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 358KD UT WOS:000089556500006 PM 10660671 ER PT J AU Moldin, SO AF Moldin, SO TI National Institutes of Health Statistical Genetics Initiative Symposium - New quantitative methods to map genes for complex traits - Preface SO GENETIC EPIDEMIOLOGY LA English DT Editorial Material C1 NIMH, Bethesda, MD 20892 USA. RP Moldin, SO (reprint author), NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 2000 VL 19 SU 1 BP SVII EP SVIII PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 360TQ UT WOS:000089683700001 ER PT J AU Martin, ER Kaplan, NL AF Martin, ER Kaplan, NL TI A Monte Carlo procedure for two-stage tests with correlated data SO GENETIC EPIDEMIOLOGY LA English DT Article DE case-control test; transmission/disequilibrium test (TDT); genome scan; allelic association; linkage disequilibrium; linkage ID DEPENDENT DIABETES-MELLITUS; CANDIDATE-GENE ASSOCIATION; HLA-DISEASE ASSOCIATIONS; TRANSMISSION/DISEQUILIBRIUM TESTS; LINKAGE DISEQUILIBRIUM; RELATIVE RISKS; LOCI; PARENTS; POWER; TDT AB One strategy for mapping disease loci using marker-disease associations is to test for association with case-control samples and follow up a positive result with a family-based test. Using a family-based test in the second stage can help provide protection against false-positive results that can result from use of inappropriate controls and provides assurance that association identified in the first stage is occurring between linked loci. It is crucial for this two-stage strategy that the first stage be as powerful as possible to detect association since only positive results are tested in the second stage. In certain situations, the power of the first-stage test can be increased by combining the case-control and family data. However, this introduces correlation between the first- and second-stage tests, and treating them as independent tests causes a bias. Here we propose a Monte Carlo method that accounts for the correlation and provides the correct significance level for the second-stage test. We also discuss the use of a two-stage procedure when doing a genome scan for the data presented in the Genetic Analysis Workshop 9 study. Genet. Epidemiol. 18:48-62, 2000. (C) 2000 Wiley-Liss, Inc. C1 Duke Univ, Med Ctr, Dept Med, Med Genet Sect, Durham, NC 27710 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Martin, ER (reprint author), Duke Univ, Med Ctr, Dept Med, Med Genet Sect, Box 3468, Durham, NC 27710 USA. NR 27 TC 8 Z9 9 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JAN PY 2000 VL 18 IS 1 BP 48 EP 62 DI 10.1002/(SICI)1098-2272(200001)18:1<48::AID-GEPI4>3.0.CO;2-S PG 15 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 270RR UT WOS:000084550400004 PM 10603458 ER PT J AU Baffoe-Bonnie, AB Beaty, TH Bailey-Wilson, JE Kiemeney, LALM Sigvaldason, H Olafsdottir, G Tryggvadottir, L Tulinius, H AF Baffoe-Bonnie, AB Beaty, TH Bailey-Wilson, JE Kiemeney, LALM Sigvaldason, H Olafsdottir, G Tryggvadottir, L Tulinius, H TI Genetic epidemiology of breast cancer: Segregation analysis of 389 Icelandic pedigrees SO GENETIC EPIDEMIOLOGY LA English DT Article DE Mendelian inheritance; BRCA2; segregation analyses; population-based study; Iceland ID SINGLE BRCA2 MUTATION; OVARIAN-CANCER; LINKAGE ANALYSIS; FAMILIES; RISK; HETEROGENEITY; SUSCEPTIBILITY; POPULATION; ONSET; FREQUENCY AB A genetic epidemiologic investigation of breast cancer involving 389 breast cancer pedigrees including information on 14,721 individuals from the Icelandic population-based cancer registry is presented. Probands were women born in or after 1920 and reported to have breast cancer in the cancer registry. The average age of the 389 probands was 45.5 years (SD 8.92). Segregation analyses was performed evaluating residual maternal effects, a dichotomous cohort effect, and assuming the age at diagnosis followed a logistic distribution after log-transformation. Familial aggregation could be best explained by the inheritance of a high-risk allele leading to early onset breast cancer among the homozygotes, which represent approximately 2.6% of the population. A Mendelian codominant model was selected as the best fitting model, with an estimated age at diagnosis of 51.8 years among these high-risk homozygotes, 64.0 years for heterozygotes and 76.3 years for the low-risk genotype. The predicted cumulative risk for homozygote carriers of the high-risk allele is 32.2% by age 60, compared to 16.4% for heterozygotes and 5.0% for non-carriers of the same age. These predicted age profiles in the current study complement recent reports from Iceland of a majority of BRCA2 mutation carriers being diagnosed with breast cancer below the age of 50 years, and 60 years being the mean age at diagnosis for non-carriers. This model also predicted a high background risk of breast cancer for women in this population (estimated susceptibility gamma = 0.44 +/- 0.08). This implies that if carriers and non-carriers did not die of competing causes, the estimated risk of being diagnosed with breast cancer by age 80 years irrespective of carrier status is 11.4%. Genet. Epidemiol. 18:81-94, 2000. (C) 2000 Wiley-Liss, Inc. C1 Johns Hopkins Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. NIH, Natl Human Genome Res Inst, Div Stat Genet, Bethesda, MD USA. Univ Nijmegen, Dept Epidemiol, Nijmegen, Netherlands. Univ Nijmegen, Dept Urol, Nijmegen, Netherlands. Iceland Canc Soc, Canc Registry, Reykjavik, Iceland. RP Beaty, TH (reprint author), Johns Hopkins Sch Hyg & Publ Hlth, Dept Epidemiol, 615 N Wolfe St,Rm 6507, Baltimore, MD 21205 USA. RI Kiemeney, Lambertus/D-3357-2009; OI Kiemeney, Lambertus/0000-0002-2368-1326; Bailey-Wilson, Joan/0000-0002-9153-2920 FU NCI NIH HHS [5R25CA57708, 5T32CA09314] NR 58 TC 9 Z9 9 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JAN PY 2000 VL 18 IS 1 BP 81 EP 94 DI 10.1002/(SICI)1098-2272(200001)18:1<81::AID-GEPI6>3.0.CO;2-H PG 14 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 270RR UT WOS:000084550400006 PM 10603460 ER PT J AU Mason, JM Haoudi, A Konev, AY Kurenova, E Walter, MF Biessmann, H AF Mason, JM Haoudi, A Konev, AY Kurenova, E Walter, MF Biessmann, H TI Control of telomere elongation and telomeric silencing in Drosophila melanogaster SO GENETICA LA English DT Article; Proceedings Paper CT 4th International Conference on Drosophila Heterochromatin CY JUN 20-24, 1999 CL ALFRED STATE COLL, ALFRED, NEW YORK HO ALFRED STATE COLL DE Drosophila; heterochromatin; telomere; transcription; transposition ID POSITION-EFFECT VARIEGATION; SALIVARY-GLAND NUCLEI; TRANSPOSON HET-A; SACCHAROMYCES-CEREVISIAE; CHROMOSOME ENDS; DNA-SEQUENCES; CHROMATIN STRUCTURE; REGULATORY DNA; SIR4 PROTEINS; WHITE GENE AB Chromosome length in Drosophila is maintained by the targeted transposition of two families of non-LTR retrotransposons, HeT-A and TART. Although the rate of transposition to telomeres is sufficient to counterbalance loss from the chromosome ends due to incomplete DNA replication, transposition as a mechanism for elongating chromosome ends raises the possibility of damaged or deleted telomeres, because of its stochastic nature. Recent evidence suggests that HeT-A transposition is controlled at the levels of transcription and reverse transcription. HeT-A transcription is found primarily in mitotically active cells, and transcription of a w(+) reporter gene inserted into the 2L telomere increases when the homologous telomere is partially or completely deleted. The terminal HeT-A array may be important as a positive regulator of this activity in cis, and the subterminal satellite appears to be an important negative regulator in cis. A third chromosome modifier has been identified that increases the level of reverse transcriptase activity on a HeT-A RNA template and greatly increases the transposition of HeT-A. Thus, the host appears to play a role in transposition of these elements. Taken together, these results suggest that control of HeT-A transposition is more complex than previously thought. C1 Natl Inst Environm Hlth Sci, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Thurston Arthrit Res Ctr, Chapel Hill, NC 27599 USA. Univ Calif Irvine, Ctr Dev Biol, Irvine, CA 92697 USA. RP Mason, JM (reprint author), Natl Inst Environm Hlth Sci, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RI Konev, Alexander/J-4401-2015 OI Konev, Alexander/0000-0002-4497-6377 FU NIGMS NIH HHS [GM-56729] NR 70 TC 24 Z9 24 U1 1 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0016-6707 J9 GENETICA JI Genetica PY 2000 VL 109 IS 1-2 BP 61 EP 70 DI 10.1023/A:1026548503320 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 382HL UT WOS:000165816800009 PM 11293796 ER PT J AU Natale, DA Galperin, MY Tatusov, RL Koonin, EV AF Natale, DA Galperin, MY Tatusov, RL Koonin, EV TI Using the COG database to improve gene recognition in complete genomes SO GENETICA LA English DT Article; Proceedings Paper CT 7th Conference on Small Genomes CY NOV 13-17, 1999 CL ARLINGTON, VIRGINIA DE essential genes; microbial genomes; phylogenetic patterns; short proteins ID ANALOGOUS ENZYMES; EVOLUTION; SEQUENCE AB A complete understanding of the biology of an organism necessarily starts with knowledge of its genetic makeup. Proteins encoded in a genome must be identified and characterized, and the presence or absence of specific sets of proteins must be noted in order to determine the possible biochemical pathways or functional systems utilized by that organism. The COG database presents a set of tools suited to these purposes, including the ability to select protein families (COGs) that contain proteins from a specified set of species. The selection is based upon a phylogenetic pattern, which is a shorthand representation of the presence or absence of a particular species in a COG. Here we present the use of phylogenetic patterns as a means to perform targeted searches for undetected protein-coding genes in complete genomes. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 NR 14 TC 54 Z9 55 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0016-6707 J9 GENETICA JI Genetica PY 2000 VL 108 IS 1 BP 9 EP 17 DI 10.1023/A:1004031323748 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 372UW UT WOS:000165253300003 PM 11145426 ER PT J AU Makarova, KS Aravind, L Daly, MJ Koonin, EV AF Makarova, KS Aravind, L Daly, MJ Koonin, EV TI Specific expansion of protein families in the radioresistant bacterium Deinococcus radiodurans SO GENETICA LA English DT Article; Proceedings Paper CT 7th Conference on Small Genomes CY NOV 13-17, 1999 CL ARLINGTON, VIRGINIA DE Deinococcus; genome analysis; protein family; specific expansion ID COMPLETE GENOME SEQUENCE; BACILLUS-SUBTILIS; ESCHERICHIA-COLI; IONIZING-RADIATION; CLONING; GENE; RESISTANCE; HYDROLASE; TOBACCO AB Computer analysis of the complete genome of Deinococcus radiodurans R1 reveals a number of protein families, which are over-represented in this organism, compared to most other bacteria with known genome sequences. These families include both previously characterized and uncharacterized proteins. Most of the families whose functions are known or could be predicted seem to be related to stress-response and elimination of damage products (cell-cleaning). The two most prominent family expansions are the Nudix (MutT) family of pyrophosphohydrolases and a previously unnoticed family of proteins related to Bacillus subtilis DinB that could possess a metal-dependent enzymatic activity whose exact nature remains to be determined. Several proteins of the expanded families, particularly the Nudix family, are fused to other domains and form multidomain proteins that are so far unique for Deinococcus. The domain composition of some of these proteins indicates that they could be involved in novel DNA-repair pathways. Such unique proteins are good targets for knock-out and gene expression studies, which are aimed to shed light on the unusual features of this interesting bacterium. C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20814 USA. Russian Acad Sci, Inst Cytol & Genet, Novosibirsk 630090, Russia. RP Makarova, KS (reprint author), Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. FU NIGMS NIH HHS [5R01-GM39933-09] NR 39 TC 24 Z9 24 U1 1 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0016-6707 J9 GENETICA JI Genetica PY 2000 VL 108 IS 1 BP 25 EP 34 DI 10.1023/A:1004035424657 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 372UW UT WOS:000165253300005 PM 11145417 ER PT J AU Natale, DA Shankavaram, UT Ggalerin, MY Wolf, YI Aravind, L Koonin, EV AF Natale, Darren A. Shankavaram, Uma T. Ggalerin, Michael Y. Wolf, Yuri I. Aravind, L. Koonin, Eugene V. TI Towards understanding the first genome sequence of a crenarchaeon by genome annotation using clusters of orthologous groups of proteins (COGs) SO GENOME BIOLOGY LA English DT Article AB Background: Standard archival sequence databases have not been designed as tools for genome annotation and are far from being optimal for this purpose. We used the database of Clusters of Orthologous Groups of proteins (COGs) to reannotate the genomes of two archaea, Aeropyrum pernix, the first member of the Crenarchaea to be sequenced, and Pyrococcus abyssi. Results: A. pernix and P. abyssi proteins were assigned to COGs using the COGNITOR program; the results were verified on a case-by-case basis and augmented by additional database searches using the PSI-BLAST and TBLASTN programs. Functions were predicted for over 300 proteins from A. pernix, which could not be assigned a function using conventional methods with a conservative sequence similarity threshold, an approximately 50% increase compared to the original annotation. A. pernix shares most of the conserved core of proteins that were previously identified in the Euryarchaeota. Cluster analysis or distance matrix tree construction based on the co-occurrence of genomes in COGs showed that A. pernix forms a distinct group within the archaea, although grouping with the two species of Pyrococci, indicative of similar repertoires of conserved genes, was observed. No indication of a specific relationship between Crenarchaeota and eukaryotes was obtained in these analyses. Several proteins that are conserved in Euryarchaeota and most bacteria are unexpectedly missing in A. pernix, including the entire set of de novo purine biosynthesis enzymes, the GTPase FtsZ (a key component of the bacterial and euryarchaeal cell-division machinery), and the tRNA-specific pseudouridine synthase, previously considered universal. A. pernix is represented in 48 COGs that do not contain any euryarchaeal members. Many of these proteins are TCA cycle and electron transport chain enzymes, reflecting the aerobic lifestyle of A. pernix. Conclusions: Special-purpose databases organized on the basis of phylogenetic analysis and carefully curated with respect to known and predicted protein functions provide for a significant improvement in genome annotation. A differential genome display approach helps in a systematic investigation of common and distinct features of gene repertoires and in some cases reveals unexpected connections that may be indicative of functional similarities between phylogenetically distant organisms and of lateral gene exchange. C1 [Natale, Darren A.; Shankavaram, Uma T.; Ggalerin, Michael Y.; Wolf, Yuri I.; Aravind, L.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 NR 56 TC 20 Z9 20 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2000 VL 1 IS 5 AR 0009.1 PG 19 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA V12EU UT WOS:000207583300007 ER PT J AU Wolf, YI Kondrashov, AS Koonin, EV AF Wolf, Yuri I. Kondrashov, Alexey S. Koonin, Eugene V. TI Interkingdom gene fusions SO GENOME BIOLOGY LA English DT Article AB Background: Genome comparisons have revealed major lateral gene transfer between the three primary kingdoms of life - Bacteria, Archaea, and Eukarya. Another important evolutionary phenomenon involves the evolutionary mobility of protein domains that form versatile multidomain architectures. We were interested in investigating the possibility of a combination of these phenomena, with an invading gene merging with a pre-existing gene in the recipient genome. Results: Complete genomes of fifteen bacteria, four archaea and one eukaryote were searched for interkingdom gene fusions (IKFs); that is, genes coding for proteins that apparently consist of domains originating from different primary kingdoms. Phylogenetic analysis supported 37 cases of IKF, each of which includes a 'native' domain and a horizontally acquired 'alien' domain. IKFs could have evolved via lateral transfer of a gene coding for the alien domain (or a larger protein containing this domain) followed by recombination with a native gene. For several IKFs, this scenario is supported by the presence of a gene coding for a second, stand-alone version of the alien domain in the recipient genome. Among the genomes investigated, the greatest number of IKFs has been detected in Mycobacterium tuberculosis, where they are almost always accompanied by a stand-alone alien domain. For most of the IKF cases detected in other genomes, the stand-alone counterpart is missing. Conclusions: The results of comparative genome analysis show that IKF formation is a real, but relatively rare, evolutionary phenomenon. We hypothesize that IKFs are formed primarily via the proposed two-stage mechanism, but other than in the Actinomycetes, in which IKF generation seems to be an active, ongoing process, most of the stand-alone intermediates have been eliminated, perhaps because of functional redundancy. C1 [Wolf, Yuri I.; Kondrashov, Alexey S.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov NR 27 TC 4 Z9 4 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2000 VL 1 IS 6 AR 0013.1 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA V12EV UT WOS:000207583400009 ER PT J AU Leipe, DD Aravind, L Grishin, NV Koonin, EV AF Leipe, DD Aravind, L Grishin, NV Koonin, EV TI The bacterial replicative helicase DnaB evolved from a RecA duplication SO GENOME RESEARCH LA English DT Article ID N-TERMINAL DOMAIN; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; STRAND-EXCHANGE; REPAIR GENE; ATP-BINDING; PSI-BLAST; PROTEIN; RECOMBINATION; RAD51 AB The RecA/Rad51/DCM1 family of ATP-dependent recombinases plays a crucial role in genetic recombination and double-stranded DNA break repair in Archaea, Bacteria, and Eukaryota. DnaB is the replication fork helicase in all Bacteria. We show here that DnaB shares significant sequence similarity with RecA and Rad51/DMCI and two other related families of ATPases, Sms and KaiC. The conserved region spans the entire ATP- and DNA-binding domain that consists of about 250 amino acid residues and includes 7 distinct motifs. Comparison with the three-dimensional structure of Escherichia coli RecA and phage T7 DnaB (gp4) reveals that the area of sequence conservation includes the central parallel beta-sheet and most of the connecting helices and loops as well as a smaller domain that consists of a amino-terminal helix and a carboxy-terminal beta-meander. Additionally, we show that animals, plants, and the malarial Plasmodium but not Saccharomyces cerevisiae encode a previously undetected DnaB homolog that might function in the mitochondria. The DnaB homolog from Arabidopsis also contains a DnaG-primase domain and the DnaB homolog from the nematode seems to contain an inactivated version of the primase. This domain organization is reminiscent of bacteriophage primases-helicases and suggests that DnaB might have been horizontally introduced into the nuclear eukaryotic genome via a phage vector. We hypothesize that DnaB originated from a duplication of a RecA-like ancestor after the divergence of the bacteria from Archaea and eukaryotes, which indicates that the replication fork helicases in Bacteria and Archaea/Eukaryota have evolved independently. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Texas A&M Univ, Dept Biol, College Stn, TX USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NR 75 TC 125 Z9 131 U1 0 U2 3 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 JAN PY 2000 VL 10 IS 1 BP 5 EP 16 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 284QV UT WOS:000085344200002 PM 10645945 ER PT J AU Rhim, H Dunn, KJ Aronzon, A Mac, S Cheng, M Lamoreux, ML Tilghman, SM Pavan, WJ AF Rhim, H Dunn, KJ Aronzon, A Mac, S Cheng, M Lamoreux, ML Tilghman, SM Pavan, WJ TI Spatially restricted hypopigmentation associated with an Ednrb(s)-modifying locus on mouse chromosome 10 SO GENOME RESEARCH LA English DT Article ID ENDOTHELIN-B RECEPTOR; TYROSINE KINASE RECEPTOR; STEM-CELL FACTOR; C-KIT ANTIBODY; NEURAL CREST; MELANOCYTE DEVELOPMENT; W-LOCUS; EPIDERMAL MELANOCYTES; STRIA VASCULARIS; PROTO-ONCOGENE AB We have used the varied expressivity of white spotting (hypopigmentation) observed in intrasubspecific crosses of Ednrb(5) mice (Mayer Ednrb(5)/Ednrb(5) and C3HeB/Fe) Ednrb(5)/Ednrb(5) to analyze the effects of modifier loci on the patterning of hypopigmentation. We have confirmed that an Ednrb(5) modifier locus is present on mouse Chromosome 10. This locus is now termed k10, using the nomenclature established by Dunn in 1920. The k10(Mayer) allele is a recessive modifier that accounts For almost all of the genetic variance of dorsal hypopigmentation. Using intercross analyses we identified a second allele of this locus or a closely linked gene termed k10(C3H). Th, k10(C3H) allele is semidominant and is associated with the penetrance and expressivity of a white forelock phenotype similar to that seen in Waardenburg syndrome. Molecular linkage analysis was used to determine that the k10 critical interval was Ranked by D10Mit10 and D10Mit162/D10Mir122 and cosegregates with mast cell growth Factor (Mgf). Complementation crosses with a Mpf(SI) allele (a 3-5-cM deletion) confirm the semidominant white forelock feature of the k10(C3H) allele and the dorsal spotting feature of K10(Mayer) allele. MgF was assessed as a candidate gene for k10(Mayer) and k10(C3H) by sequence and genomic analyses. No molecular differences were observed between the Mayer and C57BL/6J alleles of MgF; however, extensive genomic differences were observed between the C3HeB/FeJ and C57BL/6J alleles. This suggests that alteration of MgF expression in C3H mice may account for the k10(C3H) action on white forelock hypopigmentation. Crosses of Ednrb(5) with Kit(WJ-2) (the receptor for MGF)-deficient mice confirmed the hypothesis that synergistic interaction between the Endothelin and MCF signaling pathways regulates proper neural crest-derived melanocyte development in vivo. C1 Natl Human Genome Res Inst, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. Catholic Univ, Res Inst Mol Genet, Catholic Res Inst Med Sci, Seoul, South Korea. Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA. Princeton Univ, Howard Hughes Med Inst, Princeton, NJ 08544 USA. Texas A&M Univ, Dept Vet Pathobiol, College Stn, TX 77843 USA. RP Pavan, WJ (reprint author), Natl Human Genome Res Inst, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. FU NEI NIH HHS [EY10233] NR 68 TC 17 Z9 17 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 JAN PY 2000 VL 10 IS 1 BP 17 EP 29 PG 13 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 284QV UT WOS:000085344200003 PM 10645946 ER PT B AU Dean, M Allikmets, R Carrington, M AF Dean, M Allikmets, R Carrington, M BE Gustafson, JP TI The identification of genes for complex genetic diseases SO GENOMES SE STADLER GENETICS SYMPOSIA SERIES LA English DT Proceedings Paper CT 22nd Stadler Genetics Symposium CY JUN 08-10, 1998 CL UNIV MISSOURI, COLUMBIA, MO HO UNIV MISSOURI ID IMMUNODEFICIENCY-VIRUS TYPE-1; CHEMOKINE RECEPTOR GENE; MULTICENTER AIDS COHORT; HIV-1 INFECTION; MOLECULAR-CLONING; FUNCTIONAL EXPRESSION; RESISTANCE; HEMOPHILIA; ENTRY; DNA AB The identification of genes that are involved in complex genetic diseases remains a difficult task for researchers in the field of human genetics. While genes involved in a wide array of Mendelian disorders have been identified, the same approaches are not necessarily suitable for diseases that involve several genes and/or environmental influences. We have used the direct analysis of candidate gene loci, in which there was compelling biological evidence for involvement in the disease, to identify loci that play a role in HIV infection, development of AIDS, and age-related macular degeneration. C1 NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP Dean, M (reprint author), NCI, Lab Genom Divers, Frederick, MD 21702 USA. NR 58 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA BN 0-306-46360-1 J9 STADLER GEN PY 2000 BP 35 EP 41 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA BQ62A UT WOS:000088991900003 ER PT J AU Morell, RJ Friderici, KH Wei, SN Elfenbein, JL Friedman, TB Fisher, RA AF Morell, RJ Friderici, KH Wei, SN Elfenbein, JL Friedman, TB Fisher, RA TI A new locus for late-onset, progressive, hereditary hearing loss DFNA20 maps to 17q25 SO GENOMICS LA English DT Article ID HORMONE RECEPTOR-BETA; THYROID-HORMONE; CHROMOSOMAL LOCALIZATION; GENES; REGION; GENOME; ERBA2; PANEL AB We report the localization of DFNA20, a gene causing dominant, nonsyndromic, progressive hearing loss in a three-generation Midwestern family, to chromosome 17q25, Affected family members show a bilateral, sloping, progressive, sensorineural hearing loss, first evident at 6000 and 8000 Hz, that can be identified in some family members in the early teens and is clearly evident by the early twenties. As age increases, the degree of hearing loss increases with threshold shifts seen at all frequencies. Linkage to known hereditary hearing loss loci was excluded. A genome-wide screen detected positive linkage to D17S784 (LOD(Z) = 6.62; theta = 0), Haplotype analysis refines the DFNA20 critical region to 12 cM between D17S1806 and D17S668, Radiation hybrid mapping with Stanford G3 and TNG panels was used to evaluate the genes ACTG1, GRIN2C, FKHL13, P4HB, SPARC, and ARHGDIA as candidates for DFNA20, (C) 2000 Academic Press. C1 Michigan State Univ, Dept Pediat & Human Dev, E Lansing, MI 48824 USA. Michigan State Univ, Dept Microbiol, E Lansing, MI 48824 USA. Michigan State Univ, Dept Audiol & Speech Sci, E Lansing, MI 48824 USA. NIDCD, Mol Genet Lab, NIH, Rockville, MD 20850 USA. RP Fisher, RA (reprint author), Michigan State Univ, Dept Pediat & Human Dev, B236 Life Sci Bldg, E Lansing, MI 48824 USA. OI Morell, Robert/0000-0003-1537-7356 FU NIDCD NIH HHS [Z01DC00039-02, Z01DC00035-02] NR 26 TC 27 Z9 28 U1 0 U2 0 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 JAN 1 PY 2000 VL 63 IS 1 BP 1 EP 6 DI 10.1006/geno.1999.6058 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 286FC UT WOS:000085432100001 PM 10662538 ER PT J AU Tian, HJ Jaquins-Gerstl, A Munro, N Trucco, M Brody, LC Landers, JP AF Tian, HJ Jaquins-Gerstl, A Munro, N Trucco, M Brody, LC Landers, JP TI Single-strand conformation polymorphism analysis by capillary and microchip electrophoresis: A fast, simple method for detection of common mutations in BRCA1 and BRCA2 SO GENOMICS LA English DT Article ID PCR-SSCP ANALYSIS; BREAST-CANCER; OVARIAN-CANCER; ZONE ELECTROPHORESIS; GENE; HETERODUPLEX; FAMILIES; DNA; FREQUENCY AB As a result of intensive studies on hereditary breast and ovarian cancers, two breast cancer susceptibility genes, BRCA1 and BRCA2, have been identified. In each gene, a small number of specific mutations have been found at relatively high frequency in certain ethnic populations, The mutations, 185delAG and 5382insC in BRCA1 and 6174delT in BRCA2, have been identified as common mutations in the Ashkenazi Jewish population, with a combined frequency of 2.0 to 2.5%, Women who have one of the above three common mutations are at a high risk of developing breast or ovarian cancer. Consequently, accurate and cost-effective detection of these three mutations may have important implications for risk assessment in susceptible women and men. In this report, we describe a fast and simple capillary electrophoresis (CE)-based method using a polymer network for screening the three common mutations in BRCA1 and BRCA2, Fluorescent dye-labeled primers (B-FAM-tagged) were used to amplify three DNA fragments of 258, 296, and 201 bp for detection of the 185delAG, 5382insC, and 6174delT mutations, respectively. After the PCR products were denatured, a single-strand conformation polymorphism (SSCP) profile could be obtained for each mutation in less than 10 min by CE in a polymer network. We demonstrate the potential provided by translating this assay to the microchip format where the SSCP analysis is complete in 120 s, representing only a fraction of the reduction ill analysis time that can be achieved with microchip technology. The speed and simplicity of the SSCP methodology for detection of these mutations make it attractive for use in the clinical diagnostic laboratory. (C) 2000 Academic Press. C1 Univ Virginia, Dept Chem, Charlottesville, VA 22901 USA. Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Childrens Hosp Pittsburgh, Med Ctr, Dept Pediat, Pittsburgh, PA 15213 USA. Natl Human Genome Res Inst, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Univ Virginia, Hlth Sci Ctr, Dept Pathol, Charlottesville, VA 22901 USA. RP Landers, JP (reprint author), Univ Virginia, Dept Chem, Mccormick Rd, Charlottesville, VA 22901 USA. FU NIAMS NIH HHS [AR07591] NR 48 TC 93 Z9 97 U1 1 U2 5 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 JAN 1 PY 2000 VL 63 IS 1 BP 25 EP 34 DI 10.1006/geno.1999.6067 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 286FC UT WOS:000085432100004 PM 10662541 ER PT J AU Gardner, HP Wertheim, GBW Ha, SI Copeland, NG Gilbert, DJ Jenkins, NA Marquis, ST Chodosh, LA AF Gardner, HP Wertheim, GBW Ha, SI Copeland, NG Gilbert, DJ Jenkins, NA Marquis, ST Chodosh, LA TI Cloning and characterization of Hunk, a novel mammalian SNF1-related protein kinase SO GENOMICS LA English DT Article ID TYROSINE KINASE; CARBON METABOLISM; SACCHAROMYCES-CEREVISIAE; NUCLEOTIDE-SEQUENCE; CONSERVED FEATURES; MOLECULAR ANALYSIS; SKELETAL-MUSCLE; DOWN-SYNDROME; EXPRESSION; GENE AB We previously identified a novel protein kinase, Hunk, by means of a degenerate PCR screen designed to isolate kinases expressed in the murine mammary gland. We now describe the molecular cloning, chromosomal localization, and activity of this kinase and characterize its spatial and temporal pattern of expression in the mouse. We have isolated a 5.0-kb full-length cDNA clone that contains the 714-amino-acid open reading frame encoding Hunk. Analysis of this cDNA reveals that Hunk is most closely related to the SNF1 family of serine/threonine kinases and contains a newly described SNF1 homology domain. Accordingly, antisera specific for Hunk detect an 80-kDa polypeptide with associated phosphotransferase activity. Hunk is located on distal mouse chromosome 16 in a region of conserved synteny with human chromosome 21q22. During fetal development and in the adult mouse, Hunk mRNA expression is developmentally regulated and tissue-specific. Moreover, in situ hybridization analysis reveals that Hunk expression is restricted to subsets of cells within a variety of organs in the adult mouse. These findings suggest a role for Hunk in murine development. (C) 2000 Academic Press. C1 Univ Penn, Sch Med, Dept Mol & Cellular Engn, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. RP Univ Penn, Sch Med, Dept Mol & Cellular Engn, 421 Curie Blvd,612 Biomed Res Bldg 2-3, Philadelphia, PA 19104 USA. EM chodosh@mail.med.upenn.edu FU NCI NIH HHS [CA71513, CA78410, CA83849] NR 65 TC 23 Z9 29 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 EI 1089-8646 J9 GENOMICS JI Genomics PD JAN 1 PY 2000 VL 63 IS 1 BP 46 EP 59 DI 10.1006/geno.1999.6078 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 286FC UT WOS:000085432100007 PM 10662544 ER PT J AU Zhang, NA Copeland, NG Gilbert, DJ Jenkins, NA Gridley, T AF Zhang, NA Copeland, NG Gilbert, DJ Jenkins, NA Gridley, T TI Cloning, expression, and chromosomal localization of a mouse gene homologous to the germ cell migration regulator wunen and to Type 2 phosphatidic acid phosphatases SO GENOMICS LA English DT Article ID IDENTIFICATION; PROTEIN; PHOSPHOHYDROLASES; ISOFORM; GENOME AB The wunen gene of Drosophila melanogaster encodes a multipass membrane-spanning protein that negatively regulates primordial germ cell migration. Here we describe the cloning of a mouse gene that encodes a protein homologous to wunen and to the Type 2 phosphatidic acid phosphatases, This gene encodes a 251-amino-acid protein that most closely resembles the human Type 2 phosphatidic acid phosphatase PAP-2c, Northern blot analysis revealed the presence of a single 1.9-kb Ppap2c transcript. The Ppap2c gene was localized to the central portion of mouse Chromosome 10 by interspecific backcross analysis, (C) 2000 Academic Press. C1 Jackson Lab, Bar Harbor, ME 04609 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. RP Gridley, T (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. FU NCI NIH HHS [CA34196]; NICHD NIH HHS [R01HD34883]; NINDS NIH HHS [R01NS36437] NR 13 TC 3 Z9 4 U1 0 U2 0 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 JAN 1 PY 2000 VL 63 IS 1 BP 142 EP 144 DI 10.1006/geno.1999.6055 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 286FC UT WOS:000085432100018 PM 10662554 ER PT J AU Zhao, XF Nowak, NJ Shows, TB Aplan, PD AF Zhao, XF Nowak, NJ Shows, TB Aplan, PD TI MAGOH interacts with a novel RNA-binding protein SO GENOMICS LA English DT Article ID GERM PLASM; DROSOPHILA AB MAGOH is the human homologue of Drosophila mago nashi, a protein that is required for normal germ plasm development in the Drosophila embryo, Using human MAGOH as a bait protein in a yeast two-hybrid screen, we recovered four independent cDNA clones that encode different lengths of a novel protein containing a conserved RNA-binding region. This gene, designated RBM8, encodes a 173-aa protein that was shown to have an apparent molecular mass of 26 kDa, as demonstrated by in vitro translation assay. The interaction between MAGOH and RBM8 was demonstrated by both yeast two-hybrid and GST fusion protein pull-down assays. Like MAGOH, RBM8 gene is expressed ubiquitously in human tissues; three species of RBM8 mRNA were detected. Also similar to MAGOH, RBM8 expression is serum inducible in quiescent NIH3T3 fibroblast cells. (C) 2000 Academic Press. C1 Roswell Pk Canc Inst, Dept Pediat, Buffalo, NY 14263 USA. Roswell Pk Canc Inst, Dept Canc Genet, Buffalo, NY 14263 USA. RP Aplan, PD (reprint author), Natl Canc Inst, Div Clin Sci, Ctr Adv Technol, 8717 Grovemont Circle, Gaithersburg, MD 20877 USA. RI Aplan, Peter/K-9064-2016 FU NCI NIH HHS [CA16056-21, CA67177-01] NR 11 TC 52 Z9 57 U1 0 U2 0 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 JAN 1 PY 2000 VL 63 IS 1 BP 145 EP 148 DI 10.1006/geno.1999.6064 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 286FC UT WOS:000085432100019 PM 10662555 ER PT B AU Bittner, M Chen, YD Amundson, SA Khan, J Fornace, AJ Dougherty, ER Meltzer, PS Trent, JM AF Bittner, M Chen, YD Amundson, SA Khan, J Fornace, AJ Dougherty, ER Meltzer, PS Trent, JM BE Suhai, S TI Obtaining and evaluating gene expression profiles with cDNA microarrays SO GENOMICS AND PROTEOMICS: FUNCTIONAL AND COMPUTATIONAL ASPECTS LA English DT Proceedings Paper CT International Symposium on Genomics and Proteomics CY OCT 04-07, 1998 CL HEIDELBERG, GERMANY SP European Commiss, BASF AG, BASF LYNX Biosci AG, Bayer AG, BIOMEVA GmbH, Boehringer Mannheim GmbH, Hoffmann La Roche Ltd, Knoll AG, Merck KGaA, Schering AG ID ALVEOLAR RHABDOMYOSARCOMA; MESSENGER-RNA; HUMAN GENOME; HYBRIDIZATION; PATTERNS; CANCER; SCALE C1 NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA. RP NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA. RI Khan, Javed/P-9157-2014 OI Khan, Javed/0000-0002-5858-0488 NR 33 TC 3 Z9 3 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA BN 0-306-46312-1 PY 2000 BP 5 EP 25 PG 21 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA BR72W UT WOS:000167336300002 ER PT J AU South, SA Deibler, GE Tzeng, SF Badache, A Kirchner, MG Muja, N De Vries, GH AF South, SA Deibler, GE Tzeng, SF Badache, A Kirchner, MG Muja, N De Vries, GH TI Myelin basic protein (MBP) and MBP peptides are mitogens for cultured astrocytes SO GLIA LA English DT Article DE myelin basic protein; proliferation; calcium; fibroblast growth factor; ganglioside G(M1) ID SCHWANN-CELLS; CHOLERA-TOXIN; ASTROGLIAL PROLIFERATION; REACTIVE ASTROCYTES; NEURITE OUTGROWTH; B-SUBUNIT; MICROGLIA; INJURY; GROWTH; BRAIN AB After CNS demyelination, astrogliosis interferes with axonal regeneration and remyelination. We now provide evidence that myelin basic protein (MBP) can contribute to this observed astrocyte proliferation. We found that astrocytes grown in either serum-containing or serum-free medium proliferate in response to MBP. The mitogenic regions of MBP in both media were MBP1-44, MBP88-151 and MBP152-167. The mitogenic effect of these individual peptides was potentiated by simultaneous treatment with microglia conditioned media (CM). MBP-induced proliferation was inhibited by suramin at concentrations known to block the fibroblast growth factor receptor (FGFR), whereas neither MBP1-44, MBP88-151 nor MBP152-167 were affected. Cholera toxin B, that binds to ganglioside GM(1), inhibited the mitogenicity of MBP1-44 and had no significant effect on the mitogenicity of MBP, MBP88-151 or MBP152-167. Treatment of astrocytes with MBP and MBP152-167 caused a modest and transitory elevation of intracellular calcium, whereas treatment with MBP1-44 resulted in a substantial and sustained increase in intracellular calcium. These results suggest that for cultured astrocytes 1) FGFR and extracellular calcium play a major role in MBP mitogenicity; 2) MBP1-44, MBP88-151 and MBP152-167 are the mitogenic regions of MBP; 3) MBP1-44 and MBP152-167 interact with ganglioside GM(1) and FGFR, respectively; 4) Component(s) present in microglial CM potentiate the mitogenicity of MBP1-44, MBP88-151 and MBP152-167. These data support the hypothesis that MBP related peptides in conjunction with microglial secreted factors may stimulate astrogliosis after demyelination in vivo. GLIA 29:81-90, 2000. (C) 2000 Wiley-Liss, Inc. C1 Edward Hines Vet Adm Hosp, Res Serv 151, Hines, IL 60141 USA. Loyola Univ, Stritch Sch Med, Dept Cell Biol Neurobiol & Anat, Maywood, IL USA. Loyola Univ, Stritch Sch Med, Program Neurosci, Maywood, IL USA. NIMH, Cerebral Metab Lab, NIH, Bethesda, MD USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Biochem & Mol Biophys, Richmond, VA 23298 USA. RP De Vries, GH (reprint author), Edward Hines Vet Adm Hosp, Res Serv 151, 5th Ave & Roosevelt Rd,Rm C423, Hines, IL 60141 USA. OI Badache, Ali/0000-0001-7710-2505 FU NINDS NIH HHS [NS15408] NR 38 TC 11 Z9 14 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 0894-1491 J9 GLIA JI Glia PD JAN 1 PY 2000 VL 29 IS 1 BP 81 EP 90 DI 10.1002/(SICI)1098-1136(20000101)29:1<81::AID-GLIA8>3.0.CO;2-O PG 10 WC Neurosciences SC Neurosciences & Neurology GA 267ZF UT WOS:000084388600008 PM 10594925 ER PT J AU Miller, MA McCann, L AF Miller, MA McCann, L TI Policy analysis of the use of hepatitis B, Haemophilus influenzae type b-, Streptococcus pneumoniae-conjugate and rotavirus vaccines in national immunization schedules SO HEALTH ECONOMICS LA English DT Article DE immunization programmes; hepatitis B; Haemophilus influenzae type b; Streptococcus; rotavirus; cost; outcome ID YOUNG-CHILDREN; UNITED-STATES; HOSPITALIZED CHILDREN; PNEUMOCOCCAL DISEASE; DEVELOPING-COUNTRIES; DIARRHEAL DISEASE; GLOBAL PROBLEM; INFANTS; INFECTIONS; EFFICACY AB After the development of national vaccine programmes to deliver six vaccines to infants, new vaccine adoption has been Limited. Analysis of the health and economic implications of new vaccination options can help national policy-makers. Country specific quantitative policy analyses were conducted to estimate the impact of vaccination against hepatitis B (HB), Haemophilus influenzae type b (Hib), Streptococcus pneumoniae (SP) and rotavirus. Disease burden, programme costs and the potential reduction of disease from vaccination was assessed for each vaccine. Without vaccination, these four vaccine preventable diseases contribute up to 4.1 million deaths in each successive birth cohort. Routine scheduled use of HE and Hib vaccines could prevent up to 1.7 million deaths; SP and rotavirus vaccines, an additional 1.4 million deaths, annually. The global cost per life-year saved ranged from $29 to $150 with great variation by income and economic groups. With a few exceptions for a few countries, these vaccines would cost a fraction of average per-capita gross domestic product to save a life-year. The addition of HE and Hib vaccines, should be considered for integration in all national immunization programmes. SP and rotavirus vaccines, with the given assumptions, would also be cost-effective. Proactive analysis of the economic and epidemiologic impact of these vaccines can hasten their introduction into national vaccination schedules. Copyright (C) 2000 John Wiley & Sons, Ltd. C1 WHO, Childrens Vaccine Initiat Secretariat, Geneva, Switzerland. RP Miller, MA (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. NR 63 TC 111 Z9 116 U1 3 U2 8 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1057-9230 J9 HEALTH ECON JI Health Econ. PD JAN PY 2000 VL 9 IS 1 BP 19 EP 35 DI 10.1002/(SICI)1099-1050(200001)9:1<19::AID-HEC487>3.3.CO;2-3 PG 17 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 283MH UT WOS:000085279000003 PM 10694757 ER PT J AU Jeffery, RW Drewnowski, A Epstein, LH Stunkard, AJ Wilson, GT Wing, RR Hill, DR AF Jeffery, RW Drewnowski, A Epstein, LH Stunkard, AJ Wilson, GT Wing, RR Hill, DR TI Long-term maintenance of weight loss: Current status SO HEALTH PSYCHOLOGY LA English DT Article DE obesity; treatment; maintenance review ID NUTRITION EXAMINATION SURVEYS; HEALTHY WORKER PROJECT; LOW-CALORIE DIET; BEHAVIORAL TREATMENT; COCAINE ABSTINENCE; SMOKING CESSATION; RANDOMIZED TRIAL; NATIONAL-HEALTH; FOOD PROVISION; FOLLOW-UP AB Intervention strategies for promoting long-term weight loss are examined empirically and conceptually. Weight control research over the last 20 years has dramatically improved short-term treatment efficacy but has been less successful in improving long-term success. Interventions in preadolescent children show greater long-term efficacy than in adults. Extending treatment length and putting more emphasis on energy expenditure have modestly improved long-term weight loss in adults. Fresh ideas are needed to push the field forward. Suggested research priorities are patient retention, natural history, assessment of intake and expenditure, obesity phenotypes, adolescence at a critical period, behavioral preference-reinforcement value, physical activity and social support, better linkage of new conceptual models to behavioral treatments, and the interface between pharmacological and behavioral methods. C1 Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55454 USA. Univ Washington, Nutrit Sci Program, Seattle, WA 98195 USA. SUNY Buffalo, Dept Psychol, Buffalo, NY 14260 USA. Univ Penn, Sch Med, Dept Psychiat & Med, Philadelphia, PA 19104 USA. Rutgers State Univ, Grad Sch Appl & Profess Psychol, Piscataway, NJ 08855 USA. Brown Univ, Weight Control & Diabet Res Ctr, Sch Med, Providence, RI 02912 USA. Miriam Hosp, Providence, RI 02906 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. NHLBI, Bethesda, MD 20892 USA. RP Jeffery, RW (reprint author), Univ Minnesota, Sch Publ Hlth, Div Epidemiol, 1300 S 2nd St,Suite 300,Twin Cities Campus, Minneapolis, MN 55454 USA. FU NHLBI NIH HHS [HL 41330, HL 41332]; NIDDK NIH HHS [DK50456] NR 52 TC 524 Z9 528 U1 6 U2 53 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD JAN PY 2000 VL 19 IS 1 SU S BP 5 EP 16 DI 10.1037//0278-6133.19.Suppl1.5 PG 12 WC Psychology, Clinical; Psychology SC Psychology GA 290RW UT WOS:000085692500002 PM 10709944 ER PT J AU Ockene, JK Emmons, KM Mermelstein, RJ Perkins, KA Bonollo, DS Voorhees, CC Hollis, JF AF Ockene, JK Emmons, KM Mermelstein, RJ Perkins, KA Bonollo, DS Voorhees, CC Hollis, JF TI Relapse and maintenance issues for smoking cessation SO HEALTH PSYCHOLOGY LA English DT Review DE smoking cessation; smoking treatment; adherence; smoking intervention ID SELF-HELP MATERIALS; WEIGHT-GAIN; RANDOMIZED TRIAL; CIGARETTE-SMOKING; UNITED-STATES; QUIT SMOKING; LONGITUDINAL ANALYSIS; NICOTINE DEPENDENCE; INTERVENTION TRIAL; TOBACCO SMOKING AB This article reviews short-term (6 months) and longer term (12-24 months) maintenance of cessation and relapse in adult smokers and the factors and treatments that affect these outcomes. MedLine and PsycLIT searches were done for research published in English between 1988 and 1998 meeting a defined set of criteria. Intensive intervention, telephone counseling, and use of pharmacotherapy were found to improve outcomes; however, compared with public health approaches, they reach relatively few smokers. Brief interventions during medical visits are cost-effective and could potentially reach most smokers but are not consistently delivered. Predictors of relapse include slips, younger age, nicotine dependence, low self-efficacy, weight concerns, and previous quit attempts. Potential areas for research, recommendations for longer follow-up assessments, and standard definitions for slip, relapse, and long-term maintenance are discussed. C1 Univ Massachusetts, Sch Med, Worcester, MA 01655 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. Univ Illinois, Dept Psychol, Chicago, IL 60680 USA. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. RP Ockene, JK (reprint author), Univ Massachusetts, Sch Med, 55 Lake Ave N, Worcester, MA 01655 USA. RI Perkins, Kenneth/E-4085-2010 NR 127 TC 185 Z9 189 U1 3 U2 22 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD JAN PY 2000 VL 19 IS 1 SU S BP 17 EP 31 DI 10.1037//0278-6133.19.Suppl1.17 PG 15 WC Psychology, Clinical; Psychology SC Psychology GA 290RW UT WOS:000085692500003 PM 10709945 ER PT J AU Marcus, BH Dubbert, PM Forsyth, LH McKenzie, TL Stone, EJ Dunn, AL Blair, SN AF Marcus, BH Dubbert, PM Forsyth, LH McKenzie, TL Stone, EJ Dunn, AL Blair, SN TI Physical activity behavior change: Issues in adoption and maintenance SO HEALTH PSYCHOLOGY LA English DT Article DE physical activity; exercise; behavioral interventions; maintenance ID CARDIOVASCULAR-DISEASE PREVENTION; HEART-HEALTH-PROGRAM; LONG-TERM OUTCOMES; LIFE-STYLE; CARDIAC REHABILITATION; ACTIVITY INTERVENTIONS; ADOLESCENT TRIAL; MASS-MEDIA; EXERCISE; PROJECT AB The many benefits of participation in regular moderate- or vigorous-intensity physical activity are well established, yet more than 60% of the population is sedentary or insufficiently active. Published studies have revealed that behavior modification and cognitive behavior modification can be successfully used to assist patients, healthy adults, and youth in the adoption of physically active lifestyles. However, few studies with adults and youth have examined the maintenance of physical activity behavior beyond 6 months of adoption of this behavior. Maintenance of physical activity is critically important because ongoing participation in the behavior is necessary to sustain health benefits. Knowledge of effective intervention strategies for long-term maintenance of physical activity is at an early stage. The authors provide a summary of what is known about the maintenance of physical activity behavior in adults and youth and how physical activity behavior relates to other health behaviors such as smoking, as well as recommendations for research on physical activity behavior change and maintenance. C1 Brown Univ, Miriam Hosp, Ctr Behav & Prevent Med, Providence, RI 02906 USA. Vet Affairs Med Ctr, Jackson, MS USA. San Diego State Univ, Dept Exercise & Nutrit Sci, San Diego, CA 92182 USA. NHLBI, Bethesda, MD 20892 USA. Cooper Inst Aerob Res, Dallas, TX USA. RP Marcus, BH (reprint author), Brown Univ, Miriam Hosp, Ctr Behav & Prevent Med, 164 Summit Ave, Providence, RI 02906 USA. NR 62 TC 224 Z9 230 U1 9 U2 51 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD JAN PY 2000 VL 19 IS 1 SU S BP 32 EP 41 DI 10.1037/0278-6133.19.Suppl1.32 PG 10 WC Psychology, Clinical; Psychology SC Psychology GA 290RW UT WOS:000085692500004 PM 10709946 ER PT J AU Kumanyika, SK Van Horn, L Bowen, D Perri, MG Rolls, BJ Czajkowski, SM Schron, E AF Kumanyika, SK Van Horn, L Bowen, D Perri, MG Rolls, BJ Czajkowski, SM Schron, E TI Maintenance of dietary behavior change SO HEALTH PSYCHOLOGY LA English DT Article DE cardiovascular diseases; diet; nutrition; intervention studies ID HIGH BLOOD CHOLESTEROL; LONG-TERM MAINTENANCE; ECONOMIC-ANALYSIS; UNITED-STATES; BASE-LINE; CONTROLLED TRIALS; NATIONAL-HEALTH; OBESE CHILDREN; FOOD CHOICE; US ADULTS AB Reducing dietary fat, saturated fat, and sodium and increasing intakes of dietary fiber and fruits and vegetables are important far cardiopulmonary risk reduction. Behaviorally, these dietary changes are very challenging, and in different ways. Fewer than half of U.S. adults have diets meeting recommended intakes of these constituents, and many do not see a need to align their diets with recommendations. Various nutrition education and behavioral counseling approaches have been shown to facilitate changes in fat, fiber, sodium, and fruits and vegetables, but primarily in research settings and among the highly motivated. Practice-based and interdisciplinary studies are needed to refine strategies to effect long-term dietary changes, to differentiate behavioral issues for changes involving additions versus deletions from the diet, and to elucidate the roles of sensory, psychosocial, and contextual factors in adoption and maintenance. C1 Univ Penn, Ctr Clin Epidemiol & Biostat, Sch Med, Philadelphia, PA 19104 USA. Northwestern Univ, Sch Med, Dept Prevent Med, Evanston, IL 60208 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Florida, Hlth Sci Ctr, Gainesville, FL 32611 USA. Penn State Univ, Dept Nutr, University Pk, PA 16802 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. RP Kumanyika, SK (reprint author), Univ Penn, Ctr Clin Epidemiol & Biostat, Sch Med, 8th Floor,Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. NR 74 TC 95 Z9 98 U1 2 U2 14 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD JAN PY 2000 VL 19 IS 1 SU S BP 42 EP 56 DI 10.1037//0278-6133.19.Suppl1.42 PG 15 WC Psychology, Clinical; Psychology SC Psychology GA 290RW UT WOS:000085692500005 PM 10709947 ER PT J AU Rehermann, B Chisari, FV AF Rehermann, B Chisari, FV TI Cell mediated immune response to the hepatitis C virus SO HEPATITIS C VIRUSES SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID CYTOTOXIC T-LYMPHOCYTES; HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; BLOOD MONONUCLEAR-CELLS; NITRIC-OXIDE SYNTHASE; MAJOR HISTOCOMPATIBILITY COMPLEX; PEPTIDE-MHC COMPLEXES; CHRONIC LIVER-DISEASE; NATURAL-KILLER-CELLS; INTERFERON-GAMMA C1 NIDDK, Liver Dis Sect, DDB, NIH, Bethesda, MD 20892 USA. Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. RP Rehermann, B (reprint author), NIDDK, Liver Dis Sect, DDB, NIH, Bldg 10,Room 9B16,10 Ctr Dr MSC 1800, Bethesda, MD 20892 USA. RI Chisari, Francis/A-3086-2008 NR 198 TC 99 Z9 101 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2000 VL 242 BP 299 EP 325 PG 27 WC Immunology; Microbiology SC Immunology; Microbiology GA BP10M UT WOS:000084132500014 PM 10592666 ER PT J AU Cote, PJ Korba, BE Miller, RH Jacob, JR Baldwin, BH Hornbuckle, WE Purcell, RH Tennant, BC Gerin, JL AF Cote, PJ Korba, BE Miller, RH Jacob, JR Baldwin, BH Hornbuckle, WE Purcell, RH Tennant, BC Gerin, JL TI Effects of age and viral determinants on chronicity as an outcome of experimental woodchuck hepatitis virus infection SO HEPATOLOGY LA English DT Article; Proceedings Paper CT IX Triennial International Symposium on Viral Hepatitis and Liver Disease CY APR 21-25, 1996 CL ROME, ITALY ID B VIRUS; NUCLEOTIDE-SEQUENCE; NATURAL HOST; GENOME; ANTIGEN; PRECORE; CYCLOSPORINE; MOTHERS AB Acute hepadnavirus infections either resolve or progress to chronicity. Factors that influence chronicity as an outcome of hepatitis B virus (HBV) infection in humans can be studied experimentally in the woodchuck model. Accordingly, several woodchuck hepatitis virus (WHV) inocula were characterized. Representative inocula had high titers of infectious virus (approximately 10(7.7)-10(9.5) Woodchuck 50% infectious doses per milliliter [WID50%/mL] by subcutaneous inoculation), with 1 WID50% ranging between 21 and 357 physical virion particles. WHV7P1 (standard high dose, 5 x 10(6) WID50%) produced a 72% chronicity rate (i.e., percent chronic of total infected) in neonatal woodchucks (1-3 days old). Comparable doses of WHV8P1 resulted in a lower chronicity rate in neonates (34% chronic) indicating that it represented a strain different from WHV7P1, Neonatal woodchucks were more susceptible to chronic infection by high doses of WHV7P1 (range, 65%-75% chronic) compared with 8-week-old weanlings (33% chronic) and adult woodchucks (0% chronic; i.e., all resolved). High doses of cloned wild-type viruses also induced high rates of chronicity in neonates (70%-80% chronic), Chronicity rates in neonates were decreased for low doses of WHV7P1 (500 WID50%, 9% chronic) and for high doses of a precore WHeAg-minus mutant WHV8 clone (17% chronic). Thus, both age and viral determinants can influence chronicity as an outcome of experimental WHV infection. Standardized inocula will enable the study of mechanisms that initiate and maintain chronic hepadnavirus infection and also provide a means for developing WHV carriers for therapeutic studies. C1 Georgetown Univ, Ctr Med, Div Mol Virol & Immunol, Dept Microbiol & Immunol, Rockville, MD 20852 USA. NIAID, Infect Dis Lab, Hepatitis Viruses Sect, Bethesda, MD 20892 USA. Cornell Univ, New York State Coll Vet Med, Dept Clin Sci, Ithaca, NY 14853 USA. RP Cote, PJ (reprint author), Georgetown Univ, Ctr Med, Div Mol Virol & Immunol, Dept Microbiol & Immunol, 5640 Fishers Lane, Rockville, MD 20852 USA. FU NIAID NIH HHS [AI-22665, AI-45179, AI-72623] NR 26 TC 72 Z9 77 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 2000 VL 31 IS 1 BP 190 EP 200 DI 10.1002/hep.510310128 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 270RV UT WOS:000084550700028 PM 10613745 ER PT J AU Alesci, S Bornstein, SR AF Alesci, S Bornstein, SR TI Neuroimmunoregulation of androgens in the adrenal gland and the skin SO HORMONE RESEARCH LA English DT Article; Proceedings Paper CT Meeting of the 3rd Teupitzer Colloquium 2000 CY SEP 17-20, 2000 CL BERLIN, GERMANY DE adrenal androgens; DHEA; hyperandrogenism; hirsutism; acne; androgenic; alopecia; hair loss ID HUMAN ADRENOCORTICAL-CELLS; TUMOR-NECROSIS-FACTOR; CORTICOTROPIN-RELEASING-HORMONE; HUMAN HAIR FOLLICLE; TRANSFORMING GROWTH FACTOR-BETA-1; ZONA GLOMERULOSA CELLS; DEHYDROEPIANDROSTERONE-SULFATE; CHROMAFFIN CELLS; CORTICAL-CELLS; HUMAN PROOPIOMELANOCORTIN-(79-96) AB Human adrenals produce large quantities of androgens, especially DHEA which is the most abundant circulating hormone in the human body. Adrenal androgens are regulated by several factors, including pituitary ACTH and an intricate intraadrenal network involving immune cells, cytokines and neuroendocrine factors. The skin is a major target of androgens and androgen receptors are expressed in the epidermis, dermis, sebaceous glands and hair. In addition, the skin has the capacity to metabolize androgens into more powerful compounds. Similar to the adrenal gland, there is an intradermal neuroimmune network involving the local expression of cytokines and neuropeptides. Dysregulation of androgens in the adrenals and/or the skin is associated with acne, hirsutism and androgenic alopecia. Therefore, understanding the mechanisms of these intricate networks is of both basic and clinical relevance and may help to develop new strategies for the treatment of androgen-dependent skin disorders. Copyright (C) 2001 S. Karger AG, Basel. C1 NICHHD, Pediat & Reprod Endocriol Branch, NIH, Bethesda, MD 20892 USA. RP Alesci, S (reprint author), NICHHD, Pediat & Reprod Endocriol Branch, NIH, Bldg 10,Room 10N242,10 Ctr Dr,MSC1583, Bethesda, MD 20892 USA. EM alescis@mail.nih.gov NR 83 TC 23 Z9 23 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0163 EI 1663-2826 J9 HORM RES JI Horm. Res. PY 2000 VL 54 IS 5-6 BP 281 EP 286 DI 10.1159/000053272 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 480MB UT WOS:000171464200010 PM 11595818 ER PT J AU Stratakis, CA AF Stratakis, CA TI Genetics of Peutz-Jeghers syndrome, Carney complex and other familial lentiginoses SO HORMONE RESEARCH LA English DT Article; Proceedings Paper CT Meeting of the 3rd Teupitzer Colloquium 2000 CY SEP 17-20, 2000 CL BERLIN, GERMANY DE Peutz-Jeghers syndrome; Carney complex; lentigines multiple neoplasia syndromes; STK11 gene; protein kinase A; PRKAR1A gene; Cowden disease; PTEN gene ID SPOTTY SKIN PIGMENTATION; RILEY-RUVALCABA-SYNDROME; NODULAR ADRENOCORTICAL DISEASE; PSAMMOMATOUS MELANOTIC SCHWANNOMA; INCLUDING CARDIAC MYXOMA; ENDOCRINE OVERACTIVITY; CUSHING SYNDROME; COWDEN-DISEASE; PROTEIN-KINASE; CHROMOSOME INSTABILITY AB Peutz-Jeghers syndrome (PJS, #175200) and Carney complex (CNC, OMIM#160980) are the two most common multiple neoplasia syndromes associated with lentiginosis. Both disorders are inherited in an autosomal dominant manner and they have recently been elucidated at the molecular level. PJS and CNC share manifestations with Cowden syndrome (or Cowden, disease) (CS, OMIM#158350) and Bannayan-Riley-Ruvalcaba syndrome (BRR, OMIM#153480). The endocrine tumors of CS and PJS, which could classify these disorders as variant types of multiple endocrine neoplasias (MENs), are not present in most CS and BRR patients, but lentigines are shared by PJS, CNC and BRR. The serine-threonine kinase STK11 (or LKB1), located on 19p13, is mutated in more than half of all PJS kindreds. The R1 alpha subunit of c-AMP-dependent protein kinase A, located on 17q22-24, is mutated in 40% of CNC kindred's. The protein phosphatase PTEN is mutated in most cases of CS and in almost 50% of BRR kindreds, despite significant clinical heterogeneity in these syndromes. The molecular elucidation of the lentiginoses and their related syndromes identifies new pathways of growth control and cellular regulation that are important for endocrine signaling, tumorigenesis, cutaneous function and embryonic development. Copyright (C) 2001 S. Karger AG, Basel. 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, Bethesda, MD 20892 USA. NR 104 TC 19 Z9 19 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0163 J9 HORM RES JI Horm. Res. PY 2000 VL 54 IS 5-6 BP 334 EP 343 DI 10.1159/000053283 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 480MB UT WOS:000171464200021 PM 11595829 ER PT J AU Spiegel, AM AF Spiegel, AM TI G protein defects in signal transduction SO HORMONE RESEARCH LA English DT Article; Proceedings Paper CT 11th hGH Symposium CY MAR 30-APR 02, 2000 CL SORRENTO, ITALY DE receptors; G proteins; mutations; pseudohypoparathyroidism; McCune-Albright syndrome ID ALBRIGHT-HEREDITARY-OSTEODYSTROPHY; PSEUDOHYPOPARATHYROIDISM TYPE IB; CELL-SURFACE RECEPTORS; STIMULATORY G-PROTEIN; G(S)ALPHA GENE GNAS1; ALPHA GENE; PARATHYROID-HORMONE; DEOXYRIBONUCLEIC-ACID; COUPLED RECEPTORS; DELETION MUTATION AB G proteins couple receptors for many hormones to effecters that regulate second messenger metabolism. Several endocrine disorders have been shown to be caused by either loss- or gain-of-function mutations in G proteins or G protein-coupled receptors. In pseudohypoparathyroidism type Ia (PHP Ia), there are generalized hormone resistance (parathyroid hormone [PTH], thyroid-stimulating hormone, gonadotropins) and associated abnormal physical features, Albright hereditary osteodystrophy. Subjects with PHP Ib are normal in appearance and show renal resistance to PTH. In McCune-Albright syndrome (MAS), subjects show autonomous endocrine hyperfunction associated with fibrous dysplasia of bone and skin hyperpigmentation. Germline loss-of-function mutations have been identified in the G(s)-alpha gene in PHP Ia, and recent evidence suggests that the G(s)-alpha gene is paternally imprinted in a tissue-specific manner. Abnormal imprinting of the G(s)-alpha gene may be the cause of PHP Ib. MAS, in contrast, is caused by gain-of-function missense mutations of the G(s)-alpha gene. Copyright (C) 2000 S. Karger AG. Basel. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Spiegel, AM (reprint author), NIDDKD, NIH, Bldg 31,Room 9A-52, Bethesda, MD 20892 USA. NR 40 TC 22 Z9 23 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0163 J9 HORM RES JI Horm. Res. PY 2000 VL 53 SU 3 BP 17 EP 22 DI 10.1159/000023526 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 352AE UT WOS:000089191700003 PM 10971097 ER PT J AU Schumacher, RF Mella, P Badolato, R Fiorini, M Savoldi, G Giliani, S Villa, A Candotti, F Tampalini, A O'Shea, JJ Notarangelo, LD AF Schumacher, RF Mella, P Badolato, R Fiorini, M Savoldi, G Giliani, S Villa, A Candotti, F Tampalini, A O'Shea, JJ Notarangelo, LD TI Complete genomic organization of the human JAK3 gene and mutation analysis in severe combined immunodeficiency by single-strand conformation polymorphism SO HUMAN GENETICS LA English DT Article ID WISKOTT-ALDRICH SYNDROME; CONSTITUTIVE ACTIVATION; TYROSINE KINASES; MYELOID CELLS; T-CELLS; PROTEIN; EXPRESSION; TRANSPLANTATION; IDENTIFICATION; INTERLEUKIN-2 AB JAK3 deficiency in humans results in autosomal recessive T-B+ severe combined immunodeficiency disease (SCID), a severe immunodeficiency that can only be cured by bone marrow transplantation. We unraveled the complete organization of the human JAK3 gene, which includes 23 exons. This information allowed us to set up a molecular screening test that enabled us to diagnose JAK3 deficiency in 14 patients from 12 unrelated families with T-B+ SCID. In order to define the mutations, we used a nonradioactive single-strand conformation polymorphism (SSCP)/heteroduplex (HD) assay based on exon-specific polymerase chain reaction (PCR). In this cohort of patients, 15 independent JAK3 gene mutations have been identified, including 7 that have not been described previously. Mutation analysis information was used for genetic counseling and prenatal diagnosis. C1 Univ Brescia, Pediat Clin, I-25123 Brescia, Italy. Ist Med Mol Angelo Nocivelli, I-25123 Brescia, Italy. CNR, Ist Tecnol Biomed Avanzate, I-20090 Milan, Italy. NHGRI, Clin Gene Therapy Branch, NIH, Bethesda, MD 20892 USA. NIAMS, Arthrit Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Schumacher, RF (reprint author), Univ Brescia, Pediat Clin, Piazzale Spedali Civili, I-25123 Brescia, Italy. RI Badolato, Raffaele/A-8081-2010; Notarangelo, Luigi/F-9718-2016; OI Badolato, Raffaele/0000-0001-7375-5410; Notarangelo, Luigi/0000-0002-8335-0262; Villa, Anna/0000-0003-4428-9013 FU Telethon [E.0668] NR 50 TC 18 Z9 22 U1 0 U2 2 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 JAN PY 2000 VL 106 IS 1 BP 73 EP 79 DI 10.1007/s004390051012 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 285GG UT WOS:000085380900011 PM 10982185 ER PT J AU Takeda, K Takemoto, C Kobayashi, I Watanabe, A Nobukuni, Y Fisher, DE Tachibana, M AF Takeda, K Takemoto, C Kobayashi, I Watanabe, A Nobukuni, Y Fisher, DE Tachibana, M TI Ser298 of MITF, a mutation site in Waardenburg syndrome type 2, is a phosphorylation site with functional significance SO HUMAN MOLECULAR GENETICS LA English DT Article ID GLYCOGEN-SYNTHASE KINASE-3; TRANSCRIPTION FACTOR; DNA-BINDING; MICROPHTHALMIA GENE; HUMAN HOMOLOG; PROTEIN; ACTIVATION; EXPRESSION; IDENTIFICATION; DOMAINS AB MITF (microphthalmia-associated transcription factor) is a basic-helix-loop-helix-leucine zipper (bHLHZip) factor which regulates expression of tyrosinase and other melanocytic genes via a CATGTG promoter sequence, and is involved in melanocyte differentiation. Mutations of MITF in mice or humans with Waardenburg syndrome type 2 (WS2) often severely disrupt the bHLHZip domain, suggesting the importance of this structure. Here, we show that Ser298, which locates downstream of the bHLHZip and was previously found to be mutated in individuals with WS2, plays an important role in MITF function. Glycogen synthase kinase 3 (GSK3) was found to phosphorylate Ser298 in vitro, thereby enhancing the binding of MITF to the tyrosinase promoter. The same serine was found to be phosphorylated in vivo, and expression of dominant-negative GSK3 beta selectively suppressed the ability of MITF to transactivate the tyrosinase promoter. Moreover, mutation of Ser298, as found in a WS2 family, disabled phosphorylation of MITF by GSK3 beta and impaired MITF function. These findings suggest that the Ser298 is important for MITF function and is phosphorylated probably by GSK3 beta. C1 Natl Inst Deafness & Other Commun Disorders, Bethesda, MD 20892 USA. Tohoku Univ, Sch Med, Dept Mol Biol & Appl Physiol, Sendai, Miyagi 9808575, Japan. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NIMH, Bethesda, MD 20892 USA. Saitama Canc Ctr, Res Inst, Ina, Saitama 3620806, Japan. RP Natl Inst Deafness & Other Commun Disorders, Bethesda, MD 20892 USA. EM mtachiba@cancer-c.pref.saitama.jp RI Kobayashi, Ichiro/G-8638-2012 FU NHLBI NIH HHS [KO8 HL3700]; NIAMS NIH HHS [AR43369] NR 36 TC 96 Z9 99 U1 2 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JAN 1 PY 2000 VL 9 IS 1 BP 125 EP 132 DI 10.1093/hmg/9.1.125 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 274VJ UT WOS:000084785500015 PM 10587587 ER PT J AU Boardman, LA Couch, FJ Burgart, LJ Schwartz, D Berry, R McDonnell, SK Schaid, DJ Hartmann, LC Schroeder, JJ Stratakis, CA Thibodeau, SN AF Boardman, LA Couch, FJ Burgart, LJ Schwartz, D Berry, R McDonnell, SK Schaid, DJ Hartmann, LC Schroeder, JJ Stratakis, CA Thibodeau, SN TI Genetic heterogeneity in Peutz-Jeghers syndrome SO HUMAN MUTATION LA English DT Article DE Peutz-Jeghers syndrome; PJS; linkage analysis; LKB1; serine-threonine kinase 11; STK11 ID SERINE THREONINE KINASE; GERMLINE MUTATIONS; JUVENILE POLYPOSIS; CHROMOSOME 19P13.3; INCREASED RISK; BREAST-CANCER; FAMILIES; LOCUS; STK11; LINKAGE AB LKB1, the human gene encoding a serine threonine kinase, was recently identified as a susceptibility gene for Peutz-Jeghers syndrome (PJS), a disease characterized by the constellation of intestinal hamartomata, oral mucocutaneous hyperpigmentation, and an increased risk for gastrointestinal as well as extraintestinal malignancies. To date, the majority of individuals with PJS have been found to have genetic alterations in LKB1, most of which result in protein truncation. Additionally, linkage analyses have suggested a modicum of genetic heterogeneity, with the majority of PJS families showing linkage to the LKB1 locus. In this study, we evaluated five kindreds with greater than two affected family members, five PJS probands with only one other affected family member, as well as 23 individuals with sporadic PJS for mutations within the LKB1 gene. Conformation sensitive gel electrophoresis was utilized for the initial screen, followed by direct sequence analysis for characterization. Long-range PCR was used for the detection of larger genetic insertions or deletions. Mutation analysis revealed generic alterations in LKB1 in two probands who had a family history of PJS. LKB1 mutations were detected in only four of the remaining 23 cases of sporadic PJS, These data suggest the presence of significant genetic heterogeneity for PJS and the involvement of other loci in this syndrome. Hum Mutat 16:23-30, 2000. (C) 2000 Wiley-Liss, Inc. C1 Mayo Clin & Mayo Fdn, Dept Lab Med & Pathol, Lab Med & Pathol HI 970, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Internal Med, Div Gastroenterol, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Biostat, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Med Oncol, Rochester, MN 55905 USA. NICHD, Unit Genet & Endocrinol, DEB, SPE,NIH, Bethesda, MD USA. RP Thibodeau, SN (reprint author), Mayo Clin & Mayo Fdn, Dept Lab Med & Pathol, Lab Med & Pathol HI 970, 200 1st St SW, Rochester, MN 55905 USA. NR 32 TC 87 Z9 91 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 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 2000 VL 16 IS 1 BP 23 EP 30 DI 10.1002/1098-1004(200007)16:1<23::AID-HUMU5>3.0.CO;2-M PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 330QQ UT WOS:000087973100005 PM 10874301 ER PT J AU Nickerson, ML Weirich, G Zbar, B Schmidt, LS AF Nickerson, ML Weirich, G Zbar, B Schmidt, LS TI Signature-based analysis of MET proto-oncogene mutations using DHPLC SO HUMAN MUTATION LA English DT Article DE DHPLC; MET proto-oncogene; mutation detection; pedigree analysis; single nucleotide polymorphism; SNP ID PERFORMANCE LIQUID-CHROMATOGRAPHY; SINGLE-NUCLEOTIDE POLYMORPHISMS; PAPILLARY RENAL CARCINOMAS; CONFORMATION POLYMORPHISM; GERMLINE MUTATIONS; DNA; IDENTIFICATION; PROTOONCOGENE; DISEASE; CANCER AB Research tools which improve mutation detection, SNP discovery, and allele characterization will facilitate studies of cancer, inherited disease, and genomic evolution. Denaturing High-Performance Liquid Chromatography (DHPLC) is a recently developed methodology for detection of heteroduplexes formed in DNA samples containing mismatches between wild type and mutant strands. In an effort to develop a rapid, sensitive mutation detection method for studies of families with inherited kidney cancer, we evaluated DHPLC for detection and analysis of MET protooncogene mutations in papillary renal carcinomas (PRC), We found DHPLC to be 100% accurate in detecting 15 known disease-associated MET mutations. Significantly, each MET mutation and two novel SNPs generated a characteristic chromatographic profile or signature with reproducible distinguishing features. Standardization of DHPLC reagents and improved methods design were critical to the reliability and accuracy of mutation prediction. Improvements included addition of a 75% acetonitrile wash followed by a rejuvenating gradient, and detailed analysis of signature shape, retention time (RT), RT differences (Delta RT), and temperature-dependent (melt) profiling, We used signatures to predict mutations in new PRC samples, mutation carriers in asymptomatic hereditary PRC family members, and in a blind study of previously characterized DNAs. Application to SNP discovery is discussed, Hum Mutat 16:68-76, 2000, Published 2000 (C) Wiley-Liss, Inc.(dagger) C1 NCI, Immunobiol Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Nickerson, ML (reprint author), NCI, Immunobiol Lab, Frederick Canc Res & Dev Ctr, Bldg 560 Room 12-71, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 35 TC 34 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 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 2000 VL 16 IS 1 BP 68 EP 76 DI 10.1002/1098-1004(200007)16:1<68::AID-HUMU12>3.0.CO;2-U PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 330QQ UT WOS:000087973100012 PM 10874308 ER PT J AU Wallis, D Muenke, M AF Wallis, D Muenke, M TI Mutations in holoprosencephaly SO HUMAN MUTATION LA English DT Article DE holoprosencephaly; HPE; brain development; Sonic Hedgehog; SHH; ZIC2; SIX3; TGIF ID SONIC-HEDGEHOG GENE; MURINE HOMEOBOX GENE; EYE DEVELOPMENT; RETINOIC ACID; SINE OCULIS; CRITICAL REGION; VISUAL-SYSTEM; NEURAL PLATE; DROSOPHILA; EXPRESSION AB Holoprosencephaly (HPE) is the most common developmental defect of the forebrain and midface in humans. In holoprosencephaly the cerebral hemispheres of the brain fail to separate into distinct left and right hemispheres. This malformation is due to the improper specification and formation of the forebrain during early development. When one considers the great number and kinds of genetic interactions that must occur to properly pattern the developing forebrain, it is nor surprising that HPE is extremely heterogeneous. In addition to teratogenic agents, several genes are implicated as the cause of HPE, At least 12 different loci have been associated with HPE and now several distinct human genes for holoprosencephaly have been identified. These genes include Sonic Hedgehog (SHH), ZIC2, SIX3, and TG-interacting factor (TGIF). Here we present an overview of the presently known genes causing human holoprosencephaly, We discuss their functional role in development of the forebrain and summarize the mutations and polymorphisms that have been identified within them, Hum Mutat 16:99-108, 2000, Published 2000 Wiley Liss, Inc.dagger. C1 Natl Human Genome Res Inst, 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. RP Muenke, M (reprint author), Natl Human Genome Res Inst, Med Genet Branch, NIH, Bld 10,10C101, Bethesda, MD 20892 USA. FU NICHD NIH HHS [HD28732, HD29862] NR 69 TC 128 Z9 130 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 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 2000 VL 16 IS 2 BP 99 EP 108 DI 10.1002/1098-1004(200008)16:2<99::AID-HUMU2>3.0.CO;2-0 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 339JG UT WOS:000088473500001 PM 10923031 ER PT J AU Szabo, C Masiello, A Ryan, JF Brody, LC AF Szabo, C Masiello, A Ryan, JF Brody, LC CA BIC Consortium TI The breast cancer information core: Database design, structure, and scope SO HUMAN MUTATION LA English DT Article DE BRCA1; BRCA2; breast cancer; mutation database; MDI ID ASHKENAZI-JEWISH INDIVIDUALS; EARLY-ONSET BREAST; OVARIAN-CANCER; SUSCEPTIBILITY GENE; BRCA1 GENE; PHENOTYPE ANALYSIS; CARRIER FREQUENCY; MUTATIONS; FAMILIES; IDENTIFICATION AB The Breast Cancer Information Core (BIC) is an open access, on line mutation database for breast cancer susceptibility genes, In addition to creating a catalogue of all mutations and poly morphisms in breast cancer susceptibility genes, a principle aim of the BIC is to facilitate the detection and characterization of these genes by providing technical support in the form of mutation detection protocols, primer sequences, and reagent access. Additional information at the site includes a literature review compiled from published studies, links to other internet based, breast cancer information and research resources, and an interactive discussion forum which enables investigators to post or respond to questions and/of comments on a bulletin board. Hum Mutat 16:123-131, 2000, Published 2000 Wiley Liss, Inc.dagger. C1 Natl Human Genome Res Inst, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Int Agcy Res Canc, Unite Genet Epidemiol, F-69372 Lyon, France. RP Brody, LC (reprint author), Natl Human Genome Res Inst, Genet & Mol Biol Branch, NIH, 49 Convent Dr,Room 3A14, Bethesda, MD 20892 USA. NR 38 TC 97 Z9 98 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 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 2000 VL 16 IS 2 BP 123 EP 131 DI 10.1002/1098-1004(200008)16:2<123::AID-HUMU4>3.0.CO;2-Y PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 339JG UT WOS:000088473500003 PM 10923033 ER PT J AU Laake, K Jansen, L Hahnemann, JM Brondum-Nielsen, K Lonnqvist, T Kaariainen, H Sankila, R Lahdesmaki, A Hammarstrom, L Yuen, J Tretli, S Heiberg, A Olsen, JH Tucker, M Kleinerman, R Borresen-Dale, AL AF Laake, K Jansen, L Hahnemann, JM Brondum-Nielsen, K Lonnqvist, T Kaariainen, H Sankila, R Lahdesmaki, A Hammarstrom, L Yuen, J Tretli, S Heiberg, A Olsen, JH Tucker, M Kleinerman, R Borresen-Dale, AL TI Characterization of ATM mutations in 41 Nordic families with ataxia telangiectasia SO HUMAN MUTATION LA English DT Article DE ataxia telangiectasia; ATM; ethnology; DNA mutational analysis; founder effect; nordic population ID DNA-DAMAGE RESPONSE; STRAND BREAK REPAIR; GENE-MUTATIONS; CANCER; SEQUENCE; PROTEIN; HETEROZYGOTES; EXPRESSION; KINASE; PHOSPHORYLATION AB The Ataxia Telangiectasia Mutation (ATM) gene is mutated in the rare recessive syndrome Ataxia Telangiectasia (AT), which is characterized by cerebellar degeneration, immunodeficiency, and cancer predisposition. In this study, 41 AT families from Denmark, Finland, Norway, and Sweden were screened for ATM mutations. The protein truncation test (PTT), fragment length and heteroduplex analyses of large (0.8-1.2 kb) cDNA fragments were used, In total, 67 of 82 (82%) of the disease-causing alleles were characterized. Thirty-seven unique mutations were detected of which 25 have not previously been reported. The mutations had five different consequences for the ATM transcript: mutations affecting splicing (43%); frameshift mutations (32%); nonsense mutations (16%); small in-frame deletions (5%); and one double substitution (3%). In 28 of the probands mutations were found in both alleles, in 11 of the probands only one mutated allele was detected, and no mutations were detected in two Finnish probands, One-third of the probands (13) were homozygous, whereas the majority of the probands (26) were compound heterozygote with at least one identified allele. Ten alleles were found more than once; one Norwegian founder mutation constituted 57% of the Norwegian alleles. Several sequence variants were identified, none of them likely to be disease-causing. Some of them even involved partial skipping of exons, leading to subsequent truncation of the ATM protein. Hum Mutat 16:232-246, 2000. (C) 2000 Wiley-Liss, Inc. C1 Norwegian Radium Hosp, Dept Genet, N-0310 Oslo, Norway. John F Kennedy Inst, Dept Med Genet, DK-2600 Glostrup, Denmark. Univ Helsinki, Childrens Hosp, Helsinki, Finland. Family Federat Finland, Dept Med Genet, Helsinki, Finland. Finnish Canc Registry, FIN-00170 Helsinki, Finland. Karolinska Inst, Huddinge Hosp, Div Clin Immunol, Huddinge, Sweden. Norwegian Canc Registry, Oslo, Norway. Natl Hosp Norway, Oslo, Norway. Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Swedish Univ Agr Sci, Uppsala, Sweden. RP Borresen-Dale, AL (reprint author), Norwegian Radium Hosp, Dept Genet, N-0310 Oslo, Norway. RI Tucker, Margaret/B-4297-2015; OI Kleinerman, Ruth/0000-0001-7415-2478 FU NCI NIH HHS [N01-CP-61038-50] NR 66 TC 36 Z9 37 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 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 2000 VL 16 IS 3 BP 232 EP 246 DI 10.1002/1098-1004(200009)16:3<232::AID-HUMU6>3.0.CO;2-L PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 349VH UT WOS:000089065900006 PM 10980530 ER PT J AU Svojanovsky, SR Schneider, TD Rogan, PK AF Svojanovsky, SR Schneider, TD Rogan, PK TI Redundant designations of BRCA1 intron 11 splicing mutation; c. 4216-2A > G; IVS11-2A > G; L78833, 37698, A > G SO HUMAN MUTATION LA English DT Letter C1 Childrens Mercy Hosp & Clin, Sect Med Genet & Mol Med, Kansas City, MO 64108 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, Frederick, MD USA. RP Rogan, PK (reprint author), Childrens Mercy Hosp & Clin, Sect Med Genet & Mol Med, 2801 Wyandotte, Kansas City, MO 64108 USA. RI Rogan, Peter/B-9845-2017 OI Rogan, Peter/0000-0003-2070-5254 NR 4 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 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 2000 VL 16 IS 3 BP 264 EP 264 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 349VH UT WOS:000089065900009 PM 10980533 ER PT J AU Hacia, JG Edgemon, K Fang, N Mayer, RA Sudano, D Hunt, N Collins, FS AF Hacia, JG Edgemon, K Fang, N Mayer, RA Sudano, D Hunt, N Collins, FS TI Oligonucleotide microarray based detection of repetitive sequence changes SO HUMAN MUTATION LA English DT Article DE oligonucleotide microarray; DNA chip; mutation detection; double labeling; repetitive sequences; loss of hybridization signal analysis; BRCA1; tripler repeat expansion ID SINGLE-NUCLEOTIDE POLYMORPHISMS; PROBE ARRAYS; DNA ARRAYS; HYBRIDIZATION; MICROCHIPS; MUTATIONS; GENOME; GENES AB Prior studies of oligonucleotide microarray-based mutational analysis have demonstrated excellent sensitivity and specificity except in circumstances where a frameshift mutation occurs in the context of a short repeated sequence. To further evaluate this circumstance, a series of nucleic acid samples having heterozygous mutations within repetitive BRCA1 sequence tracts was prepared and evaluated. These mutations included single nucleotide insertions and deletions in homopolymer runs, insertions and deletions of trinucleotide repeats, and duplications. Two-color comparative hybridization experiments were used wherein wild type reference and test targets are co-hybridized to microarrays designed to screen the entire BRCA1 coding sequence for all possible sequence changes. Mutations in simulated heterozygote samples were detected by observing relative losses of test target hybridization signal to select perfect match oligonucleotide probes. While heterozygous mutations could be readily distinguished above background noise in 9/19 cases, it was not possible to detect alterations in a poly dA/dT tract, small tripler repeat expansions, and a 10 bp direct repeat. Unexpectedly, samples containing (GAT)(3) tripler repeat expansions showed significantly higher affinity toward specific perfect match probes relative to their wild type counterparts. Therefore, markedly increased as well as decreased test sample hybridization to perfect march probes should be used to raise a suspicion of repetitive sequence changes. Hum Mutat 16:354-363, 2000. (C) 2000 Wiley-Liss, Inc. C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Collins, FS (reprint author), NHGRI, NIH, Bldg 49,Room 3A14, Bethesda, MD 20892 USA. NR 30 TC 21 Z9 23 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 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 2000 VL 16 IS 4 BP 354 EP 363 DI 10.1002/1098-1004(200010)16:4<354::AID-HUMU8>3.0.CO;2-V PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 361WG UT WOS:000089746800008 PM 11013446 ER PT J AU Sherry, ST Ward, M Sirotkin, K AF Sherry, ST Ward, M Sirotkin, K TI Use of molecular variation in the NCBI dbSNP database SO HUMAN MUTATION LA English DT Article DE MDI; mutation database; variation; SNP; NCBI ID HUMAN-POPULATIONS; HUMAN GENOME; GENETIC-MAP; POLYMORPHISMS; MUTATION; LINKAGE AB While high quality information regarding variation in genes is currently available in locus-specific or specialized mutation databases, the need remains for a general catalog of genome variation to address the large scale sampling designs required by association studies, gene mapping, and evolutionary biology. In response to this need, the National Center for Biotechnology Information (NCBI) has established the dbSNP database http://ncbi.nlm.nih.gov/SNP/ to serve as a generalized, central variation database. Submissions to dbSNP will be integrated with other sources of information at NCBI such as GenBank, PubMed, LocusLink, and the Human Genome Project data, and the complete contents of dbSNP are available to the public via anonymous FTP. Hum Mutat 15:68-75, 2000, Published 2000 Wiley-Liss, Inc.dagger C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Sherry, ST (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Room 8N805,Bldg 38A, Bethesda, MD 20894 USA. NR 35 TC 37 Z9 39 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 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 2000 VL 15 IS 1 BP 68 EP 75 DI 10.1002/(SICI)1098-1004(200001)15:1<68::AID-HUMU14>3.0.CO;2-6 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 271VE UT WOS:000084613900013 PM 10612825 ER PT J AU Stone, DL Tayebi, N Orvisky, E Stubblefield, B Madike, V Sidransky, E AF Stone, DL Tayebi, N Orvisky, E Stubblefield, B Madike, V Sidransky, E TI Glucocerebrosidase gene mutations in patients with type 2 Gaucher disease SO HUMAN MUTATION LA English DT Article DE Gaucher disease; acute neuronopathic; genotype-phenotype correlation; glucocerebrosidase; GBA; hydrops fetalis; congenital ichthyosis ID TARGETED DISRUPTION; JAPANESE PATIENTS; POINT MUTATIONS; MOUSE MODEL; IDENTIFICATION; ALLELES; JEWISH; HETEROGENEITY; EXPRESSION; PSEUDOGENE AB Gaucher disease, the most common lysosomal storage disorder, results from the inherited deficiency of the enzyme glucocerebrosidase, Three clinical types are recognized: type 1, non-neuronopathic; type 2, acute neuronopathic; and type 3, subacute neuronopathic, Type 2 Gaucher disease, the rarest type, is progressive and fatal. We have performed molecular analyses of a cohort of 31 patients with type 2 Gaucher disease. The cases studied included fetuses presenting prenatally with hydrops fetalis, infants with the collodion baby phenotype, and infants diagnosed after several months of life. All 62 mutant glucocerebrosidase (GBA) alleles were identified. Thirty three different mutant alleles were found, including point mutations, splice junction mutations, deletions, fusion alleles and recombinant alleles. Eleven novel mutations were identified in these patients: R131L, H255Q, R285H, S196P, H311R, c.330delA, V398F, F259L, c.533delC, Y304C and A190E, Mutation L444P was found on 25 patient alleles. Southern blots and direct sequencing demonstrated that mutation L444P occurred alone on 9 alleles, with E326K on one allele and as part of a recombinant allele on 15 alleles. There were no homozygotes for point mutation L444P, The recombinant alleles that included L444P resulted from either reciprocal recombination or gene conversion with the nearby glucocerebrosidase pseudogene, and seven different sites of recombination were identified. Homozygosity fur a recombinant allele was associated with early lethality. We have also summarized the literature describing mutations associated with type 2 disease, and list 50 different mutations. This report constitutes the most comprehensive molecular study to date of type 2 Gaucher disease, and it demonstrates that there is significant phenotypic and genotypic heterogeneity among patients with type 2 Gaucher disease. Hum Mutat 15:181-188, 2000, Published 2000 Wiley-Liss, Inc.dagger C1 NIMH, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. RP Sidransky, E (reprint author), NIMH, Clin Neurosci Branch, NIH, Bldg 49,Room B1EE16,49 Convent Dr,MSC4405, Bethesda, MD 20892 USA. NR 50 TC 116 Z9 121 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 2000 VL 15 IS 2 BP 181 EP 188 DI 10.1002/(SICI)1098-1004(200002)15:2<181::AID-HUMU7>3.0.CO;2-S PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 278BV UT WOS:000084968800007 PM 10649495 ER PT J AU Harlow, SD Baird, DD Weinberg, CR Wilcox, AJ AF Harlow, SD Baird, DD Weinberg, CR Wilcox, AJ TI Urinary oestrogen patterns in long follicular phases SO HUMAN REPRODUCTION LA English DT Article DE follicular phase; menstrual cycle; oligomenorrhoea; urinary oestrone-3-glucuronide ID BREAST-CANCER RISK; MENSTRUAL-CYCLE; PROGESTERONE METABOLITES; STIMULATING-HORMONE; POLYCYSTIC OVARIES; DOMINANT FOLLICLE; LENGTH; WOMEN; CONCEPTION; OVULATION AB Long menstrual cycles have been associated with reduced risk of breast cancer and increased risk of osteoporosis. These observations have led to assumptions about the endogenous oestrogen exposure of women with long cycles, However, daily oestrogen profiles in long menstrual cycles have not been described. This paper examines daily urinary oestrogen profiles during the follicular phases of 416 conception and non-conception cycles. Women were aged 21-42 years, had no history of infertility and were not under treatment. Twenty-eight cycles were defined as long, with a follicular phase that lasted 23 days or more. Five patterns mere observed among these long cycles, the most common being a pattern consistent with delayed emergence of a dominant follicle, Other patterns were a pattern consistent with demise and replacement of a dominant follicle, one consistent with delayed follicular recruitment, one showing a prolonged initial drop in oestrogen and one with an extended oestrogen peak. Average follicular phase oestrogen concentrations were highest in cycles with short follicular phases (7-11 days). Oestrogen concentrations from long follicular phases (24-59 days) did not differ substantially from follicular phases of usual length (12-17 days), The oestrogen profiles in long follicular phases are heterogeneous and not necessarily hypo-oestrogenic. C1 Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Harlow, SD (reprint author), Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. OI Wilcox, Allen/0000-0002-3376-1311; Baird, Donna/0000-0002-5544-2653 FU NICHD NIH HHS [HD30373] NR 31 TC 18 Z9 18 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD JAN PY 2000 VL 15 IS 1 BP 11 EP 16 DI 10.1093/humrep/15.1.11 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 274EL UT WOS:000084750700004 PM 10611180 ER PT B AU Shatkay, H Wilbur, WJ AF Shatkay, H Wilbur, WJ BE Hoppenbrouwers, J Lima, TD Papazoglou, M Sheth, A TI Finding themes in Medline documents - Probabilistic similarity search SO IEEE ADVANCES IN DIGITAL LIBRARIES 2000, PROCEEDINGS LA English DT Proceedings Paper CT IEEE Advances in Digital Libraries 2000 Meeting CY MAY 22-24, 2000 CL WASHINGTON, D.C. SP IEEE, Comp Soc, Tech Comm Digital Lib, Natl Lib Med AB Large on-line document databases, such as Medline, pose a major challenge of retrieving the few documents most relevant to the user's needs, while minimizing the return rate of nonrelevant documents. Retrieval of documents similar to a user-provided example document is a promising query paradigm towards meeting this goal. We present a new theme-based probabilistic approach for finding documents relevant to a given query document, and summarizing their contents. Preliminary experiments conducted over a subset of Medline documents related to AIDs demonstrate the effectiveness of our approach. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Shatkay, H (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NR 24 TC 7 Z9 7 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-7695-0659-3 PY 2000 BP 183 EP 192 DI 10.1109/ADL.2000.848381 PG 10 WC Computer Science, Information Systems SC Computer Science GA BQ59P UT WOS:000088908500017 ER PT B AU Pham, DL Prince, JL AF Pham, DL Prince, JL GP IEEE COMPUTER SOCIETY IEEE COMPUTER SOCIETY TI Unsupervised partial volume estimation in single-channel image data SO IEEE WORKSHOP ON MATHEMATICAL METHODS IN BIOMEDICAL IMAGE ANALYSIS, PROCEEDINGS LA English DT Proceedings Paper CT IEEE Workshop on Mathematical Methods in Biomedical Image Analysis CY JUN 11-12, 2000 CL HILTON HEAD ISL, SC SP IEEE Comp Soc Tech Comm Pattern Anal & Machine Intelligence ID MAGNETIC-RESONANCE IMAGES; GRAY-MATTER VOLUMES; QUANTIFICATION; SEGMENTATION; WHITE AB Partial volume effects are present in nearly all medical imaging data. These artifacts blur the boundaries between different regions, making accurate delineation of anatomical structures difficult. In this paper; we propose a method for unsupervised estimation of partial volume effects in single-channel image data. Based oil a statistical image model, an algorithm is derived for estimating both partial volumes and the means of the different tissue classes in the image. To compensate for the ill-posed nature of the estimation problem, we employ a Batesian approach that places a prior probability model on the parameters. We demonstrate on simulated and real images that the new algorithm is superior in several respects to the fuzzy and Gaussian clustering algorithms that have previously been used for modeling partial volume effects. C1 NIA, Gerontol Res Ctr, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA. RP Pham, DL (reprint author), NIA, Gerontol Res Ctr, Lab Personal & Cognit, NIH, 4940 Eastern Ave, Baltimore, MD 21224 USA. RI Prince, Jerry/A-3281-2010 OI Prince, Jerry/0000-0002-6553-0876 NR 12 TC 4 Z9 4 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-7695-0738-7 PY 2000 BP 170 EP 177 DI 10.1109/MMBIA.2000.852375 PG 8 WC Engineering, Biomedical; Mathematics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Mathematics; Radiology, Nuclear Medicine & Medical Imaging GA BQ44B UT WOS:000088359800021 ER PT B AU Reynolds, JH Desimone, R AF Reynolds, JH Desimone, R BE Marantz, A Miyashita, Y ONeil, W TI Competitive mechanisms subserve selective visual attention SO IMAGE, LANGUAGE, BRAIN LA English DT Proceedings Paper CT 1st Mind Articulation Project Symposium CY NOV 16-17, 1998 CL TOKYO, JAPAN SP Japan Sci & Technol Program Int Cooperat Res ID INFERIOR TEMPORAL CORTEX; TARGET SELECTION; NEURONAL RESPONSES; NEURAL MECHANISMS; RECEPTIVE-FIELD; MACAQUE MONKEY; CORTICAL AREAS; MST; MT; V4 C1 NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. NR 25 TC 3 Z9 3 U1 1 U2 2 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 0-262-13371-7 PY 2000 BP 233 EP 247 PG 15 WC Language & Linguistics; Neurosciences SC Linguistics; Neurosciences & Neurology GA BS52Z UT WOS:000170232200012 ER PT J AU Chen, WS Anton, LC Bennink, JR Yewdell, JW AF Chen, WS Anton, LC Bennink, JR Yewdell, JW TI Dissecting the multifactorial causes of immunodominance in class I-restricted T cell responses to viruses SO IMMUNITY LA English DT Article ID RECEPTOR REPERTOIRE; ANTIVIRAL CTL; INFECTION; EPITOPE; MEMORY; ANTIGEN AB Following influenza virus infection, the numbers of mouse T-CD8+ cells responding to five different determinants vary more than 50-fold in primary responses but less so in secondary responses. Surprisingly, each determinant elicits a highly diverse and highly sensitive T-CD8+ response. Inefficient antigen processing by virus-infected cells accounts for the poor immunogenicity of just one of the subdominant determinants. Over-expressing class I-peptide complexes using vaccinia virus revealed that the poor immunogenicity of two subdominant determinants reflects limitations in T cell responses unrelated to TCR diversity or sensitivity. Despite greatly enhanced expression, the immunodominant determinant is actually less immunogenic when overexpressed by vaccinia virus. Immunodominance is also modulated by determinant-specific variations in the capacity of T-CD8+ to suppress responses to other determinants. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Bennink, JR (reprint author), NIAID, Viral Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RI yewdell, jyewdell@nih.gov/A-1702-2012; Anton, Luis/C-4740-2013; Chen, Weisan/E-7828-2012 OI Anton, Luis/0000-0001-9665-011X; NR 22 TC 232 Z9 236 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JAN PY 2000 VL 12 IS 1 BP 83 EP 93 DI 10.1016/S1074-7613(00)80161-2 PG 11 WC Immunology SC Immunology GA 278WL UT WOS:000085011900009 PM 10661408 ER PT J AU Yeager, M Carrington, M Hughes, AL AF Yeager, M Carrington, M Hughes, AL TI Class I and class II MHC bind self peptide sets that are strikingly different in their evolutionary characteristics SO IMMUNOGENETICS LA English DT Article DE antigen presentation; autoimmune disease; evolution; MHC; self peptides ID MAJOR-HISTOCOMPATIBILITY-COMPLEX; INFLUENZA-VIRUS PEPTIDE; HLA-DM; NUCLEOTIDE SUBSTITUTION; OVERDOMINANT SELECTION; ANTIGEN PRESENTATION; MOLECULES; DISSOCIATION; AUTOIMMUNITY; GENES AB Comparison of peptides eluted from human class I and class II major histocompatibility complex (MHC) molecules and the proteins from which they are derived (source proteins) revealed that class I MHC bind peptides derived from proteins that are highly conserved, hydrophilic, and universally expressed, while the peptides themselves are hydrophobic and even more conserved than their source proteins. In contrast, source proteins for class II-bound peptides were not significantly more conserved than a random sample of proteins. Class II-bound peptides were generally more conserved than their source proteins but were significantly less conserved than class I-bound peptides. The characteristics of class I-bound peptides can probably be explained by the selectivity of processing and transport of peptides for binding by class I, while the relative lack of selectivity of peptide binding for class II may explain the high incidence of autoimmune diseases associated with alleles of these molecules. C1 Penn State Univ, Dept Biol, Mueller Lab 208, University Pk, PA 16802 USA. Penn State Univ, Dept Biol, Inst Mol Evolutionary Genet, University Pk, PA 16802 USA. NCI, Biol Carcinogenesis & Dev Program, SAIC Frederick, Frederick, MD 21702 USA. RP Hughes, AL (reprint author), Penn State Univ, Dept Biol, Mueller Lab 208, University Pk, PA 16802 USA. FU NCI NIH HHS [N01CO56000]; NIGMS NIH HHS [K04GM00614, R01GM34940] NR 42 TC 10 Z9 10 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD JAN PY 2000 VL 51 IS 1 BP 8 EP 15 DI 10.1007/s002510050002 PG 8 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 277TW UT WOS:000084950500002 PM 10663556 ER PT J AU Masat, L Liddell, RA Mock, BA Kuo, WL Jessberger, R Wabl, M Morse, HC AF Masat, L Liddell, RA Mock, BA Kuo, WL Jessberger, R Wabl, M Morse, HC TI Mapping of the SWAP70 gene to mouse Chromosome 7 and human Chromosome 11p15 SO IMMUNOGENETICS LA English DT Article DE B lymphocytes; activation; heavy chain class switch; B-cell receptor; signalling protein ID MAP AB The protein SWAP-70 was isolated as part of a DNA recombination complex in B lymphocytes, where it is predominantly expressed. In resting B cells, SWAP-70 is found in the cytoplasm; upon B-cell activation, it is transported both into the nucleus and to the cell membrane, where it is associated with the B-cell receptor complex and may play a role in signal transduction. In the nucleus, its involvement in heavy-chain class switch recombination has been suggested. In this report, using restriction fragment length polymorphism, simple sequence length polymorphism, and fluorescence in situ hybridization, we map the chromosomal localization of the mouse and the human genes to syntenic regions of mouse mid Chromosome (Chr) 7 and human Chr 11p15. C1 Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. NCI, Genet Lab, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. Basel Inst Immunol, Basel, Switzerland. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. RP Masat, L (reprint author), Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. OI Morse, Herbert/0000-0002-9331-3705 FU NIGMS NIH HHS [GM37699] NR 9 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD JAN PY 2000 VL 51 IS 1 BP 16 EP 19 DI 10.1007/s002510050003 PG 4 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 277TW UT WOS:000084950500003 PM 10663557 ER PT J AU Bream, JH Carrington, M O'Toole, S Dean, M Gerrard, B Shin, HD Kosack, D Modi, W Young, HA Smith, MW AF Bream, JH Carrington, M O'Toole, S Dean, M Gerrard, B Shin, HD Kosack, D Modi, W Young, HA Smith, MW TI Polymorphisms of the human IFNG gene noncoding regions SO IMMUNOGENETICS LA English DT Article DE interferon gamma; polymorphism; promoter; AIOS; 3 ' UTR ID INTERFERON-GAMMA GENE; HIV-1 DISEASE PROGRESSION; FACTOR-ALPHA PROMOTER; NF-KAPPA-B; IMMUNE DYSFUNCTION; IN-VIVO; AIDS; INFECTION; EXPRESSION; ACTIVATION AB Interferon gamma (IFN-gamma) is a multifunctional cytokine that is essential in the development of Th1 cells and in cellular responses to a variety of intracellular pathogens including human immunodeficiency virus (HIV-1). We screened genomic DNA samples from a predominately Caucasian male population of HIV-infected and healthy donors for polymorphisms in the human IFNG gene from -777 to +5608 by single-stranded conformational polymorphism. Surprisingly, the proximal promoter (-777 to transcription start) is invariant as no polymorphisms were found in over 100 samples tested. However, further screening revealed polymorphisms in other regions of the gene including a single base insertion in a poly-T tract in the first intron, three single base pair substitutions in the third intron, and another single base pair substitution in the 3' untranslated region (UTR), Electrophoretic mobility shift assay was used to investigate whether these variants have altered DNA-binding abilities, since intronic enhancer elements have been reported for the IFNG gene. Oligonucleotides constructed for two third intron variants showed no difference in DNA-binding abilities as compared with wild-type sequences. However, the 3'UTR variant showed the formation of unique DNA-binding complexes to radiolabeled oligonucleotide probes as compared with the wild-type sequence. The influence of a CA-repeat microsatellite on AIDS disease progression in HIV-1 seroconverters was tested by a Cox proportional hazards model. There is no evidence of an association between alleles and infection with HIV-1 or progression to AIDS. We report an invariant proximal human IFNG promoter and the existence of multiple intronic variants and a potentially functional 3'UTR polymorphism. C1 NCI, Expt Immunol Lab, Frederick, MD 21702 USA. SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP Young, HA (reprint author), NCI, Expt Immunol Lab, Frederick, MD 21702 USA. RI Young, Howard/A-6350-2008; Smith, Michael/B-5341-2012; OI Young, Howard/0000-0002-3118-5111; Dean, Michael/0000-0003-2234-0631 FU NCI NIH HHS [N01-CO56000] NR 67 TC 58 Z9 61 U1 0 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD JAN PY 2000 VL 51 IS 1 BP 50 EP 58 DI 10.1007/s002510050008 PG 9 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 277TW UT WOS:000084950500008 PM 10663562 ER PT J AU Makrigiannis, AP Anderson, SK AF Makrigiannis, AP Anderson, SK TI Ly49 gene expression in different inbred mouse strains SO IMMUNOLOGIC RESEARCH LA English DT Article DE natural killer cells; Ly49; cell surface molecules; signal transduction; inbred mouse strains ID NATURAL-KILLER-CELLS; SIGNAL-TRANSDUCTION; NK CELLS; FAMILY; COMPLEX; CHROMOSOME-6; CYTOTOXICITY; PHOSPHATASE AB Mouse natural killer cells express receptors for class I MHC in the form of the Ly49 family of proteins. The Ly49 family contains at least 13 expressed members (A, B, C, D, E, F, G, H, I, J, L, O, and P) and is further subdivided into activating and inhibitory subfamilies based on intracellular and transmembrane characteristics. The level of sequence identity between different members varies dramatically. However, comparison of the extracellular domain has revealed that several of the Ly49 molecules also form "pairs," where one member is activating and the other is inhibitory. Until recently, most Ly49 molecules described have come from the C57B1/6 strain of inbred mice. Using molecular cloning and immunochemical analysis we have found that different mouse strains express novel Ly49 molecules. Comparison of the allelic forms of some Ly49 molecules has shown that the dividing line between different genes and different alleles is blurred. C1 NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Expt Immunol Lab, Div Basic Sci, Frederick, MD 21702 USA. RP Anderson, SK (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Intramural Res Support Program, Bldg 560,Rm 31-93, Frederick, MD 21702 USA. RI Anderson, Stephen/B-1727-2012 OI Anderson, Stephen/0000-0002-7856-4266 FU NCI NIH HHS [N01-CO-56000] NR 28 TC 27 Z9 27 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PY 2000 VL 21 IS 1 BP 39 EP 47 DI 10.1385/IR:21:1:39 PG 9 WC Immunology SC Immunology GA 303ZH UT WOS:000086457700005 PM 10803882 ER PT J AU Sogn, JA AF Sogn, JA TI The status of tumor immunology and cancer immunotherapy - Introduction SO IMMUNOLOGICAL INVESTIGATIONS LA English DT Editorial Material ID TUMOR-ANTIGENS; CELLS; IMMUNITY C1 NCI, DCB, NIH, Canc Immunol Branch, Rockville, MD USA. RP Sogn, JA (reprint author), NCI, DCB, NIH, Canc Immunol Branch, 6130 Executive Blvd, Rockville, MD USA. NR 13 TC 1 Z9 1 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0882-0139 J9 IMMUNOL INVEST JI Immunol. Invest. PY 2000 VL 29 IS 2 BP 81 EP 84 DI 10.3109/08820130009062286 PG 4 WC Immunology SC Immunology GA 312YH UT WOS:000086971200002 PM 10854171 ER PT B AU Wang, J Lenardo, MJ AF Wang, J Lenardo, MJ BE Manns, MP Paumgartner, G Leuschner, U TI Caspase-10 mutations in the autoimmune lymphoproliferative syndrome type II SO IMMUNOLOGY & LIVER SE FALK SYMPOSIUM LA English DT Proceedings Paper CT 114th Falk Symposium CY OCT 20-21, 1999 CL BASEL, SWITZERLAND SP Falk Fdn ID TUMOR-NECROSIS-FACTOR; FADD-DEPENDENT APOPTOSIS; CYTOTOXIC LIGAND TRAIL; FAS GENE-MUTATIONS; MATURE T-CELLS; NF-KAPPA-B; TNF FAMILY; TUMORICIDAL ACTIVITY; DEATH DOMAIN; IN-VIVO C1 NIH, NIAID, Immunol Lab, Bethesda, MD 20892 USA. NR 42 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-8759-7 J9 FALK SYMP PY 2000 VL 114 BP 35 EP 45 PG 11 WC Gastroenterology & Hepatology; Immunology SC Gastroenterology & Hepatology; Immunology GA BT29Y UT WOS:000172548400004 ER PT J AU Capodicasa, E Russano, AM Ciurnella, E De Bellis, F Rossi, R Scuteri, A Biondi, R AF Capodicasa, E Russano, AM Ciurnella, E De Bellis, F Rossi, R Scuteri, A Biondi, R TI Neutrophil peripheral count and human leukocyte elastase during chronic lithium carbonate therapy. SO IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY LA English DT Article ID DEPRESSION; PROTEINS; CELLS; BLOOD AB Plasma levels of human polymorphonuclear elastase (PMN-E) are considered a marker of granulocyte activation and can potentially complement the peripheral neutrophil count in laboratory and pathophysiological settings. Neutrophilic leukocytosis is a well known effect of lithium therapy, but there is no information about the concomitant behaviour of PMN-E in these patients. The aim of this study was to evaluate both polymorphonuclear leukocyte count and plasma PMN-E levels in depression patients undergoing chronic lithium therapy. Absolute and differential leukocyte count in venous peripheral blood was determined by an automated method, and PMN-E evaluated by enzyme immunoassay. 39 patients (11 males, 28 females; mean age 43. +/- 6.02) with depression disorders were studied, during lithium carbonate therapy. Neutrophilia (neutrophil count > 7.500x10(9) cells per liter) was found in 7 (18 %) patients and an increase in plasma PMN-E levels (PMN-E > 56 mug per liter) in 6 (15 %) No correlations were found between neutrophil count, plasma concentration of PMN-E, plasma level of lithium and duration of therapy. The results show that in these patients, not only the PMN count but also elastase levels can exceed the normal range. The absence of correlation between these two parameters suggests that the state of PMN activation is not linked to their number in peripheral blood. C1 Univ Perugia, Sez Med Interna & Sci Oncol, Dipartimento Med Clin & Sperimentale, Monteluce Policlin, I-06100 Perugia, Italy. NIA, NIH, Baltimore, MD 21224 USA. RP Capodicasa, E (reprint author), Univ Perugia, Sez Med Interna & Sci Oncol, Dipartimento Med Clin & Sperimentale, Monteluce Policlin, I-06100 Perugia, Italy. NR 23 TC 4 Z9 4 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0892-3973 J9 IMMUNOPHARM IMMUNOT JI Immunopharmacol. Immunotoxicol. PY 2000 VL 22 IS 4 BP 671 EP 683 DI 10.3109/08923970009016431 PG 13 WC Immunology; Pharmacology & Pharmacy; Toxicology SC Immunology; Pharmacology & Pharmacy; Toxicology GA 376DV UT WOS:000165443700004 PM 11105780 ER PT J AU Buck, TB Hall, AL Sinha, CC Bunce, OR Thorgeirsson, UP AF Buck, TB Hall, AL Sinha, CC Bunce, OR Thorgeirsson, UP TI cis-hydroxyproline stimulates the growth of rat mammary carcinoma cells SO IN VIVO LA English DT Article DE cis-hydroxyproline; extracellular matrix; nude mice ID TISSUE INHIBITOR; COLLAGEN; EXPRESSION; MATRIX AB With the ever-increasing evidence that the extracellular matrix (ECM) can stimulate tumor growth, if follows that inhibiting the synthesis of tumor-derived stroma may be a potential therapeutic ta,get of cancel progression. The proline analog cis-hydoxyproline (CHP), an inhibitor of collagen deposition, was examined for, its effects on the growth of clonal tumor cells that differentially produce type IV collagen and laminin. Two separate clones derived fi om rat mammary carcinoma cells that produce high and low amounts of type IV collagen and laminin were injected into the flanks of nude mice. Tumors in animals receiving CHP treatment grew en! faster than tumors in control animals receiving saline, although statistically nor significant. Furthermore, upon administration of CHP to these clones in culture, ina eased proliferation rates of both cell types were observed. These results show that CHP is not useful in preventing stromal development and growth of rat mammary tumor xenografts. C1 NCI, NIH, Div Basic Sci,Tumor Biol & Carcinogenesis Sect, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. Univ Georgia, Coll Pharm, Dept Pharmaceut & Biomed Sci, Athens, GA 30602 USA. RP Thorgeirsson, UP (reprint author), NCI, NIH, Div Basic Sci,Tumor Biol & Carcinogenesis Sect, Cellular Carcinogenesis & Tumor Promot Lab, Bldg 37,Room 2A19, Bethesda, MD 20892 USA. NR 17 TC 1 Z9 1 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 JAN-FEB PY 2000 VL 14 IS 1 BP 7 EP 11 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 298YD UT WOS:000086167600003 ER PT J AU Gillespie, JW Nasir, A Kaiser, HE AF Gillespie, JW Nasir, A Kaiser, HE TI Loss of heterozygosity in papillary and follicular thyroid carcinoma: A mini review. SO IN VIVO LA English DT Review DE papillary; follicular; carcinoma; thyroid; loss of heterozygosity; pathology; review ID LASER CAPTURE MICRODISSECTION; ALLELOTYPE; TUMORS AB Inactivation of tumor suppressor genes is an important mechanism in the development of most cancers. This call be detected by determining loss of heterozygosity (LOH) on highly polymorphic loci on chromosomes. Many investigations to determine LOH in papillary and follicular thyroid carcinoma hale been performed using bulk tissue which was fresh, snap frozen, ol has been fomalin-fixed/paraffin-embedded. Loss of heterozygosity is more frequently encountered in follicular than papillary carcinoma. Laser Capture Microdissection (LCM) may be useful to ascertain if there is a pattern of LOH for various histologic forms and variants of thyroid carcinoma. C1 NCI, NIH, Pathol Lab, Dept Pathogenet, Bethesda, MD 20892 USA. George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 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. Int Inst Anticanc Res, Kapandriti, Greece. RP Gillespie, JW (reprint author), NCI, NIH, Pathol Lab, Dept Pathogenet, Bethesda, MD 20892 USA. NR 9 TC 13 Z9 14 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 JAN-FEB PY 2000 VL 14 IS 1 BP 139 EP 140 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 298YD UT WOS:000086167600018 ER PT J AU Schoeffner, DJ Thorgeirsson, UP AF Schoeffner, DJ Thorgeirsson, UP TI Susceptibility of nonhuman primates to carcinogens of human relevance SO IN VIVO LA English DT Review DE carcinogens; nonhuman primates ID FOOD MUTAGEN 2-AMINO-3-METHYLIMIDAZO<4,5-F>QUINOLINE; DNA ADDUCT LEVELS; CYNOMOLGUS MONKEYS; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE PHIP; 2-AMINO-3,8-DIMETHYLIMIDAZO<4,5-F>QUINOXALINE MEIQX; HEPATOCELLULAR-CARCINOMA; METABOLIC-ACTIVATION; HETEROCYCLIC AMINES; SODIUM SACCHARIN; COOKED FOOD AB Nonhuman primates are a valuable experimental model for the evaluation of human carcinogenic risk but hale not been widely used for various reasons, such as high cost and lack of availability. The present review, discusses the findings from a long-term carcinogenesis study in nonhuman primates that was carried out under contract by the National Cancel Institute from 1961 to 1997. Among the classes of compounds investigated were model rodent carcinogens, food additives, food and environmental contaminants, heterocyclic amines, Nitroso compounds, and antineoplastic and immuno-suppressives. Of the model rodent carcinogens tested only urethane was carcinogenic in monkeys. Long-term administration of saccharin ol cyclamate did not result in toxicity carcinogenicity, in nonhuman primates, which is commonly seen in rodent models. Similar to rodent models and suspected in the human population, the fungal toxins, aflatoxin BI and sterimatocystin, induced malignant liver tumors in monkeys. Relatively few animals administered DDT developed malignant tumors, however; hepatic and CNS toxicity was commonly observed. Hepatocellular carcinoma developed in a majority of monkeys administered the heterocyclic amine, IQ but not the structurally similar MeIQx. Resultant toxicity and carcinogenicity from N-nitroso compounds was variable. While diethyl-nitrosnmine proved to be be the most potent hepatocarcinogen tested no malignant tumors were seen in animals administered N-metyl-N-nitro-N-nitrosoquanidine. Susceptibility of nonhuman primates to chemotherapeutic agents was also variable. Only procarbazine and N-methyl-N-nitrosourea were highly carcinogenic, whereas few tumors were seen as a result of cyclophosphamide, Adriamycin, melphalan or azathioprine. C1 NCI, NIH, Cellular Carcinogenesis & Tumor Promot Lab, Div Basic Sci, Bethesda, MD 20892 USA. RP Thorgeirsson, UP (reprint author), NCI, NIH, Cellular Carcinogenesis & Tumor Promot Lab, Div Basic Sci, Bldg 37,Room 2A19, Bethesda, MD 20892 USA. NR 69 TC 14 Z9 16 U1 1 U2 4 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 JAN-FEB PY 2000 VL 14 IS 1 BP 149 EP 156 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 298YD UT WOS:000086167600020 PM 10757072 ER PT S AU Tylavsky, FA Fuerst, T Nevitt, M Dockrell, M Wan, JY Cauley, J Harris, T AF Tylavsky, FA Fuerst, T Nevitt, M Dockrell, M Wan, JY Cauley, J Harris, T CA Hlth ABC Study BE Yasumura, S Wang, J Pierson, RN TI Measurement of changes in soft tissue mass and fat mass with weight change: Pencil- versus fan-beam dual-energy X-ray absorptiometry SO IN VIVO BODY COMPOSITION STUDIES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 5th International Symposium on In Vivo Body Composition Studies CY OCT 07-09, 1999 CL BROOKHAVEN NATL LAB, UPTON, NEW YORK SP Serono Labs Inc, Lunar Corp, Tanita Corp Amer, Xitron Technologies Corp, Akern (Italy) SRL, RJL Syst, Brookhaven Sci Associates HO BROOKHAVEN NATL LAB C1 Univ Tennessee, Dept Prevent Med, Memphis, TN 38105 USA. SYNARC Inc, San Francisco, CA 94105 USA. Univ Calif San Francisco, San Francisco, CA 94105 USA. Univ Pittsburgh, Pittsburgh, PA 15213 USA. NIA, Bethesda, MD 20892 USA. RP Tylavsky, FA (reprint author), Univ Tennessee, Dept Prevent Med, 66 N Pauline St,Suite 633, Memphis, TN 38105 USA. RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 NR 2 TC 12 Z9 12 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-257-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 904 BP 94 EP 97 PG 4 WC Multidisciplinary Sciences; Radiology, Nuclear Medicine & Medical Imaging SC Science & Technology - Other Topics; Radiology, Nuclear Medicine & Medical Imaging GA BQ56F UT WOS:000088775500013 PM 10865715 ER PT S AU Visser, M Newman, AB Nevitt, MC Kritchevsky, SB Stamm, EB Goodpaster, BH Harris, TB AF Visser, M Newman, AB Nevitt, MC Kritchevsky, SB Stamm, EB Goodpaster, BH Harris, TB CA Hlth Aging Body Composition Study BE Yasumura, S Wang, J Pierson, RN TI Reexamining the sarcopenia hypothesis - Muscle mass versus muscle strength SO IN VIVO BODY COMPOSITION STUDIES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 5th International Symposium on In Vivo Body Composition Studies CY OCT 07-09, 1999 CL BROOKHAVEN NATL LAB, UPTON, NEW YORK SP Serono Labs Inc, Lunar Corp, Tanita Corp Amer, Xitron Technologies Corp, Akern (Italy) SRL, RJL Syst, Brookhaven Sci Associates HO BROOKHAVEN NATL LAB ID WOMEN; ABSORPTIOMETRY; MEN; FAT AB The association of muscle mass and muscle strength with lower-extremity performance, as measured by timed repeated chair stands, was investigated using preliminary data from 3,075 Black and White participants (70-79 years old) in the Health, Aging, and Body Composition Study. Leg muscle mass (LM) was measured by dual-energy X-ray absorptiometry (Hologic QDR 4500), The maximal isokinetic torque of the leg extensors (LS) was measured at 60% using a Kin-Com isokinetic dynamometer, Men were stronger, had greater LM, and better performance than women, As expected, low LS was associated with poorer performance after adjusting for race, study site, and body fat. Low LM was associated with poorer performance in men and women, with a potential threshold effect in women only. When LS and I,hl were modeled simultaneously, only LS remained independently associated with performance. In conclusion, muscle strength, but not muscle mass, is independently associated with lower-extremity performance. C1 Free Univ Amsterdam, Fac Med, Inst Res Extramural Med, NL-1081 BT Amsterdam, Netherlands. NIA, Demog & Biometry Program, Bethesda, MD 20892 USA. Univ Pittsburgh, Div Geriatr Med, Pittsburgh, PA 15213 USA. Univ Calif San Francisco, Prevent Sci Grp, San Francisco, CA 94105 USA. Univ Tennessee, Dept Prevent Med, Memphis, TN 38105 USA. Univ Colorado, Hlth Sci Ctr, Dept Radiol, Sch Med, Denver, CO 80262 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA 15261 USA. RP Visser, M (reprint author), Free Univ Amsterdam, Fac Med, Inst Res Extramural Med, Van Der Boechorststr 7, NL-1081 BT Amsterdam, Netherlands. RI Newman, Anne B./C-6408-2013 OI Newman, Anne B./0000-0002-0106-1150 FU NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] NR 10 TC 88 Z9 88 U1 1 U2 5 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-257-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 904 BP 456 EP 461 PG 6 WC Multidisciplinary Sciences; Radiology, Nuclear Medicine & Medical Imaging SC Science & Technology - Other Topics; Radiology, Nuclear Medicine & Medical Imaging GA BQ56F UT WOS:000088775500087 PM 10865789 ER PT S AU Harris, TB Visser, M Everhart, J Cauley, J Tylavsky, F Fuerst, T Zamboni, M Taaffe, D Resnick, HE Scherzinger, A Nevitt, M AF Harris, TB Visser, M Everhart, J Cauley, J Tylavsky, F Fuerst, T Zamboni, M Taaffe, D Resnick, HE Scherzinger, A Nevitt, M CA Hlth Aging Body Composition Study BE Yasumura, S Wang, J Pierson, RN TI Waist circumference and sagittal diameter reflect total body fat better than visceral fat in older men and women - The health, aging and body composition study SO IN VIVO BODY COMPOSITION STUDIES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 5th International Symposium on In Vivo Body Composition Studies CY OCT 07-09, 1999 CL BROOKHAVEN NATL LAB, UPTON, NEW YORK SP Serono Labs Inc, Lunar Corp, Tanita Corp Amer, Xitron Technologies Corp, Akern (Italy) SRL, RJL Syst, Brookhaven Sci Associates HO BROOKHAVEN NATL LAB ID RISK; SEX AB The validity of waist circumference and sagittal diameter as surrogate measures of visceral fat were assessed using preliminary cross-sectional data from the Health, Aging and Body Composition Study, a cohort of 3,075 men and women aged 70-79, Weight, body mass Index, waist circumference, waist/thigh ratio, and sagittal diameter were compared by correlation, graphical analysis, and regression to total body fat as measured by dual-energy Xray absorptiometry (Hologic 4500A), and to visceral fat area as measured by computerized tomography, We included 2,830 persons, 1, 439 women and 1,391 men with complete data on all measurements, For both men and women, all measurements were strongly correlated with both total body fat and visceral fat except the waist/thigh ratio. However, waist circumference, sagittal diameter, weight, and body mass index were more closely related to total body fat than to visceral fat area (R-2 for the linear regression of waist circumference on total body fat was 0.69 in women and men; R-2 for linear regression of waist circumference on visceral fat area was 0.40 in women, and 0.49 in men). These data suggest that the contribution of visceral fat to health risks will be better assessed by directly measuring this fat depot. C1 NIA, Geriatr Epidemiol Off, Epidemiol Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. Vrije Univ Amsterdam, Inst Res Extramural Med, Amsterdam, Netherlands. NIDDKD, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Tennessee, Memphis, TN USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Synarc Inc, San Francisco, CA USA. Univ Verona, Osped Maggiore, I-37100 Verona, Italy. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. RP Harris, TB (reprint author), NIA, Geriatr Epidemiol Off, Epidemiol Demog & Biometry Program, NIH, Gateway Bldg,Room 3C-309,7201 Wisconsin Ave, Bethesda, MD 20892 USA. RI Cauley, Jane/N-4836-2015; OI Cauley, Jane/0000-0003-0752-4408; ZAMBONI, Mauro/0000-0001-6961-9483 FU NIA NIH HHS [N01-AG-6-2102, N01-AG-6-2103, N01-AG-6-2106] NR 8 TC 84 Z9 88 U1 0 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-257-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 904 BP 462 EP 473 PG 12 WC Multidisciplinary Sciences; Radiology, Nuclear Medicine & Medical Imaging SC Science & Technology - Other Topics; Radiology, Nuclear Medicine & Medical Imaging GA BQ56F UT WOS:000088775500088 PM 10865790 ER PT J AU Suess, PE Bornstein, MH AF Suess, Patricia E. Bornstein, Marc H. TI Task-to-Task Vagal Regulation: Relations With Language and Play in 20-Month-Old Children SO INFANCY LA English DT Article ID VOCABULARY COMPETENCE; SUSTAINED ATTENTION; EARLY-CHILDHOOD; SYMBOLIC PLAY; INFANTS; REACTIVITY; GENDER; MODEL; VARIABILITY AB In this article we report patterns of task-to-task vagal tone change across multiple language and play tasks as well as associations between these patterns of task-to-task vagal tone change and language and play performance in 20-month-old girls and boys. Although initially different in vagal tone suppression during solitary play, girls and boys exhibited similar group patterns of vagal reengagement during successive language and play tasks with their mothers and with an experimenter. In terms of individual differences, vagal suppression during solitary play and vagal reengagement during social interactive tasks predicted language and play performance. Gender differences emerged in patterns of predictive relations: Task-to-task vagal changes predicted primarily play performance in girls and language performance in boys. These findings expose the effects of social context on directional changes in task-to-task vagal tone and speak to the functional role of appropriate vagal regulation in young children's language and play performance. C1 [Suess, Patricia E.; Bornstein, Marc H.] NICHHD, Bethesda, MD 20892 USA. RP Suess, PE (reprint author), Gettysburg Coll, Dept Psychol, Gettysburg, PA 17325 USA. EM PSuess9689@aol.com; Marc_H_Bornstein@nih.gov NR 42 TC 20 Z9 20 U1 3 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1525-0008 J9 INFANCY JI Infancy PY 2000 VL 1 IS 3 BP 303 EP 322 DI 10.1207/S15327078IN0103_2 PG 20 WC Psychology, Developmental SC Psychology GA V73UX UT WOS:000204989100002 ER PT J AU Cote, LR Bornstein, MH AF Cote, Linda R. Bornstein, Marc H. TI Social and Didactic Parenting Behaviors and Beliefs Among Japanese American and South American Mothers of Infants SO INFANCY LA English DT Article AB Mothers of Japanese or South American ancestry living in the United States participated. Similarities and differences in mothers' social and didactic parenting behaviors and beliefs, and direct relations between behaviors and beliefs in these 2 domains of interaction, are reported. In accordance with a common collectivist orientation, Japanese American and South American mothers reported that they engaged in more social than didactic interactions with their infants, and South American mothers more than Japanese American mothers. However, in actuality, both of these acculturating groups engaged in more didactic than social behaviors with their infants and did so for longer periods of time. Not surprisingly, no belief-behavior relations emerged in either group. C1 [Cote, Linda R.; Bornstein, Marc H.] NICHHD, Bethesda, MD 20892 USA. RP Cote, LR (reprint author), NICHHD, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. EM lc140v@nih.gov; Marc_H_Bornstein@nih.gov NR 47 TC 22 Z9 22 U1 0 U2 1 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 1525-0008 J9 INFANCY JI Infancy PY 2000 VL 1 IS 3 BP 363 EP 374 DI 10.1207/S15327078IN0103_5 PG 12 WC Psychology, Developmental SC Psychology GA V73UX UT WOS:000204989100005 ER PT J AU Ahnert, L Lamb, ME Seltenheim, K AF Ahnert, L Lamb, ME Seltenheim, K TI Infant-care provider attachments in contrasting child care settings I: Group-oriented care before German reunification SO INFANT BEHAVIOR & DEVELOPMENT LA English DT Article DE child care; changes in child care practice; care provider behavior; attachment security; strange situation ID CAREGIVER STABILITY; STRANGE-SITUATION; BEHAVIOR; MOTHER; QUALITY; ORGANIZATION; METAPELET; SECURITY; PATTERNS; FATHER AB Before the reunification of Germany, East German child care authorities instructed care providers to foster peer interactions. We investigated the extent to which group-level (empathy, punitiveness, dedication, and permissiveness) and dyadic-level (attentiveness and responsiveness) measures of the care providers' behavior predicted the security of infant-care provider attachment. In 1987-1989, 40 German 11-to 13-month-olds were observed 1 to 2 days, 2 to 4 weeks, acid 3 to 4 months after entry into child care. In Month 5, infants were also seen in the Strange Situation with their primary care providers. Insecure infant-care provider attachments, including high levels of disorganized behavior, were quite common, suggesting that many infants received inadequate care, Secure infant-care provider attachments were best predicted by measures of the care providers' empathy, whereas dyadic-level measures of the care providers' behaviors were not predictive. (C) 2000 Elsevier Science Inc, All rights reserved. C1 Univ Jena, D-6900 Jena, Germany. NICHHD, Bethesda, MD 20892 USA. Interdisciplinary Ctr Appl Res Socializat, Berlin, Germany. RP Ahnert, L (reprint author), Univ Jena, D-6900 Jena, Germany. EM lieselotte.ahnert@karowberlin.de NR 56 TC 9 Z9 9 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-6383 J9 INFANT BEHAV DEV JI Infant Behav. Dev. PY 2000 VL 23 IS 2 BP 197 EP 209 DI 10.1016/S0163-6383(01)00036-4 PG 13 WC Psychology, Developmental SC Psychology GA 449RV UT WOS:000169701700005 ER PT J AU Ahnert, L Lamb, ME AF Ahnert, L Lamb, ME TI Infant-care provider attachments in contrasting child care settings II: Individual-oriented care after German reunification SO INFANT BEHAVIOR & DEVELOPMENT LA English DT Article DE child care; changes in child care practice; infant-mother attachment; infant-care provider attachment; strange situation; care provider behavior ID PROFESSIONAL CAREGIVERS; QUALITY; SENSITIVITY; STABILITY; BEHAVIOR; TEACHERS; SECURITY; PLAY AB Following the reunification of Germany, East German child care providers were urged to foster individual care provider-child relationships rather than peer relationships. In 1993-1997, the extent to which group- and dyadic-level measures of the care providers' behavior predicted variations in the security of infant-care provider attachment was studied in a sample of 70 German 11- to 30-month olds who were enrolled in child care facilities. Procedures and measures were the same as reported by Ahnert, Lamb, and Seltenheim (2000). Levels of care provider sensitivity and empathy were greater after reunification than before, and infants were more likely than those assessed prior to reunification to be securely attached to their care providers. Even though insecure attachments appeared to be common, disorganized patterns were infrequent. Measures of the care providers' sensitivity to individual infants did not predict attachment security although group-level differences in empathy were predictive. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Univ Jena, D-6900 Jena, Germany. NICHHD, Bethesda, MD 20892 USA. RP Ahnert, L (reprint author), Univ Jena, D-6900 Jena, Germany. NR 37 TC 10 Z9 10 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0163-6383 J9 INFANT BEHAV DEV JI Infant Behav. Dev. PY 2000 VL 23 IS 2 BP 211 EP 222 DI 10.1016/S0163-6383(01)00042-X PG 12 WC Psychology, Developmental SC Psychology GA 449RV UT WOS:000169701700006 ER PT J AU Gopinath, R Hanna, LE Kumaraswami, V Perumal, V Kavitha, V Vijayasekaran, V Nutman, TB AF Gopinath, R Hanna, LE Kumaraswami, V Perumal, V Kavitha, V Vijayasekaran, V Nutman, TB TI Perturbations in eosinophil homeostasis following treatment of lymphatic filariasis SO INFECTION AND IMMUNITY LA English DT Article ID MAJOR BASIC-PROTEIN; POSTTREATMENT EOSINOPHILIA; ONCHOCERCA-VOLVULUS; GRANULE PROTEINS; BANCROFTIAN FILARIASIS; SCHISTOSOMA-MANSONI; MAZZOTTI REACTION; CATIONIC PROTEIN; SERUM LEVELS; IN-VITRO AB Treatment of patients with patent Wuchereria bancrofti infection results in an acute clinical reaction and peripheral eosinophilia. To investigate the dynamics of the eosinophil response, changes in eosinophil activation and degranulation and plasma levels of eosinophil-active chemokines and cytokines were studied in 15 microfilaremic individuals in south India by sequential blood sampling before and after administration of 300 mg of diethylcarbamazine (DEC). Clinical symptoms occurred within 24 h. Plasma interleukin-5 (IL-5) and RANTES levels peaked 1 to 2 days posttreatment, preceding a peak peripheral eosinophil count at day 4. Major basic protein secretion from eosinophils paralleled IL-5 secretion, while levels of eosinophil-derived neurotoxin peaked at day 13 after treatment. Expression of the activation markers HLA-DR and CD25 on eosinophils rose markedly immediately after treatment, while expression of VLA-4 and alpha 4 beta 7 showed an early peak within 24 h and a second peak at day 13. Thus, the posttreatment reactions seen in filarial infections can be divided into an early phase with killing of microfilariae, clinical symptomatology, increases in plasma IL-5 and RANTES levels, and eosinophil activation and degranulation and a later phase with expression of surface integrins on eosinophils, recruitment of eosinophils from the bone marrow to tissues, and clearance of parasite antigen. C1 NIAID, Helminth Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. TB Res Ctr, Madras, Tamil Nadu, India. Govt Gen Hosp, Madras, Tamil Nadu, India. RP Gopinath, R (reprint author), NIAID, Helminth Immunol Sect, Parasit Dis Lab, NIH, Bldg 4,Room 126, Bethesda, MD 20892 USA. NR 40 TC 13 Z9 13 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 JAN PY 2000 VL 68 IS 1 BP 93 EP 99 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 266LQ UT WOS:000084301800014 PM 10603373 ER PT J AU Singer, SM Nash, TE AF Singer, SM Nash, TE TI T-cell-dependent control of acute Giardia lamblia infections in mice SO INFECTION AND IMMUNITY LA English DT Article ID NODULAR LYMPHOID HYPERPLASIA; ANTIGENIC VARIATION; MURIS INFECTION; DEFICIENT MICE; PROTECTIVE IMMUNITY; CYTOKINE PRODUCTION; ANTIBODY-RESPONSE; ORAL TOLERANCE; MAST-CELLS; IMMUNOGLOBULIN AB We have studied immune mechanisms responsible for control of acute Giardia lamblia and Giardia muris infections in adult mice. Association of chronic G. lamblia infection with hypogammaglobulinemia and experimental infections of mice with G. muris have led to the hypothesis that antibodies are required to control these infections. We directly tested this hypothesis by infecting B-cell-deficient mice with either G. lamblia or G. muris. Both wild-type mice and B-cell-deficient mice eliminated the vast majority of parasites between 1 and 2 weeks postinfection with G. lamblia. G. muris was also eliminated in both wild-type and B-cell-deficient mice. In contrast, T-cell-deficient and scid mice failed to control G. lamblia infections, as has been shown previously for G. muris. Treatment of wild-type or B-cell-deficient mice with antibodies to CD4 also prevented elimination of G. lamblia, confirming a role for T cells in controlling infections. By infecting mice deficient in either alpha beta- or gamma delta-T-cell receptor (TCR)-expressing T cells, we show that the alpha beta-TCR-expressing T cells are required to control parasites but that the gamma delta-TCR-expressing T cells are not. Finally, infections in mice deficient in production of gamma interferon or interleukin 4 (IL-4) and mice deficient in responding to IL-4 and IL-13 revealed that neither the Th1 nor the Th2 subset is absolutely required for protection from G. lamblia. We conclude that a T-cell-dependent mechanism is essential for controlling acute Giardia infections and that this mechanism is independent of antibody and B cells. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Singer, SM (reprint author), Georgetown Univ, Dept Biol, Reiss 306A, Washington, DC 20057 USA. NR 57 TC 88 Z9 92 U1 0 U2 5 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 JAN PY 2000 VL 68 IS 1 BP 170 EP 175 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 266LQ UT WOS:000084301800025 PM 10603384 ER PT J AU Su, H Messer, R Whitmire, W Hughes, S Caldwell, HD AF Su, H Messer, R Whitmire, W Hughes, S Caldwell, HD TI Subclinical chlamydial infection of the female mouse genital tract generates a potent protective immune response: Implications for development of live attenuated chlamydial vaccine strains SO INFECTION AND IMMUNITY LA English DT Article ID GENE KNOCKOUT MICE; OUTER-MEMBRANE PROTEIN; GAMMA-INTERFERON; ECTOPIC PREGNANCY; IFN-GAMMA; TRACHOMATIS; CELLS; PNEUMONITIS; INFERTILITY; HUMANS AB Chlamydia trachomatis is a major cause of sexually transmitted disease (STD) for which a vaccine is needed. CD4(+) T-helper type 1 (Th1) cell-mediated immunity is an important component of protective immunity against murine chlamydial genital infection, Conventional vaccine approaches have not proven effective in eliciting chlamydial-specific CD4 Th1 immunity at the genital mucosa. Thus, it is possible that the development of a highly efficacious vaccine against genital infection will depend on the generation of a live attenuated C. trachomatis vaccine. Attenuated strains of C. trachomatis do not exist, so their potential utility as vaccines cannot be tested in animal models of infection. We have developed a surrogate model to study the effect of chlamydial attenuation on infection and immunity of the female genital tract by treating mice with a subchlamydiacidal concentration of oxytetracycline following vaginal infection. Compared to untreated control mice, antibiotic-treated mice shed significantly fewer infectious organisms (3 log(10)) from the cervico-vagina, produced a minimal inflammatory response in urogenital tissue, and did not experience infection-related sequelae. Antibiotic-treated mice generated levels of chlamydia-specific antibody and cell-mediated immunity equivalent to those of control mice. Importantly, antibiotic-treated mice were found to be as immune as control untreated mice when rechallenged vaginally. These findings demonstrate that subclinical chlamydial infection of the murine female genital tract is sufficient to stimulate a potent protective immune response. They also present indirect evidence supporting the possible use of live attenuated chlamydial organisms in the development of vaccines against chlamydial STDs. C1 NIAID, Intracellular Parasites Lab, Rocky Mt Lab, NIH, Hamilton, MT 59840 USA. RP Caldwell, HD (reprint author), NIAID, Intracellular Parasites Lab, Rocky Mt Lab, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 28 TC 22 Z9 24 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 JAN PY 2000 VL 68 IS 1 BP 192 EP 196 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 266LQ UT WOS:000084301800028 PM 10603387 ER PT J AU Nagineni, CN Detrick, B Hooks, JJ AF Nagineni, CN Detrick, B Hooks, JJ TI Toxoplasma gondii infection induces gene expression and secretion of interleukin 1 (IL-1), IL-6, granulocyte-macrophage colony-stimulating factor, and intercellular adhesion molecule 1 by human retinal pigment epithelial cells SO INFECTION AND IMMUNITY LA English DT Article ID OCULAR TOXOPLASMOSIS; ULTRASTRUCTURAL PATHOLOGY; RETINOCHOROIDITIS; CYTOKINES; UVEITIS; MORPHOLOGY; INTERFERON; ICAM-1 AB We have used human retinal pigment epithelial (HRPE) cultures to investigate the primary cellular responses of retinal resident cells to intracellular Toxoplasma gondii replication. At 4 days postinoculation, when all of the cells were infected, the secretion of interleukin 1 beta (IL-1 beta), IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), and intercellular adhesion molecule 1 (ICAM-1) was augmented by 23-, 10-, 8-, and 5-fold, respectively, over the control. Northern and reverse transcriptase PCR analyses showed significant upregulation of steady-state levels of mRNA for IL-1 beta, IL-6, GM-CSF, and ICAM-1. The secretion of these molecules by HRPE cells may play a critical immunoregulatory role in the pathophysiological processes associated with T. gondii-induced retinochoroiditis. C1 NEI, Immunol & Virol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. George Washington Univ, Med Ctr, Dept Pathol, Washington, DC 20037 USA. RP Hooks, JJ (reprint author), NEI, Immunol & Virol Sect, Immunol Lab, NIH, Bldg 10,Room 6N 228, Bethesda, MD 20892 USA. NR 31 TC 45 Z9 45 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 JAN PY 2000 VL 68 IS 1 BP 407 EP 410 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 266LQ UT WOS:000084301800059 PM 10603418 ER PT S AU Lindberg, DAB AF Lindberg, DAB BE Balas, EA Boren, SA Brown, GD TI Transferring research through high performance computing SO INFORMATION TECHNOLOGY STRATEGIES FROM THE UNITED STATES AND THE EUROPEAN UNION: TRANSFERRING RESEARCH TO PRACTICE FOR HEALTH CARE IMPROVEMENT SE STUDIES IN HEALTH TECHNOLOGY AND INFORMATICS LA English DT Proceedings Paper CT Conference on Transferring Research to Practice in the Information Age CY NOV 12-13, 1998 CL UNIV MISSOURI, KANSAS CITY, MO SP Univ Missouri HO UNIV MISSOURI C1 Natl Lib Med, Bethesda, MD 20209 USA. RP Lindberg, DAB (reprint author), Natl Lib Med, Bethesda, MD 20209 USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 1-58603-054-X J9 ST HEAL T PY 2000 VL 76 BP 3 EP 10 PG 8 WC Computer Science, Information Systems; Medical Informatics SC Computer Science; Medical Informatics GA BP98X UT WOS:000086825300001 PM 10947499 ER PT S AU McCray, AT AF McCray, AT BE Balas, EA Boren, SA Brown, GD TI Digital library research and application SO INFORMATION TECHNOLOGY STRATEGIES FROM THE UNITED STATES AND THE EUROPEAN UNION: TRANSFERRING RESEARCH TO PRACTICE FOR HEALTH CARE IMPROVEMENT SE Studies in Health Technology and Informatics LA English DT Proceedings Paper CT Conference on Transferring Research to Practice in the Information Age CY NOV 12-13, 1998 CL UNIV MISSOURI, KANSAS CITY, MO SP Univ Missouri HO UNIV MISSOURI ID MEDICAL-LANGUAGE-SYSTEM; WORLD-WIDE-WEB; BIOMEDICAL INFORMATION; INTERNET AB The last decade has seen an exponential rise in the amount and the nature of information that is available on the Internet. Internet and World Wide Web technology have raised many technical as well as social and economic issues. The paper begins with a description of the recent digital library research initiative funded by the U.S. federal government. Digital library research addresses a host of informatics issues relevant to the current Internet-based environment. The paper continues with a discussion of some problems in information access, including a discussion of the potential of the Unified Medical Language System for navigating among multiple biomedical information systems. Next, some issues in creating Web-accessible resources for health care consumers are addressed, with a focus on recent work at the National Library of Medicine, including a description of the MEDLINEplus system. The paper ends with a brief discussion of some implications of digital library research for the health informatics community. C1 Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bethesda, MD 20894 USA. RP McCray, AT (reprint author), Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bethesda, MD 20894 USA. NR 31 TC 0 Z9 0 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 1-58603-054-X J9 STUD HEALTH TECHNOL PY 2000 VL 76 BP 51 EP 62 PG 12 WC Computer Science, Information Systems; Medical Informatics SC Computer Science; Medical Informatics GA BP98X UT WOS:000086825300005 PM 10947501 ER PT S AU Cantor, KP Ward, MH Scanlan, LP Slattery, M AF Cantor, KP Ward, MH Scanlan, LP Slattery, M BE Reichard, EG Hauchman, FS Sancha, AM TI Arsenic in drinking water and bladder cancer: a case-control study in Utah, USA SO INTERDISCIPLINARY PERSPECTIVES ON DRINKING WATER RISK ASSESSMENT AND MANAGEMENT SE IAHS PUBLICATION LA English DT Meeting Abstract CT 2nd International Symposium on Assessing and Managing Health Risk From Drinking Water Contamination: Approaches and Applications CY SEP 07-10, 1998 CL UNIV CHILE, SANTIAGO, CHILE SP Int Assoc Hydrol Sci, Int Commiss Groundwater, Int Assoc Hydrol Sci, Int Commiss Water Qual, US Geol Survey, Univ Chile HO UNIV CHILE C1 NCI, Occupat Epidemiol Branch, Bethesda, MD 20892 USA. Univ Utah, Salt Lake City, UT 84112 USA. RP Cantor, KP (reprint author), NCI, Occupat Epidemiol Branch, 418 Execut Plaza N, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT ASSOC HYDROLOGICAL SCIENCES PI WALLINGFORD PA INST OF HYDROLOGY, WALLINGFORD OX10 8BB, ENGLAND SN 0144-7815 BN 1-901502-11-2 J9 IAHS-AISH P PY 2000 IS 260 BP 27 EP 27 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Water Resources SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Water Resources GA BR04W UT WOS:000165502300005 ER PT S AU Ferreccio, C Gonzalez, C Milosavjlevic, V Marshall, G Sancha, AM AF Ferreccio, C Gonzalez, C Milosavjlevic, V Marshall, G Sancha, AM BE Reichard, EG Hauchman, FS Sancha, AM TI Exposure to arsenic in air and drinking water: results of a case-control study in northern Chile SO INTERDISCIPLINARY PERSPECTIVES ON DRINKING WATER RISK ASSESSMENT AND MANAGEMENT SE IAHS PUBLICATION LA English DT Meeting Abstract CT 2nd International Symposium on Assessing and Managing Health Risk From Drinking Water Contamination: Approaches and Applications CY SEP 07-10, 1998 CL UNIV CHILE, SANTIAGO, CHILE SP Int Assoc Hydrol Sci, Int Commiss Groundwater, Int Assoc Hydrol Sci, Int Commiss Water Qual, US Geol Survey, Univ Chile HO UNIV CHILE C1 NCI, Occupational Epidemiol Branch, Bethesda, MD 20892 USA. Univ Utah, Salt Lake City, UT 84112 USA. RP Ferreccio, C (reprint author), NCI, Occupational Epidemiol Branch, 418 Execut Plaza N, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT ASSOC HYDROLOGICAL SCIENCES PI WALLINGFORD PA INST OF HYDROLOGY, WALLINGFORD OX10 8BB, ENGLAND SN 0144-7815 BN 1-901502-11-2 J9 IAHS-AISH P PY 2000 IS 260 BP 27 EP 28 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Water Resources SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Water Resources GA BR04W UT WOS:000165502300006 ER PT J AU Epstein, SL Stack, A Misplon, JA Lo, CY Mostowski, H Bennink, J Subbarao, K AF Epstein, SL Stack, A Misplon, JA Lo, CY Mostowski, H Bennink, J Subbarao, K TI Vaccination with DNA encoding internal proteins of influenza virus does not require CD8(+) cytotoxic T lymphocytes: either CD4(+) or CD8(+) T cells can promote survival and recovery after challenge SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE infectious immunity-virus; influenza; T lymphocytes; lung; transgenic/knockout ID I-DEFICIENT MICE; A VIRUS; BETA(2)-MICROGLOBULIN-DEFICIENT MICE; VACCINIA VIRUS; BETA-2-MICROGLOBULIN-DEFICIENT MICE; RESPIRATORY-INFECTION; MONOCLONAL-ANTIBODIES; HETEROTYPIC IMMUNITY; PROTECTIVE IMMUNITY; EFFECTOR FUNCTION AB DNA vaccination offers the advantages of viral gene expression within host cells without the risks of infectious virus. Like viral vaccines, DNA vaccines encoding internal influenza virus proteins can induce immunity to conserved epitopes and so may defend the host against a broad range of viral variants, CD8(+) cytotoxic T lymphocytes (CTL) have been described as essential effecters in protection by influenza nucleoprotein (NP), although a lesser role of CD4(+) cells has been reported. We immunized mice with plasmids encoding influenza virus NP and matrix (M). NP + M DNA allowed B6 mice to survive otherwise lethal challenge infection, but did not protect BG-beta(2)m(-/-) mice defective in CD8(+) CTL. However, this does not prove CTL are required, because beta(2)m(-/-) mice have multiple immune abnormalities. We used acute T cell depletion in vivo to identify effecters critical for defense against challenge infection. Since lung lymphocytes are relevant to virus clearance, surface phenotypes and cytolytic activity of lung lymphocytes were analyzed in depleted animals, along with lethal challenge studies. Depletion of either CD4(+) or CD8(+) T cells in NP + M DNA-immunized BALB/c mice during the challenge period did not significantly decrease survival, while simultaneous depletion of CD4+ and CD8(+) cells or depletion of all CD90(+) cells completely abrogated survival. We conclude that T cell immunity induced by NP + M DNA vaccination is responsible for immune defense, but CD8(+) T cells are not essential in the active response to this vaccination. Either CD4(+) or CD8(+) T cells can promote survival and recovery in the absence of the other subset. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Mol Immunol Lab, Bethesda, MD 20892 USA. NIAID, Viral Dis Lab, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Influenza Branch, Atlanta, GA 30333 USA. RP Epstein, SL (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Mol Immunol Lab, HFM-521,Bldg 29B,Room 2G15,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 75 TC 54 Z9 56 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 JAN PY 2000 VL 12 IS 1 BP 91 EP 101 DI 10.1093/intimm/12.1.91 PG 11 WC Immunology SC Immunology GA 277HD UT WOS:000084925900011 PM 10607754 ER PT J AU Katoh, T Boissy, R Nagata, N Kitagawa, K Kuroda, Y Itoh, H Kawamoto, T Bell, DA AF Katoh, T Boissy, R Nagata, N Kitagawa, K Kuroda, Y Itoh, H Kawamoto, T Bell, DA TI Inherited polymorphism in the N-acetyltransferase 1 (NAT1) and 2 (NAT2) genes and susceptibility to gastric and colorectal adenocarcinoma SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID CIGARETTE-SMOKING; BLADDER-CANCER; RISK; ASSOCIATION; CARCINOMA; EXPOSURE; DIET AB The polymorphic arylamine N-acetyltransferases (NAT1 and NAT2) have been implicated in increased susceptibility to certain malignancies. We analyzed genetic polymorphisms in both the NAT1 and NAT2 genes among 140 gastric adenocarcinoma patients, 103 colorectal adenocarcinoma patients and 122 healthy controls from Japan. The frequency of the specific genotype NAT1*10 allele, which contains a variant polyadenylation signal, was higher among all gastric adenocarcinoma cases, but this increase did not reach statistical significance. After grouping according to tumor differentiation of gastric adenocarcinoma patients, NAT1 polymorphism was a risk factor among the well-differentiated type of tumors (OR = 3.03, 95% CI 1.08-8.46). Stratifying by smoking status, we found that the OR for heavy smokers with the NAT1*10 allele was 2.97 (95% CI 1.23-7.14). When the combined risk of NAT1*10 allele from smoking and tumor differentiation was calculated, we found that the risk of the NAT1*10 allele with heavy smoking was increased among the well-differentiated type of gastric adenocarcinoma (OR = 4.24, 95% Cl 0.87-20.6). The NAT1*10 genotype was not a significant risk factor in colorectal adenocarcinoma. No statistically significant differences were observed in the frequency of NAT2 rapid acetylation genotype in gastric (91.4%) or colorectal (95.2%) adenocarcinoma patients when compared with the control population (94.3%). Our results suggest the NAT1*10 allele may be an important genetic determinant of the well-differentiated type of gastric adenocarcinoma, which may be induced by smoking. (C) 2000 Wiley-Liss. Inc. C1 Univ Occupat & Environm Hlth, Sch Hlth Sci, Kitakyushu, Fukuoka 807, Japan. Natl Inst Environm Hlth Sci, Lab Computat Biol & Risk Assessment, Res Triangle Pk, NC USA. UOEH, Sch Med, Dept Surg 1, Kitakyushu, Fukuoka, Japan. UOEH, Sch Med, Dept Environm Hlth, Kitakyushu, Fukuoka, Japan. RP Katoh, T (reprint author), Univ Occupat & Environm Hlth, Sch Hlth Sci, Kitakyushu, Fukuoka 807, Japan. NR 22 TC 49 Z9 57 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 1 PY 2000 VL 85 IS 1 BP 46 EP 49 DI 10.1002/(SICI)1097-0215(20000101)85:1<46::AID-IJC8>3.0.CO;2-0 PG 4 WC Oncology SC Oncology GA 261YW UT WOS:000084039800009 PM 10585581 ER PT J AU Hsing, AW Tsao, L Devesa, SS AF Hsing, AW Tsao, L Devesa, SS TI International trends and patterns of prostate cancer incidence and mortality SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID ANDROGEN RECEPTOR GENE; PHYSICAL-ACTIVITY; RISING INCIDENCE; RISK-FACTORS; SHANGHAI; JAPANESE; CHINA; RATES; BELIEFS; BREAST AB Prostate cancer is the most commonly diagnosed cancer in western men, and incidence is rising rapidly in most countries, including low-risk populations. Age-adjusted incidence and mortality rates from 15 and 13 countries between 1973-77 and 1988-92, respectively, were compared to provide leads for future analytic studies. Large increases in both incidence and mortality rates of prostate cancer were seen for all countries. For incidence, increases were more pronounced in the United States, Canada, Australia, France and the Asian countries, while the increases in medium-risk countries were moderate. Increases in incidence ranged from 25%-114%, 24%-55% and 15%-104% in high-, medium- and low-risk countries, respectively. Mortality rates rose more rapidly in Asian countries than in high-risk countries. Substantial differences in incidence and mortality across countries were evident, with U.S. blacks having rates that were 50-60 times higher than the rates in Shanghai, China. Increasing incidence rates in the United States and Canada are likely to be due in part to the widespread use of transurethral resection of the prostate and prostate-specific antigen testing, while increases in the Asian countries are probably related to westernization in these low-risk populations. The large disparities in incidence between high- and low-risk countries may be due to a combination of genetic and environmental factors. Future studies are needed to examine gene-gene and gene-environment interactions in various countries concurrently to shed light on the etiology of prostate cancer and to help elucidate reasons for the large differences in risk between populations. (dagger)Published 2000 Wiley-liss, Inc. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA. RP Hsing, AW (reprint author), NCI, Div Canc Epidemiol & Genet, EPS-MSC 7234,6120 Execut Blvd, Bethesda, MD 20852 USA. NR 46 TC 534 Z9 555 U1 0 U2 17 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 1 PY 2000 VL 85 IS 1 BP 60 EP 67 DI 10.1002/(SICI)1097-0215(20000101)85:1<60::AID-IJC11>3.3.CO;2-2 PG 8 WC Oncology SC Oncology GA 261YW UT WOS:000084039800012 PM 10585584 ER PT J AU Matera, L Geuna, M Pastore, C Buttiglieri, S Gaidano, G Savarino, A Marengo, S Vonderhaar, BK AF Matera, L Geuna, M Pastore, C Buttiglieri, S Gaidano, G Savarino, A Marengo, S Vonderhaar, BK TI Expression of prolactin and prolactin receptors by non-Hodgkin's lymphoma cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID NATURAL-KILLER-CELLS; MONOCLONAL-ANTIBODY; GROWTH-HORMONE; LINE; INTERLEUKIN-2; PROLIFERATION; ESTABLISHMENT; ENDOCRINE AB Prolactin (PRL) interacts with lymphocyte-signaling molecules and cytokines. Previous work has shown independent: and synergistic effects of PRL on the generation of IL-2-driven anti-tumor lymphokine activated killer (LAK) activity by peripheral blood mononuclear cells (PBMC), The potential importance of PRL as a biological immunomodifier, however, is challenged by its ability to influence normal lymphocyte mitogenesis and hence lymphoid tumor growth. Since non-Hodgkin's lymphoma (NHL) cell lines were efficiently killed by LAK generated with native (n) or recombinant (r) human PRL combined with low, per se ineffective doses of IL-2, we have addressed here the question of whether PRL acts as a growth factor for LAK targets. NHL cells were analyzed for: I. expression of the PRL receptor (PRL-R); 2. responsiveness to nPRL or rPRL; 3. constitutive expression and release of PRL; 4. existence of a PRL autocrine loop. PRL-R, defined by multiple antibodies, was detected in 3 of IZ NHL cell lines. However, nPRL or rPRL, in a wide range of concentrations (0.75-50 ng/ml), were not mitogenic for growth-arrested, PRL-R positive NHL cell lines. PRL mRNA was detected by RT-PCR in 10 of the 12 cell lines examined with a higher frequency among AIDS-related NHL cell lines. PRL protein in the immunoprecipitate of S-35-methionine-labeled cell lysates and supernatants paralleled mRNA expression, and Western blotting analysis showed the presence of the pituitary/lymphocyte non-glycosylated (23.5 kDa) and glycosylated (25 kDa) isoforms. Experiments with blocking antibodies showed the independence from endogenous PRL for NHL cell growth. (C) 2000 Wiley-Liss, Inc. C1 Univ Turin, Dept Internal Med, I-10126 Turin, Italy. IRCC, Inst Canc Res & Treatment, Turin, Italy. Scripps Res Inst, Dept Immunol, La Jolla, CA USA. Amedeo Avogadro Univ Eastern Piedmont, Dept Med Sci, Novara, Italy. Univ Turin, Dept Med & Surg Sci, Turin, Italy. NCI, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. RP Matera, L (reprint author), Univ Turin, Dept Internal Med, Corso AM Dogliotti 14, I-10126 Turin, Italy. NR 30 TC 16 Z9 17 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 1 PY 2000 VL 85 IS 1 BP 124 EP 130 DI 10.1002/(SICI)1097-0215(20000101)85:1<124::AID-IJC22>3.0.CO;2-U PG 7 WC Oncology SC Oncology GA 261YW UT WOS:000084039800023 PM 10585595 ER PT J AU Merlo, GR Zerega, B Paleari, L Trombino, S Mantero, S Levi, G AF Merlo, GR Zerega, B Paleari, L Trombino, S Mantero, S Levi, G TI Multiple functions of Dlx genes SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE Dlx; craniofacial; limb; osteogenesis; brain development ID IN-SITU HYBRIDIZATION; PROXIMAL-DISTAL AXIS; HOMEOBOX GENE; LIMB DEVELOPMENT; MICE LACKING; INNER-EAR; OSTEOBLAST DIFFERENTIATION; CHROMOSOME 17Q21.3-Q22; DEVELOPING FOREBRAIN; DROSOPHILA EMBRYO AB Dixgenes comprise a highly conserved family of homeobox genes homologous to the distal-less (Dll) gene of Drosophila. They are thought to act as transcription factors. All Dir genes are expressed in spatially and temporally restricted patterns in craniofacial primordia, basal telencephalon and diencephalon, and in distal regions of extending appendages, including the limb and the genital bud. Most of them are expressed during morphogenesis of sensory organs and during migration of neural crest cells and interneurons. In addition, Dlx5 and Dlx6 are expressed in differentiating osteoblasts. Gene targeting of Dlx7, Dlx2, Dlx3 and Dlx5in the mouse germ-line has revealed functions in craniofacial patterning, sensory organ morphogenesis, osteogenesis and placental formation. However, no effect on limb development has yet been revealed from gene inactivation studies. A role for these genes in limb development is however suggested by the linkage of the Split Foot/Hand Malformation human syndrome to a region containing DLX5 and DLXG. As for most transcription factors, these genes seem to have multiple functions at different stages of development or in different tissues and cell types. C1 IST, Adv Biotechnol Ctr, CBA, Lab Mol Mutagenesis,Natl Canc Inst, I-16132 Genoa, Italy. Museum Natl Hist Nat, Lab Physiol Gen & Comparee, UMR 8572, CNRS, F-75231 Paris, France. RP Levi, G (reprint author), IST, Adv Biotechnol Ctr, CBA, Lab Mol Mutagenesis,Natl Canc Inst, Largo R Benzi 10, I-16132 Genoa, Italy. RI Levi, Giovanni/B-4416-2013; OI Mantero, Stefano/0000-0003-0608-2724 FU Telethon [D.076] NR 63 TC 100 Z9 105 U1 0 U2 4 PU UNIV BASQUE COUNTRY PRESS PI BILBAO PA POST BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PY 2000 VL 44 IS 6 SI SI BP 619 EP 626 PG 8 WC Developmental Biology SC Developmental Biology GA 367QX UT WOS:000090073900013 PM 11061425 ER PT J AU Striegel-Moore, RH Schreiber, GB Lo, A Crawford, P Obarzanek, E Rodin, J AF Striegel-Moore, RH Schreiber, GB Lo, A Crawford, P Obarzanek, E Rodin, J TI Eating disorder symptoms in a cohort of 11 to 16-year-old black and white girls: The NHLBI growth and health study SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE Eating Disorder Inventory; black and white girls; adolescents ID ADOLESCENT GIRLS; BODY-IMAGE; SOCIOECONOMIC-STATUS; ANOREXIA-NERVOSA; COMMUNITY SAMPLE; BULIMIA-NERVOSA; ATTITUDES TEST; BEHAVIORS; INVENTORY; CHILDREN AB Objective: This study sought to provide reference data for the Eating Disorder Inventory (EDI) with use of young adolescent black and white girls. Moreover, the study examined the relationship between race, age, socioeconomic status, and adiposity and each of the eight EDI scales. Method: To achieve these aims, data were used that had been collected in Years 3, 5, and 7 as part of the National Heart, Lung, and Blood institute Growth and Health Study, a longitudinal cohort study of risk factors for obesity in black and white girls. For the present report, data were available from 2,228 girls in Year 3, 2,056 girls in Year 5, and 1,902 girls in Year 7 Results: EDI scores were found to vary by race, age, socioeonomic status, and body weight of respondents. Black girls scored different from white girls on all EDI subscales. Scores on all but two subscales (Body Dissatisfaction, Drive for Thinness) decreased significantly with increasing age. Significant inverse associations were found between maximum parental education and all EDI subscales except Body Dissatisfaction and Perfectionism. Elevated body weight was associated significantly with Body Dissatisfaction, Drive for Thinness, Bulimia, Interoceptive Awareness, and Ineffectiveness. Discussion: Our results illustrate the importance of taking into consideration the potentially confounding role of demographic characteristics and body weight when comparing different race or ethnic groups on the EDI. (C) 2000 by John Wiley & Sons, Inc. C1 Wesleyan Univ, Dept Psychol, Middletown, CT 06459 USA. WESTAT Corp, Rockville, MD 20850 USA. Univ Calif Berkeley, Dept Publ Hlth, Berkeley, CA 94720 USA. NHLBI, Rockville, MD USA. Univ Penn, Off President, Philadelphia, PA 19104 USA. RP Striegel-Moore, RH (reprint author), Wesleyan Univ, Dept Psychol, 207 High St, Middletown, CT 06459 USA. FU NHLBI NIH HHS [N01-HC-55023]; NIMH NIH HHS [R01MH52348-01A1]; PHS HHS [N01-55026] NR 54 TC 83 Z9 85 U1 4 U2 16 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD JAN PY 2000 VL 27 IS 1 BP 49 EP 66 DI 10.1002/(SICI)1098-108X(200001)27:1<49::AID-EAT6>3.0.CO;2-E PG 18 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 270JC UT WOS:000084531300006 PM 10590449 ER PT J AU Esparza, J Fox, C Harper, IT Bennett, PH Schulz, LO Valencia, ME Ravussin, E AF Esparza, J Fox, C Harper, IT Bennett, PH Schulz, LO Valencia, ME Ravussin, E TI Daily energy expenditure in Mexican and USA Pima Indians: low physical activity as a possible cause of obesity SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE Pima Indians; doubly labeled water; total energy expenditure; resting metabolic rate; physical activity level ID DOUBLY LABELED WATER; 5-YEAR-OLD CHILDREN; BODY-COMPOSITION; FAT DISTRIBUTION; METABOLIC-RATE; DIET; WEIGHT; MANAGEMENT; VALIDATION; WOMEN AB BACKGROUND: Obesity is caused by an imbalance between energy intake and energy expenditure. However, it is unknown whether increased physical activity protects susceptible populations against the development of obesity and type 2 diabetes. OBJECTIVE: To investigate the potential protective role of environment and physical activity against obesity by measuring total energy expenditure in Mexican and USA Pima Indians. METHODS: We compared the physical activity level of 40 (17 female and 23 male; 37 +/- 11 y, 66 +/- 13 kg) Mexican Pima Indians from a remote, mountainous area of Northwest Mexico, with 40 age-and-sex matched (17 female and 23 male; 37 +/- 12 y, 93 +/- 22 kg) Pima Indians from the Gila River Indian Community in Arizona, USA. We measured total energy expenditure (TEE) by doubly labeled water and calculated physical activity by different methods: physical activity level (PAL) as the ratio of TEE on resting metabolic rate (RMR), TEE adjusted for RMR by linear regression, activity energy expenditure adjusted for body weight (AEE), and activity questionnaire. RESULTS: Physical activity was higher in Mexican Pima Indians when compared with USA Pima Indians as assessed by PAL (1.97 +/- 0.34 vs 1.57 +/- 0.16, P < 0.0001), TEE adjusted for RMR (3289 +/- 454 vs 2671 +/- 454 kcal/day, P < 0.0001) and AEE adjusted for body weight (1243 +/- 415 vs 711 +/- 415 kcal/day, P < 0.0001). Questionnaires revealed more time spent on occupational activities among Mexican Pima compared with USA Pima (23.9 +/- 13.3 vs 12.6 +/- 13.9h/week, P < 0.001). CONCLUSION: These data support a significant role for physical activity in the prevention of obesity in genetically susceptible populations. C1 Ctr Invest Alimentac & Desarrollo, Hermosillo, Sonora, Mexico. NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA. Univ Wisconsin, Milwaukee, WI 53201 USA. RP Ravussin, E (reprint author), Lilly Corp Ctr, Lilly Res Labs, Endocrine Res, Drop Code 0545, Indianapolis, IN 46285 USA. FU NIDDK NIH HHS [DK45957] NR 42 TC 92 Z9 94 U1 2 U2 13 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD JAN PY 2000 VL 24 IS 1 BP 55 EP 59 DI 10.1038/sj.ijo.0801085 PG 5 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 281QW UT WOS:000085173100009 PM 10702751 ER PT J AU Nakamura, S Gelber, RD Blattner, S Sallan, SE Chanock, SJ AF Nakamura, S Gelber, RD Blattner, S Sallan, SE Chanock, SJ TI Long-term follow-up and infectious complications of therapy for acute lymphoblastic leukemia in children SO INTERNATIONAL JOURNAL OF PEDIATRIC HEMATOLOGY/ONCOLOGY LA English DT Article DE infection; neutropenia; antibiotics; cancer ID COLONY-STIMULATING FACTOR; PATIENTS RECEIVING CIPROFLOXACIN; PNEUMOCYSTIS-CARINII PNEUMONIA; CANCER-PATIENTS; NEUTROPENIC PATIENTS; PRIMARY IMMUNODEFICIENCIES; INTENSIVE CHEMOTHERAPY; RISK-FACTORS; FEVER; STREPTOCOCCI AB Infection is a major complication of therapy for acute lymphoblastic leukemia (ALL) in children. Recent advances in supportive care have contributed to improvements in long-term survivorship following treatment for ALL. Of 220 children treated for ALL on Dana-Farber Cancer Institute (DFCI) Consortium Protocol 85-001, a retrospective study of all 72 children at the DFCI and Maine Children's Cancer Program was conducted to determine the incidence and impact of infection in pediatric patients not on hematopoietic growth factor support. There were two deaths on therapy, both of which were associated with infection. Our results show that severe infection, requiring hospitalization is far more likely to occur during induction therapy. The risk for hospitalization decreased during therapy, after remission was achieved with fewer children hospitalized during the continuation phase of therapy than during the intensification phase. Fever and neutropenia was the most common reason for hospitalization and in less than 30% of instances an etiology was determined. At a median follow-up of 9 years, the event-free survival (EFS) of the 220 patients enrolled on Protocol 85-001 was 78%. The 9 years EFS by risk groups (standard, high and very high risk) was 89%, 75% and 58%, respectively (p = 0.0005). In conclusion, serious infectious complications were more likely to occur during induction and intensification. Thus, strategies to prevent infection should be targeted to induction and intensification phases of therapy for childhood ALL. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Maine Childrens Canc Program, Portland, ME USA. RP Chanock, SJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, 10-13N240, Bethesda, MD 20892 USA. NR 38 TC 4 Z9 4 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 1070-2903 J9 INT J PEDIAT HEM ONC JI Int. J. Pediatr. Hematol-Oncol. PY 2000 VL 6 IS 5 BP 321 EP 330 PG 10 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 287TQ UT WOS:000085522900002 ER PT J AU Rao, CR Franklin, J Lalitha, N Bhatia, K O'Conor, G Magrath, I AF Rao, CR Franklin, J Lalitha, N Bhatia, K O'Conor, G Magrath, I TI Frequency of Epstein-Barr virus (EBV) association and p53 expression in childhood and adult Hodgkin's disease in India SO INTERNATIONAL JOURNAL OF PEDIATRIC HEMATOLOGY/ONCOLOGY LA English DT Article DE Hodgkin's disease; Epstein-Barr virus; developing countries; p53 ID REED-STERNBERG CELLS; LATENT MEMBRANE-PROTEIN; NUCLEAR ANTIGEN; INSITU HYBRIDIZATION; LYMPHOID-TISSUE; GENE-EXPRESSION; UNITED-STATES; MUTATIONS; DNA; INFECTION C1 NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Kidwai Mem Inst Oncol, Bangalore, Karnataka, India. RP Magrath, I (reprint author), Inst Pasteur, Int Network Canc Treatment & Res, Rue Engeland 642, B-1180 Brussels, Belgium. NR 52 TC 4 Z9 4 U1 1 U2 1 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1070-2903 J9 INT J PEDIAT HEM ONC JI Int. J. Pediatr. Hematol-Oncol. PY 2000 VL 6 IS 6 BP 377 EP + PG 11 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 340TR UT WOS:000088551500001 ER PT J AU Pettersson, B Tully, JG Bolske, G Johansson, KE AF Pettersson, B Tully, JG Bolske, G Johansson, KE TI Updated phylogenetic description of the Mycoplasma hominis cluster (Weisburg et al. 1989) based on 16S rDNA sequences SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Article DE 16S rRNA; Mollicutes; Mycoplasma hominis cluster; phylogeny ID RIBOSOMAL-RNA GENE; SP-NOV; BACTERIAL SYSTEMATICS; PLASMID DNA; CLASSIFICATION; STRAINS; CAPRICOLUM; DEFINITION; EVOLUTION; TAXONOMY AB The fastidious nature of the mollicutes (mycoplasmas), their lack of a classic bacterial cell wall, and their very small genome, make phylogenetic placements of new species in this enlarging group of prokaryotes an important and valuable aid in their classification, In this report we have determined the phylogeny of the Mycoplasma hominis cluster of the hominis group. The 16S rDNA sequences from several previously described Mycoplasma species were determined and ten species were found to belong to the M. hominis cluster. With almost complete sequences available, the phylogenetic analysis revealed that the M, hominis cluster currently comprises 19 species, forming a distinct clade as judged from branch lengths, bootstrap percentage values, nucleotide signature analysis, and structural elements in the 165 rRNA molecule. The 16S rRNA gene sequences of species in the M, hominis cluster were found to be greater than or equal to 94% similar and the range within which similarities can be used in the classification of new species is discussed. Members of the M. hominis cluster all share a major biochemical property of M, hominis, in that they hydrolyse arginine and are incapable of fermenting glucose. This consistency in phenotypic pattern has not been found in any of the other phylogenetic clusters of the hominis group. Two species, the non-cultivable agent of Grey Lung disease in rodents (tentatively named 'Candidatus Mycoplasma ravipulmonis') and the avian species Mycoplasma gypis strain B1/T1(T), were regarded as close relatives to the M. hominis cluster, but are clearly separated from the species of this cluster. Both species formed early branches of the M, hominis cluster and should be regarded as individual lines containing one species. C1 Royal Inst Technol, Dept Biotechnol, S-10044 Stockholm, Sweden. NIAID, Mycoplasma Sect, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Natl Vet Inst, Dept Bacteriol, S-75007 Uppsala, Sweden. RP Pettersson, B (reprint author), Royal Inst Technol, Dept Biotechnol, S-10044 Stockholm, Sweden. EM bertil@biochem.kth.se NR 51 TC 29 Z9 30 U1 0 U2 2 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1466-5026 J9 INT J SYST EVOL MICR JI Int. J. Syst. Evol. Microbiol. PD JAN PY 2000 VL 50 BP 291 EP 301 PN 1 PG 11 WC Microbiology SC Microbiology GA 290JR UT WOS:000085673600036 PM 10826816 ER PT J AU Santamarina-Fojo, S Haudenschild, C AF Santamarina-Fojo, S Haudenschild, C TI Role of hepatic and lipoprotein lipase in lipoprotein metabolism and atherosclerosis: Studies in transgenic and knockout animal models and somatic gene transfer SO INTERNATIONAL JOURNAL OF TISSUE REACTIONS-EXPERIMENTAL AND CLINICAL ASPECTS LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; ADENOVIRUS-MEDIATED EXPRESSION; DIET-INDUCED ATHEROSCLEROSIS; DEFICIENT MICE; APOLIPOPROTEIN-E; IN-VIVO; REMNANT LIPOPROTEINS; OVEREXPRESSION; PLASMA; CHOLESTEROL AB Hepatic lipase (HL) and lipoprotein lipase (LPL) are the two major lipolytic enzymes responsible for the hydrolysis of triglycerides and phospholipids present in circulating plasma lipoproteins. Both lipases are attached to the vascular endothelium via cell surface proteoglycans. HL is primarily involved in the metabolism of chylomicron remnants, intermediate density lipoproteins and high-density lipoproteins whereas IPL catalyzes the hydrolysis of triglycerides from chylomicrons and very low-density lipoproteins. In addition to their traditional function as lipolytic enzymes, HL and LPL appear to serve as ligands that mediate the interaction of lipoproteins to cell surface receptors and/or proteoglycans. Over the past several years significant advances have been made in our understanding of new alternative mechanisms by which HL and LPL modulate lipoprotein metabolism and the development of atherosclerosis in vivo. This review will summarize some of the new insights generated from the study of transgenic and knockout HL and LPL animal models as well as somatic gene transfer of these two lipases. C1 NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. RP Santamarina-Fojo, S (reprint author), 10-7NI 15,10 Ctr Crive, Bethesda, MD 20892 USA. NR 46 TC 19 Z9 19 U1 0 U2 0 PU BIOSCIENCE EDIPRINT INC PI CAROUGE PA RUE ALEXANDRE-GAVARD 16, 1227 CAROUGE, SWITZERLAND SN 0250-0868 J9 INT J TISSUE REACT JI Int. J. Tissue React.-Exp. Clin. Asp. PY 2000 VL 22 IS 2-3 BP 39 EP 47 PG 9 WC Cell Biology SC Cell Biology GA 339YC UT WOS:000088504600002 PM 10937353 ER PT J AU Lebowitz, BD AF Lebowitz, BD TI Behavioral and psychological symptoms of dementia: A clinical and research update SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Editorial Material C1 NIMH, Bethesda, MD 20892 USA. RP Lebowitz, BD (reprint author), NIMH, Room 7160,MSC 9635,6001 Execut Blvd, Bethesda, MD 20892 USA. NR 7 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1041-6102 J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PY 2000 VL 12 SU 1 BP 19 EP 21 DI 10.1017/S1041610200006712 PG 3 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA 410HL UT WOS:000167434500003 ER PT J AU Sunderland, T AF Sunderland, T TI Cholinergic contributions to behavioral disturbances in Alzheimer's disease SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Article; Proceedings Paper CT Meeting of the International-Psychogeriatric-Association on Behavioral and Psychological Symptoms of Dementia CY 1999 CL LANSDOWNE, VIRGINIA SP Int Psychogeriatr Assoc ID MEMORY C1 NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. RP Sunderland, T (reprint author), NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. NR 9 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1041-6102 J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PY 2000 VL 12 SU 1 BP 231 EP 235 DI 10.1017/S1041610200007080 PG 5 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA 410HL UT WOS:000167434500040 ER PT S AU Walker, FL Thoma, GR AF Walker, FL Thoma, GR BE Beretta, GB Schettini, R TI Web-based document image processing SO INTERNET IMAGING SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Internet Imaging CY JAN 26-28, 2000 CL SAN JOSE, CA SP SPIE, Soc Imaging Sci & Technol DE DocMorph Server; image processing; World Wide Web; TIFF; PDF; OCR; DocView; NLM; Ariel; Internet; speech synthesis AB Increasing numbers of research libraries are turning to the Internet for electronic interlibrary loan and for document delivery to patrons. This has been made possible through the widespread adoption of software such as Ariel and DocView. Ariel, a product of the Research Libraries Group, converts paper-based documents to monochrome bitmapped images, and delivers them over the Internet. The National Library of Medicine's DocView is primarily designed for library patrons to receive, display and manage documents received from Ariel systems. While libraries and their patrons are beginning to reap the benefits of this new technology, barriers exist, e.g., differences in image file format, that lead to difficulties in the use of library document information. To research how to overcome such barriers, the Communications Engineering Branch of the Lister Bill National Center for Biomedical Communications, an R&D division of NLM, has developed a web site called the DocMorph Server. This is part of an ongoing intramural R&D program in document imaging that has spanned many aspects of electronic document conversion and preservation, Internet document transmission and document usage. The DocMorph Server web site is designed to fill two roles. First, in a role that will benefit both libraries and their patrons, it allows Internet users to upload scanned image files for conversion to alternative formats, thereby enabling wider delivery and easier usage of library document information. Second, the DocMorph Server provides the design team an active test bed for evaluating the effectiveness and utility of new document image processing algorithms and functions, so that they may be evaluated for possible inclusion in other image processing software products being developed at NLM or elsewhere. This paper describes the design of the prototype DocMorph Server and the image processing functions being implemented on it. C1 Natl Lib Med, Lister Hill Natl Biomed Commun, Bethesda, MD 20894 USA. RP Walker, FL (reprint author), Natl Lib Med, Lister Hill Natl Biomed Commun, Bethesda, MD 20894 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3582-1 J9 P SOC PHOTO-OPT INS PY 2000 VL 3964 BP 268 EP 277 PG 10 WC Computer Science, Information Systems; Optics SC Computer Science; Optics GA BP40B UT WOS:000085027900028 ER PT J AU Contoreggi, C Jones, S Simpson, P Lange, WR Meyer, WA AF Contoreggi, C Jones, S Simpson, P Lange, WR Meyer, WA TI Effects of varying concentrations of bleach on in vitro HIV-1 replication and the relevance to injection drug use SO INTERVIROLOGY LA English DT Article DE HIV replication; bleach disinfection; hypochlorite; injection drug use; oxidative stress ID DISINFECTION AB The use of bleach (hypochlorite) as a disinfectant for drug injection equipment in the intravenous-drug-using population was recommended early in the HIV-1/AIDS epidemic. Epidemiological studies have challenged the use of bleach as an effective measure to prevent HIV-1 transmission. However, in vitro HIV-1 coculture studies have shown that a high concentration of bleach is an effective cytotoxic and potentially virucidal agent. In this study, we demonstrate that HIV-1 peripheral blood mononuclear cell cocultures containing low concentrations of hypochlorite in the media showed earlier conversion to HIV-1 positivity, as measured by the presence of p24 antigen. HIV-1 cocultures with high concentrations of hypochlorite in the culture media, which appeared to be highly cytotoxic, and HIV-1 cocultures without bleach in the media did not exhibit this early p24 antigen positivity. Hypochlorite chemically disinfects by releasing free chlorine that is a potent oxidant. In injection drug equipment, a low residual concentration of bleach is likely to remain in cleaned equipment despite rinsing with water. Low concentrations of oxidants have been shown to enhance tissue inflammation, in vivo, as well as HIV-1 replication in vitro. Previous studies have shown that despite vigorous cleaning of blood-contaminated injection syringes with bleach followed by water, microaggregates of residual blood remained in bleach-cleaned blood-contaminated syringes. Hypothetically, oxidant effects of the residual bleach in the bleach-cleaned syringes could enhance the possibility of infection by remaining HIV-1 contained in a contaminated syringe. We suggest that the likelihood of an injection drug user contracting HIV-1 through the sharing of a bleach-cleaned blood-contaminated syringe may be increased by the cotransmission of residual bleach and its localized tissue-inflammatory effects; however, this has not been statistically proven in epidemiological studies. Copyright (C) 2000 S. Karger AG, Basel. C1 NIDA, Addict Res Ctr, Intramural Res Program, NIH, Baltimore, MD 21224 USA. CARE, Dept Pediat, Little Rock, AR USA. Qual Biol Inc, Gaithersburg, MD USA. Johns Hopkins Hosp, Med Advisors Off, Baltimore, MD 21287 USA. Quest Diagnost, Baltimore, MD USA. RP Contoreggi, C (reprint author), NIDA, Addict Res Ctr, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 19 TC 6 Z9 6 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0300-5526 J9 INTERVIROLOGY JI Intervirology PD JAN-FEB PY 2000 VL 43 IS 1 BP 1 EP 5 DI 10.1159/000025015 PG 5 WC Virology SC Virology GA 308LD UT WOS:000086712100001 PM 10773730 ER PT J AU Avichezer, D Silver, PB Chan, CC Wiggert, B Caspi, RR AF Avichezer, D Silver, PB Chan, CC Wiggert, B Caspi, RR TI Identification of a new epitope of human IRBP that induces autoimmune uveoretinitis in mice of the H-2(b) haplotype SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID RETINOID-BINDING PROTEIN; MODEL AB Purpose. Experimental autoimmune uveoretinitis (EAU) is a T-cell-mediated disease induced by immunization with interphotoreceptor retinoid binding protein (IRBP). Major uveitogenic sites have been identified for mice of the H-2(r) and H-2(k) haplotypes but not for the H-2(b) haplotype. The present communication describes the characterization of an epitope contained in residues 1 to 20 of human IRBP that induces EAU in H-2(b) mice. Methods. H-2(b) (C57BL/6, 129/J) and H-2(r) (B10.RIII) mice were immunized with peptide 1-20 or with whole (bovine) IRBP. MU (histopathology) and immunologic responses (delayed-type hypersensitivity [DTH], lymphocyte proliferation, and cytokine production) were assessed after 21 days Results. C57BL/6 mice, 129/J and (129/JxC57BL/6)F1 mice, immunized with 200 to 300 mu g of peptide, developed DTH and MU with scores comparable to those induced by 100 mu g IRBP. Their lymphocytes proliferated to the peptide and produced interferon-gamma (but not interleukin-4) and transferred EAU to syngeneic recipients. Lymphocytes of IRBP-immunized mice also responded to the peptide. Peptide 1-20-immunized B10.RIII mice failed to develop either disease or immunologic responses. Conclusions. Human IRBP peptide 1-20 contains a major epitope for the H-2(b) haplotype, which is apparently not presented by the H-2(r) haplotype. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Lab Celll & Mol Biol, NIH, Bethesda, MD 20892 USA. RP Caspi, RR (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N222, Bethesda, MD 20892 USA. EM rcaspi@helix.nih.gov NR 16 TC 90 Z9 91 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 2000 VL 41 IS 1 BP 127 EP 131 PG 5 WC Ophthalmology SC Ophthalmology GA 272DA UT WOS:000084634200021 PM 10634611 ER PT J AU Konda, SD Aref, M Brechbiel, M Wiener, EC AF Konda, SD Aref, M Brechbiel, M Wiener, EC TI Development of a tumor-targeting MR contrast agent using the high-affinity folate receptor - Work in progress SO INVESTIGATIVE RADIOLOGY LA English DT Article DE folate; contrast agents; gadolinium; dendrimer; cancer ID HUMAN OVARIAN-CARCINOMA; LIPOSOMAL GD-DTPA; BINDING-PROTEIN; MONOCLONAL-ANTIBODY; CELL-LINES; IRON-OXIDE; IN-VIVO; TISSUES; CANCER; CYTOTOXICITY AB RATIONALE AND OBJECTIVES. Macromolecular contrast agents enhance tumors by means of active or passive targeting. Active targeting requires surface receptors, Many tumors of epithelial origin express the high-affinity folate receptor (hFR), including ovarian tumors, The objective of this research was to enhance tumors that express hFR using macromolecular contrast agents conjugated to folic acid. METHODS. The authors prepared a folate-conjugated dendrimer polychelate by attaching folic acid to a fourth-generation ammonia-core polyamidoamine dendrimer. The remaining amines were reacted with 2-(4-isothiocyanatobenzyl)-6-methyl-diethylenetriamine pentaacetic acid. Relaxivity measurements (r(1) and r(2)) and MRI were conducted at 4.7 T. RESULTS. The dendrimer r(2) exceeded that of Gd-HP-DO3A by 8.2 times at 4.7 T, It increased the tumor percentage contrast enhancement, 24 hours after injection, of T2-weighted images by 33%, CONCLUSIONS. This new agent accumulates in turners expressing hFR, These results do not differentiate between active and passive targeting mechanisms, Receptor-negative tumors suggest a mechanism other than a nonspecific blood pool effect. C1 Beckman Inst, Urbana, IL 61801 USA. Univ Illinois, Coll Med, Biomed Magnet Resonance Lab, Urbana, IL 61801 USA. Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL 61801 USA. Univ Illinois, Dept Nucl Engn, Urbana, IL 61801 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Wiener, EC (reprint author), 4247 Beckman Inst, 405 N Mathews, Urbana, IL 61801 USA. FU NCI NIH HHS [PHS-1-R29-CA61918]; NCRR NIH HHS [IS10RR06243, PHS-5-P41-RR05964] NR 39 TC 94 Z9 102 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD JAN PY 2000 VL 35 IS 1 BP 50 EP 57 DI 10.1097/00004424-200001000-00006 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 271UL UT WOS:000084611900006 PM 10639036 ER PT J AU Allen, JP AF Allen, JP TI Biomarkers for alcohol problems in general medical patients SO JOURNAL OF ADDICTIVE DISEASES LA English DT Meeting Abstract C1 NIAAA, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1055-0887 J9 J ADDICT DIS JI J. Addict. Dis. PY 2000 VL 19 IS 2 MA 1A BP 131 EP 131 PG 1 WC Substance Abuse SC Substance Abuse GA 306NA UT WOS:000086601700015 ER PT J AU Akin, C Schwartz, LB Kitoh, T Obayashi, H Worobec, AS Semere, T Scott, LM Metcalfe, DD AF Akin, C Schwartz, LB Kitoh, T Obayashi, H Worobec, AS Semere, T Scott, LM Metcalfe, DD TI Plasma soluble KIT levels in mastocytosis and in systemic anaphylaxis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Richmond, VA USA. Nichirei Diagnost, Tokyo, Japan. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2000 VL 105 IS 1 SU S MA 809 BP S274 EP S274 DI 10.1016/S0091-6749(00)91237-5 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 287WR UT WOS:000085530100805 ER PT J AU Chegini, S Dale, J Doo, E Keiner, D Straus, S AF Chegini, S Dale, J Doo, E Keiner, D Straus, S TI Immune-mediated cholestasis and hypercholesterolemia associated with autoimmune lymphoproliferative syndrome (ALPS) SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIAID, Bethesda, MD USA. NIDDK, Bethesda, MD USA. NCI, Bethesda, MD USA. NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2000 VL 105 IS 1 SU S MA 79 BP S28 EP S28 DI 10.1016/S0091-6749(00)90510-4 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 287WR UT WOS:000085530100078 ER PT J AU Derrien, A Druey, K AF Derrien, A Druey, K TI Importance of tyrosine phosphorylation of RGS16 in the inhibition of G-protein-coupled MAP kinase stimulation SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2000 VL 105 IS 1 SU S MA 523 BP S172 EP S173 DI 10.1016/S0091-6749(00)91579-3 PN 2 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 287WR UT WOS:000085530100519 ER PT J AU Foster, B Schwartz, LB Metcalfe, DD Prussin, C AF Foster, B Schwartz, LB Metcalfe, DD Prussin, C TI Tryptase is expressed by human basophils independent of disease status SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Dept Med, Richmond, VA 23284 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2000 VL 105 IS 1 SU S MA 268 BP S89 EP S89 DI 10.1016/S0091-6749(00)90698-5 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 287WR UT WOS:000085530100266 ER PT J AU Fouda, ED Hussein, M Oskeritzian, CA Irani, AA Schwartz, LB AF Fouda, ED Hussein, M Oskeritzian, CA Irani, AA Schwartz, LB TI Intestinal parasitic infestations appear to upregulate both total IgE and numbers of rectal mucosal mast cells SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Univ Cologne, Dept Dermatol, D-5000 Cologne 41, Germany. Univ Cologne, Dept Pathol, D-5000 Cologne, Germany. NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. Humboldt Univ, D-1086 Berlin, Germany. Meir Gen Hosp, Dept Med, Tel Aviv, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2000 VL 105 IS 1 SU S MA 204 BP S66 EP S66 DI 10.1016/S0091-6749(00)90634-1 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 287WR UT WOS:000085530100202 ER PT J AU Gruchalla, RS AF Gruchalla, RS TI Allergy skin test results of 942 urban asthmatic children: The Inner City Asthma Study (ICAS) SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIH, Inner City Asthman Study Grp, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2000 VL 105 IS 1 SU S MA 1082 BP S368 EP S369 DI 10.1016/S0091-6749(00)91508-2 PN 2 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 287WR UT WOS:000085530101076 ER PT J AU Hartmann, K Zirbes, TK Hasan, S Gilfilian, AM Henz, BM Metcalfe, DD Mekori, YA AF Hartmann, K Zirbes, TK Hasan, S Gilfilian, AM Henz, BM Metcalfe, DD Mekori, YA TI Expression of the anti-apoptotic protein Bcl-X in human mast cells and mastocytosis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Univ Cologne, D-5000 Cologne 41, Germany. NIAID, Dept Pathol, NIH, Bethesda, MD 20892 USA. NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. Humboldt Univ, Berlin, Germany. Meir Gen Hosp, Dept Med, Tel Aviv, Israel. NR 0 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2000 VL 105 IS 1 SU S MA 203 BP S66 EP S66 DI 10.1016/S0091-6749(00)90633-X PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 287WR UT WOS:000085530100201 ER PT J AU Kagami, S Nakajima, H Suzuki, K Saito, Y Takatsu, K Leonard, W Iwamoto, I AF Kagami, S Nakajima, H Suzuki, K Saito, Y Takatsu, K Leonard, W Iwamoto, I TI Both Stat5a and Stat5b are required for antigen-induced eosinophil and T cell recruitment into the tissue SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Chiba Univ, Dept Internal Med 2, Sch Med, Chiba, Japan. Univ Tokyo, Inst Med Sci, Dept Immunol, Tokyo, Japan. NIH, HNLBI, Lab Mol Immunol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2000 VL 105 IS 1 SU S MA 1045 BP S355 EP S355 DI 10.1016/S0091-6749(00)91471-4 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 287WR UT WOS:000085530101039 ER PT J AU Larsen, JN Spangfort, MD van Neerven, RJJ Ipsen, H AF Larsen, JN Spangfort, MD van Neerven, RJJ Ipsen, H TI Toward a unifying theory for the mechanism of specific allergy vaccination SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, Sch Med, Dept Med, La Jolla, CA 92093 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2000 VL 105 IS 1 SU S MA 915 BP S311 EP S311 DI 10.1016/S0091-6749(00)91343-5 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 287WR UT WOS:000085530100911 ER PT J AU Magone, T Chan, CC Whitcup, S Raz, E AF Magone, T Chan, CC Whitcup, S Raz, E TI Systemic or mucosal administration of immunostimulatory DNA inhibits early and late phases of murine allergic conjunctivitis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, Sch Med, Dept Med, La Jolla, CA 92093 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2000 VL 105 IS 1 SU S MA 913 BP S311 EP S311 DI 10.1016/S0091-6749(00)91341-1 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 287WR UT WOS:000085530100909 ER PT J AU McConnell, R Berhane, K Gilliland, R Islam, T Avol, E London, S Gauderman, J Margolis, H Peters, J AF McConnell, R Berhane, K Gilliland, R Islam, T Avol, E London, S Gauderman, J Margolis, H Peters, J TI Risk factors for asthma in a cohort of adolescents SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Univ So Calif, Los Angeles, CA 90089 USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2000 VL 105 IS 1 SU S MA 374 BP S125 EP S125 DI 10.1016/S0091-6749(00)90803-0 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 287WR UT WOS:000085530100371 ER PT J AU Michalec, L Choudhury, BK Lett-Brown, M Postlethwait, EM Sur, S AF Michalec, L Choudhury, BK Lett-Brown, M Postlethwait, EM Sur, S TI Defining the role of CC and CXC chemokines that mediate airway inflammation from ozone-induced oxidative lung injury SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Univ Texas, Med Branch, Dept Internal Med, Galveston, TX 77550 USA. NIH, Asthma Ctr, Galveston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2000 VL 105 IS 1 SU S MA 373 BP S124 EP S125 DI 10.1016/S0091-6749(00)90802-9 PN 2 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 287WR UT WOS:000085530100370 ER PT J AU Okayama, Y Kirshenbaum, AS Metcalfe, DD AF Okayama, Y Kirshenbaum, AS Metcalfe, DD TI The high affinity IgG receptor, Fc gamma RI, is expressed on human mast cells SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2000 VL 105 IS 1 SU S MA 253 BP S84 EP S84 DI 10.1016/S0091-6749(00)90683-3 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 287WR UT WOS:000085530100251 ER PT J AU Prussin, C Foster, B AF Prussin, C Foster, B TI Asthmatic and healthy control subjects demonstrate differential responsiveness to ubiquitous aeroallergens SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIAID, NIH, Lab Allerg Dis, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2000 VL 105 IS 1 SU S MA 997 BP S338 EP S338 DI 10.1016/S0091-6749(00)91423-4 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 287WR UT WOS:000085530100991 ER PT J AU Schatz, M AF Schatz, M TI The relationship of asthma severity classification during pregnancy to gestational asthma morbidity SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NICHD, Maternal Fetal Med Unit Network, Bethesda, MD USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2000 VL 105 IS 1 SU S MA 835 BP S284 EP S284 DI 10.1016/S0091-6749(00)91263-6 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 287WR UT WOS:000085530100831 ER PT J AU Suzuki, K Nakajima, H Saito, Y Saito, T Leonard, W Iwamoto, I AF Suzuki, K Nakajima, H Saito, Y Saito, T Leonard, W Iwamoto, I TI Jak3 is essential for common cytokine receptor gamma chain (gc)-dependent signaling: Comparative analysis of gc, Jak3, and gc and Jak3 double deficient mice SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. Chiba Univ, Sch Med, Dept Internal Med 2, Chiba, Japan. Chiba Univ, Grad Sch Med, Mol Genet Lab, Chiba, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2000 VL 105 IS 1 SU S MA 644 BP S217 EP S217 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 287WR UT WOS:000085530100640 ER PT J AU Taylor, ML Dastych, Y Nilsson, G Metcalfe, DD AF Taylor, ML Dastych, Y Nilsson, G Metcalfe, DD TI The activating mutation V816D of the c-kit catalytic domain enhances stem cell factor-dependent cell migration SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. Int Inst Mol & Cell Biol, Lab Med Immunol, Warsaw, Poland. Univ Uppsala, Dept Pathol, S-75105 Uppsala, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2000 VL 105 IS 1 SU S MA 240 BP S79 EP S79 DI 10.1016/S0091-6749(00)90670-5 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 287WR UT WOS:000085530100238 ER EF