FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Gasperini, S Marchi, M Calzetti, F Laudanna, C Vicentini, L Olsen, H Murphy, M Liao, F Farber, J Cassatella, MA AF Gasperini, S Marchi, M Calzetti, F Laudanna, C Vicentini, L Olsen, H Murphy, M Liao, F Farber, J Cassatella, MA TI Gene expression and production of the monokine induced by IFN-gamma (MIG), IFN-inducible T cell alpha chemoattractant (I-TAC), and IFN-gamma-inducible protein-10 (IP-10) chemokines by human neutrophils SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; INTERFERON-GAMMA; PROINFLAMMATORY CYTOKINES; HEMATOPOIETIC PROGENITORS; BLOOD EOSINOPHILS; RECEPTOR CXCR3; C CHEMOKINE; LYMPHOCYTES; LIPOPOLYSACCHARIDE; IL-10 AB Monokine induced by IFN-gamma (MIG), IFN-inducible T cell alpha chemoattractant (I-TAC), and IFN-gamma-inducible protein of 10 kDa (IP-10) are related members of the CXC chemokine subfamily that bind to a common receptor, CXCR3, and that are produced by different cell types in response to IFN-gamma. We have recently reported that human polymorphonuclear neutrophils (PMN) have the capacity to release IP-10, Herein, we show. that PMN also hare the ability to produce MIG; and to express I-TAC mRNA in response to IFN-gamma in combination with either TNF-alpha or LPS. While IFN-gamma, alone or in association with agonists such as fMLP, IL-8, granulocyte (G)-CSF and granulocyte-macrophage (GM)-CSF, failed to influence MIG, IP-10, and I-TAC gene expression, IFN-alpha, in combination with TNF-alpha, LPS, or IL-1 beta. resulted in a considerable induction of IP-10 release by neutrophils. Furthermore, IL-10 and IL-4 significantly suppressed the expression of MIG, IP-10, and I-TAC mRNA and the extracellular production of MIG and IP-10 in neutrophils stimulated with IFN-gamma plus either I-PS or TNF-alpha. Finally, supernatants harvested from stimulated PMN induced migration and rapid integrin-dependent adhesion of CXCR3-expressing lymphocytes; these activities were significantly reduced by neutralizing anti-MIG and anti-IP-10 Abs, suggesting that they were mediated by MIG and IP-10 present in the supernatants, Since MIG, IP-10, and I-TAC are potent chemoattractants for NK cells and Th1 lymphocytes, the ability of neutrophils to produce these chemokines might contribute not only. to the progression and evolution of the inflammatory response, but also to the regulation of the immune response. C1 Univ Verona, Dept Gen Pathol, I-37100 Verona, Italy. Univ Verona, Dept Pediat Clin, I-37100 Verona, Italy. Human Genome Sci Inc, Mol Biol & Cell Biol Dept, Rockville, MD 20850 USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Cassatella, MA (reprint author), Ist Patol Gen, Strada Grazie 4, I-37134 Verona, Italy. EM MCNCSS@borgoroma.univr.it NR 61 TC 241 Z9 247 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1999 VL 162 IS 8 BP 4928 EP 4937 PG 10 WC Immunology SC Immunology GA 184KV UT WOS:000079612100070 PM 10202039 ER PT J AU Zhang, SM Youn, BS Gao, JL Murphy, PM Kwon, BS AF Zhang, SM Youn, BS Gao, JL Murphy, PM Kwon, BS TI Differential effects of leukotactin-1 and macrophage inflammatory protein-1 alpha on neutrophils mediated by CCR1 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN BETA-CHEMOKINE; MOLECULAR-CLONING; FUNCTIONAL-CHARACTERIZATION; SIGNAL-TRANSDUCTION; LYMPHOCYTES; EXPRESSION; RECEPTOR-1; CELLS; CHEMOATTRACTANT; LYMPHOTACTIN AB The human CC chemokine leukotactin-1 (Lkn-1) is both a strong chemoattractant for neutrophils, monocytes, and lymphocytes and a potent agonist for CCR1 and CCR3. However, human neutrophils do not migrate when the cells are stimulated with other human CC chemokines, such as human macrophage inflammatory protein-1 alpha (hMIP-1 alpha) and eotaxin, which also use the CCR1 and CCR3 as their receptors. In this report, we demonstrate that while hMIP-1 alpha induced a negligible level of calcium flux and chemotaxis, Lkn-1 produced a high level of calcium Bus and chemotaxis in human neutrophils. Lkn-1 cross-desensitized hMIP-1 alpha-induced calcium Bus, but hl hMIP-1 alpha had little effect on the Lkn-1-induced response in human neutrophils. The same pattern was observed in peritoneal neutrophils from wild-type mice, whereas neutrophils from CCR1(-/-) mice failed to respond to either MIP-1 alpha or Lkn-1. Scatchard anal-sis revealed a single class of receptor for both hMIP-1 alpha: and Lkn-1 on human neutrophils with dissociation constants (K-d) of 3.2 nM and 1.1 nM, respectively. We conclude that CCR1 is a receptor mediating responses to both MIP-1 alpha and Lkn-1 on neutrophils and produces different biological responses depending on the ligand bound. C1 Indiana Univ, Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Walther Oncol Ctr, Indianapolis, IN 46202 USA. Walther Canc Inst, Indianapolis, IN 46202 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Univ Ulsan, Dept Biol Sci, Ulsan 680749, South Korea. Univ Ulsan, Immunomodulat Res Ctr, Ulsan 680749, South Korea. RP Kwon, BS (reprint author), Indiana Univ, Sch Med, Dept Microbiol & Immunol, 635 Barnhill Dr, Indianapolis, IN 46202 USA. FU NIAID NIH HHS [AI 28125]; NIDCR NIH HHS [DE 12156] NR 25 TC 60 Z9 61 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1999 VL 162 IS 8 BP 4938 EP 4942 PG 5 WC Immunology SC Immunology GA 184KV UT WOS:000079612100071 PM 10202040 ER PT J AU Ludviksson, BR Strober, W Nishikomori, R Hasan, SK Ehrhardt, RO AF Ludviksson, BR Strober, W Nishikomori, R Hasan, SK Ehrhardt, RO TI Administration of mAb against alpha(E)beta(7) prevents and ameliorates immunization-induced colitis in IL-2(-/-) mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; INFLAMMATORY BOWEL-DISEASE; COTTON-TOP TAMARIN; E-CADHERIN; T-CELLS; INTEGRIN ALPHA(E)BETA(7); DIFFERENTIAL EXPRESSION; INTERLEUKIN-2 DEFICIENT; COLONIC INFLAMMATION; MONOCLONAL-ANTIBODY AB We previously demonstrated that 2,4,6-trinitrophenol (TNP)-OVA immunization leads to a transmural colitis in the IL-2(-/-) mouse that is caused by IL-12-driven CD4(+) Th1 T cells and resembles human Crohn's disease. The integrin alpha(E)beta(7), is highly expressed on colonic intraepithelial lymphocytes and has been suggested to function as a homing or retention molecule for intraepithelial lymphocytes. To evaluate the role of alpha(E)beta(7) in colitis, we administered a mAb against alpha(E)beta(7) to IL-2(-/-) mice that were immunized at the same time with TNP-OVA in CFA, To our surprise, this treatment resulted in a significantly reduced colitis severity score, 0-2 vs 3-4, that was associated with a significant reduction in CD4(+) lamina propria lymphocyte subpopulation (p < 0.01). In contrast, the total number of splenic CD4(+) T cells of treated animals was significantly elevated compared with that of untreated animals (3.2 +/- 0.6 x 10(7) vs 1.2 +/- 0.2 x 10(7); p < 0.05). Similarly, functional studies revealed that IFN-gamma production by lamina propria lymphocytes isolated from IL-2-/- TNP-OVA-immunized mice treated with anti-alpha(E)beta(7), was significantly lower than in untreated IL-2(-/-) TNP-OVA-immunized mice. In contrast, IFN-gamma production by splenic cells isolated from treated IL-2(-/-) TNP-OVA-immunized mice was significantly higher than in untreated mice. Finally, TNP-OVA-immunized IL-2(-/-) mice that were treated after the colitis had been established also showed a significant decrease in mucosal inflammation after alpha(E)beta(7), mAb administration. Thus, the above findings demonstrate that the onset and maintenance of inflammatory bowel disease depends on the colonic localization of lamina propria CD4(+) lymphocytes ex-pressing alpha(E)beta(7). C1 NIAID, Mucosal Immun Sect, LCI, NIH, Bethesda, MD 20892 USA. Prot Design Labs Inc, Mt View, CA 94043 USA. RP Ludviksson, BR (reprint author), NIAID, Mucosal Immun Sect, LCI, NIH, Bldg 10,Room 11N238, Bethesda, MD 20892 USA. OI Ludviksson, Bjorn/0000-0002-6445-148X NR 41 TC 52 Z9 53 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1999 VL 162 IS 8 BP 4975 EP 4982 PG 8 WC Immunology SC Immunology GA 184KV UT WOS:000079612100076 PM 10202045 ER PT J AU Espey, MG Basile, AS AF Espey, MG Basile, AS TI Glutamate augments retrovirus-induced immunodeficiency through chronic stimulation of the hypothalamic-pituitary-adrenal axis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; MESSENGER-RNA; IN-VITRO; T-CELLS; ANTERIOR-PITUITARY; RIBONUCLEIC-ACID; VIRAL-INFECTION; MICE; GLUCOCORTICOIDS; EXPRESSION AB The mechanisms for activating the hypothalamic-pituitary-adrenal (HPA) axis and the roles glucocorticoids play in the pathogenesis of chronic infectious disease are largely undefined. Using the LP-BM5 model of retrovirus-induced immunodeficiency, we found alterations in HPA axis function, manifested as an increase in circulating levels of adrenocorticotropic hormone and corticosterone, beginning after only 3 mo of infection. These changes occurred contemporaneously Kith a shift in the profile of circulating cytokines from a Th1-dominant (IFN-gamma) to Th2-dominant (IL-4, IL-10) phenotype. No significant changes in either circulating IL-1 beta, IL-6, or TNF-alpha levels were observed in infected mice. Administering the N-methyl-D-aspartate receptor antagonist MK-801 to infected mice normalized plasma adrenocorticotropic hormone and corticosterone levels, indicating that glutamate Has a major activator of the HPA axis. Moreover, MK-801 treatment of late-stage mice also reversed the type 1 to type 2 cytokine shift to a degree comparable or superior to treatment with the glucocorticoid receptor antagonist RU-486. These findings indicate that HPA asis activation during LP-BM5 retrovirus infection is mediated by the chronic hyperactivation of glutamatergic pathways in the hypothalamus, Through this mechanism, the degree of peripheral immunodeficiency observed in the late-stage disease is profoundly augmented. C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Espey, MG (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bldg 8,Room 121, Bethesda, MD 20892 USA. NR 43 TC 16 Z9 17 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1999 VL 162 IS 8 BP 4998 EP 5002 PG 5 WC Immunology SC Immunology GA 184KV UT WOS:000079612100079 PM 10202048 ER PT J AU Stewart, DM Tian, L Nelson, DL AF Stewart, DM Tian, L Nelson, DL TI Mutations that cause the Wiskott-Aldrich syndrome impair the interaction of Wiskott-Aldrich syndrome protein (WASP) with WASP interacting protein SO JOURNAL OF IMMUNOLOGY LA English DT Article ID X-LINKED THROMBOCYTOPENIA; SRC HOMOLOGY-3 DOMAINS; ACTIN-BASED MOTILITY; B-CELL LINES; LISTERIA-MONOCYTOGENES; SIGNALING PATHWAYS; TYROSINE KINASES; GENE-MUTATIONS; T-CELLS; N-WASP AB Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder characterized by thrombocytopenia, eczema, immune deficiency, and a proclivity toward lymphoid malignancy. Lymphocytes of affected individuals show defects of activation, motility, and cytoskeletal structure, The disease gene encodes a 502-amino acid protein named the WAS protein (WASP), Studies have identified a number of important interactions that place WASP in a role of integrating signaling pathways with cytoskeletal function. We performed a two-hybrid screen to identify proteins interacting with WASP and cloned a proline-rich protein as a specific WASP interactor, Our clone of this protein, termed WASP interacting protein (WIP) by others, shows a difference in seven amino acid residues, compared with the previously published sequence revealing an additional profilin binding moth, Deletion mutant analysis reveals that WASP residues 101-151 are necessary for WASP-WIP interaction. Point mutant analyses in the two-hybrid system and in vitro show impairment of WASP-WIP interaction with three WASP missense mutants known to cause WAS. We conclude that impaired WASP-WIP interaction may contribute to WAS. C1 NCI, Immunophysiol Sect, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Nelson, DL (reprint author), NCI, Immunophysiol Sect, Metab Branch, NIH, Bldg 10,Room 4N-115,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 50 TC 75 Z9 77 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1999 VL 162 IS 8 BP 5019 EP 5024 PG 6 WC Immunology SC Immunology GA 184KV UT WOS:000079612100082 PM 10202051 ER PT J AU Liang, TJ AF Liang, TJ TI Combination therapy for hepatitis C infection SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID INTERFERON-ALPHA C1 NIH, Bethesda, MD 20892 USA. RP Liang, TJ (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 15 PY 1999 VL 340 IS 15 BP 1208 EP 1209 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 185TZ UT WOS:000079687700015 ER PT J AU Pourquier, P Jensen, AD Gong, SS Pommier, Y Rogler, CE AF Pourquier, P Jensen, AD Gong, SS Pommier, Y Rogler, CE TI Human DNA topoisomerase I-mediated cleavage and recombination of duck hepatitis B virus DNA in vitro SO NUCLEIC ACIDS RESEARCH LA English DT Article ID EUKARYOTIC TOPOISOMERASE; VIRAL-DNA; NONHOMOLOGOUS RECOMBINATION; RELIGATION REACTIONS; HEPADNAVIRUS DNA; STRAND TRANSFER; CELL-LINE; CAMPTOTHECIN; TRANSCRIPTION; SITES AB In this study, we report that eukaryotic topoisomerase I (top1) can linearize the open circular DNA of duck hepatitis B virus (DHBV). Using synthetic oligonucleotides mimicking the three-strand flap DR1 region of the DHBV genome, we found that top1 cleaves the DNA plus strand in a suicidal manner, which mimics the linearization of the virion DNA. We also report that top1 can cleave the DNA minus strand at specific sites and can linearize the minus strand via a non-homologous recombination reaction. These results are consistent with the possibility that top1 can act as a DNA endonuclease and strand transferase and play a role in the circularization, linearization and possibly integration of viral replication intermediates. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Med, Marion Bessin Liver Res Ctr, Bronx, NY 10461 USA. NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Rogler, CE (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Med, Marion Bessin Liver Res Ctr, Jack & Pearl Resnick Campus,1300 Morris Pk Ave, Bronx, NY 10461 USA. FU NCI NIH HHS [P30CA13330, R01CA37232]; NIDDK NIH HHS [DK-17702] NR 42 TC 20 Z9 20 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD APR 15 PY 1999 VL 27 IS 8 BP 1919 EP 1925 DI 10.1093/nar/27.8.1919 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 190ML UT WOS:000079966900020 PM 10101202 ER PT J AU Souza-Pinto, NC Croteau, DL Hudson, EK Hansford, RG Bohr, VA AF Souza-Pinto, NC Croteau, DL Hudson, EK Hansford, RG Bohr, VA TI Age-associated increase in 8-oxo-deoxyguanosine glycosylase/AP lyase activity in rat mitochondria SO NUCLEIC ACIDS RESEARCH LA English DT Article ID BASE EXCISION-REPAIR; OXIDATIVE DAMAGE; DNA-DAMAGE; HEART-MITOCHONDRIA; LIPID OXIDATION; ENDONUCLEASE-G; HEPATOCYTES; EXPRESSION; INDUCTION; ENZYMES AB The mitochondrial theory of aging postulates that organisms age due to the accumulation of DNA damage and mutations in the multiple mitochondrial genomes, leading to mitochondrial dysfunction. Among the wide variety of DNA damage, 8-oxo-deoxyguanosine (8-oxo-dG) has received the most attention due to its mutagenicity and because of the possible correlation between its accumulation and pathological processes like cancer, degenerative diseases and aging. Although still controversial, many studies show that 8-oxo-dG accumulates with age in the mitochondrial (mt) DNA, However, little is known about the processing of this lesion and no study has yet examined whether mtDNA repair changes with age. Here, we report the first study on age-related changes in mtDNA repair, accomplished by assessing the cleavage activity of mitochondrial extracts towards an 8-oxo-dG-containing substrate. In this study, mitochondria obtained from rat heart and liver were used. We find that this enzymatic activity is higher in 12 and 23 month-old vats than in 6 month-old rats, in both liver and heart extracts. These mitochondrial extracts also cleave oligonucleotides containing a U:A mismatch, at the uracil position, reflecting the combined action of mitochondrial uracil DNA glycosylase (mtUDG) and mitochondrial apurinic/apyrimidinic (AP) endonucleases, The mtUDG activity did not change with age in liver mitochondria, but there was a small increase in activity from 6 to 23 months in rat heart extracts, after normalization to citrate synthase activity. Endonuclease G activity, measured by a plasmid relaxation assay, did not show any age-associated change in river, but there was a significant decrease from 6 to 23 months in heart mitochondria. Our results suggest that the mitochondrial capacity to repair 8-oxo-dG, the main oxidative base damage suggested to accumulate with age in mtDNA, does not decrease, but rather increases with age. The specific increase in 8-oxo-dG endonuclease activity, rather than a general up-regulation of DNA repair in mitochondria, suggests an induction of the 8-oxo-dG-specific repair pathway with age. C1 NIA, Genet Mol Lab, NIH, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), NIA, Genet Mol Lab, NIH, Box 1,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Souza-Pinto, Nadja/C-3462-2013 OI Souza-Pinto, Nadja/0000-0003-4206-964X NR 32 TC 90 Z9 94 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD APR 15 PY 1999 VL 27 IS 8 BP 1935 EP 1942 DI 10.1093/nar/27.8.1935 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 190ML UT WOS:000079966900022 PM 10101204 ER PT J AU Cereseto, A Parks, RW Rivadeneira, E Franchini, G AF Cereseto, A Parks, RW Rivadeneira, E Franchini, G TI Limiting amounts of p27(Kip1) correlates with constitutive activation of cyclin E-CDK2 complex in HTLV-I-transformed T-cells SO ONCOGENE LA English DT Article DE p27(Kip1); cyclin E; HTLV-I infection ID DEPENDENT KINASE INHIBITOR; LEUKEMIA-LYMPHOMA VIRUS; P21(WAF1/CIP1) EXPRESSION; INTERLEUKIN-2 RECEPTOR; MOLECULAR MECHANISMS; POTENTIAL MEDIATOR; RESTRICTION POINT; BREAST-CANCER; MICE LACKING; PROTEIN AB Human T-cells immortalized (interleukin-2 [IL-2] dependent) by the human T-cell lymphotropic/leukemia virus type I (HTLV-I), in time, become transformed (IL-2 independent). To understand the biochemical basis of this transition, we have used the sibling HTLV-I-infected T-cell lines, N1186 (IL-2 dependent) and N1186-94 (IL-2 independent), as models to assess the responses to antiproliferative signals. In N1186 cells arrested in G1 after serum/interleukin-2 (IL-2) deprivation, downregulation of the cyclin E-CDK2 kinase activity correlated with decreased phosphorylation of CDK2 and accumulation of p27(Kip1) bound to the cyclin E-CDK2 complex, as seen in normal activated PBMCs (peripheral blood mononuclear cells). In contrast, N1186-94 cells failed to arrest in G1 upon serum starvation, displayed constitutive cyclin E-associated kinase activity, and, although CDK2 was partially dephosphorylated, the amount of p27(Kip1) bound to the complex did not increase. This observation, extended to two other IL-2-dependent as well as to three IL-2-independent HTLV-I-infected T-cell lines, suggests that the lack of cyclin E-CDK2 kinase downregulation found in the late phase of HTLV-I transformation may correlate with insufficient amounts of p27(Kip1) associated with the cyclin E-CDK2 complex. Reconstitution experiments demonstrated that the addition of p27(Kip1) to lysates from N1186-94 starved cells resulted in the downregulation of cyclin E-associated kinase activity supporting the notion that the unresponsiveness of the cyclin E-CDK2 complex to growth inhibitory signals may be due to inadequate amounts of p27(Kip1) assembled with the complex in HTLV-I-transformed T-cells, In fact, the amount of p27(Kip1) protein was lower in most HTLV-I-transformed (IL-2-independent) than in the immortalized (IL-2-dependent) HTLV-I-infected T-cells, Furthermore, specific inhibitors of the phosphatidylinositol 3-kinase (PI3K) induced an increase of p27(Kip1) protein levels, which correlated,vith G1 arrest, in both IL-2-dependent and IL-2-independent HTLV-I-infected T-cells, Altogether, these results suggest that maintaining a low level of expression of p27(Kip1) is a key event in HTLV-I transformation. C1 NCI, Basic Res Lab, Div Basic Sci, Bethesda, MD 20892 USA. RP Cereseto, A (reprint author), NCI, Basic Res Lab, Div Basic Sci, Bethesda, MD 20892 USA. NR 42 TC 31 Z9 31 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 15 PY 1999 VL 18 IS 15 BP 2441 EP 2450 DI 10.1038/sj.onc.1202567 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 186AC UT WOS:000079703300004 PM 10229195 ER PT J AU Taitelbaum, H Koza, Z Yanir, T Weiss, GH AF Taitelbaum, H Koza, Z Yanir, T Weiss, GH TI Tiger and Rabbits: a single trap and many random walkers SO PHYSICA A LA English DT Article; Proceedings Paper CT International Conference on Percolation and Disordered Systems - Theory and Applications CY JUL 14-17, 1998 CL UNIV GIESSEN, SCHLOSS RAUISCHHOLZHAUSEN, GIESSEN, GERMANY SP Deutsch Forsch Gemeinschaft, Minerva Ctr Mesoscopics HO UNIV GIESSEN, SCHLOSS RAUISCHHOLZHAUSEN ID DIFFUSION-CONTROLLED REACTIONS; NEAREST-NEIGHBOR DISTANCES; MOBILE TRAP; REACTION-KINETICS; ANNIHILATION; DENSITY; CHAINS; MOTION; MODEL AB We study a one-dimensional system with a single trap (Tiger) initially located at the origin, and many random-walkers (Rabbits) initially uniformly distributed throughout the infinite or the semi-infinite space. For a mobile imperfect trap, we study the spatiotemporal properties of the system, such as the trapping rate, the particle distribution and the segregation around the trap, all as a function of the diffusivities of both the trap and the walkers. For a static trap, we present results of various measures of segregation, in particular on a few types of disordered chains, such as random local bias fields (the Sinai model) and random transition rates. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Bar Ilan Univ, Dept Phys, IL-52900 Ramat Gan, Israel. Univ Wroclaw, Inst Theoret Phys, PL-50204 Wroclaw, Poland. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Taitelbaum, H (reprint author), Bar Ilan Univ, Dept Phys, IL-52900 Ramat Gan, Israel. RI Koza, Zbigniew/J-7768-2012 OI Koza, Zbigniew/0000-0003-2856-015X NR 27 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4371 J9 PHYSICA A JI Physica A PD APR 15 PY 1999 VL 266 IS 1-4 BP 280 EP 290 DI 10.1016/S0378-4371(98)00604-9 PG 11 WC Physics, Multidisciplinary SC Physics GA 194AR UT WOS:000080170400040 ER PT J AU Proschan, MA AF Proschan, MA TI A multiple comparison procedure for three- and four-armed controlled clinical trials SO STATISTICS IN MEDICINE LA English DT Article AB Multi-armed controlled trials are becoming increasingly popular. With them comes the issue of how to deal with the possibility of multiple Type I errors, This paper recommends a simple and appealing method for three- and four-armed trials in which one is a control. This article is a US Government work and is in the public domain in the United States. C1 NHLBI, Rockledge Ctr 2, Bethesda, MD 20892 USA. RP Proschan, MA (reprint author), NHLBI, Rockledge Ctr 2, 6701 Rockledge Dr,MSC 7938, Bethesda, MD 20892 USA. NR 12 TC 11 Z9 11 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD APR 15 PY 1999 VL 18 IS 7 BP 787 EP 798 DI 10.1002/(SICI)1097-0258(19990415)18:7<787::AID-SIM77>3.0.CO;2-M PG 12 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 183XT UT WOS:000079580200003 PM 10327527 ER PT J AU van Birgelen, APJM Hebert, CD Wenk, ML Grimes, LK Chapin, RE Mahler, J Trevlos, GS Bucher, JR AF van Birgelen, APJM Hebert, CD Wenk, ML Grimes, LK Chapin, RE Mahler, J Trevlos, GS Bucher, JR TI Toxicity of 3,3 ',4,4 '-tetrachloroazobenzene in rats and mice SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID DIBENZO-P-DIOXINS; UDP-GLUCURONOSYLTRANSFERASE INDUCERS; INDUCED HEMOLYTIC-ANEMIA; THYROID-HORMONE LEVELS; ZERO DOSE CONTROL; RISK ASSESSMENT; CHICK-EMBRYO; METABOLISM; EXPOSURE; PROPANIL AB The toxicity of 3,3',4,4'-tetrachloroazobenzene (TCAB) was evaluated in 13-week gavage studies in male and female F344/N rats and B6C3F(1) mice. In addition to histopathology, evaluations included clinical chemistry, hematology, thyroid hormone analyses, and reproductive parameters. Groups of 10 rats and 10 mice of each sex were exposed to TCAB at dose levels of 0, 0.1, 1, 3, 10, or 30 mg/kg for 5 days a week for 13 weeks. In the rat studies, the major effects for both males and females included a 10% decrease in terminal body weight at 30 mg/kg/day, an increase in hematopoietic cell proliferation in the spleen at 10 and 30 mg/kg/day, and a responsive anemia at 10 and 30 mg/kg/day. A 15 to 30% decrease in platelet counts and a 20 to 40% decrease in thymus weights was observed at 10 and 30 mg/kg/day. An increase in liver weight up to 15% was found at 3 mg/kg/day and higher doses in males and at 10 and 30 mg/kg/day in females, respectively. An increase in spleen weights up to 15% was observed at 10 and 30 mg/kg/day in males and at 30 mg/kg/day in females. A marked decrease in circulating total thyroxine (TT4) was found in both males and females at all dose levels tested. TT4 could hardly be detected at 10 and 30 mg TCAB/kg/day. In addition, hyperplasia of the forestomach was increased at 3 mg/kg/day and higher doses in males and at 30 mg/kg/day in females. In the mouse studies, an increase in liver and spleen weight was observed up to approximately 25% in bath males and females at 10 and 30 mg/kg/day. Hyperplasia of the forestomach was observed at 1 mg/kg/day and higher doses in both males and females. In males, a 30% decrease in thymus weights at 30 mg/kg/day and a 60% decrease in epididymal sperm density at 3 and 30 mg/kg/day was observed. Also in males, centrilobular hypertrophy of hepatocytes and an increase in hematopoietic cell proliferation in the spleen was observed at 3 mg/kg/day and higher doses. Based on the current study and information in the literature, TCAB has dioxin-like properties. Comparison of the effects of TCAB in the present study and in the literature to those with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) indicates that TCAB is from two to six orders of magnitude less potent than TCDD depending on the end point. (C) 1999 Academic Press. C1 NIEHS, Res Triangle Pk, NC 27709 USA. MA Bioserv Inc, Rockville, MD 20850 USA. Environm Hlth Res & Testing Inc, Lexington, KY USA. RP van Birgelen, APJM (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. OI Chapin, Robert/0000-0002-5997-1261 NR 73 TC 8 Z9 8 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD APR 15 PY 1999 VL 156 IS 2 BP 147 EP 159 DI 10.1006/taap.1999.8640 PG 13 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 190MC UT WOS:000079966000008 PM 10198280 ER PT J AU Fuchimoto, Y Huang, C Chang, Q Yamada, K Neville, D White-Scharf, ME Sachs, DH AF Fuchimoto, Y Huang, C Chang, Q Yamada, K Neville, D White-Scharf, ME Sachs, DH TI Stable mixed chimerism and donor specific tolerance without whole body irradiation in a large animal model SO TRANSPLANTATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, MGH, Transplantat Biol Res Ctr, Boston, MA 02115 USA. BioTransplant Inc, Boston, MA USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 1999 VL 67 IS 7 MA 112 BP S34 EP S34 DI 10.1097/00007890-199904150-00140 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 189ND UT WOS:000079910700140 ER PT J AU Goebel, J Forrest, K Franks, A Emmrich, F Mikovits, J Robey, F Volk, HD Lowry, RP AF Goebel, J Forrest, K Franks, A Emmrich, F Mikovits, J Robey, F Volk, HD Lowry, RP TI Anti-CD4 antibody attenuates interleukin-2 receptor signaling SO TRANSPLANTATION LA English DT Meeting Abstract C1 Univ Kentucky, Lexington, KY USA. Univ S Alabama, Mobile, AL 36688 USA. NIH, Frederick, MD USA. NIH, Bethesda, MD 20892 USA. Univ Leipzig, D-7010 Leipzig, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 1999 VL 67 IS 7 MA 1021 BP S262 EP S262 DI 10.1097/00007890-199904150-01045 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 189ND UT WOS:000079910701044 ER PT J AU Hubbard, WJ Ma, SL Neville, DM Contreras, J Wang, B Moore, J Thomas, JM AF Hubbard, WJ Ma, SL Neville, DM Contreras, J Wang, B Moore, J Thomas, JM TI Comparison of anti-CD3 epsilon immunotoxin constructed with either intact MAB or F(AB)(2) for tolerance induction in a rhesus transplant model SO TRANSPLANTATION LA English DT Meeting Abstract C1 Univ Alabama, Transplant Ctr, Birmingham, AL USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 1999 VL 67 IS 7 MA 877 BP S226 EP S226 DI 10.1097/00007890-199904150-00901 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 189ND UT WOS:000079910700900 ER PT J AU Thomas, J Jiang, X Wang, W Contreras, J Eckhoff, D Hubbard, W Thomas, F Neville, D AF Thomas, J Jiang, X Wang, W Contreras, J Eckhoff, D Hubbard, W Thomas, F Neville, D TI Transient arrest of dendritic cell maturation: A window of opportunity for primate tolerance induction? SO TRANSPLANTATION LA English DT Meeting Abstract C1 Univ Alabama, Transplant Ctr, Birmingham, AL USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 1999 VL 67 IS 7 MA 813 BP S210 EP S210 DI 10.1097/00007890-199904150-00837 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 189ND UT WOS:000079910700836 ER PT J AU Wu, A Yamada, K Awwad, M Shimizu, A Watts, A Gojo, S Neville, D Cooper, DKC Sykes, M Sachs, DH AF Wu, A Yamada, K Awwad, M Shimizu, A Watts, A Gojo, S Neville, D Cooper, DKC Sykes, M Sachs, DH TI Prolonged xenogeneic skin graft survival after xenogenic porcine thymic transplantation in a non-human primate model SO TRANSPLANTATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. Biotransplant Inc, Boston, MA USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 1999 VL 67 IS 7 MA 1011 BP S259 EP S259 DI 10.1097/00007890-199904150-01035 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 189ND UT WOS:000079910701033 ER PT J AU Wilson, MA Hoch, RV Ashcroft, NR Kosinski, ME Golden, A AF Wilson, MA Hoch, RV Ashcroft, NR Kosinski, ME Golden, A TI A Caenorhabditis elegans wee1 homolog is expressed in a temporally and spatially restricted pattern during embryonic development SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE cell cycle; gene family; genomic database; tyrosine kinase ID C-ELEGANS; FISSION YEAST; SCHIZOSACCHAROMYCES-POMBE; SUBCELLULAR-LOCALIZATION; PHOSPHORYLATES P34(CDC2); BLASTOMERE IDENTITY; TYROSINE KINASE; GENE-EXPRESSION; LEADER SEQUENCE; ARREST MUTANTS AB A wee1 homolog, wee-1.1, is expressed in both a temporally and spatially restricted pattern during early Caenorhabditis elegans embryogenesis, and is undetectable throughout the remainder of embryogenesis. The wee-1.1 message appears to be zygotically expressed in the somatic founder cell E of the 12-cell embryo. This expression disappears when the E blastomere divides for the first time. The wee-1.1 message then appears transiently in the nuclei of the eight great-granddaughter cells of the AB somatic founder cell, just before these cells divide in the 16-cell embryo. Following this division, the wee-1.1 mRNA is no longer detectable throughout the remainder of embryogenesis. The expression of wee-1.1 in the E blastomere and in the AB progeny appears to be restricted to nuclei in prophase and metaphase of the cell cycle. Analysis of the wee-1.1 mRNA expression pattern in maternal-effect lethal mutants suggests that this expression pattern is restricted to cells of the E and AB fates in the early embryo. This mRNA expression pattern is restricted to a 10-15-min span of embryonic development and may be regulating the timing of crucial cell divisions at this early stage of development. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NCI, Gene Regulat & Chromosome Biol Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP NCI, Gene Regulat & Chromosome Biol Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, POB B,Bldg 539, Frederick, MD 21702 USA. EM golden@ncifcrf.gov OI Hoch, Renee/0000-0003-0042-3751 NR 50 TC 18 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD APR 14 PY 1999 VL 1445 IS 1 BP 99 EP 109 DI 10.1016/S0167-4781(99)00027-5 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 189EU UT WOS:000079892100009 PM 10209262 ER PT J AU Shlay, JC Cohn, DL Chaloner, K Max, MB Reichelderfer, P Flaws, B Wentworth, D Hillman, S Brizz, B AF Shlay, JC Cohn, DL Chaloner, K Max, MB Reichelderfer, P Flaws, B Wentworth, D Hillman, S Brizz, B TI Acupuncture and amitriptyline for HIV-related peripheral neuropathic pain - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID DIABETIC NEUROPATHY C1 Denver Community Programs Clin Res AIDS, Denver, CO USA. Univ Minnesota, Sch Stat, St Paul, MN 55108 USA. NIH, Bethesda, MD 20892 USA. Univ Minnesota, Minneapolis, MN USA. Social Syst Inc, Rockville, MD USA. RP Shlay, JC (reprint author), Denver Community Programs Clin Res AIDS, Denver, CO USA. RI Chaloner, Kathryn/B-5090-2013 NR 6 TC 0 Z9 0 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 14 PY 1999 VL 281 IS 14 BP 1271 EP 1272 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 184TC UT WOS:000079628700023 ER PT J AU Gu, K Cowie, CC Harris, MI AF Gu, K Cowie, CC Harris, MI TI Diabetes and decline in heart disease mortality in US adults SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RISK-FACTORS; CARDIOVASCULAR-DISEASE; UNITED-STATES; POPULATION; PREVALENCE; TRENDS; MELLITUS; AGREEMENT; GLUCOSE AB Context Mortality from coronary heart disease has declined substantially in the United States during the past 30 years. However, it is unknown whether patients with diabetes have also experienced a decline in heart disease mortality. Objective To compare adults with diabetes with those without diabetes for time trends in mortality from all causes, heart disease, and ischemic heart disease. Design, Setting, and Participants Representative cohorts of subjects with and without diabetes were derived from the First National Health and Nutrition Examination Survey (NHANES I) conducted between 1971 and 1975 (n = 9639) and the NHANES I Epidemiologic Follow-Lap Survey conducted between 1982 and 1984 (n = 8463), The cohorts were followed up prospectively for mortality for an average of 8 to 9 years. Main Outcome Measure Changes in mortality rates per 1000 person-years for all causes, heart disease, and ischemic heart disease for the 1982-1984 cohort compared with the 1971-1975 cohort. Results For the 2 periods, nondiabetic men experienced a 36.4% decline in age-adjusted heart disease mortality compared with a 13.1 % decline far diabetic men, Age-adjusted heart disease mortality declined 27% in nondiabetic women but increased 23% in diabetic women. These patterns were also found for all-cause mortality and ischemic heart disease mortality. Conclusions The decline in heart disease mortality in the general US population has been attributed to reduction in cardiovascular risk factors and improvement in treatment of heart disease, The smaller declines in mortality for diabetic subjects in the present study indicate that these changes may have been less effective for people with diabetes, particularly women. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Harris, MI (reprint author), NIDDKD, NIH, Natcher Bldg,Room 5AN24,45 Ctr Dr,MSC 6600, Bethesda, MD 20892 USA. EM harrism@ep.niddk.nih.gov NR 22 TC 487 Z9 502 U1 1 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 14 PY 1999 VL 281 IS 14 BP 1291 EP 1297 DI 10.1001/jama.281.14.1291 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 184TC UT WOS:000079628700033 PM 10208144 ER PT J AU Nakamura, S Tatuno, I Noguchi, Y Kitagawa, M Kohn, LD Saito, Y Hirai, A AF Nakamura, S Tatuno, I Noguchi, Y Kitagawa, M Kohn, LD Saito, Y Hirai, A TI 73-kDa heat shock cognate protein interacts directly with P27Kip1,a cyclin-dependent kinase inhibitor, during G1/S transition SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE heat shock protein; 73hsc; P27Kip1; cell cycle; G1/S transition ID FRTL-5 CELLS; P27(KIP1); REGION; PHASE; BINDS; G(1) AB Although heat shock proteins (HSPs) were discovered as inducible proteins by the physical stress to protect cells, recent evidence has suggested that HSPs are likely involved in cell cycle control under normal conditions without stress. In the present study, we demonstrated that 73hsc (heat shock cognate protein), which belongs to the HSP70 family of molecular chaperones, interacts with P27Kip1, an inhibitor of cyclin-dependent kinase, during G1/S transition. 73hsc was detected in the immunoprecipitates with anti-P27Kip1 antibody and, vice versa, P27Kip1 was present in the immunoprecipitates with anti-73hsc antibody by Western blotting using growth-stimulated rat thyroid FRTL-5 cells. This complex formation of 73hsc and P27Kip1 was cell cycle dependent and its maximum formation was observed at G1/S transition where the level of P27Kip1 dramatically decreased. ATP dissociated this complex formation in a dose-dependent manner. These data indicated that 73hsc might be involved in the cell cycle progression through the regulation of cell cycle regulators such as P27Kip1. (C) 1999 Academic Press. C1 Chiba Univ, Sch Med, Dept Internal Med 2, Chuo Ku, Chiba 260, Japan. Kyushu Univ, Med Inst Bioregulat, Dept Mol & Cellular Biol, Higashi Ku, Fukuoka 81282, Japan. Tougane Prefectural Hosp, Tougane, Chiba 283, Japan. NIDDKD, Metab Dis Branch, Cell Regulat Sect, NIH, Bethesda, MD 20892 USA. RP Nakamura, S (reprint author), Chiba Univ, Sch Med, Dept Internal Med 2, Chuo Ku, 1-8-1 Inohana, Chiba 260, Japan. NR 13 TC 26 Z9 27 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 13 PY 1999 VL 257 IS 2 BP 340 EP 343 DI 10.1006/bbrc.1999.0442 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 189UR UT WOS:000079925000016 PM 10198213 ER PT J AU Rafferty, SP Boyington, JC Kulansky, R Sun, PD Malech, HL AF Rafferty, SP Boyington, JC Kulansky, R Sun, PD Malech, HL TI Stoichiometric arginine binding in the oxygenase domain of inducible nitric oxide synthase requires a single molecule of tetrahydrobiopterin per dimer SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID FORMS; HEME AB In addition to its catalytic roles, the nitric oxide synthase (NOS) cofactor tetrahydrobiopterin (H4B) is required for substrate binding and for stabilization of the dimeric structure. We expressed and purified the core of the iNOS oxygenase domain consisting of residues 75-500 (CODiNOS) in the presence (H4B(+)) and absence (H4B(-)) of this cofactor. Both forms bound stoichiometric amounts of heme (>0.9 heme per protein subunit). H4B(-) CODiNOS was unable to bind arginine, gave an unstable ferrous carbonyl adduct, and was a mixture of monomer and dimer. H4B(+) CODiNOS bound arginine, gave a stable ferrous carbonyl adduct, and was exclusively dimeric. The H4B cofactor content of this species was only one per dimer yet this was sufficient to form two competent arginine binding sites as determined by optical stoichiometric titrations. (C) 1999 Academic Press. C1 NIAID, Off Sci Directors, Struct Biol Sect, NIH, Bethesda, MD 20892 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Rafferty, SP (reprint author), Trent Univ, Dept Chem, 1600 W Bank Dr, Peterborough, ON K9J 7B8, Canada. NR 10 TC 13 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 13 PY 1999 VL 257 IS 2 BP 344 EP 347 DI 10.1006/bbrc.1999.0450 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 189UR UT WOS:000079925000017 PM 10198214 ER PT J AU Frank, S Kohler, U Schackert, G Schackert, HK AF Frank, S Kohler, U Schackert, G Schackert, HK TI Expression of TRAIL and its receptors in human brain tumors SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE apoptosis; TRAIL; TRAIL receptors; death receptors; signaling; brain neoplasms ID NF-KAPPA-B; FADD-DEPENDENT APOPTOSIS; DEATH DOMAIN; CELL-DEATH; FAMILY; MEMBER; LIGAND; ACTIVATE; CASPASES; SIGNAL AB Recently, TRAIL has been demonstrated to selectively induce apoptosis in transformed cell lines, and subsequently four receptors (TRAIL-R1-TRAIL-R4) have been identified. The ability to transduce death signals is restricted to TRAIL-R1/TRAIL-R2. In contrast, TRAIL-R3/TRAIL-R4 are unable to activate apoptotic pathways and have therefore been suggested to act as "decoys" protecting normal tissues from cell death, However, the biological role of the TRAIL system remains incompletely understood. We analyzed the expression of TRAIL and its receptors in a panel of human brain tumors (n = 34) and in four glioma cell lines in comparison to normal brain tissue. Constant co-expression of TRAIL and of receptors TRAIL-R1, TRAIL-R2, and TRAIL-R3 in different tumor entities as well as in normal brain indicates that additional mechanisms might modulate the previously proposed "decoy" model. Furthermore, in contrast to previous reports, we demonstrate TRAIL and TRAIL-R2 to be present on a transcriptional level in normal brain tissue. Exceptional expression of TRAIL-R4 transcripts does not suggest a significant regulatory role of this receptor in the human brain and its tumors. (C) 1999 Academic Press. C1 NINDS, Surg Neurol Branch, Biochem Sect, NIH, Bethesda, MD 20892 USA. Tech Univ Dresden, Dept Surg Res, Dresden, Germany. RP Frank, S (reprint author), NINDS, Surg Neurol Branch, Biochem Sect, NIH, Bldg 10,Room 4N 244, Bethesda, MD 20892 USA. NR 33 TC 71 Z9 76 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 13 PY 1999 VL 257 IS 2 BP 454 EP 459 DI 10.1006/bbrc.1999.0493 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 189UR UT WOS:000079925000037 PM 10198234 ER PT J AU Ritter, LM Garfield, SH Thorgeirsson, UP AF Ritter, LM Garfield, SH Thorgeirsson, UP TI Tissue inhibitor of metalloproteinases-1 (TIMP-1) binds to the cell surface and translocates to the nucleus of human MCF-7 breast carcinoma cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID GREEN FLUORESCENT PROTEIN; GROWTH-FACTOR; EXPRESSION; TRANSPORT; CANCER; RNA; GOLGI; K562; GFP AB To study cellular and subcellular localization of TIMP-1, we constructed a cDNA which would express a chimeric protein. TIMP-1-EGFP, having the enhanced green fluorescent protein of the jelly fish Aequorea victoria fused to the carboxyl-terminus of TIMP-1. Chinese Hamster Ovary (CHO) cells were stably transfected with the TIRIPP-1-EGFP expressing plasmid. The secreted chimera was processed through the endoplasmic reticulum and Golgis, as was shown by fluorescent confocal microscopy after incubations at temperatures which block processing at the intermediate compartment and the trans-Golgi network. In a co-culture system, secreted TIMP-1-EGFP could be visualized binding to the surface of MCF-7 breast carcinoma cells but not non-neoplastic HBL-100 breast epithelial cells. TIMP-1-EGFP localized to the nucleus of MCF-7 cells after 72 hrs in co-culture. These findings suggest that TIMP-1 may preferentially bind to and be taken up by malignant breast epithelial cells and that TGIMP-1 may play a yet unidentified role in nuclear functions. (C) 1999 Academic Press. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, Tumor Biol & Carcinogenesis Sect, NIH, Bethesda, MD 20892 USA. NCI, Div Basic Sci, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Thorgeirsson, UP (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, Tumor Biol & Carcinogenesis Sect, NIH, Bldg 37, Bethesda, MD 20892 USA. NR 25 TC 77 Z9 82 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 13 PY 1999 VL 257 IS 2 BP 494 EP 499 DI 10.1006/bbrc.1999.0408 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 189UR UT WOS:000079925000043 PM 10198240 ER PT J AU Shackelford, RE AF Shackelford, RE TI Interferon-gamma, bacterial lipopolysaccharide, and tumor necrosis factor-alpha induce CD11a mRNA and protein via Na+/H+ exchange and protein kinase C dependent mechanisms in tissue macrophages SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID MURINE PERITONEAL-MACROPHAGES; FUNCTION-ASSOCIATED MOLECULE-1; COUNTER-RECEPTOR; (LFA)-1 ANTIGEN; EXPRESSION; ACTIVATION; CLONING; ADHERENCE; ICAM-3; LFA-1 AB Previously CD11a or leukocyte function-associated antigen alpha-1 was found to be induced at the surface protein level in thioglycolate-elicited peritoneal macrophages by bacterial lipopolysaccharide and interferon-gamma. To investigate this induction further, Northern blotting and enzyme-linked immunosorbent assays were used to examine the role of second messengers in CD11a gene product induction by these agents. Here I report that CD11a RNA and cell surface protein induced by bacterial lipopolysaccharide and tumor necrosis factor-alpha are sensitive to inhibition of protein kinase C, while insensitive to inhibition of Na+/H+ exchange. CD11a induction by interferon-gamma conversely is sensitive to inhibition of Na+/H+ exchange and insensitive to inhibition of protein kinase C. These observations indicate that CD11a may be induced by multiple and separate second messenger systems in primary macrophages. (C) 1999 Academic Press. C1 Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27709 USA. RP Shackelford, RE (reprint author), NIEHS, POB 12233,F1-05,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 26 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 13 PY 1999 VL 257 IS 2 BP 635 EP 641 DI 10.1006/bbrc.1999.0517 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 189UR UT WOS:000079925000066 PM 10198263 ER PT J AU Singh, JP Larson, MG Manolio, TA O'Donnell, CJ Lauer, M Evans, JC Levy, D AF Singh, JP Larson, MG Manolio, TA O'Donnell, CJ Lauer, M Evans, JC Levy, D TI Blood pressure response during treadmill testing as a risk factor for new-onset hypertension - The Framingham Heart Study SO CIRCULATION LA English DT Article DE tests; hypertension; trials ID EXERCISE HYPERTENSION; SUBMAXIMAL EXERCISE; YOUNG-ADULTS; FOLLOW-UP; DISEASE; GENDER; AGE; MEN AB Background-Although systolic blood pressure (SBP) response to exercise has been shown to predict subsequent hypertension in small samples of men, this association has not been studied in a large population-based sample of middle-aged men and women. The purpose of this study was to examine, in normotensive subjects, the relations of SEP and diastolic blood pressure (DBP) during the exercise and recovery periods of a graded treadmill test to the risk of developing new-onset hypertension. Methods and Results-BP data from exercise testing in 1026 men and 1284 women (mean age, 42+/-10 years; range, 20 to 69 years) from the Framingham Offspring Study who were normotensive at baseline were related to the incidence of hypertension 8 years later. New-onset hypertension, defined as an SEP greater than or equal to 140 mm Hg or DBP greater than or equal to 90 mm Hg or the initiation of antihypertensive drug treatment, occurred in 228 men (22%) and 207 women (16%). Exaggerated SEP (Ex-SBP 2) and DBP (Ex-DBP 2) response and delayed recovery of SEP (R-SBP 3) and DBP (R-DBP 3) were defined as an age-adjusted BP greater than the 95th percentile during the second stage of exercise and third minute of recovery, respectively. After multivariable adjustment, Ex-DBP 2 was highly predictive of incident hypertension in both men (OR, 4.16; 95% CI, 2.15, 8.05) and women (OR, 2.17; CI, 1.19, 3.96). R-SBP 3 was predictive of hypertension in men in a multivariable model that included exercise duration and peak exercise BP (OR, 1.92; CI, 1.00, 3.69). Baseline resting SEP (chi(2), 23.4 in men and 34.7 in women) and DBP (chi(2), 11.3 in men and 13.1 in women) had stronger associations with new-onset hypertension than exercise DBP (chi(2), 16.4 in men and 6.1 in women) and recovery SEP (chi(2), 6.5 in men and 2.1 in women) responses. Conclusions-An exaggerated DBP response to exercise was predictive of risk for new-onset hypertension in normotensive men and women. An elevated recovery SEP was predictive of hypertension in men. These findings may reflect subtle pathophysiological features in the preclinical stage of hypertension. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. NHLBI, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Div Epidemiol & Prevent Med, Boston, MA 02118 USA. Cleveland Clin Fdn, Dept Cardiol, Cleveland, OH 44195 USA. Beth Israel Hosp, Div Cardiol, Boston, MA 02215 USA. Beth Israel Hosp, Div Clin Epidemiol, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Levy, D (reprint author), NHLBI, Framingham Heart Study, 5 Thurber St, Framingham, MA 01702 USA. EM dan@fram.nhlbi.nih.gov NR 31 TC 230 Z9 249 U1 3 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 13 PY 1999 VL 99 IS 14 BP 1831 EP 1836 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 184WC UT WOS:000079635900009 PM 10199879 ER PT J AU Jacobs, AK Kelsey, SF Brooks, MM Faxon, DP Chaitman, BR Bittner, V Dean, L Mock, MB Weiner, BH Winston, C Drew, L Sopko, G AF Jacobs, AK Kelsey, SF Brooks, MM Faxon, DP Chaitman, BR Bittner, V Dean, L Mock, MB Weiner, BH Winston, C Drew, L Sopko, G TI Women versus men regarding outcome of CABG or PTCA - Response SO CIRCULATION LA English DT Letter ID REVASCULARIZATION INVESTIGATION BARI; CORONARY REVASCULARIZATION C1 Boston Med Ctr, Boston, MA 02101 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ So Calif, Los Angeles, CA USA. St Louis Univ, St Louis, MO 63103 USA. Univ Alabama, Birmingham, AL USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Univ Massachusetts, Med Ctr, Worcester, MA USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Duke Univ, Med Ctr, Durham, NC USA. NIH, Cardiol Branch, Bethesda, MD 20892 USA. RP Jacobs, AK (reprint author), Boston Med Ctr, Boston, MA 02101 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 13 PY 1999 VL 99 IS 14 BP 1926 EP 1926 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 184WC UT WOS:000079635900031 ER PT J AU Warner, DR Weinstein, LS AF Warner, DR Weinstein, LS TI A mutation in the heterotrimeric stimulatory guanine nucleotide binding protein alpha-subunit with impaired receptor-mediated activation because of elevated GTPase activity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SIGNAL-TRANSDUCTION; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; ADENYLYL-CYCLASE; SWITCH-III; GS-ALPHA; G(S-ALPHA); HYDROLYSIS; DOMAIN; GDP AB It has been reported that substitution of Arg(258), a residue within the GTPase domain of the heterotrimeric guanine nucleotide binding protein (G protein) alpha-subunit (alpha(s)), to alanine (alpha(s)-R258A) results in decreased activation by receptor or aluminum fluoride (AlF4-) and increased basal GDP release. Arg(258) interacts with Gln(170) in the helical domain, and, presumably, Loss of this interaction between the GTPase and helical domain leads to more rapid GDP release, resulting in decreased activation by AlF4- and increased thermolability. In this study, me mutate Gln(170) to alanine (alpha(s)-Q170A) and demonstrate that this mutant, like alpha(s)-R258A, has decreased activation by AlF4-, increased thermolability (both reversed in the presence of excess guanine nucleotide), and an increased rate of GDP release. However, unlike alpha(s)-R258A, alpha(s)-Q170A does not have impaired receptor-mediated activation. Therefore, this interdomain interaction is critical to maintain normal guanine nucleotide binding (and hence normal activation by AlF4-) but is not important for receptor-mediated activation. In single turnover GTPase assays, the catalytic rate for GTP hydrolysis of alpha(s)-R258A was 14-fold higher than normal whereas that of alpha(s)-Q170A was unaffected. Examination of the cr, crystal structure suggests that Arg(258), through interactions with Glu(50), might constrain the position of Arg(201), a residue critical for catalyzing the GTPase reaction. This is an example of a mutation in a heterotrimeric G protein that results in an increased intrinsic GTPase activity and provides another mechanism by which G protein mutations can impair signal transduction. C1 NINDS, Membrane Biochem Sect, Mol & Cellular Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Warner, DR (reprint author), NINDS, Membrane Biochem Sect, Mol & Cellular Neurobiol Lab, NIH, Bldg 49,Room 2A28, Bethesda, MD 20892 USA. RI Weinstein, Lee/I-5575-2015 NR 34 TC 25 Z9 26 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 13 PY 1999 VL 96 IS 8 BP 4268 EP 4272 DI 10.1073/pnas.96.8.4268 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 187BP UT WOS:000079766500014 PM 10200251 ER PT J AU Lee, JH Choi, SK Roll-Mecak, A Burley, SK Dever, TE AF Lee, JH Choi, SK Roll-Mecak, A Burley, SK Dever, TE TI Universal conservation in translation initiation revealed by human and archaeal homologs of bacterial translation initiation factor IF2 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE eukaryotic translation initiation factor; FUN12; initiator tRNA ID ELONGATION-FACTOR-TU; PROTEIN-BIOSYNTHESIS; SEQUENCE ALIGNMENT; ESCHERICHIA-COLI; EF-TU; MECHANISM; RIBOSOMES; BINDING; DOMAIN; YEAST AB Binding of initiator methionyl-tRNA to ribosomes is catalyzed in prokaryotes by initiation factor (IF) IF2 and in eukaryotes by eIF2. The discovery of both IF2 and eIF2 homologs in yeast and archaea suggested that these microbes possess an evolutionarily intermediate protein synthesis apparatus. We describe the identification of a human IF2 homolog, and we demonstrate by using in vivo and in vitro assays that human IF2 functions as a translation factor. In addition, we show that archaea IF2 can substitute for its yeast homolog both in vivo and in vitro. We propose a universally conserved function for IF2 in facilitating the proper binding of initiator methionyl-tRNA to the ribosomal P site. C1 NICHHD, Lab Eukaryot Gene Regulat, NIH, Bethesda, MD 20892 USA. Rockefeller Univ, Labs Mol Biophys, New York, NY 10021 USA. Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA. RP Dever, TE (reprint author), NICHHD, Lab Eukaryot Gene Regulat, NIH, Bldg 6A,Room B1A-02,6 Ctr Dr, Bethesda, MD 20892 USA. NR 27 TC 73 Z9 75 U1 2 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 13 PY 1999 VL 96 IS 8 BP 4342 EP 4347 DI 10.1073/pnas.96.8.4342 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 187BP UT WOS:000079766500027 PM 10200264 ER PT J AU Belyakov, IM Moss, B Strober, W Berzofsky, JA AF Belyakov, IM Moss, B Strober, W Berzofsky, JA TI Mucosal vaccination overcomes the barrier to recombinant vaccinia immunization caused by preexisting poxvirus immunity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; IMMUNODEFICIENCY-VIRUS TYPE-1; ATTENUATED MVA STRAIN; CLASS-I; ENVELOPE GLYCOPROTEIN; PROTECTIVE IMMUNITY; HOST-RANGE; MICE; HIV; INDUCTION AB Overcoming preexisting immunity to vaccinia virus in the adult population is a key requirement for development of otherwise potent recombinant vaccinia vaccines. Based on our observation that s.c. immunization with vaccinia induces cellular and antibody immunity to vaccinia only in systemic lymphoid tissue and not in mucosal sites, we hypothesized that the mucosal immune system remains naive to vaccinia and therefore amenable to immunization with recombinant vaccinia vectors despite earlier vaccinia exposure, We show that mucosal immunization of vaccinia-immune BALB/c mice with recombinant vaccinia expressing HIV gp160 induced specific serum antibody and strong HIV-specific cytotoxic T lymphocyte responses. These responses occurred not only in mucosal but also in systemic lymphoid tissue, whereas systemic immunization was ineffective under these circumstances. In this context, intrarectal immunization was more effective than intranasal immunization. Boosting with a second dose of recombinant vaccinia was also more effective via the mucosal route. The systemic HIV-specific cytotoxic T lymphocyte response was enhanced by coadministration of IL-12 at the mucosal site. These results also demonstrate the independent compartmentalization of the mucosal versus systemic immune systems and the asymmetric trafficking of lymphocytes between them. This approach to circumvent previous vaccinia immunity may be useful for induction of protective immunity against infectious diseases and cancer in the sizable populations with preexisting immunity to vaccinia from smallpox vaccination. C1 NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, NIH, Bethesda, MD 20892 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Mucosal Immun Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Berzofsky, JA (reprint author), NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, NIH, Bldg 10,Room 6B-12, Bethesda, MD 20892 USA. NR 28 TC 138 Z9 141 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 13 PY 1999 VL 96 IS 8 BP 4512 EP 4517 DI 10.1073/pnas.96.8.4512 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 187BP UT WOS:000079766500056 PM 10200293 ER PT J AU Martin, DA Zheng, LX Siegel, RM Huang, BH Fisher, GH Wang, J Jackson, CE Puck, JM Dale, J Straus, SE Peter, ME Krammer, PH Fesik, S Lenardo, MJ AF Martin, DA Zheng, LX Siegel, RM Huang, BH Fisher, GH Wang, J Jackson, CE Puck, JM Dale, J Straus, SE Peter, ME Krammer, PH Fesik, S Lenardo, MJ TI Defective CD95/APO-1/Fas signal complex formation in the human autoimmune lymphoproliferative syndrome, type Ia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FAS-INDUCED APOPTOSIS; DEATH DOMAIN; LYMPHOCYTE APOPTOSIS; GENE-MUTATIONS; T-LYMPHOCYTES; PROTEIN; RECEPTOR; DISEASE; LIGAND; MICE AB Heterozygous mutations in the CD95 (APO-1/Fas) receptor occur in most individuals with autoimmune lymphoproliferative syndrome (ALPS) and dominantly interfere with apoptosis by an unknown mechanism. We show that local or global alterations in the structure of the cytoplasmic death domain from nine independent ALPS CD95 death-domain mutations result in a: failure to bind the FADD/MORT1 signaling protein. Despite heterozygosity for the abnormal allele, lymphocytes from ALPS patients showed markedly decreased FADD association and a loss of caspase recruitment and activation after CD95 crosslinking. These data suggest that intracytoplasmic CD95 mutations in ALPS impair apoptosis chiefly by disrupting death-domain interactions with the signaling protein FADD/MORT1. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Howard Hughes Med Inst, Natl Inst Hlth, Res Scholars Program, D-69120 Heidelberg, Germany. German Canc Res Ctr, D-69120 Heidelberg, Germany. Abbott Labs, Abbott Pk, IL 60064 USA. RP Lenardo, MJ (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. RI Siegel, Richard/C-7592-2009 OI Siegel, Richard/0000-0001-5953-9893 NR 39 TC 135 Z9 139 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 13 PY 1999 VL 96 IS 8 BP 4552 EP 4557 DI 10.1073/pnas.96.8.4552 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 187BP UT WOS:000079766500063 PM 10200300 ER PT J AU Hayward, RE Tiwari, B Piper, KP Baruch, DI Day, KP AF Hayward, RE Tiwari, B Piper, KP Baruch, DI Day, KP TI Virulence and transmission success of the malarial parasite Plasmodium falciparum SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; INFECTED ERYTHROCYTES; ANTIGENIC VARIATION; CEREBRAL MALARIA; EXPRESSION; RECEPTOR; SURFACE; CD36; CYTOADHERENCE; GENE AB Virulence of Plasmodium falciparum is associated with the expression of variant surface antigens designated PfEMP1 (P. falciparum erythrocyte membrane protein 1) that are encoded by a family of var genes. Data presented show that the transmission stages of P. falciparum also express PfEMP1 variants. Virulence in this host-parasite system can be considered a variable outcome of optimizing the production of sexual transmission stages from the population of disease-inducing asexual stages. Immunity to PfEMP1 will contribute to the regulation of this trade-off by controlling the parasite population with potential to produce mature transmission stages. C1 Univ Oxford, Dept Zool, Wellcome Trust Ctr Epidemiol Infect Dis, Oxford OX1 3PS, England. NIAID, LPD, NIH, Bethesda, MD 20892 USA. RP Day, KP (reprint author), Univ Oxford, Dept Zool, Wellcome Trust Ctr Epidemiol Infect Dis, S Parks Rd, Oxford OX1 3PS, England. RI Day, Karen/F-3697-2015 OI Day, Karen/0000-0002-6115-6135 FU Wellcome Trust NR 50 TC 60 Z9 60 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 13 PY 1999 VL 96 IS 8 BP 4563 EP 4568 DI 10.1073/pnas.96.8.4563 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 187BP UT WOS:000079766500065 PM 10200302 ER PT J AU Tataranni, PA Gautier, JF Chen, KW Uecker, A Bandy, D Salbe, AD Pratley, RE Lawson, M Reiman, EM Ravussin, E AF Tataranni, PA Gautier, JF Chen, KW Uecker, A Bandy, D Salbe, AD Pratley, RE Lawson, M Reiman, EM Ravussin, E TI Neuroanatomical correlates of hunger and satiation in humans using positron emission tomography SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; INSULIN-RESISTANCE; WORKING-MEMORY; WEIGHT-GAIN; BRAIN; OBESITY; TRANSPORT; LOBE; GENE AB The central role of the hypothalamus in the origination and/or processing of feeding-related stimuli may be modulated by the activity of other functional areas of the brain including the insular cortex (involved in enteroceptive monitoring) and the prefrontal cortex (involved in the inhibition of inappropriate response tendencies). Regional cerebral blood flow (rCBP), a marker of neuronal activity, was measured in 11 healthy, normal-weight men by using positron emission tomography in a state of hunger (after 36-h fast) and a state of satiation (after a liquid meal). Hunger was associated with significantly increased rCBF in the vicinity of the hypothalamus and insular cortex and in additional paralimbic and limbic areas (orbitofrontal cortex, anterior cingulate cortex, and parahippocampal and hippocampal formation), thalamus, caudate, precuneus, putamen, and cerebellum. Satiation was associated with increased rCBP in the vicinity of the ventromedial prefrontal cortex, dorsolateral prefrontal cortex, and inferior parietal lobule. Changes in plasma insulin concentrations in response to the meal were negatively correlated with changes in rCBF in the insular and orbitofrontal cortex. Changes in plasma free fatty acid concentrations in response to the meal were negatively correlated with changes in rCBF in the anterior cingulate and positively correlated with changes in rCBF in the dorsolateral prefrontal cortex. In conclusion, these findings raise the possibility that several regions of the brain participate in the regulation of hunger and satiation and that insulin and free fatty acids may be metabolic modulators of postprandial brain neuronal events. Although exploratory, the present study provides a foundation for investigating the human brain regions and cognitive operations that respond to nutritional stimuli. C1 NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. Good Samaritan Reg Med Ctr, Positron Emiss Tomog Ctr, Phoenix, AZ 85006 USA. Univ Arizona, Dept Psychiat, Tucson, AZ 85724 USA. RP Tataranni, PA (reprint author), NIDDKD, Clin Diabet & Nutr Sect, NIH, 4212 N 16Th St, Phoenix, AZ 85016 USA. RI Frank, David/E-8213-2012; Chen, kewei/P-6304-2015 OI Chen, kewei/0000-0001-8497-3069 NR 40 TC 367 Z9 374 U1 1 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 13 PY 1999 VL 96 IS 8 BP 4569 EP 4574 DI 10.1073/pnas.96.8.4569 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 187BP UT WOS:000079766500066 PM 10200303 ER PT J AU Ma, W Grant, GM Pancrazio, JJ Kao, WY Shaffer, KM Liu, QY Barker, JL Cohen, NA Stenger, DA AF Ma, W Grant, GM Pancrazio, JJ Kao, WY Shaffer, KM Liu, QY Barker, JL Cohen, NA Stenger, DA TI K-ir 4.1 channel expression in neuroblastoma X glioma hybrid NG108-15 cell line SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE K+ channels; inward rectifier; development; RT-PCR; immunocytochemistry; patch-clamp recording ID RECTIFYING POTASSIUM CHANNELS; CENTRAL-NERVOUS-SYSTEM; INWARD RECTIFIER; RECEPTOR SUBTYPES; MESSENGER-RNA; HERG-LIKE; MEMBRANE; TUMORS; K-AB-2/KIR4.1; CURRENTS AB study a possible involvement of inwardly rectifying K+ 4.1 (K-ir 4.1) channels in neural cell development, RT-PCR, immunocytochemistry and whole-cell patch-clamp techniques were used to assess expression of K-ir 4.1 channels in proliferating and differentiated NG108-15 cells. RT-PCR revealed co-expression of K-ir 4.1 and rat ether-a-go-go-related gene (R-ERG) mRNAs in both proliferating and differentiated cells. The relative K-ir 4.1 mRNA concentration increased markedly as cells progressed from undifferentiated to differentiated cells, K-ir 4.1-immunoreactivity was barely detectable in undifferentiated cells, but clearly detected in differentiated cells, indicating that K-ir 4.1 gene and protein expressions are developmentally regulated. However, corresponding K-ir 4.1 current could not be detected in differentiated cells using whole-cell patch-clamp recording. The 'silent' channel/receptor, often found in tumor cells, may carry genetic defects, which prevent functional expression of the channel. NG108-15 may serve as unique model for studying the relationship between the expression of an ion channel gene and the electrophysiological phenotype it encodes. (C) 1999 Published by Elsevier Science B.V. All rights reserved. C1 USN, Res Lab, Ctr Biomol Sci & Engn, Washington, DC 20375 USA. NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Stenger, DA (reprint author), USN, Res Lab, Ctr Biomol Sci & Engn, Code 6900,4555 Overlook Ave SW, Washington, DC 20375 USA. RI Pancrazio, Joseph/M-3206-2015; OI Pancrazio, Joseph/0000-0001-8276-3690; Cohen, Noam/0000-0002-9462-3932 NR 29 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD APR 12 PY 1999 VL 114 IS 1 BP 127 EP 134 DI 10.1016/S0165-3806(99)00015-2 PG 8 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 188BV UT WOS:000079825100014 ER PT J AU Scott, LJC Griffin, JW Luciano, C Barton, NW Banerjee, T Crawford, T McArthur, JC Tournay, A Schiffmann, R AF Scott, LJC Griffin, JW Luciano, C Barton, NW Banerjee, T Crawford, T McArthur, JC Tournay, A Schiffmann, R TI Quantitative analysis of epidermal innervation in Fabry disease SO NEUROLOGY LA English DT Article ID CUTANEOUS INNERVATION; NEUROPATHY; SKIN; INVOLVEMENT AB Article abstract-Objective: To use skin biopsy specimens to quantitate the cutaneous innervation density of Fabry patients who had preserved renal function. Background: The small fiber neuropathy of Fabry disease is difficult to detect and quantitate by conventional methods. Because this neuropathy is a common characteristic of Fabry disease, quantitating changes in this parameter would be helpful in demonstrating the effectiveness of enzyme or gene replacement therapy. Methods: Patients underwent skin biopsy at the thigh and foot. Innervation density was determined by counting free nerve endings in the epidermis. These data were compared with nerve conduction studies, and in selected patients, fiber quantitation of sural nerve biopsy specimens. Results: The Fabry patients had normal results of nerve conduction studies and large fiber quantitation by sural nerve biopsy. However, the involvement of small cutaneous fibers in these patients was easily demonstrable and quantifiable by skin biopsy. All patients showed severe loss of intraepidermal innervation at the ankle, but fiber loss at the distal thigh was proportionately less severe. Conclusions: The nerve damage in Fabry patients with preserved renal function involves exclusively small myelinated and unmyelinated fibers, and skin biopsy is a useful in detecting and quantitating such damage. Comparison of cutaneous innervation density with quantitation of sural nerve biopsy specimens demonstrated that skin biopsy specimens were as sensitive in detecting the presence of neuropathy as were the nerve specimens. It is speculated that analysis of cutaneous innervation may provide a useful marker of the nervous system's response to specific therapy for Fabry disease. C1 Univ Vermont, Coll Med, Dept Neurol, Burlington, VT 05405 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. NINDS, Natl Inst Hlth, Dev & Metab Neurol Branch, Bethesda, MD USA. NINDS, NIH, NDS, Med Neurol Branch, Bethesda, MD 20892 USA. RP Scott, LJC (reprint author), Univ Vermont, Coll Med, Dept Neurol, Given Med Bldg Room B-218, Burlington, VT 05405 USA. FU PHS HHS [P01 26643] NR 27 TC 89 Z9 92 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 12 PY 1999 VL 52 IS 6 BP 1249 EP 1254 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 186KR UT WOS:000079728900025 PM 10214752 ER PT J AU Kim, JM Hong, YY Kim, SJ Cho, MH Yoshida, M Jeang, KT Burns, W Kim, SY AF Kim, JM Hong, YY Kim, SJ Cho, MH Yoshida, M Jeang, KT Burns, W Kim, SY TI Sequences downstream of the RNA initiation site of the HTLV type I long terminal repeat are sufficient for trans-activation by human cytomegalovirus immediate-early proteins SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID VIRUS TYPE-I; T-CELL LEUKEMIA; BASAL GENE-EXPRESSION; RETROVIRAL VECTORS; PROMOTER ELEMENTS; TRANSACTIVATION; ANTIBODIES; INTERACTS; LYMPHOMA; DISEASE AB Human T cell leukemia virus type I infection is associated with a low incidence of morbidity in the form of adult T cell leukemia and neurologic disease, suggesting that there are other factors determining the pathogenic outcome of infection, We found that HCMV could infect various human cell lines known to be susceptible to HTLV-I infection, including T cell lines already harboring HTLV-I, and that HCMV infection could highly activate gene expression from the HTLV-I LTR, In addition, the coexpression of IE1 and IE2 genes of HCMV increased transcription from the HTLV-I LTR, The deletion analysis indicated that the entire U3 region is not required, but that the 216-bp region from +101 to +316 is sufficient for activation of the LTR by IE1 and IE2, These results suggest that HCMV IE proteins may affect the level of HTLV-I gene expression in coinfected individuals by interacting with HTLV-I LTR sequences. C1 Seoul Natl Univ, Inst Mol Biol & Genet, Kwan Ak Gu, Seoul 151742, South Korea. Konkuk Univ, Coll Sci, Dept Biol, Seoul 143701, South Korea. Univ Tokyo, Inst Med Sci, Tokyo 108, Japan. NIAID, Bethesda, MD 20892 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. RP Kim, SY (reprint author), Seoul Natl Univ, Inst Mol Biol & Genet, Kwan Ak Gu, BLDG 105, Seoul 151742, South Korea. EM sunyoung@plaza.snu.ac.kr RI Jeang, Kuan-Teh/A-2424-2008 NR 26 TC 5 Z9 5 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR 10 PY 1999 VL 15 IS 6 BP 545 EP 550 DI 10.1089/088922299311060 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 185JL UT WOS:000079665700006 PM 10221531 ER PT J AU Quinnan, GV Zhang, PF Fu, DW Dong, M Alter, HJ AF Quinnan, GV Zhang, PF Fu, DW Dong, M Alter, HJ CA Int Collaborators TI Expression and characterization of HIV type 1 envelope protein associated with a broadly reactive neutralizing antibody response SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODY; SURFACE GLYCOPROTEIN; GP120 GLYCOPROTEIN; MOLECULAR CLONE; FAMILY PROTEINS; GP41; V3; RESISTANCE; INFECTION AB We have studied envelope protein from a donor with nonprogressive HIV-1 infection whose serum contains broadly cross-reactive, primary virus NA. DNA was extracted from lymphocytes, which had been collected approximately 6 and 12 months prior to the time of collection of the cross-reactive serum, and env genes were synthesized, cloned, expressed on pseudoviruses, and phenotyped in NA assays. Two clones from each time point had identical V3 region nucleotide sequences, utilized CCR5 but not CXCR4 for cell entry, and had similar reactivities with reference sera. Analysis of the full nucleotide sequence of one clone (R2) demonstrated it to be subtype B and have normal predicted glycosylation, R2 pseudovirus was compared with others expressing env genes of various clades for neutralization by sera from U.S. donors (presumed or known subtype B infections), and from individuals infected with subtypes A, C, D, E, and F viruses. Neutralization by the U.S. sera of R2 and other clade B pseudoviruses was low to moderate, although R2 was uniquely neutralized by all. R2 was neutralized by 3/3, 3/3, 2/5, 5/8, and 3/4 clade A, C, D, E, and F sera, respectively. R2 and a clade E pseudovirus were neutralized by largely complementary groups of sera, potentially defining two antigenic subgroups of HIV-1, The results suggest that the epitope(s) that induced the cross-clade reactive NA in donor 2 may be expressed on the R2 envelope. C1 Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Div Trop Publ Hlth, Bethesda, MD 20814 USA. NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Quinnan, GV (reprint author), Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Div Trop Publ Hlth, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. FU NIAID NIH HHS [AI37438] NR 49 TC 40 Z9 41 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR 10 PY 1999 VL 15 IS 6 BP 561 EP 570 DI 10.1089/088922299311088 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 185JL UT WOS:000079665700008 PM 10221533 ER PT J AU Rosfjord, EC Maemura, M Johnson, MD Torri, JA Akiyama, SK Woods, VL Dickson, RB AF Rosfjord, EC Maemura, M Johnson, MD Torri, JA Akiyama, SK Woods, VL Dickson, RB TI Activation of protein kinase C by phorbol esters modulates alpha(2)beta(1) integrin on MCF-7 breast cancer cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE integrin; breast carcinoma; Rho; PKC; collagen; adhesion ID BOTULINUM ADP-RIBOSYLTRANSFERASE; TUMOR-NECROSIS-FACTOR; METASTATIC VARIANTS; ADHESION MOLECULES; PLASMA-MEMBRANE; GENE-EXPRESSION; MELANOMA-CELLS; MESSENGER-RNA; RECEPTORS; COLLAGEN AB Cellular adhesions to other cells and to the extracellular matrix play crucial roles in the malignant progression of cancer. In this study, we investigated the role of protein kinase C (PKC) in the regulation of cell-substratum adhesion by the breast adenocarcinoma cell line MCF-7, A PKC activator, 12-O-tetradecanoylphorbol-1,3-acetate (TPA), stimulated cell adhesion to laminin and collagen I in a dose-dependent manner over a 1- to 4-h interval. This enhanced adhesion was mediated by alpha(2)beta(1) integrin, since both anti-alpha(2) and anti-beta(1) blocking antibodies each completely abrogated the TPA-induced adhesion. FACS analysis determined that TPA treatment does not change the cell surface expression of alpha(2)beta(1) integrin over a 4-h time interval. However, alpha(2)beta(1) levels were increased after 24 h of TPA treatment, Thus, the enhanced avidity of alpha(2)beta(1)-dependent cellular adhesion preceded the induction of alpha(2)beta(1) cell surface expression. Northern blot analysis revealed that mRNA levels of both alpha(2) and beta(1) subunits were increased after exposure to TPA for 4 h, indicating that the induction of alpha(2)beta(1) mRNA preceded that of its cell surface expression, This further suggested that the TPA-induced avidity of alpha(2)beta(1) was independent of increased expression of alpha(2)beta(1). Pretreatment of cells with the PKC inhibitor calphostin C partially antagonized the TPA-induced increase in expression of alpha(2)beta(1) integrin expression and of alpha(2)beta(1)-mediated cellular adhesion. To identify a possible mechanism by which TPA could be acting to promote the rapid induction of alpha(2)beta(1) adhesion, we treated the cells with the Rho-GTPase inhibitor Clostridium botulinumexotoxin C3. C3 inhibited TPA-induced adhesion to laminin and collagen I in a dose-dependant manner, suggesting a likely role for Rho in TPA-induced adhesion. Together, these results suggest that PKC can modulate the alpha(2)beta(1)-dependent adhesion of MCF-7 cells by two distinct mechanisms: altering the gene expression of integrins alpha(2) and beta(1) and altering the avidity of the alpha(2)beta(1) integrin by a Rho-dependant mechanism. (C) 1999 Academic Press. C1 Georgetown Univ, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. Gunma Univ, Dept Surg 2, Maebashi, Gumma 371, Japan. NIEHS, Res Triangle Pk, NC 27709 USA. Univ Calif San Diego, Sch Med, Div Rheumat Dis, San Diego, CA 92103 USA. RP Dickson, RB (reprint author), Georgetown Univ, Vincent T Lombardi Canc Res Ctr, 3970 Reservoir Rd NW, Washington, DC 20007 USA. FU NCI NIH HHS [IP50CA58185, 2P50-CA58185-04, 2P30-CA-51008] NR 76 TC 21 Z9 22 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD APR 10 PY 1999 VL 248 IS 1 BP 260 EP 271 DI 10.1006/excr.1998.4390 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 189YW UT WOS:000079935100026 PM 10094832 ER PT J AU Mansoura, MK Biwersi, J Ashlock, MA Verkman, AS AF Mansoura, MK Biwersi, J Ashlock, MA Verkman, AS TI Fluorescent chloride indicators to assess the efficacy of CFTR cDNA delivery SO HUMAN GENE THERAPY LA English DT Review ID TRANSMEMBRANE CONDUCTANCE REGULATOR; AIRWAY EPITHELIAL-CELLS; FIBROSIS GENE-THERAPY; CYSTIC-FIBROSIS; BIOLOGICAL APPLICATIONS; AROMATIC-MOLECULES; NASAL EPITHELIUM; PROXIMAL TUBULE; R-DOMAIN; TRANSPORT AB Cl--sensitive fluorescent indicators have been used extensively in cell culture systems to measure the Cl--transporting function of the cystic fibrosis transmembrane conductance regulator protein CFTR. These indicators have been used in establishing a surrogate end point to assess the efficacy of CFTR cDNA delivery in human gene therapy trials. The ability to measure Cl- transport with high sensitivity in small and heterogeneous tissue samples makes the use of Cl- indicators potentially attractive in gene delivery studies. In this review article, the important technical aspects of Cl- transport measurements by fluorescent indicators such as SPQ are described, applications of Cl- indicators to assay CFTR function are critically evaluated, and new methodological developments are discussed. The available Cl- indicators have been effective in quantifying Cl- transport rates in cell culture models and in vitro systems such as isolated membrane vesicles and liposomes. However, the imperfect photophysical properties of existing Cl- indicators limit their utility in performing measurements in airway tissues, where gene transfer vectors are delivered in CF gene therapy trials. The low efficiency of gene transfer and the cellular heterogeneity in airway samples pose substantial obstacles to functional measurements of CFTR expression. Significant new developments in generating long-wavelength and dual-wavelength halide indicators are described, and recommendations are proposed for the use of the indicators in gene therapy trials. C1 Univ Calif San Francisco, Inst Cardiovasc Res, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Inst Cardiovasc Res, Dept Physiol, San Francisco, CA 94143 USA. NIH, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. RP Verkman, AS (reprint author), Univ Calif San Francisco, Inst Cardiovasc Res, Dept Med, 1246 Hlth Sci E Tower, San Francisco, CA 94143 USA. FU NHLBI NIH HHS [HL60288]; NIDDK NIH HHS [DK35124, DK43840] NR 57 TC 33 Z9 33 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD APR 10 PY 1999 VL 10 IS 6 BP 861 EP 875 DI 10.1089/10430349950018274 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 188KG UT WOS:000079844900002 PM 10223721 ER PT J AU Park, BJ Brown, CK Hu, Y Alexander, HR Horti, J Raje, S Figg, WD Bartlett, DL AF Park, BJ Brown, CK Hu, Y Alexander, HR Horti, J Raje, S Figg, WD Bartlett, DL TI Augmentation of melanoma-specific gene expression using a tandem melanocyte-specific enhancer results in increased cytotoxicity of the purine nucleoside phosphorylase gene in melanoma SO HUMAN GENE THERAPY LA English DT Article ID THYMIDINE KINASE GENE; LUNG-CANCER CELLS; PROSTATE-SPECIFIC ANTIGEN; HUMAN TYROSINASE GENE; TISSUE-SPECIFIC EXPRESSION; IN-VIVO; CARCINOEMBRYONIC ANTIGEN; HEPATOCELLULAR-CARCINOMA; CYTOSINE DEAMINASE; RETROVIRAL VECTORS AB The lineage-specific human tyrosinase promoter has been used to successfully target gene expression at the transcriptional level to melanoma cells. The tyrosinase promoter, alone and in combination with a single, or a dual, tandem melanocyte-specific enhancer, was used to regulate expression of the firefly luciferase reporter gene. Transient transfections of these tissue-specific luciferase constructs in human and murine melanoma (Pmel, B16mel) and colon carcinoma (WiDr, MC38) cell lines resulted in melanoma-specific luciferase expression that was amplified 5- and 500-fold with the addition of a single or double enhancer, respectively, to the tyrosinase promoter. When the double enhancer-promoter construct expressed the highly toxic Escherichia coli purine nucleoside phosphorylase (PNP) gene, transfection of the same cell lines followed by administration of the prodrug 6-methyl purine deoxyriboside (6-MPDR) at a concentration of 50 mu M caused melanoma-specific in vitro cell killing. Within 5 days after prodrug administration methylthiazol-tetrazolium (MTT) cytotoxicity assays showed that only 15 and 9% of Pmel and B16mel cells, respectively, remained viable compared with controls. This effect was highly specific, as 90 and 96% of WiDr and MC38 colon carcinoma cells remained viable 5 days after identical treatment. This effect was a direct result of increased tissue-specific conversion of 6-MPDR to the toxic metabolite 6-methylpurine (6-MP), as documented by HPLC analysis of culture supernatants. These results show that the dual tandem melanocyte-specific enhancer provides powerful amplification of the transcriptional targeting of gene expression afforded by use of the tyrosinase promoter. This amplification translates into increased, highly specific cytotoxicity to melanoma by the PNP/6-MPDR enzyme/prodrug system and, therefore, has potential efficacy in the use of gene therapy for the treatment of metastatic melanoma. C1 NCI, Surg Branch, Metab Sect, NIH, Bethesda, MD 20892 USA. NCI, Div Clin Sci, Med Branch, NIH, Bethesda, MD 20892 USA. RP Bartlett, DL (reprint author), NCI, Surg Branch, Metab Sect, NIH, 10 Ctr Dr,Room 2B16, Bethesda, MD 20892 USA. EM David_Bartlett@nih.gov RI Figg Sr, William/M-2411-2016 NR 41 TC 34 Z9 37 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD APR 10 PY 1999 VL 10 IS 6 BP 889 EP 898 DI 10.1089/10430349950018292 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 188KG UT WOS:000079844900004 PM 10223723 ER PT J AU Hafkemeyer, P Brinkmann, U Gottesman, MM Pastan, I AF Hafkemeyer, P Brinkmann, U Gottesman, MM Pastan, I TI Apoptosis induced by Pseudomonas exotoxin: A sensitive and rapid marker for gene delivery in vivo SO HUMAN GENE THERAPY LA English DT Article ID GREEN FLUORESCENT PROTEIN; IN-VIVO; CELL-DEATH; CHLORAMPHENICOL ACETYLTRANSFERASE; BETA-GALACTOSIDASE; DNA FRAGMENTATION; MAMMALIAN-CELLS; TRANSGENIC MICE; REPORTER GENES; CANCER-CELLS AB The rapid progress in gene therapy has expanded our ability to alter genetic structure, necessitating the development of methods for detecting the activity of new vectors, The central concept of a reporter gene is simple: it is a defined nucleotide sequence, which when introduced into a biological system, yields a readily measurable phenotype on expression, This provides a convenient parameter that is correlated to the molecular events associated with genetic expression. In this study we demonstrate that Pseudomonas exotoxin A (PE) can serve as a sensitive reporter gene to detect gene expression in single cells of mouse lung on cationic liposome delivery of RE-encoding DNA in vivo. Furthermore, we show that PE expression can be detected as early as 2 hr after systemic gene delivery in lungs of recipient mice. We compared PE with the widely used P-galactosidase gene for this purpose. PE induces apoptosis that can be detected by TdT end labeling of DNA fragments (TUNEL assay) Since few expressed PE molecules are necessary to trigger the apoptosis cascade, the minimal amount of RE-encoding plasmid DNA needed for detection of apoptotic cells after systemic delivery was 0.1 mu g per animal compared with at least 1 mu g for the beta-galactosidase-encoding plasmid DNA, The maximum number of apoptotic cells detected in lungs was about 15-20 times higher than the maximum number of P-galactosidase-positive cells. Specificity of apoptosis due to PE expression on delivery of the PE-encoding plasmid was shown by prevention of the apoptotic cascade by the caspase inhibitor Z-VAD-fmk. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, NIH, Bldg 37,Room 4E16,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 46 TC 21 Z9 21 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD APR 10 PY 1999 VL 10 IS 6 BP 923 EP 934 DI 10.1089/10430349950018328 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 188KG UT WOS:000079844900007 PM 10223726 ER PT J AU McCann, UD Szabo, Z Scheffel, U Dannais, RF Ricaurte, GA AF McCann, UD Szabo, Z Scheffel, U Dannais, RF Ricaurte, GA TI Toxic effect of MDMA on brain serotonin neurons - Reply SO LANCET LA English DT Letter C1 Johns Hopkins Med Inst, Dept Neurol, Baltimore, MD 21224 USA. Johns Hopkins Med Inst, Dept Nucl Med, Baltimore, MD 21224 USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. RP Ricaurte, GA (reprint author), Johns Hopkins Med Inst, Dept Neurol, Baltimore, MD 21224 USA. NR 3 TC 0 Z9 0 U1 2 U2 2 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD APR 10 PY 1999 VL 353 IS 9160 BP 1270 EP 1271 DI 10.1016/S0140-6736(05)66944-9 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 186TB UT WOS:000079744100048 ER PT J AU Holbrook, PG Geetha, V Beaven, MA Munson, PJ AF Holbrook, PG Geetha, V Beaven, MA Munson, PJ TI Recognizing the pleckstrin homology domain fold in mammalian phospholipase D using hidden Markov models SO FEBS LETTERS LA English DT Article DE phospholipase D; pleckstrin homology domain; hidden Markov models; phosphatidylinositol-3,4,5-trisphosphate binding protein; beta-adrenergic receptor kinase; lipid signalling ID ADP-RIBOSYLATION-FACTOR; SECONDARY STRUCTURE; PROTEIN STRUCTURES; COMMON FOLD; DATABASE; SEQUENCES; BINDING; RECOGNITION; ACTIVATION; SUBUNITS AB Phospholipase D was first described in plant tissue but has recently been shown to occur in mammalian cells where it is activated by cell surface receptors. Its mode of activation by receptors in unclear. Biochemical studies suggest that it may occur downstream of other effector proteins and that small GTP-dependent regulatory proteins may be involved. The sequence in a non-designated region of mammalian phospholipase D1 and 2 shows similarity to a structural domain that is present in signalling proteins that are regulated by protein kinases or heterotrimeric G-proteins. Mammalian phospholipase D has structural similarities with other lipid signalling phospholipases and thus may be regulated by receptors in an analogous fashion. (C) 1999 Federation of European Biochemical Societies. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NIH, Analyt Biostat Sect, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Holbrook, PG (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10,Room 8N-109, Bethesda, MD 20892 USA. NR 33 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD APR 9 PY 1999 VL 448 IS 2-3 BP 269 EP 272 DI 10.1016/S0014-5793(99)00366-X PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 187JE UT WOS:000079782900015 PM 10218490 ER PT J AU Delphin, C Ronjat, M Deloulme, JC Garin, G Debussche, L Higashimoto, Y Sakaguchi, K Baudier, J AF Delphin, C Ronjat, M Deloulme, JC Garin, G Debussche, L Higashimoto, Y Sakaguchi, K Baudier, J TI Calcium-dependent interaction of S100B with the C-terminal domain of the tumor suppressor p53 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; WILD-TYPE P53; DNA-BINDING; S-100 PROTEINS; IMMUNOHISTOCHEMICAL LOCALIZATION; OLIGOMERIZATION DOMAIN; CA2+-DEPENDENT MANNER; TRANSCRIPTION FACTORS; IONS BINDING; CELL-CYCLE AB Irt vitro, the S100B protein interacts with baculovirus recombinant p53 protein and protects p53 from thermal denaturation, This effect is isoform-specific and is not observed with S100A1, S100A6, or calmodulin, Using truncated p53 proteins in the N-terminal (p53(1-320)) and C-terminal (p53(73-393)) domains, we localized the S100B-binding region to the C-terminal region of p53, We have confirmed a calcium-dependent interaction of the S100B with a synthetic peptide corresponding to the C-terminal region of p53 (residues 319-393 in human p53) using plasmon resonance experiments on a BIAcore system. In the presence of calcium, the equilibrium affinity of the S100B for the C-terminal region of p53 immobilized on the sensor chip was 24 +/- 10 nM. To narrow down the region within p53 involved in S100B binding, two synthetic peptides, O1(357-381) (residues 357-381 in mouse p53) and YF-O2(320-346) (residues 320-346 in mouse p53), covering the C-terminal region of p53 were compared for their interaction with purified S100B, Only YF-O2 peptide interacts with S100B with high affinity. The YF-O2 motif is a critical determinant for the thermostability of p53 and also corresponds to a domain responsible for cytoplasmic sequestration of p53, Our results may explain the rescue of nuclear wild type p53 activities by S100B in fibroblast cell lines expressing the temperature-sensitive p53val135 mutant at the nonpermissive temperature. C1 CEA Grenoble, INSERM, U244,DBMS,BRCE, Ctr Etud Nucl Grenoble, F-38054 Grenoble 9, France. Ctr Etud Nucl Grenoble, Lab Chim Prot, F-38054 Grenoble, France. Ctr Etud Nucl Grenoble, Lab Canaux Ion & Signalizat, F-38054 Grenoble, France. Rhone Poulenc Rorer SA, Ctr Rech Vitry Alfortville, Inst Biotechnol, F-94403 Vitry, France. NIH, Cell Biol Lab, Bethesda, MD 20892 USA. RP Baudier, J (reprint author), CEA Grenoble, INSERM, U244,DBMS,BRCE, Ctr Etud Nucl Grenoble, 17 Rue Martyrs, F-38054 Grenoble 9, France. EM jbaudier@cea.fr RI Baudier, Jacques/O-2183-2016 NR 47 TC 56 Z9 59 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 9 PY 1999 VL 274 IS 15 BP 10539 EP 10544 DI 10.1074/jbc.274.15.10539 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 185HT UT WOS:000079663500086 PM 10187847 ER PT J AU Bagrov, YY Dmitrieva, NI Manusova, NB Zvartau, EE Patkina, NA Bagrov, AY AF Bagrov, YY Dmitrieva, NI Manusova, NB Zvartau, EE Patkina, NA Bagrov, AY TI Involvement of endogenous digitalis-like factors in voluntary selection of alcohol by rats SO LIFE SCIENCES LA English DT Article DE Na/K ATPase; alcohol consumption inhibitor; ouabain; bufodienolide; ethanol; voluntary alcohol consumption ID OUABAIN-LIKE COMPOUND; ETHANOL; PLASMA; BRAIN; INHIBITOR; ILLNESS; SODIUM; NA+ AB This study tested the hypothesis that endogenous digitalis-like factor (DLF) is involved in the development of alcohol dependence in rats. In 33 male Wistar rats in conditioned place preference (CPP) experiment, ethanol evoked increase in time spent in the ethanol-associated compartment (702+/-82, in ethanol-treated vsi 426+/-86 sec in the controls). Digoxin pretreatment (125 mu g/kg, i/p) did not affect the time spent in the water-associated compartment (476+/-80 sec) but prevented the acquisition of ethanol CPP (385+/-112 sec in ethanol-paired side, P<0.05). In a two bottle choice test, where rats (n=6 per group) chose between drinking water and 9% ethanol, immunization against two putative DLFs, marinobufagenin and ouabain (MBG and OLC) resulted in a 60% increase of ethanol consumption. Acute intragastric administration of 9% ethanol to the rats was associated with increased OLC in cerebrospinal fluid, and stimulated urinary excretion of MBG and OLC. Thus, in rats, digoxin, which mimics the effects of ULFs, suppresses the free choice of alcohol, while immunization against DLFs is associated with alcohol seeking behavior, Published by Elsevier Science Inc. C1 NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. IM Sechenov Evolut Physiol & Biochem Inst, Lab Membrane Barrier Funct, St Petersburg 194223, Russia. Ivan Pavlov Med Univ, Waldman Inst Pharmacol, St Petersburg, Russia. RP Bagrov, AY (reprint author), NIA, Cardiovasc Sci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Dmitrieva, Natalia/A-2924-2013 OI Dmitrieva, Natalia/0000-0001-8074-6950 NR 31 TC 6 Z9 6 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD APR 9 PY 1999 VL 64 IS 20 BP PL219 EP PL225 DI 10.1016/S0024-3205(99)00131-9 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 188LW UT WOS:000079849300010 PM 10350362 ER PT J AU Zhang, L Chang, YH Feldman, AN Ma, W Lahjouji, F Barker, JL Hu, Q Maric, D Li, BS Li, W Rubinow, DR AF Zhang, L Chang, YH Feldman, AN Ma, W Lahjouji, F Barker, JL Hu, Q Maric, D Li, BS Li, W Rubinow, DR TI The expression of GABA(A) receptor alpha 2 subunit is upregulated by testosterone in rat cerebral cortex SO NEUROSCIENCE LETTERS LA English DT Article DE testosterone; GABA; in situ hybridization; mRNA; cortex ID GAMMA-AMINOBUTYRIC-ACID; SEX-DIFFERENCES; BRAIN-AREAS; A RECEPTOR; RESPONSES; BEHAVIOR; MICE AB The GABAergic system is sexually dimorphic in certain brain regions and can be regulated by testosterone (T). However, the contribution of T to sex-specific developmental processes in the brain is less clear. We have examined whether T regulates expression of GABA(A) receptor alpha 2 subunit in the cerebral cortex of embryonic and postnatal female rats using in situ hybridization and Western blotting. We found that both alpha 2 mRNA and protein levels are significantly increased by T treatment at embryonic day 20 (E20) and birth (P0). The observed modulation of the expression of GABA(A) receptor alpha 2 subunit by T may be translated into changes in the levels or composition of GABA(A) receptor, either of which would be expected to alter neuronal functional response to GABA activation. As the effects of T are developmental-stage-specific, they may have an organizational impact on brain development. (C) 1999 Elsevier Science ireland Ltd. All rights reserved. C1 NIMH, Behav Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. NINDS, Dev Neurogenet, NIH, Bethesda, MD 20892 USA. NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Zhang, L (reprint author), NIMH, Behav Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NR 24 TC 17 Z9 17 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD APR 9 PY 1999 VL 265 IS 1 BP 25 EP 28 DI 10.1016/S0304-3940(99)00193-7 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 191JR UT WOS:000080019700007 PM 10327197 ER PT J AU Forns, X Emerson, SU Tobin, GJ Mushahwar, IK Purcell, RH Bukh, J AF Forns, X Emerson, SU Tobin, GJ Mushahwar, IK Purcell, RH Bukh, J TI DNA immunization of mice and macaques with plasmids encoding hepatitis C virus envelope E2 protein expressed intracellularly and on the cell surface SO VACCINE LA English DT Article DE hepatitis C virus; DNA vaccine; surface-expressed E2; non-human primates ID IMMUNE-RESPONSES; HYPERVARIABLE REGION-1; MEDIATED IMMUNIZATION; PROTECTIVE IMMUNITY; HYPERIMMUNE SERUM; ANTIBODY-RESPONSE; ESCHERICHIA-COLI; VIRAL-INFECTION; GLYCOPROTEIN; CHIMPANZEES AB We analyzed the humoral immune response elicited by hepatitis C virus (HCV) E2 protein expressed in vivo after injection of plasmid DNA into mice and rhesus macaques, Three plasmids were used for immunization: a plasmid containing the entire sequence of the E2 and p7 genes (pE2); a plasmid encoding a truncated form of the E2 protein targeted to the cell surface (pE2surf); a control plasmid (pDisplay) lacking an HCV insert. Each plasmid was injected intramuscularly into 5 mice and intraepidermally (via gene gun) into 5 mice. Immunization was repeated three times at three week intervals. Five macaques were injected intramuscularly (two with pE2., two with pE2surf and one with pDisplay) and immunization was repeated after 8 weeks. All mice immunized via gene gun with pE2 or pE2surf developed anti-E2, the animals immunized With pE2surf developed an earlier and stronger humoral immune response than those immunized with pE2.. Only 2 of the mice injected by the intramuscular route, both immunized with pE2surf, developed detectable anti-E2. One of the two macaques immunized with pE2 and both macaques immunized with pE2surf developed anti-E2; the humoral immune response was much stronger in the animals immunized with pE2surf. Our results suggest that presentation of HCV E2. on the cell surface may increase its immunogenicity while preserving its ability to react with antibodies generated during a natural infection. Published by Elsevier Science Ltd. C1 NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NCI, SAIC Frederick, Lab Cell & Mol Struct, Frederick, MD 21701 USA. NIAID, Mol Hepatitis Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Abbott Labs, Virus Discovery Grp, N Chicago, IL 60064 USA. RP Bukh, J (reprint author), NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bldg 7,Room 201,7 Ctr Dr MSC 0740, Bethesda, MD 20892 USA. FU NCI NIH HHS [CO-56000]; NIAID NIH HHS [AI-52705] NR 56 TC 52 Z9 56 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD APR 9 PY 1999 VL 17 IS 15-16 BP 1992 EP 2002 DI 10.1016/S0264-410X(98)00448-4 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 182XC UT WOS:000079522600023 PM 10217599 ER PT J AU Parodi, S AF Parodi, S TI Grant agencies must be seen to be fair SO NATURE LA English DT Letter C1 Natl Canc Inst, Ligurian Canc Registry, I-16132 Genoa, Italy. RP Parodi, S (reprint author), Natl Canc Inst, Ligurian Canc Registry, Largo R Benzi 10, I-16132 Genoa, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 8 PY 1999 VL 398 IS 6727 BP 455 EP 455 DI 10.1038/18959 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 185HQ UT WOS:000079662800019 PM 10206636 ER PT J AU Skjaerven, R Wilcox, AJ Lie, RT AF Skjaerven, R Wilcox, AJ Lie, RT TI A population-based study of survival and childbearing among female subjects with birth defects and the risk of recurrence in their children SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CONGENITAL-MALFORMATIONS; MATERNAL AGE; CLEFT-LIP AB Background and Methods Persons with birth defects are at high risk for death during the perinatal period and infancy. Less is known about the rater survival or reproduction of such persons. We studied a cohort that comprised 8192 women and adolescent girls with registered birth defects and 451,241 women and adolescent girls with no birth defects, all of whom were born in Norway from 1967 through 1982. The rate of survival was determined through 1992, and the rate of childbearing was determined through October 1997. We also estimated the risk of birth defects in the children of these subjects. Results Among the subjects with birth defects, 80 percent survived to 15 years of age, as compared with 98 percent of those with no birth defects. Among the surviving subjects, 53 percent of those with birth defects gave birth to at least one infant by the age of 30 years, as compared with 67 percent of those with no birth defects. The subjects with birth defects were one third less likely to give birth by the age of 30 than those with no birth defects. The children of the subjects with birth defects had a significantly higher risk of birth defects than the children of those with no birth defects (relative risk, 1.6; 95 percent confidence interval, 1.3 to 2.1). This increased risk was confined entirely to the specific defect carried by the mother, with the relative risk of recurrence varying from 5.5 to 82 according to the defect. In contrast, there was no increase in the risk of having an infant with a different type of defect. Conclusions Women and girls with birth defects have decreased survival as compared with those with no birth defects, especially in the first years of life, and are less likely to have children. in addition, they have an increased risk of having children with the same defect. (N Engl J Med 1999;340:1057-62.) (C) 1999, Massachusetts Medical Society. C1 Univ Bergen, Sect Med Stat, N-5021 Bergen, Norway. Univ Bergen, Med Birth Registry Norway, Bergen, Norway. NIEHS, Res Triangle Pk, NC 27709 USA. RP Skjaerven, R (reprint author), Univ Bergen, Sect Med Stat, Armauer Hansens Bldg, N-5021 Bergen, Norway. OI Wilcox, Allen/0000-0002-3376-1311 NR 13 TC 40 Z9 41 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 8 PY 1999 VL 340 IS 14 BP 1057 EP 1062 DI 10.1056/NEJM199904083401401 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 184AK UT WOS:000079587000001 PM 10194234 ER PT J AU Merke, DP Bornstein, SR Braddock, D Chrousos, GP AF Merke, DP Bornstein, SR Braddock, D Chrousos, GP TI Adrenal lymphocytic infiltration and adrenocortical tumors in a patient with 21-hydroxylase deficiency SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID HYPERPLASIA C1 NIH, Bethesda, MD 20892 USA. RP Merke, DP (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 5 TC 17 Z9 17 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 8 PY 1999 VL 340 IS 14 BP 1121 EP 1122 DI 10.1056/NEJM199904083401416 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 184AK UT WOS:000079587000024 PM 10206837 ER PT J AU Schmidt, L Junker, K Nakaigawa, N Kinjerski, T Weirich, G Miller, M Lubensky, I Neumann, HPH Brauch, H Decker, J Vocke, C Brown, JA Jenkins, R Richard, S Bergerheim, U Gerrard, B Dean, M Linehan, WM Zbar, B AF Schmidt, L Junker, K Nakaigawa, N Kinjerski, T Weirich, G Miller, M Lubensky, I Neumann, HPH Brauch, H Decker, J Vocke, C Brown, JA Jenkins, R Richard, S Bergerheim, U Gerrard, B Dean, M Linehan, WM Zbar, B TI Novel mutations of the MET proto-oncogene in papillary renal carcinomas SO ONCOGENE LA English DT Article DE papillary renal carcinoma; MET protooncogene mutations; receptor tyrosine kinase ID TYROSINE KINASE DOMAIN; TUMOR-SUPPRESSOR GENE; GROWTH-FACTOR RECEPTORS; ACTIVATING MUTATIONS; CRYSTAL-STRUCTURE; INSULIN-RECEPTOR; POINT MUTATIONS; CELL CARCINOMA; PROTOONCOGENE; ERBB AB Hereditary papillary renal carcinoma (HPRC) is characterized by multiple, bilateral papillary renal carcinomas. Previously, we demonstrated missense mutations in the tyrosine kinase domain of the MET proto-oncogene in HPRC and a subset of sporadic papillary renal carcinoma In this study, me screened a large panel of sporadic papillary renal carcinomas and various solid tumors for mutations in the MET protooncogene, Summarizing these and previous results, mutations of the MET proto-oncogene were detected in 17/129 sporadic papillary renal carcinomas but not in other solid tumors. We detected five novel: missense mutations; three of five mutations were located in the ATP-binding region of the tyrosine kinase domain of MET. One novel mutation in MET, V1110I, was located at a codon homologous to an activating mutation in the c-erbB proto-oncogene, These mutations caused constitutive phosphorylation of MET when transfected into NIH3T3 cells. Molecular modeling studies suggest that these activating mutations interfere with the intrasteric mechanism of tyrosine kinase autoinhibition and facilitate transition to the active form of the MET kinase, The low frequency of MET mutations in noninherited papillary renal carcinomas (PRC) suggests that noninherited PRC may develop by a different mechanism than hereditary papillary renal carcinoma. C1 NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Macromol Struct Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Frederick, MD 21702 USA. NIH, Urol Oncol Branch, Bethesda, MD 20892 USA. NIH, Pathol Lab, Bethesda, MD 20892 USA. Univ Freiburg, D-79106 Freiburg, Germany. Univ Hamburg, Womens Clin, Hamburg Eppendorf UKE, D-20246 Hamburg, Germany. Univ Mainz, D-55131 Mainz, Germany. Mayo Clin & Mayo Fdn, Div Lab Genet, Rochester, MN 55905 USA. Karolinska Inst, Stockholm, Sweden. Hop Bicetre, Dept Urol, Paris, France. EPHE, Lab Neuoroncol, F-75006 Paris, France. Univ Jena, Dept Urol, D-07743 Jena, Germany. David Grant Med Ctr, Travis AFB, CA 94535 USA. RP Schmidt, L (reprint author), NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Bldg 560 Rm 12-29, Frederick, MD 21702 USA. RI Dean, Michael/G-8172-2012; Miller, Maria/I-1636-2013 OI Dean, Michael/0000-0003-2234-0631; Miller, Maria/0000-0003-0252-5348 FU NCI NIH HHS [N01-CO-56000] NR 37 TC 320 Z9 329 U1 2 U2 7 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 8 PY 1999 VL 18 IS 14 BP 2343 EP 2350 DI 10.1038/sj.onc.1202547 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 184DT UT WOS:000079595500006 PM 10327054 ER PT J AU Osganian, SK Stampfer, MJ Spiegelman, D Rimm, E Cutler, JA Feldman, HA Montgomery, DH Webber, LS Lytle, LA Bausserman, L Nader, PR AF Osganian, SK Stampfer, MJ Spiegelman, D Rimm, E Cutler, JA Feldman, HA Montgomery, DH Webber, LS Lytle, LA Bausserman, L Nader, PR TI Distribution of and factors associated with serum homocysteine levels in children - Child and Adolescent Trial for Cardiovascular Health SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CORONARY-ARTERY DISEASE; PLASMA HOMOCYST(E)INE; RISK FACTOR; MYOCARDIAL-INFARCTION; VASCULAR-DISEASE; DIETARY PATTERNS; BLOOD-PRESSURE; UNITED-STATES; FOLIC-ACID; FOLATE AB Context Although evidence suggests that homocysteine is a risk factor for cardiovascular disease in adults, little information exists on homocysteine levels in children. Objectives To describe the distribution of serum homocysteine concentrations among children and to examine the association between homocysteine levels and several characteristics, including serum levels of folic acid and vitamins B-12 and B-6. Design Cross-sectional analysis. Setting School-based cohort from California, Louisiana, Minnesota, and Texas. Participants A total of 3524 US schoolchildren, aged 13 and 14 years, from the Child and Adolescent Trial for Cardiovascular Health (completed in 1994). Measurement conducted in 1997. Main Outcome Measure Nonfasting serum total homocysteine concentration. Results The distribution of homocysteine values ranged from 0.1 to 25.7 mu mol/L (median, 4.9 mu mol/L). Geometric mean homocysteine concentration was significantly higher in boys (5.22 mu mol/L) than girls (4.84 mu mol/L); blacks (5.51 mu mol/L) than whites (4.96 mu mol/L) or Hispanics (4.93 mu mol/L); nonusers of multivitamins (5.09 mu mol/L) than users (4.82 mu mol/L); and smokers (5.19 mu mol/L) than nonsmokers (5.00 mu mol/ L). Serum homocysteine was significantly inversely correlated with serum levels of folic acid (r = -0.36; P = .001), vitamin B-12 (r = -0.21; P = .001), and vitamin B, (r = -0.18; P = .001). Serum homocysteine was not significantly associated with serum lipid levels or family history of cardiovascular disease and was only weakly related to body mass index and systolic blood pressure. After multivariate adjustment, homocysteine remained independently associated with sex, race, serum folic acid and vitamin B-12 levels, and systolic blood pressure. Conclusions The distribution of homocysteine levels in children is substantially lower than that observed for adults; however, a small percentage of children are still potentially at elevated risk for future cardiovascular disease. Serum folic acid may be an important determinant of homocysteine levels in children. C1 New England Res Inst, Watertown, MA 02472 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Tulane Univ, Sch Publ Hlth & Trop Med, Dept Biostat, New Orleans, LA USA. Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA. Univ Texas, Hlth Sci Ctr, Ctr Hlth Promot Res & Dev, Houston, TX USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN USA. Univ Calif San Diego, Div Community Pediat, San Diego, CA USA. Miriam Hosp, Lipoprot Anal Lab, Providence, RI USA. Brown Univ, Sch Med, Providence, RI 02912 USA. RP Osganian, SK (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. EM voulao@neri.org FU NHLBI NIH HHS [U01-HL-39880, U01-HL-39852, U01-HL-39906] NR 58 TC 105 Z9 111 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 7 PY 1999 VL 281 IS 13 BP 1189 EP 1196 DI 10.1001/jama.281.13.1189 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 181VW UT WOS:000079464400033 PM 10199428 ER PT J AU Burroughs, KD Dunn, SE Barrett, JC Taylor, JA AF Burroughs, KD Dunn, SE Barrett, JC Taylor, JA TI Insulin-like growth factor-I: a key regulator of human cancer risk? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID BREAST-CANCER; IGF-I; RECEPTOR GENE; PLASMA; APOPTOSIS; MECHANISM; CHILDREN; PROTEIN; STAGE; P53 C1 NIEHS, Mol Carcinogenesis Lab, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Taylor, JA (reprint author), NIEHS, Mol Carcinogenesis Lab, Epidemiol Branch, POB 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA. EM taylor@niehs.nih.gov OI taylor, jack/0000-0001-5303-6398 NR 32 TC 46 Z9 48 U1 0 U2 2 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 7 PY 1999 VL 91 IS 7 BP 579 EP 581 DI 10.1093/jnci/91.7.579 PG 3 WC Oncology SC Oncology GA 185KK UT WOS:000079668000002 PM 10203270 ER PT J AU Smith, MA Freidlin, B Ries, LAG Simon, R AF Smith, MA Freidlin, B Ries, LAG Simon, R TI Trends in reported incidence of primary malignant brain tumors in children in the United States - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID CHILDHOOD; GLIOMAS C1 NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. NCI, Canc Surveillance Res Program, Bethesda, MD USA. RP Smith, MA (reprint author), NIH, Plaza North,Rm 741, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 7 PY 1999 VL 91 IS 7 BP 649 EP 649 DI 10.1093/jnci/91.7.649 PG 1 WC Oncology SC Oncology GA 185KK UT WOS:000079668000024 ER PT J AU Straus, SE Sneller, M Lenardo, MJ Puck, JM Strober, W AF Straus, SE Sneller, M Lenardo, MJ Puck, JM Strober, W TI An inherited disorder of lymphocyte apoptosis: The autoimmune lymphoproliferative syndrome SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID SYSTEMIC LUPUS-ERYTHEMATOSUS; FAS GENE-MUTATIONS; NEGATIVE T-CELLS; MONOCLONAL-ANTIBODY; AUTOANTIBODY PRODUCTION; CYTOKINE PRODUCTION; ICE/CED-3 PROTEASE; IL-12 PRODUCTION; DEATH DOMAIN; IFN-GAMMA C1 NIAID, Mucosal Immun Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Immunol Genet Branch, NIH, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Straus, SE (reprint author), NIAID, Mucosal Immun Sect, Clin Invest Lab, NIH, Bldg 10,Room 11N228,10 Ctr Dr, Bethesda, MD 20892 USA. EM sstraus@nih.gov NR 68 TC 213 Z9 216 U1 0 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 6 PY 1999 VL 130 IS 7 BP 591 EP 601 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 183BG UT WOS:000079533300008 PM 10189330 ER PT J AU Mizuuchi, K Nobbs, TJ Halford, SE Adzuma, K Qin, J AF Mizuuchi, K Nobbs, TJ Halford, SE Adzuma, K Qin, J TI A new method for determining the stereochemistry of DNA cleavage reactions: Application to the SfiI and HpaII restriction endonucleases and to the MuA transposase SO BIOCHEMISTRY LA English DT Article ID DIASTEREOMERIC PHOSPHOROTHIOATE ANALOGS; RECOGNITION SEQUENCE; STRAND TRANSFER; RECOMBINATION; MECHANISM; SITE; TOPOISOMERASE; INTEGRATION; PHOSPHORUS AB A new method was developed for tracking the stereochemical path of enzymatic cleavage of DNA, DNA with a phosphorothioate of known chirality at the scissile bond is cleaved by the enzyme in (H2O)-O-18. The cleavage produces a DNA molecule with the 5'-[O-16,O-18,S]-thiophosphoryl group, whose chirality depends pn:whether the cleavage reaction proceeds by a single-step hydrolysis mechanism or by a-two-step mechanism involving a protein-DNA covalent intermediate. To determine this chirality, the cleaved DNA is joined to an oligonucleotide by DNA ligase. Given the strict stereochemistry of the DNA ligase reaction, determined here, the original chirality of the phosphorothioate dictates whether the O-18 is retained or lost in the ligation product, which can be determined by mass spectrometry. This method has advantages over previews methods in that it is not restricted to particular NA sequences, requires substantially less material, and avoids purification of the products at intermediate stages in the procedure. The method was validated by confirming that DNA cleavage by the EcoRI restriction endonuclease causes inversion of configuration at the scissile phosphate. It was then applied to the reactions of the SfiI and HpaII endonucleases and the MuA transposase. In all three cases, DNA cleavage proceeded with inversion of configuration, indicating direct hydrolysis of the phosphodiester bond by water as opposed to a reaction involving a covalent enzyme-DNA intermediate. C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Bristol, Sch Med Sci, Dept Biochem, Bristol BS8 1TD, Avon, England. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Mizuuchi, K (reprint author), NIDDKD, Mol Biol Lab, NIH, Bldg 5,Rm 237, Bethesda, MD 20892 USA. FU Wellcome Trust NR 33 TC 38 Z9 38 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 6 PY 1999 VL 38 IS 14 BP 4640 EP 4648 DI 10.1021/bi990054p PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 188EP UT WOS:000079834100046 PM 10194386 ER PT J AU Tanaka, K Zou, JP Takeda, K Ferrans, VJ Sandford, GR Johnson, TM Finkel, T Epstein, SE AF Tanaka, K Zou, JP Takeda, K Ferrans, VJ Sandford, GR Johnson, TM Finkel, T Epstein, SE TI Effects of human cytomegalovirus immediate-early proteins on p53-mediated apoptosis in coronary artery smooth muscle cells SO CIRCULATION LA English DT Article DE viruses; proteins; apoptosis; restenosis ID TRANSCRIPTIONAL REPRESSION; P53; RESTENOSIS AB Background-Restenotic and atherosclerotic lesions often contain smooth muscle cells (SMCs), which display high rates of proliferation and apoptosis. Human cytomegalovirus (HCMV) may increase the incidence of restenosis and predispose to atherosclerosis. Although the mechanisms contributing to these processes are unclear, studies demonstrate that one of the immediate-early (IE) gene products of HCMV, IE2-84, binds to and inhibits p53 transcriptional activity. Given the role of p53 in mediating apoptosis, we studied the ability of IE2-84 to inhibit p53-dependent apoptosis in human coronary artery SMCs. Methods and Results-Apoptosis of SMCs was induced either by use of an adenovirus vector encoding human wild-type p53 protein or by treatment with doxorubicin. HCMV IE1-72 and IE2-84, the major IE proteins of HCMV, were overexpressed separately with adenovirus vectors encoding each protein, and the effects on p53-induced apoptosis were examined by both nick end-labeling (TUNEL) assay and flow cytometry. Expression of IE2-84, but not IE1-72, protected SMCs fi om p53-mediated apoptosis, Conclusions-These data indicate that an HCMV IE protein antagonizes p53-mediated apoptosis, suggesting a pathway by which HCMV infection predisposes to SMC accumulation and thereby contributes to restenosis and atherosclerosis. C1 NHLBI, Cardiol Branch, Bethesda, MD 20892 USA. NHLBI, Pathol Branch, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Med Coll Wisconsin, Madison, WI USA. Cardiovasc Res Fdn, Washington, DC USA. RP Epstein, SE (reprint author), Washington Hosp Ctr, Cardiovasc Res Fdn, 110 Irving St NW,Suite 4B-1, Washington, DC 20010 USA. NR 15 TC 84 Z9 95 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 6 PY 1999 VL 99 IS 13 BP 1656 EP 1659 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 181WP UT WOS:000079466200003 PM 10190872 ER PT J AU Denissenko, MF Cahill, J Koudriakova, TB Gerber, N Pfeifer, GP AF Denissenko, MF Cahill, J Koudriakova, TB Gerber, N Pfeifer, GP TI Quantitation and mapping of aflatoxin B1-induced DNA damage in genomic DNA using aflatoxin B1-8,9-epoxide and microsomal activation systems SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE aflatoxin; mutation; adduct; microsome; hepatocellular carcinoma ID HUMAN P53 GENE; RAT-LIVER; HEPATOCELLULAR-CARCINOMA; MUTATIONAL HOTSPOTS; HUMAN CANCERS; HOT-SPOTS; ADDUCTS; IDENTIFICATION; B-1; CARCINOGENESIS AB Aflatoxin BI (AFB1) is a mutagenic and carcinogenic mycotoxin which may play a role in the etiology of human liver cancer. In vitro studies have shown that AFB1 adducts form primarily at the N7 position of guanine. Using quantitative PCR (QPCR) and ligation-mediated PCR (LMPCR), we have mapped total AFB1 adducts in genomic DNA treated with AFB1-8,9-epoxide and in hepatocytes exposed to AFB1 activated by rat liver microsomes or human liver and enterocyte microsomal preparations. The p53 gene-specific adduct frequencies in DNA, modified in cells with 40-400 mu M AFB1, were 0.07-0.74 adducts per kilobase (kb). In vitro modification with 0.1-4 ng AFB1-8,9-epoxide per microgram DNA produced 0.03-0.58 lesions per kb. The adduct patterns obtained with the epoxide and the different microsomal systems were virtually identical indicating that adducts form with a similar sequence-specificity in vitro and in vivo. The lesions were detected exclusively at guanines with a preference towards GpG and methylated CpG sequences. The methods utilizing QPCR and LMPCR thus provide means to assess gene-specific and sequence-specific AFB1 damage, The results also prove that microsomally-mediated damage is a suitable method for avoiding manipulations with very unstable DNA-reactive metabolites and that this damage can be detected by QPCR and LMPCR. (C) 1999 Elsevier Science B.V. All rights reserved. C1 City Hope Natl Med Ctr, Beckman Res Inst, Dept Biol, Duarte, CA 91010 USA. NCI, Frederick Canc Res & Dev Ctr, Chem Carcinogenesis Lab, Frederick, MD 21702 USA. Ohio State Univ, Dept Pharmacol, Columbus, OH 43210 USA. RP Pfeifer, GP (reprint author), City Hope Natl Med Ctr, Beckman Res Inst, Dept Biol, Duarte, CA 91010 USA. FU NCI NIH HHS [P01CA69449] NR 36 TC 45 Z9 53 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD APR 6 PY 1999 VL 425 IS 2 BP 205 EP 211 DI 10.1016/S0027-5107(99)00038-X PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 189NE UT WOS:000079910800004 PM 10216213 ER PT J AU Basile, AS Hanus, L Mendelson, WB AF Basile, AS Hanus, L Mendelson, WB TI Characterization of the hypnotic properties of oleamide SO NEUROREPORT LA English DT Article DE cerebrospinal fluid; EEG; hypnotic; oleamide; rat; sleep ID CANNABINOID RECEPTOR; SLEEP INDUCTION; BRAIN LIPIDS; RAT; ACID; ANANDAMIDE; ENZYME AB WHILE preliminary studies associated oleamide with sleep regulation, we now characterize the involvement of oleamide in sleep using a number of techniques. Peripheral administration of oleamide to rats dose dependently suppressed motor activity in the open field, with an ED50 of 17+/-1.5 mg/kg for the decrease in distance traveled. Moreover, endogenous oleamide concentrations increased 3- to 4-fold in the cerebrospinal fluid of rats sleep-deprived for 6 h or longer. Oleamide also decreased sleep latency to 44-64% of control values without altering other sleep parameters. Unlike many putative endogenous sleep-inducing agents, oleamide potently induces behavioral and electroencephalographic manifestations of sleep. Moreover, its endogenous concentrations and temporal associations are consistent with previous reports of its enhancement of serotonergic and GABAergic neurotransmission, which may be involved in sleep induction. NeuroReport 10:947-951 (C) 1999 Lippincott Williams & Wilkins. C1 NIDDK, Neurosci Grp, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Chicago, Dept Psychiat, Sleep Res Lab, Chicago, IL 60637 USA. RP Basile, AS (reprint author), NIDDK, Neurosci Grp, Bioorgan Chem Lab, NIH, Bldg 8,Room 121,MSC 0826, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [1KO7HL03640-01A1]; NIDA NIH HHS [1RO1DA10682-01A2] NR 25 TC 69 Z9 70 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD APR 6 PY 1999 VL 10 IS 5 BP 947 EP 951 DI 10.1097/00001756-199904060-00010 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 189KZ UT WOS:000079904900012 PM 10321465 ER PT J AU Cramer, H Player, MR Torrence, PF AF Cramer, H Player, MR Torrence, PF TI Discrimination between ribonuclease H- and ribonuclease L-mediated RNA degradation by 2 '-O-methylated 2-5A-antisense oligonucleotides SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID ANTISENSE OLIGONUCLEOTIDES; TARGETING RNA; NUCLEIC-ACID; 2-5A; CHIMERAS; AFFINITY; CELLS AB 2',5'-Oligoadenylate (2-5A) antisense chimeric oligonucleotides were synthesized containing varying 2'-O-methyl-ribonucleotide substitution patterns in the antisense domain. The ability of these composite oligonucleotides to mediate RNase H- and RNase L-catalyzed RNA degradation showed that these two enzymes have different activation requirements. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 NIDDKD, Med Chem Lab, Sect Biomed Chem, NIH, Bethesda, MD 20892 USA. RP Torrence, PF (reprint author), Gemini Technol Inc, 11000 Cedar Ave, Cleveland, OH 44106 USA. NR 25 TC 10 Z9 10 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD APR 5 PY 1999 VL 9 IS 7 BP 1049 EP 1054 DI 10.1016/S0960-894X(99)00134-1 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 187EX UT WOS:000079774900029 PM 10230638 ER PT J AU Sharp, AH Nucifora, FC Blondel, O Sheppard, CA Zhang, CY Snyder, SH Russell, JT Ryugo, DK Ross, CA AF Sharp, AH Nucifora, FC Blondel, O Sheppard, CA Zhang, CY Snyder, SH Russell, JT Ryugo, DK Ross, CA TI Differential cellular expression of isoforms of inositol 1,4,5-triphosphate receptors in neurons and glia in brain SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE Ca2+ release; electron microscopy; synapse; second messengers; neuropeptides; limbic system ID CENTRAL-NERVOUS-SYSTEM; RECONSTITUTED LIPID VESICLES; CEREBELLAR PURKINJE NEURONS; 1,4,5-TRISPHOSPHATE RECEPTOR; TRISPHOSPHATE RECEPTOR; ENDOPLASMIC-RETICULUM; RAT-BRAIN; IMMUNOHISTOCHEMICAL LOCALIZATION; INSP3 RECEPTOR; CA2+ RELEASE AB Inositol 1,4,5-trisphosphate receptors (IP3R) are mediators of second messenger-induced intracellular calcium release. Three isoforms are known to be expressed in brain, but their regional distributions and cellular localizations are little known. In order to better understand the roles of IP3 receptor isoforms in brain function, a first step is to define their distributions. We have used affinity-purified antibodies directed against peptides unique to each isoform to determine their sites of expression in rat brain. Type 1 IP3R (IP(3)R1) is dramatically enriched in Purkinje neurons in cerebellum and neurons in other regions, consistent with previous studies. By contrast, IP(3)R2 is only detected in glia, whereas IP(3)R3 is predominantly neuronal, with little detected in glia. IP(3)R3 is enriched in neuropil, especially in neuronal terminals (which often contain large dense core vesicles) in limbic and basal forebrain regions including olfactory tubercle, central nucleus of the amygdala, and bed nucleus of the stria terminalis. In addition, IP(3)R1 and IP(3)R3 have clearly distinct time courses of expression in developing brains. These data suggest separate roles for inositol 1,4,5-trisphosphate receptor isoforms in development, and for glial and neuronal function. The IP(3)R3 may be involved in regulation of neurotransmitter or neuropeptide release in terminals within specific nuclei of the basal forebrain and limbic system. J. Comp. Neurol. 406:207-220, 1999. (C) 1999 Wiley-Liss, Inc. C1 Johns Hopkins Univ, Sch Med, Lab Cellular Neurobiol, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Mol Neurobiol Lab, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21287 USA. NINCDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NICCHD, Cellular & Mol Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21205 USA. RP Sharp, AH (reprint author), Johns Hopkins Univ, Sch Med, Lab Cellular Neurobiol, 600 N Wolfe St,Meyer Bldg,Rm 2-181, Baltimore, MD 21287 USA. EM ahsharp@welchlink.welch.jhu.edu FU NIDCD NIH HHS [DC-00232]; NIMH NIH HHS [MH18501, MH43040] NR 96 TC 113 Z9 116 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 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD APR 5 PY 1999 VL 406 IS 2 BP 207 EP 220 PG 14 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 171RK UT WOS:000078877700006 PM 10096607 ER PT J AU Rockland, KS Andresen, J Cowie, RJ Robinson, DL AF Rockland, KS Andresen, J Cowie, RJ Robinson, DL TI Single axon analysis of pulvinocortical connections to several visual areas in the macaque SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE arbor size; attention; cortical layers; cortical uniformity; lateral pulvinar ID ADJACENT LATERAL PULVINAR; MONKEY MACACA-MULATTA; STRIATE CORTEX; RHESUS-MONKEY; INFERIOR PULVINAR; INTRINSIC CONNECTIONS; CORTICAL CONNECTIONS; LAMINAR DISTRIBUTION; SPATIAL ATTENTION; SQUIRREL-MONKEY AB The pulvinar nucleus is a major source of input to visual cortical areas, but many important facts are still unknown concerning the organization of pulvinocortical (PC) connections and their possible interactions with other connectional systems. In order to address some of these questions, we labeled PC connections by extracellular injections of biotinylated dextran amine into the lateral pulvinar of two monkeys, and analyzed 25 individual axons in several extrastriate areas by serial section reconstruction. This approach yielded four results: (1) in all extrastriate areas examined (V2, V3, V4, and middle temporal area [MT]/V5), PC axons consistently have 2-6 multiple, spatially distributed arbors; (2) in each area, there is a small number of larger caliber axons, possibly originating from a subpopulation of calbindin-positive giant projection neurons in the pulvinar; (3) as previously reported by others, most terminations in extrastriate areas are concentrated in layer 3, but they can occur in other layers (layers 4,5,6, and, occasionally, layer 1) as collaterals of a single axon; in addition, (4) the size of individual arbors and of the terminal field as a whole varies with cortical area. In areas V2 and V3, there is typically a single principal arbor (0.25-0.50 mm in diameter) and several smaller arbors. In area V4, the principal arbor is larger (2.0- to 2.5-mm-wide), but in area MT/V5, the arbors tend to be smaller (0.15 mm in diameter). Size differences might result from specializations of the target areas, or may be more related to the particular injection site and how this projects to individual cortical areas. Feedforward cortical axons, except in area V2, have multiple arbors, but these do not show any obvious size progression. Thus, in areas V2, V3, and especially V4, PC fields are larger than those of cortical axons, but in MT/V5 they are smaller. Terminal specializations of PC connections tend to be larger than those of corticocortical, but the projection foci are less dense. Further work is necessary to determine the differential interactions within and between systems, and how these might result in the complex patterns of suppression and enhancement, postulated as gating mechanisms in cortical attentional effects, or in different states of arousal. J. Comp. Neurol. 406:221-250, 1999. Published 1999 Wiley-Liss, Inc. C1 Univ Iowa, Dept Neurol, Div Behav Neurol & Cognit Neurosci, Iowa City, IA 52242 USA. NEI, Sect Visual Behavior, Sensorimotor Res Lab, Bethesda, MD 20892 USA. Howard Univ, Coll Med, Dept Anat, Washington, DC 20059 USA. RP Rockland, KS (reprint author), Univ Iowa, Dept Neurol, Div Behav Neurol & Cognit Neurosci, 200 Hawkins Dr, Iowa City, IA 52242 USA. EM rockland@blue.weeg.uiowa.edu FU NIMH NIH HHS [MH53598] NR 77 TC 50 Z9 50 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 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD APR 5 PY 1999 VL 406 IS 2 BP 221 EP 250 DI 10.1002/(SICI)1096-9861(19990405)406:2<221::AID-CNE7>3.0.CO;2-K PG 30 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 171RK UT WOS:000078877700007 PM 10096608 ER PT J AU Yap, GS Sher, A AF Yap, GS Sher, A TI Effector cells of both nonhemopoietic and hemopoietic origin are required for interferon (IFN)-gamma- and tumor necrosis factor (TNF)-alpha-dependent host resistance to the intracellular pathogen, Toxoplasma gondii SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE toxoplasma; interferon gamma; tumor necrosis factor alpha; inducible nitric oxide synthase; cell-mediated immunity ID INDUCIBLE NITRIC-OXIDE; ENDOGENOUS IFN-GAMMA; INDOLEAMINE 2,3-DIOXYGENASE; HUMAN-FIBROBLASTS; ACTIVATED MACROPHAGES; MURINE TOXOPLASMOSIS; LEISHMANIA-MAJOR; ACUTE INFECTION; MICE LACKING; FACTOR-ALPHA AB Although interferon (IFN)-gamma-activated, mononuclear phagocytes are considered to be the major effectors of resistance to intracellular pathogens, it is unclear how they control the growth of microorganisms that reside in nonhemopoietic cells. Pathogens within such cells may be killed by metabolites secreted by activated macrophages or, alternatively, directly controlled by cytokine-induced microbicidal mechanisms triggered within infected nonphagocytic cells. To distinguish between these two basic mechanisms of cell-mediated immunity, reciprocal bone marrow chimeras were constructed between wild-type and IFN-gamma receptor-deficient mice and their survival assessed following infection with Toxoplasma gondii, a protozoan parasite that invades both hemopoietic and nonhemopoietic cell lineages. Resistance to acute and persistent infection was displayed only by animals in which IFN-gamma receptors were expressed in both cellular compartments. Parallel chimera experiments performed with tumor necrosis factor (TNF) receptor-deficient mice also indicated a codependence on hemopoietic and nonhemopoietic lineages for optimal control of the parasite. In contrast, in mice chimeric for inducible nitric oxide synthase (iNOS), an enzyme associated with IFN-gamma-induced macrophage microbicidal activity, expression by cells of hemopoietic origin was sufficient for host resistance. Together, these findings suggest that, in concert with bone marrow-derived effectors, nonhemopoietic cells can directly mediate, in the absence of endogenous iNOS, IFN-gamma- and TNF-alpha-dependent host resistance to intracellular infection. C1 NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Yap, GS (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. EM gyap@atlas.niaid.nih.gov NR 50 TC 124 Z9 134 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 5 PY 1999 VL 189 IS 7 BP 1083 EP 1091 DI 10.1084/jem.189.7.1083 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 185BR UT WOS:000079648700009 PM 10190899 ER PT J AU Rajagopalan, S Long, EO AF Rajagopalan, S Long, EO TI A human histocompatibility leukocyte antigen (HLA)-G-specific receptor expressed on all natural killer cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE natural killer cell; human histocompatibility leukocyte antigen G killer cell immunoglobulin-like receptor pregnancy; trophoblast ID CLASS-I MOLECULES; INHIBITORY RECEPTOR; HLA-G; NK CELLS; MYELOMONOCYTIC CELLS; PERIPHERAL-BLOOD; MEDIATED LYSIS; CUTTING EDGE; RECOGNITION; COMPLEX AB Human natural killer (NK) cells express several killer cell immunoglobulin (Ig)-like receptors (KIRs) that inhibit their cytotoxicity upon recognition of human histocompatibility leukocyte antigen (HLA) class I molecules on target cells. Additional members of the KIR family, including some that deliver activation signals, have unknown ligand specificity and function. One such KIR, denoted KIR2DL4, is structurally divergent from other KIRs in the configuration of its two extracellular Ig domains and of its transmembrane and cytoplasmic domains. Here we show that recombinant soluble KIR2DL4 binds to cells expressing HLA-G but not to cells expressing other HLA class I molecules. Unlike other HLA class I-specific KIRs, which are clonally distributed on NK cells, KIR2DL4 is expressed at the surface of all NK cells. Furthermore, functional transfer of KIR2DL4 into the cell line NK-92 resulted in inhibition of lysis of target cells that express HLA-G, but not target cells that express other class I molecules including HLA-E. Therefore, given that HLA-G expression is restricted to fetal trophoblast cells, KIR2DL4 may provide important signals to maternal NK decidual cells that interact with trophoblast cells at the maternal-fetal interface during pregnancy. C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Long, EO (reprint author), NIAID, Immunogenet Lab, NIH, Twinbrook 2,12441 Parklawn Dr, Rockville, MD 20852 USA. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 35 TC 470 Z9 491 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 5 PY 1999 VL 189 IS 7 BP 1093 EP 1099 DI 10.1084/jem.189.7.1093 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 185BR UT WOS:000079648700010 PM 10190900 ER PT J AU Ashe, JM Wiest, DL Abe, R Singer, A AF Ashe, JM Wiest, DL Abe, R Singer, A TI ZAP-70 protein promotes tyrosine phosphorylation of T cell receptor signaling motifs (ITAMs) in immature CD4(+)8(+) thymocytes with limiting p56(lck) SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE T cell receptor; development; signaling; thymus; phosphorylation ID CD4+CD8+ THYMOCYTES; MURINE THYMOCYTES; KINASE; TCR; EXPRESSION; ACTIVATION; DOMAIN; ZETA; CD4 AB As a result of interaction with epithelial cells in the thymic cortex, immature CD4(+)8(+) (double positive, DP) thymocytes express relatively few T cell receptors (TCRs) and contain diminished numbers of coreceptor-associated p56(lck) (lck) PTK molecules. As a result, TCR signal transduction in DP thymocytes is significantly impaired, despite its importance for repertoire selection. We report here that, ill DP thymocytes, tyrosine phosphorylation of TCR signaling motifs (ITAMs) by Ick, an early event in TCR signal transduction, is dependent upon ZAP-70 protein independent of ZAP-70's kinase activity. Furthermore, the: dependence on ZAP-70 protein for ITAM phosphorylation diminishes as available Ick increases. Importantly, ZAP-70's role in ITAM phosphorylation in DP thymocytes is not limited to protecting phosphorylated ITAMs from dephosphorylation. Rather, this study indicates that ZAP-70 protein augments ITAM phosphorylation in DP thymocytes and so compensates in part for the relative deficiency of coreceptor-associated Ick. C1 NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Sci Univ Tokyo, Res Inst Biol Sci, Dept Immunobiol, Noda, Chiba 278, Japan. RP Ashe, JM (reprint author), NCI, Expt Immunol Branch, Bldg 10,Rm 4B-17, Bethesda, MD 20892 USA. OI Wiest, David/0000-0002-0792-3188 NR 15 TC 24 Z9 25 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 5 PY 1999 VL 189 IS 7 BP 1163 EP 1167 DI 10.1084/jem.189.7.1163 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 185BR UT WOS:000079648700018 PM 10190908 ER PT J AU Kim, HC Bing, GY Jhoo, WK Ko, KH Kim, WK Lee, DC Shin, EJ Hong, JS AF Kim, HC Bing, GY Jhoo, WK Ko, KH Kim, WK Lee, DC Shin, EJ Hong, JS TI Dextromethorphan modulates the AP-1 DNA-binding activity induced by kainic acid SO BRAIN RESEARCH LA English DT Article DE dextromethorphan; neuroprotection; hippocampus; kainic acid; activator protein-1; Fos-related antigen ID TRANSCRIPTION FACTORS; RAT-BRAIN; PROLONGED EXPRESSION; PHENCYCLIDINE; FOS; HIPPOCAMPUS; RECEPTOR; SEIZURES; DRUGS AB We have recently reported that dextromethorphan attenuates the neurotoxicity induced by kainic acid in a dose-related fashion. Pretreatments with dextromethorphan (50 mg/kg, p.o. x2) significantly reduced the activator protein-1 DNA-binding activity and the Fos-related antigen-immunoreactive protein induced by kainic acid (10 mg/kg, i.p.) in the CA1, but not the CA3 or the dentate gyrus sector of the rat hippocampus. Paradoxically, dextromethorphan itself caused an elevated activator protein-1 DNA-binding activity and Fos-related antigen-immunoreactive protein in the CA1 region which lasted for at least 4 days. The results suggest that the CA1 area is the critical site for mediating the putative neuroprotective effect induced by dextromethorphan. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Kangweon Natl Univ, Korea Inst Drug Abuse, Coll Pharm, Dept Pharm,Sect Pharmacol & Toxicol, Chunchon 200701, South Korea. Oklahoma Med Res Fdn, Free Radical Biol & Aging Res Program, Oklahoma City, OK 73104 USA. Seoul Natl Univ, Coll Pharm, Ctr Biofunct Mol, Seoul 151742, South Korea. Ewha Womans Univ, Ewha Med Res Ctr, Coll Med, Dept Pharmacol, Seoul 151056, South Korea. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Kim, HC (reprint author), Kangweon Natl Univ, Korea Inst Drug Abuse, Coll Pharm, Dept Pharm,Sect Pharmacol & Toxicol, Chunchon 200701, South Korea. OI Bing, Guoying/0000-0003-0609-8152 NR 29 TC 32 Z9 32 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD APR 3 PY 1999 VL 824 IS 1 BP 125 EP 132 DI 10.1016/S0006-8993(99)01155-5 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 180GL UT WOS:000079377700015 PM 10095051 ER PT J AU Taylor, SI AF Taylor, SI TI Deconstructing type 2 diabetes SO CELL LA English DT Review ID INSULIN-RECEPTOR GENE; IMPAIRED GLUCOSE-TOLERANCE; TARGETED DISRUPTION; MUTATIONS; MICE; MELLITUS; MUSCLE; RESISTANCE; SECRETION; LESSONS C1 NIDDKD, Diabet Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Taylor, SI (reprint author), NIDDKD, Diabet Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA. NR 26 TC 202 Z9 210 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD APR 2 PY 1999 VL 97 IS 1 BP 9 EP 12 DI 10.1016/S0092-8674(00)80709-6 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 188JW UT WOS:000079843900003 PM 10199397 ER PT J AU Ban, C Junop, M Yang, W AF Ban, C Junop, M Yang, W TI Transformation of MutL by ATP binding and hydrolysis: A switch in DNA mismatch repair SO CELL LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; HSP90 MOLECULAR CHAPERONE; N-TERMINAL FRAGMENT; GYRASE-B-PROTEIN; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; SACCHAROMYCES-CEREVISIAE; REPLICATION FIDELITY; NUCLEOTIDE-BINDING; IN-VIVO AB The MutL DNA mismatch repair protein has recently been shown to be an ATPase and to belong to an emerging ATPase superfamily that includes DNA topoisomerase II and Hsp90. We report here the crystal structures of a 40 kDa ATPase fragment of E. coli MutL (LN40) complexed with a substrate analog, ADPnP, and with product ADP. More than 60 residues that are disordered in the apoprotein structure become ordered and contribute to both ADPnP binding and dimerization of LN40. Hydrolysis of ATP, signified by subsequent release of the gamma-phosphate, releases two key loops and leads to dissociation of the LN40 dimer. Dimerization of the LN40 region is required for and is the rate-limiting step in ATP hydrolysis by Mutt. The ATPase activity of MutL is stimulated by DNA and likely acts as a switch to coordinate DNA mismatch repair. C1 NIDDKD, Mol Biol Lab, 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 42 TC 286 Z9 290 U1 2 U2 13 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD APR 2 PY 1999 VL 97 IS 1 BP 85 EP 97 DI 10.1016/S0092-8674(00)80717-5 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 188JW UT WOS:000079843900011 PM 10199405 ER PT J AU McDermott, MF Aksentijevich, I Galon, J McDermott, EM Ogunkolade, BW Centola, M Mansfield, E Gadina, M Karenko, L Pettersson, T McCarthy, J Frucht, DM Aringer, M Torosyan, Y Teppo, AM Wilson, M Karaarslan, HM Wan, Y Todd, I Wood, G Schlimgen, R Kumarajeewa, TR Cooper, SM Vella, JP Amos, CI Mulley, J Quane, KA Molloy, MG Ranki, A Powell, RJ Hitman, GA O'Shea, JJ Kastner, DL AF McDermott, MF Aksentijevich, I Galon, J McDermott, EM Ogunkolade, BW Centola, M Mansfield, E Gadina, M Karenko, L Pettersson, T McCarthy, J Frucht, DM Aringer, M Torosyan, Y Teppo, AM Wilson, M Karaarslan, HM Wan, Y Todd, I Wood, G Schlimgen, R Kumarajeewa, TR Cooper, SM Vella, JP Amos, CI Mulley, J Quane, KA Molloy, MG Ranki, A Powell, RJ Hitman, GA O'Shea, JJ Kastner, DL TI Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes SO CELL LA English DT Article ID TUMOR-NECROSIS-FACTOR; PERIODIC-FEVER; LYMPHOPROLIFERATIVE SYNDROME; ERYTHROPOIETIN RECEPTOR; RHEUMATOID-ARTHRITIS; MEDITERRANEAN FEVER; MONOCLONAL-ANTIBODY; MOLECULAR-CLONING; HUMAN NEUTROPHILS; CHROMOSOME 12P13 AB Autosomal dominant periodic fever syndromes are characterized by unexplained episodes of fever and severe localized inflammation. In seven affected families, we found six different missense mutations of the 55 kDa tumor necrosis factor receptor (TNFR1), five of which disrupt conserved extracellular disulfide bonds. Soluble plasma TNFR1 levels in patients were approximately half normal. Leukocytes bearing a C52F mutation showed increased membrane TNFR1 and reduced receptor cleavage following stimulation. We propose that the autoinflammatory phenotype results from impaired downregulation of membrane TNFR1 and diminished shedding of potentially antagonistic soluble receptor. TNFR1-associated periodic syndromes (TRAPS) establish an important class of mutations in TNF receptors. Detailed analysis of one such mutation suggests impaired cytokine receptor clearance as a novel mechanism of disease. C1 St Bartholomews & Royal London Hosp Sch Med & Den, Med Unit, London E1 1BB, England. NIAMSD, Genet Sect, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. NIAMSD, Lymphocyte Cell Biol Sect, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. NIAMSD, Clin Invest Sect, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. Univ Nottingham, Queens Med Ctr, Sch Clin Lab Sci, Div Mol & Clin Immunol, Nottingham NG7 2UH, England. Univ Helsinki, Cent Hosp, Dept Dermatol, Helsinki 00029, Finland. Univ Helsinki, Cent Hosp, Dept Med, Div Internal Med, Helsinki 00029, Finland. Univ Helsinki, Cent Hosp, Dept Med, Div Nephrol, Helsinki 00029, Finland. Natl Univ Ireland Univ Coll Cork, Dept Med, Cork, Ireland. Natl Univ Ireland Univ Coll Cork, Dept Rheumatol, Cork, Ireland. New Childrens Hosp, Dept Clin Genet, Westmead, NSW, Australia. Univ Vermont, Coll Med, Rheumatol & Clin Immunol Unit, Burlington, VT 05405 USA. Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Womens & Childrens Hosp, Ctr Med Genet, Dept Cytogenet & Mol Genet, Adelaide, SA 5006, Australia. RP Kastner, DL (reprint author), St Bartholomews & Royal London Hosp Sch Med & Den, Med Unit, London E1 1BB, England. EM m.f.mcdermott@mds.qmw.ac.uk; kastnerd@arb.niams.nih.gov FU NIAMS NIH HHS [AR44422]; NIGMS NIH HHS [GM52607]; Wellcome Trust NR 51 TC 672 Z9 684 U1 2 U2 18 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD APR 2 PY 1999 VL 97 IS 1 BP 133 EP 144 DI 10.1016/S0092-8674(00)80721-7 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 188JW UT WOS:000079843900015 PM 10199409 ER PT J AU Ponce, ML Nomizu, M Delgado, MC Kuratomi, Y Hoffman, MP Powell, S Yamada, Y Kleinman, HK Malinda, KM AF Ponce, ML Nomizu, M Delgado, MC Kuratomi, Y Hoffman, MP Powell, S Yamada, Y Kleinman, HK Malinda, KM TI Identification of endothelial cell binding sites on the laminin gamma 1 chain SO CIRCULATION RESEARCH LA English DT Article DE angiogenesis; laminin; endothelium; extracellular matrix; adhesion ID CAPILLARY-LIKE STRUCTURES; EGF-LIKE MOTIF; BASEMENT-MEMBRANE; SYNTHETIC PEPTIDES; NIDOGEN BINDING; TUMOR-GROWTH; DIFFERENTIATION; ANGIOGENESIS; INVITRO; MATRIX AB The laminins belong to a family of trimeric basement membrane glycoproteins with multiple domains, structures, and functions. Endothelial cells bind laminin-1 and form capillary-like structures when plated on a laminin-1-rich basement membrane matrix, Matrigel. Laminin-1 is composed of 3 chains, alpha 1, beta 1, and gamma 1. Because laminin-1 is known to contain multiple biologically active sites, we have screened 156 synthetic overlapping peptides spanning the entire laminin gamma 1 chain for potential angiogenic sequences. Only 7 of these peptides, designated as C16, C25, C30, C38, C64, C75, and C102, disrupted the formation of capillary-like structures by human umbilical vein endothelial cells on Matrigel. Dose-response experiments in the presence of 50 to 200 mu g/mL showed that tube formation was prevented by most peptides at 150 and 200 mu g/mL, except for C16, which showed strong activity at all concentrations. Active peptides promoted vessel sprouting from aorta rings and angiogenesis in the chick chorioallantoic membrane assay. In addition, the active peptides also promoted endothelial cell adhesion to dishes coated with 0.1 mu g of peptide and inhibited attachment to laminin-1 but not to plastic or fibronectin. Four of the active peptides, C25, C38, C75, and C102, may have cell-type specificity with endothelial cells, since they did not promote PC12 neurite outgrowth or adhesion of B16-F10 melanoma and human submandibular gland cells. These results suggest that specific laminin gamma 1-chain peptides have angiogenic activity with potential therapeutic applications. C1 NIDR, CDBRB, NIH, Bethesda, MD 20892 USA. RP Kleinman, HK (reprint author), NIDR, CDBRB, NIH, Bldg 30,Rm 433, Bethesda, MD 20892 USA. NR 24 TC 70 Z9 73 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD APR 2 PY 1999 VL 84 IS 6 BP 688 EP 694 PG 7 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 182WV UT WOS:000079521900007 PM 10189356 ER PT J AU Dikalov, SI Vitek, MP Maples, KR Mason, RP AF Dikalov, SI Vitek, MP Maples, KR Mason, RP TI Amyloid beta peptides do not form peptide-derived free radicals spontaneously, but can enhance metal-catalyzed oxidation of hydroxylamines to nitroxides SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ALZHEIMERS-DISEASE; SPIN-TRAP; HYDROGEN-PEROXIDE; PROTEIN; NEUROTOXICITY; INHIBITION; TOXICITY; ADDUCT; IRON; DECOMPOSITION AB Amyloid beta (A beta) peptides play an important, role in the pathogenesis of Alzheimer's disease. Free radical generation by A beta peptides was suggested to be a key mechanism of their neurotoxicity. Reports that neurotoxic free radicals derived from A beta-(1-40) and A beta-(25-35) peptides react with the spin trap N-tert-butyl-alpha-phenylnitrone (PBN) to form a PBN/*A beta peptide radical adduct with a specific triplet ESR. signal assert that the peptide itself was the source of free radicals. We now report that three A beta peptides, A beta-(1-40), A beta-(25-35), and A beta-(40-1), do not yield radical adducts with PEN from the Oklahoma Medical Research Foundation (OMRF). Incontrast to OMRF PEN, incubation of Sigma PEN in phosphate buffer without A beta peptides produced a three-line ESR spectrum, It was shown that this nitroxide is di-tert-butylnitroxide and is formed in the Sigma PEN solution as a result of transition metal-catalyzed auto-oxidation of the respective hydroxylamine present as an impurity in the Sigma PEN. Under some conditions, incubation of PEN from Sigma with A beta-(1-40) or A beta-(25-35) can stimulate the formation of di-tert-butylnitroxide. It was shown that A beta peptides enhanced oxidation of cyclic hydroxylamine 1-hydroxy-4-oxo-2,2,6,6-tetramethylpiperidine (TEMPONE-H), which was strongly inhibited by the treatment of phosphate buffer with Chelex-100. It was shown that ferric and cupric ions are effective oxidants of TEMPONE-H. The data obtained allow us to conclude that under some conditions toxic A beta peptides A beta-(1-40) and A beta-(25-35) enhance metal-catalyzed oxidation of hydroxylamine derivatives, but do not spontaneously form peptide-derived free radicals. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Med, Div Neurol, Durham, NC 27710 USA. Centaur Pharmaceut Inc, Sunnyvale, CA 94086 USA. Novosibirsk Chem Kinet & Combust Inst, Novosibirsk 630090, Russia. RP Dikalov, SI (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 39 TC 95 Z9 96 U1 0 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 2 PY 1999 VL 274 IS 14 BP 9392 EP 9399 DI 10.1074/jbc.274.14.9392 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 181PX UT WOS:000079451800038 PM 10092619 ER PT J AU Sharma, P Steinbach, PJ Sharma, M Amin, ND Barchi, JJ Pant, HC AF Sharma, P Steinbach, PJ Sharma, M Amin, ND Barchi, JJ Pant, HC TI Identification of substrate binding site of cyclin-dependent kinase 5 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NEURONAL CDK5 ACTIVATOR; CRYSTAL-STRUCTURE; PROTEIN-KINASE; PHOSPHORYLASE-KINASE; CATALYTIC SUBUNIT; CELL-CYCLE; COMPLEX; RECOGNITION; DYNAMICS; PROGRAM AB Cyclin-dependent kinase 5 (CDK5), unlike other CDKs, is active only in neuronal cells where its neuron-specific activator p35 is present. However, it phosphorylates serines/threonines in S/TPXK/R-type motifs Like other CDKs. The tail portion of neurofilament-H contains more than 50 KSP repeats, and CDK5 has been shown to phosphorylate S/T specifically only in KS/ TPXK motifs, indicating highly specific interactions in substrate recognition. CDKs have been shown to have a high preference for a basic residue (lysine or arginine) as the n+3 residue, n being the location in the primary sequence of a phosphoacceptor serine or threonine, Because of the lack of a crystal structure of a CDK-substrate complex, the structural basis for this specific interaction is unknown, me have used site-directed mutagenesis ("charged to alanine") and molecular modeling techniques to probe the recognition interactions for substrate peptide (PKTPKKAKKL) derived from histone H1 docked in the active site of CDK5, The experimental data and computer simulations suggest that Asp(86) and Asp(91) are key residues that interact with the lysines at positions n+2 and/or n+3 of the substrates. C1 NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. NINDS, Ctr Mol Modeling, Ctr Informat Technol, NIH, Bethesda, MD 20892 USA. NINDS, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Pant, HC (reprint author), NINDS, Neurochem Lab, NIH, Bldg 36,Rm 4D20, Bethesda, MD 20892 USA. EM hcp@codon.nih.gov RI Barchi Jr., Joseph/N-3784-2014 NR 31 TC 33 Z9 35 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 2 PY 1999 VL 274 IS 14 BP 9600 EP 9606 DI 10.1074/jbc.274.14.9600 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 181PX UT WOS:000079451800065 PM 10092646 ER PT J AU Lee, B Sharron, M Blanpain, C Doranz, BJ Vakili, J Setoh, P Berg, E Liu, G Guy, HR Durell, SR Parmentier, M Chang, CN Price, K Tsang, M Doms, RW AF Lee, B Sharron, M Blanpain, C Doranz, BJ Vakili, J Setoh, P Berg, E Liu, G Guy, HR Durell, SR Parmentier, M Chang, CN Price, K Tsang, M Doms, RW TI Epitope mapping of CCR5 reveals multiple conformational states and distinct but overlapping structures involved in chemokine and coreceptor function SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; AMINO-TERMINAL DOMAIN; HIV-1 INFECTION; ENVELOPE GLYCOPROTEINS; DISEASE PROGRESSION; EXTRACELLULAR LOOP; CELL-LINES; V3 LOOP; TYPE-1; RECEPTOR AB The chemokine receptor CCR5 is the major coreceptor for R5 human immunodeficiency virus type-1 strains. We mapped the epitope specificities of 18 CCR5 monoclonal antibodies (mAbs) to identify domains of CCR5 required for chemokine binding, gp120 binding, and for inducing conformational changes in Env that lead to membrane fusion, We identified mAbs that bound to N-terminal epitopes, extracellular loop 2 (ECL2) epitopes, and multidomain (MD) epitopes composed of more than one single extracellular domain. N-terminal mAbs recognized specific residues that span the first 13 amino acids of CCR5, while nearly all ECL2 mAbs recognized residues Tyr-184 to Phe-189. In addition, all MD epitopes involved ECL2, including at least residues Lys-171. and Glu-172, We found that ECL2-specific mAbs were more efficient than NH2- or MD-antibodies in blocking RANTES or MIP-1 beta binding. By contrast, N-terminal mAbs blocked gp120-CCR5 binding more effectively than ECL2 mAbs. Surprisingly, ECL2 mAbs were more potent inhibitors of viral infection than N-terminal mAbs, Thus, the ability to block virus infection did not correlate with the ability to block gp120 binding. Together, these results imply that chemokines and Env bind to distinct but overlapping sites in CCR5, and suggest that the N-terminal domain of CCR5 is more important for gp120 binding while the extracellular loops are more important for inducing conformational changes in Env that lead to membrane fusion and virus infection. Measurements of individual antibody affinities coupled with kinetic analysis of equilibrium binding states also suggested that there are multiple conformational states of CCR5. A previously described mAb, 2D7, was unique in its ability to effectively block both chemokine and Env binding as well as coreceptor activity. 2D7 bound to a unique antigenic determinant in the first half of ECL2 and recognized a far greater proportion of cell surface CCR5 molecules than the other mAbs examined. Thus, the epitope recognized by 2D7 may represent a particularly attractive target for CCR5 antagonists. C1 Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Free Univ Brussels, Inst Interdisciplinary Res, B-1070 Brussels, Belgium. PDL Inc, Fremont, CA USA. NCI, Math Biol Lab, NIH, Bethesda, MD 20892 USA. R&D Syst, Minneapolis, MN 55413 USA. Wistar Inst, Philadelphia, PA 19104 USA. RP Doms, RW (reprint author), Hosp Univ Penn, Dept Pathol & Lab Med, 806 Abramson,34th & Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM doms@mail.med.upenn.edu RI Lee, Benhur/A-8554-2016 OI Lee, Benhur/0000-0003-0760-1709 FU NHLBI NIH HHS [K08 HL03923-01]; PHS HHS [R01-40880, R44 A141299-02] NR 58 TC 287 Z9 294 U1 1 U2 10 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 2 PY 1999 VL 274 IS 14 BP 9617 EP 9626 DI 10.1074/jbc.274.14.9617 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 181PX UT WOS:000079451800067 PM 10092648 ER PT J AU Neufeld, EB Wastney, M Patel, S Suresh, S Cooney, AM Dwyer, NK Roff, CF Ohno, K Morris, JA Carstea, ED Incardona, JP Strauss, JF Vanier, MT Patterson, MC Brady, RO Pentchev, PG Blanchette-Mackie, EJ AF Neufeld, EB Wastney, M Patel, S Suresh, S Cooney, AM Dwyer, NK Roff, CF Ohno, K Morris, JA Carstea, ED Incardona, JP Strauss, JF Vanier, MT Patterson, MC Brady, RO Pentchev, PG Blanchette-Mackie, EJ TI The Niemann-Pick C1 protein resides in a vesicular compartment linked to retrograde transport of multiple lysosomal cargo SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; DISEASE TYPE-C; METHYLAMINE ACCUMULATION; CHOLESTEROL HOMEOSTASIS; INTRACELLULAR-TRANSPORT; MEMBRANE GLYCOPROTEIN; KINETIC EVIDENCE; GM2 GANGLIOSIDE; PLASMA-MEMBRANE; CULTURED-CELLS AB Niemann-Pick C disease (NP-C) is a neurovisceral lysosomal storage disorder. A variety of studies have highlighted defective sterol trafficking from lysosomes in NP-C cells. However, the heterogeneous nature of additional accumulating metabolites suggests that the cellular lesion may involve a more generalized block in retrograde lysosomal trafficking. Immunocytochemical studies in fibroblasts reveal that the NPC1 gene product resides in a novel set of lysosome-associated membrane protein-2 (LAMPS)(+)/ mannose g-phosphate receptor(-) vesicles that can be distinguished from cholesterol-enriched LAMP2(+) lysosomes, Drugs that block sterol transport out of lysosomes also redistribute NPC1 to cholesterol-laden lysosomes. Sterol relocation from lysosomes in cultured human fibroblasts can be blocked at 21 degrees C, consistent with vesicle-mediated transfer. These findings suggest that NPC1(+) vesicles may transiently interact with lysosomes to facilitate sterol relocation. Independent of defective sterol trafficking, NP-C fibroblasts are also deficient in vesicle-mediated clearance of endocytosed [C-14]sucrose. Compartmental modeling of the observed [C-14]sucrose clearance data targets the trafficking defect caused by mutations in NPC1 to an endocytic compartment proximal to lysosomes, Low density lipoprotein uptake by normal cells retards retrograde transport of [C-14]sucrose through this same kinetic compartment, further suggesting that it may contain the sterol-sensing NPC1 protein. We conclude that a distinctive organelle containing NPC1 mediates retrograde lysosomal transport of endocytosed cargo that is not restricted to sterol. C1 NIDDK, Lipid Cell Biol Sect, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Pediat, Div Neonatol, Washington, DC 20007 USA. Vet Affairs Med Ctr, Neurobiol Res Lab, Newington, CT 06111 USA. Tottori Univ, Fac Med, Yanago 6838503, Japan. St Marys Hosp, Saccomanno Res Inst, Grand Junct, CO 81502 USA. Univ Washington, Dept Pediat & Biol Struct, Seattle, WA 98195 USA. Univ Penn, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. Fac Med Lyon Sud, Dept Biochem, F-69921 Oullins, France. Fac Med Lyon Sud, INSERM U189, F-69921 Oullins, France. Mayo Clin & Mayo Fdn, Dept Neurol, Rochester, MN 55905 USA. RP Blanchette-Mackie, EJ (reprint author), NIDDK, Lipid Cell Biol Sect, Lab Cell Biochem & Biol, NIH, Bldg 8,Rm 427,8 Ctr Dr,MSC 0850, Bethesda, MD 20892 USA. EM joanbm@bdg8.niddk.nih.gov OI Patterson, Marc/0000-0002-1116-126X NR 52 TC 291 Z9 295 U1 1 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 2 PY 1999 VL 274 IS 14 BP 9627 EP 9635 DI 10.1074/jbc.274.14.9627 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 181PX UT WOS:000079451800068 PM 10092649 ER PT J AU Li, WM Nagineni, CN Ge, H Efiok, B Chepelinsky, AB Egwuagu, CE AF Li, WM Nagineni, CN Ge, H Efiok, B Chepelinsky, AB Egwuagu, CE TI Interferon consensus sequence-binding protein is constitutively expressed and differentially regulated in the ocular lens SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FACTOR FAMILY; TRANSCRIPTION FACTORS; GAMMA-INTERFERON; ALPHA-CRYSTALLIN; GENE-EXPRESSION; TRANSGENIC MICE; HISTONE GENE; ICSBP GENE; IFN; RESPONSES AB Interferon signaling is mediated by STATs and interferon regulatory factor (IRF) families of transcription factors. Ten distinct IRFs have been described and most are expressed in a variety of cells except for interferon consensus sequence-binding protein (ICSBP) and lymphoid-specific IRF/Pip that are thought to be exclusively expressed in lymphoid cells. We show here for the first time that ICSBP is constitutively and inducibly expressed in the mouse lens, In contrast to lymphoid cells with exclusive expression of ICSBP in the nucleus, ICSBP is present in both the cytoplasm and nucleus of the lens cell. However, ICSBP in the nucleus is of lower apparent molecular weight. We further show that the ICSBP promoter is constitutively bound by lens nuclear factors and that its activation requires binding of additional factors including STAT1. Furthermore, transcriptional activation of ICSBP gene by interferon gamma is accompanied by selective nuclear localization of ICSBP in proliferating epithelial cells but not in the nuclei of nondividing cells in the lens fiber compartment. Constitutive and inducible expression of ICSBP in the ocular lens and differential regulation of its subcellular localization in the developing lens suggest that ICSBP may have nonimmunity related functions and that the commonly held view that it is lymphoid-specific be modified. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Lab Mol Hematol, NIH, Bethesda, MD 20892 USA. RP Egwuagu, CE (reprint author), NEI, Immunol Lab, NIH, Bldg 10,10-10N116,10 Ctr Dr,1858, Bethesda, MD 20892 USA. NR 36 TC 20 Z9 20 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 2 PY 1999 VL 274 IS 14 BP 9686 EP 9691 DI 10.1074/jbc.274.14.9686 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 181PX UT WOS:000079451800075 PM 10092656 ER PT J AU Steinert, PM Chou, YH Prahlad, V Parry, DAD Marekov, LN Wu, KC Jang, SI Goldman, RD AF Steinert, PM Chou, YH Prahlad, V Parry, DAD Marekov, LN Wu, KC Jang, SI Goldman, RD TI A high molecular weight intermediate filament-associated protein in BHK-21 cells is nestin, a type VI intermediate filament protein - Limited co-assembly in vitro to form heteropolymers with type III vimentin and type IV alpha-internexin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COILED-COIL; NF-L; END DOMAINS; ROD DOMAIN; IN-VIVO; INVITRO; EXPRESSION; MOUSE; RAT; GENE AB BHK-21 fibroblasts contain type III vimentin/desmin intermediate filament (IF) proteins that typically coisolate and co-cycle in in vitro experiments with certain high molecular weight proteins. Here, we report purification of one of these and demonstrate that it is in fact the type VI IF protein nestin, Nestin is expressed in several fibroblastic but not epithelioid cell lines. We show that nestin forms homodimers and homotetramers but does not form IF by itself in vitro, In mixtures, nestin preferentially co-assembles with purified vimentin or the type IV IF protein alpha-internexin to form heterodimer coiled-coil molecules. These molecules may co-assemble into 10 nm IF provided that the total amount of nestin does not exceed about 25%. However, nestin does not dimerize with types I/II keratin IF chains. The bulk of the nestin protein consists of a long carboxyl-terminal tail composed of various highly charged peptide repeats. By analogy with the larger neurofilament chains, we postulate that these sequences serve as cross-bridgers or spacers between IF and/or other cytoskeletal constituents. In this way, we propose that direct incorporation of modest amounts of nestin into the backbone of cytoplasmic types III and IV Ifs affords a simple yet flexible method for the regulation of their dynamic supramolecular organization and function in cells. C1 NIAMSD, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. Northwestern Univ, Sch Med, Dept Cell & Mol Biol, Chicago, IL 60611 USA. Massey Univ, Inst Fundamental Sci, Palmerston North, New Zealand. RP Steinert, PM (reprint author), NIAMSD, Skin Biol Lab, NIH, Bldg 6,Rm 425,9000 Rockville Pike, Bethesda, MD 20892 USA. EM pemast@helix.nih.gov FU NIGMS NIH HHS [GM36806-4] NR 70 TC 125 Z9 132 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 2 PY 1999 VL 274 IS 14 BP 9881 EP 9890 DI 10.1074/jbc.274.14.9881 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 181PX UT WOS:000079451800099 PM 10092680 ER PT J AU Bartolotti, L Kakuta, Y Pedersen, L Negishi, M Pedersen, L AF Bartolotti, L Kakuta, Y Pedersen, L Negishi, M Pedersen, L TI A quantum mechanical study of the transfer of biological sulfate SO JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM LA English DT Article DE sulfuryl transfer; transition state; DFT; enzyme mechanism; sulfotransferases ID 3'-PHOSPHOADENOSINE 5'-PHOSPHOSULFATE; SULFOTRANSFERASES; HYDROLYSIS AB The biological process of enzymatic sulfuryl group transfer has been studied by ab initio (density-functional and Hartree-Fock) and semiempirical quantum mechanical methods. The active site of estrogen sulfotransferase in ternary complex with a sulfate donor(PAPS) and sulfate acceptor (estradiol) is modeled. The mechanism proposed in a recent X-ray crystal structure paper (Kakuta et al., Nat. Struct. Biol. 4 (1997) 904) serves as the basis for the calculations. We find that the mechanism proposed in the crystallographic paper is reasonable. The sulfonation takes place in several key steps: neutralization of the charge on PAPS, lengthening of the bridging S-O bond with no cost in energy, activation of the attacking oxygen and proton transfer from estradiol to histidine and then to the sulfuryl group. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Natl Inst Environm Hlth Sci, N Carolina Supercomp Ctr, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. RP Pedersen, L (reprint author), Natl Inst Environm Hlth Sci, N Carolina Supercomp Ctr, Res Triangle Pk, NC 27709 USA. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 NR 14 TC 4 Z9 4 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-1280 J9 J MOL STRUC-THEOCHEM JI Theochem-J. Mol. Struct. PD APR 2 PY 1999 VL 461 BP 105 EP 111 DI 10.1016/S0166-1280(98)00424-2 PG 7 WC Chemistry, Physical SC Chemistry GA 178KR UT WOS:000079265300011 ER PT J AU Zamostiano, R Pinhasov, A Bassan, M Perl, O Steingart, RA Atlas, R Brenneman, DE Gozez, I AF Zamostiano, R Pinhasov, A Bassan, M Perl, O Steingart, RA Atlas, R Brenneman, DE Gozez, I TI A femtomolar-acting neuroprotective peptide induces increased levels of heat shock protein 60 in rat cortical neurons: a potential neuroprotective mechanism SO NEUROSCIENCE LETTERS LA English DT Article DE hsp60; activity-dependent neurotrophic factor; stress proteins; neurons ID DEPENDENT NEUROTROPHIC FACTOR; FATTY NEUROPEPTIDE; CELL-DEATH; DISEASE AB Activity-dependent neurotrophic factor (ADNF) was recently isolated from conditioned media of astrocytes stimulated with vasoactive intestinal peptide (VIP). ADNF provided neuroprotection at femtomolar concentration against a wide variety of toxic insults. A nine amino acid peptide (ADNF-9) captured with even greater potency the neuroprotective activity exhibited by the parent protein. Utilizing Northern and Western blot analyses, it was now shown that ADNF-9 increased the expression of heat shock protein 60 (hsp60) in rat cerebral cortical cultures. In contrast, treatment with the Alzheimer's toxin, the beta-amyloid peptide, reduced the amount of intracellular hsp60. Treatment with ADNF-9 prevented the reduction in hsp60 produced by the beta-amyloid peptide. The protection against the beta-amyloid peptide-associated cell death provided by ADNF-9 may be mediated in part by intracellular increases in hsp60. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Tel Aviv Univ, Sackler Sch Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. NICHD, Dev Neurobiol Lab, Sect Dev & Mol Pharmacol, NIH, Bethesda, MD 20892 USA. RP Gozez, I (reprint author), Tel Aviv Univ, Sackler Sch Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. NR 17 TC 37 Z9 38 U1 0 U2 7 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD APR 2 PY 1999 VL 264 IS 1-3 BP 9 EP 12 DI 10.1016/S0304-3940(99)00168-8 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 189LR UT WOS:000079906900003 PM 10320001 ER PT J AU Grigoriev, V Escaig-Haye, F Streichenberger, N Kopp, N Langeveld, J Brown, P Fournier, JG AF Grigoriev, V Escaig-Haye, F Streichenberger, N Kopp, N Langeveld, J Brown, P Fournier, JG TI Submicroscopic immunodetection of PrP in the brain of a patient with a new-variant of Creutzfeldt-Jakob disease SO NEUROSCIENCE LETTERS LA English DT Article DE prion protein; synapse; florid plaques; immune-electron microscopy; Creutzfeldt-Jakob disease ID PRION-PROTEIN; LOCALIZATION; SCRAPIE; TISSUE; CJD AB We analyzed the distribution and organization of the pathological prion protein isoform (PrPsc) in the brain of new variant Creutzfeldt-Jakob disease using a sensitive post-embedding immunogold electron microscopy method. On methacrylate semithin sections, silver-PrP staining showed florid plaques, containing microvacuoles. It also revealed scattered granular and perivacuolar deposits. At the electron microscope level, plaque PrP-gold labeling was associated with filaments and flocculent amorphous material sometimes observed inside microvacuoles, considered as degenerative neurites. Outside the plaques, PrP-gold labeling was predominantly found over flocculent amorphous material and the presynaptic domain of synapses. Some lysosome-like organelles seen in the neuron perikaryon, were also found to be PrP-immunoreactive. These results are consistent with the hypothesis that the synapse is a privileged target in prion disease. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Hop La Pitie Salpetriere, Inst Myol, INSERM, U523, F-75651 Paris 13, France. Hop Neurol, Neuropathol Lab, F-69394 Lyon, France. DLO, ID, Inst Anim Sci & Hlth, NL-8200 Lelystad, Netherlands. NINDS, Cent Nervous Syst Studies Lab, NIH, Bethesda, MD 20892 USA. RP Fournier, JG (reprint author), Hop La Pitie Salpetriere, Inst Myol, INSERM, U523, 47 Blvd Hop, F-75651 Paris 13, France. NR 20 TC 30 Z9 33 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD APR 2 PY 1999 VL 264 IS 1-3 BP 57 EP 60 DI 10.1016/S0304-3940(99)00146-9 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 189LR UT WOS:000079906900015 PM 10320013 ER PT J AU Beam, CA Guse, CE Sullivan, DC AF Beam, CA Guse, CE Sullivan, DC TI A sequential chart for the audit-based evaluation of screening mammogram interpretation SO ACADEMIC RADIOLOGY LA English DT Article DE breast radiography; quality assurance ID DATA-COLLECTION; MEDICAL AUDIT; COMMUNITY AB Rationale and Objectives, Auditing has received much attention recently as a method for radiologists to use to evaluate their interpretation of screening mammograms, U.S. Food and Drug Administration regulations require that some sort of audit be in place before a mammography screening facility can receive accreditation. Auditing presents a unique opportunity to monitor accuracy continually and identify problems early. Audit data present unique challenges, however, and appropriate methods must be used to control the risk of errors. Materials and Methods. This article introduces a simple method for the task of deciding if a radiologist yields an acceptable positive predictive value based on audit. The method is based on "sequential" decision-making techniques that have found wide application in quality control problems. These techniques are developed for diagnostic radiology and embodied in an easy-to-use decision-making chart. Results. Several examples, based on audit data from actual mammography facilities, provide insights into the use of these charts and the influence of (a) the selection of standards, (b) the selection of error risks, and (c) radiologist variability. The tramples also serve to demonstrate another important property of this method-that is, it specifies the minimum amount of data that has to be collected before any decision can reliably be made. Conclusion. The chart presented in this article provides a method by which audit data can be used objectively to evaluate the accuracy of screening mammogram interpretation. The method controls the risk of either falsely accepting an unqualified radiologist or falsely rejecting a qualified radiologist, It should be a useful tool to radiologists who must evaluate their own practices. C1 Northwestern Univ, Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. Med Coll Wisconsin, Dept Family & Community Med, Milwaukee, WI 53226 USA. Natl Canc Inst, Rockville, MD USA. RP Beam, CA (reprint author), Northwestern Univ, Sch Med, Robert H Lurie Comprehens Canc Ctr, 680 N Lake Shore Dr,Suite 1102, Chicago, IL 60611 USA. NR 16 TC 2 Z9 2 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD APR PY 1999 VL 6 IS 4 BP 216 EP 223 DI 10.1016/S1076-6332(99)80208-6 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 296PH UT WOS:000086032500004 PM 10894079 ER PT J AU Leube, B Kessler, KR Ferbert, A Ebke, M Schwendemann, G Erbguth, F Benecke, R Auburger, G AF Leube, B Kessler, KR Ferbert, A Ebke, M Schwendemann, G Erbguth, F Benecke, R Auburger, G TI Phenotypic variability of the DYT1 mutation in German dystonia patients SO ACTA NEUROLOGICA SCANDINAVICA LA English DT Article DE dystonia; DYT1; phenotype ID IDIOPATHIC TORSION DYSTONIA; ASHKENAZI JEWS; GENE DYT1; ONSET; EXPRESSION AB Primary dystonia is a clinically and genetically heterogeneous movement disorder characterized by sustained involuntary muscle contractions causing repetitive movements and/or abnormal pastures. Recently, the gene locus (DYT1) and mutation responsible for a substantial number of cases suffering from early-onset primary dystonia was described. Here we report 2 German families and 1 sporadic patient with early-onset dystonia due to the DYT1 mutation in order to illustrate the variability of clinical manifestation within this molecularly defined entity. We demonstrate that writer's cramp or focal cervical dystonia is a clinical presentation of DYT1 as well as generalized dystonia. C1 Univ Dusseldorf, Dept Neurol, D-40001 Dusseldorf, Germany. Stadt Kliniken, Dept Neurol, D-34112 Kassel, Germany. Zent Krankenhaus Bremen Ost, Dept Neurol, D-28325 Bremen, Germany. Univ Erlangen, Dept Neurol, D-91054 Erlangen, Germany. Univ Rostock, Dept Neurol, D-18147 Rostock, Germany. Natl Human Genome Res Inst, NIH, Bethesda, MD USA. RP Leube, B (reprint author), Univ Dusseldorf, Dept Human Genet, POB 101007, D-40001 Dusseldorf, Germany. NR 14 TC 32 Z9 33 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-6314 J9 ACTA NEUROL SCAND JI Acta Neurol. Scand. PD APR PY 1999 VL 99 IS 4 BP 248 EP 251 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 184HT UT WOS:000079606400009 PM 10225357 ER PT J AU Knight, RT Staines, WR Swick, D Chao, LL AF Knight, RT Staines, WR Swick, D Chao, LL TI Prefrontal cortex regulates inhibition and excitation in distributed neural networks SO ACTA PSYCHOLOGICA LA English DT Review DE prefrontal; inhibition; excitation; attention; schizophrenia ID EVENT-RELATED POTENTIALS; FRONTAL-LOBE LESIONS; CEREBRAL BLOOD-FLOW; SOMATOSENSORY EVOKED-POTENTIALS; AUDITORY SELECTIVE ATTENTION; WORKING-MEMORY TASKS; CYTOARCHITECTONIC DEFINITION; VENTROPOSTERIOR THALAMUS; AFFERENT TRANSMISSION; BRAIN POTENTIALS AB Prefrontal cortex provides both inhibitory and excitatory input to distributed neural circuits required to support performance in diverse tasks. Neurological patients with prefrontal damage are impaired in their ability to inhibit task-irrelevant information during behavioral tasks requiring performance over a delay. The observed enhancements of primary auditory and somatosensory cortical responses to task-irrelevant distracters suggest that prefrontal damage disrupts inhibitory modulation of inputs to primary sensory cortex, perhaps through abnormalities in a prefrontal-thalamic sensory gating system. Failure to suppress irrelevant sensory information results in increased neural noise, contributing to the deficits in decision making routinely observed in these patients. In addition to a critical role in inhibitory control of sensory flow to primary cortical regions, and tertiary prefrontal cortex also exerts excitatory input to activity in multiple sub-regions of secondary association cortex. Unilateral prefrontal damage results in multi-modal decreases in neural activity in posterior association cortex in the hemisphere ipsilateral to damage. This excitatory modulation is necessary to sustain neural activity during working memory. Thus, prefrontal cortex is able to sculpt behavior through parallel inhibitory and excitatory regulation of neural activity in distributed neural networks. (C) 1999 Elsevier Science B.V. All rights reserved. PsycINFO classifications: 2346; 2520; 2530; 2540; 3213; 3297. C1 Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA. Univ Calif Davis, Dept Neurol, Ctr Vet Med, Martinez, CA 94553 USA. Univ Calif Davis, Ctr Neurosci, Ctr Vet Med, Martinez, CA 94553 USA. NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Knight, RT (reprint author), Univ Calif Berkeley, Dept Psychol, 3210 Tolman Hall, Berkeley, CA 94720 USA. FU NINDS NIH HHS [NS21135]; PHS HHS [P017778] NR 113 TC 295 Z9 297 U1 4 U2 24 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0001-6918 J9 ACTA PSYCHOL JI Acta Psychol. PD APR PY 1999 VL 101 IS 2-3 BP 159 EP 178 DI 10.1016/S0001-6918(99)00004-9 PG 20 WC Psychology, Experimental SC Psychology GA 197VP UT WOS:000080386800003 PM 10344184 ER PT J AU DePetrillo, PB White, KV Liu, M Hommer, D Goldman, D AF DePetrillo, PB White, KV Liu, M Hommer, D Goldman, D TI Effects of alcohol use and gender on the dynamics of EKG time-series data SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcoholism; EKG; nonlinear dynamics; fractals ID HEART-RATE-VARIABILITY; AUTONOMIC NEUROPATHY; SEROTONIN; MORTALITY; RESPONSES; DISEASE AB Hurst analysis of EKG data obtained from a population of alcoholic (n = 13) and nonalcoholic (n = 48) subjects was undertaken. Potential subjects (n = 120) were screened using the Schedule for Affective Disorders and Schizophrenia and Structured Clinical Interview for DSM-III instruments. Data from subjects with a diagnosis of current alcohol dependence were analyzed. Subjects with diagnoses such as major depression, bipolar disorder or schizophrenia (Axis I diagnoses), or personality disorders (Axis II diagnoses) were excluded from analysis. Subjects undergoing testing were free of alcohol and illicit drugs. Alcoholic subjects had no clinical evidence of alcohol withdrawal symptoms at the time of testing. EKG data were obtained with eyes open or with eyes closed. Approximately 3.5 min of data were obtained for each condition. Alcoholic subjects had less complex heart rate dynamics as evidenced by higher values of H = 0.18 +/- 0.05 (mean +/- SEM), compared with healthy comparison subjects with H = 0.09 +/- 0.02, p < 0.014 for the eyes closed condition, and H = 0.17 +/- 0.05 (mean +/- SEM) compared with healthy comparison subjects with H = 0.07 +/- 0.02, p < 0.011 for the eyes open condition. A gender effect was seen, with female subjects showing evidence of more complex heart rate dynamics than male subjects. C1 NIAAA, Clin Studies Lab, Intramural Res Program, NIH, Bethesda, MD 20892 USA. NIAAA, Neurogenet Lab, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP DePetrillo, PB (reprint author), NIAAA, Clin Studies Lab, Intramural Res Program, NIH, 10-3C103,10 Ctr Dr,MSC 1256, Bethesda, MD 20892 USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 32 TC 13 Z9 13 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD APR PY 1999 VL 23 IS 4 BP 745 EP 750 DI 10.1097/00000374-199904001-00022 PG 6 WC Substance Abuse SC Substance Abuse GA 189XK UT WOS:000079931300024 PM 10235312 ER PT J AU Asthana, S Raffaele, KC Greig, NH Schapiro, MB Blackman, MR Soncrant, TT AF Asthana, S Raffaele, KC Greig, NH Schapiro, MB Blackman, MR Soncrant, TT TI Neuroendocrine responses to intravenous infusion of physostigmine in patients with Alzheimer disease SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE physostigmine; HPA-axis; Alzheimer disease; memory; cortisol ID CORTICOTROPIN-RELEASING HORMONE; CEREBROSPINAL-FLUID; MEMORY; ARECOLINE; PITUITARY; ACETYLCHOLINE; CORTISOL; DEMENTIA; TACRINE; SYSTEM AB We have reported that physostigmine, a reversible cholinesterase inhibitor, enhances verbal memory in patients with Alzheimer disease (AD). To elucidate the mechanism of cognition enhancement, plasma hormones were measured during high-dose acute and low-dose chronic steady-state intravenous infusions of physostigmine in nine subjects with AD. High-dose hormone responses were measured during and for 24 h after the infusion of physostigmine 1-1.5 mg over 45-60 min. Chronic responses were measured during continuous intravenous infusions of physostigmine at doses (0.5-25 mg/day) that escalated over 2 weeks, and then during 1 week infusion of the dose that optimized cognition (2-12 mg/day) or placebo administered in a randomized double-blind, crossover design. A replicable improvement in verbal memory was found in five subjects. High-dose physostigmine infusion that produced noxious side effects resulted in significant elevation above baseline in plasma levels of adrenocorticotrophic hormone (ACTH) (p = 0.0001), cortisol (p = 0.0001), and beta-endorphin (p = 0.0001). Chronic physostigmine administration, in the absence of adverse effects, produced no significant elevation in ACTH (p = 0.08), cortisol (p = 0.70), or beta-endorphin (p = 0.82). These results indicate that high-dose physostigmine activates the hypothalamic-pituitary-adrenal (HPA) axis, likely representing a "stress response." In contrast, cognition-enhancing doses do not produce a peripheral corticosteroid response. Thus, physostigmine-induced memory improvement is independent of the activation of the HPA axis. C1 NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. US FDA, Washington, DC 20204 USA. Johns Hopkins Univ, Sch Med, Hopkins Bayview Med Ctr, Baltimore, MD USA. RP Asthana, S (reprint author), VA Puget Sound Hlth Care Syst, Amer Lake Div, GRECC 182 B, Tacoma, WA 98493 USA. NR 40 TC 5 Z9 5 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD APR-JUN PY 1999 VL 13 IS 2 BP 102 EP 108 DI 10.1097/00002093-199904000-00008 PG 7 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 268NQ UT WOS:000084422800008 PM 10372954 ER PT J AU Shiota, T Jones, M Agler, DA McDonald, RW Marcella, CP Qin, JX Zetts, AD Greenberg, NL Cardon, LA Sun, JP Sahn, DJ Thomas, JD AF Shiota, T Jones, M Agler, DA McDonald, RW Marcella, CP Qin, JX Zetts, AD Greenberg, NL Cardon, LA Sun, JP Sahn, DJ Thomas, JD TI New echocardiographic windows for quantitative determination of aortic regurgitation volume using color Doppler flow convergence and vena contracta SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID MITRAL REGURGITATION; VALVULAR REGURGITATION; ORIFICE AREA; IN-VITRO; QUANTIFICATION; INSUFFICIENCY; VISUALIZATION; CONSTRAINT; VALIDATION; SEVERITY AB Color Doppler images of aortic regurgitation (AR) flow acceleration, flow convergence (FC), and the vena contracta (VC) have been reported to be useful for evaluating severity of AR. However, clinical application of these methods has been limited because of the difficulty in clearly imaging the FC and VC. This study aimed to explore new windows for imaging the FC and VC to evaluate AR volumes in patients and to validate this in animals with chronic AR. Forty patients with AR and 17 hemodynamic states in 4 sheep with strictly quantified AR volumes were evaluated. A Toshiba SSH 380A with a 3.75-MHz transducer was used to image the FC and VC. After routine echo Doppler imaging, patients were repositioned in the right lateral decubitus position, and the FC and VC were imaged from high right parasternal windows. In only 15 of the 40 patients was it possible to image clearly and measure accurately the FC and VC from conventional (left decubitus) apical or parasternal views. In contrast, 31 of 40 patients had clearly imaged FC regions and VCs using the new windows. In patients, AR volumes derived from the FC and VC methods combined with continuous velocity agreed well with each other (r = 0.97, mean difference = -7.9 ml +/- 9.9 ml/beat). In chronic animal model studies, AR volumes derived from both the VC and the FC agreed well with the electromagnetically derived AR volumes (r = 0.92, mean difference = -1.3 +/- 4.0 ml/beat). By imaging from high right parasternal windows in the right decubitus position, complementary use of the FC and VC methods can provide clinically valuable information about AR volumes.. (C) 1999 by Excerpta Medica, Inc. C1 Cleveland Clin Fdn, Dept Cardiol, Cleveland, OH 44195 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Oregon Hlth Sci Univ, Ctr Congenital Heart Dis, Portland, OR 97201 USA. RP Shiota, T (reprint author), Cleveland Clin Fdn, Dept Cardiol, F15,9500 Euclid Ave, Cleveland, OH 44195 USA. NR 21 TC 10 Z9 11 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 1 PY 1999 VL 83 IS 7 BP 1064 EP 1068 DI 10.1016/S0002-9149(99)00016-8 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 179ZK UT WOS:000079360100015 PM 10190521 ER PT J AU Tucker, KL Hannan, MT Chen, HL Cupples, LA Wilson, PWF Kiel, DP AF Tucker, KL Hannan, MT Chen, HL Cupples, LA Wilson, PWF Kiel, DP TI Potassium, magnesium, and fruit and vegetable intakes are associated with greater bone mineral density in elderly men and women SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE bone mineral density; dietary intake; magnesium; potassium; fruit; vegetables; elderly; osteoporosis; food-frequency questionnaire ID FOOD FREQUENCY QUESTIONNAIRE; DUAL-PHOTON ABSORPTIOMETRY; POSTMENOPAUSAL WOMEN; OSTEOPOROTIC FRACTURES; PREMENOPAUSAL WOMEN; CONTROLLED TRIAL; TRABECULAR BONE; DIETARY-INTAKE; UNITED-STATES; ENERGY-INTAKE AB Background: Osteoporosis and related fractures will be growing public health problems as the population ages. It is therefore of great importance to identify modifiable risk factors. Objective: We investigated associations between dietary components contributing to an alkaline environment (dietary potassium, magnesium, and fruit and vegetables) and bone mineral density (BMD) in elderly subjects. Design: Dietary intake measures were associated with both cross-sectional (baseline) and 4-y longitudinal change in BMD among surviving members of the original cohort of the Framingham Heart Study. Dietary and supplement intakes were assessed by food-frequency questionnaire, and BMD was measured at 3 hip sites and 1 forearm site. Results: Greater potassium intake was significantly associated with greater BMD at all 4 sites for men and at 3 sites for women (P < 0.05). Magnesium intake was associated with greater BMD at one hip site for both men and women and in the forearm for men. Fruit and vegetable intake was associated with BMD at 3 sites for men and 2 for women. Greater intakes of potassium and magnesium were also each associated with less decline in BMD at 2 hip sites, and greater fruit and vegetable intake was associated with less decline at 1 hip site, in men. There were no significant associations between baseline diet and subsequent bone loss in women. Conclusion: These results support the hypothesis that alkaline-producing dietary components, specifically, potassium, magnesium, and fruit and vegetables, contribute to maintenance of BMD. C1 Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Harvard Univ, Sch Med, Div Aging, Boston, MA 02115 USA. Hebrew Rehabil Ctr Aged, Boston, MA 02131 USA. Boston Univ, Sch Publ Hlth, Dept Biostat & Epidemiol, Boston, MA 02215 USA. NHLBI, Bethesda, MD 20892 USA. RP Tucker, KL (reprint author), Tufts Univ, USDA, Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA. RI Tucker, Katherine/A-4545-2010; OI Kiel, Douglas/0000-0001-8474-0310; Tucker, Katherine/0000-0001-7640-662X; Chen, Honglei/0000-0003-3446-7779 FU NHLBI NIH HHS [N01-HC-38038]; NIAMS NIH HHS [R01 AR/AG 41398] NR 55 TC 356 Z9 364 U1 3 U2 20 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 1999 VL 69 IS 4 BP 727 EP 736 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 181GX UT WOS:000079434100020 PM 10197575 ER PT J AU Story, M Evans, M Fabsitz, RR Clay, TE Rock, BH Broussard, B AF Story, M Evans, M Fabsitz, RR Clay, TE Rock, BH Broussard, B TI The epidemic of obesity in American Indian communities and the need for childhood obesity-prevention programs SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE obesity; risk factors; American Indians; Native Americans; physical activity; diet; children; school-based programs; cardiovascular disease; diabetes mellitus ID BODY-MASS INDEX; NUTRITION SURVEY; NAVAJO INDIANS; DIABETES-MELLITUS; PIMA-INDIANS; RISK-FACTORS; PRESCHOOL-CHILDREN; PHYSICAL-ACTIVITY; NATIVE-AMERICANS; BLOOD-PRESSURE AB American Indians of all ages and both sexes have a high prevalence of obesity. The high prevalence of diabetes mellitus in American Indians shows the adverse effects that obesity has in these communities. Obesity has become a major health problem in American Indians only in the past 1-2 generations and is believed to be associated with the relative abundance of high-fat foods and the rapid change from active to sedentary lifestyles. Intervention studies are urgently needed in American Indian communities to develop and test effective strategies for weight reduction. The poor success rate of adult obesity treatment programs in the general population points to the need to develop prevention approaches aimed toward children. Because eating and physical activity practices are formed early in life and may be carried into adulthood, prevention programs that encourage increased physical activity and healthful eating habits targeted toward young people need to be developed and tested. To be most effective, interventions must be developed with full participation of the American Indian communities. Am J Clin Nutr 1999;69(suppl):747S-54S. C1 Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55454 USA. NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. Univ New Mexico, Dept Pediat, Albuquerque, NM 87131 USA. Hlth Care Consultants, Albuquerque, NM USA. RP Story, M (reprint author), Univ Minnesota, Sch Publ Hlth, Div Epidemiol, 1300 S 2nd St,Suite 300, Minneapolis, MN 55454 USA. EM story@epivax.epi.unm.edu FU NHLBI NIH HHS [U01-HL-50905, U01-HL-50867, U01-HL-50885] NR 78 TC 100 Z9 101 U1 0 U2 13 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 1999 VL 69 IS 4 SU S BP 747S EP 754S PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 183PU UT WOS:000079562800002 PM 10195597 ER PT J AU Davis, CE Hunsberger, S Murray, DM Fabsitz, RR Himes, JH Stephenson, LK Caballero, B Skipper, B AF Davis, CE Hunsberger, S Murray, DM Fabsitz, RR Himes, JH Stephenson, LK Caballero, B Skipper, B TI Design and statistical analysis for the Pathways study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE American Indians; Native Americans; obesity prevention; study design; school-based studies; children; percentage body fat AB We report the design, rationale, and statistical procedures used in Pathways, a randomized, school-based intervention for the primary prevention of obesity in American Indian children. The intervention, which is now being implemented in 7 American Indian communities around thr country, includes a health-promotion curriculum, a physical education program, a school meal program, and a family involvement component. Forty-one schools serving American Indian children were randomly assigned to be either intervention or control groups. The intervention will begin in the third grade and continue through the end of the fifth grade. Efficacy of intervention will be assessed by differences in mean percentage body fat, calculated by a prediction equation, between intervention and control schools at the end of the fifth grade. Power computations indicate that the study has power to detect a mean difference of 2.8% in body fat. Data analysis will, use intention-to-treat concepts and the mixed linear model. The study will be completed in 2000. Am J Clin Nutr 1999; 69(suppl):760S-3S. C1 Univ N Carolina, Dept Biostat, Sch Publ Hlth, Chapel Hill, NC 27514 USA. NHLBI, NIH, Bethesda, MD USA. Univ Minnesota, Sch Publ Hlth, Dept Epidemiol, Minneapolis, MN 55455 USA. Gila River Indian Community, Sacatron, AZ USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Nutr, Baltimore, MD 21218 USA. Univ New Mexico, Ctr Hlth Promot & Dis Prevent, Albuquerque, NM 87131 USA. RP Davis, CE (reprint author), Univ N Carolina, Dept Biostat, Sch Publ Hlth, CB 8030, Chapel Hill, NC 27514 USA. EM Ed_davis@unc.edu FU NHLBI NIH HHS [U01-HL-50867, U01-HL-50869, U01-HL-50905] NR 14 TC 31 Z9 31 U1 0 U2 2 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 1999 VL 69 IS 4 SU S BP 760S EP 763S PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 183PU UT WOS:000079562800004 PM 10195599 ER PT J AU Lohman, TG Caballero, B Himes, JH Hunsberger, S Reid, R Stewart, D Skipper, B AF Lohman, TG Caballero, B Himes, JH Hunsberger, S Reid, R Stewart, D Skipper, B TI Body composition assessment in American Indian children SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE body composition; obesity; body fat; adiposity; American Indians; Native Americans; school-age children; schoolchildren; skinfold thickness; bioelectrical impedance; body mass index ID TRENDS AB Although the high prevalence of obesity in American Indian children was documented in several surveys that used body mass index (BMI, in kg/m(2)) as the measure, there is limited information on more direct measurements of body adiposity in this population. The present study evaluated body composition in 81 boys (aged 11.2 +/- 0.6 y) and 75 girls (aged 11.0 +/- 0.4 y) attending public schools in 6 American Indian communities: White Mountain Apache, Pima, and Tohono O'Odham in Arizona: Oglala Lakota and Sicangu Lakota in South Dakota; and Navajo in New Mexico and Arizona. These communities were participating in the feasibility phase of Pathways, a multicenter intervention for the primary prevention of obesity. Body composition was estimated by using a combination of skinfold thickness and bioelectrical impedance measurements, with a prediction equation validated previously in this same population. The mean BMI was 20.4 +/- 4.2 for boys and 21.1 +/- 5.0 for girls. The sum of the triceps plus subscapular skinfold thicknesses averaged 28.6 +/- 7.0 mm in boys and 34.0 +/- 8.0 mm in girls. Mean percentage body fat was 35.6 +/- 6.9 in boys and 38.8 +/- 8.5 in girls. The results from this study confirmed the high prevalence of excess body fatness in school-age American Indian children and permitted the development of procedures, training, and quality control for measurement of the main outcome variable in the full-scale Pathways study. Am J Clin Nutr 1999;69(suppl):764S-6S. C1 Univ Arizona, Dept Physiol, Tucson, AZ 85721 USA. Johns Hopkins Univ, Ctr Human Nutr, Baltimore, MD USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. Univ New Mexico, Albuquerque, NM 87131 USA. RP Lohman, TG (reprint author), Univ Arizona, Dept Physiol, 114 Ina Gittings Bldg, Tucson, AZ 85721 USA. NR 5 TC 26 Z9 26 U1 0 U2 2 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 1999 VL 69 IS 4 SU S BP 764S EP 766S PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 183PU UT WOS:000079562800005 ER PT J AU Gittelsohn, J Evans, M Story, M Davis, SM Metcalfe, L Helitzer, DL Clay, TE AF Gittelsohn, J Evans, M Story, M Davis, SM Metcalfe, L Helitzer, DL Clay, TE TI Multisite formative assessment for the Pathways study to prevent obesity in American Indian schoolchildren SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE formative assessment methods; formative research; obesity prevention; American Indian children; schools; social learning theory; Pathways; eating behaviors; physical activity ID OJIBWAY-CREE; INTERVENTION; CHEMOPROPHYLAXIS; COMMUNITY; PREGNANCY; CHILDREN AB We describe the formative assessment process, using an approach based on social learning theory, for the development of a school-based obesity-prevention intervention into which cultural perspectives are integrated. The feasibility phase of the Pathways study was conducted in multiple settings in 6 American Indian nations. The Pathways formative assessment collected both qualitative and quantitative data. The qualitative data identified key social and environmental issues and enabled local people to express their own needs and views. The quantitative, structured data permitted comparison across sites. Both types of data were integrated by using a conceptual and procedural model. The formative assessment results were used to identify and rank the behavioral risk factors that were to become the focus of the Pathways intervention and to provide guidance on developing common intervention strategies that would be culturally appropriate and acceptable to all sites. Am J Clin Nutr 1999;69(suppl):767S-72S. C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Int Hlth, Div Human Nutr, Baltimore, MD 21205 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. Univ New Mexico, Sch Med, Ctr Hlth Promot Amer Indian Communities, Albuquerque, NM 87131 USA. Univ Arizona, Coll Med, Tucson, AZ USA. RP Gittelsohn, J (reprint author), Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Int Hlth, Div Human Nutr, 615 N Wolfe St, Baltimore, MD 21205 USA. FU NHLBI NIH HHS [U01 HL050905, U01 HL050907, U01 HL050867, U01 HL050869, U01 HL050885] NR 39 TC 39 Z9 39 U1 2 U2 9 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 1999 VL 69 IS 4 SU S BP 767S EP 772S PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 183PU UT WOS:000079562800006 PM 10195601 ER PT J AU Going, SB Levin, S Harrell, J Stewart, D Kushi, L Cornell, CE Hunsberger, S Corbin, C Sallis, J AF Going, SB Levin, S Harrell, J Stewart, D Kushi, L Cornell, CE Hunsberger, S Corbin, C Sallis, J TI Physical activity assessment in American Indian schoolchildren in the Pathways study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE physical activity; assessment; American Indians; children; obesity; energy expenditure; accelerometers; Pathways study; recall questionnaire ID DOUBLY LABELED WATER; ENERGY-EXPENDITURE; SELF-REPORT; 5TH-GRADE STUDENTS; ACTIVITY MONITOR; YOUNG-CHILDREN; MOTION SENSORS; HEART-RATE; VALIDATION; ACCELEROMETER AB The objective of the Pathways physical activity feasibility study was to develop methods for comparing type and amount of activity between intervention and control schools participating in a school-based obesity prevention program. Two methods proved feasible: I) a specially designed 24-h physical activity recall questionnaire for assessing the frequency and type of activities and 2) use of a triaxial accelerometer for assessing amount of activity. Results from pilot studies supporting the use of these methods are described. Analyses of activity during different segments of the day showed that children were most active after school. The activities reported most frequently (eg, basketball and mixed walking and running) were also the ones found to be most popular in the study population on the basis of formative assessment surveys. Both the physical activity recall questionnaire and the triaxial accelerometer methods will be used to assess the effects of the full-scale intervention on physical activity. Ain J Clin Nutr 1999;69(suppl):788S-95S. C1 Univ Arizona, Dept Physiol, Tucson, AZ 85721 USA. Univ New Mexico, Sch Med, Ctr Hlth Promot & Dis Prevent, Albuquerque, NM 87131 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. Univ Alabama, Birmingham, AL USA. NHLBI, NIH, Bethesda, MD 20892 USA. Arizona State Univ, Tempe, AZ USA. San Diego State Univ, San Diego, CA 92182 USA. RP Going, SB (reprint author), Univ Arizona, Dept Physiol, Room 107 Ina E Gittings Bldg, Tucson, AZ 85721 USA. RI Schmoelz, Camilie/D-1707-2012 OI Schmoelz, Camilie/0000-0003-2221-9954 FU NHLBI NIH HHS [U01-HL-50905, U01-HL-50867, U01-HL-50885] NR 52 TC 28 Z9 28 U1 3 U2 5 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 1999 VL 69 IS 4 SU S BP 788S EP 795S PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 183PU UT WOS:000079562800009 PM 10195604 ER PT J AU Davis, SM Going, SB Helitzer, DL Teufel, NI Snyder, P Gittelsohn, J Metcalfe, L Arviso, V Evans, M Smyth, M Brice, R Altaha, J AF Davis, SM Going, SB Helitzer, DL Teufel, NI Snyder, P Gittelsohn, J Metcalfe, L Arviso, V Evans, M Smyth, M Brice, R Altaha, J TI Pathways: a culturally appropriate obesity-prevention program for American Indian schoolchildren SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE obesity prevention; culturally appropriate intervention; American Indians; schoolchildren; school-based prevention; physical activity; Pathways ID HEALTH PROMOTION; INTERVENTION; CATCH AB Pathways, a culturally appropriate obesity prevention study for third-, fourth-, and fifth-grade American Indian schoolchildren includes an intervention that promotes increased physical activity and healthful eating behaviors. The Pathways intervention, developed through a collaboration of universities and American Indian nations, schools, and families, focuses on individual, behavioral, and environmental factors and merges constructs from social learning theory with American Indian customs and practices. We describe the Pathways program developed during 3 y of feasibility testing in American Indian schools, with special emphasis on the activities developed for the third grade; review the theoretical and cultural underpinnings of the program; outline the construction process of the intervention; detail the curriculum and physical education components of the intervention; and summarize the formative assessment and the school food service and family components of the intervention. Aln J Clin Nutr 1999;69(suppl):796S-802S. C1 Univ New Mexico, Sch Med, Dept Pediat, Ctr Hlth Promot & Dis Prevent, Albuquerque, NM 87131 USA. Univ Arizona, Tucson, AZ USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Int Hlth, Div Human Nutr, Baltimore, MD USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Chapel Hill, NC USA. RP Davis, SM (reprint author), Univ New Mexico, Sch Med, Dept Pediat, Ctr Hlth Promot & Dis Prevent, 2701 Frontier NE,Surge Bldg,Room 251, Albuquerque, NM 87131 USA. FU NHLBI NIH HHS [U01 HL050907, U01 HL050867, U01 HL050869, U01 HL050885, U01 HL050905] NR 34 TC 51 Z9 52 U1 1 U2 14 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 1999 VL 69 IS 4 SU S BP 796S EP 802S PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 183PU UT WOS:000079562800010 PM 10195605 ER PT J AU Snyder, P Anliker, J Cunningham-Sabo, L Dixon, LB Altaha, J Chamberlain, A Davis, S Evans, M Hurley, J Weber, JL AF Snyder, P Anliker, J Cunningham-Sabo, L Dixon, LB Altaha, J Chamberlain, A Davis, S Evans, M Hurley, J Weber, JL TI The Pathways study: a model for lowering the fat in school meals SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE food service; school meals; nutrient guidelines; behavior change; children; fat intake; food preparation; obesity; Pathways study; American Indians ID INTERVENTION; CATCH AB We describe the development and implementation of the Pathways school food service intervention during the feasibility phase of the Pathways study. The purpose of the intervention was to lower the amount of fat in school meals to 30% of energy to promote obesity prevention in third- through fifth-grade students. The Pathways nutrition staff and the food service intervention staff worked together to develop 5 interrelated components to implement the intervention. These components were nutrient guidelines, 8 skill-building behavioral guidelines, hands-on materials, twice yearly trainings, and monthly visits to the kitchens by the Pathways nutrition staff. The components were developed and implemented over 18 mo in a pilot intervention in 4 schools. The results of an initial process evaluation showed that 3 of the 4 schools had implemented 6 of the 8 behavioral guidelines. In an analysis of 5 d of school menus from 3 control schools. the lunch menus averaged from 34% to 40% of energy from fat; when the menus were analyzed by using the food preparation and serving methods in the behavioral guidelines, they averaged 31% of energy from total fat. This unique approach of 5 interrelated food service intervention components was accepted in the schools and is now being implemented in the full-scale phase of the Pathways study in 40 schools for 5 y. Ain J Clin Nutr 1999:69(suppl):810S-5S. C1 Univ Minnesota, Div Epidemiol, Minneapolis, MN 55454 USA. Johns Hopkins Univ, Bowie, MD USA. Univ New Mexico, Ctr Hlth Promot & Dis Prevent, Albuquerque, NM 87131 USA. Stanford Univ, Stanford, CA 94305 USA. Todd Cty Sch Dist, Mission, SD USA. NIH, Bethesda, MD 20892 USA. Gila River Indian Community, Sacaton, AZ USA. Univ Arizona, Dept Physiol, Tucson, AZ USA. RP Snyder, P (reprint author), Univ Minnesota, Div Epidemiol, 1300 S 2nd St,Suite 300, Minneapolis, MN 55454 USA. FU NHLBI NIH HHS [U01 HL050907, U01 HL050885, U01 HL050905, U01 HL050867, U01 HL050869] NR 23 TC 21 Z9 21 U1 0 U2 3 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 1999 VL 69 IS 4 SU S BP 810S EP 815S PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 183PU UT WOS:000079562800012 PM 10195607 ER PT J AU Boni, R Wellmann, A Man, YG Hofbauer, G Brinkmann, U AF Boni, R Wellmann, A Man, YG Hofbauer, G Brinkmann, U TI Expression of the proliferation and apoptosis-associated CAS protein in benign and malignant cutaneous melanocytic lesions SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Article DE cellular apoptosis susceptibility protein; cutaneous melanocytic lesions; melanoma ID SEGREGATION GENE CSE1; CHROMOSOME SEGREGATION; SUSCEPTIBILITY GENE; HUMAN HOMOLOG; CANCER-CELLS; MELANOMA; LOCALIZATION; CLONING; ALPHA AB We have examined the expression of the cellular apoptosis susceptibility protein, a nuclear transport factor that plays a role in apoptosis and cell proliferation, in benign and malignant melanocytic lesions. Tissue samples of 55 formalin-fixed, paraffin-embedded melanoma (primary n = 32, metastatic n = 23) and of 27 control cases (junctional dermal, compound, Spitz, Reed, blue nevi, balloon-cell nevus, lentigo maligna) were analyzed by immunohistochemistry with anti-cellular apoptosis susceptibility antibodies. The percentage of cellular apoptosis susceptibility-positive cells as well as the intensity on a four-point scale was evaluated. In normal skin, expression of cellular apoptosis susceptibility was primarily found in the basal cell layer of the epidermis. Benign melanocytic lesions that stained positive for cellular apoptosis susceptibility (13 of 27) showed a homogeneously distributed staining pattern with a mean of 5 +/- 12% cellular apoptosis susceptibility positive cells. Five out of 7 lentigo maligna melanoma, 11 out of 12 superficial spreading melanoma and all acrolentiginous (n = 7) and nodular (n = 6) melanoma showed immunoreactivity of medium (++) to high (+++) intensity. Vertical growth phases of primary cutaneous melanoma stained stronger than horizontally growing cell clusters. All metastases (n = 23) stained strongly positive, the staining pattern being inhomogeneous. Cellular apoptosis susceptibility detection in clinical stages according to UICC showed an increase from 43 +/- 34% cellular apoptosis susceptibility positive cells in stage I, to 53 +/- 26% in stage II, 68 +/- 24% in stage III and 72 +/- 24% in stage TV, respectively, Because the expression of cellular apoptosis susceptibility correlates predominantly with advanced stages of melanoma, staining with anti-cellular apoptosis susceptibility antibodies may be useful for diagnosis of melanoma and possibly as an immunohistochemical prognostic factor in cutaneous melanocytic lesions. C1 Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. Armed Forces Inst Pathol, Pathol Lab, Div Canc Biol, Hematopathol Sect, Washington, DC 20306 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Boni, R (reprint author), Univ Zurich Hosp, Dept Dermatol, Gloriastr 31, CH-8091 Zurich, Switzerland. RI Hofbauer, Gunther/B-2671-2010 OI Hofbauer, Gunther/0000-0003-0542-7989 NR 18 TC 34 Z9 35 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0193-1091 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD APR PY 1999 VL 21 IS 2 BP 125 EP 128 DI 10.1097/00000372-199904000-00003 PG 4 WC Dermatology SC Dermatology GA 183KX UT WOS:000079553700003 PM 10218671 ER PT J AU Ferrucci, L Izmirlian, G Leveille, S Phillips, CL Corti, MC Brock, DB Guralnik, JM AF Ferrucci, L Izmirlian, G Leveille, S Phillips, CL Corti, MC Brock, DB Guralnik, JM TI Smoking, physical activity, and active life expectancy SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE activities of daily living; aging; exercise; longevity; longitudinal studies; Markov chains; motor activity; smoking ID CORONARY HEART-DISEASE; OLDER PERSONS; CIGARETTE-SMOKING; 3 COMMUNITIES; RISK-FACTORS; FOLLOW-UP; MEN; MORTALITY; WOMEN; HEALTH AB The effect of smoking and physical activity on active and disabled life expectancy was estimated using data from the Established Populations for Epidemiologic Studies of the Elderly (EPESE). Population-based samples of persons aged greater than or equal to 65 years from the East Boston, Massachusetts, New Haven, Connecticut, and Iowa sites of the EPESE were assessed at baseline between 1981 and 1983 and followed for mortality and disability over six annual follow-ups. A total of 8,604 persons without disability at baseline were classified as "ever" or "never" smokers and doing "low" "moderate," or "high" level physical activity. Active and disabled life expectancies were estimated using a Markov chain model. Compared with smokers, men and women nonsmokers survived 1.6-3.9 and 1.6-3.6 years longer, respectively, depending on level of physical activity. When smokers were disabled and close to death, most nonsmokers were still nondisabled, Physical activity, from low to moderate to high, was significantly associated with more years of life expectancy in both smokers (9.5, 10.5, 12.9 years in men and 11.1, 12.6, 15.3 years in women at age 65) and nonsmokers (11.0, 14.4, 16.2 years in men and 12.7, 16.2, 18.4 years in women at age 65), Higher physical activity was associated with fewer years of disability prior to death. These findings provide strong and explicit evidence that refraining from smoking and doing regular physical activity predict a long and healthy life. C1 NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Natl Res Inst, I Fraticini, Dept Geriatr, Florence, Italy. Univ Padua, Dept Internal Med, I-35100 Padua, Italy. RP Ferrucci, L (reprint author), NIA, Epidemiol Demog & Biometry Program, 7201 Wisconsin Ave,Gateway Bldg,Suite 3C-309, Bethesda, MD 20892 USA. NR 47 TC 160 Z9 165 U1 0 U2 4 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD APR 1 PY 1999 VL 149 IS 7 BP 645 EP 653 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 181QQ UT WOS:000079453500009 PM 10192312 ER PT J AU Leveille, SG Guralnik, JM Ferrucci, L Langlois, JA AF Leveille, SG Guralnik, JM Ferrucci, L Langlois, JA TI Aging successfully until death in old age: Opportunities for increasing active life expectancy SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE activities of daily living; aged; body mass index; disabled; exercise; health behavior; mortality; smoking ID CORONARY HEART-DISEASE; PHYSICAL-ACTIVITY LEVELS; BODY-MASS INDEX; WEIGHT-LOSS; KNEE OSTEOARTHRITIS; ALCOHOL-CONSUMPTION; 3 COMMUNITIES; HEALTH-STATUS; NHANES-I; RISK AB The purpose of this study was to estimate the prevalence of having no disability in the year prior to death in very old age and to examine factors associated with this outcome. Participants were men and women aged 65 years and older who were followed prospectively between 1981 and 1991 from three communities: New Haven, Connecticut; Iowa and Washington counties, Iowa; and East Boston, Massachusetts. Persons who died in late old age with known disability status within 15 months of death (n = 1,097) were studied for predictors of dying without disability at the last follow-up interview prior to death,The probability of a nondisabled 65-year-old man's surviving to age 80 and then being nondisabled prior to death was 26% and, for a 65-year-old woman, the probability of surviving to age 85 and being nondisabled before death was 18%, Physical activity was a key factor predicting nondisability before death. There was nearly a twofold increased likelihood of dying without disability among the most physically active group compared with sedentary adults (adjusted odds ratio = 1.86, 95% confidence interval 1.24-2.79). These findings provide encouraging evidence that disability prior to death is not an inevitable part of a long life but may be prevented by moderate physical activity. C1 NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Natl Res Inst, I Fraticini, Dept Geriatr, Florence, Italy. RP Leveille, SG (reprint author), NIA, Epidemiol Demog & Biometry Program, Gateway Bldg,Suite 3C309,7201 Wisconsin Ave, Bethesda, MD 20892 USA. NR 39 TC 168 Z9 172 U1 2 U2 11 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD APR 1 PY 1999 VL 149 IS 7 BP 654 EP 664 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 181QQ UT WOS:000079453500010 PM 10192313 ER PT J AU Rehm, JT Bondy, SJ Sempos, CT Vuong, CV AF Rehm, JT Bondy, SJ Sempos, CT Vuong, CV TI Alcohol consumption and coronary heart disease morbidity and mortality - Reply SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter C1 Fachhsch Hamburg, D-21033 Hamburg, Germany. Inst Clin Evaluat Sci, Toronto, ON M4N 3M5, Canada. NHLBI, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. RP Rehm, JT (reprint author), Fachhsch Hamburg, D-21033 Hamburg, Germany. RI Rem, Jurgen/H-1309-2011; Bondy, Susan/C-6737-2014 OI Bondy, Susan/0000-0002-6516-4159 NR 9 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD APR 1 PY 1999 VL 149 IS 7 BP 683 EP 683 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 181QQ UT WOS:000079453500017 ER PT J AU Aksentijevich, I Torosyan, Y Samuels, J Centola, M Pras, E Chae, JJ Oddoux, C Wood, G Azzaro, MP Palumbo, G Giustolisi, R Pras, M Ostrer, H Kastner, DL AF Aksentijevich, I Torosyan, Y Samuels, J Centola, M Pras, E Chae, JJ Oddoux, C Wood, G Azzaro, MP Palumbo, G Giustolisi, R Pras, M Ostrer, H Kastner, DL TI Mutation and haplotype studies of familial Mediterranean fever reveal new ancestral relationships and evidence for a high carrier frequency with reduced penetrance in the Ashkenazi Jewish population SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID HIGH GENE-FREQUENCY; PERIODIC FEVER; ETHNIC-GROUPS; FMF; INHERITANCE; LINKAGE; 12P13 AB Familial Mediterranean fever (FMF) is a recessive disorder characterized by episodes of fever with serositis or synovitis. The FMF gene (MEFV) was cloned recently, and four missense mutations were identified. Here we present data from non-Ashkenazi Jewish and Arab patients in whom we had not originally found mutations and from a new, more ethnically diverse panel. Among 90 symptomatic mutation-positive individuals, 11 mutations accounted for 79% of carrier chromosomes. Of the two mutations that are novel, one alters the same residue (680) as a previously known mutation, and the other (P369S) is located in exon 3. Consistent with another recent report, the E148Q mutation was observed in patients of several ethnicities and on multiple microsatellite haplotypes, but haplotype data indicate an ancestral relationships between non-Jewish Italian and Ashkenazi Jewish patients with FMF and other affected populations. Among similar to 200 anonymous Ashkenazi Jewish DNA samples, the MEFV carrier frequency was 21%, with E148Q the most common mutation. Several lines of evidence indicate reduced penetrance among Ashkenazi Jews, especially for E148Q, P369S, and K695R. Nevertheless, E148Q helps account for recessive inheritance in an Ashkenazi family previously reported as an unusual case of dominantly inherited FMF The presence of three frequent MEFV mutations in multiple Mediterranean populations strongly suggests a heterozygote advantage in this geographic region. C1 NIAMSD, Genet Sect, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NYU Med Ctr, Dept Pediat, Human Genet Program, New York, NY 10016 USA. Chaim Sheba Med Ctr, Dept Med C, IL-52621 Tel Hashomer, Israel. Chaim Sheba Med Ctr, Heller Inst Med Res, IL-52621 Tel Hashomer, Israel. Univ Catania, Inst Hematol, Catania, Italy. RP Aksentijevich, I (reprint author), NIAMSD, Genet Sect, Arthrit & Rheumatism Branch, NIH, Bldg 10,Room 9N-214, Bethesda, MD 20892 USA. EM aksentii@exchange.nih.gov NR 30 TC 209 Z9 212 U1 1 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR PY 1999 VL 64 IS 4 BP 949 EP 962 DI 10.1086/302327 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 184UV UT WOS:000079632900006 PM 10090880 ER PT J AU Hartge, P Struewing, JP Wacholder, S Brody, LC Tucker, MA AF Hartge, P Struewing, JP Wacholder, S Brody, LC Tucker, MA TI The prevalence of common BRCA1 and BRCA2 mutations among Ashkenazi Jews SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID BREAST-OVARIAN CANCER; FAMILY HISTORY; GERMLINE MUTATIONS; JEWISH INDIVIDUALS; 185DELAG MUTATION; CARRIER FREQUENCY; SEQUENCE-ANALYSIS; GENE BRCA1; RISK; WOMEN AB Three founder mutations in the cancer-associated genes BRCA1 and BRCA2 occur frequently enough among Ashkenazi Jews to warrant consideration of genetic testing outside the setting of high-risk families with multiple cases of breast or ovarian cancer. We estimated the prevalence of these founder mutations in BRCA1 and BRCA2 in the general population of Ashkenazi Jews according to age at testing, personal cancer history, and family cancer history. We compared the results of anonymous genetic testing of blood samples obtained in a survey of >5,000 Jewish participants from the Washington, DC, area with personal and family cancer histories obtained from questionnaires completed by the participants. In all subgroups defined by age and cancer history, fewer mutations were found,in this community sample than in clinical series studied to date. For example, 11 (10%) of 109 Jewish women who had been given a diagnosis of breast cancer in their forties carried one of the mutations. The most important predictor of mutation status was a previous diagnosis of breast or ovarian cancer. In men and in women never given a diagnosis of cancer, family history of breast cancer before age 50 years was the strongest predictor. As interest in genetic testing for BRCA1 and BRCA2 in the Jewish community broadens, community-based estimates such as these help guide those seeking and those offering such testing. Even with accurate estimates of the likelihood of carrying a mutation and the likelihood of developing cancer if a mutation is detected, the most vexing clinical problems remain. C1 NCI, Div Canc Epidemiol & Stat, NIH, Bethesda, MD 20892 USA. NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD USA. RP Hartge, P (reprint author), NCI, Div Canc Epidemiol & Stat, NIH, Bldg EPN,Room 443, Bethesda, MD 20892 USA. RI Struewing, Jeffery/C-3221-2008; Tucker, Margaret/B-4297-2015; Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 NR 23 TC 121 Z9 121 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR PY 1999 VL 64 IS 4 BP 963 EP 970 DI 10.1086/302320 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 184UV UT WOS:000079632900007 PM 10090881 ER PT J AU Jackson, CE Fischer, RE Hsu, AP Anderson, SM Choi, YN Wang, J Dale, JK Fleisher, TA Middelton, LA Sneller, MC Lenardo, MJ Straus, SE Puck, JM AF Jackson, CE Fischer, RE Hsu, AP Anderson, SM Choi, YN Wang, J Dale, JK Fleisher, TA Middelton, LA Sneller, MC Lenardo, MJ Straus, SE Puck, JM TI Autoimmune lymphoproliferative syndrome with defective fas: Genotype influences penetrance SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID NECROSIS-FACTOR-ALPHA; SYSTEMIC LUPUS-ERYTHEMATOSUS; GENE POLYMORPHISM; LYMPHOCYTE APOPTOSIS; CELL ACTIVATION; DEATH DOMAIN; MUTATIONS; MICE; DISEASE; EXPRESSION AB Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of lymphocyte homeostasis and immunological tolerance. Most patients have a heterozygous mutation in the APT1 gene, which encodes Fas (CD95, APO-1), mediator of an apoptotic pathway crucial to lymphocyte homeostasis. Of 17 unique APT1 mutations in unrelated ALPS probands, 12 (71%) occurred in exons 7-9, which encode the intracellular portion of Fas. In vitro, activated lymphocytes from all 17 patients showed apoptotic defects when exposed to an anti-Fas agonist monoclonal antibody. Similar defects were found in a Fas-negative cell line transfected with cDNAs bearing each of the mutations. In cotransfection experiments, Fas constructs with either intra- or extracellular mutations caused dominant inhibition of apoptosis mediated by wild-type Fas. Two missense Fas variants, not restricted to patients with ALPS, were identified. Variant A(-1)T at the Fas signal-sequence:cleavage site, which mediates;apoptosis less well than wild-type Fas and is partially inhibitory, was present in 13% of African American alleles. Among the ALPS-associated Eas mutants, dominant inhibition of apoptosis was much more pronounced in mutants affecting the intracellular, versus extracellular, portion of the Fas receptor. Mutations causing disruption of the intracellular Fas death domain also showed a higher penetrance of ALPS phenotype features in mutation-bearing relatives. Significant ALPS-related morbidity occurred in 44% of relatives with intracellular mutations, versus 0% of relatives with extracellular mutations. Thus, the location of mutations within APT1 strongly influences the development and the severity of ALPS. C1 NHGRI, Branch Genet & Mol Biol, NIH, Bethesda, MD 20892 USA. NHGRI, Branch Med Genet, Bethesda, MD 20892 USA. NIAID, Immunol Lab, Bethesda, MD 20892 USA. NIAID, Clin Invest Lab, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. NIH, Ctr Clin, Pathol Lab, Bethesda, MD 20892 USA. RP Puck, JM (reprint author), NHGRI, Branch Genet & Mol Biol, NIH, 49 Convent Dr,Bldg 49,Room 3W14, Bethesda, MD 20892 USA. NR 47 TC 141 Z9 142 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR PY 1999 VL 64 IS 4 BP 1002 EP 1014 DI 10.1086/302333 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 184UV UT WOS:000079632900011 PM 10090885 ER PT J AU Shields, DC Kirke, PN Mills, JL Ramsbottom, D Molloy, AM Burke, H Weir, DG Scott, JM Whitehead, AS AF Shields, DC Kirke, PN Mills, JL Ramsbottom, D Molloy, AM Burke, H Weir, DG Scott, JM Whitehead, AS TI The "thermolabile" variant of methylenetetrahydrofolate reductase and neural tube defects: An evaluation of genetic risk and the relative importance of the genotypes of the embryo and the mother SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID METHYLENE TETRAHYDROFOLATE REDUCTASE; SPINA-BIFIDA; 5,10-METHYLENETETRAHYDROFOLATE REDUCTASE; HOMOCYSTEINE METABOLISM; LINKAGE DISEQUILIBRIUM; METHIONINE SYNTHASE; TRANSMISSION TEST; VASCULAR-DISEASE; COMMON MUTATION; FOLATE STATUS AB Recent reports have implicated the "thermolabile" (T) variant of methylenetetrahydrofolate reductase (MTHFR) in the causation of folate-dependent neural tube defects (NTDs). We report herein the largest genetic study of NTD cases (n = 271) and families (n = 218) to date, establishing that, in Ireland, the "TT" genotype is found in 18.8% of cases versus 8.3% of controls (odds ratio 2.57; confidence interval [CI] 1.48-4.45; P=.0005). The maternal and paternal TT genotypes have intermediate frequencies of 13.8% and 11.9%, respectively, indicating that the predominant MTHFR-related genetic effect acts via the TT genotype of the developing embryo. Analysis of the 218 family triads of mother, father, and affected child with log-linear models supports this interpretation, providing significant evidence that the case TT genotype is associated with NTDs (P =.02) but no evidence of a maternal TT genotypic effect (P =.83). The log-linear model predicted that the risk of NTDs conferred by the case TT genotype is 1.61 (CI 1.06-2.46), consistent with the paramount importance of the case TT genotype in determining risk. There is no compelling evidence for more than a modest additional risk conferred by a maternal TT genotype. These results favor a biological model of MTHFR-related NTD pathogenesis in which suboptimal maternal folate status imposes biochemical stress on the developing embryo, a stress it is ill-equipped to tolerate if it has a TT genotype. C1 Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Expt Therapeut, Philadelphia, PA 19104 USA. NICHHD, Bethesda, MD 20892 USA. Univ Dublin Trinity Coll, Dept Genet, Dublin 2, Ireland. Univ Dublin Trinity Coll, Dept Clin Med, Dublin 2, Ireland. Univ Dublin Trinity Coll, Dept Biochem, Dublin 2, Ireland. Univ Dublin Trinity Coll, Hlth Res Board, Dublin 2, Ireland. Royal Coll Surg Ireland, Dept Clin Pharmacol, Dublin 2, Ireland. RP Whitehead, AS (reprint author), Univ Penn, Sch Med, Dept Pharmacol, 3620 Hamilton Walk, Philadelphia, PA 19104 USA. EM aswhitehead@pharm.med.upenn.edu NR 43 TC 167 Z9 173 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR PY 1999 VL 64 IS 4 BP 1045 EP 1055 DI 10.1086/302310 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 184UV UT WOS:000079632900015 PM 10090889 ER PT J AU Lee, HS Sambuughin, N Cervenakova, L Chapman, J Pocchiari, M Litvak, S Qi, HY Budka, H del Ser, T Furukawa, H Brown, P Gajdusek, DC Long, JC Korczyn, AD Goldfarb, LG AF Lee, HS Sambuughin, N Cervenakova, L Chapman, J Pocchiari, M Litvak, S Qi, HY Budka, H del Ser, T Furukawa, H Brown, P Gajdusek, DC Long, JC Korczyn, AD Goldfarb, LG TI Ancestral origins and worldwide distribution of the PRNP 200K mutation causing familial Creutzfeldt-Jakob disease SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID AMYLOID PRECURSOR GENE; MACHADO-JOSEPH-DISEASE; PRION PROTEIN; LIBYAN JEWS; CODON-200 MUTATION; SLOVAKIA; SCRAPIE; LOCUS; CJD; EPIDEMIOLOGY AB Creutzfeldt-Jakob disease (CJD) belongs to a group of prion diseases that may be infectious, sporadic, or hereditary. The 200K point mutation in the PRNP gene is the most frequent cause of hereditary CJD, accounting for >70% of families with CJD worldwide. Prevalence of the 200K variant of familial CJD is especially high in Slovakia, Chile, and Italy, and among populations of Libyan and Tunisian Jews. To study ancestral origins of the 200K mutation-associated chromosomes, we selected microsatellite markers flanking the PRNP gene on chromosome 20p12-pter and an intragenic single-nucleotide polymorphism at the PRNP codon 129. Haplotypes were constructed for 62 CJD families originating from 11 world populations. The results show that Libyan, Tunisian, Italian, Chilean, and Spanish families share a major haplotype, suggesting that the 200K mutation may have originated from a single mutational event, perhaps in Spain, and spread to all these populations with Sephardic migrants expelled from Spain in the Middle Ages. Slovakian families and a family of Polish origin show another unique haplotype. The haplotypes in families from Germany, Sicily, Austria, and Japan are different from the Mediterranean or eastern European haplotypes. On the bais of this study, we conclude that founder effect and independent mutational events are responsible for the current geographic distribution of hereditary CJD associated with the 200K mutation. C1 NINDS, Clin Neurogenet Unit, NIH, Bethesda, MD 20892 USA. NINDS, Cent Nervous Syst Studies Lab, NIH, Bethesda, MD 20892 USA. NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. Amer Red Cross, Jerome H Holland Lab, Rockville, MD 20852 USA. Tel Aviv Univ, Dept Neurol, Sieratzki Chair Neurol, Ramat Aviv, Israel. Tel Aviv Univ, Dept Physiol & Pharmacol, Ramat Aviv, Israel. Ist Super Sanita, Virol Lab, I-00161 Rome, Italy. Univ Vienna, Inst Neurol, Vienna, Austria. Hosp Severo Ochoa Leganes, Secc Neurol, Madrid, Spain. Kyushu Univ, Dept Neuropathol, Maidashi, Japan. Inst Alfred Fessard, CNRS, Gif Sur Yvette, France. RP Goldfarb, LG (reprint author), NINDS, Clin Neurogenet Unit, NIH, Room 4B37,Bldg 10,10 Ctr Dr MS 1361, Bethesda, MD 20892 USA. RI Chapman, Joab/E-4598-2010; Korczyn, Amos/C-3461-2017; OI Korczyn, Amos/0000-0003-0125-2579; Budka, Herbert/0000-0002-1933-1577 NR 37 TC 57 Z9 57 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR PY 1999 VL 64 IS 4 BP 1063 EP 1070 DI 10.1086/302340 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 184UV UT WOS:000079632900017 PM 10090891 ER PT J AU Weinberg, CR AF Weinberg, CR TI Allowing for missing parents in genetic studies of case-parent triads SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID TRANSMISSION DISEQUILIBRIUM TEST; LINKAGE DISEQUILIBRIUM; RELATIVE RISKS; ASSOCIATION; DESIGN AB In earlier work, my colleagues and I described a loglinear model for genetic data from triads composed of affected probands and their parents. This model allows detection of and discrimination between effects of an inherited haplotype versus effects of the maternal,haplotype, which presumably would be mediated by prenatal factors. Like the transmission disequilibrium test (TDT), the likelihood-ratio test (LRT) based on this model is not sensitive to associations that are due to genetic admixture. When used as a method for testing for linkage disequilibrium, the LRT can-be regarded as an alternative:to the TDT. When one or both parents are missing, the resulting incomplete triad must be discarded to ensure validity of the TDT, thereby sacrificing information. By contrast, when the problem is set in a likelihood framework, the :expectation-maximization algorithm allows the incomplete triads to contribute their information to the LRT without invalidation of the analysis. Simulations demonstrate that much of the lost statistical power can be recaptured by means of this missing-data technique. In fact, power is reasonably good even when no triad is complete-for example; when a study is designed to include only mothers of cases. Information from siblings also can be incorporated to further improve the statistical power when genetic data from parents or probands are missing. C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Weinberg, CR (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 13 TC 157 Z9 160 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR PY 1999 VL 64 IS 4 BP 1186 EP 1193 DI 10.1086/302337 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 184UV UT WOS:000079632900030 PM 10090904 ER PT J AU Badner, JA Gershon, ES Goldin, LR AF Badner, JA Gershon, ES Goldin, LR TI Optimal ascertainment strategies to detect linkage to common disease alleles - Reply to Baron SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Letter ID BIPOLAR DISORDER; CHROMOSOME-18; PEDIGREES; MARKERS; ILLNESS C1 Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. Natl Canc Inst, Genet Epidemiol Branch, Bethesda, MD USA. RP Badner, JA (reprint author), Univ Chicago, Dept Psychiat, 5841 S Maryland Ave,MC 3077, Chicago, IL 60637 USA. NR 12 TC 0 Z9 0 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR PY 1999 VL 64 IS 4 BP 1246 EP 1248 DI 10.1086/302349 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 184UV UT WOS:000079632900043 ER PT J AU Anderson, DE Eyster, C AF Anderson, DE Eyster, C TI Association of end tidal CO2 with rate of change in blood pressure over 20 years SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Meeting Abstract DE blood pressure; gender; hypertension; pCO2 C1 NIA, Lab Cardiovasc Sci, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD APR PY 1999 VL 12 IS 4 SU S BP 20A EP 20A PN 2 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 188FR UT WOS:000079836600060 ER PT J AU Roccella, EJ AF Roccella, EJ TI Blood pressure control - Getting the message out. SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Meeting Abstract DE hypertension awareness C1 NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD APR PY 1999 VL 12 IS 4 SU S BP 216A EP 216A PN 2 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 188FR UT WOS:000079836600774 ER PT J AU Roccella, EJ AF Roccella, EJ TI Hypertension (HTN) and unmet needs, a global perspective SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Meeting Abstract DE hypertension awareness; treatment and control C1 NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD APR PY 1999 VL 12 IS 4 SU S BP 223A EP 223A PN 2 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 188FR UT WOS:000079836600799 ER PT J AU Zhang, J Klebanoff, MA DerSimonian, R AF Zhang, J Klebanoff, MA DerSimonian, R TI Epidural analgesia in association with duration of labor and mode of delivery: A quantitative review SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Review DE cesarean delivery; delivery; epidural analgesia; instrumental delivery; labor; labor duration; oxytocin ID CESAREAN DELIVERY; NULLIPAROUS WOMEN; 2ND STAGE; ANESTHESIA; BUPIVACAINE; DYSTOCIA; INFUSION; PATIENT; BLOCK; TRIAL AB OBJECTIVE: This study was undertaken to quantitatively summarize previous literature on the effects of epidural analgesia in labor on the duration of labor and mode of delivery. STUDY DESIGN: Original studies published in English from 1965 through December 1997 were reviewed and assigned a quality score independently by 2 of the authors. Studies that met the minimal requirements were evaluated further. Data syntheses were performed separately according to study design and outcome measurements, including cesarean delivery, instrumental delivery, oxytocin augmentation, and durations of the first and second stages of labor. RESULTS: Seven randomized clinical trials and 5 observational studies met the minimal requirements. Among them 4 studies of each sort were included in the data synthesis. Both types of studies showed that epidural analgesia increased risk of oxytocin augmentation 2-fold. Clinical trials suggested that epidural analgesia did not increase the risk of cesarean delivery either overall or for dystocia, nor did it significantly increase the risk of instrumental vaginal delivery; however, observational studies reported a more than 4-fold increased risk of cesarean and instrumental deliveries. Although most studies showed a longer labor among women with epidural analgesia than without it, especially during the second stage, most of the studies used inappropriate statistical analysis. CONCLUSION: Epidural analgesia with low-dose bupivacaine may increase the risk of oxytocin augmentation but not that of cesarean delivery. C1 NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. RP Zhang, J (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, Bldg 6100,Room 7B03, Bethesda, MD 20892 USA. NR 22 TC 58 Z9 66 U1 0 U2 6 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD APR PY 1999 VL 180 IS 4 BP 970 EP 977 DI 10.1016/S0002-9378(99)70669-1 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 188JB UT WOS:000079842100044 PM 10203666 ER PT J AU Moch, H Schraml, P Bubendorf, L Mirlacher, M Kononen, J Gasser, T Mihatsch, MJ Kallioniemi, OP Sauter, G AF Moch, H Schraml, P Bubendorf, L Mirlacher, M Kononen, J Gasser, T Mihatsch, MJ Kallioniemi, OP Sauter, G TI High-throughput tissue microarray analysis to evaluate genes uncovered by cDNA microarray screening in renal cell carcinoma SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; INTERMEDIATE-SIZED FILAMENTS; VIMENTIN EXPRESSION; FACTOR-ALPHA; C-MYC; TUMORS; CLASSIFICATION; ONCOCYTOMA; CANCER AB Many genes and signaling pathways are involved in renal cell carcinoma (RCC) development, However, genetic tumor markers have not gained use in RCC diagnostics and prognosis prediction. Identification and evaluation of new molecular parameters are of utmost importance in cancer research and cancer treatment. Here we present a novel approach to rapidly identify clinically relevant molecular changes in cancer, To identify genes with relevance to RCC, a cDNA array analysis was first performed on 5184 cDNA clones on a filter to screen for genes with differential expression between the renal cancer cell line CRL-1933 and normal kidney tissue. There were 89 differentially expressed genes in the cancer cell line, one of them coding for vimentin, a cytoplasmic intermediate filament. In a second step, a renal cancer tissue microarray containing 532 RCC specimen was used to determine vimentin expression by immunohistochemistry, Vimentin expression was seen frequently in clear cell (51%) and papillary RCC (61%), but rarely in chromophobe RCC (4%) and oncocytomas (12%). Furthermore, vimentin expression was significantly associated with poor patient prognosis (P < 0.007) independent of grade and stage. These results obtained from minute arrayed tumor samples match well with previous findings on vimentin expression in renal tumors. It is concluded that the combination of tumor arrays and cDNA arrays is a powerful approach to rapidly identify and further evaluate genes that play a role in tumor biology. C1 Univ Basel, Inst Pathol & Clin Urol, Basel, Switzerland. Natl Inst Hlth, Natl Human Genome Res Inst, Bethesda, MD USA. RP Moch, H (reprint author), Univ Basel, Inst Pathol, Schonbeinstr 40, CH-4003 Basel, Switzerland. RI Kallioniemi, Olli/H-5111-2011; Bubendorfl, Lukas/H-5880-2011; Kallioniemi, Olli/H-4738-2012 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 27 TC 302 Z9 343 U1 0 U2 5 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 1999 VL 154 IS 4 BP 981 EP 986 DI 10.1016/S0002-9440(10)65349-7 PG 6 WC Pathology SC Pathology GA 184MU UT WOS:000079616600005 PM 10233835 ER PT J AU Vortmeyer, AO Devouassoux-Shisheboran, M Li, G Mohr, V Tavassoli, F Zhuang, ZP AF Vortmeyer, AO Devouassoux-Shisheboran, M Li, G Mohr, V Tavassoli, F Zhuang, ZP TI Microdissection-based analysis of mature ovarian teratoma SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ORIGIN; GENETICS; BIOLOGY AB The genotypic features of mature ovarian teratomas (MOTs) are controversial. Early studies detected a homozygous genotype in MOTs suggesting that these tumors are composed of germ cells that have undergone meiosis I. Other studies, however, revealed a heterozygous genotype in a substantial proportion of MOTs suggesting an origin either from premeiotic germ cells or from a somatic cell line. In view of the complex morphology of MOTs and to increase the sensitivity of teratoma genotyping, we applied tissue microdissection before genetic analysis of teratomatous tissue. This approach allowed selective analysis of different heterotopic tissue elements as well as the lymphoid tissues within MOTs the origin of which is unknown. After DNA extraction, the tissue samples were polymerase chain reaction amplified using a random panel of highly informative genetic markers for different chromosomes to evaluate heterozygosity versus homozygosity, In all seven cases that were analyzed, heterotopic tissues consistently revealed a homozygous genotype with several markers; in two cases, heterozygosity was detected with a single marker, indicating a meiotic recombination event. Lymphoid aggregates within MOTs were heterozygous and derived from host tissue rather than from teratomatous growth. However, well differentiated thymic tissue was consistently homozygous, suggesting lymphoid differentiation capability of MOTs, We conclude that potential pitfalls in genotyping of teratomas including meiotic recombination and host cell participation can be avoided by a microdissection-based approach in combination with a panel of genetic markers. C1 NIH, Natl Canc Inst, Pathol Lab, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. RP Zhuang, ZP (reprint author), NIH, Natl Canc Inst, Pathol Lab, Bldg 10 Room 2A33,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 17 TC 31 Z9 31 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 1999 VL 154 IS 4 BP 987 EP 991 DI 10.1016/S0002-9440(10)65350-3 PG 5 WC Pathology SC Pathology GA 184MU UT WOS:000079616600006 PM 10233836 ER PT J AU Facchetti, F Chan, JKC Zhang, WG Tironi, A Chilosi, M Parolini, S Notarangelo, LD Samelson, LE AF Facchetti, F Chan, JKC Zhang, WG Tironi, A Chilosi, M Parolini, S Notarangelo, LD Samelson, LE TI Linker for activation of T cells (LAT), a novel immunohistochemical marker for T cells, NK cells, mast cells, and megakaryocytes - Evaluation in normal and pathological conditions SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID PARAFFIN-EMBEDDED TISSUE; NATURAL-KILLER-CELLS; TERMINAL DEOXYNUCLEOTIDYL TRANSFERASE; NON-HODGKINS-LYMPHOMA; TYROSINE PHOSPHORYLATION; B-CELL; ADAPTER PROTEIN; MICE LACKING; CD3 ANTIGEN; RECEPTOR AB LAT (linker for activation of T cells) is an integral membrane protein of 36-38 kd that plays an important role in T cell activation. Using a rabbit polyclonal antibody generated against the cytosolic portion of LAT, we investigated the immunohistochemical expression of LAT in normal and pathological hematolymphoid tissues. LAT reacts with human T cells in paraffin sections, including decalcified bone marrow trephines, LAT appears early in T cells at the thymocyte stage and before TdT expression in embryos, and is expressed in peripheral lymphoid tissues, without restriction to any T cell subpopulations. in addition to T cells, natural killer (NK) cells (evaluated with now cytometry), megakaryocytes and mast cells are also LAT-positive, whereas B cells and other myeloid and monocytic derived cells are negative. Tested on a total of 264 paraffin-embedded tissue biopsies, LET reacted with the great majority (96.8%) of T/NK-cell neoplasms, covering the full range of T cell maturation. Although antibodies to both LAT and CD3 had a similarly high sensitivity in the staining of T/NK-cell lymphomas, when used in conjunction, they successfully identified a higher number of cases (98.4%). Atypical megakaryocytes from different hematological disorders, as well as mast cells in mastocytosis were also LAT-positive, but all neoplasms of B cell origin, Hodgkin's lymphomas, and several nonlymphoid malignancies were negative. These data indicate that the anti-LAT antibody may be of value to diagnostic histopathologists for the identification of T cell neoplasms. C1 Univ Brescia, Dept Pathol, Spedali Civili Brescia, I-25124 Brescia, Italy. Univ Brescia, Dept Biomed Sci & Biotechnol, Brescia, Italy. Univ Brescia, Dept Pediat, Brescia, Italy. Queen Elizabeth Hosp, Hong Kong, Hong Kong. Univ Verona, I-37100 Verona, Italy. NIH, Sect Lymphocyte Signaling, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. RP Facchetti, F (reprint author), Univ Brescia, Dept Pathol, Spedali Civili Brescia, I-25124 Brescia, Italy. EM facchett@master.cci.unibs.it RI Facchetti, Fabio/E-7190-2010; Notarangelo, Luigi/F-9718-2016 OI Facchetti, Fabio/0000-0003-4975-2388; Notarangelo, Luigi/0000-0002-8335-0262 NR 42 TC 40 Z9 41 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 1999 VL 154 IS 4 BP 1037 EP 1046 DI 10.1016/S0002-9440(10)65356-4 PG 10 WC Pathology SC Pathology GA 184MU UT WOS:000079616600012 PM 10233842 ER PT J AU Sargent, LM Zhou, X Keck, CL Sanderson, ND Zimonjic, DB Popescu, NC Thorgeirsson, SS AF Sargent, LM Zhou, X Keck, CL Sanderson, ND Zimonjic, DB Popescu, NC Thorgeirsson, SS TI Nonrandom cytogenetic alterations in hepatocellular carcinoma from transgenic mice overexpressing c-myc and transforming growth factor-alpha in the liver SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID TUMOR-SUPPRESSOR GENES; IN-SITU HYBRIDIZATION; II PHOSPHOLIPASE A(2); PRIMARY BREAST-CANCER; FREQUENT LOSS; CHROMOSOME 13Q; LUNG-CANCER; ALLELOTYPE ANALYSIS; MOUSE CHROMOSOME-1; DISTINCT REGIONS AB Identification of specific and primary chromosomal alterations during the course of neoplastic development is an essential part of defining the genetic basis of cancer. We have developed a transgenic mouse model for liver neoplasia in which chromosomal lesions associated with both the initial stages of the neoplastic process and the acquisition of malignancy can be analyzed. Here we analyze chromosomal alterations in 11 hepatocellular carcinomas from the c-myc/TGF-alpha double-transgenic mice by fluorescent in situ hybridization with whole chromosome probes, single-copy genes, and 4'-6-diamidino-2-phenylindole (DAPI-) and G-banded chromosomes and report nonrandom cytogenetic alterations associated with the tumor development. All tumors were aneuploid and exhibited nonrandom structural and numerical alterations. A balanced translocation t(5:6)(G1;F2) was identified by two-color fluorescent in situ hybridization in all tumors, and, using a genomic probe, the c-myc transgene was localized near the breakpoint on derivative chromosome der 6. Partial or complete loss of chromosome 4 was observed in all tumors with nonrandom breakage in band C2. Deletions of chromosome 1 were observed in 80% of the tumors, with the most frequent deletion at the border of bands C4 and C5. An entire copy of chromosome 7 was lost in 80% of the tumors cells. Eighty-five percent of the tumor cells had lost one copy of chromosome 12, and the most common breakpoint on chromosome 12 occurred at band D3 (28%). A copy of chromosome 14 was lost in 72%, and band 14E1 was deleted in 32% of the tumor cells. The X chromosome was lost in the majority of the tumor cells. The most frequent deletion on the X chromosome involved band F1. We have previously shown that breakages of chromosomes 1, 6, 7, and 12 were observed before the appearance of morphologically distinct neoplastic liver lesions in this transgenic mouse model. Thus breakpoints on chromosome 4, 9, 14, and X appear to be later events in this model of Liver neoplasia. This is the first study to demonstrate that specific sites of chromosomal breakage observed during a period of chromosomal instability in early stages of carcinogenesis are later involved in stable rearrangements in solid tumors. The identification of the 5;6 translocation in all of the tumors has a special significance, being the first balanced translocation reported in human and mouse hepatocellular carcinoma and having the breakpoint near a tumor susceptibility gene and myc transgene site of integration. Moreover, its early occurrence indicates that this is a primary and relevant alteration to the initiation of the neoplastic process. In addition, the concordance between the breakpoints observed during the early dysplastic stage of hepatocarcinogenesis and the stable deletions of chromosomes 1, 4, 6, 7, 9, and 12 in the tumors provides evidence for preferential site of genetic changes in hepatocarcinogenesis. C1 NCI, Expt Carcinogenesis Lab, Div Basic Sci, Bethesda, MD 20892 USA. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Div Basic Sci, Bldg 37,Room 3C28,37 Convent Dr,MSC4255, Bethesda, MD 20892 USA. EM snorri_thorgeirsson@nih.gov NR 83 TC 50 Z9 51 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 1999 VL 154 IS 4 BP 1047 EP 1055 DI 10.1016/S0002-9440(10)65357-6 PG 9 WC Pathology SC Pathology GA 184MU UT WOS:000079616600013 PM 10233843 ER PT J AU Shah, M Revis, D Herrick, S Baillie, R Thorgeirson, S Ferguson, M Roberts, A AF Shah, M Revis, D Herrick, S Baillie, R Thorgeirson, S Ferguson, M Roberts, A TI Role of elevated plasma transforming growth factor-beta 1 levels in wound healing SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID TGF-BETA; TRANSGENIC MICE; NEUTRALIZING ANTIBODY; COMPLEX REGULATION; EXPRESSION; GROWTH-FACTOR-BETA-1; FIBROSIS; TGF-BETA-1; ANGIOGENESIS; LESIONS AB Transforming growth factor (TGF)-beta 1 plays a central role in wound healing. Wounds treated with neutralizing antibody to TGF-beta 1 have a lower inflammatory response, reduced early extracellular matrix deposition, and reduced later cutaneous scarring, indicating the importance of local tissue TGF-beta 1. By contrast, increasing the local, tissue levels of TGF-beta 1 increases the early extracellular matrix deposition but does not alter scar formation. Increased levels of plasma TGF-beta 1 correlate with increased fibrogenesis in the lung, kidneys, and liver. The aim of the present study was to investigate the role of elevated systemic levels of TGF-beta 1 on wound healing. We used transgenic mice that express high levels of active TGF-beta 1 and have elevated plasma levels of TGF-beta 1 and wild-type mice of the same strain as controls. Incisional wounds and subcutaneously implanted polyvinyl alcohol (PVA) sponges were analyzed. Surprisingly, cutaneous wounds in transgenic, TGF-beta 1-overexpressing mice healed with reduced scarring accompanied by an increase in the immunostaining for TGF-beta 3 and TGF-beta-receptor RII and a decrease in immunostaining for TGF-beta 1 compared with wounds in control mice. By contrast, the PVA sponges showed the opposite response, with PVA sponges from transgenic mice demonstrating an enhanced rate of cellular influx and matrix deposition into the sponges accompanied by an increase in the immunostaining for all three TGF-beta isoforms and their receptors compared with PVA sponges from control mice. Together, the data demonstrate that increased circulating levels of TGF-beta 1 do not always result in increased expression or activity in selected target tissues such as the skin. The two wound models, subcutaneously implanted PVA sponges and cutaneous incisional wounds, differ significantly in terms of host response patterns. Finally, the data reinforce our previous observations that the relative ratios of the three TGF-beta isoforms is critical for control of scarring. C1 Univ Manchester, Sch Biol Sci, Div CID, Manchester M13 9PT, Lancs, England. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Shah, M (reprint author), Univ Manchester, Sch Biol Sci, Div CID, Room 3-239,Stopford Bldg, Manchester M13 9PT, Lancs, England. RI herrick, sarah/A-3121-2015 OI herrick, sarah/0000-0002-9085-5664 FU Wellcome Trust NR 33 TC 106 Z9 108 U1 0 U2 6 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 1999 VL 154 IS 4 BP 1115 EP 1124 DI 10.1016/S0002-9440(10)65364-3 PG 10 WC Pathology SC Pathology GA 184MU UT WOS:000079616600020 PM 10233850 ER PT J AU Salcedo, R Wasserman, K Young, HA Grimm, MC Howard, OMZ Anver, MR Kleinman, HK Murphy, WJ Oppenheim, JJ AF Salcedo, R Wasserman, K Young, HA Grimm, MC Howard, OMZ Anver, MR Kleinman, HK Murphy, WJ Oppenheim, JJ TI Vascular endothelial growth factor and basic fibroblast growth factor induce expression of CXCR4 on human endothelial cells - In vivo neovascularization induced by stromal-derived factor-1 alpha SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID CHEMOKINE RECEPTOR CXCR4; NECROSIS-FACTOR-ALPHA; ANGIOGENESIS; INTERLEUKIN-8; CYTOKINES; HIV-1; IL-8; CXCR4/FUSIN; INHIBITION; CORECEPTOR AB Furthermore, subcutaneous SDF-1 alpha injections into mice induced formation of local small blood vessels that was accompanied by leukocytic infiltrates. To test whether these effects were dependent on circulating leukocytes, we successfully obtained SDF-1 alpha-induced neovascularization from cross sections of leukocyte-free rat aorta. Taken together, our data indicate that SDF-1 alpha acts as a potent chemoattractant for endothelial cells of different origins bearing CXCR4 and is a participant in angiogenesis that is regulated at the receptor level by VEGF and bFGF, The contribution of chemokines toward angiogenesis is currently a focus of intensive investigation. Certain members of the CXC chemokine family can induce bovine capillary endothelial cell migration in vitro and corneal angiogenesis in vivo, and apparently act via binding to their receptors CXCR1 and CXCR2, We used an RNAse protection assay that permitted the simultaneous detection of mRNA for various CXC chemokine receptors in resting human umbilical vein endothelial cells (HUVECs) and detected low levels of only CXCR4 mRNA, Stimulation of HUVECs with vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF) up-regulated levels of only CXCR4 mRNA, CXCR4 specifically binds the chemokine stromal-derived factor-1 alpha (SDF-1 alpha), Competitive binding studies using I-125-labeled SDF-1 alpha with Scatchard analysis indicated that VEGF or bFGF induced an average number of approximately 16,600 CXCR4 molecules per endothelial cell, with a K-d = 1.23 x 10(-9) mol/L, These receptors were functional as HUVECs and human aorta endothelial cells (HAECs) migrated toward SDF-1 alpha. Although SDF-1 alpha-induced chemotaxis was inhibited by the addition of a neutralizing monoclonal CXCR4 antibody, endothelial chemotaxis toward VEGF was not altered; therefore, the angiogenic effect of VEGF is independent of SDF-1 alpha. C1 NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, Mol Immunoregulat Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, Expt Immunol Lab, Frederick, MD 21702 USA. SAIC Frederick, Intramural Res Support Program, Pathol Histotechnol Lab, Frederick, MD USA. NIDR, Cell Biol Sect, Bethesda, MD 20892 USA. St George Clin Sch, Dept Med, Kogarah, NSW, Australia. RP Oppenheim, JJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, Mol Immunoregulat Lab, Bldg 560,Rm 21-89A, Frederick, MD 21702 USA. RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 NR 40 TC 386 Z9 412 U1 0 U2 5 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 1999 VL 154 IS 4 BP 1125 EP 1135 DI 10.1016/S0002-9440(10)65365-5 PG 11 WC Pathology SC Pathology GA 184MU UT WOS:000079616600021 PM 10233851 ER PT J AU Giannelli, G Pozzi, A Stetler-Stevenson, WG Gardner, HA Quaranta, V AF Giannelli, G Pozzi, A Stetler-Stevenson, WG Gardner, HA Quaranta, V TI Expression of matrix metalloprotease-2-cleaved laminin-5 in breast remodeling stimulated by sex steroids SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID MAMMARY EPITHELIAL-CELLS; INTEGRIN ALPHA-6-BETA-4; BRANCHING MORPHOGENESIS; BASEMENT-MEMBRANE; GENE-EXPRESSION; IV COLLAGENASE; DEVELOPMENTAL REGULATION; TISSUE INHIBITOR; RECEPTORS; ADHESION AB The extracellular matrix plays an important role in breast remodeling. We have shown that matrix metalloprotease-2 (MMP2) cleaves laminin-5 (Ln-5), a basement membrane component, generating a fragment called gamma 2x. Human breast epithelial cells, while constitutively immobile on intact Ln-5, acquire a motile phenotype on MMP2-cleaved Ln-5, We hypothesize that this mechanism may underlie cell mobilization across the basement membrane during branching morphogenesis in breast development regulated by sex steroids. We report that the expression of MMP2 and cleavage of Ln-5 correlate well with tissue remodeling and epithelial rearrangement of the breast both in vivo and in vitro. Thus, the Ln-5 gamma 2x fragment was detected by immunoblotting in sexually mature, pregnant, and postweaning, but not in prepubertal or lactating mammary glands. Furthermore, cleaved Ln-5, as web as MMP2, became detectable in remodeling glands from sexually immature rats treated with sex steroids, In. rat mammary gland explants, epithelial reorganization and luminal cell morphological changes were induced by the addition of exogenous MMP2, in parallel to the appearance of cleaved Ln-5, Similar effects were observed in epithelial monolayers plated on human Ln-5 and exposed to MMP2. These results suggest that cleavage of Ln-5 by MMP2 might be regulated by sex steroids and that it may contribute to breast remodeling under physiological and possibly pathological conditions. C1 Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA. Univ Bari, Inst Med Clin 2, Bari, Italy. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Giannelli, G (reprint author), Scripps Res Inst, Dept Cell Biol, 10550 N Torrey Pines,SBR-12, La Jolla, CA 92037 USA. EM gianlu@scripps.edu RI giannelli, gianluigi/A-8169-2012; Stetler-Stevenson, William/H-6956-2012; Quaranta, Vito/G-6512-2016; OI Stetler-Stevenson, William/0000-0002-5500-5808; Quaranta, Vito/0000-0001-7491-8672; Giannelli, Gianluigi/0000-0002-5140-8060 FU NCI NIH HHS [CA47858, R01 CA047858]; NIGMS NIH HHS [GM46902] NR 42 TC 66 Z9 66 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 1999 VL 154 IS 4 BP 1193 EP 1201 DI 10.1016/S0002-9440(10)65371-0 PG 9 WC Pathology SC Pathology GA 184MU UT WOS:000079616600027 PM 10233857 ER PT J AU Kittles, RA Bergen, AW Urbanek, M Virkkunen, M Linnoila, M Goldman, D Long, JC AF Kittles, RA Bergen, AW Urbanek, M Virkkunen, M Linnoila, M Goldman, D Long, JC TI Autosomal, mitochondrial, and Y chromosome DNA variation in Finland: Evidence for a male-specific bottleneck SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Article DE Y-chromosome compound haplotypes; Y-haplotype phylogeny; microsatellite DNA; mtDNA control region; population bottleneck ID STEPWISE MUTATION MODEL; HUMAN-POPULATIONS; LINKAGE DISEQUILIBRIUM; FINNISH POPULATION; ALLELE FREQUENCIES; MICROSATELLITE LOCI; GENETIC-DIFFERENCES; SEQUENCE DIVERSITY; REPEAT LOCI; EUROPE AB The high prevalence of rare genetic diseases in Finland has been attributed to a founder effect some 2,000 years ago. However, this hypothesis has not been supported from mtDNA sequence and autosomal microsatellite data which indicate high levels of gene diversity. Here we have identified genetic evidence for a population bottleneck by examining variable microsatellite loci on the nonrecombining portion of Y chromosomes from Finland and four populations from Europe and the Americas. Sequence data from segment I of the control region (HVS-1) of mtDNA (360 bases) and 20 autosomal dinucleotide repeat markers were also analyzed. Partitions of genetic variance within and between populations revealed significant levels of Y-chromosome differentiation between populations. Phylogenetic and diversity analyses revealed divergent Finnish Y-haplotype clades and significantly lower Y-haplotype diversity among Finns as compared to other populations. Surprisingly, Finnish Y-haplotype diversity was even lower than the Native American populations, These results provide support for the Finnish bottleneck hypothesis. Evidence for two separate founding Finnish Y-chromosome lineages was also observed from the Y-chromosome phylogeny, A limited number of closely related founding males may have contributed to the low number of paternal lineages in the Finnish population. In contrast, high levels of genetic diversity for mtDNA and autosomal STRs may be the result of sex-biased gene flow and recent immigration to urban areas from established internal isolates within Finland. Published 1999 Wiley-Liss, Inc. C1 Natl Inst Alcohol Abuse & Alcoholism, Sect Populat Genet & Linkage, Natl Inst Hlth, Bethesda, MD 20892 USA. George Washington Univ, Dept Biol Sci, Washington, DC 20052 USA. NIAAA, Neurogenet Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. NIAAA, Clin Studies Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. Univ Helsinki, Dept Psychiat, SF-00180 Helsinki, Finland. RP Kittles, RA (reprint author), Howard Univ, Ctr Canc, 2041 Georgia Ave,Rm 507, Washington, DC 20060 USA. EM rkittles@howard.edu RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Bergen, Andrew/0000-0002-1237-7644 NR 82 TC 70 Z9 71 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 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PD APR PY 1999 VL 108 IS 4 BP 381 EP 399 DI 10.1002/(SICI)1096-8644(199904)108:4<381::AID-AJPA1>3.0.CO;2-5 PG 19 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA 183GU UT WOS:000079546500001 PM 10229384 ER PT J AU Miller, DS Villalobos, AR Pritchard, JB AF Miller, DS Villalobos, AR Pritchard, JB TI Organic cation transport in rat choroid plexus cells studied by fluorescence microscopy SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE compartmentation; confocal microscopy; endosomes; microtubules; monensin; vesicle fusion ID EPITHELIAL-CELLS; ATP; ORGANELLES; SECRETION AB Quinacrine uptake and distribution were studied in a primary culture of rat choroid plexus epithelial cells using conventional and confocal fluorescence microscopy and image analysis. Quinacrine rapidly accumulated in cells, with steady-state levels being achieved after 10-20 min. Uptake was reduced by other organic cations, e.g., tetraethylammonium (TEA), and by KCN. Quinacrine fluorescence was distributed in two cytoplasmic compartments, one diffuse and the other punctate. TEA efflux experiments indicated that more than one-half of intracellular organic cation was in a slowly emptying compartment. The protonophore monensin both emptied that TEA compartment and abolished punctate quinacrine fluorescence, suggesting that a large fraction of total intracellular organic cation was sequestered in acidic vesicles, e.g., endosomes. Finally, quinacrine-loaded vesicles were seen to move within the cytoplasm and to abruptly release their contents at the blood side of the cell; the rate of release was greatly reduced by the microtubule disrupter nocodazole. C1 NIEHS, LPC, NIH, Res Triangle Pk, NC 27709 USA. RP Miller, DS (reprint author), NIEHS, LPC, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM miller@niehs.nih.gov NR 13 TC 30 Z9 30 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD APR PY 1999 VL 276 IS 4 BP C955 EP C968 PG 14 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 184UT UT WOS:000079632700023 PM 10199828 ER PT J AU Wang, WC O'Connell, B Dykeman, R Sakai, T Delporte, C Swaim, W Zhu, X Birnbaumer, L Ambudkar, IS AF Wang, WC O'Connell, B Dykeman, R Sakai, T Delporte, C Swaim, W Zhu, X Birnbaumer, L Ambudkar, IS TI Cloning of Trp1 beta isoform from rat brain: immunodetection and localization of the endogenous Trp1 protein SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE store-operated calcium channel; Trp protein; plasma membrane; nonexcitable cells ID CAPACITATIVE CALCIUM-ENTRY; GLAND ACINAR-CELLS; STORE DEPLETION; DROSOPHILA TRP; FUNCTIONAL EXPRESSION; HUMAN HOMOLOG; CA2+ CHANNEL; RECEPTOR; ACTIVATION; MEMBRANE AB The Trp gene product has been proposed as a candidate protein for the store-operated Ca2+ channel, but the Trp protein(s) has not been identified in any nonexcitable cell. We report here the cloning of a rat brain Trp1 beta cDNA and detection and immunolocalization of the endogenous and expressed Trp1 protein. A 400-bp product, with >95% homology to mouse Trp1, was amplified from rat submandibular gland RNA. Rat-specific primers were used for cloning of a full-length rat brain Trp1 beta cDNA(rTrp1), encoding a protein of 759 amino acids. Northern blot analysis demonstrated the transcript in several rat and mouse tissues. The peptide (amino acids 523-536) was used to generate a polyclonal antiserum. The affinity-purified antibody 1) immunoprecipitated human Trp1 (hTrp1) from transfected HEK-293 cells, 2) reacted with a protein of similar to 92 kDa, but not with hTrp3, in membranes of hTrp3-expressing HEK-293 cells, and 3) reacted with proteins of 92 and 56 kDa in human and rat brain membranes. Confocal microscopy and cell fractionation demonstrated that endogenous and expressed hTrp1 and expressed hTrp3 proteins were localized in the plasma membrane of HEK-293 cells, consistent with their proposed role in Ca2+ influx. The data demonstrate for the first time the presence of Trp1 protein in a nonexcitable cell. C1 Natl Inst Dent & Craniofacial Res, Secretory Physiol Sect, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Gene Regulat & Express Unit, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Imaging Core Facil, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Anesthesiol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90024 USA. Ohio State Univ, Dept Pharmacol, Columbus, OH 43210 USA. Ohio State Univ, Neurobiotechnol Ctr, Columbus, OH 43210 USA. RP Ambudkar, IS (reprint author), Natl Inst Dent & Craniofacial Res, Secretory Physiol Sect, NIH, Bldg 10,Room 1N-113, Bethesda, MD 20892 USA. EM ambudkar@yoda.nidr.nih.gov FU NHLBI NIH HHS [HL-45198]; NIGMS NIH HHS [GM-54235] NR 32 TC 45 Z9 47 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD APR PY 1999 VL 276 IS 4 BP C969 EP C979 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 184UT UT WOS:000079632700024 PM 10199829 ER PT J AU Horska, A Brant, LJ Ingram, DK Hansford, RG Roth, GS Spencer, RGS AF Horska, A Brant, LJ Ingram, DK Hansford, RG Roth, GS Spencer, RGS TI Effect of long-term caloric restriction and exercise on muscle bioenergetics and force development in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE skeletal muscle; energy metabolism; nuclear magnetic resonance spectroscopy ID NUCLEAR-MAGNETIC-RESONANCE; SKELETAL-MUSCLE; DIETARY RESTRICTION; INTRACELLULAR PH; P-31 NMR; SPECTROSCOPY; FATIGUE; HUMANS; ENERGETICS; LACTATE AB We evaluated the hypothesis that long-term caloric restriction and exercise would have beneficial effects on muscle bioenergetics and performance in the rat. By themselves, each of these interventions is known to increase longevity, and bioenergetic improvements are thought to be important in this phenomenon. Accordingly, we investigated rats that underwent long-term caloric restriction and were sedentary, ad libitum-fed rats permitted to exercise by daily spontaneous wheel running (AE), and the combination of the dietary and exercise interventions (RE). Adlibitum-fed, sedentary rats comprised the control group. P-31 NMR spectra of the gastrocnemius muscle (GM) were collected in vivo at rest and during two periods of electrical stimulation. Neither Caloric restriction nor exercise affected the ratio of phosphocreatine to ATP or pH at rest. During the first stimulation and after recovery, the RE group had a significantly smaller decline in pH than did the other groups (P < 0.05). During the second period of stimulation, the decrease in pH was much smaller in all groups than during the first stimulation, with no differences observed among the groups. The combination of caloric restriction and exercise-resulted in a significant attenuation in the decline in developed force during the second period of stimulation (P < 0.05). A biochemical correlate of this was a significantly higher concentration of citrate synthase in the GM samples from the RE rats (32.7 +/- 5.4 mu mol . min-1 . g(-1)) compared with the AE rats (17.6 +/- 5.7 mu mol . min(-1) . g(-1); P ( 0.05). Our experiments thus demonstrated a synergistic effect of long-term caloric restriction and free exercise on muscle bioenergetics during electrical stimulation. C1 NIA, Nucl Magnet Resonance Unit, NIH, Baltimore, MD 21224 USA. NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. NIA, Longitudinal Studies Branch, NIH, Baltimore, MD 21224 USA. NIA, Genet Mol Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Horska, A (reprint author), NIA, Nucl Magnet Resonance Unit, NIH, GRC 4D-08,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ahorska@mri.jhu.edu; spencer@helix.nih.gov NR 37 TC 13 Z9 14 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD APR PY 1999 VL 276 IS 4 BP E766 EP E773 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 185CG UT WOS:000079650100022 PM 10198315 ER PT J AU Vinet, R Vargas, FF AF Vinet, R Vargas, FF TI L- and T-type voltage-gated Ca2+ currents in adrenal medulla endothelial cells SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE whole cell patch clamp; voltage-dependent calcium channels; single microvascular endothelial cells; BAY K 8644; dihydropyridines ID CALCIUM-DEPENDENT INACTIVATION; PANCREATIC BETA-CELLS; PITUITARY GONADOTROPHS; CHROMAFFIN CELLS; SENSORY NEURONS; CHANNELS; SELECTIVITY; KINETICS; CULTURE; DENSITY AB We investigated voltage-dependent Ca2+ channels of bovine adrenal medulla endothelial cells with the whole cell version of the patch-clamp technique. Depolarization elicited an inward current that was carried by Ca2+ and was composed of a transient (T) current, present in all the cells tested, and a sustained (L) current, present in 65% of them. We separated these currents and measured their individual kinetic and gating properties. The activation threshold for T current was approximately -50 mV, and its maximum amplitude was -49.8 +/- 4.8 pA(means +/- SE, n = 19) at 0 mV. The time constant was 10.2 +/- 1.5 ms (n = 4) for activation and 18.4 +/- 2.8 ms (n = 4) for inactivation. The L current activated at -40 mV, and it reached a plateau at -20.1 +/- 2.3 pA(n = 6). Its activation time course was a single exponential with an activation time contant of 26.8 +/- 2.3 ms (n = 4). Current-voltage curves, kinetics, gating, response to BAY K 8644, nifedipine, amiloride, and different selectivity for Ba2+ and Ca2+ indicated that the underlying channels for the observed currents are only of the T- and L-types that resemble those of the endocrine secretory cells. C1 Univ Valparaiso, Escuela Quim & Farm, Valparaiso, Chile. NIDDK, Lab Cell Biol & Genet, Natl Inst Hlth, Bethesda, MD 20892 USA. Univ Calif Davis, Dept Human Physiol, Sch Med, Davis, CA 95616 USA. RP Vinet, R (reprint author), Univ Valparaiso, Escuela Quim & Farm, Casilla 5001, Valparaiso, Chile. EM rvinet@uv.cl NR 39 TC 28 Z9 28 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD APR PY 1999 VL 276 IS 4 BP H1313 EP H1322 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 183LC UT WOS:000079554200026 PM 10199857 ER PT J AU Jayawickreme, SP Gray, T Nettesheim, P Eling, T AF Jayawickreme, SP Gray, T Nettesheim, P Eling, T TI Regulation of 15-lipoxygenase expression and mucus secretion by IL-4 in human bronchial epithelial cells SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE airway epithelium; mucin; cytokines; eicosanoids ID ARACHIDONIC-ACID METABOLISM; MONOHYDROXYEICOSATETRAENOIC ACID; ENDOTHELIAL-CELLS; GENE-EXPRESSION; OXIDIZED LDL; PPAR-GAMMA; LIPOXYGENASE; GENERATION; CYTOKINES; INDUCTION AB Our laboratory has recently shown that mucus differentiation of cultured normal human tracheobronchial epithelial (NHTBE) cells is accompanied by the increased expression of 15-lipoxygenase (15-LO). We used differentiated NHTBE cells to investigate the regulation of 15-LO expression and mucus secretion by inflammatory cytokines. Interleukin (IL)-4 and IL-13 dramatically enhanced the expression of 15-LO whereas tumor necrosis factor-alpha, IL;1 beta, and interferon (IFN)-gamma had no effect. These cytokines did not increase the expression of cyclooxygenase-2, with the exception of a modest induction by IL-1 beta. The IL-4-induced 15-LO expression was concentration dependent, and mRNA and protein expression increased within 3 and 6 h, respectively, after IL-4 treatment. In metabolism studies with intact cells, 15-hydroxyeicosatetraenoic acid (15-HETE) and 13-hydroxyoctadecadienoic acid (13-HODE) were the major metabolites formed from exogenous arachidonic acid and linoleic acid. No prostaglandins were detected. IL-4 treatment dramatically increased the formation of 15-HODE and 15-HETE compared with that in untreated NHTBE cells, and several additional 15-LO metabolites were observed. Pretreatment of NHTBE cells with IFN-gamma or dexamethasone did not inhibit the IL-4-induced expression of 15-LO except at high concentrations (100 ng/ml of IFN-gamma and 10 mu M dexamethasone). IL-4 treatment inhibited mucus secretion and attenuated the expression of the mucin genes MUC5AC and MUC5B at 12-24 h after treatment. Addition of 15-HETE precursor and 13-HODE precursor to the cultures did not alter mucin secretion or mucin gene expression. On the basis of the data presented, we conclude that the increase in 15-LO expression by IL-4 and attenuation of mucus secretion may be independent biological events. C1 NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Pulm Pathobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Eling, T (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, MDA2-01,POB 12233, Res Triangle Pk, NC 27709 USA. NR 40 TC 65 Z9 65 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD APR PY 1999 VL 276 IS 4 BP L596 EP L603 PG 8 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 183TP UT WOS:000079569800006 PM 10198357 ER PT J AU Inoue, T Terris, J Ecelbarger, CA Chou, CL Nielsen, S Knepper, MA AF Inoue, T Terris, J Ecelbarger, CA Chou, CL Nielsen, S Knepper, MA TI Vasopressin regulates apical targeting of aquaporin-2 but not of UT1 urea transporter in renal collecting duct SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE surface biotinylation; immunocytochemistry; differential centrifugation; urinary concentrating mechanism ID RAT TERMINAL IMCD; WATER PERMEABILITY; KIDNEY; MEMBRANE; CHANNEL; ACTIVATION; EXPRESSION; CALCIUM AB In the renal inner medullary collecting duct (IMCD), vasopressin regulates two key transporters, namely aquaporin-2 (AQP2) and the vasopressin-regulated urea transporter (VRUT). Both are present in intracellular vesicles as well as the apical plasma membrane. Short-term regulation of AQP2 has been demonstrated to occur by vasopressin-induced trafficking of AQP2-containing vesicles to the apical plasma membrane. Here, we have carried out studies to determine whether short-term regulation of VRUT occurs by a similar process. Cell surface labeling with NHS-LC-biotin in rat IMCD suspensions revealed that vasopressin causes a dose-dependent increase in the amount of AQP2 labeled at the cell surface, whereas VRUT labeled at the cell surface did not increase in response to vasopressin. Immunoperoxidase labeling of inner medullary thin sections from Brattleboro rats treated with 1-desamina-8-D-arginine vasopressin (DDAVP) for 20 min revealed dramatic translocation of AQP2 to the apical region of the cell, with no change in the cellular distribution of VRUT. in addition, differential centrifugation of inner medullary homogenates from Brattleboro rats treated with DDAVP for 60 min revealed a marked depletion of AQP2 from the low-density membrane fraction (enriched in intracellular vesicles) but did not alter the quantity of VRUT in this fraction. Finally, AQP2-containing vesicles immunoisolated from a low-density membrane fraction from renal inner medulla did not contain immunoreactive VRUT. Thus vasopressin-mediated regulation of AQP2, but not of VRUT, depends on regulated vesicular trafficking to the plasma membrane. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Physiol, Bethesda, MD 20814 USA. Aarhus Univ, Dept Cell Biol, DK-8000 Aarhus, Denmark. RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bldg 10,Rm 6N260,10 Ctr Dr MSC 1603, Bethesda, MD 20892 USA. EM knep@helix.nih.gov FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]; NHLBI NIH HHS [Z01-HL-01282-KE] NR 31 TC 52 Z9 52 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD APR PY 1999 VL 276 IS 4 BP F559 EP F566 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 185JK UT WOS:000079665500009 PM 10198415 ER PT J AU Kim, J Kim, WY Han, KH Knepper, MA Nielsen, S Madsen, KM AF Kim, J Kim, WY Han, KH Knepper, MA Nielsen, S Madsen, KM TI Developmental expression of aquaporin 1 in the rat renal vasculature SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE kidney development; vasa recta; renal lymphatics; immunohistochemistry ID CHIP28 WATER-CHANNEL; INTEGRAL MEMBRANE-PROTEIN; LOCALIZATION; SEGMENTS; FAMILY; KIDNEY AB Aquaporin 1 (AQP-1) is a water channel protein that is constitutively expressed in renal proximal tubule and descending thin limb cells as well as in endothelial cells of the descending vasa recta. Studies in the developing rat kidney have demonstrated that AQP-1 is expressed in renal tubules before birth. However, nothing is known about the expression of AQP-1 in the renal vasculature during kidney development. The purpose of this study was to establish the distribution of AQP-1 in the renal vasculature of the developing rat kidney and follow the differentiation of the vascular system during kidney development. Kidneys from 16-, 17-, 18-, and 20-day-old fetuses and 1-, 4-, 7-, 14-, 21-, and 28-day-old pups were preserved and processed for immunohistochemical studies using a preembedding immunoperoxidase procedure. AQP-1 immunoreactivity was detected using affinity-purified rabbit polyclonal antibodies to AQP-1. AQP-1 was expressed throughout the arterial portion of the renal vasculature of the fetal and neonatal kidney from gestational age 17 days to 1 wk after birth. AQP-1 immunoreactivity gradually disappeared from the renal vasculature between 1 and 2 wk of age and remained only in the descending vasa recta. In contrast, AQP-1 immunoreactivity was not observed in lymphatic vessels until 3 wk of age and persisted in the adult kidney. AQP-1 was also expressed in a population of interstitial cells in the terminal part of the renal papilla at 3 wk of age as well as in the adult kidney. The transient expression of AQP-1 in the arterial portion of the renal vasculature in the developing rat kidney suggests that AQP-1 is important for fluid equilibrium and/or drainage in the developing kidney or, alternatively, plays a role in the regulation of growth and/or branching of the vascular tree during kidney development. C1 Catholic Univ, Coll Med, Dept Anat, Socho Ku, Seoul 137701, South Korea. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. Aarhus Univ, Inst Anat, Dept Cell Biol, DK-8000 Aarhus, Denmark. Univ Florida, Coll Med, Div Nephrol Hypertens & Transplantat, Gainesville, FL 32610 USA. RP Kim, J (reprint author), Catholic Univ, Coll Med, Dept Anat, Socho Ku, 505 Banpo Dong, Seoul 137701, South Korea. EM jinkim@cmc.cuk.ac.kr; madsekm@medicine.ufl.edu FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]; NIDDK NIH HHS [DK-28330] NR 24 TC 24 Z9 25 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD APR PY 1999 VL 276 IS 4 BP F498 EP F509 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 185JK UT WOS:000079665500002 PM 10198408 ER PT J AU Yoon, JH Koo, JS Norford, D Guzman, K Gray, T Nettesheim, P AF Yoon, JH Koo, JS Norford, D Guzman, K Gray, T Nettesheim, P TI Lysozyme expression during metaplastic squamous differentiation of retinoic acid-deficient human tracheobronchial epithelial cells SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID CHICKEN LYSOZYME; EXTRACELLULAR-MATRIX; TRACHEAL EPITHELIUM; TRANSGENIC MICE; GENE; LOCALIZATION; SKIN; MACROPHAGES; PHENOTYPE; SECRETION AB We previously reported (Gray, T. E., K. Guzman, C. W. Davis, L. H. Abdullah, and P. Nettesheim. 1996. Mucociliary differentiation of serially passaged normal human tracheobronchial epithelial cells. Am. J. Respir. Cell Mol. Biol. 14:104-112) that retinoic acid (RA)-deprived cultures of normal human tracheobronchial epithelial (NHTBE) cells became squamous, failed to produce mucin, and instead secreted or released large amounts of lysozyme (LZ). The purpose of the studies reported here was to elucidate the relationship between RA deficiency-induced squamous differentiation and increased LZ, and to determine what mechanisms were involved. We found that intracellular LZ began to accumulate in RA-deficient NHTBE cultures early during squamous differentiation. Between Days 10 and 18 of culture, cellular LZ levels were more than 10 times higher in RA-deficient than in RA-sufficient cultures. On Day 12, large numbers of cells began to exfoliate in RA-deficient cultures and extracellular LZ appeared at the apical surface, presumably released from the exfoliated cells. Metabolic labeling studies showed that the rate of LZ synthesis was not increased in RA-deficient cultures over that in RA-sufficient cultures; however, intracellular LZ half-life was much longer in RA-deficient cultures. We concluded that the increased accumulation of both intra- and extracellular LZ in RA-deficient cultures was due to increased LZ stability and was not the result of increased LZ synthesis. When RA-deficient cultures were treated on Day 7 with 10(-6) M RA, intracellular LZ levels did not substantially decrease until 3 d later, coinciding with a marked increase in mucin secretion. LZ messenger RNA levels were unchanged at 24 h, but were modestly increased (rather than decreased) at all subsequent time points. We concluded that RA does not directly regulate LZ, and that the excessive accumulation of LZ in RA-deprived NHTBE cells is a consequence of vitamin A deficiency-induced abnormal differentiation. C1 NIEHS, Pulm Pathobiol Lab, Res Triangle Pk, NC 27709 USA. Yonsei Univ, Coll Med, Dept Otorhinolaryngol, Seoul, South Korea. RP Nettesheim, P (reprint author), NIEHS, Pulm Pathobiol Lab, MD D2-01,POB 12233, Res Triangle Pk, NC 27709 USA. RI Yoon, Joo-Heon/E-5781-2016; OI Yoon, Joo-Heon/0000-0003-2404-7156 FU NHLBI NIH HHS [HL 36982] NR 29 TC 13 Z9 13 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD APR PY 1999 VL 20 IS 4 BP 573 EP 581 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 186YF UT WOS:000079758200005 PM 10100988 ER PT J AU Ostrowski, LE Andrews, K Potdar, P Matsuura, H Jetten, A Nettesheim, P AF Ostrowski, LE Andrews, K Potdar, P Matsuura, H Jetten, A Nettesheim, P TI Cloning and characterization of KPL2, a novel gene induced during ciliogenesis of tracheal epithelial cells SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID AXONEME-ASSOCIATED PROTEIN; HEAVY-CHAIN GENES; DROSOPHILA-HYDEI; EXPRESSION; BINDING; SITE; DIFFERENTIATION; IDENTIFICATION; TISSUES; DOMAIN AB To identify genes upregulated during the process of ciliated cell differentiation of airway epithelial cells, differential display was used to compare RNA from rat tracheal epithelial (RTE) cells cultured under conditions that inhibit/promote ciliated cell differentiation. Several partial complementary DNAs (cDNAs) were identified whose expression was regulated coordinately with ciliated cell differentiation. One of these, KPL2, detected a messenger RNA transcript of similar to 6 kb when used as a probe on Northern blots of RNA from ciliated cultures but was undetectable in RNA from nonciliated cultures. Sequencing of overlapping clones obtained by a modified rapid amplification of cDNA ends procedure generated a complete cDNA sequence that exhibited no significant homology to sequences in GenBank, indicating that KPL2 is a novel gene. Southern analysis demonstrated that KPL2 exists as a single-copy gene. KPL2 contains a long open reading frame predicted to code for a protein of > 200 kD. Several putative functional motifs are present in the protein, including a calponin homology domain, three nuclear localization signals, a consensus P-loop, and a proline-rich region, suggesting that KPL2 has a unique function. KPL2 was undetectable in heart and liver samples, but was expressed in brain and testis, tissues that contain axonemal structures. In seminiferous tubules of the testis, KPL2 expression was stage-specific and appeared to be highest in spermatocytes and round spermatids. During differentiation of RTE cells, the expression of KPL2 closely paralleled that of an axonemal dynein heavy chain. These results suggest that KPL2 plays an important role in the differentiation or function of ciliated cells in the airway. C1 NIEHS, Pulm Pathobiol Lab, Res Triangle Pk, NC 27709 USA. RP Ostrowski, LE (reprint author), Univ N Carolina, Cyst Fibrosis Pulm Res & Treatment Ctr, 6019 Thurston Bowles Bldg, Chapel Hill, NC 27599 USA. OI Jetten, Anton/0000-0003-0954-4445 NR 32 TC 26 Z9 28 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD APR PY 1999 VL 20 IS 4 BP 675 EP 683 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 186YF UT WOS:000079758200016 PM 10100999 ER PT J AU Avila, NA Premkumar, A Merke, DP AF Avila, NA Premkumar, A Merke, DP TI Testicular adrenal rest tissue in congenital adrenal hyperplasia: Comparison of MR imaging and sonographic findings SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID TUMORS; MASSES AB OBJECTIVE. The purpose of our study was to describe the MR features of testicular adrenal rest tissue in patients with congenital adrenal hyperplasia and to compare the usefulness of MR imaging with that of sonography for the detection of testicular adrenal rest tissue. SUBJECTS AND METHODS. Nineteen patients with congenital adrenal hyperplasia underwent MR imaging and gray-scale and color Doppler sonography of the testicles during the same visit to our institution. Findings were compared. RESULTS. MR features of testicular adrenal rest tissue included the following: isointensity (71% of the masses) and slight hyperintensity (29% of the masses) relative to normal testicular tissue on T1-weighted images; hypointensity relative to normal testicular tissue on T2-weighted images (100% of the masses); and diffuse enhancement on contrast-enhanced T1-weighted images (85% of the masses). MR imaging and sonography revealed the testicular lesions equally well. Eleven (58%) of 19 patients had normal findings on MR imaging and sonography. Eight (42%) of 19 patients had 14 intratesticular masses detected by both imaging techniques. CONCLUSION. MR imaging and sonography are equally useful in the detection of testicular adrenal rest tissue. Because sonography is more accessible to most institutions and is less expensive, it is the imaging technique of choice for the detection of testicular adrenal rest tissue. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Avila, NA (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, 10 Ctr Dr,MSC 1182,Bldg 10,Rm 1C660, Bethesda, MD 20892 USA. NR 17 TC 50 Z9 56 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 1999 VL 172 IS 4 BP 1003 EP 1006 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 178VJ UT WOS:000079289600024 PM 10587136 ER PT J AU Shapiro, S Issaragrisil, S Kaufman, DW Anderson, T Chansung, K Thamprasit, T Sirijirachai, J Piankijagum, A Porapakkham, Y Vannasaeng, S Leaverton, PE Young, NS AF Shapiro, S Issaragrisil, S Kaufman, DW Anderson, T Chansung, K Thamprasit, T Sirijirachai, J Piankijagum, A Porapakkham, Y Vannasaeng, S Leaverton, PE Young, NS CA Aplastic Anemia Study Grp TI Agranulocytosis in Bangkok, Thailand: A predominantly drug-induced disease with an unusually low incidence SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID INDUCED NEUTROPENIA; BLOOD DYSCRASIAS; APLASTIC-ANEMIA; AMINOPHENAZONE; DIPYRONE; TRIALS AB Agranulocytosis, a syndrome characterized by a marked reduction in circulating granulocytes, is strongly associated with medical drug use in Europe and the United States. Unregulated use of common pharmaceutical agents in developing countries has been suspected of causing large numbers of cases of agranulocytosis and deaths, especially among children. To elucidate the incidence and etiology of agranulocytosis in Thailand, a population-based case-control study of symptomatic agranulocytosis that resulted in hospital admission was conducted in Bangkok from 1990 to 1994. An attempt was also made to study the disease in Khonkaen tin northeastern Thailand) and Songkla tin southern Thailand), but there were insufficient cases in the latter regions, and the analysis was confined to subjects from Bangkok. In that region, the overall incidence of agranulocytosis was 0.8 per million per year; there were no deaths. As expected, the incidence was higher in females (0.9 per million), and it increased with age (4.3 per million beyond age 60). Among 25 cases and 529 controls the relative risk estimate for a combined category of all suspect drugs was 9.2 (95% confidence interval = 3.9-21), and the proportion of cases that could be attributed to drug use was 68%. For individual drugs and drug classes the data were sparse; within these Limitations, the strongest association appeared to be with antithyroid drugs. One case and three controls were exposed to dipyrone, a drug known to cause agranulocytosis; with such scanty data the risk could not be evaluated. Exposure to pesticides or solvents was not associated with an increased risk. This is the first formal epidemiologic study of agranulocytosis in a developing country. As in the West, most cases are attributable to medical drug use. However, the incidence of agranulocytosis in Bangkok, and apparently, in Thailand as a whole, is unusually low, and the disease does not pose a public health risk. C1 Siriraj Hosp, Dept Med, Div Hematol, Bangkok 10700, Thailand. Boston Univ, Sch Med, Sch Publ Hlth, Slone Epidemiol Unit, Brookline, MA 02146 USA. Mahidol Univ, Asean Inst Hlth Dev, Bangkok 10700, Thailand. Khon Kaen Univ, Fac Med, Dept Med, Khon Kaen 40002, Thailand. Prince Songkla Univ, Dept Med, Songkla, Thailand. Univ S Florida, Dept Epidemiol & Biostat, Tampa, FL 33612 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Issaragrisil, S (reprint author), Siriraj Hosp, Dept Med, Div Hematol, Bangkok 10700, Thailand. OI Issaragrisil, Surapol/0000-0002-8924-0646 FU NHLBI NIH HHS [HL 35068] NR 31 TC 35 Z9 35 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD APR PY 1999 VL 60 IS 4 BP 573 EP 577 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 198TA UT WOS:000080439200015 PM 10348230 ER PT J AU Savory, J Herman, MM AF Savory, J Herman, MM TI Advances in instrumental methods for the measurement and speciation of trace metals SO ANNALS OF CLINICAL AND LABORATORY SCIENCE LA English DT Article ID ATOMIC-ABSORPTION SPECTROMETRY; CHROMATOGRAPHY-MASS-SPECTROMETRY; STABLE ISOTOPE-DILUTION; BIOLOGICAL-MATERIALS; ULTRASTRUCTURAL-LOCALIZATION; CAPILLARY ELECTROPHORESIS; SELENIUM SPECIATION; GEL-FILTRATION; BLOOD-SERUM; ICP-MS AB Progress in understanding the role of trace metals in biology has been largely dependent on the development of sensitive, accurate and precise analytical methods. Atomic spectroscopic techniques, particularly atomic absorption, have made the greatest contribution. Key to the success of such analytical techniques has been the simplification of sample processing so that contamination is minimized. Electrothermal atomization has allowed sensitivity limits to be lowered sufficiently so that even ultra-trace metals can be detected. More recently, mass spectrometric detection of metal ions has added to the repertoire of available instrumentation, particularly with the use of inductively coupled plasma to introduce ions into the mass analyzer. These analyzers are suitable for multielement analysis. More conventional mass spectrometric analysis of metal chelates offer an alternate solution but require considerable specimen preparation time. Intracellular localization of trace metals necessitates complex specimen processing prior to analysis on instruments that are highly sophisticated and expensive. Metal speciation is a rapidly growing area of trace metal research, with. the major advances coming from coupling of the separation process, such as capillary electrophoresis or high performance liquid chromatography, with the analytical instrument for metal detection. Inductively coupled plasma-mass spectrometry has proved to be an excellent choice for such detection purposes. Refinement of these methods as well as more widely available instruments for microanalysis will add greatly to continued advances in our knowledge of the role of trace metals in biology and medicine. C1 Univ Virginia, Hlth Sci Ctr, Dept Pathol, Charlottesville, VA 22908 USA. Univ Virginia, Hlth Sci Ctr, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA. NIMH, Clin Brain Disorders Branch, Sect Neuropathol, NIH, Bethesda, MD 20892 USA. RP Savory, J (reprint author), Univ Virginia, Hlth Sci Ctr, Dept Pathol, Box 168, Charlottesville, VA 22908 USA. NR 47 TC 14 Z9 15 U1 0 U2 3 PU INST CLINICAL SCIENCE INC PI PHILADELPHIA PA 1833 DELANCEY PLACE, PHILADELPHIA, PA 19103 USA SN 0091-7370 J9 ANN CLIN LAB SCI JI Ann. Clin. Lab. Sci. PD APR-JUN PY 1999 VL 29 IS 2 BP 118 EP 126 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 184TQ UT WOS:000079629900005 PM 10219699 ER PT J AU Sorlie, PD Sharrett, AR Patsch, W Schreiner, PJ Davis, CE Heiss, G Hutchinson, R AF Sorlie, PD Sharrett, AR Patsch, W Schreiner, PJ Davis, CE Heiss, G Hutchinson, R TI The relationship between lipids/lipoproteins and atherosclerosis in African Americans and whites: The atherosclerosis risk in communities study SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE lipoproteins; cholesterol; atherosclerosis; ethnic groups; prospective studies ID CORONARY HEART-DISEASE; HIGH-DENSITY-LIPOPROTEIN; ARTERY WALL THICKNESS; B-MODE ULTRASOUND; APOLIPOPROTEIN-A-I; CARDIOVASCULAR-DISEASE; SERUM-CHOLESTEROL; EVANS COUNTY; CAROTID ATHEROSCLEROSIS; BLOOD COLLECTION AB PURPOSE: The relationships between lipids/lipoproteins and atherosclerosis were determined in African Americans and whites to assess the consistency of the relationship between these two groups. Differences could suggest varying biological, environmental, or life-style cofactors influencing development of atherosclerosis. METHODS: In the Atherosclerosis Risk in Communities Study, 2966 African Americans and 9399 whites had determinations of LDL, HDL, HDL2, and HDL3 cholesterol, triglycerides, apolipoprotein A1 and B, and lipoprotein (a). Carotid intimal-medial thickening (IMT) was measured using B-mode ultrasound imaging. RESULTS: The associations, using linear regression, between carotid IMT and LDL cholesterol, HDL cholesterol, and other lipid measurements were significantly weaker in African Americans than whites. Averaging men and women, a 1.034 mmol/L (40 mg/dl) difference in LDL cholesterol was associated with a 0.028 mm IMT difference in whites but a 0.019 difference in African Americans. Similarly, for HDL cholesterol, a 0.44 mmol/L (17 mg/dl) difference is associated with 0.026 mm difference in carotid IMT in whites and 0.011 mm difference in African Americans. The associations are much weaker in African Americans than whites at the bifurcation and internal carotid, the carotid sites most prone to atherosclerosis. Analysis was done stratifying for risk factors that differ between African Americans and whites, but within most, the relationships remained substantially weaker in African Americans. CONCLUSIONS: We have observed a statistically significant difference in the association between many lipids/lipoproteins and carotid IMT between African Americans and whites. Analysis of many potential cofactors have not provided an explanation for the weaker association. Although possible differences in prior levels of these lipids may provide one explanation for the finding, these results need confirmation in other studies. Ann Epidemiol 1999;9:149-158. Published by Elsevier Science Inc. C1 NHLBI, Epidemiol & Biometry Program, NIH, Bethesda, MD 20892 USA. Landeskrankenanstalten, Dept Lab Med, Salzberg, Austria. Univ Minnesota, Dept Epidemiol, Minneapolis, MN USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA. RP Sorlie, PD (reprint author), NHLBI, Epidemiol & Biometry Program, NIH, Rockledge Ctr 2,MSC 7934,Room 8176,6701 Rockledge, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [N01-HC-55015, N01-HC-55016, N01-HC-55018] NR 57 TC 12 Z9 12 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD APR PY 1999 VL 9 IS 3 BP 149 EP 158 DI 10.1016/S1047-2797(98)00063-5 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 177HU UT WOS:000079205200002 PM 10192646 ER PT J AU Moorman, PG Newman, B Millikan, RC Tse, CKJ Sandler, DP AF Moorman, PG Newman, B Millikan, RC Tse, CKJ Sandler, DP TI Participation rates in a case control study: The impact of age, race, and race of interviewer SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE response rates; epidemiologic methods; breast cancer; blacks ID BREAST-CANCER; CLINICAL-TRIALS; RISK; RESPONDENTS; REFUSAL; BIAS AB PURPOSE: Despite concerns about declining participation rates in epidemiologic studies in recent years, relatively few papers have discussed obstacles to recruiting study participants or strategies for optimizing response rates. This report describes factors associated with nonparticipation in a population-based, case-control study of breast cancer and discusses ways to overcome barriers to participation. METHODS: Contact and cooperation rates were calculated for participants in the Carolina Breast Cancer Study (CBCS), stratified by case status, age, race, and race of interviewer. Demographic and breast cancer risk factor characteristics of partial and full responders also were compared. RESULTS: Contact rates and cooperation rates varied by case/control status and demographic characteristics. Contact rates were lower among controls, younger women, and black women. Cooperation rates were lower among controls, older women, and black cases. Cooperation rates were higher among both black and nonblack women when participants and interviewers were concordant on race. CONCLUSIONS: Obstacles to recruitment seem to differ among race and age subgroups, suggesting chat recruitment strategies may need to be tailored to potential participants based upon demographic characteristics. Strategies have been implemented to improve response rates in this and other epidemiologic studies; however, additional research and innovation in this area are needed. Ann Epidemiol 1999;9:188-195. (C) 1999 Elsevier Science Inc. All rights reserved. C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Moorman, PG (reprint author), Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, 60 Coll St,POB 208034, New Haven, CT 06520 USA. OI Sandler, Dale/0000-0002-6776-0018 FU NCI NIH HHS [P50-CA58223, R29-CA67285] NR 26 TC 131 Z9 131 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD APR PY 1999 VL 9 IS 3 BP 188 EP 195 DI 10.1016/S1047-2797(98)00057-X PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 177HU UT WOS:000079205200007 PM 10192651 ER PT J AU Cohen, LG Weeks, RA Sadato, N Celnik, P Ishii, K Hallett, M AF Cohen, LG Weeks, RA Sadato, N Celnik, P Ishii, K Hallett, M TI Period of susceptibility for cross-modal plasticity in the blind SO ANNALS OF NEUROLOGY LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; EARLY VISUAL DEPRIVATION; ACTIVATION PATTERNS; CONGENITALLY BLIND; OCCIPITAL CORTEX; SENSITIVE PERIOD; COIL SUPPRESSION; BRAILLE READERS; CEREBRAL-CORTEX; HUMANS AB Cross-modal plasticity in blind subjects contributes to sensory compensation when vision is lost early in life, but it is not known if it does so when visual loss occurs at an older age. We used (H2O)-O-15 positron emission tomography to identify cerebral regions activated in association with Braille reading, and repetitive transcranial magnetic stimulation to induce focal transient disruption of function during Braille reading, in 8 subjects who became blind after age 14 years (late-onset blind), after a lengthy period of normal vision. Results were compared with those previously reported obtained from congenitally and early-onset blind subjects. As shown by (H2O)-O-15 positron emission tomographic scanning, the occipital cortex was strongly activated in the congenitally blind and early-onset blind groups but not in the late-onset blind group. Occipital repetitive transcranial magnetic stimulation disrupted the Braille reading task in congenitally blind and early-onset blind subjects but not in late-onset blind subjects. These results indicate that the susceptible period for this form of functionally relevant cross-modal plasticity does not extend beyond 14 years. C1 NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. Fukui Med Sch, Biomed Imaging Res Ctr, Fukui 91011, Japan. RP Cohen, LG (reprint author), NINDS, Human Cort Physiol Sect, NIH, Bldg 10,Room 5N234, Bethesda, MD 20892 USA. NR 63 TC 177 Z9 182 U1 3 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 1999 VL 45 IS 4 BP 451 EP 460 DI 10.1002/1531-8249(199904)45:4<451::AID-ANA6>3.0.CO;2-B PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 182ND UT WOS:000079504300006 PM 10211469 ER PT J AU Koch, CA Krahling, KH AF Koch, CA Krahling, KH TI Porencephalic cysts in children with epilepsy: Treatment by cyst fenestration SO ANNALS OF NEUROLOGY LA English DT Letter ID SEIZURE C1 NICHHD, NIH, Bethesda, MD 20892 USA. Univ Munster, Dept Surg, D-4400 Munster, Germany. RP Koch, CA (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. RI Koch, Christian/A-4699-2008 OI Koch, Christian/0000-0003-3127-5739 NR 3 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 1999 VL 45 IS 4 BP 547 EP 547 DI 10.1002/1531-8249(199904)45:4<547::AID-ANA24>3.0.CO;2-O PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 182ND UT WOS:000079504300024 PM 10211486 ER PT J AU Sikora, K Advani, S Koroltchouk, V Magrath, I Levy, L Pinedo, H Schwartsmann, G Tattersall, M Yan, S AF Sikora, K Advani, S Koroltchouk, V Magrath, I Levy, L Pinedo, H Schwartsmann, G Tattersall, M Yan, S TI Essential drugs for cancer therapy: A World Health Organization consultation SO ANNALS OF ONCOLOGY LA English DT Article DE chemotherapy; drugs; generics; prioritization ID OVARIAN-CANCER; ADJUVANT CHEMOTHERAPY; PHASE-II; PACLITAXEL; SURVIVAL AB The WHO has previously produced recommendations on the essential drugs required for cancer therapy. Over the last five years several new anti cancer drugs have been aggressively marketed. Most of these are costly and produce only limited benefits. We have divided currently available anti-cancer drugs into three priority groups. Curable cancers and those cancers where the cost-benefit ratio clearly favours drug treatment can be managed appropriately with regimens based on only 17 drugs. All of these are available, at relatively low cost, as generic preparations. The wide availability of these drugs should be the first priority. The second group of drugs may have some advantages in certain clinical situations. Based on current evidence, drugs in the third group are judged as currently not essential for the effective delivery of cancer care. Adequate supportive care programmes with the widespread availability of effective drugs for pain control are of considerably greater importance. The adoption of these priorities will help to optimise the effectiveness and efficiency of chemotherapy and ensure equitable access to essential drugs especially in low resource environments. Clearly this paper represents the views of its contributors. The WHO welcomes feedback from all oncologists so that the advice it gives to governments in prioritising the procurement of anti cancer drugs can be as comprehensive as possible. C1 Int Agcy Res Canc, WHO, Programme Canc Control, F-69372 Lyon 08, France. Tata Mem Hosp, Dept Med Oncol, Bombay, Maharashtra, India. Natl Canc Inst, Bethesda, MD USA. Univ Zimbabwe, Dept Med, Harare, Zimbabwe. Vrije Univ Amsterdam, Dept Med Oncol, Amsterdam, Netherlands. Univ Fed Rio Grande Sul, Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil. Univ Sydney, Dept Canc Med, Sydney, NSW 2006, Australia. Chinese Acad Med Sci, Canc Hosp, Dept Med Oncol, Beijing, Peoples R China. RP Sikora, K (reprint author), Int Agcy Res Canc, WHO, Programme Canc Control, 150 Cours Albert Thomas, F-69372 Lyon 08, France. RI Schwartsmann, Gilberto/G-4256-2016 OI Schwartsmann, Gilberto/0000-0002-7850-1644 NR 29 TC 62 Z9 64 U1 0 U2 6 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD APR PY 1999 VL 10 IS 4 BP 385 EP 390 DI 10.1023/A:1008367822016 PG 6 WC Oncology SC Oncology GA 202XX UT WOS:000080678400010 PM 10370779 ER PT J AU Queirolo, P Ponte, M Gipponi, M Cafiero, F Peressini, A Semino, C Pietra, G Lionetto, R Vecchio, S Ribizzi, I Melioli, G Sertoli, MR AF Queirolo, P Ponte, M Gipponi, M Cafiero, F Peressini, A Semino, C Pietra, G Lionetto, R Vecchio, S Ribizzi, I Melioli, G Sertoli, MR CA Melanoma Ist Sci Tumori Grp TI Adoptive immunotherapy with tumor-infiltrating lymphocytes and subcutaneous recombinant interleukin-2 plus interferon alfa-2a for melanoma patients with nonresectable distant disease: A phase III pilot trial SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE tumor-infiltrating lymphocytes; interleukin-2; interferon alfa-2a; adoptive immunotherapy ID ACTIVATED KILLER-CELLS; CONTINUOUS INFUSION INTERLEUKIN-2; ESTABLISHED PULMONARY METASTASES; HIGH-DOSE INTERLEUKIN-2; EXPANDED IN-VITRO; MALIGNANT-MELANOMA; ADVANCED CANCER; CARCINOMA; COMBINATION; THERAPY AB Background: On the basis of our previous experience, we designed this study to determine the activity and toxicity of outpatient treatment with autologous tumor-infiltrating lymphocytes (TIL) together with intermediate-dose recombinant interleukin-2 (rIL-2) and low-dose recombinant interferon alfa-2a (rIFN-alpha 2a), for patients with metastatic melanoma. Methods: Between April 1992 and October 1994, we processed 38 melanoma samples derived from 36 patients with metastases. Proliferative cultures of expanded lymphocytes (TIL) were infused only once into patients with metastatic melanoma. rIL-2 was administered subcutaneously for 1 month, starting on the day of TIL infusion, at an escalating dose of 6-18 x 10(6) IU/m(2)/day for the first week and at the maximum-tolerated dose for the subsequent 3 weeks and then, after a 15-day interval, for 1 week/month for 3 months. rIFN-alpha 2a was administered subcutaneously at 3 x 10(6) TCT three times each week until progression. Results: Of 38 melanoma samples, 19 (50%) resulted in proliferative cultures and were infused. The median number of expanded lymphocytes was 18 x 10(9) (range, 1-43 x 10(9)), and the median period of culture was 52 days (range, 45-60). rIL-2 was administered at doses ranging between 6 and is x 10(6) IU/m(2)/day. Toxicity was mild or moderate, and no Life-threatening side effects were encountered. Two of 19 treated patients experienced complete responses of their metastatic sites (soft tissue), 10 had stable disease, and 7 showed progressive disease. The response rate was 11% (95% confidence interval, 2-35%). Conclusions: Outpatient treatment with TIL plus rIL-2 and rIFN-alpha 2a is feasible, although, within the context of the small sample size, the activity of the combination was no different from the reported activity of any of the components used alone. C1 Univ Genoa, Natl Inst Canc Res, Dept Med Oncol, I-16132 Genoa, Italy. Univ Genoa, Natl Inst Canc Res, Dept Surg Oncol, I-16132 Genoa, Italy. Natl Canc Inst, Adv Biotechnol Ctr, Genoa, Italy. RP Queirolo, P (reprint author), Univ Genoa, Natl Inst Canc Res, Dept Med Oncol, Largo Rosanna Benzi 10, I-16132 Genoa, Italy. RI Queirolo, Paola/K-6778-2016; pietra, gabriella/J-7204-2016 OI Queirolo, Paola/0000-0002-9917-6633; pietra, gabriella/0000-0002-7080-531X NR 33 TC 14 Z9 14 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD APR-MAY PY 1999 VL 6 IS 3 BP 272 EP 278 DI 10.1007/s10434-999-0272-4 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA 194DV UT WOS:000080177600010 PM 10340886 ER PT J AU Callender, DP Jayaprakash, N Bell, A Petraitis, V Petratienes, R Candelario, M Schaufele, R Dunn, JM Sei, S Walsh, TJ Balis, FM AF Callender, DP Jayaprakash, N Bell, A Petraitis, V Petratienes, R Candelario, M Schaufele, R Dunn, JM Sei, S Walsh, TJ Balis, FM TI Pharmacokinetics of oral zidovudine entrapped in biodegradable nanospheres in rabbits SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID MICROSPHERES; CHILDREN AB The pharmacokinetic profile of oral zidovudine entrapped in a 50:50 polyactide-coglycolide matrix (nanospheres) was compared to those of standard oral and parenteral zidovudine formulations in rabbits. The bioavailability of zidovudine nanospheres at 50 mg/kg of body weight was 76%, and this dose achieved prolonged exposure to zidovudine compared to standard formulations without an increase in the drug's peak concentration. C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. NCI, Div Clin Sci, Bethesda, MD 20892 USA. Verex Labs Inc, Englewood, CO 80112 USA. RP Balis, FM (reprint author), NCI, Pediat Oncol Branch, Bldg 10,Rm 13N240,10 Ctr Dr, Bethesda, MD 20892 USA. NR 13 TC 10 Z9 10 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD APR PY 1999 VL 43 IS 4 BP 972 EP 974 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 183LQ UT WOS:000079555400042 PM 10103214 ER PT J AU Barnard, DL Sidwell, RW Xiao, W Player, MR Adah, SA Torrence, PF AF Barnard, DL Sidwell, RW Xiao, W Player, MR Adah, SA Torrence, PF TI 2-5A-DNA conjugate inhibition of respiratory syncytial virus replication: effects of oligonucleotide structure modifications and RNA target site selection SO ANTIVIRAL RESEARCH LA English DT Article DE respiratory syncytial virus; oligonucleotides; antiviral; 2-5A-antisense; RNase L ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN CYTOMEGALOVIRUS; ANTIVIRAL ACTIVITY; PHOSPHOROTHIOATE OLIGONUCLEOTIDE; 2-5A-ANTISENSE CHIMERAS; ANTISENSE CHIMERAS; COMPLEMENTARY; OLIGODEOXYNUCLEOTIDES; DEGRADATION; CELLS AB To define more fully the conditions for 2-5A-antisense inhibition of respiratory syncytial virus (RSV), relationships between 2-5A antisense oligonucleotide structure and the choice of RNA target sites to inhibition of RSV replication have been explored. The lead 2-5A-antisense chimera for this study was the previously reported NIH8281 that targets the RSV M2 RNA. We have confirmed and extended the earlier study by showing that NIH8281 inhibited RSV strain A2 replication in a variety of antiviral assays, including virus yield reduction assays performed in monkey (EC90 = 0.02 mu M) and human cells (EC90 = 1 mu M). This 2-5A-antisense chimera also inhibited other A strains, B strains and bovine RSV in cytopathic effect inhibition and Neutral Red Assays (EC50 values = 0.1-1.6 mu M). The 2'-O-methylation modification of NIH8281 to increase affinity for the complementary RNA and provide nuclease resistance, the introduction of phosphothioate groups in the antisense backbone to enhance resistance to exo- and endonucleases, and the addition of cholesterol to the 3'-terminus of the antisense oligonucleotide to increase cellular uptake, all resulted in loss of activity. Of the antisense chimeras targeting other RSV mRNAs (NS1, NS2, P, M. G, F, and L), only those complementary to L mRNA were inhibitory. These results suggest that lower abundance mRNAs may be the best targets for 2-5A-antisense; moreover, the active 2-5A antisense chimeras in this study may serve as useful guides for the development of compounds with improved stability, uptake and anti-RSV activity. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NIDDKD, Sect Biomed Chem, Med Chem Lab, NIH, Bethesda, MD 20892 USA. Utah State Univ, Inst Antiviral Res, Logan, UT 84322 USA. RP Torrence, PF (reprint author), NIDDKD, Sect Biomed Chem, Med Chem Lab, NIH, Bldg 8 Rm B2A02, Bethesda, MD 20892 USA. EM torrence@helix.nih.gov FU NIAID NIH HHS [N01-AI-35178] NR 60 TC 22 Z9 23 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD APR PY 1999 VL 41 IS 3 BP 119 EP 134 DI 10.1016/S0166-3542(99)00005-4 PG 16 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 185CD UT WOS:000079649800004 PM 10320045 ER PT J AU Castellanos, FX AF Castellanos, FX TI Stimulants and tic disorders - From dogma to data SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Editorial Material ID DEFICIT HYPERACTIVITY DISORDER; LA-TOURETTES SYNDROME; NERVOUS-SYSTEM STIMULANTS; METHYLPHENIDATE TREATMENT; GILLES; CHILDREN; BOYS C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Castellanos, FX (reprint author), NIMH, Child Psychiat Branch, 10 Ctr Dr,Room 3B-19,MSC 1251, Bethesda, MD 20892 USA. NR 18 TC 8 Z9 9 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD APR PY 1999 VL 56 IS 4 BP 337 EP 338 DI 10.1001/archpsyc.56.4.337 PG 2 WC Psychiatry SC Psychiatry GA 182NE UT WOS:000079504400005 PM 10197828 ER PT J AU Agartz, I Momenan, R Rawlings, RR Kerich, MJ Hommer, DW AF Agartz, I Momenan, R Rawlings, RR Kerich, MJ Hommer, DW TI Hippocampal volume in patients with alcohol dependence SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID ALZHEIMERS-DISEASE; SEX-DIFFERENCES; TEMPORAL-LOBE; BODY-WEIGHT; US ADULTS; BRAIN; WOMEN; MRI; ETHANOL; METABOLISM AB Background: Smaller hippocampal volumes have been reported in the brains of alcoholic patients than in those of healthy subjects, although it is unclear if the hippocampus is disproportionally smaller than the brain as a whole. There is evidence that alcoholic women are more susceptible than alcoholic men to liver and cardiac damage from alcohol. It is not known whether the hippocampi of the female brain are more vulnerable to alcohol. Methods: We compared the hippocampal volumes in 52 hospitalized alcoholic men and women with those of 36 healthy nonalcoholic men and women. All subjects were between 27 and 53 years of age. The hippocampal volumes were measured from sagittal T-1-weighted high-resolution magnetic resonance images. Results: The alcoholic women had less lifetime drinking and a later age at onset of heavy drinking than alcoholic men. Both alcoholic men and women had significantly smaller right hippocampi and larger cerebrospinal fluid volumes than healthy subjects of the same sea. Only among women were the left hippocampus anti the non-hippocampal brain volume also significantly smaller. The proportion of hippocampal volume relative to the rest of the brain volume was the same in alcoholic patients and healthy subjects, in both men and women. The right hippocampus was larger than the left among all subjects. Women demonstrated larger hippocampal volumes relative to total brain volume than men. Psychiatric comorbidity, including posttraumatic stress disorder, did not affect hippocampal volume. Conclusions: In chronic alcoholism, the reduction of hippocampal volume is proportional to the reduction of the brain volume. Alcohol consumption should he accounted for in studies of hippocampal damage. C1 NIAAA, Sect Electrophysiol & Brain Imaging, Clin Studies Lab, NIH, Bethesda, MD 20892 USA. RP Agartz, I (reprint author), Karolinska Hosp, MR Res Ctr, Dept Clin Neurosci, S-17176 Stockholm, Sweden. EM Ingrid.Agartz@knv.ki.se NR 59 TC 221 Z9 224 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD APR PY 1999 VL 56 IS 4 BP 356 EP 363 DI 10.1001/archpsyc.56.4.356 PG 8 WC Psychiatry SC Psychiatry GA 182NE UT WOS:000079504400010 PM 10197833 ER PT J AU Teipel, SJ Hampel, H Pietrini, P Alexander, GE Horwitz, B Daley, E Moller, HJ Schapiro, MB Rapoport, SI AF Teipel, SJ Hampel, H Pietrini, P Alexander, GE Horwitz, B Daley, E Moller, HJ Schapiro, MB Rapoport, SI TI Region-specific corpus callosum atrophy correlates with the regional pattern of cortical glucose metabolism in Alzheimer disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; RHESUS-MONKEY; DEMENTIA; NEURONS; LAMINAR; DISTRIBUTIONS; ASYMMETRIES; PROJECTIONS; PLAQUES; RATES AB Background: Positron emission tomographic studies of patients with Alzheimer disease (AD) suggest a loss of metabolic functional interactions between different cortical regions. Atrophy of the corpus callosum as the major tract of intracortical connective fibers may reflect decreased cortical functional integration in AD. Objectives: To investigate whether regional atrophy of the corpus callosum is correlated with regional reductions of cortical glucose metabolism, as shown by positron emission tomography, and whether primary white matter degeneration is a possible cofactor of corpus callosum atrophy in AD. Patients and Methods: We measured total and regional cross-sectional areas of the corpus callosum on midsagittal magnetic resonance imaging scans from 12 patients with AD and 15 age-matched control subjects. Regional cerebral metabolic rates for glucose in cortical lobes were measured by positron emission tomography using fludeoxyglucose F 18. White matter hyperintensities were rated in T-2-weighted magnetic resonance imaging scans. Results: The total cross-sectional area of corpus callosum was significantly reduced in patients with AD, with the most prominent changes in the rostrum and splenium and relative sparing of the body of the corpus callosum. Frontal and parietal lobe metabolism was correlated with the truncal area of the corpus callosum in AD. The ratios of frontal to parietal and of frontal to occipital metabolism were correlated with the ratio of anterior to posterior corpus callosum area in the group with AD. White matter hyperintensities did not correlate with corpus callosum atrophy in the patients with AD. Conclusion: The regional pattern of corpus callosum atrophy correlated with reduced regional glucose metabolism independently of primary white matter degeneration in the patients with AD. C1 Univ Munich, Sch Med, Dept Psychiat,Dementia & Neuroimaging Res Grp, Geriatr Psychiat Branch,Res Unit D2, D-80336 Munich, Germany. NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. RP Teipel, SJ (reprint author), Univ Munich, Sch Med, Dept Psychiat,Dementia & Neuroimaging Res Grp, Geriatr Psychiat Branch,Res Unit D2, Nussbaumstr 7, D-80336 Munich, Germany. NR 47 TC 44 Z9 44 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD APR PY 1999 VL 56 IS 4 BP 467 EP 473 DI 10.1001/archneur.56.4.467 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 184NA UT WOS:000079617200013 PM 10199337 ER PT J AU Marchetti, C Cornaglia, I Casasco, A Bernasconi, G Baciliero, U Stetler-Stevenson, WG AF Marchetti, C Cornaglia, I Casasco, A Bernasconi, G Baciliero, U Stetler-Stevenson, WG TI Immunolocalization of gelatinase-A (matrix metalloproteinase-2) in damaged human temporomandibular joint discs SO ARCHIVES OF ORAL BIOLOGY LA English DT Article DE human temporomandibular joint; altered articular discs; matrix metalloproteinase-2; tissue remodelling; immunocytochemistry ID CRANIOMANDIBULAR JOINT; ARTICULAR DISC; SURGICAL INDUCTION; CATHEPSIN-L; RABBIT; DISPLACEMENT; COLLAGEN; TISSUES; IDENTIFICATION; INHIBITOR AB The fibrous tissue of the articular disc of the dysfunctional temporomandibular joint undergoes deep and variable structural modifications. Here the concurrence of morphological changes and the expression of matrix metalloproteinase-2 (MMP-7) in damaged discs from individuals suffering joint dysfunction was investigated. Microscopic, ultrastructural and immunocytochemical investigations were made on variously damaged articular discs and on one control sample. Disaggregation of collagen fibres, an increase in cellular components and calcification of large areas of tissue were observed in the damaged discs. These modifications were accompanied by a positive immunoreaction pattern for MMP-2. Fibroblast-, chondroblast- and osteoblast-like cells displayed a positive cytoplasmic reaction. In samples displaying evidence of synovial hyperplasia, some cells of the synovial protrusions were MMP-2 immunoreactive. No MMP-2 staining was observed in the control sample. These findings demonstrate that structural modifications of the articular disc could be specific responses to changes in the function of the temporomandibular joint. Variations in extrinsic stimuli may activate intrinsic factors, such as MMPs, that induce structural modifications in the discal tissue. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Univ Pavia, Ist Istol & Embriol Gen, I-27100 Pavia, Italy. Univ Pavia, Ist Discipline Odontostomatol, I-27100 Pavia, Italy. San Bortolo Hosp, Div Chirurg Maxillofacciale, Vicenza, Italy. NCI, Extracellular Matrix Pathol Sect, Pathol Lab, Bethesda, MD 20892 USA. RP Marchetti, C (reprint author), Univ Pavia, Ist Istol & Embriol Gen, Via Palestro 3, I-27100 Pavia, Italy. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 36 TC 9 Z9 11 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0003-9969 J9 ARCH ORAL BIOL JI Arch. Oral Biol. PD APR PY 1999 VL 44 IS 4 BP 297 EP 304 DI 10.1016/S0003-9969(98)00107-1 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 191ER UT WOS:000080009900001 PM 10348355 ER PT J AU Grizzle, W Grody, WW Noll, WW Sobel, ME Stass, SA Trainer, T Travers, H Weedn, V Woodruff, K AF Grizzle, W Grody, WW Noll, WW Sobel, ME Stass, SA Trainer, T Travers, H Weedn, V Woodruff, K TI Recommended policies for uses of human tissue in research, education, and quality control SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID GENETIC PRIVACY; SAMPLES AB As recipients of tissue and medical specimens, pathologists and other medical specialists regard themselves as stewards of patient tissues and consider it their duty to protect the best interests of both the individual patient and the public. The stewardship of slides, blocks, and other materials includes providing, under appropriate circumstances, patient materials for research, education, and quality control. The decision to provide human tissue for such purposes should be based on the specific (ie, direct patient care) and general (ie, furthering medical knowledge) interests of the patient and of society. The same standards of responsibility should apply to all medical professionals who receive and use specimens. This document proposes specific recommendations whereby both interests can be fostered safely, ethically, and reasonably. C1 Physicians Lab Ltd, Sioux Falls, SD 57105 USA. Univ Alabama, Sch Med, Dept Clin Pathol, Birmingham, AL USA. Univ Calif Los Angeles, Div Med Genet & Mol Pathol, Los Angeles, CA 90024 USA. Dartmouth Hitchcock Med Ctr, Dept Pathol, Lebanon, NH 03766 USA. Natl Canc Inst, Mol Pathol Sect, Bethesda, MD USA. Univ Maryland, Dept Pathol, Baltimore, MD 21201 USA. Med Ctr Hosp Vermont, Dept Pathol, Burlington, VT USA. Alabama Dept Forens Sci, Northport, NY USA. Brookside Hosp, Dept Pathol, San Pablo, CA USA. RP Travers, H (reprint author), Physicians Lab Ltd, 1000 E 21st St,Suite 4100, Sioux Falls, SD 57105 USA. NR 11 TC 37 Z9 37 U1 0 U2 2 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD APR PY 1999 VL 123 IS 4 BP 296 EP 300 PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 184UH UT WOS:000079631800008 PM 10320140 ER PT J AU Anreder, MB Freeman, SM Merogi, A Halabi, S Marrogi, AJ AF Anreder, MB Freeman, SM Merogi, A Halabi, S Marrogi, AJ TI p53, c-erbB2, and PCNA status in benign, proliferative, and malignant ovarian surface epithelial neoplasms - A study of 75 cases SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID CELL NUCLEAR ANTIGEN; STAGE-I CARCINOMAS; BORDERLINE TUMORS; GENE-MUTATIONS; ONCOGENIC EXPRESSION; EMBEDDED TISSUE; BREAST-CANCER; OVEREXPRESSION; PROTEIN; ANTIBODY AB Low malignant potential tumors of the ovary are believed to behave in a manner intermediate to their benign and malignant counterparts. However, recent evidence suggests these lesions are in fact benign and better classified as proliferative. Based on our previous work and evaluating p53, c-erbB2, and PCNA status in a full spectrum of ovarian surface epithelial tumors, with emphasis on low malignant potential tumors, we tested this hypothesis. Immunohistochemical stains with monoclonal antibodies were used an 75 archival ovarian neoplasms. The results demonstrated anti-p53 reactivity in 30 carcinomas (40%), 2 of which were proliferative, and no reactivity in the benign tumors. Overexpression of c-erbB2 was seen in 31 malignant neoplasms (64.5%), 4 of which were proliferative (22.1%), and none in benign tumors. The PCNA proliferative index showed means of 42.8%, 22.8%, and 14.9% with benign, low malignant potential, and malignant tumors, respectively. Predicting immunoreactivity in carcinomas for anti-PCNA (Student t test), anti-p53, and anti-c-erbB2 (Pearson chi(2) test) versus a lack of immunoreactivity in proliferative tumors indicate P values of .001, <.001, and <.001, respectively. These data show significant differences in the expression of these markers in ovarian tumors and suggest a possible role for these oncogenes as supplemental tools in diagnostic pathology. Further, our findings also support the designation of proliferative as opposed to the current nomenclature of low malignant potential tumors. C1 Baptist Mercy Med Ctr, Dept Pathol, New Orleans, LA USA. Tulane Univ, Sch Med & Publ Hlth, Dept Pathol & Lab Med, New Orleans, LA 70118 USA. Tulane Univ, Sch Med & Publ Hlth, Dept Epidemiol & Biostat, New Orleans, LA 70118 USA. S Harbor Hosp, Dept Med, Baltimore, MD USA. Louisiana State Univ, Sch Med, Dept Surg, New Orleans, LA USA. RP Marrogi, AJ (reprint author), NCI, Human Carcinogenesis Lab, NIH, Bldg 37,Room 2C25, Bethesda, MD 20892 USA. NR 60 TC 24 Z9 27 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD APR PY 1999 VL 123 IS 4 BP 310 EP 316 PG 7 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 184UH UT WOS:000079631800011 PM 10320143 ER PT J AU Nelson, KB Grether, JK AF Nelson, KB Grether, JK TI Selection of neonates for neuroprotective therapies - One set of criteria applied to a population SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID FACTOR-V-LEIDEN; MATERNAL ANTICARDIOLIPIN ANTIBODIES; HYPOXIC-ISCHEMIC ENCEPHALOPATHY; NORMAL BIRTH-WEIGHT; CEREBRAL-PALSY; BRAIN INJURY; APGAR SCORES; HYPOTHERMIA; INFECTION; CYTOKINES AB Objectives: To estimate the proportion of children with cerebral palsy (CP) who had signs of "birth asphyxia" in the early hours of life, and to examine the nature of the illnesses in those infants. Design: Population-based case-control study. Setting: All births in 4 northern California counties, 1983 through 1985. Subjects: Eighty-four full-term singleton children surviving to age 3 years with spastic CP and 366 full-term control children. Main Outcome Measure: Moderate or severe spastic CP. Results: Of 84 full-term children with spastic CP, 18 had 5-minute Apgar scores of less than 6, 20 required intuba-tion for ventilation in the delivery room, and 5 had an initial blood pH of 7.00 or less. Three (3.6%) of the 84 children had all 3 signs evaluated, a prevalence of 0.019 per 1000 survivors. All 3 had neonatal seizures. When we relaxed the pH cutoff to 7.10 or less, there were 19 children with CP who met at least 2 criteria. Eight of these 19 infants were born in level I facilities. In these children there was evidence of maternal or infant infection (n = 7); abnormal coagulation factor, thrombosis, or thrombocytopenia (n = 8); or other complication predating birth (n = 9). Conclusions: Neuroprotective therapy offered to neonates with these early characteristics, even if perfectly effective, would be unlikely to prevent most CP. Most of these depressed infants with CP had nonasphyxial conditions that may have contributed to adverse neurological outcome. C1 NINDS, Neuroepidemiol Branch, Bethesda, MD 20892 USA. Calif Dept Hlth Serv, Calif Birth Defects Monitoring Program, Emeryville, CA USA. RP Nelson, KB (reprint author), 7550 Wisconsin Ave,Room 714, Bethesda, MD 20892 USA. EM knelson@helix.nih.gov NR 40 TC 18 Z9 18 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD APR PY 1999 VL 153 IS 4 BP 393 EP 398 PG 6 WC Pediatrics SC Pediatrics GA 184TN UT WOS:000079629700011 PM 10201723 ER PT J AU Feng, DL Lindpaintner, K Larson, MG Rao, VS O'Donnell, CJ Lipinska, I Schmitz, C Sutherland, PA Silbershatz, H D'Agostino, RB Muller, JE Myers, RH Levy, D Tofler, GH AF Feng, DL Lindpaintner, K Larson, MG Rao, VS O'Donnell, CJ Lipinska, I Schmitz, C Sutherland, PA Silbershatz, H D'Agostino, RB Muller, JE Myers, RH Levy, D Tofler, GH TI Increased platelet aggregability associated with platelet GPIII alpha Pl(A2) polymorphism - The Framingham Offspring Study SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE platelets; genetics; glycoprotein; epinephrine ID CORONARY HEART-DISEASE; MYOCARDIAL-INFARCTION; GLYCOPROTEIN IIIA; RANDOMIZED TRIAL; RISK; RECEPTOR; THROMBOSIS; INTEGRIN; IIB/IIIA; DEATH AB The platelet glycoprotein IIb/IIIa (GP IIb/IIIa) plays a pivotal role in platelet aggregation. Recent data suggest that the Pl(A2) polymorphism of GPIIIa may be associated with an increased risk for cardiovascular disease. However, it is unknown if there is any association between this polymorphism and platelet reactivity. We determined GP IIIa genotype and platelet reactivity phenotype data in 1422 subjects from the Framingham Offspring Study. Genotyping was performed using PCR-based restriction fragment length polymorphism analysis. Platelet aggregability was evaluated by the Born method. The threshold concentrations of epinephrine and ADP were determined. Allele frequencies of Pl(A1) and Pl(A2) were 0.84 and 0.16, respectively. The presence of 1 or 2 Pl(A2) alleles was associated with increased platelet aggregability as indicated by incrementally lower threshold concentrations for epinephrine and ADP. For epinephrine, the mean concentrations were 0.9 mu mol/L (0.9 to 1.0) for homozygous Pl(A1), 0.7 mmol/L (0.7 to 0.9) for the heterozygous Pl(A1)/Pl(A2), and 0.6 mu mol/L (0.4 to 1.0) for homozygous Pl(A2) individuals, P=0.009. The increase in aggregability induced by epinephrine remained highly significant (P=0.007) after adjustment for covariates. For ADP-induced aggregation, the respective mean concentrations were 3.1 mu mol/L (3.0 to 3.2), 3.0 mu mol/L (2.9 to 3.2), and 2.8 mu mol/L (2.4 to 3.3); P=0.19 after adjustment for covariates. Our findings indicate that molecular variants of the gene encoding GP IIIa play a role in platelet reactivity in vitro. Our observations are compatible with and provide an explanation for the reported association of the Pl(A2) allotype with increased risk for cardiovascular disease. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Inst Prevent Cardiovasc Dis, Boston, MA 02215 USA. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Cardiol, Cambridge, MA 02138 USA. NHLBI, Framingham Heart Study, Bethesda, MD 20892 USA. Boston Univ, Dept Math, Stat & Consulting Unit, Boston, MA 02215 USA. Univ Kentucky, Med Ctr, Div Cardiol, Lexington, KY 40506 USA. Boston Univ, Dept Neurol, Boston, MA 02215 USA. RP Tofler, GH (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Inst Prevent Cardiovasc Dis, 1 Autumn St,5th Floor, Boston, MA 02215 USA. EM gtofler@bidmc.harvard.edu FU NCRR NIH HHS [1P41 RR03655]; NHLBI NIH HHS [KO4-HL-03138]; PHS HHS [N01-38038] NR 39 TC 205 Z9 216 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD APR PY 1999 VL 19 IS 4 BP 1142 EP 1147 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 184NE UT WOS:000079617600044 PM 10195947 ER PT J AU Cervantes, R Horwitz, B Barrett, N Karayanidis, F Kavanagh, D Large, M Michie, P Smith, G Woodham, B O'Sullivan, BT AF Cervantes, R Horwitz, B Barrett, N Karayanidis, F Kavanagh, D Large, M Michie, P Smith, G Woodham, B O'Sullivan, BT TI Abnormal neuronal circuitry for switching of attention and working memory in schizophrenic patients. SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Meeting Abstract C1 Royal Prince Alfred Hosp, Psychiat Res Unit, Sydney, NSW, Australia. NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. Concord Hosp, Dept Psychol Med, Sydney, NSW, Australia. RI Kavanagh, David/A-8521-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 0004-8674 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD APR PY 1999 VL 33 SU S BP A15 EP A15 PG 1 WC Psychiatry SC Psychiatry GA 197FW UT WOS:000080355400027 ER PT J AU Baxter, MG Hadfield, WS Murray, EA AF Baxter, MG Hadfield, WS Murray, EA TI Rhinal cortex lesions produce mild deficits in visual discrimination learning for an auditory secondary reinforcer in rhesus monkeys SO BEHAVIORAL NEUROSCIENCE LA English DT Article ID PERIRHINAL CORTEX; INTERTRIAL INTERVALS; RECOGNITION MEMORY; AMYGDALA; ASSOCIATION; ABLATIONS; HIPPOCAMPUS; DISRUPT; REMOVAL; FAIL AB Aspiration, but not neurotoxic, lesions of the amygdala impair performance on a visual discrimination learning task in which an auditory secondary reinforcer signals which of 2 stimuli will be reinforced with food. Because aspiration lesions of the amygdala interrupt projections of the rhinal cortex traveling close to the amygdala, it was hypothesized that damage to the rhinal cortex would severely impair learning in this task. Rhesus monkeys (Macaca mulatta) were trained to solve visual discrimination problems based on an auditory secondary reinforcer, were given lesions of the rhinal cortex or the perirhinal cortex alone, and were then retested. The monkeys displayed a reliable, albeit mild, deficit in postoperative performance. It is concluded that the aspiration lesions of the amygdala that produced a severe impairment did so because they interrupted connections of temporal cortical fields beyond the rhinal cortex that are also involved in learning in this task. C1 NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Baxter, MG (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St,984 William James Hall, Cambridge, MA 02138 USA. OI Murray, Elisabeth/0000-0003-1450-1642 NR 30 TC 16 Z9 16 U1 0 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD APR PY 1999 VL 113 IS 2 BP 243 EP 252 DI 10.1037//0735-7044.113.2.243 PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 197AJ UT WOS:000080342200002 PM 10357449 ER PT J AU Devan, BD McDonald, RJ White, NM AF Devan, BD McDonald, RJ White, NM TI Effects of medial and lateral caudate-putamen lesions on place- and cue-guided behaviors in the water maze: relation to thigmotaxis SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE dorsal striatum; medial caudate-putamen; lateral caudate-putamen; water maze; place navigation; cue navigation; competition; thigmotaxis; rat ID PHASEOLUS-VULGARIS LEUCOAGGLUTININ; LIMBIC-STRIATAL INTERACTIONS; REWARD-RELATED PROCESSES; PREFRONTAL CORTEX; BASAL GANGLIA; SPATIAL NAVIGATION; KAINIC ACID; PARALLEL ORGANIZATION; HIPPOCAMPAL-FORMATION; NUCLEUS-ACCUMBENS AB Rats with dorsomedial or dorsolateral caudate-putamen lesions and sham-operated controls were trained on the standard hidden platform (place) task in the water maze. Compared to controls. rats with dorsomedial, but not dorsolateral lesions were slower to escape to the hidden platform and spent significantly more time swimming near the wall of the pool (thigmotaxis) on the early trials, but eventually achieved control levels of performance. When the platform was removed from the pool, all groups exhibited a significant bias for swimming in the training quadrans and crossing the former location of the platform. In the second phase of the experiment rats were given visible platform (cue) training in a different room/pool with the platform moved to a new location each day. Rats with dorsomedial, but not dorsolateral lesions required more trials to reach criterion; again, thigmotaxis was observed on the early trials. The third phase, carried out in the original room/pool, included a place-retention trial followed by a place-cue competition test, (i.e. a choice between the learned spatial location of the hidden platform and the visible platform in a new location). The rats with dorsomedial, but not dorsolateral lesions swam to the visible platform more frequently than the controls. In the final phase, the rats in both lesion groups exhibited slightly lower thigmotactic tendencies than controls in a standard dry-land open field, a finding inconsistent with the hypothesis that thigmotaxis in the water maze is due to increased fear or anxiety. Taken together with other behavioral and anatomical findings, the results suggest that the dorsomedial caudate-putamen, by virtue of its connections with limbic and prefrontal cortical regions, may mediate a response selection process that integrates cognitive information with stimulus-response tendencies. (C) 1999 Elsevier Science B.V. All rights reserved. C1 McGill Univ, Dept Psychol, Montreal, PQ H3A 1B1, Canada. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. Univ Toronto, Dept Psychol, Toronto, ON M5S 1A1, Canada. RP White, NM (reprint author), McGill Univ, Dept Psychol, 1205 Dr Penfield Ave, Montreal, PQ H3A 1B1, Canada. EM nwhite@psych.mcgill.ca OI White, Norman/0000-0002-4616-5252 NR 78 TC 208 Z9 209 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD APR PY 1999 VL 100 IS 1-2 BP 5 EP 14 DI 10.1016/S0166-4328(98)00107-7 PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 176EG UT WOS:000079137600002 PM 10212049 ER PT J AU Fawcett, TW Martindale, JL Guyton, KZ Hai, T Holbrook, NJ AF Fawcett, TW Martindale, JL Guyton, KZ Hai, T Holbrook, NJ TI Complexes containing activating transcription factor (ATF)/cAMP-responsive-element-binding protein (CREB) interact with the CCAAT enhancer-binding protein (C/EBP)-ATF composite site to regulate Gadd153 expression during the stress response SO BIOCHEMICAL JOURNAL LA English DT Article DE GADD153 protein; gene regulation; stress response; transcription factors ID TUBULAR EPITHELIAL-CELLS; MESSENGER-RNA STABILITY; ACUTE-PHASE RESPONSE; DNA-DAMAGE; GROWTH ARREST; CHOP GADD153; GENE GADD153; ENDOPLASMIC-RETICULUM; (C/EBP)-RELATED GENE; LEUCINE ZIPPER AB Gadd153, also known as chop, encodes a member of the CCAAT/enhancer-binding protein (C/EBP) transcription factor family and is transcriptionally activated by cellular stress signals. We recently demonstrated that arsenite treatment of rat pheochromocytoma PC12 cells results in the biphasic induction of Gadd153 mRNA expression, controlled in part through binding of C/EBP beta and two uncharacterized protein complexes to the C/EBP-ATF (activating transcription factor) composite site in the Gadd153 promoter. In this report, we identified components of these additional complexes as two ATF/CREB (cAMP-responsive-element-binding protein) transcription factors having differential binding activities dependent upon the time of arsenite exposure, During arsenite treatment of PC12 cells, we observed enhanced binding of ATF4 to the C/EBP-ATF site at 2 h as Gadd153 mRNA levels increased, and enhanced binding of ATF3 complexes at 6 h as Gadd153 expression declined. We further demonstrated that ATF4 activates, while ATF3 represses, Gadd153 promoter activity through the C/EBP-ATF site. ATF3 also repressed ATF4-mediated transactivation and arsenite-induced activation of the Gadd153 promoter. Our results suggest that numerous members of the ATF/CREB family are involved in the cellular stress response, and that regulation of stress-induced biphasic Gadd153 expression in PC12 cells involves the ordered, sequential binding of multiple transcription factor complexes to the C/EBP-ATF composite site. C1 NIA, Gene Express & Aging Sect, Biol Chem Lab, NIH, Baltimore, MD 21224 USA. Ohio State Univ, Dept Med Biochem, Ohio State Biochem Program, Columbus, OH 43210 USA. Ohio State Univ, Neurobiotechnol Ctr, Columbus, OH 43210 USA. RP Holbrook, NJ (reprint author), NIA, Gene Express & Aging Sect, Biol Chem Lab, NIH, 5600 Nathan Shock Dr,Box 12, Baltimore, MD 21224 USA. RI Hai, Tsonwin/H-4480-2011; Hai, Tsonwin/E-3185-2011 OI Hai, Tsonwin/0000-0003-4510-0315; Hai, Tsonwin/0000-0003-4510-0315 NR 56 TC 283 Z9 286 U1 3 U2 7 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD APR 1 PY 1999 VL 339 BP 135 EP 141 DI 10.1042/0264-6021:3390135 PN 1 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 185ZV UT WOS:000079702300018 PM 10085237 ER PT J AU Momchilova, A Markovska, T Pankov, R AF Momchilova, A Markovska, T Pankov, R TI Arachidonoyl-CoA : lysophosphatidylcholine acyltransferase activity in ras-transformed NIH 3T3 fibroblasts depends on the membrane composition SO BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL LA English DT Article DE acyltransferase; ras; sphingomyelin; diacylglycerol; ceramide ID PROTEIN-KINASE-C; ACID; PHOSPHOLIPIDS; CELLS; INHIBITION; METABOLISM; LIVER AB Investigations were performed on the influence of membrane lipids on arachidonoyl-CoA:lysophosphatidylcholine acyltransferase in microsomal membranes from control and ras-transformed NIH 3T3 fibroblasts. Of all the tested phospholipids only sphingomyelin induced activation of acyltransferase in membranes from ras-transformed cells. No specific phospholipid effect on the acyltransferase was observed in microsomal membranes from control fibroblasts. Diacylglycerol was found to inhibit acyltransferase in both cell lines, whereas ceramide accumulation induced inhibition only in membranes from the transformed cells. The effects of diacylglycerol ceramide, sphingomyelin and sphingomyelinase are discussed with respect to their putative roles in the signal transduction pathways in oncogene-expressing cells. C1 Bulgarian Acad Sci, Inst Biophys, BU-1113 Sofia, Bulgaria. NIDR, Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Momchilova, A (reprint author), Bulgarian Acad Sci, Inst Biophys, BU-1113 Sofia, Bulgaria. RI Pankov, Roumen/B-3284-2014 OI Pankov, Roumen/0000-0002-3157-3659 NR 23 TC 10 Z9 10 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1039-9712 J9 BIOCHEM MOL BIOL INT JI Biochem. Mol. Biol. Int. PD APR PY 1999 VL 47 IS 4 BP 555 EP 561 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 189XD UT WOS:000079930700002 PM 10319406 ER PT J AU Lee, J Choi, YH Nguyen, PM Kim, JS Lee, SJ Trepel, JB AF Lee, J Choi, YH Nguyen, PM Kim, JS Lee, SJ Trepel, JB TI Cyclic AMP induces inhibition of cyclin A expression and growth arrest in human hepatoma cells SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE cyclic AMP; apoptosis; cell cycle arrest; cyclin A; HepG2; hepatocellular carcinoma ID PROSTATE CARCINOMA-CELLS; DEPENDENT PROTEIN-KINASE; E2F TRANSCRIPTION FACTOR; C-MYC; A GENE; HEPATOCELLULAR-CARCINOMA; S-PHASE; RESPONSIVE ELEMENT; DNA-REPLICATION; CANCER AB Classical cytotoxic therapy has been minimally useful in the treatment of hepatocellular carcinoma. In an effort to develop a new approach to the treatment of this neoplasm, we have investigated the signal transduction pathways regulating the growth of human hepatoma cells. In the data reported here, cyclic AMP (cAMP), a negative growth regulator for many cells of epithelial origin, induced G1 synchronization and apoptosis in the HepG2 human hepatoma cell line. The effects of cAMP on the components of the G1/S transition were analyzed. There was no detectable effect of two different cAMP analogs, 8-bromo cAMP or dibutyryl cAMP on the level of the D-type cyclins, cyclin E, cyclin-dependent kinase 2, cyclin-dependent kinase 4, p53, or the cyclin-dependent kinase inhibitors p21 or p27. In contrast, the cAMP analogs induced a dramatic downregulation of cyclin A protein, cyclin A messenger RNA, and cyclin A-dependent kinase activity. Cyclin A-dependent kinase has been shown to be required for the G1-S transition. Furthermore, cyclin A deregulation has been implicated in the pathogenesis of hepatocellular carcinoma. The data reported here suggest a novel signal transduction-based approach to hepatoma therapy. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NCI, Med Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Trepel, JB (reprint author), NCI, Med Branch, Div Clin Sci, NIH, Bldg 10,Room 12N230, Bethesda, MD 20892 USA. NR 46 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD APR 1 PY 1999 VL 1449 IS 3 BP 261 EP 268 DI 10.1016/S0167-4889(99)00019-1 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 187FE UT WOS:000079775600007 PM 10209305 ER PT J AU Kimura, S Ward, JM Minoo, P AF Kimura, S Ward, JM Minoo, P TI Thyroid-specific enhancer-binding protein thyroid transcription factor 1 is not required for the initial specification of the thyroid and lung primordia SO BIOCHIMIE LA English DT Article DE thyroid-specific enhancer-binding protein (T/EBP); thyroid transcription factor 1 (TTF1); NKX2.1; T/ebp-null mouse; thyroid morphogenesis; lung morphogenesis ID EMBRYONIC MOUSE LUNG; TISSUE-SPECIFIC EXPRESSION; THYROTROPIN RECEPTOR GENE; FACTOR-I; BRANCHING MORPHOGENESIS; THYROGLOBULIN PROMOTER; PEROXIDASE GENE; B GENE; TTF-1; GROWTH AB Targeted disruption of the homeobox gene T/ebp (Ttf1) in mice results in ablation of the thyroid and pituitary, and severe deformities in development of the lung and hypothalamus. T/ebp is expressed in the thyroid, lung, and ventral forebrain during normal embryogenesis. Examination of thyroid development in T/ebp homozygous null mutant embryos revealed that the thyroid rudiment is initially formed but is eliminated through apoptosis. Absence of T/EBP expression in the lung primordium does not activate apoptosis since a lung tissue, albeit dysmorphic, is nevertheless formed in T/ebp(-/-) embryos. These results demonstrate that T/EBP is not required for the initial specification of thyroid or lung primordia, but is absolutely essential for the development and morphogenesis of these organs. (C) Societe francaise de biochimie et biologie moleculaire / Elsevier, Paris. C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. NCI, Vet & Tumor Pathol Sect, Frederick, MD 21702 USA. Univ So Calif, Sch Med, Dept Pediat, Los Angeles, CA 90033 USA. RP Kimura, S (reprint author), NCI, Lab Metab, NIH, Bldg 37,Room 3E-24,9000 Rockville Pike, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [HL56221, HL56590] NR 53 TC 61 Z9 63 U1 0 U2 1 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0300-9084 J9 BIOCHIMIE JI Biochimie PD APR PY 1999 VL 81 IS 4 BP 321 EP 327 DI 10.1016/S0300-9084(99)80077-7 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 208VZ UT WOS:000081013700008 PM 10401665 ER PT J AU Suzuki, K Mori, A Lavaroni, S Ulianich, L Miyagi, E Saito, J Nakazato, M Pietrarelli, M Shafran, N Grassadonia, A Kim, WB Consiglio, E Formisano, S Kohn, LD AF Suzuki, K Mori, A Lavaroni, S Ulianich, L Miyagi, E Saito, J Nakazato, M Pietrarelli, M Shafran, N Grassadonia, A Kim, WB Consiglio, E Formisano, S Kohn, LD TI Thyroglobulin regulates follicular function and heterogeneity by suppressing thyroid-specific gene expression SO BIOCHIMIE LA English DT Article DE thyroglobulin; follicular function; thyroid-specific gene expression ID THYROTROPIN RECEPTOR GENE; TRANSCRIPTION FACTOR-I; GROWTH FACTOR-I; PROMOTER ACTIVITY; IODIDE TRANSPORT; NUCLEAR-PROTEIN; BINDING-SITE; FRTL-5 CELLS; RAT; STIMULATION AB Thyroglobulin (TG) is the primary synthetic product of the thyroid and the macromolecular precursor of thyroid hormones. TG synthesis, iodination, storage in follicles, and lysosomal degradation can each modulate thyroid hormone formation and secretion into the circulation. Thyrotropin (TSH), via its receptor (the TSHR), increases thyroid hormone levels by upregulating expression of the sodium iodide symporter (NIS), thyroid peroxidase (TPO), and TG genes. TSH does this by modulating the expression and activity of the thyroid-specific transcription factors, thyroid transcription factor (TTF)-1, TTF-2, and Pax-8, which coordinately regulate NIS, TPO, TG, and the TSHR. Major histocompatibility complex (MHC) class I gene expression, which is also regulated by TTF-1 and Pax-8 in the thyroid, is simultaneously decreased; this maintains self tolerance in the face of TSH-increased gene products necessary for thyroid hormone formation. We now show that follicular TG, 27S > 19S > 12S, counter-regulates TSH-increased thyroid-specific gene transcription by suppressing the expression of the TTF-1, TTF-2, and Pax-8 genes. This decreases expression of the TG, TPO, NIS and TSHR genes, but increases class I expression. TG action involves an apical membrane TG-binding protein; however, it acts transcriptionally, targeting, for example, a sequence within 1.15 kb of the start of TTF-1 transcription. TG does not affect ubiquitous transcription factors regulating TG, TPO, MS and/or TSHR gene expression. TG activity is not duplicated by thyroid hormones or iodide. We hypothesize that TG-initiated, transcriptional regulation of thyroid-restricted genes is a normal, feedback, compensatory mechanism which regulates follicular function, regulates thyroid hormone secretion, and contributes to follicular heterogeneity. (C) Societe francaise de biochimie et biologie moleculaire / Elsevier, Paris. C1 NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Naples, Fac Med 2, Inst Gen Pathol, Dipartimento Biol & Patol Cellulare & Mol L Calif, I-80131 Naples, Italy. RP Kohn, LD (reprint author), NIDDKD, Metab Dis Branch, NIH, Bldg 10,Room 9C101B, Bethesda, MD 20892 USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 77 TC 25 Z9 26 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0300-9084 J9 BIOCHIMIE JI Biochimie PD APR PY 1999 VL 81 IS 4 BP 329 EP 340 DI 10.1016/S0300-9084(99)80078-9 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 208VZ UT WOS:000081013700009 PM 10401666 ER PT J AU Wollman, SH AF Wollman, SH TI Summary of observations on transplantable tumors of the rat thyroid gland SO BIOCHIMIE LA English DT Article DE Fischer 344 rat; thiouracil; tumor progression; histology; blood capillaries; connective tissue AB Transplantable tumors of the thyroid gland have been produced by feeding of thiouracil (TU) to inbred Fischer 344 rats followed by the transplantation, initially, of pieces of hyperplastic thyroid gland, and in later generations, of pieces of transplanted tissue into similar rats or into rats fed a high iodine diet. In early generations, transplants grew only in the rats fed the TU diet, and this tissue was called dependent, whereas if the tissue grew in rats fed the high iodine diet in the abscence of TU, it was called independent. Dependent tumors were, initially, either papillary or of follicles distended with colloid. Later generations of some sublines were cellular or microfollicular in pattern and some became progressively more heterogeneous with later generations. Independent tumors began to appear by the third transplant generation. They were, initially, relatively uniform in pattern, and some tended to remain so, whereas other sublines exhibited some heterogeneity. Tumors had patterns that were cellular, or microfollicular, or follicular or had open follicles, etc.; there was one cellular ascites tumor subline. Other observations were made of vascular patterns, connective tissue, necrosis, and metastases. (C) Societe francaise de biochimie et biologie moleculaire / Elsevier, Paris. C1 NCI, Lab Mol Biol, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Wollman, SH (reprint author), NCI, Lab Mol Biol, Div Basic Sci, NIH, Bldg 37,Room 1 E20,37 Crescent Dr MSC 4255, Bethesda, MD 20892 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0300-9084 J9 BIOCHIMIE JI Biochimie PD APR PY 1999 VL 81 IS 4 BP 409 EP 412 DI 10.1016/S0300-9084(99)80089-3 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 208VZ UT WOS:000081013700020 PM 10401677 ER PT J AU Kammula, US Marincola, FM AF Kammula, US Marincola, FM TI Cancer immunotherapy: Is there real progress at last? SO BIODRUGS LA English DT Review ID TUMOR-INFILTRATING LYMPHOCYTES; CYTOLYTIC T-LYMPHOCYTES; MELANOMA ANTIGEN GP100; HIGH-DOSE INTERLEUKIN-2; ACTIVATED KILLER-CELLS; PULSED DENDRITIC CELLS; HUMAN GENE MAGE-3; METASTATIC MELANOMA; IN-VIVO; RECOMBINANT INTERLEUKIN-2 AB This review summarises the evolution of recent major advances in cancer immunotherapy, using metastatic melanoma as a model. The first true clinical progress with immunotherapy developed from the application of recombinant DNA technology for the large scale production of immunostimulant cytokines. Clinical trials demonstrated that the systemic administration of recombinant high dose bolus intravenous interleukin-2 (IL-2; 720 000 IU/kg every 8 hours) mediated objective tumour progression in 20% of patients with metastatic renal cancer and in 17% of patients with metastatic melanoma, with complete responses of 9% and 7%, respectively. The use of adoptive immunotherapy (the transfer of immune cells with antitumour activity to the tumour-bearing host) focused interest on T lymphocyte-mediated tumour recognition. Clinical trials described the systemic administration of lymphokine activated killer (LAK) cells and subsequently tumour infiltrating lymphocytes (TIL) to patients with advanced cancer. Although able to kill tumour targets in vitro, LAK cells did not prove useful for the treatment of patients with metastatic melanoma and renal cancer. A randomised trial. in which IL-2 was administered alone or with LAK cells, failed to show a difference in response rate or survival. In contrast, the treatment of 86 patients with metastatic melanoma using TIL plus IL-2 resulted in a 34% objective response rate, which included patients who had previously failed treatment with high-dose IL-2 alone. The focus on cellular immune responses, combined with rapid biotechnological advances, resulted in the identification of tumour specific antigens, such as MART-1 and gp100, that could be recognised by autologous TIL. This provided fundamental evidence of the existence of melanoma-associated antigens that were recognised in vivo by effector cells of the immune system. In vitro studies demonstrated immunodominant epitopes from MART-1 and gp100 that could induce in vitro-specific cytotoxic T lymphocyte reactivity. To enhance in vitro immunogenicity. single amino acid substitutions were made to identify peptides with higher affinity for HLB-A*0201. Modified peptides from trp 100 were compared with the parental peptide for increased immunogenicity based on their ability to induce anti-tumour lymphocytes in vitro. From these studies, a candidate peptide was identified (G9-209-2M) which had increased immunogenic reactivity in vitro. Clinical trials demonstrated that the modified G9-209-2M peptide was more effective. Unfortunately, objective tumor repression war; still low. However, when high-dose IL-2 was combined with G9-209-2M objective clinical responses increased to 42%. Efforts to find better ways to immunise against self antigens are ongoing and involve further peptide immunisations. as well as recombinant viral vectors, adjuvant cytokine therapy and cellular adjuvants such as dendritic cells. C1 NCI, Surg Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), NCI, Surg Branch, Div Clin Sci, NIH, Bldg 10,Room 2B42, Bethesda, MD 20892 USA. NR 96 TC 8 Z9 9 U1 1 U2 1 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 APR PY 1999 VL 11 IS 4 BP 249 EP 260 DI 10.2165/00063030-199911040-00004 PG 12 WC Oncology; Immunology; Pharmacology & Pharmacy SC Oncology; Immunology; Pharmacology & Pharmacy GA 186YR UT WOS:000079759400004 PM 18031135 ER PT J AU Koonin, EV AF Koonin, EV TI The emerging paradigm and open problems in comparative genomics SO BIOINFORMATICS LA English DT Editorial Material C1 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. NR 0 TC 24 Z9 24 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD APR PY 1999 VL 15 IS 4 BP 265 EP 266 DI 10.1093/bioinformatics/15.4.265 PG 2 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 197KF UT WOS:000080363400001 PM 10438229 ER PT J AU Serova, LI Nankova, BB Feng, ZH Hong, JS Hutt, M Sabban, EL AF Serova, LI Nankova, BB Feng, ZH Hong, JS Hutt, M Sabban, EL TI Heightened transcription for enzymes involved in norepinephrine biosynthesis in the rat locus coeruleus by immobilization stress SO BIOLOGICAL PSYCHIATRY LA English DT Article DE stress; locus coeruleus; tyrosine hydroxylase; dopamine b-hydroxylase; GTP cyclohydrolase I; mRNA; transcription ID DOPAMINE-BETA-HYDROXYLASE; MESSENGER-RNA LEVELS; CORTICOTROPIN-RELEASING FACTOR; CAMP-RESPONSE ELEMENT; EARLY GENE-EXPRESSION; TYROSINE-HYDROXYLASE; NORADRENERGIC NEURONS; CYCLIC-AMP; PC12 CELLS; BRAIN NUCLEI AB Background: The locus coeruleus (LC), a target for CRH neurons, is critically involved in responses to stress. Various physiological stresses increase norepinephrine turnover, tyrosine hydroxylase (TH) enzymatic activity, protein and mRNA levels in LC cell bodies and terminals; however, the effect of stress on other enzymes involved in norepinephrine biosynthesis in the LC in unknown. Methods: Rats were exposed to single (2 hour) or repeated (2 hour daily) immobilization stress (IMO). Recombinant rat dopamine b-hydroxylase (DBH) cDNA was expressed in E. coli and used to generate antisera for immunohistochemistry and immunoblots in LC. Northern blots were used to assess changes in mRNA levels for TH, DBH, and GTP cyclohydrolase I (GTPCH) in the LC in response to the stress. Conditions were found to isolate nuclei from LC and to use them for run-on assays of transcription. Results: Repeated stress elevated the DBH immunoreactive protein levels in LC. Parallel increases in TH, DBH and GTPCH mRNA levels of about 300% to 400% over control levels were observed with single IMO, and remained at similar levels after repeated IMO. This effect was transcriptionally mediated, and even 30 min of a single IMO significantly increased the relative rate of transcription. Conclusions: This study is the first to reveal transcriptional activation of the genes encoding catecholamine biosynthetic enzymes in the LC by stress. In addition to TH, changes in DBH and GTPCH gene expression may also contribute to the development of stress-triggered affective disorders. (C) 1999 Society of Biological Psychiatry. C1 New York Med Coll, Dept Biochem & Mol Biol, Valhalla, NY 10595 USA. NIEHS, US Dept HHS, US PHS, NIH, Res Triangle Pk, NC 27709 USA. RP Sabban, EL (reprint author), New York Med Coll, Dept Biochem & Mol Biol, Valhalla, NY 10595 USA. FU NINDS NIH HHS [NS28869, NS32166] NR 62 TC 58 Z9 58 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1999 VL 45 IS 7 BP 853 EP 862 DI 10.1016/S0006-3223(98)90360-2 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 182VM UT WOS:000079518900008 PM 10202573 ER PT J AU Altemus, M Jacobson, KR Debellis, M Kling, M Pigott, T Murphy, DL Gold, PW AF Altemus, M Jacobson, KR Debellis, M Kling, M Pigott, T Murphy, DL Gold, PW TI Normal CSF oxytocin and NPY levels in OCD SO BIOLOGICAL PSYCHIATRY LA English DT Article DE anxiety; cerebrospinal fluid; gender differences; NPY; OCD; oxytocin ID OBSESSIVE-COMPULSIVE DISORDER; CORTICOTROPIN-RELEASING-FACTOR; CEREBROSPINAL-FLUID; VASOPRESSIN; BEHAVIOR; PLASMA AB Background: Attention has recently been focused on central nervous system neuropeptides as potential mediators of th symptom profile of obsessive-compulsive disorder (OCD). Increased CSF levels of the anxiolytic neuropeptide oxytocin have been reported in OCD. CSF levels of NPY, another anxiolytic neuropeptide, have not been studied. Methods: We measured CSF oxytocin and NPY in 14 OCD patients and 26 healthy normal volunteers. Results: There were no significant differences between the OCD patients and control subjects in CSF oxytocin or NPY levels. In both the OCD and control groups, women had significantly higher CSF oxytocin levels than men. Conclusions: These results do not support a prior finding of elevated CSF oxytocin in OCD patients and do not provide any evidence for an abnormality of NPY regulation in OCD. Biol Psychiatry 1999;45:931-933 (C) 1999 Society of Biological Psychiatry. C1 Cornell Univ, Coll Med, Dept Psychiat, New York, NY USA. Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA USA. VA Med Ctr, Mood Disorders Program, Baltimore, MD USA. UTMB, Dept Psychiat, Galveston, TX USA. NIMH, Div Intramural Res Programs, Bethesda, MD 20892 USA. RP Altemus, M (reprint author), New York Hosp, Cornell Med Ctr, Box 244,1300 York Ave, New York, NY 10021 USA. NR 14 TC 35 Z9 38 U1 0 U2 3 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 APR 1 PY 1999 VL 45 IS 7 BP 931 EP 933 DI 10.1016/S0006-3223(98)00263-7 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 182VM UT WOS:000079518900018 PM 10202583 ER PT J AU Sun, W Lou, YH Dean, J Tung, KSK AF Sun, W Lou, YH Dean, J Tung, KSK TI A contraceptive peptide vaccine targeting sulfated glycoprotein ZP2 of the mouse zona pellucida SO BIOLOGY OF REPRODUCTION LA English DT Article ID MONOCLONAL-ANTIBODIES; AUTOIMMUNE-DISEASE; PROTEIN; IDENTIFICATION; ZP-2; DETERMINANTS; IMMUNIZATION; EPITOPE; INVITRO AB In this study, we have mapped and characterized a B cell epitope of sulfated glycoprotein ZP2 (ZP2) as a step toward the development of a multi-epitope zona pellucida (ZP) vaccine. Recombinant polypeptides expressed by random deoxyribonuclease-digested fragments of ZP2 cDNA were screened for binding to IE-3, a monoclonal antibody to murine ZP2. Positive clones contained cDNA inserts encoding polypeptide corresponding to ZP2(103-134). When normal or ovariectomized female mice were immunized with three overlapping peptides that span this region of ZP2 (101-120, 111-130, 121-140), only ZP2(121-140) elicited IgG antibodies that reacted with mouse ovarian ZP, indicative of the presence of native B epitope and helper T cell epitope in ZP2(121-140). To more finely map the ZP2 B cell epitope, a random peptide display library was screened with the IE-3 antibody, and a consensus tetramer sequence VxYK that matched the ZP2(123-126) sequence VRYK was located. Competitive immunofluorescence analysis with single alanine-substituted VxYK peptides ranked the relative contribution of the three critical B cell epitope residues as Y > V > K. A chimeric peptide was constructed that contained the YRYK motif of ZP2 and a bovine RNase T cell epitope. Although (C57BL/6xA/J) F1 (B6AF1) female mice immunized with the chimeric peptide developed ZP antibody response, this peptide elicited antibody only in mice of the histocompatibility complex (MHC) H-2(k or b) haplotype. In contrast, ZP2(121-140) peptide elicited antibody in inbred mice with three additional mouse MHC haplotypes, Moreover, although ZP2(121-140) contained a T cell epitope, no oophoritis was observed after immunization of B6AF1 mice with ZP2(121-140) in complete Freund's adjuvant (CFA), In a preliminary trial, female B6AF1 mice immunized with ZP2(121-140) in CFA had reduced litter sizes as compared with mice injected with CFA alone. C1 Univ Virginia, Old Med Sch, Dept Pathol, Charlottesville, VA 22908 USA. NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Tung, KSK (reprint author), Univ Virginia, Old Med Sch, Dept Pathol, 4th Floor,Room 4888, Charlottesville, VA 22908 USA. EM kst7k@virginia.edu FU NIAID NIH HHS [R01 AI-41236]; NICHD NIH HHS [U54 HD29099] NR 28 TC 35 Z9 44 U1 0 U2 2 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD APR PY 1999 VL 60 IS 4 BP 900 EP 907 DI 10.1095/biolreprod60.4.900 PG 8 WC Reproductive Biology SC Reproductive Biology GA 179QZ UT WOS:000079341300017 PM 10084964 ER PT J AU Korobko, VG Boichenko, VE Kuprash, DV Turetskaya, RL Nedospasov, SA AF Korobko, VG Boichenko, VE Kuprash, DV Turetskaya, RL Nedospasov, SA TI Heterologous expression of murine lymphotoxins in Escherichia coli and the preparation of antibodies SO BIOORGANICHESKAYA KHIMIYA LA Russian DT Article DE lympotoxin-alpha(LT alpha); lymphotoxin-beta(LT beta); antibodies; recombinant proteins; expression in E-coli ID TUMOR-NECROSIS-FACTOR; BETA-DEFICIENT MICE; FACTOR TNF-ALPHA; ABNORMAL-DEVELOPMENT; GENES; PURIFICATION; RECEPTORS; SURFACE; CLONING; FORMS AB Genes encoding fragments of polypeptide chains of murine lymphotoxins (LT), namely, LT-alpha truncated from the N-terminus and the LT-beta extracellular domain, containing N-terminal hepta- and hexahistidine epitopes, respectively, were expressed in E. coli cells. The recombinant proteins purified by metallochelate chromatography were used to obtain polyclonal antibodies that specifically recognize murine LT. C1 Russian Acad Sci, VA Engelhardt Mol Biol Inst, Moscow 117984, Russia. Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow 117871, Russia. Moscow MV Lomonosov State Univ, Belozersky Inst Physicochem Biol, Moscow 119899, Russia. NIH, Frederick, MD 21702 USA. RP Nedospasov, SA (reprint author), Russian Acad Sci, VA Engelhardt Mol Biol Inst, Ul Vavilova 32, Moscow 117984, Russia. RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Kuprash, Dmitry/O-4899-2015; Nedospasov, Sergei/Q-7319-2016 OI Kuprash, Dmitry/0000-0002-1488-4148; NR 23 TC 0 Z9 0 U1 0 U2 0 PU MEZHDUNARODNAYA KNIGA PI MOSCOW PA 39 DIMITROVA UL., 113095 MOSCOW, RUSSIA SN 0132-3423 J9 BIOORG KHIM+ JI Bioorg. Khim. PD APR PY 1999 VL 25 IS 4 BP 270 EP 274 PG 5 WC Biochemistry & Molecular Biology; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 207AQ UT WOS:000080913500006 PM 10422593 ER PT J AU Ramadas, N Rifkind, JM AF Ramadas, N Rifkind, JM TI Molecular dynamics of human methemoglobin: The transmission of conformational information between subunits in an alpha beta dimer SO BIOPHYSICAL JOURNAL LA English DT Article ID DEOXY QUATERNARY CONFORMATION; HEME-HEME INTERACTIONS; LONG-RANGE FORCES; HUMAN HEMOGLOBIN; ELECTROSTATIC INTERACTIONS; HUMAN OXYHEMOGLOBIN; PROTEIN DYNAMICS; DOMAIN-STRUCTURE; LIGAND-BINDING; SIMULATION AB Spectroscopic studies indicate an interaction of the distal histidine with the heme iron as well as the transmission of dietal heme perturbations across the alpha(1)beta(1) interface. Molecular dynamics simulations have been used to explain the molecular basis for these processes, Using a human methemoglobin ap dimer, it has been shown that at 235 K after 61 ps, a rearrangement Occurs in the alpha-chain corresponding to the formation of a bond with the distal histidine, This transition does not take place in the beta-chain during a 100-ps simulation and is reversed at 300 K, The absence of the distal histidine transition in the isolated chains and with the interface frozen indicate the involvement of the alpha beta interface. A detailed analysis of the simulation has been performed in terms of RMS fluctuations, domain cross-correlation maps, the disruption of helix hydrogen bonds, as well:changes in electrostatic interactions and dihedral angles. This analysis shows that the rearrangements in the alpha-chain necessary to bring the histidine closer to their on involve alterations primarily in the CD loop and at the interface. Communication to the beta-chain distal pocket is propagated by increased interactions of the alpha-chain B helix with the beta-chain G-GH-H segment and the flexibility in the EF loop. The G helices shown to be involved in propagation of perturbation across the alpha(1)beta(1) interface extend into the alpha(1)beta(2) interfaces, providing a mechansim whereby distal interactions can modulate the T reversible arrow R transition in hemoglobin. C1 NIA, Mol & Cellular Biol Lab, Mol Dynam Sect, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA. RP Rifkind, JM (reprint author), NIA, Mol & Cellular Biol Lab, Mol Dynam Sect, Gerontol Res Ctr,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 54 TC 32 Z9 32 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 APR PY 1999 VL 76 IS 4 BP 1796 EP 1811 PG 16 WC Biophysics SC Biophysics GA 184ZJ UT WOS:000079643400008 PM 10096879 ER PT J AU Schuck, P Demeler, B AF Schuck, P Demeler, B TI Direct sedimentation analysis of interference optical data in analytical ultracentrifugation SO BIOPHYSICAL JOURNAL LA English DT Article ID RAPID PRECISION INTERFEROMETRY; VELOCITY EXPERIMENTS; BOUNDARY ANALYSIS; LAMM EQUATION; SOLUTES; SYSTEMS; TIME AB Sedimentation data acquired with the interference optical scanning system of the Optima XL-I analytical ultracentrifuge can exhibit time-invariant noise components, as well as small radial-invariant baseline offsets, both superimposed onto the radial fringe shift data resulting from the macromolecular solute distribution. A well-established method for the interpretation of such ultracentrifugation data is based on the analysis of time-differences of the measured fringe profiles, such as employed in the g(s*) method. We demonstrate how the technique of separation of linear and nonlinear parameters can be used in the modeling of interference data by unraveling the time-invariant and radial-invariant noise components. This allows the direct application of the recently developed approximate analytical and numerical solutions of the Lamm equation to the analysis of interference optical fringe profiles. The presented method is statistically advantageous since it does not require the differentiation of the data and the model functions. The method is demonstrated on experimental data and compared with the results of a g(s*) analysis. It is also demonstrated that the calculation of time-invariant noise components can be useful in the analysis of absorbance optical data. They can be extracted from:data acquired during the approach to equilibrium, and can be used to increase the reliability of the results obtained from a:sedimentation equilibrium analysis. C1 NIH, Mol Interact Resource Bioengn & Phys Sci Program, ORS, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA. RP Schuck, P (reprint author), NIH, Mol Interact Resource Bioengn & Phys Sci Program, ORS, Bldg 14,Rm 3N17,14 S Dr, Bethesda, MD 20892 USA. OI Schuck, Peter/0000-0002-8859-6966 NR 41 TC 114 Z9 115 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 APR PY 1999 VL 76 IS 4 BP 2288 EP 2296 PG 9 WC Biophysics SC Biophysics GA 184ZJ UT WOS:000079643400052 PM 10096923 ER PT J AU Kolenko, V Rayman, P Roy, B Cathcart, MK O'Shea, J Tubbs, R Rybicki, L Bukowski, R Finke, J AF Kolenko, V Rayman, P Roy, B Cathcart, MK O'Shea, J Tubbs, R Rybicki, L Bukowski, R Finke, J TI Downregulation of JAK3 protein levels in T lymphocytes by prostaglandin E-2 and other cyclic adenosine monophosphate-elevating agents: Impact on interleukin-2 receptor signaling pathway SO BLOOD LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; MICE LACKING JAK3; C-MYC INDUCTION; IL-2 RECEPTOR; GAMMA-CHAIN; CELL-PROLIFERATION; JANUS KINASE; BETA-CHAIN; TYROSINE PHOSPHORYLATION; INDEPENDENT PATHWAYS AB The Janus kinase, JAK3 plays an important role in interleukin-a (IL-a)-dependent signal transduction and proliferation of T lymphocytes. Our findings show that prostaglandin E-2 (PGE(2)) can inhibit upregulation of JAK3 protein in naive T cells and can downregulate its expression in primed cells. Reduction in JAK3 was selective because expression of other tyrosine kinases (JAK1, p56(lck), and p59(fyn)) and signal transducer and activator of transcription (STAT)5, which are linked to IL-2 receptor (IL-2R) signaling pathway, were not affected. Inhibition of JAK3 may be controlled by intracellular cyclic adenosine monophosphate (cAMP) levels, as forskolin, a direct activator of adenylate cyclase and dibutyryl cAMP (dbcAMP), a membrane permeable analogue of cAMP suppressed JAK3 expression. Moreover, 8-isobutyl-1-methyl-xanthine (IBMX), an inhibitor of cAMP phosphodiesterase, potentiated PGE(2)-induced suppression of JAK3, In naive T cells, but not primed T cells, PGE(2) and other cAMP elevating agents also caused a modest reduction in surface expression of the common gamma chain (gamma c) that associates with JAK3, The absence of JAK3, but not IL-SR in T cells correlated with impaired IL-2-dependent signal transduction and proliferation. The alteration in IL-2 signaling included decreased tyrosine phosphorylation and DNA binding activity of STAT5 and poor induction of the c-Myc and c-Jun pathways, In contrast, IL-2-dependent induction of Bcl-2 was unaffected, These findings suggest that suppression of JAK3 levels may represent one mechanism by which PGE(2) and other cAMP elevating agents can inhibit T-cell proliferation. (C) 1999 by The American Society of Hematology. C1 Cleveland Clin Fdn, Dept Immunol, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Cell Biol, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Clin Pathol, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Biostat & Epidemiol, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Hematol Oncol, Cleveland, OH 44195 USA. NIAMSD, Lymphocyte Cell Biol Sect, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. RP Kolenko, V (reprint author), Cleveland Clin Fdn, Dept Immunol, 9500 Euclid Ave, Cleveland, OH 44195 USA. FU NCI NIH HHS [CA56937] NR 56 TC 51 Z9 54 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 1999 VL 93 IS 7 BP 2308 EP 2318 PG 11 WC Hematology SC Hematology GA 180GH UT WOS:000079377400022 PM 10090941 ER PT J AU de Caestecker, M Wang, D Parks, T Shioda, T Roberts, A Lechleider, R AF de Caestecker, M Wang, D Parks, T Shioda, T Roberts, A Lechleider, R TI Transcriptional activity of Smad4: Rule of the Smad4 activation domain SO BONE LA English DT Meeting Abstract C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. MGH, Ctr Canc, Lab Tumor Biol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 1999 VL 24 IS 4 MA 50 BP 421 EP 421 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 184DN UT WOS:000079594900063 ER PT J AU Lin, Y Martin, J Meng, X Li, BY Lechleider, R Higgins, D Wang, T AF Lin, Y Martin, J Meng, X Li, BY Lechleider, R Higgins, D Wang, T TI Protein-protein interaction in BMP-mediated signaling SO BONE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Surg Genet, Pediat Surg Res Lab, Boston, MA 02114 USA. SUNY Buffalo, Dept Pharmacol, Buffalo, NY 14214 USA. NCI, Chemoprevent Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 APR PY 1999 VL 24 IS 4 MA 49 BP 421 EP 421 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 184DN UT WOS:000079594900066 ER PT J AU Tanawattanacharoen, S Mozes, MM Nosti, AJ Oppermann, H Kopp, JB AF Tanawattanacharoen, S Mozes, MM Nosti, AJ Oppermann, H Kopp, JB TI Bone morphogenetic protein-7 partially rescues p53-induced oligomeganephronia in dual transgenic mice. SO BONE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Creat BioMol, Hopkinton, MA USA. RI Mozes, Miklos/E-9003-2011 NR 0 TC 1 Z9 1 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 APR PY 1999 VL 24 IS 4 MA 87 BP 430 EP 430 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 184DN UT WOS:000079594900100 ER PT J AU Eintrei, C Sakoloff, E Smith, CB AF Eintrei, C Sakoloff, E Smith, CB TI Effects of diazepam and ketamine administered individually or in combination on regional rates of glucose utilization in rat brain SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE anaesthetics i.v., ketamine; hypnotics benzodiazepine, diazepam; brain, metabolism; rat ID CEREBRAL-CORTEX; ANESTHESIA; LOCALIZATION; RECEPTORS; SYSTEM AB The effects of diazepam, which acts at GABAA receptors to enhance the effects of GABA, and ketamine, a non-competitive N-methyl-D-aspartate receptor antagonist, on local rates of cerebral glucose utilization (ICMRglc) were examined in unrestrained rats. Four groups were studied: vehicle-injected controls; and ketamine-treated, diazepam-treated and combined ketamine- and diazepam-treated animals. Ketamine alone produced a heterogeneous pattern of changes in lCMR(glc) (e.g. significant increases in the corpus callosum, olfactory tubercle and the entire Papez circuit, in addition to other limbic areas, and significant decreases in lateral habenula and some components of the auditory system). Diazepam alone statistically significantly decreased ICMRglc in the brain as a whole and in most areas of the cerebral cortex, thalamus and limbic system. The most remarkable effects of the two drugs administered together on ICMRglc occurred in the limbic system where the dramatic increases observed with ketamine alone were prevented by treatment with diazepam. C1 Linkoping Univ Hosp, Dept Anaesthesia, S-58185 Linkoping, Sweden. NIMH, Cerebral Metab Lab, US Publ Hlth Serv, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Eintrei, C (reprint author), Linkoping Univ Hosp, Dept Anaesthesia, S-58185 Linkoping, Sweden. NR 20 TC 35 Z9 35 U1 0 U2 2 PU PROF SCI PUBL PI LONDON PA TAVISTOCK HOUSE EAST, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0007-0912 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD APR PY 1999 VL 82 IS 4 BP 596 EP 602 PG 7 WC Anesthesiology SC Anesthesiology GA 189FC UT WOS:000079893000022 PM 10472230 ER PT J AU Klein, JLD Roberts, JD George, MD Kurtzberg, J Breton, P Chermann, JC Olden, K AF Klein, JLD Roberts, JD George, MD Kurtzberg, J Breton, P Chermann, JC Olden, K TI Swainsonine protects both murine and human haematopoietic systems from chemotherapeutic toxicity SO BRITISH JOURNAL OF CANCER LA English DT Article DE swainsonine; cancer; bone marrow; cyclophosphamide; AZT ID COLONY-STIMULATING FACTOR; TETRAPEPTIDE ACSDKP; PROGENITOR CELLS; AZT; ZIDOVUDINE; MICE; AIDS; GLYCOPROTEINS; LENOGRASTIM; INHIBITION AB The haematopoietic system is sensitive to cytotoxic damage and is often the site of dose-limiting toxicity. We previously reported that swainsonine, an inhibitor of protein glycosylation, reduced the bone marrow toxicity resulting from a single dose of anticancer drugs in otherwise healthy mice. However, more important questions are (1) can swainsonine protect tumour-bearing mice without interfering with the anti-tumour effects of the drugs, and (2) can swainsonine stimulate haematopoietic activity of human, as well as murine, bone marrow. We demonstrate here that swainsonine protects C57BL/6 mice bearing melanoma-derived tumours from cyclophosphamide-induced toxicity without interfering with the drug's ability to inhibit tumour growth. Similar results were obtained in vivo with 3'-azido-3'-deoxythymidine (AZT), a myelosuppressive agent often used in therapy for acquired immune deficiency syndrome. Swainsonine increased both total bone marrow cellularity and the number of circulating white blood cells in mice treated with doses of AZT that typically lead to severe myelosuppression. Swainsonine also increased the number of erythroid and myeloid colony forming cells (CFCs) in short-term cultures of murine bone marrow, restoring the number of progenitor cells to the control level in the presence of ATT doses that reduced CFCs by 80%. With respect to the sensitivity of human haematopoietic cells to swainsonine, we show that swainsonine protected human myeloid progenitor cells from AZT toxicity in vitro. These results suggest that swainsonine may be useful as an adjuvant in several types of human chemotherapy. C1 NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. Duke Univ, Pedait Bone Marrow Lab, Durham, NC 27710 USA. Labs UPSA, F-92506 Rueil Malmaison, France. INSERM, U322, F-13273 Marseille 9, France. RP Roberts, JD (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. NR 36 TC 32 Z9 36 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 APR PY 1999 VL 80 IS 1-2 BP 87 EP 95 DI 10.1038/sj.bjc.6690326 PG 9 WC Oncology SC Oncology GA 191NP UT WOS:000080028700015 PM 10389983 ER PT J AU Bishop, JAN Harland, M Bennett, DC Bataille, V Goldstein, AM Tucker, MA Ponder, BAJ Cuzick, J Selby, P Bishop, DT AF Bishop, JAN Harland, M Bennett, DC Bataille, V Goldstein, AM Tucker, MA Ponder, BAJ Cuzick, J Selby, P Bishop, DT TI Mutation testing in melanoma families: INK4A, CDK4 and INK4D SO BRITISH JOURNAL OF CANCER LA English DT Article DE INK4A; INK4D; familial melanoma ID MALIGNANT-MELANOMA; GENETIC-HETEROGENEITY; GERMLINE MUTATIONS; DYSPLASTIC NEVUS; FAMMM SYNDROME; CHROMOSOME 9P; CANCER; LOCUS; LINKAGE; P16 AB The INK4A gene which codes for the cyclin-dependent kinase (CDK) inhibitor INK4A or p16 underlies susceptibility to melanoma in some families. Germline mutations in the gene that codes for the target protein of p16, CDK4, underlie susceptibility in very rare families. We report mutation screening of the INK4A and CDK4 genes in 42 UK families. A total of nine families were identified with INK4A mutations and none with CDK4 exon 2 mutations. These mutations were in 8/22 (35%) families with three or more cases of melanoma and 1/20 (5%) families with only two cases. In one of these nine families a novel single base pair substitution was identified, Gly67Arg. In an attempt to identify another melanoma susceptibility gene, a member of the INK4 family, the p19 INK4D gene has been studied. The p19 gene was sequenced in DNA from the 42 UK families and six additional US families. No mutations were identified. C1 Imperial Canc Res Fund, Leeds, W Yorkshire, England. St James Univ Hosp, Imperial Canc Res Fund, Canc Med Res Unit, Leeds LS9 7TF, W Yorkshire, England. Univ London St Georges Hosp, Sch Med, London SW17 0RE, England. Royal London Hosp, Imperial Canc Res Fund, Skin Tumor Lab, London E1 1BB, England. NCI, Genet Epidemiol Branch, Bethesda, MD USA. Addenbrookes Hosp, CRC, Human Canc Genet Grp, Cambridge, England. Imperial Canc Res Fund, London WC2A 3PX, England. RP Bishop, JAN (reprint author), Imperial Canc Res Fund, Leeds, W Yorkshire, England. RI Bennett, Dorothy/C-2418-2008; Tucker, Margaret/B-4297-2015 OI Bishop, Tim/0000-0002-8752-8785; Newton Bishop, Julia/0000-0001-9147-6802; Bennett, Dorothy/0000-0002-3639-7527; NR 38 TC 44 Z9 45 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD APR PY 1999 VL 80 IS 1-2 BP 295 EP 300 DI 10.1038/sj.bjc.6690354 PG 6 WC Oncology SC Oncology GA 191NP UT WOS:000080028700043 ER PT J AU Taniuchi, K Takata, M Matsui, C Fushida, Y Uchiyama, K Mori, T Kawara, S Yancey, KB Takehara, K AF Taniuchi, K Takata, M Matsui, C Fushida, Y Uchiyama, K Mori, T Kawara, S Yancey, KB Takehara, K TI Antiepiligrin (laminin 5) cicatricial pemphigoid associated with an underlying gastric carcinoma producing laminin 5 SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article DE antibasement membrane zone antibodies; epiligrin; gastric carcinoma; laminin 5 cicatricial pemphigoid ID EPIDERMAL BASEMENT-MEMBRANE; ANCHORING FILAMENTS; AUTOANTIBODIES; EPILIGRIN; DISEASE; IMMUNOFLUORESCENT; SUBUNITS; TARGET; CELLS AB Although bullous pemphigoid and cicatricial pemphigoid are sometimes associated with malignancy, it remains uncertain whether such an association is pathogenetically related or just a coincidence attributable to the advanced age of the patients, We report a 61-year-old patient with antiepiligrin (laminin 5) cicatricial pemphigoid (AeCP) associated with an advanced gastric carcinoma. The gastric carcinoma cells in this patient were shown to produce laminin 5 by immunofluorescence microscopy, and the patient's serum contained autoantibodies directed against laminin 5 on immunoprecipitation. Furthermore, the blistering symptoms and the titre of antibasement membrane zone antibodies coordinately changed with the resection and subsequent relapse of the gastric cancer. These observations suggest that the gastric carcinoma producing laminin 5 may have induced the production of autoantibodies to this laminin, which were pathogenic to the skin and mucous membranes in this patient. This report demonstrates a link between this autoimmune subepithelial blistering disease and malignancy. It is of interest and potential great importance to examine other cases of AeCP for such a potential association. C1 Kanazawa Univ, Sch Med, Dept Dermatol, Kanazawa, Ishikawa 9208641, Japan. Kanazawa Univ, Sch Med, Dept Surg 2, Kanazawa, Ishikawa 9208641, Japan. Kanazawa Univ, Sch Med, Dept Ophthalmol, Kanazawa, Ishikawa 9208641, Japan. Toyama Med & Pharmaceut Univ, Fac Med, Dept Dermatol, Toyama 93001, Japan. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP Taniuchi, K (reprint author), Kanazawa Univ, Sch Med, Dept Dermatol, 13-1 Takara Machi, Kanazawa, Ishikawa 9208641, Japan. NR 21 TC 28 Z9 29 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD APR PY 1999 VL 140 IS 4 BP 696 EP 700 PG 5 WC Dermatology SC Dermatology GA 189VD UT WOS:000079926100021 PM 10233324 ER PT J AU Hertl, M Budinger, L Christophoridis, S Yancey, KB Borradori, L AF Hertl, M Budinger, L Christophoridis, S Yancey, KB Borradori, L TI IgG and IgA antibodies in linear IgA/IgG bullous dermatosis target the ectodomain of bullous pemphigoid antigen 2 SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Letter ID AUTOANTIBODIES; SUBSET; LAD-1; SERA C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. Rhein Westfal TH Klinikum, Hautklin, D-52074 Aachen, Germany. Hop Cantonal Geneva, Dermatol Clin, CH-1211 Geneva, Switzerland. RP Hertl, M (reprint author), NCI, Dermatol Branch, Bldg 10, Bethesda, MD 20892 USA. NR 9 TC 7 Z9 8 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD APR PY 1999 VL 140 IS 4 BP 750 EP 752 PG 3 WC Dermatology SC Dermatology GA 189VD UT WOS:000079926100033 PM 10233336 ER PT J AU Whitcup, SM Chan, CC Geiger, GL AF Whitcup, SM Chan, CC Geiger, GL TI Diagnosis of corticosteroid resistant ocular sarcoidosis by chorioretinal biopsy SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Letter ID POSTERIOR UVEITIS C1 NEI, NIH, Bethesda, MD 20892 USA. Brockwood Eye Inst, Birmingham, AL USA. RP Whitcup, SM (reprint author), NEI, NIH, 10-10S221 10 Ctr Dr MSC 1863, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD APR PY 1999 VL 83 IS 4 BP 504 EP 505 PG 2 WC Ophthalmology SC Ophthalmology GA 184ZV UT WOS:000079644400037 PM 10434881 ER PT J AU Goebel, SU Serrano, J Yu, F Gibril, F Venzon, DJ Jensen, RT AF Goebel, SU Serrano, J Yu, F Gibril, F Venzon, DJ Jensen, RT TI Prospective study of the value of serum chromogranin A or serum gastrin levels in the assessment of the presence, extent, or growth of gastrinomas SO CANCER LA English DT Article DE gastrinoma; pancreatic endocrine tumor; tumor marker; gastrin; chromogranin ID ZOLLINGER-ELLISON-SYNDROME; SOMATOSTATIN RECEPTOR SCINTIGRAPHY; MULTIPLE ENDOCRINE NEOPLASIA; NEURON-SPECIFIC ENOLASE; ISLET CELL TUMORS; LONG-TERM; OXYNTIC MUCOSA; METASTATIC GASTRINOMAS; NEUROENDOCRINE TUMORS; PANCREATIC TUMORS AB BACKGROUND. Serum chromogranin A levels (CgA) are reported by some authors to be of clinical utility for assessing the presence or absence of a pancreatic endocrine tumor and tumor extent or growth. The aim of the current study was to assess this finding and compare the results with those from serum gastrin determinations (FSG) in a large cohort of patients with gastrinomas. METHODS, In 112 consecutive patients with the Zollinger-Ellison syndrome serum CgA and FSG levels were measured and correlated with disease activity, extent of disease, and the presence of multiple endocrine neoplasia type-1 (MEN-1) or gastric carcinoid tumors. RESULTS, Serum CgA levels drawn on 2 consecutive days correlated closely (P < 0.00001) as did serum gastrin levels. Serum CgA levels correlated significantly with FSG levels (P < 0.00001). Serum CgA and FSG levels were significantly higher in patients with active disease than in disease free patients (P < 0.00001). The sensitivity for the presence of disease was higher for CgA compared with FSG (92% vs. 80%; P = 0.021). However, the specificity of CgA was 67%. Serum Cgh levels were not significantly different in the four disease categories (stable extrahepatic disease, increasing extrahepatic disease, stable liver metastases, and increasing liver metastases). FSG levels were significantly lower in patients with stable extrahepatic disease compared with those with increasing extrahepatic disease. However, both tumor markers decreased significantly with a gastrinoma resection in five patients. The presence of MEN-1 or a gastric carcinoid tumor did not influence the results. CONCLUSIONS. The results of the current study showed that serum CgA and FSG levels both are sensitive tumor markers for the detection of a gastrinoma; however, CgA levels have a relatively low specificity. Neither the magnitude of the serum CgA nor gastrin level correlated with tumor growth or tumor extent and therefore cannot be used to determine these variables. However, in contrast to some other studies, the results of the current study show that changes in serum CgA or gastrin in a given patient with time are related to the tumor extent and not to gastric mucosal changes due to hypergastrinemia. (C) 1999 American Cancer Society. C1 NIDDK, NIH, DDB, Bethesda, MD 20892 USA. Natl Canc Inst, Biostat & Data Management Sect, Bethesda, MD USA. RP Jensen, RT (reprint author), NIDDK, NIH, DDB, 10 Ctr Dr,MSC 1804,Bldg 10 Rm 9C-103, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008 NR 99 TC 62 Z9 63 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 0008-543X J9 CANCER JI Cancer PD APR 1 PY 1999 VL 85 IS 7 BP 1470 EP 1483 PG 14 WC Oncology SC Oncology GA 179FU UT WOS:000079316000007 PM 10193936 ER PT J AU Finn, LS Viswanatha, DS Belasco, JB Snyder, H Huebner, D Sorbara, L Raffeld, M Jaffe, ES Salhany, KE AF Finn, LS Viswanatha, DS Belasco, JB Snyder, H Huebner, D Sorbara, L Raffeld, M Jaffe, ES Salhany, KE TI Primary follicular lymphoma of the testis in childhood SO CANCER LA English DT Article DE testicular lymphoma; follicular lymphoma; pediatric lymphoma; testicular neoplasm; bcl-2; bcl-6; p53 ID NON-HODGKINS-LYMPHOMA; LARGE-CELL LYMPHOMA; GERMINAL-CENTER FORMATION; FINGER ENCODING GENE; CENTER B-CELLS; LYMPHOPROLIFERATIVE DISORDERS; MALIGNANT-LYMPHOMA; BCL-6 PROTEIN; P53; REARRANGEMENTS AB BACKGROUND. Follicular lymphoma in childhood is rare. The authors present four unusual primary follicular lymphomas of the testis in children. METHODS. Tumor tissue was evaluated using light microscopy, immunohistochemistry, flow cytometry, and polymerase chain reaction (PCR) for immunoglobulin heavy chain (IgH) and bcl-2 gene rearrangements. Southern blot and immunohistochemical analyses were used to detect bcl-6 gene rearrangements and protein expression, respectively. RESULTS. Four young boys ranging in age from 3 to 10 pears were diagnosed with Stage IE follicular large cell lymphoma (Grade 3). A B-cell phenotype was documented in all four cases; monoclonality was confirmed in three cases by demonstration of light chain restriction or clonal IgH gene rearrangement. None of the lymphomas expressed Bcl-2 or p53 protein, and bcl-2 gene rearrangements were not found in the three lymphomas studied. In contrast, Bcl-6 protein was expressed by all three lymphomas studied, and a bcl-6 gene rearrangement was detected in the one case analyzed by Southern blot. All four boys were treated by orchiectomy and combination chemotherapy and are alive with no evidence of disease 18-44 months following their initial diagnoses. CONCLUSIONS. Follicular lymphomas map rarely occur as primary testicular tumors in prepubertal boys and, when localized, appear to be associated with a favorable prognosis. In contrast to follicular lymphoma in adults, pediatric follicular lymphomas of the testis are usually of large cell type (Grade 3) and lack bcl-2 or p53 abnormalities. The identification, in one case, of a bcl-6 gene rearrangement suggests an alternate molecular pathogenesis for pediatric follicular lymphoma. (C) 1999 American Cancer Society. C1 Childrens Hosp Philadelphia, Dept Pathol, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Dept Oncol, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Dept Urol, Philadelphia, PA 19104 USA. British Columbia Canc Agcy, Dept Pathol, Vancouver, BC V5Z 4E6, Canada. Kaiser Permanente Med Ctr, Dept Pathol, Fontana, CA USA. NCI, Dept Pathol, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Finn, LS (reprint author), Childrens Hosp & Med Ctr, Dept Lab, Ch-37,4800 Sand Point Way NE, Seattle, WA 98105 USA. NR 51 TC 50 Z9 54 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 0008-543X J9 CANCER JI Cancer PD APR 1 PY 1999 VL 85 IS 7 BP 1626 EP 1635 DI 10.1002/(SICI)1097-0142(19990401)85:7<1626::AID-CNCR27>3.0.CO;2-0 PG 10 WC Oncology SC Oncology GA 179FU UT WOS:000079316000027 PM 10193956 ER PT J AU Chakrabarti, MC Paik, CH Carrasquillo, JA AF Chakrabarti, MC Paik, CH Carrasquillo, JA TI Preparation and in vitro studies of [I-125]IUDR-T101 antibody conjugate SO CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS LA English DT Article DE CD5; monoclonal antibody; IUDR; endocytosis; iodine ID T101 MONOCLONAL-ANTIBODY; T-CELL LYMPHOMA; MAMMALIAN-CELLS; INTRACELLULAR CATABOLISM; CYTO-TOXICITY; RADIOTOXICITY; I-125; RADIOIMMUNODETECTION; LEUKEMIA; BINDING AB Idoxuridine labeled with I-125 was conjugated to polylysine. This conjugate was then coupled to the carbohydrate side chains of T101 monoclonal antibodiy anti-CD5. The immunoreactivity, cell retention, cytotoxicity, and intracellular localization of this conjugate was tested in CCRF-CEM cells (CD5 positive). The conjugate had 68% immunoreactivity. The retention of I-125 by CCRF-CEM cells was higher for the conjugate than for T101 directly labeled with I-125 and more of it localized in the nucleus than did the I-125 labeled T101. The I-125 IUDR-polylysine-T101 conjugate was move cytotoxic than the I-125-labeled T101. In conclusion, the conjugation of [I-125]IUDR to T101 is feasible, and preferential targeting of the I-125 to the nucleus is obtained. C1 NIH, Dept Nucl Med, CC, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Carrasquillo, JA (reprint author), NIH, Dept Nucl Med, CC, Warren G Magnuson Clin Ctr, 10 Ctr Dr,MSC 1180,Bld 10-1C-401, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 34 TC 3 Z9 3 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1084-9785 J9 CANCER BIOTHER RADIO JI Cancer Biother. Radiopharm. PD APR PY 1999 VL 14 IS 2 BP 91 EP 98 DI 10.1089/cbr.1999.14.91 PG 8 WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging GA 191PZ UT WOS:000080031900005 PM 10850292 ER PT J AU Tseng, M Weinberg, CR Umbach, DM Longnecker, MP AF Tseng, M Weinberg, CR Umbach, DM Longnecker, MP TI Calculation of population attributable risk for alcohol and breast cancer (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE alcohol; breast-neoplasms; population attributable risk ID CONFIDENCE-INTERVALS; MEASUREMENT ERROR; CONSUMPTION; WOMEN; BIAS AB Objectives: Because of increasing evidence that alcohol may be causally associated with breast cancer, we reconsider the population attributable risk (PAR) for alcohol and breast cancer for the US adult female population using an effect estimate from a meta-analysis and incorporating a revised perspective on measurement error correction. Methods: To estimate PAR, we employed a formula appropriate to use with an adjusted effect estimate. To estimate intermediate quantities needed to apply that formula, we used adjusted relative risk estimates from a previously published meta-analysis, as well as SEER cancer statistics and general population data from the third National Health and Nutrition Examination Survey. We used relative risk estimates uncorrected for measurement error. Results: The estimated age-adjusted PAR for alcohol and breast cancer was 2.1%. Conclusions: Because of the modest association between alcohol and breast cancer and the generally moderate level of alcohol intake among US women, the proportion of breast cancer attributable to alcohol intake is small. Widespread efforts to reduce alcohol consumption would not have a substantial impact on breast cancer rates in this population. While selected subgroups of women might benefit from decreasing alcohol consumption, specific profiles for such women have yet to be defined and defended. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Longnecker, MP (reprint author), NIEHS, Epidemiol Branch, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. RI Tseng, Marilyn/B-9334-2016; OI Tseng, Marilyn/0000-0002-9969-9055; Longnecker, Matthew/0000-0001-6073-5322 NR 19 TC 26 Z9 26 U1 0 U2 5 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD APR PY 1999 VL 10 IS 2 BP 119 EP 123 DI 10.1023/A:1008853115901 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 190CT UT WOS:000079944600004 PM 10231160 ER PT J AU Negri, E Ron, E Franceschi, S Dal Maso, L Mark, SD Preston-Martin, S McTiernan, A Kolonel, L Kleinerman, R Land, C Jin, F Wingren, G Galanti, MR Hallquist, A Glattre, E Lund, E Levi, F Linos, D Braga, C La Vecchia, C AF Negri, E Ron, E Franceschi, S Dal Maso, L Mark, SD Preston-Martin, S McTiernan, A Kolonel, L Kleinerman, R Land, C Jin, F Wingren, G Galanti, MR Hallquist, A Glattre, E Lund, E Levi, F Linos, D Braga, C La Vecchia, C TI A pooled analysis of case-control studies of thyroid cancer - I. Methods SO CANCER CAUSES & CONTROL LA English DT Article DE case-control studies; methods; thyroid cancer ID HORMONAL FACTORS; RISK-FACTORS; WOMEN; HISTORY; CARCINOMA; PAPILLARY; DISEASE; METAANALYSIS; RADIATION; EXPOSURE AB Objective. Because the etiology of thyroid cancer is not well described, we conducted a pooled analysis of all published case-control studies, as well as two identified unpublished studies. This paper describes the major characteristics of the 14 studies included in the analysis, as well as the statistical methods employed. Four studies were conducted in the United States (1 each in Washington State, California, Connecticut and Hawaii), 8 in Europe (3 in Sweden, 2 in Norway, 1 in Switzerland, 1 in Italy and 1 in Greece), and 2 in Asia (1 in China and 1 in Japan). Methods: The original datasets were obtained and restructured in a uniform format. Data on socio-demographic characteristics, anthropometric measures, smoking and alcohol consumption, history of benign thyroid diseases and of other selected medical conditions and treatments, family history of cancer and of benign thyroid conditions, occupation, residence in endemic goitre areas, and dietary habits were analyzed. For women, we also analyzed menstrual and reproductive factors and use of female hormones. Radiotherapy and, in Japan, exposure to the A-bombs were considered as potential confounding factors. Results: A total of 2,725 cases (2,247 females and 478 males) and 4,776 controls (3,699 females and 1,077 males) were included in this study. Of the cases, 79% were classified as papillary thyroid carcinomas, 14% as follicular, 2% medullary, 1% anaplastic, 1% other histologies, and 3% histological type unknown. Each of the datasets was checked for outliers and consistency. Data were analysed separately by study center, gender, and the two major histologic types (papillary, follicular). Frequency tables and simple statistics were computed for each variable under study. Conditional logistic regression was used to compute odds ratios. For matched studies, the original matching was preserved, whereas, for unmatched ones, five-year age groups were used for matching. Study-specific analyses were computed, and then the data from all the studies were pooled conditioning on study. Heterogeneity between studies, geographic areas and study designs was assessed, and the modifying effect of age was also evaluated. C1 Ist Ric Farmacol Mario Negri, Lab Gen Epidemiol, I-20157 Milan, Italy. NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Ctr Riferimento Oncol, I-33081 Aviano, PN, Italy. Univ So Calif, Dept Prevent Med, Los Angeles, CA 90033 USA. Univ Hawaii Manoa, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. Radiat Effects Res Fdn, Hiroshima 732, Japan. Shanghai Canc Inst, Shanghai, Peoples R China. Linkoping Univ, Fac Hlth Sci, Div Environm & Occupat Med, SE-58185 Linkoping, Sweden. Karolinska Inst, Dept Oncol, SE-11235 Stockholm, Sweden. Univ Hosp, Dept Canc Epidemiol, SE-57185 Uppsala, Sweden. Stockholms Sjukhem, SE-11235 Stockholm, Sweden. Canc Registry Norway, NO-3010 Oslo, Norway. Univ Tromso, Inst Community Med, NO-9037 Tromso, Norway. Registre Vaudois Tumeurs, CH-1011 Lausanne, Switzerland. Inst Prevent Med, GR-14561 Kifissia, Greece. Univ Milan, Ist Stat Med & Biometria, I-20133 Milan, Italy. RP Negri, E (reprint author), Ist Ric Farmacol Mario Negri, Lab Gen Epidemiol, Via Eritrea 62, I-20157 Milan, Italy. RI Negri, Eva/B-7244-2013; OI Negri, Eva/0000-0001-9712-8526; Kleinerman, Ruth/0000-0001-7415-2478; La Vecchia, Carlo/0000-0003-1441-897X NR 29 TC 38 Z9 39 U1 1 U2 3 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 APR PY 1999 VL 10 IS 2 BP 131 EP 142 DI 10.1023/A:1008851613024 PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 190CT UT WOS:000079944600006 PM 10231162 ER PT J AU Negri, E Dal Maso, L Ron, E La Vecchia, C Mark, SD Preston-Martin, S McTiernan, A Kolonel, L Yoshimoto, Y Jin, F Wingren, G Galanti, MR Hardell, L Glattre, E Lund, E Levi, F Linos, D Braga, C Franceschi, S AF Negri, E Dal Maso, L Ron, E La Vecchia, C Mark, SD Preston-Martin, S McTiernan, A Kolonel, L Yoshimoto, Y Jin, F Wingren, G Galanti, MR Hardell, L Glattre, E Lund, E Levi, F Linos, D Braga, C Franceschi, S TI A pooled analysis of case-control studies of thyroid cancer - II. Menstrual and reproductive factors SO CANCER CAUSES & CONTROL LA English DT Article DE case-control studies; menarche; menopause; pregnancy; thyroid cancer ID HORMONAL FACTORS; ESTROGEN-RECEPTOR; BREAST-CANCER; RISK-FACTORS; WOMEN; PREGNANCY; EPIDEMIOLOGY; PARITY; SERUM; THYROTROPIN AB Objective: It has been suggested that female hormones, and hence menstrual and reproductive factors, play a role in thyroid cancer etiology. Epidemiological data, however, are limited and inconsistent, partly because of the small number of cases included in each study. To clarify the etiology of thyroid cancer, we conducted a pooled analysis of original data from 14 case-control studies, 4 from the United States, 2 from Asia, and 8 from Europe. Methods: This analysis included a total of 2,247 female cases of thyroid cancer (80% papillary) and 3,699 control women. Pooled odds ratios (OR) were estimated using logistic regression, conditioning on study and (i) matching sets for individually matched studies, or (ii) quinquennia of age for the other studies. Additional terms for age and history of radiation exposure were included in the regression equations. Results: The OR per year of later menarche was 1.04 (95% confidence interval (CI) 1.0-1.1). Compared to premenopausal women, the OR was 1.3 for women with natural menopause, and 1.8 for those with artificial menopause, but the studies were heterogeneous and the association may be due, at least in part, to diagnostic or ascertainment bias. Parity, spontaneous or induced abortions and history of infertility were not associated with thyroid cancer risk. The OR was above unity in women reporting later age at first birth (OR = 1.1, 95% CI 1.0-1.3 for 5-year delay) and higher in the first years after a birth. Conclusions: The associations of menstrual and reproductive factors with thyroid cancer risk were generally weak, but appeared stronger among women diagnosed with thyroid cancer at younger ages. C1 Ist Ric Farmacol Mario Negri, Lab Gen Epidemiol, I-20157 Milan, Italy. Ctr Riferimento Oncol, I-33081 Aviano, PN, Italy. NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Univ Milan, Ist Stat Med & Biometria, I-20133 Milan, Italy. Univ So Calif, Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Univ Hawaii Manoa, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. Natl Inst Radiol Sci, Chiba 2630024, Japan. Shanghai Canc Inst, Shanghai, Peoples R China. Linkoping Univ, Fac Hlth Sci, Div Environm & Occupat Med, SE-58185 Linkoping, Sweden. Univ Hosp, Dept Canc Epidemiol, SE-57185 Uppsala, Sweden. Orebro Med Ctr, Dept Oncol, SE-70185 Orebro, Sweden. Canc Registry Norway, NO-3010 Oslo, Norway. Univ Tromso, Inst Community Med, NO-9037 Tromso, Norway. Registre Vaudois Tumeurs, CH-1011 Lausanne, Switzerland. Inst Prevent Med, GR-14561 Kifissia, Greece. RP Negri, E (reprint author), Ist Ric Farmacol Mario Negri, Lab Gen Epidemiol, Via Eritrea 62, I-20157 Milan, Italy. RI Negri, Eva/B-7244-2013; OI Negri, Eva/0000-0001-9712-8526; La Vecchia, Carlo/0000-0003-1441-897X NR 38 TC 102 Z9 102 U1 1 U2 3 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 APR PY 1999 VL 10 IS 2 BP 143 EP 155 DI 10.1023/A:1008880429862 PG 13 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 190CT UT WOS:000079944600007 PM 10231163 ER PT J AU La Vecchia, C Ron, E Franceschi, S Dal Maso, L Mark, SD Chatenoud, L Braga, C Preston-Martin, S McTiernan, A Kolonel, L Mabuchi, K Jin, F Wingren, G Galanti, MR Hallquist, A Lund, E Levi, F Linos, D Negri, E AF La Vecchia, C Ron, E Franceschi, S Dal Maso, L Mark, SD Chatenoud, L Braga, C Preston-Martin, S McTiernan, A Kolonel, L Mabuchi, K Jin, F Wingren, G Galanti, MR Hallquist, A Lund, E Levi, F Linos, D Negri, E TI A pooled analysis of case-control studies of thyroid cancer - III. Oral contraceptives, menopausal replacement therapy and other female hormones SO CANCER CAUSES & CONTROL LA English DT Article DE case-control studies; hormone replacement therapy; oral contraceptives; thyroid cancer ID WOMEN; RISK; EPIDEMIOLOGY; HISTORY; DISEASE AB Objective: The relations between oral contraceptives (OC), hormone replacement therapy (HRT) for menopause, and other female hormone use and thyroid cancer risk was analyzed using the original data from 13 studies from North America, Asia and Europe. Methods: Based on 2,132 cases and 3,301 controls, odds ratios (OR) and the corresponding 95% confidence intervals (CI) were obtained by conditional regression models, conditioning on study and age at diagnosis, and adjusting for age, radiation exposure and parity. Results: Overall, 808 (38%) cases versus 1,290 (39%) controls had ever used OCs, corresponding to an OR of 1.2 (95% CI 1.0 to 1.4). There was no relation with duration of use, age at first use, or use before first birth. The OR was significantly increased for current OC users (OR = 1.5, 95% 1.0 to 2.1), but declined with increasing time since stopping (OR = 1.1 for > 10 years since stopping). The association was stronger for papillary cancers (OR = 1.6 for current users) than for other histologic types. No significant heterogeneity was observed across studies or geographic areas. Eight studies had data on HRT, for a total of 1,305 cases and 2,300 controls: 110 (8%) cases and 205 (9%) controls reported ever using HRT (OR = 0.8; 95% CI 0.6 to 1.1). The ORs were 1.6 (95% to 0.9 to 2.9) for use of fertility drugs, and 1.5 (95% CI 1.1 to 2.1) for lactation suppression treatment. Conclusions: The studies considered in these analyses include most of the epidemiological data on the role of exogenous hormone use in the, etiology of thyroid cancer, and they provide reassuring evidence on the absence of an association of practical relevance. The moderate excess risk in current OC users, if not due to increased surveillance for thyroid masses among OC users, is similar to that described for breast cancer, and would imply a role of female hormones on thyroid cancer promotion. There was no indication of increased thyroid cancer risk 10 or more years after discontinuing OC use. C1 Ist Ric Farmacol Mario Negri, Lab Gen Epidemiol, I-20157 Milan, Italy. Univ Milan, Ist Stat Med & Biometria, I-20133 Milan, Italy. NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Ctr Riferimento Oncol, I-33081 Aviano, PN, Italy. Univ So Calif, Dept Prevent Med, Los Angeles, CA 90033 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Univ Hawaii Manoa, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. Radiat Effects Res Fdn, Hiroshima 732, Japan. Shanghai Canc Inst, Shanghai, Peoples R China. Linkoping Univ, Fac Hlth Sci, Div Environm & Occupat Med, SE-58185 Linkoping, Sweden. Univ Hosp, Dept Canc Epidemiol, SE-57185 Uppsala, Sweden. Karolinska Inst, Dept Oncol, SE-11235 Stockholm, Sweden. Stockholms Sjukhem, SE-11235 Stockholm, Sweden. Univ Tromso, Inst Community Med, NO-9037 Tromso, Norway. Registre Vaudois Tumeurs, CH-1011 Lausanne, Switzerland. Inst Prevent Med, GR-14561 Kifissia, Greece. RP Negri, E (reprint author), Ist Ric Farmacol Mario Negri, Lab Gen Epidemiol, Via Eritrea 62, I-20157 Milan, Italy. RI Negri, Eva/B-7244-2013; OI Negri, Eva/0000-0001-9712-8526; La Vecchia, Carlo/0000-0003-1441-897X NR 19 TC 77 Z9 77 U1 0 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 APR PY 1999 VL 10 IS 2 BP 157 EP 166 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 190CT UT WOS:000079944600008 PM 10231164 ER PT J AU Goedert, JJ Sauter, ME Jacobson, LP Vessella, RL Hilgartner, MW Leitman, SF Fraser, MC Mueller-Lantzsch, NG AF Goedert, JJ Sauter, ME Jacobson, LP Vessella, RL Hilgartner, MW Leitman, SF Fraser, MC Mueller-Lantzsch, NG TI High prevalence of antibodies against HERV-K10 in patients with testicular cancer but not with AIDS SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GERM-CELL; TUMORS; EXPRESSION; PROTEIN; VIRUS AB Human endogenous retrovirus K10 (HERV-K10) env and gag expression has been detected in placenta. embryonic tissue, and cell lines. By transfection, these sequences have been expressed in insect cells and developed into serological assays, revealing HERV-K10 antibodies in patients with testicular cancer. Patients with BIDS are at an increased risk for testicular cancer and frequently reactivate latent infections. We postulated that HERV-K10 seroprevalence might be increased with HIV infection or AIDS. Stored, frozen serum samples from 52 patients with testicular cancer (8 patients with HIV and 30 patients with samples near the time of diagnosis) and 84 controls (40 patients with HIV) were diluted 1:40 and tested by immunofluorescence against SF158 cells transfected with HERV-K10 env [ENV1.9(+)] or gag (pACGAG), Seroprevalence rates were compared cross-sectionally in cases and controls, excluding those with indeterminate results (3 of 30 cases and 7 of 84 controls), and also were examined longitudinally in the cases before or after diagnosis of testicular cancer. Seroprevalence to HERV-K10 Env or Gag was 17 of 27 testicular cancer patients (63%) around the time of diagnosis, compared to 4 of 77 controls (5%; P < 0.0001). Seroprevalence was similar (50% to 60%) with seminoma, teratocarcinoma, or embryonal carcinoma, and it was not increased with HIV infection in either cases (33%) or controls (3%). HERV-K10 antibodies were detected in 12 of 19 cases (63%) more than 6 months before seminoma diagnosis, as well as in four cases with residual or recurrent malignancy more than 1 month after initial diagnosis. Thus, HERV-K10 antibodies are detected frequently with testicular cancer and seem to resolve rapidly with effective therapy of the malignancy, Antibody reactivity also occurs in similar to 5% of controls, perhaps because of nonspecific or cross-reactive epitopes, HIV and AIDS were not associated with HERV-K10 antibodies, thus, leaving their higher risk of testicular cancer unexplained. C1 NCI, Viral Epidemiol Branch, Rockville, MD 20852 USA. NCI, Genet Epidemiol Branch, Rockville, MD 20852 USA. Univ Saarlandes Kliniken, Abt Virol, Homburg, Germany. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Univ Washington, Dept Urol, Seattle, WA 98195 USA. Cornell Univ, Med Ctr, New York Hosp, Dept Pediat, New York, NY 10021 USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. RP Goedert, JJ (reprint author), 6120 Execut Blvd,Suite 8012, Rockville, MD 20852 USA. FU NCRR NIH HHS [5-MO1-RR-00722]; NIAID NIH HHS [UO1-AI-35043, UO1-AI-35042] NR 15 TC 32 Z9 32 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 APR PY 1999 VL 8 IS 4 BP 293 EP 296 PN 1 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 187CT UT WOS:000079769200004 PM 10207631 ER PT J AU Collins, FJ Thomson, EJ AF Collins, FJ Thomson, EJ TI Psychosocial aspects of cancer genetic testing findings from the Cancer Genetics Studies Consortium - Foreword SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material C1 Natl Human Genome Res Inst, Eth Legal & Social Implicat Res Program, Bethesda, MD 20892 USA. RP Collins, FJ (reprint author), Natl Human Genome Res Inst, Eth Legal & Social Implicat Res Program, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 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 APR PY 1999 VL 8 IS 4 BP 325 EP 325 PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 187DB UT WOS:000079770100001 ER PT J AU Lerman, C Hughes, C Benkendorf, JL Biesecker, B Kerner, J Willison, J Eads, N Hadley, D Lynch, J AF Lerman, C Hughes, C Benkendorf, JL Biesecker, B Kerner, J Willison, J Eads, N Hadley, D Lynch, J TI Racial differences in testing motivation and psychological distress following pretest education for BRCA1 gene testing SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID AFRICAN-AMERICAN FAMILIES; FIRST-DEGREE RELATIVES; BREAST-CANCER; RISK PERCEPTION; WOMEN; SUSCEPTIBILITY; IMPACT; TRIAL AB Objectives. We conducted a randomized trial to investigate racial differences in response to two alternate pretest education strategics for BRCA1 genetic testing: a standard education model and an education plus counseling (E+C) model. Materials and Methods. Two hundred twenty-eight Caucasian women and 70 African American women with a family history of breast or ovarian cancer were contacted for a baseline telephone interview to assess sociodemographic characteristics, number of relatives affected with cancer, and race before pretest education. Outcome variables included changes from baseline to 1-month follow-up in cancer-related distress and genetic testing intentions, as well as provision of a blood sample after the education session. Results. African American women were found to differ significantly from Caucasian women in the effects of the interventions on testing intentions and provision of a blood sample. Specifically, in African American women, E+C led to greater increases than education only in intentions to be tested and provision of a blood sample. These effects were independent of socioeconomic status and referral mechanisms. In Caucasian women, there were no differential effects of the interventions on these outcomes. Reductions in cancer-specific distress a ere evidenced in all study groups. However, this decrease, although not significantly different, was smallest among African American women who received E+C, Conclusions. In low- to moderate-risk African American women, pretest education and counseling may motivate BRCA1 testing. Further research is needed to explore the mechanisms of impact of the alternate pretest education strategies and to increase the cultural sensitivity of education and counseling protocols. C1 Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Div Genet, Washington, DC 20007 USA. Natl Human Genome Res Inst, Bethesda, MD 20892 USA. Washington Hosp Ctr, Inst Canc, Washington, DC 20010 USA. RP Lerman, C (reprint author), Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, 2233 Wisconsin Ave NW,Suite 317, Washington, DC 20007 USA. FU NIMH NIH HHS [MH/HG54435] NR 25 TC 99 Z9 99 U1 0 U2 4 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 APR PY 1999 VL 8 IS 4 BP 361 EP 367 PN 2 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 187DB UT WOS:000079770100008 PM 10207641 ER PT J AU Brinkmann, U Vasmatzis, G Lee, B Pastan, I AF Brinkmann, U Vasmatzis, G Lee, B Pastan, I TI Novel genes in the PAGE and GAGE family of tumor antigens found by homology walking in the dbEST database SO CANCER RESEARCH LA English DT Article ID CYTOLYTIC T-LYMPHOCYTES; HUMAN-MELANOMA; SEQUENCE; PROSTATE; CANCER AB We have developed a computer-based screening strategy to search the dbEST database to find differentiation antigens that are expressed by cancers arising in nonessential normal tissues such as prostate, breast, and ovary (G. Vasmatzis et at, Proc. Natl. Acad, Sci, USA, 95: 300-304, 1998), Here, we report the identification of three new members of the GAGE/ PAGE family, termed XAGEs. XAGE-1 and XAGE-2 are expressed in Ewing's sarcoma, rhabdomyosarcoma, a breast cancer, and a germ cell tumor. We also describe the relationship of the XAGEs to the GAGE/ PAGE family. XAGE-1 and XAGE-2 should be evaluated as possible targets for vaccine-based therapies of cancer. C1 NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, Div Basic Sci, NIH, Bldg 37,Room 4E16,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 19 TC 78 Z9 89 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 APR 1 PY 1999 VL 59 IS 7 BP 1445 EP 1448 PG 4 WC Oncology SC Oncology GA 182ZJ UT WOS:000079527800013 PM 10197611 ER PT J AU Ochs, K Sobol, RW Wilson, SH Kaina, B AF Ochs, K Sobol, RW Wilson, SH Kaina, B TI Cells deficient in DNA polymerase beta are hypersensitive to alkylating agent-induced apoptosis and chromosomal breakage SO CANCER RESEARCH LA English DT Article ID CHINESE-HAMSTER CELLS; SISTER-CHROMATID EXCHANGES; BASE-EXCISION-REPAIR; METHYLTRANSFERASE MGMT; ESCHERICHIA-COLI; DAMAGING AGENTS; EXPRESSION; ADDUCTS; O-6-ALKYLGUANINE; SENSITIVITY AB DNA polymerase beta (beta-pol), which is involved in base excision repair, was investigated for its role in protection of cells against various genotoxic agents and cytostatic drugs using beta-pol knockout mouse fibroblasts. We show that cells lacking beta-pol are highly sensitive to induction of apoptosis and chromosomal breakage by methylating agents, such as N-methyl-N-nitro-N-nitrosoguanidine and methyl methanesulfonate and the crosslinking antineoplastic drugs mitomycin C and mafosfamide, The cross-sensitivity between the agents observed suggests that beta-pol is involved in repair not only of DNA methylation lesions but also of other kinds of DNA damage induced by various cytostatic drugs. Cells deficient in beta-pol were not hypersensitive to cisplatin, melphalan, benzo(n)pyrene diol epoxide, chloroethylnitrosourea, or UV light. Because both established and primary beta-pol knockout fibroblasts displayed the hypersensitive phenotype, which, moreover, was complemented by transfection with a beta-pol expression vector, the alkylating agent hypersensitivity can clearly be attributed to the beta-pol deficiency. The results demonstrate that beta-pol-driven base excision repair is highly important for protection of cells against cell killing due to apoptosis and induced chromosomal breakage and suggest that incompletely repaired DNA damage causes chromosomal changes and may act as a trigger of DNA damage-induced apoptosis. C1 Univ Mainz, Inst Toxicol, Div Appl Toxicol, D-55131 Mainz, Germany. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Kaina, B (reprint author), Univ Mainz, Inst Toxicol, Div Appl Toxicol, Obere Zahlbacher Str 67, D-55131 Mainz, Germany. EM kaina@mail.uni-mainz.de RI Sobol, Robert/E-4125-2013 OI Sobol, Robert/0000-0001-7385-3563 NR 41 TC 119 Z9 121 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 1999 VL 59 IS 7 BP 1544 EP 1551 PG 8 WC Oncology SC Oncology GA 182ZJ UT WOS:000079527800029 PM 10197627 ER PT J AU Conner, EA Teramoto, T Wirth, PJ Kiss, A Garfield, S Thorgeirsson, SS AF Conner, EA Teramoto, T Wirth, PJ Kiss, A Garfield, S Thorgeirsson, SS TI HGF-mediated apoptosis via p53/bax-independent pathway activating JNK1 SO CARCINOGENESIS LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; LIVER EPITHELIAL-CELLS; HEPATOCELLULAR-CARCINOMA CELLS; MYC-INDUCED APOPTOSIS; NF-KAPPA-B; CYCLIN-A; FACTOR-RECEPTOR; C-MYC; PHOSPHATIDYLINOSITOL 3-KINASE; SPONTANEOUS TRANSFORMATION AB Current studies have indicated both positive and negative roles for the hepatocyte growth factor (HGF)/c-met receptor signaling system in tumor development. Recently, we have shown that HGF has the capacity to induce both growth inhibition and programmed cell death in aflatoxin-transformed (AFLB8) rat liver epithelial cells. Using the same cell line, we have now investigated a potential mechanism for HGF-induced apoptosis, Immunoblot analysis of bcl-2 gene family member (bax, bcl-2, bclX-s/l) expression showed no correlation with HGF treatment, suggesting that HGF-mediated apoptosis is bax independent. Following HGF treatment retinoblastoma protein (pRB) was present in the hypophosphorylated state, HGF treatment increased cyclin A, cyclin G1 and nuclear transcriptional factor (NF kappa B) protein expression. However, electrophoretic mobility shift analysis showed that NF kappa B activity decreased with HGF treatment, Under these apoptotic conditions, c-Jun N-terminal kinase (JNK1) and extracellular signal-regulated kinase (ERK2) were activated with lower level activation of ERK2, while no involvement of phosphatidylinositol-3 kinase was observed. Epidermal growth factor (EGF) was not protective, and actually induced cells to undergo apoptosis to a level similar to that of HGF alone or EGF/HGF in combination. These results suggest the possibility of cross-talk between HGF/c-met and EGF/EGFR signaling pathways, and the involvement of JNK1 induction in HGF-mediated apoptotic cell death. C1 NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. EM snorri_thorgeirsson@nih.gov NR 60 TC 40 Z9 40 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 1999 VL 20 IS 4 BP 583 EP 590 DI 10.1093/carcin/20.4.583 PG 8 WC Oncology SC Oncology GA 186EL UT WOS:000079714300009 PM 10223185 ER PT J AU Sills, RC Hong, HL Melnick, RL Boorman, GA Devereux, TR AF Sills, RC Hong, HL Melnick, RL Boorman, GA Devereux, TR TI High frequency of codon 61 K-ras A -> T transversions in lung and Harderian gland neoplasms of B6C3F1 mice exposed to chloroprene (2-chloro-1,3-butadiene) for 2 years, and comparisons with the structurally related chemicals isoprene and 1,3-butadiene SO CARCINOGENESIS LA English DT Article ID H-RAS; PROTOONCOGENE ACTIVATION; EPOXIDE METABOLITES; INHALATION EXPOSURE; DNA-POLYMERASE; MUTATIONS; TUMORS; MUTAGENICITY; ADDUCTS; MOUSE AB Chloroprene is the 2-chloro analog of 1,3-butadiene, a potent carcinogen in laboratory animals. Following 2 years of inhalation exposure to 12.8, 32 or 80 p.p.m. chloroprene, increased incidences of lung and Harderian gland (HG) neoplasms were observed in B6C3F1 mice at all exposure concentrations. The present study was designed to characterize genetic alterations in the K- and H-ras protooncogenes in chloroprene-induced lung and HG neoplasms, K-ras mutations were detected in 80% of chloroprene-induced lung neoplasms (37/46) compared with only 30% in spontaneous lung neoplasms (25/82), Both K- and H-ras codon 61 A-->T transversions were identified in 100% of HG neoplasms (27/27) compared with a frequency of 56% (15/27) in spontaneous HG neoplasms. The predominant mutation in chloroprene-induced lung and HG neoplasms was an A-->T transversion at K-ras codon 61, This mutation has not been detected in spontaneous lung tumors of B6C3F1 mice and was identified in only 7% of spontaneous HG neoplasms. In lung neoplasms, greater percentages (80 and 71%) of A-->T transversions were observed at the lower exposures (12.8 and 32 p.p.m.), respectively, compared with 18% at the high exposure. In HG neoplasms, the percentage of A-->T transversions was the same at all exposure concentrations. The chloroprene-induced ras mutation spectra was similar to that seen with isoprene, where the predominant base change was an A-->T transversion at K-ras codon 61, This differed from 1,3-butadiene, where K-ras codon 13 G-->C transitions and H-ras codon 61 A-->G transitions were the predominant mutations. The major finding of K-ras A-->T transversions in lung and Harderian gland neoplasms suggests that this mutation may be important for tumor induction by this class of carcinogens. C1 NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. NIEHS, Environm Carcinogenesis Program, Res Triangle Pk, NC 27709 USA. RP Sills, RC (reprint author), NIEHS, Environm Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. NR 48 TC 38 Z9 39 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 1999 VL 20 IS 4 BP 657 EP 662 DI 10.1093/carcin/20.4.657 PG 6 WC Oncology SC Oncology GA 186EL UT WOS:000079714300020 PM 10223196 ER PT J AU Ding, M Li, JJ Leonard, SS Ye, JP Shi, XL Colburn, NH Castranova, V Vallyathan, V AF Ding, M Li, JJ Leonard, SS Ye, JP Shi, XL Colburn, NH Castranova, V Vallyathan, V TI Vanadate-induced activation of activator protein-1: role of reactive oxygen species SO CARCINOGENESIS LA English DT Article ID PROMOTER-INDUCED TRANSFORMATION; MOUSE JB6 CELLS; NF-KAPPA-B; C-JUN; NEOPLASTIC TRANSFORMATION; GENE-EXPRESSION; TRANSCRIPTIONAL ACTIVATION; AMMONIUM METAVANADATE; HYDROGEN-PEROXIDE; REDOX REGULATION AB The present study was undertaken to test the hypothesis that the toxicity and carcinogenicity of vanadium might arise from elevation of reactive oxygen species leading to activation of the transcription factor activator protein-1 (AP-1), The AP-1 transactivation response has been implicated as causal in transformation responses to phorbol esters and growth factors. To investigate the possible activity of vanadium in the activation of AP-1, we treated mouse epidermal JB6 P+ cells stably transfected with an AP-1 luciferase reporter plasmid with various concentrations of vanadate, This resulted in concentration-dependent transactivation of AP-1, Superoxide dismutase (SOD) and catalase inhibited AP-1 activation induced by vanadate, indicating the involvement of superoxide anion radical (O-2(-.)), hydroxyl radical (. OH) and/or H2O2 in the mechanism of vanadate-induced AP-1 activation. However, sodium formate, a specific .OH scavenger, did not alter vanadate-induced AP-1 activation, suggesting a minimal role for the . OH radical. NADPH enhanced AP-1 activation by increasing vanadate-mediated generation of O-2(-.). N-acetylcysteine, a thiol-containing antioxidant, decreased activation, further showing that vanadate-induced AP-1 activation involved redox reactions. Calphostin C, a specific inhibitor of protein kinase C (PKC), inhibited activation of AP-1, demonstrating that PKC is involved in the cell signal cascades leading to vanadate-induced AP-1 activation. Electron spin resonance (ESR) measurements show that JB6 P+ cells are able to reduce vanadate to generate vanadium(IV) in the presence of NADPH, Molecular oxygen was consumed during the vanadate reduction process to generate O-2(-.) as measured by ESR spin trapping using 5,5-dimethyl-L-pyrroline N-oxide as the spin trapping agent. SOD inhibited the ESR spin adduct signal, further demonstrating the generation of O-2(-.) in the cellular reduction of vanadate, These results provide support for a model in which vanadium, like other classes of tumor promoters, transactivates AP-l-dependent gene expression. In the case of vanadium, AP-1 transactivation is dependent on the generation of O-2(-.) and H2O2, but not . OH. C1 NIOSH, Hlth Effects Lab Div, Pathol & Physiol Res Branch, Morgantown, WV 26505 USA. NCI, Lab Biochem Physiol, Frederick, MD 21702 USA. RP Vallyathan, V (reprint author), NIOSH, Hlth Effects Lab Div, Pathol & Physiol Res Branch, 1095 Willowdale Rd, Morgantown, WV 26505 USA. EM vav1@cdc.gov RI Shi, Xianglin/B-8588-2012 NR 46 TC 75 Z9 80 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 1999 VL 20 IS 4 BP 663 EP 668 DI 10.1093/carcin/20.4.663 PG 6 WC Oncology SC Oncology GA 186EL UT WOS:000079714300021 PM 10223197 ER PT J AU Mei, JM Hord, NG Winterstein, DF Donald, SP Phang, JM AF Mei, JM Hord, NG Winterstein, DF Donald, SP Phang, JM TI Differential expression of prostaglandin endoperoxide H synthase-2 and formation of activated beta-catenin-LEF-1 transcription complex in mouse colonic epithelial cells contrasting in Apc SO CARCINOGENESIS LA English DT Article ID BETA-CATENIN; CYCLOOXYGENASE-2 LEVELS; FACTOR LEF-1; CANCER; GENE; CARCINOMA; PROTEIN; LINES; MICE AB Mutations in Ape underlie the intestinal lesions in familial adenomatous polyposis and are found in >85% of sporadic colon cancers. They are frequently associated with overexpression of prostaglandin endoperoxide H synthase-2 (PGHS-2) in colonic adenomas. It has been suggested that Ape mutations are linked mechanistically to increased PGHS-2 expression by elevated nuclear accumulation of beta-catenin-Tcf-LEF transcription complex. In the present study, we show that PGHS-2 is differentially expressed in mouse colonic epithelial cells with distinct Ape status. Cells with a mutated Ape expressed markedly higher levels of PGHS-2 mRNA and protein and produced significantly more prostaglandin E-2 than cells with normal Ape. Using electrophoretic mobility shift assays, we demonstrate that DNA-beta-catenin-LEF-1 complex formation is differentially induced in these two cell lines in an Ape-dependent manner. Our data indicate that the differential induction of beta-catenin-LEF-1 complex correlates closely with differential expression of PGHS-2. These findings support the hypothesis that the differential expression of PGHS-2 is mediated through the proposed beta-catenin/Tcf-LEF signaling pathway. C1 NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, Lab Nutr & Mol Regulat, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. RP Phang, JM (reprint author), NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, Lab Nutr & Mol Regulat, Frederick, MD 21702 USA. EM phang@mail.ncifcrf.gov NR 26 TC 42 Z9 42 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 APR PY 1999 VL 20 IS 4 BP 737 EP 740 DI 10.1093/carcin/20.4.737 PG 4 WC Oncology SC Oncology GA 186EL UT WOS:000079714300032 PM 10223208 ER PT J AU Mackem, S Knezevic, V AF Mackem, S Knezevic, V TI Do 5'Hoxd genes play a role in initiating or maintaining A-P polarizing signals in the limb? SO CELL AND TISSUE RESEARCH LA English DT Article DE 5 ' Hoxd genes; Hoxd-12; limb development; sonic hedgehog; luxate mutants; luxoid mutants; extra-toes; Gli3 ID CHICK WING DEVELOPMENT; SONIC-HEDGEHOG; MUTANT MICE; HOMEOTIC TRANSFORMATIONS; SEQUENCE RECOGNITION; AXIAL SKELETON; HOX GENES; EXPRESSION; MOUSE; HOXD-11 AB The analysis of multiple null mutants generated through targeted disruption indicates that the 5' members of the Hoxd and Hoxa clusters determine the skeletal pattern in the limb by regulating the formation and growth of the different chondrogenic precursors for the skeletal elements. While these studies have established that together these genes are the major players in regulating formation of the limb skeleton, the roles of individual members have often been difficult to evaluate fully due to extensive functional overlap between various 5'Hoxd and 5'Hoxa genes. The analysis of gain-of-function mutants provides a complementary approach to elucidate gene function in the presence of multiple redundancies. This approach has recently revealed that Hosd-12 can induce Sonic hedgehog and suggests a new role for certain 5'Hoxd genes in the initiation of Sonic hedgehog expression and its maintenance through feedback regulation. Thus, some 5'Hoxd genes may be a pan of the regulatory network that positions and reinforces polarizing signals in the posterior-distal limb bud. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Mackem, S (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2A33, Bethesda, MD 20892 USA. NR 43 TC 13 Z9 13 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD APR PY 1999 VL 296 IS 1 BP 27 EP 31 DI 10.1007/s004410051263 PG 5 WC Cell Biology SC Cell Biology GA 188BN UT WOS:000079824500004 PM 10199962 ER PT J AU Xu, XL Weinstein, M Li, CL Deng, CX AF Xu, XL Weinstein, M Li, CL Deng, CX TI Fibroblast growth factor receptors (FGFRs) and their roles in limb development SO CELL AND TISSUE RESEARCH LA English DT Review DE FGF-FGF receptors; limb initiation; progress zone activity; hand and foot anomalies ID IMMUNOGLOBULIN-LIKE DOMAIN; APICAL ECTODERMAL RIDGE; VERTEBRATE LIMB; SONIC-HEDGEHOG; NERVOUS-SYSTEM; TARGETED DISRUPTION; PATTERNING ACTIVITY; CROUZON SYNDROME; GENE-EXPRESSION; SUGGESTS ROLES AB Fibroblast growth factor (FGF) receptors constitute a family of four membrane-spanning tyrosine kinases (FGFR1-4) which serve as high-affinity receptors for 17 growth factors (FGF1-17). To study functions of FGF/FGFR signals in development, mice that carry mutations in each receptor have been created by gene targeting. Analysis of these mutant mice revealed essential functions of FGF receptors in multiple biological processes, including mesoderm induction and patterning, cell growth and migration, organ formation and bone growth. In this review we discuss recent work with FGF receptors to illustrate mechanisms. through which the FGF/FGFR signals specify vertebrate limb initiation, outgrowth and patterning. C1 NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Deng, CX (reprint author), NIDDKD, Genet Dev & Dis Branch, NIH, 10-9N105,10 Ctr Dr, Bethesda, MD 20892 USA. RI deng, chuxia/N-6713-2016 NR 102 TC 111 Z9 114 U1 0 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD APR PY 1999 VL 296 IS 1 BP 33 EP 43 DI 10.1007/s004410051264 PG 11 WC Cell Biology SC Cell Biology GA 188BN UT WOS:000079824500005 PM 10199963 ER PT J AU Rakkar, ANS Katayose, Y Kim, M Craig, C Ohri, E Li, ZQ Cowan, KH Seth, P AF Rakkar, ANS Katayose, Y Kim, M Craig, C Ohri, E Li, ZQ Cowan, KH Seth, P TI A novel adenoviral vector expressing human Fas/CD95/APO-1 enhances p53-mediated apoptosis SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE adenovirus; Fas/CD95/APO-1; p53; apoptosis; gene therapy ID TUMOR-NECROSIS-FACTOR; WILD-TYPE P53; CELL-CYCLE; RECEPTOR SUPERFAMILY; DEATH; CD95; GROWTH; CANCER; FAS; ASSOCIATION AB Recent evidence suggests an intriguing link between p53 and the Fas pathway. To evaluate this association further, we utilized a recombinant adenoviral vector (AdWTp53) to overexpress wild-type p53 in lung cancer (A549, H23, EKVX and HOP92) and breast cancer(MDA-MB-231 and MCF-7) cell lines and observed an increase in the Fas/CD95/APO-1 protein levels. Furthermore, this increase correlated with the sensitivity of the cell lines to p53-mediated cytotoxicity, To examine the effects of Fas over-expression in cells resistant to p53 over-expression, we constructed AdFas, an adenoviral vector capable of transferring functional human Fas to cancer cells. Interestingly, infection of p53 resistant MCF-7 cells with AdFas sensitized them to p53-mediated apoptosis, These studies indicate that combined over-expression of Fas and wild-type p53 may be an effective cancer gene therapy approach, especially in cells relatively resistant to p53 overexpression. C1 NCI, Med Breast Canc Sect, Med Branch, Div Clin Sci,NIH, Bethesda, MD 20892 USA. RP Seth, P (reprint author), NCI, Med Breast Canc Sect, Med Branch, Div Clin Sci,NIH, Bldg 10 Rm 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM pseth@box-p.nih.gov NR 28 TC 20 Z9 20 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD APR PY 1999 VL 6 IS 4 BP 326 EP 333 DI 10.1038/sj.cdd.4400498 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 185EL UT WOS:000079655100003 PM 10381625 ER PT J AU Nicol, R Zheng, G Sutrave, P Foster, DN Stavnezer, E AF Nicol, R Zheng, G Sutrave, P Foster, DN Stavnezer, E TI Association of specific DNA binding and transcriptional repression with the transforming and myogenic activities of c-Ski SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID RETINOIC ACID RECEPTOR; ZINC-FINGER PROTEIN; V-SKI; THYROID-HORMONE; SKELETAL-MUSCLE; RETROVIRUS VECTORS; CDNA CLONES; ONCOGENE; DOMAIN; GENE AB The ski oncogene encodes a transcription factor that induces both transformation and muscle differentiation in avian fibroblasts. The first 304 amino acids of chicken Ski, the transformation domain, are both necessary and sufficient to mediate these biological activities. Ski's biological duality is mirrored by its transcriptional activities: it coactivates or corepresses transcription depending on its interactions with other transcription factors. Ski represses transcription through specific binding to GTCTAGAC (GTCT element) but it possesses a transferable repression activity that can function independently of this DNA element. In this study, we locate this repression domain to the NH2-terminal two-thirds and the GTCT binding region to the COOH-terminal one-third of Ski's transformation domain. Mutations in the transformation domain of c-Ski reveal a strong correlation between GTCT-mediated transcriptional repression and the biological activities of transformation and myogenesis. We also show that a dimerization domain located at the COOH terminal end of the Ski protein increases its transforming activity and its binding to GTCTAGAC. C1 Case Western Reserve Univ, Dept Biochem, Cleveland, OH 44106 USA. Univ Cincinnati, Coll Med, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Univ Minnesota, Dept Anim Sci, St Paul, MN 55108 USA. RP 10900 Euclid Ave, Cleveland, OH 44106 USA. EM exs44@po.cwru.edu FU NCI NIH HHS [CA-43600] NR 56 TC 16 Z9 16 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD APR PY 1999 VL 10 IS 4 BP 243 EP 254 PG 12 WC Cell Biology SC Cell Biology GA 189HY UT WOS:000079900100004 PM 10319994 ER PT J AU Pennie, WD Hegamyer, GA Young, MR Colburn, NH AF Pennie, WD Hegamyer, GA Young, MR Colburn, NH TI Specific methylation events contribute to the transcriptional repression of the mouse tissue inhibitor of metalloproteinases-3 gene in neoplastic cells SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID TUMOR-SUPPRESSOR GENE; DNA METHYLATION; IN-VIVO; INDUCED TRANSFORMATION; MOLECULAR-CLONING; EPIDERMAL-CELLS; BINDING-SITES; MESSENGER-RNA; PROMOTER; EXPRESSION AB The tissue inhibitor of metalloproteinases-3 (TIMP-3) gene is specifically down-regulated in neoplastic cells of the mouse JB6 progression model, suggesting a role for TIMP-3 inactivation in neoplastic progression. On the basis of 5-azacytidine reversal, the mechanism for this down-regulation appears to involve changes in the methylation state of the TIMP-3 promoter. Although total genomic methylation levels are comparable, specific differences in the methylation of the TIMP-3 promoter were observed between preneoplastic and neoplastic JB6 cells at three HpaII sites, with preneoplastic cells being less methylated. Expression of antisense methyltransferase in a neoplastic JB6 variant known to be hypermethylated in TIMP-3 resulted in reactivation of the endogenous TIMP-3 gene and restoration of hypomethylated status to the three implicated HpaII sites. Thus, hypermethylation at specific sequences in the TIMP-3 promoter appears to contribute to the silencing of the gene in neoplastic cells. C1 NCI, Gene Regulat Sect, Lab Biochem Physiol, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Colburn, NH (reprint author), NCI, Gene Regulat Sect, Lab Biochem Physiol, Frederick Canc Res & Dev Ctr, POB B,Bldg 560, Frederick, MD 21702 USA. NR 42 TC 19 Z9 19 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 APR PY 1999 VL 10 IS 4 BP 279 EP 286 PG 8 WC Cell Biology SC Cell Biology GA 189HY UT WOS:000079900100008 PM 10319998 ER PT J AU Heemskerk, FMJ Zorad, S Xu, NZ Gutkind, SJ Saavedra, JM AF Heemskerk, FMJ Zorad, S Xu, NZ Gutkind, SJ Saavedra, JM TI Characterization of AT(2) receptor expression in NIH 3T3 fibroblasts SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Article DE AT(2) receptor; growth curve; cell-cell contact; angiotensin converting enzyme; NIH3T3 fibroblasts; neoplastic transformation ID ANGIOTENSIN-CONVERTING ENZYME; II TYPE-2 RECEPTOR; AT2 BINDING-SITES; LIGAND-BINDING; CELL-GROWTH; R3T3 CELLS; SUBTYPES; CLONING; IDENTIFICATION; TRANSFORMATION AB 1. A high expression of angiotensin II receptors and of angiotensin-converting enzyme (ACE) activity was detected in confluent NIH 3T3 fibroblasts. 2. Characterization with selective ligands, dithiothreitol, and GTP gamma S, indicated that only the AT(2) subtype was expressed. 3. AT(2) receptors and ACE expression were strictly dependent on the cell density and growth phase of the cells, with AT(2) receptors being expressed earlier than ACE. In contrast, high expression of AT(2) receptors irrespective of their growth state was observed in NIH 3T3 cells lacking contact inhibition upon neoplastic transformation with ras. 4. Our results imply a possible relation of AT(2) receptors to cell growth and cell-cell contact. C1 NIMH, Pharmacol Sect, Bethesda, MD 20892 USA. NIDR, Cellular Dev & Oncol Lab, Bethesda, MD 20892 USA. RP Saavedra, JM (reprint author), NIMH, Pharmacol Sect, 10 Ctr Dr,Bldg 10-2D57, Bethesda, MD 20892 USA. EM Saavedrj@irp.nimh.nih.gov RI Gutkind, J. Silvio/A-1053-2009 NR 38 TC 7 Z9 7 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0272-4340 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD APR PY 1999 VL 19 IS 2 BP 277 EP 288 DI 10.1023/A:1006985329240 PG 12 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA 169CT UT WOS:000078730500008 PM 10081610 ER PT J AU Beauchamp, MS Haxby, JV Jennings, JE DeYoe, EA AF Beauchamp, MS Haxby, JV Jennings, JE DeYoe, EA TI An fMRI version of the Farnsworth-Munsell 100-Hue test reveals multiple color-selective areas in human ventral occipitotemporal cortex SO CEREBRAL CORTEX LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; HUMAN VISUAL-CORTEX; CEREBRAL-ACHROMATOPSIA; FUNCTIONAL-ANATOMY; ATTENTION; DISCRIMINATION; SENSITIVITY; TOPOGRAPHY; PERCEPTION; PATHWAY AB Studies of patients with cerebral achromatopsia have suggested that ventral occipitotemporal cortex is important for color perception. We created a functional magnetic resonance imaging (fMRI) version of a clinical test commonly used to assess achromatopsia, the Farnsworth-Munsell 100-Hue test. The test required normal subjects to use color information in the visual stimulus to perform a color sequencing task. A modification of the test requiring ordering by luminance was used as a control task. Subjects were also imaged as they passively viewed colored stimuli. A limited number of areas responded more to chromatic than achromatic stimulation, including primary visual cortex. Most color-selective activity was concentrated in ventral occipitotemporal cortex. Several areas in ventral cortex were identified. The most posterior, located in posterior fusiform gyrus, corresponded to the area activated by passive viewing of colored stimuli. More anterior and medial color-selective areas were located in the collateral sulcus and fusiform gyrus. These more anterior areas were not identified in previous imaging studies which used passive viewing of colored stimuli, and were most active in our study when visual color information was behaviorally relevant, suggesting that attention influences activity in color-selective areas, The fMRI version of the Farnsworth-Munsell test may be useful in the study of achromatopsia. C1 NIMH, Sect Funct Brain Imaging, Lab Brain & Cognit, Bethesda, MD 20892 USA. Med Coll Wisconsin, Dept Cellular Biol & Anat, Milwaukee, WI 53226 USA. RP Beauchamp, MS (reprint author), NIMH, Sect Funct Brain Imaging, Lab Brain & Cognit, 10 Ctr Dr,MSC 1366,Bldg 10,Room 4C104, Bethesda, MD 20892 USA. FU NEI NIH HHS [EY-10244]; NIMH NIH HHS [MH-51358] NR 35 TC 123 Z9 129 U1 0 U2 10 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 APR-MAY PY 1999 VL 9 IS 3 BP 257 EP 263 DI 10.1093/cercor/9.3.257 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 195MP UT WOS:000080255100007 PM 10355906 ER PT J AU Szeliga, J Amin, S Zhang, FJ Harvey, RG AF Szeliga, J Amin, S Zhang, FJ Harvey, RG TI Reactions of dihydrodiol epoxides of 5-methylchrysene and 5,6-dimethylchrysene with DNA and deoxyribonucleotides SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID COVALENT NUCLEOSIDE ADDUCTS; REGION 3,4-DIOL 1,2-EPOXIDES; DIOL-EPOXIDE; 11,12-DIHYDRODIOL 13,14-EPOXIDE; 1,2-DIHYDRODIOL 3,4-EPOXIDES; CHEMICAL CARCINOGENESIS; CYTOSINE BASES; MOUSE SKIN; BINDING; IDENTIFICATION AB Both syn and anti dihydrodiol epoxides from 5-methylchrysene (5-MCDE) and 5,6-dimethylchrysene (5,6-DMCDE) were reacted under the same conditions with native DNA, denatured DNA, and purine deoxyribonucleotides, and the products were quantified. The extents of reaction with the deoxyribonucleotides were consistently greater for 5,6-DMCDE than for 5-MCDE. The yield of adducts in the reaction with DNA ranged from being a few-fold to 50-fold greater than those found in the corresponding deoxyribonucleotide reactions for both 6-MCDE and 5,6-DMCDE. The DNA-dependent enhancement of product yield was greater for 5-MCDE than for 5,6-DMCDE with a few exceptions among cis and trans deoxyadenosine adducts. The most substantial differences in DNA-dependent enhancement were found for deoxyguanosine adducts; thus, steric hindrance between the B-methyl group in the 5,6-DMCDE and the minor groove in the DNA double helix may account for the greater DNA-dependent enhancement found in the 5-MCDE reactions. C1 NCI, Chem Carcinogenesis Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Amer Hlth Fdn, Naylor Dana Inst Dis Prevent, Valhalla, NY 10595 USA. Univ Chicago, Ben May Inst Canc Res, Chicago, IL 60637 USA. RP Szeliga, J (reprint author), NCI, Chem Carcinogenesis Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. FU NCI NIH HHS [CA-17613, CA 67937] NR 28 TC 9 Z9 10 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD APR PY 1999 VL 12 IS 4 BP 347 EP 352 DI 10.1021/tx980228o PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 188KQ UT WOS:000079845900008 PM 10207124 ER PT J AU Sekiya, F Bae, YS Rhee, SG AF Sekiya, F Bae, YS Rhee, SG TI Regulation of phospholipase C isozymes: activation of phospholipase C-gamma in the absence of tyrosine-phosphorylation SO CHEMISTRY AND PHYSICS OF LIPIDS LA English DT Article; Proceedings Paper CT Internation Symposium on PI Signaling CY AUG 27-30, 1998 CL SENDAI, JAPAN SP Minist Educ, Sci & Culture Japan, Sankyo Life Sci Res Promot Fdn Tokyo, Asaoka Eye Clinic Fdn Hammamatsu, Nishijima Neurosurgery Clinic ID HUMAN GENE AHNAK; PLECKSTRIN HOMOLOGY DOMAIN; EPIDERMAL GROWTH-FACTOR; ADP-RIBOSYLATION FACTOR; HIGH-AFFINITY; PLASMA-MEMBRANE; BETA-GAMMA; PROTEIN; C-GAMMA-1; TAU AB Activation of PLC-gamma isozymes in response to various agonists involves tyrosine phosphorylation of the effector enzymes. Recent evidence indicates that PLC-gamma isozymes are additionally activated by phosphatidic acid, phosphatidylinositol 3,4,5-trisphosphate and arachidonic acid in the absence of PLC-gamma tyrosine phosphorylation. These lipid-derived messengers are the immediate products of phospholipase D, phosphatidylinositol 3-kinase, and phospholipase A(2), enzymes which are often stimulated along with PLC-gamma in response to an agonist. Furthermore, phosphatidylinositol 4,5-bisphosphate acts as a substrate for both PLC-gamma and phosphatidylinositol 3-kinase and as an activator for phospholipase D and phospholipase A(2). These results reveal an elaborate mechanism of cross-talk and mutual regulation between four effector enzymes that participate in receptor signaling by acting on phospholipids. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. RP Sekiya, F (reprint author), NHLBI, Lab Cell Signaling, NIH, Bldg 3,Room 122,3 Ctr Dr MSC 0320, Bethesda, MD 20892 USA. NR 41 TC 53 Z9 54 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0009-3084 J9 CHEM PHYS LIPIDS JI Chem. Phys. Lipids PD APR PY 1999 VL 98 IS 1-2 BP 3 EP 11 DI 10.1016/S0009-3084(99)00013-4 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 217TM UT WOS:000081515100002 PM 10358923 ER PT J AU Chu, SC Horiba, K Usuki, J Avila, NA Chen, CC Travis, WD Ferrand, VJ Moss, J AF Chu, SC Horiba, K Usuki, J Avila, NA Chen, CC Travis, WD Ferrand, VJ Moss, J TI Comprehensive evaluation of 35 patients with lymphangioleiomyomatosis SO CHEST LA English DT Article DE angiomyolipoma; bronchoalveolar lavage; lymphangioleiomyomatosis; pneumothorax; smooth muscle cell proliferation ID PULMONARY LYMPHANGIOLEIOMYOMATOSIS; TUBEROUS SCLEROSIS; RENAL ANGIOMYOLIPOMA; LUNG; LYMPHANGIOMYOMATOSIS; MANAGEMENT; DIAGNOSIS; DISEASE; LAVAGE AB Objectives: To evaluate comprehensively the characteristics of lymphangioleiomyomatosis (LAM), with emphasis on the application of imaging and immunohistochemical methods. Design: Prospective study. Patients: Thirty-five female subjects with LAM, Setting: Clinical Center, National Institutes of Health. Interventions: BAL, pulmonary function test, ventilation/perfusion lung scans, CT of the chest and abdomen, ultrasonography of abdomen, and immunohistochemical study of lung biopsy specimens. Results: Most patients had exertional dyspnea (83%) and pneumothorax (69%). BAL did not show diagnostic changes. The most common abnormalities on pulmonary function tests were decreased diffusing capacity of carbon monoxide (83%), hypoxemia (57%), and airway obstruction (51%), Bronchodilator response was found in 26% of patients. CT, which is almost pathognomonic, showed numerous thin-walled cysts throughout both lungs in all patients, Thirty-four patients (97%) had abnormal ventilation and/or perfusion lung scans. An unusual "speckling" pattern was observed on ventilation scans of 74% of patients. Common extrapulmonary features were retroperitoneal adenopathy (77%) and renal angiomyolipomas (60%). The percentage of abnormal smooth muscle cells (LAM cells), reactive with HMB45, varied from 17 to 67% in 10 lung biopsy specimens. Conclusions: Improved diagnostic methods have defined the abnormalities in patients with pulmonary LAM and increased the potential for early recognition and treatment of this disorder. Patients with LAM should be evaluated for bronchodilator responsiveness and may benefit from a trial of bronchodilators. C1 NHLBI, Natl Inst Hlth, Pulm Crit Care Med Branch, Bethesda, MD 20892 USA. NHLBI, Natl Inst Hlth, Pathol Sect, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. RP Moss, J (reprint author), NHLBI, Natl Inst Hlth, Pulm Crit Care Med Branch, Bldg 10,Room 6D03,10 Ctr Dr,MSC 1590, Bethesda, MD 20892 USA. NR 36 TC 176 Z9 192 U1 0 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 APR PY 1999 VL 115 IS 4 BP 1041 EP 1052 DI 10.1378/chest.115.4.1041 PG 12 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 185EV UT WOS:000079655900027 PM 10208206 ER PT J AU Eisenhofer, G Coughtrie, MWH Goldstein, DS AF Eisenhofer, G Coughtrie, MWH Goldstein, DS TI Dopamine sulphate: An enigma resolved SO CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY LA English DT Article; Proceedings Paper CT 7th International Conference on Peripheral Dopamine CY AUG 03-05, 1998 CL DUBLIN, IRELAND DE catecholamines; dopamine; gastrointestinal tract; liver; phenolsulphotransferase ID PLATELET PHENOLSULFOTRANSFERASE ACTIVITY; LIVER PHENOL SULFOTRANSFERASE; CONGESTIVE-HEART-FAILURE; CONJUGATED CATECHOLAMINES; ESTROGEN SULFOTRANSFERASE; PARKINSONS-DISEASE; PLASMA-FREE; HUMAN-BRAIN; DEHYDROEPIANDROSTERONE SULFOTRANSFERASE; SULFOCONJUGATED CATECHOLAMINES AB 1. The source and physiological significance of dopamine (DA) sulphate, which exists in plasma at much higher concentrations than free DA, have long been a puzzle. The present article reviews how the convergence of modern molecular and traditional clinical approaches is shedding new light on the origins and meaning of DA sulphate, 2. The sulphotransferase isoenzyme responsible for production of DA sulphate in humans (SULT1A3) has been cloned and shown to be expressed in large quantities in the gastrointestinal tract, but not in liver. No orthologue of SULT1A3 has yet been identified in other species, consistent with the greater importance of sulphate conjugation of DA in humans than in most animals. 3. Diet has a major impact on plasma DA sulphate, with dramatic increases after ingestion of meals and foods rich in bioi genic amines; however, substantial amounts of DA sulphate remaining after prolonged fasting indicate the presence of a mainly endogenous source. The lack of influence of acute or chronic changes in sympathetic outflow or of sympathoneural degeneration on plasma DA sulphate indicates that DA sulphate does not derive from sympathetic nerve. Relatively low rates of production from intravenously infused DA indicate that very little DA sulphate (< 2%) derives from metabolism of circulating DA, such as in red cells or platelets. 4. Consistent increments in DA sulphate from arterial to the outflowing venous plasma draining mesenteric organs, without increments across other organs or tissues (e.g. heart, lungs, liver), indicate that the gastrointestinal tract is a major source of more than 75% of DA sulphate produced in the body. The gastro intestinal tract is also the site of a novel DA autocrine/paracrine system that produces nearly 50% of the DA in the body. Therefore, production of DA sulphate appears to reflect an enzymatic 'gut-blood' barrier for detoxifying dietary biogenic amines and delimiting autocrine/paracrine effects of endogenous DA generated in a novel 'third catecholamine system'. C1 NINCDS, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. Univ Dundee, Ninewells Hosp & Med Sch, Dept Mol & Cellular Pathol, Dundee, Scotland. RP Eisenhofer, G (reprint author), NINCDS, Clin Neurosci Branch, NIH, Bldg 10,Room 6N252,10 Ctr Dr MSC 1620, Bethesda, MD 20892 USA. RI Coughtrie, Michael/C-3855-2009 OI Coughtrie, Michael/0000-0003-1989-1416 NR 117 TC 66 Z9 68 U1 1 U2 9 PU BLACKWELL SCIENCE ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 0305-1870 J9 CLIN EXP PHARMACOL P JI Clin. Exp. Pharmacol. Physiol. PD APR PY 1999 VL 26 SU S BP S41 EP S53 PG 13 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA 197FR UT WOS:000080355000008 PM 10386253 ER PT J AU Mezey, E Eisenhofer, G Hansson, S Harta, G Hoffman, BJ Gallatz, K Palkovits, M Hunyady, B AF Mezey, E Eisenhofer, G Hansson, S Harta, G Hoffman, BJ Gallatz, K Palkovits, M Hunyady, B TI Non-neuronal dopamine in the gastrointestinal system SO CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY LA English DT Article; Proceedings Paper CT 7th International Conference on Peripheral Dopamine CY AUG 03-05, 1998 CL DUBLIN, IRELAND DE chemical sympathectomy; gastrointestinal system; mucosal protection; non-neuronal dopamine ID MUCOSAL BLOOD-FLOW; VESICULAR MONOAMINE TRANSPORTER; GASTRIC-ACID SECRETION; DIFFERENTIAL EXPRESSION; BICARBONATE SECRETION; PANCREATIC-SECRETION; MOLECULAR-CLONING; PORCINE JEJUNUM; NERVOUS-SYSTEM; RAT AB 1. Dopamine CDA) is a protective agent in the gastrointestinal (Gn tract in both rats and humans, Therefore, we have studied the site of DA production in rat and human GI tract using a variety of techniques, including immunocytochemistry (ICC), in situ hybridization histochemistry, reverse transcription-polymerase chain reaction, HPLC, western blotting and immunoelectron microscopy, 2. We found very high concentrations of DA that persisted after chemical sympathectomy (CS) in the gastric juice, the stomach mucosa and in the pancreas. Both the stomach mucosa and the pancreas also had tyrosine hydroxylase (TN) activity, most of which remained after CS, Double-labelling ICC showed that acid-producing parietal cells and the exocrine pancreas must also be capable of producing DA, 3. We isolated rat stomach parietal cells by cell fractionation and found that both DA and TN activity are present in isolated (denervated) parietal cells, These cells also have other features of aminergic cells: they are immuno- (and mRNA) positive for the DA plasma membrane transporter and vesicular monoamine transporter(s), In both gastric and duodenal mucosa, we demonstrated the presence of significant amounts of the D5 receptor that could serve as a target for locally produced DA, 4. Because DA, its biosynthetic enzymes and ifs transporters are also found in parietal cells in the human stomach, a mucosal protective system involving DA could be important clinically. C1 NINDS, Basic Neurosci Program, Bethesda, MD 20892 USA. NINDS, Clin Neurosci Branch, Bethesda, MD 20892 USA. NIMH, Lab Cellular & Mol Regulat, Bethesda, MD USA. Semmelweis Univ Med, Neuromorphol Lab, H-1085 Budapest, Hungary. RP Mezey, E (reprint author), NINDS, Basic Neurosci Program, Bldg 36,M3D10, Bethesda, MD 20892 USA. RI Palkovits, Miklos/F-2707-2013 NR 89 TC 27 Z9 29 U1 1 U2 2 PU BLACKWELL SCIENCE ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 0305-1870 J9 CLIN EXP PHARMACOL P JI Clin. Exp. Pharmacol. Physiol. PD APR PY 1999 VL 26 SU S BP S14 EP S22 PG 9 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA 197FR UT WOS:000080355000004 PM 10386249 ER PT J AU Seibel, NL Blaney, SM O'Brien, M Krailo, M Hutchinson, R Mosher, RB Balis, FM Gregory, H AF Seibel, NL Blaney, SM O'Brien, M Krailo, M Hutchinson, R Mosher, RB Balis, FM Gregory, H TI Phase I trial of docetaxel with filgrastim support in pediatric patients with refractory solid tumors: A collaborative Pediatric Oncology Branch, National Cancer Institute and Children's Cancer Group trial SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; INTRAVENOUS-INFUSION; TAXOTERE RP-56976; CLINICAL-TRIAL; CHEMOTHERAPY; NSC-628503 AB Neutropenia is the dose-limiting toxicity of docetaxel in children. This Phase I trial was designed to determine the maximum tolerated dose, the dose-limiting toxicities, and the incidence and severity of other toxicities of docetaxel with filgrastim (G-CSF) support in children with refractory solid tumors. Docetaxel was administered as an i.v, infusion for 1 h every 21 days with a starting dose of 150 mg/m(2) and an escalation to 185 mg/m(2) and 235 mg/m(2) in subsequent patient cohorts. G-CSF (5 mu g/kg/day) was administered s.c., starting 48 h after docetaxel and continuing until the postnadir neutrophil count reached 10,000/mu l. Seventeen patients received 27 courses of docetaxel with G-CSF support. Generalized erythematous desquamating skin rash and myalgias were dose-limiting at 235 mg/m(2). Localized and generalized rashes were seen at all of the three dose levels. Neutropenia (median nadir, 95/mu l) occurred at all of the dose levels but was brief in duration and not dose-limiting. Thrombocytopenia was minimal (median platelet count nadir, 139,000/mu l), and the severity of neutropenia and thrombocytopenia did not seem to be related to the docetaxel dose. Other docetaxel-related toxicities included hemorrhage (associated with mucositis), sepsis, hypersensitivity reaction, transient elevation of liver enzymes, stomatitis, back pain, asthenia, and neuropathy, One minor response was observed in a patient with colon cancer. The maximum tolerated dose of docetaxel with G-CSF support in children is 185 mg/m(2), which is 50% higher than the maximum tolerated dose of docetaxel alone in children and 85% higher than the recommended adult dose. C1 Childrens Natl Med Ctr, Dept Hematol Oncol, Washington, DC 20010 USA. George Washington Univ, Sch Med, Dept Pediat, Washington, DC 20010 USA. Texas Childrens Canc Ctr, Houston, TX 77030 USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. Univ So Calif, Dept Prevent Med, Los Angeles, CA 90033 USA. Univ Michigan, Dept Pediat Hematol Oncol, Ann Arbor, MI 48109 USA. RP Seibel, NL (reprint author), Childrens Canc Grp, POB 60012, Arcadia, CA 91066 USA. FU NCI NIH HHS [U10CA57746] NR 20 TC 37 Z9 37 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 APR PY 1999 VL 5 IS 4 BP 733 EP 737 PG 5 WC Oncology SC Oncology GA 185QD UT WOS:000079680300003 PM 10213206 ER PT J AU Huijgen, HJ Sanders, R Cecco, SA Rehak, NN Sanders, GT Elin, RJ AF Huijgen, HJ Sanders, R Cecco, SA Rehak, NN Sanders, GT Elin, RJ TI Serum ionized magnesium: Comparison of results obtained with three ion-selective analyzers SO CLINICAL CHEMISTRY AND LABORATORY MEDICINE LA English DT Article DE magnesium; ion-selective electrodes; comparison study; reference values ID NOVA MAGNESIUM; WHOLE-BLOOD; ELECTRODE; CALCIUM; STABILITY; PLASMA; ISES; AVL AB In a two-center (Academic Medical Center, The Netherlands, and National Institutes of Health, USA) study, we compared ionized magnesium (iMg(2+)) results in serum determined with the AVL 988/4, KONE Microlyte 6 and NOVA CRT, which are the currently available analyzers equipped with a magnesium ion-selective electrode. The comparison was performed with frozen serum samples from normal individuals and patients. Imprecision and reference intervals were established. We found the best agreement between the KONE(x) and AVL(y) magnesium ion-selective electrodes (y = 0.972x-0.013; n = 138) with samples from patients. With samples from normals, all three analyzers reported significantly different results (p < 0.05). Best precision was found using the NOVA; coefficients of variation established at three levels were all <4.0%. Coefficients of variation for the AVL and KONE were <5% at normal and high iMg(2+), but 10.7 and 9.4%, respectively, at iMg(2+) approximate to 0.30 mmol/l. The reference intervals (mean +/- standard deviation) based on measurements in fresh serum samples were different for each analyzer: 0.55-0.63 mmol/l for AVL, 0.470.57 mmol/l for KONE and 0.43-0.55 mmol/l for NOVA. Thus, significant differences among the ionized magnesium concentration obtained with the three analyzers, limit comparison of results in clinical practice, and need to be resolved (e.g. by improvement of specificity and standardization of calibrators). C1 Univ Amsterdam, Acad Med Ctr, Dept Clin Chem, NL-1105 AZ Amsterdam, Netherlands. NIH, Clin Chem Serv, Dept Clin Pathol, Bethesda, MD 20892 USA. RP Huijgen, HJ (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Clin Chem F1 217, POB 22700, NL-1100 DE Amsterdam, Netherlands. NR 23 TC 29 Z9 29 U1 0 U2 1 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1434-6621 J9 CLIN CHEM LAB MED JI Clin. Chem. Lab. Med. PD APR PY 1999 VL 37 IS 4 BP 465 EP 470 DI 10.1515/CCLM.1999.075 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 212MM UT WOS:000081220500013 PM 10369119 ER PT J AU Gan, XH Zhang, L Berger, O Stins, MF Way, D Taub, DD Chang, SL Kim, KS House, SD Weinand, M Witte, M Graves, MC Fiala, M AF Gan, XH Zhang, L Berger, O Stins, MF Way, D Taub, DD Chang, SL Kim, KS House, SD Weinand, M Witte, M Graves, MC Fiala, M TI Cocaine enhances brain endothelial adhesion molecules and leukocyte migration SO CLINICAL IMMUNOLOGY LA English DT Article DE cocaine; endothelial cells; blood-brain barrier; monocytes; ICAM-1; vasculopathy ID TUMOR-NECROSIS-FACTOR; TNF-ALPHA; IN-VITRO; EXPRESSION; ICAM-1; CELLS; VASCULITIS; MODULATION; MONOCYTES; DISTINCT AB Leukocyte infiltration of cerebral vessels in cocaine-associated vasculopathy suggests that cocaine may enhance leukocyte migration. We have investigated cocaine's effects on leukocyte adhesion in human brain microvascular endothelial cell (BMVEC) cultures and monocyte migration in an in vitro blood-brain barrier (BBB) model constructed with BMVEC and astrocytes. Cocaine (10(-5) to 10(-9) M) enhanced adhesion of monocytes and neutrophils to BMVEC. In the BBB model, cocaine (10(-4) to 10(-8) M) enhanced monocyte transmigration. Cocaine increased expression of endothelial adhesion molecules, intercellular adhesion molecule-1 (ICAI-1, CD54), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-l (ELAM-1) on BMVEC. The peak effect on ICAM-1 expression was between 6 and 18 h after treatment. ICAM-1 was increased by cocaine in BMVEC, but not in human umbilical vein endothelial cells, and the enhancement was greater in a coculture of BMVEC with monocytes. ICAM-1 expression was enhanced by a transcriptional mechanism. Polymyxin B inhibited up-regulation of adhesion molecules by LPS but not by cocaine. In LPS-activated BMVEC/monocyte coculture, cocaine increased secretion of-tumor necrosis factor-alpha and interIeukin-6. Taken together, these findings indicate that cocaine enhances leukocyte migration across the cerebral vessel wall, in particular under inflammatory conditions, but the effects are variable in different individuals. Cocaine's effects are exerted through a cascade of augmented expression of inflammatory cytokines and endothelial adhesion molecules. These could underlie the cerebrovascular complications of cocaine abuse, (C) 1999 Academic Press. C1 Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Microbiol & Immunol, Los Angeles, CA 90095 USA. Seton Hall Univ, Dept Biol, S Orange, NJ 07079 USA. NIA, Immunol Lab, Baltimore, MD 21224 USA. Childrens Hosp, Div Infect Dis, Los Angeles, CA 90027 USA. Univ Arizona, Dept Surg, Tucson, AZ 85724 USA. RP Gan, XH (reprint author), Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. FU NIDA NIH HHS [DA 07058, DA 10442]; NINDS NIH HHS [NS 36126] NR 29 TC 74 Z9 76 U1 0 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD APR PY 1999 VL 91 IS 1 BP 68 EP 76 DI 10.1006/clim.1998.4683 PG 9 WC Immunology SC Immunology GA 184KR UT WOS:000079611800009 PM 10219256 ER PT J AU Domachowske, JB Rosenberg, HF AF Domachowske, JB Rosenberg, HF TI Respiratory syncytial virus infection: Immune response, immunopathogenesis, and treatment SO CLINICAL MICROBIOLOGY REVIEWS LA English DT Review ID AEROSOLIZED IMMUNOGLOBULIN TREATMENT; HUMAN-IMMUNODEFICIENCY-VIRUS; EOSINOPHIL CATIONIC PROTEIN; CELL-MEDIATED-IMMUNITY; SUBUNIT VACCINE PFP-2; REPLICATION IN-VITRO; CYTOTOXIC T-CELLS; RSV F-PROTEIN; ANTIVIRAL ACTIVITY; COTTON RATS AB Respiratory syncytial virus (RSV) is the single most important cause of lower respiratory tract infection during infancy and early childhood. Once RSV infection is established, the host immune response includes the production of virus-neutralizing antibodies and T-cell-specific immunity. The humoral immune response normally results in the development of anti-RSV neutralizing-antibody titers, but these are often suboptimal during art infant's initial infection. Even when the production of RSV neutralizing antibody following RSV infection is robust, humoral immunity wanes over time. Reinfection during subsequent seasons is common. The cellular immune response to RSV infection is also important for the clearance of virus. This immune response, vital for host defense against RSV is also implicated in the immunopathogenesis of severe lower respiratory tract RSV bronchiolitis. Many details of the immunology and immunopathologic mechanisms of RSV disease known at present have been learned from rodent models of RSV disease and are discussed in some detail. In addition, the roles of immunoglobulin E, histamine, and eosinophils in the immunopathogenesis of RSV disease are considered. Although the treatment of RSV bronchiolitis is primarily supportive, the role of ribavirin is briefly discussed. Novel approaches to the development of new antiviral drugs with promising anti-RSV activity in vitro are also described. C1 SUNY Hlth Sci Ctr, Dept Pediat, Syracuse, NY 13210 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Domachowske, JB (reprint author), SUNY Hlth Sci Ctr, Dept Pediat, 750 E Adams St, Syracuse, NY 13210 USA. EM domachoj@vax.cs.bscsyr.edu NR 193 TC 109 Z9 123 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0893-8512 J9 CLIN MICROBIOL REV JI Clin. Microbiol. Rev. PD APR PY 1999 VL 12 IS 2 BP 298 EP + PG 13 WC Microbiology SC Microbiology GA 186DU UT WOS:000079712600007 PM 10194461 ER PT J AU Boroojerdi, B Foltys, H Krings, T Spetzger, U Thron, A Topper, R AF Boroojerdi, B Foltys, H Krings, T Spetzger, U Thron, A Topper, R TI Localization of the motor hand area using transcranial magnetic stimulation and functional magnetic resonance imaging SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE transcranial magnetic stimulation; functional magnetic resonance imaging; hand knob; motorcortex mapping ID LIMB AMPUTATION; HUMAN BRAIN; CORTEX; REORGANIZATION; REPRESENTATION; NEUROSURGERY; FRAMELESS; PATHWAYS AB Objective: The anatomical location of the motor area of the hand may be revealed using functional magnetic resonance imaging (fMRI). The motor cortex representation of the intrinsic hand muscles consists of a knob-like structure. This is omega- or epsilon-shaped in the axial plane and hook-shaped in the sagittal plane. As this knob lies on the surface of the brain, it can be stimulated non-invasively by transcranial magnetic stimulation (TMS). It was the aim of our study to identify the hand knob using fMRI and to reveal if the anatomical hand knob corresponds to the hand area of the motor cortex, as identified by TMS, by means of a frameless MRI-based neuronavigation system. Methods: Suprathreshold transcranial magnetic stimuli were applied over a grid on the left side of the scalp of 4 healthy volunteers. The motor evoked potentials (MEPs) were recorded from the contralateral small hand muscles, and the centers of gravity (CoG) of the MEPs were calculated. The exact anatomical localization of each point on the grid was determined using a frameless MRI-based neuronavigation system. In each subject, the hand area of the motor cortex was visualized using fMRI during sensorimotor activation achieved by clenching the right hand. Results: In all 4 subjects, the activated precentral site in the fMRI and the CoG of the MEP of all investigated muscles lay within the predicted anatomical area, the so-called hand knob. This knob had the form of an omega in two subjects and an epsilon in the other two subjects. Conclusions: TMS is a reliable method for mapping the motor cortex. The CoG calculated from the motor output maps may be used as an accurate estimation of the location of the represented muscle in the motor cortex. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Rhein Westfal TH Aachen, Univ Hosp, Dept Neurol, D-5100 Aachen, Germany. Rhein Westfal TH Aachen, Univ Hosp, Dept Neuroradiol, D-5100 Aachen, Germany. Rhein Westfal TH Aachen, Univ Hosp, Dept Neurosurg, D-5100 Aachen, Germany. NINDS, Human Cort Physiol Unit, NIH, Bethesda, MD 20892 USA. RP Topper, R (reprint author), Rhein Westfal TH Aachen, Univ Hosp, Dept Neurol, D-5100 Aachen, Germany. NR 35 TC 123 Z9 123 U1 0 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD APR PY 1999 VL 110 IS 4 BP 699 EP 704 DI 10.1016/S1388-2457(98)00027-3 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 197YT UT WOS:000080394800016 PM 10378741 ER PT J AU Shepherd, AMM Atkinson, AJ AF Shepherd, AMM Atkinson, AJ TI Report from the American Board of Clinical Pharmacology SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID INC C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Div Clin Pharmacol, Dept Med, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Div Clin Pharmacol, Dept Pharmacol, San Antonio, TX USA. RP Atkinson, AJ (reprint author), NIH, Ctr Clin, Bldg 10,Room 1C-227,10 Ctr Dr, Bethesda, MD 20892 USA. NR 4 TC 4 Z9 5 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD APR PY 1999 VL 65 IS 4 BP 355 EP 356 DI 10.1016/S0009-9236(99)70127-X PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 190AZ UT WOS:000079940500001 PM 10223770 ER PT J AU Wittes, J Lakatos, E Black, D Geraci, B Davis, B Moye, L Probstfield, J AF Wittes, J Lakatos, E Black, D Geraci, B Davis, B Moye, L Probstfield, J TI Selecting screening criteria for clinical trials: An example from the systolic hypertension in the elderly program SO CONTROLLED CLINICAL TRIALS LA English DT Article DE screening rules; recruitment; blood pressure; isolated systolic hypertension; clinical trials ID BLOOD-PRESSURE; SHEP AB In clinical trials that study people with a continuous measure defined categorically, even repeated measurements within a visit and over successive visits do not prevent error-free classification. We describe the design of a screening procedure for the Systolic Hypertension in the Elderly Program (SHEP), a randomized clinical trial designed to test whether regular administration of antihypertensive medication reduces the risk of stroke in elderly persons with isolated systolic hypertension. Data from a pilot study performed before the inauguration of SHEP allowed empirical study of a variety df possible screening rules for SHEP. A desirable screening rule would require only two screening visits, would lead to a randomized cohort with high mean systolic blood pressure, and would not impede recruitment. We emphasize two classes of rules, "serial" and "conditional." A serial rule uses only the values observed at a given screen to determine eligibility to proceed to the next screen. A conditional rule uses the value observed at a given screen along with values already observed to determine eligibility to proceed. For the SHEP study, we chose a conditional rule for screening because of its efficiency in identifying eligible participants. Our approach to selection of screening rules should be applicable to other clinical trials in which the measurement that defines the primary entry criterion has considerable measurement error. Controlled Clin Trials 1999; 20:121-132 (C) Elsevier Science Inc. 1999. C1 Stat Collaborat Inc, Washington, DC 20036 USA. Forest Labs, New York, NY USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NHLBI, Bethesda, MD 20892 USA. Univ Texas, Sch Publ Hlth, Houston, TX USA. Univ Washington, Sch Med, Seattle, WA USA. Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. RP Wittes, J (reprint author), Stat Collaborat Inc, 1710 Rhode Isl Ave NW,Suite 200, Washington, DC 20036 USA. NR 18 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD APR PY 1999 VL 20 IS 2 BP 121 EP 132 DI 10.1016/S0197-2456(98)00047-6 PG 12 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 183MY UT WOS:000079558400001 PM 10227413 ER PT J AU Cosgrove, N Borhani, NO Bailey, G Borhani, P Levin, J Hoffmeier, M Krieger, S Lovato, LC Petrovitch, H Vogt, T Wilson, AC Breeson, V Probstfield, JL AF Cosgrove, N Borhani, NO Bailey, G Borhani, P Levin, J Hoffmeier, M Krieger, S Lovato, LC Petrovitch, H Vogt, T Wilson, AC Breeson, V Probstfield, JL CA Systol Hypertens Elderly Program Cooperat Res G TI Mass mailing and staff experience in a total recruitment program for a clinical trial: The SHEP experience SO CONTROLLED CLINICAL TRIALS LA English DT Article DE accrual aged; comparative studies; mass mailing; multicenter studies; randomized controlled trials; recruitment; overall recruitment plan ID LUNG HEALTH; PARTICIPANTS; STRATEGIES; EFFICACY; HYPERTENSION; CAROTENE; CARET AB The Systolic Hypertension in the Elderly Program (SHEP) staff contacted 447,921 screenees, of whom 11,919 (2.7%) were originally eligible and 4,736 (1.1%) maintained eligibility and were randomized. The total number of participants enrolled at the 16 clinical centers ranged from 133 to 559. The low yield of screenees to randomizations resulted from the study design, not from low levels of agreement to participate, and required the employment of a variety of recruitment strategies in a prudent overall plan. SHEP was one of the first clinical trials to use mass mailing as a primary strategy of recruitment. The study used mailing lists from seven generic sources. More than 3.4 million letters of invitation were mailed; they yielded an overall response rate of 4.3%. Motor vehicle and voter registration lists provided the greatest numbers of names. Mailings to members of health maintenance organizations (HMOs) and registrants of the Health Care Finance Administration (HCFA) provided the greatest response rates. Considerable variability in response rates existed among clinical centers using generically similar mailing lists. Generally, the number of hours spent on recruitment showed a positive, but not statistically significant, association with randomization yields. The recruitment yield was statistically significantly higher in clinics with experienced recruitment coordinators than in clinics with inexperienced ones (p = 0.0008). From these findings we conclude that mass mailing is an important strategy in an overall recruitment program, that the involvement of experienced recruitment staff is important, and that although the total time spent by staff on recruitment may also improve results, it matters less than the staff's level of recruiting experience. Controlled Clin Trials 1999;20:133-148. (C) Elsevier Science Inc. 1999. C1 Univ Calif Davis, Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Davis, CA USA. Pacific Presbyterian Med Ctr, Med Res Inst San Francisco, San Francisco, CA 94115 USA. Univ Minnesota, Minneapolis, MN 55455 USA. John A Burns Sch Med, Honolulu, HI USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. NHLBI, CTB, DECA, Bethesda, MD 20892 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. RP Probstfield, JL (reprint author), 1100 Fairview Ave N,MP 525, Seattle, WA 98109 USA. FU NHLBI NIH HHS [N0-HC-48052, N0-HC-48053, N0-HC-48054] NR 35 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD APR PY 1999 VL 20 IS 2 BP 133 EP 148 DI 10.1016/S0197-2456(98)00055-5 PG 16 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 183MY UT WOS:000079558400002 PM 10227414 ER PT J AU Secchi, EF Lizak, MJ Sato, S Kador, PF AF Secchi, EF Lizak, MJ Sato, S Kador, PF TI 3-fluoro-3-deoxy-D-galactose: A new probe for studies on sugar cataract SO CURRENT EYE RESEARCH LA English DT Article DE aldose reductase; dog; lens; polyol pathway; 3-fluoro-3-deoxy-D-galactose; F-19 NMR ID ALDOSE REDUCTASE INHIBITOR; LENS EPITHELIAL-CELLS; F-19 NMR; SORBITOL DEHYDROGENASE; 3-FDG NMR; METABOLISM; PREVENTION; RATS; 3-DEOXY-3-FLUORO-D-GLUCOSE; 2-DEOXY-2-FLUORO-D-GLUCOSE AB Purpose. Aldose reductase (AR) activity and flux through the polyol pathway can conveniently be monitored in dog lenses by measuring the metabolism of 3-fluoro-3-deoxy-D-glucose by F-19 nuclear magnetic resonance (NMR) spectroscopy. Since AR has broad substrate specificity and preferentially utilizes galactose over glucose as substrate, the ability of AR to utilize 3-fluoro-3-deoxy-D-galactose (3-FDGal) as substrate as well as the metabolism of 3-FDGal in intact dog lens and cultured lens epithelial cells has been investigated. Methods. The suitableness of 3FDGal as a substrate was examined by incubating 3FDGal with purified dog lens aldose reductase in the presence of an NADPH generating system or with galactitol dehydrogenase in the presence of NAD(+). Dog lenses and dog lens epithelial cells were cultured in 3-FDGal medium with and without the AR inhibitor AL 1576. Metabolism was studied using F-19 NMR. Results. AR activity with 3-FDGal as substrate is higher than that with D-galactose and its Km of 4.2 mM is ca 10-fold higher than that of D-galactose. Purified dog lens AR incubated with 3-FDGal resulted in the formation of 3-fluoro-3 -deoxy-D-galactitol. Galactitol formation was prevented by the addition of AL 1576. Incubation of 3-FDGal with galactitol dehydrogenase resulted in the formation of 3-fluoro-3-deoxy-D-galactonic acid. Dog lenses cultured in 3-FDGal medium formed NMR peaks corresponding to 3-fluoro-3-deoxy-D-galactitol and 3-fluoro-3-deoxy-D-galactonic acid. The presence of AL 1576 inhibited the formation of galactitol but not galactonic acid. Lens epithelial cells cultured in 3-FDGal medium formed only 3-fluoro-3-deoxy-D-galactitol. These cells developed multiple cytoplasmic vacuoles which was prevented by the aldose reductase inhibitor AL 1576. Conclusions. The high affinity of this fluorinated sugar for aldose reductase makes this an excellent probe for investigating aldose reductase activity in dog lens tissues. C1 NEI, Lab Ocular Therapeut, NIH, Bethesda, MD 20892 USA. RP Lizak, MJ (reprint author), NEI, Lab Ocular Therapeut, NIH, 10-10B11,10 Ctr Dr,MSC 1850, Bethesda, MD 20892 USA. NR 24 TC 5 Z9 5 U1 1 U2 5 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. PD APR PY 1999 VL 18 IS 4 BP 277 EP 282 PG 6 WC Ophthalmology SC Ophthalmology GA 194HL UT WOS:000080186400005 PM 10372987 ER PT J AU Adams, CR Kamakaka, RT AF Adams, CR Kamakaka, RT TI Chromatin assembly: biochemical identities and genetic redundancy SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Review ID NEWLY SYNTHESIZED HISTONES; DNA-REPLICATION INVITRO; XENOPUS-LAEVIS OOCYTES; FACTOR-I; SACCHAROMYCES-CEREVISIAE; YEAST; DROSOPHILA; H4; PROTEIN; COMPLEXES AB Investigations on chromatin assembly in vitro implicate chromatin assembly factor 1 (CAF1) as a chaperone for histones H3/H4 and nucleosome assembly protein 1 (NAP1) as a chaperone for histones H2A/H2B, Deletion analysis of CAF1 in vivo suggests multiple redundant pathways for deposition of the histones. Histone deposition requires acetylation of the amino-terminal tails and analysis of mutants suggests a specific but redundant role for acetylation of the tails in assembly. Furthermore, studies on the HAT1 acetyltransferase raise the possibility that acetylation of histones occurs following their transport into the nucleus but prior to their deposition onto DNA. Identification of the factors involved in the redundant pathways of assembly is awaited. C1 NICHHD, Unit Chromatin & Transcript, Bethesda, MD 20892 USA. RP Kamakaka, RT (reprint author), NICHHD, Unit Chromatin & Transcript, Bldg 18T,Room 106,18 Lib Dr, Bethesda, MD 20892 USA. EM Rohinton@helix.nih.gov NR 45 TC 84 Z9 88 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD APR PY 1999 VL 9 IS 2 BP 185 EP 190 DI 10.1016/S0959-437X(99)80028-8 PG 6 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 184CK UT WOS:000079591600010 PM 10322140 ER PT J AU Bell, AC Felsenfeld, G AF Bell, AC Felsenfeld, G TI Stopped at the border: boundaries and insulators SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Review ID ENHANCER-PROMOTER INTERACTIONS; CHROMATIN DOMAIN BOUNDARY; WING MARGIN ENHANCER; DROSOPHILA-MELANOGASTER; BITHORAX COMPLEX; CHROMOSOMAL DOMAINS; BLOCKING ACTIVITY; SU(HW) INSULATOR; GENE; ELEMENT AB Boundaries in chromatin are often marked by the presence of insulator elements. New results in Drosophila have identified an insulator with a proven boundary function essential for development. Other studies suggest a connection between the activity of some insulators and Drosophila tritihorax-Group and Polycomb-Group genes. Several examples of vertebrate insulators have now been found; their locations suggest important boundary functions. Enhancer-blocking studies in oocytes and position-effect studies in transformed cells shed new light on insulator mechanisms. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Bell, AC (reprint author), NIDDKD, Mol Biol Lab, NIH, Bldg 5,Room 212,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 49 TC 178 Z9 179 U1 0 U2 7 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD APR PY 1999 VL 9 IS 2 BP 191 EP 198 DI 10.1016/S0959-437X(99)80029-X PG 8 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 184CK UT WOS:000079591600011 PM 10322134 ER PT J AU Nemazee, D Fowlkes, BJ AF Nemazee, D Fowlkes, BJ TI Lymphocyte development - Overview SO CURRENT OPINION IN IMMUNOLOGY LA English DT Editorial Material C1 Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. NIAID, Cellular & Mol Immunol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Nemazee, D (reprint author), Scripps Res Inst, Dept Immunol, 10550 N Torrey Pines Rd,IMM-29, La Jolla, CA 92037 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD APR PY 1999 VL 11 IS 2 BP 127 EP 128 DI 10.1016/S0952-7915(99)80022-3 PG 2 WC Immunology SC Immunology GA 183ZL UT WOS:000079584800001 ER PT J AU Pinilla, C Martin, R Gran, B Appel, JR Boggiano, C Wilson, DB Houghten, RA AF Pinilla, C Martin, R Gran, B Appel, JR Boggiano, C Wilson, DB Houghten, RA TI Exploring immunological specificity using synthetic peptide combinatorial libraries SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID T-CELL RECEPTOR; HIV-1 MONOCLONAL-ANTIBODY; AMINO-ACID; ANTIGENIC DETERMINANT; CROSS-REACTIVITY; IDENTIFICATION; BINDING; COMPLEX; RECOGNITION; EPITOPES AB The definition of epitopes for human B and T cells is fundamental for the understanding of the immune response mechanism and its role in the prevention and cause of human disease. This understanding can be applied to the design of diagnostics and synthetic vaccines. In recent years, the understanding of the specificity of B and T cells has been advanced significantly by the development and use of combinatorial libraries made up of thousands to millions of synthetic peptides. The use of this approach has had four major effects: first, the definition of high affinity ligands both for T cells and antibodies; second, the application of alternative means for identifying immunologically relevant peptides for use as potential preventive and therapeutic vacc nes; third, a new appreciation of the requirements for TCR interactions with peptide-MHC complexes in immunogenicity; fourth, the establishment of new principles regarding the level of cross-reactivity in immunological recognition. C1 Torrey Pines Inst Mol Studies, San Diego, CA 92121 USA. NINDS, Cellular Immunol Sect, Neuroimmunol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Houghten, RA (reprint author), Torrey Pines Inst Mol Studies, 3550 Gen Atom Court, San Diego, CA 92121 USA. RI Gran, Bruno/A-2288-2013 OI Gran, Bruno/0000-0001-6384-2342 NR 65 TC 80 Z9 82 U1 1 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD APR PY 1999 VL 11 IS 2 BP 193 EP 202 DI 10.1016/S0952-7915(99)80033-8 PG 10 WC Immunology SC Immunology GA 183ZL UT WOS:000079584800012 PM 10322159 ER PT J AU Gottesman, S AF Gottesman, S TI Regulation by proteolysis: developmental switches SO CURRENT OPINION IN MICROBIOLOGY LA English DT Review ID ATP-DEPENDENT PROTEASE; N-END RULE; ESCHERICHIA-COLI MRSC; BACTERIAL-CELL-CYCLE; MESSENGER-RNA DECAY; HEAT-SHOCK PROTEIN; BACILLUS-SUBTILIS; CLP PROTEASE; LON PROTEASE; IN-VIVO AB The energy-dependent proteases originally defined in Escherichia coli have proven to have particularly important roles in bacterial developmental systems, including sporulation in Bacillus subtilis and cell cycle in Caulobacter. Degradation of key regulatory proteins participates, with regulation of synthesis and activity of the regulators, to ensure tight control and, where required, irreversible commitment of the cell to specific developmental pathways. C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. RP Gottesman, S (reprint author), NCI, Mol Biol Lab, Bldg 37,Room 2E18, Bethesda, MD 20892 USA. EM susang@helix.nih.gov NR 76 TC 85 Z9 89 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5274 J9 CURR OPIN MICROBIOL JI Curr. Opin. Microbiol. PD APR PY 1999 VL 2 IS 2 BP 142 EP 147 DI 10.1016/S1369-5274(99)80025-3 PG 6 WC Microbiology SC Microbiology GA 182YY UT WOS:000079526800005 PM 10322171 ER PT J AU Storz, G Imlay, JA AF Storz, G Imlay, JA TI Oxidative stress SO CURRENT OPINION IN MICROBIOLOGY LA English DT Review ID ESCHERICHIA-COLI K-12; MULTIPLE-ANTIBIOTIC-RESISTANCE; ORGANIC-SOLVENT TOLERANCE; FE-S CLUSTER; NITRIC-OXIDE; TRANSCRIPTION FACTOR; HYDROGEN-PEROXIDE; IN-VIVO; DNA-DAMAGE; SUPEROXIDE-DISMUTASE AB Much has been learnt about oxidative stress from studies of Escherichia coli. Key regulators of the adaptive responses in this organism are the SoxRS and OxyR transcription factors, which induce the expression of antioxidant activities in response to O-2.(-) and H2O2 stress, respectively Recently, a variety of biochemical assays together, with the characterization of strains carrying mutations affecting the antioxidant activities and the regulators have given general Insights into the sources of oxidative stress, the damage caused by oxidative stress, defenses against the oxidative stress, and the mechanisms by which the stress is perceived. These studies have also shown that the oxidative stress responses are intimately coupled to other regulatory networks in the cell. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Univ Illinois, Dept Microbiol, Urbana, IL 61801 USA. RP Storz, G (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. OI Storz, Gisela/0000-0001-6698-1241 FU NIGMS NIH HHS [GM49640] NR 70 TC 702 Z9 739 U1 6 U2 67 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5274 J9 CURR OPIN MICROBIOL JI Curr. Opin. Microbiol. PD APR PY 1999 VL 2 IS 2 BP 188 EP 194 DI 10.1016/S1369-5274(99)80033-2 PG 7 WC Microbiology SC Microbiology GA 182YY UT WOS:000079526800013 PM 10322176 ER PT J AU Hinshaw, JE AF Hinshaw, JE TI Dynamin spirals SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Review ID CLATHRIN-MEDIATED ENDOCYTOSIS; COATED VESICLE FORMATION; PLECKSTRIN HOMOLOGY DOMAINS; BINDING-SITE; MECHANOCHEMICAL ENZYME; ACIDIC PHOSPHOLIPIDS; TRANSPORT VESICLES; CRYSTAL-STRUCTURE; NERVE-TERMINALS; PLASMA-MEMBRANE AB Dynamin is an important component of membrane recycling at the plasma membrane and, potentially, within the cell. The role of dynamin in clathrin-mediated endocytosis has been based on numerous endocytosis assays, as well as on the discovery and gross characterization of the assembled spiral structure of dynamin. Recently it has been shown that dynamin can also bind to liposomes and form helical tubes that constrict and vesiculate upon GTP addition. This suggests that dynamin is capable of and may be responsible for the pinching off of clathrin-coated vesicles from the plasma membrane during clathrin-mediated endocytosis. C1 NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. RP Hinshaw, JE (reprint author), NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. NR 64 TC 22 Z9 22 U1 1 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD APR PY 1999 VL 9 IS 2 BP 260 EP 267 DI 10.1016/S0959-440X(99)80036-0 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 282LP UT WOS:000085219800016 PM 10322220 ER PT J AU Shin, HCK Benbernou, N Esnault, S Guenounou, M AF Shin, HCK Benbernou, N Esnault, S Guenounou, M TI Expression of IL-17 in human memory CD45RO(+) T lymphocytes and its regulation by protein kinase A pathway SO CYTOKINE LA English DT Article DE IL-17; cAMP; CD45RO; CD45RA; T lymphocytes ID INTERFERON-GAMMA PRODUCTION; LYMPHOKINE GENE-EXPRESSION; HUMAN PERIPHERAL-BLOOD; MESSENGER-RNA; CELL SUBSETS; DIFFERENTIAL REGULATION; INTERLEUKIN (IL)-4; HELPER CELLS; IFN-GAMMA; COSTIMULATORY SIGNALS AB In the present study, the authors compared the interleukin 17 (IL-17 expression of human naive and phenotypically defined memory T cells as well as its regulation by cAMP pathway. Our data showed that IL-17 mRNA was highly expressed in memory human peripheral CD8(+) 45RO(+) T cells and CD4(+) 45RO(+) T cells when peripheral blood mononuclear cells were first stimulated with ionomycin/PMA. IL-17 expression in memory CD8(+) T cells required accessory signals since culture of ionomycin/PMA-activated CD8(+) 45RO(+) T cells alone did not result to IL-17 expression. In contrast, memory CD4(+) T cell population seems to be more independent. IL-17 and interferon gamma (IFN-gamma) mRNA were both inhibited in the presence of PGE(2) or the cAMP analogue (dibutyryl-cAMP), while the anti-inflammatory cytokine IL-10 was highly increased, In contrast, naive CD45RA(+) T cells mere unable to express IL-17 whatever the culture conditions, Naive CD4(+) and CD8(+) T cells were sensitive to the PKA regulatory pathway since they represent a significant source of IL-10 when PBMC were first cultured with ionomycin/PMA in the presence of either PGE(2) or db-cAMP. The authors showed that naive cells are highly dependent to their microenvironment, since culture of ionomycin/PMA-activated CD45RA(+) T cells alone did not result in detectable levels of cytokines even in the presence of PGE(2). Results also showed that PGE(2) induced quite the same levels of intracellular cAMP in naive and memory cells suggesting that these cell populations are equally sensitive to PGE,, However, we suggest that PGE(2) may be more efficient in blocking both IL-17 and IFN-gamma expression in already primed memory T cells, rather than in suppressing naive T cells that could represent a significant source of IL-10. Data suggest that PKA activation pathway plays a critical role in the regulation of cytokine profiles and consequently the functional properties of both human naive and memory CD4(+) acid CD8(+) T cells during the immune and inflammatory processes. (C) 1999 Academic Press. C1 Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53792 USA. Fac Pharm Reims, Immunol Lab, F-51096 Reims, France. RP Benbernou, N (reprint author), NCI, Mol Immunoregulat Lab, NIH, Frederick Canc Res & Dev Ctr, Bldg 560,Room 31-56, Frederick, MD 21702 USA. NR 65 TC 112 Z9 117 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 1043-4666 J9 CYTOKINE JI Cytokine PD APR PY 1999 VL 11 IS 4 BP 257 EP 266 DI 10.1006/cyto.1998.0433 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 192VV UT WOS:000080101000002 PM 10328864 ER PT J AU Di Vinci, A Infusini, E Peveri, C Sciutto, A Orecchia, R Geido, E Monaco, R Giaretti, W AF Di Vinci, A Infusini, E Peveri, C Sciutto, A Orecchia, R Geido, E Monaco, R Giaretti, W TI Intratumor heterogeneity of chromosome 1, 7, 17, and 18 aneusomies obtained by FISH and association with flow cytometric DNA index in human colorectal adenocarcinomas SO CYTOMETRY LA English DT Article DE colorectal carcinomas; interphase FISH; numerical chromosome aberrations; 1p deletions; DNA flow cytometry ID IN-SITU HYBRIDIZATION; K-RAS2 MUTATIONS; P53 MUTATIONS; CANCER; TUMORIGENESIS; ADENOMAS; ANEUPLOIDY; DELETIONS; ABERRATION; EVOLUTION AB Background: The origin and evolution of somatic chromosome aberrations in colorectal cancer is still poorly understood. The data in the literature suggest that some specific chromosome aberrations are more common. It is not known, however, if there is a correlation of these with near-diploid and high aneuploidy previously proposed to be a characteristic of the adenoma-carcinoma sequence. Methods: Chromosome 1, 7, 17 and 18 numerical aberrations and Ip deletions were evaluated by fluorescence in situ hybridization analysis for 20 human sporadic colorectal adenocarcinomas in 70 distinct tumor sectors and correlated with flow cytometric DNA index (DI) values. Results: Aneusomy for at least one of the investigated chromosomes was observed in 60 of 70 tumor sectors corresponding to 19 of 20 adenocarcinomas (95%) Deletions at 1p, observed in 8 of 18 adenocarcinomas (44%), were intratumor homogeneous in 7 of 8 tumors. In contrast, the other aberrations were intratumor heterogeneous. Aneusomies of chromosomes 1, 7, and 17 were strongly associated with DNA high aneuploidy (DI greater than or equal to 1.4), whereas aneusomy of chromosome 18 and 1p deletions were equally common among DNA diploid and near-diploid tumors (DI < 1.4 and DI not equal 1). Conclusions: Overall, these data suggest the existence of different aneuploidization routes correlated with specific chromosome aberrations. In addition, intratumor homogeneity of Ip deletions appears to be an indication of early occurrence or strong selection. We also suggest that tumors with monosomies and in particular monosomies-trisomies for the same chromosomes support a model of aneuploidization and chromosome instability during the colorectal tumor progression based on loss of symmetry during chromosome segregation (Giaretti: Lab Invest 71:904-910, 1994). (C) 1999 Wiley-Liss, Inc. C1 Natl Canc Inst, Lab Biophys Cytometry, I-16132 Genoa, Italy. Cardarelli Hosp, Pathol Serv, Naples, Italy. RP Giaretti, W (reprint author), Natl Canc Inst, Lab Biophys Cytometry, Largo Rosanna Benzi 10, I-16132 Genoa, Italy. NR 30 TC 13 Z9 13 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 0196-4763 J9 CYTOMETRY JI Cytometry PD APR 1 PY 1999 VL 35 IS 4 BP 369 EP 375 PG 7 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 183GJ UT WOS:000079545600010 PM 10213203 ER PT J AU Acampora, D Avantaggiato, V Tuorto, F Barone, P Perera, M Choo, D Wu, D Corte, G Simeone, A AF Acampora, D Avantaggiato, V Tuorto, F Barone, P Perera, M Choo, D Wu, D Corte, G Simeone, A TI Differential transcriptional control as the major molecular event in generating Otx1-/- and Otx2-/- divergent phenotypes SO DEVELOPMENT LA English DT Article DE Otx1; Otx2; transcriptional control; cortex; inner ear; evolution; mouse ID DROSOPHILA HEAD DEVELOPMENT; ROSTRAL BRAIN; MOUSE OTX2; ANTERIOR NEUROECTODERM; ORTHODENTICLE GENE; CEREBRAL-CORTEX; NERVOUS-SYSTEM; HOMEOBOX GENE; INNER-EAR; EXPRESSION AB Otx1 and Otx2, two murine homologs of the Drosophila orthodenticle (otd) gene, show a limited amino acid sequence divergence, Their embryonic expression patterns overlap in spatial and temporal profiles with two major exceptions: until 8 days post coitum (d,p,c.) only Otx2 is expressed in gastrulating embryos, and from 11 d.p,c, onwards only Otx1 is transcribed within the dorsal telencephalon. Otx1 null mice exhibit spontaneous epileptic seizures and multiple abnormalities affecting primarily the dorsal telencephalic cortex and components of the acoustic and visual sense organs. Otx2 null mice show heavy gastrulation abnormalities and lack the rostral neuroectoderm corresponding to the forebrain, midbrain and rostral hindbrain, In order to define whether these contrasting phenotypes reflect differences in expression pattern or coding sequence of Otx1 and Otx2 genes, we replaced Otx1 with a human Otx2 (hOtx2) full-coding cDNA, Interestingly, homozygous mutant mice (hOtx2(1)/hOtx2(1)) fully rescued epilepsy and corticogenesis abnormalities and showed a significant improvement of mesencephalon, cerebellum, eye and lachrymal gland defects, In contrast, the lateral semicircular canal of the inner ear was never recovered, strongly supporting an Otx1-specific requirement for the specification of this structure. These data indicate an extended functional homology between OTX1 and OTX2 proteins and provide evidence that, with the exception of the inner ear, in Otx1 and Otx2 null mice contrasting phenotypes stem from differences in expression patterns rather than in amino acid sequences. C1 CNR, Int Inst Genet & Biophys, I-80125 Naples, Italy. Univ Naples Federico II, Dept Neurol Sci, I-80131 Naples, Italy. Univ Genoa, Natl Inst Canc Res, CBA, Dipartimento Oncol Clin & Sperimentale, I-16132 Genoa, Italy. Natl Inst Deafness & Other Commun Disorders, Rockville, MD 20850 USA. RP Simeone, A (reprint author), CNR, Int Inst Genet & Biophys, Via G Marconi 12, I-80125 Naples, Italy. RI Acampora, Dario/C-2156-2013 FU Telethon [D.037] NR 39 TC 59 Z9 59 U1 0 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD APR PY 1999 VL 126 IS 7 BP 1417 EP 1426 PG 10 WC Developmental Biology SC Developmental Biology GA 188LJ UT WOS:000079848200007 PM 10068635 ER PT J AU Yang, X Castilla, LH Xu, XL Li, CL Gotay, J Weinstein, M Liu, PP Deng, CX AF Yang, X Castilla, LH Xu, XL Li, CL Gotay, J Weinstein, M Liu, PP Deng, CX TI Angiogenesis defects and mesenchymal apoptosis in mice lacking SMAD5 SO DEVELOPMENT LA English DT Article DE SMAD5; gene targeting; yolk sac; vasculogenesis; angiogenesis; mouse; apoptosis ID GROWTH-FACTOR-BETA; RECEPTOR TYROSINE KINASE; BLOOD-VESSEL FORMATION; TGF-BETA; TUMOR-SUPPRESSOR; SIGNALING PATHWAYS; MESODERM INDUCTION; EMBRYOS LACKING; MOUSE EMBRYO; MUTANT MICE AB The transforming growth factor-beta (TGF-beta) signals are mediated by a family of at least nine SMAD proteins, of which SMAD5 is thought to relay signals of the bone morphogenetic protein (BMP) pathway. To investigate the role of SMAD5 during vertebrate development and tumorigenesis, we disrupted the Smad5 gene by homologous recombination. We showed that Smad5 was expressed predominantly in mesenchyme and somites during embryogenesis, and in many tissues of the adult. Mice homozygous for the mutation died between days 10.5 and 11.5 of gestation due to defects in angiogenesis. The mutant yolk sacs lacked normal vasculature and had irregularly distributed blood cells, although they contained hematopoietic precursors capable of erythroid differentiation. Smad5 mutant embryos had enlarged blood vessels surrounded by decreased numbers of vascular smooth muscle cells, suffered massive apoptosis of mesenchymal cells, and were unable to direct angiogenesis in vitro. These data suggest that SMAD5 may regulate endothelium-mesenchyme interactions during angiogenesis and that it is essential for mesenchymal survival. C1 NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Deng, CX (reprint author), NIDDKD, Genet Dev & Dis Branch, NIH, 10-9N105, Bethesda, MD 20892 USA. RI Liu, Paul/A-7976-2012; deng, chuxia/N-6713-2016 OI Liu, Paul/0000-0002-6779-025X; NR 51 TC 282 Z9 297 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD APR PY 1999 VL 126 IS 8 BP 1571 EP 1580 PG 10 WC Developmental Biology SC Developmental Biology GA 192GP UT WOS:000080070400002 PM 10079220 ER PT J AU Hosokawa, Y Takahashi, Y Kadoya, Y Yamashina, S Nomizu, M Yamada, Y Nogawa, H AF Hosokawa, Y Takahashi, Y Kadoya, Y Yamashina, S Nomizu, M Yamada, Y Nogawa, H TI Significant role of laminin-1 in branching morphogenesis of mouse salivary epithelium cultured in basement membrane matrix SO DEVELOPMENT GROWTH & DIFFERENTIATION LA English DT Article DE branching morphogenesis; laminin-1; Matrigel; mesenchyme-free culture; mouse salivary gland ID EPIDERMAL GROWTH-FACTOR; TERMINAL GLOBULAR DOMAIN; SUBMANDIBULAR-GLAND; CELL-ADHESION; A-CHAIN; SYNTHETIC PEPTIDES; IN-VITRO; MONOCLONAL-ANTIBODIES; NEURITE OUTGROWTH; SUSTAINED GROWTH AB Mouse submandibular epithelium shows branching morphogenesis in mesenchyme-free conditions when covered with a basement membrane matrix (Matrigel) in medium supplemented with epidermal growth factor. In the present study, the role of laminin-1 (LN1), a major glycoprotein of Matrigel, in this culture system was defined. When the epithelium was cultured in a LN1-nidogen gel, the epithelium showed much branching, comparable to that observed with Matrigel. By electron microscopy, only a felt-like matrix was formed on the epithelial surface in the LN1-nidogen gel cultures, while an organized basal lamina structure was formed on the epithelial surface in direct or transfilter recombination cultures with mesenchyme. Next, the epithelium covered with Matrigel was cultured in medium containing either biologically active peptides from LN1, IKVAV-including peptide (2097-2108), AG10 (2183-2194), AG32 (2370-2381) or AG73 (2719-2730) from the alpha 1 chain, or YIGSR-including peptide (926-933) from the beta 1 chain. Only AG73 (RKRLQVQLSIRT from the alpha 1 chain carboxyl-terminal globular domain) inhibited the epithelial branching in Matrigel. These results suggest that LN1-nidogen can support the branching morphogenesis of submandibular epithelium even if LN1-nidogen is not assembled into an intact basal lamina, and that the AG73 sequence is an important site on LN1, which interacts with submandibular epithelial cells. C1 Chiba Univ, Fac Sci, Dept Biol, Inage Ku, Chiba 2638522, Japan. Teikyo Univ, Fac Pharmaceut Sci, Dept Microbiol & Mol Pathol, Sagamiko, Kanagawa 199, Japan. Kitasato Univ, Sch Med, Dept Anat, Sagamihara, Kanagawa 228, Japan. NIDR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Nogawa, H (reprint author), Chiba Univ, Fac Sci, Dept Biol, Inage Ku, Yayoi Cho, Chiba 2638522, Japan. RI Nogawa, Hiroyuki/D-7156-2014 OI Nogawa, Hiroyuki/0000-0003-3100-3936 NR 45 TC 35 Z9 35 U1 0 U2 1 PU BLACKWELL SCIENCE ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 0012-1592 J9 DEV GROWTH DIFFER JI Dev. Growth Diff. PD APR PY 1999 VL 41 IS 2 BP 207 EP 216 PG 10 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 223MG UT WOS:000081844400010 PM 10223717 ER PT J AU Sievers, ML Bennett, PH Nelson, RG AF Sievers, ML Bennett, PH Nelson, RG TI Effect of glycemia on mortality in Pima Indians with type 2 diabetes SO DIABETES LA English DT Article ID CORONARY HEART-DISEASE; RISK-FACTORS; CARDIOVASCULAR MORTALITY; POPULATION SAMPLES; INSULIN; NIDDM; MELLITUS; GLUCOSE; HYPERGLYCEMIA; ABNORMALITIES AB The effect of plasma glucose concentration on overall and cause-specific mortality was examined in 1,745 Pima Indians (725 men, 1,020 women) greater than or equal to 15 years old with type 2 diabetes. During a median follow-up of 10.6 years (range 0.1-24.8), 533 subjects (275 men, 258 women) died; 113 of the deaths were attributable to cardiovascular disease, 96 to diabetes-related diseases (diabetic nephropathy for 92 of these), 249 to other natural causes, and 75 to external causes. After adjusting for age, sex, duration of diabetes, and BMI in a generalized additive proportional hazards model, higher baseline 2-h postload plasma glucose concentration predicted deaths from cardiovascular disease (P = 0.007) and diabetes-related diseases (P = 0.003), but not from other natural causes (P = 0.73), An increment of 5.6 mmol/l (100 mg/dl) in the 2-h plasma glucose concentration was associated with 1.2 times (95% CI 1.1-1.4) the death rate from cardiovascular disease, 1.3 times (95% CI 1.1-1.5) the death rate from diabetes-related diseases, and almost no change in the death rate from other natural causes (rate ratio = 1.0; 95% CI 0.94-1.1), In Pima Indians with type 2 diabetes, higher plasma glucose concentration predicts deaths from cardiovascular and diabetes-related diseases but has little or no effect on deaths from other natural or external causes. C1 NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85014 USA. RP Nelson, RG (reprint author), NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. RI Nelson, Robert/B-1470-2012 NR 45 TC 21 Z9 21 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD APR PY 1999 VL 48 IS 4 BP 896 EP 902 DI 10.2337/diabetes.48.4.896 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 180UG UT WOS:000079403100029 PM 10102709 ER PT J AU Haffner, SM D'Agostino, R Mykkanen, L Tracy, R Howard, B Rewers, M Selby, J Savage, PJ Saad, MF AF Haffner, SM D'Agostino, R Mykkanen, L Tracy, R Howard, B Rewers, M Selby, J Savage, PJ Saad, MF TI Insulin sensitivity in subjects with type 2 diabetes - Relationship to cardiovascular risk factors: the Insulin Resistance Atherosclerosis Study SO DIABETES CARE LA English DT Article ID PLASMINOGEN-ACTIVATOR INHIBITOR-1; CORONARY-ARTERY DISEASE; GLUCOSE-TOLERANCE; ADIPOSE-TISSUE; CAROTID ATHEROSCLEROSIS; ESSENTIAL-HYPERTENSION; PLASMA-INSULIN; VISCERAL FAT; WOMEN; NIDDM AB OBJECTIVE - Among nondiabetic subjects, insulin resistance has been associated with increased cardiovascular risk factors, including dyslipidemia, hypertension, impaired fibrinolysis, and coagulation. Less is known about the relationship between insulin resistance and cardiovascular risk factors in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS - to examine this issue, we determined insulin sensitivity (S-1) in 479 type 2 diabetic subjects by minimal model analyses of frequently sampled intravenous glucose tolerance tests in the Insulin Resistance Atherosclerosis Study (IRAS), a large multicenter study of insulin sensitivity and cardiovascular disease in African-Americans, Hispanics, and non-Hispanic whites. We defined insulin-sensitive subjects as having S-1 greater than or equal to 1.61 X 10(-4) min(-1) . mu U-1 . ml(-1) (above median in nondiabetic subjects of all ethnic groups in the IRAS). Using this definition, only 37 type 2 diabetic subjects were insulin sensitive, and the remaining 442 were insulin resistant. RESULTS - After adjustment for age, sex, ethnicity and clinic, insulin resistance was significantly correlated with total triglycerides, VLDL cholesterol, VLDL triglyceride, fibrinogen, PAI-1, and fasting glucose, and was inversely correlated with HDL cholesterol level and LDL size. Carotid intimal-medial thickness was greater in insulin-resistant than in insulin-sensitive subjects, but this difference was nor statistically significant. After further adjustment for waist circumference (marker of visceral adiposity), insulin resistant subjects continued to have higher plasminogen activator inhibitor 1 and VLDL triglyceride levels, lower HDL cholesterol levels, and smaller LDL particle size than did insulin-sensitive subjects. After further adjustment for fasting glucose levels, these results were very similar. CONCLUSIONS - We conclude that insulin-resistant type 2 diabetic subjects have more atherogenic cardiovascular risk factor profiles than insulin-sensitive type 2 diabetic subjects and that this is only partially related to increased obesity and an adverse body fat distribution. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27103 USA. Univ Vermont, Sch Med, Dept Pathol, Burlington, VT 05405 USA. Medlant Res Inst, Penn Med Lab, Washington, DC USA. Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO 80262 USA. Kaiser Permanente, Div Res, Oakland, CA USA. Univ So Calif, Med Ctr, Div Diabet Hypertens & Nutr, Los Angeles, CA USA. NHLBI, Div Epidemiol & Clin Applicat, Rockville, MD USA. RP Haffner, SM (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. RI Dagostino Jr, Ralph/C-4060-2017 OI Dagostino Jr, Ralph/0000-0002-3550-8395 FU NHLBI NIH HHS [HL47887, HL47889, HL47890] NR 48 TC 193 Z9 218 U1 1 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD APR PY 1999 VL 22 IS 4 BP 562 EP 568 DI 10.2337/diacare.22.4.562 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 179GJ UT WOS:000079317900005 PM 10189532 ER PT J AU Bray, GA Culbert, IW Champagne, CM Dawson, L Eberhardt, B Greenway, FL Guillory, FG Hebert, AA Jeffirs, ML Kennedy, BM Lovejoy, JC Morris, LH Melancon, LE Reed, L Perault, J Ryan, DH Sanford, DA Smith, KG Smith, LL St Amant, JA Tulley, RT Vicknair, PC Williamson, D Zachwieja, JJ Polonsky, KS Matulik, MJ Clarke, B DeSandre, C Ehrmann, DA Hilbrich, RM McNabb, WL Morrone, D Semenske, AR Stepp, KA Tobian, JA Watson, PG Caro, JF Goldstein, BJ Graziani, CM Kunkel, EJ Laine, CA Louis, DZ Smith, KA Spandirfer, J Yuen, EJ Goldberg, RB Rowe, P Calles, J Donahue, RP Florez, HJ Giannella, A O'Hara, P Prineas, R Haffner, SM Montez, MG Miettinen, H Mobley, CM Mykkanen, LA Hamman, RF Nash, PV Calonge, BN Hill, JO Jortberg, BT Regensteiner, JG Reusch, J Schiltz, CM Seagle, H VanDorsten, B Horton, ES Lawton, KE Arky, RA Bryant, M Burke, JP Caballero, E Callaphan, KM Ganda, OP Franklin, T Jackson, SD Jacobsen, AM Kula, LM Kocal, M Malloy, MA Nicosia, M Oldmixon, CF Pan, J Quitingon, M Rubtchinsky, S Seely, EW Schweizer, D Simonson, D Smith, F Solomon, CG Warram, J Kahn, SE Montgomery, BK Berger, M Boyko, EJ Fujimoto, WY Greenbaum, CJ Knopp, RH McCann, BS Lipkin, EW Nguyen, TT Palmer, JP Schwartz, RS Talbot-Lawson, C Wan, D Kitabchi, AE Murphy, ME Applegate, WB Bryer-Ash, M Frieson, SL Imseis, R Kennedy, CL Lambeth, HC Lichtermann, LC Oktaei, H O'Toole, ML Rutledge, LMK Sherman, AR Smith, CM Soberman, JE Williams-Cleaves, BJ Metzger, BE Johnson, MK Fitzgibbon, M Heard, D Johnson, CKH McPherson, D Molitch, ME Moore, M Pitts, T Schinleber, PA Nathan, DM McKitrick, C Abbott, K Anderson, E Cagliero, E Cohen, M Crowell, S Delahanty, L Levina, E Michel, T O'Keefe, J Poulos, A Ronan, L Rosal, M Salerno, M Shagensky, C Steiner, B Young, A Olefsky, JM Carrion-Petersen, ML Barrett-Connor, E Beltran, M Caenepeel, K Edelman, SV Ford, RO Garcia, J Henry, RR Hill, M Horne, J Leos, D Mudaliar, S Pollard, A Torio, J Pi-Sunyer, FX Lee, JE Allison, DB Aronoff, NJ Barreras, IM Crandall, JP Foo, ST Orlando, SJ Parkes, K Rooney, ES Van Wye, GEH Viscovich, KA Prince, MJ Kukman, SM Dotson, YF Fineberg, ES Guare, JC Ignaut, JM Jackson, MA Kirkman, MS Marrero, DG Porter, DB Rowland, ND Wheeler, ML Ratner, RE Youssef, G Bronsord, M Cheatham, WW Boggs, G Evans, C Levatan, C Kellum, T Nair, AK Passaro, MD Saad, MF Khan, A Aziz, A Bernaba, B Budgett, MD Cosenza, C Hagar, JE Isagholian, K Jinagouda, SD Kamdar, VV Kumar, D Khawaja, Q Kelada, BL Lui, G Marston, AR Mehta, V Sharma, AR Szamos, K Vargas, A Vargas, B Zambrana, N Dagogo-Jack, S Santiago, AE Brendle, JS Fisher, EB Gherardini, DC Heins, JM Marsala, JM Raspberry, CC Santiago, JV Stephan, CL Saudek, CD Bradley, VL Brancati, FL Cappelli, S Charleston, JB Rubin, RR Stewart, KJ Sullivan, E Schade, DS Adams, KS Atler, LF Bowling, DA Boyle, PJ Burge, MR Canady, JL Chai, L Dorin, RI Facio, E Guillen, M Gutierrez, M Johannes, C Katz, P King, C McCalman, R Rassam, A Senter, W Waters, D Shamoon, H Brown, JO Cox, L Duffy, H Engel, S Friedler, A Howard-Century, CJ Longchamp, N Pompi, D Walker, EA Wylie-Rosett, J Zonszein, J Wing, RR Kramer, MK Barr, S Clifford, L Culyba, R Frazier, M Harris, L Harrier, S Henderson, W Jeffries, S Koenning, G Maholic, K Mullen, M Noel, A Orchard, T Smith, CF Smith, M Viteri, J Wilson, T Williams, KV Zgibor, J Arakaki, RF Latimer, RW Baker-Ladao, NK Beddow, RM Dias, LM Dupont, DA Fukuhara, LL Mau, MK Odom, SK Perry, RU Tokunaga, JS Knowler, WC Hoskin, MA Andre, VL Acton, KJ Antone, S Baptisto, NM Bennett, PH Bird, EC Dacawyma, TS Hanson, RL Jackson, MC Jay, PA Kobus, KM Roumain, J Rowse, DH Roy, RJ Yazzie, M Cooeyate, NJ Chavez, M Broussard, BA Ghahate, JM Hughte, G Ingraham, LE Kaskalla, RS Kessler, D Nashboo, Y Poirier, S Percy, CA Barber, R Benson, MB Duncan, R Glass, M Gohdes, D Grant, W Horse, E Morgan, T Reidy, M Bain, R Bambad, J Brenneman, T Dunegan, C Edelstein, SL Grimes, KL Jones, S Jones, TL Klepac, H Lachin, JM Mucik, P Orlosky, R Rochon, J Stimpson, CE Van Aerden, C Eastman, R Garfield, S Harris, M Andres, R Engelgau, M Narayan, V Williamson, D Herman, W Chandler, WL Marcovina, SM McMillan, T Rautaharju, PM Rautaharju, FSR Mayer-Davis, EJ O'Leary, DH Funk, LRC O'Leary, KA Scherzinger, AL Stamm, ER Gillis, BP Kriska, AM Huffmyer, C Meier, A Venditti, EM Wing, RR Haffner, SM Ratner, RE Olefsky, JM Santiago, JV Saudek, CD Knowler, WC Montez, MG Fujimoto, WY Hamman, RF Nathan, DM AF Bray, GA Culbert, IW Champagne, CM Dawson, L Eberhardt, B Greenway, FL Guillory, FG Hebert, AA Jeffirs, ML Kennedy, BM Lovejoy, JC Morris, LH Melancon, LE Reed, L Perault, J Ryan, DH Sanford, DA Smith, KG Smith, LL St Amant, JA Tulley, RT Vicknair, PC Williamson, D Zachwieja, JJ Polonsky, KS Matulik, MJ Clarke, B DeSandre, C Ehrmann, DA Hilbrich, RM McNabb, WL Morrone, D Semenske, AR Stepp, KA Tobian, JA Watson, PG Caro, JF Goldstein, BJ Graziani, CM Kunkel, EJ Laine, CA Louis, DZ Smith, KA Spandirfer, J Yuen, EJ Goldberg, RB Rowe, P Calles, J Donahue, RP Florez, HJ Giannella, A O'Hara, P Prineas, R Haffner, SM Montez, MG Miettinen, H Mobley, CM Mykkanen, LA Hamman, RF Nash, PV Calonge, BN Hill, JO Jortberg, BT Regensteiner, JG Reusch, J Schiltz, CM Seagle, H VanDorsten, B Horton, ES Lawton, KE Arky, RA Bryant, M Burke, JP Caballero, E Callaphan, KM Ganda, OP Franklin, T Jackson, SD Jacobsen, AM Kula, LM Kocal, M Malloy, MA Nicosia, M Oldmixon, CF Pan, J Quitingon, M Rubtchinsky, S Seely, EW Schweizer, D Simonson, D Smith, F Solomon, CG Warram, J Kahn, SE Montgomery, BK Berger, M Boyko, EJ Fujimoto, WY Greenbaum, CJ Knopp, RH McCann, BS Lipkin, EW Nguyen, TT Palmer, JP Schwartz, RS Talbot-Lawson, C Wan, D Kitabchi, AE Murphy, ME Applegate, WB Bryer-Ash, M Frieson, SL Imseis, R Kennedy, CL Lambeth, HC Lichtermann, LC Oktaei, H O'Toole, ML Rutledge, LMK Sherman, AR Smith, CM Soberman, JE Williams-Cleaves, BJ Metzger, BE Johnson, MK Fitzgibbon, M Heard, D Johnson, CKH McPherson, D Molitch, ME Moore, M Pitts, T Schinleber, PA Nathan, DM McKitrick, C Abbott, K Anderson, E Cagliero, E Cohen, M Crowell, S Delahanty, L Levina, E Michel, T O'Keefe, J Poulos, A Ronan, L Rosal, M Salerno, M Shagensky, C Steiner, B Young, A Olefsky, JM Carrion-Petersen, ML Barrett-Connor, E Beltran, M Caenepeel, K Edelman, SV Ford, RO Garcia, J Henry, RR Hill, M Horne, J Leos, D Mudaliar, S Pollard, A Torio, J Pi-Sunyer, FX Lee, JE Allison, DB Aronoff, NJ Barreras, IM Crandall, JP Foo, ST Orlando, SJ Parkes, K Rooney, ES Van Wye, GEH Viscovich, KA Prince, MJ Kukman, SM Dotson, YF Fineberg, ES Guare, JC Ignaut, JM Jackson, MA Kirkman, MS Marrero, DG Porter, DB Rowland, ND Wheeler, ML Ratner, RE Youssef, G Bronsord, M Cheatham, WW Boggs, G Evans, C Levatan, C Kellum, T Nair, AK Passaro, MD Saad, MF Khan, A Aziz, A Bernaba, B Budgett, MD Cosenza, C Hagar, JE Isagholian, K Jinagouda, SD Kamdar, VV Kumar, D Khawaja, Q Kelada, BL Lui, G Marston, AR Mehta, V Sharma, AR Szamos, K Vargas, A Vargas, B Zambrana, N Dagogo-Jack, S Santiago, AE Brendle, JS Fisher, EB Gherardini, DC Heins, JM Marsala, JM Raspberry, CC Santiago, JV Stephan, CL Saudek, CD Bradley, VL Brancati, FL Cappelli, S Charleston, JB Rubin, RR Stewart, KJ Sullivan, E Schade, DS Adams, KS Atler, LF Bowling, DA Boyle, PJ Burge, MR Canady, JL Chai, L Dorin, RI Facio, E Guillen, M Gutierrez, M Johannes, C Katz, P King, C McCalman, R Rassam, A Senter, W Waters, D Shamoon, H Brown, JO Cox, L Duffy, H Engel, S Friedler, A Howard-Century, CJ Longchamp, N Pompi, D Walker, EA Wylie-Rosett, J Zonszein, J Wing, RR Kramer, MK Barr, S Clifford, L Culyba, R Frazier, M Harris, L Harrier, S Henderson, W Jeffries, S Koenning, G Maholic, K Mullen, M Noel, A Orchard, T Smith, CF Smith, M Viteri, J Wilson, T Williams, KV Zgibor, J Arakaki, RF Latimer, RW Baker-Ladao, NK Beddow, RM Dias, LM Dupont, DA Fukuhara, LL Mau, MK Odom, SK Perry, RU Tokunaga, JS Knowler, WC Hoskin, MA Andre, VL Acton, KJ Antone, S Baptisto, NM Bennett, PH Bird, EC Dacawyma, TS Hanson, RL Jackson, MC Jay, PA Kobus, KM Roumain, J Rowse, DH Roy, RJ Yazzie, M Cooeyate, NJ Chavez, M Broussard, BA Ghahate, JM Hughte, G Ingraham, LE Kaskalla, RS Kessler, D Nashboo, Y Poirier, S Percy, CA Barber, R Benson, MB Duncan, R Glass, M Gohdes, D Grant, W Horse, E Morgan, T Reidy, M Bain, R Bambad, J Brenneman, T Dunegan, C Edelstein, SL Grimes, KL Jones, S Jones, TL Klepac, H Lachin, JM Mucik, P Orlosky, R Rochon, J Stimpson, CE Van Aerden, C Eastman, R Garfield, S Harris, M Andres, R Engelgau, M Narayan, V Williamson, D Herman, W Chandler, WL Marcovina, SM McMillan, T Rautaharju, PM Rautaharju, FSR Mayer-Davis, EJ O'Leary, DH Funk, LRC O'Leary, KA Scherzinger, AL Stamm, ER Gillis, BP Kriska, AM Huffmyer, C Meier, A Venditti, EM Wing, RR Haffner, SM Ratner, RE Olefsky, JM Santiago, JV Saudek, CD Knowler, WC Montez, MG Fujimoto, WY Hamman, RF Nathan, DM CA Diabet Prevention Program Res Grp TI The Diabetes Prevention Program - Design and methods for a clinical trial in the prevention of type 2 diabetes SO DIABETES CARE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; POLYCYSTIC-OVARY-SYNDROME; INSULIN-RESISTANCE; BLOOD-PRESSURE; METABOLIC ABNORMALITIES; PHYSICAL-ACTIVITY; LONGITUDINAL DATA; PIMA-INDIANS; METFORMIN; MELLITUS AB The Diabetes Prevention Program is a randomized clinical trial testing strategies to prevent or delay the development of type 2 diabetes in high-risk individuals with elevated fasting plasma glucose concentrations and impaired glucose tolerance. The 27 clinical centers in the U.S. are recruiting at least 3,000 participants of both sexes, similar to 50% of whom are minority patients and 20% of whom are greater than or equal to 65 years old, to be assigned at random to one of three intervention groups. an intensive lifestyle intervention focusing on a healthy diet and exercise and two masked medication treatment groups-metformin or placebo-combined with standard diet and exercise recommendations. Participants are being recruited during a 2 2/3-year period, and all will be followed for an additional 3 1/3 to 5 years after the close of recruitment to a common closing dare in 2002. The primary outcome is the development of diabetes, diagnosed by fasting or post-challenge plasma glucose concentrations meeting the 1997 American Diabetes Association criteria. The 3,000 participants will provide 90% power to detect a 33% reduction in an expected diabetes incidence rate of at least 6.5% per year in the placebo group. Secondary outcomes include cardiovascular disease and its risk factors; changes in glycemia, beta-cell function, insulin sensitivity obesity diet, physical activity and health-related quality; of life: and occurrence of adverse events. A fourth treatment group troglitazone combined with standard diet and exercise recommendations-was included initially but discontinued because of the liver toxicity of the drug. This randomized clinical trial will test the possibility of preventing or delaying the onset of type 2 diabetes in individuals at high risk. C1 Pennington Biomed Res Ctr, Baton Rouge, LA USA. Univ Chicago, Chicago, IL 60637 USA. Jefferson Med Coll, Philadelphia, PA USA. Univ Miami, Coral Gables, FL 33124 USA. Univ Colorado, Hlth Sci Ctr, Computed Tomog Scan Reading Unit, Boulder, CO 80309 USA. Joslin Diabet Ctr, Boston, MA USA. Univ Washington, Seattle, WA 98195 USA. Univ Tennessee, Knoxville, TN 37996 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. St Lukes Roosevelt Hosp, New York, NY USA. Indiana Univ, Bloomington, IN 47405 USA. Medlantic Res Inst, Washington, DC USA. Univ So Calif, UCLA Sch Med, Los Angeles, CA 90089 USA. Washington Univ, St Louis, MO USA. Johns Hopkins Sch Med, Baltimore, MD USA. Univ New Mexico, Sch Med, Albuquerque, NM 87131 USA. Albert Einstein Coll Med, Bronx, NY USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ Hawaii, Honolulu, HI 96822 USA. NIDDKD, Program Off, Bethesda, MD USA. NIA, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Univ Michigan, Ann Arbor, MI 48109 USA. Bowman Gray Sch Med, Epicare Ctr, Winston Salem, NC USA. Univ S Carolina, Nutr Coding Ctr, Columbia, SC 29208 USA. New England Med Ctr, Cent Carotid Ultrasound Unit, Boston, MA USA. RP Bray, GA (reprint author), George Washington Univ, Ctr Biostat, DPP Coordinating Ctr, 6110 Execut Blvd 750, Rockville, MD 20852 USA. OI Shamoon, Harry/0000-0002-5014-5211; Kahn, Steven/0000-0001-7307-9002 NR 67 TC 343 Z9 345 U1 3 U2 31 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD APR PY 1999 VL 22 IS 4 BP 623 EP 634 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 179GJ UT WOS:000079317900016 ER PT J AU Fetsch, PA Marincola, FM Abati, A AF Fetsch, PA Marincola, FM Abati, A TI Cytokeratin positivity in fine-needle aspirates of metastatic malignant melanoma: Fact or fiction? SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Letter ID DIFFERENTIAL-DIAGNOSIS; MONOCLONAL-ANTIBODIES; IN-VIVO; EXPRESSION; CELLS; CYTOLOGY; KERATINS; COEXPRESSION; MESOTHELIOMA; EFFUSIONS C1 NCI, Cytopathol Sect, NIH, Bethesda, MD 20892 USA. RP Fetsch, PA (reprint author), NCI, Cytopathol Sect, NIH, Bethesda, MD 20892 USA. NR 24 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 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD APR PY 1999 VL 20 IS 4 BP 249 EP 252 DI 10.1002/(SICI)1097-0339(199904)20:4<249::AID-DC14>3.0.CO;2-6 PG 4 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 182BD UT WOS:000079477900014 PM 10204112 ER PT J AU Preston, KL Silverman, K Umbricht, A DeJesus, A Montoya, ID Schuster, CR AF Preston, KL Silverman, K Umbricht, A DeJesus, A Montoya, ID Schuster, CR TI Improvement in naltrexone treatment compliance with contingency management SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE naltrexone; opioid-dependence; treatment; contingency management; treatment compliance ID REINFORCEMENT THERAPY; HEROIN DEPENDENCE; DRUG; ABSTINENCE; ADDICTION; EFFICACY; SEVERITY; VALIDITY; RISK AB The efficacy of a voucher-based incentive program for improving adherence to outpatient, thrice weekly naltrexone maintenance was tested in a three group, randomized, la-week clinical trial. Voucher incentives were given as follows: contingent group (n = 19) for each consecutive naltrexone dose ingested; non-contingent group (n = 19) on unpredictable schedule independently of taking naltrexone; no-voucher group (pr = 20) none. Vouchers were exchangeable for goods and services. The contingent group had significantly longer treatment retention and ingested significantly more doses of naltrexone (consecutive and total) than either control group. Voucher incentives can significantly increase adherence to naltrexone maintenance in recently detoxified opioid dependent individuals. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 NIH, Addict Res Ctr, NIDA, Intramural Res Program, Baltimore, MD 21224 USA. RP Preston, KL (reprint author), NIH, Addict Res Ctr, NIDA, Intramural Res Program, 550 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Preston, Kenzie/J-5830-2013; OI Preston, Kenzie/0000-0003-0603-2479; Silverman, Kenneth/0000-0003-2724-1413 NR 33 TC 99 Z9 101 U1 2 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD APR 1 PY 1999 VL 54 IS 2 BP 127 EP 135 DI 10.1016/S0376-8716(98)00152-5 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 179NE UT WOS:000079333400004 PM 10217552 ER PT J AU Alexander, D AF Alexander, D TI The Pediatric pharmacology Research Unit Network of the National Institute of Child Health and Human Development SO DRUG INFORMATION JOURNAL LA English DT Article DE Pediatric Pharmacology Research Unit Network; pediatrics; pharmacology AB The Pediatric Pharmacology Research Unit (PPRU) Network was established to help address a long-standing problem that was a barrier to optimal health and well-being of children: lack of testing in children of drugs used to treat children. The PPRU Network was developed in 1994 to address the industry concern that there was no satisfactory place to test drugs in children, to provide top quality data that would facilitate pediatric labeling, and to demonstrate that this could be done. The network accomplishes these goals by solicited cooperative agreement grants from leading pediatric pharmacology experts. The network's developments, accomplishments to date, and plans for the 21st century are covered. C1 NICHHD, Bethesda, MD 20892 USA. RP Alexander, D (reprint author), NICHHD, 31 Ctr Dr,Bldg 31,Rm 2A03,MSC 2425, Bethesda, MD 20892 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU DRUG INFORMATION ASSOCIATION PI FORT WASHINGTON PA 501 OFFICE CENTER DR, STE 450, FORT WASHINGTON, PA 19034-3212 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD APR-JUN PY 1999 VL 33 IS 2 BP 385 EP 391 PG 7 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 204GP UT WOS:000080756000009 ER PT J AU Geller, NL Proschan, MA Follmann, DA AF Geller, NL Proschan, MA Follmann, DA TI Group sequential monitoring of multi-armed clinical trials SO DRUG INFORMATION JOURNAL LA English DT Article DE group sequential monitoring; multi-armed clinical trials AB Monitoring of two-armed clinical trials using group sequential methods has been implemented for over 20 years. This paper considers analogous monitoring procedures for multi-armed clinical trials. Monitoring the trial based on repeated tests of a global null hypothesis, monitoring of comparisons of several treatments to a control, and monitoring of all pairwise comparisons are considered. The procedure of choice for a given situation will depend on how the application at hand is best formulated. C1 NHLBI, Off Biostat Res, Rockledge Ctr 2, Bethesda, MD 20892 USA. RP Geller, NL (reprint author), NHLBI, Off Biostat Res, Rockledge Ctr 2, Room 8210,6701 Rockledge Dr, Bethesda, MD 20892 USA. NR 14 TC 1 Z9 1 U1 0 U2 2 PU DRUG INFORMATION ASSOCIATION PI FORT WASHINGTON PA 501 OFFICE CENTER DR, STE 450, FORT WASHINGTON, PA 19034-3212 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD APR-JUN PY 1999 VL 33 IS 2 BP 479 EP 486 PG 8 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 204GP UT WOS:000080756000019 ER PT J AU Strober, W Fuss, IJ AF Strober, W Fuss, IJ TI Alternative patterns of experimental mucosal inflammation provide models for Crohn's disease and ulcerative colitis SO DRUGS OF TODAY LA English DT Article ID CD4(+) T-CELLS; ALPHA MUTANT MICE; ANTIGEN-PRESENTING CELLS; TUMOR-NECROSIS-FACTOR; HAPTEN-INDUCED MODEL; BOWEL-DISEASE; IFN-GAMMA; INTERLEUKIN-10-DEFICIENT MICE; CONTACT SENSITIVITY; BACTERIAL-ANTIGENS AB Many diseases, including those characterized by inflammation of the gastrointestinal tract (Crohn's disease and ulcerative colitis), are due to an array of factors that act together to produce pathological abnormalities. The immunological factors that mediate the development of such inflammation have been the focus of intense research. Recently, a clearer understanding of the mechanisms involved in mucosal homeostasis and the occurrence of inflammatory bowel disease (IBD) has been accomplished with the advent of animal models of mucosal inflammation. This review discusses two of these models and the insights they provide into the pathogenesis and treatment of IBD. C1 NIAID, Clin Invest Lab, Mucosal Immun Sect, NIH, Bethesda, MD 20892 USA. RP Strober, W (reprint author), NIAID, Clin Invest Lab, Mucosal Immun Sect, NIH, Bldg 10,Room 11 N238,10 Ctr Dr,MSC 1888, Bethesda, MD 20892 USA. NR 53 TC 0 Z9 0 U1 0 U2 0 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0025-7656 J9 DRUGS TODAY JI Drugs Today PD APR PY 1999 VL 35 SU A BP 71 EP 83 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 206JL UT WOS:000080874600007 ER PT J AU Modesti, M Hesse, JE Gellert, M AF Modesti, M Hesse, JE Gellert, M TI DNA binding of Xrcc4 protein is associated with V(D)J recombination but not with stimulation of DNA ligase IV activity SO EMBO JOURNAL LA English DT Article DE DNA ligase IV; end joining; V(D)J recombination; XRCC4 ID STRAND BREAK REPAIR; RAY-SENSITIVE MUTANTS; HAMSTER OVARY CELL; SACCHAROMYCES-CEREVISIAE; MAMMALIAN-CELLS; IDENTIFICATION; INTERACTS; PATHWAY; COMPLEX; KINASE AB Mammalian cells are protected from the effects of DNA double-strand breaks by end-joining repair, Cells lacking the Xrcc4 protein are hypersensitive to agents that induce DNA double-strand breaks, and are unable to complete V(D)J recombination, The residual repair of broken DNA ends in XRCC4-deficient cells requires short sequence homologies, thus possibly implicating Xrcc4 in end alignment. We show that Xrcc4 binds DNA, and prefers DNA with nicks or broken ends. Xrcc4 also binds to DNA ligase IV and enhances its joining activity. This stimulatory effect is shown to occur at the adenylation of the enzyme. DNA binding of Xrcc4 is correlated with its complementation of the V(D)J recombination defects in XRCC4-deficient cells, but is not required for stimulation of DNA ligase IV. Thus, the ability of Xrcc4 to bind to DNA suggests functions independent of DNA ligase IV. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Gellert, M (reprint author), NIDDKD, Mol Biol Lab, NIH, Bldg 5 Room 241, Bethesda, MD 20892 USA. NR 36 TC 131 Z9 133 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD APR 1 PY 1999 VL 18 IS 7 BP 2008 EP 2018 DI 10.1093/emboj/18.7.2008 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 185FW UT WOS:000079658300028 PM 10202163 ER PT J AU Ward, PP Mendoza-Meneses, M Mulac-Jericevic, B Cunningham, GA Saucedo-Cardenas, O Teng, CT Conneely, OM AF Ward, PP Mendoza-Meneses, M Mulac-Jericevic, B Cunningham, GA Saucedo-Cardenas, O Teng, CT Conneely, OM TI Restricted spatiotemporal expression of lactoferrin during murine embryonic development SO ENDOCRINOLOGY LA English DT Article ID ESTROGEN-RECEPTOR; MOUSE UTERUS; BINDING PROTEIN; LACTOTRANSFERRIN; CELLS; IRON; IDENTIFICATION; IMPLANTATION; INVITRO; GROWTH AB Lactoferrin is a member of the transferrin family of iron-binding glycoproteins. Lactoferrin is induced by estrogen in the mouse uterus during early pregnancy. However, the expression and function, if any, of lactoferrin in the preimplantation embryo during this developmental period has not been investigated. In the current study, the spatiotemporal expression of lactoferrin during murine embryogenesis was examined using in situ hybridization and immunohistochemical analyses. Lactoferrin expression was first detected in the 2-4 cell fertilized embryo and continued until the blastocyst stage of development. Interestingly, at the 16-cell stage, coinciding with the first major differentiation step in the embryo, lactoferrin messenger RNA (mRNA) is synthesized by the inner cells, whereas the protein is selectively taken up by the outside cells. This differential pattern of lactoferrin messenger RNA and protein localization continues until the blastocyst stage, with expression almost absent in the hatched blastocyst. Lactoferrin expression does not resume in the embryo until the latter half of gestation, where it is first detected in neutrophils of the fetal Liver at embryonic day 11.5 and later in epithelial cells of the respiratory and digestive systems. Our results show that lactoferrin is expressed in a tightly regulated spatiotemporal manner during murine embryogenesis and suggest a novel paracrine role for this protein in the development of the trophoectodermal lineage during preimplantation development. C1 Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Conneely, OM (reprint author), Baylor Coll Med, Dept Cell Biol, Room M513A,1 Baylor Plaza, Houston, TX 77030 USA. NR 49 TC 43 Z9 44 U1 1 U2 6 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 1999 VL 140 IS 4 BP 1852 EP 1860 DI 10.1210/en.140.4.1852 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 178CH UT WOS:000079248200044 PM 10098524 ER PT J AU Carpenter, DO Cikrt, M Suk, WA AF Carpenter, DO Cikrt, M Suk, WA TI Hazardous wastes in eastern and central Europe: Technology and health effects SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material DE arsenic; cadmium; dioxins; human health; incineration; lead; metals; PCBs; persistent organic pollutants; pesticides AB Issues of hazardous waste management are major concerns in the countries of eastern and central Europe. A National Institute of Environmental Health Sciences-supported conference was held in Prague, Czech Republic, as a part of a continuing effort to provide information and promote discussion among the countries of eastern and central Europe on issues related to hazardous wastes. The focus was on incineration as a means of disposal of hazardous wastes, with discussions on both engineering methods for safe incineration, and possible human health effects from incineration by-products. Representatives from government agencies, academic institutions, and local industries from 14 countries in the region participated along with a few U.S. and western European experts in this field. A series of 12 country reports documented national issues relating to the environment, with a focus on use of incineration for hazardous waste disposal. A particularly valuable contribution was made by junior scientists from the region, who described results of environmental issues in their countries. C1 SUNY Albany, Dept Environm Hlth & Toxicol, Sch Publ Hlth, Rensselaer, NY 12144 USA. Natl Publ Hlth Inst, Ctr Ind Hygiene & Occupat Dis, Prague 10, Czech Republic. NIEHS, Div Extramural Res & Training, Res Triangle Pk, NC 27709 USA. RP Carpenter, DO (reprint author), SUNY Albany, Dept Environm Hlth & Toxicol, Sch Publ Hlth, 1 Univ Pl,B242, Rensselaer, NY 12144 USA. FU NIEHS NIH HHS [P42 ES049130] NR 6 TC 0 Z9 0 U1 1 U2 4 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 APR PY 1999 VL 107 IS 4 BP 249 EP 250 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 187HZ UT WOS:000079782400013 PM 10090701 ER PT J AU Gulson, BL Mahaffey, KR Jameson, CW Patison, N Law, AJ Mizon, KJ Korsch, MJ Pederson, D AF Gulson, BL Mahaffey, KR Jameson, CW Patison, N Law, AJ Mizon, KJ Korsch, MJ Pederson, D TI Impact of diet on lead in blood and urine in female adults and relevance to mobilization of lead from bone stores SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE adult females; bone; diet; lead isotopes; pregnancy ID PRIMATE MACACA-FASCICULARIS; PETROL LEAD; CHILDREN; ISOTOPES; PREGNANCY; SKELETON; IDENTIFICATION; ABSORPTION; EXPOSURE; INFANT AB We measured high precision lead isotope ratios and lead concentrations in blood, urine, and environmental samples to assess the significance of diet as a contributing factor to blood and urine lead levels in a cohort of 23 migrant women and 5 Australian-born women. We evaluated possible correlations between levels of dietary lead intake and changes observed in blood and urine lead levels and isotopic composition during pregnancy and postpartum. Mean blood lead concentrations for both groups were approximately 3 mu g/dl. The concentration of lead in the diet was 5.8 +/- 3 mu g Pb/kg [geometric mean (GM) 5.2] and mean daily dietary intake was 8.5 mu g/kg/day (GM 7.4), with a range of 2-39 mu g/kg/day. Analysis of 6-day duplicate dietary samples for individual subjects commonly showed major spikes in lead concentration and isotopic composition that were not reflected by associated changes in either blood lead concentration or isotopic composition Changes in blood lead levels and isotopic composition observed during and after pregnancy could not be solely explained by dietary lead. These data are consistent with earlier conclusions that, in cases where levels of environmental lead exposure and dietary lead intake are low, skeletal contribution is the dominant contributor to blood lead, especially during pregnancy and postpartum. C1 Macquarie Univ, Grad Sch Environm, Sydney, NSW 2109, Australia. CSIRO, N Ryde, NSW 2113, Australia. US EPA, Natl Ctr Environm Assessment, Cincinnati, OH 45268 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Univ Canberra, Fac Informat Sci & Engn, Belconnen, ACT 2616, Australia. RP Gulson, BL (reprint author), Macquarie Univ, Grad Sch Environm, Sydney, NSW 2109, Australia. FU NIEHS NIH HHS [N01-ES-05292] NR 34 TC 35 Z9 38 U1 0 U2 1 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 APR PY 1999 VL 107 IS 4 BP 257 EP 263 DI 10.2307/3434591 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 187HZ UT WOS:000079782400015 PM 10090703 ER PT J AU van der Schalie, WH Gardner, HS Bantle, JA De Rosa, CT Finch, RA Reif, JS Reuter, RH Backer, LC Burger, J Folmar, LC Stokes, WS AF van der Schalie, WH Gardner, HS Bantle, JA De Rosa, CT Finch, RA Reif, JS Reuter, RH Backer, LC Burger, J Folmar, LC Stokes, WS TI Animals as sentinels of human health hazards of environmental chemicals SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE environmental chemicals; FETAX; health hazards; public health; risk assessment; sentinel species ID MILITARY WORKING DOGS; 2,4-DICHLOROPHENOXYACETIC ACID; VIETNAM SERVICE; PET DOGS; EXPOSURE; RISK; LYMPHOMA; OWNERS; CANCER AB A workshop titled "Using Sentinel Species Data to Address the potential Human Health Effects of Chemicals in the Environment," sponsored by the U.S. Army Center for Environmental Health Research, the National Center for Environmental Assessment of the EPA, and the Agency for Toxic Substances and Disease Registry, was held to consider the use of sentinel and surrogate animal species data for evaluating the potential human health effects of chemicals in the environment. The workshop took a broad view of the sentinel species concept, and included mammalian and nonmammalian species, companion animals, food animals, fish, amphibians, and other wildlife. Sentinel species data included observations of wild animals in field situations as well as experimental animal data. Workshop participants identified potential applications for sentinel species data derived from monitoring programs or serendipitous observations and explored the potential use of such information in human health hazard and risk assessments and for evaluating causes or mechanisms of effect. Although it is unlikely that sentinel species data will be used as the sole determinative factor in evaluating human health concerns, such data can be useful as for additional weight of evidence in a risk assessment, for providing early warning of situations requiring further study, or for monitoring the course of remedial activities. Attention was given to the factors impeding the application of sentinel species approaches and their acceptance in the scientific and regulatory communities. Workshop participants identified a number of critical research needs and opportunities for interagency collaboration that could help advance the use of sentinel species approaches. C1 USA, Ctr Environm Hlth Res, Ft Detrick, MD 21702 USA. Oklahoma State Univ, Stillwater, OK 74078 USA. Agcy Tox Subst & Dis Registry, Atlanta, GA 30333 USA. Colorado State Univ, Ft Collins, CO 80521 USA. Life Syst Inc, Cleveland, OH 44122 USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30333 USA. Rutgers State Univ, Piscataway, NJ 08854 USA. US EPA, Natl Hlth & Environm Effects Res Lab, Gulf Breeze, FL 32561 USA. NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP van der Schalie, WH (reprint author), US EPA, Natl Ctr Environm Assessment, 8623D,401 M St SW, Washington, DC 20460 USA. NR 55 TC 93 Z9 98 U1 1 U2 16 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 APR PY 1999 VL 107 IS 4 BP 309 EP 315 DI 10.2307/3434599 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 187HZ UT WOS:000079782400023 PM 10090711 ER PT J AU Thigpen, JE Setchell, KDR Goelz, MF Forsythe, DB AF Thigpen, JE Setchell, KDR Goelz, MF Forsythe, DB TI The phytoestrogen content of rodent diets SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Letter ID ESTROGENIC ACTIVITY; MAMMARY-CANCER; CARCINOGENESIS; ISOFLAVONES; GENISTEIN; RATS; TOXICOLOGY; NTP-2000; MODELS C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Thigpen, JE (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 26 TC 43 Z9 44 U1 0 U2 2 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 APR PY 1999 VL 107 IS 4 BP A182 EP A183 DI 10.2307/3434577 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 187HZ UT WOS:000079782400002 PM 10383244 ER PT J AU van Birgelen, APJM AF van Birgelen, APJM TI The TEF approach for hexachlorobenzene - Response SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Letter C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP van Birgelen, APJM (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 3 TC 0 Z9 0 U1 0 U2 1 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 APR PY 1999 VL 107 IS 4 BP A184 EP A184 DI 10.2307/3434579 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 187HZ UT WOS:000079782400004 ER PT J AU Siegel, H Kelley, K Stertz, B Reeves-Tyer, P Flamini, R Malow, B Gaillard, WD Ko, D Theodore, WH AF Siegel, H Kelley, K Stertz, B Reeves-Tyer, P Flamini, R Malow, B Gaillard, WD Ko, D Theodore, WH TI The efficacy of felbamate as add-on therapy to valproic acid in the Lennox-Gastaut syndrome SO EPILEPSY RESEARCH LA English DT Article DE atonic seizures; FBM; VPA; Lennox-Gastaut; anticonvulsant drugs ID INFANTILE SPASMS; ANTICONVULSANT AB We studied the efficacy of felbamate (FBM) in combination with valproic acid (VPA) in 13 patients with the Lennox-Gastaut syndrome and evaluated the contribution of each drug. Following stabilization on VPA monotherapy, FBM or placebo titration was performed for two observation periods lasting 7 weeks with a washout period between them. 6-h video-electroencephalography was recorded following each observation period. In addition to examining the effects of the drugs with parental reports and video-EEG, we compared video-EEG data with families' seizure reports. Based on parental counts for the 7-week observation periods, patients had 40% fewer drop attacks (p < 0.03, Wilcoxon rank sum test) and 60% fewer total seizures (p < 0.02) on VPA and FBM. VPA level rose by 12.7% when FBM was added (p < 0.01). When the effect of FBM was factored out, VPA had a significant effect on drop attack frequency, although not total number of seizures. FBM's therapeutic effect on drop attacks is due in part to increased VPA levels, although the combination may be synergistic for the effect on total seizure number. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NINCDS, Clin Epilepsy Sect, Epilepsy Res Branch, NIH, Bethesda, MD 20892 USA. RP Siegel, H (reprint author), CUNY, Mt Sinai Med Ctr, Box 1052,1 Gustave L Levy Pl, New York, NY 10029 USA. NR 21 TC 32 Z9 33 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD APR PY 1999 VL 34 IS 2-3 BP 91 EP 97 DI 10.1016/S0920-1211(98)00119-3 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 194MC UT WOS:000080196600002 PM 10210023 ER PT J AU Juhng, KN Kokate, TG Yamaguchi, S Kim, BY Rogowski, RS Blaustein, MP Rogawski, MA AF Juhng, KN Kokate, TG Yamaguchi, S Kim, BY Rogowski, RS Blaustein, MP Rogawski, MA TI Induction of seizures by the potent K+ channel-blocking scorpion venom peptide toxins tityustoxin-K alpha and pandinustoxin-K alpha SO EPILEPSY RESEARCH LA English DT Article DE pandinustoxin-K alpha; tityustoxin-K alpha; 4-aminopyridine; paxilline; K+ channel blocker; AMPA receptor antagonist ID ACTIVATED POTASSIUM CHANNELS; HIPPOCAMPUS IN-VITRO; EPILEPTIFORM ACTIVITY; RAT HIPPOCAMPUS; ANTICONVULSANT DRUGS; GYKI 52466; 4-AMINOPYRIDINE; DENDROTOXIN; NEURONS; SYNAPTOSOMES AB The scorpion venom peptide toxins tityustoxin-K alpha (TsTx-K alpha) and pandinustoxin-K alpha (PiTx-K alpha) are novel, highly potent and selective blockers of voltage-activated K+ channels. PiTx-K alpha preferentially blocks rapidly inactivating (A-type) K+ channels whereas TsTx-K alpha is selective for slowly inactivating (delayed rectifier-type) channels. K+ channel blockers are known to induce seizures, but the specific K+ channel types that can serve as convulsant targets are not well defined. To address this issue, we examined for convulsant activity the K+ channel type-specific scorpion toxins and the selective K+ channel antagonists il-aminopyridine (4-AP), an inhibitor of A-type voltage-activated K+ channels, and paxilline, a selective blocker of large conductance (maxi K) Ca2+-activated K+ channels. Intracerebroventricular injection of recombinant TsTx-K alpha and PiTx-K alpha in mice produced limbic and clonic-tonic seizures. The severity of the seizures increased during the 60-min period following injection, culminating in continuous clonic seizure activity (status epilepticus), tonic hindlimb extension, and eventually in death. The estimated doses producing limbic and clonic seizures in 50% of animals (CD50) for TsTx-K alpha and PiTx-K alpha were 9 and 33 ng, respectively. 4-AP produced seizure activity similar to the toxins (CD50, 76 ng) whereas paxilline failed to induce seizures at doses up to 13.5 mu g. Carbamazepine protected fully against the toxin- and 4-AP-induced seizures whereas phenytoin had variable activity against the clonic component although it was protective against tonic hindlimb extension. The AMPA receptor antagonist GYKI 52466 also conferred full protection against toxin-induced seizures, but the NMDA receptor antagonists (R)-CPP and dizocilpine failed to affect limbic and clonic seizures, although they protected against hindlimb extension. We conclude that selective blockade of delayed rectifier- or A-type voltage-activated K+ channels can produce limbic, clonic and tonic seizures, whereas blockade of maxi K-type Ca2+-activated K+ channels does not. The convulsant effects may be related to enhanced glutamate release and, in the case of the limbic and clonic convulsions, activation of AMPA receptors. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NINCDS, Neuronal Excitabil Sect, Epilepsy Res Branch, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. RP Rogawski, MA (reprint author), NINCDS, Neuronal Excitabil Sect, Epilepsy Res Branch, NIH, Bldg 10,Room 5N-250,10 Ctr Dr MSC 1408, Bethesda, MD 20892 USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 FU NINDS NIH HHS [NS16106] NR 34 TC 37 Z9 38 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD APR PY 1999 VL 34 IS 2-3 BP 177 EP 186 DI 10.1016/S0920-1211(98)00111-9 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 194MC UT WOS:000080196600012 PM 10210033 ER PT J AU Emanuel, EJ AF Emanuel, EJ TI What is the great benefit of legalizing euthanasia or physican-assisted suicide? SO ETHICS LA English DT Article ID VOLUNTARY ACTIVE EUTHANASIA; UNITED-STATES; ATTITUDES; FAMILIES; PATIENT; LIFE; END C1 NIH, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Emanuel, EJ (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bethesda, MD 20892 USA. NR 23 TC 7 Z9 8 U1 3 U2 17 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0014-1704 J9 ETHICS JI Ethics PD APR PY 1999 VL 109 IS 3 BP 629 EP 642 DI 10.1086/233925 PG 14 WC Ethics; Philosophy SC Social Sciences - Other Topics; Philosophy GA 187JU UT WOS:000079784100007 PM 11657615 ER PT J AU Shohat, M Magal, N Shohat, T Chen, X Dagan, T Mimouni, A Danon, Y Lotan, R Ogur, G Sirin, A Schlezinger, M Halpern, GJ Schwabe, A Kastner, D Rotter, JI Fischel-Ghodsian, N AF Shohat, M Magal, N Shohat, T Chen, X Dagan, T Mimouni, A Danon, Y Lotan, R Ogur, G Sirin, A Schlezinger, M Halpern, GJ Schwabe, A Kastner, D Rotter, JI Fischel-Ghodsian, N TI Phenotype-genotype correlation in familial Mediterranean fever: evidence for an association between Met694Val and amyloidosis SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE phenotype-genotype correlation; amyloidosis; specific mutation ID HIGH GENE-FREQUENCY; ARMENIANS; COLCHICINE; FMF AB Familial Mediterranean fever (FMF) is an autosomal recessive disease characterised by recurrent attacks of inflammation of serosal membranes. Amyloidosis is the most severe complication of the disease. The aim of this study was to investigate the genotype-phenotype correlation and specifically the association between amyloidosis and the four common mutations in exon 10 of the gene causing FMF (MEFV) in a total of 83 FMF families from three ethnic groups: North African Jews, Armenians and Turks. A significant association was found between amyloidosis and the specific mutation at the MEFV gene: Met694Val (RR = 1.41, P = 0.02). Amyloidosis was present in 18 out of 87 homozygous FMF patients (20.7%) and in only two out of the 41 compound heterozygous FMF patients (4.9%). No patients carrying other mutations had amyloidosis. There was no significant association between the various mutations and the type or severity of the FMF symptoms. This finding underscores the importance of performing molecular studies on all suspect FMF patients. In addition to providing accurate diagnosis, these tests allow identification of presymptomatic genetically affected individuals, detection of carriers and assessment of the risk for amyloidosis in later life. C1 Tel Aviv Univ, Rabin Med Ctr, Dept Med Genet, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. Cedars Sinai Med Ctr, Ctr Med Genet Birth Defects, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Tel Aviv Univ, Rabin Med Ctr, Dept Immunol, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. Ankara Univ, Fac Med, Gata Med Ctr, Ankara, Turkey. Ankara Univ, Fac Med, Dept Immunol, Ankara, Turkey. Univ Istanbul, Istanbul Med Fac, Istanbul, Turkey. Barzilai Med Ctr, Immunol Unit, Ashkelon, Israel. NIAMSD, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. RP Shohat, M (reprint author), Beilinson Med Ctr, Dept Med Genet, Beilinson Campus, IL-49100 Petah Tiqwa, Israel. OI Mimouni Bloch, Aviva/0000-0001-6457-0262 NR 20 TC 147 Z9 150 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD APR PY 1999 VL 7 IS 3 BP 287 EP 292 DI 10.1038/sj.ejhg.5200303 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 193FN UT WOS:000080125400003 PM 10234504 ER PT J AU Mullbacher, A Lobigs, M Yewdell, JW Bennink, JR Hla, RT Blanden, RV AF Mullbacher, A Lobigs, M Yewdell, JW Bennink, JR Hla, RT Blanden, RV TI Spontaneous mutation at position 114 in H-2K(d) affects cytotoxic T cell responses to influenza virus infection SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE MHC class 1; cytotoxic T cell; nucleoprotein peptide ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-I MOLECULES; LYMPHOCYTES-T; WEST NILE; PEPTIDE; ANTIGEN; RECOGNITION; FLAVIVIRUS AB Vaccinia virus (VV)-encoded MHC class I K-d molecules which differ by a single amino acid change from glutamine (K-dw, Wild type) to histidine (K-dm, mutant) at position 114 located in the floor of the peptide binding groove were compared in terms of peptide binding and cytotoxic T Ire) cell recognition. Most anti-viral Tc cells were not affected or only marginally affected. However, the K-dm molecule did not detectably present the immunodominant peptide (NPP147-155) Of influenza virus nucleoprotein (NP), encoded by the full-length NP gene either in influenza A virus or recombinant VV. This defect could be overcome by using exogenous synthetic NPP147-155 Or translation from a minigene encoding NPP147-155 in VV. K-dw presented NPP147-155 encoded by the full-length NP gene, but K-dw-NPP147-155 complexes were at least 100-fold less abundant than after translation from a minigene. C1 Australian Natl Univ, John Curtin Sch Med Res, Div Cell Biol & Immunol, Canberra, ACT 2601, Australia. NIAID, Viral Immunol & Cellular Biol Lab Viral Dis, NIH, Bethesda, MD 20892 USA. RP Mullbacher, A (reprint author), Australian Natl Univ, John Curtin Sch Med Res, Div Cell Biol & Immunol, POB 334, Canberra, ACT 2601, Australia. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 17 TC 2 Z9 2 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 APR PY 1999 VL 29 IS 4 BP 1228 EP 1234 PG 7 WC Immunology SC Immunology GA 188MB UT WOS:000079849800020 PM 10229090 ER PT J AU Shinkai, T Roth, GS AF Shinkai, T Roth, GS TI Mechanisms of age-related changes in gonadotropin-releasing hormone receptor messenger ribonucleic acid content in the anterior pituitary of male rats SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE GnRH receptor; gene expression; pituitary; aging ID RNA; NEURONS; LH AB To determine the mechanism(s) of age-related changes in gonadotropin release from pituitary gonadotrophs in male rats, we measured the number of GnRH (gonadotropin-releasing hormone) receptor containing cells and expression of GnRH receptor mRNA per cell in the anterior pituitary. An in situ hybridization procedure was performed using young (six months) and old (24-25 months) Wister rats. An image analysis system was employed for the autoradiographic analysis, The number of pituitary cells increased during aging (approximately 45%, p < 0.01). On the other hand, the number of GnRH receptor mRNA-containing cells decreased (approximately 25%, p < 0.05), The percentage of these cells in old rats decreased to less than a half of that in young animals (p < 0.01). GnRH receptor mRNA per cell in old rats was only 7% lower than in young (p < 0.01), These results suggest that loss of pituitary gonadotroph GnRH receptors and response is primarily due to the loss of gonadotrophs, and that the death mechanism(s) are responsible for decreased stimulation of Gn release during aging, (C) 1999 Elsevier Science Inc. All rights reserved. C1 NIA, Mol Physiol & Genet Sect, Cellular & Mol Biol Lab, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA. RP Roth, GS (reprint author), NIA, Mol Physiol & Genet Sect, Cellular & Mol Biol Lab, Gerontol Res Ctr,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM geor@vax.grc.nia.nih.gov NR 18 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD APR PY 1999 VL 34 IS 2 BP 267 EP 273 DI 10.1016/S0531-5565(98)00074-6 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 180JK UT WOS:000079382300011 PM 10363792 ER PT J AU Miller, JL Njoroge, JM Gubin, AN Rodgers, GP AF Miller, JL Njoroge, JM Gubin, AN Rodgers, GP TI Prospective identification of erythroid elements in cultured peripheral blood SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE erythropoiesis; flow cytometry; CD48 ID 2-STEP LIQUID CULTURE; HUMAN-BONE-MARROW; STEM-CELL FACTOR; PROGENITOR CELLS; EXPRESSION; DIFFERENTIATION; ERYTHROPOIETIN; PROLIFERATION; MATURATION; PRECURSORS AB We have developed a prospective approach to identify the generation of erythroid cells derived from cultured peripheral blood mononuclear cells (PBMC) by monitoring the expression of the cell surface protein CD48, Unpurified populations of PBMC obtained from the buffy coats of normal volunteers Here grown in suspension culture in the absence or presence of erythropoietin. A profile of surface CD48 expression permitted a now cytometric identification of erythropoietin responsive populations at various stages of their maturation. In the absence of erythropoietin (EPO) supplemented media, the CD-48(-) cells represented <5% of the total population of PBMC remaining in culture, In cultures supplemented with 1 U/mL EPO, the mean percentage of CD48(-) cells increased to 33.7 + 14.9%, (p < 0.01) after 14 days in culture, Coordinated CD34 and CD71 (transferrin receptor) expression, morphology. gamma-globin transcription, and colony formation in methyl-celluose were observed during the 14-day culture period. Flea cytometric monitoring of bulk cultured PBMC provides a simple and reliable means for the prospective or real-time study of human erythropoiesis. (C) 1999 International Society for Experimental Hematology. Published by Elsevier Science Inc. C1 NIDDKD, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Miller, JL (reprint author), NIDDKD, Biol Chem Lab, NIH, Bldg 10,Room 9N308, Bethesda, MD 20892 USA. NR 23 TC 24 Z9 25 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD APR PY 1999 VL 27 IS 4 BP 624 EP 629 DI 10.1016/S0301-472X(98)00086-1 PG 6 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 185VB UT WOS:000079690600006 PM 10210320 ER PT J AU Su, XZ Wellems, TE AF Su, XZ Wellems, TE TI Plasmodium falciparum: Assignment of microsatellite markers to chromosomes by PFG-PCR SO EXPERIMENTAL PARASITOLOGY LA English DT Article ID GENETIC CROSS; MAP; GENOME C1 NIAID, NIH, LPD, Bethesda, MD 20892 USA. RP Su, XZ (reprint author), NIAID, NIH, LPD, Bldg 4,Room 126,4 Ctr Dr MSC 0425, Bethesda, MD 20892 USA. OI Su, Xinzhuan/0000-0003-3246-3248 NR 14 TC 12 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD APR PY 1999 VL 91 IS 4 BP 367 EP 369 DI 10.1006/expr.1998.4390 PG 3 WC Parasitology SC Parasitology GA 183ET UT WOS:000079541800011 PM 10092482 ER PT J AU Lagrue, AH Francischetti, IMB Guimaraes, JA Jandrot-Perrus, M AF Lagrue, AH Francischetti, IMB Guimaraes, JA Jandrot-Perrus, M TI Phosphatidylinositol 3 '-kinase and tyrosine-phosphatase activation positively modulate Convulxin-induced platelet activation. Comparison with collagen SO FEBS LETTERS LA English DT Article DE Convulxin; phospholipase C gamma; protein tyrosine phosphorylation; phenylarsine oxide; phosphatidylinositol 3-kinase; tyrosine phosphatase; Wortmannin; Crotalus durissus terrificus ID CROTALUS-DURISSUS-TERRIFICUS; RECEPTOR-GAMMA-CHAIN; PHOSPHOLIPASE C-GAMMA; SRC FAMILY KINASES; GLYCOPROTEIN-VI; INCLUDING PLC-GAMMA-2; AGGREGATING PROTEIN; MEDIATED ACTIVATION; PHENYLARSINE OXIDE; PHOSPHORYLATION AB In this report we have studied the role of phosphatidylinositol 3'-kinase (PI3-K) and tyrosine phosphatase activation on platelet activation by Convulxin (Cvx), Wortmannin, a specific PI3-K inhibitor, and phenylarsine oxide (PAO), a sulfhydryl reagent that inhibits tyrosine phosphatase (PTPase), block Cvx-induced platelet aggregation, granule secretion, inositol phosphate production, and increase in [Ca2+](i). However, PAO does not inhibit Cvx-induced tyrosine phosphorylation of platelet proteins, including Syk and PLC gamma 2, but blocked collagen-induced platelet aggregation as well as tyrosine phosphorylation of PLC gamma 2. In contrast, Cvx-induced PLC gamma 2 tyrosyl phosphorylation was partially inhibited by wortmannin, We conclude that (i) although Cvx and collagen activate platelets by a similar mechanism, different regulatory processes are specific to each agonist; (ii) mechanisms other than tyrosine phosphorylation regulate PLC gamma 2, activity; and (iii) besides protein tyrosine kinases, PI3-K land PTPase) positively modulate platelet activation by both Cvx and collagen, and this enzyme is required for effective transmission of GPVI-Fc receptor gamma chain signal to result in full activation and tyrosine phosphorylation of PLC gamma 2 in Cvx-stimulated platelets. (C) 1999 Federation of European Biochemical Societies. C1 Fac Xavier Bichat, Lab Rech Hemostase & Thrombose, F-75870 Paris 18, France. Univ Fed Rio de Janeiro, CCS, ICB, Dept Med Biochem,Ilha Fundao, BR-21941590 Rio De Janeiro, Brazil. RP Francischetti, IMB (reprint author), NIAID, Parasit Dis Lab, NIH, 9000 Rockville Pike,Bldg 4,Room 126, Bethesda, MD 20892 USA. OI JANDROT-PERRUS, Martine/0000-0002-8450-9247; Guimaraes, Jorge A./0000-0001-6354-6789 NR 44 TC 22 Z9 24 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD APR 1 PY 1999 VL 448 IS 1 BP 95 EP 100 DI 10.1016/S0014-5793(99)00340-3 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 186VD UT WOS:000079750100021 PM 10217417 ER PT J AU Zhao, XM Hauache, O Goldsmith, PK Collins, R Spiegel, AM AF Zhao, XM Hauache, O Goldsmith, PK Collins, R Spiegel, AM TI A missense mutation in the seventh transmembrane domain constitutively activates the human Ca2+ receptor SO FEBS LETTERS LA English DT Article DE G protein-coupled receptor; constitutive activation; calcium-sensing receptor ID CALCIUM-SENSING RECEPTOR; LUTEINIZING-HORMONE RECEPTOR; PUTATIVE PHEROMONE RECEPTORS; CA2+-SENSING RECEPTOR; CELL-SURFACE; SPORADIC HYPOPARATHYROIDISM; MONOCLONAL-ANTIBODIES; FUNCTIONAL EXPRESSION; EXTRACELLULAR DOMAIN; SIGNAL-TRANSDUCTION AB A missense mutation, A843E, in the seventh transmembrane domain of the human Ca2+ receptor, identified in a subject with autosomal dominant hypocalcemia, was found to cause a constitutive activation while at the same time lowering the maximal response of the receptor to Ca2+. A truncated human Ca2+ receptor lacking the majority of the N-terminal extracellnlar domain failed to respond to Ca2+ despite an excellent cell surface expression. The A843E mutant version of this truncated receptor showed constitutive activation. These results identify A843 as a critical residue for maintaining the inactive conformation of the human Ca2+ receptor. Substitution of glutamate, but not lysine or valine, for alanine 843 leads to activation of the human Ca2+ receptor in a manner that no longer depends upon Ca2+ binding to the extracellular domain. (C) 1999 Federation of European Biochemical Societies. C1 NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Spiegel, AM (reprint author), NIDDKD, Metab Dis Branch, NIH, Bldg 10,Room 9N-222, Bethesda, MD 20892 USA. NR 27 TC 44 Z9 46 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD APR 1 PY 1999 VL 448 IS 1 BP 180 EP 184 DI 10.1016/S0014-5793(99)00368-3 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 186VD UT WOS:000079750100040 PM 10217436 ER PT J AU Znamenskaya, LV Vershinina, OA Vershinina, VI Leshchinskaya, IB Hartley, RW AF Znamenskaya, LV Vershinina, OA Vershinina, VI Leshchinskaya, IB Hartley, RW TI Expression of the genes for guanyl-specific ribonucleases from Bacillus intermedius and Bacillus pumilus is regulated by the two component signal transduction system PhoP-PhoR in B-subtilis SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE ribonuclease; Bacillus; gene regulation; PHO regulon ID PROMOTER; REGULON AB Promoters of the genes for guanyl-specific ribonucleases, secreted by B. intermedius (binase) and B. pumilus (Rnase Bp) in phosphate deficient conditions, contain regions similar to appropriate consensus sequences in promoters of the PHO regulated genes of B. subtilis. A number of genes expressed in response to phosphate starvation in B. subtilis are regulated by the two component signal transduction system PhoP-PhoR. Expression of recombinant genes for binase and RNase Bp in B. subtilis strains with mutations in the regulatory protein genes of the PHO regulon was studied. Their expression is strongly regulated by the regulatory proteins of the B. subtilis PHO regulon. (C) 1999 Published by Elsevier Science B.V. All rights reserved. C1 Kazan State Univ, Dept Microbiol, Lab Biosynth & Bioengn Enzymes, Kazan 420008, Russia. NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA. RP Znamenskaya, LV (reprint author), Kazan State Univ, Dept Microbiol, Lab Biosynth & Bioengn Enzymes, Kazan 420008, Russia. EM lilia.znamenskaya@ksu.ru RI Vershinina, Valentina/N-1744-2016 OI Vershinina, Valentina/0000-0001-5712-3325 NR 14 TC 8 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD APR 1 PY 1999 VL 173 IS 1 BP 217 EP 222 PG 6 WC Microbiology SC Microbiology GA 178ZU UT WOS:000079299700029 PM 10220898 ER PT J AU Nutan, MTH Hasan, CM Rashid, MA AF Nutan, MTH Hasan, CM Rashid, MA TI Bismurrayafoline E: a new dimeric carbazole alkaloid from Murraya koenigii SO FITOTERAPIA LA English DT Article DE Murraya koenigii; bismurrayafoline E; dimeric carbazoles ID EUCHRESTIFOLIA; NMR AB The ethanolic extract of the leaves of M. koenigii afforded a new carbazole alkaloid, which was identified as bismurrayafoline E (1) on the basis of spectroscopic analysis. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ Dhaka, Fac Pharm, Dhaka 1000, Bangladesh. RP Rashid, MA (reprint author), NCI, SAIC Frederick, Frederick Canc Res & Dev Ctr, Room 32-63B,Post Box B,Bldg 560, Frederick, MD 21702 USA. NR 16 TC 22 Z9 24 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0367-326X J9 FITOTERAPIA JI Fitoterapia PD APR PY 1999 VL 70 IS 2 BP 130 EP 133 DI 10.1016/S0367-326X(98)00021-5 PG 4 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 207UD UT WOS:000080953400002 ER PT J AU McNamara, PE Ranney, CK Kantor, LS Krebs-Smith, SM AF McNamara, PE Ranney, CK Kantor, LS Krebs-Smith, SM TI The gap between food intakes and the Pyramid recommendations: measurement and food system ramifications SO FOOD POLICY LA English DT Article DE dietary patterns; food intakes; dietary recommendations; food guide pyramid; CSFII; US diet ID DIETARY SOURCES; ENERGY-INTAKE; US CHILDREN; NUTRIENTS; ADULTS AB This paper measures the current gap in food consumption between dietary guidelines and estimated food intakes. Information on the adherence of the US diet to the guidelines comes from two sources: the Continuing Survey of Food Intakes by Individuals (CSFII) and the USDA's annual Food Supply Data (FSD) Series. We review previous studies and supplement these with our own analysis of the 1994 CSFII and Food Supply data with Food Guide Pyramid serving recommendations. These analyses show that the greatest relative gaps occur in the fruit and dairy groups, and added sugars; smaller gaps exist for the other food groups. We also consider how future demographic changes will influence the size of these gaps. If current dietary patterns are maintained in each category of age, sex, and ethnicity, then we project substantial future increases in the gap at the aggregate food supply level for most food groups. The magnitude of the gap between current intakes and the Pyramid recommendations suggests the need for continued increases in agricultural productivity, higher resource use, and greater levels of international trade if the gap is to be closed. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Cornell Univ, Dept Agr Resource & Managerial Econ, Ithaca, NY 14853 USA. Econ Res Serv, Food & Rural Econ Div, USDA, Washington, DC 20036 USA. NCI, NIH, Bethesda, MD 20892 USA. RP McNamara, PE (reprint author), Cornell Univ, Dept Agr Resource & Managerial Econ, Ithaca, NY 14853 USA. NR 23 TC 13 Z9 13 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0306-9192 J9 FOOD POLICY JI Food Policy PD APR-JUN PY 1999 VL 24 IS 2-3 BP 117 EP 133 DI 10.1016/S0306-9192(99)00020-2 PG 17 WC Agricultural Economics & Policy; Economics; Food Science & Technology; Nutrition & Dietetics SC Agriculture; Business & Economics; Food Science & Technology; Nutrition & Dietetics GA 209YT UT WOS:000081078300002 ER PT J AU Lands, WEM AF Lands, WEM TI Fatty acids article unclear - Author Lands responds SO FOOD TECHNOLOGY LA English DT Letter C1 Univ Maryland, Bethesda, MD USA. NIAAA, Natl Inst Hlth, Bethesda, MD USA. RP Lands, WEM (reprint author), Univ Maryland, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INST FOOD TECHNOLOGISTS PI CHICAGO PA SUITE 300 221 N LASALLE ST, CHICAGO, IL 60601-1291 USA SN 0015-6639 J9 FOOD TECHNOL-CHICAGO JI Food Technol. PD APR PY 1999 VL 53 IS 4 BP 112 EP 112 PG 1 WC Food Science & Technology SC Food Science & Technology GA 187JM UT WOS:000079783600026 ER PT J AU Misik, V Riesz, P AF Misik, V Riesz, P TI EPR characterization of free radical intermediates formed during ultrasound exposure of cell culture media SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE ultrasound; cell culture media; free radicals; spin trapping; EPR spectroscopy ID AQUEOUS-SOLUTION; CYTOCHROME-C; IN-VITRO; SONOCHEMISTRY; CYTOTOXICITY; CAVITATION; GENERATION AB Free radicals and/or hydrogen peroxide produced by exposure of cells to ultrasound are potentially cytotoxic and mutagenic. The formation and type of free radical species can be substantially modulated by the chemical composition of the media in which the ultrasound exposures of cells are carried out. In the current study, we examined the free radical intermediates formed during ultrasound exposure of a typical cell culture medium (RPMI-1640); the dominant free radicals that were identified by spin trapping were derived from the hydrophobic amino acids Trp, Leu, and Phe, and were formed by hydrogen abstraction from these amino acids. Compared to exposures in phosphate-buffered saline, the yield of (OH)-O-. radicals and H2O2 was significantly reduced in the cell culture medium, glucose (the main organic component in the medium), and the hydrophobic amino acids (Trp, Phe, Tyr, Leu, Val, Met) being chiefly responsible for this effect. In contrast, other nonhydrophobic amino acids did not contribute significantly to the (OH)-O-. or H2O2 decrease. These findings are consistent with the accumulation of hydrophobic solutes at the liquid-gas interface of the collapsing cavitation bubbles resulting in increased efficiency of radical scavenging. (C) 1999 Elsevier Science Inc. C1 NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. RP Riesz, P (reprint author), NCI, Radiat Biol Branch, NIH, Bldg 10,Room B3-B69, Bethesda, MD 20892 USA. NR 26 TC 18 Z9 21 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD APR PY 1999 VL 26 IS 7-8 BP 936 EP 943 DI 10.1016/S0891-5849(98)00282-2 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 188KP UT WOS:000079845800017 PM 10232837 ER PT J AU Misik, V Miyoshi, N Riesz, P AF Misik, V Miyoshi, N Riesz, P TI Effects of cysteamine and cystamine on the sonochemical accumulation of hydrogen peroxide - Implications for their mechanisms of action in ultrasound-exposed cells SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE ultrasound; cysteamine; free radicals; spin trapping; EPR spectroscopy ID FREE-RADICAL FORMATION; PULSE-RADIOLYSIS; IN-VITRO; INVITRO; CAVITATION; FREQUENCY; SYSTEM; DNA AB Based on the observed cytoprotective effect of the intracellularly permeable radical scavenger cysteamine (+NH3CH2CH2SH) in cells exposed to ultrasound and the lack of protection by its oxidized cell-nonpermeable form, cystamine (+NH3CH2CH2S-SCH2CH2NH3+), it was suggested that inertial cavitation (the growth of small gas bubbles present in the liquid exposed to ultrasound and their subsequent violent collapse) and associated free radical production may occur intracellularly (Radiat. Res. 89:369; 1982). Here we demonstrate that high concentrations (>10 mM) of the thiol cysteamine effectively lower H2O2 yields following ultrasound exposure in argon- and air-saturated phosphate buffered saline (PBS), while cystamine is less effective under argon and practically without effect in air-saturated PBS. Direct removal of H2O2 by cysteamine is the dominant mechanism while scavenging of the H2O2 precursors (OH)-O-. and superoxide plays a lesser role. Since H2O2 is a known cytotoxic species capable of penetrating cells if produced extracellularly, these results offer an alternative hypothesis for the protective effect of cysteamine and the lack of protection by cystamine, based on their differential ability to lower ultrasound-dependent H2O2 yields, without the necessity of invoking intracellular cavitation. (C) 1999 Elsevier Science Inc. C1 NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. Fukui Med Univ, Dept Pathol, Fukui, Japan. RP Riesz, P (reprint author), NCI, Radiat Biol Branch, NIH, Bldg 10,Room B3-B69, Bethesda, MD 20892 USA. NR 25 TC 17 Z9 18 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD APR PY 1999 VL 26 IS 7-8 BP 961 EP 967 DI 10.1016/S0891-5849(98)00279-2 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 188KP UT WOS:000079845800020 PM 10232840 ER PT J AU Anlauf, M Schaefer, MKH Eiden, L Rothmund, M Eissele, R Arnold, R Weihe, E AF Anlauf, M Schaefer, MKH Eiden, L Rothmund, M Eissele, R Arnold, R Weihe, E TI Differentiation of dopaminergic, cholinergic and VIPergic phenotypes in the human gastrointestinal nervous system SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIMH, Bethesda, MD USA. Univ Marburg, Marburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G2584 BP A590 EP A590 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402585 ER PT J AU Bouma, G Garcia-Gonzalez, MA Danze, PM Crusius, JBA Felt-Bersma, RJF Meuwissen, SGM Schreuder, GMT Colombel, JF Pena, AS AF Bouma, G Garcia-Gonzalez, MA Danze, PM Crusius, JBA Felt-Bersma, RJF Meuwissen, SGM Schreuder, GMT Colombel, JF Pena, AS TI Decreased frequency of HLA-DR3 in filtulising Crohn's disease SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Mucosal Immun Sect, Bethesda, MD 20892 USA. NIH, Dept Gastroenterol, Bethesda, MD 20892 USA. Vrije Univ Amsterdam, Amsterdam, Netherlands. Hosp Huriez, Lille, France. Dept Immunohematol, Lille, France. Blood Bank, Lille, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G2931 BP A672 EP A672 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402932 ER PT J AU Bouma, G Garcia-Gonzalez, MA Danze, PM Crusius, JBA Felt-Bersma, RJF Meuwissen, S Schreuder, GMT Colombel, JF Pena, AS AF Bouma, G Garcia-Gonzalez, MA Danze, PM Crusius, JBA Felt-Bersma, RJF Meuwissen, S Schreuder, GMT Colombel, JF Pena, AS TI Decreased frequency of HLA-DR3 in fistulising Cohn's disease SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Vrije Univ Amsterdam, Dept Gastroenterol, Amsterdam, Netherlands. Hosp Claude Huriez, Dept Hepatogastroenterol, Lille, France. Free Univ Amsterdam Hosp, Dept Gastroenterol, Amsterdam, Netherlands. LUMC, Dept Immunohematol, Leiden, Netherlands. LUMC, Blood Bank, Leiden, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G2930 BP A672 EP A672 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402931 ER PT J AU Brant, SR LaBuda, MC Lee, S Mann, J Pickles, M Rohal, PM Picco, MF Bailey-Wilson, JE Kirschner, BS Hanauer, SB Cho, JH Bayless, TM AF Brant, SR LaBuda, MC Lee, S Mann, J Pickles, M Rohal, PM Picco, MF Bailey-Wilson, JE Kirschner, BS Hanauer, SB Cho, JH Bayless, TM TI Younger age of diagnosis identifies families with greater linkage evidence for IBD loci on chromosomes 1p, 3q, and 16 SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Johns Hopkins Univ, Baltimore, MD USA. Univ Chicago, Chicago, IL 60637 USA. NHGRI, NIH, Baltimore, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G2932 BP A673 EP A673 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402933 ER PT J AU Breidert, M Miehlke, S Orban, Z Glasow, A Stolte, M Ehninger, G Bayerdoerffer, E Nettesheim, O Halm, U Haidan, A Bornstein, SR AF Breidert, M Miehlke, S Orban, Z Glasow, A Stolte, M Ehninger, G Bayerdoerffer, E Nettesheim, O Halm, U Haidan, A Bornstein, SR TI Expression of leptin and its receptor in normal human gastric mucosa and Helicobacter pylori-associated gastritis SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Tech Univ Hosp Dresden, Dept Med 1, Dresden, Germany. NIH, Dev Endocrinol Branch, Bethesda, MD 20892 USA. Univ Hosp, Dept Med 3, Leipzig, Germany. Clinum Bayreuth, Inst Pathol, Bayreuth, Germany. Univ Leipzig, D-7010 Leipzig, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G0550 BP A128 EP A128 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778400551 ER PT J AU Cohen, MB Giannella, RA Lang, D Parker, S Brunner, L Hawkins, J Gunther, C Schiff, GM AF Cohen, MB Giannella, RA Lang, D Parker, S Brunner, L Hawkins, J Gunther, C Schiff, GM TI Development of a human volunteer challenge model for cholera using frozen bacteria of the epidemic serotype, V-cholerae O139 SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Childrens Hosp & Med Ctr, Cincinnati, OH USA. VA Med Ctr, Cincinnati, OH USA. Univ Cincinnati, Cincinnati, OH USA. NIDDK, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G2978 BP A683 EP A683 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402979 ER PT J AU Corleto, VD Annibale, B Gibril, F Angeletti, S Serrano, J Jensen, RT Delle Fave, G AF Corleto, VD Annibale, B Gibril, F Angeletti, S Serrano, J Jensen, RT Delle Fave, G TI Could the widespread use of proton pump inhibitors (PPI) mask, delay and or complicate the diagnosis of Zollinger-Ellison syndrome(ZES)? SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ La Sapienza, Rome, Italy. NIH, Bethesda, MD 20892 USA. Policlin Umberto I, Med Clin 2, I-00161 Rome, Italy. NR 0 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G4844 BP A1117 EP A1117 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778404845 ER PT J AU Franchimont, D Martens, H Louis, E Geenen, V Belaiche, J AF Franchimont, D Martens, H Louis, E Geenen, V Belaiche, J TI Opposite effect of interleukin-10 and tumor necrosis factor alpha on the corticosensitivity of human monocytes: Basic implications for cytokine therapies SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G3119 BP A718 EP A718 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778403120 ER PT J AU Franchimont, D Bouma, G Haidan, A Fuss, I Chrousos, GP Strober, W Bornstein, SR AF Franchimont, D Bouma, G Haidan, A Fuss, I Chrousos, GP Strober, W Bornstein, SR TI Functional and morphological changes in adrenals of TNBS-induced colitis in mice SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G3118 BP A718 EP A718 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778403119 ER PT J AU Fuss, IJ Kitani, A Nakamura, K Chua, K Strober, W AF Fuss, IJ Kitani, A Nakamura, K Chua, K Strober, W TI Successful treatment of experimental (TNBS) colitis by intranasal transfer of DNA encoding active TGF-beta. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G3130 BP A721 EP A721 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778403131 ER PT J AU Garcia-Marin, LJ Ferris, HA Tapia, JA Jensen, RT AF Garcia-Marin, LJ Ferris, HA Tapia, JA Jensen, RT TI A role for PYK2 in linking CCKA receptors with MAPK signaling pathway activation in rat pancreatic acini SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 UEX, Sch Vet, Caceres, Spain. NIDDK, DDB, NIH, Bethesda, MD USA. RI Tapia, Jose/C-5181-2008 OI Tapia, Jose/0000-0002-3614-6867 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G4885 BP A1127 EP A1127 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778404886 ER PT J AU Gaspard, JP Graeme-Cook, F Warshaw, AL Jensen, RT Chung, DC AF Gaspard, JP Graeme-Cook, F Warshaw, AL Jensen, RT Chung, DC TI Loss of imprinting and overexpression of IGF-II in pancreatic endocrine tumors. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G4836 BP A1115 EP A1115 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778404837 ER PT J AU Gibril, F Feigenbaum, K Roy, PK Peghini, PL Goebel, SU Serrano, J Jensen, RT AF Gibril, F Feigenbaum, K Roy, PK Peghini, PL Goebel, SU Serrano, J Jensen, RT TI Does the magnitude of gastric acid output correlate with the extent of hypergastrinemia in patients with Zollinger-Ellison syndrome (ZES)? A prospective study SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G0742 BP A170 EP A171 PN 2 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778400743 ER PT J AU Gibril, F Norton, JA Alexander, HR Roy, PK Serrano, J Goebel, SU Peghini, PL Jensen, RT AF Gibril, F Norton, JA Alexander, HR Roy, PK Serrano, J Goebel, SU Peghini, PL Jensen, RT TI Does gastrinoma location affect the ability to render patients with Zollinger-Ellison syndrome (ZES) disease-free? A prospective study SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G4887 BP A1127 EP A1127 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778404888 ER PT J AU Goebel, S Heppner, C Burns, AL Marx, SJ Spiegel, AM Zhuang, Z Lubensky, IA Gibril, F Jensen, RT Serrano, J AF Goebel, S Heppner, C Burns, AL Marx, SJ Spiegel, AM Zhuang, Z Lubensky, IA Gibril, F Jensen, RT Serrano, J TI Genotype phenotype correlation of MEN 1 gene mutations in sporadic gastrinomas SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G1807 BP A412 EP A412 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778401808 ER PT J AU Gonsky, R Deem, RL Young, HA Targan, SR AF Gonsky, R Deem, RL Young, HA Targan, SR TI Mucosal specific targets for regulation of IFN-gamma expression: Lamina propria T cells utilize different cis elements compared to peripheral blood T cells for regulating transactivation of IFN-gamma expression SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NCI, Frederick Canc Res & Dev Ctr, Expt Immunol Lab, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G3148 BP A725 EP A725 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778403149 ER PT J AU Grimm, MC Hassim, Z Lloyd, AR Oppenheim, JJ AF Grimm, MC Hassim, Z Lloyd, AR Oppenheim, JJ TI Chemokine receptors are inhibited by vasoactive intestinal peptide: Desensitization of HIV-1 co-receptors SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. Univ New S Wales, Kensington, NSW 2033, Australia. NR 1 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G3160 BP A728 EP A728 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778403161 ER PT J AU Grubel, P Frenck, RW Willis, DH Goddard, PJ Abu-Elyazeed, RR Naficy, A Cave, DR AF Grubel, P Frenck, RW Willis, DH Goddard, PJ Abu-Elyazeed, RR Naficy, A Cave, DR TI HPSA enzyme immunoassay for detection of H-pylori from stool samples collected from a field setting in Egypt SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 St Elizabeths Med Ctr, Boston, MA USA. Naval Med Res Unit 3, Cairo, Egypt. Meridian Diagnost, Cincinnati, OH USA. NICHHD, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G0772 BP A177 EP A177 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778400773 ER PT J AU Habib, KE Negro, PJ Negro, PP Gold, PW AF Habib, KE Negro, PJ Negro, PP Gold, PW TI Endogenous opioids contribute to gastric ulcerogenesis during immobilization stress in male Sprague-Dawley rats. Recognition of beta-endorphin immunoreactivity in the gastric mucosa. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Georgetown Univ, Washington, DC USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G0782 BP A179 EP A179 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778400783 ER PT J AU Habib, KE Sciullo, D Negro, PJ Gold, PW AF Habib, KE Sciullo, D Negro, PJ Gold, PW TI Implication of oxidative damaging mechanisms during stress ulcerogenesis: Remarkable protection by antioxidant vitamins. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G0784 BP A180 EP A180 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778400785 ER PT J AU Habib, KE Negro, PJ Sciullo, D Dib, A Gold, PW AF Habib, KE Negro, PJ Sciullo, D Dib, A Gold, PW TI Protective role of the sympathoadrenal system against stress-induced gastric mucosal injury in the rat. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G0783 BP A180 EP A180 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778400784 ER PT J AU Hou, W Ito, T Katsuno, T Mantey, S Pradhan, T Coy, DH Jensen, RT AF Hou, W Ito, T Katsuno, T Mantey, S Pradhan, T Coy, DH Jensen, RT TI Rat and guinea pig pancreatic acini possess both VIP1 and VIP2 receptors which mediate enzyme secretion SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, NIH, DDB, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G4917 BP A1134 EP A1134 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778404918 ER PT J AU Hunyady, BI Palkovits, M Mezey, E AF Hunyady, BI Palkovits, M Mezey, E TI Differential distribution of two distinct isoforms of vesicular monoamine transporters in the rat stomach SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Semmelweis Univ Med, H-1085 Budapest, Hungary. NINDS, Bethesda, MD 20892 USA. RI Palkovits, Miklos/F-2707-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G2676 BP A611 EP A611 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402677 ER PT J AU Ito, T Hou, W Mantey, SA Pradhan, T Coy, DH Jensen, RT AF Ito, T Hou, W Mantey, SA Pradhan, T Coy, DH Jensen, RT TI Differences in VIP structural requirements for high affinity interaction with human VIP receptor subtypes compared to those in rat and guinea pig SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, DDB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G2680 BP A612 EP A612 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402681 ER PT J AU Katayose, Y Suzuki, M Unno, M Takemura, S Fujiwara, K Yamamoto, K Yoshida, H Cowan, KH Seth, P Matsuno, S AF Katayose, Y Suzuki, M Unno, M Takemura, S Fujiwara, K Yamamoto, K Yoshida, H Cowan, KH Seth, P Matsuno, S TI Adenoviral expression of the cyclin-dependent kinase inhibitor p27(kip1): A strategy for cholangiocarcinoma SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Tohoku Univ, Sch Med, Sendai, Miyagi 980, Japan. NCI, Bethesda, MD 20892 USA. RI Unno, Michiaki/A-8633-2010 OI Unno, Michiaki/0000-0002-2145-6416 NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G1903 BP A434 EP A434 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778401904 ER PT J AU Khurana, S Bae, YS AF Khurana, S Bae, YS TI Tyrosine phosphorylated villin binds to the COOH-terminal SH2 domain of phospholipase C-(gamma 1) SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G2695 BP A616 EP A616 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402696 ER PT J AU Lee, H Benjamin, S Tio, L Bertagnolli, M Johnston, M Fitzgerald, W Ferrin, L AF Lee, H Benjamin, S Tio, L Bertagnolli, M Johnston, M Fitzgerald, W Ferrin, L TI Long-term primary culture of Barrett's esophagus and esophageal adenocarcinoma SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Natl Naval Med Ctr, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G1976 BP A450 EP A450 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778401977 ER PT J AU Lee, H Ferrin, LJ AF Lee, H Ferrin, LJ TI Amplified genes in gastric adenocarcinoma cell lines SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G1974 BP A449 EP A449 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778401975 ER PT J AU Limburg, PJ Dawsey, SM Qiao, YL Mark, SM Wang, GQ Perez-Perez, GI Blaser, MJ Dong, ZW Taylor, PR AF Limburg, PJ Dawsey, SM Qiao, YL Mark, SM Wang, GQ Perez-Perez, GI Blaser, MJ Dong, ZW Taylor, PR TI Helicobacter pylori seropositivity and gastric cardia cancer: Positive association in a prospective, nested case-cohort study from Linxian, China. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Beijing 100037, Peoples R China. Vanderbilt Univ, Sch Med, Nashville, TN USA. RI Qiao, You-Lin/B-4139-2012 OI Qiao, You-Lin/0000-0001-6380-0871 NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G1034 BP A238 EP A238 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778401035 ER PT J AU Liu, MT Roche, KW Wenthold, RJ Kirchgessner, A AF Liu, MT Roche, KW Wenthold, RJ Kirchgessner, A TI Agonist- and reflex-evoked internalization of the group 1 metabotropic glutamate receptor, MGLUR5, in neurochemically-identified enteric neurons SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Columbia Univ, New York, NY USA. NIH, NIDCD, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G4478 BP A1031 EP A1031 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778404479 ER PT J AU Logsdon, CD Battey, JF Ji, BA AF Logsdon, CD Battey, JF Ji, BA TI Adenoviral mediated expression of bombesin receptors in pancreatic acinar cells from receptor knock-out animals restores bombesin responsiveness SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Michigan, Ann Arbor, MI 48109 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G4966 BP A1146 EP A1146 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778404967 ER PT J AU Mantey, SA Ryan, RR Pradhan, TK Coy, DH Battey, JF Jensen, RT AF Mantey, SA Ryan, RR Pradhan, TK Coy, DH Battey, JF Jensen, RT TI Ability of a newly described, non-peptide neuromedin B receptor antagonist to interact with mammalian bombesin receptors SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G2731 BP A625 EP A625 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402732 ER PT J AU Mayoral, W Levy, HP Collier, K Francomano, CA Tio, TL AF Mayoral, W Levy, HP Collier, K Francomano, CA Tio, TL TI GI manifestations in classical (CL) and hypermobile (HM) Ehlers-Danlos syndrome (EDS): Preliminary results SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Genome Res Inst, Washington, DC USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G3941 BP A906 EP A906 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778403942 ER PT J AU Mishra, L Tang, Y Monga, SPS Weinstein, M Yang, X Rashid, A Diehl, AM Deng, CX AF Mishra, L Tang, Y Monga, SPS Weinstein, M Yang, X Rashid, A Diehl, AM Deng, CX TI Ontogeny and role in liver regeneration of SMAD2 and SMAD3; Essential components in liver formation SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 VAMC, Washington, DC USA. DVAMC, Washington, DC USA. NIDDK, NIH, Bethesda, MD USA. Johns Hopkins Univ, Baltimore, MD USA. RI deng, chuxia/N-6713-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA L0297 BP A1248 EP A1248 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778405406 ER PT J AU Mishra, L Monga, SPS Weinstein, M Rashid, A Laxman, R Deng, CX AF Mishra, L Monga, SPS Weinstein, M Rashid, A Laxman, R Deng, CX TI Effects of ethanol and lipopolysaccharine on livers of FGFR4 and FGFR3/4 knockout mice. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 VAMC, Washington, DC USA. DVAMC, Washington, DC USA. NIDDK, NIH, Bethesda, MD USA. JHU, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA L0295 BP A1247 EP A1247 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778405404 ER PT J AU Monga, SPS Danovitch, S Rashid, A Mishra, B Fleury, T Mishra, L AF Monga, SPS Danovitch, S Rashid, A Mishra, B Fleury, T Mishra, L TI Correlation of inhibition studies of ELF-3, a beta spectrin with primary biliary cirrhosis SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 DVAMC, Washington, DC USA. GWU, Washington, DC USA. JHU, Baltimore, MD USA. NHGRI, CGTB, NIH, Bethesda, MD USA. Sibley Hosp, Washington, DC USA. VAMC, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA L0296 BP A1248 EP A1248 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778405405 ER PT J AU Monga, SPS Tang, Y Rashid, A Mishra, B Diehl, AM Mishra, L AF Monga, SPS Tang, Y Rashid, A Mishra, B Diehl, AM Mishra, L TI Ontogeny, function and role in liver regeneration of ITIH-4, a liver specific serine protease inhibitor SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 DVAMC, Washington, DC USA. NHGRI, CGTB, NIH, Bethesda, MD USA. VAMC, Washington, DC USA. Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA L0294 BP A1247 EP A1247 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778405403 ER PT J AU Monga, SPS Rashid, A Wildner, O Condotti, F Mishra, B Blaese, RM Mishra, L AF Monga, SPS Rashid, A Wildner, O Condotti, F Mishra, B Blaese, RM Mishra, L TI Growth and culture of hepatic stem cells utilizing liver explant cultures SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 VAMC, Washington, DC USA. NHGRI, CGTB, NIH, Bethesda, MD USA. DVAMC, Washington, DC USA. JHU, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA L0293 BP A1247 EP A1247 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778405402 ER PT J AU Monga, SPS Kennedy, J Mishra, B Dhanasekaran, D Mishra, L AF Monga, SPS Kennedy, J Mishra, B Dhanasekaran, D Mishra, L TI Praja-1, a novel ring finger protein involved in hepatocyte apoptosis is selectively expressed in hepatocyte stem cells SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 DVAMC, Washington, DC USA. Temple Univ, Fels Inst, Philadelphia, PA 19122 USA. NHGRI, CGTB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G2045 BP A465 EP A465 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402046 ER PT J AU Roy, P Gibril, F Peghini, P Goebel, S Serrano, J Ferraro, G Delle Fave, G Jensen, RT Bordi, C AF Roy, P Gibril, F Peghini, P Goebel, S Serrano, J Ferraro, G Delle Fave, G Jensen, RT Bordi, C TI Determinants of abnormal enterochromaffin-like cell (ECL) hyperplasia in patients with sporadic Zollinger-Ellison syndrome (ZES) SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, DDB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G1296 BP A295 EP A295 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778401297 ER PT J AU Ruhl, CE Everhart, JE AF Ruhl, CE Everhart, JE TI Respiratory complications of gastroesophageal reflux disease (GERD) in a prospective, population based study SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDKD, Bethesda, MD 20892 USA. Social & Sci Syst Inc, Bethesda, MD USA. NR 0 TC 5 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G0396 BP A92 EP A92 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778400397 ER PT J AU Ryan, R Mantey, SA Pradhan, TK Coy, DH Battey, JF Jensen, RT AF Ryan, R Mantey, SA Pradhan, TK Coy, DH Battey, JF Jensen, RT TI The peptoid PD 168368 is a potent antagonist on human and rodent neuromedin B receptors SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Tulane Univ, New Orleans, LA 70118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G4655 BP A1072 EP A1072 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778404656 ER PT J AU Sebastiano, S Peluso, M Munnia, A Bonassi, S Aste, H Parodi, S AF Sebastiano, S Peluso, M Munnia, A Bonassi, S Aste, H Parodi, S TI DNA adducts and neoplastic lesions of the colon SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Natl Canc Inst, Genoa, Italy. Univ Genoa, Genoa, Italy. NR 0 TC 0 Z9 0 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G2194 BP A500 EP A500 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402195 ER PT J AU Serrano, J Goebel, SU Gibril, F Jensen, RT AF Serrano, J Goebel, SU Gibril, F Jensen, RT TI Genetic alterations in gastrinomas: An analysis of p16/CDKN2A tumor suppressor gene SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, NIH, DDB, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G5037 BP A1162 EP A1162 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778405038 ER PT J AU Serrano, J Goebel, S Jensen, RT AF Serrano, J Goebel, S Jensen, RT TI Genetic alterations of gastrinomas: An analysis of p16(INK4A)/CDKN2A tumor suppressor gene. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G2198 BP A501 EP A501 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402199 ER PT J AU Sherman, KE Eyster, ME Rouster, SD Goedert, JJ AF Sherman, KE Eyster, ME Rouster, SD Goedert, JJ TI Genotype change in hepatitis C virus infected hemophiliacs SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Penn State Univ, Coll Med, Hershey, PA USA. Univ Cincinnati, Sch Med, Cincinnati, OH USA. NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA L0417 BP A1274 EP A1274 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778405526 ER PT J AU Tapia, JA Jensen, RT Garcia, LJ AF Tapia, JA Jensen, RT Garcia, LJ TI Timulation of translocation and tyrosine phosphorylation [Try Phos] of PKC-delta in rat pancreatic acinar cells by CCK SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, DDB, NIH, Bethesda, MD USA. Univ Extremadura, Caceres, Spain. RI Tapia, Jose/C-5181-2008 OI Tapia, Jose/0000-0002-3614-6867 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G2831 BP A649 EP A649 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402832 ER PT J AU Tokita, K Katsuno, T Llinares, M Martinez, J Battey, JF Jensen, RT AF Tokita, K Katsuno, T Llinares, M Martinez, J Battey, JF Jensen, RT TI Comparison of the role of extracellular domains of the gastrin-releasing peptide receptor (GRP-R) and the neuromedin B receptor (NMB-R) for determining affinity for peptide antagonists SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G2840 BP A651 EP A651 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402841 ER PT J AU Weinstein, M Monga, SPS Rashid, A Mishra, L Deng, CX AF Weinstein, M Monga, SPS Rashid, A Mishra, L Deng, CX TI SMAD2/3 deficiency defines an essential developmental checkpoint in liver formation SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD USA. DVAMC, Washington, DC USA. JHU, Baltimore, MD USA. VAMC, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G2484 BP A566 EP A567 PN 2 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402485 ER PT J AU Weissfeld, JL Schoen, RE Hayes, RB AF Weissfeld, JL Schoen, RE Hayes, RB TI Lack of association between screen detection of colorectal adenoma and family history of colorectal cancer SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh Canc Inst, Pittsburgh, PA USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1999 VL 116 IS 4 MA G2321 BP A528 EP A529 PN 2 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 187GJ UT WOS:000079778402322 ER PT J AU Fleischer, DE Wang, GQ Dawsey, SM Strader, DB Liu, PY Zhou, B Barros, SGS Krebs, R AF Fleischer, DE Wang, GQ Dawsey, SM Strader, DB Liu, PY Zhou, B Barros, SGS Krebs, R TI Endoscopic therapy for esophageal dysplasia (ED) and early esophageal cancer (EEC) in linxian, China 1998: Implications for America SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. VAMC, Washington, DC USA. Fed RS, Porto Alegre, RS, Brazil. Olympus Amer Inc, Melville, NY 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 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1999 VL 49 IS 4 MA 198 BP AB102 EP AB102 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 188LH UT WOS:000079848100199 ER PT J AU Murphy, WJ Menotti-Raymond, M Lyons, LA Thompson, MA O'Brien, SJ AF Murphy, WJ Menotti-Raymond, M Lyons, LA Thompson, MA O'Brien, SJ TI Development of a feline whole genome radiation hybrid panel and comparative mapping of human chromosome 12 and 22 loci SO GENOMICS LA English DT Article ID DOMESTIC CAT; MAP; SEQUENCES; FELIDAE; GENES AB A 5000-rad whole genome radiation hybrid panel is described for the domestic cat, derived from irradiated male feline fibroblasts fused to a recipient hamster cell line. A panel of 93 cell lines has an estimated retention frequency of 0.39 (range 0.13-0.71) based upon PCR typing of 54 feline markers. To test the panel's utility, we determined the order of 16 Type I (coding gene) loci, 14 Type II (microsatellite) loci, and 1 endogenous retroviral element on feline chromosomes B4 and D3. Assessment of marker order derived from the RH panel was compared to assignments of the same loci using interspecies backcross mapping data, human homologue positions, and human-cat chromosome painting homologies. Assessment of concordant and discordant marker order for these loci provides improved resolution into the evolution of subchromosomal genome organizations and the methods to track them in these species. (C) 1999 Academic Press. C1 NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP Murphy, WJ (reprint author), NCI, Lab Genom Divers, Bldg 560, Frederick, MD 21702 USA. EM murphywi@mail.ncifcrf.gov NR 35 TC 36 Z9 37 U1 0 U2 3 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 APR 1 PY 1999 VL 57 IS 1 BP 1 EP 8 DI 10.1006/geno.1998.5695 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 187KN UT WOS:000079785900001 PM 10191078 ER PT J AU Menotti-Raymond, M David, VA Lyons, LA Schaffer, AA Tomlin, JF Hutton, MK O'Brien, SJ AF Menotti-Raymond, M David, VA Lyons, LA Schaffer, AA Tomlin, JF Hutton, MK O'Brien, SJ TI A genetic linkage map of microsatellites in the domestic cat (Felis catus) SO GENOMICS LA English DT Article ID MUCOPOLYSACCHARIDOSIS-TYPE-VI; GENOME; LOCI; DISEASE; POLYMORPHISMS; CONSERVATION; DEFICIENCY; EVOLUTION; SEQUENCES; MARKERS AB Of the nonprimate mammalian species with developing comparative gene maps, the feline gene map (Felis catus, Order Carnivora, 2N = 38) displays the highest level of syntenic conservation with humans, with as few as 10 translocation exchanges discriminating the human and feline genome organization. To extend this model, a genetic linkage map of microsatellite loci in the feline genome has been constructed including 246 autosomal and 7 X-linked loci. Two hundred thirty-five dinucleotide (dC . dA)(n) . (dG . dT)(n) and 18 tetranucleotide repeat loci were identified and genotyped in a two-family, 108-member multigeneration interspecies backcross pedigree between the domestic cat (F. catus) and the Asian leopard cat (Prionailurus bengalensis), Two hundred twenty-nine loci were linked to at least one other marker with a lod score greater than or equal to 3.0, identifying 34 linkage groups, Representative markers from each linkage group were assigned to specific cat chromosomes by somatic cell hybrid analysis, resulting in chromosomal assignments to 16 of the 19 feline chromosomes. Genome coverage spans approximately 2900 cM, and we estimate a genetic length for the sex-averaged map as 3300 cM. The map has an average intragroup intermarker spacing of 11 cM and provides a valuable resource for mapping phenotypic variation in the species and relating it to gene maps of other mammals, including human. (C) 1999 Academic Press. C1 NCI, Lab Genom Divers, FCRDC, Frederick, MD 21702 USA. CIT, CBEL, BIMAS, NIH, Bethesda, MD 20892 USA. PE AgGen Inc, Davis, CA 95616 USA. RP Menotti-Raymond, M (reprint author), NCI, Lab Genom Divers, FCRDC, Bldg 560,Room 11-38, Frederick, MD 21702 USA. RI Schaffer, Alejandro/F-2902-2012 NR 60 TC 259 Z9 266 U1 1 U2 34 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 APR 1 PY 1999 VL 57 IS 1 BP 9 EP 23 DI 10.1006/geno.1999.5743 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 187KN UT WOS:000079785900002 PM 10191079 ER PT J AU Fujii, T Tamura, K Copeland, NG Gilbert, DJ Jenkins, NA Yomogida, K Tanaka, H Nishimune, Y Nojima, H Abiko, Y AF Fujii, T Tamura, K Copeland, NG Gilbert, DJ Jenkins, NA Yomogida, K Tanaka, H Nishimune, Y Nojima, H Abiko, Y TI Sperizin is a murine RING zinc-finger protein specifically expressed in haploid germ cells SO GENOMICS LA English DT Article ID INTRONLESS GENE; MOUSE; TRANSCRIPTION; CDNA; DNA; SPERMATOGENESIS; IDENTIFICATION; ORGANIZATION; LIBRARIES; SEQUENCE AB Through the preparation of a subtracted cDNA library, we have extensively isolated genes whose expression is induced in mouse spermatogenic cells. One of the genes encoded a protein with a RING zinc-finger motif, which we termed sperizin (spermatid-specific ring zinc finger). Transcription of the sperizin gene was not observed in prepubertal testis, but became detectable at day 23. Northern and in situ hybridization analyses indicated that the sperizin gene was exclusively expressed in the round spermatid. The sperizin gene is intronless, and GFP-tagged sperizin was found to be localized in the cytoplasm of ectopically expressed somatic cultured cells. We assigned the chromosomal localization of the sperizin gene to chromosome 17 using an interspecific backcross mapping panel. The data suggest that we have identified a new member of the RING-finger family of proteins that may be involved in spermatogenesis. (C) 1999 Academic Press. C1 Osaka Univ, Microbial Dis Res Inst, Dept Mol Genet, Suita, Osaka 565, Japan. Osaka Univ, Microbial Dis Res Inst, Dept Sci Lab Anim Experimentat, Suita, Osaka 565, Japan. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. Nihon Univ, Sch Dent, Dept Biochem, Matsudo, Chiba 2718587, Japan. RP Nojima, H (reprint author), Osaka Univ, Microbial Dis Res Inst, Dept Mol Genet, 3-1 Yamadaoka, Suita, Osaka 565, Japan. NR 25 TC 42 Z9 43 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 APR 1 PY 1999 VL 57 IS 1 BP 94 EP 101 DI 10.1006/geno.1998.5738 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 187KN UT WOS:000079785900011 PM 10191088 ER PT J AU Downes, GB Gilbert, DJ Copeland, NG Gautam, N Jenkins, NA AF Downes, GB Gilbert, DJ Copeland, NG Gautam, N Jenkins, NA TI Chromosomal mapping of five mouse G protein gamma subunits SO GENOMICS LA English DT Article ID NERVOUS-SYSTEM; GENE STRUCTURE; LINKAGE MAP; LOCALIZATION; EXPRESSION; RECEPTOR; KINASE; FAMILY; ORGANIZATION AB Heterotrimeric G proteins, composed of alpha, beta, and gamma subunits, transduce signals from transmembrane receptors to a wide range of intracellular effecters. The G protein gamma subunits, which play an indispensible role in this communication, constitute a large and diverse multigene family. Using an interspecific back cross panel, we have determined the mouse chromosomal locations of five gamma subunit genes: gamma 2, gamma 8, gamma 10, gamma 12, and gamma Cone. Combined with previous mapping studies, these data indicate that, with the possible exception of gamma 1 and gamma 11, the G protein gamma subunit genes are well dispersed within the mouse and human genomes. (C) 1999 Academic Press. C1 Washington Univ, Sch Med, Dept Anesthesiol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. NCI, Frederick Canc Res & Dev Ctr, Mammalian Genet Lab, Frederick, MD 21702 USA. RP Gautam, N (reprint author), Washington Univ, Sch Med, Dept Anesthesiol, St Louis, MO 63110 USA. FU NIGMS NIH HHS [R01 GM046963, GM 17289-04, GM 46963] NR 27 TC 7 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD APR 1 PY 1999 VL 57 IS 1 BP 173 EP 176 DI 10.1006/geno.1999.5763 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 187KN UT WOS:000079785900023 PM 10191100 ER PT J AU Butler, RN August, P Phillips, RA Ferdinand, KC Roccella, EJ AF Butler, RN August, P Phillips, RA Ferdinand, KC Roccella, EJ TI Hypertension: Setting new goals for lower readings - Part one of a roundtable discussion SO GERIATRICS LA English DT Editorial Material ID BLOOD-PRESSURE; HEALTH; POPULATION; MEN AB Mean systolic; blood pressures increase and mean diastolic pressures decrease with aging, primarily in response to the stiffening of blood vessels. These trends are related to the interplay of genetic factors that control renal, vascular, and hormonal functions. The prevalence of hypertension and the rate of blood pressure control vary among population groups; only one-fourth (24%) of all Americans with hypertension are controlled. Some persistent myths:about: hypertension may interfere with its diagnosis and treatment, Other barriers to control appear to be:the side effects and cost of medications. Control rates improve when physicians increase their emphasis on patient education. C1 Mt Sinai Med Ctr, Dept Geriatr & Adult Dev, New York, NY 10029 USA. Cornell Univ, Coll Med, New York, NY 10021 USA. New York Hosp, Div Hypertens, New York, NY 10021 USA. Xavier Univ, Coll Pharm, New Orleans, LA 70125 USA. Heartbeats Life Ctr, New Orleans, LA USA. Mt Sinai Sch Med, New York, NY 10029 USA. Mt Sinai Med Ctr, Zena & Michael A Wiener Cardiovasc Inst, Hypertens & Cardiac Hlth Programs, New York, NY 10029 USA. NHLBI, Natl High Blood Pressure Educ Program, NIH, Bethesda, MD 20892 USA. RP Butler, RN (reprint author), Mt Sinai Med Ctr, Dept Geriatr & Adult Dev, New York, NY 10029 USA. NR 17 TC 4 Z9 4 U1 0 U2 0 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 USA SN 0016-867X J9 GERIATRICS JI Geriatrics PD APR PY 1999 VL 54 IS 4 BP 20 EP + PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 185DG UT WOS:000079652400003 PM 10212625 ER PT J AU Ory, MG Hoffman, RR Yee, JL Tennstedt, S Schulz, R AF Ory, MG Hoffman, RR Yee, JL Tennstedt, S Schulz, R TI Prevalence and impact of caregiving: A detailed comparison between dementia and nondementia caregivers SO GERONTOLOGIST LA English DT Article DE national survey; stressors; families; services ID ALZHEIMERS-DISEASE; FAMILY CAREGIVERS; PHYSICAL HEALTH; COMMUNITY CARE; PREDICTORS; CHILDREN; COSTS AB Analyzing data from more than 1,500 family caregivers from the 1996 National Caregiver Survey, this study documents the ways in which dementia care is different from other types of family caregiving. Not only do dementia caregivers spend significantly more hours per week providing care than nondementia caregivers, they also report greater impacts in terms of employment complications, caregiver strain, mental and physical health problems, time for leisure and of her family members, and family conflict. Differential impacts remain even after controlling for intensity of caregiving involvement and sociodemographic factors. Study findings suggest the need to tailor programs and services to the unique challenges faced by dementia caregivers. C1 NIA, BSR, NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. Univ Pittsburgh, Ctr Social & Urban Res, Pittsburgh, PA 15260 USA. New England Res Inst, Watertown, MA 02172 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. RP Ory, MG (reprint author), NIA, BSR, NIH, Gateway Bldg Suite 533,7201 Wisconsin Ave,MSC 920, Bethesda, MD 20892 USA. NR 26 TC 328 Z9 333 U1 1 U2 21 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD APR PY 1999 VL 39 IS 2 BP 177 EP 185 PG 9 WC Gerontology SC Geriatrics & Gerontology GA 187JT UT WOS:000079784000006 PM 10224714 ER PT J AU Makuc, DM Breen, N Freid, V AF Makuc, DM Breen, N Freid, V TI Low income, race, and the use of mammography SO HEALTH SERVICES RESEARCH LA English DT Article DE mammography; trends; race ID UNITED-STATES; BLACK-WOMEN; BREAST; PROGRAMS; CARE AB Objective. To describe national trends in mammography use by race and income and to test whether higher use of mammography among low-income African American women than low-income white women can be explained by health insurance coverage, usual place of health care, or place of residence. Data Sources/Study Setting. Data from five years of the National Health Interview Survey spanning the period 1987-1994. Study Design. Trends in the percentage of women 50-64 years of age with a mammogram within the past two years were analyzed by race and income. Data for 1993-1994 were pooled, and with logistic regression analysis, variation in use of recent mammography for low-income women was investigated. Independent variables are age, race, family income, education, health insurance coverage, place of usual source of health care, metropolitan residence, and geographic region. Data Collection/Extraction Methods. The National Health Interview Survey is a cross-sectional national survey conducted by the National Center for Health Statistics. Data are collected through household interviews. [Editor's note: in keeping with HSR policy, the term black is used to conform to its use in the surveys studied. In other references to race, the term African American is used.] Principal Findings. Among women 50-64 years of age use of recent mammograms increased rapidly between 1987 and 1991 for all groups of women, and between 1991 and 1991 the increases slowed. However, increases between 1991 and 1994 have been more rapid among low-income black women than among low-income white women. In 1993-1994, low-income black women were about one-third more likely than low-income white women to report mammography within the past two years. This difference could not be explained by health insurance coverage, usual source of health care, metropolitan status, or region of residence. Conclusions. These results, which provide some evidence of success for screening programs targeted to the poor, raise the question of why low-income black women appear to be to more likely than low-income white women to have benefited from recent efforts to promote mammography. Continued evaluation of mammography programs focused on women who are underserved as well as the monitoring of trends and variations in service use by race and income are needed. C1 Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Hlth & Utilizat Anal, Hyattsville, MD 20782 USA. NCI, Bethesda, MD 20892 USA. RP Makuc, DM (reprint author), Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Hlth & Utilizat Anal, Room 790,6525 Belcrest Rd, Hyattsville, MD 20782 USA. NR 17 TC 70 Z9 71 U1 0 U2 0 PU HEALTH ADMINISTRATION PRESS PI MELROSE PARK PA C/O FOUNDATION AMER COLL HEALTHCARE EXECUTIVES 1951 CORNELL AVE, MELROSE PARK, IL 60160 USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD APR PY 1999 VL 34 IS 1 BP 229 EP 239 PN 2 PG 11 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 180CY UT WOS:000079368800004 PM 10199671 ER PT J AU Zimonjic, DB Keck, CL Thorgeirsson, SS Popescu, NC AF Zimonjic, DB Keck, CL Thorgeirsson, SS Popescu, NC TI Novel recurrent genetic imbalances in human hepatocellular carcinoma cell lines identified by comparative genomic hybridization SO HEPATOLOGY LA English DT Article ID C-MYC; FREQUENT LOSS; SOLID TUMORS; ALLELIC LOSS; SUPPRESSOR GENES; BREAST-CANCER; LUNG-CANCER; CYCLIN D1; HETEROZYGOSITY; CHROMOSOMES AB To search for recurrent and specific genomic alterations in human hepatocellular carcinoma (HCC), we examined 18 cell lines by comparative genomic hybridization (CGH), a molecular cytogenetic approach that allows positional identification of gains and losses of DNA sequences of the entire tumor genome. We report here a distinct pattern of multiple recurrent DNA copy-number gains and losses that include alterations frequently seen in other neoplasias as well as changes potentially specific for HCC. The most frequent gains were localized on 1p34.3-35, 1p33-34.1, 1q21-23, 1q31-32, 6p11-12, 7p21, 7q11.2, 8q24.1-24.2, 11q11-13, 12q11-13, 12q23, 17q11.2-21, 17q23-24, and 20p11.1-q13.2. Recurrent losses were mapped on 3p12-14, 3q25, 4p12-14, 4q13-34, 5q21, 6q25-26, 8p11.2-23, 9p12-24, 11q23-24, 13q12-33, 14q12-13, 15q25-26, 18q11.2-22.2, and 21q21-22. Seventeen genomic imbalances are novel in HCC, thus extending significantly the map of genetic changes and providing a starting point for the isolation of new genes relevant in pathogenesis of liver neoplasia, as well as providing molecular probes for both diagnosis and monitoring treatment of the disease. 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 69 TC 92 Z9 96 U1 0 U2 2 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 APR PY 1999 VL 29 IS 4 BP 1208 EP 1214 DI 10.1002/hep.510290410 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 180MV UT WOS:000079390500029 PM 10094966 ER PT J AU Everhart, JE Wei, YL Eng, H Charlton, MR Persing, DH Wiesner, RH Germer, JJ Lake, JR Zetterman, RK Hoofnagle, JH AF Everhart, JE Wei, YL Eng, H Charlton, MR Persing, DH Wiesner, RH Germer, JJ Lake, JR Zetterman, RK Hoofnagle, JH TI Recurrent and new hepatitis C virus infection after liver transplantation SO HEPATOLOGY LA English DT Article ID ORGAN-TRANSPLANTATION; INTERFERON THERAPY; ANTIBODY TESTS; TRANSMISSION; GENOTYPES; RNA AB Chronic infection with the hepatitis C virus (HCV) is the most common reason for liver transplantation. We examined the results of laboratory tests for HCV on a cohort of patients who received a liver transplant between 1990 and 1994 at three large centers, Seven hundred twenty-two recipients and 604 donors were tested for antibody to HCV (anti-HCV) using a second-generation enzyme-linked immunoassay (EIA-2), followed by recombinant immunoblot (RIBA-2) and HCV RNA confirmation by reverse-transcription polymerase chain reaction (RT-PCR) (with genotyping and viral quantification). Diagnosis of posttransplantation infection required detection of serum HCV RNA that could be genotyped by sequencing or was repeatedly positive despite being unsequenceable, Twenty-five percent of transplantation candidates were seropositive for anti-HCV, Approximately 86% of anti-HCV-positive, 93% of RIBA-positive, and 97% of HCV RNA-positive candidates developed infection after transplantation. Pretransplantation HCV RNA was superior to RIBA-2 for predicting posttransplantation infection. Whereas HCV genotype was identified in nearly all candidates and changed little after transplantation, serum viral levels rose markedly after transplantation. Fifteen donors were either anti-HCV- or HCV RNA-positive. Recipients of grafts from donors with HCV RNA all developed infection, whereas infection was not detected in recipients of grafts from donors with anti-HCV but without detectable HCV RNA. The rate of new infection fell significantly (P = .02) after the introduction of EIA-2 screening of blood. Donor and candidate markers for HCV predict posttransplantation infection. C1 NIDDKD, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Nebraska, Med Ctr, Omaha, NE 68105 USA. RP Everhart, JE (reprint author), Natcher Bldg,Room 6AN-12J,45 Ctr Dr MSC 6600, Bethesda, MD 20892 USA. FU NIDDK NIH HHS [N01-DK-0-2251, N01-DK-0-2252, N01-DK-0-2253] NR 25 TC 84 Z9 88 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD APR PY 1999 VL 29 IS 4 BP 1220 EP 1226 DI 10.1002/hep.510290412 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 180MV UT WOS:000079390500031 PM 10094968 ER PT J AU Jain, P Spande, TF Garraffo, HM Daly, JW AF Jain, P Spande, TF Garraffo, HM Daly, JW TI The isolation and structure of pumiliotoxin 341A: A novel cyclic ether from the frog Epipedobates tricolor SO HETEROCYCLES LA English DT Article ID ENANTIOSELECTIVE TOTAL SYNTHESIS; ION VINYLSILANE CYCLIZATIONS; A ALKALOIDS; POISON FROG; ENTRY; 339B AB An alkaloid 341A isolated by HPLC from skin extracts of the Ecuadoran poison frog Epipedobates tricolor was characterized by FTIR, MS and H-1-NMR spectral analysis and assigned a spiro-fused pyranoindolizidine structure (1). It represents the first member of a small group of pumiliotoxin alkaloids to contain a cyclic ether moiety. C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Jain, P (reprint author), Care Of Jain R, Natl Inst Pharmaceut Educ & Res, Dept Med Chem, Sector 67,SAS Nagar Mohali, Punjab 160062, India. NR 13 TC 5 Z9 5 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0385-5414 J9 HETEROCYCLES JI Heterocycles PD APR 1 PY 1999 VL 50 IS 2 BP 903 EP 912 PG 10 WC Chemistry, Organic SC Chemistry GA 186LG UT WOS:000079730300029 ER PT J AU Glasow, A Bornstein, SR Chrousos, GP Brown, JW Scherbaum, WA AF Glasow, A Bornstein, SR Chrousos, GP Brown, JW Scherbaum, WA TI Detection of Ob-receptor in human adrenal neoplasms and effect of leptin on adrenal cell proliferation SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE immunostaining; leptin receptor; adrenal pathologies ID ACTIVATED PROTEIN-KINASE; EXPRESSION; SECRETION; LINE AB Leptin, a hormone mainly secreted from adipose tissue, communicates a metabolic signal to the adrenal gland. Ob-Receptor (Ob-R) expression was reported in rat, mice and human adrenal glands. This study intended to investigate possible differences in the Ob-R expression acid distribution of Ob-R protein in human adrenal tumors as compared to normal adrenal tissue. Proliferative effects of leptin were analyzed in the human adrenocortical carcinoma cell line (NCl-H295). The full length Ob-R mRNA and the isoforms B219.1 and B219.3 could be demonstrated by RT-PCR in all adrenal tumors (n=8), the tumor cell line (NCl-H295) and normal tissue. In contrast the Ob-R isoform B219.2 was absent in the carcinoma cell line and in most of the adrenal tumors (n = 5), whereas it was present in normal adrenals. The Ob-R protein could be demonstrated in benign and malignant adrenocortical tumors. Pheochromocytomas showed only a weak immunostaining with the human Ob-R antibody. Human leptin did not affect the proliferation or variability of adrenal tumor cells as demonstrated by [H-3]-thymidine assay and WST-1 test. In conclusion, although functional leptin receptors are expressed in human adrenal tumors, leptin does not regulate tumor cell proliferation. C1 Univ Leipzig, Med Klin & Poliklin 3, Dept Internal Med 3, D-04103 Leipzig, Germany. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Miami, Sch Med, Dept Med, Miami, FL USA. US Dept Vet Affairs, Ctr Med, Miami, FL USA. Univ Dusseldorf, Diabet Res Inst, D-4000 Dusseldorf, Germany. RP Glasow, A (reprint author), Univ Leipzig, Med Klin & Poliklin 3, Dept Internal Med 3, Philipp Rosenthal Str 27, D-04103 Leipzig, Germany. NR 21 TC 32 Z9 33 U1 0 U2 0 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD APR PY 1999 VL 31 IS 4 BP 247 EP 251 DI 10.1055/s-2007-978726 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 190ZA UT WOS:000079994400001 PM 10333078 ER PT J AU Lau, EK Tayebi, N Ingraham, LJ Winfield, SL Koprivica, V Stone, DL Zimran, A Ginns, EI Sidransky, E AF Lau, EK Tayebi, N Ingraham, LJ Winfield, SL Koprivica, V Stone, DL Zimran, A Ginns, EI Sidransky, E TI Two novel polymorphic sequences in the glucocerebrosidase gene region enhance mutational screening and founder effect studies of patients with Gaucher disease SO HUMAN GENETICS LA English DT Article ID PYRUVATE-KINASE PKLR; NUCLEOTIDE-SEQUENCE; N370S MUTATION; GBA GENES; LINKAGE; HAPLOTYPE; IDENTIFICATION; HETEROGENEITY; POPULATION; PSEUDOGENE AB Gaucher disease, an inherited glycolipid storage disorder, is caused by a deficiency of the catabolic enzyme glucocerebrosidase (EC 3.2.1.45). The gene for human glucocerebrosidase is located on chromosome 1q21 and has a highly homologous pseudogene situated 16 kb downstream. We report two novel polymorphic sequences in the glucocerebrosidase gene region: the first consists of a variable number of dinucleotide (CT) repeats located 3.2 kb upstream from the glucocerebrosidase gene, and the second is a tetranucleotide (AAAT) repeat found between the glucocerebrosidase gene and its pseudogene, 9.8 kb downstream from the functional gene. These polymorphic sequences, along with a previously reported PvuII polymorphism in intron 6 of the glucocerebrosidase gene, were analyzed in patients with Gaucher disease (n=106) and in two normal control populations, one of Ashkenazi Jewish ancestry (n=72) and the second comprising non-Jewish individuals (n=46). In these samples, strong linkage disequilibrium was found between mutations N370S, c.84-85insG, and R463C and specific haplotypes; no significant linkage disequilibrium was found when examining haplotypes of patients with the L444P mutation. Studies of these polymorphic sites in several instances also led to the recognition of genotyping errors and the identification of unusual recombinant alleles. These new polymorphic sites provide additional tools for mutational screening and founder effect studies of Gaucher disease. C1 NIMH, Clin Neurosci Branch, Bethesda, MD 20892 USA. George Washington Univ, Ctr Profess Psychol, Washington, DC USA. Shaare Zedek Med Ctr, Dept Med, Gaucher Clin, IL-91000 Jerusalem, Israel. RP Sidransky, E (reprint author), NIMH, Clin Neurosci Branch, Bldg 49,Room B1EE16,49 Convent Dr,MSC4405, Bethesda, MD 20892 USA. NR 31 TC 14 Z9 15 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD APR PY 1999 VL 104 IS 4 BP 293 EP 300 DI 10.1007/s004390050957 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 201LX UT WOS:000080597200001 PM 10369158 ER PT J AU Baker, M Litvan, I Houlden, H Adamson, J Dickson, D Perez-Tur, J Hardy, J Lynch, T Bigio, E Hutton, M AF Baker, M Litvan, I Houlden, H Adamson, J Dickson, D Perez-Tur, J Hardy, J Lynch, T Bigio, E Hutton, M TI Association of an extended haplotype in the tau gene with progressive supranuclear palsy SO HUMAN MOLECULAR GENETICS LA English DT Article ID FRONTOTEMPORAL DEMENTIA; ALZHEIMERS-DISEASE; PROTEIN-TAU; CHROMOSOME-17; MUTATIONS; INVOLVEMENT; PATHOLOGY AB We describe two extended haplotypes that cover the human tau gene. In a total of similar to 200 unrelated caucasian individuals there is complete disequilibrium between polymorphisms which span the gene (which covers similar to 100 kb of DNA), This suggests that the establishment of the two haplotypes was an ancient event and either that recombination is suppressed in this region, or that recombinant genes are selected against. Furthermore, we shaw that the more common haplotype (H1) is significantly over-represented in patients with progressive supranuclear palsy (PSP), extending earlier reports of an association between an intronic dinucleotide polymorphism and PSP. C1 Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. NINDS, NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dallas, TX 75235 USA. Mater Misericordiae Hosp, Dublin 7, Ireland. RP Hutton, M (reprint author), Mayo Clin Jacksonville, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. RI Houlden, Henry/C-1532-2008; Perez-Tur, Jordi/A-2143-2010; Hardy, John/C-2451-2009; OI Houlden, Henry/0000-0002-2866-7777; Perez-Tur, Jordi/0000-0002-9111-1712; Dickson, Dennis W/0000-0001-7189-7917; Litvan, Irene/0000-0002-3485-3445 FU NIA NIH HHS [U24 AG021886]; NINDS NIH HHS [R01 NS37143-01] NR 19 TC 513 Z9 520 U1 1 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD APR PY 1999 VL 8 IS 4 BP 711 EP 715 DI 10.1093/hmg/8.4.711 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 182AU UT WOS:000079477000020 PM 10072441 ER PT J AU Fogt, F Vortmeyer, AO Poremba, C AF Fogt, F Vortmeyer, AO Poremba, C TI Bcl-2 staining in pheochromocytomas SO HUMAN PATHOLOGY LA English DT Letter C1 Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. NIH, Pathol Lab, Bethesda, MD 20892 USA. Univ Muenster, Dept Pathol, Muenster, Germany. RP Fogt, F (reprint author), Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD APR PY 1999 VL 30 IS 4 BP 486 EP 487 DI 10.1016/S0046-8177(99)90129-6 PG 2 WC Pathology SC Pathology GA 184NY UT WOS:000079619300021 PM 10208474 ER PT J AU Hilbers, U Peters, J Bornstein, SR Correa, FMA Johren, O Saavedra, JM Ehrhart-Bornstein, M AF Hilbers, U Peters, J Bornstein, SR Correa, FMA Johren, O Saavedra, JM Ehrhart-Bornstein, M TI Local renin-angiotensin system is involved in K+-induced aldosterone secretion from human adrenocortical NCI-H295 cells SO HYPERTENSION LA English DT Article DE NCI-H295 cell line; renin-angiotensin system; angiotensin II; aldosterone; potassium ID HUMAN ADRENAL-GLAND; CONVERTING ENZYME; MESSENGER-RNA; POTASSIUM; RECEPTOR; STEROIDOGENESIS; EXPRESSION; INHIBITION; RATS; CORTICOTROPIN AB NCI-H295, a human adrenocarcinoma cell line, has been proposed as a model system to define the role of the renin-angiotensin system in the regulation of aldosterone production in humans. Because the precise cellular localization of the components of the renin-angiotensin system in human adrenal cortical cells remains unclear, we investigated their localization in this defined cell system. NCI-H295 cells expressed both angiotensinogen and renin as shown by reverse transcriptase polymerase chain reaction and immunohistochemistry. Human angiotensin-converting enzyme (ACE) was not detectable by immunocytochemistry, ACE binding, or reverse transcriptase polymerase chain reaction. However, 3.5 mmol/L K+ stimulated the formation of both angiotensin I and angiotensin II 1.9- and 2.5-fold, respectively, and increased aldosterone release 3.0-fold. The K+-induced stimulation of aldosterone release was decreased by captopril and enalaprilat (24% and 26%, respectively) and by the angiotensin type 1 (AT(1))-receptor antagonist losartan (28%). Angiotensin II-induced stimulation of aldosterone release was abolished by losartan treatment. Specific [I-125]Sar1-angiotensin II binding was detected by receptor autoradiography. The binding of [I-125]Sar(1)-angiotensin II was completely displaced by the AT(1) antagonist losartan but not by the AT(2) receptor ligand PD 123319, confirming the expression of angiotensin II AT(1) receptors in NCI-H295 cells. Our results demonstrate that NCI-H295 cells express most of the components of the renin-angiotensin system. Our failure to detect ACE, however, suggests that the production of angiotensin II in NCI-H295 cells may be ACE independent. NCI-H295 cells are able to produce angiotensin II, and K+ increases aldosterone secretion in part through an angiotensin-mediated pathway. The production of angiotensin II in NCI-H295 cells demonstrates that this human cell line can be useful to characterize the role of locally produced angiotensin II in the regulation of aldosterone release. C1 NICHD, NIH, Bethesda, MD 20892 USA. Univ Leipzig, Dept Internal Med 3, D-7010 Leipzig, Germany. Univ Heidelberg, Dept Pharmacol, D-6900 Heidelberg, Germany. NIMH, Pharmacol Sect, Bethesda, MD 20892 USA. RP Ehrhart-Bornstein, M (reprint author), NICHD, NIH, Bldg 10,Room 10N262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. RI Johren, Olaf/G-6967-2011; Correa, Fernando /D-1614-2012 OI Correa, Fernando /0000-0003-4067-9524 NR 35 TC 37 Z9 37 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD APR PY 1999 VL 33 IS 4 BP 1025 EP 1030 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 188JM UT WOS:000079843100020 PM 10205242 ER PT J AU Hermel, E Han, M Hague, B Kindt, T Monaco, JJ AF Hermel, E Han, M Hague, B Kindt, T Monaco, JJ TI Isolation and mapping of the rabbit DM genes SO IMMUNOGENETICS LA English DT Article DE major histocompatibility complex; class II; antigen processing; evolution ID CLASS-II MHC; HLA-DM; PEPTIDE; POLYMORPHISM; PSEUDOGENE; EXPRESSION; ALPHA; CELLS; DISSOCIATION; SELECTION AB Proper peptide presentation by major histocompatibility complex (MHC)-encoded class II antigens is dependent on the products of the MHC DM loci. We identified the rabbit orthologues (RLA-DMA and -DMB) of human HLA-DMA and -DMB and found that they have 76.9% and 78.8% identity with HLA-DMA and -DMB, respectively. Like classical class II MHC genes, RLA-DM genes are more closely related to human HLA-DM genes than to mouse H2-DM. Among the DM family, there is a high degree of variability at the amino terminus of the DMa chains, and length variability in the cytoplasmic tails of both DMa and DM beta, The rabbit DM genes are coexpressed with class II genes in lymphoid tissues, as are the DM genes of other mammals. The RLA-DM locus maps to the class II region of the rabbit MHC, and is flanked by the DP and DOE loci. Despite having some similarities to class II genes of bony fishes, the DM family represents a separate branch of the MHC class II family. C1 Univ Cincinnati, Dept Mol Genet, Cincinnati, OH 45267 USA. Univ Cincinnati, Howard Hughes Med Inst, Cincinnati, OH 45267 USA. NIAID, Immunogenet Lab, NIH, Bethesda, MD 20892 USA. RP Hermel, E (reprint author), Indiana Univ Sch Med, Evansville Ctr, 8600 Univ Blvd, Evansville, IN 47712 USA. FU NIAID NIH HHS [AI 32761] NR 39 TC 6 Z9 7 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 APR PY 1999 VL 49 IS 4 BP 295 EP 302 DI 10.1007/s002510050496 PG 8 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 176LT UT WOS:000079153300007 PM 10079293 ER PT J AU Finke, J Ferrone, S Frey, A Mufson, A Ochoa, A AF Finke, J Ferrone, S Frey, A Mufson, A Ochoa, A TI Where have all the T cells gone? Mechanisms of immune evasion by tumors SO IMMUNOLOGY TODAY LA English DT Article ID BEARING MICE AB The immune system of tumor-bearing patients and experimental animals is adversely affected by the tumor, even early in the course of disease. A recent meeting* focused on the mechanisms involved in this phenomenon and their implications for cancer immunotherapy. C1 Cleveland Clin Fdn, Dept Immunol, Cleveland, OH 44195 USA. New York Med Coll, Dept Microbiol & Immunol, Valhalla, NY 10595 USA. NYU, Dept Cell Biol, Ctr Med, New York, NY 10016 USA. NCI, Canc Immunol Branch, Bethesda, MD 20892 USA. Louisiana State Univ, Med Ctr, New Orleans, LA 70112 USA. RP Finke, J (reprint author), Cleveland Clin Fdn, Dept Immunol, 9500 Euclid Ave, Cleveland, OH 44195 USA. NR 15 TC 135 Z9 139 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD APR PY 1999 VL 20 IS 4 BP 158 EP 160 DI 10.1016/S0167-5699(98)01435-2 PG 3 WC Immunology SC Immunology GA 181BP UT WOS:000079421000002 PM 10203710 ER PT J AU Dunn, DE Ware, RE Parker, CJ Mishoe, HO Young, NS AF Dunn, DE Ware, RE Parker, CJ Mishoe, HO Young, NS TI Research directions in paroxysmal nocturnal hemoglobinuria SO IMMUNOLOGY TODAY LA English DT Article AB Paroxysmal nocturnal hemoglobinuria (PNH) is a non-neoplastic hematopoietic stem cell disorder that can produce a life threatening syndrome of hemolysis, thrombosis and bone marrow failure. The pathophysiology and models of PNH evolution were debated at it recent workshop*. C1 NIH, NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Duke Univ, Dept Pediat Hematol Oncol, Durham, NC USA. Univ Utah, Div Hematol Oncol, Salt Lake City, UT USA. NIH, NHLBI, Div Blood Dis & Resources, Bethesda, MD 20892 USA. RP Dunn, DE (reprint author), NIH, NHLBI, Hematol Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD APR PY 1999 VL 20 IS 4 BP 168 EP 171 DI 10.1016/S0167-5699(98)01424-8 PG 4 WC Immunology SC Immunology GA 181BP UT WOS:000079421000005 PM 10203713 ER PT J AU Segal, BH Doherty, TM Wynn, TA Cheever, AW Sher, A Holland, SM AF Segal, BH Doherty, TM Wynn, TA Cheever, AW Sher, A Holland, SM TI The p47(phox-/-) mouse model of chronic granulomatous disease has normal granuloma formation and cytokine responses to Mycobacterium avium and Schistosoma mansoni eggs SO INFECTION AND IMMUNITY LA English DT Article ID MEDIATED REDOX REGULATION; VACCINE-INDUCED IMMUNITY; NECROSIS-FACTOR-ALPHA; NEUTROPHIL APOPTOSIS; HYDROGEN-PEROXIDE; RESPIRATORY BURST; T-CELLS; INFECTION; MICE; IL-12 AB Chronic granulomatous disease (CGD) is a genetic disorder of NADPH oxidase in which phagocytes are defective in generating reactive oxidants. CGD patients suffer from recurrent infections and exuberant and persistent tissue granuloma formation. We hypothesized that abnormal granulomata in CGD may result from aberrant T-cell-mediated cytokine responses. To assess Th-1-type cytokine responses and granulomata, we challenged p47(phox-/-) and wild-type mice with avirulent (SmD) or virulent (SmT) variants of Mycobacterium avium 2-151. To assess Th-2-type cytokine responses and granulomata, we used Schistosoma mansoni eggs (SME). Mononuclear cells were harvested, and cytokine responses were determined by enzyme-linked immunosorbent assay or reverse transcriptase PCR. Following SmD or SmT challenge, splenocytes from p47(phox-/-) and mild-type mice generated similar polar Th-l responses (increased levels of gamma interferon and basal levels of interleukin 4 [IL-4] and IL-5). By 8 weeks after SmT challenge, exuberant splenic granulomata developed in p47(phox-/-) and wild-type mice. After SME challenge, thoracic lymph node mononuclear cells from p47(phox-/-) and wild-type mice generated similar mixed Th-1 and Th-2 cytokine responses to SME antigen and concanavalin A. Peak lung granuloma sizes and rates of regression were similar in p47(phox-/-) and wild-type mice. These results suggest that exuberant granulomatous inflammation in CGD is probably not the result of skewing of T-cell responses toward the Th-1 or Th-2 pole. Appropriate regression of established tissue granulomata in p47(phox-/-) mice challenged with SME suggests that abnormal granuloma formation in CGD is stimulus dependent and is not an invariant feature of the disease. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Holland, SM (reprint author), NIAID, Host Def Lab, NIH, 10 Ctr Dr,Dr MSc 1886, Bethesda, MD 20892 USA. EM smh@nih.gov RI Wynn, Thomas/C-2797-2011 NR 38 TC 25 Z9 25 U1 0 U2 1 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 APR PY 1999 VL 67 IS 4 BP 1659 EP 1665 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 178QZ UT WOS:000079278700017 PM 10085000 ER PT J AU Chaussee, MS Ajdic, D Ferretti, JJ AF Chaussee, MS Ajdic, D Ferretti, JJ TI The rgg gene of Streptococcus pyogenes NZ131 positively influences extracellular SPE B production SO INFECTION AND IMMUNITY LA English DT Article ID GROUP-A STREPTOCOCCI; ERYTHROGENIC TOXIN-B; CYSTEINE PROTEASE; REGULATES EXPRESSION; PROTEINASE PRECURSOR; NUCLEOTIDE-SEQUENCE; STREPTOKINASE GENE; ESCHERICHIA-COLI; VIR REGULON; INACTIVATION AB Streptococcus pyogenes produces several extracellular proteins, including streptococcal erythrogenic toxin B (SPE B), also known as streptococcal pyrogenic exotoxin B and streptococcal proteinase. Several reports suggest that SPE B contributes to the virulence associated with S. pyogenes; however, little is known about its regulation. Nucleotide sequence data revealed the presence, upstream of the speB gene, of a gene, designated rgg, that was predicted to encode a polypeptide similar to previously described positive regulatory factors. The putative Rgg polypeptide of S. pyogenes NZ131 consisted of 280 amino acids and had a predicted molecular weight of 33,246. To assess the potential role of Rgg in the production of SPE B, the rgg gene was insertionally inactivated in S. pyogenes NZ131, which resulted in markedly decreased SPE B production, as determined both by immunoblotting and caseinolytic activity on agar plates. However, the production of other extracellular products, including streptolysin O, streptokinase, and DNase, was not affected. Complementation of the rgg mutant with an intact rgg gene copy in S. pyogenes NZ131 could restore SPE B production and confirmed that the rgg gene product is involved in the production of SPE B. C1 NIAID, Rocky Mt Labs, Microbial Struct & Funct Lab, NIH, Hamilton, MT 59840 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73190 USA. RP Chaussee, MS (reprint author), NIAID, Rocky Mt Labs, Microbial Struct & Funct Lab, NIH, 903 S 4th St, Hamilton, MT 59840 USA. FU NIAID NIH HHS [AI38406] NR 56 TC 94 Z9 96 U1 0 U2 1 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 APR PY 1999 VL 67 IS 4 BP 1715 EP 1722 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 178QZ UT WOS:000079278700026 PM 10085009 ER PT J AU Fox, JG Gorelick, PL Kullberg, MC Ge, ZM Dewhirst, FE Ward, JM AF Fox, JG Gorelick, PL Kullberg, MC Ge, ZM Dewhirst, FE Ward, JM TI Novel urease-negative Helicobacter species associated with colitis and typhlitis in IL-10-deficient mice SO INFECTION AND IMMUNITY LA English DT Article ID INFLAMMATORY BOWEL-DISEASE; SP-NOV; INTERLEUKIN-10-DEFICIENT MICE; BACTERIAL-INFECTION; HEPATICUS; ENTEROCOLITIS; LIVERS; PYLORI AB A spiral-shaped bacterium with bipolar, single-sheathed flagella was isolated from the intestines of IL-10 (interleukin-10) deficient (IL-10(-/-)) mice with inflammatory bowel disease. The organism aas microaerobic, grew at 37 and 42 degrees C, and was oxidase and catalase positive but urease negative. On the basis of 16S rRNA gene sequence analysis and biochemical and phenotypic criteria, the organism is classified as a novel helicobacter. Cesarean section-rederived IL-10(-/-) mice without helicobacter infection did not have histological evidence of intestinal inflammation. However, helicobacter-free IL-10(-/-), SCID/NCr, and A/JNCr mice experimentally inoculated with the novel urease-negative Helicobacter sp. developed variable degrees of inflammation in the lower intestine, and in immunocompetent mice, the experimental infection was accompanied by a corresponding elevated immunoglobulin G antibody response to the novel Helicobacter sp. antigen. These data support other recent studies which demonstrate that multiple Helicobacter spp. in both naturally and experimentally infected mice can induce inflammatory bowel disease. The mouse model of helicobacter-associated intestinal inflammation should prove valuable in understanding how specific microbial antigens influence a complex disease process. C1 MIT, Div Comparat Med, Cambridge, MA 02139 USA. NCI, Anim Hlth Diagnost Lab, Lab Anim Sci Program, FCRDC,Sci Applicat Int Corp, Frederick, MD 21702 USA. NCI, Vet & Tumor Pathol Sect, Anim Sci Branch, Off Lab Anim Resources,Div Basic Sci, Frederick, MD 21702 USA. NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Forsyth Dent Ctr, Boston, MA 02115 USA. RP Fox, JG (reprint author), MIT, Div Comparat Med, Cambridge, MA 02139 USA. EM jgfox@mit.edu FU NCI NIH HHS [P01 CA026731, P01CA26731, R01 CA067529, R01CA67529]; NCRR NIH HHS [RR010146]; NIDDK NIH HHS [R01 DK052413] NR 29 TC 86 Z9 88 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 APR PY 1999 VL 67 IS 4 BP 1757 EP 1762 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 178QZ UT WOS:000079278700032 PM 10085015 ER PT J AU Singh, Y Klimpel, KR Goel, S Swain, PK Leppla, SH AF Singh, Y Klimpel, KR Goel, S Swain, PK Leppla, SH TI Oligomerization of anthrax toxin protective antigen and binding of lethal factor during endocytic uptake into mammalian cells SO INFECTION AND IMMUNITY LA English DT Article ID RECEPTOR-MEDIATED ENDOCYTOSIS; BACILLUS-ANTHRACIS; ADENYLATE-CYCLASE; SURFACE; SEQUENCE; FURIN; MACROPHAGES; PRECURSOR; PROTEASE; BLOCK AB The protective antigen (PA) protein of anthrax toxin binds to a cellular receptor and is cleaved by cell surface furin to produce a 63-kDa fragment (PA63). The receptor-bound PA63 oligomerizes to a heptamer and acts to translocate the catalytic moieties of the toxin, lethal factor (LF) and edema factor (EF), from endosomes to the cytosol. In this report, we used nondenaturing gel electrophoresis to show that each PA63 subunit in the heptamer can bind one LF molecule. Studies using PA immobilized on a plastic surface showed that monomeric PA63 is also able to bind LF. The internalization of PA and LF by cells was studied,vith radiolabeled and biotinylated proteins. Uptake was relatively slow, with a half-time of 30 min. The number of moles of LF internalized was nearly equal to the number of moles of PA subunit internalized. The essential role of PA oligomerization in LF translocation was shown with PA protein cleaved at residues 313-314. The oligomers formed by these proteins during uptake into cells were not as stable when subjected to heat and detergent as were those formed by native PA. The results show that the structure of the toxin proteins and the kinetics of proteolytic activation, LF binding, and internalization are balanced in a way that allows each PA63 subunit to internalize an LF molecule, This set of proteins has evolved to achieve highly efficient internalization and membrane translocation of the catalytic components, LP and EF. C1 Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. Ctr Biochem Technol, Delhi 110007, India. RP Leppla, SH (reprint author), Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bldg 30,Rm 309, Bethesda, MD 20892 USA. NR 34 TC 84 Z9 89 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 APR PY 1999 VL 67 IS 4 BP 1853 EP 1859 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 178QZ UT WOS:000079278700044 PM 10085027 ER PT J AU Varughese, M Teixeira, AV Liu, SH Leppla, SH AF Varughese, M Teixeira, AV Liu, SH Leppla, SH TI Identification of a receptor-binding region within domain 4 of the protective antigen component of anthrax toxin SO INFECTION AND IMMUNITY LA English DT Article ID BACILLUS-ANTHRACIS; DIPHTHERIA-TOXIN; LETHAL FACTOR; MONOCLONAL-ANTIBODIES; FUSION PROTEIN; CELLS; SURFACE; SEQUENCE; DNA; MUTAGENESIS AB Anthrax toxin from Bacillus anthracis is a three-component toxin consisting of lethal factor (LF), edema factor (EF), and protective antigen (PA). LF and EF are the catalytic components of the toxin, whereas PA is the receptor-binding component. To identify residues of PA that are involved in interaction with the cellular receptor, two solvent-exposed loops of domain 4 of PA (amino acids [aa] 679 to 693 and 704 to 723) were mutagenized, and the altered proteins purified and tested for toxicity in the presence of LF. In addition to the intended substitutions, novel mutations were introduced by errors that occurred during PCR. Substitutions within the large loop (aa 704 to 723) had no effect on PA activity. A mutated protein, LST-35, with three substitutions in the small loop (aa 679 to 693), bound weakly to the receptor and was nontoxic. A mutated protein, LST-8, with changes in three separate regions did not bind to receptor and was nontoxic, Toxicity was greatly decreased by truncation of the C-terminal 3 to 5 aa, but not by their substitution with nonnative residues or the extension of the terminus with nonnative sequences. Comparison of the 28 mutant proteins described here showed that the large loop (aa 704 to 722) is not involved in receptor binding, whereas residues in and near the small loop (aa 679 to 693) play an important role in receptor interaction. Other regions of domain 4, in particular residues at the extreme C terminus, appear to play a role in stabilizing a conformation needed for receptor-binding activity. C1 Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Leppla, SH (reprint author), Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bldg 30,Room 316,30 Convent Dr MSC 4350, Bethesda, MD 20892 USA. NR 35 TC 75 Z9 81 U1 0 U2 6 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 APR PY 1999 VL 67 IS 4 BP 1860 EP 1865 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 178QZ UT WOS:000079278700045 PM 10085028 ER PT J AU Mahana, W AF Mahana, W TI Mapping of staphylococcal enterotoxin A functional binding sites and presentation by monoclonal antibodies and fusion proteins SO INFECTION AND IMMUNITY LA English DT Article ID SHOCK SYNDROME TOXIN-1; COMPLEX CLASS-II; CRYSTAL-STRUCTURE; 3-DIMENSIONAL STRUCTURE; HLA-DR; SUPERANTIGEN; BACTERIAL; MOLECULES; HLA-DR1; CELLS AB Staphylococal enterotoxins (SE) bind with high affinity to major histocompatibility complex (MHC) class II proteins and stimulate large number of T cells via the V beta region of the T-cell receptor (TCR). To map the epitopes of SE type A (SEA) involved in MHC binding and cell proliferation, 20 specific anti-SEA, monoclonal antibodies (MAbs) and two large glutathione S-transferase fusion proteins corresponding to the amino and carboxy termini, respectively, of SEA were used. The functionality of these antibodies was tested, by MHC binding inhibition, interleukin-2 production, and T-cell proliferation assays. Moreover, I studied the ability of the MAbs to present SEA in vitro to human and murine cells and their reactivity with the two fusion proteins. This study showed that ail of the MAbs have a defined effect on one or both immunological properties of SEA and were able to present SEA to human and murine cells. However, one MAb (4H8) recognized SEA but without any interference with its biological activities. When the MAbs were tested to react with the two fusion proteins representing the SEA molecule, all of the MAbs were negative except for two. These results confirmed the presence of two functionally different binding sites of SEA with MHC class II molecules and the importance of the disulfide loop for the mitogenic activity of SEA. I further demonstrated that MAbs can present SEA to immune cells independent of the site recognized by the antibody and that the integrity of the SEA molecule is very important for its functions. C1 NIAID, Immunogenet Lab, NIH, Twinbrook Facil 2, Rockville, MD 20852 USA. CHU Laval, Ctr Rech Rumathol & Immunol, Quebec City, PQ G1V 4G2, Canada. RP Mahana, W (reprint author), NIAID, Immunogenet Lab, NIH, Twinbrook Facil 2, 12441 Parklawn Dr, Rockville, MD 20852 USA. NR 34 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 1999 VL 67 IS 4 BP 1894 EP 1900 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 178QZ UT WOS:000079278700050 PM 10085033 ER PT J AU Fahey, BJ Henderson, DK AF Fahey, BJ Henderson, DK TI Reducing occupational risks in the health care workplace SO INFECTIONS IN MEDICINE LA English DT Article DE human immunodeficiency virus (HIV; hepatitis B virus (HBV; hepatitis C virus (HCV; needle stick ID NEEDLELESS INTRAVENOUS SYSTEM; HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATITIS-C VIRUS; NEEDLESTICK INJURIES; UNIVERSAL PRECAUTIONS; HOSPITAL EMPLOYEES; SHARPS INJURIES; DISPOSAL BOXES; FINAL REPORT; WORKERS AB Despite 15 years of study of occupational exposure to bloodborne pathogens and methods of prevention, health care workers continue to be exposed to human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). Medical devices designed to reduce bloodborne occupational risks have become a critical element of prevention programs. This review summarizes important device-design principles, describes a variety of safer medical devices designed, and analyzes approaches to device selection and introduction into the workplace. C1 NIH, Hosp Epidemiol Serv, Bethesda, MD 20892 USA. RP Fahey, BJ (reprint author), NIH, Hosp Epidemiol Serv, Bldg 10, Bethesda, MD 20892 USA. NR 56 TC 1 Z9 1 U1 0 U2 1 PU SCP COMMUNICATIONS INC PI NEW YORK PA 134 W 29TH ST, NEW YORK, NY 10001-5304 USA SN 0749-6524 J9 INFECT MED JI Infect. Med. PD APR PY 1999 VL 16 IS 4 BP 269 EP + PG 7 WC Infectious Diseases SC Infectious Diseases GA 190KB UT WOS:000079960800008 ER PT J AU Sun, SH Silver, PB Caspi, RR Du, Y Chan, CC Wilder, RL Remmers, EF AF Sun, SH Silver, PB Caspi, RR Du, Y Chan, CC Wilder, RL Remmers, EF TI Identification of genomic regions controlling experimental autoimmune uveoretinitis in rats SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE experimental autoimmune uveoretinitis; rat; QTL ID RHEUMATOID-ARTHRITIS FAMILIES; LINKAGE CONSERVATION; MOUSE CHROMOSOME-6; GENETIC DISSECTION; BB RAT; LOCI; SUSCEPTIBILITY; DISEASES; ENCEPHALOMYELITIS; COMMON AB The present study attempts to identify specific genetic loci contributing to experimental autoimmune uveoretinitis (EAU) susceptibility in F-2 progeny of resistant Fischer (F344/N) and susceptible Lewis (LEW/N) inbred rats. F-2 progeny of F344/N x LEW/N inbred rats were immunized with the R16 peptide of interphotoreceptor retinoid-binding protein (IRBP), A genome-wide scan was conducted using 125 simple sequence length polymorphism markers in selected F-2 animals that developed severe eye disease or remained unaffected to identify phenotype:genotype cosegregation. The F-2 population (n = 1287) demonstrated a wide range of histologically assessed EAU scores (assessed on a scale of 0-4), The disease incidence and severity were not consistent with a simple Mendelian inheritance model. Of the F-2 hybrid rats, 60% developed EAU, implying the existence of a potent susceptibility locus with incomplete penetrance associated with the LEW genome or a more complex polygenic model of inheritance. Two genomic regions, on chromosomes 4 and 12, showed strong genetic linkage to the EAU phenotype (P < 0.0016), suggesting the presence of susceptibility loci in these chromosomal regions. In conclusion, we have identified two genomic candidate intervals from D4Arb8 to D4Mit17 on chromosome 4 and from the chromosome end to D12Arb8 on chromosome 12, that appear to influence EAU susceptibility in LEW/F344 rats. Further analysis of these genomic regions may lead to identification of the susceptibility genes and to characterization of their function. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NIAMSD, Arthritis & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Caspi, RR (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N222,10 Ctr Dr,MSC 1857, Bethesda, MD 20892 USA. NR 28 TC 28 Z9 28 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 APR PY 1999 VL 11 IS 4 BP 529 EP 534 DI 10.1093/intimm/11.4.529 PG 6 WC Immunology SC Immunology GA 189LV UT WOS:000079907200006 PM 10323205 ER PT J AU Sherman, ME Lee, JS Burks, RT Struewing, JP Kurman, RJ Hartge, P AF Sherman, ME Lee, JS Burks, RT Struewing, JP Kurman, RJ Hartge, P TI Histopathologic features of ovaries at increased risk for carcinoma - A case-control analysis SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 87th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 28-MAR 06, 1998 CL BOSTON, MASSACHUSETTS SP US & Canadian Acad Pathol DE ovary; carcinoma; pathogenesis; epidemiology; precursor; carcinogenesis ID INCLUSION CYSTS; INTERACTIVE MORPHOMETRY; SURFACE EPITHELIUM; DYSPLASIA; CANCER; TUMORS AB In this study, the pathogenesis of ovarian carcinoma was investigated by women predicted to be at increased risk for developing carcinoma (cases) with ovaries removed from 121 women without known predisposing conditions (controls). The cases included 26 women who had a unilateral invasive carcinoma and 35 women undergoing prophylactic oophorectomy for a family history of ovarian cancer. As predicted by previously developed models, epithelial inclusion cysts were identified more frequently with advancing age in both cases and controls. However, the mean and maximum number of cysts per slide in a woman were not increased among cases. Surface epithelial "atypia," a designation based on a composite impression of multiple features, was found in 13% of cases compared with 3% of controls (relative risk 7.1; 95% confidence interval, 1.9 to 26.1), but this result was based on small numbers, None of the other histologic features examined was found more often in cases following age-adjustment. Reexamination of sections with well-preserved surface epithelium or inclusion cysts under oil immersion demonstrated several differences in the detection of specific features between cases and controls and increased detection of "atypia" among cases, but none of these findings reached statistical significance, It is concluded that there may be subtle differences in the surface epithelium of ovaries predisposed to developing cancer as compared with controls, but these changes are difficult to identify reliably with light microscopy. Future etiologic studies should attempt to optimize specific handling and include molecular studies and epidemiologic analyses. C1 NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20892 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Obstet & Gynecol, Baltimore, MD 21205 USA. Howard Hughes Med Inst, Bethesda, MD 20817 USA. Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. RP Hartge, P (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, EPN 443,6130 Execut Blvd, Rockville, MD 20892 USA. RI Struewing, Jeffery/C-3221-2008; Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 NR 22 TC 34 Z9 36 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD APR PY 1999 VL 18 IS 2 BP 151 EP 157 DI 10.1097/00004347-199904000-00009 PG 7 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 180EE UT WOS:000079372000009 PM 10202673 ER PT J AU Williamson, DL Sakaguchi, B Hackett, KJ Whitcomb, RF Tully, JG Carle, P Bove, JM Adams, JR Konai, M Henegar, RB AF Williamson, DL Sakaguchi, B Hackett, KJ Whitcomb, RF Tully, JG Carle, P Bove, JM Adams, JR Konai, M Henegar, RB TI Spiroplasma poulsonii sp. nov., a new species associated with male-lethality in Drosophila willistoni, a neotropical species of fruit fly SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article DE Spiroplasma poulsonii sp. nov.; mollicute; sex ratio; Drosophila willistoni ID CORN STUNT DISEASE; GENUS SPIROPLASMA; CLASS MOLLICUTES; CLASSIFICATION; PATHOGENICITY; CULTIVATION; MYCOPLASMAS; DEFORMATION; MORPHOLOGY; GROWTH AB Progenies from some wild-caught females of Drosophila willistoni and three other sibling species are entirely female. The proclivity for production of unisexual female progeny by these flies was named the sex ratio (SR) trait and was originally thought to be genetic. However, experiments in the laboratory of Donald F. Poulson in the early 1960s demonstrated that this 'trait' was vertically transmitted and infectious, in that it could be artificially transferred by injection from infected females to non-infected females. Motile, helical micro-organisms were observed in females showing the trait. In 1979, the SR organisms were designated as group II in the informal spiroplasma classification system. The organisms proved to be extremely fastidious, but were eventually cultivated in a very complex cell-free medium (H-2) after initial co-cultivation with insect cells. Cultivation in the H-2 medium and the subsequent availability of a triply cloned strain (DW-1(T)) permitted comparative studies. Cells of strain DW-1T were helical, motile filaments 200-250 nm in diameter and were bound by a single trilaminar membrane. Cells plated on 1.8% Noble agar formed small satellite-free colonies 60-70 mu m in diameter with dense centres and uneven edges. The temperature range for growth was 26-30 degrees C; optimum growth occurred at 30 degrees C, with a doubling time in H-2 medium of 15.8 h. The strain passed through filters with 220 nm, but not 100 nm, pores. Reciprocal serological comparisons of strain DW-1T with representatives of other spiroplasma groups showed an extensive pattern of one-way crossing when strain DW-1T was used as antigen. However, variable, usually low-level reciprocal cross-reactions were observed between strain DW-1(T) and representatives of group I sub-groups. The genome size of strain DW-1T was 2040 kbp, as determined by PFGE. The G+C content was 26+/-1 mol%, as determined by buoyant density and melting point methods. The serological and molecular data indicate that strain DW-1T is separated from group I representative strains sufficiently to justify retention of its group status. Continued group designation is also indicated by the ability of SR spiroplasmas to induce male lethality in Drosophila, their vertical transmissibility and their extremely fastidious growth requirements. Group II spiroplasmas, represented by strain DW-1T (ATCC 43153(T)), are designated Spiroplasma poulsonii. C1 SUNY Stony Brook, Dept Anat Sci, Stony Brook, NY 11794 USA. Kyushu Univ, Fac Agr, Fukuoka 812, Japan. USDA, Insect Biocontrol Lab, Beltsville, MD 20705 USA. USDA, Vegetable Lab, Beltsville, MD 20705 USA. NIAID, Mycoplasma Sect, Mol Microbiol Lab, Frederick Canc Res Facil, Frederick, MD 21702 USA. INRA, Lab Biol Cellulaire & Mol, F-33883 Villenave Dornon, France. Univ Bordeaux 2, F-33883 Villenave Dornon, France. RP Williamson, DL (reprint author), SUNY Stony Brook, Dept Anat Sci, Stony Brook, NY 11794 USA. NR 44 TC 47 Z9 54 U1 1 U2 7 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING, BERKS, ENGLAND RG7 1AE SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD APR PY 1999 VL 49 BP 611 EP 618 PN 2 PG 8 WC Microbiology SC Microbiology GA 191LU UT WOS:000080024500032 PM 10319483 ER PT J AU Xu, H Strassmann, G Chan, CC Rizzo, LV Silver, PB Wiggert, B Caspi, RR AF Xu, H Strassmann, G Chan, CC Rizzo, LV Silver, PB Wiggert, B Caspi, RR TI Protective effect of the type IV phosphodiesterase inhibitor rolipram in EAU: Protection is independent of IL-10-inducing activity SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; BLOOD MONONUCLEAR-CELLS; CYTOKINE GENE-EXPRESSION; RETINOID-BINDING PROTEIN; NECROSIS-FACTOR-ALPHA; S-ANTIGEN; MICE; RAT; PROLIFERATION; DISEASE AB PURPOSE. Experimental autoimmune uveoretinitis (EAU) is a cell-mediated model of retinal autoimmunity that is negatively regulated by interleukin (IL)-10. The antidepressant drug rolipram, a type IV phosphodiesterase inhibitor, enhances IL-10 production by monocyte/macrophages. The effect of rolipram on induction of EAU and its associated immunologic responses was investigated. METHODS. Mice were challenged for EAU induction by immunization with the retinal antigen interphotoreceptor retinoid-binding protein (IRBP) or by adoptive transfer of uveitogenic T cells and were treated with rolipram. EAU severity and immunologic responses to IRBP were analyzed. In addition, the effect of rolipram added to the culture on antigen-driven responses of primed lymph node cells was tested. RESULTS. Rolipram treatment from days -1 to 7 after immunization (afferent phase) was not protective, but severity of EAU was reduced to 50% by treatment from days 8 to 16 after immunization or when EAU was induced by adoptive transfer (efferent phase). Antigen-specific proliferation and interferon (IFN)-gamma production ex vivo by lymph node cells of protected mice were not reduced. However, the addition of rolipram directly to the culture suppressed IRBP-driven proliferation and IFN-gamma production by primed lymph node cells. Freshly explanted lymph node cells of treated mice showed inhibition of IFN-gamma mRNA but no parallel enhancement of IL-LO mRNA by quantitative polymerase chain reaction. Rolipram inhibited EAU in IL-10 knockout mice equally well compared with controls and suppressed their primed lymph node cells in culture. CONCLUSIONS. Rolipram appears to inhibit the expansion and effector function of uveitogenic T cells, raising the possibility that it may be useful for treatment of established disease. Contrary to expectations based on in vitro studies, the protective effects in vivo appear to be independent of IL-10. The observation that suppression of antigen-specific responses is demonstrable only in the physical presence of the drug suggests that, in a clinical setting, continuous administration of rolipram might be needed to sustain its therapeutic effect. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Metamorphix Inc, Baltimore, MD USA. RP Caspi, RR (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N222, Bethesda, MD 20892 USA. RI Rizzo, Luiz Vicente/B-4458-2009 NR 36 TC 13 Z9 13 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 1999 VL 40 IS 5 BP 942 EP 950 PG 9 WC Ophthalmology SC Ophthalmology GA 180DZ UT WOS:000079371500015 PM 10102291 ER PT J AU Li, WM Nagineni, C Hooks, JJ Chepelinsky, AB Egwuagu, CE AF Li, WM Nagineni, C Hooks, JJ Chepelinsky, AB Egwuagu, CE TI Interferon-gamma signaling in human retinal pigment epithelial cells mediated by STAT1, ICSBP, and IRF-1 transcription factors SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID GENE-EXPRESSION; RETINITIS PIGMENTOSA; NUCLEOTIDE-SEQUENCE; TOXOPLASMA-GONDII; TRANSGENIC MICE; CYTOKINES; CDNA; ANTIGEN; PROTEIN; INTERLEUKIN-6 AB PURPOSE. Studies have shown that interferon (IFN)-gamma stimulates expression of intercellular adhesion molecule-1 (ICAM-1), major histocompatibility complex (MHC) class II, interleukin (IL)-6, and inducible nitric oxide synthase and inhibits replication of Toxoplasma gondii in human retinal pigment epithelial (HRPE) cells. The present study was undertaken to investigate the molecular mechanisms of IFN-gamma action. METHODS. RNA, whole-cell extracts, and nuclear extracts were prepared from HRPE cells cultured in the presence or absence of IFN-gamma. Activation of IFN-gamma-responsive genes was analyzed by electrophoretic mobility shift assay, reverse transcription-polymerase chain reaction (RT-PCR), western blot analysis, and immunoprecipitation. RESULTS. HRPE cells constitutively expressed two members of the IFN regulatory factor (IRF) family of transcription factors, IRF-1 and IRF-2. After exposure to IFN-gamma, transcription of IRF-1 and IFN consensus sequence binding protein (ICSBP) genes were induced; TRF-2 gene transcription was not upregulated. Activation of IFN-gamma-responsive genes was mediated by tyrosine phosphorylation of the signal transducer and activator of transcription (STAT)-1 factor. CONCLUSIONS. This study characterized the IFN-gamma signaling pathway in HRPE cells and identified IRF-1, ICSBP, and tyrosine-phosphorylated STAT1 as mediators of IFN-gamma action in these cells. ICSBP is thought to be exclusively used in immunologic responses and has previously been detected only in lymphoid cells. However, the current study shows that ICSBP expression is inducible in HRPE cells, suggesting that it may regulate gene transcription in RPE cells and possibly in other nonimmunologic cell types. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Egwuagu, CE (reprint author), NEI, Immunol Lab, NIH, 10-10N116,10 Ctr Dr,MCS 1858, Bethesda, MD 20892 USA. NR 48 TC 22 Z9 22 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 1999 VL 40 IS 5 BP 976 EP 982 PG 7 WC Ophthalmology SC Ophthalmology GA 180DZ UT WOS:000079371500019 PM 10102295 ER PT J AU Tasaki, I AF Tasaki, I TI Rapid structural changes in nerve fibers and cells associated with their excitation processes SO JAPANESE JOURNAL OF PHYSIOLOGY LA English DT Review DE cooperative structural changes; nervous tissues; calcium-sodium ion-exchange ID DISCONTINUOUS VOLUME TRANSITIONS; SQUID GIANT-AXON; ACTION-POTENTIALS; PROPAGATED IMPULSE; MECHANICAL CHANGES; ELECTRIC ORGAN; EXCITABILITY; MEMBRANE; AXOLEMMA; GANGLION AB In a variety of nerve fibers, cells and other excitable tissues, the electric responses to electric stimuli were found to be accompanied by a transient swelling of the tissues. The rising phase of this swelling coincides with that of the electric response. By use of a heat-sensor made of polyvinylidene fluoride film, it was also shown that the electric responses of many types of excitable tissues are accompanied by simultaneous heat production, To elucidate the origin of this swelling and heat production, the process of Ca2+-Na+ exchange in synthetic anionic gel beads and rods was investigated. It is asserted that the observed signs of nerve excitation are manifestations of a rapid structural change of the cortical gel layer of the protoplasm, plasmalemma-ectoplasm complex. The importance of the rapid movement and rearrangement of water molecules in the cortical gel layer in association with excitation processes is emphasized. C1 NIMH, LCMR, NIH, Bethesda, MD 20892 USA. NICHD, LIMB, NIH, Bethesda, MD 20892 USA. RP Tasaki, I (reprint author), NIMH, LCMR, NIH, Rm 3N-17,Bldg 13, Bethesda, MD 20892 USA. NR 62 TC 63 Z9 65 U1 0 U2 4 PU CENTER ACADEMIC PUBL JAPAN PI TOKYO PA 4-16 YAYOI 2-CHOME, BUNKYO-KU, TOKYO, 113, JAPAN SN 0021-521X J9 JPN J PHYSIOL JI Jpn. J. Physiol. PD APR PY 1999 VL 49 IS 2 BP 125 EP 138 DI 10.2170/jjphysiol.49.125 PG 14 WC Physiology SC Physiology GA 211GJ UT WOS:000081152300001 PM 10393347 ER PT J AU Hertle, RW Dell'Osso, LF AF Hertle, RW Dell'Osso, LF TI Clinical and ocular motor analysis of congenital nystagmus in infancy SO JOURNAL OF AAPOS LA English DT Article ID FOVEATION DYNAMICS; VISUAL-ACUITY; MANIFEST LATENT; EYE-MOVEMENT; ALBINISM; OSCILLOPSIA; FIXATION AB Purpose: The purpose of this study was to identify the clinical and ocular motility characteristics of congenital nystagmus and to establish the range of waveforms present in infancy. Background: The clinical condition of congenital nystagmus usually begins in infancy and may or may not be associated with visual sensory system abnormalities. Little is known about its specific waveforms in infancy or their relationship to the developing visual system. Methods: Forty-three infants with involuntary ocular oscillations typical of congenital nystagmus were included in this analysis. They were evaluated both clinically and with motility recordings. Eye movement analysis was performed off line from both chart recordings and computer analysis of digitized data. Variables analyzed included age, sex, vision, ocular abnormalities, head position, null-zone or neutral-zone characteristics, symmetry, conjugacy, waveforms, frequencies, foveation times, and responses to convergence and to monocular cover. Results: Patient ages ranged from 3 to 18 months (average, 9.2 months). Seventeen patients (40%) had abnormal vision, 3 had a positive family history of nystagmus, 11 had strabismus, 16 (37%) had a head posture, 26 (60%) had null and neutral positions, 14 (33%) had binocular asymmetry, and all were horizontally conjugate. Average binocular frequency was 2.8 Hz, and average monocular frequency was 4.6 Hz. The waveforms were both jerk and pendular; average foveation periods in patients with normal vision were more than twice as long as those in patients with abnormal vision. Conclusions: Common clinical characteristics and eye-movement waveforms of congenital nystagmus begin in infancy, and waveform analysis at this time helps with both diagnosis and visual status. C1 Childrens Hosp Philadelphia, Div Ophthalmol, Philadelphia, PA USA. Univ Penn, Philadelphia, PA 19104 USA. Case Western Reserve Univ, Vet Affairs Med Ctr, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Neurol, Cleveland, OH 44106 USA. RP Hertle, RW (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,Room 2A50, Bethesda, MD 20892 USA. NR 37 TC 43 Z9 47 U1 0 U2 4 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1091-8531 J9 J AAPOS JI J. AAPOS PD APR PY 1999 VL 3 IS 2 BP 70 EP 79 DI 10.1016/S1091-8531(99)70073-X PG 10 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA 201UB UT WOS:000080613000004 PM 10221798 ER PT J AU Silva, N O'Bryan, L Medeiros, E Holand, H Suleiman, J de Mendonca, JS Patronas, N Reed, SG Klein, HG Masur, H Badaro, R AF Silva, N O'Bryan, L Medeiros, E Holand, H Suleiman, J de Mendonca, JS Patronas, N Reed, SG Klein, HG Masur, H Badaro, R TI Trypanosoma cruzi meningoencephalitis in HIV-infected patients SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE Chagas' disease; HIV; AIDS; meningoencephalitis; toxoplasmosis ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; CENTRAL-NERVOUS-SYSTEM; CHAGAS-DISEASE; IMMUNOSUPPRESSED PATIENTS; CEREBRAL MASS; AIDS; REACTIVATION; ENCEPHALITIS; PATHOLOGY; THERAPY AB Five cases of Trypanosoma cruzi meningoencephalitis in HIV-infected patients an reported. All patients presented with mass lesions on head computed tomographic scan, trypanosomes in the cerebrospinal fluid and failure to respond to antitoxoplasmosis therapy. Benznidazole therapy was associated with clinical improvement in 1 patient. Another 4 patients had T cruzi identified in a peripheral smear. T cruzi needs to be considered in the differential diagnosis of HIV-infected patients with central nervous system mass lesions if they have a history of appropriate exposure. C1 NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. Hosp Servidor Publ, Sao Paulo, Brazil. Inst Infectol Emilio Ribas, Sao Paulo, Brazil. Univ Fed Bahia, BR-41170290 Salvador, BA, Brazil. RP Masur, H (reprint author), NIH, Dept Crit Care Med, Bldg 10,Room 7D43,10 Ctr Dr MSC 1662, Bethesda, MD 20892 USA. NR 27 TC 32 Z9 34 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD APR 1 PY 1999 VL 20 IS 4 BP 342 EP 349 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 177GT UT WOS:000079202800004 PM 10096578 ER PT J AU Rogers, AS Kinsman, SB Santelli, JS Silber, TJ AF Rogers, AS Kinsman, SB Santelli, JS Silber, TJ TI Code of research ethics - Position paper of the Society for Adolescent Medicine SO JOURNAL OF ADOLESCENT HEALTH LA English DT Editorial Material C1 NICHHD, Bethesda, MD 20892 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. NR 12 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD APR PY 1999 VL 24 IS 4 BP 277 EP 282 PG 6 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 187PN UT WOS:000079795600008 ER PT J AU Rogers, AS AF Rogers, AS TI The Society for Adolescent Medicine's Code of Research Ethics SO JOURNAL OF ADOLESCENT HEALTH LA English DT Editorial Material RP Rogers, AS (reprint author), NICHHD, Pediat Adolescent & Maternal AIDS Branch, Execut Bldg Rm 4 B11,611 Execut Blvd,MSC 7510, Bethesda, MD 20892 USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD APR PY 1999 VL 24 IS 4 BP 283 EP 283 PG 1 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 187PN UT WOS:000079795600009 PM 11645151 ER PT J AU Suppes, T Brown, ES McElroy, SL Keck, PE Nolen, W Kupka, R Frye, M Denicoff, KD Altshuler, L Leverich, GS Post, RM AF Suppes, T Brown, ES McElroy, SL Keck, PE Nolen, W Kupka, R Frye, M Denicoff, KD Altshuler, L Leverich, GS Post, RM TI Lamotrigine for the treatment of bipolar disorder: a clinical case series SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE lamotrigine; treatment; bipolar disorder; bipolar depression; mood lability ID ILLNESS AB Background: Recently, a number of new agents have become available to treat bipolar disorder, however many patients may not respond fully even when used in combination. Early reports in epilepsy studies suggested mood-related effects of lamotrigine treatment, as have preliminary reports in bipolar patients. Methods: Seventeen patients meeting DSM-IV criteria for bipolar I (n = 9) or bipolar II (n = 8) disorder displaying affective symptoms and a past history of inadequate response or tolerability to at least two standard mood stabilizing agents were recruited through the Stanley Foundation Bipolar Network and treated with the new anticonvulsant lamotrigine in an add-on, open-label study. Response to therapy was assessed using the Clinical Global Impression Scale modified for bipolar disorder. Results: The mean dose of lamotrigine was 187+/-157 mg/day (range 50-600 mg/day) for a mean duration of 159+/-109 days (range 14-455 days). Eleven (65%) patients were rated as very much or much improved. Lamotrigine was well tolerated, and may have mood stabilizing and antidepressant properties in some patients with bipolar disorder. Limitations: The study is hypothesis generating because it was uncontrolled and open. Controlled studies are warranted. Conclusions: This preliminary report supports clinical improvement for both mood cycling and depression in patients with bipolar disorder treated with lamotrigine. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Stanley Fdn Bipolar Network, Dallas, TX 75235 USA. Univ Texas, SW Med Ctr, Dallas, TX 75235 USA. Univ Cincinnati, Coll Med, Dept Psychiat, Stanley Fdn Bipolar Network,Biol Psychiat Program, Cincinnati, OH 45267 USA. NIMH, Stanley Fdn Bipolar Network, Biol Psychiat Branch, Bethesda, MD USA. Univ Calif Los Angeles, Stanley Fdn Bipolar Network, Los Angeles, CA USA. HC Rumke Grp, SFBN, Utrecht, Netherlands. RP Suppes, T (reprint author), Stanley Fdn Bipolar Network, Dallas, TX 75235 USA. RI Nolen, Willem/E-9006-2014 NR 11 TC 54 Z9 54 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD APR PY 1999 VL 53 IS 1 BP 95 EP 98 DI 10.1016/S0165-0327(98)00077-9 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 196JU UT WOS:000080305900012 PM 10363672 ER PT J AU Vliagoftis, H Hutson, AM Mahmudi-Azer, S Kim, H Rumsaeng, V Oh, CK Moqbel, R Metcalfe, DD AF Vliagoftis, H Hutson, AM Mahmudi-Azer, S Kim, H Rumsaeng, V Oh, CK Moqbel, R Metcalfe, DD TI Mast cells express connexins on their cytoplasmic membrane SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE mast cells; connexins; gap junctions; fibroblasts; cell communication ID GAP JUNCTIONAL COMMUNICATION; EPITHELIAL-CELLS; MESSENGER-RNA; FIBROBLASTS; RAT; LIVER; BETA; GROWTH; IL-3; MICE AB Background: Because of the close association between mast cells and fibroblasts in the microenvironment and the importance of connexins (Cxs) in fibroblast communication with other cells, we hypothesized that mast cells also express Cxs, allowing them to similarly communicate with other cells through gap junctions. Objectives: We sought to identify the expression of Cxs (particularly Cx43, Cx32, and Cx26) by murine mast cells. Methods: The expression of Cxs was studied by RT-PCR, Northern blot analysis, Western blot analysis, flow cytometry, and confocal laser scanning microscopy. Results: In this report we demonstrate that murine bone marrow cultured mast cells and the growth factor-independent murine mast cell line C57, express Cx43 and Cx32 as assessed by RT-PCR, Northern blot analysis, Western blot analysis, and flow cytometry, but do not express Cx26, We also show, by confocal laser scanning microscopy, that Cx43 localizes to the cytoplasmic membrane of mast cells in a pattern similar to that seen in fibroblasts, Conclusions: Mast cells express Cx43 and Cx32, and Cx43 is associated with the cytoplasmic membrane, suggesting that mast cells have the potential to communicate with other cells in their microenvironment in part through gap junctions. C1 Univ Alberta, Dept Med, Pulm Res Grp, Edmonton, AB T6G 2S2, Canada. NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA. RP Vliagoftis, H (reprint author), Univ Alberta, Dept Med, Pulm Res Grp, 574 HMRC, Edmonton, AB T6G 2S2, Canada. RI Vliagoftis, Harissios/C-6480-2013 NR 25 TC 23 Z9 25 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 APR PY 1999 VL 103 IS 4 BP 656 EP 662 DI 10.1016/S0091-6749(99)70239-3 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 186HY UT WOS:000079723900020 PM 10200016 ER PT J AU Itaya, M Omori, A Kanaya, S Crouch, RJ Tanaka, T Kondo, K AF Itaya, M Omori, A Kanaya, S Crouch, RJ Tanaka, T Kondo, K TI Isolation of RNase H genes that are essential for growth of Bacillus subtilis 168 SO JOURNAL OF BACTERIOLOGY LA English DT Article ID THERMUS-THERMOPHILUS HB8; COLI RIBONUCLEASE HI; ESCHERICHIA-COLI; SEQUENCE-ANALYSIS; CRYSTAL-STRUCTURE; RNHB GENE; REPLICATION; CHROMOSOME; INITIATION; CLONING AB Two genes encoding functional RNase H (EC 3.1.26.4) were isolated from a gram-positive bacterium, Bacillus subtilis 168. Two DNA clones exhibiting RNase H activities both in vivo and in vitro were obtained from a B. subtilis DNA library. One (28.1 kDa) revealed high similarity to Escherichia coli RNase HII, encoded by the rnhB gene. The other (33.9 kDa) was designated rnhC and encodes B. subtilis RNase HIII. The B. subtilis genome has an rnhA homologue, the product of which has not yet shown RNase H activity. Analyses of all three B. subtilis genes revealed that rnhB and rnhC cannot be simultaneously inactivated. This observation indicated that in B. subtilis both the rnhB and rnhC products are involved in certain essential cellular processes that are different from those suggested by E. coli rnh mutation studies. Sequence conservation between the rnhR and rnhC genes implies that both originated from a single ancestral RNase H gene. The roles of bacterial RNase H may be indicated by the single rnhC homologue in the small genome of Mycoplasma species. C1 Mitsubishi Kasei Inst Life Sci, Machida, Tokyo 1948511, Japan. Osaka Univ, Grad Sch Engn, Suita, Osaka 5650871, Japan. NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. RP Itaya, M (reprint author), Mitsubishi Kasei Inst Life Sci, 11 Minamiooya, Machida, Tokyo 1948511, Japan. EM ita@libra.ls.m-kagaku.co.jp NR 44 TC 61 Z9 64 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 1999 VL 181 IS 7 BP 2118 EP 2123 PG 6 WC Microbiology SC Microbiology GA 180CV UT WOS:000079368400018 PM 10094689 ER PT J AU Paterson, ES More, MI Pillay, G Cellini, C Woodgate, R Walker, GC Iyer, VN Winans, SC AF Paterson, ES More, MI Pillay, G Cellini, C Woodgate, R Walker, GC Iyer, VN Winans, SC TI Genetic analysis of the mobilization and leading regions of the IncN plasmids pKM101 and pCU1 SO JOURNAL OF BACTERIOLOGY LA English DT Article ID SITE-SPECIFIC RECOMBINATION; CONJUGATIVE TRANSFER SYSTEM; CLEAVING-JOINING REACTION; SINGLE-STRANDED-DNA; ESCHERICHIA-COLI; RELAXASE TRAI; BACTERIAL CONJUGATION; KLEBSIELLA-OXYTOCA; ENTRY EXCLUSION; ORIT REGION AB The conjugative IncN plasmids pKM101 and pCU1 have previously been shown to contain identical oriT sequences as well as conserved restriction endonuclease cleavage patterns within their tra regions. Complementation analysis and sequence data presented here indicate that these two plasmids encode essentially identical conjugal DNA-processing proteins. This region contains three genes, traI, traJ, and traK, transcribed in the same orientation from a promoter that probably lies within or near the conjugal transfer origin (oriT). Three corresponding proteins were visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and complementation analysis confirmed that this region contains three tm complementation groups. All three proteins resemble proteins of the IncW plasmid R388 and other plasmids thought to have roles in processing of plasmid DNA during conjugation. The hydropathy profile of TraJ suggests a transmembrane topology similar to that of several homologous proteins. Both traK and traI were required for efficient interplasmid site-specific recombination at oriT, while traJ was not required. The leading region of pKM101 contains three genes (stbA, stbB, and stbC), null mutations in which cause elevated levels of plasmid instability. Plasmid instability was observed only in hosts that are proficient in interplasmid recombination, suggesting that this recombination can potentially lead to plasmid loss and that Stb proteins somehow overcome this, possibly via site-specific multimer resolution. C1 Cornell Univ, Dept Microbiol, Microbiol Sect, Ithaca, NY 14853 USA. Carleton Univ, Dept Biol, Ottawa, ON K1S 5B6, Canada. MIT, Dept Biol, Cambridge, MA 02139 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Winans, SC (reprint author), Cornell Univ, Dept Microbiol, Microbiol Sect, Ithaca, NY 14853 USA. EM scw2@cornell.edu OI /0000-0001-7243-8261 FU NCI NIH HHS [CA21615, R01 CA021615]; NIGMS NIH HHS [R01 GM042893, GM42893] NR 75 TC 36 Z9 36 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 1999 VL 181 IS 8 BP 2572 EP 2583 PG 12 WC Microbiology SC Microbiology GA 186BH UT WOS:000079706600035 PM 10198024 ER PT J AU Mauras, N Hayes, VY Vieira, NE Yergey, AL O'Brien, KO AF Mauras, N Hayes, VY Vieira, NE Yergey, AL O'Brien, KO TI Profound hypogonadism has significant negative effects on calcium balance in males: A calcium kinetic study SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID GROWTH-HORMONE SECRETION; BONE-MINERAL CONTENT; MEN; TESTOSTERONE; OSTEOPOROSIS; ANDROGENS; DENSITY; PUBERTY; MASS; 1,25-DIHYDROXYVITAMIN-D AB The impact of estrogen deficiency on bone has been extensively studied in the female; however, the effects of androgen deficiency on calcium fluxes in males have been less well characterized. We investigated the effect of short-term, severe androgen deficiency on measures of calcium absorption and kinetics as well as on markers of bone turnover in males. To accomplish this, 11 healthy male volunteers were recruited (mean age 23.3 +/- 0.5 years [SEM], body mass index 25.3 +/- 0.8 kg/m(2)). They consumed a weight maintenance diet for at least 3 days prior to admission to our Research Unit, with a calcium intake of similar to 1200 mg/day. At baseline (D1), subjects received Ca-42 intravenously as well as Ca-44 PO mixed with milli or juice. A 29-h urine collection was begun and blood samples collected at frequent intervals for the measurement of the isotopic enrichment of Ca-42 and Ca-44 using thermal ionization mass spectrometry. Twice daily urine samples were collected for 5 days after the administration of the isotopes. A gonadotropin-releasing hormone agonist (Lupron) was given after D1, again 3 weeks later, and studies repeated identically 4 weeks (D2, n = 6) and 10 weeks from baseline (D3, n = 7) (two subjects completed three studies). Testosterone concentrations were markedly suppressed on both D2 and D3 (-95%, p < 0.006), whereas there were no detectable changes in growth hormone and insulin-like growth factor-1 concentrations. Urinary calcium excretion increased significantly after 4 weeks (43%, p = 0.0007) and 10 weeks (73%, p = 0.003) of sustained hypogonadism. Using a multicompartmental kinetic model, the contribution of oral calcium to the urinary losses was decreased by D3 (-41%, p = 0.01), get the contribution of bone calcium to urine losses increased by 10 weeks (+11%,p = 0.01). There was a 21% decrease in bone calcium deposition (Vo(+)) by D3 (p < 0.05) with no significant change in bone resorption rates (Vo(-)). There was a significant correlation between the decrease in testosterone concentration and the increase in urinary calcium excretion, especially at 10 weeks (R-2 = 0.84, p = 0.004). These kinetic changes were accompanied by a decrease in osteocalcin concentrations on D2, with improvements by D3. Urinary N telopeptide, a measure of bone resorption, also increased during the studies. In summary, profound hypogonadism in young males is associated,with marked increases in urinary calcium losses, with a greater contribution of bone calcium to those losses and decreased kinetic markers of bone calcium deposition. We conclude that even short-term, severe deficiency in gonadal steroids can have profound negative effects on calcium and bone metabolism in males. C1 Nemours Childrens Clin, Jacksonville, FL 32207 USA. NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA. RP Mauras, N (reprint author), Nemours Childrens Clin, 807 Nira St, Jacksonville, FL 32207 USA. FU NCRR NIH HHS [RR00585]; NIDDK NIH HHS [DK 51360] NR 31 TC 24 Z9 24 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD APR PY 1999 VL 14 IS 4 BP 577 EP 582 DI 10.1359/jbmr.1999.14.4.577 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 178LL UT WOS:000079267100013 PM 10234579 ER PT J AU Orsulic, S Huber, O Aberle, H Arnold, S Kemler, R AF Orsulic, S Huber, O Aberle, H Arnold, S Kemler, R TI E-cadherin binding prevents beta-catenin nuclear localization and beta-catenin/LEF-1-mediated transactivation SO JOURNAL OF CELL SCIENCE LA English DT Article DE APC; beta-catenin; E-cadherin; LEF/TCF; Wnt signaling ID APC TUMOR-SUPPRESSOR; CELL CELL-ADHESION; GLYCOGEN-SYNTHASE KINASE-3; TRANSCRIPTION FACTOR LEF-1; WNT SIGNALING PATHWAY; XENOPUS EMBRYOS; FUNCTIONAL INTERACTION; PROTEIN INTERACTIONS; EPITHELIAL-CELLS; AXIS FORMATION AB beta-catenin is a multifunctional protein found in three cell compartments: the plasma membrane, the cytoplasm and the nucleus. The cell has developed elaborate ways of regulating the level and localization of beta-catenin to assure its specific function in each compartment. One aspect of this regulation is inherent in the structural organization of beta-catenin itself; most of its protein-interacting motifs overlap so that interaction with one partner can block binding of another at the same time. Using recombinant proteins, we found that E-cadherin and lymphocyte-enhancer factor-1 (LEF-1) form mutually exclusive complexes with beta-catenin; the association of beta-catenin with LEF-1 was competed out by the E-cadherin cytoplasmic domain. Similarly, LEF-1 and adenomatous polyposis coli (APC) formed separate, mutually exclusive complexes with beta-catenin, In Wnt-1-transfected C57MG cells, free beta-catenin accumulated and was able to associate with LEF-1. The absence of E-cadherin in E-cadherin-/- embryonic stem (ES) cells also led to an accumulation of free beta-catenin and its association with LEF-1, thereby mimicking Wnt signaling. beta-catenin/LEF-1-mediated transactivation in these cells was antagonized by transient expression of wildtype E-cadherin, but not of E-cadherin lacking the beta-catenin binding site. The potent ability of E-cadherin to recruit beta-catenin to the cell membrane and prevent its nuclear localization and transactivation was also demonstrated using SW480 colon carcinoma cells. C1 Max Planck Inst Immunbiol, D-79108 Freiburg, Germany. RP Orsulic, S (reprint author), NCI, NIH, Bldg 49-4A56,49 Convent Dr, Bethesda, MD 20892 USA. NR 64 TC 345 Z9 348 U1 0 U2 8 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD APR PY 1999 VL 112 IS 8 BP 1237 EP 1245 PG 9 WC Cell Biology SC Cell Biology GA 193MX UT WOS:000080141300012 PM 10085258 ER PT J AU Otsuki, T Nagakura, S Wang, JX Bloom, M Grompe, M Liu, JM AF Otsuki, T Nagakura, S Wang, JX Bloom, M Grompe, M Liu, JM TI Tumor necrosis factor-alpha and CD95 ligation suppress erythropoiesis in fanconi anemia C gene knockout mice SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID HEMATOPOIETIC PROGENITOR CELLS; INTERFERON-GAMMA; IN-VITRO; INDUCED APOPTOSIS; EXPRESSION; THERAPY; LIGAND; P53; COMPLEMENTATION; OVERPRODUCTION AB Fanconi anemia (FA) is a genetic syndrome predisposing to hematopoietic failure. Little is known about the pathophysiology of FA, except that tumor necrosis factor-alpha (TNF-alpha) is overexpressed in patients. FA group C (Fac) gene knockout mice have been developed in order to model the human disease, but the mice do not spontaneously exhibit aplasia. To investigate secondary influences on hematopoiesis in the Fac-null mice, we studied the sensitivity of hematopoietic progenitor cells (HPC) to death receptor triggering by TNF-alpha and Fas receptor (CD95) ligation. Previously we had found that overexpression of a human FAC transgene protects hematopoietic progenitors from Fas-mediated apoptosis (Wang et al., 1998, Cancer Res 58:3538-3541). In the present experiments with Fac-null mice, growth of erythroid burst-forming units (BFU-E) was significantly inhibited by TNF-alpha and CD95 ligation. Flow cytometric analysis revealed that CD95 was induced more readily in the Fac-null CD34+ cell fraction. Apoptosis induced by TNF-alpha alone or with CD95 ligation also occurred more frequently in null mouse HPC. We then bred null mice against transgenic mice overexpressing TNF-alpha (at serum levels in the range of 100 pg/ml). Resultant Fac-null mice that overexpressed TNF-alpha not only yielded decreased numbers of BFU-E but also expressed higher levels of CD95 in the CD34+ fraction. We conclude that mutation in the Fac protein induces heightened sensitivity to TNF-alpha and Fas receptor ligation, results that may explain the mechanism of anemia in FA-C patients. J. Cell. Physiol. 179:79-86, 1999. Published 1999 Wiley-Liss, Inc.(dagger) C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Oregon Hlth Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. RP Liu, JM (reprint author), NHLBI, Hematol Branch, NIH, 10-ACRF-7C103, Bethesda, MD 20892 USA. EM LiuJ@gwgate.nhlbi.nih.gov NR 47 TC 48 Z9 48 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD APR PY 1999 VL 179 IS 1 BP 79 EP 86 DI 10.1002/(SICI)1097-4652(199904)179:1<79::AID-JCP10>3.0.CO;2-O PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 172CU UT WOS:000078905400010 PM 10082135 ER PT J AU Cruz, NF Adachi, K Dienel, GA AF Cruz, NF Adachi, K Dienel, GA TI Rapid efflux of lactate from cerebral cortex during K+-induced spreading cortical depression SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE cerebral glucose utilization; glucose; lactate; metabolite trafficking; cerebral arteriovenous differences ID GLUCOSE-UTILIZATION; RAT-BRAIN; CULTURED ASTROCYTES; CYTOCHROME-OXIDASE; METABOLISM; TRANSPORT; <6-C-14>GLUCOSE; STIMULATION; CONSUMPTION; GLYCOLYSIS AB Rapid transport of lactate from activated brain regions to blood, perhaps reflecting enhanced metabolite trafficking, would prevent local trapping of labeled metabolites of [6-C-14]glucose and cause underestimation of calculated CMR-(glc). Because the identities of glucose metabolites lost from activated structures and major routes of their removal are not known, arteriovenous differences across brains of conscious normoxic rats for derivatives of [6-C-14]glucose were determined under steady-state conditions in blood during K+-induced spreading cortical depression. Lactate was identified as the major labeled product lost from brain. Its entry to blood was detected within 2 minutes after a pulse of [6-C-14]glucose, and it accounted for 96% of the C-14 lost from brain within approximately 8 minutes. Lactate efflux corresponded to 20% of glucose influx, but accounted for only half the magnitude of underestimation of CMRglc, when [C-14]glucose is the tracer, suggesting extensive [C-14]lactate trafficking within brain. [C-14]Lactate spreading within brain is consistent with (1) relatively uniform pattern labeling of K+-treated cerebral cortex by [6-C-14]glucose contrasting heterogeneous labeling by [C-14]deoxyglucose, and(2)transport of C-14-labeled lactate and inulin up to 1.5 and 2.4 min, respectively, within 10 minutes. Thus, newly synthesized lactate exported from activated cells rapidly flows to blood and probably other brain structures. C1 NIMH, Cerebral Metab Lab, Bethesda, MD 20892 USA. RP Dienel, GA (reprint author), Univ Arkansas Med Sci, Dept Neurol, Slot 500,4301 W Markham St, Little Rock, AR 72205 USA. NR 64 TC 46 Z9 47 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD APR PY 1999 VL 19 IS 4 BP 380 EP 392 PG 13 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 263FP UT WOS:000084115000004 PM 10197508 ER PT J AU Madsen, PL Cruz, NF Sokoloff, L Dienel, GA AF Madsen, PL Cruz, NF Sokoloff, L Dienel, GA TI Cerebral oxygen/glucose ratio is low during sensory stimulation and rises above normal during recovery: Excess glucose consumption during stimulation is not accounted for by lactate efflux from or accumulation in brain tissue SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE anaerobic glycolysis; energy metabolism; functional activation; cerebral glucose utilization; cerebral oxygen consumption ID HUMAN VISUAL-CORTEX; MAGNETIC-RESONANCE; BLOOD-FLOW; PHYSIOLOGICAL STIMULATION; OXIDATIVE-METABOLISM; CORTICAL ASTROCYTES; PRIMARY CULTURES; GLYCOGENOLYSIS; NORADRENALINE; SPECTROSCOPY AB Functional activation stimulates CMRglc more than CMRO2 and raises lactate levels in brain. This has been interpreted as evidence that brain work is supported mainly by energy derived from anaerobic glycolysis, To determine if lactate production accounts for the "excess" glucose consumption, cerebral arteriovenous differences were measured in conscious rats before, during, and 15 minutes after sensory stimulation; the brains were rapidly frozen in situ immediately after completion of blood sampling and assayed for metabolite levels. The molar O-2/glucose uptake ratio fell from 6.1 +/- 1.1 (mean +/- SD) before stimulation to 5.0 +/- 1.1 during activation (P < 0.01); lactate efflux from brain to blood was detectable at rest but not during stimulation. By 15 minutes after activation, O-2 and lactate arteriovenous differences normalized, whereas that for glucose fell, causing the O-2/glucose ratio to rise above preactivation levels to 7.7 +/- 2.6 (P < 0.01). Brain glucose levels remained stable through all stages of activity. Brain lactate levels nearly doubled during stimulation but normalized within 15 minutes of recovery. Brain glycogen content fell during activation and declined further during recovery. These results indicate that brain glucose metabolism is not in a steady state during and shortly after activation. Furthermore, efflux from and increased content of lactate in the brain tissue accounted for less than 54% of the "excess" glucose used during stimulation, indicating that a shift to anaerobic glycolysis does not fully explain the disproportionately greater increases in CMRglc above that of CMRO2 in functionally activated brain. These results also suggest that the apparent dissociation between glucose utilization and O-2 consumption during functional activation reflects only a temporal displacement; during activation, glycolysis increases more than oxidative metabolism, leading to accumulation of products in intermediary metabolic pools that are subsequently consumed and oxidized during recovery. C1 NIMH, Cerebral Metab Lab, Bethesda, MD 20902 USA. RP Sokoloff, L (reprint author), NIMH, Cerebral Metab Lab, Bldg 36,Room 1A-05, Bethesda, MD 20902 USA. NR 42 TC 102 Z9 104 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD APR PY 1999 VL 19 IS 4 BP 393 EP 400 PG 8 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 263FP UT WOS:000084115000005 PM 10197509 ER PT J AU Torpy, DJ Chen, CC Mullen, N Doppman, JL Carrasquillo, JA Chrousos, GP Nieman, LK AF Torpy, DJ Chen, CC Mullen, N Doppman, JL Carrasquillo, JA Chrousos, GP Nieman, LK TI Lack of utility of In-111-pentetreotide scintigraphy in localizing ectopic ACTH producing tumors: Follow-up of 18 patients SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BRONCHIAL CARCINOID-TUMOR; SOMATOSTATIN-RECEPTOR SCINTIGRAPHY; CORTICOTROPIN-RELEASING HORMONE; DEPENDENT CUSHINGS-SYNDROME; DIFFERENTIAL-DIAGNOSIS; LOCALIZATION; SECRETION; PEPTIDES; SUBTYPE; ANALOGS AB Octreotide scintigraphy has been advocated as the principal imaging modality for localizing ectopic ACTH-secreting tumors in Cushing's syndrome. To assess its usefulness we reviewed the course of 18 consecutive patients with ectopic ACTH-producing tumor. Imaging included In-111-pentetreotide scintigraphy, computed tomography (CT), and/or magnetic resonance imaging (MRI). Tumor was detected initially in 7/18 patients, and in 3/18 during follow-up. No ACTH-secreting tumor was detected by octreotide scintigraphy when CT/ MRI were negative. Seventeen of forty octreotide scintigrams were abnormal. CT and/or MRI confirmed tumors in 10, but demonstrated nonendocrine lesions in association with 6 false positive octreotide scintigrams. Hepatic venous sampling for ACTH refuted one lesion detected by octreotide and CT scans. Twenty-three of forty octreotide scintigrams were normal. Of these, 8 were false negative, as CT and/or MRI detected tumor: 10 agreed with negative CT and MRI, and 5 correctly refuted false positive CT and/or,MRI scans. Repeated CT/ NIR, but not octreotide scintigraphy, led to tumor resection in 2 patients. We conclude that octreotide scintigraphy does not offer greater sensitivity than CT/MRI and that false positive scans are common. Although octreotide scintigraphy may he helpful in selected cases, it is not a significant advance over conventional imaging for ectopic ACTH-secreting tumors. C1 NICHHD, Dev Endocrinol Branch, Ctr Clin, NIH, Bethesda, MD 20892 USA. NIH, Dept Radiol, Ctr Clin, Bethesda, MD 20892 USA. NIH, Dept Nursing, Ctr Clin, Bethesda, MD 20892 USA. RP Nieman, LK (reprint author), NICHHD, Dev Endocrinol Branch, Ctr Clin, NIH, Bldg 10,Room 10N262,10 Ctr Dr, Bethesda, MD 20892 USA. EM NiemanL@nih.gov RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 30 TC 51 Z9 54 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 1999 VL 84 IS 4 BP 1186 EP 1192 DI 10.1210/jc.84.4.1186 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 183RN UT WOS:000079567400005 PM 10199751 ER PT J AU Stratakis, CA AF Stratakis, CA TI Carney complex and related syndromes and their genetic loci - Response SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Letter C1 NICHHD, Unit Genet & Endocrinol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), NICHHD, Unit Genet & Endocrinol, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262,10 Ctr Dr,MSC-1862, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 1999 VL 84 IS 4 BP 1491 EP 1492 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 183RN UT WOS:000079567400063 ER PT J AU Ioannidis, JPA Contopoulos-Ioannidis, DG Lau, J AF Ioannidis, JPA Contopoulos-Ioannidis, DG Lau, J TI Recursive cumulative meta-analysis: A diagnostic for the evolution of total randomized evidence from group and individual patient data SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE meta analysis; randomized trials; bias; study design; publication bias ID IMMUNODEFICIENCY-VIRUS INFECTION; HIGH-DOSE ACYCLOVIR; AIDS-RELATED COMPLEX; CLINICAL-TRIALS; DOUBLE-BLIND; MYOCARDIAL-INFARCTION; STOPPING RULES; METAANALYSIS; ZIDOVUDINE; EFFICACY AB Meta-analyses of randomized evidence may include published, unpublished, and updated data in an ongoing estimation process that continuously accommodates more data. Synthesis may be performed either with group data or with meta-analysis of individual patient data (MIPD). Although MIPD with updated data is considered the gold standard of evidence, there is a need for a careful study of the impact different sources of data have on a meta-analysis and of the change in the treatment effect estimates over sequential information steps. Unpublished data and late-appearing data may be different from early-appearing data. Updated information after the end of the main study follow-up may be affected by cross-overs, missing information, and unblinding. The estimated treatment effect may thus depend on the completeness and updating of the available evidence. To address these issues, we present recursive cumulative meta-analysis (RCM) as an extension of cumulative metaanalysis. Recursive cumulative meta-analysis is based on the principle of recalculating the results of a cumulative meta-analysis with each new or updated piece of information and focuses on the evolution of the treatment effect as a more complete and updated picture of the evidence becomes available. An examination of the perturbations of the cumulative treatment effect over sequential information steps may signal the presence of bias or heterogeneity in a meta-analysis. Recursive cumulative meta-analysis may suggest whether then is a true underlying treatment effect to which the meta-analysis is converging and how treatment effects are sequentially altered by new or modified evidence. The method is illustrated with an example from the conduct of an MIPD on acyclovir in human immunodeficiency virus infection. The relative strengths and limitations of both meta analysis of group data and MIPD are discussed through the RCM perspective. (C) 1999 Elsevier Science Inc. C1 NIAID, Therapeut Res Program, Div AIDS, NIH, Bethesda, MD 20892 USA. George Washington Univ, Sch Med, Dept Pediat, Washington, DC 20052 USA. Tufts Univ, Sch Med, Div Clin Care Res, New England Med Ctr Hosp, Boston, MA 02111 USA. RP Ioannidis, JPA (reprint author), 23A Kalavryton St, Ano Voula 16673, Greece. RI Ioannidis, John/G-9836-2011 NR 49 TC 59 Z9 60 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD APR PY 1999 VL 52 IS 4 BP 281 EP 291 DI 10.1016/S0895-4356(98)00159-0 PG 11 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 192BM UT WOS:000080058300002 PM 10235168 ER PT J AU Jain, A Atkinson, TP Lipsky, PE Slater, JE Nelson, DL Strober, W AF Jain, A Atkinson, TP Lipsky, PE Slater, JE Nelson, DL Strober, W TI Defects of T-cell effector function and post-thymic maturation in X-linked hyper-IgM syndrome SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HUMAN B-CELLS; CD40 LIGAND; IMMUNOGLOBULIN DEFICIENCY; DENDRITIC CELLS; ELEVATED IGM; IMMUNODEFICIENCY; EXPRESSION; RESPONSES; INTERLEUKIN-12; HELP AB X-linked hyper-IgM syndrome (XHIM) results from mutations in the gene encoding for CD40 ligand (CD154). Patients with the syndrome suffer from infections with opportunistic pathogens such as Cryptosporidium and Pneumocystis carinii. In this study, we demonstrate that activated T cells from patients with XHIM produce markedly reduced levels of IFN-l, fail to induce antigen-presenting cells to synthesize IL-12, and induce greatly reduced levels of TNF-alpha. In addition, we show that the patients' circulating T lymphocytes of both the CD4(+) and CD8(+) subsets contain a markedly reduced antigen-primed population, as determined by CD45RO expression. Finally, we demonstrate that the defects in antigen priming are likely due to the lack of CD154 expression and insufficient costimulation of T cells by CD80/CD86 interactions. Taken together, this study offers a basis for the increased susceptibility of patients with XHIM to certain opportunistic infections. C1 NIAID, Mucosal Immun Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. Univ Alabama, Dept Pediat, Birmingham, AL 35294 USA. Univ Texas, SW Med Ctr, Dept Rheumatol & Immunol, Dallas, TX 75235 USA. Childrens Natl Med Ctr, Dept Pediat, Washington, DC 20010 USA. NCI, Immunophysiol Sect, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Strober, W (reprint author), NIAID, Mucosal Immun Sect, Clin Invest Lab, NIH, Room 11N238,Bldg 10, Bethesda, MD 20892 USA. NR 47 TC 67 Z9 68 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 1999 VL 103 IS 8 BP 1151 EP 1158 DI 10.1172/JCI5891 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 189ED UT WOS:000079890400007 PM 10207167 ER PT J AU Swan, DC Tucker, RA Tortolero-Luna, G Mitchell, MF Wideroff, L Unger, ER Nisenbaum, RA Reeves, WC Icenogle, JP AF Swan, DC Tucker, RA Tortolero-Luna, G Mitchell, MF Wideroff, L Unger, ER Nisenbaum, RA Reeves, WC Icenogle, JP TI Human papillomavirus (HPV) DNA copy number is dependent on grade of cervical disease and HPV type SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; INTRAEPITHELIAL NEOPLASIA; PHYSICAL STATE; CANCER; PREVALENCE; MANAGEMENT; LESIONS; GENE AB The association between human papillomavirus (HPV) DNA copy number and cervical disease was investigated. Viral DNA copy number for the most common high-risk HPV types in cervical cancer (types 16, 18, 31, and 45) was determined in cervical cytobrush specimens from 149 women with high-grade cervical intraepithelial neoplasias (CIN II-CIN III), 176 with low-grade CIN (CIN I), and 270 with normal cytology. Quantitative, PCR-based fluorescent assays for each of the HPV genotypes and for the beta-globin gene were used. The amount of cellular DNA increased significantly with increasing disease; thus, HPV was expressed as copies per microgram of cellular DNA. The assay had a dynamic range of >10(7), allowing documentation for the first time of the wide range of HPV copy numbers seen in clinical specimens, Median HPV DNA copy number varied by more than 10(4) among the viral types. HPV16 was present in the highest copy number; over 55% of HPV16-positive samples contained more than 10(8) copies/mu g. Median copy number for HPV16 sheared dramatic increases with increasing epithelial abnormality, an effect not seen with the of her HPV types. HPV16 increased from a median of 2.2 x 10(7) in patients with normal cytology, to 4.1 x 10(7) in CIN 1 patients, to 1.3 x 10(9) copies/mu g in CIN II-III patients. Even when stratified by cervical disease and viral type, the range of viral DNA copies per microgram of cellular DNA was quite large, precluding setting a clinically significant cutoff value for "high" copy numbers predictive of disease. This study suggests that the clinical usefulness of HPV quantitation requires reassessment and is assay dependent. C1 Ctr Dis Control & Prevent, Natl Ctr Infect Dis, US PHS, US Dept HHS, Atlanta, GA 30333 USA. Univ Texas, MD Anderson Cancer Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. NCI, Div Canc Control & Populat Serv, Bethesda, MD 20892 USA. RP Swan, DC (reprint author), Ctr Dis Control & Prevent, Natl Ctr Infect Dis, US PHS, US Dept HHS, Mail Stop G-18,1600 Clifton Rd, Atlanta, GA 30333 USA. RI Hernandez, Jessica/G-6527-2011; OI Unger, Elizabeth/0000-0002-2925-5635 NR 21 TC 168 Z9 176 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD APR PY 1999 VL 37 IS 4 BP 1030 EP 1034 PG 5 WC Microbiology SC Microbiology GA 175QF UT WOS:000079105500027 PM 10074522 ER PT J AU Cox, JD Gallagher, MJ Hammond, EH Kaplan, RS Schellhammer, PF Crook, JM Leibel, SA Forman, JD Grimm, PD Zietman, AL Hudson, MA Schild, SA Beyer, DC Hussey, DH Thames, H Shipley, WU AF Cox, JD Gallagher, MJ Hammond, EH Kaplan, RS Schellhammer, PF Crook, JM Leibel, SA Forman, JD Grimm, PD Zietman, AL Hudson, MA Schild, SA Beyer, DC Hussey, DH Thames, H Shipley, WU CA Amer Soc Therapeutic Radiol & Oncol Consensus P TI Consensus statements on radiation therapy of prostate cancer: Guidelines for prostate re-biopsy after radiation and for radiation therapy with rising prostate-specific antigen levels after radical prostatectomy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT American-Society-for-Therapeutic-Radiology-and-Oncology Consensus Conference for Prostate Cancer CY SEP 06, 1997 CL ATLANTA, GEORGIA SP Amer Soc Therapeut Radiol & Oncol ID INTERSTITIAL BRACHYTHERAPY; DOSE-ESCALATION; RADIOTHERAPY; ADJUVANT; IRRADIATION AB Purpose: To develop evidence-based guidelines for (1) prostate re-biopsy after radiation and (2) radiation therapy with rising prostate-specific antigen (PSA) levels after radical prostatectomy in the management of patients with localized prostatic cancer. Design: The American Society of Therapeutic Radiology and Oncology (ASTRO) challenged a multidisciplinary consensus panel to address consensus on specific issues in each of the two topics. Four well-analyzed patient data sets were presented for review and questioning by the panel. The panel sought criteria that would be valid for patients in standard clinical practice as well as for patients enrolled in clinical trials. Subsequent to an executive session that followed these presentations, the panel presented its consensus guidelines. Results and Conclusions: Based on the data presented, the prostate re-biopsy negative rates ranged from 62% to 80% for patients with stage T1-2 tumors. The panel judged that prostate re-biopsy is not necessary as standard follow-up care and that the absence of a rising PSA level after radiation therapy is the most rigorous end paint of total tumor eradication. Further, the panel judged that re-biopsy may be an important research tool. Based on the data presented, the longterm (5 years or more) PSA remission rate after salvage radiation therapy ranges from 27% to 45%. The panel requested results from prospective randomized trials to evaluate optimally this information. The panel judged that the total dose of radiation should be 64 Gy or slightly higher and that, in patients with or without radiation therapy, there is no standard role for androgen suppressant therapy for rising PSA values after prostatectomy. (C) 1999 by American Society of Clinical Oncology. C1 MD Anderson Cancer Ctr, Houston, TX USA. Upper Delaware Valley Canc Ctr, Milford, PA USA. Latter Day St Hosp, Salt Lake City, UT 84143 USA. NCI, Clin Invest Branch, Canc Therapy Evaluat Program, Bethesda, MD USA. Eastern Virginia Med Sch, Dept Urol, Norfolk, VA 23501 USA. RP Shipley, WU (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 17 TC 244 Z9 250 U1 1 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR PY 1999 VL 17 IS 4 BP 1155 EP 1163 PG 9 WC Oncology SC Oncology GA 182JR UT WOS:000079496300010 PM 10561174 ER PT J AU Cheson, BD Horning, SJ Coiffier, B Shipp, MA Fisher, RI Connors, JM Lister, TA Vose, J Grillo-Lopez, A Hagenbeek, A Cabanillas, F Klippensten, D Hiddemann, W Castellino, R Harris, NL Armitage, JO Carter, W Hoppe, R Canellos, GP AF Cheson, BD Horning, SJ Coiffier, B Shipp, MA Fisher, RI Connors, JM Lister, TA Vose, J Grillo-Lopez, A Hagenbeek, A Cabanillas, F Klippensten, D Hiddemann, W Castellino, R Harris, NL Armitage, JO Carter, W Hoppe, R Canellos, GP TI Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BONE-MARROW INVOLVEMENT; POSITRON-EMISSION-TOMOGRAPHY; CHRONIC LYMPHOCYTIC-LEUKEMIA; SPONSORED-WORKING-GROUP; LARGE-CELL LYMPHOMA; CORE-NEEDLE BIOPSY; COMPUTED-TOMOGRAPHY; MAGNETIC-RESONANCE; MALIGNANT-LYMPHOMA; COMBINATION CHEMOTHERAPY AB Standardized guidelines for response assessment are needed to ensure comparability among clinical trials in non-Hodgkin's lymphomas (NHL). To achieve this, two meetings were convened among United States and international lymphoma experts representing medical hematology/oncology, radiology, radiation oncology, and pathology to review currently used response definitions and to develop a uniform set of criteria for assessing response in clinical trials. The criteria that were developed include anatomic definitions of response, with normal lymph node size after treatment of 1.5 cm in the longest transverse diameter by computer-assisted tomography scan. A designation of complete response/unconfirmed was adopted to include patients with a greater than 75% reduction in tumor size after therapy bur with a residual mass, to include patients - especially those with large cell NHL - who may not have residual disease, Single-photon emission computed tomography gallium scans are encouraged as a valuable adjunct to assessment of patients with large-cell NHL, but such scans require appropriate expertise. Flow cytometric, cytogenetic, and molecular studies are not currently included in response definitions. Response Kites may be the most important objective in phase II trials where the activity of a new agent is important and may provide support for approval by regulatory agencies. However, the goals of most phase III trials are to identify therapies that will prolong the progression-free survival, if not the overall survival, of the treated patients, We hope that these guidelines will serve to improve communication among investigators and comparability among clinical trials until clinically relevant laboratory and imaging studies are identified and become more widely available. (C) 1999 by American Society of Clinical Oncology. C1 NCI, Bethesda, MD 20892 USA. Stanford Univ, Palo Alto, CA 94304 USA. Ctr Hosp Lyon Sud, Lyon, France. Dana Farber Canc Inst, Boston, MA 02115 USA. Loyola Univ, Maywood, IL 60153 USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. St Bartholomews Hosp, London, England. Univ Nebraska, Omaha, NE 68182 USA. Idec Pharmaceut Corp, San Diego, CA USA. Univ Utrecht, Utrecht, Netherlands. MD Anderson Cancer Ctr, Houston, TX 77030 USA. Roswell Pk Canc Inst, Buffalo, NY USA. Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Sharp Mem Hosp & Rehabil Ctr, San Diego, CA 90034 USA. RP Cheson, BD (reprint author), NCI, Execut Plaza N,Rm 741, Bethesda, MD 20892 USA. EM chesonb@ctep.nci.nih.gov NR 51 TC 2362 Z9 2469 U1 1 U2 82 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR PY 1999 VL 17 IS 4 BP 1244 EP 1253 PG 10 WC Oncology SC Oncology GA 182JR UT WOS:000079496300021 PM 10561185 ER PT J AU Cho, HK Lush, RM Bartlett, DL Alexander, HR Wu, PC Libutti, SK Lee, KB Venzon, DJ Bauer, KS Reed, E Figg, WD AF Cho, HK Lush, RM Bartlett, DL Alexander, HR Wu, PC Libutti, SK Lee, KB Venzon, DJ Bauer, KS Reed, E Figg, WD TI Pharmacokinetics of cisplatin administered by continuous hyperthermic peritoneal perfusion (CHPP) to patients with peritoneal carcinomatosis SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID INTRAPERITONEAL CHEMOTHERAPY; CELLS; THIOSULFATE; PLATINUM; CANCER; TUMOR AB The pharmacokinetics of cisplatin administered by continuous hyperthermic peritoneal perfusion (CHPP) was characterized in patients with peritoneal carcinomatosis. Cisplatin was added into the perfusate with escalating doses from 100 mg/m(2) to 400 mg/m(2). The hyperthermic perfusion was maintained for 90 minutes with a flow rate of 1.5 L/min and a target peritoneal temperature of 42.5 degrees C after a tumor debulking procedure. Samples of both the perfusate and blood were obtained during the perfusion and 30 minutes after the perfusion. Cisplatin plasma and perfusate concentrations were determined by flameless atomic absorption spectrometry with a lower limit of detection of 2 ng/ml and a coefficient of variation (CV) < 10%. Fifty-six patients were enrolled in the study. The mean (+/- SD) percentage of cisplatin present in the perfusate at the completion of perfusion was 27.8% +/- 20% of the total dose. The maximum cisplatin concentrations in the perfusate were 10 times higher than those in plasma. The area under the concentration-time curve (AUC) of the perfusate was 13 times higher than the AUC of plasma. A two-compartment model with an additional peritoneal cavity compartment fits to the data best based on the Akaike information criterion. However, the interpatient variability was considerably high (CV < 100%). In conclusion, cisplatin administered by hyperthermic peritoneal perfusion resulted in a pharmacological advantage by obtaining higher and direct drug exposure to the tumor in the peritoneal cavity while limiting systemic absorption and toxicity. Using a complex two-compartment model, the authors were able to characterize the pharmacokinetics of cisplatin given intraperitoneally via this technique. (C) 1999 the American College of Clinical Pharmacology. C1 NCI, Clin Pharmacokinet Sect, Med Branch, NIH, Bethesda, MD 20892 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Clin Pharmacokinet Sect, Med Branch, NIH, Bldg 10,Room 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008; Figg Sr, William/M-2411-2016 NR 16 TC 22 Z9 26 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD APR PY 1999 VL 39 IS 4 BP 394 EP 401 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 181DB UT WOS:000079424400007 PM 10197298 ER PT J AU Alfaro, CL Lam, YWF Simpson, J Ereshefsky, L AF Alfaro, CL Lam, YWF Simpson, J Ereshefsky, L TI CYP2D6 status of extensive metabolizers after multiple-dose fluoxetine, fluvoxamine, paroxetine, or sertraline SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID SEROTONIN REUPTAKE INHIBITORS; OBSESSIVE-COMPULSIVE DISORDER; HUMAN-LIVER-MICROSOMES; DRUG-INTERACTIONS; PLASMA-CONCENTRATIONS; POOR METABOLIZERS; MAJOR DEPRESSION; HEALTHY-SUBJECTS; IN-VITRO; DESIPRAMINE AB The aim of this study was to evaluate the CYP2D6 inhibitory effects of four selective cerotonin reuptake inhibitors (SSRIs). Thirty-one healthy subjects were phenotyped as extensive metabolizers using the dextromethorphan/dextrorphan (DM/DX) urinary ratio as a marker for CYP2D6 activity before and after 8 days of administration of fluoxetine 60 mg (loading dose strategy), fluvoxamine 100 mg, paroxetine 20 mg, or sertraline 100 mg in a parallel-group design. Statistical analysis was performed on log-transformed DM/DX ratios because of variability within and between treatment groups. DM/DX ratios before (DM/DXBL) and after (DM/DXSSRI) were compared within and between the four SSRI groups. DM/DXBL ratios were not significantly different between the four SSRI treatment groups. Comparing within groups, significant differences between DM/DXBL and DM/DXBL were found for the fluoxetine (p < 0.001; ratio values, 0.020 vs. 0.364) and paroxetine (p = 0.0005, ratio values 0.028 vs. 1.085) but not for the fluvoxamine or sertraline groups. Comparing between groups, significant differences in DM/DXSSRI ratios were found for fluoxetine versus sertraline (p = 0.0019, DM/DX = 0.364 vs. 0.057), fluoxetine versus fluvoxamine (p < 0.0001, DM/DX = 0.364 vs. 0.019), paroxetine versus sertraline (p = 0.0026, DM/DX = 1.085 vs. 0.057), and paroxetine versus fluvoxamine (p < 0.0001, DM/DX = 1.085 vs. 0.019). No significant differences were noted between the two potent CYP2D6 inhibitors, fluoxetine and paroxetine, or the two weakest inhibitors, fluvoxamine and sertraline. Five subjects in dhe fluoxetine and four subjects in the paroxetine groups changed to poor metabolizer phenotype (DM/DX greater than or equal to 0.3) after treatment, Although CYP2D6 inhibitory effects of fluvoxamine and sertraline did not yield significant differences from baseline, some subjects exhibited DM/DX ratio increases of 150 to 200%. One paroxetine-treated subject did not exhibit any CYP2D6 inhibition. SSRI dose and plasma concentration may be correlated with the extent of CYP2D6 inhibition and should be further investigated. C1 Univ Texas, Hlth Sci Ctr, Div Pharmacotherapy, Dept Pharmacol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Univ Texas, Coll Pharm, Austin, TX 78712 USA. Alamo Mental Hlth Grp, San Antonio, TX USA. NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA. RP Ereshefsky, L (reprint author), Univ Texas, Hlth Sci Ctr, Div Pharmacotherapy, Dept Pharmacol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 36 TC 67 Z9 69 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD APR PY 1999 VL 19 IS 2 BP 155 EP 163 DI 10.1097/00004714-199904000-00011 PG 9 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 181VX UT WOS:000079464500009 PM 10211917 ER PT J AU Yasui, T Murakami, T Maeda, T Oka, T AF Yasui, T Murakami, T Maeda, T Oka, T TI Involvement of gonadal steroid hormone disturbance in altered prolactin receptor gene expression in the liver of diabetic mice SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; RAT-LIVER; GROWTH-HORMONE; BINDING-SITES; MULTIPLE FORMS; MAMMARY-GLAND; MESSENGER-RNA; FEMALE RATS; LONG-FORM; INSULIN AB The levels of mRNA for long and three short forms of prolactin receptor (PRLR) were examined in the livers of normal (db+/db -) and insulin-resistant diabetic (db+/db+) mice to assess the role of gonadal steroid hormones in the regulation of PRLR gene expression in diabetes mellitus. In females, plasma levels of testosterone in diabetic mice were higher, and those of 17 beta-estradiol were lower when compared with levels in normal mice. By contrast, diabetic male mice bad lower plasma levels of testosterone than normal males and showed no significant difference in the low circulating level of 17 beta-estradiol compared with normal males. The short 3 form of PRLR (PRLR3) mRNA was the most abundant in the liver of both normal and diabetic mice. In addition, the level of PRLR3 mRNA in normal females was 8-fold higher than in normal males. The level of PRLR3 mRNA in diabetic females was approximately a quarter lower than in normal females, whereas the level of PRLR3 mRNA in diabetic males was approximately 2-fold higher than in normal males. During postnatal development, the level of PRLR3 mRNA increased during puberty in normal females, while the level in diabetic females decreased to a nadir at 7 weeks of age followed by a progressive rise. On the other hand, the levels of PRLR3 mRNA in both normal and diabetic males decreased gradually during 5 to :14 weeks of age. Testosterone treatment of diabetic males and females resulted in a 49.1 and 49.8% decrease of PRLR3 mRNA respectively. 17 beta-Estradiol treatment slightly (18%) increased levels of PRLR3 mRNA in diabetic males. These results suggest that the hepatic level of PRLR mRNA is regulated by the inhibitory effect of testosterone and the stimulatory effect of estrogen in both normal and diabetic mice. C1 NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. RP Oka, T (reprint author), NIDDKD, Lab Genet & Physiol, NIH, Bldg 8,Room 106,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 36 TC 13 Z9 14 U1 0 U2 0 PU SOC ENDOCRINOLOGY PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4NQ, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD APR PY 1999 VL 161 IS 1 BP 33 EP 40 DI 10.1677/joe.0.1610033 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 184RE UT WOS:000079626100004 PM 10194526 ER PT J AU Little, RE AF Little, RE TI Weight gain and relation to maternal smoking SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Letter C1 NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. RP Little, RE (reprint author), NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD APR PY 1999 VL 53 IS 4 BP 256 EP 256 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 180KQ UT WOS:000079385400016 PM 10396556 ER PT J AU Ribeiro, JMC Valenzuela, JG AF Ribeiro, JMC Valenzuela, JG TI Purification and cloning of the salivary peroxidase/catechol oxidase of the mosquito Anopheles albimanus SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Article DE catechol oxidase; peroxidase; vasodilator; salivary gland; myeloperoxidase; mosquito; Anopheles albimanus ID NITRIC-OXIDE; AEDES-AEGYPTI; BLOODSUCKING INSECT; CIMEX LECTULARIUS; CELL-ADHESION; PROTEIN; BLOOD; MYELOPEROXIDASE; INACTIVATION; NITROPHORIN AB Salivary homogenates of the adult female mosquito Anopheles albimanus have been shown previously to contain a vasodilatory activity associated with a catechol oxidase/peroxidase activity. We have now purified the salivary peroxidase using high-performance liquid chromatography. The pure enzyme is able to relax rabbit aortic rings pre-constricted with norepinephrine. The peroxidase has a relative molecular mass of 66907 as estimated by mass spectrometry. Amino-terminal sequencing allowed us to design oligonucleotide probes for isolation of cDNA clones derived from the salivary gland mRNA from female mosquitoes. The full sequence of the cDNA demonstrated homology between A. albimanus salivary peroxidase and several members of the myeloperoxidase gene family. A close comparison of A. albimanus salivary peroxidase with canine myeloperoxidase, for which the crystal structure is known, showed that all six disulfide bridges were conserved and demonstrated identity for all five residues associated with a Ca2+-binding site. In addition, 16 of 26 residues shown to be in close proximity to the heme moiety in the canine myeloperoxidase were identical. We conclude that the salivary peroxidase of A. albimanus belongs to the myeloperoxidase gene family. Other possible functions for this molecule in blood feeding are discussed. C1 NIAID, Parasit Dis Lab, Sect Med Entomol, Bethesda, MD 20892 USA. RP Ribeiro, JMC (reprint author), NIAID, Parasit Dis Lab, Sect Med Entomol, Bldg 4,Room 126,4 Ctr Dr,MSC-0425, Bethesda, MD 20892 USA. OI Ribeiro, Jose/0000-0002-9107-0818 NR 30 TC 44 Z9 47 U1 0 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0022-0949 J9 J EXP BIOL JI J. Exp. Biol. PD APR PY 1999 VL 202 IS 7 BP 809 EP 816 PG 8 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 187XK UT WOS:000079813700006 PM 10069970 ER PT J AU Drake, JW Smith, LA AF Drake, JW Smith, LA TI Some puzzling observations on heat-induced transversion mutagenesis in bacteriophage T4 SO JOURNAL OF GENETICS LA English DT Article ID DNA; REPAIR; DAMAGE; RATES C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Drake, JW (reprint author), NIEHS, Mol Genet Lab, POB 12233, Res Triangle Pk, NC 27709 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU INDIAN ACADEMY SCIENCES PI BANGALORE PA P B 8005 C V RAMAN AVENUE, BANGALORE 560 080, INDIA SN 0022-1333 J9 J GENET JI J. Genet. PD APR PY 1999 VL 78 IS 1 BP 3 EP 5 DI 10.1007/BF02994696 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 228FH UT WOS:000082126100003 ER PT J AU Rabin, RL Park, MK Liao, F Swofford, R Stephany, D Farber, JM AF Rabin, RL Park, MK Liao, F Swofford, R Stephany, D Farber, JM TI Chemokine receptor responses on T cells are achieved through regulation of both receptor expression and signaling SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; C-C CHEMOKINES; LYMPHOCYTE CHEMOATTRACTANT; FREE CALCIUM; FUNCTIONAL-CHARACTERIZATION; BORDETELLA-PERTUSSIS; CHEMOTAXIS; MIGRATION; INDUCE; MCP-1 AB To address the issues of redundancy and specificity of chemokines and their receptors in lymphocyte biology, we investigated the expression of CC chemokine receptors CCR1, CCR2, CCR3, CCR5, CXCR3, and CXCR4 and responses to their ligands on memory and naive, CD4 and CD8 human T cells, both freshly isolated and after short term activation in vitro. Activation through CD3 for 3 days had the most dramatic effects on the expression of CXCR3, which was up-regulated and functional on all T cell populations including naive CD4 cells, In contrast, the effects of short term activation on expression of other chemokine receptors was modest, and expression of CCR2, CCR3, and CCR5 on CD4 cells was restricted to memory subsets, In general, patterns of chemotaxis in the resting cells and calcium responses in the activated cells corresponded to the patterns of receptor expression among T cell subsets. In contrast, the pattern of calcium signaling among subsets of freshly isolated cells did not show a simple correlation with receptor expression, so the propensity to produce a global rise in the intracellular calcium concentration differed among the various receptors within a given T cell subset and for an individual receptor depending on the cell where it was expressed. Our data suggest that individual chemokine receptors and their ligands function on T tells at different stages of T cell activation/differentiation, with CXCR3 of particular importance on newly activated cells, and demonstrate T cell subset-specific and activation state-specific responses to chemokines that are achieved by regulating receptor signaling as well as receptor expression. C1 NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NIAID, Flow Cytometry Unit, Off Sci Director, NIH, Bethesda, MD 20892 USA. RP Farber, JM (reprint author), NIAID, Clin Invest Lab, NIH, Bldg 10,Room 11N-228 MSC 1888, Bethesda, MD 20892 USA. NR 60 TC 209 Z9 213 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 1999 VL 162 IS 7 BP 3840 EP 3850 PG 11 WC Immunology SC Immunology GA 178QT UT WOS:000079278000015 PM 10201901 ER PT J AU Wang, LH Kirken, RA Erwin, RA Yu, CR Farrar, WL AF Wang, LH Kirken, RA Erwin, RA Yu, CR Farrar, WL TI JAK3, STAT, and MAPK signaling pathways as novel molecular targets for the tyrphostin AG-490 regulation of IL-2-mediated T cell response SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERLEUKIN-2 RECEPTOR-GAMMA; FUNCTIONAL COMPONENT; TRANSCRIPTION FACTOR; LYMPHOID DEVELOPMENT; ACTIVATION; KINASE; TYROSINE; GENE; TRANSDUCTION; ALPHA AB AG-490 is a member of the tyrphostin family of tyrosine kinase inhibitors. While AG-490 has been considered to be a Janus kinase (JAK)2-specific inhibitor, these conclusions were primarily drawn from acute lymphoblastic leukemia cells that lack readily detectable levels of JAK3, In the present study, evidence is provided that clearly demonstrates AG-490 potently suppresses IL-2-induced T cell proliferation, a non-JAK2-dependent signal, in a dose-dependent manner in T cell lines D10 and CTLL-2, AG-490 blocked JAK3 activation and phosphorylation of its downstream counterpart substrates, STATs. Inhibition of JAK3 by AG-490 also compromised the Shc/Ras/Raf/mitogen-activated protein kinase (MAPK) signaling pathways as measured by phosphorylation of Shc and extracellular signal-related kinase 1 and 2 (ERK1/2), AG-490 effectively inhibited tyrosine phosphorylation and DNA binding activities of several transcription factors including STAT1, -3, -5a, and -5b and activating protein-1 (AP-1) as judged by Western blot analysis and electrophoretic mobility shift assay. These data suggest that AG-490 is a potent inhibitor of the JAK3/STAT, JAK3/AP-1, and JAK3/MAPK pathways and their cellular consequences. Taken together, these findings support the notion that AG-490 possesses previously unrecognized clinical potential as an immunotherapeutic drug due to its inhibitory effects on T cell-derived signaling pathways. C1 NCI, Cytokine Mol Mechanisms Sect, Mol Immunoregulat Lab, Div Basic Sci, Frederick, MD 21702 USA. NCI, Expt Immunol Lab, Frederick, MD 21702 USA. Sci Applicat Int Corp, Intramural Res Support Porgram, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Univ Texas, Dept Integrat Biol Pharmacol & Physiol, Houston, TX 77030 USA. RP Farrar, WL (reprint author), NCI, Cytokine Mol Mechanisms Sect, Mol Immunoregulat Lab, Div Basic Sci, POB B,Bldg 560,Room 31-68, Frederick, MD 21702 USA. EM farrar@mail.ncifcrf.gov FU NCI NIH HHS [N01-CO-56000] NR 46 TC 135 Z9 141 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 1999 VL 162 IS 7 BP 3897 EP 3904 PG 8 WC Immunology SC Immunology GA 178QT UT WOS:000079278000022 PM 10201908 ER PT J AU Schiaffella, E Sehgal, D Anderson, AO Mage, RG AF Schiaffella, E Sehgal, D Anderson, AO Mage, RG TI Gene conversion and hypermutation during diversification of V-H sequences in developing splenic germinal centers of immunized rabbits SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FOLLICULAR DENDRITIC CELLS; CENTER B-CELLS; AFFINITY MATURATION; HEAVY-CHAIN; SOMATIC DIVERSIFICATION; IN-SITU; REPERTOIRE; MUTATION; ANTIGEN; (4-HYDROXY-3-NITROPHENYL)ACETYL AB The young rabbit appendix and the chicken bursa of Fabricius are primary lymphoid organs where the B cell Ab repertoire develops in germinal centers (GCs) mainly by a gene conversion-like process, In human and mouse, V-gene diversification by somatic hypermutation in GCs of secondary lymphoid organs leads to affinity maturation. We asked whether gene conversion, somatic hypermutation, or both occur in rabbit splenic GCs during responses to the hapten DNP. We determined DNA sequences of rearranged heavy and light chain V region gene segments in single cells from developing DNP-specific GCs after immunization with DNP-bovine gamma-globulin and conclude that the changes at the DNA level that may lead to affinity maturation occur by both gene conversion and hypermutation. Selection was suggested by finding some recurrent amino acid replacements that may contribute increased affinity for antigen in the complementarity-determining region sequences of independently evolved clones, and a narrower range of complementarity-determining region 3 lengths at day 15, Some of the alterations of sequence may also lead to new members of the B cell repertoire in adult rabbits comparable with those produced in gut associated lymphoid tissues of young rabbits. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. USA, Med Res Inst Infect Dis, Ft Detrick, Frederick, MD 21702 USA. RP Mage, RG (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. EM rm3z@nih.gov NR 65 TC 28 Z9 28 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 1999 VL 162 IS 7 BP 3984 EP 3995 PG 12 WC Immunology SC Immunology GA 178QT UT WOS:000079278000033 PM 10201919 ER PT J AU Kuprash, DV Udalova, IA Turetskaya, RL Kwiatkowski, D Rice, NR Nedospasov, SA AF Kuprash, DV Udalova, IA Turetskaya, RL Kwiatkowski, D Rice, NR Nedospasov, SA TI Similarities and differences between human and murine TNF promoters in their response to lipopolysaccharide SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NF-KAPPA-B; FACTOR-ALPHA GENE; IFN-BETA GENE; TRANSCRIPTIONAL ACTIVATION; P65 SUBUNIT; PRIMARY MACROPHAGES; VIRUS INDUCTION; FAMILY MEMBERS; EXPRESSION; CELLS AB Transcription of the TNF gene is rapidly and transiently induced by LPS in cells of monocyte/macrophage lineage. Previous data suggested that multiple NF-kappa B/Rel binding sites play a role in the transcriptional response to LPS of the murine gene. However, the relevance of homologous sites in the human TNF gene remained a matter of controversy, partly because the high affinity NF-kappa B/Rel site located at -510 in the murine promoter is not conserved in humans. Here we used two sets of similarly designed human and mouse TNF promoter deletion constructs and overexpression of I kappa B in the murine macrophage cell line ANA-1 to show remarkable similarity in the pattern of the transcriptional response to LPS, further demonstrating the functional role of the distal promoter region located between -600 and -650, This region was characterized by mutagenesis of protein binding sites, including two relatively low affinity NF-kappa B/Rel sites, #2 and 2a. Mutation in each of the NF-kappa B sites resulted in 2- to 3-fold lower transcriptional activity in response to LPS, In contrast to LPS activation, the response to PMA was substantially lower in magnitude and required only the proximal promoter region. In summary, the functional topography of human and murine promoters when assayed in the same system has some marked similarities. Our observations support the notion that full LPS response of TNF gene requires both NF-kappa B and non-NF-kappa B nuclear proteins. Our data also suggest that the functional activity of a given kappa B site depends on the entire DNA sequence context in the promoter region. C1 Russian Acad Sci, VA Engelhardt Mol Biol Inst, Moscow 117984, Russia. Sci Applicat Int Corp, Intramural Res Support Program, Frederick, MD 21702 USA. NCI, Mol Immunoregulat Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Mol Basis Carcinogenesis Lab, Adv Biosci Labs, Basic Res Program,Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Univ Oxford, John Radcliffe Hosp, Inst Mol Med, Oxford OX3 9DU, England. Univ Oxford, John Radcliffe Hosp, Dept Paediat, Oxford OX3 9DU, England. Moscow State Univ, Belozersky Inst Physicochem Biol, Moscow, Russia. RP Kuprash, DV (reprint author), Russian Acad Sci, VA Engelhardt Mol Biol Inst, 32 Vavilov St, Moscow 117984, Russia. RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Kuprash, Dmitry/O-4899-2015; Nedospasov, Sergei/Q-7319-2016 OI Kuprash, Dmitry/0000-0002-1488-4148; FU NCI NIH HHS [N01-CO-56000] NR 46 TC 119 Z9 122 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 1999 VL 162 IS 7 BP 4045 EP 4052 PG 8 WC Immunology SC Immunology GA 178QT UT WOS:000079278000041 PM 10201927 ER PT J AU Wu, HL Kuritzkes, DR McClernon, DR Kessler, H Connick, E Landay, A Spear, G Heath-Chiozzi, M Rousseau, F Fox, L Spritzler, J Leonard, JM Lederman, MM AF Wu, HL Kuritzkes, DR McClernon, DR Kessler, H Connick, E Landay, A Spear, G Heath-Chiozzi, M Rousseau, F Fox, L Spritzler, J Leonard, JM Lederman, MM TI Characterization of viral dynamics in human immunodeficiency virus type 1-infected patients treated with combination antiretroviral therapy: Relationships to host factors, cellular restoration, and virologic end points SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 12th World AIDS Conference CY JUN 28-JUL 03, 1998 CL GENEVA, SWITZERLAND ID CD8(+) T-CELLS; HIV-1 INFECTION; IN-VIVO; LYMPHOCYTES; LOAD AB Biphasic plasma viral decays were modeled in 48 patients treated with ritonavir, zidovudine, and lamivudine, Estimated first- and second-phase decay rates were d(1) as 0.47/day and d(2) as 0.04/day. Interpatient differences in both decay rates were significant. The d(1) was directly correlated with baseline CD4(+), CD4(+)CD28(+), and CD8(+)CD28(+) T lymphocyte counts (P<.05) and inversely correlated with baseline virus load (P=.044) and the magnitude of CD4(+) and CD8(+) T lymphocyte recovery (P<.01). The d(2) was directly correlated with baseline percentage of CD8(+) T lymphocytes (P=.023), the CD8(+)CD38(+) cell number (P=.024), and the level of IgG that binds to human immunodeficiency virus (HIV) type 1 gp120 (P=.02), Viral decay rates were not predictive of treatment failure or durability of viral suppression. These exploratory findings are consistent with a model in which immunologic factors contribute to elimination of HIV-infected cells and suggest a dynamic interplay between regulation of HIV expression and lymphocyte activation and recovery. C1 Frontier Sci & Technol Res Fdn Inc, Chestnut Hill, MA 02467 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Vet Affairs Med Ctr, Denver, CO USA. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Abbott Labs, Abbott Pk, IL 60064 USA. NIAID, HIV Res Branch, Bethesda, MD 20892 USA. Case Western Reserve Univ, Univ Hosp Cleveland, Cleveland, OH 44106 USA. RP Wu, HL (reprint author), Frontier Sci & Technol Res Fdn Inc, 1244 Boylston St,Suite 303, Chestnut Hill, MA 02467 USA. FU NIAID NIH HHS [AI-38858, AI-38855, AI-43220] NR 26 TC 89 Z9 90 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR PY 1999 VL 179 IS 4 BP 799 EP 807 DI 10.1086/314670 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 182MY UT WOS:000079503800006 PM 10068574 ER PT J AU Davey, RT Chaitt, DG Albert, JM Piscitelli, SC Kovacs, JA Walker, RE Falloon, J Polis, MA Metcalf, JA Masur, H Dewar, R Baseler, M Fyfe, G Giedlin, MA Lane, HC AF Davey, RT Chaitt, DG Albert, JM Piscitelli, SC Kovacs, JA Walker, RE Falloon, J Polis, MA Metcalf, JA Masur, H Dewar, R Baseler, M Fyfe, G Giedlin, MA Lane, HC TI A randomized trial of high- versus low-dose subcutaneous interleukin-2 outpatient therapy for early human immunodeficiency virus type 1 infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 12th International Conference on AIDS CY JUN, 1998 CL GENEVA, SWITZERLAND ID ANTIRETROVIRAL THERAPY; ZIDOVUDINE; INDINAVIR AB Forty-nine outpatients infected with human immunodeficiency virus with baseline CD4 cell counts greater than or equal to 500/mm(3), who were on stable antiretroviral therapy, were randomized to receive 5-day cycles of either low-dose (1.5 million IU [MIU] twice a day) or high-dose (7.5 MIU twice a day) subcutaneous (sc) interleukin (IL)-2 every 4 or every 8 weeks. High-dose recipients experienced mean slopes of +116.1 cells/month and +2.7%/month in CD4 cells and percents, respectively, whereas low-dose recipients displayed mean slopes of +26.7 and +1.3% in the same parameters. At month 6, high-dose recipients achieved a 94.8% increase in mean CD4 cells over baseline compared with a 19.0% increase in low-dose recipients, While high-dose recipients encountered more constitutional side effects, these were generally not dose-limiting. High-dose scIL-2 therapy in outpatients with early HIV-1 infection was well tolerated and induced dramatic, sustained rises in CD4 cells. C1 NIAID, Dept Crit Care Med, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NIAID, Dept Pharm, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Frederick, MD USA. Chiron Corp, Emeryville, CA 94608 USA. RP Davey, RT (reprint author), NIAID, Dept Crit Care Med, Warren G Magnuson Clin Ctr, NIH, Bldg 10,Room 11C103, Bethesda, MD 20892 USA. OI Polis, Michael/0000-0002-9151-2268 NR 17 TC 122 Z9 125 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR PY 1999 VL 179 IS 4 BP 849 EP 858 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 182MY UT WOS:000079503800012 PM 10068580 ER PT J AU Thio, CL Carrington, M Marti, D O'Brien, SJ Vlahov, D Nelson, KE Astemborski, J Thomas, DL AF Thio, CL Carrington, M Marti, D O'Brien, SJ Vlahov, D Nelson, KE Astemborski, J Thomas, DL TI Class II HLA alleles and hepatitis B virus persistence in African Americans SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HIV-1 INFECTION; DRUG-USERS; COMPLEX; GENE AB Persistence of hepatitis B virus (HBV) infection is likely due to the interplay of the virus and host immune response. Given its critical role in antigen presentation, allelic differences in the HLA complex may affect HBV persistence. In a prospectively followed African American cohort, molecular class I and class II HLA typing was done on 31 subjects with persistent HBV infection:and 60 controls who cleared the infection. HBV persistence was significantly associated with two class II alleles, DQA1*0501 (odds ratio [OR], 2.6; P=.05) and DQB1*0301 (OR, 3.9; P = .01), the two-locus haplotype consisting of these same two alleles (OR, 3; P = .005) and the three-locus haplotype, DQA1*0501, DQB1*0301; and DRB1*1102 (OR, 10.7; P = .01). In addition, HBV persistence was associated with class II allelic homozygosity. Several class I associations with persistence were also noted but were not statistically significant after correction for multiple comparisons. These results underscore the importance of the class II-mediated immune response in recovery from HBV infection. C1 Johns Hopkins Univ, Div Infect Dis, Sch Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. NCI, Frederick, MD 21701 USA. RP Thomas, DL (reprint author), Johns Hopkins Univ, Div Infect Dis, Sch Med, 1147 Ross Res Bldg,720 Rutland Ave, Baltimore, MD 21205 USA. FU NIDA NIH HHS [DA-8009, DA-04334, DA-05911] NR 16 TC 83 Z9 102 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR PY 1999 VL 179 IS 4 BP 1004 EP 1006 DI 10.1086/314684 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 182MY UT WOS:000079503800030 PM 10068598 ER PT J AU Farci, P Munoz, SJ Shimoda, A Govindarajan, S Wong, DC Coiana, A Peddis, G Rubin, R Purcell, RH AF Farci, P Munoz, SJ Shimoda, A Govindarajan, S Wong, DC Coiana, A Peddis, G Rubin, R Purcell, RH TI Experimental transmission of hepatitis C virus-associated fulminant hepatitis to a chimpanzee SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID NON-B HEPATITIS; POLYMERASE CHAIN-REACTION; NON-A; FAILURE; RNA AB Hepatitis C virus (HCV) was transmitted from a patient with fulminant hepatitis C to a chimpanzee. The patient had developed two episodes of fulminant hepatitis C, each occurring after a separate liver transplantation. Serial serum and liver samples from the patient and the chimpanzee were analyzed for HCV replication, genotype, quasispecies heterogeneity, and antibodies. In the patient, the levels of HCV replication in serum and liver correlated with the degree of hepatocellular necrosis and the clinical expression of fulminant hepatitis. The same HCV strain, genotype la, was recovered from both episodes of fulminant hepatitis. An unusually severe acute hepatitis was also observed in the chimpanzee. The viruses recovered from the patient and the chimpanzee were almost identical and displayed relatively little quasispecies heterogeneity. Thus, the same HCV strain induced two episodes of fulminant hepatitis in a single patient and severe hepatitis in a chimpanzee, suggesting that the pathogenicity or virulence of a specific HCV strain may be important in the pathogenesis of fulminant hepatitis C. C1 Univ Cagliari, Dept Internal Med, I-09124 Cagliari, Italy. Kanazawa Univ, Sch Med, Dept Internal Med 1, Kanazawa, Ishikawa 920, Japan. NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Jefferson Med Coll, Albert Einstein Med Ctr, Ctr Liver Dis, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Pathol, Philadelphia, PA 19107 USA. Rancho Los Amigos Med Ctr, Dept Pathol, Downey, CA USA. RP Farci, P (reprint author), Univ Cagliari, Dept Internal Med, Via San Giorgio 12, I-09124 Cagliari, Italy. OI Coiana, Alessandra/0000-0002-1039-5486 NR 13 TC 31 Z9 31 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR PY 1999 VL 179 IS 4 BP 1007 EP 1011 DI 10.1086/314653 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 182MY UT WOS:000079503800031 PM 10068599 ER PT J AU Bornstein, SR Preas, HL Chrousos, GP Suffredini, AF AF Bornstein, SR Preas, HL Chrousos, GP Suffredini, AF TI Salmonella abortus equi endotoxin does not affect leptin plasma levels in healthy humans - Reply SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter C1 NICHHD, Dev Endocrinol Branch, Pediat Endocrinol Sect,Clin Ctr, NIH, Bethesda, MD 20892 USA. RP Bornstein, SR (reprint author), NICHHD, Dev Endocrinol Branch, Pediat Endocrinol Sect,Clin Ctr, NIH, Bldg 10,Rm 10N262,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR PY 1999 VL 179 IS 4 BP 1048 EP 1048 DI 10.1086/314694 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 182MY UT WOS:000079503800043 ER PT J AU Olasz, E Yamada, N Linton, J Katz, SI AF Olasz, E Yamada, N Linton, J Katz, SI TI Assessment of bone-marrow derived dendritic cells for protein and contact hypersensitivity SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Derm Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 006 BP 523 EP 523 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800029 ER PT J AU Saeki, H Yamada, N Brown, MJ Moore, AM Hwang, ST AF Saeki, H Yamada, N Brown, MJ Moore, AM Hwang, ST TI Secondary lymphoid-tissue chemokine (SLC) and CCR7 participate in the emigration pathway of mature dendritic cells from the skin to regional lymph nodes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 038 BP 529 EP 529 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800063 ER PT J AU Cohen, SS Qalbani, M Aquilino, EA Neurath, AR Blauvelt, A AF Cohen, SS Qalbani, M Aquilino, EA Neurath, AR Blauvelt, A TI HIV-1 primary isolate infection of immature Langerhans cells within epithelial sheets: A novel model to study primary HIV infection SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. New York Blood Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 044 BP 530 EP 530 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800069 ER PT J AU Pacheco, HA Riley, GF Potosky, AL Federman, DG Kirsner, RS AF Pacheco, HA Riley, GF Potosky, AL Federman, DG Kirsner, RS TI Differences in melanoma stage at diagnosis between HMO and FFS are due to access to health care SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Univ Miami, Sch Med, Dept Dermatol, Miami, FL 33152 USA. Hlth Care Financing Ctr, Baltimore, MD USA. NCI, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 091 BP 538 EP 538 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800114 ER PT J AU Uchida, Y Sidransky, E Ginns, GI Elias, PM Holleran, WM AF Uchida, Y Sidransky, E Ginns, GI Elias, PM Holleran, WM TI Formation of the lipid-bound envelope (LBE): Insights from glucocerebrosidase-deficient Gaucher mouse epidermis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. Vet Adm Med Ctr, Dermatol Serv, San Francisco, CA 94121 USA. Kaneba Basic Res Lab, Odawara, Japan. NIMH, Sect Mol Neurogenet, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 121 BP 543 EP 543 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800144 ER PT J AU Abdel-Malek, Z Furumura, M Lamoreux, L Ollmann, M Barsh, G Hearing, V AF Abdel-Malek, Z Furumura, M Lamoreux, L Ollmann, M Barsh, G Hearing, V TI Agouti signaling protein inhibits melanogenesis primarily by binding to the melanocortin-1 receptor SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Univ Cincinnati, Dept Dermatol, Cincinnati, OH USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Texas A&M Univ, Dept Vet Pathol, College Stn, TX USA. Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 153 BP 548 EP 548 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800175 ER PT J AU Bale, S White, T Munro, C Taylor, A Richard, G AF Bale, S White, T Munro, C Taylor, A Richard, G TI Functional defects of Cx26 due to mutations in two families with dominant palmoplantar keratoderma and deafness SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS, Genet Studies Sect, NIH, Bethesda, MD USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. So Gen Hosp, Dept Dermatol, Glasgow G51 4TF, Lanark, Scotland. Royal Victoria Infirm, Dept Dermatol, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. Thomas Jefferson Univ, Jefferson Med Coll, Dept Dermatol & Cutaneous Biol, Philadelphia, PA 19107 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 168 BP 550 EP 550 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800191 ER PT J AU Richard, G Melino, G DiGiovanna, J Bale, S AF Richard, G Melino, G DiGiovanna, J Bale, S TI The spectrum of GJB3 mutations in Erythrokeratodermia variabilis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Thomas Jefferson Univ, Jefferson Med Coll, Dept Dermatol & Cutaneous Biol, Philadelphia, PA 19107 USA. IRCCS, IDI, Biochem Lab, Rome, Italy. NIAMS, Gen Studies Sect, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 171 BP 551 EP 551 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800193 ER PT J AU Pfutzner, W Joari, MA Hengge, UR Vogel, JC AF Pfutzner, W Joari, MA Hengge, UR Vogel, JC TI A raft culture model demonstrates the feasibility of topical selection for keratinocytes expressing a desired gene SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Univ Essen Gesamthsch, Dept Dermatol, D-4300 Essen 1, Germany. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 176 BP 552 EP 552 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800201 ER PT J AU Papadopoulos, E Yamada, N Saraf, M Fitzhugh, D Saeki, H Blauvelt, A Hwang, S AF Papadopoulos, E Yamada, N Saraf, M Fitzhugh, D Saeki, H Blauvelt, A Hwang, S TI Expression of a membrane-bound chemokine, fractalkine, and its receptor in skin dendritic cells is regulated by maturation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 198 BP 555 EP 555 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800221 ER PT J AU Yamada, N Katz, S AF Yamada, N Katz, S TI Gene regulation during dendritic cell maturation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 197 BP 555 EP 555 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800218 ER PT J AU von Stebut, E Udey, M AF von Stebut, E Udey, M TI Langerhans cell-like dendritic cells (DC) from both susceptible and resistant mice release IL-12 p70 after infection with Leishmania major SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 199 BP 556 EP 556 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800222 ER PT J AU Hildesheim, J Foster, R Kuhn, U Vogel, J AF Hildesheim, J Foster, R Kuhn, U Vogel, J TI Skn-1a POU transcription factor enhances terminal differentiation in HACaT cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 222 BP 559 EP 559 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800245 ER PT J AU Emmert, S Kobayashi, N Khan, SG Kraemer, KH AF Emmert, S Kobayashi, N Khan, SG Kraemer, KH TI The xeroderma pigmentosum group C gene leads to preferential repair of UV-induced cyclobutane pyrimidine dimers SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 233 BP 561 EP 561 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800254 ER PT J AU Walker, PS Krieg, AM Udey, MC Vogel, JC AF Walker, PS Krieg, AM Udey, MC Vogel, JC TI Immunostimulatory oligodeoxynucleotides provide systemic therapy for leishmaniasis via IL-12 and IFNgamma-dependent mechanisms SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. NCI, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 249 BP 564 EP 564 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800271 ER PT J AU Luke, M Darling, T Hsu, R Summers, R Smith, J Solomon, B Thomas, G Yancey, K AF Luke, M Darling, T Hsu, R Summers, R Smith, J Solomon, B Thomas, G Yancey, K TI Mucosal morbidity in patients with epidermolysis bullosa acquisita (EBA) SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NIDCD, Dept Rehabil Med, NIH, Bethesda, MD USA. NIDCD, Head & Neck Surg Branch, Tumor Biol Sect, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 267 BP 567 EP 567 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800289 ER PT J AU Lazarova, Z Yee, C Lazar, J Yancey, K AF Lazarova, Z Yee, C Lazar, J Yancey, K TI Laminin 01 alpha 3-specific autoantibodies in patients with anti-epiligrin cicatricial pemphigoid (AECP) recognize the G domain of this polypeptide SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. VAMC, Res Ctr, Baltimore, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 271 BP 568 EP 568 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800294 ER PT J AU Jarnik, M Lichti, U Simon, M Steven, AC AF Jarnik, M Lichti, U Simon, M Steven, AC TI Perturbed assembly of the cornified cell envelope in cultured keratinocytes and papilloma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS, LSB, NIH, Bethesda, MD USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 304 BP 573 EP 573 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800328 ER PT J AU Fleischmajer, R Utani, A McDonald, E Sapadin, A Yamada, Y AF Fleischmajer, R Utani, A McDonald, E Sapadin, A Yamada, Y TI Expression of laminin 01 alpha 1, 01 alpha 2, 01 alpha 3, 01 alpha 4 chains during skin morphogenesis requires an epithelial-mesenchymal interaction SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Mt Sinai Med Ctr, Dept Dermatol, New York, NY 10029 USA. NIDR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 372 BP 584 EP 584 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800395 ER PT J AU Khan, SG Schneider, TD Kraemer, KH AF Khan, SG Schneider, TD Kraemer, KH TI Splice mutations in xeroderma pigmentosum group C DNA: Intron retention, exon skipping and Internal neoplasms SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 420 BP 592 EP 592 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800443 ER PT J AU Kuhn, U Vogel, JC AF Kuhn, U Vogel, JC TI Transduction of human keratinocytes with a lentiviral vector SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 419 BP 592 EP 592 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800440 ER PT J AU Zoeteweij, J Eyes, S Kawamura, T Chandran, B Forghani, B Cohen, S Blauveir, A AF Zoeteweij, J Eyes, S Kawamura, T Chandran, B Forghani, B Cohen, S Blauveir, A TI Characterization and rapid quantification of human herpesvirus B lytic replication in single cells: Implications for designing treatment for and understanding pathogenesis of Kaposi's sarcoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. Howard Hughes Med Inst, Bethesda, MD 20817 USA. Univ Kansas, Kansas City, KS USA. Calif Dept Hlth Serv, Berkeley, CA 94704 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 488 BP 604 EP 604 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800513 ER PT J AU Wang, H Bellincampi, L Jones, L Steinert, P AF Wang, H Bellincampi, L Jones, L Steinert, P TI In vitro assembly of mouse hard 01 alpha-keratins into intermediate filaments SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA. CSIRO, Div Wool Technol, Belmont, Australia. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 577 BP 619 EP 619 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800600 ER PT J AU Wu, K Jang, S Steinert, P Bryan, J Morasso, M AF Wu, K Jang, S Steinert, P Bryan, J Morasso, M TI Role of homeobox transcription factor Dlx3 in the regulation of the trichohyalin gene SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 580 BP 619 EP 619 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800604 ER PT J AU Yoon, K Yoon, M Moir, R Steinert, P Omary, M Goldman, R AF Yoon, K Yoon, M Moir, R Steinert, P Omary, M Goldman, R TI Motile properties of keratin intermediate filament network SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Northwestern Univ, Dept Cell & Mol Biol, Chicago, IL 60611 USA. Yonsei Univ, Dept Dermatol, Seoul, South Korea. NIH, Skin Biol Lab, Bethesda, MD USA. VA Palo Alto Hlth Care Syst, Dept Med, Palo Alto, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 583 BP 620 EP 620 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800606 ER PT J AU Nemes, Z Marekov, L Steinert, P AF Nemes, Z Marekov, L Steinert, P TI Membrane binding directs transglutaminase 1 to specific glutamines in involucrin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS, NIH, Skin Biol Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 604 BP 623 EP 623 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800628 ER PT J AU Wu, K Jang, S Marekov, L Parry, D Yang, J Lee, J Steinert, P AF Wu, K Jang, S Marekov, L Parry, D Yang, J Lee, J Steinert, P TI Keratin intermediate filaments are stabilized by conserved sets of ionic charged residues SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA. Massey Univ, Inst Fundamental Sci, Palmerston North, New Zealand. Samsung Med Ctr, Dept Dermatol, Seoul, South Korea. Chungnam Natl Univ, Dept Dermatol, Taejon 305764, South Korea. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 603 BP 623 EP 623 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800625 ER PT J AU Blauvelt, A Glushakova, S Margolis, L AF Blauvelt, A Glushakova, S Margolis, L TI HIV-infected human epidermal Langerhans cells migrate into and infect human lymphoid tissue SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NICHD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 624 BP 626 EP 626 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800647 ER PT J AU Kim, S Steinert, P Choi, YC AF Kim, S Steinert, P Choi, YC TI Increased expression of transglutaminases 1 and 2 colocalizes with amyloid deposition in muscle of inclusion body myositis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA. Yonsei Univ, Coll Med, Dept Neurol, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 665 BP 633 EP 633 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800685 ER PT J AU Park, G Kee, S Kim, S Steinert, P AF Park, G Kee, S Kim, S Steinert, P TI Expression of antisense transglutaminase 1 in fibroblasts affects cytoskeletal organization and cellular adhesion SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 664 BP 633 EP 633 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800687 ER PT J AU Darling, T Koh, B Yancey, K AF Darling, T Koh, B Yancey, K TI Delineation of genes expressed in human epidermis by large-scale sequencing of a cDNA library generated from laser capture microdissected skin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 673 BP 635 EP 635 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800700 ER PT J AU Jang, S Morasso, M Rossi, A Steinert, P AF Jang, S Morasso, M Rossi, A Steinert, P TI Does a conformational change of the promoter region repress human loricrin expression? SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA. Univ Roma Tor Vergata, Dept Expt Med, Rome, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 682 BP 636 EP 636 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800704 ER PT J AU Morasso, M Park, G AF Morasso, M Park, G TI Transcriptional regulation of distal-less 3 (Dlx3) homeobox gene upon differentiation of mouse keratinocytes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 684 BP 636 EP 636 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800705 ER PT J AU DiGiovanna, J Bale, S Fleckman, P AF DiGiovanna, J Bale, S Fleckman, P TI A novel autosomal dominant ichthyosis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Univ Washington, Dept Med Dermatol, Seattle, WA 98195 USA. NIAMS, Genet Studies Sect, LSB, NIH, Bethesda, MD USA. Brown Univ, Div Dermpharm, Providence, RI 02912 USA. Univ Washington, Dept Med Dermatol, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 706 BP 640 EP 640 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800728 ER PT J AU Lee, C Kim, S Steinert, P Park, M AF Lee, C Kim, S Steinert, P Park, M TI The correlation between the expression of cytokines and transglutaminase 1 and 2 in human head and neck squamous cell carcinoma cell lines (HNSCCs) SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMSD, Skin Biol Lab, Bethesda, MD 20892 USA. NIDR, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 759 BP 649 EP 649 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800777 ER PT J AU Suzuki, H Shivji, G Wang, B Kraemer, K Sauder, D AF Suzuki, H Shivji, G Wang, B Kraemer, K Sauder, D TI Impaired ultraviolet B induced cytokine induction in xeroderma pigmentosum fibroblasts SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Univ Toronto, Sunnybrook Hlth Sci Ctr, Div Dermatol, Toronto, ON, Canada. NCI, Mol Carcinogenesis Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 823 BP 660 EP 660 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800848 ER PT J AU Khan, SG Bohr, V Metter, J Grossman, L Hedayati, M Bale, S Tarone, R Kraemer, KH AF Khan, SG Bohr, V Metter, J Grossman, L Hedayati, M Bale, S Tarone, R Kraemer, KH TI Xeroderma pigmentosum group C poly-AT intron insertion/deletion polymorphism associated with prostate cancer susceptibility in normal donors SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NIH, Baltimore, MD USA. Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA I06 BP 663 EP 663 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800864 ER PT J AU Ecelbarger, CA Kim, GH Mitchell, CW Terris, J Wade, JB Masilamani, S Bradford, AD Knepper, MA AF Ecelbarger, CA Kim, GH Mitchell, CW Terris, J Wade, JB Masilamani, S Bradford, AD Knepper, MA TI Regulation of the abundance of sodium and urea transporters along the nephron by vasopressin. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NHLBI, LKEM, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD APR PY 1999 VL 47 IS 4 SU S BP 187A EP 187A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 182AV UT WOS:000079477100045 ER PT J AU Frucht, DM Aringer, M Galon, J Danning, C Boumpas, D O'Shea, J AF Frucht, DM Aringer, M Galon, J Danning, C Boumpas, D O'Shea, J TI STAT4 is expressed by activated peripheral blood monocytes dendritic cells, and macrophages at sites of Th-1-mediated inflammation. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIAMS, NIH, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD APR PY 1999 VL 47 IS 4 SU S BP 190A EP 190A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 182AV UT WOS:000079477100059 ER PT J AU Gowda, DC Gluska, J von Halbeek, H Thotakura, RN Bredehorst, R Vogel, CW AF Gowda, DC Gluska, J von Halbeek, H Thotakura, RN Bredehorst, R Vogel, CW TI Structures of N-linked oligosaccharides from cobra venom factor. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Georgetown Univ, Dept Biochem & Mol Biol, Washington, DC 20007 USA. Univ Georgia, Complex Carbohydrate Res Ctr, Athens, GA 30602 USA. NIDDK, Mol & Cellular Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD APR PY 1999 VL 47 IS 4 SU S BP 192A EP 192A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 182AV UT WOS:000079477100071 ER PT J AU Thomas, A Fields, R Jeong, S Gainer, H AF Thomas, A Fields, R Jeong, S Gainer, H TI Use of the gene gun as a complement to transgenic mice to study neuronal gene expression. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD APR PY 1999 VL 47 IS 4 SU S BP 210A EP 210A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 182AV UT WOS:000079477100182 ER PT J AU Wang, WH Wang, SB Madara, P Cintron, AD Danner, RL AF Wang, WH Wang, SB Madara, P Cintron, AD Danner, RL TI Endothelial nitric oxide synthase upregulates TNF alpha production in transfected U937 cells through superoxide-dependent activated of P44/42 mitogen activated protein kinase. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD APR PY 1999 VL 47 IS 4 SU S BP 213A EP 213A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 182AV UT WOS:000079477100196 ER PT J AU Jensen, PN Major, EO AF Jensen, PN Major, EO TI Viral variant nucleotide sequences help expose leukocytic positioning in the JC virus pathway to the CNS SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article; Proceedings Paper CT Meeting on the Dedication of the Center-for-Neurovirology-and-Neurodegenerative-Disorders CY NOV 11, 1997 CL NEBRASKA MED CTR, OMAHA, NEBRASKA SP Ctr Neurovirol & Neurodegenerat Disorders HO NEBRASKA MED CTR DE progressive multifocal leukoencephalopathy; pathogenesis; JCV regulatory region; B lymphocytes ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; PERIPHERAL-BLOOD LEUKOCYTES; POLYMERASE CHAIN-REACTION; RENAL-TRANSPLANT PATIENTS; NEUROBLASTOMA CELL-LINES; EMBRYONIC KIDNEY-CELLS; HUMAN POLYOMA-VIRUS; FETAL GLIAL-CELLS; LARGE T-ANTIGENS; BK-VIRUS AB The human polyomavirus JCV lytically infects oligodendrocytes of immunosuppressed individuals leading to the fatal demyelinating disease termed progressive multifocal leukoencephalopathy (PML). Dementia, hemiparesis, and hemianopsia are the predominant presenting signs of PML. Asymptomatic JCV infection is common worldwide with approximately 80%; of adults testing positive for JCV antibodies. In addition to the brain, JCV has been shown to infect tonsil, lymphoid, Lose marrow, and kidney tissues, Viral variants, classified according to the nucleotide sequences of their regulatory regions, are being mapped in human tissues and cell types to help trace the pathway of JCV from a site of initial infection to target oligodendrocytes. In most literature, a dichotomy of the JCV regulatory region structure exists Ly tissue, B lymphocytes, however, have demonstrated the capacity to harbor JCV of diverse regulatory regions, which helps position their interaction with virus amid every stage of infection and implicates a lymphocytic role in latency. C1 NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. RP Jensen, PN (reprint author), NINDS, Lab Mol Med & Neurosci, NIH, Bldg 36,Rooms 5W21, Bethesda, MD 20892 USA. NR 99 TC 41 Z9 41 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD APR PY 1999 VL 65 IS 4 BP 428 EP 438 PG 11 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 184BV UT WOS:000079590200004 PM 10204570 ER PT J AU Rausch, DM Murray, EA Eiden, LE AF Rausch, DM Murray, EA Eiden, LE TI The SIV-infected rhesus monkey model for HIV-associated dementia and implications for neurological diseases SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article; Proceedings Paper CT Meeting on the Dedication of the Center-for-Neurovirology-and-Neurodegenerative-Disorders CY NOV 11, 1997 CL NEBRASKA MED CTR, OMAHA, NEBRASKA SP Ctr Neurovirol & Neurodegenerat Disorders HO NEBRASKA MED CTR DE neuropathogenesis; animal model; CNS inflammation; GFAP; quinolinic acid ID HUMAN-IMMUNODEFICIENCY-VIRUS; CENTRAL-NERVOUS-SYSTEM; QUINOLINIC ACID; CEREBROSPINAL-FLUID; ALZHEIMERS-DISEASE; MEDIODORSAL NUCLEUS; AIDS PATIENTS; RISK-FACTORS; HUMAN BRAIN; ENCEPHALOPATHY AB The neuropathogenesis of human immunodeficiency virus (HIV)-associated dementia has remained elusive, despite identification of HIV as the causal agent, Although a number of contributing factors have been identified, the series of events that culminate in motor and cognitive impairments after HIV infection of the central nervous system (CNS) are still not known. Rhesus monkeys infected with simian immunodeficiency virus (SIV) manifest immunosuppression and CNS disease that is pathologically [L. R. Sharer et al, (1991) J, Med, Primatol. 20, 211-217] and behaviorally [E, A. Murray et al, (1992) Science 255, 1246-1249] similar to humans. The SIV model of HIV-associated dementia (HAD) is widely recognized as a highly relevant model in,which to investigate neuropathogenesis. With better understanding of neuropathogenesis comes the opportunity to interrupt progression and to design better treatments for HAD. This becomes increasingly important as patients live longer yet still harbor HIV-infected cells in the CNS. The use of the SIV model has allowed the identification of neurochemical markers of neuropathogenesis Important not only for HAD, but also for other inflammatory neurological diseases. C1 NIMH, Off AIDS Res, Div Mental Disorders Behav Res & AIDS, Bethesda, MD 20892 USA. NIMH, Neurophysiol Lab, Bethesda, MD 20892 USA. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. NIMH, Cellular & Mol Neurobiol Lab, Bethesda, MD 20892 USA. RP Rausch, DM (reprint author), NIMH, Off AIDS Res, Div Mental Disorders Behav Res & AIDS, 6001 Execut Blvd,Rm 6212,MSC 9623, Bethesda, MD 20892 USA. OI Eiden, Lee/0000-0001-7524-944X; Murray, Elisabeth/0000-0003-1450-1642 NR 74 TC 27 Z9 29 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD APR PY 1999 VL 65 IS 4 BP 466 EP 474 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 184BV UT WOS:000079590200009 PM 10204575 ER PT J AU Subramanian, S Murugesan, R Devasahayam, N Cook, JA Afeworki, M Pohida, T Tschudin, RG Mitchell, JB Krishna, MC AF Subramanian, S Murugesan, R Devasahayam, N Cook, JA Afeworki, M Pohida, T Tschudin, RG Mitchell, JB Krishna, MC TI High-speed data acquisition system and receiver configurations for time-domain radiofrequency electron paramagnetic resonance spectroscopy and imaging SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article ID FOURIER-TRANSFORM; LOW-FREQUENCY; HIGH-RESOLUTION; SPECTROMETER; HEART; METABOLISM; OXIMETRY; TISSUES; PROBE; BRAIN AB Design strategies, system configuration, and operation of a dual-channel data acquisition system for a radiofrequency (RF) time-domain electron paramagnetic resonance (EPR) spectrometer/imager operating at 300 MHz are described. This system was configured to incorporate high-speed analog-to-digital conversion (ADC) and summation capabilities with both internal and external triggering via GPIB interface. The sampling rate of the ADC is programmable up to a maximum of 1 GS/s when operating in a dual-channel mode or 2 GS/s when the EPR data are collected in a single-channel mode, By using high-speed flash ADCs, a pipelined 8-bit adder, and a 24-bit accumulator, a repetition rate of 230 kHz is realized to sum FIDs of 4096 points. The record length is programmable up to a maximum of 8K points and a large number of FIDs (2(24)) can be summed without overflow before the data can be transferred to a host computer via CRIB interface for further processing. The data acquisition system can operate in a two-channel (quadrature) receiver mode for the conventional mixing to baseband, For detection using the single-channel mode, the resonance signals around the center frequency of 300 MHz were mixed with a synchronized local oscillator of appropriate frequency leading to an intermediate frequency (IF) which is sampled at a rate of 2 GS/s, Comparison of quadrature-mode and an IF-mode operation for EPR detection is presented by studying the FID signal intensity across a bandwidth of 10 MHz and as a function of transmit RF power, Imaging of large-sized phantoms accommodated in appropriately sized resonators indicates that IF-mode operation can be used to obtain distortion-free images in resonators of size 50 mm diameter and 50 mm length. (C) 1999 Academic Press. C1 NCI, Radiat Biol Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NCI, Signal Proc & Control Syst Grp, Computat Biosci & Engn Lab, NIH, Bethesda, MD 20892 USA. RP Subramanian, S (reprint author), NCI, Radiat Biol Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NR 31 TC 32 Z9 32 U1 1 U2 6 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD APR PY 1999 VL 137 IS 2 BP 379 EP 388 DI 10.1006/jmre.1998.1697 PG 10 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 184PE UT WOS:000079620300010 PM 10089172 ER PT J AU Gillis, P Roch, A Brooks, RA AF Gillis, P Roch, A Brooks, RA TI Corrected equations for susceptibility-induced T-2-shortening SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE susceptibility-induced relaxation; Curie relaxation; superparamagnetic particles; relaxometry; nuclear magnetic relaxation dispersion (NMRD) ID RELAXATION AB Local held gradients created by paramagnetic entities shorten water proton relaxation times, particularly T-2. This "novel" relaxation mechanism, now known as susceptibility-induced relaxation, was described twenty years ago by Gueron, and later extended by others to superparamagnetic particles which have a much larger magnetization. Unfortunately, because of subtle but significant errors, those results are valid only in the strict zero-field limit. These errors are corrected in the present article, and new versions of the relaxation equations are presented. The correction is shown to be significant, not only for transverse and longitudinal relaxation in aqueous superparamagnetic colloids, where the "Gueron" effect is known to be important, but even in some cases for transverse paramagnetic relaxation. (C) 1999 Academic Press. C1 Univ Mons, Fac Med, Biol Phys Dept, B-7000 Mons, Belgium. Univ Mons, Dept Organ Chem, NMR Lab, B-7000 Mons, Belgium. NINDS, Neuroimaging Branch, NIH, Bethesda, MD 20892 USA. RP Gillis, P (reprint author), Univ Mons, Fac Med, Biol Phys Dept, Ave Champ de Mars 24, B-7000 Mons, Belgium. NR 6 TC 51 Z9 52 U1 0 U2 24 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD APR PY 1999 VL 137 IS 2 BP 402 EP 407 DI 10.1006/jmre.1998.1691 PG 6 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 184PE UT WOS:000079620300013 PM 10089175 ER PT J AU Bulte, JWM de Cuyper, M Despres, D Frank, JA AF Bulte, JWM de Cuyper, M Despres, D Frank, JA TI Preparation, relaxometry, and biokinetics of PEGylated magnetoliposomes as MR contrast agent SO JOURNAL OF MAGNETISM AND MAGNETIC MATERIALS LA English DT Article; Proceedings Paper CT 2nd International Conference on Scientific and Clinical Applications of Magnetic Carriers (SCAMC2) CY MAY 28-30, 1998 CL CLEVELAND, OHIO DE superparamagnetic iron oxide; liposome; contrast agent; MR imaging ID SUPERPARAMAGNETIC IRON-OXIDE; FREQUENCY-DEPENDENCE; RELAXATION-TIMES; LIPOSOMES; PARTICLES AB We prepared PEGylated magnetoliposomes (ML-PEG) with a diameter of 40 nm and containing 1-6 superparamagnetic iron oxide crystals per vesicle. The T1 and T2 relaxivities were 3 and 240 s(-1)/mM at 1.5 T and 37 degrees C. In rats, ML-PEG showed a biexponential clearance with a long blood half-life of 53.2 +/- 13.2 min. Using MR imaging, ML-PEG was found to have excellent properties as a bone marrow-seeking MR contrast agent. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NIH, Lab Diagnost Radiol Res, Ctr Clin, Bethesda, MD 20892 USA. Katholieke Univ Leuven, Interdisciplinary Res Ctr, B-8500 Kortrijk, Belgium. NINDS, Anim Hlth & Care Sect, NIH, Bethesda, MD 20892 USA. RP Bulte, JWM (reprint author), NIH, Lab Diagnost Radiol Res, Ctr Clin, Room BIN256,10 Ctr Dr MSC 1074, Bethesda, MD 20892 USA. RI Bulte, Jeff/A-3240-2008 OI Bulte, Jeff/0000-0003-1202-1610 NR 15 TC 79 Z9 79 U1 2 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-8853 J9 J MAGN MAGN MATER JI J. Magn. Magn. Mater. PD APR PY 1999 VL 194 IS 1-3 BP 204 EP 209 DI 10.1016/S0304-8853(98)00556-3 PG 6 WC Materials Science, Multidisciplinary; Physics, Condensed Matter SC Materials Science; Physics GA 184RQ UT WOS:000079627300030 ER PT J AU Bulte, JWM Brooks, RA Moskowitz, BM Bryant, LH Frank, JA AF Bulte, JWM Brooks, RA Moskowitz, BM Bryant, LH Frank, JA TI Relaxometry, magnetometry, and EPR evidence for three magnetic phases in the MR contrast agent MION-46L SO JOURNAL OF MAGNETISM AND MAGNETIC MATERIALS LA English DT Article; Proceedings Paper CT 2nd International Conference on Scientific and Clinical Applications of Magnetic Carriers (SCAMC2) CY MAY 28-30, 1998 CL CLEVELAND, OHIO DE superparamagnetic iron oxide; magnetic nanoparticles; relaxometry; antiferromagnetism; electron-spin relaxation ID FREQUENCY-DEPENDENCE; RELAXATION-TIMES; SPIN RELAXATION; IRON AB Magnetization curves, EPR spectra, and T1 and T2 nuclear magnetic relaxation times versus Larmor frequency have been measured for the MRI contrast agent MION-46L. The resulting data can be successfully explained by adding paramagnetic and antiferromagnetic terms to the known superparamagnetic component. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NIH, Ctr Clin, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. NINDS, Neuroimaging Branch, Bethesda, MD 20892 USA. Univ Minnesota, Dept Geol & Geophys, Minneapolis, MN 55455 USA. RP Bulte, JWM (reprint author), NIH, Ctr Clin, Lab Diagnost Radiol Res, B10,B1N256,10 Ctr Dr MSC 1074, Bethesda, MD 20892 USA. RI Bulte, Jeff/A-3240-2008 OI Bulte, Jeff/0000-0003-1202-1610 NR 12 TC 10 Z9 11 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-8853 J9 J MAGN MAGN MATER JI J. Magn. Magn. Mater. PD APR PY 1999 VL 194 IS 1-3 BP 217 EP 223 DI 10.1016/S0304-8853(98)00555-1 PG 7 WC Materials Science, Multidisciplinary; Physics, Condensed Matter SC Materials Science; Physics GA 184RQ UT WOS:000079627300032 ER PT J AU Humphreys, RC AF Humphreys, RC TI Programmed cell death in the terminal endbud SO JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA LA English DT Article DE terminal endbud; apoptosis; ductal development; mammary gland ID EPIDERMAL GROWTH-FACTOR; MAMMARY-GLAND DEVELOPMENT; EXTRACELLULAR-MATRIX; DUCTAL MORPHOGENESIS; TRANSGENIC MICE; PROGESTERONE RECEPTORS; EPITHELIAL-CELLS; FACTOR-I; APOPTOSIS; CARCINOGENESIS AB Ductal development in the pubertal mouse mammary gland is characterized by dramatic morphological changes in the epithelium driven by proliferation of cap and body cells in the terminal endbuds. Recent experiments revealed a coincident and abundant apoptosis in the body cells of these structures. The cells undergoing apoptosis are occasionally restricted to defined regions within the terminal endbud. Localization adjacent to the presumptive lumina suggests that this process functions to sculpt the lumina of the subtending duct. Members of the Bcl-2 family of apoptosis regulatory molecules; Bcl-2 and Bcl-x, appear to have some role in regulating apoptosis in the terminal endbud. Other possible signals which could regulate this developmental process and a model are presented. C1 NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. RP Humphreys, RC (reprint author), NIDDK, Lab Genet & Physiol, NIH, Bldg 8,Room 111, Bethesda, MD 20892 USA. NR 46 TC 26 Z9 26 U1 0 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1083-3021 J9 J MAMMARY GLAND BIOL JI J. Mammary Gland Biol. Neoplasia PD APR PY 1999 VL 4 IS 2 BP 213 EP 220 DI 10.1023/A:1018733426625 PG 8 WC Oncology; Endocrinology & Metabolism; Physiology SC Oncology; Endocrinology & Metabolism; Physiology GA 213EE UT WOS:000081258900011 PM 10426400 ER PT J AU Lacaz-Vieira, F Jaeger, MMM Farshori, P Kachar, B AF Lacaz-Vieira, F Jaeger, MMM Farshori, P Kachar, B TI Small synthetic peptides homologous to segments of the first external loop of occludin impair tight junction resealing SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE tight junction; occludin; ZO-1; transepithelial resistance ID MEMBRANE-PROTEIN; PERMEABILITY; IDENTIFICATION; POLYPEPTIDE; EPITHELIA; COMPONENT; SEQUENCE; CINGULIN; BARRIER; STRANDS AB This study shows that resealing of opened tight junctions (TJs) is impaired by interaction with oligopeptides homologous to the external domain of chick occludin, The experiments were carried out with confluent A6 cell monolayers grown on collagen supports under stable transepithelial electrical resistance (TER). The monolayers were bathed on the apical side with a 75 mM KCl solution and on the basolateral side by NaCl-Ringer's solution. TJ opening was induced by basolateral Ca2+ removal and was characterized by a marked drop of TER. The reintroduction of Ca2+ triggered junction resealing as indicated by an elevation of TER to control values. Custom-made peptides SNYYGSGLSY (corresponding to the residues 100 to 109) and SNYYGSGLS (residues 100 to 108), homologous to segments of the first external loop of chick occludin molecule, impaired junction resealing when the peptides were included in the apical bathing fluid (concentrations in the range of 0.5 to 1.5 mg/ml), Peptide removal from the apical solution usually triggered a slow recovery of TER, indicating a slow recovery of the TJ seal. Changes in localization of ZO-1, a cytoplasmic protein that underlies the membrane at the TJs, were evaluated immunocytochemically following Ca2+ removal and reintroduction. The presence or absence of the oligopeptides showed no influence on the pattern of change of ZO-1 localization. These observations support the hypothesis that the TJ seal results from the interaction of specific homologous segments of occludin on the surface of adjacent cells. Additionally, our results show that small peptides homologous to segments of the occludin first external loop can be used as specific reagents to manipulate the permeability of tight junctions. C1 NIDODS, Sect Struct Cell Biol, NIH, Bethesda, MD 20892 USA. Univ Sao Paulo, Inst Ciencias Biomed, Dept Fisiol & Biofis, BR-05508 Sao Paulo, Brazil. Univ Sao Paulo, Fac Odontol, Disciplina Patol Bucal, BR-05508 Sao Paulo, Brazil. RP Kachar, B (reprint author), NIDODS, Sect Struct Cell Biol, NIH, Bethesda, MD 20892 USA. RI Marques, Marcia/F-3780-2012 OI Marques, Marcia/0000-0002-9398-1252 NR 29 TC 84 Z9 87 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD APR 1 PY 1999 VL 168 IS 3 BP 289 EP 297 DI 10.1007/s002329900518 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA 183RV UT WOS:000079568000009 PM 10191363 ER PT J AU Frisbie, SM Reedy, MC Yu, LC Brenner, B Chalovich, JM Kraft, T AF Frisbie, SM Reedy, MC Yu, LC Brenner, B Chalovich, JM Kraft, T TI Sarcomeric binding pattern of exogenously added intact caldesmon and its C-terminal 20-kDa fragment in skinned fibers of skeletal muscle SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY LA English DT Article ID SMOOTH-MUSCLE; THIN-FILAMENTS; ATPASE ACTIVITY; PARALLEL INHIBITION; MYOSIN SUBFRAGMENTS; GIZZARD CALDESMON; FORCE GENERATION; IONIC-STRENGTH; ACTIN; TROPOMYOSIN AB Intact caldesmon and particularly the actin-binding C-terminal fragment (20-kDa) of caldesmon have been shown in skeletal muscle fibers to selectively displace low affinity, weakly bound cross-bridges from actin without significantly altering the actin attachment of force producing, strong binding cross-bridges (Brenner et al., 1991; Kraft et al., 1995a). However, the sarcomeric distribution and the specific binding of externally added caldesmon to the myofilaments of skeletal muscle fibers was not known. It was e.g., unclear whether caldesmon binds along actin in a manner similar to tropomyosin or whether it also binds to myosin. In this study, we determined the binding pattern of exogenously added intact caldesmon and its C-terminal 20-kDa fragment, respectively, in MgATP-relaxed rabbit skeletal muscle fibers using electron (EM) and confocal fluorescence microscopy (CFM). EM showed that similar to what has been demonstrated earlier for smooth muscle thin filaments (Lehman et al., 1989), intact caldesmon binds periodically every 38 nm along the thin filaments. CFM revealed that rhodamine-labeled intact caldesmon and the 20-kDa caldesmon fragment bind along nearly the entire length of the thin filaments. A portion of the I-band near the Z-line appears unlabeled, both when equilibrated at normal and long sarcomere lengths. The width of the unlabeled region seems to depend on ionic strength. The 20-kDa C-terminal caldesmon fragment binds in essentially the same pattern as intact caldesmon. This indicates that the high fluorescence intensity in the overlap region seen with intact caldesmon does not depend on caldesmon binding to myosin. X-ray diffraction was used to monitor the effects on filament lattice. Intact caldesmon at > 0.3 mg/ml induced disorder in the myofilament lattice. No such disordering was observed, however, when fibers were equilibrated with up to 0.8 mg/ml of the 20-kDa caldesmon fragment. C1 Med Hsch Hannover, D-30625 Hannover, Germany. Duke Univ, Med Ctr, Durham, NC 27710 USA. E Carolina Univ, Sch Med, Greenville, NC 27834 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Kraft, T (reprint author), Med Hsch Hannover, D-30625 Hannover, Germany. OI Chalovich, Joseph/0000-0002-1243-4055 FU NIAMS NIH HHS [AR35216, AR14317] NR 45 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0142-4319 J9 J MUSCLE RES CELL M JI J. Muscle Res. Cell Motil. PD APR PY 1999 VL 20 IS 3 BP 291 EP 303 DI 10.1023/A:1005490405222 PG 13 WC Cell Biology SC Cell Biology GA 235UF UT WOS:000082560400005 PM 10471992 ER PT J AU Bokesch, HR Blunt, JW Westergaard, CK Cardellina, JH Johnson, TR Michael, JA McKee, TC Hollingshead, MG Boyd, MR AF Bokesch, HR Blunt, JW Westergaard, CK Cardellina, JH Johnson, TR Michael, JA McKee, TC Hollingshead, MG Boyd, MR TI Alertenone, a dimer of suberosenone from Alertigorgia sp. SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID ASPERGILLUS-TERREUS AB Bioassay-guided fractionation of organic extracts of the gorgonian Alertigorgia sp. has yielded the previously known suberosenone (1), a cytotoxic tricyclic sesquiterpene of the quadrone class, and alertenone (2), a dimer of suberosenone. The structure of 2 was determined by spectral analysis; the 1D TOCSY experiment was particularly useful in the structure elucidation. Comparison of the in vitro cytotoxicity of alertenone and suberosenone revealed that the dimeric alertenone was devoid of cytotoxicity below 35 mu g/mL. In a hollow-fiber assay model of in vivo activity, suberosenone exhibited some growth inhibition of two of six tumor cell lines tested. C1 NCI, Frederick Canc Res & Dev Ctr, Div Canc Treatment & Diag, Lab Drug Discovery Res & Dev,Dev Therapeut Progra, Frederick, MD 21702 USA. RP Boyd, MR (reprint author), NCI, Frederick Canc Res & Dev Ctr, Div Canc Treatment & Diag, Lab Drug Discovery Res & Dev,Dev Therapeut Progra, Bldg 1052,Room 121, Frederick, MD 21702 USA. OI Blunt, John/0000-0003-4053-4376 FU NCI NIH HHS [N01 CO 56000] NR 8 TC 44 Z9 44 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD APR PY 1999 VL 62 IS 4 BP 633 EP 635 DI 10.1021/np980464z PG 3 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 190JL UT WOS:000079959300026 PM 10217729 ER PT J AU Dijoux, MG Gamble, WR Hallock, YF Cardellina, JH van Soest, R Boyd, MR AF Dijoux, MG Gamble, WR Hallock, YF Cardellina, JH van Soest, R Boyd, MR TI A new discorhabdin from two sponge genera SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID CYTOTOXIC MACROLIDES C1 NCI, Frederick Canc Res & Dev Ctr, Div Canc Treatment & Diag, Lab Drug Discovery Res & Dev,Dev Therapeut Progra, Frederick, MD 21702 USA. RP Boyd, MR (reprint author), NCI, Frederick Canc Res & Dev Ctr, Div Canc Treatment & Diag, Lab Drug Discovery Res & Dev,Dev Therapeut Progra, Bldg 1052,Room 121, Frederick, MD 21702 USA. NR 11 TC 40 Z9 41 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD APR PY 1999 VL 62 IS 4 BP 636 EP 637 DI 10.1021/np980465r PG 2 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 190JL UT WOS:000079959300027 PM 10217730 ER PT J AU Rall, JE AF Rall, JE TI The unity of knowledge. SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review C1 NIDDK, NIH, Bethesda, MD 20892 USA. RP Rall, JE (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD APR PY 1999 VL 187 IS 4 BP 254 EP 255 DI 10.1097/00005053-199904000-00013 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 186LY UT WOS:000079732300013 ER PT J AU Mason, RP Leeds, PR Jacob, RF Hough, CJ Zhang, KG Mason, PE Chuang, DM AF Mason, RP Leeds, PR Jacob, RF Hough, CJ Zhang, KG Mason, PE Chuang, DM TI Inhibition of excessive neuronal apoptosis by the calcium antagonist amlodipine and antioxidants in cerebellar granule cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Ca2+ channel blockers; apoptosis; antioxidants; cerebellar granule cells ID CHANNEL BLOCKERS; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; PRIMARY CULTURES; AGING RABBITS; HEART-FAILURE; BRAIN; LOCATION; SURVIVAL; BINDING; CA-2+ AB Neuronal cell death as a result of apoptosis is associated with cerebrovascular stroke and various neurodegenerative disorders. Pharmacological agents that maintain normal intracellular Ca2+ levels and inhibit cellular oxidative stress may be effective in blocking abnormal neuronal apoptosis. In this study, a spontaneous (also referred to as age-induced) model of apoptosis consisting of rat cerebellar granule cells was used to evaluate the antiapoptotic activities of voltage-sensitive Ca2+ channel blockers and various antioxidants, The results of these experiments demonstrated that the charged, dihydropyridine Ca2+ channel blocker amlodipine had very potent neuroprotective activity in this system, compared with antioxidants and neutral Ca2+ channel blockers (nifedipine and nimodipine). Within its effective pharmacological range (10-100 nM), amlodipine attenuated intracellular neuronal Ca2+ increases elicited by KCI depolarization but did not affect Ca2+ changes triggered by N-methyl-D-aspartate receptor activation. Amlodipine also inhibited free radical-induced damage to lipid constituents of the membrane in a dose-dependent manner, independent of Ca2+ channel modulation. In parallel experiments, spontaneous neuronal apoptosis was inhibited in dose- and time-dependent manners by antioxidants (U-78439G, alpha-tocopherol, and melatonin), nitric oxide synthase inhibitors (N-nitro-L-arginine and N-nitro-o-arginine), and a nitric oxide chelator (hemoglobin) in the micromolar range. These results suggest that spontaneous neuronal apoptosis is associated with excessive Ca2+ influx, leading to further intracellular Ca2+ increases and the generation of reactive oxygen species. Agents such as amlodipine that block voltage-sensitive Ca2+ channels and inhibit cellular oxidative stress may be effective in the treatment of cerebrovascular stroke and neurodegenerative diseases associated with excessive apoptosis. C1 Allegheny Univ Hlth Sci, MCP Hahnemann Sch Med, Cardiovasc & Pulm Res Inst, Pittsburgh, PA 15212 USA. NIMH, Mol Neurobiol Sect, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP Mason, RP (reprint author), Allegheny Univ Hlth Sci, MCP Hahnemann Sch Med, Cardiovasc & Pulm Res Inst, 320 E North Ave 15ST, Pittsburgh, PA 15212 USA. NR 41 TC 84 Z9 88 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD APR PY 1999 VL 72 IS 4 BP 1448 EP 1456 DI 10.1046/j.1471-4159.1999.721448.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 177HJ UT WOS:000079204300015 PM 10098848 ER PT J AU Christie, JM Wenthold, RJ Monaghan, DT AF Christie, JM Wenthold, RJ Monaghan, DT TI Insulin causes a transient tyrosine phosphorylation of NR2A and NR2B NMDA receptor subunits in rat hippocampus SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE N-methyl-D-aspartate; insulin; phosphorylation; kinase; hippocampus; growth factor ID LONG-TERM POTENTIATION; CENTRAL-NERVOUS-SYSTEM; GROWTH FACTOR-I; NEUROTROPHIC FACTOR; PHOSPHATIDYLINOSITOL 3-KINASE; SYNAPTIC PLASTICITY; SIGNALING SYSTEM; BRAIN; EXPRESSION; SUBSTRATE-1 AB NMDA receptors play a critical role in various aspects of CNS function. Hence, it is important to identify mechanisms that regulate NMDA receptor activity. We have shown previously that insulin rapidly potentiates NMDA receptor activity in both native and recombinant expression systems, Here we report that insulin causes a transient phosphorylation of NR2A and NR2B NMDA receptor subunits on tyrosine residues, Rat hippocampal slices were exposed to 1 mu M insulin for 20 and 60 min and then solubilized, NR2A and NR2B subunits were immunoprecipitated and probed for tyrosine phosphorylation. Insulin incubation of hippocampal slices for 20 min elicited an increase in tyrosine phosphorylation to 176 +/- 16% (NR2A) and 203 +/- 15% (NR2B) of control levels. In contrast, 60 min of insulin incubation did not alter NR2 tyrosine phosphorylation levels (NR2A: 85 +/- 13% of control; NR2B: 93 +/- 10% of control). Although the consequence of insulin-stimulated tyrosine phosphorylation is unknown, it is possible that this site(s) is responsible for insulin potentiation of NMDA receptor activity. This possibility is consistent with our earlier finding that insulin potentiates hippocampal NMDA receptor activity after 20 min, but not after 60 min, of insulin exposure. C1 Univ Nebraska, Med Ctr, Dept Pharmacol, Omaha, NE 68198 USA. NIDCD, Neurochem Lab, NIH, Bethesda, MD USA. RP Monaghan, DT (reprint author), Univ Nebraska, Med Ctr, Dept Pharmacol, 600 S 42 St, Omaha, NE 68198 USA. NR 48 TC 57 Z9 57 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD APR PY 1999 VL 72 IS 4 BP 1523 EP 1528 DI 10.1046/j.1471-4159.1999.721523.x PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 177HJ UT WOS:000079204300024 PM 10098857 ER PT J AU Williams, WA Shoaf, SE Hommer, D Rawlings, R Linnoila, M AF Williams, WA Shoaf, SE Hommer, D Rawlings, R Linnoila, M TI Effects of acute tryptophan depletion on plasma and cerebrospinal fluid tryptophan and 5-hydroxyindoleacetic acid in normal volunteers SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE serotonin; CSF; tryptophan; depletion; plasma; 5-hydroxyindoleacetic acid ID OBSESSIVE-COMPULSIVE DISORDER; SEROTONIN REUPTAKE INHIBITORS; HEALTHY-VOLUNTEERS; BRAIN TRYPTOPHAN; RAPID DEPLETION; ANTIDEPRESSANT ACTION; RAT HIPPOCAMPUS; NORMAL MALES; FREE DIET; RELEASE AB Brain serotonin synthesis and metabolism (turnover), as indicated by CSF concentrations of 5-hydroxyindoleacetic acid (5-HIAA), may depend on plasma concentrations of the essential amino acid L-tryptophan (TRP). We investigated the biochemical effects of acute plasma TRP depletion (ATD) in normal volunteers undergoing a 36-h CSF collection via lumbar drain. Six subjects who were in good health were put on a low-TRP diet (160 mg/day) 24 h before lumbar puncture; this diet was continued for the first 22 h of the CSF collection. At hour 22, subjects ingested a TRP-deficient 15-amino acid drink shown previously to deplete plasma TRP. Total plasma TRP, free plasma TRP, and CSF TRP subsequently decreased 86.3, 86.5, and 92.3%, respectively. CSF 5-HIAA decreased by 32.8%. Plasma total and free TRP concentrations were both decreased at similar to 2 h following ingestion of the TRP-free amino acid drink and were lowest similar to 6 h after ATD; CSF TRP and 5-HIAA were decreased at 2.5 h and similar to 4 h after ATD, respectively. CSF TRP was lowest 8.0 h later. CSF 5-HIAA continued to decrease 14 h after the TRP-deficient amino acid drink was given. C1 NIAAA, LCS, NIH, Bethesda, MD 20892 USA. RP Williams, WA (reprint author), NIAAA, LCS, NIH, Bldg 10,Room 6S240,10 Ctr Dr, Bethesda, MD 20892 USA. NR 43 TC 159 Z9 160 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD APR PY 1999 VL 72 IS 4 BP 1641 EP 1647 DI 10.1046/j.1471-4159.1999.721641.x PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 177HJ UT WOS:000079204300039 PM 10098872 ER PT J AU Bartoszewicz, ZP Jaffe, H Sasaki, M Moller, JR Stebbins, JW Gebrekristos, H Quarles, RH AF Bartoszewicz, ZP Jaffe, H Sasaki, M Moller, JR Stebbins, JW Gebrekristos, H Quarles, RH TI Prominent 85-kDa oligomannosidic glycoproteins of rat brain are signal regulatory proteins and include the SHP substrate-1 for tyrosine phosphatases SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE glycoprotein; mannose-rich oligosaccharides; phosphotyrosine phosphatases; signal-regulatory proteins (SIRPs); SHP substrate-1 ID MYELIN-ASSOCIATED GLYCOPROTEIN; FLUOROPHORE 8-AMINONAPHTHALENE-1,3,6-TRISULFONIC ACID; POLYACRYLAMIDE-GEL ELECTROPHORESIS; CENTRAL-NERVOUS-SYSTEM; NEURITE OUTGROWTH; ADHESION MOLECULE; GLYCANS; ANTIGEN; EXPRESSION; CONTAINS AB The glycoprotein component in rat brain reacting most strongly with Galanthus nivalis agglutinin (GNA) on western blots migrates as an 85-kDa band. GNA identifies mannose-rich oligosaccharides because it is highly specific for terminal alpha-mannose residues. After purification of this 85-kDa glycoprotein band by chromatography on GNA-agarose and preparative gel etectrophoresis, binding of other lectins demonstrated the presence of fucose and a trace of galactose, but no sialic acid. Treatment with N-Glycanase or endoglycosidase H produced a 65-kDa band, indicating that it consisted of about one-fourth N-linked oligomannosidic carbohydrate moieties. High-performance anion-exchange chromatography and fluorescence-assisted carbohydrate electrophoresis indicated that the major carbohydrate moiety is a heptasaccharide with the structure Man alpha 1-6(Man alpha 1-3)Man alpha 1-6(Man alpha 1-3)Man beta 1-4Glc-NAc beta 1-4GlcNAc (Man(5)GlcNAc(2)). Determination of amino acid sequences of peptides produced by endoproteinase digestion demonstrated that this 85-kDa mannose-rich glycoprotein component contained the SHP substrate-1 for phosphotyrosine phosphatases and at least one other member of the signal-regulatory protein (SIRP) family. The unusually high content of oligomannosidic carbohydrate moieties on these receptor-like members of the immunoglobulin superfamily in neural tissue could be of functional significance for intercellular adhesion or signaling. C1 NINDS, Mol & Cellular Neurobiol Lab, Myelin & Brain Dev Sect, NIH, Bethesda, MD 20892 USA. NINDS, LNC, Protein Peptide Sequencing Fac, NIH, Bethesda, MD 20892 USA. Polish Acad Sci, Med Res Ctr, Dept Endocrinol, Warsaw, Poland. RP Quarles, RH (reprint author), Bldg 49,Rm 2A28,49 Convent Dr,MSC 4440, Bethesda, MD 20892 USA. NR 26 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD APR PY 1999 VL 72 IS 4 BP 1688 EP 1693 DI 10.1046/j.1471-4159.1999.721688.x PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 177HJ UT WOS:000079204300045 PM 10098878 ER PT J AU Singer, JH Berger, AJ AF Singer, JH Berger, AJ TI Contribution of single-channel properties to the time course and amplitude variance of quantal glycine currents recorded in rat motoneurons SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID INHIBITORY SYNAPTIC CURRENTS; CEREBELLAR GRANULE CELLS; RECEPTOR-ALPHA-SUBUNITS; GABA MINI AMPLITUDE; HYPOGLOSSAL MOTONEURONS; SPINAL-CORD; DEVELOPMENTAL-CHANGES; HIPPOCAMPAL SLICES; MESSENGER-RNAS; NEURONS AB The amplitude of spontaneous. glycinergic miniature inhibitory postsynaptic currents (mIPSCs) recorded in hypoglossal motoneurons (HMs) in an in vitro brain stem slice preparation increased over the first 3 postnatal weeks, from 42 +/- 6 pA in neonate (P0-3) to 77 +/- ii pA in juvenile (P11-18) HMs. Additionally, mIPSC amplitude distributions were highly variable: CV 0.68 +/- 0.05 (means +/- SE) for neonates and 0.83 +/- 0.06 for juveniles, We wished to ascertain the contribution of glycine receptor (GlyR)channel properties to this change in quantal amplitude and to the amplitude variability and time course of mIPSCs. To determine whether a postnatal increase in GlyR-channel conductance accounted for the postnatal change in quantal amplitude, the conductance of synaptic GlyR channels was determined by nonstationary, variance analysis of mIPSCs. It was 48 +/- 8 pS in neonate and 46 +/- 10 pS in juvenile HMs, suggesting that developmental changes in mIPSC amplitude do not result from a postnatal alteration of GlyR-channel conductance. Next we determined the open probability (P-open) of GlyR channels in outside-out patches excised from HMs to estimate the contribution of stochastic channel behavior to quantal amplitude variability. Brief (1 ms) pulses Of glycine (I mM) elicited patch currents that closely resembled mIPSCs. The GlyR channels' P-open, calculated by nonstationary variance analysis of these currents, was similar to 0.70 (0.66 +/- 0.09 in neonates and 0.72 +/- 0.05 in juveniles). The decay rate of patch currents elicited bq brief application of saturating concentrations of glycine (10 mM) increased postnatally, mimicking previously documented changes in mIPSC time course, Paired pulses of glycine (10 mM) were used to determine if rapid GlyR-channel desensitization contributed to either patch current time course or quantal amplitude variability. Because we did not observe any fast desensitization of patch currents, we believe that fast desensitization of GlyRs underlies neither phenomenon. From our analysis of glycinergic patch currents and mIPSCs, ne draw three conclusions. First, channel deactivation is the primary determinant of glycinergic mIPSC time course, and postnatal changes in channel deactivation rate account for observed developmental changes in mIPSC decay rate. Second, because GlyR-channel P-open is high, differences in receptor number between synapses rather than stochastic channel behavior are likely to underlie the majority of quantal variability seen at glycinergic synapses throughout postnatal development. Wr estimate the number of GlyRs available at a synapse to be on average 27 in neonate neurons and 39 in juvenile neurons. Third, this change in the calculated number of GlyRs at each synapse may account for the postnatal increase in mIPSC amplitude. C1 Univ Washington, Sch Med, Dept Physiol & Biophys, Seattle, WA 98195 USA. RP Singer, JH (reprint author), NINDS, NIH, 36 Convent Dr,MSC-4156,Bldg 36,Rm 5B21, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [HL-49657]; NINDS NIH HHS [NS-14857] NR 57 TC 65 Z9 65 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD APR PY 1999 VL 81 IS 4 BP 1608 EP 1616 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 186VW UT WOS:000079752000018 PM 10200197 ER PT J AU Gibril, F Reynolds, JC Chen, CC Yu, F Goebel, SU Serrano, J Doppman, JL Jensen, RT AF Gibril, F Reynolds, JC Chen, CC Yu, F Goebel, SU Serrano, J Doppman, JL Jensen, RT TI Specificity of somatostatin receptor scintigraphy: A prospective study and effects of false-positive localizations on management in patients with gastrinomas SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE somatostatin receptor scintigraphy; gastroenteropancreatic tumors; Zollinger-Ellison syndrome; neuroendocrine tumor ID ZOLLINGER-ELLISON-SYNDROME; ENDOCRINE NEOPLASIA TYPE-1; PRIMARY BREAST-CANCER; OCTREOTIDE SCINTIGRAPHY; GALLBLADDER VISUALIZATION; THYROID-CARCINOMA; IN-VIVO; METASTASES; RESECTION; TUMORS AB Somatostatin receptor scintigraphy (SRS) is being increasingly used both for localization and, in some cases, diagnosis of various diseases. There are no prospective studies of its specificity or occurrence of false-positive results and their effects on management. This study was designed to address both of these issues. Methods: Over a 40-mo period, 146 consecutive patients with Zollinger-Ellison syndrome (ZES) undergoing 480 SRS examinations were studied prospectively. Patients were admitted at least yearly and underwent SRS as well as conventional imaging studies (ultrasonography, CT, MRI) and angiography, if necessary. All admissions were assigned to one of five different clinical categories in which imaging studies had different purposes. SRS localizations were classified as true-positive or false-positive based on preset criteria. A false-positive result was determined to change clinical management based on five preset criteria. Results: Of all SRS examinations, 12% resulted in a false-positive localization for a neuroendocrine tumor or its metastases, resulting in a sensitivity of 71%, specificity of 86% and positive and negative predictive values of 85% and 52%, respectively. Extra-abdominal false-positive localizations (2/3) were more common than intra-abdominal (1/3). Thyroid disease, breast disease and granulomatosis lung disease were the most frequent causes of extra-abdominal false-positive localizations. Accessory spleens, localization to previous operative sites, renal parapelvic cysts and various procedural aspects were the most frequent causes of intra-abdominal false-positive localizations. Of all SRS studies, 2.7% resulted in a false-positive result that altered management. Conclusion: False-positive SRS localization occurs in 1 of 10 patients with ZES. By having a thorough understanding of diseases or circumstances that result in false-positive localization and comparing the SRS result with the clinical context, the percentage of patients in whom false-positive localization results in altered management can be reduced to below 3% and the correct diagnosis made in almost every case. C1 NIDDK, NIH, DDB, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDK, NIH, DDB, Bldg 10,Rm 9C-103,10 Ctr Dr,MSC 1804, Bethesda, MD 20892 USA. NR 40 TC 113 Z9 115 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD APR PY 1999 VL 40 IS 4 BP 539 EP 553 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182WU UT WOS:000079521800012 PM 10210211 ER PT J AU Wang, SL Baum, BJ Kagami, H Zheng, CY O'Connell, BC Atkinson, JC AF Wang, SL Baum, BJ Kagami, H Zheng, CY O'Connell, BC Atkinson, JC TI Effect of clodronate on macrophage depletion and adenoviral-mediated transgene expression in salivary glands SO JOURNAL OF ORAL PATHOLOGY & MEDICINE LA English DT Article DE clodronate; gene therapy; macrophages; saliva; salivary glands ID TRANSFER IN-VIVO; GENE-TRANSFER; RECOMBINANT ADENOVIRUSES; DELIVERY; EFFICACY; THERAPY; CELLS; LUNG; RESPONSES; LIPOSOMES AB Expression of transgenes from adenoviral vectors is short-lived in salivary glands, in part because of immune responses to the virus and/or transgene product. Previous studies demonstrated that depletion of macrophages with multilamellar liposomes containing clodronate (Cl2MBP) increases adenoviral-mediated transgene expression in the liver. This technique was tested in salivary glands. Rats were treated with Cl2MBP-liposomes or control liposomes by femoral vein, intraperitoneal, or carotid artery injections. Thereafter, a recombinant adenovirus, AdCMVluciferase, was instilled intraductally in submandibular glands (SMGs), or delivered to the liver via femoral vein injection. Marked depletion (>94%) of liver macrophages and increased levels of luciferase activity in the liver (45-fold higher than controls) were present in animals receiving Cl2MBP-liposomes. In contrast, the same treatment never depleted more than 41% of SMG macrophages nor increased luciferase activity in SMGs, regardless of the route of administration. In conclusion, while macrophage depletion with Cl2MBP-liposomes is associated with markedly increased adenoviral-mediated transgene expression, this strategy was ineffective for salivary glands. C1 NIDR, GTTB, NIH, Bethesda, MD 20892 USA. Capital Univ Med Sci, Beijing Hosp Stomatol, Salivary Gland Dis Ctr, Beijing, Peoples R China. Nagoya Univ, Sch Med, Dept Oral Surg, Nagoya, Aichi 466, Japan. RP Atkinson, JC (reprint author), NIDR, GTTB, NIH, Bldg 10,1N113,MSC-1190, Bethesda, MD 20892 USA. OI O'Connell, Brian/0000-0003-4529-7664 NR 31 TC 16 Z9 17 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0904-2512 J9 J ORAL PATHOL MED JI J. Oral Pathol. Med. PD APR PY 1999 VL 28 IS 4 BP 145 EP 151 PG 7 WC Dentistry, Oral Surgery & Medicine; Pathology SC Dentistry, Oral Surgery & Medicine; Pathology GA 186JB UT WOS:000079724200001 PM 10235366 ER PT J AU Spiegel, AM AF Spiegel, AM TI Hormone resistance caused by mutations in G proteins and G protein-coupled receptors SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 2nd Serono Symposia Workshop on Clinical Paediatric Endocrinology CY SEP 07-08, 1998 CL SALZBURG, AUSTRIA SP Serono Symposia 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; DELETION MUTATION; ADENYLYL-CYCLASE 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, Pseudohypoparathyroidism (PHP), the first described example of a hormone resistance disorder, is characterized by renal resistance to parathyroid hormone (PTH) proximal to generation of the second messenger, cAMP, In PHP Ia there is more generalized hormone resistance (PTH, TSH, gonadotropins) and associated abnormal physical features, Albright hereditary osteodystrophy (AHO). Subjects with PHP Ib are normal in appearance and resistant exclusively to PTH. 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, In PHP Ib, several studies have excluded PTH receptor gene mutations, and the molecular basis has not yet been defined. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Spiegel, AM (reprint author), NIDDKD, NIH, Bldg 10,Rm 9N-222, Bethesda, MD 20892 USA. NR 39 TC 5 Z9 5 U1 0 U2 0 PU FREUND PUBLISHING HOUSE LTD PI LONDON PA STE 500, CHESHAM HOUSE, 150 REGENT ST, LONDON W1R 5FA, ENGLAND SN 0334-018X J9 J PEDIATR ENDOCR MET JI J. Pediatr. Endocrinol. Metab. PD APR PY 1999 VL 12 SU 1 BP 303 EP 309 PG 7 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 213CW UT WOS:000081255300008 PM 10698594 ER PT J AU Diehl, SR Wang, YF Brooks, CN Burmeister, JA Califano, JV Wang, SB Schenkein, HA AF Diehl, SR Wang, YF Brooks, CN Burmeister, JA Califano, JV Wang, SB Schenkein, HA TI Linkage disequilibrium of interleukin-1 genetic polymorphisms with early-onset periodontitis SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE periodontitis, juvenile, etiology; periodontitis, early-onset, etiology; polymorphism; racial stocks; interleukin-1 ID LOCALIZED JUVENILE PERIODONTITIS; GINGIVAL CREVICULAR FLUID; DENTINOGENESIS IMPERFECTA; DOMINANT INHERITANCE; HERITABLE MAC-1; INSULIN GENE; RISK-FACTORS; DISEASES; ASSOCIATION; MODERATE AB Background: Genetic polymorphisms at interleukin (IL)-1 alpha and IL-ln were recently suggested to be associated with severity of adult periodontitis. We evaluated whether these polymorphisms might also be associated with early-onset periodontitis (EOP) in 28 African American families and 7 Caucasian American families with 2 or more affected members. Methods: Genomic DNA from peripheral blood was amplified, followed by restriction endonuclease digestion and acrylamide gel electrophoresis to distinguish alleles of different fragment sizes. Genetic epidemiological methods suitable for family data were used that are robust to false-positive findings due to mismatching of cases and controls or mixed subpopulations of different ethnic or geographic origin. The 2 major EOP subtypes, localized juvenile periodontitis (WP), and generalized early-onset periodontitis (G-EOP, encompassing rapidly progressive periodontitis and generalized juvenile periodontitis), were analyzed both separately and together. Results: We obtained highly significant evidence of linkage disequilibrium for both African American and Caucasian G-EOP subjects. A similar trend was noted for WP. The IL-l alleles associated with high risk of EOP had been suggested previously to be correlated with low risk for severe adult periodontitis. Disequilibrium with G-EOP was equally strong for smoking and non-smoking subjects. IL-la and IL-IR polymorphisms were in strong disequilibrium with each other in Caucasians, but not in African Americans. Haplotype analyses evaluating both polymorphisms simultaneously indicated that the IL-ln variant is likely to be most important for EOP risk. Sibpair linkage analyses, by contrast, provided only marginal support for a gene of very major effect on EOP risk attributable to these IL-l polymorphisms. Conclusions: Recent theoretical analyses indicate that our findings are most consistent with an interpretation of EOP as a complex, oligogenic disorder, with IL-l genetic variation contributing an important but not exclusive influence on disease risk. C1 NIDCR, Div Intramural Res, NIH, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Sch Dent, Clin Res Ctr Periodontal Dis, Richmond, VA USA. RP Diehl, SR (reprint author), NIDCR, Div Intramural Res, NIH, Bldg 45,Room 4AS-43G, Bethesda, MD 20892 USA. FU NCRR NIH HHS [1 P41 RR03655]; NIDCR NIH HHS [Z01DE00622, P50DE10703] NR 63 TC 110 Z9 116 U1 0 U2 0 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD APR PY 1999 VL 70 IS 4 BP 418 EP 430 DI 10.1902/jop.1999.70.4.418 PG 13 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 192RU UT WOS:000080093400010 PM 10328654 ER PT J AU Hoare, SRJ Usdin, TB AF Hoare, SRJ Usdin, TB TI Quantitative cell membrane-based radioligand binding assays for parathyroid hormone receptors SO JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS LA English DT Article DE agonist; antagonist; G-protein-coupled receptor; parathyroid hormone; ligand binding ID TERNARY COMPLEX MODEL; PEPTIDE PTHRP; AGONIST; LIGAND; EXPRESSION AB Most current assays of PTH receptor ligand binding employ whole cells as the vehicle for receptor. Whole cell binding does not easily permit the estimation of physically meaningful binding parameters, the detection of multiple receptor states, or the evaluation of the effects of receptor modulators such as guanine nucleotides. We have developed quantitative methods for the measurement of equilibrium ligand binding parameters at cloned parathyroid hormone (PTH) receptors in cell membrane preparations. Centrifugation is used to separate bound and free [I-125]-labeled peptide radioligands, and nonfat dried milk is used as a blocking agent to reduce nonspecific binding. This method is useful for measurement of agonist and antagonist radioligand binding at the PTH-1 receptor and binding of [I-125]PTH(1-34) at the PTH-2 receptor. Less than 25% of [I-125]PTH(1-34) or [I-125]PTHrP(1-36) is degraded during the assay incubation. We demonstrated the utility of the assay using measurements of ligand binding properties at the PTH-1 receptor. (I) Homologous displacement experiments provided estimates of K-d and B-max for the radioligands. (2) Displacement of radiolabeled antagonist binding ([I-125]PTH(3-34)) by an unlabeled agonist (RS-66271) revealed multiple affinity states of agonist-receptor interaction. (3) Comparison of RS-66271 displacement in the presence and absence of GTP gamma S demonstrated that the highest affinity state is guanine nucleotide-sensitive, suggesting that this state requires stabilization by G-protein. This assay thus allows more mechanistic interpretation of binding data than PTH binding assays in current use. A more convenient rapid-filtration method was also developed for measurement of radioligand binding at PTH-1 and PTH-2 receptors. (C) 1999 Elsevier Science Inc. All rights reserved. C1 NIMH, Cell Biol Unit, Genet Lab, Bethesda, MD 20892 USA. RP Usdin, TB (reprint author), NIMH, Cell Biol Unit, Genet Lab, Rm 3B27,Bldg 36,36 Convent Dr, Bethesda, MD 20892 USA. NR 21 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1056-8719 J9 J PHARMACOL TOXICOL JI J. Pharmacol. Toxicol. Methods PD APR-JUN PY 1999 VL 41 IS 2-3 BP 83 EP 90 DI 10.1016/S1056-8719(99)00024-6 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 260JG UT WOS:000083945300005 PM 10598679 ER PT J AU Tolliver, BK Newman, AH Katz, JL Ho, LB Fox, LM Hsu, K Berger, SP AF Tolliver, BK Newman, AH Katz, JL Ho, LB Fox, LM Hsu, K Berger, SP TI Behavioral and neurochemical effects of the dopamine transporter ligand 4-chlorobenztropine alone and in combination with cocaine in vivo SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID BIOGENIC-AMINE TRANSPORTERS; INDUCED LOCOMOTOR-ACTIVITY; UPTAKE INHIBITORS; NONHUMAN-PRIMATES; NUCLEUS-ACCUMBENS; BINDING-SITES; EXTRACELLULAR DOPAMINE; INVIVO MICRODIALYSIS; RAT STRIATUM; GBR-12909 AB The current studies evaluated the novel diphenylmethoxytropane analog 4-chlorobenztropine (4-Cl-BZT), cocaine, and combinations of the two drugs for their abilities to stimulate locomotor activity, produce cocaine-like discriminative stimulus effects, and elevate extracellular dopamine (DA) in the nucleus accumbens (NAc) as measured by in vivo microdialysis. Peripherally administered cocaine was approximately twice as efficacious as 4-Cl-BZT as a locomotor stimulant and was behaviorally active at a lower dose than was 4-Cl-BZT. Cocaine also was more efficacious than 4-Cl-BZT in producing discriminative-stimulus effects in rats trained to discriminate i.p. injections of 10 mg/kg cocaine from saline. The time course of behavioral activation differed markedly between the two drugs, with much shorter onset and duration of locomotor stimulant effects for cocaine relative to 4-Cl-BZT. Similarly, i.p. cocaine (10 and 40 mg/kg) induced a pronounced, rapid, and short-lived increase in DA in the NAc, whereas i.p, 4-Cl-BZT was effective only at the higher dose and produced a more gradual, modest, and sustained (greater than or equal to 2 h) elevation in accumbens DA. In contrast to i.p. administration, local infusion of 4-Cl-BZT (1-100 mu M) into the NAc through the microdialysis probe elevated extracellular DA to a much greater extent than did local cocaine (nearly 2000% of baseline maximally for 4-Cl-BZT versus 400% of baseline for cocaine) and displayed a much longer duration of action than cocaine. However, when microinjected bilaterally into the NAc at 30 or 300 nmol/side, cocaine remained a more efficacious locomotor stimulant than 4-Cl-BZT. Finally, pretreatment with i.p. 4-Cl-BZT dose dependently enhanced the locomotor stimulant, discriminative stimulus effects, and NAc DA response to a subsequent low-dose i.p. cocaine challenge. The diphenylmethoxytropane analog also facilitated the emergence of stereotyped behavior and convulsions induced by high-dose cocaine. The current results demonstrate that DA transporter ligands that do not share the neurochemical and behavioral profiles of cocaine nevertheless may enhance the effects of cocaine in vivo. C1 Univ Calif San Francisco, Vet Affairs Med Ctr, Dept Psychiat, San Francisco, CA 94121 USA. NIDA, Psychobiol Sect, Intramural Res Program, NIH, Baltimore, MD USA. RP Tolliver, BK (reprint author), Univ Calif San Francisco, Vet Affairs Med Ctr, Dept Psychiat, 127,4150 Clement St, San Francisco, CA 94121 USA. OI Katz, Jonathan/0000-0002-1068-1159 FU NIDA NIH HHS [DA 07376, DA 05715] NR 69 TC 28 Z9 28 U1 1 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD APR PY 1999 VL 289 IS 1 BP 110 EP 122 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 180BU UT WOS:000079365700015 PM 10086994 ER PT J AU Liu, J Liu, YP Hartley, D Klaassen, CD Shehin-Johnson, SE Lucas, A Cohen, SD AF Liu, J Liu, YP Hartley, D Klaassen, CD Shehin-Johnson, SE Lucas, A Cohen, SD TI Metallothionein-I/II knockout mice are sensitive to acetaminophen-induced hepatotoxicity SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID LIPID-PEROXIDATION; OXIDATIVE STRESS; COVALENT BINDING; PROTEIN ADDUCTS; FREE-RADICALS; LIVER-INJURY; CELL-DEATH; CADMIUM; ZINC; HEPATOCYTES AB The purpose of this study was to examine whether intracellular metallothionein (MT) protects against acetaminophen hepatotoxicity. MT-I/II knockout (MT-null) and control mice were given acetaminophen (150-500 mg/kg i.p.), and liver injury was assessed 24 h later. MT-null mice were more susceptible than controls to acetaminophen-induced lethality and hepatotoxicity, as evidenced by elevated serum enzyme activities and histopathology. Zinc pretreatment, a method of MT induction, protected against acetaminophen hepatotoxicity in control mice, but not in MT-null mice. The susceptibility of MT-null mice to acetaminophen hepatotoxicity was not due to the increased acetaminophen bioactivation, as cytochrome P-450 enzymes, and acetaminophen-reactive metabolites in bile and urine were not increased in MT-null mice. Western blots of liver cytosol indicated that acetaminophen covalent binding at 4h increased with acetaminophen dose, but there was nd consistent difference between control and MT-null mice. Acetaminophen injection depleted cellular glutathione similarly in both control and MT-null mice, but produced more lipid peroxidation in MT-null mice, as evidenced by the abundance of thiobarbiturate-reactive substances, and by immunohistochemical localization of 4-hydroxynonenal and malondialdehyde protein adducts. MT-null hepatocytes were more susceptible than control Cells to oxidative stress and cytotoxicity produced by N-acetylbenzoquinoneimine, a reactive metabolite of acetaminophen, as determined by oxidation of 2',7'-dichlorofluorescin diacetate and lactate dehydrogenase leakage. In summary, this study demonstrated that MT deficiency renders animals more vulnerable to acetaminophen-induced hepatotoxicity. The Increased sensitivity does not appear to be due to increased acetaminophen activation, glutathione depletion, or covalent binding, but appears to be associated with the antioxidant role of MT. C1 Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. Univ Connecticut, Storrs, CT USA. RP Liu, J (reprint author), NIEHS, NCI, MD F0-09,Room F017,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM liu6@niehs.nih.gov FU NIEHS NIH HHS [ES-01142, ES 07163, ES-06190] NR 40 TC 65 Z9 68 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD APR PY 1999 VL 289 IS 1 BP 580 EP 586 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 180BU UT WOS:000079365700074 PM 10087053 ER PT J AU Petranka, J Baldwin, W Biermann, J Jayadev, S Barrett, JC Murphy, E AF Petranka, J Baldwin, W Biermann, J Jayadev, S Barrett, JC Murphy, E TI The oncostatic action of melatonin in an ovarian carcinoma cell line SO JOURNAL OF PINEAL RESEARCH LA English DT Article DE calcium; CGP52608; flow cytometry ID GLAND HORMONE MELATONIN; BREAST-CANCER; MAGNETIC-FIELDS; MELANOMA-CELLS; ORPHAN RECEPTOR; LYMPHOID-CELLS; PROLIFERATION; GROWTH; ESTROGEN; CULTURE AB Melatonin is reported to reduce proliferation in many cell types, but the effect is small and the results are inconsistent. Information on the mechanism by which melatonin exerts its antiproliferative effects might provide insight into the variability of the response. In an ovarian adenocarcinoma cell line (BG-1), we find that melatonin at concentrations of 10(-9)-10(-7) M caused a 20-25% reduction in cell number. Melatonin also resulted in a similar reduction in [H-3]-thymidine incorporation with no significant increase in cell death as measured by trypan blue incorporation. The K-d for melatonin reduction in cell number was similar to 5 x 10(-10) M. Melatonin ML2 receptors have a K-d for melatonin binding in the low nM range and are linked to the production of the calcium mobilizing agent inositol-1,4,5-trisphosphate (IP3). To investigate whether melatonin signaling involves an increase in cytosolic-free calcium, BG-1 cells were loaded with the calcium sensitive indicator, fura-2. Acute addition of melatonin (10(-5)-10(-9) M) did not alter cytosolic calcium. Addition of the putative nuclear receptor agonist CGP52608 caused a dose-dependent inhibition of cell number with a K-d of similar to 2 x 10(-9) M. Addition of CGP52608 caused a similar reduction in [H-3]-thymidine incorporation. Neither melatonin (10(-8) M-10(-5) M) nor CGP52608 at concentrations below 10(-7) M induced cell death associated with the inhibition of cell proliferation; however, addition of CGP52608 at a high dose (10-7 M) caused an increase in cell death, consistent with apoptosis. Growth inhibition by melatonin or CGP52608 did not alter the percentage of cells in G1 versus S/G2/M. C1 NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Petranka, J (reprint author), NIEHS, Mol Carcinogenesis Lab, POB 12233, Res Triangle Pk, NC 27709 USA. NR 30 TC 77 Z9 78 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0742-3098 J9 J PINEAL RES JI J. Pineal Res. PD APR PY 1999 VL 26 IS 3 BP 129 EP 136 DI 10.1111/j.1600-079X.1999.tb00574.x PG 8 WC Endocrinology & Metabolism; Neurosciences; Physiology SC Endocrinology & Metabolism; Neurosciences & Neurology; Physiology GA 186YD UT WOS:000079758000001 PM 10231725 ER PT J AU Rosenman, RH Maser, JD AF Rosenman, RH Maser, JD TI Bizarre images and beta-adrenergic blocking agents: A unique case report SO JOURNAL OF PSYCHOACTIVE DRUGS LA English DT Article DE adrenergic blockers; beta blockers; bizarre images; pindolol; propranolol AB Vivid imagery and hallucinations are occasionally reported by patients on beta-adrenergic blocking agents. The authors document this side effect with drawings by a well-known commercial artist. C1 Univ Calif San Francisco, Dept Med, Mt Zion Med Ctr, San Francisco, CA 94143 USA. SRI Int, Hlth Sci Program, Menlo Park, CA 94025 USA. RP Maser, JD (reprint author), NIMH, 6001 Execut Blvd,Room 6150, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU HAIGHT-ASHBURY PUBL PI SAN FRANCISCO PA 409 CLAYTON ST, SAN FRANCISCO, CA 94117 USA SN 0279-1072 J9 J PSYCHOACTIVE DRUGS JI J. Psychoact. Drugs PD APR-JUN PY 1999 VL 31 IS 2 BP 163 EP 166 PG 4 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 215ZZ UT WOS:000081417000010 PM 10437999 ER PT J AU Kumon, Y Suehiro, T Hashimoto, K Nakatani, K Sipe, JD AF Kumon, Y Suehiro, T Hashimoto, K Nakatani, K Sipe, JD TI Local expression of acute phase serum amyloid A mRNA in rheumatoid arthritis synovial tissue and cells SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE SAA isoforms; rheumatoid arthritis; osteoarthritis; synovium; synovial fluid ID C-REACTIVE PROTEIN; A PROTEIN; APOLIPOPROTEIN; COLLAGENASE; SAA3; GENE; IDENTIFICATION; INTERLEUKIN-1; INDUCTION; RABBIT AB Objective, Serum amyloid A (SAA) protein, a bioactive protein produced during inflammation, is present in synovial fluid (SF) of patients with rheumatoid arthritis (RA). Based on our recent finding that SF SAA concentration exceeded the serum counterpart in some patients with RA, we examined the local steady state concentration of SAA mRNA isoforms in synovia and in synovial cells cultured from patients with RA and osteoarthritis (OA). Methods. Total cellular RNA from synovial membranes of patients with RA or OA and from cultured synovial cells of patients with RA was analyzed by reverse transcription polymerase chain reaction and Northern blot. Results. Acute phase SAA (A-SAA) mRNA isoforms were detected only in RA synovia, but not in OA synovia; however, the constitutive SAA (C-SAA) mRNA isoform was detected in similar abundance in both OA and RA synovia. There was evidence of C-SAA, but not A-SAA mRNA in cultured synovial cells at quiescence. After stimulation with both 1 mM dexamethasone and 10 ng/ml interleukin 1 beta (IL-1 beta), the quantity of steady state A-SAA mu RNA in cultured synovial cells was markedly increased. Conclusion. Both A-SAA and C-SAA mRNA are detectable in RA synovia, while only C-SAA mRNA is detectable in OA and in quiescent cultured synovial cells. The steady state A-SAA mRNA isoform in cultured synovial cells was markedly increased in the presence of dexamethasone plus IL-1 beta. The local synthesis of A-SAA may contribute, at least in part, to the concentration of A-SAA protein in SF and may contribute to the altered molecular and cellular physiology in RA joints. C1 Kochi Med Sch, Dept Internal Med 2, Nanko Ku, Kochi 7838505, Japan. Bayside Misato Med Ctr, Kochi, Japan. NIH, Ctr Sci Review, Biochem Sci IRG, Bethesda, MD USA. RP Kumon, Y (reprint author), Kochi Med Sch, Dept Internal Med 2, Nanko Ku, Okoh Cho, Kochi 7838505, Japan. NR 32 TC 51 Z9 53 U1 0 U2 2 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD APR PY 1999 VL 26 IS 4 BP 785 EP 790 PG 6 WC Rheumatology SC Rheumatology GA 185JZ UT WOS:000079667000006 PM 10229397 ER PT J AU Caston, JR Belnap, DM Steven, AC Trus, BL AF Caston, JR Belnap, DM Steven, AC Trus, BL TI A strategy for determining the orientations of refractory particles for reconstruction from cryo-electron micrographs with particular reference to round, smooth-surfaced, icosahedral viruses SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE 3D reconstruction; capsid structure; common lines ID X-RAY CRYSTALLOGRAPHY; DOUBLE-STRANDED-RNA; 3-DIMENSIONAL RECONSTRUCTION; CRYOELECTRON MICROSCOPY; BIOLOGICAL MACROMOLECULES; VISUALIZATION; CAPSIDS; CRYOMICROSCOPY; REPLICATION; RESOLUTION AB Cryo-electron microscopy and three-dimensional image reconstruction are powerful tools for analyzing icosahedral virus capsids at resolutions that now extend below 1 nm, However, the validity of such density maps depends critically on correct identification of the viewing geometry of each particle in the data set. In some cases-for example, round capsids with low surface relief-it is difficult to identify orientations by conventional application of the two most widely used approaches-"common lines" and model-based iterative refinement. We describe here a strategy for determining the orientations of such refractory specimens. The key step is to determine reliable orientations for a base set of particles, For each particle, a list of candidate orientations is generated by common lines: correct orientations are then identified by computing a single-particle reconstruction for each candidate and then systematically matching their reprojections with the original images by visual criteria and crosscorrelation analysis. This base set yields a first-generation reconstruction that is fed into the model-based procedure. This strategy has led to the structural determination of two viruses that, ill our hands, resisted solution by other means. C1 NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. NIH, Computat Biosci & Engn Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Trus, BL (reprint author), NIAMSD, Struct Biol Res Lab, NIH, Bldg 12A,Room 2033,MSC 5624, Bethesda, MD 20892 USA. RI Caston, Jose/L-5896-2014 OI Caston, Jose/0000-0003-2350-9048 NR 31 TC 11 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD APR-MAY PY 1999 VL 125 IS 2-3 BP 209 EP 215 DI 10.1006/jsbi.1999.4085 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 194XM UT WOS:000080220100012 PM 10222276 ER PT J AU Mulshine, JL AF Mulshine, JL TI Reflections on early cancer control efforts SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Editorial Material C1 NCI, Dept Cell & Canc Biol, Intervent Sect, Bethesda, MD 20892 USA. RP Mulshine, JL (reprint author), NCI, Dept Cell & Canc Biol, Intervent Sect, Bldg 10,Room 12N226,10 Ctr Dr,MSC 1906, 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 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD APR PY 1999 VL 70 IS 4 BP 207 EP 208 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 186YX UT WOS:000079760000001 PM 10219014 ER PT J AU Weinberg, NZ AF Weinberg, NZ TI Commentary: Behavioral inhibition and developmental risk SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material ID PSYCHIATRIC-DISORDERS; LONGITUDINAL EVIDENCE; BIRTH COHORT; CHILDHOOD; CHILDREN; LANGUAGE; ABUSE; ALCOHOLISM; DEFICITS C1 NIDA, Div Epidemiol & Prevent Res, NIH, Bethesda, MD 20892 USA. RP Weinberg, NZ (reprint author), NIDA, Div Epidemiol & Prevent Res, NIH, 6001 Execut Blvd,Room 5N-5160,MSC 9589, Bethesda, MD 20892 USA. NR 27 TC 0 Z9 0 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD APR PY 1999 VL 38 IS 4 BP 417 EP 420 DI 10.1097/00004583-199904000-00014 PG 4 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 179ZJ UT WOS:000079360000014 PM 10199113 ER PT J AU Susman, EJ Schmeelk, KH Worrall, BK Granger, DA Ponirakis, A Chrousos, GP AF Susman, EJ Schmeelk, KH Worrall, BK Granger, DA Ponirakis, A Chrousos, GP TI Corticotropin-releasing hormone and cortisol: Longitudinal associations with depression and antisocial behavior in pregnant adolescents SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE corticotropin-releasing hormone; conduct disorder; depression; pregnancy ID DEXAMETHASONE SUPPRESSION TEST; PITUITARY-ADRENAL AXIS; HUMAN-PLACENTA; SALIVARY CORTISOL; VIOLENT OFFENDERS; STEROID-HORMONES; BETA-ENDORPHIN; PLASMA; POSTPARTUM; CHILDREN AB Objective: To examine the concurrent and longitudinal associations between corticotropin-releasing hormone (CRH) and cortisol concentrations and depression and antisocial behavior (conduct disorder symptoms) in pregnant adolescents. Method: Fifty-nine adolescents were evaluated in early pregnancy (9-21 weeks' gestation), late pregnancy (32-34 weeks' gestation), and the postpartum period (4-5 weeks postpartum). Symptoms of depression and conduct disorder were obtained from the Diagnostic Interview Schedule for Children. Results: Lower concentrations of CRH were related to a greater number of depression symptoms in early pregnancy (p < .05) and in late pregnancy (p < .05). Lower concentrations of CRH also were related to a greater number of conduct disorder symptoms in early pregnancy (p < .06) and in the postpartum period (p < .05). Conclusion: The findings support the long-standing hypothesis that stress-related products of the hypothalamic-pituitary-ad renal axis are associated with emotions and behavior during pregnancy. C1 Penn State Univ, Dept Biobehav Hlth, University Pk, PA 16802 USA. Penn State Univ, Behav Endocrinol Lab, University Pk, PA 16802 USA. NICHD, Sect Pediat Endocrinol, NIH, Bethesda, MD USA. RP Susman, EJ (reprint author), Penn State Univ, Dept Biobehav Hlth, University Pk, PA 16802 USA. FU NICHD NIH HHS [R01 HD26004] NR 45 TC 38 Z9 38 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 EI 1527-5418 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD APR PY 1999 VL 38 IS 4 BP 460 EP 467 DI 10.1097/00004583-199904000-00020 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 179ZJ UT WOS:000079360000020 PM 10199119 ER PT J AU Fujimoto, W Toi, Y Okazaki, F Lazarova, Z Yancey, KB Arata, J AF Fujimoto, W Toi, Y Okazaki, F Lazarova, Z Yancey, KB Arata, J TI Anti-epiligrin cicatricial pemphigoid with IgG autoantibodies to the beta and gamma subunits of laminin 5 SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID MEMBRANE AB Anti-epiligrin cicatricial pemphigoid is an autoimmune subepithelial blistering disorder of mucous membranes and skin. By immunoblot analyses, sera of most patients with anti-epiligrin cicatricial pemphigoid have been shown to react specifically with the alpha 3 chain of laminin 5, We describe the first patient with anti-epiligrin cicatricial pemphigoid in whom circulating Ige autoantibodies directed against the beta 3 and gamma 2-chains of laminin 5 were detected. Treatment with oral prednisolone was beneficial in controlling the disease. C1 Okayama Univ, Sch Med, Dept Dermatol, Okayama 7008558, Japan. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP Fujimoto, W (reprint author), Okayama Univ, Sch Med, Dept Dermatol, 2-5-1 Shikata, Okayama 7008558, Japan. NR 10 TC 24 Z9 24 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD APR PY 1999 VL 40 IS 4 BP 637 EP 639 DI 10.1016/S0190-9622(99)70453-6 PG 3 WC Dermatology SC Dermatology GA 179TA UT WOS:000079344100022 PM 10188690 ER PT J AU Berger, AC Libutti, SK Bartlett, DL Skarulis, MG Marx, SJ Spiegel, AM Doppman, JL Alexander, HR AF Berger, AC Libutti, SK Bartlett, DL Skarulis, MG Marx, SJ Spiegel, AM Doppman, JL Alexander, HR TI Heterogeneous gland size in sporadic multiple gland parathyroid hyperplasia SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID UNILATERAL NECK EXPLORATION; ENDOCRINE NEOPLASIA TYPE-1; PRIMARY HYPERPARATHYROIDISM; PREOPERATIVE LOCALIZATION; MULTIGLANDULAR DISEASE; ADENOMAS; MONOCLONALITY; MANAGEMENT; TUMORS; SCAN AB Background: The success rate for bilateral exploration in patients with primary hyperparathyroidism approaches 95%. Multiglandular parathyroid hyperplasia accounts for approximately 10% to 30% of primary hyperparathyroidism. The incidence of recurrent or persistent hyperparathyroidism is highest in familial forms of the disease, in which multiglandular disease is more common; this may be due to asymmetric enlargement of parathyroid glands. Because of improvements in tumor-imaging capability, some surgeons are now advocating unilateral exploration for primary hyperparathyroidism, but there: is limited experience concerning how often these imaging methods fail. Study Design: The outcomes of 7 patients who had sporadic primary hyperparathyroidism with multigland hyperplasia were reviewed. We gathered demographic data and laboratory values and reviewed radiologic tests, surgical findings, pathologic findings, and postoperative followup. Results: All patients underwent preoperative localization with ultrasonography and technetium/sestamibi scans. The sensitivity of these two tests for the dominantly enlarged gland was 100% for both, but dropped to 0% and 5%, respectively, for all other enlarged glands. The sensitivity of CT and MRI for the dominant tumor was 67% (2 of 3) and 50% (1 of 2), respectively. Six of 7 patients underwent subtotal (3 1/2 gland) parathyroidectomy. The mean volume of all glands was 1.51 +/- 5.89 cm(3) compared with a mean of 5.66 +/- 11.4 cm(3) for all dominant glands and 0.123 +/- 0.1 cm(3) for all nondominant hyperplastic glands. There was a large amount of variability between the volumes of dominant and other glands as demonstrated by large SDs from the mean. Conclusions: There is a marked heterogeneity in gland size in patients with sporadic multigland hyperplasia, which is similar to that found in multiple endocrine neoplasia type I. This heterogeneity may result in failure to recognize multigland disease if a unilateral neck exploration is performed. Intraoperative parathyroid hormone assay may prove to be an important adjunct in this population of patients who have unsuspected multigland disease. (J Am Coil Surg 1999;188:382-389, (C) 1999 by the American College of Surgeons). C1 NCI, Surg Branch, Bethesda, MD 20892 USA. NIDDKD, Metab Dis Branch, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Radiol, Bethesda, MD 20892 USA. RP Alexander, HR (reprint author), Bldg 10,Room 2B05,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 34 TC 17 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD APR PY 1999 VL 188 IS 4 BP 382 EP 389 DI 10.1016/S1072-7515(98)00317-2 PG 8 WC Surgery SC Surgery GA 182EA UT WOS:000079484500007 PM 10195722 ER PT J AU Slavkin, HC AF Slavkin, HC TI Toward a common theme for autoimmunity SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article C1 Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. RP Slavkin, HC (reprint author), Natl Inst Dent & Craniofacial Res, 31 Ctr Dr,MSC 2290,Bldg 31,Room 2C39, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD APR PY 1999 VL 130 IS 4 BP 561 EP 566 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 183TX UT WOS:000079570500032 PM 10203908 ER PT J AU Topol, IA Burt, SK Russo, N Toscano, M AF Topol, IA Burt, SK Russo, N Toscano, M TI Theoretical calculations of glycine and alanine gas-phase acidities SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID DENSITY-FUNCTIONAL THEORY; GASEOUS ALPHA-ALANINE; ELECTRON-DIFFRACTION; MOLECULAR-ENERGIES; PROTON AFFINITIES; 2ND-ROW COMPOUNDS; EXCHANGE-ENERGY; AMINO-ACIDS; APPROXIMATION; THERMOCHEMISTRY AB The gas-phase acidities of glycine and alanine were determined by using a variety of high level theoretical methods to establish which of these would give the best results with accessible computational efforts. MP2, MP4, QCISD, G2 ab initio procedures, hybrid Becke3-LYP (B3LYP) and gradient corrected Becke-Perdew (BP) and Perdew-Wang and Perdew (PWP) nonlocal density functionals were used for the calculations. A maximum deviation of approximately 13 and 18 kJ/mol from experimental data was observed for the computed Delta H(acid) and Delta G(acid) values, respectively. The best result was obtained at G2 level, but comparable reliability was reached when the considerably less time consuming B3LYP, BP, and PWP density functional approaches were employed. (C) 1999 American Society for Mass Spectrometry. C1 Univ Calabria, Dipartimento Chim, I-87030 Arcavacata Di Rende, CS, Italy. NCI, Frederick Canc Res & Dev Ctr, Struct Biochem Program, Frederick Biomed Supercomp Ctr,SAIC, Frederick, MD USA. RP Russo, N (reprint author), Univ Calabria, Dipartimento Chim, I-87030 Arcavacata Di Rende, CS, Italy. EM russo@fis.unical.it OI Nino, Russo/0000-0003-3826-3386 NR 30 TC 31 Z9 31 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD APR PY 1999 VL 10 IS 4 BP 318 EP 322 DI 10.1016/S1044-0305(98)00160-3 PG 5 WC Biochemical Research Methods; Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy GA 221PP UT WOS:000081735700004 PM 10197352 ER PT J AU Bostom, AG Culleton, BF AF Bostom, AG Culleton, BF TI Hyperhomocysteinemia in chronic renal disease SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID PLASMA HOMOCYSTEINE CONCENTRATIONS; MAINTENANCE DIALYSIS PATIENTS; FOLIC-ACID SUPPLEMENTATION; ENDOTHELIAL-CELL INJURY; CORONARY-ARTERY DISEASE; CONTAINING AMINO-ACIDS; TRANSPLANT RECIPIENTS; VASCULAR-DISEASE; CARDIOVASCULAR-DISEASE; RISK FACTOR C1 Brown Univ, Mem Hosp Rhode Isl, Div Gen Internal Med, Pawtucket, RI 02860 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Bostom, AG (reprint author), Brown Univ, Mem Hosp Rhode Isl, Div Gen Internal Med, 11 Brewster St, Pawtucket, RI 02860 USA. EM abostom@loa.com NR 93 TC 184 Z9 194 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD APR PY 1999 VL 10 IS 4 BP 891 EP 900 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 180BW UT WOS:000079365900025 PM 10203375 ER PT J AU Lewis, AM Alling, DW Banks, SM Soddu, S Cook, JL AF Lewis, AM Alling, DW Banks, SM Soddu, S Cook, JL TI Evaluating virus-transformed cell tumorigenicity SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE tumorigenicity; tumorigenicity assays; transformed phenotype; animal models; DNA tumor viruses; adenovirus type 12; simian virus 40 ID SYRIAN-HAMSTER CELLS; HETEROGENEITY; INHIBITION; GROWTH AB The tumorigenicity of adenovirus (Ad) 12-transformed mouse cells was evaluated by analyzing the relationship of tumor cell dose to tumor incidence and tumor latency. The tumor producing dose 50% endpoint values used to define these relationships remained stable during 52 weeks of serial passage in tissue culture and were not determined by low frequency events within the cell population. The data from these analyses suggest that the phenotype of Ad12-transformed mouse cells is influenced by two set of traits-those traits that determine the threshold number of cells required for tumor formation and those that extend the cell dose-dependent tumor latency period. Both traits are established independently of cell immortalization, and both can be influenced by the immunological status of tumor-challenged animals. These observations were verified by using mouse cells transformed by Ad5 and SV40. The biological and molecular processes that contribute to these traits remain to be determined. The approach developed by this analysis provides a reliable, quantitative means of evaluating endogenous traits that determine transformed cell tumorigenicity. This method can also be used to test the effects of tumor cell manipulations or changes in host response that could alter expression or detection of these neoplastic cell traits. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NIH, Viral Pathogenesis Sect, Immunopathol Lab, Bethesda, MD 20892 USA. NIAID, Off Intramural Director, NIH, Bethesda, MD 20892 USA. Natl Jewish Med & Res Ctr, Dept Med, Robert W Lisle Res Lab Immunol & Tumor Cell Biol, Denver, CO 80206 USA. RP Lewis, AM (reprint author), US FDA, OVRR, CBER, HFM 400,1401 Rockville Pike, Rockville, MD 20852 USA. NR 17 TC 12 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD APR PY 1999 VL 79 IS 1 BP 41 EP 50 DI 10.1016/S0166-0934(98)00182-7 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 191PQ UT WOS:000080031100005 PM 10328534 ER PT J AU Benard, L Carroll, K Valle, RCP Masison, DC Wickner, RB AF Benard, L Carroll, K Valle, RCP Masison, DC Wickner, RB TI The Ski7 antiviral protein is an EF1-alpha homolog that blocks expression of non-poly(A) mRNA in Saccharomyces cerevisiae SO JOURNAL OF VIROLOGY LA English DT Article ID DOUBLE-STRANDED-RNA; L-A-HN; MESSENGER-RNA; TRANSLATIONAL EFFICIENCY; KILLER SYSTEMS; POLY(A) TAIL; YEAST; GENE; DEGRADATION; TURNOVER AB We mapped and cloned SK17, a gene that negatively controls the copy number of L-A and M double-stranded RNA viruses in Saccharomyces cerevisiae. We found that it encodes a nonessential 747-residue protein with similarities to two translation factors, Hbs1p and EF1-alpha. The ski7 mutant was hypersensitive to hygromycin B, a result also suggesting a role in translation. The SK17 product repressed the expression of nonpolyadenylated [non-poly(A)] mRNAs, whether capped or uncapped, thus explaining why Ski7p inhibits the propagation of the yeast viruses, whose mRNAs lack poly(A). The dependence of the Ski7p effect on 3' RNA structures motivated a study of the expression of capped non-poly(A) luciferase mRNAs containing 3' untranslated regions (3'UTRs) differing in length. In a wild-type strain, increasing the length of the 3'UTR increased luciferase expression due to both increased rates and duration of translation. Overexpression of Ski7p efficiently cured the satellite virus M-2 due to a twofold-increased repression of non-poly(A) mRNA expression. Our experiments showed that Ski7p is part of the Ski2p-Ski3p-Ski8p antiviral system because a single ski7 mutation derepresses the expression of non-poly(A) mRNA as much as a quadruple ski2 ski3 ski7 ski8 mutation, and the effect of the overexpression of Ski7p is not obtained unless other SKI genes are functional, ski1/xrn1 Delta ski2 Delta and ski1/xrn1 Delta ski7 Delta mutants were viable but temperature sensitive for growth. C1 NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Wickner, RB (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bldg 8,Room 225,8 Ctr Dr,MSC 0830, Bethesda, MD 20892 USA. EM wickner@helix.nih.gov NR 53 TC 42 Z9 46 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1999 VL 73 IS 4 BP 2893 EP 2900 PG 8 WC Virology SC Virology GA 175XY UT WOS:000079122400037 PM 10074137 ER PT J AU Liu, BD Dai, RK Tian, CJ Dawson, L Gorelick, R Yu, XF AF Liu, BD Dai, RK Tian, CJ Dawson, L Gorelick, R Yu, XF TI Interaction of the human immunodeficiency virus type 1 nucleocapsid with actin SO JOURNAL OF VIROLOGY LA English DT Article ID ROUS-SARCOMA VIRUS; PROVIRAL DNA-SYNTHESIS; IN-VITRO; REVERSE-TRANSCRIPTASE; GAG PROTEINS; STRAND TRANSFER; MATRIX PROTEIN; BINDING-SITE; INTRACELLULAR-TRANSPORT; PARTICLE-PRODUCTION AB The nucleocapsid (NC) domain of the retrovirus Gag protein plays several important roles in the viral life cycle, including virus assembly, viral genomic RNA encapsidation, primer tRNA placement, and enhancement of viral reverse transcription. In this study, deletion of NC domain of human immunodeficiency virus type I (HIV-1) Gag was found to drastically reduce virus particle production in CD4(+) T cells. Cellular fractionation experiments showed that although most of the uncleaved wild-type HIV-1 Gag, unmyristylated Gag, and p6(Gag) domain-truncated Gag molecules copurified with the host cell cytoskeleton, most of the mutant Gag molecules lacking both the NC and p6(Gag) domains failed to cofractionate with cytoskeleton. In wild-type virus-infected cells, in which the viral protease was active, the cleaved NCp7 copurified with the cytoskeleton, whereas most of the MAp17 and CAp24 did not. Monoclonal antibody against actin coimmunoprecipitated full-length Gag and p6(Gag) domain-truncated Gag molecules from cell lysates but failed to precipitate the truncated mutant Gag molecules lacking NC plus p6(Gag). Purified recombinant NCp7, but not CAp24, was able to bind F-actin in cosedimentation experiments. Furthermore, wild-type NCp7 and a zinc finger mutant NCp7(F16A), like a cellular actin-binding protein (the villin headpiece), bound F-actin in a dose-dependent fashion in vitro. Taken together, these results suggest that HIV-1 NCp7 can bind F-actin directly and that interaction between HIV-1 Gag and the actin cytoskeleton through the NC domain may play an important role in HIV-1 assembly and/or other steps of the viral life cycle. C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. NCI, Mol Carcinogenesis Lab, Bethesda, MD 20892 USA. NCI, AIDS Vaccine Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Yu, XF (reprint author), Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mol Microbiol & Immunol, Room E4012,615 N Wolfe ST, Baltimore, MD 21205 USA. FU NCI NIH HHS [N01-CO-56000]; NIAID NIH HHS [AI-35525] NR 71 TC 104 Z9 105 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1999 VL 73 IS 4 BP 2901 EP 2908 PG 8 WC Virology SC Virology GA 175XY UT WOS:000079122400038 PM 10074138 ER PT J AU Chaudry, GJ Farrell, KB Ting, YT Schmitz, C Lie, YS Petropoulos, CJ Eiden, MV AF Chaudry, GJ Farrell, KB Ting, YT Schmitz, C Lie, YS Petropoulos, CJ Eiden, MV TI Gibbon ape leukemia virus receptor functions of type III phosphate transporters from CHOK1 cells are disrupted by two distinct mechanisms SO JOURNAL OF VIROLOGY LA English DT Article ID RETROVIRUS INFECTION; CELLULAR RECEPTOR; HAMSTER-CELLS; MURINE; PIT1; INTERFERENCE; RECOGNITION; INHIBITORS; RESIDUE; FAMILY AB The Chinese hamster cell lines E36 and CHOK1 dramatically differ in susceptibility to amphotropic murine leukemia virus (A-MuLV) and gibbon ape leukemia virus (GALV); E36 cells are highly susceptible to both viruses, CHOK1 cells are not. We have previously shown that GALV can infect E36 cells by using both its own receptor, HaPit1, and the A-MuLV receptor, HaPit2. Given that the two cell lines are from the same species, the loss of function of both of these receptors in CHOK1 cells is surprising. Other studies have shown that CHOK1 cells secrete proteins that block A-MuLV entry into CHOK1 as well as E36, suggesting the two A-MuLV receptors are functionally identical. However, CHOK1 conditioned medium does not block GALV entry into E36, indicating the secreted inhibitors do not block HaPit1. HaPit1 and ChoPit1 therefore differ as receptors for GALV; ChoPit1 is either inactivated by secreted factors or intrinsically nonfunctional. To determine why GALV cannot infect CHOK1, we cloned and sequenced ChoPit1 and ChoPit2, ChoPit2 is almost identical to HaPit2, which explains why CHOK1 conditioned medium blocks A-MuLV entry via both receptors, Although ChoPit1 and HaPit1 are 91% identical, a notable difference is at position 550 in the fourth extracellular region, shown by several studies to be crucial for GALV infection. Pit1 and HaPit1 have aspartate at 550, whereas ChoPit1 has threonine at this position. We assessed the significance of this difference fur GALV infection by replacing the aspartate 550 in Pit1 with threonine, This single substitution rendered Pit1 nonfunctional fur GALV and suggests that threonine at 550 inactivates ChoPit1 as a GALV receptor. Whether native ChoPit1 functions for GALV was determined by interference assays using Lec8, a glycosylation-deficient derivative of CHOK1 that is susceptible to both viruses and that has the same receptors as CHOK1. Unlike with E36, GALV and A-MuLV exhibited reciprocal interference when infecting Lec8, suggesting that they use the same receptor. We conclude both viruses can use ChoPit2 in the absence of the inhibitors secreted by CHOK1 and ChoPit1 is nonfunctional. C1 NIMH, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. Genentech Inc, S San Francisco, CA 94080 USA. RP Eiden, MV (reprint author), NIMH, Lab Cellular & Mol Regulat, NIH, Bldg 36,Room 2A11,36 Convent Dr,MSC 4068, Bethesda, MD 20892 USA. RI Chaudry, Ghulam/F-9761-2011 NR 30 TC 18 Z9 19 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1999 VL 73 IS 4 BP 2916 EP 2920 PG 5 WC Virology SC Virology GA 175XY UT WOS:000079122400040 PM 10074140 ER PT J AU Sakurai, H Williamson, RA Crowe, JE Beeler, JA Poignard, P Bastidas, RB Chanock, RM Burton, DR AF Sakurai, H Williamson, RA Crowe, JE Beeler, JA Poignard, P Bastidas, RB Chanock, RM Burton, DR TI Human antibody responses to mature and immature forms of viral envelope in respiratory syncytial virus infection: Significance for subunit vaccines SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODIES; COMBINATORIAL LIBRARIES; FUSION GLYCOPROTEIN; SYNTHETIC PEPTIDES; F-GLYCOPROTEIN; FAB FRAGMENTS; RSV; MICE; PROTECTION; CHILDREN AB A number of antibodies generated during human respiratory syncytial virus (RSV) infection have been cloned by the phage library approach. Antibodies reactive with an immunodominant epitope on the F glycoprotein of this virus have a high affinity for affinity-purified F antigen. These antibodies, however, have a much lower affinity for mature F glycoprotein on the surface of infected cells and are nonneutralizing. In contrast, a patent neutralizing antibody has a high affinity for mature F protein but a much lower affinity for purified F protein or F protein in viral lysates. The data indicate that at least two F protein immunogens are produced during natural RSV infection: immature F, found in viral lysates, and mature F, found on infected cells or virions. Binding studies with polyclonal human immunoglobulin G suggest that the antibody responses to the two immunogens are of similar magnitudes. Competitive binding studies suggest that overlap between the responses is relatively limited. A mature envelope with an antigenic configuration different from that of the immature envelope has an evolutionary advantage in that the infecting virus is less subject to neutralization by the humoral response to the immature envelope that inevitably arises following lysis of infected cells. Subunit vaccines may be at a disadvantage because they most often resemble immature envelope molecules and ignore this aspect of viral evasion. C1 Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. Kaneka Corp, Takasago Inst, Takasago, Hyogo 676, Japan. Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37232 USA. US FDA, Rockville, MD 20857 USA. NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. RP Williamson, RA (reprint author), Scripps Res Inst, Dept Immunol, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM anthony@scripps.edu; burton@scripps.edu RI Crowe, James/B-5549-2009 OI Crowe, James/0000-0002-0049-1079 FU NIAID NIH HHS [AI 39162] NR 41 TC 42 Z9 43 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1999 VL 73 IS 4 BP 2956 EP 2962 PG 7 WC Virology SC Virology GA 175XY UT WOS:000079122400045 PM 10074145 ER PT J AU Polacino, P Stallard, V Montefiori, DC Brown, CR Richardson, BA Morton, WR Benveniste, RE Hu, SL AF Polacino, P Stallard, V Montefiori, DC Brown, CR Richardson, BA Morton, WR Benveniste, RE Hu, SL TI Protection of macaques against intrarectal infection by a combination immunization regimen with recombinant simian immunodeficiency virus SIVmne gp160 vaccines SO JOURNAL OF VIROLOGY LA English DT Article ID RHESUS MACAQUES; NEUTRALIZING ANTIBODIES; SELECTIVE AMPLIFICATION; ENVELOPE GLYCOPROTEIN; VAGINAL CHALLENGE; RECTAL MUCOSA; TRANSMISSION; TYPE-1; HIV-1; INOCULATION AB We previously reported that immunization with recombinant simian immunodeficiency virus SIVmne envelope (gp160) vaccines protected macaques against intravenous challenge by the cloned homologous virus E11S but that this protection was only partially effective against the uncloned virus, SIVmne. In the present study, we examine the protective efficacy of this immunization regimen against infection by a mucosal route. We found that the same gp160-based vaccines were highly effective against intrarectal infection not only with the E11S clone but also with the uncloned SIVmne, Protection against mucosal infection is therefore achievable by parenteral immunization with recombinant envelope vaccines. Protection appears to correlate with high levels of SIV-specific antibodies and, in animals protected against the uncloned virus, the presence of serum-neutralizing activities, To understand the basis for the differential efficacies against the uncloned virus by the intravenous versus the intrarectal routes, me examined viral sequences recovered from the peripheral blood mononuclear cells of animals early after infection by both routes. We previously showed that the majority (85%) of the uncloned SIVmne challenge stock contained V1 sequences homologous to the molecular clone from which the vaccines were made (E11S type), with the remainder (15%) containing multiple conserved changes (the variant types). In contrast to intravenously infected animals, from which either E11S-type or the variant type V1 sequences could be recovered in significant proportions, animals infected intrarectally had predominantly E11S-type sequences. Preferential transmission or amplification of the E11S-type viruses may therefore account in part for the enhanced efficacy of the recombinant gp160 vaccines against the uncloned virus challenge by the intrarectal route compared with the intravenous route. C1 Univ Washington, Reg Primate Res Ctr, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Bristol Myers Squibb Pharmaceut Res Inst, Seattle, WA 98121 USA. Duke Univ, Med Ctr, Durham, NC USA. NCI, Frederick, MD 21701 USA. Henry M Jackson Fdn, Rockville, MD USA. RP Hu, SL (reprint author), Univ Washington, Dept Pharmaceut, Box 357331, Seattle, WA 98195 USA. EM hus@u.washington.edu RI Hu, Shiu-Lok/A-3196-2008 OI Hu, Shiu-Lok/0000-0003-4336-7964 FU NCRR NIH HHS [P51 RR000166, RR00166]; NIAID NIH HHS [AI26503, AI65302] NR 50 TC 44 Z9 44 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1999 VL 73 IS 4 BP 3134 EP 3146 PG 13 WC Virology SC Virology GA 175XY UT WOS:000079122400065 PM 10074165 ER PT J AU Major, ME Mihalik, K Fernandez, J Seidman, J Kleiner, D Kolykhalov, AA Rice, CM Feinstone, SM AF Major, ME Mihalik, K Fernandez, J Seidman, J Kleiner, D Kolykhalov, AA Rice, CM Feinstone, SM TI Long-term follow-up of chimpanzees inoculated with the first infectious clone for hepatitis C virus SO JOURNAL OF VIROLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; HUMORAL IMMUNE-RESPONSE; NON-B HEPATITIS; HYPERVARIABLE REGION-1; NON-A; NONSTRUCTURAL PROTEIN-3; ANTIBODY-RESPONSE; HYPERIMMUNE SERUM; ENVELOPE PROTEINS; CELL EPITOPE AB Two chimpanzees (Ch1535 and Ch1536) became infected with hepatitis C virus (HCV) following intrahepatic inoculation with RNA transcribed from a full-length cDNA clone of the virus. Both animals were persistently infected and have been followed for 60 weeks. They showed similar responses to infection, with transient liver enzyme elevations and liver inflammatory responses, which peaked at weeks 17 (Ch1535) and 12 (Ch1536) postinoculation (p.i.). Antibody responses to structural and nonstructural proteins were first detected at weeks 13 (Ch1535) and 10 (Ch1536) p.i. Serum RNA titers increased steadily during the first 10 to 13 weeks but decreased sharply in both animals following antibody and inflammatory responses. Despite direct evidence of humoral immune responses to multiple viral antigens, including hypervariable region 1 (HVR1), both animals remained chronically infected. Detailed sequence analysis of serum HCV RNA revealed no change in the majority HVR1 sequence in Ch1535 and a single-amino-acid mutation in Ch1536, with very little clonal variation in either animal. Full-length genome analysis at week 60 revealed several amino acid substitutions localized to antigens E1, E2, p7, NS3, and NS5. Of these, 55.6 and 40% were present as the majority sequence in serum RNA isolated at week 26 p.i. (Ch1535) and week 22 p.i. (Ch1536), respectively, and could represent immune escape mutations. Mutations accumulated at a rate of 1.57 x 10(-3) and 1.48 x 10(-3) nucleotide substitutions/site/year for Ch1535 and Ch1536, respectively. Taken together, these data indicate that establishment of a persistent HCV infection in these chimpanzees is not due to changes in HVR1; however, the possibility remains that mutations arising in other parts of the genome contributed to this persistence. C1 US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Hepatatis Res Lab, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. RP Feinstone, SM (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Hepatatis Res Lab, Bldg 29A,Rm 1D14,HFM 448,8800 Rockville Pike, Bethesda, MD 20892 USA. EM feinstone@cber.fda.gov OI Kleiner, David/0000-0003-3442-4453 FU NCI NIH HHS [CA57973, R01 CA057973]; NIAID NIH HHS [N01AI40034] NR 71 TC 105 Z9 111 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1999 VL 73 IS 4 BP 3317 EP 3325 PG 9 WC Virology SC Virology GA 175XY UT WOS:000079122400086 PM 10074186 ER PT J AU Whitehead, SS Bukreyev, A Teng, MN Firestone, CY St Claire, M Elkins, WR Collins, PL Murphy, BR AF Whitehead, SS Bukreyev, A Teng, MN Firestone, CY St Claire, M Elkins, WR Collins, PL Murphy, BR TI Recombinant respiratory syncytial virus bearing a deletion of either the NS2 or SH gene is attenuated in chimpanzees SO JOURNAL OF VIROLOGY LA English DT Article ID VACCINE CANDIDATE; TEMPERATURE SENSITIVITY; TS PHENOTYPE; INFECTION; MUTATIONS; PROTEIN; MUTANT; ADULTS AB The NS2 and SH genes of respiratory syncytial virus (RSV) have been separately deleted from a recombinant wild-type RSV strain, A2 (M. N. Teng and P. L. Collins, J. Virol. 73:466-473, 1998; A. Bukreyev et al., J. Virol. 71:8973-8982, 1997; and this study). The resulting viruses, designated rA2 Delta NS2 and rA2 Delta SH, were administered to chimpanzees to evaluate their levels of attenuation and immunogenicity. Recombinant virus rA2 Delta NS2 replicated to moderate levels in the upper respiratory tract, was highly attenuated in the lower respiratory tract, and induced significant resistance to challenge with wild-type RSV. The replication of rA2 Delta SH virus was only moderately reduced in the lower, but not the upper, respiratory tract. However, chimpanzees infected with either virus developed significantly less rhinorrhea than those infected with wild-type RSV, These findings demonstrate that a recombinant RSV mutant lacking either the NS2 or SH gene is attenuated and indicate that these deletions may he useful as attenuating mutations in ne cv, live recombinant RSV vaccine candidates for both pediatric and elderly populations. The Delta SH mutation was incorporated into a recombinant form of the cpts248/404 vaccine candidate, was evaluated fur safety in seronegative chimpanzees, and can now be evaluated as a vaccine for humans. C1 NIAID, Infect Dis Lab, Resp Viruses Sect, Bethesda, MD 20892 USA. NIAID, Infect Dis Lab, Expt Primate Virol Sect, Bethesda, MD 20892 USA. Bioqual Inc, Rockville, MD 20850 USA. RP Whitehead, SS (reprint author), NIAID, Infect Dis Lab, Resp Viruses Sect, 7 Ctr Dr,MSC 0720, Bethesda, MD 20892 USA. EM sswhitehead@nih.gov RI Teng, Michael/I-5006-2012 OI Teng, Michael/0000-0002-0722-3659 FU NIAID NIH HHS [AI-000030, AI-000087] NR 35 TC 153 Z9 161 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1999 VL 73 IS 4 BP 3438 EP 3442 PG 5 WC Virology SC Virology GA 175XY UT WOS:000079122400099 PM 10074199 ER PT J AU Demaimay, R Race, R Chesebro, B AF Demaimay, R Race, R Chesebro, B TI Effectiveness of polyene antibiotics in treatment of transmissible spongiform encephalopathy in transgenic mice expressing syrian hamster PrP only in neurons SO JOURNAL OF VIROLOGY LA English DT Article ID AMPHOTERICIN-B DELAYS; PRION PROTEIN; INCUBATION PERIOD; SCRAPIE AGENT; MINK ENCEPHALOPATHY; DEXTRAN SULFATE; REPLICATION; INFECTION; MS-8209; MOUSE AB To date very few drugs have favorably influenced the course of transmissible spongiform encephalopathies. In previous studies, the polyene antibiotics amphotericin B (AmB) and MS-8209 prolonged the incubation time in Syrian hamsters of the 263K strain of scrapie, but AmB had no effect against other scrapie strains in Syrian hamsters. In the present experiments using transgenic mice expressing Syrian hamster PrP in neurons only, MS-8209 extended the life spans of animals infected with the 263K strain but not the DY strain. AmB was effective against both 263K and DY and prevented death in 18% of DY-infected animals. The AmB effect against strain 263K was more prominent in mice whose endogenous PrP gene had been inactivated by homologous recombination. It was unclear whether this difference was due to a change in the duration of the disease or to possible interactive effects between the mouse PrP gene and the drugs themselves. The effectiveness of treatment after intracerebral scrapie infection in transgenic mice expressing PrP only in neurons suggested that neurons are important sites of action for these drugs. C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. RP Chesebro, B (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 23 TC 30 Z9 31 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1999 VL 73 IS 4 BP 3511 EP 3513 PG 3 WC Virology SC Virology GA 175XY UT WOS:000079122400111 PM 10074211 ER PT J AU Rantanen, T Guralnik, JM Ferrucci, L Leveille, S Fried, LP AF Rantanen, T Guralnik, JM Ferrucci, L Leveille, S Fried, LP TI Coimpairments: Strength and balance as predictors of severe walking disability SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID LOWER-EXTREMITY FUNCTION; MUSCLE STRENGTH; PHYSICAL PERFORMANCE; 75-YEAR-OLD MEN; OLDER WOMEN; ASSOCIATION; MOBILITY; ABILITY; PEOPLE; FALLS AB Background, Little information is available on the joint effects of multiple impairments (coimpairments) on the risk of disability. Our aim was to study the joint effects of strength and balance impairments on severe walking disability. Methods. The data are from the baseline of the Women's Health and Aging Study (WHAS), a study of moderately to severely disabled women. A total of 1,002 women aged 65 and older participated in the tests, which took place in their homes. Severe walking disability was defined as self-reported inability to walk one-quarter mile and customary walling speed in a 4-meter test of less than or equal to 0.4 m/s. Balance was measured as an ability to hold progressively more difficult stands (feet side-by-side, semi-tandem and tandem stands). Maximal knee extension strength was measured using a hand-held dynamometer. Results. There were 129 women who were severely walking disabled but able to walk at least minimally. In logistic regression analysis, balance and knee extension strength were independent predictors of severe walking disability. To study the combined effects, nine groups were formed on the basis of strength tertiles by balance categories in the entire population. In the best balance category, the crude prevalences of severe walking disability were 1.2%, 4.9%, and 14.3% in the highest to lowest strength tertiles. In the middle balance category, the rates were 2.9%, 10.0%, and 45.4.1%, and in the poorest balance category 4.9%, 22.1%, and 42.6%, correspondingly. The age, body weight, and height-adjusted odds ratios (OR) showed that the risk of severe walking disability in the subgroup with best balance and strength was less than 5% of the risk in the subgroup with poorest balance and strength (OR.034, 95% confidence interval [CI].007-. 166). Correspondingly, in the subgroups with poorest strength and best balance (OR.097, 95% CI.025-.38) or poorest balance and best strength (OR.102, 95% CI.012-.866) the risk was about 10%. The age-specific estimates of prevalence of severe walking disability in women were: 2.0% for ages 65-74 years, 3.4% for ages 75-84 years, and 9.1% for ages 85 pears and older. Conclusions. The burden of coimpairments seems to be greater than the sum of single impairments involved. An effective way to reduce severe disabilities could be prevention of coimpairments. C1 NIA, Epidemiol Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. Natl Res Inst, INCRA, Dept Geriatr, Florence, Italy. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. RP Rantanen, T (reprint author), Univ Jyvaskyla, Dept Hlth Sci, POB 35, FIN-40351 Jyvaskyla, Finland. RI Rantanen, Taina/O-6579-2016 OI Rantanen, Taina/0000-0002-1604-1945 NR 30 TC 78 Z9 80 U1 3 U2 6 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD APR PY 1999 VL 54 IS 4 BP M172 EP M176 DI 10.1093/gerona/54.4.M172 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 186WU UT WOS:000079754400009 PM 10219007 ER PT J AU Kim, WY Han, KH Knepper, M Neilsen, S Madsen, KM Kim, J AF Kim, WY Han, KH Knepper, M Neilsen, S Madsen, KM Kim, J TI Expression of Aquaporin-1 in blood vessels in the developing rat kidney SO KIDNEY INTERNATIONAL LA English DT Meeting Abstract C1 Catholic Univ, Coll Med, Dept Anat, Seoul, South Korea. NIH, Lab Kidney & Electrolyte Metab, Bethesda, MD 20892 USA. Univ Aarhus, Dept Cell Biol, DK-8000 Aarhus C, Denmark. Univ Florida, Div Nephrol, Gainesville, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD APR PY 1999 VL 55 IS 4 BP 1598 EP 1598 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 177ZL UT WOS:000079240900055 ER PT J AU Borlongan, CV Sanberg, PR Freeman, TB AF Borlongan, CV Sanberg, PR Freeman, TB TI Neural transplantation for neurodegenerative disorders SO LANCET LA English DT Article ID PARKINSONS-DISEASE; NEURONS; GRAFTS C1 Univ S Florida, Coll Med, Dept Neurol Surg, Dept Pharmacol & Expt Therapeut, Tampa, FL 33613 USA. NIDA, Cellular Neurobiol Branch, NIH, Baltimore, MD USA. RP Freeman, TB (reprint author), Univ S Florida, Coll Med, Dept Neurol Surg, Dept Pharmacol & Expt Therapeut, Tampa, FL 33613 USA. NR 11 TC 1 Z9 1 U1 0 U2 1 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD APR PY 1999 VL 353 SU 1 BP SL29 EP SL30 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 192NH UT WOS:000080084900013 ER PT J AU Hall, PD Willingham, MC Kreitman, RJ Frankel, AE AF Hall, PD Willingham, MC Kreitman, RJ Frankel, AE TI DT388-GM-CSF, a novel fusion toxin consisting of a truncated diphtheria toxin fused to human granulocyte-macrophage colony-stimulating factor, prolongs host survival in a SCID mouse model of acute myeloid leukemia SO LEUKEMIA LA English DT Article DE huGM-CSF diphtheria toxin fusion protein; SCID mouse leukemia model ID FACTOR-RECEPTOR; GM-CSF; CELLS; MICE; CHEMOTHERAPY AB Despite significant advances in the treatment of acute myeloid leukemia (AML), the majority of patients will succumb to drug-resistant AML. To overcome this resistance, we have developed a novel fusion toxin consisting of the catalytic and translocation subunits of diphtheria toxin (DT388) linked to human granulocyte-macrophage colony-stimulating factor (GM-CSF). In vitro, DT388-GM-CSF demonstrated significant activity against numerous AML cell lines and fresh AML blasts. To determine its in vivo efficacy, we developed an in vivo model of human AML in severe combined immunodeficiency (SCID) mice injected intravenously with 1 x 10(7) HL-60 cells (AML-MS cell line). The SCID mice developed abdominal masses, infiltration of the liver and bone marrow, and peripheral blasts with a median survival of 42.5 days. We tested DT388-GM-CSF, ara-C, human GM-CSF, and DAB(389)IL-5, which were injected intraperitoneally on days 2-6 in this model. DT388-GM-CSF significantly improved survival of the SCID mice over Ara-C, DAB(389)IL-2, or control (P < 0.001). DT388-GM-CSF-treated mice who developed leukemia exhibited no difference in the number of GM-CSF receptors (P = 0.39), ligand affinity (P = 0.77), or sensitivity (P = 0.56) to DT388-GM-CSF as compared to the controls. Frank leukemia in DT388-GM-CSF-treated mice may be due to incomplete penetration of drug into tissues rather than cellular resistance. DT388-GM-CSF is an active therapeutic agent in our SCID mouse model of AML with a unique mechanism of action and differing toxicities than current cytotoxic agents. C1 Wake Forest Univ, Ctr Comprehens Canc, Dept Canc Biol, Winston Salem, NC 27157 USA. Med Univ S Carolina, Dept Pharmaceut Sci, Charleston, SC 29425 USA. Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Wake Forest Univ, Ctr Comprehens Canc, Dept Pathol, Winston Salem, NC 27109 USA. RP Frankel, AE (reprint author), Wake Forest Univ, Ctr Comprehens Canc, Dept Canc Biol, Med Ctr Blvd, Winston Salem, NC 27157 USA. FU NCI NIH HHS [CA76178] NR 17 TC 33 Z9 37 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD APR PY 1999 VL 13 IS 4 BP 629 EP 633 DI 10.1038/sj.leu.2401357 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 188LM UT WOS:000079848500020 PM 10214872 ER PT J AU Bies, J Nazarov, V Wolff, L AF Bies, J Nazarov, V Wolff, L TI Alteration of proteolytic processing of c-Myb as a consequence of its truncation in murine myeloid leukemia SO LEUKEMIA LA English DT Article; Proceedings Paper CT XIX Symposium of the International-Association-for-Comparative-Research-on-Leukemia-and-Relat ed-Diseases CY JUL 12-18, 1997 CL MANNHEIM, GERMANY SP Int Assoc Comparat Res Leukemia & Related Dis C1 NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. SAS, Canc Res Inst, Kosice, Slovakia. RP Bies, J (reprint author), NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD APR PY 1999 VL 13 SU 1 BP S116 EP S117 DI 10.1038/sj.leu.2401326 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA 197GA UT WOS:000080356000028 PM 10232384 ER PT J AU Orlic, D Girard, LJ Anderson, SM Bodine, DM AF Orlic, D Girard, LJ Anderson, SM Bodine, DM TI Retrovirus receptor mRNA expression correlates with gene transfer efficiency in pluripotent hematopoietic stem cells SO LEUKEMIA LA English DT Article; Proceedings Paper CT XIX Symposium of the International-Association-for-Comparative-Research-on-Leukemia-and-Relat ed-Diseases CY JUL 12-18, 1997 CL MANNHEIM, GERMANY SP Int Assoc Comparat Res Leukemia & Related Dis DE retrovirus receptors; hemotopoietic stem cells; gene transfer AB Hematopoietic stem cells (HSC) from bone marrow, peripheral blood and cord blood are important in clinical transplantation. However, their use in gene therapy protocols is still limited by a low level of transduction efficiency. In addition to the cell cycling block to retrovirus transduction, we recently demonstrated that the low level of retrovirus receptor mRNA in mouse HSC correlated with the low level of amphotropic retrovirus transduction in these cells. Similarly, we found low levels of mRNA encoding the amphotropic retrovirus receptor in human hone marrow Lin(-) CD34(+) CD38(-) HSC. In an effort to identify an alternative population of human HSC that might be more efficiently transduced, we assayed HSC populations from cord blood for mRNA encoding the amphotropic retrovirus receptor. High levels of receptor mRNA were present in HSC from previously cryopreserved cord. blood compared with HSC from fresh bone marrow and fresh cord blood. The HSC from cryopreserved cord blood are excellent candidates for gene therapy protocols. C1 NHGRI, Hematopoiesis Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Orlic, D (reprint author), NHGRI, Hematopoiesis Sect, Genet & Mol Biol Branch, NIH, Bldg 49,Room 3A11,49 Convent Dr, Bethesda, MD 20892 USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD APR PY 1999 VL 13 SU 1 BP S52 EP S54 DI 10.1038/sj.leu.2401287 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA 197GA UT WOS:000080356000010 PM 10232366 ER PT J AU Lundbom, N Barnett, A Bonavita, S Patronas, N Rajapakse, J Tedeschi, G Di Chiro, G AF Lundbom, N Barnett, A Bonavita, S Patronas, N Rajapakse, J Tedeschi, G Di Chiro, G TI MR image segmentation and tissue metabolite contrast in H-1 spectroscopic imaging of normal and aging brain SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE aging; atrophy; HSI; segmentation ID WHITE-MATTER; GRAY-MATTER; SPECTRA; QUANTITATION; INVIVO; WATER AB The impact of image segmentation on 0.84-ml nominal voxel volume proton spectroscopic imaging in normal brain and in age-related cortical atrophy was investigated. Segmentation improved the gray matter-white matter (GM-WM) contrast for N-acetyl aspartate (NAA)/creatine (Cr) and choline (Cho)/Cr in normal brain, and for NAA/Cho and NAA/Cr in atrophic brain, NAA(GM/WM) (similar to 0.7), Cho(GM/WM) (similar to 0.8), and Cr-GM/WM (similar to 1.3) in normal brain obtained with segmentation agreed with values obtained with quantitative magnetic resonance spectroscopy. Age-related cortical atrophy led to decreased cortical GM NAA/Cho and NAA/Cr; no changes were evident in WM or in NAA(GM/WM) Cho(GM/WM) or Cr-GM/WM GM/WM metabolite analysis may be of limited use in conditions in which parallel metabolite changes occur in WM and GM. Published 1999 Wiley-Liss, Inc.dagger. C1 NINDS, Neuroimaging Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. Univ Helsinki, Dept Radiol, Helsinki, Finland. RP Lundbom, N (reprint author), Univ Helsinki Hosp, Dept Radiol, Meilahti Clin, Haartmanink 4, FIN-00290 Helsinki, Finland. RI Rajapakse, Jagath/B-8485-2008 OI Rajapakse, Jagath/0000-0001-7944-1658 NR 19 TC 44 Z9 45 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD APR PY 1999 VL 41 IS 4 BP 841 EP 845 DI 10.1002/(SICI)1522-2594(199904)41:4<841::AID-MRM25>3.0.CO;2-T PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 216CD UT WOS:000081422200025 PM 10332862 ER PT J AU Listwak, S Barrientos, RM Koike, G Ghosh, S Gomez, M Misiewicz, B Sternberg, EM AF Listwak, S Barrientos, RM Koike, G Ghosh, S Gomez, M Misiewicz, B Sternberg, EM TI Identification of a novel inflammation-protective locus in the Fischer rat SO MAMMALIAN GENOME LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; GENETIC-LINKAGE MAP; EXPERIMENTAL ARTHRITIS; NERVOUS-SYSTEM; LEWIS RATS; MOUSE; CARRAGEENAN; RESPONSES; COMPLEX AB Inbred LEW/N rats are relatively susceptible, while histocompatible inbred F344/N rats are relatively resistant to development of a wide variety of inflammatory diseases in response to a range of pro-inflammatory stimuli. In a LEW/N vs. F344/N F2 intercross, we identified a quantitative trait locus (QTL) on Chr 10 that protects in a dominant fashion against the exudate volume component of innate inflammation in the F344/N rat, as well as a suggestive QTL on Chr 2 near the Fibrinogen cluster region. The exudate volume linkage region on Chr 10 may be similar to one of the multiple regions found to link to inflammatory arthritis phenotypes in other crosses. The suggestive linkage on Chr 2 has not been previously reported and does not seem to contribute to this phenotype in the same manner as the QTL on Chr 10. These findings are consistent with the hypothesis that the innate exudate volume trait is a sub-phenotype of more complex inflammatory phenotypes, such as arthritis, and genes within the Chr 10 linkage region could account for differences in this non-specific acute phase component of the inflammatory response. Since the rat Chr 10 exudate volume linkage region we have identified is syntenic with a region of human Chr 17 that has been shown to link to a variety of autoimmune/inflammatory diseases, including insulin-dependent diabetes mellitus, multiple sclerosis, and psoriasis, identification of genes within this linkage region will shed light on genes relevant to the earliest inflammatory component and to susceptibility and resistance to such human autoimmune/inflammatory diseases. C1 NIMH, Sect Neuroendocrine Immunol & Behav, CNE, NIH, Bethesda, MD 20892 USA. Med Coll Wisconsin, Lab Genet Res, Cardiovasc Res Ctr, Milwaukee, WI 53226 USA. Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. RP Sternberg, EM (reprint author), NIMH, Sect Neuroendocrine Immunol & Behav, CNE, NIH, Bldg 10,Rm 2D-46,10 Ctr Dr,MSC 1284, Bethesda, MD 20892 USA. RI Barrientos, Ruth/E-3244-2013 OI Barrientos, Ruth/0000-0001-7224-4109 NR 25 TC 28 Z9 28 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD APR PY 1999 VL 10 IS 4 BP 362 EP 365 DI 10.1007/s003359901002 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 179HT UT WOS:000079321300006 PM 10087293 ER PT J AU Fletcher, CF Jenkins, NA Copeland, NG Chaudhry, AZ Gronostajski, RM AF Fletcher, CF Jenkins, NA Copeland, NG Chaudhry, AZ Gronostajski, RM TI Exon structure of the nuclear factor I DNA-binding domain from C-elegans to mammals SO MAMMALIAN GENOME LA English DT Article ID ADENOVIRUS DNA; TRANSCRIPTIONAL ACTIVATOR; TERMINAL DOMAIN; CTF/NF-I; NFI-X; GENES; REPLICATION; PROMOTER; ORGANIZATION; PROTEINS AB The Nuclear Factor I (NFI) family of DNA-binding proteins is essential for adenovirus DNA replication and the transcription of many cellular genes. Mammals have four genes encoding NFI. proteins, C. elegans has only a single NFI gene, and prokaryotes have none. To assess the relationship between members of this unusually small family of transcription/replication factors, we mapped the chromosomal locations of the four murine NFI genes and analyzed the exons encoding the DNA-binding domains of the mouse, Amphioxus, and C. elegans NFI genes. The four murine NFI genes are on Chrs 4 (Nfia and Nfib), 8 (Nfix), and 10 (Nfic), suggesting early duplication of the genes and dispersal throughout the genome. The DNA-binding domains of all four NFI genes are encoded by large (532 bp) exons with identical splice acceptor and donor sites in each. In contrast, the C. elegans nfi-1 gene has four phased introns interrupting this DNA-binding, domain-encoding exon, and the last exon extends 213 bp past the splice site used in all four murine genes. In addition, the introns present in C. elegans nfi-1 are missing from the NFI genes of Amphioxus and all mammalian genomes examined. This analysis of the exon structure of the C. elegans and murine NFI genes indicates that the murine genes were probably generated by duplication of a C. elegans-like ancestral gene, but that significant changes have occurred in the genomic organization of either the C. elegans or murine NFI genes during evolution. C1 Cleveland Clin Fdn, Lerner Res Inst, Dept Canc Biol NB40, Cleveland, OH 44195 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. Case Western Reserve Univ, Dept Biochem, Cleveland, OH 44106 USA. RP Gronostajski, RM (reprint author), Cleveland Clin Fdn, Lerner Res Inst, Dept Canc Biol NB40, 9500 Euclid Ave, Cleveland, OH 44195 USA. FU NCI NIH HHS [N01-CO-74101]; NICHD NIH HHS [HD34908] NR 53 TC 21 Z9 26 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD APR PY 1999 VL 10 IS 4 BP 390 EP 396 DI 10.1007/s003359901008 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 179HT UT WOS:000079321300012 PM 10087299 ER PT J AU Ji, WZ Herron, B Jones, JM Jenkins, NA Gilbert, DJ Copeland, NG Swank, R Flaherty, L Meisler, MH AF Ji, WZ Herron, B Jones, JM Jenkins, NA Gilbert, DJ Copeland, NG Swank, R Flaherty, L Meisler, MH TI Identification of genes within the Krd deletion on mouse chromosome 19 SO MAMMALIAN GENOME LA English DT Article ID HERMANSKY-PUDLAK-SYNDROME; RENAL-COLOBOMA SYNDROME; PALE EAR EP; MUTATION; KIDNEY; FAMILY; MOUSE-CHROMOSOME-19; DEFECTS C1 Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. Wadsworth Ctr, Albany, NY 12201 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. New York State Dept Hlth, Roswell Pk Canc Inst, Dept Mol Genet & Cell Biol, Buffalo, NY 14263 USA. RP Meisler, MH (reprint author), Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. FU NHLBI NIH HHS [HL51480]; NIGMS NIH HHS [GM50283, GM24872] NR 17 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD APR PY 1999 VL 10 IS 4 BP 399 EP 401 DI 10.1007/s003359901010 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 179HT UT WOS:000079321300014 PM 10087301 ER PT J AU Lee, CG Morse, HC Kay, BK Kozak, CA AF Lee, CG Morse, HC Kay, BK Kozak, CA TI Genetic mapping of eight SH3 domain genes on seven mouse chromosomes SO MAMMALIAN GENOME LA English DT Article ID FAMILY; PROTEINS; IDENTIFICATION; SYNAPTOJANIN; LEUKEMIA; MEMBER; BRAIN C1 NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA. NIAID, Immunopathol Lab, Bethesda, MD 20892 USA. Univ Wisconsin, Dept Pharmacol, Madison, WI 53706 USA. RP Kozak, CA (reprint author), NIAID, Mol Microbiol Lab, Bldg 4,Room 329,4 Ctr Dr MSC 0460, Bethesda, MD 20892 USA. OI Morse, Herbert/0000-0002-9331-3705 NR 16 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD APR PY 1999 VL 10 IS 4 BP 402 EP 404 DI 10.1007/s003359901011 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 179HT UT WOS:000079321300015 PM 10087302 ER PT J AU Miller, GF Owens, JW AF Miller, GF Owens, JW TI Ultrastructural characterization of the agent of systemic yeast infection of owl monkeys SO MEDICAL MYCOLOGY LA English DT Article DE aotus monkeys; Loboa loboi; mycosis; owl monkeys AB Systemic infection by an unclassified yeast-like organism has been encountered sporadically in wild-caught owl monkeys (Aotus sp.) from South America. The infection is presumably acquired in the wild, the incubation period ranges from months to years. The disease is indolent and clinical signs are non-specific. The diagnosis is based on histopathologic observation of yeast-like cells in multiple internal organs. Most cells appear to be phagocytized by macrophages, however, many are apparently free in the extracellular space. Other inflammatory infiltrates, including neutrophils, lymphocytes, plasma cells, and multinucleated giant cells, are conspicuously absent. Cells are thick-walled, globose to oval, range from 5 to 8 mu m in diameter, and reproduce by narrow-based budding of single daughter cells. Attempts to cultivate the organism on artificial media have failed. Yeast cell ultrastructure was studied using transmission electron microscopy. The cell wall is multilayered, and the internal structure is markedly heterogenous. In some cells, the cytoplasm is lightly electron-opaque, finely granular and lacks recognizable organelles or nuclei. In others, the cytoplasm is electron dense and contains mitochondria, ribosome-like granules, and a multilobulated nucleus. This organism differs from other recognized pathogenic yeast in its combined light microscopic appearance, organ involvement and host response. Ultrastructurally, it most closely resembles Loboa loboi. C1 NIH, VRP, ORS, Bethesda, MD 20892 USA. RP Miller, GF (reprint author), NIH, VRP, ORS, Bldg 28A,Room 117,28A Lib DR MSC 5230, Bethesda, MD 20892 USA. NR 5 TC 3 Z9 4 U1 0 U2 0 PU B I O S SCIENTIFIC PUBLISHERS LTD PI OXFORD PA 9 NEWTEC PLACE, MAGDALEN RD, OXFORD OX4 1RE, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PD APR PY 1999 VL 37 IS 2 BP 139 EP 145 DI 10.1080/02681219980000221 PG 7 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 203CC UT WOS:000080689100010 PM 10361271 ER PT J AU Singh, A Papanicolaou, DA Lawrence, LL Howell, EA Chrousos, GP Deuster, PA AF Singh, A Papanicolaou, DA Lawrence, LL Howell, EA Chrousos, GP Deuster, PA TI Neuroendocrine responses to running in women after zinc and vitamin E supplementation SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE ACTH; cortisol; lactate; exercise; prolactin; eumenorrheic women; growth hormone; catecholamines; interleukin 6 ID GROWTH-HORMONE; METABOLIC RESPONSES; MENSTRUAL-CYCLE; EXERCISE; CYTOKINES; PLASMA; PHASE; INTERLEUKIN-6; PROLACTIN; INDUCTION AB Purpose: The study was undertaken to determine whether acute supplementation with zinc or vitamin E would modify neuroendocrine responses to physiologic stress. Methods: Specifically, the effects of exhaustive running on blood glucose, lactate, ACTH, cortisol, growth hormone, prolactin, catecholamine, and interleukin 6 (IL-6) concentrations were determined in 10 eumenorrheic runners after supplementation with zinc (25 mg), vitamin E (400 IU), or placebo. Subjects ran at 65-70% of their (V)over dot O-2max, to exhaustion, on a treadmill during the follicular phase of their menstrual cycles over three cycles. Results: There were no significant differences associated with supplementation for any of the hormonal and metabolic measures. Exercise, however, significantly (P < 0.05) increased plasma lactate, ACTH, prolactin, and catecholamine concentrations, all of which peaked immediately after exercise (POST). Plasma cortisol concentrations were significantly (P < 0.05) elevated at POST, and a further increase was noted 1 h after exercise. IL-6 concentrations rose linearly throughout exercise and reached peak values at POST. Exercise-induced changes were transient in that all measures returned to baseline within 24 h. Conclusions: Acute supplementation with zinc or vitamin E did not influence the effects of exhaustive running on metabolic and endocrine responses in women. The effects of chronic supplementation on neuroendocrine responses to exercise remain to be determined. C1 Uniformed Serv Univ Hlth Sci, Dept Mil & Emergency Med, Bethesda, MD 20814 USA. NICHHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. RP Singh, A (reprint author), Uniformed Serv Univ Hlth Sci, Dept MIM, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. RI Deuster, Patricia/G-3838-2015 OI Deuster, Patricia/0000-0002-7895-0888 NR 30 TC 24 Z9 24 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD APR PY 1999 VL 31 IS 4 BP 536 EP 542 DI 10.1097/00005768-199904000-00007 PG 7 WC Sport Sciences SC Sport Sciences GA 184CP UT WOS:000079592000007 PM 10211848 ER PT J AU Zahm, SH Hoffman-Goetz, L Dosemeci, M Cantor, KP Blair, A AF Zahm, SH Hoffman-Goetz, L Dosemeci, M Cantor, KP Blair, A TI Occupational physical activity and non-Hodgkin's lymphoma SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE cancer; epidemiologic study ID COLON CANCER RISK; BREAST-CANCER; ANTITUMOR CYTOTOXICITY; IMMUNE-SYSTEM; EXERCISE; MEN; INTERLEUKIN-1; CYTOKINES; SUBSITE; RELEASE AB Purpose: The purpose of this study was to evaluate the role of physical activity in the development of non-Hodgkin's lymphoma (NHL). Methods: Incident NHL cases and population-based controls were identified from three case-control studies conducted in four midwestern states: Iowa, Kansas, Minnesota, and Nebraska,A total of 1177 cases (993 men, 184 women) and 3625 controls (2918 men, 707 women) were interviewed. Usual occupation (all states) and lifetime occupational histories (Iowa and Minnesota only), obtained from interviews, were classified for energy expenditure (EE) and sitting time. Odds ratios (QR) and 95% confidence intervals were calculated comparing moderate and high activity levels with sedentary levels. Results: There was no evidence of an association between NHL and occupational physical activity measured either by EE or sitting time. Among men, the OR associated with usual occupation moderate and high EE were 1.1 and 1.0, respectively. For sitting time the OR were also 1.1 and 1.0 for moderate and hi,oh activity, respectively. Among women, slight nonsignificant elevations in risk of NHL were observed among the high energy level and high activity sitting categories. The trends were not significant; There was no evidence of confounding or effect modification by vital status, hair dye use, or solvent exposure. Among subjects with lifetime occupational histories, there were no significant increases or trends for cumulative or average EE or sitting time. There was no association between occupational physical activity and NHL. Conclusion: Research on nonoccupational physical activity, which in the U.S. is likely the more important component of daily activity than occupational activity, may still be warranted given the laboratory evidence linking physical activity and immune function, an important factor in the etiology of NHL. C1 Univ Waterloo, Fac Appl Hlth Sci, Dept Hlth Studies & Gerontol, Waterloo, ON N2L 3G1, Canada. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Hoffman-Goetz, L (reprint author), Univ Waterloo, Fac Appl Hlth Sci, Dept Hlth Studies & Gerontol, Waterloo, ON N2L 3G1, Canada. EM lhgoetz@healthy.uwaterloo.ca RI Zahm, Shelia/B-5025-2015 NR 58 TC 24 Z9 24 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD APR PY 1999 VL 31 IS 4 BP 566 EP 571 DI 10.1097/00005768-199904000-00012 PG 6 WC Sport Sciences SC Sport Sciences GA 184CP UT WOS:000079592000012 PM 10211853 ER PT J AU Kukielczak, B Romanowska, B Bryk, J AF Kukielczak, B Romanowska, B Bryk, J TI Gamma radiation and MC540 photosensitization of melanoma in the hamster's eye SO MELANOMA RESEARCH LA English DT Article DE anterior chamber of eye; combined treatment; eye melanoma; gamma-irradiation; photosensitization ID POSTERIOR UVEAL MELANOMA; PHOTODYNAMIC THERAPY; MALIGNANT-MELANOMA; RABBIT; TISSUE; DAMAGE; CELLS; DYE AB The purpose of this study was to evaluate the effects of cobalt-60 gamma-radiation and argon laser irradiation using injected merocyanine (MC540) as a photosensitizer on pigmented and non-pigmented Bomirski hamster melanomas growing in the eye. The animals were treated with one of four regimens, receiving gamma-irradiation only, photosensitization only, a combination of gamma-irradiation and photosensitization, or a combined time-fractionated treatment. Tumours were exposed to laser light 24 h after injection, when the photosensitizing dye concentration was highest. The degree of tissue damage was evaluated by observation of the area for necrosis, interruption of blood circulation, and the shape and dissemination of the tumour cells. Additionally, tumour growth was monitored through the measurement of tumour volume and also calculated from histological cross sections on the assumption that the tumour morphology is hemi-ellipsoidal. A single treatment of tumours by a combination of photodynamic therapy and ionizing radiation resulted in an additive effect, inhibiting tumour growth for 2-4 days. A time-fractionated treatment, given four times every 24 h, markedly delayed tumour growth for up to 6 weeks. The results indicate that MC540-mediated photodynamic treatment in combination with gamma-radiation exerts a significant therapeutic effect on a rapidly growing melanoma. (C) 1999 Lippincott Williams & Wilkins. C1 Jagiellonian Univ, Inst Mol Biol, Dept Radiospectroscopy & Radiobiol Canc, PL-31120 Krakow, Poland. Jagiellonian Univ, Coll Med, Dept Ophthalmol, PL-31501 Krakow, Poland. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Kukielczak, B (reprint author), Jagiellonian Univ, Inst Mol Biol, Dept Radiospectroscopy & Radiobiol Canc, Al Mickiewicza 3, PL-31120 Krakow, Poland. NR 26 TC 9 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-8931 J9 MELANOMA RES JI Melanoma Res. PD APR PY 1999 VL 9 IS 2 BP 115 EP 124 DI 10.1097/00008390-199904000-00002 PG 10 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA 203NX UT WOS:000080714700002 PM 10380933 ER PT J AU Klimes-Dougan, B Kopp, CB AF Klimes-Dougan, B Kopp, CB TI Children's conflict tactics with mothers: A longitudinal investigation of the toddler and preschool years SO MERRILL-PALMER QUARTERLY-JOURNAL OF DEVELOPMENTAL PSYCHOLOGY LA English DT Article ID INTERPERSONAL NEGOTIATION STRATEGIES; YOUNG-CHILDREN; DEVELOPMENTAL MODEL; SELF-ASSERTION; COMPETENCE; NONCOMPLIANCE; BEHAVIOR; TALK AB To document the normative developmental progression of mother-child conflict and conflict resolution strategies, two cohorts of children, spanning the toddler to preschool years, were observed longitudinally. Children's verbal negotiations were emphasized, and a multidimensional definition of negotiation permitted delineation of their conflict resolution strategies. The developmental findings, central to this study, showed that mother-child conflicts reach a peak at 30 months. The results increasingly on negotiation during conflict. The on refusing and preschoolers rely suggest that toddlers may rely predominantly results also indicate that patterns of conflict and negotiation are similar in different settings, and may elucidate important individual differences in young children. Implications and limitations for these normative developmental patterns are discussed. C1 Univ Calif Los Angeles, Los Angeles, CA USA. RP Klimes-Dougan, B (reprint author), NIMH, Sect Dev Psychopathol, Bldg 15K,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 41 TC 21 Z9 21 U1 1 U2 3 PU WAYNE STATE UNIV PRESS PI DETROIT PA 4809 WOODWARD AVE, DETROIT, MI 48201-1309 USA SN 0272-930X J9 MERRILL PALMER QUART JI Merrill-Palmer Q.-J. Dev. Psychol. PD APR PY 1999 VL 45 IS 2 BP 226 EP 241 PG 16 WC Psychology, Developmental SC Psychology GA 210VN UT WOS:000081125500003 ER PT J AU Sherman, ME Tabbara, SO Scott, DR Kurman, RJ Glass, AG Manos, MM Burk, RD Rush, BB Schiffman, M AF Sherman, ME Tabbara, SO Scott, DR Kurman, RJ Glass, AG Manos, MM Burk, RD Rush, BB Schiffman, M TI "ASCUS, rule out HSIL": Cytologic features, histologic correlates, and human papillomavirus detection SO MODERN PATHOLOGY LA English DT Article; Proceedings Paper CT 86th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-08, 1997 CL ORLANDO, FLORIDA SP US & Canadian Acad Pathol DE ASCUS; Bethesda system; atypical squamous cells; cervix; papillomavirus ID ATYPICAL SQUAMOUS CELLS; CERVICAL INTRAEPITHELIAL NEOPLASIA; NEGATIVE PAPANICOLAOU SMEARS; UNDETERMINED SIGNIFICANCE; QUALITY ASSURANCE; RAPID PROGRESSION; RISK; INFECTION; LESIONS; DIAGNOSES AB Risk factors, cytologic and histopathologic features, and human papillomavirus (HPV) detection associated with 75 cervical smears classified as atypical squamous cells of undetermined significance, rule out high-grade squamous intraepithelial lesion (ASCUS, rule out HSIL) were reviewed, Cases were identified in a pathology panel review of material collected from 1953 women participating in a 5-year prospective study of HPV infection and squamous intraepithelial lesions at Kaiser Permanente, Portland, Oregon, sponsored by the National Cancer Institute. Initial abnormal smears diagnosed as ASCUS, rule out HSIL by one panelist or diagnosed as ASCUS by one pathologist and as HSIL by another were included. The 75 ASCUS, rule out HSIL smears identified were examined again by two pathologists after the study. These cases were compared with cases of ASCUS, not otherwise specified (ASCUS, NOS) and HSIL identified in the same group of 1953 women. Findings in ASCUS, rule out HSIL included tissue fragments (21%); atypical immature metaplasia (17%); atypical mature metaplasia (15%); small atypical cells (9%); and atypical repair (4%). A final patient classification of HSIL, reflecting all available data, was assigned to 11 (24%) of 46 women with ASCUS, rule out HSIL and to 1(1%) of 80 women with ASCUS, NOS in the original review (P < .001). Detection of oncogenic HPV types at diagnosis in ASCUS, rule out HSIL; ASCUS, NOS; and HSIL was similar, but data were unavailable for many subjects. Among women not tested at diagnosis, enrollment testing (1 to 4 years earlier) revealed that HPV detection in women with ASCUS, rule out HSIL was intermediate in frequency between ASCUS, NOS and HSIL. These data suggest that ASCUS, rule out HSIL is a distinct diagnosis from ASCUS, NOS because it is more often associated with an underlying HSIL. Consequently, women with ASCUS, rule out HSIL should be referred for colposcopic examination. C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Obstet & Gynecol, Baltimore, MD 21205 USA. George Washington Univ, Med Ctr, Dept Pathol, Washington, DC 20037 USA. Kaiser Permanente, Portland, OR USA. No Calif Permanente Med Grp, Div Res, Oakland, CA USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. RP Sherman, ME (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Execut Plaza N,Room 443,6130 Execut Blvd,MSC 7374, Bethesda, MD 20892 USA. NR 25 TC 66 Z9 71 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD APR PY 1999 VL 12 IS 4 BP 335 EP 342 PG 8 WC Pathology SC Pathology GA 187RA UT WOS:000079799500001 PM 10229496 ER PT J AU Liao, MJ Yin, CY Barlow, C Wynshaw-Boris, A Van Dyke, T AF Liao, MJ Yin, CY Barlow, C Wynshaw-Boris, A Van Dyke, T TI Atm is dispensable for p53 apoptosis and tumor suppression triggered by cell cycle dysfunction SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID WILD-TYPE P53; VIRUS-40 T-ANTIGEN; ATAXIA-TELANGIECTASIA; GENE AMPLIFICATION; DEFICIENT MICE; IN-VIVO; CANCER; GROWTH; PROGRESSION; CHECKPOINT AB Both p53 and ATM are checkpoint regulators with roles in genetic stabilization and cancer susceptibility. ATM appears to function in the same DNA damage checkpoint pathway as p53. However, ATM's role in p53-dependent apoptosis and tumor suppression in response to cell cycle dysregulation is unknown. In this study, we tested the role of murine ataxia telangiectasia protein (Atm) in a transgenic mouse brain tumor model in which p53-mediated apoptosis results in tumor suppression. These p53-mediated activities are induced by tissue-specific inactivation of pRb family proteins by a truncated simian virus 40 large T antigen in brain epithelium. We show that p53-dependent apoptosis, transactivation, and tumor suppression are unaffected by Atm deficiency, suggesting that signaling in the DNA damage pathway is distinct from that in the oncogene induced pathway. In addition, we show that Atm deficiency has no overall effect on tumor growth and progression in this model. C1 Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. Natl Human Genome Res Inst, Lab Genet Dis Res, NIH, Bethesda, MD 20892 USA. RP Van Dyke, T (reprint author), Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, CB 3280,Fordham Hall, Chapel Hill, NC 27599 USA. EM tvdlab@med.unc.edu FU NCI NIH HHS [R01 CA046283, CA46283, CA65773, R01 CA065773] NR 44 TC 34 Z9 34 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 1999 VL 19 IS 4 BP 3095 EP 3102 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 178MG UT WOS:000079269300068 PM 10082576 ER PT J AU Simmen, T Nobile, M Bonifacino, JS Hunziker, W AF Simmen, T Nobile, M Bonifacino, JS Hunziker, W TI Basolateral sorting of furin in MDCK cells requires a phenylalanine-isoleucine motif together with an acidic amino acid cluster SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANS-GOLGI NETWORK; TOXIN PROTECTIVE ANTIGEN; CANINE KIDNEY-CELLS; CYTOPLASMIC DOMAIN; FC-RECEPTORS; INTRACELLULAR TRAFFICKING; STRUCTURAL REQUIREMENTS; BIOSYNTHETIC TRANSPORT; PROPROTEIN CONVERTASE; PRECURSOR PROTEINS AB Furin is a subtilisin-related endoprotease which processes a wide range of bioactive proteins. Furin is concentrated in the trans-Golgi network (TGN), where proteolytic activation of many precursor proteins takes place, A significant fraction of furin, however, cycles among the TGN, the plasma membrane, and endosomes, indicating that the accumulation in the TGN reflects a dynamic localization process. The cytosolic domain of furin is necessary and sufficient for TGN localization, and two signals are responsible for retrieval of furin to the TGN, A tyrosine-based (YKGL) motif mediates internalization of furin from the cell surface into endosomes, An acidic cluster that is part of two casein kinase II phosphorylation sites (SDSEEDE) is then responsible for retrieval of furin from endosomes to the TGN. In addition, the acidic EEDE sequence also mediates endocytic activity. Here, we analyzed the sorting of furin in polarized epithelial cells. We show that furin is delivered to the basolateral surface of MDCK cells, from where a significant fraction of the protein can return to the TGN, A phenylalanine-isoleucine motif together with the acidic EEDE duster is required for basolateral sorting and constitutes a novel signal regulating intracellular traffic of furin. C1 Univ Lausanne, BIL Biomed Res Ctr, Inst Biochem, CH-1066 Epalinges, Switzerland. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Hunziker, W (reprint author), Univ Lausanne, BIL Biomed Res Ctr, Inst Biochem, CH-1066 Epalinges, Switzerland. RI Hunziker, Walter/B-3140-2010; OI Hunziker, Walter/0000-0002-5265-4933; Bonifacino, Juan S./0000-0002-5673-6370 NR 44 TC 53 Z9 54 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 1999 VL 19 IS 4 BP 3136 EP 3144 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 178MG UT WOS:000079269300072 PM 10082580 ER PT J AU Shcherbakova, PV Kunkel, TA AF Shcherbakova, PV Kunkel, TA TI Mutator phenotypes conferred by MLH1 overexpression and by heterozygosity for mlh1 mutations SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; DNA MISMATCH REPAIR; SACCHAROMYCES-CEREVISIAE; REPLICATION FIDELITY; GERMLINE MUTATIONS; SHUTTLE VECTORS; COLON-CANCER; YEAST; GENES; CELLS AB Loss of DNA mismatch repair due to mutation or diminished expression of the MLH1 gene is associated with genome instability and cancer. In this study, we used a yeast model system to examine three circumstances relevant to modulation of MLH1 function. First, overexpression of wild-type MLH1 was found to cause a strong elevation of mutation rates at three different loci, similar to the mutator effect of MLH1 gene inactivation, Second, haploid yeast strains with any of six mlh1 missense mutations that mimic germ line mutations found in human cancer patients displayed a strong mutator phenotype consistent with loss of mismatch repair function, Five of these mutations affect amino acids that are homologous to residues suggested by recent crystal structure and biochemical analysis of Escherichia coli MutL to participate in ATP binding and hydrolysis, Finally, using a highly sensitive reporter gene, we detected a mutator phenotype of diploid yeast strains that are heterozygous for mlh1 mutations. Evidence suggesting that this mutator effect results not from reduced mismatch repair in the MLH1/mlh1 cells but rather from loss of the wild-type MLH1 allele in a fraction of cells is presented. Exposure to bleomycin or to UV irradiation strongly enhanced mutagenesis in the heterozygous strain but had little effect on the mutation rate in the wild-type strain, This damage-induced hypermutability may be relevant to cancer in humans with germ line mutations in only one MLH1 allele. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Kunkel, TA (reprint author), NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. EM kunkel@niehs.nih.gov NR 50 TC 121 Z9 123 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 1999 VL 19 IS 4 BP 3177 EP 3183 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 178MG UT WOS:000079269300076 PM 10082584 ER PT J AU Zhang, CF Snell, CR Loh, YP AF Zhang, CF Snell, CR Loh, YP TI Identification of a novel prohormone sorting signal-binding site on carboxypeptidase E, a regulated secretory pathway-sorting receptor SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID TRANS-GOLGI NETWORK; CPE(FAT)/CPE(FAT) MICE; MEMBRANE-PROTEINS; ENZYME-ACTIVITY; DISULFIDE BOND; CHROMOGRANIN-B; CPE(FAT) MICE; ATT-20 CELLS; E MUTATION; PROINSULIN AB Sorting of the prohormone POMC to the regulated secretory pathway necessitates the binding of a sorting signal to a sorting receptor, identified as membrane carboxypeptidase E (CPE). The sorting signal, located at the N terminus of POMC consists of two acidic (Asp(10),Glu(14)) and two hydrophobic (Leu(11), Leu(18)) residues exposed on the surface of an amphipathic loop. In this study, molecular modeling of CPE predicted that the acidic residues in the POMC-sorting signal bind specifically to two basic residues, Arg(255) and Lys(260), present in a loop unique to CPE, compared with other carboxypeptidases. To test the model, these two residues on CPE were mutated to Ser or Ala, followed by baculovirus expression of the mutant CPEs in Sf9 cells. Sf9 cell membranes containing CPE mutants with either Arg(255) or Lys(260), or both residues substituted, showed no binding of [I-125]N-POMC1-26 (which contains the POMC-sorting signal motif), proinsulin, or proenkephalin. In contrast, substitution of an Arg(147) to Ala(147) at a substrate-binding site, Arg(259) to Ala(259) and Ser(202) to Pro(202), in CPE did not affect the level of [I-125]N-POMC1-26 binding when compared with-wild type CPE. Furthermore, mutation of the POMC-sorting signal motif (Asp(10), Leu(11), Glu(14), Leu(18)) eliminated binding to wild-type CPE. These results indicate that the sorting signal of POMC, proinsulin, and proenkephalin specifically interacts with Arg(255) and Lys(260) at a novel binding site, independent of the active site on CPE. C1 NICHHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. Novartis Inst Med Res, London WC1E 6BN, England. RP Loh, YP (reprint author), NICHHD, Dev Neurobiol Lab, NIH, Bldg 49,Room 5A38, Bethesda, MD 20892 USA. NR 28 TC 36 Z9 36 U1 1 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD APR PY 1999 VL 13 IS 4 BP 527 EP 536 DI 10.1210/me.13.4.527 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 180LD UT WOS:000079386700002 PM 10194759 ER PT J AU Richardson, J Vinson, C Bodwell, J AF Richardson, J Vinson, C Bodwell, J TI Cyclic adenosine-3 ',5 '-monophosphate-mediated activation of a glutamine synthetase composite glucocorticoid response element SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID EMBRYONIC NEURAL RETINA; GENE-EXPRESSION; RECEPTOR; TRANSCRIPTION; INDUCTION; UPSTREAM; BINDING; VECTORS AB The glutamate synthetase gene (GS) contains a composite glucocorticoid response element (cGRE) comprised of a GRE and an adjacent element with features of both a cAMP-response element (CRE) and a 12-O-tetradecanoylphorbol 13-acetate (TPA) response element (TRE). The CRE/TRE element of the cGRE contributed to two modes of transcriptional activation: 1) enhancement of the response to cortisol and 2) a synergistic response to cortisol and increased cAMP. COS-7 cells transfected with a cGRE-luciferase construct show minimal expression under basal conditions or forskolin treatment. After cortisol treatment, luciferase activity from the cGRE is enhanced 4- to 8-fold greater than the GRE portion of the cGRE or a GRE from the tyrosine aminotransferase gene. Treatment with both forskolin and cortisol produced a 2- to 4-fold synergistic response over cortisol alone. Synergy is also seen with 8-bromo-cAMP, is specific for the cGRE, and occurs in a number of established cell lines. Elimination of the GRE or CRE/TRE reduces the synergy by 70-100%, Altering the CRE/TRE to GRE spacing changed both enhancement and synergy. Moving the elements 3 bp closer or extending 15 bp reduced enhancement. Synergy was markedly reduced when elements were one half of a helical turn out of phase. Western blots verified that ORES (cAMP-responsive binding protein) and ATF-1 (activating transcription factor-1) binds to the cGRE sequence. A specific dominant negative inhibitor of the ORES family, A-CREB, reduced synergy by 50%, These results suggest that the GS cGRE can potentially integrate signaling from both the cAMP and glucocorticoid receptor transduction pathways and that CREB/ATF-1 may play an important role in this process. C1 Dartmouth Med Sch, Dept Physiol, Lebanon, NH 03756 USA. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Bodwell, J (reprint author), Dartmouth Med Sch, Dept Physiol, Lebanon, NH 03756 USA. FU NIDDK NIH HHS [DK-45337, DK-03535] NR 28 TC 8 Z9 8 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD APR PY 1999 VL 13 IS 4 BP 546 EP 554 DI 10.1210/me.13.4.546 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 180LD UT WOS:000079386700004 PM 10194761 ER PT J AU Van Goor, F Krsmanovic, LZ Catt, KJ Stojilkovic, SS AF Van Goor, F Krsmanovic, LZ Catt, KJ Stojilkovic, SS TI Control of action potential-driven calcium influx in GT1 neurons by the activation status of sodium and calcium channels SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; IMMORTALIZED HYPOTHALAMIC NEURONS; GNRH NEURONS; PITUITARY-CELLS; PATCH-CLAMP; RECEPTORS; LACTOTROPHS; SECRETION; DURATION; CURRENTS AB An analysis of the relationship between electrical membrane activity and Ca2+ influx in differentiated GnRH-secreting (GT1) neurons revealed that most cells exhibited spontaneous, extracellular Ca2+-dependent action potentials (APs). Spiking was initiated by a slow pacemaker depolarization from a baseline potential between -75 and -50 mV, and AP frequency increased with membrane depolarization. More hyperpolarized cells fired sharp APs with limited capacity to promote Ca2+ influx, whereas more depolarized cells fired broad APs with enhanced capacity for Ca2+ influx. Characterization of the inward currents in GT1 cells revealed the presence of tetrodotoxin-sensitive Na+, Ni2+-sensitive T-type Ca2+, and dihydropyridine-sensitive L-type Ca2+ components. The availability of Na+ and T-type Ca2+ channels was dependent on the baseline potential, which determined the activation/inactivation status of these channels. Whereas all three channels were involved in the generation of sharp APs, L-type channels were solely responsible for the spike depolarization in cells exhibiting broad APs. Activation of GnRH receptors led to biphasic changes in cytosolic Ca2+ concentration ([Ca2+](i)), with an early, extracellular Ca2+-independent peak and a sustained, extracellular Ca2+-dependent phase. During the peak [Ca2+](i) response, electrical activity was abolished due to transient hyperpolarization. This was followed by sustained depolarization of cells and resumption of firing of increased frequency with a shift from sharp to broad APs. The GnRH-induced change in firing pattern accounted for about 50% of the elevated Ca2+ influx, the remainder being independent of spiking. Basal [Ca2+](i) was also dependent on Ca2+ influx through AP-driven and voltage-insensitive pathways. Thus, in both resting and agonist-stimulated GT1 cells, membrane depolarization limits the participation of Na+ and T-type channels in firing, but facilitates AP-driven Ca2+ influx. 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-36,49 Convent Dr, Bethesda, MD 20892 USA. EM stankos@helix.nih.gov NR 40 TC 54 Z9 54 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD APR PY 1999 VL 13 IS 4 BP 587 EP 603 DI 10.1210/me.13.4.587 PG 17 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 180LD UT WOS:000079386700008 PM 10194765 ER PT J AU Greene, NDE Bernard, DL Taschner, PEM Lake, BD de Vos, N Breuning, MH Gardiner, RM Mole, SE Nussbaum, RL Mitchison, HM AF Greene, NDE Bernard, DL Taschner, PEM Lake, BD de Vos, N Breuning, MH Gardiner, RM Mole, SE Nussbaum, RL Mitchison, HM TI A murine model for juvenile NCL: Gene targeting of mouse Cln3 SO MOLECULAR GENETICS AND METABOLISM LA English DT Article; Proceedings Paper CT 7th International Congress on the Neuronal Ceroid-Lipofuscinoses (NCL-98) CY JUN 13-16, 1998 CL DALLAS, TEXAS DE JNCL; neuronal ceroid lipofuscinosis; CLN3; gene targeting ID NEURONAL CEROID-LIPOFUSCINOSES; BATTEN-DISEASE GENE; MANIPULATION AB JNCL is a neurodegenerative disease of childhood caused by mutations in the CLN3 gene. A mouse model for JNCL was created by disrupting exons 1-6 of Cln3, resulting in a null allele, Cln3 null mice appear clinically normal at 5 months of age; however, like JNCL patients, they exhibit intracellular accumulation of autofluorescent material, A second approach will generate mice in which exons 7 and 8 of Cln3 are deleted, mimicking the common mutation in JNCL patients, (C) 1999 Academic Press. C1 Univ London Univ Coll, Sch Med, Dept Paediat, London WC1E 6JJ, England. NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD USA. Leiden Univ, Dept Human Genet, NL-2300 RA Leiden, Netherlands. Great Ormond St Hosp Children, Dept Histopathol, London WC1N 3JH, England. RP Greene, NDE (reprint author), Univ London Univ Coll, Sch Med, Dept Paediat, Torrington Pl, London WC1E 6JJ, England. RI Mitchison, Hannah/C-1891-2008; Mole, Sara/C-2024-2008; Breuning, Martijn/E-3429-2010; Taschner, Peter/J-8853-2014; OI Taschner, Peter/0000-0001-9621-465X; Greene, Nicholas/0000-0002-4170-5248; Mole, Sara/0000-0003-4385-4957 NR 15 TC 21 Z9 21 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD APR PY 1999 VL 66 IS 4 BP 309 EP 313 DI 10.1006/mgme.1999.2828 PG 5 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 190BJ UT WOS:000079941400015 PM 10191119 ER PT J AU Grant, CCR Bos, MP Belland, RJ AF Grant, CCR Bos, MP Belland, RJ TI Proteoglycan receptor binding by Neisseria gonorrhoeae MS11 is determined by the HV-1 region of OpaA SO MOLECULAR MICROBIOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; OUTER-MEMBRANE PROTEINS; SURFACE HEPARAN-SULFATE; EPITHELIAL-CELLS; HYPERVARIABLE REGIONS; GONOCOCCUS INFECTION; OPACITY PROTEINS; GENE DUPLICATION; HELA-CELLS; FAMILY AB The interaction of the OpaA protein of Neisseria gonorrhoeae MS11mk with heparan sulphate-containing proteoglycan receptors on Chang conjunctiva epithelial cells was examined using isolated receptor binding and cell adherence/internalization assays. OpaA deletion proteins, in which the four surface-exposed regions of the protein were deleted individually, and chimeric OpaA/B proteins, in which the surface-exposed regions of the OpaA and OpaB proteins were exchanged, were expressed in N. gonorrhoeae. The recombinant deletion proteins and the chimeric OpaA/B proteins were surface exposed in the outer membrane of N. gonorrhoeae. Isolated receptor-binding assays and Chang cell infection assays with OpaA deletion variants indicated that hypervariable region 1 was essential for the interaction of N, gonorrhoeae with the proteoglycan receptor. Expression of chimeric OpaA/B proteins confirmed the central role of hypervariable region 1 in receptor binding and demonstrated that this domain alone confers the invasive biological phenotype in a non-heparan sulphate proteoglycan-binding Cpa protein. The other variable regions of OpaA enhanced receptor binding in the presence of region 1, but did not constitute binding domains on their own. The results indicate that proteoglycan receptor binding results from a hierarchical interaction between the variable domains of the OpaA protein of MS11mk. C1 NIAID, Microbial Struct & Funct Lab, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Belland, RJ (reprint author), NIAID, Microbial Struct & Funct Lab, Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA. NR 47 TC 19 Z9 19 U1 0 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD APR PY 1999 VL 32 IS 2 BP 233 EP 242 DI 10.1046/j.1365-2958.1999.01293.x PG 10 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 191RE UT WOS:000080034700002 PM 10231481 ER PT J AU Picardeau, M Lobry, JR Hinnebusch, BJ AF Picardeau, M Lobry, JR Hinnebusch, BJ TI Physical mapping of an origin of bidirectional replication at the centre of the Borrelia burgdorferi linear chromosome SO MOLECULAR MICROBIOLOGY LA English DT Article ID COMPLETE GENOME SEQUENCE; ESCHERICHIA-COLI K-12; 2 DNA STRANDS; NUCLEOTIDE-SEQUENCE; PLASMIDS; BACTERIA; GENE; SPIROCHETE; INITIATION; EVOLUTION AB The Borrelia burgdorferi chromosome is linear, with telomeres characterized by terminal inverted repeats and covalently closed single-stranded hairpin loops. The replication mechanism of these unusual molecules is unknown. Previous analyses of bacterial chromosomes for which the complete sequence has been determined, including that of B, burgdorferi, revealed an abrupt switch in polarity of Co skew at known or putative origins of replication. We used nascent DNA strand analysis to physically map the B. burgdorferi origin to within a 2 kb region at the centre of the linear chromosome, and to show that replication proceeds bidirectionally from this origin. The results are consistent with replication models in which termination occurs at the telomeres after bidirectional, symmetrical elongation from the central origin. Sequences typical of origins of other bacterial chromosomes were not found at the origin of this spirochete. The most likely location of the replication origin of the linear chromosome is the 240 bp sequence between dnaA and dnaN where the switch in CG skew occurs. C1 NIAID, NIH, Rocky Mt Labs, Microbial Struct & Funct Lab, Hamilton, MT 59840 USA. Univ Lyon 1, Lab Biometrie, CNRS, UMR 5558, F-69622 Villeurbanne, France. RP Hinnebusch, BJ (reprint author), NIAID, NIH, Rocky Mt Labs, Microbial Struct & Funct Lab, 903 S 4th St, Hamilton, MT 59840 USA. NR 34 TC 70 Z9 71 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD APR PY 1999 VL 32 IS 2 BP 437 EP 445 DI 10.1046/j.1365-2958.1999.01368.x PG 9 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 191RE UT WOS:000080034700019 PM 10231498 ER PT J AU Sakaue, M Adachi, H Jetten, AM AF Sakaue, M Adachi, H Jetten, AM TI Post-transcriptional regulation of MyD118 and GADD45 in human lung carcinoma cells during 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid-induced apoptosis SO MOLECULAR PHARMACOLOGY LA English DT Article ID RETINOID-INDUCED APOPTOSIS; RESPONSE GENE MYD118; SELECTIVE RETINOIDS; GROWTH-INHIBITION; LEUKEMIA-CELLS; CANCER CELLS; IN-VITRO; EXPRESSION; INDUCTION; PROTEINS AB Recently, the novel synthetic retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (AHPN) has been shown to inhibit cell growth and induce apoptosis in several human carcinoma cell lines. To understand the mechanism of AHPN action, we identified, using the differential display method, several genes that are differentially regulated by AHPN. The sequence of one of these genes was highly homologous to mouse MyD118, a gene closely related to GADD45. Both of these genes have been reported to play a role in negative growth control and apoptosis. hMyD118 was expressed in a variety of tissues, including liver, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, and peripheral blood leukocytes. The levels of both hMyD118 and GADD45 mRNA was rapidly increased in a number of carcinoma cell lines after treatment with AHPN. This increase was specific for AHPN because retinoic acid, a retinoic acid receptor-selective retinoid, and an retinoid X receptor-selective retinoid were ineffective. These results suggest that this action of AHPN involves a novel mechanism that is independent of the nuclear retinoid receptors. AHPN increases the half-life of hMyD118 and GADD45 mRNA by >9-fold, indicating that it causes an increase in the stability of these mRNAs. The caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp fluoro-methylketone (ZVAD. fmk) had no effect on the induction of hMyD118, indicating that this increase occurred independently of caspase activation. Our study demonstrates that the inhibition of cell growth by AHPN is accompanied by an increase in hMyD118 and GADD45 mRNA, and that this enhancement is regulated ata post-transcriptional level. Our results support a role for MyD118 and GADD45 in the negative growth control by AHPN. C1 NIEHS, Cell Biol Sect, Pulm Pathobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Jetten, AM (reprint author), NIEHS, Cell Biol Sect, Pulm Pathobiol Lab, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. OI Jetten, Anton/0000-0003-0954-4445 NR 40 TC 27 Z9 27 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD APR PY 1999 VL 55 IS 4 BP 668 EP 676 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 182RB UT WOS:000079511000006 PM 10101024 ER PT J AU Arteel, GE Kadiiska, MB Rusyn, I Bradford, BU Mason, RP Raleigh, JA Thurman, RG AF Arteel, GE Kadiiska, MB Rusyn, I Bradford, BU Mason, RP Raleigh, JA Thurman, RG TI Oxidative stress occurs in perfused rat liver at low oxygen tension by mechanisms involving peroxynitrite SO MOLECULAR PHARMACOLOGY LA English DT Article ID HYPOXIA; ALCOHOL; METABOLISM; INVIVO; INJURY; STATE AB Ethanol increases free radical formation; however, it was recently demonstrated that it also causes extensive hypoxia in rat liver in vivo. To address this issue, it was hypothesized that peroxynitrite formed in normoxic periportal regions of the liver lobule has its reactivity enhanced in hypoxic pericentral regions where the pH is lower. Via this pathway, peroxynitrite could lead to free radical formation in the absence of oxygen. Livers from fed vats were perfused at low flow rates for 75 min. Under these conditions, periportal regions were well oxygenated but pericentral areas became hypoxic. Low-flow perfusion caused a significant 6-fold increase in nitrotyrosine accumulation in pericentral regions. During the last 20 min of perfusion, the spin-trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone was infused and adducts were collected for electron-spin resonance analysis. A six-line radical adduct signal was detected in perfusate. Direct infusion of peroxynitrite produced a radical adduct with identical coupling constants, and a similar pattern of nitrotyrosine accumulation was observed. Retrograde perfusion at low rates resulted in accumulation of nitrotyrosine in periportal regions. Although the magnitude of the radical in perfusate was increased by ethanol, it was not derived directly from it. Both nitrotyrosine accumulation and radical formation were reduced by inhibition of nitric oxide synthase with N-nitro-L-arginine methyl ester, but not with the inactive D-isomer. Radical formation was decreased nearly completely by superoxide dismutase and N-nitro-L-arginine methyl ester, consistent with the hypothesis that the final prooxidant is a derivative from both NO and superoxide (i.e., peroxynitrite). These results support the hypothesis that oxidative stress occurs in hypoxic regions of the liver lobule by mechanisms involving peroxynitrite. C1 Univ N Carolina, Dept Pharmacol, Hepatobiol & Toxicol Lab, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Radiat Oncol, Chapel Hill, NC 27599 USA. Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC 27599 USA. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Thurman, RG (reprint author), Univ N Carolina, Dept Pharmacol, Hepatobiol & Toxicol Lab, CB 7365,Mary Ellen Jones Bldg, Chapel Hill, NC 27599 USA. RI Rusyn, Ivan/S-2426-2016 FU NCI NIH HHS [CA50995]; NIAAA NIH HHS [AA03624]; NIEHS NIH HHS [ES07126] NR 40 TC 35 Z9 35 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD APR PY 1999 VL 55 IS 4 BP 708 EP 715 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 182RB UT WOS:000079511000011 PM 10101029 ER PT J AU Murphy, WJ Nguyen, TNP Taylor, EB Collier, GE AF Murphy, WJ Nguyen, TNP Taylor, EB Collier, GE TI Mitochondrial DNA phylogeny of West African aplocheiloid killifishes (Cyprinodontiformes, Aplocheilidae) SO MOLECULAR PHYLOGENETICS AND EVOLUTION LA English DT Article ID DEVELOPMENTAL BIOLOGY; ANNUAL FISHES; EVOLUTION; TREES; SEQUENCES; EGGS AB African killifishes (Cyprinodontiformes, Aplocheilidae) historically associated with the genus Aphyosemion occur in two geographically distinct regions. One assemblage from far West Africa has been previously shown to be monophyletic and not closely related to the remaining eastern species of Aphyosemion (W. J. Murphy and G. E. Collier, 1997, Mol. Biol. Evol. 14, 790-799). This is supported by further analysis of mitochondrial DNA sequences from 19 species from 21 different localities, representing 19 of the putative 22 species of this western group, Phylogenetic analyses of these data corroborate the monophyly and sister-group relationship of two distinct groups of taxa: Callopanchax and Scriptaphyosemion. Many of the relationships within Scriptaphyosemion suggest that these taxa may have radiated within a short period of time relative to the rate of substitutions within these sequences. A third, and possibly paraphyletic group of species, Archiaphyosemion, is suggested to be the sister taxon to the first two groups. These three groups are elevated to generic rank and together represent the sister group to the genus Epiplatys. Biogeographic inference suggests that the ancestors of this group diversified westward through upland habitat and have only relatively recently entered the lowland habitats in which Scriptaphyosemion and Callopanchax have diversified, with the latter genus reacquiring a suite of traits collectively referred to as annualism. (C) 1999 Academic Press. C1 Univ Tulsa, Dept Biol Sci, Tulsa, OK 74104 USA. Univ British Columbia, Dept Zool, Vancouver, BC V6T 1Z4, Canada. RP Murphy, WJ (reprint author), NCI, Lab Genom Divers, FCRDC, Frederick, MD 21702 USA. NR 39 TC 15 Z9 18 U1 1 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1055-7903 J9 MOL PHYLOGENET EVOL JI Mol. Phylogenet. Evol. PD APR PY 1999 VL 11 IS 3 BP 343 EP 350 DI 10.1006/mpev.1998.0567 PG 8 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 188RK UT WOS:000079862100001 PM 10196076 ER PT J AU Murphy, WJ Collier, GE AF Murphy, WJ Collier, GE TI Phylogenetic relationships of African killifishes in the genera Aphyosemion and Fundulopanchax inferred from mitochondrial DNA sequences SO MOLECULAR PHYLOGENETICS AND EVOLUTION LA English DT Article ID EVOLUTION; TREES; FISH; BOOTSTRAP AB We have analyzed the phylogenetic relationships of 52 species representing all defined species groups (J. J. Scheel, 1990, Atlas of Killifishes of the Old World, 448 pp.) of the African aplocheiloid fish genera Aphyosemion and Fundulopanchax in order to examine their interrelationships and to reveal trends of karyotypic evolution. The data set comprised 785 total nucleotides from the mitochondrial 12S rRNA and cytochrome b genes. The molecular-based topologies analyzed by both maximum parsimony and neighbor-joining support the monophyly of most previously defined species groups within these two killifish genera. The genus Aphyosemion is monophyletic except for the nested position of Fundulopanchax kunzi (batesi group; subgenus Raddaella) within this clade, suggesting that this taxon was improperly assigned to Fundulopanchax. The remaining Fundulopanchax species sampled were supported as being monophyletic in most analyses. Relationships among the species groups in both genera were not as strongly supported, suggesting that further data will be required to resolve these relationships. Additional sampling from the 16S rRNA gene allowed further resolution of relationships within Fundulopanchax, more specifically identifying the nonannual scheeli group as the basal lineage of this otherwise annual genus. Chromosomal evolution within Aphyosemion has been episodic, with the evolution of a reduced n = 9-10 metacentric complement having occurred in multiple, independent lineages. Polarity of chromosomal reductions within the elegans species group appears to support previous hypotheses concerning mechanisms of karyotypic change within the genus Aphyosemion. (C) 1999 Academic Press. C1 Univ Tulsa, Dept Biol Sci, Tulsa, OK 74104 USA. RP Murphy, WJ (reprint author), NCI, Lab Genom Divers, FCRDC, Frederick, MD 21702 USA. RI Langerhans, R./A-7205-2009 NR 43 TC 26 Z9 29 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1055-7903 J9 MOL PHYLOGENET EVOL JI Mol. Phylogenet. Evol. PD APR PY 1999 VL 11 IS 3 BP 351 EP 360 DI 10.1006/mpev.1998.0566 PG 10 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 188RK UT WOS:000079862100002 PM 10196077 ER PT J AU Hsieh, JC Kodjabachian, L Rebbert, ML Rattner, A Smallwood, PM Samos, CH Nusse, R Dawid, IB Nathans, J AF Hsieh, JC Kodjabachian, L Rebbert, ML Rattner, A Smallwood, PM Samos, CH Nusse, R Dawid, IB Nathans, J TI A new secreted protein that binds to Wnt proteins and inhibits their activities SO NATURE LA English DT Article ID XENOPUS EMBRYOS AB The Wnt proteins constitute a large family of extracellular signalling molecules that are found throughout the animal kingdom and are important for a wide variety of normal and pathological developmental processes(1,2). Here we describe Wnt-inhibitory factor-1 (WIF-1), a secreted protein that binds to Wnt proteins and inhibits their activities. WIF-1 is present in fish, amphibia and mammals, and is expressed during Xenopus and zebrafish development in a Complex pattern that includes paraxial presomitic mesoderm, notochord, branchial arches and neural crest derivatives. We use Xenopus embryos to show that WIF-1 overexpression affects somitogenesis (the generation of trunk mesoderm segments), in agreement with its normal expression in paraxial mesoderm. In vitro, WIF-1 binds to Drosophila Wingless and Xenopus Wnt8 produced by Drosophila S2 cells. Together with earlier results obtained with the secreted Frizzled-related proteins(1.2), our results indicate that Wnt proteins interact with structurally diverse extracellular inhibitors, presumably to fine-tune the spatial and temporal patterns of Wnt activity. C1 Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA. NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. Stanford Univ, Med Ctr, Sch Med, Howard Hughes Med Inst,Dept Dev Biol, Stanford, CA 94305 USA. RP Nathans, J (reprint author), Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. NR 17 TC 421 Z9 448 U1 1 U2 20 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 1 PY 1999 VL 398 IS 6726 BP 431 EP 436 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 182PW UT WOS:000079508200054 PM 10201374 ER PT J AU Gilles, PN Wu, DJ Foster, CB Dillon, PJ Chanock, SJ AF Gilles, PN Wu, DJ Foster, CB Dillon, PJ Chanock, SJ TI Single nucleotide polymorphic discrimination by an electronic dot blot assay on semiconductor microchips SO NATURE BIOTECHNOLOGY LA English DT Article DE single nucleotide polymorphism; mannose binding protein; microarray; chip ID MANNOSE-BINDING PROTEIN; HUMAN GENOME; DNA; HYBRIDIZATION; INFECTION; GENE; MUTATIONS; ALLELE; CHIPS AB We have developed a rapid assay for single nucleotide polymorphism (SNP) detection that utilizes electronic circuitry on silicon microchips. The method was validated by the accurate discrimination of blinded DNA samples for the complex quadra-allelic SNP of mannose binding protein. The microchip directed the transport, concentration, and attachment of amplified patient DNA to selected electrodes (test sites) creating an array of DNA samples. Through control of the electric field, the microchip enabled accurate genetic identification of these samples using fluorescently labeled DNA reporter probes. The accuracy of this approach was established by internal controls of dual labeled reporters and by using mismatched sequences in addition to the wild-type and variant reporter sequences to validate the SNP-genotype. The ability to customize this assay for multiple genes has advantages over other existing approaches. C1 Nanogen Inc, San Diego, CA 92121 USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Wu, DJ (reprint author), Nanogen Inc, 10398 Pacific Ctr Ct, San Diego, CA 92121 USA. EM dwu@nanogen.com NR 37 TC 182 Z9 196 U1 2 U2 8 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD APR PY 1999 VL 17 IS 4 BP 365 EP 370 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 183VH UT WOS:000079574400025 PM 10207885 ER PT J AU Griffith, AJ Friedman, TB AF Griffith, AJ Friedman, TB TI Making sense out of sound SO NATURE GENETICS LA English DT Editorial Material C1 Natl Inst Deafness Other Commun Disorders, Genet Mol Lab, NIH, Rockville, MD 20850 USA. RP Griffith, AJ (reprint author), Natl Inst Deafness Other Commun Disorders, Genet Mol Lab, NIH, 5 Res Court, Rockville, MD 20850 USA. NR 11 TC 6 Z9 6 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 1999 VL 21 IS 4 BP 347 EP 349 DI 10.1038/7668 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 181KC UT WOS:000079439700005 PM 10192378 ER PT J AU Barlow, C Eckhaus, MA Schaffer, AA Wynshaw-Boris, A AF Barlow, C Eckhaus, MA Schaffer, AA Wynshaw-Boris, A TI Atm haploinsufficiency results in increased sensitivity to sublethal doses of ionizing radiation in mice SO NATURE GENETICS LA English DT Letter ID ATAXIA-TELANGIECTASIA; BREAST-CANCER; DEFICIENT MICE; MUTATIONS; DEFECTS C1 NIH, Vet Resources Program, Off Res Serv, Off Director, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Inherited Dis Res Branch, NIH, Baltimore, MD 21224 USA. Natl Human Genome Res Inst, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Wynshaw-Boris, A (reprint author), Univ Calif San Diego, Sch Med, 9500 Gilman Dr, La Jolla, CA 92093 USA. RI Schaffer, Alejandro/F-2902-2012 NR 15 TC 87 Z9 88 U1 0 U2 3 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 1999 VL 21 IS 4 BP 359 EP 360 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 181KC UT WOS:000079439700013 PM 10192382 ER PT J AU Wilcox, AJ Taylor, JA Sharp, RR London, SJ AF Wilcox, AJ Taylor, JA Sharp, RR London, SJ TI Genetic determinism and the overprotection of human subjects SO NATURE GENETICS LA English DT Letter C1 NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Off Sci Director, NIH, Res Triangle Pk, NC 27709 USA. RP Wilcox, AJ (reprint author), NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. OI Wilcox, Allen/0000-0002-3376-1311; taylor, jack/0000-0001-5303-6398; London, Stephanie/0000-0003-4911-5290 NR 8 TC 13 Z9 13 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 1999 VL 21 IS 4 BP 362 EP 362 DI 10.1038/7692 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 181KC UT WOS:000079439700015 PM 10192384 ER PT J AU Jouanguy, E Lamhamedi-Cherradi, S Lammas, D Dorman, SE Fondaneche, MC Dupuis, S Doffinger, R Altare, F Girdlestone, J Emile, JF Ducoulombier, H Edgar, D Clarke, J Oxelius, VA Brai, M Novelli, V Heyne, K Fischer, A Holland, SM Kumararatne, DS Schreiber, RD Casanova, JL AF Jouanguy, E Lamhamedi-Cherradi, S Lammas, D Dorman, SE Fondaneche, MC Dupuis, S Doffinger, R Altare, F Girdlestone, J Emile, JF Ducoulombier, H Edgar, D Clarke, J Oxelius, VA Brai, M Novelli, V Heyne, K Fischer, A Holland, SM Kumararatne, DS Schreiber, RD Casanova, JL TI A human IFNGR1 small deletion hotspot associated with dominant susceptibility to mycobacterial infection SO NATURE GENETICS LA English DT Article ID INTERFERON-GAMMA-RECEPTOR; CALMETTE-GUERIN INFECTION; GENE; IDENTIFICATION; RESISTANCE; SEQUENCE; BCG; DEFICIENCY; CHILDREN; BINDING AB The immunogenetic basis of severe infections caused by bacille Calmette-Guerin vaccine and environmental mycobacteria in humans remains largely unknown. We describe 18 patients from several generations of 12 unrelated families who were heterozygous for 1 to 5 overlapping IFNCR1 frameshift small deletions and a wild-type IFNGR1 allele. There were 12 independent mutation events at a single mutation site, defining a small deletion hotspot. Neighbouring sequence analysis favours a small deletion model of slipped mispairing events during replication. The mutant alleles encode cell-surface IFN gamma receptors that lack the intra-cytoplasmic domain, which, through a combination of impaired recycling, abrogated signalling and normal binding to IFN gamma exert a dominant-negative effect. We thus report a hotspot for human IFNGR1 small deletions that confer dominant susceptibility to infections caused by poorly virulent mycobacteria. C1 Hop Necker Enfants Malad, INSERM, U429, F-75015 Paris, France. Univ Birmingham, Sch Med, MRC, Ctr Immune Regulat, Birmingham B15 2TT, W Midlands, England. NIH, Host Def Lab, Bethesda, MD 20892 USA. Univ Birmingham, Sch Med, Dept Anat, Birmingham B15 2TT, W Midlands, England. Hop Paul Brousse, Serv Anat Pathol, F-94804 Villejuif, France. Hop St Antoine, Serv Pediat, F-59019 Lille, France. Royal Victoria Hosp, Reg Immunol Serv, Belfast BT12 6BN, Antrim, North Ireland. Childrens Hosp, Resp & Cyst Fibrosis Unit, Birmingham B4 6NH, W Midlands, England. Univ Lund, Dept Pediat, S-22185 Lund, Sweden. Ist Patol Gen, I-90134 Palermo, Italy. Great Ormond St Hosp Children, Infect Dis Unit, London WC1N 3JH, England. Hop Necker Enfants Malad, Unite Immunol & Hematol Pediat, F-75015 Paris, France. Birmingham Heartlands Hosp, Reg Dept Immunol, Birmingham, W Midlands, England. Washington Univ, Dept Pathol, St Louis, MO 63110 USA. RP Casanova, JL (reprint author), Hop Necker Enfants Malad, INSERM, U429, F-75015 Paris, France. EM casanova@ceylan.necker.fr RI Schreiber, Robert/A-1276-2013 OI Schreiber, Robert/0000-0001-6311-0432 NR 50 TC 303 Z9 315 U1 2 U2 12 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 1999 VL 21 IS 4 BP 370 EP 378 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 181KC UT WOS:000079439700017 PM 10192386 ER PT J AU Eaton, WA Henry, ER Hofrichter, J Mozzarelli, A AF Eaton, WA Henry, ER Hofrichter, J Mozzarelli, A TI Is cooperative oxygen binding by hemoglobin really understood? SO NATURE STRUCTURAL BIOLOGY LA English DT Review ID ALLOSTERIC MODEL; CONFORMATIONAL-CHANGES; ADULT HEMOGLOBIN; LIGAND-BINDING; FREE-ENERGIES; PROTEINS; HAEMOGLOBIN; MYOGLOBIN; KINETICS; CRYSTALS AB The enormous success of structural biology challenges the physical scientist. Can biophysical studies provide a truly deeper understanding of how a protein works than can be obtained from static structures and qualitative analysis of biochemical data? We address this question in a case study by presenting the key concepts and experimental results that have led to our current understanding of cooperative oxygen binding by hemoglobin, the paradigm of structure function relations in multisubunit proteins. We conclude that the underlying simplicity of the two-state allosteric mechanism could not have been demonstrated without novel physical experiments and a rigorous quantitative analysis. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Univ Parma, Inst Biochem Sci, I-43100 Parma, Italy. Univ Parma, Natl Inst Phys Matter, I-43100 Parma, Italy. RP Eaton, WA (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. EM eaton@helix.nih.gov RI Henry, Eric/J-3414-2013; Mozzarelli, Andrea/C-3615-2014 OI Henry, Eric/0000-0002-5648-8696; Mozzarelli, Andrea/0000-0003-3762-0062 NR 45 TC 184 Z9 184 U1 10 U2 42 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD APR PY 1999 VL 6 IS 4 BP 351 EP 358 DI 10.1038/7586 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 182MT UT WOS:000079503300018 PM 10201404 ER PT J AU Gambello, MJ Hirotsune, S Wynshaw-Boris, A AF Gambello, MJ Hirotsune, S Wynshaw-Boris, A TI Murine modelling of classical lissencephaly SO NEUROGENETICS LA English DT Review ID PLATELET-ACTIVATING-FACTOR; MILLER-DIEKER SYNDROME; LONG-TERM POTENTIATION; NEURONAL MIGRATION; CORTICAL DEVELOPMENT; ZELLWEGER-SYNDROME; EMBRYONIC LETHALITY; CHROMOSOME 17P13.3; GENE ENCODES; PROTEIN AB Classical lissencephaly is a severe human neuronal migration disorder characterized by a smooth cerebral surface and a paucity of gyri, Isolated lissencephaly sequence (ILS, OMIM 601545) and Miller-Dieker syndrome (MDS, OMIM 247200) are human malformation syndromes characterized by classical lissencephaly, MDS and some cases of ILS are caused by haploinsufficiency at chromosome 17p13.3, Recent evidence suggests that mutations or deletions of the LIS1 gene, within band 17p13.3, are responsible for classical lissencephaly, LIS1 codes for a subunit of platelet-activating factor acetylhydrolase isoform Ib (PAFAH1B1 or LIS1), To investigate the pathophysiological mechanisms responsible for these two developmental defects, we have undertaken strategies to model these neuronal migration disorders in the mouse, We present a brief review of MDS and ILS, several mouse mutants with cortical neuronal migration defects, and our strategies to model ILS and MDS in the mouse. C1 Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA. Natl Human Genome Res Inst, Genet Dis Res Lab, Bethesda, MD 20892 USA. Inst Anim Genet, Fukushima, Japan. RP Gambello, MJ (reprint author), Univ Calif San Diego, Dept Pediat, 9600 Gilman Dr, La Jolla, CA 92093 USA. NR 71 TC 6 Z9 6 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1364-6745 J9 NEUROGENETICS JI Neurogenetics PD APR PY 1999 VL 2 IS 2 BP 77 EP 86 DI 10.1007/s100480050056 PG 10 WC Genetics & Heredity; Clinical Neurology SC Genetics & Heredity; Neurosciences & Neurology GA 200GD UT WOS:000080530500001 PM 10369882 ER PT J AU Jacoby, LB MacCollin, M Parry, DM Kluwe, L Lynch, J Jones, D Gusella, JF AF Jacoby, LB MacCollin, M Parry, DM Kluwe, L Lynch, J Jones, D Gusella, JF TI Allelic expression of the NF2 gene in neurofibromatosis 2 and schwannomatosis SO NEUROGENETICS LA English DT Article DE neurofibromatosis 2; schwannomatosis; allelic expression; polymorphism ID GERM-LINE MUTATIONS; TUMOR-SUPPRESSOR GENE; SPORADIC MENINGIOMAS; TYPE-2 GENE; MERLIN; EPENDYMOMAS; PROTEIN; DISEASE; SEVERITY; FAMILY AB Neurofibromatosis type 2 (NF2) is a genetic disorder characterized by formation of multiple schwannomas and meningiomas due to inactivating mutations in the NF2 tumor suppressor gene on chromosome 22, We describe a polymorphism in the 3' untranslated region of the NF2 gene that is informative in about one-third of individuals, This polymorphism permitted an assessment of the relative expression of NF2 transcripts in lymphoblastoid cell RNA from 22 unrelated NF2 patients heterozygous for a germline NF2 mutation, along with 6 schwannomatosis patients, and 14 unaffected controls, Unequal allelic expression (1,8- to 20-fold) was detected in 15 of the NF2 cases, but in none of the schwannomatosis or control individuals, Underexpression of the NF2 mutant allele was documented for all 6 nonsense or frameshift mutations, 3 of 6 splice mutations, and 1 of 4 missense mutations, which, unexpectedly, was shown to alter the NF2 transcript and create a premature stop codon, In contrast, equal expression or slight overexpression of NF2 mutant alleles was observed for 2 in-frame deletions, 2 splice alterations, and 3 missense mutations, In the remaining 5 cases, the allele representing the mutant transcript was not known. Thus, truncating NF2 mutations, which are the most frequent alterations in NF2 patients and NF2-associated tumors, were associated with underexpression of the mutant allele, whereas the less common inframe alterations usually showed normal or slight overexpression of the mutant transcript. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Serv Neurol, Charlestown, MA 02129 USA. NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. Univ Hamburg, Hosp Eppendorf, D-20246 Hamburg, Germany. RP Jacoby, LB (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, 149 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA51410]; NINDS NIH HHS [NS24279] NR 38 TC 14 Z9 14 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1364-6745 J9 NEUROGENETICS JI Neurogenetics PD APR PY 1999 VL 2 IS 2 BP 101 EP 108 DI 10.1007/s100480050060 PG 8 WC Genetics & Heredity; Clinical Neurology SC Genetics & Heredity; Neurosciences & Neurology GA 200GD UT WOS:000080530500005 PM 10369886 ER PT J AU Dagli, MS Ingeholm, JE Haxby, JV AF Dagli, MS Ingeholm, JE Haxby, JV TI Localization of cardiac-induced signal change in fMRI SO NEUROIMAGE LA English DT Article ID CEREBROSPINAL-FLUID; BRAIN MOTION; SENSORY STIMULATION; CIRCULATION; FLOW AB Signal detection in the analysis of blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) may be greatly hindered by cardiac pulsatility artifacts. Vessel pulsation, cerebrospinal fluid movement, and tissue deformation are all associated with the cardiac cycle and all can produce fMRI signal variance. Most cognitive fMRI studies do not utilize a method of cardiac-related noise reduction, in part because of the lack of information on the regional significance and magnitude of cardiac-related signal variance in the brain. In this paper we present a topographical description of the regions showing significant contributions of cardiac-related signal variance. The results are highly consistent across subjects and suggest that reduced sensitivity due to cardiac-induced noise in the BOLD signal is systematically greater in specific areas, typically near major blood vessels. Significant effects of cardiac-related variability were found on average in 27.5 +/- 8.0% of voxels. Strong influences were found along the vertebrobasilar arterial system near the medial areas of the brain, along the middle cerebral artery near the anterior temporal lobes and in the insula, and along the anterior cerebral artery in the anterior interhemispheric fissure in the medial frontal lobes. Significant effects were also observed in the sigmoid transverse and superior sagittal sinus regions. These results identify regions in which fMRI mill have reduced sensitivity due to increased signal variation produced by cardiac pulsatility. C1 NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. RP Dagli, MS (reprint author), NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. NR 20 TC 186 Z9 186 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD APR PY 1999 VL 9 IS 4 BP 407 EP 415 DI 10.1006/nimg.1998.0424 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 188TB UT WOS:000079863600005 PM 10191169 ER PT J AU Yang, YH Wen, H Mattay, VS Balaban, RS Frank, JA Duyn, JP AF Yang, YH Wen, H Mattay, VS Balaban, RS Frank, JA Duyn, JP TI Comparison of 3D BOLD functional MRI with spiral acquisition at 1.5 and 4.0 T SO NEUROIMAGE LA English DT Article DE functional MRI; spiral scan; high field ID HUMAN BRAIN; VISUAL-CORTEX; CONTRAST; FIELD; FMRI AB In order to investigate the merit of high field strength for BOLD-contrast-based functional magnetic resonance imaging (fMRI) studies, multishot gradient echo fMRI experiments during motor cortex activation were performed on 1.5- and 4.0-T scanners with equivalent hardware, on the same volunteers, in these studies, artifactual vascular enhancement related to inflow effects was minimized, and large brain areas were covered by using a 3D scan technique. Temporal signal stability was optimized by using spiral readout gradients. The sensitivity for detection of activated regions was assessed by measuring the number of "activated voxels" and their average t score in predefined regions of interest. When comparing fMRI experiments with the same total scan time, performed on six subjects, and with acquisition parameters optimized for each field strength separately the 4.0-T scanner proved to give superior results, with a 70% greater number of activated voxels and a 20% higher average t score for the activated voxels. C1 NIH, OIR, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Yang, YH (reprint author), NIH, OIR, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. RI Duyn, Jozef/F-2483-2010; Balaban, Robert/A-7459-2009; Wen, Han/G-3081-2010 OI Balaban, Robert/0000-0003-4086-0948; Wen, Han/0000-0001-6844-2997 NR 27 TC 37 Z9 37 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD APR PY 1999 VL 9 IS 4 BP 446 EP 451 DI 10.1006/nimg.1998.0422 PG 6 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 188TB UT WOS:000079863600009 PM 10191173 ER PT J AU Feller, MB AF Feller, MB TI Spontaneous correlated activity in developing neural circuits SO NEURON LA English DT Review ID SPONTANEOUS RHYTHMIC ACTIVITY; NEONATAL HIPPOCAMPUS; SPINAL NETWORKS; TRANSMISSION; OSCILLATIONS; TRANSIENTS; RETINA C1 NIH, Natl Inst Neurol Disorders & Stroke, Synapse Format & Funct Unit, Bethesda, MD 20892 USA. RP Feller, MB (reprint author), NIH, Natl Inst Neurol Disorders & Stroke, Synapse Format & Funct Unit, Bldg 10, Bethesda, MD 20892 USA. NR 19 TC 234 Z9 236 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD APR PY 1999 VL 22 IS 4 BP 653 EP 656 DI 10.1016/S0896-6273(00)80724-2 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 190QR UT WOS:000079976200008 PM 10230785 ER PT J AU Kastner, S Pinsk, MA De Weerd, P Desimone, R Ungerleider, LG AF Kastner, S Pinsk, MA De Weerd, P Desimone, R Ungerleider, LG TI Increased activity in human visual cortex during directed attention in the absence of visual stimulation SO NEURON LA English DT Article ID LATERAL INTRAPARIETAL AREA; INFERIOR TEMPORAL CORTEX; FRONTAL EYE FIELDS; POSITRON EMISSION TOMOGRAPHY; POSTERIOR PARIETAL CORTEX; MONKEY CEREBRAL-CORTEX; SELECTIVE ATTENTION; NEURAL MECHANISMS; BEHAVIORAL ENHANCEMENT; VISUOSPATIAL ATTENTION AB When subjects direct attention to a particular location in a visual scene, responses in the visual cortex to stimuli presented at that location are enhanced, and the suppressive influences of nearby distracters are reduced. What is the top-down signal that modulates the response to an attended versus an unattended stimulus? Here, we demonstrate increased activity related to attention in the absence of visual stimulation in extrastriate cortex when subjects covertly directed attention to a peripheral location expecting the onset of visual stimuli. Frontal and parietal areas showed a stronger signal increase during this expectation than did visual areas. The increased activity in visual cortex in the absence of visual stimulation may reflect a top-down bias of neural signals in favor of the attended location, which derives from a fronto-parietal network. C1 NIH, NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. NIH, NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Kastner, S (reprint author), NIH, NIMH, Lab Brain & Cognit, Bldg 10, Bethesda, MD 20892 USA. NR 54 TC 930 Z9 942 U1 10 U2 47 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD APR PY 1999 VL 22 IS 4 BP 751 EP 761 DI 10.1016/S0896-6273(00)80734-5 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 190QR UT WOS:000079976200018 PM 10230795 ER PT J AU Balijepalli, S Boyd, MR Ravindranath, V AF Balijepalli, S Boyd, MR Ravindranath, V TI Inhibition of mitochondrial complex I by haloperidol: the role of thiol oxidation SO NEUROPHARMACOLOGY LA English DT Article DE haloperidol; complex I; brain; glutathione; protein thiol; neuroleptic ID NEUROTOXIC PYRIDINIUM METABOLITE; ELECTRON-TRANSPORT CHAIN; PARKINSONS-DISEASE; ANTIPSYCHOTIC-DRUGS; BRAIN-SLICES; DOPAMINE; STRESS; GLUTATHIONE; CLOZAPINE; BINDING AB We have examined the: effects of a variety of classical and atypical neuroleptic drugs on mitochondrial NADH ubiquinone oxido-reductase (complex I) activity. Sagittal slices of mouse brain incubated in vitro with haloperidol (10 nM) showed time- and concentration-dependent inhibition of complex I. Similar concentrations of the pyridinium metabolite of haloperidol (HPP+) failed to inhibit complex I activity in this model; indeed, comparable inhibition was obtained only at a 10 000-fold higher concentration of HPP+ (100 mu M). Treatment of brain slices with haloperidol resulted in a loss of glutathione (GSH), while pretreatment of slices with GSH and alpha-lipoic acid abolished haloperidol-induced loss of complex I activity. Incubation of mitochondria from haloperidol treated brain slices with the thiol reductant, dithiothreitol, completely regenerated complex I activity demonstrating thiol oxidation as a feasible mechanism of inhibition. In a comparison of different neuroleptic drugs, haloperidol was the most potent inhibitor of complex I, followed by chlorpromazine, fluphenazine and risperidone while the atypical neuroleptic, clozapine (100 mu M) did not inhibit complex I activity in mouse brain slices. The present studies support the view that classical neuroleptics such as haloperidol inhibit mitochondrial complex I through oxidative modification of the enzyme complex. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Natl Inst Mental Hlth & Neurosci, Dept Neurochem, Bangalore 560029, Karnataka, India. NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program, FCRDC, Frederick, MD 21702 USA. RP Ravindranath, V (reprint author), Natl Inst Mental Hlth & Neurosci, Dept Neurochem, Hosur Rd, Bangalore 560029, Karnataka, India. NR 36 TC 52 Z9 52 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD APR PY 1999 VL 38 IS 4 BP 567 EP 577 DI 10.1016/S0028-3908(98)00215-9 PG 11 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 182DP UT WOS:000079483500011 PM 10221760 ER PT J AU Breier, A Su, TP Malhotra, AK Elman, I Adler, CM Weisenfeld, NI Pickar, D AF Breier, A Su, TP Malhotra, AK Elman, I Adler, CM Weisenfeld, NI Pickar, D TI Effects of atypical antipsychotic drug treatment on amphetamine-induced striatal dopamine release in patients with psychotic disorders SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE clozapine; risperidone; positron emission tomography; raclopride; schizophrenia ID D2-DOPAMINE RECEPTOR OCCUPANCY; POSITRON EMISSION TOMOGRAPHY; SCHIZOPHRENIC-PATIENTS; C-11 RACLOPRIDE; FOS EXPRESSION; C-FOS; CLOZAPINE; NEURONS; RISPERIDONE; HALOPERIDOL AB Clozapine, risperidone, and other new "atypical" antipsychotic agents are distinguished from traditional neuroleptic drugs by having clinical efficacy with either no or low levels of extrapyramidal symptoms (EPS). Preclinical models have focused on striatal dopamine systems to account for their atypical profile. In this study, we examined the effects of clozapine and risperidone on amphetamine-induced striatal dopamine release in patients with psychotic disorders. A novel C-11-raclopride/PET paradigm was used to derive estimates of amphetamine-induced changes in striatal synaptic dopamine concentrations and patients were scanned while antipsychotic drug-free and during chronic treatment with either clozapine or risperidone. We found that amphetamine produced significant reductions in striatal C-11-raclopride binding during the drug-free and antipsychotic drug treatment phases of the study which reflects enhanced dopamine release in both conditions. There were no significant differences in % C-11-raclopride changes between the two conditions indicating that these atypical agents do not effect amphetamine-related striatal dopamine release. The implications for these data for antipsychotic drug action are discussed. C1 NIMH, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. NIMH, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Breier, A (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Drop Code 0538, Indianapolis, IN 46285 USA. NR 43 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD APR PY 1999 VL 20 IS 4 BP 340 EP 345 DI 10.1016/S0893-133X(98)00126-2 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 174TA UT WOS:000079050000003 PM 10088134 ER EF