FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Fisher, ER AF Fisher, ER TI Pathological findings from National Surgical Adjuvant Breast Project (NSABP) eight-year update of protocol B-17 - Intraductal carcinoma - Reply SO CANCER LA English DT Letter C1 Allegheny Univ, Allegheny Gen Hosp, Bowel Project, Pittsburgh, PA USA. Allegheny Univ, Allegheny Gen Hosp, Bowel Project, Pittsburgh, PA 15212 USA. RP Fisher, ER (reprint author), Allegheny Univ, Allegheny Gen Hosp, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15201 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 0008-543X J9 CANCER JI Cancer PD APR 15 PY 2000 VL 88 IS 8 BP 1977 EP 1977 PG 1 WC Oncology SC Oncology GA 303RM UT WOS:000086437800030 ER PT J AU Chen, TS Wang, LH Farrar, WL AF Chen, TS Wang, LH Farrar, WL TI Interleukin 6 activates androgen receptor-mediated gene expression through a signal transducer and activator of transcription 3-dependent pathway in LNCaP prostate cancer cells SO CANCER RESEARCH LA English DT Article ID CARCINOMA-CELLS; TYROSINE KINASE; GROWTH-FACTOR; PROTEIN; STAT3; PROGRESSION; LINES AB Interleukin 6 (IL-6) is a cytokine that regulates not only immune and inflammatory responses but also the growth of some tumors, including prostate carcinomas. IL-6 signals through Janus kinase, signal transducer and activator of transcription 3 (STAT3), and mitogen-activated protein kinase and is also able to induce androgen receptor (AR)-mediated gene activation in prostate cancer, which is an important process in prostate cancer androgen-independent progression. We now show that IL-6-induced AR-mediated gene activation requires the activation of STAT3 by IL-6 in LNCaP prostate cancer cells. In particular, STAT3 associates with AR in an androgen-independent but IL-6-dependent manner, Inhibition of STAT3 rather than mitogen-activated protein kinase results in inhibition of AR-mediated gene activation in response to IL-6, These findings not only identify STAT3 as an important signaling molecule required for IL-6-signaling to induce AR-mediated gene activation in prostate carcinoma cells but also reveal the importance of activated STAT3 in human tumor development and progression. C1 NCI, Intramural Res Support Program, Sci Applicat Int Corp Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Cytokine Mol Mechanisms Sect, Mol Immunoregulat Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Chen, TS (reprint author), NCI, Intramural Res Support Program, Sci Applicat Int Corp Frederick, Frederick Canc Res & Dev Ctr, POB B,Bldg 560, Frederick, MD 21702 USA. RI Chen, Taosheng/I-6351-2013 FU NCI NIH HHS [N01-CO-56000] NR 30 TC 173 Z9 176 U1 1 U2 6 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 15 PY 2000 VL 60 IS 8 BP 2132 EP 2135 PG 4 WC Oncology SC Oncology GA 308EA UT WOS:000086696500015 PM 10786674 ER PT J AU Boffa, LC Scarfi, S Mariani, MR Damonte, G Allfrey, VG Benatti, U Morris, PL AF Boffa, LC Scarfi, S Mariani, MR Damonte, G Allfrey, VG Benatti, U Morris, PL TI Dihydrotestosterone as a selective cellular/nuclear localization vector for anti-gene peptide nucleic acid in prostatic carcinoma cells SO CANCER RESEARCH LA English DT Article ID ANDROGEN RECEPTOR; PNA; DNA; INVASION; MYC; OLIGONUCLEOTIDE; TRANSCRIPTION; EXPRESSION; POLYAMIDE; TRANSPORT AB Peptide nucleic acids (PNAs) are synthetic structural analogues of DNA and RNA that, if allowed to enter the cell, bind to the complementary polynucleotide sequence and inhibit DNA transcription and mRNA translation, Although PNAs have a very limited ability in penetrating nuclei of living cells, there are indications that covalent linkage of the PNA to appropriate vectors, e.g., a nuclear localization signal, permits access to the genome. Here we test the ability of dihydrotestosterone (T) covalently linked to PNA to act as a vector for targeting c-myc DNA to prostatic cancer cell nuclei. LNCaP cells, which express the androgen receptor gene, and DU145 cells, in which me androgen receptor gene is silent, offer a model to test this biologically active hormone as a cell-specific vector, T vector was covalently linked to the NH2-terminal position of a PNA complementary to a unique sequence of c-myc oncogene (PNAmyc-T), To localize PNAmyc-T and vector-free PNA within the cells, a rhodamine (R) group was attached at the COOH-terminal position (PNAmyc-R, PNAmyc-TR); cellular uptake was monitored by confocal fluorescence microscopy, PNAmyc-R was detected only in the cytoplasm of both prostatic cell lines, whereas PNAmyc-TR was localized in nuclei as well as in cytoplasm of LNCaP cells. In contrast, PNAmyc-TR uptake in DU145 cells was minimal and exclusively cytoplasmic, In LNCaP cells, MYC protein remained unchanged by exposure to vector-free PNAmyc, whereas a significant and persistent decrease was induced by PNAmyc-T, In DU145 cells, MYC expression was unaltered by PNAmyc with or without the T vector. Our data show that the T vector facilitates cell-selective nuclear localization of PNA and its consequent inhibition of c-myc expression. These findings suggest a strategy for targeting of cell-specific anti-gene therapy in prostatic carcinoma. C1 Natl Canc Inst, Dept Expt Oncol, IST, I-16132 Genoa, Italy. Univ Genoa, Dept Expt Med, Biochem Sect, I-16132 Genoa, Italy. Rockefeller Univ, New York, NY 10021 USA. Populat Council, New York, NY 10021 USA. RP Boffa, LC (reprint author), Natl Canc Inst, Dept Expt Oncol, IST, L R Benzi 10, I-16132 Genoa, Italy. EM boffa@hp380.ist.unige.it OI Scarfi, Sonia/0000-0002-7079-6919 FU NICHD NIH HHS [HD-13541, HD-29428] NR 29 TC 76 Z9 86 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2000 VL 60 IS 8 BP 2258 EP 2262 PG 5 WC Oncology SC Oncology GA 308EA UT WOS:000086696500034 PM 10786693 ER PT J AU Xie, XY Filie, AC Jasper, GA Fukushima, PI Stetler-Stevenson, M AF Xie, XY Filie, AC Jasper, GA Fukushima, PI Stetler-Stevenson, M TI Diagnosis of unexpected acute myeloid leukemia and chronic lymphocytic leukemia: A case report demonstrating the perils of restricted panels in flow cytometric immunophenotyping SO CYTOMETRY LA English DT Article DE immunophenotypic panels; acute myeloid leukemia; chronic lymphocytic leukemia; flow cytometry ID NEOPLASIA AB We report on the flow cytometric identification of concomitant acute myeloid leukemia and chronic lymphocytic leukemia in cytology specimens submitted with minimal clinical information. A 64-year-old man presented with fever and progressive dyspnea on exertion. Chest X-ray and computed tomography scan showed a left upper lobe pulmonary mass. Pulmonary capillary pullback specimens were collected to determine infectious verses neoplastic etiology. The pulmonary capillary pullback specimens showed atypical mononuclear cells with enlarged, slightly irregular nuclei; visible nucleoli; and basophilic cytoplasm. Flow cytometric analysis of the specimen for lymphoma was requested. Flow cytometric immunophenotypic studies showed that 78% of the cells were CD34 positive, CD45 dim positive and CD11c positive, consistent with acute myeloid leukemia. About 0.75% of the cells expressed CD5 as well as dim CD20 and were monoclonal for kappa light chains: consistent with chronic lymphocytic leukemia/small lymphocytic lymphoma. At this time the clinician communicated a history of myelodysplastic syndrome of refractory anemia subtype. Peripheral blood was obtained for further immunophenotyping and the patient was immediately treated for his acute myeloid leukemia. This case demonstrates that a diagnostic antibody panel should allow evaluation of all cell types as per the U.S./Canadian consensus recommendations on the immunophenotypic analysis of hematologic neoplasia by flow cytometry (Stewart et al.: Cytometry 30:231-235, 1997). Cytometry (Comm. Clin. Cytometry) 42:114-117, 2000. Published 2000 Wiley-Liss, Inc. C1 NCI, Flow Cytometry Unit, Pathol Lab, Div Clin Sci,NIH, Bethesda, MD 20892 USA. NCI, Sect Cytopathol, Pathol Lab, Div Clin Sci,NIH, Bethesda, MD 20892 USA. RP Stetler-Stevenson, M (reprint author), NCI, Flow Cytometry Unit, Pathol Lab, Div Clin Sci,NIH, Bethesda, MD 20892 USA. NR 7 TC 3 Z9 4 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 0196-4763 J9 CYTOMETRY JI Cytometry PD APR 15 PY 2000 VL 42 IS 2 BP 114 EP 117 DI 10.1002/(SICI)1097-0320(20000415)42:2<114::AID-CYTO5>3.0.CO;2-L PG 4 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 312DV UT WOS:000086928700005 PM 10797449 ER PT J AU Robinson, GW Hennighausen, L Johnson, PF AF Robinson, GW Hennighausen, L Johnson, PF TI Side-branching in the mammary gland: the progesterone-Wnt connection SO GENES & DEVELOPMENT LA English DT Editorial Material ID EPITHELIAL-CELLS; DUCTAL MORPHOGENESIS; GENE-EXPRESSION; TRANSGENIC MICE; FEMALE MICE; C/EBP-BETA; CYCLIN D1; MOUSE; RECEPTOR; TRANSFORMATION C1 NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Regulat Cell Growth Lab, Eukaryot Transcript Regulat Sect, Frederick, MD 21702 USA. RP Robinson, GW (reprint author), NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. EM gertraur@bdg10.niddk.nih.gov RI Johnson, Peter/A-1940-2012; Robinson, Gertraud/I-2136-2012 OI Johnson, Peter/0000-0002-4145-4725; NR 45 TC 65 Z9 67 U1 2 U2 5 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD APR 15 PY 2000 VL 14 IS 8 BP 889 EP 894 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 309YJ UT WOS:000086796900001 PM 10783160 ER PT J AU Cooper, MP Machwe, A Orren, DK Borsh, RM Ramsden, D Bohr, VA AF Cooper, MP Machwe, A Orren, DK Borsh, RM Ramsden, D Bohr, VA TI Ku complex interacts with and stimulates the Werner protein SO GENES & DEVELOPMENT LA English DT Article DE Werner syndrome; Ku proteins; WRNp; exonuclease activity ID DNA HELICASE; BINDING PROPERTIES; SYNDROME GENE; REPLICATION; REPAIR; WRN; EXONUCLEASE; CELLS; SENESCENCE; MUTATIONS AB Werner syndrome (WS) is the hallmark premature aging disorder in which affected humans appear older than their chronological age. The protein WRNp, defective in WS, has helicase function, DNA-dependent ATPase, and exonuclease activity. Although WRNp functions in nucleic acid metabolism, there is little or no information about the pathways or protein interactions in which it participates. Here we identify Ku70 and Ku86 as proteins that interact with WRNp. Although Ku proteins had no effect on ATPase or helicase activity, they strongly stimulated specific exonuclease activity. These results suggest that WRNp and the Ku complex participate in a common DNA metabolic pathway. C1 NIA, Mol Genet Lab, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21218 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. RP Bohr, VA (reprint author), NIA, Mol Genet Lab, NIH, Baltimore, MD 21224 USA. NR 30 TC 248 Z9 252 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD APR 15 PY 2000 VL 14 IS 8 BP 907 EP 912 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 309YJ UT WOS:000086796900004 PM 10783163 ER PT J AU Tsutsui, T Tamura, YH Suzuki, A Hirose, Y Kobayashi, M Nishimura, H Metzler, M Barrett, JC AF Tsutsui, T Tamura, YH Suzuki, A Hirose, Y Kobayashi, M Nishimura, H Metzler, M Barrett, JC TI Mammalian cell transformation and aneuploidy induced by five bisphenols SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID HAMSTER EMBRYO CELLS; DNA ADDUCT FORMATION; NEOPLASTIC TRANSFORMATION; CHROMOSOMAL-ABERRATIONS; CHEMICALS; DIETHYLSTILBESTROL; TESTS AB Bisphenol-A (BP-A), a monomer of plastics used in numerous consumer products and a xenoestrogen, induces cellular transformation and aneuploidy in Syrian hamster embryo (SHE) cells. In this study, the abilities of 4 other bisphenols to Induce cellular transformation and genetic effects in SHE cells were examined and compared to BP-A, Cellular growth was inhibited by all bisphenols in a concentration-related manner. The growth inhibitory effect of the bisphenols ranked: BP-5 > BP-4 > BP-3 > BP-2 or BP-A. Morphological transformation of SHE cells was induced by BE-A, BP-3, BP-4 and BP-5, and the induced-transformation frequencies were highest with BP-4, None of the bisphenols induced gene mutations at the Na+/K+ ATPase locus or the hprt locus, or chromosomal aberrations in SHE cells. By contrast, aneuploidy induction in the near-diploid range was exhibited by BP-A, BP-3, BP-4 or BP-5, corresponding to the transforming activity of each compound. The results indicate that BP-A, BP-3, BP-4 and BP-5 exhibit transforming activity in SHE cells, while BP-2 does not, and that aneuploidy induction may be a causal mechanism of the transforming activity. Int. J. Cancer 86:151-154, 2000. Published 2000 Wiley-Liss, Inc. C1 NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. Nippon Dent Univ, Dept Pharmacol, Tokyo, Japan. Univ Karlsruhe, Inst Food Chem, Karlsruhe, Germany. RP Barrett, JC (reprint author), NIEHS, Mol Carcinogenesis Lab, MD C2-15, Res Triangle Pk, NC 27709 USA. NR 21 TC 42 Z9 50 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD APR 15 PY 2000 VL 86 IS 2 BP 151 EP 154 DI 10.1002/(SICI)1097-0215(20000415)86:2<151::AID-IJC1>3.0.CO;2-0 PG 4 WC Oncology SC Oncology GA 299VT UT WOS:000086219100001 PM 10738239 ER PT J AU Kalechman, Y Longo, DL Catane, R Shani, A Albeck, M Sredni, B AF Kalechman, Y Longo, DL Catane, R Shani, A Albeck, M Sredni, B TI Synergistic anti-tumoral effect of paclitaxel (taxol)+AS101 in a murine model of B16 melanoma: Association with Ras-dependent signal-transduction pathways SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID PROTEIN-KINASE; TAXOL; PHOSPHORYLATION; APOPTOSIS; CELLS; AS101; EXPRESSION; C-RAF-1; DEATH; BCL2 AB Optimal doses of paclitaxel (Taxol) combined with the immunomodulator AS101, previously shown to have antitumoral effects, administered to B16 melanoma-bearing mice decreased tumor volume and resulted in over 60% cure. Paclitaxel+AS101 directly inhibited the clonogenicity of B16 melanoma cells in a synergistic, dose-dependent manner. We suggest that this results from both reduced paclitaxel-induced bone marrow toxicity and induction of differential signal-transduction pathways, which lead to apoptosis of tumor cells. Paclitaxel+AS101 synergistically activated c-raf-1 and MAPK ERK1 and ERK2, This activation was essential for the synergistic induction of p21(Waf) protein. Cell-cycle analysis of B16 cells treated with both compounds revealed an increased accumulation in G(2)M, though AS101 alone produced significant G(1) arrest, These activities were ras dependent. AS101+paclitaxel induced significant synergistic phosphorylation (inactivation) of the anti-apoptotic protein Bcl-2, Whereas phosphorylation of Bcl-2 by paclitaxel was raf-dependent only, the synergistic effect of both compounds together was ras-, raf- and MAPK-dependent. No effect of the combined treatment on Bar protein expression was observed. We suggest that AS101 renders more cells susceptible to Bcl-2 phosphorylation by paclitaxel, possibly by increasing the accumulation of paclitaxel-induced cells in G(2)M, Exposure of Bib cells to clinically achievable concentrations of paclitaxel+AS101 increased the rate of apoptosis of treated cells. Apoptosis induced by AS101 alone was both raf- and MAPK-dependent, while that induced by paclitaxel was raf-dependent only. Int. J, Cancer 86:281-288, 2000. (C) 2000 Wiley-Liss, Inc. C1 Bar Ilan Univ, Fac Life Sci, Marilyn Finkler Canc Res Ctr, CAIR Inst, IL-52900 Ramat Gan, Israel. NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Shaare Zedek Med Ctr, Div Oncol, Jerusalem, Israel. Kaplan Hosp, Dept Oncol, IL-76100 Rehovot, Israel. RP Sredni, B (reprint author), Bar Ilan Univ, Fac Life Sci, Marilyn Finkler Canc Res Ctr, CAIR Inst, IL-52900 Ramat Gan, Israel. NR 20 TC 41 Z9 44 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD APR 15 PY 2000 VL 86 IS 2 BP 281 EP 288 DI 10.1002/(SICI)1097-0215(20000415)86:2<281::AID-IJC20>3.0.CO;2-X PG 8 WC Oncology SC Oncology GA 299VT UT WOS:000086219100020 PM 10738258 ER PT J AU Masel, J Arnaout, RA O'Brien, TR Goedert, JJ Lloyd, AL AF Masel, J Arnaout, RA O'Brien, TR Goedert, JJ Lloyd, AL TI Fluctuations in HIV-1 viral load are correlated to CD4(+) T-lymphocyte count during the natural course of infection SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE CD4(+) cell count; prognosis; predictive value of tests; longitudinal HIV; viral load ID RNA LEVELS; ASYMPTOMATIC PATIENTS; PLASMA; MARKERS; VIRUS; AIDS; PROGRESSION; PROGNOSIS; RESPONSES; COHORT AB Viral load fluctuates during the natural course of asymptomatic HIV-I infection. It is often assumed that these fluctuations are random around a set point or underlying growth trend. Using longitudinal data, we tested whether fluctuations in viral load can be better explained by changes in CD4(+) T-cell count than by a set point or trend of exponential growth. The correspondence between viral load and CD4(+) T-cell count could be described by a simple mathematical relation. Using a bootstrapping approach, the hypothesis that viral load fluctuations are random around a set point was rejected with p < .00005. The hypothesis that viral load fluctuations are random around a trend of exponential growth was rejected with p < .005. Viral load data was explained better by changes in CD4(+) T-cell counts than by a set point or by a trend of exponential growth. The implications of this finding for improved prognostication are discussed. C1 Univ Oxford, Dept Zool, Wellcome Trust Ctr Epidemiol Infect Dis, Oxford, England. NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. Dept Hlth & Human Serv, Rockville, MD USA. RP Lloyd, AL (reprint author), Inst Adv Study, Program Theoret Biol, Einstein Dr, Princeton, NJ 08540 USA. RI Lloyd, Alun/H-4944-2012 NR 21 TC 8 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD APR 15 PY 2000 VL 23 IS 5 BP 375 EP 379 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 324CD UT WOS:000087603500002 PM 10866229 ER PT J AU Lerner, CG Horton, MR Schwartz, RH Powell, JD AF Lerner, CG Horton, MR Schwartz, RH Powell, JD TI Distinct requirements for C-C chemokine and IL-2 production by naive, previously activated, and anergic T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GENE-EXPRESSION; SIGNAL-TRANSDUCTION; MONOCLONAL-ANTIBODY; IN-VITRO; ANTIGEN; COSTIMULATION; STIMULATION; MIP-1-ALPHA; CLONES; ENCEPHALOMYELITIS AB Ag presented by activated APCs promote inmunogenic responses whereas Ag presented by resting APCs leads to tolerance. In such a model, the regulation of cytokine release by the presence or absence of costimulation might potentially play a critical role in dictating the ultimate outcome of Ag recognition, C-C chemokines are a structurally defined family of chemoattractants that have diverse effects on inflammation. We were interested in determining the activation requirements for chemokine production by CD4(+) T cells. Our data demonstrate for T cell clones and previously activated T cells from TCR-transgenic mice that stimulation with anti-TCR alone results in the production of copious amounts of macrophage-inflammatory protein-1 alpha (MIP-1 alpha) and other C-C chemokines, and that addition of anti-CD28 gives very little augmentation. Furthermore, MIP-1 alpha production is nearly equivalent from both anergic and nonanergic cells. For naive T cells, anti-CD3 stimulation alone led to as much MIP-1 alpha production as Ag + APC stimulation, The addition of costimulation gave a 3-10-fold enhancement, but this was 70-fold less than the effect of costimulation on IL-2 production. Thus, although C-C chemokines play a broad role in influencing inflammation, their production by signal 1 alone makes them unlikely to play a critical role in the decision between a tolerogenic and an immunogenic response, Furthermore, the production of MIP-1 alpha by anergic T cells, as well as following signal 1 alone, raises the possibility that in vivo this chemokine serves to recruit activated T cells to become tolerant. C1 NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Div Pulm, Baltimore, MD 21205 USA. RP Powell, JD (reprint author), NIAID, Cellular & Mol Immunol Lab, NIH, Bldg 4,Room 111, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [K08 HL003993] NR 48 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 2000 VL 164 IS 8 BP 3996 EP 4002 PG 7 WC Immunology SC Immunology GA 303GZ UT WOS:000086415300009 PM 10754290 ER PT J AU Kenny, JJ Rezanka, LJ Lustig, A Fischer, RT Yoder, J Marshall, S Longo, DL AF Kenny, JJ Rezanka, LJ Lustig, A Fischer, RT Yoder, J Marshall, S Longo, DL TI Autoreactive B cells escape clonal deletion by expressing multiple antigen receptors SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNE-DEFICIENT MICE; REACTIVE LYMPHOCYTES-B; HEAVY-CHAIN GENE; TRANSGENIC MICE; ALLELIC EXCLUSION; STREPTOCOCCUS-PNEUMONIAE; BONE-MARROW; ANTIPHOSPHORYLCHOLINE ANTIBODIES; IMMUNOGLOBULIN GENES; FEEDBACK INHIBITION AB IgH and L chain transgenes encoding a phosphocholine (PC)-specific Ig receptor were introduced into recombinase-activating gene (Rag-2(-/-)) knockout mice. The PC-specific B' cells that developed behaved like known autoreactive lymphocytes. They were 1) developmentally arrested in the bone marrow, 2) unable to secrete Ab, 3) able to escape clonal deletion and develop into B1 B cells in the peritoneal cavity, and 4) rescued by overexpression of bcl-2, A second IgL chain was genetically introduced into Rag-2(-/-) knockout mice expressing the autoreactive PC-specific Ig receptor. These dual L chain-expressing mice had B cells in peripheral lymphoid organs that coexpressed both anti-PC Ab as well as Ab employing the second available L chain that does not generate an autoreactive PC-specific receptor. Coexpression of the additional Ig molecules rescued the autoreactive anti-PC B cells and relieved the functional anergy of the anti-PC-specific B cells, as demonstrated by detection of circulating autoreactive anti-PC-Abs. We call this novel mechanism by which autoreactive B cells can persist by compromising allelic exclusion receptor dilution. Rescue of autoreactive PC-specific B cells would be beneficial to the host because these Abs are vital for protection against pathogens such as Streptococcus pneumoniae. C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Kenny, JJ (reprint author), NIA, Gerontol Res Ctr, NIH, Room 4C19,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 64 TC 47 Z9 47 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 2000 VL 164 IS 8 BP 4111 EP 4119 PG 9 WC Immunology SC Immunology GA 303GZ UT WOS:000086415300024 PM 10754305 ER PT J AU Hochleitner, EO Gorny, MK Zolla-Pazner, S Tomer, KB AF Hochleitner, EO Gorny, MK Zolla-Pazner, S Tomer, KB TI Mass spectrometric characterization of a discontinuous epitope of the HIV envelope protein HIV-gp120 recognized by the human monoclonal antibody 1331A SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PBL-SCID MICE; CHEMICAL MODIFICATION; PASSIVE-IMMUNIZATION; T4 MOLECULE; TYPE-1; NEUTRALIZATION; GP120; BINDING; GLYCOPROTEIN AB The characterization of a discontinuous epitope in the C5 region of the HIV envelope protein HIV-gp120, recognized by 1331A, a human mAb, is reported. Regions involved in affinity binding in the HIV-gp120 molecule were identified by epitope excision/extraction methods followed by matrix assisted laser desorption-time of flight mass spectrometry. In epitope excision, the protein is bound in its native conformation to an immobilized Ab and then digested with proteolytic enzymes, In epitope extraction, the protein is first digested and subsequently allowed to react with the Ab, A series of proteolytic digestions of the 1331A/HIV-gp120 complex allowed the identification of protected amino acids in two noncontinuous regions of the C5 region of HIV-gpl20. Interaction of the Ab with amino acids I487 and E507 of HIV-gp120 is essential for efficient binding, This is the first application of this approach for the identification and characterization of a discontinuous epitope, The results are consistent with molecular modeling results, indicating that these amino acids are located on opposite sides of a hydrophobic pocket, This pocket is thought to be of importance for the interaction of HIV-gpl20 with the transmembrane protein HIV-gp41. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NYU, Sch Med, New York, NY 10016 USA. Vet Affairs Med Ctr, Res Ctr AIDS & HIV Infect, New York, NY 10010 USA. RP Tomer, KB (reprint author), NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RI Tomer, Kenneth/E-8018-2013 FU NIAID NIH HHS [AI07382, AI32424, AI36085] NR 38 TC 37 Z9 37 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 15 PY 2000 VL 164 IS 8 BP 4156 EP 4161 PG 6 WC Immunology SC Immunology GA 303GZ UT WOS:000086415300030 PM 10754311 ER PT J AU Liu, HT Sidiropoulos, P Song, GB Pagliari, LJ Birrer, MJ Stein, B Anrather, J Pope, RM AF Liu, HT Sidiropoulos, P Song, GB Pagliari, LJ Birrer, MJ Stein, B Anrather, J Pope, RM TI TNF-alpha gene expression in macrophages: Regulation by NF-kappa B is independent of c-Jun or C/EBP beta SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN MONOCYTIC CELLS; ADENOVIRUS VAI RNA; TISSUE FACTOR GENE; TRANSCRIPTION FACTORS; PROMOTER REGION; LIPOPOLYSACCHARIDE INDUCTION; RHEUMATOID-ARTHRITIS; BINDING-PROTEIN; P50 SUBUNIT; IN-VITRO AB The interaction of transcription factors is critical in the regulation of gene expression. This study characterized the mechanism by which NF-kappa B family members interact to regulate the human TNF-alpha gene. A 120-bp TNF-alpha promoter-reporter, possessing binding sites for NF-kappa B (kappa B3), C/EBP beta (CCAAT/enhancer binding protein beta), and c-Jun, was activated by cotransfection of plasmids expressing the wild-type version of each of these transcription factors. Employing adenoviral vectors, dominant-negative versions of NF-kappa B p65, and c-Jun, but not C/EBP beta, suppressed (p < 0.05-0.001) LPS-induced TNF-alpha secretion in primary human macrophages. Following LPS stimulation, NF-kappa B p50/p65 heterodimers bound to the kappa B3 site and c-Jun to the -103 AP-1 site of the TNF-alpha promoter. By transient transfection, NF-kappa B p65 and p50 synergistically activated the TNF-alpha promoter. In contrast, no synergy was observed between NF-kappa B p65, with or without NF-kappa B p50, and c-Jun or C/EBP beta, even in the presence of the coactivator p300. The contribution of the upstream kappa B binding sites was also examined. Following LPS stimulation, the kappa B1 site bound both NF-kappa B p50/p65 heterodimers and p50 homodimers, The binding by NF-kappa B p50 homodimers to the kappa B1, but not to the kappa B3, site contributed to the inability of macrophages to respond to a second LPS challenge. In summary, adjacent kappa B3 and AP-1 sites in the human TNF-alpha promoter contribute independently to LPS-induced activation. Although both the kappa B1 and kappa B3 sites bound transcriptionally active NF-kappa B p50/p65 heterodimers, only the kappa B1 site contributed to down-regulation by NF-kappa B p50 homodimers, The Journal of Immunology, 2000, 164: 4277-4285. C1 Northwestern Univ, Sch Med, Dept Med, Div Rheumatol, Chicago, IL 60611 USA. Vet Adm Lakeside Med Ctr, Dept Med, Div Arthritis, Chicago, IL 60611 USA. NCI, Biomarkers & Prevent Res Branch, NIH, Rockville, MD 20805 USA. Signal Pharmaceut Inc, San Diego, CA 92121 USA. Beth Israel Deaconess Med Ctr, Immunobiol Res Ctr, Boston, MA 02215 USA. RP Pope, RM (reprint author), Northwestern Univ, Sch Med, Dept Med, Div Rheumatol, Ward 3-315,303 E Chicago Ave, Chicago, IL 60611 USA. FU NIAMS NIH HHS [AR30692, AR43642, AR62229] NR 42 TC 145 Z9 152 U1 0 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2000 VL 164 IS 8 BP 4277 EP 4285 PG 9 WC Immunology SC Immunology GA 303GZ UT WOS:000086415300046 PM 10754326 ER PT J AU Okayama, Y Kirshenbaum, AS Metcalfe, DD AF Okayama, Y Kirshenbaum, AS Metcalfe, DD TI Expression of a functional high-affinity IgG receptor, Fc gamma RI, on human mast cells: Up-regulation by IFN-gamma SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NEGATIVE REGULATION; HUMAN NEUTROPHILS; PHOSPHATASE SHIP; ARTHUS REACTION; MESSENGER-RNA; CROSS-LINKING; INTERFERON; ACTIVATION; MONOCYTES; GENE AB Biologically relevant activation of human mast cells through Fc receptors is believed to occur primarily through the high-affinity IgE receptor Fc epsilon RI, However, the demonstration in animal models that allergic reactions do not necessarily require Ag-specific IgE, nor the presence of a functional IgE receptor, and the clinical occurrence of some allergic reactions in situations where Ag-specific IgE appears to be lacking, led us to examine the hypothesis that human mast cells might express the high-affinity IgG receptor Fc gamma RI and in turn be activated through aggregation of this receptor. We thus first determined by RT-PCR that resting human mast cells exhibit minimal message for Fc gamma RI, We next found that IFN-gamma up regulated the expression of Fc gamma RI. This was confirmed by flow cytometry, where Fc gamma RI expression on human mast cells was increased from similar to 2 to 44% by IFN-gamma exposure. Fc epsilon RI, Fc gamma RII, and Fc gamma RIII expression was not affected. Scatchard plots were consisted with these data where the average binding sites for monomeric IgG1 (K-a = 4-5 x 10(8) M-1) increased from similar to 2,400 to 12,100-17,300 per cell. aggregation of Fc gamma RI on human mast cells, and only after IFN-gamma exposure, led to significant degranulation as evidenced by histamine release (24.5 +/- 4.4%): and up-regulation of mRNA expression for specific cytokines including TNF-alpha, GM-CSF, IL-3 and IL-13, These findings thus suggest another mechanism by which human mast cells may be recruited into the inflammatory processes associated with some immunologic and infectious diseases. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Okayama, Y (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C206,10 Ctr Dr MSC 1881, Bethesda, MD 20892 USA. NR 50 TC 121 Z9 133 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2000 VL 164 IS 8 BP 4332 EP 4339 PG 8 WC Immunology SC Immunology GA 303GZ UT WOS:000086415300053 PM 10754333 ER PT J AU Panelli, MC Bettinotti, MP Lally, K Ohnmacht, GA Li, Y Robbins, P Riker, A Rosenberg, SA Marincola, FM AF Panelli, MC Bettinotti, MP Lally, K Ohnmacht, GA Li, Y Robbins, P Riker, A Rosenberg, SA Marincola, FM TI A tumor-infiltrating lymphocyte from a melanoma metastasis with decreased expression of melanoma differentiation antigens recognizes MAGE-12 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOLYTIC T-LYMPHOCYTES; PEPTIDE-BASED IMMUNOTHERAPY; CELL-LINES; IN-VIVO; HETEROGENEOUS EXPRESSION; SYNTHETIC PEPTIDE; HLA-A2 SUBTYPES; IDENTIFICATION; MART-1; GP100 AB Twenty separate tumor infiltrating lymphocyte (TIL) bulk cultures and a tumor cell line were originated simultaneously from a fine needle aspiration biopsy of a metastasis in a patient with melanoma (F001) previously immunized with the HLA-A*0201-associated gp100:209-217(210 M) peptide. None of the TIL recognized gp100, However, 12 recognized autologous (F001-MEL) and allogeneic melanoma cells expressing the HLA haplotype A*0201, B*0702, Cw*0702, Further characterization of F001-MEL demonstrated loss of gp100/PMel17, severely decreased expression of other melanoma differentiation Ags and retained expression of tumor-specific Ags, Transfection of HLA class I alleles into B*0702/Cw*0702-negative melanoma cell lines identified HLA-Cw*0702 as the restriction element for F001-TIL, A cDNA library from F001-MEL was used to transfect IFN-alpha-stimulated 293 human embryonal kidney (293-HEK) cells expressing HLA-Cw*0702, A 100-gene pool was identified that induced recognition of 293-HEK cells by F001-TIL, Subsequent cloning of the pool identified a cDNA sequence homologous, except for one amino acid (aa 187 D-->A), to MAGE-12. Among 25 peptide sequences from MAGE-12 with the HLA-Cw*0702 binding motif, MAGE 12: 170-178 (VRIGHLYIL) induced IFN-gamma release by F001-TIL when pulsed on F001-EBV-B cells at concentrations as low as 10 pg/ml, Peptide sequences from MAGE-1, 2, 3, 4a, and 6 aligned to MAGE-12:170-178 were not recognized by F001-TIL, In summary a TIL recognizing a MAGE protein was developed from an HLA-A*0201 expressing tumor with strongly reduced expression of melanoma differentiation Ags, Persisting tumor-specific Ag expression maintained tumor immune competence suggesting that tumor-specific Ags/melanoma differentiation Ags may complement each other in the context of melanoma Ag-specific vaccination. C1 NCI, Surg Branch, Div Clin Sci, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), NCI, Surg Branch, Div Clin Sci, Bldg 10,Room 2B42,10 Ctr Dr,MSC 1502, Bethesda, MD 20892 USA. RI Riker, Adam/A-6065-2011 NR 63 TC 46 Z9 50 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 2000 VL 164 IS 8 BP 4382 EP 4392 PG 11 WC Immunology SC Immunology GA 303GZ UT WOS:000086415300059 PM 10754339 ER PT J AU Vorechovsky, I Cullen, M Carrington, M Hammarstrom, L Webster, ADB AF Vorechovsky, I Cullen, M Carrington, M Hammarstrom, L Webster, ADB TI Fine mapping of IGAD1 in IgA deficiency and common variable immunodeficiency: Identification and characterization of haplotypes shared by affected members of 101 multiple-case families SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CLASS-II REGION; MAJOR HISTOCOMPATIBILITY COMPLEX; IMMUNOGLOBULIN-A DEFICIENCY; HUMAN MHC; POLYMORPHIC MARKERS; AUTOIMMUNE-DISEASE; SUSCEPTIBILITY; ASSOCIATION; GENES; DQ AB To limit the region containing a mutation predisposing to selective IgA deficiency (IgAD) and common variable immunodeficiency (CVID), 554 informative members of 101 multiple-case families were haplotyped at the IGAD1 candidate locus in the MHC. Microsatellite markers were placed onto the physical map of IGAD1 to establish their order and permit rapid haplotype analyses. Linkage analysis of this extended family set provided additional support for a strong susceptibility locus at IGAD1 with a maximum multipoint nonparametric linkage score in excess of 3, Although the transmission of maternal IGAD1 haplotypes from unaffected heterozygous parents to the affected offspring was in excess, this was not apparent in multiple-case families with a predominance of affected mothers, suggesting that this parental bias is influenced by the affection status of transmitting parents and supporting a maternal effect in disease susceptibility, Of 110 haplotypes shared by 258 affected family members, a single haplotype (H1) was found in 44 pairs of affected relatives, accounting for the majority of the IGAD1 contribution to the development of IgAD/CVID in our families. The H1 allelic variability was higher in the telomeric part of the class III region than in the distal part of the class II region in both single- and multiple-case families. Incomplete H1 haplotypes had most variant alleles in the telomeric part of the analyzed region in homozygous IgAD/CVID patients, whereas this was not observed in unaffected homozygotes, These data suggest that a telomeric part of the class II region or centromeric part of the class III region is the most likely location of IGAD1. C1 Karolinska Inst, Novum, Dept Biosci, SE-14157 Huddinge, Sweden. UCL, Sch Med, MRC, Immunodeficiency Res Grp,Dept Clin Immunol, London W1N 8AA, England. NCI, Frederick Canc Res & Dev Ctr, Biol Carcinogenesis & Dev Program, Frederick, MD 21702 USA. RP Vorechovsky, I (reprint author), Karolinska Inst, Novum, Dept Biosci, CBT Halsovagen 7, SE-14157 Huddinge, Sweden. EM igvo@smip.biosci.ki.se FU NCI NIH HHS [N01CO56000] NR 38 TC 83 Z9 83 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 15 PY 2000 VL 164 IS 8 BP 4408 EP 4416 PG 9 WC Immunology SC Immunology GA 303GZ UT WOS:000086415300062 PM 10754342 ER PT J AU Tabak, J Senn, W O'Donovan, MJ Rinzel, J AF Tabak, J Senn, W O'Donovan, MJ Rinzel, J TI Modeling of spontaneous activity in developing spinal cord using activity-dependent depression in an excitatory network SO JOURNAL OF NEUROSCIENCE LA English DT Article DE spontaneous activity; oscillations; depression; developing spinal network; recurrent excitation; rate model ID SPONTANEOUS RHYTHMIC ACTIVITY; CHICK-EMBRYO; MOTOR-ACTIVITY; SYNAPTIC DEPRESSION; RETINAL WAVES; ANTAGONISTS; MOTONEURONS; DRIVE AB Spontaneous episodic activity is a general feature of developing neural networks. In the chick spinal cord, the activity comprises episodes of rhythmic discharge (duration 5-90 sec; cycle rate 0.1-2 Hz) that recur every 2-30 min. The activity does not depend on specialized connectivity or intrinsic bursting neurons and is generated by a network of functionally excitatory connections. Here, we develop an idealized, qualitative model of a homogeneous, excitatory recurrent network that could account for the multiple time-scale spontaneous activity in the embryonic chick spinal cord. We show that cycling can arise from the interplay between excitatory connectivity and fast synaptic depression. The slow episodic behavior is attributable to a slow activity-dependent network depression that is modeled either as a modulation of cellular excitability or as synaptic depression. Although the two descriptions share many features, the model with a slow synaptic depression accounts better for the experimental observations during blockade of excitatory synapses. C1 NINDS, Neural Control Lab, NIH, Bethesda, MD 20892 USA. Univ Bern, Inst Physiol, CH-3012 Bern, Switzerland. NYU, Ctr Neural Sci, New York, NY 10003 USA. NYU, Courant Inst Math Sci, New York, NY 10003 USA. RP Tabak, J (reprint author), NINDS, Neural Control Lab, NIH, Room 3A50,Bldg 49, Bethesda, MD 20892 USA. RI tabak, joel/K-1549-2013; Senn, Walter/D-6308-2014; o'donovan, michael/A-2357-2015 OI Senn, Walter/0000-0003-3622-0497; o'donovan, michael/0000-0003-2487-7547 NR 29 TC 127 Z9 127 U1 1 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 15 PY 2000 VL 20 IS 8 BP 3041 EP 3056 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 303FR UT WOS:000086412100034 PM 10751456 ER PT J AU Madsen, BW Beglan, CL Spivak, CE AF Madsen, BW Beglan, CL Spivak, CE TI Fluorescein-labeled naloxone binding to mu opioid receptors on live Chinese hamster ovary cells using confocal fluorescent microscopy SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE mu opioid receptor; confocal fluorescent microscopy; ligand kinetics; radioligand binding; Chinese hamster ovary cells; live cells; fluorescent probe ID DOPAMINE-RECEPTORS; IN-VIVO; LIGANDS; NEURONS; INTERNALIZATION; LOCALIZATION; EXPRESSION; PROBES; SITES AB A general method of confocal laser scanning microscopy was used to demonstrate specific binding of fluorescein-labeled naloxone (FNAL, 10-50 nM) to stably transfected mu opioid receptors on live Chinese hamster ovary cells. Nonspecific binding was visually indistinguishable from autofluorescence in cells with intact cell membranes. Fluorescent labeling of cell perimeters, not present in control nontransfected cells, reversed in transfected cells upon washout of FNAL or following the addition of either unlabeled naloxone (25 mu M) or the mu specific antagonist CTOP (1 mu M). The addition of the delta and kappa specific agonists DPDPE (1 mu M) and U50 488 (1 mu M), respectively, failed to reverse the labeling. Further evidence of specific binding was obtained from kinetic experiments, where it was observed that only transfected cells showed a time-dependent exponential change in fluorescence that permitted estimation of association and dissociation binding rate constants of (5.8 +/- 0.5, mean +/- S.E.M.) x 10(5) M-1 s(-1) and (3.3 +/- 0.6) x 10(-3) s(-1), respectively and a kinetically derived dissociation constant of 5.7 +/- 1.4 nM. These estimates were comparable to those obtained under similar conditions in radioligand binding experiments using [H-3]-naloxone. (C) 2000 Elsevier Science B.V. All rights reserved. C1 NIDA, Addict Res Ctr, Baltimore, MD 21224 USA. Univ Western Australia, Dept Pharmacol, Nedlands, WA 3907, Australia. RP Spivak, CE (reprint author), NIDA, Addict Res Ctr, POB 5180, Baltimore, MD 21224 USA. NR 21 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD APR 15 PY 2000 VL 97 IS 2 BP 123 EP 131 DI 10.1016/S0165-0270(00)00175-8 PG 9 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 312NW UT WOS:000086950200004 PM 10788666 ER PT J AU Liesi, P Stewart, RR Wright, JM AF Liesi, P Stewart, RR Wright, JM TI Involvement of GIRK2 in postnatal development of the weaver cerebellum SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE GIRK2; neuronal death; weaver mouse ID GRANULE CELLS; MOUSE CEREBELLUM; K+ CHANNELS; MUTANT MICE; INWARD RECTIFIER; MUTATION; NEURONS; DOMAIN; MIGRATION; SECONDARY AB We demonstrate that the homozygous weaver granule neurons cultured on a laminin substratum fail to express inwardly rectifying potassium currents, including a functional G-protein coupled inwardly rectifying potassium (GIRK)2 potassium channel. By contrast, both normal and weaver Purkinje cells express inwardly rectifying potassium currents, and normal granule cells exhibit inwardly rectifying potassium currents inducible with GTP gamma-S. In protein extracts of the vermal postnatal day (P)5-9 weaver cerebellum, the GIRK2 protein could not be detected by Western analysis, although the GIRK2 protein was detectable in extracts of the normal vermis. Northern analysis indicated that during early postnatal cerebellar development, the GIRK2 mRNA is expressed at extremely low levels being detectable at P18-23 in the normal but not yet in the homozygous weaver cerebellum. Using reverse transcriptase-polymerase chain reaction (RT-PCR), the GIRK2 mRNA was detected in both normal and weaver cerebella, but quantitative PCR confirmed that the weaver cerebellum expressed the GIRK2 gene at significantly lower levels as compared to the normal cerebellum (P = 0.01, paired t-test). Sequencing indicated that the weaver GIRK2 channel gene had the point mutation proposed to be responsible for the weaver phenotype. Rescue of both survival and neurite outgrowth of the cultured vermal weaver granule neurons by verapamil (Liesi and Wright, 1996; Liesi et al., 1999) induced expression of immunocytochemically detectable levels of the GIRK2 protein. Sequencing revealed that the GIRK2 mRNA of the rescued weaver granule neurons remained the mutated variant of the GIRK2 channel gene. Our results indicate that expression of the mutated GIRK2 protein and/or mRNA in the weaver granule neurons may be an indicator of rescue rather than death of the weaver granule neurons. That the weaver granule neurons expressed no functional GIRK2 receptors during a time period of neuronal death and migration failure suggests that the point mutation in the H5 membrane spanning region of the GIRK2 gene may associate. with, but not be responsible for the weaver phenotype. (C) 2000 Wiley-Liss, Inc. C1 Univ Helsinki, Inst Biomed, Brain Lab, FIN-00014 Helsinki, Finland. NIAAA, NIH, Rockville, MD 20852 USA. Johns Hopkins Med Inst, Dept Physiol, Baltimore, MD 21205 USA. RP Liesi, P (reprint author), Univ Helsinki, Inst Biomed, Brain Lab, POB 9,Siltavuorenpenger 20A, FIN-00014 Helsinki, Finland. NR 27 TC 5 Z9 5 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD APR 15 PY 2000 VL 60 IS 2 BP 164 EP 173 DI 10.1002/(SICI)1097-4547(20000415)60:2<164::AID-JNR5>3.0.CO;2-M PG 10 WC Neurosciences SC Neurosciences & Neurology GA 300MW UT WOS:000086257600005 PM 10740221 ER PT J AU Koch, CA Bornstein, SR Chrousos, GP Stratakis, CA AF Koch, CA Bornstein, SR Chrousos, GP Stratakis, CA TI Primary pigmented adrenocortical dysplasia (PPNAD) in the context of the Carney complex causing Cushing syndrome SO MEDIZINISCHE KLINIK LA German DT Article DE PPNAD; Cushing syndrome; Carney complex ID HUMAN ADRENAL-GLAND; PERIODIC HORMONOGENESIS; NODULAR DYSPLASIA; CARDIAC MYXOMAS; DISEASE; HYPERCORTISOLISM; DEXAMETHASONE; HYPERPLASIA; SECRETION; RECEPTORS AB Background: Primary pigmented adrenocortical dysplasia (PPNAD) represents a rare disorder of the adrenal glands and frequently occurs in patients with the so-called Carney complex. Carney complex is an autosomal dominant neoplasia syndrome including skin and mucosal lentigines, myxomas, and PPNAD. Case Report: A 37-year-old woman suffered from several episodes of weight gain/depression and weight loss/mania indicating cyclic hypercortisolism. Finally, she developed a full-blown Cushing's syndrome (CS) treated by bilateral adrenalectomy. She had PPNAD in the setting of Carney complex. Conclusion: PPNAD may lead to different clinical manifestations: 1. sub-clinical hypercortisolism, 2. intermittent hypercortisolemia, and 3. full-blown CS. It can be diagnosed with the 6-day Liddle test that typically shows a paradoxical stimulation of cortisol secretion after dexamethasone administration. The treatment of choice for PPNAD is bilateral adrenalectomy in order to prevent devastating long-term effects of hypercortisolism. C1 NICHD, NIH, Dev Endocrinol Branch, Bethesda, MD 20892 USA. RP Bornstein, SR (reprint author), NICHD, NIH, Dev Endocrinol Branch, Bldg 10,Rm 10N262, Bethesda, MD 20892 USA. RI Koch, Christian/A-4699-2008; OI Koch, Christian/0000-0003-3127-5739; Koch, Christian/0000-0003-0678-1242 NR 56 TC 7 Z9 7 U1 0 U2 0 PU URBAN & VOGEL PI MUNICH PA LINDWURMSTRASSE 95, D-80337 MUNICH, GERMANY SN 0723-5003 J9 MED KLIN JI Med. Klin. PD APR 15 PY 2000 VL 95 IS 4 BP 224 EP 230 DI 10.1007/PL00002112 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 311HG UT WOS:000086878200008 PM 10808306 ER PT J AU Hayward, RE AF Hayward, RE TI Plasmodium falciparum phosphoenolpyruvate carboxykinase is developmentally regulated in gametocytes SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE Plasmodium falciparum; gametocyte; zygote; carbon dioxide fixation; phosphoenolpyruvate carboxykinase; DNA microarray ID TRANSMISSION-BLOCKING ANTIBODIES; TRYPANOSOMA-BRUCEI; MALARIA PARASITES; ESCHERICHIA-COLI; BLOOD-STREAM; EXPRESSION; PROTEIN; ERYTHROCYTES; INVITRO; MOSQUITO AB Plasmodium species have the capacity to fix carbon dioxide during intracellular development. This process contributes to the pool of free amino acids and metabolites, which are the end products of glucose metabolism in the malaria parasite. A gene encoding phosphoenolpyruvate carboxykinase (PEPCK), an enzyme known to catalyze CO2 fixation was identified in the genome of the human parasite Plasmodium falciparum by DNA microarray analysis experiments and was cloned and characterized. PfPEPCK is a 66.2 kDa, ATP-dependent enzyme which is closely related to PEPCK from plants and yeast but markedly different from the host enzyme human PEPCK. PfPEPCK transcript anti active enzyme levels are upregulated in the transmissible and zygote stages of parasite development relative to the asexual blood stages. Elevated expression of PfPEPCK during the extracellular zygote phase of P. falciparum development within the microenvironment of the mosquito midgut may reflect a glucose-rare medium and suggests a possible switch in carbohydrate metabolism to a gluconeogenesis pathway. (C) 2000 Elsevier Science B.V. All rights reserved. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Hayward, RE (reprint author), NIAID, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 59 TC 22 Z9 23 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD APR 15 PY 2000 VL 107 IS 2 BP 227 EP 240 DI 10.1016/S0166-6851(00)00191-2 PG 14 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 311BA UT WOS:000086863400008 PM 10779599 ER PT J AU Lutz, M Burke, LJ Barreto, G Goeman, F Greb, H Arnold, R Schultheiss, H Brehm, A Kouzarides, T Lobanenkov, V Renkawitz, R AF Lutz, M Burke, LJ Barreto, G Goeman, F Greb, H Arnold, R Schultheiss, H Brehm, A Kouzarides, T Lobanenkov, V Renkawitz, R TI Transcriptional repression by the insulator protein CTCF involves histone deacetylases SO NUCLEIC ACIDS RESEARCH LA English DT Article ID THYROID-HORMONE RECEPTOR; ZINC-FINGER PROTEIN; ACUTE MYELOID-LEUKEMIA; C-MYC GENE; N-COR; ACTIVATION DOMAIN; BINDING-PROTEIN; FUSION PARTNER; DNA-SEQUENCE; V-ERBA AB The highly conserved zinc-finger protein, CTCF, is a candidate tumor suppressor protein that binds to highly divergent DNA sequences. CTCF has been connected to multiple functions in chromatin organization and gene regulation including chromatin insulator activity and transcriptional enhancement and silencing, Here we show that CTCF harbors several autonomous repression domains. One of these domains, the zinc-finger cluster, silences transcription in all cell types tested and binds directly to the co-repressor SIN3A, Two distinct regions of SIN3A, the PAH3 domain and the extreme C-terminal region, bind independently to this zinc-finger cluster, Analysis of nuclear extract from HeLa cells revealed that CTCF is also capable of retaining functional histone deacetylase activity, Furthermore, the ability of regions of CTCF to retain deacetylase activity correlates with the ability to bind to SIN3A and to repress gene activity, We suggest that CTCF driven repression is mediated in part by the recruitment of histone deacetylase activity by SIN3A. C1 Univ Giessen, Inst Genet, D-35392 Giessen, Germany. Univ Cambridge, Dept Pathol, Wellcome CRC Inst Dev & Canc Biol, Cambridge CB2 1QR, England. NIAID, NIH, Mol Pathol Sect, Bethesda, MD 20892 USA. RP Renkawitz, R (reprint author), Univ Giessen, Inst Genet, Heinrich Buff Ring 58-62, D-35392 Giessen, Germany. OI Barreto, Guillermo/0000-0002-7777-4712 NR 53 TC 85 Z9 87 U1 3 U2 5 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 2000 VL 28 IS 8 BP 1707 EP 1713 DI 10.1093/nar/28.8.1707 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 308FG UT WOS:000086699400006 PM 10734189 ER PT J AU Lutz, M Burke, LJ Barreto, G Goeman, F Greb, H Arnold, R Schultheiss, H Brehm, A Kouzarides, T Lobanenkov, V Renkawitz, R AF Lutz, Marcus Burke, Les J. Barreto, Guillermo Goeman, Frauke Greb, Heiko Arnold, Ruediger Schultheiss, Holger Brehm, Alexander Kouzarides, Tony Lobanenkov, Victor Renkawitz, Rainer TI Transcriptional repression by the insulator protein CTCF involves histone deacetylases SO NUCLEIC ACIDS RESEARCH LA English DT Article AB The highly conserved zinc-finger protein, CTCF, is a candidate tumor suppressor protein that binds to highly divergent DNA sequences. CTCF has been connected to multiple functions in chromatin organization and gene regulation including chromatin insulator activity and transcriptional enhancement and silencing. Here we show that CTCF harbors several autonomous repression domains. One of these domains, the zinc-finger cluster, silences transcription in all cell types tested and binds directly to the co-repressor SIN3A. Two distinct regions of SIN3A, the PAH3 domain and the extreme C-terminal region, bind independently to this zinc-finger cluster. Analysis of nuclear extract from HeLa cells revealed that CTCF is also capable of retaining functional histone deacetylase activity. Furthermore, the ability of regions of CTCF to retain deacetylase activity correlates with the ability to bind to SIN3A and to repress gene activity. We suggest that CTCF driven repression is mediated in part by the recruitment of histone deacetylase activity by SIN3A. C1 [Lutz, Marcus; Burke, Les J.; Barreto, Guillermo; Goeman, Frauke; Greb, Heiko; Arnold, Ruediger; Schultheiss, Holger; Renkawitz, Rainer] Univ Giessen, Genet Inst, D-35392 Giessen, Germany. [Brehm, Alexander; Kouzarides, Tony] Univ Cambridge, Dept Pathol, Wellcome CRC Inst Dev & Canc Biol, Cambridge CB2 1QR, England. [Lobanenkov, Victor] NIAID, NIH, Mol Pathol Sect, Bethesda, MD 20892 USA. RP Renkawitz, R (reprint author), Univ Giessen, Genet Inst, Heinrich Buff Ring 58-62, D-35392 Giessen, Germany. EM rainemenkawitz@gen.bio.uni-giessen.de OI Barreto, Guillermo/0000-0002-7777-4712 FU Deutsche Forschungsgemeinschaft; Fonds der Chemischen Industrie FX We would like to thank Dr Eisenman for the gift of the pVZ-mSin3A expression plasmid, Dr Rosenfeld for the gift of pCMX-Gal4 NCoR1-312. We would also like to thank L. Schaefer-Pfeiffer for excellent technical assistance. This work contains parts of the Ph.D thesis of M.L. The work was supported by a grant from the Deutsche Forschungsgemeinschaft and by the Fonds der Chemischen Industrie. NR 53 TC 85 Z9 87 U1 3 U2 5 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 2000 VL 28 IS 8 BP 1707 EP 1713 DI 10.1093/nar/28.8.1707 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA V17CX UT WOS:000207916400016 PM 10734189 ER PT J AU Zeng, HW Kaul, S Simons, SS AF Zeng, Huawei Kaul, Sunil Simons, S. Stoney, Jr. TI Genomic organization of human GMEB-1 and rat GMEB-2: structural conservation of two multifunctional proteins SO NUCLEIC ACIDS RESEARCH LA English DT Article AB The glucocorticoid modulatory element binding proteins 1 and 2 (GMEB-1 andGMEB-2) are of interest both for their multiple activities (e. g. modulation of transactivation by the glucocorticoid receptor and initiation of parvovirus replication) and their membership in the emerging family of KDWK proteins. The genomic sequence of these proteins was desired in order to begin studies on the control of GMEB expression and to pursue previous evidence for significant homologies between the GMEBs. We now report the genomic sequence of human GMEB-1 and rat GMEB-2. The structure of both genes, including portions of the introns, is highly conserved. However, GMEB-1 and GMEB-2 were found to reside on chromosomes 1 and 20, respectively, demonstrating that they are encoded by distinctly different genes. Several isoforms of the GMEBs have been reported or detected in this study, and the splicing patterns were determined. The tissue distribution of each GMEB is not the same and is highest in fetal and developing tissues, consistent with previous suggestions that both homo-and hetero-oligomers may possess biological activity. The promoter region of both genes has been identified and both display high levels of transcription activity in transiently transfected cells when fused upstream of a promoterless reporter. These results indicate that the GMEBs are proteins that evolved from a single parent gene, have been highly conserved since the divergence of rats and humans and probably play important roles in development and differentiation. C1 [Zeng, Huawei; Kaul, Sunil; Simons, S. Stoney, Jr.] NIDDK, Steroid Hormones Sect, LMCB, NIH, Bethesda, MD 20892 USA. RP Simons, SS (reprint author), NIDDK, Steroid Hormones Sect, LMCB, NIH, Bldg 8,Room B2A-07, Bethesda, MD 20892 USA. EM steroids@helix.nih.gov NR 23 TC 14 Z9 15 U1 1 U2 1 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 2000 VL 28 IS 8 BP 1819 EP 1829 DI 10.1093/nar/28.8.1819 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA V17CX UT WOS:000207916400029 PM 10734202 ER PT J AU Zeng, HW Kaul, S Simons, SS AF Zeng, HW Kaul, S Simons, SS TI Genomic organization of human GMEB-1 and rat GMEB-2: structural conservation of two multifunctional proteins SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GLUCOCORTICOID MODULATORY ELEMENT; MOLECULAR-CLONING; GENE-EXPRESSION; BINDING-FACTOR; TRANSCRIPTION; INDUCTION; CELL; SEQUENCE AB The glucocorticoid modulatory element binding proteins 1 and 2 (GMEB-1 and GMEB-2) are of interest both for their multiple activities (e.g. modulation of transactivation by the glucocorticoid receptor and initiation of parvovirus replication) and their membership in the emerging family of KDWK proteins. The genomic sequence of these proteins was desired in order to begin studies on the control of GMEB expression and to pursue previous evidence for significant homologies between the GMEBs, We now report the genomic sequence of human GMEB-1 and rat GMEB-2, The structure of both genes, including portions of the introns, is highly conserved. However, GMEB-1 and GMEB-2 were found to reside on chromosomes 1 and 20, respectively, demonstrating that they are encoded by distinctly different genes. Several isoforms of the GMEBs have been reported or detected in this study, and the splicing patterns were determined. The tissue distribution of each GMEB is not the same and is highest in fetal and developing tissues, consistent with previous suggestions that both homo- and hetero-oligomers may possess biological activity, The promoter region of both genes has been identified and both display high levels of transcription activity in transiently transfected cells when fused upstream of a promoterless reporter, These results indicate that the GMEBs are proteins that evolved from a single parent gene, have been highly conserved since the divergence of rats and humans and probably play important roles in development and differentiation. C1 NIDDK, Steroid Hormones Sect, LMCB, NIH, Bethesda, MD 20892 USA. RP Simons, SS (reprint author), NIDDK, Steroid Hormones Sect, LMCB, NIH, Bldg 8,Room B2A-07, Bethesda, MD 20892 USA. NR 22 TC 14 Z9 15 U1 1 U2 1 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 2000 VL 28 IS 8 BP 1819 EP 1829 DI 10.1093/nar/28.8.1819 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 308FG UT WOS:000086699400019 PM 10734202 ER PT J AU Blauvelt, A Glushakova, S Margolis, LB AF Blauvelt, A Glushakova, S Margolis, LB TI HIV-infected human Langerhans cells transmit infection to human lymphoid tissue ex vivo SO AIDS LA English DT Article DE Langerhans cells; dendritic cells; skin; lymphoid tissue; tonsils; HIV; AIDS; sexual transmission ID SIMIAN IMMUNODEFICIENCY VIRUS; DENDRITIC CELLS; T-CELLS; PRODUCTIVE INFECTION; SEXUAL TRANSMISSION; EXPRESSION; CXCR4; CORECEPTORS; TARGETS; MODEL AB Objectives: To create a novel ex vivo model for early biologic events involved in sexual transmission of HIV and to demonstrate that Langerhans cells (LC), the purported initial mucosal target cells for HIV, play a critical role in this process. Methods: Epidermal cells containing FC were isolated from normal-appearing skin of healthy volunteers and exposed to a panel of primary and laboratory-adapted R5- and X4-HIV isolates, washed and applied to the surfaces of allogeneic tonsil tissue blocks. Viral replication was followed by measuring HIV p24 protein in culture supernatants by ELISA. Results: Both R5- and X4-HIV isolates could be transmitted by LC and established high levels of infection in lymphoid tissue (p24 > 10 ng/ml). Depletion of LC within epidermal cell suspensions abrogated the ability of HIV-exposed suspensions to transmit virus to tonsil histocultures. Conclusions: Using a novel ex vivo model, human LC are shown for the first time to be the major epidermal cell type that is involved in transmission of HIV infection to human lymphoid tissue. Importantly, this system could prove useful in further understanding LC trafficking and other early biological events involved in primary HIV Introduction infection. (C) 2000 Lippincott Williams & Wilkins. C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NICHHD, Lab Mol & Cellular Biophys, Bethesda, MD 20892 USA. RP Blauvelt, A (reprint author), NCI, Dermatol Branch, Bldg 10 Room 12N238,10 Ctr Dr,MSC 1908, Bethesda, MD 20892 USA. NR 29 TC 33 Z9 33 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD APR 14 PY 2000 VL 14 IS 6 BP 647 EP 651 DI 10.1097/00002030-200004140-00003 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 307XH UT WOS:000086679100003 PM 10807187 ER PT J AU Halpern, MT Read, JS Ganoczy, DA Harris, DR AF Halpern, MT Read, JS Ganoczy, DA Harris, DR TI Cost-effectiveness of cesarean section delivery to prevent mother-to-child transmission of HIV-1 SO AIDS LA English DT Article; Proceedings Paper CT 7th Conference on Retroviruses and Opportunistic Infections CY FEB, 2000 CL SAN FRANCISCO, CALIFORNIA DE HIV; vertical transmission; prevention; cost-effectiveness; decision analysis; economic models ID HUMAN-IMMUNODEFICIENCY-VIRUS; ZIDOVUDINE COMBINATION THERAPY; PERINATAL TRANSMISSION; INFECTED WOMEN; PREGNANCY; EFFICACY; MONOTHERAPY; EXPOSURE; DISEASE; SAFETY AB Objective: To evaluate costs and outcomes of cesarean section performed before onset of labor and before rupture of membranes (elective cesarean section) compared to vaginal delivery among HIV-infected women. Design: Cost-effectiveness and cost-benefit analysis. Participants and setting: Pregnant HIV-infected women in the US who refrain from breastfeeding. Intervention: Elective cesarean section versus vaginal delivery by antiretroviral therapy regimen. Main outcome measures: Pediatric HIV cases avoided, years of life saved, and direct medical costs for maternal interventions and pediatric HIV treatment. Results: Elective cesarean section (versus vaginal delivery) was cost-effective among women receiving zidovudine prophylaxis (US$1131 per case avoided, US$17 per year of life saved) and combination antiretroviral therapy (US$112 693 per case avoided, US$1697 per year of life saved), and cost saving among women receiving no antiretroviral therapy during pregnancy (benefit-cost ratio of 2.23). Although elective cesarean section remained cost-effective, results were sensitive to variations in vertical transmission rates and to pediatric HIV treatment costs. Population-based analyses indicated that elective cesarean section could prevent 239 pediatric HIV cases annually with a savings of over US$4 million. Conclusions: Elective cesarean section is a cost-effective intervention to prevent vertical transmission of HIV among women receiving various antiretroviral therapy regimens, who refrain from breastfeeding. (C) 2000 Lippincott Williams & Wilkins. C1 NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD 20892 USA. MEDTAP Int Inc, Bethesda, MD USA. Westat, Rockville, MD USA. RP Read, JS (reprint author), NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Execut Bldg,Room 4B11F,6100 Execut Blvd MSC 7510, Bethesda, MD 20892 USA. FU NICHD NIH HHS [N01 HD 43208] NR 45 TC 27 Z9 27 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD APR 14 PY 2000 VL 14 IS 6 BP 691 EP 700 DI 10.1097/00002030-200004140-00008 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 307XH UT WOS:000086679100008 PM 10807192 ER PT J AU Yu, JJ Bicher, A Ma, YK Bostick-Bruton, F Reed, E AF Yu, JJ Bicher, A Ma, YK Bostick-Bruton, F Reed, E TI Absence of evidence for allelic loss or allelic gain for ERCC1 or for XPD in human ovarian cancer cells and tissues SO CANCER LETTERS LA English DT Article DE ovarian cancer; cisplatin; ERCC1; XPD; XPA; nucleotide excision repair ID NUCLEOTIDE EXCISION-REPAIR; MESSENGER-RNA EXPRESSION; DNA-REPAIR; ANTICANCER CHEMOTHERAPY; CARCINOMA CELLS; CISPLATIN; GENE; LINES; COMPLEX; PROTEIN AB We have previously reported on mRNA expression of ERCC1, XPA and XPD in human ovarian cancer cells and tissues. Several factors can influence mRNA expression for any given gene. Alterations in gene copy number for ERCC1 and/or XPD have been reported to occur in malignant glioma specimens. Human ovarian cancer cell lines and tissues were therefore examined for evidence of altered gene copy number in selected genes within the nucleotide excision repair (NER) pathway. Six ovarian cancer cell lines were studied: A2780, A2780/CP70, SKOV3, MCAS, QvCar3 and Caov4. Cellular sensitivity to cisplatin varies by more than 1 log between some of these cells. In each of these cell lines, the genes examined included ERCC1, XPA, XPB, XPD. XPG, CSB and p53. Genomic DNA was also extracted from ovarian cancer specimens taken from 22 patients and assessed for evidence of allelic loss and/or allelic gain for ERCC1 and XPD. Twelve of the clinical specimens were from patients with platinum-sensitive tumors and ten were from patients with platinum-resistant tumors. In no case could we demonstrate a reproducible variation in gene copy number in any cell line. Among the human tissues studied, there was one case of allelic gain out of 22 specimens. We therefore conclude that alterations in gene copy number is not a common event in human ovarian cancer. Other mechanisms must be invoked to explain differences in mRNA expression for these genes. Published by Elsevier Science Ireland Ltd. C1 NCI, Med Ovarian Canc Sect, Med Branch, DCS, Bethesda, MD 20892 USA. RP Reed, E (reprint author), NCI, Med Ovarian Canc Sect, Med Branch, DCS, Bldg 10,Room 12N226, Bethesda, MD 20892 USA. NR 37 TC 11 Z9 11 U1 2 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD APR 14 PY 2000 VL 151 IS 2 BP 127 EP 132 DI 10.1016/S0304-3835(99)00390-0 PG 6 WC Oncology SC Oncology GA 396WQ UT WOS:000166661000002 PM 10738106 ER PT J AU Thompson, DC Perera, K London, R AF Thompson, DC Perera, K London, R TI Spontaneous hydrolysis of 4-trifluoromethylphenol to a quinone methide and subsequent protein alkylation SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article DE 4-TFMP; quinone methide; protein alkylation ID RAT-LIVER SLICES; MUSCLE GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; MECHANISM-BASED INACTIVATION; PROSTATIC ACID-PHOSPHATASE; IDENTIFICATION; METABOLISM; CRESOL; SITE; SUBSTITUTION; REACTIVITY AB 4-Trifluoromethylphenol (4-TFMP) was cytotoxic to precision-cut rat liver slices as indicated by loss of intracellular potassium. Intracellular glutathione levels decreased and fluoride ion levels increased in a time and concentration-dependent manner. The cytotoxicity of 4-TFMP did not appear to be due to the release of fluoride, however, since equimolar concentrations of sodium fluoride or potassium fluoride were not toxic. The ortho isomer (2-TFMP), which had a threefold slower rate of fluoride release, was much less toxic to liver slices. Ln incubations without slices, 4-TFMP spontaneously hydrolyzed in aqueous buffer at physiological pH to form 4-hydroxybenzoic acid via a quinone methide intermediate. The quinone methide was trapped by the addition of glutathione. Analysis of the glutathione adduct indicated that all of the fluorine atoms were lost during the hydrolysis, yielding a cresol derivative with the glutathione moiety attached to a benzylic carbonyl group. The glutathione conjugate was the primary product formed at low alkylphenol/glutathione ratios; however, at higher 4-TFMP concentrations additional unidentified products were observed. 4-TFMP also inhibited the in vitro enzyme activity of purified glyceraldehyde-3-phosphate dehydrogenase, a sulfhydryl-dependent enzyme, in a time and concentration-dependent manner. Loss of thiol residues closely paralleled the loss in enzyme activity. The coaddition of glutathione prevented 4-TFMP-induced loss of enzyme activity. The cytotoxicity of 4-TFMP therefore appears to be due to spontaneous quinone methide formation and subsequent alkylation of cellular macromolecules. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Texas A&M Univ, Hlth Sci Ctr, Dept Med Pharmacol & Toxicol, College Stn, TX 77843 USA. NIEHS, Lab Mol Biophys, Res Triangle Pk, NC 27709 USA. RP Thompson, DC (reprint author), Monsanto Co, Metab & Safety Evaluat, 04G,800 N Lindbergh Blvd, St Louis, MO 63167 USA. FU NIEHS NIH HHS [5 R 29 ES06016] NR 29 TC 14 Z9 16 U1 4 U2 6 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD APR 14 PY 2000 VL 126 IS 1 BP 1 EP 14 DI 10.1016/S0009-2797(99)00162-3 PG 14 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 307YB UT WOS:000086680800001 PM 10826650 ER PT J AU Senzaki, H Paolocci, N Gluzband, YA Lindsey, ML Janicki, JS Crow, MT Kass, DA AF Senzaki, H Paolocci, N Gluzband, YA Lindsey, ML Janicki, JS Crow, MT Kass, DA TI beta-blockade prevents sustained metalloproteinase activation and diastolic stiffening induced by angiotensin II combined with evolving cardiac dysfunction SO CIRCULATION RESEARCH LA English DT Article DE angiotensin II; heart failure; metalloproteinase; diastole; beta-receptor blocker ID CONGESTIVE-HEART-FAILURE; REGULATE GENE-EXPRESSION; FAILING HUMAN HEART; DILATED CARDIOMYOPATHY; MYOCARDIAL COLLAGEN; INDUCED HYPERTROPHY; ALDOSTERONE SYSTEM; UP-REGULATION; HUMAN FOREARM; IN-VITRO AB Angiotensin II (Ang II)-mediated sympathostimulation may worsen the progression of cardiac failure, although the nature and mechanisms of such interactions are largely unknown. We previously demonstrated that Ang II combined with evolving cardiodepression (48-hour tachycardia pacing, 48hP) induces marked chamber stiffening and increases metalloproteinases (MMPs). Here, we test the hypothesis that both abnormalities stem from sympathostimulatory effects of Ang II. Forty-eight dogs were instrumented to serially assess conscious ventricular mechanics, MMP abundance and activity, and myocardial histopathology. 48hP combined with 5 days of Ang II (15 +/- 5 ng . kg(-1) min(-1) IV) more than doubled chamber stiffness (end-diastolic pressure >25 mm Hg, P<0.001), whereas stiffness was unchanged by Ang II or 48hP alone. In vitro and in situ zymography revealed increased MMP abundance and activity (principally 92-kDa gelatinase) from Ang II+4XhP. Both stiffening and MMP changes were prevented by cotreatment with high-dose atenolol (which nearly fully inhibited isoproterenol-induced inotropy) but not partial P-blockade. Myocellular damage with fibroblast/neutrophil infiltration from Ang II+48hP was also inhibited by high- but not low-dose atenolol, whereas collagen content was not elevated with either dose. These data support a role of sympathostimulation by Ang II in modulating myocardial MMP abundance and activity and diastolic stiffening in evolving heart failure and suggest a novel mechanism by which beta-blockade may limit chamber remodeling and diastolic dysfunction. C1 Johns Hopkins Med Inst, Div Cardiol, Dept Med, Baltimore, MD 21287 USA. NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. Methodist Hosp, Dept Med, DeBakey Heart Ctr, Cardiovasc Sci Sect, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Auburn Univ, Dept Anat Physiol & Pharmacol, Auburn, AL 36849 USA. RP Kass, DA (reprint author), Johns Hopkins Med Inst, Div Cardiol, Dept Med, Halsted 500,600 N Wolfe St, Baltimore, MD 21287 USA. RI Lindsey, Merry/B-2650-2012; OI Senzaki, Hideaki/0000-0002-8289-0953 FU NHLBI NIH HHS [1T32HL781603, P01HL42550]; PHS HHS [P50-52307] NR 57 TC 67 Z9 70 U1 0 U2 3 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 14 PY 2000 VL 86 IS 7 BP 807 EP 815 PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 307FW UT WOS:000086643600016 PM 10764416 ER PT J AU Liu, QY Coulombe, M Dumm, J Shaffer, KM Schaffner, AE Barker, JL Pancrazio, JJ Stenger, DA Ma, W AF Liu, QY Coulombe, M Dumm, J Shaffer, KM Schaffner, AE Barker, JL Pancrazio, JJ Stenger, DA Ma, W TI Synaptic connectivity in hippocampal neuronal networks cultured on micropatterned surfaces SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE synaptogenesis; spontaneous synaptic current; evoked synaptic current; autaptic response; neuronal circuit; rat hippocampus ID EARLY POSTNATAL LIFE; EXCITATORY TRANSMITTER; NEUROBLASTOMA-CELLS; GABA; OUTGROWTH; SURVIVAL; GROWTH; CNS AB Embryonic rat hippocampal neurons were grown on patterned silane surface in order to organize synapse formations in a controlled manner. The surface patterns were composed of trimethoxysilylpropyl-diethylenetriamine (DETA) lines separated by tridecafluoro-1,1,2,2-tetrahydrooctyl-1-dimethylchlorosilane (13F) spaces. Pre- and post-synaptic specializations were identified by immunostaining for synapsin I and microtubule-associated protein-2 (MAP-2). Functional synaptic connections were examined by recording simultaneously from pairs of neurons using the whole-cell configuration of the patch-clamp technique. Spontaneous and evoked synaptic currents were recorded in neurons cultured for 2-14 days. The formation of functional connections was accompanied by the appearance of spontaneous synaptic currents (SSCs), which could be detected after similar to 3 days in culture in the absence of evoked synaptic currents (ESCs). ESCs were detected only after similar to 7 days in culture, mostly in the form of unidirectional synaptic connections. Other forms of synaptic connectivity, such as bidirectional and autaptic connections, were also identified. Both transient GABAergic and glutamatergic signals mediated the transmissions between communicating cells. These results demonstrate the combination of various types of synaptic connections forming simple and complex networks in neurons cultured on line (DETA)-space (13F) patterns. Finally, precisely synchronized SSCs were recorded in neuron pairs cultured on pattern indicating the existence of a fast-acting feedback mechanism mediated by pre-synaptic GABAA receptors. (C) 2000 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. Sci Applicat Int Corp, Rockville, MD 20850 USA. RP Ma, W (reprint author), USN, Res Lab, Ctr Biomol Sci & Engn, Code 6910,4555 Overlook Ave SW, Washington, DC 20375 USA. RI Pancrazio, Joseph/M-3206-2015 OI Pancrazio, Joseph/0000-0001-8276-3690 NR 25 TC 26 Z9 26 U1 0 U2 2 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 14 PY 2000 VL 120 IS 2 BP 223 EP 231 DI 10.1016/S0165-3806(00)00014-6 PG 9 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 307ZQ UT WOS:000086684400010 ER PT J AU Shou, MG Lu, T Krausz, KW Sai, Y Yang, TJ Korzekwa, KR Gonzalez, FJ Gelboin, HV AF Shou, MG Lu, T Krausz, KW Sai, Y Yang, TJ Korzekwa, KR Gonzalez, FJ Gelboin, HV TI Use of inhibitory monoclonal antibodies to assess the contribution of cytochromes P450 to human drug metabolism SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE cytochrome P450; monoclonal antibody; cDNA-expression; inhibition; liver microsome, human; drug metabolism ID HUMAN-LIVER-MICROSOMES; DIAZEPAM METABOLISM; ENZYMES; RAT; CHLORZOXAZONE; EXPRESSION; 6-HYDROXYLATION; SPECIFICITY; SELECTIVITY; ACTIVATION AB Three inhibitory monoclonal antibodies specific to cytochrome P450 3A4/5 (CYP3A3/5), CYP2C8/9/19 and CYP2E1, respectively, were used to assess the contribution of the P450s to the metabolism of seven substrates in liver microsomes from 18 human donors, as measured by monoclonal antibody inhibition phenotyping of the substrate conversion to product(s). Metabolism of seven substrates by recombinant cytochromes P450 and human liver microsomes was performed in the presence of monoclonal antibodies and their metabolites were analyzed by high-performance liquid chromatography (HPLC) or gas chromatography-mass spectrophotometry (GC-MS) to measure the magnitude of inhibition. Our results showed that CYP3A4/5 contributes to testosterone 6 beta-hydroxylation, taxol phenol formation, diazepam 3-hydroxylation, diazepam N-demethylation, and aflatoxin B1 3-hydroxylation in human liver by 79.2%, 81.5%, 73.2%, 34.5% and 80%, respectively. CYP2E1 contributes to chlorzoxazone 6-hydroxylation, p-nitroanisole O-demethylation, and toluene hydroxylation by 45.8%, 27.7% and 44.2% respectively, and CYP2C8/9/19 contribute to diazepam N-demethylation by 30.6%. The additive contribution (75.3%) of human CYP3A and CYP2C to diazepam N-demethylation was also observed in the presence of both anti-CYP3A4/5 and anti-CYP2C8/9/19 monoclonal antibodies. The contribution of individual P450s to the specific metabolic reaction in human liver varies greatly in the individual donors and the substrates examined. Thus, inhibitory monoclonal antibodies could play a unique role in defining the single or subfamily of cytochrome P450 that is responsible for the metabolism of specific drugs. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Merck Res Labs, Dept Drug Metab, W Point, PA 19486 USA. NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Camitro Corp, Menlo Park, CA 94025 USA. NCI, Met Lab, NIH, Bethesda, MD 20892 USA. RP Shou, MG (reprint author), Merck Res Labs, Dept Drug Metab, WP75A-203, W Point, PA 19486 USA. NR 36 TC 28 Z9 30 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD APR 14 PY 2000 VL 394 IS 2-3 BP 199 EP 209 DI 10.1016/S0014-2999(00)00079-0 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 306DV UT WOS:000086582800005 PM 10771285 ER PT J AU Elliot, EE White, JM AF Elliot, EE White, JM TI Long-term abecarnil administration produces tolerance and withdrawal signs in the rat SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE radiotelemetry; abecarnil; withdrawal, precipitated ID BETA-CARBOLINE ABECARNIL; GENERALIZED ANXIETY DISORDER; BENZODIAZEPINE RECEPTOR LIGANDS; PLACEBO-CONTROLLED TRIAL; DIFFERENT SEIZURE MODELS; ANTICONVULSANT TOLERANCE; DOUBLE-BLIND; DIAZEPAM; MICE; ALPRAZOLAM AB Abecarnil is a non-benzodiazepine that possesses anxiolytic and anticonvulsant properties. Conflicting reports of tolerance and withdrawal signs following chronic abecarnil administration have emerged from animal studies using different species and different models of tolerance and dependence. This study used a radiotelemetric method to examine any emergence of tolerance and abstinence signs in the rat following long-term abecarnil administration. Hooded Wistar rats, n = 6 per group, were administered either abecarnil (8 mg/kg/bidaily, i.p.) or vehicle for 24 days. Locomotor activity, body temperature and electromyographic (EMG) activity were measured daily immediately following abecarnil administration. Tolerance to the abecarnil induced muscle relaxant effects and decreased locomotor activity developed within 21 days. Administration of the benzodiazepine antagonist flumazenil (25 mg/kg), 18 h after abecarnil cessation, precipitated abstinence signs that included decreases in body temperature, and large increases in locomotor activity and muscle tone. Moreover, continuous recording of these measures over the 4 days after flumazenil administration indicated a prolonged increase in daytime locomotor activity, suggestive of spontaneous withdrawal. These data support earlier findings that reported signs of tolerance during administration of abecarnil and abstinence signs following abecarnil cessation. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Univ Adelaide, Dept Clin & Expt Pharmacol, Adelaide, SA 5005, Australia. RP Elliot, EE (reprint author), NIDA, Dept Psychobiol, NIH, Bldg C,Room 327,5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI White, Jason /A-2795-2011 OI White, Jason /0000-0001-6750-1078 NR 21 TC 3 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD APR 14 PY 2000 VL 394 IS 2-3 BP 237 EP 245 DI 10.1016/S0014-2999(00)00165-5 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 306DV UT WOS:000086582800009 PM 10771289 ER PT J AU Sekiya, I Tsuji, K Koopman, P Watanabe, H Yamada, Y Shinomiya, K Nifuji, A Noda, M AF Sekiya, I Tsuji, K Koopman, P Watanabe, H Yamada, Y Shinomiya, K Nifuji, A Noda, M TI SOX9 enhances aggrecan gene promoter/enhancer activity and is up-regulated by retinoic acid in a cartilage-derived cell line, TC6 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SRY-RELATED GENE; CHONDROCYTE-SPECIFIC ENHANCER; AUTOSOMAL SEX REVERSAL; RAT OSTEO-SARCOMA; II COLLAGEN GENE; TRANSGENIC MICE; CAMPOMELIC DYSPLASIA; MOUSE; DNA; CHONDROGENESIS AB SOX9 is a transcription factor that plays a key role in chondrogenesis, Aggrecan is one of the major structural components in cartilage; however, the molecular mechanism of aggrecan gene regulation has not yet been fully elucidated, TC6 is a clonal chondrocytic cell line derived from articular cartilage, The purpose of this study was to examine whether SOX9 modulates aggrecan gene expression and to further identify molecules that regulate Sox9 expression in TC6 cells. SOX9 overexpression in TC6 cells enhanced by similar to 3-fold the transcriptional activity of the AgCAT-8 construct containing S-kilobase (kb) promoter/first exon/first intron fragments of the aggrecan gene. SOX9 enhancement of aggrecan promoter activity was lost when we deleted a 4.5-kb fragment from the 3'-end of the 8-kb fragment corresponding to the region including the first intron, In TC6 cells, SOX9 enhanced the transcriptional activity of a reporter construct containing the Sry/Sox consensus sequence >10-fold. SOX9 enhancement of aggrecan gene promoter activity and SOX9 transactivation through the Sry/Sox consensus sequence were not observed in osteoblastic osteosarcoma cells (ROS17/2.8), indicating the dependence on the cellular background. Northern blot analysis indicated that TC6 cells constitutively express Sox9 mRNA at relatively low levels. To examine regulation of Sox9 gene expression, we investigated the effects of calciotropic hormones and cytokines, Among these, retinoic acid (RA) specifically enhanced Sox9 mRNA expression in TC6 cells. The basal levels of Sox9 expression and its enhancement by RA were observed similarly at both permissive (33 degrees C) and nonpermissive (39 degrees C) temperatures. Furthermore, RA treatment enhanced the transcriptional activity of a reporter construct containing the Sry/Sox consensus sequence in TC6 cells. Moreover, RA treatment also enhanced the transcriptional activity of another reporter construct containing the enhancer region of the type II procollagen gene in TC6 cells. These observations indicate that SOX9 enhances aggrecan promoter activity and that its expression is up-regulated by RA in TC6 cells. C1 Tokyo Med & Dent Univ, Inst Med Res, Dept Mol Pharmacol, Chiyoda Ku, Tokyo 1010062, Japan. Tokyo Med & Dent Univ, Dept Orthopaed Surg, Tokyo 101, Japan. Univ Queensland, Ctr Cellular & Mol Biol, Brisbane, Qld 4072, Australia. NIDCR, Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Noda, M (reprint author), Tokyo Med & Dent Univ, Inst Med Res, Dept Mol Pharmacol, Chiyoda Ku, 2-3-10 Kanda Surugadai, Tokyo 1010062, Japan. RI Koopman, Peter /C-9416-2009 OI Koopman, Peter /0000-0001-6939-0914 NR 38 TC 290 Z9 307 U1 1 U2 11 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 14 PY 2000 VL 275 IS 15 BP 10738 EP 10744 DI 10.1074/jbc.275.15.10738 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 304DB UT WOS:000086466600006 PM 10753864 ER PT J AU Chiang, JYL Kimmel, R Weinberger, C Stroup, D AF Chiang, JYL Kimmel, R Weinberger, C Stroup, D TI Farnesoid X receptor responds to bile acids and represses cholesterol 7 alpha-hydroxylase gene (CYP7A1) transcription SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ORPHAN NUCLEAR RECEPTOR; HEPG2 CELLS; IDENTIFICATION; PROMOTER; ELEMENT; METABOLITES; ACTIVATION; EXPRESSION; PATHWAY; LIGANDS AB Cholesterol 7 alpha-hydroxylase gene (CYP7A1) transcription is repressed by bile acids. The goal of this study is to elucidate the mechanism of CYP7A1 transcription by bile acid-activated farnesoid X receptor (FXR) in its native promoter and cellular context and to identify FXR response elements in the gene. In Chinese hamster ovary cells transfected with retinoid X receptor alpha (RXR alpha)/FXR, only chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA) were able to stimulate a heterologous promoter/reporter containing an ecdysone response element. In HepG2 cells, all bile acids (25 mu M) were able to repress CYP7A1/luciferase reporter activity, and only CDCA and DCA further repressed reporter activity when cotransfected with RXR alpha/FXR, The concentration of CDCA required to inhibit 50% of reporter activity (IC(50)) was determined to be approximately 25 mu M without FXR and 10 mu M with FXR. Deletion analysis revealed that the bile acid response element located between nucleotides -148 and -128 was the FXR response element, but RXR alpha/FXR did not bind to this sequence. These results suggest that bile acid-activated FXR exerts its inhibitory effect on CYP7A1 transcription by an indirect mechanism, in contrast to the stimulation and binding of FXR to intestinal bile acid-binding protein gene promoter. Results also reveal that bile acid receptors other than FXR are present in HepG2 cells. C1 NE Ohio Univ, Coll Med, Dept Biochem & Mol Pathol, Rootstown, OH 44272 USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Chiang, JYL (reprint author), NE Ohio Univ, Coll Med, Dept Biochem & Mol Pathol, POB 95, Rootstown, OH 44272 USA. EM jchiang@neoucom.edu OI Chiang, John/0000-0001-9360-7650 FU NIDDK NIH HHS [DK44442, R01 DK044442, R01 DK058379]; NIGMS NIH HHS [GM31584] NR 31 TC 187 Z9 191 U1 2 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 14 PY 2000 VL 275 IS 15 BP 10918 EP 10924 DI 10.1074/jbc.275.15.10918 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 304DB UT WOS:000086466600032 PM 10753890 ER PT J AU Lubas, WA Hanover, JA AF Lubas, WA Hanover, JA TI Functional expression of O-linked GlcNAc transferase - Domain structure and substrate specificity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-N-ACETYLGLUCOSAMINYLTRANSFERASE; INSULIN-RESISTANCE; CYTOPLASMIC PROTEINS; NUCLEAR-PORE; TETRATRICOPEPTIDE REPEATS; GLYCOSYLATION; PATHWAY; GLYCOPROTEINS; GLUCOSAMINE; TPR AB O-GlcNAc transferase (OGT) modifies nuclear pore proteins and transcription factors. In Arabidopsis, the OGT homolog participates in the gibberellin signaling pathway. We and others have proposed that mammalian OGT is the terminal step in a glucose-sensitive signal transduction pathway that becomes disregulated in insulin resistance. To facilitate mutational analysis of OGT in the absence of competing endogenous activity, we expressed the 103-kDa human. OGT in Escherichia coli. Kinetic parameters for the purified recombinant enzyme (K-m = 1.2 mu M for Nup 62; K-m = 0.5 mu M for UDP-GlcNAc) are nearly identical to purified mammalian OGT. Deletions in the highly conserved C terminus result in a complete loss of activity. The N-terminal tetratricopeptide repeat domain is required for optimal recognition of substrates, Removal of the first three tetratricopeptide repeats greatly reduces the O-GlcNAc addition to macromolecular substrates. However, this altered enzyme retains full activity against appropriate synthetic peptides. Autoglycosylation of OGT is augmented when the first six tetratricopeptide repeats are removed showing that these repeats are not required for catalysis. Given its proposed role in modulating insulin action, OGT may modify kinases involved in this signaling cascade. Among the many kinases tested, OGT glycosylates glycogen synthase kinase-3 and casein kinase II, two enzymes critical in the regulation of glycogen synthesis. C1 NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. RP Hanover, JA (reprint author), NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. NR 32 TC 178 Z9 186 U1 3 U2 21 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 14 PY 2000 VL 275 IS 15 BP 10983 EP 10988 DI 10.1074/jbc.275.15.10983 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 304DB UT WOS:000086466600041 PM 10753899 ER PT J AU Paine, E Palmantier, R Akiyama, SK Olden, K Roberts, JD AF Paine, E Palmantier, R Akiyama, SK Olden, K Roberts, JD TI Arachidonic acid activates mitogen-activated protein (MAP) kinase-activated protein kinase 2 and mediates adhesion of a human breast carcinoma cell line to collagen type IV through a p38 MAP kinase-dependent pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL-TRANSDUCTION PATHWAYS; HEAT-SHOCK PROTEIN-27; CAP-BINDING-PROTEIN; N-TERMINAL KINASE; GENE-EXPRESSION; EXTRACELLULAR-MATRIX; CANCER METASTASIS; LINOLEIC-ACID; TYROSINE PHOSPHORYLATION; HELA-CELLS AB Adhesion of metastatic human mammary carcinoma MDA-MB-435 cells to the basement membrane protein collagen type TV can be activated by treatment with arachidonic acid. We initially observed that this arachidonic acid-mediated adhesion was inhibited by the tyrosine kinase inhibitor genistein, Therefore, we examined the role of the mitogen-activated protein (MAP) kinase family tyrosine phosphorylation-regulated pathways in arachidonic acid-stimulated cell adhesion. Arachidonic acid stimulated the phosphorylation of p38, the activation of MAP kinase-activated protein kinase 2 (MAPKAPK2, a downstream substrate of p38), and the phosphorylation of heat shock protein 27 (a downstream substrate of MAP kinase-activated protein kinase 2), Treatment with the p38 inhibitor PD169316 completely and specifically inhibited arachidonic acid-mediated cell adhesion to collagen type TV. p38 activity was specifically associated with arachidonic acid-stimulated adhesion; this was demonstrated by the observation that 12-O-tetradecanoylphorbol 13-acetate-activated cell adhesion was not blocked by inhibiting p38 activity. Extracellular signal-regulated protein kinases (ERKs) 1 and 2 were also activated by arachidonic acid; however, cell adhesion to collagen type TV was not highly sensitive to PD98059, an inhibitor of MAP kinase kinase/ERK kinase 1 (MEK1) that blocks activation of the ERKs. c-Jun NH2-terminal kinase was not activated by arachidonic acid treatment of these cells. Together, these data suggest a novel role for p38 MAP kinase in regulating adhesion of breast cancer cells to collagen type IV. C1 NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP NIEHS, Mol Carcinogenesis Lab, NIH, Mail Drop C2-14, Res Triangle Pk, NC 27709 USA. EM Roberts1@niehs.nih.gov NR 90 TC 75 Z9 81 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD APR 14 PY 2000 VL 275 IS 15 BP 11284 EP 11290 DI 10.1074/jbc.275.15.11284 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 304DB UT WOS:000086466600081 PM 10753939 ER PT J AU Espey, MG Miranda, KM Pluta, RM Wink, DA AF Espey, MG Miranda, KM Pluta, RM Wink, DA TI Nitrosative capacity of macrophages is dependent on nitric-oxide synthase induction signals SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STIMULATED MACROPHAGES; MOUSE MACROPHAGES; IN-VITRO; OXIDATION; KINETICS; NITRATE; ASSOCIATION; HEPATOCYTES; MECHANISMS; INHIBITION AB Nitrosative stress can occur when reactive nitric oxide (NO) species compromise the function of biomolecules via formation of NO adducts on critical amine and thiol residues. The capacity of inducible nitric-oxide synthase (iNOS) to generate nitrosative stress was investigated in the murine macrophage line ANA-1. Sequential activation with the cytokines IFN-gamma and either tumor necrosis factor-alpha or interleukin-1 beta resulted in the induction of iNOS and production of nitrite (20 nM/min) but failed to elicit nitrosation of extracellular 2,3-diaminonapthalene. Stimulation with IFN-gamma and bacterial lipopolysaccharide increased the relative level of iNOS protein and nitrite production of ANA-1 cells S-fold; however, a substantial level of NO in the media was also observed, and nitrosation of 2,3-diaminonapthalene was increased greater than 30-fold. Selective scavenger compounds suggested that the salient nitrosating mechanism was the NO/O-2 reaction leading to N2O3 formation. These data mimicked the pattern observed with a 5 mu M concentration of the synthetic NO donor (Z)-1-[N-ammoniopropyl) -N-(n-propyl) aminoldiazen-1-ium- 1,2-diolate (PAPA/NO), The NO profiles derived from iNOS can be distinct and depend on the inductive signal cascades. The diverse consequences of NO production in macrophages may reside in the cellular mechanisms that control the ability of iNOS to form N2O3 and elicit nitrosative stress. C1 NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Espey, MG (reprint author), NCI, Radiat Biol Branch, NIH, Bldg 10,Rm B3-B69, Bethesda, MD 20892 USA. RI Miranda, Katrina/B-7823-2009 NR 43 TC 66 Z9 66 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 14 PY 2000 VL 275 IS 15 BP 11341 EP 11347 DI 10.1074/jbc.275.15.11341 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 304DB UT WOS:000086466600089 PM 10753947 ER PT J AU Yee, J Mowatt, MR Dennis, PP Nash, TE AF Yee, J Mowatt, MR Dennis, PP Nash, TE TI Transcriptional analysis of the glutamate dehydrogenase gene in the primitive eukaryote, Giardia lamblia - Identification of a primordial gene promoter SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SINGLE-STRANDED-DNA; ARCHAEBACTERIUM HALOBACTERIUM-CUTIRUBRUM; UNUSUAL RIBOSOMAL-RNA; PROTEIN-CODING GENES; BOX-BINDING-PROTEIN; CYST WALL PROTEIN; TRYPANOSOMA-BRUCEI; MESSENGER-RNA; POLYMERASE-I; SEQUENCES AB We studied gene expression in the ancient eukaryote, Giardia lamblia, by taking advantage of assays developed recently in our laboratory, which allow new genetic analyses of this organism. We examined the transcription of a 2.2-kilobase segment of the Giardia genome that contains the glutamate dehydrogenase (GDH) gene and a portion of a second open reading frame encoding an uncharacterized gene. Nuclear firn-on analyses showed that the genes are transcribed as two separate units spaced less than 200 base pairs apart, and transcription of the GDH gene initiates just 3-6 nucleotides upstream of its translation start codon, We characterized the GDH promoter by transfecting Giardia with DNA constructs that used the GDH upstream sequence to drive the expression of a luciferase reporter gene. By deletion and mutational analyses, we localized promoter function to three motifs within a 50-base pair region of the GDH upstream sequence. Using band shift assays and UV cross-linking, we demonstrated specific binding of a 68-kDa protein from Giardia nuclear extracts to short poly(T) tracts contained within two of the sequence motifs on single-stranded DNA from the promoter region, This report describes one of the first functional gene promoter and its cognate DNA-binding protein in this primitive eukaryote. C1 NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V5Z 1M9, Canada. RP Yee, J (reprint author), Trent Univ, Dept Biol, 1600 W Bank Dr, Peterborough, ON K9J 7B8, Canada. NR 39 TC 59 Z9 61 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 14 PY 2000 VL 275 IS 15 BP 11432 EP 11439 DI 10.1074/jbc.275.15.11432 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 304DB UT WOS:000086466600102 PM 10753960 ER PT J AU Bergel, M Herrera, JE Thatcher, BJ Prymakowska-Bosak, M Vassilev, A Nakatani, Y Martin, B Bustin, M AF Bergel, M Herrera, JE Thatcher, BJ Prymakowska-Bosak, M Vassilev, A Nakatani, Y Martin, B Bustin, M TI Acetylation of novel sites in the nucleosomal binding domain of chromosomal protein HMG-14 by p300 alters its interaction with nucleosomes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HISTONE ACETYLTRANSFERASE ACTIVITY; TRANSCRIPTIONAL REPRESSION; ADA-COMPLEX; IN-VIVO; CHROMATIN; YEAST; EXPRESSION; ACTIVATION; DISTINCT; GCN5 AB The reversible acetylation of histones is associated with structural alterations in the chromatin fiber that affect various DNA-related activities. Here we show that the histone acetyltransferase p300 specifically acetylates HMG-14, a nonhistone structural protein that binds to nucleosomes and reduces the compactness of the chromatin fiber. We identify 7 major acetylation sites, 6 of which are novel and have not been known to be acetylated in either HMG-14 or the closely related HMG-17 protein. All the acetylation sites involve evolutionarily conserved residues: 3 within the HMG-14/-17 nucleosomal binding domain and 4 in or near the bipartite nuclear localization domains of the proteins. In tissue culture cells the acetylation pattern is indicative of a selective process in which a subfraction of HMG-14 is preferentially acetylated. We find that the nucleosomal binding domain is a major target for acetylation in vivo and that the specific acetylation of HMG-14 by p300 weakens its interaction with nucleosome cores. Our results suggest that p300 modulates the interaction of HMG-14 with nucleosomes. Thus, p300 may affect chromatin-related activities not only by modifying histones or transcription factors but also by targeting structural nonhistone proteins. C1 NCI, Prot Sect, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NIMH, Unit Mol Struct, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. NICHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Bergel, M (reprint author), NCI, Prot Sect, Div Basic Sci, NIH, Bldg 37,Rm 3D-20, Bethesda, MD 20892 USA. RI Bustin, Michael/G-6155-2015 NR 39 TC 47 Z9 47 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 14 PY 2000 VL 275 IS 15 BP 11514 EP 11520 DI 10.1074/jbc.275.15.11514 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 304DB UT WOS:000086466600113 PM 10753971 ER PT J AU Krishnamoorthy, R Agarwal, N Chaitin, MH AF Krishnamoorthy, R Agarwal, N Chaitin, MH TI Upregulation of CD44 expression in the retina during the rds degeneration SO MOLECULAR BRAIN RESEARCH LA English DT Article DE CD44; Muller cells; rds mouse; retina; retinal degeneration ID GENE-EXPRESSION; GROWTH-FACTOR; CELL-SURFACE; BINDING; ISOFORMS; LOCALIZATION; PROTEOGLYCAN; FIBROBLASTS; ASTROCYTES; HYALURONAN AB In adult mouse retinas the standard form of the cell surface adhesion/receptor molecule CD44 is localized to Muller cell apical microvilli. In the rds (retinal degeneration slow) mouse, however, CD44 immunolabel is increased and distributed throughout the retina by 3 months postnatal. At present, it is unclear if this labeling pattern is due to the increased expression of standard CD44, the expression of variant CD44 isoforms, or an unmasking of CD44 antigenic sites. To further characterize this response, we have studied the expression of CD44 mRNA and protein in rds retinas of different ages. RT-PCR analysis demonstrated one product which represented the message for standard CD44 in adult BALB/c mouse retina and in all ages of rds retinas studied. Upon Southern blotting, this major product was detected along with two minor bands of larger size in all samples. Northern blot analysis demonstrated a major transcript of approximately 4.0 kb and a minor one of 3.0 kb in all BALB/c and rds retinas. By 3 months postnatal in rds retinas, the expression of CD44 message was increased by at least two-fold. Western blot analysis demonstrated the presence of only the standard form of CD44 protein in all BALB/c and rds retinas. An increased amount of this standard CD44 protein was observed in 2, 3, and 6 month rds retinas. Thus, this study demonstrates that the inherited retinal degeneration exhibited by the rds mouse does not cause an altered expression of retinal CD44 isoforms, but does lead to an upregulation in the expression of mRNA and protein for standard CD44. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Univ N Texas, Hlth Sci Ctr, Div Struct & Cell Biol, Dept Pathol & Anat, Ft Worth, TX 76107 USA. Univ N Texas, Hlth Sci Ctr, Eye Res Inst, Ft Worth, TX 76107 USA. RP Chaitin, MH (reprint author), Ctr Sci Review, NIH, Rockledge 2 Bldg,Rm 5202,MSC 7850,6701 Rockledge, Bethesda, MD 20892 USA. NR 25 TC 20 Z9 20 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD APR 14 PY 2000 VL 77 IS 1 BP 125 EP 130 DI 10.1016/S0169-328X(00)00035-8 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 317WX UT WOS:000087250900013 ER PT J AU Guidetti, P Reddy, PH Tagle, DA Schwarcz, R AF Guidetti, P Reddy, PH Tagle, DA Schwarcz, R TI Early kynurenergic impairment in Huntington's Disease and in a transgenic animal model SO NEUROSCIENCE LETTERS LA English DT Article DE excitotoxicity; free radicals; huntingtin; 3-hydroxykynurenine; kynurenic acid; neurodegeneration ID QUINOLINIC ACID; BRAIN; 3-HYDROXYKYNURENINE; NEUROTOXICITY; METABOLITE; CORTEX AB Several neuroactive metabolites of the kynurenine pathway of tryptophan degradation have been speculatively linked to the pathophysiology of Huntington's Disease (HD). Here we demonstrate that the levels of two of these metabolites, the free radical generator 3-hydroxykynurenine (3HK) and the neuroprotectant kynurenate (KYNA), are increased in the neostriatum of stage 1 HD patients and in the brain of mice transgenic for full-length mutant huntingtin. In both cases, the elevation in 3HK was far more pronounced, resulting in significant increases in the 3HK/KYNA ratios. These data suggest that abnormal kynurenine pathway metabolism may play a role during the early phases of the neurodegenerative process in HD. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Maryland, Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA. Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. RP Schwarcz, R (reprint author), Univ Maryland, Maryland Psychiat Res Ctr, POB 21247, Baltimore, MD 21228 USA. FU NIMH NIH HHS [MH/NS 31862]; NINDS NIH HHS [NS 28236] NR 24 TC 65 Z9 67 U1 0 U2 2 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 14 PY 2000 VL 283 IS 3 BP 233 EP 235 DI 10.1016/S0304-3940(00)00956-3 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 305KW UT WOS:000086540100019 PM 10754231 ER PT J AU Priola, SA AF Priola, SA TI Antiscrapie drug action - Response SO SCIENCE LA English DT Letter C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. RP Priola, SA (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 14 PY 2000 VL 288 IS 5464 BP 274 EP 274 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 303YA UT WOS:000086454300021 ER PT J AU Farci, P Shimoda, A Coiana, A Diaz, G Peddis, G Melpolder, JC Strazzera, A Chien, DY Munoz, SJ Balestrieri, A Purcell, RH Alter, HJ AF Farci, P Shimoda, A Coiana, A Diaz, G Peddis, G Melpolder, JC Strazzera, A Chien, DY Munoz, SJ Balestrieri, A Purcell, RH Alter, HJ TI The outcome of acute hepatitis C predicted by the evolution of the viral quasispecies SO SCIENCE LA English DT Article ID NON-B-HEPATITIS; HYPERVARIABLE REGION-1; VIRUS-INFECTION; LONG-TERM; NON-A; HYPERIMMUNE SERUM; IMMUNE-RESPONSE; ENVELOPE; GLYCOPROTEIN; ANTIBODY AB The mechanisms by which hepatitis C virus (HCV) induces chronic infection in the vast majority of infected individuals are unknown. Sequences within the HCV E1 and E2 envelope genes were analyzed during the acute phase of hepatitis C in 12 patients with different clinical outcomes. Acute resolving hepatitis was associated with relative evolutionary stasis of the heterogeneous viral population (quasispecies), whereas progressing hepatitis correlated with genetic evolution of HCV. Consistent with the hypothesis of selective pressure by the host immune system, the sequence changes occurred almost exclusively within the hypervariable region 1 of the E2 gene and were temporally correlated with antibody seroconversion. These data indicate that the evolutionary dynamics of the HCV quasispecies during the acute phase of hepatitis C predict whether the infection will resolve or become chronic. C1 Univ Cagliari, Dept Med Sci, I-09124 Cagliari, Italy. NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Kanazawa Univ, Dept Internal Med, Kanazawa, Ishikawa 9208641, Japan. Univ Cagliari, Dept Cytomorphol, I-09124 Cagliari, Italy. NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Chiron Corp, Emeryville, CA 94507 USA. Albert Einstein Med Ctr, Philadelphia, PA 19141 USA. RP Farci, P (reprint author), Univ Cagliari, Dept Med Sci, Via San Giorgio 12, I-09124 Cagliari, Italy. OI Coiana, Alessandra/0000-0002-1039-5486 NR 50 TC 623 Z9 654 U1 0 U2 13 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 14 PY 2000 VL 288 IS 5464 BP 339 EP 344 DI 10.1126/science.288.5464.339 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 303YA UT WOS:000086454300039 PM 10764648 ER PT J AU Liang, TS Wang, JM Murphy, PM Gao, JL AF Liang, TS Wang, JM Murphy, PM Gao, JL TI Serum amyloid A is a chemotactic agonist at FPR2, a low-affinity N-formylpeptide receptor on mouse neutrophils SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE chemoattractant; inflammation; neutrophil; G-protein-coupled receptor; serum amyloid A ID HUMAN PHAGOCYTES; GENE-CLUSTER; A PROTEIN; EXPRESSION; CHOLESTEROL; CELLS; CDNA; SAA AB Serum amyloid A (SAA) is an acute-phase plasma protein and the source of amyloid A, which accumulates in lesions of secondary amyloidosis. SAA can induce phagocyte migration in vitro and in vivo, and is a specific chemotactic agonist for the human low-affinity N-formylpeptide receptor FPRL1R, a G-protein-coupled receptor expressed on phagocytes. Here we show that FPR2, a mouse counterpart of FPRL1R, is also an SAA receptor. SAA selectively induced calcium flux and chemotaxis in mouse PMN, which express FPR2, as well as in HEK 293 cells expressing recombinant FPR2 but not in HEK 293 cells expressing FPR, a closely related high affinity N-formylpeptide receptor. Consistent with this, SAA activity on PMN from FPR+/+ and FPR-/- mice was indistinguishable. Moreover, the prototype N-formylpeptide fMLF desensitized SAA-induced calcium flux in a dose-dependent manner in both mouse neutrophils and HEK 293/FPR2 transfectants. Our results suggest that FPRB specifically mediates mouse neutrophil migration in response to SAA. (C) 2000 Academic Press. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, NIH, Frederick, MD 21702 USA. RP Gao, JL (reprint author), NIAID, Host Def Lab, NIH, Bldg 10,Room 11N113, Bethesda, MD 20892 USA. NR 22 TC 49 Z9 50 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 2000 VL 270 IS 2 BP 331 EP 335 DI 10.1006/bbrc.2000.2416 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 305DY UT WOS:000086525200001 PM 10753626 ER PT J AU Cheng, QF Gonzalez, P Zigler, JS AF Cheng, QF Gonzalez, P Zigler, JS TI High level of ferritin light chain mRNA in lens SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE L-ferritin; mRNA; gene array; lens; cataract ID HYPERFERRITINEMIA-CATARACT SYNDROME; IRON-RESPONSIVE ELEMENT; L-SUBUNIT GENE; OXIDATIVE STRESS; CATALYZED OXIDATION; LIPID-PEROXIDATION; MESSENGER-RNA; CRYSTALLINS; EXPRESSION; TRANSPORT AB Ferritin is of particular interest with regard to cataract because (i) cataract occurs in individuals with hereditary hyperferritinemia cataract syndrome (HHCS), a condition in which ferritin light chain (L-ferritin) protein is overexpressed systemically, and (ii) ferritin is an important regulator of oxidative stress, a primary factor in the etiology of aging-related cataract. From gene array analysis two novel observations were made with respect to ferritin gene expression: first, lenses from guinea pigs and humans have disproportionately high levels of L-ferritin mRNA relative to the amounts of ferritin protein present, and second, L-ferritin message increased markedly in lenses from guinea pigs with hereditary nuclear cataract. The human lens L-ferritin sequence was identical to previous data from human liver; the guinea pig sequence was 86% identical to the human sequence at the amino acid level. Despite mRNA levels similar to those of major lens crystallins, lens ferritin was undetectable by Western blot techniques. (C) Academic Press. C1 NEI, Lab Mechanisms Ocular Dis, Bethesda, MD 20892 USA. RP Zigler, JS (reprint author), NEI, Lab Mechanisms Ocular Dis, 6 Ctr Dr,MSC2735, Bethesda, MD 20892 USA. NR 34 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 13 PY 2000 VL 270 IS 2 BP 349 EP 355 DI 10.1006/bbrc.2000.2425 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 305DY UT WOS:000086525200004 PM 10753629 ER PT J AU Lee, TH Kim, SJ Kang, SW Lee, KK Rhee, SG Yu, DY AF Lee, TH Kim, SJ Kang, SW Lee, KK Rhee, SG Yu, DY TI Molecular cloning and characterization of the mouse peroxiredoxin V gene SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE peroxiredoxin V; antioxidant enzyme; bacterial artificial chromosome; upstream open reading frame ID THIOL-SPECIFIC ANTIOXIDANT; MAMMALIAN PEROXIREDOXIN; EXPRESSION; FAMILY; REDUCTASE; PROTEIN; IDENTIFICATION; ORGANIZATION; SEQUENCES; MUTATION AB We have cloned two cDNA isoforms as well as genomic sequences of the mouse Prx V gene and characterized their molecular genetic features. Two isoforms of the mouse Prx V cDNA were identified from liver and testis. The testis-originated long transcripts had extra 1164-bp 5'-UTR sequences compared to the liver-originated short transcripts. Primer extension and sequence analyses revealed that the two isoforms were presumably transcribed at the same gene locus. The gene was composed of six exons spanning 3.2 kb. The short transcript was abundantly expressed in the kidney, liver, and heart of the adult mouse tissues and in the extra membrane of the 10.5 dpc embryos. The long transcript of 1985 bp was abundantly detected in testis with trace amounts in other tissues. Interestingly, in testis and fetus, only mRNA expression of the long form was identified. However, the protein expression was not found in testis, implying that the long form could not properly direct the protein expression. The long Prx V cDNA has eight uORFs in the extra 5'-UTR, which proceed the major ORF. The inability of protein expression for the long-form cDNA in testis suggests that the uORFs might inhibit translation of the major ORF and thereby confer the tissue-specific regulation of the mouse Prx V gene. (C) 2000 Academic Press. C1 Korea Res Inst Biosci & Biotechnol, Lab Anim Dev Biotechnol, Yusong Gu, Taejon 305600, South Korea. NHLBI, Lab Cell Signalling, NIH, Bethesda, MD 20892 USA. RP Yu, DY (reprint author), Korea Res Inst Biosci & Biotechnol, Lab Anim Dev Biotechnol, Yusong Gu, POB 115, Taejon 305600, South Korea. NR 24 TC 19 Z9 22 U1 0 U2 3 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 2000 VL 270 IS 2 BP 356 EP 362 DI 10.1006/bbrc.2000.2430 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 305DY UT WOS:000086525200005 PM 10753630 ER PT J AU Piegorsch, WW Simmons, SJ Margolin, BH Zeiger, E Gidrol, XM Gee, P AF Piegorsch, WW Simmons, SJ Margolin, BH Zeiger, E Gidrol, XM Gee, P TI Statistical modeling and analyses of a base-specific Salmonella mutagenicity assay SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE Ames II strains; Salmonella typhimurium; complementary log-log link function; culture-by-dose interaction; fluctuation test; generalized linear model; His(-) mutant tester strains; many-to-one testing; multiple comparisons with a control; statistical methods ID FLUCTUATION TEST; CHEMICALS; STRAINS AB Statistical features of a base-specific Salmonella mutagenicity assay are considered in detail, following up on a previous report comparing responses of base-specific Salmonella (Ames II(TM)) strains with those of traditional tester strains. In addition to using different Salmonella strains, the new procedure also differs in that it is performed as a microwell fluctuation test, as opposed to the standard plate or preincubation test. This report describes the statistical modeling of data obtained from the use of these new strains in the microwell test procedure. We emphasize how to assess any significant interactions between replicate cultures and exposure doses, and how to identify a significant increase in the mutagenic response to a series of concentrations of a test substance. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Univ S Carolina, Dept Stat, Columbia, SC 29208 USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Xenometrix Inc, Boulder, CO 80301 USA. RP Piegorsch, WW (reprint author), Univ S Carolina, Dept Stat, 216 LeConte Coll, Columbia, SC 29208 USA. OI Piegorsch, Walter/0000-0003-2725-5604 NR 18 TC 10 Z9 12 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD APR 13 PY 2000 VL 467 IS 1 BP 11 EP 19 DI 10.1016/S1383-5718(00)00019-X PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 305HT UT WOS:000086534200002 PM 10771267 ER PT J AU Schubert, U Anton, LC Gibbs, J Norbury, CC Yewdell, JW Bennink, JR AF Schubert, U Anton, LC Gibbs, J Norbury, CC Yewdell, JW Bennink, JR TI Rapid degradation of a large fraction of newly synthesized proteins by proteasomes SO NATURE LA English DT Article ID MHC CLASS-I; CHYMOTRYPSIN-LIKE ACTIVITY; MOLECULES; PEPTIDES; INHIBITION; CHAINS; CELLS AB MHC class I molecules function to present peptides eight to ten residues long to the immune system. These peptides originate primarily from a cytosolic pool of proteins through the actions of proteasomes(1), and are transported into the endoplasmic reticulum, where they assemble with nascent class I molecules(2). Most peptides are generated from proteins that are apparently metabolically stable. To explain this, we previously proposed that peptides arise from proteasomal degradation of defective ribosomal products (DRiPs). DRiPs are polypeptides that never attain native structure owing to errors in translation or post-translational processes necessary for proper protein folding(3). Here we show, first, that DRiPs constitute upwards of 30% of newly synthesized proteins as determined in a variety of cell types; second, that at least some DRiPs represent ubiquitinated proteins; and last, that ubiquitinated DRiPs are formed from human immunodeficiency virus Gag polyprotein, a long-lived viral protein that serves as a source of antigenic peptides. C1 NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. Univ Hamburg, Heinrich Pette Inst, Hamburg, Germany. RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. RI yewdell, jyewdell@nih.gov/A-1702-2012; Anton, Luis/C-4740-2013 OI Anton, Luis/0000-0001-9665-011X NR 18 TC 889 Z9 906 U1 1 U2 30 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 13 PY 2000 VL 404 IS 6779 BP 770 EP 774 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 305DF UT WOS:000086523600054 PM 10783891 ER PT J AU El-Sadr, WM Burman, WJ Grant, LB Matts, JP Hafner, R Crane, L Zeh, D Gallagher, B Mannheimer, SB Martinez, A Gordin, F AF El-Sadr, WM Burman, WJ Grant, LB Matts, JP Hafner, R Crane, L Zeh, D Gallagher, B Mannheimer, SB Martinez, A Gordin, F CA Terry Beirn Community Programs Cli TI Discontinuation of prophylaxis against Mycobacterium avium complex disease in HIV-infected patients who have a response to antiretroviral therapy. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; STREPTOCOCCUS-PNEUMONIAE; CYTOMEGALOVIRUS DISEASE; WEEKLY AZITHROMYCIN; ORAL GANCICLOVIR; CONTROLLED TRIAL; PREVENTION; AIDS; BACTEREMIA; ILLNESSES AB Background: Several agents are effective in preventing Mycobacterium avium complex disease in patients with advanced human immunodeficiency virus (HIV) infection. However, there is uncertainty about whether prophylaxis should be continued in patients whose CD4+ cell counts have increased substantially with antiviral therapy. Methods: We conducted a multicenter, double-blind, randomized trial of treatment with azithromycin (1200 mg weekly) as compared with placebo in HIV-infected patients whose CD4+ cell counts had increased from less than 50 to more than 100 per cubic millimeter in response to antiretroviral therapy. The primary end point was M. avium complex disease or bacterial pneumonia. Results: A total of 520 patients entered the study; the median CD4+ cell count at entry was 230 per cubic millimeter. In 48 percent of the patients, the HIV RNA value was below the level of quantification. The median prior nadir CD4+ cell count was 23 per cubic millimeter, and 65 percent of the patients had had an acquired immunodeficiency syndrome-defining illness. During follow-up over a median period of 12 months, there were no episodes of confirmed M. avium complex disease in either group (95 percent confidence interval for the rate of disease in each group, 0 to 1.5 episodes per 100 person-years). Three patients in the azithromycin group (1.2 percent) and five in the placebo group (1.9 percent) had bacterial pneumonia (relative risk in the azithromycin group, 0.60; 95 percent confidence interval, 0.14 to 2.50; P=0.48). Neither the rate of progression of HIV disease nor the mortality rate differed significantly between the two groups. Adverse effects led to discontinuation of the study drug in 19 patients assigned to receive azithromycin (7.4 percent) and in 3 assigned to receive placebo (1.1 percent; relative risk, 6.6; P=0.002). Conclusions: Azithromycin prophylaxis can safely be withheld in HIV-infected patients whose CD4+ cell counts have increased to more than 100 cells per cubic millimeter in response to antiretroviral therapy. (N Engl J Med 2000;342:1085-92.) (C) 2000, Massachusetts Medical Society. C1 Harlem Hosp Ctr, Div Infect Dis, New York, NY 10037 USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. Denver Publ Hlth Dept, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA. NIAID, Div Aids, Bethesda, MD 20892 USA. Wayne State Univ, Detroit, MI USA. Res & Educ Grp, Portland, OR USA. Philadelphia FIGHT, Philadelphia, PA USA. Dept Vet Affairs Med Ctr, Washington, DC USA. RP El-Sadr, WM (reprint author), Harlem Hosp Ctr, Div Infect Dis, 506 Lenox Ave,Rm 3107, New York, NY 10037 USA. FU NCRR NIH HHS [RR00032] NR 32 TC 97 Z9 101 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 13 PY 2000 VL 342 IS 15 BP 1085 EP 1092 DI 10.1056/NEJM200004133421503 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 303DZ UT WOS:000086406700003 PM 10766581 ER PT J AU Spiegel, S Milstien, S AF Spiegel, S Milstien, S TI Functions of a new family of sphingosine-1-phosphate receptors SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS LA English DT Review DE sphingosine 1-phosphate; EDG; G protein-coupled receptor; signal transduction ID PROTEIN-COUPLED RECEPTOR; SPHINGOSINE 1-PHOSPHATE RECEPTORS; CELL-SURFACE RECEPTOR; SWISS 3T3 FIBROBLASTS; LYSOPHOSPHATIDIC ACID; SIGNALING PATHWAYS; MOLECULAR-CLONING; SACCHAROMYCES-CEREVISIAE; NEURITE RETRACTION; KINASE PATHWAY C1 Georgetown Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20007 USA. NIMH, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. RP Spiegel, S (reprint author), Georgetown Univ, Med Ctr, Dept Biochem & Mol Biol, 353 Basic Sci Bldg,3900 Reservoir Rd NW, Washington, DC 20007 USA. FU NCI NIH HHS [CA61774]; NIGMS NIH HHS [GM43880] NR 93 TC 162 Z9 163 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-1981 J9 BBA-MOL CELL BIOL L JI BBA-Mol. Cell. Biol. Lipids PD APR 12 PY 2000 VL 1484 IS 2-3 BP 107 EP 116 DI 10.1016/S1388-1981(00)00010-X PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 307WN UT WOS:000086677300004 PM 10760461 ER PT J AU Liu, YJ Wu, YP Wada, R Neufeld, EB Mullin, KA Howard, AC Pentchev, PG Vanier, MT Suzuki, K Proia, RL AF Liu, YJ Wu, YP Wada, R Neufeld, EB Mullin, KA Howard, AC Pentchev, PG Vanier, MT Suzuki, K Proia, RL TI Alleviation of neuronal ganglioside storage does not improve the clinical course of the Niemann-Pick C disease mouse SO HUMAN MOLECULAR GENETICS LA English DT Article ID NCTR-BALB/C MOUSE; LYSOSOMAL STORAGE; GM2 GANGLIOSIDE; CHOLESTEROL HOMEOSTASIS; N-BUTYLDEOXYNOJIRIMYCIN; G(M2) GANGLIOSIDE; ECTOPIC DENDRITES; PYRAMIDAL NEURONS; MICE; ACCUMULATION AB Niemann-Pick disease Type C (NP-C) is a progressive neurodegenerative disorder caused by mutations in the NPC1 gene and characterized by intracellular accumulation of cholesterol and sphingolipids, The major neuronal storage material in NP-C consists of gangliosides and other glycolipids, raising the possibility that the accumulation of these lipids may participate in the neurodegenerative process, To determine if ganglioside accumulation is a crucial factor in neuropathogenesis, we bred NP-C model mice with mice carrying a targeted mutation in GalNAcT, the gene encoding the beta-1-4GalNAc transferase responsible for the synthesis of GM2 and complex gangliosides. Unlike the NP-C model mice, these double mutant mice did not exhibit central nervous system (CNS) accumulation of gangliosides GM2 or of glycolipids GA1 and GA2. Histological analysis revealed that the characteristic neuronal storage pathology of NP-C disease was substantially reduced in the double mutant mice, By contrast, visceral pathology was similar in the NP-C and double mutant mice, Most notably, the clinical phenotype of the double mutant mice, in the absence of CNS ganglioside accumulation and associated neuronal pathology, did not improve, The results demonstrate that complex ganglioside storage, while responsible for much of the neuronal pathology, does not significantly influence the clinical phenotype of the NP-C model. C1 NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. Lyon Sud Sch Med, INSERM, U189, F-69921 Oullins, France. RP Proia, RL (reprint author), NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. EM proia@nih.gov RI Proia, Richard/A-7908-2012 FU NICHD NIH HHS [HD 03110]; NINDS NIH HHS [NS 24453] NR 30 TC 75 Z9 78 U1 0 U2 1 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 12 PY 2000 VL 9 IS 7 BP 1087 EP 1092 DI 10.1093/hmg/9.7.1087 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 308DW UT WOS:000086696100009 PM 10767333 ER PT J AU Ponten, I Sayer, JM Pilcher, AS Yagi, H Kumar, S Jerina, DM Dipple, A AF Ponten, I Sayer, JM Pilcher, AS Yagi, H Kumar, S Jerina, DM Dipple, A TI Factors determining mutagenic potential for individual cis and trans opened benzo[c]phenanthrene diol epoxide-deoxyadenosine adducts SO BIOCHEMISTRY LA English DT Article ID SITE-SPECIFIC MUTAGENESIS; CARCINOGEN-DNA ADDUCTS; N-RAS CODON-61; ESCHERICHIA-COLI; SEQUENCE CONTEXT; IN-VITRO; SOLUTION CONFORMATION; DIHYDRODIOL EPOXIDES; 9,10-EPOXIDE ADDUCTS; METABOLIC-ACTIVATION AB Four adducts that would result from trans opening at C-1 of benzo[c]phenanthrene 3,4-diol 1,2-epoxide (B[c]PhDE) isomers (i.e., DE-1 enantiomers, where the epoxide oxygen and benzylic hydroxyl group are cis, and DE-2 enantiomers, where they are trans) by the N-6-amino group of dAdo, together with the two cis opened N-6-dAdo adducts of B[c]PhDE-1, were incorporated into two oligonucleotides at the underlined site in 5'-TTTAGAGTCTGCTCCC [context I(A)] and 5'-CAGATTTAGAGTCTGC [context II(A)]. After ligation of these, and the corresponding unsubstituted oligonucleotides, into single-stranded M13mp7L2 bacteriophage and transfection into SOS-induced Escherichia coli SMH77, base substitution mutations induced by the different B[c]PhDE-dAdo adducts were determined. These findings were compared with data [Ponten et al, (1999) Biochemistry 38, 1144-1152] for cis opened B[c]PhDE-2-dAdo adducts in the same sequence contexts. In most cases, adducts with S absolute configuration at the site of attachment of the nucleoside to the hydrocarbon had higher mutation frequencies (1.9-56.5%) than the corresponding adducts with R configuration (0.05-5.6%). For adducts derived from B[c]PhDE-1, the predominant mutations were A-->T transversions in context I(A) and A-->G transitions for most of these adducts in context II(A), For adducts derived from B[c]PhDE-2, A-->T base substitutions predominated for most of the trans adducts, but A-->G mutations were favored by the cis adduct with S configuration in either context. Thus, the structural feature that most dramatically affected mutagenic activity was the configuration of the carbon at the attachment point, with S configuration mostly being associated with greater mutagenicity than the R configuration, However, other structural variations and sequence context also affected mutagenicity, indicating that a combination of structure and context effects define mutagenicity. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Chem Carcinogenesis Lab, Frederick, MD 21702 USA. SUNY Coll Buffalo, Great Lakes Ctr, Buffalo, NY 14222 USA. NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Ponten, I (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Chem Carcinogenesis Lab, Frederick, MD 21702 USA. NR 52 TC 23 Z9 23 U1 0 U2 2 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 11 PY 2000 VL 39 IS 14 BP 4136 EP 4144 DI 10.1021/bi991719q PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 304HV UT WOS:000086478400033 PM 10747805 ER PT J AU Abernethy, DR Flockhart, DA AF Abernethy, DR Flockhart, DA TI Molecular basis of cardiovascular drug metabolism - Implications for predicting clinically important drug interactions SO CIRCULATION LA English DT Article DE drugs; metabolism; molecular biology ID BLOOD-BRAIN-BARRIER; TRANSPORTER P-GLYCOPROTEIN; MULTIDRUG TRANSPORTER; HEALTHY-VOLUNTEERS; CYP2C SUBFAMILY; ATPASE ACTIVITY; CYCLOSPORINE-A; IN-VITRO; PHARMACOKINETICS; DISPOSITION C1 Georgetown Univ, Med Ctr, Div Clin Pharmacol, Washington, DC 20007 USA. RP Abernethy, DR (reprint author), NIA, Gerontol Res Ctr, Clin Invest Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. FU NIA NIH HHS [AG-08226]; NIGMS NIH HHS [GM-56898, GM-08386] NR 53 TC 39 Z9 41 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 11 PY 2000 VL 101 IS 14 BP 1749 EP 1753 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 302MB UT WOS:000086367900030 PM 10758060 ER PT J AU Havlik, RJ Izmirlian, G Petrovitch, H Ross, GW Masaki, K Curb, JD Saunders, AM Foley, DJ Brock, D Launer, LJ White, L AF Havlik, RJ Izmirlian, G Petrovitch, H Ross, GW Masaki, K Curb, JD Saunders, AM Foley, DJ Brock, D Launer, LJ White, L TI APOE-epsilon 4 predicts incident AD in Japanese-American men: The Honolulu-Asia Aging Study SO NEUROLOGY LA English DT Article DE dementia; risk factors; epidemiology ID ALZHEIMERS-DISEASE; VASCULAR DEMENTIA; METAANALYSIS; POPULATION; RISK AB The authors assessed the 3-year incidence of dementia, including subtypes, in 2,603 Japanese-American men 71 to 93 years of age who were dementia free at baseline. There were 137 new cases of dementia according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised, including 51 with a primary diagnosis of AD. The rates for all subtypes increased with age. Men with an APOE4 allele had a significantly increased risk of AD of 2.39 (95% CI, 1.07, 5.31), after adjusting for age and education. There was no significant relationship of APOE4 with other subtypes of dementia. C1 NIA, Epidemiol Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. Kuakini Med Ctr, Honolulu Asia Aging Study, Honolulu, HI USA. Dept Vet Affairs, Honolulu, HI USA. Univ Hawaii, John A Burns Sch Med, Dept Med, Honolulu, HI 96822 USA. Duke Univ, Med Ctr, Joseph & Kathleen Bryan Alzheimers Dis Res Ctr, Dept Med Neurol, Durham, NC USA. RP Havlik, RJ (reprint author), NIA, Epidemiol Demog & Biometry Program, NIH, Gateway Bldg,Suite 3C-309, Bethesda, MD 20892 USA. FU NIA NIH HHS [N01-AG-4-2149] NR 10 TC 45 Z9 45 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 11 PY 2000 VL 54 IS 7 BP 1526 EP 1529 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 304AT UT WOS:000086460900027 PM 10751272 ER PT J AU Boroojerdi, B Prager, A Muellbacher, W Cohen, LG AF Boroojerdi, B Prager, A Muellbacher, W Cohen, LG TI Reduction of human visual cortex excitability using 1-Hz transcranial magnetic stimulation SO NEUROLOGY LA English DT Article DE visual cortex; transcranial magnetic stimulation; excitability AB The effects of low-frequency (l-Hz) repetitive transcranial magnetic stimulation on visual cortex excitability were investigated by measuring phosphene thresholds (PTs) and stimulus-response curves. Stimulation over the visual cortex led to significantly decreased visual cortex excitability, expressed as an increase in PT. The motor threshold of the hand muscles did not change, indicating the topographic specificity of this effect. This intervention may be useful in situations associated with a hyperexcitable visual cortex. C1 NINDS, Human Cort Physiol Sect, NIA, Bethesda, MD 20892 USA. RP Cohen, LG (reprint author), NINDS, Human Cort Physiol Sect, NIA, Bldg 10,Room 5N 234,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. NR 10 TC 172 Z9 176 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 11 PY 2000 VL 54 IS 7 BP 1529 EP 1531 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 304AT UT WOS:000086460900028 PM 10751273 ER PT J AU Donaldson, JG AF Donaldson, JG TI Filling in the GAPs in the ADP-ribosylation factor story SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID GTPASE-ACTIVATING PROTEIN C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Donaldson, JG (reprint author), NHLBI, Cell Biol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 21 TC 33 Z9 35 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 11 PY 2000 VL 97 IS 8 BP 3792 EP 3794 DI 10.1073/pnas.97.8.3792 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 304AV UT WOS:000086461100004 PM 10760251 ER PT J AU Parsegian, VA Rand, RP Rau, DC AF Parsegian, VA Rand, RP Rau, DC TI Osmotic stress, crowding, preferential hydration, and binding: A comparison of perspectives SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROTEIN HYDRATION; WATER RELEASE; HEMOGLOBIN; POLYMERS; STABILIZATION; EQUILIBRIA; EXCLUSION; SOLVATION; STABILITY; SOLVENTS AB There has been much confusion recently about the relative merits of different approaches, osmotic stress, preferential interaction, and crowding, to describe the indirect effect of solutes on macromolecular conformations and reactions. To strengthen all interpretations of measurements and to forestall further unnecessary conceptual or linguistic confusion, we show here how the different perspectives all can be reconciled. Our approach is through the Gibbs-Duhem relation, the universal constraint on the number of ways it is possible to change the temperature, pressure, and chemical potentials of the several components in any thermodynamically defined system. From this general Gibbs-Duhem equation, it is possible to see the equivalence of the different perspectives and even to show the precise identity of the more specialized equations that the different approaches use. C1 NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. Brock Univ, Dept Biol Sci, St Catharines, ON L2S 3A1, Canada. RP Parsegian, VA (reprint author), NICHHD, Lab Phys & Struct Biol, NIH, Bldg 12A,Room 2041, Bethesda, MD 20892 USA. NR 33 TC 325 Z9 330 U1 5 U2 71 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 11 PY 2000 VL 97 IS 8 BP 3987 EP 3992 DI 10.1073/pnas.97.8.3987 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 304AV UT WOS:000086461100039 PM 10760270 ER PT J AU Randazzo, PA Andrade, J Miura, K Brown, MT Long, YQ Stauffer, S Roller, P Cooper, JA AF Randazzo, PA Andrade, J Miura, K Brown, MT Long, YQ Stauffer, S Roller, P Cooper, JA TI The Arf GTPase-activating protein ASAP1 regulates the actin cytoskeleton SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ADP-RIBOSYLATION FACTOR; GUANINE-NUCLEOTIDE EXCHANGE; SRC-FAMILY KINASES; GOLGI MEMBRANES; PHOSPHOLIPASE-D; CELL-MIGRATION; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; HOMOLOGY DOMAINS; BINDING PROTEIN; FOCAL ADHESIONS AB Arf family GTP-binding proteins are best characterized as regulators of membrane traffic, but recent studies indicate an additional role in cytoskeletal organization. An Arf GTPase-activating protein of the centaurin beta family, ASAP1 (also known as centaurin beta 4), binds Arf and two other known regulators of the actin cytoskeleton, the tyrosine kinase Src and phosphatidylinositol 4,5-bisphosphate. In this paper, we show that ASAP1 localizes to focal adhesions and cycles with focal adhesion proteins when cells are stimulated to move, Overexpression of ASAP1 altered the morphology of focal adhesions and blocked both cell spreading and formation of dorsal ruffles induced by platelet-derived growth factor (PDGF), On the other hand, ASAP1, with a mutation that disrupted GTPase-activating protein activity, had a reduced effect on cell spreading and increased the number of cells forming dorsal ruffles in response to PDGF, These data support a role for an Arf GTPase-activating protein, ASAP1, as a regulator of cytoskeletal remodeling and raise the possibility that the Arf pathway is a target for PDGF signaling. C1 NCI, Div Basic Sci, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA. RP Randazzo, PA (reprint author), NCI, Div Basic Sci, Cellular Oncol Lab, NIH, 37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. FU NCI NIH HHS [R01 CA041072, R37 CA041072, CA41072] NR 61 TC 131 Z9 134 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 11 PY 2000 VL 97 IS 8 BP 4011 EP 4016 DI 10.1073/pnas.070552297 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 304AV UT WOS:000086461100043 PM 10725410 ER PT J AU Gonzalez, A Kirsch, WG Shirokova, N Pizarro, G Brum, G Pessah, IN Stern, MD Cheng, H Rios, E AF Gonzalez, A Kirsch, WG Shirokova, N Pizarro, G Brum, G Pessah, IN Stern, MD Cheng, H Rios, E TI Involvement of multiple intracellular release channels in calcium sparks of skeletal muscle SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE excitation-contraction coupling; sarcoplasmic reticulum; ryanodine receptors; caffeine; bastadin ID CA2+ RELEASE; SARCOPLASMIC-RETICULUM; RYANODINE RECEPTORS; ELEMENTARY EVENTS; CELLS; PORE AB In many types of muscle, intracellular Ca2+ release for contraction consists of brief Ca2+ sparks. Whether these result from the opening of one or many channels in the sarcoplasmic reticulum is not known. Examining massive numbers of sparks from frog skeletal muscle and evaluating their Ca2+ release current, we provide evidence that they are generated by multiple channels. A mode is demonstrated in the distribution of spark rise times in the presence of the channel activator caffeine. This finding contradicts expectations for single channels evolving reversibly, but not for channels in a group, which collectively could give rise to a stereotyped spark. The release channel agonists imperatoxin A, ryanodine, and bastadin 10 elicit fluorescence events that start with a spark, then decay to steady levels roughly proportional to the unitary conductances of 35%, 50%, and 100% that the agonists, respectively, promote in bilayer experiments. This correspondence indicates that the steady phase is produced by one open channel. Calculated Ca2+ release current decays 10- to 20-fold from spark to steady phase, which requires that six or more channels be open during the spark. C1 Rush Univ, Dept Mol Biophys & Physiol, Chicago, IL 60612 USA. Fac Med, Dept Biofis, Montevideo, Uruguay. NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. Univ Calif Davis, Sch Vet Med, Dept Mol Biosci, Davis, CA 95616 USA. RP Rios, E (reprint author), Rush Univ, Dept Mol Biophys & Physiol, 17509 W Harrison St,Suite 1279 JS, Chicago, IL 60612 USA. NR 42 TC 93 Z9 95 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 11 PY 2000 VL 97 IS 8 BP 4380 EP 4385 DI 10.1073/pnas.070056497 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 304AV UT WOS:000086461100106 PM 10759554 ER PT J AU Billington, CJ Epstein, LH Goodwin, NJ Hill, JO Pi-Sunyer, FX Rolls, BJ Stern, J Wadden, TA Weinsier, RL Wilson, GT Wing, RR Yanovski, SZ Hubbard, VS Hoofnagle, JH Everhart, J Harrison, B AF Billington, CJ Epstein, LH Goodwin, NJ Hill, JO Pi-Sunyer, FX Rolls, BJ Stern, J Wadden, TA Weinsier, RL Wilson, GT Wing, RR Yanovski, SZ Hubbard, VS Hoofnagle, JH Everhart, J Harrison, B CA Natl Task Force Prevention Treatme TI Overweight, obesity, and health risk SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID BODY-MASS INDEX; AMERICAN-HEART-ASSOCIATION; WEIGHT-LOSS; FAT DISTRIBUTION; DIABETES-MELLITUS; NONALCOHOLIC STEATOHEPATITIS; CARDIOVASCULAR RISK; UNITED-STATES; MORTALITY; WOMEN AB More than half of adult Americans are overweight or obese, and public health recommendations call for weight loss in those who are overweight with associated medical conditions or who are obese. However, some controversy exists in the lay press and in the medical literature about the health risks of obesity. We review briefly the large body of evidence indicating that higher levels of body weight and body fat are associated with an increased risk for the development of numerous adverse health consequences. Efforts to prevent further weight gain in adults at risk for overweight and obesity are essential. For those whose present or future health is at risk because of their obesity and who are motivated to make lifestyle changes, a recommendation for weight loss is appropriate. C1 SUNY Buffalo, Buffalo, NY 14260 USA. Hlth Watch Informat & Promot Serv, New York, NY USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Columbia Univ, St Lukes Roosevelt Hosp Ctr, New York, NY USA. Penn State Univ, State Coll, University Pk, PA 16802 USA. Univ Calif Davis, Davis, CA 95616 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Alabama, Birmingham, AL USA. Rutgers State Univ, New Brunswick, NJ 08903 USA. Brown Univ, Providence, RI 02912 USA. Vet Affairs Med Ctr, Minneapolis, MN 55417 USA. NIDDKD, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Yanovski, SZ (reprint author), NIDDKD, Div Digest Dis & Nutr, NIH, Bldg 45,Room 6AN-18, Bethesda, MD 20892 USA. NR 91 TC 571 Z9 585 U1 3 U2 34 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 10 PY 2000 VL 160 IS 7 BP 898 EP 904 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 300JE UT WOS:000086249200002 ER PT J AU Ernster, VL Barclay, J Kerlikowske, K Wilkie, H Ballard-Barbash, R AF Ernster, VL Barclay, J Kerlikowske, K Wilkie, H Ballard-Barbash, R TI Mortality among women with ductal carcinoma in situ of the breast in the population-based surveillance, epidemiology and end results program SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; IN-SITU; LOCAL RECURRENCE; UNITED-STATES; CANCER; RISK; IRRADIATION; ESTROGEN; THERAPY; SURGERY AB Background: Over 14% of breast cancers diagnosed in the United States annually are ductal carcinomas in situ (DCIS). There are no published population-based reports of the likelihood of breast cancer death among US women with DCIS. Methods: We used data from the Surveillance, Epidemiology and End Results program to determine the likelihood of breast cancer death at 5 and 10 years among US women aged 40 and older diagnosed with DCIS from 1978 to 1983 (before screening mammography was common; n = 1525) and from 1984 to 1989 (when screening mammography became common; n = 5547). We also calculated standardized mortality ratios (SMRs) to compare observed deaths from breast cancer, cardiovascular disease, and all causes combined among women with DCIS with deaths expected based on general population mortality rates. Results: Among women diagnosed with DCIS from 1978 to 1983, 1.5% died of breast cancer within 5 years and 3.4% within 10 years. Among women diagnosed from 1984 to 1989, 0.7% died of breast cancer within 5 years and 1.9% within 10 years. Relative to the general population, risk of breast cancer death was greater for women diagnosed from 1978 to 1983 (SMR, 3.4; 95% confidence interval [CI], 2.5-4.5) than for women diagnosed from 1984 to 1989 (10-year SMR, 1.9; 95% CI, 1.5-2.3). Women diagnosed from 1984 to 1989 were significantly less likely than women in the general population to have died of cardiovascular diseases (10-year SMR, 0.6; 95% CI, 0.5-0.7) or of all causes combined (SMR, 0.8; 95% CI, 0.7-0.8). Conclusions: Among women diagnosed with DCIS, risk of death from breast cancer was low, at least within the 10 years following diagnosis. This may reflect the effectiveness of treatment for DCIS, the "benign" nature of DCIS, or both. At 10 years, women diagnosed from 1984 to 1989 were less likely than women diagnosed from 1978 to 1983 to have died of breast cancer, and their risk of dying of all causes combined was lower than that in the general population. C1 Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Dept Vet Affairs, Gen Internal Med Sect, San Francisco, CA USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Ernster, VL (reprint author), Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, Box 0560, San Francisco, CA 94143 USA. FU NCI NIH HHS [CA 58207, U01 CA 63740] NR 26 TC 171 Z9 176 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 10 PY 2000 VL 160 IS 7 BP 953 EP 958 DI 10.1001/archinte.160.7.953 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 300JE UT WOS:000086249200009 PM 10761960 ER PT J AU Byers, MR Chudler, EH Iadarola, MJ AF Byers, MR Chudler, EH Iadarola, MJ TI Chronic tooth pulp inflammation causes transient and persistent expression of Fos in dynorphin-rich regions of rat brainstem SO BRAIN RESEARCH LA English DT Article DE dental injury; pain; lateral solitary nucleus; nucleus oralis; nucleus caudalis; trigeminal tract interstitial cell ID SPINAL-CORD NEURONS; PROTEIN-LIKE IMMUNOREACTIVITY; NOXIOUS CHEMICAL-STIMULATION; TRIGEMINAL SUBNUCLEUS ORALIS; STEM NUCLEAR-COMPLEX; C-FOS; PERIPHERAL INFLAMMATION; ELECTRICAL-STIMULATION; GENE-EXPRESSION; MECHANICAL STIMULATION AB We have analyzed central Fos immunoreactivity (Fos-IR) brainstems of adult rats after three clinically relevant dental injuries: filled dentin (DF) cavities that cause mild pulp injury and heal within 1-2 weeks; open pulp exposures (PX) that cause gradual pulp loss and subsequent periodontal lesions; and filled pulp exposures (PXF). By 1 week after Dr; cavities, no Fos-IR remained except for sites such as lateral-ventral periolivary nucleus (LVPO) that had Fos-IR in all rats including controls. PX injury induced (1) a delayed transient expression of Fos at 1-2 weeks at three loci (ipsilateral neurons :in dorsomedial nucleus oralis, paratrigeminal nucleus, and trigeminal tract), (2) persistent ipsilateral Fos for at least 4 weeks after injury in dynorphin (Dyn)-rich regions (rostral lateral solitary nucleus, periobex dorsal nucleus caudalis), and (3) late Fos-IR at 2-4 weeks (bilateral superficial cervical dorsal horn, contralateral dorsal nucleus caudalis, contralateral rostral lateral solitary nucleus). Rats with PXF injury were examined at 2 weeks, and they had greater numbers and more extensive rostro-caudal distribution of Fos neurons than the PX group. One week after PX injury, Fos-IR neurons were found in regions with strong Dyn-IR central fibers. Go-expression of Dyn and Fos was found in some unusually large neurons of the ipsilateral rostral lateral solitary nucleus, trigeminal tract, and dorsal nucleus caudalis. Immunocytochemistry for the p75 low affinity neurotrophin receptor (p75NTR) or for calcitonin gene-related peptide (CGRP) showed no consistent change in trigeminal central endings in any Fos-reactive brainstem areas, despite the extensive structural and cytochemical reorganization of the peripheral endings of the dental neurons. The Fos responses of central neurons to tooth injury have some unusual temporal and spatial patterns in adult rats compared to other trigeminal injury models. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Univ Washington, Dept Anesthesiol, Seattle, WA 98195 USA. NIDCR, Neuronal Gene Express Unit, Pain & Neurosensory Mechanisms Branch, NIH, Bethesda, MD 20892 USA. RP Byers, MR (reprint author), Univ Washington, Dept Anesthesiol, Box 356540, Seattle, WA 98195 USA. EM byersm@u.washington.edu FU NIDCR NIH HHS [DE05159] NR 82 TC 15 Z9 16 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD APR 10 PY 2000 VL 861 IS 2 BP 191 EP 207 DI 10.1016/S0006-8993(00)01936-3 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 303GL UT WOS:000086414100001 PM 10760482 ER PT J AU Christiansen, M Stevnsner, T Bohr, VA Clark, BFC Rattan, SIS AF Christiansen, M Stevnsner, T Bohr, VA Clark, BFC Rattan, SIS TI Gene-specific DNA repair of pyrimidine dimers does not decline during cellular aging in vitro SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE DNA repair; human; aging; p53; DHFR ID HUMAN FIBROBLASTS; HUMAN-CELLS; EXCISION-REPAIR; AGE; SENESCENCE; DAMAGE; PROLIFERATION; TELOMERES; CLONING AB A large number of studies have demonstrated that various kinds of DNA damage accumulate during aging and one of the causes for this could be a decrease in DNA repair capacity. However, the level of total genomic repair has not been strongly correlated with aging. DNA repair of certain kinds of damage is known to be closely connected to the transcription process; thus, we chose to investigate the level of gene-specific repair of UV-induced damage using in vitro aging of human diploid skin fibroblasts and trabecular osteoblasts as model systems for aging. We find that the total genomic repair is not significantly affected during cellular aging of cultures of both human skin fibroblasts and trabecular osteoblasts. Gene-specific repair was analyzed during cellular aging in the dihydrofolate reductase housekeeping gene, the p53 tumor suppressor gene, and the inactive region X-754. There was no clear difference in the capacity of young and old cells to repair UV-induced pyrimidine dimers in any of the analyzed genes. Thus, in vitro senescent cells can sustain the ability to repair externally induced damage. (C) 2000 Academic Press. C1 Aarhus Univ, Dana Ctr Mol Gerontol, Dept Biol Mol & Struct, DK-8000 Aarhus C, Denmark. NIA, Genet Mol Lab, Baltimore, MD 21224 USA. RP Clark, BFC (reprint author), Aarhus Univ, Dana Ctr Mol Gerontol, Dept Biol Mol & Struct, DK-8000 Aarhus C, Denmark. OI Rattan, Suresh I.S./0000-0002-3478-1381 NR 34 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 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD APR 10 PY 2000 VL 256 IS 1 BP 308 EP 314 DI 10.1006/excr.2000.4826 PG 7 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 304HB UT WOS:000086476700034 PM 10739678 ER PT J AU Lisziewicz, J Zeng, G Gratas, C Weinstein, JN Lori, F AF Lisziewicz, J Zeng, G Gratas, C Weinstein, JN Lori, F TI Combination gene therapy: Synergistic inhibition of human immunodeficiency virus Tat and Rev functions by a single RNA molecule SO HUMAN GENE THERAPY LA English DT Article ID HEMATOPOIETIC PROGENITOR CELLS; ANTITAT GENE; HIV-1 REPLICATION; TYPE-1 REPLICATION; T-CELLS; INFECTION; STRATEGY; AIDS; TRANSDUCTION; EXPRESSION AB Current drug combinations can achieve long-term suppression of HIV replication in infected individuals. Unfortunately, complicated dosing schedules and high toxicity make long-term compliance with drug regimens difficult for most patients. Gene therapy may provide a permanent solution for HIV disease by generating cells genetically resistant to virus replication, As with the highly active antiretroviral therapies, genetic drugs must have strong antiviral potency and the ability to prevent the emergence of escape mutants. We have constructed antiviral genes containing unique combinations of Tat- and Rev-binding decoys, The new antiviral molecules are chimeric TAR-RRE RNAs that are expressed only in HIV infected cells in a Tat-regulated manner. One RNA molecule competes for both Tat and Rev binding, and thus blocks the activation and the expression of all viral genes. The two functional Tat- and Rev-binding domains exhibit the highest synergy at the lowest concentration. Conservative quantitative estimates of this synergistic effect were I = 0.24 at 50% inhibition, in terms of the Berenhaum "interaction index," indicating that the combined construct was approximately fourfold more potent than would be predicted on the basis of additive effects. The possibility of HIV escape from this inhibition is unlikely, because it requires simultaneous mutation of TAR and RRE in a manner in which both Tat and Rev preserve their respective functions. TAR-RRE combination decoys represent the first example of mathematically proven synergistic antiviral activity between two domains of the same molecule. C1 Res Inst Genet & Human Therapy, Washington, DC 20007 USA. Res Inst Genet & Human Therapy, I-27100 Pavia, Italy. NCI, NIH, Bethesda, MD 20892 USA. RP Lisziewicz, J (reprint author), Res Inst Genet & Human Therapy, Med Dent Bldg SW307,3900 Reservoir Rd NW, Washington, DC 20007 USA. NR 34 TC 12 Z9 12 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD APR 10 PY 2000 VL 11 IS 6 BP 807 EP 815 DI 10.1089/10430340050015428 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 302RF UT WOS:000086378600002 PM 10779158 ER PT J AU Mautino, MR Ramsey, WJ Reiser, J Morgan, RA AF Mautino, MR Ramsey, WJ Reiser, J Morgan, RA TI Modified human immunodeficiency virus-based lentiviral vectors display decreased sensitivity to trans-dominant rev SO HUMAN GENE THERAPY LA English DT Article ID CD4(+) T-LYMPHOCYTES; TYPE-1 SPLICE SITES; ENV MESSENGER-RNA; NONDIVIDING CELLS; IN-VIVO; REVERSE TRANSCRIPTION; RETROVIRAL VECTORS; HIV-1 REPLICATION; OVERLAP EXTENSION; GENE DELIVERY AB As a first step toward the development of HIV-based conditionally replicating defective interfering particles expressing trans-dominant Rev (TdRev:,, we studied whether mutation of the splicing signals and replacement of the RRE by the SRV-1 CTE would render these vectors less sensitive to TdRev. Vectors with mutations in the splicing signals (SD-/RRE+) yielded high titers (5 x 10(6) CFU/ml) and showed higher levels of cytoplasmic unspliced mRNA than the corresponding SD+/RRE+ vectors either in the absence of Rev, in the presence of TdRev, or in the presence of both TdRev and Rev. Proviral copies of SD-/RRE+ vectors were rescued more efficiently than SD+/RRE+ vectors when TdRev was expressed. Vectors with the SRV-1 CTE (SD+/CTE+ and SD-/CTE+) expressed: high levels of cytoplasmic unspliced mRNA in the absence of Rev expression. Titers obtained with the SD-/CTE+ vectors (10(6) CFU/ml) were higher than the titers obtained with SD+/CTE+ vectors. We also tested the effect of other structural modifications such as the orientation of the expression cassette and the presence of the central polypurine tract (cPPT/CTS). We show that an expression cassette cloned in the reverse orientation with respect to the LTRs or elimination of the cPPT/CTS element severely affected vector titers. We also demonstrated that these vectors can be efficiently mobilized from their proviral state by HIV trans-complementing functions, and transduced into secondary target cells without suffering any genomic rearrangement. C1 NHGRI, Clin Gene Therapy Branch, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Morgan, RA (reprint author), NHGRI, Clin Gene Therapy Branch, NIH, 10 Ctr Dr,MSC 1851,Bldg 10,Room 10C103, Bethesda, MD 20892 USA. NR 57 TC 24 Z9 25 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD APR 10 PY 2000 VL 11 IS 6 BP 895 EP 908 DI 10.1089/10430340050015509 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 302RF UT WOS:000086378600010 PM 10779166 ER PT J AU Adams, MM Hof, PR Gattass, R Webster, MJ Ungerleider, LG AF Adams, MM Hof, PR Gattass, R Webster, MJ Ungerleider, LG TI Visual cortical projections and chemoarchitecture of macaque monkey pulvinar SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE calcium-binding proteins; primate visual system; thalamocortical connections; visual thalamus ID SUPERIOR TEMPORAL SULCUS; CALCIUM-BINDING PROTEINS; ADJACENT LATERAL PULVINAR; BEHAVING RHESUS-MONKEY; INFERIOR PULVINAR; MACACA-MULATTA; AREA MT; NEUROFILAMENT PROTEIN; STRIATE CORTEX; TOPOGRAPHIC ORGANIZATION AB We investigated the patterns of projections from the pulvinar to visual areas V1, V2, V4, and MT, and their relationships to pulvinar subdivisions based on patterns of calbindin (CB) immunostaining and estimates of visual field maps (P-1, P-2 and P-3). Multiple retrograde tracers were placed into V1, V2, V4, and/or MT in 11 adult macaque monkeys. The inferior pulvinar (PI) was subdivided into medial (PIM), posterior (PIP), central medial (PICM), and central lateral (PICL) regions, confirming earlier CB studies. The P-1 map includes PICL and the ventromedial portion of the lateral pulvinar (PL), P-2 is found in ventrolateral PL, and P-3 includes PIP, PIM, and PICM. Projections to areas V1 and V2 were found to be overlapping in P-1 and P-2, but those from P-2 to V2 were denser than those to V1. V2 also received light projections from PICM and, less reliably, from PIM. Neurons projecting to V4 and MT were more abundant than those projecting to V1 and V2. Those projecting to V4 were observed in P-1, densely in P-2, and also in PICM and PIP of P-3. Those projecting to MT were found in P-1-P-3, with the heaviest projection from P-3. Projections from P-3 to MT and V4 were mainly interdigitated, with the densest to MT arising from PIM and the densest to V4 arising from PIP and PICM. Because the calbindin-rich and -poor regions of P-3 corresponded to differential patterns of cortical connectivity, the results suggest that CB may further delineate functional subdivisions in the pulvinar. J. Comp. Neurol. 419:377-393, 2000. (C) 2000 Wiley-Liss, Inc. C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. CUNY Mt Sinai Sch Med, Kastor Neurobiol Aging Lab, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Fishberg Res Ctr Neurobiol, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Ophthalmol, New York, NY 10029 USA. Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Dept Neurobiol, BR-21941900 Rio De Janeiro, Brazil. Uniformed Serv Univ Hlth Sci, Stanley Fdn Res Program, Bethesda, MD 20814 USA. RP Ungerleider, LG (reprint author), NIMH, Lab Brain & Cognit, Bldg 10,Room 4C104,10 Ctr Dr MSC 1366, Bethesda, MD 20892 USA. NR 58 TC 78 Z9 78 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 10 PY 2000 VL 419 IS 3 BP 377 EP 393 DI 10.1002/(SICI)1096-9861(20000410)419:3<377::AID-CNE9>3.0.CO;2-E PG 17 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 289TR UT WOS:000085638500009 PM 10723012 ER PT J AU Bartzokis, G Beckson, M Lu, PH Edwards, N Rapoport, R Wiseman, E Bridge, P AF Bartzokis, G Beckson, M Lu, PH Edwards, N Rapoport, R Wiseman, E Bridge, P TI Age-related brain volume reductions in amphetamine and cocaine addicts and normal controls: implications for addiction research SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE aging; psychostimulant addiction; gray matter; white matter; frontal lobe; temporal lobe ID MAGNETIC-RESONANCE; GRAY-MATTER; IN-VIVO; MRI; ABUSERS; LOBE; HIPPOCAMPUS; DEPENDENCE; METABOLISM; ACTIVATION AB The study evaluated the relationship between age and frontal and temporal lobe volumes in young cohorts of cocaine-dependent (CD), amphetamine-dependent (Am), and normal control subjects. Ten CD, nine Am, and 16 age- and gender-matched control subjects underwent magnetic resonance imaging (MRI). The volume of the frontal and temporal lobes was measured from an identically positioned slab of seven contiguous 3-mm-thick coronal images. Follow-up measures of the gray and white matter subcomponents of these volumes were also obtained. Both CD and Am groups had a significantly smaller temporal lobe volumes, but only the CD group demonstrated a significantly greater decline in temporal lobe volume with age (intracranial volume, education, and race were controlled for in all statistical analyses). Segmenting the brain regions into gray and white matter revealed that the negative correlation between age and temporal lobe volume of CD patients was mostly due to a significant age-related decline in the gray matter subcomponent. Negative trends between age and gray matter volumes were also observed in the Am and normal groups. In the frontal lobes, age was negatively correlated with gray matter volume in the control, CD, and Am groups. Unlike the consistent decreases in gray matter volumes, white matter showed non-significant increases in volume with age. The data suggest that CD patients may have an accelerated age-related decline in temporal lobe gray matter volume and a smaller temporal lobe volume compared to normal controls. In the frontal lobe, age-related gray matter volume reductions occur in all three groups. These age-related cortical gray matter volume reductions may be a biological marker for the risk of addictive behavior, which also decreases with age. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Cent Arkansas Vet Healthcare Syst, Mental Hlth Serv Line, N Little Rock, AR 72114 USA. Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. Greater Los Angeles VA Healthcare Syst, W Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90074 USA. NIDA, Medicat Dev Div, Rockville, MD 20857 USA. RP Bartzokis, G (reprint author), Cent Arkansas Vet Healthcare Syst, Mental Hlth Serv Line, 2200 Ft Roots Dr,Bldg 170 116A-NLR, N Little Rock, AR 72114 USA. RI Bartzokis, George/K-2409-2013 FU NIDA NIH HHS [1YO1 DA 50038] NR 32 TC 77 Z9 81 U1 2 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD APR 10 PY 2000 VL 98 IS 2 BP 93 EP 102 DI 10.1016/S0925-4927(99)00052-9 PG 10 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 310BN UT WOS:000086806800002 PM 10762735 ER PT J AU Diwan, BA Olivero, OA Poirier, MC AF Diwan, BA Olivero, OA Poirier, MC TI Absence of structural or functional alterations in male and female reproductive organs of F1 and F2 generations derived from female mice exposed to 3 '-azido-3 '-deoxythymidine during pregnancy SO TOXICOLOGY LETTERS LA English DT Article DE zidovudine; AZT; in utero; reproductive organs; carcinogen ID DIETHYLSTILBESTROL; 3'-AZIDO-2',3'-DIDEOXYTHYMIDINE; ZIDOVUDINE; TOXICOLOGY; DAMAGE; TUMORS; DNA; DES AB To investigate the effects of in utero exposure to 3'-azido-3'-deoxythymidine (AZT) on male and female reproductive system development, pregnant CD-1 mice were given daily intragastric doses of 25.0 mg AZT during days 12 through Is of gestation. The offspring were examined at birth, as well as at pubertal, young adult and adult stages of development, for reproductive organ endpoints including anogenital distance, onset of testicular descent, latency to vaginal opening, and proportion of time for each of the stages of estrous cycle. These reproductive endpoints remained mostly unchanged in AZT-treated offspring as compared to the controls. Males and females exposed in utero to AZT (F1 generation) were fertile when mated to untreated females and males, respectively, and their liveborn F2 offspring showed no adverse effects for any of the reproductive parameters tested. Thus, no evidence of developmental reproductive toxicity was noted either in the Fl mice exposed to AZT during the critical period of male and female reproductive system development, or in the F2 mice born of matings between the AZT-exposed Fl mice and unexposed animals. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Diwan, BA (reprint author), NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Bldg 538,Room 205E, Ft Detrick, MD 21702 USA. EM bdiwan@mail.ncifcrf.gov FU NCI NIH HHS [1-CO-5600] NR 22 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD APR 10 PY 2000 VL 115 IS 1 BP 9 EP 15 DI 10.1016/S0378-4274(99)00298-2 PG 7 WC Toxicology SC Toxicology GA 307KH UT WOS:000086652100002 PM 10817626 ER PT J AU Zhou, YH Shimizu, YK Esumi, M AF Zhou, YH Shimizu, YK Esumi, M TI Monoclonal antibodies to the hypervariable region 1 of hepatitis C virus capture virus and inhibit virus adsorption to susceptible cells in vitro SO VIROLOGY LA English DT Article ID HUMORAL IMMUNE-RESPONSE; HYPERIMMUNE SERUM; IN-VITRO; GLYCOPROTEIN; CHIMPANZEES; INFECTION; ENVELOPE; E2; NEUTRALIZATION; PREVENTION AB To analyze the neutralizing-related activity of antibodies against the hypervariable region 1 (HVR1) of hepatitis C virus (HCV) in more detail, monoclonal antibodies (mAbs) against HVR1 were raised by immunizing various strains of mice with one of two synthetic HVR1 peptides that had been derived from two isolates of HCV. The epitope specificity of all six mAbs could be assigned by the use of a series of linear peptides in competitive ELISA. It seems that most subregions In the amino acid sequence of HVR1 can induce a humoral immune response in mice. All three mAbs specific to HVR1-6-1 had the ability to capture homologous HCV-6 and inhibit its absorption to susceptible cells in vitro despite the fact that the epitope of each mAb was at a different location in HVR1, whereas the other three mAbs specific to HVR1-7 could not capture HCV-B nor inhibit the absorption of HCV-6 to susceptible cells. The data in this study suggest that mAbs against HVR1 can prevent the infectivity of HCV in an isolate-specific and epitope position-independent manner. (C) 2000 Academic Press. C1 Nihon Univ, Sch Med, Dept Pathol, Itabashi Ku, Tokyo 1738610, Japan. NIH, Infect Dis Lab, Hepatitis Viruses Sect, Bethesda, MD 20892 USA. RP Esumi, M (reprint author), Nihon Univ, Sch Med, Dept Pathol, Itabashi Ku, 30-1 Ooyaguchikami Machi, Tokyo 1738610, Japan. NR 21 TC 26 Z9 27 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD APR 10 PY 2000 VL 269 IS 2 BP 276 EP 283 DI 10.1006/viro.2000.0227 PG 8 WC Virology SC Virology GA 304MK UT WOS:000086487800005 PM 10753706 ER PT J AU Valentin, A Trivedi, H Lu, WH Kostrikis, LG Pavlakis, GN AF Valentin, A Trivedi, H Lu, WH Kostrikis, LG Pavlakis, GN TI CXCR4 mediates entry and productive infection of syncytia-inducing (X4) HIV-1 strains in primary macrophages SO VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; GREEN FLUORESCENT PROTEIN; FUNCTIONAL CORECEPTOR; MOLECULAR BEACONS; TYPE-1 INFECTION; BLOOD MONOCYTES; CCR5; TROPISM; EXPRESSION; RECEPTOR AB CCR5 and CXCR4 are the main coreceptors for non-syncytia-inducing (NSI) and syncytia-inducing (SI) HIV-1 strains, respectively. NSI HIV-1 isolates do not infect either human lymphoid or monocytoid cell lines, and this inability correlates with the absence of CCRS expression in these cell types. The ability of SI HIV-1 isolates to infect human primary macrophages has been disputed. Here, we report that CXCR4 is expressed in primary blood-derived human mononuclear phagocytes at all stages of differentiation, although the maturation process correlates with downregulation of CXCR4 mRNA. Infection experiments with the SI molecular clone NL4-3 tagged with a mutant of the green fluorescent protein established that both monocytes and attached macrophages are susceptible to infection with CXCR4-restricted HIV-I strains. NL4-3 entry Into primary macrophages could be blocked by SDF-1 alpha in a dose-dependent manner, or by the anti-CXCR4 monoclonal antibody 12G5. HIV-1 entry led to productive infection. No evidence of postentry defects or nuclear import delay for CXCR4 restricted HIV-I strains was detected using a quantitative real-time PCR assay measuring HIV-1 DNA entry into the nucleus. Macrophages infected by HIV-1 and expressing virus were maintained in culture for long periods of time (up to 5 months). These results demonstrate that GXGR4 is the main HIV-1 SI coreceptor in human primary macrophages and underline the importance of the macrophage as a long-living viral reservoir for HIV-1. (C) 2000 Academic Press. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Human Retrovirus Sect, Frederick, MD 21702 USA. NYU, Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA. RP Pavlakis, GN (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Human Retrovirus Sect, Bldg 535,Rm 212,POB B, Frederick, MD 21702 USA. RI Kostrikis, Leondios/A-5330-2016 OI Kostrikis, Leondios/0000-0002-5340-7109 NR 54 TC 37 Z9 39 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD APR 10 PY 2000 VL 269 IS 2 BP 294 EP 304 DI 10.1006/viro.1999.0136 PG 11 WC Virology SC Virology GA 304MK UT WOS:000086487800007 PM 10753708 ER PT J AU Criado, JR Morales, M AF Criado, JR Morales, M TI Acute ethanol induction of c-Fos immunoreactivity in pre-pro-enkephalin expressing neurons of the central nucleus of the amygdala SO BRAIN RESEARCH LA English DT Article DE GAD; interneuron; CRF; drug addiction; extended amygdala ID CORTICOTROPIN-RELEASING FACTOR; ALCOHOL DEPENDENCE; EXTENDED AMYGDALA; GABAERGIC NEURONS; RATS; NALTREXONE; ANTAGONIST; RECEPTOR; REWARD AB Previous studies have shown that acute ethanol administration induces expression of c-Fos immunoreactivity in the central nucleus of the amygdala (CNA) [S.L. Chang, N.A. Patel, A.A. Romero, Activation and desensitization of Fos immunoreactivity in the rat brain following ethanol administration, Brain Res., 679 (1995) 89-98; M. Morales, J.R. Criado, P.P. Sanna, S.J. Henriksen, F.E. Bloom, Acute ethanol induces c-fos immunoreactivity in GABAergic neurons of the central nucleus of the amygdala, Brain Res., 798 (1998) 333-336; A.E. Ryabinin, J.R. Criado, S.J. Henriksen, F.E. Bloom, M.C. Wilson, Differential sensitivity of c-Fos expression in hippocampus and other brain regions to moderate and low doses of alcohol, Mel. Psychiatry, 2 (1997) 32-43]. We recently showed that over 70% of these c-Fos immunoreactive neurons are GABAergic [M. Morales, J.R. Criado, P.P. Sanna, S.J. Henriksen, F.E. Bloom, Acute ethanol induces c-fos immunoreactivity in GABAergic neurons of the central nucleus of the amygdala, Brain Res, 798 (1998) 333-336]. In the present study, we report that ethanol-induced c-Fos immunoreactivity was mainly confined to neurons that express pro-enkephalin (ENK). Ln contrast, a small number of c-Fos immunoreactive neurons express corticotrophin releasing factor (CRF). Our results thus provide anatomical evidence indicating that within the amygdala, GABAergic neurons that contain ENK are responsive to acute ethanol exposure. (C) 2000 Elsevier Science B.V, All rights reserved. C1 Natl Inst Drug Abuse, Baltimore, MD 21224 USA. Scripps Res Inst, Dept Neuropharmacol, Alcohol Res Ctr, La Jolla, CA 92037 USA. RP Morales, M (reprint author), Natl Inst Drug Abuse, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. FU NIDA NIH HHS [DA-08301] NR 20 TC 35 Z9 35 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 7 PY 2000 VL 861 IS 1 BP 173 EP 177 DI 10.1016/S0006-8993(99)02468-3 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 302DJ UT WOS:000086349900021 PM 10751579 ER PT J AU Rondinone, CM Carvalho, E Rahn, T Manganiello, VC Degerman, E Smith, UP AF Rondinone, CM Carvalho, E Rahn, T Manganiello, VC Degerman, E Smith, UP TI Phosphorylation of PDE3B by phosphatidylinositol 3-kinase associated with the insulin receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID KM CAMP PHOSPHODIESTERASE; PROTEIN-KINASE; PHOSPHOINOSITIDE 3-KINASE; GLUCOSE-TRANSPORT; TYROSINE KINASES; HUMAN ADIPOCYTES; RAT ADIPOCYTES; SH2 DOMAINS; P85 SUBUNIT; FAT-CELLS AB Phosphatidylinositol S-kinase mediates several actions of insulin including its antilipolytic effect. This effect is elicited by the insulin-stimulated serine phosphorylation and activation of cGMP-inhibited phosphodiesterase (PDE3B). In human adipocytes, we found that insulin differentially stimulated phosphatidylinositol S-kinase activity; the lipid kinase activity was associated with IRS-1, whereas the serine kinase activity was associated with the insulin receptor and phosphorylated a number of proteins including p85, p110, and a 135-kDa protein identified as PDE3B. PDE3B phosphorylation was associated with enzyme activation, thus initiating the antilipolytic effect of insulin. These results show a novel pathway for intracellular signaling through the insulin receptor leading to the serine phosphorylation of key proteins involved in insulin action. C1 NHLBI, Cellular Metab Lab, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. Gothenburg Univ, Sahlgrens Hosp, Dept Internal Med, Lundberg Lab Diabetes Res, S-41345 Gothenburg, Sweden. Univ Lund, Dept Cell & Mol Biol, Sect Mol Signaling, S-22100 Lund, Sweden. RP Smith, UP (reprint author), NHLBI, Cellular Metab Lab, Pulm Crit Care Med Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. OI Carvalho, Eugenia/0000-0001-6264-3632 NR 29 TC 52 Z9 54 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 7 PY 2000 VL 275 IS 14 BP 10093 EP 10098 DI 10.1074/jbc.275.14.10093 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 302BT UT WOS:000086345600030 PM 10744689 ER PT J AU Weissman, JDJ Howcroft, TK Singer, DS AF Weissman, JDJ Howcroft, TK Singer, DS TI TAF(II)250-independent transcription can be conferred on a TAF(II)250-dependent basal promoter by upstream activators SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CLASS-I GENE; RNA-POLYMERASE-II; NF-KAPPA-B; CELL-LINE; EXPRESSION; ELEMENTS; TBP; SEQUENCE; PROTEIN; BINDING AB TAF(II)250, a component of the general transcription factor, TFIID, is required for the transcription of a subset of genes, including those involved in regulating cell cycle progression. The tsBN462 cell line, with a temperature-sensitive mutation of TAF(II)250, grows normally at 32 degrees C, but when grown at 39.5 degrees C, it differentially arrests transcription of many, but not all, genes. The present studies examine the basis for the requirement for TAF(II)250. We show that the basal promoter of a major histocompatibility complex class I gene requires TAF(II)250. This dependence can be overcome by select upstream regulatory elements but not by basal promoter elements. Thus, the coactivator CIITA rescues the basal promoter from the requirement for TAF(II)250, whereas introduction of a canonical TATAA box does not. Similarly, the SV40 basal promoter is shown to require TAF(II)250, and the presence of the 72-base pair enhancer overcomes this requirement. Furthermore, the SV40 72-base pair enhancer when placed upstream of the basal class I promoter renders it independent of TAF(II)250. These data suggest that the assembly of transcription initiation complexes is dynamic and can be modulated by specific transcription factors. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Singer, DS (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Room 4B-36, Bethesda, MD 20892 USA. NR 31 TC 18 Z9 19 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 7 PY 2000 VL 275 IS 14 BP 10160 EP 10167 DI 10.1074/jbc.275.14.10160 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 302BT UT WOS:000086345600040 PM 10744699 ER PT J AU Chang, TLY Peng, XB Fu, XY AF Chang, TLY Peng, XB Fu, XY TI Interleukin-4 mediates cell growth inhibition through activation of Stat1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STIMULATORY FACTOR-I; JAK-3 JANUS KINASE; INSULIN-RECEPTOR; TRANSCRIPTION FACTOR; SIGNALING PATHWAYS; INTERFERON-ALPHA; MAST-CELLS; B-CELLS; T-CELLS; IL-4 AB Interleukin-4 (IL-4) activates State (signal transducer and activator of transcription 6) and plays multiple roles in regulation of the immune system. IL-4 also triggers phosphorylation of insulin receptor substrate (IRS), leading to stimulation of cell growth. Moreover, IL-4 inhibits proliferation of a variety of cells, but the molecular mechanism of its growth inhibitory effect is not understood, In this study, me demonstrated that IL-4 inhibited cell growth of colon carcinoma cell lines (HT29 and WiDr) but promoted cell growth of Burkitt's lymphoma cell lines (BL30 and BL41) in a dose-dependent manner. The growth inhibition was not dependent on Stat6 activation, because Stat6 was activated at similar levels in all cell lines in response to IL-4. Strikingly, IL-4 activated Stat1 in colon carcinoma cell lines but not in Burkitt's lymphoma cell lines. Therefore, these results suggest that IL-4 induced Stat1 activation, resulting in growth inhibition of colon carcinoma cell lines. Importantly, we present evidence that Stat1 is necessary for IL-4-mediated growth inhibition using Stat1-deficient and Stat1-reconstituted cells. The growth inhibitory effect of IL-4 was diminished in Stat1-deficient cells, whereas it was restored in Stat1-reconstituted cells. In addition, the expression of dominant-negative Stat1 in HT29 cells led to the loss of growth inhibition in response to IL-4. Taken together, our data suggest that IL-4 activates Stat1, leading to cell growth inhibition in colon cancer cells. Thus, this study demonstrates, for the first time, a molecular mechanism by which IL-4 inhibits cell growth. C1 Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA. RP Fu, XY (reprint author), Natl Inst Hlth, Bethesda, MD 20892 USA. FU ASPE HHS [KO4AE01356]; NIAID NIH HHS [R01AI34522]; NIGMS NIH HHS [R01GM55590] NR 51 TC 25 Z9 27 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 7 PY 2000 VL 275 IS 14 BP 10212 EP 10217 DI 10.1074/jbc.275.14.10212 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 302BT UT WOS:000086345600047 PM 10744706 ER PT J AU Vinetz, JM Valenzuela, JG Specht, CA Aravind, L Langer, RC Ribeiro, JMC Kaslow, DC AF Vinetz, JM Valenzuela, JG Specht, CA Aravind, L Langer, RC Ribeiro, JMC Kaslow, DC TI Chitinases of the avian malaria parasite Plasmodium gallinaceum, a class of enzymes necessary for parasite invasion of the mosquito midgut SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID YELLOW-FEVER MOSQUITO; AEDES-AEGYPTI; PERITROPHIC MEMBRANE; SERRATIA-MARCESCENS; ESCHERICHIA-COLI; SANDFLY VECTOR; TRANSMISSION; SEQUENCES; TRANSFORMATION; IMMUNIZATION AB The Plasmodium ookinete produces chitinolytic activity that allows the parasite to penetrate the chitin-containing peritrophic matrix surrounding the blood meal in the mosquito midgut, Since the peritrophic matrix is a physical barrier that the parasite must cross to invade the mosquito, and the presence of allosamidin, a chitinase inhibitor, in a blood meal prevents the parasite from invading the midgut epithelium, chitinases (3.2.1.14) are potential targets of malaria parasite transmission-blocking interventions. We have purified a chitinase of the avian malaria parasite Plasmodium gallinaceum and cloned the gene, PgCHT1, encoding it. PgCHT1 encodes catalytic and substrate-binding sites characteristic of family 18 glycohydrolases, Expressed in Escherichia coli strain AD494 (DE3), recombinant PgCHT1 was found to hydrolyze polymeric chitin, native chitin oligosaccharides, and 4-methylumbelliferone derivatives of chitin oligosaccharides. Allosamidin inhibited recombinant PgCHT1 with an IC50 of 7 mu M and differentially inhibited two chromatographically separable P. gallinaceum ookinete-produced chitinase activities with IC50 values of 7 and 12 mu M, respectively, These two chitinase activities also had different pH activity profiles. These data suggest that the P, gallinaceum oo kinete uses products of more than one chitinase gene to initiate mosquito midgut invasion. C1 Univ Texas, Med Branch, Dept Pathol, WHO,Collaborating Ctr Trop Dis, Galveston, TX 77615 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Boston Univ, Goldman Sch Dent Med, Dept Mol & Cell Biol, Boston, MA 02118 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Vinetz, JM (reprint author), Univ Texas, Med Branch, WHO, Ctr Trop Dis,Dept Pathol, Keiller 2-138,301 Univ Blvd, Galveston, TX 77615 USA. OI Vinetz, Joseph/0000-0001-8344-2004; Ribeiro, Jose/0000-0002-9107-0818 NR 40 TC 85 Z9 89 U1 1 U2 11 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 7 PY 2000 VL 275 IS 14 BP 10331 EP 10341 DI 10.1074/jbc.275.14.10331 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 302BT UT WOS:000086345600062 PM 10744721 ER PT J AU Urbaneja, MA McGrath, CF Kane, BP Henderson, LE Casas-Finet, JR AF Urbaneja, MA McGrath, CF Kane, BP Henderson, LE Casas-Finet, JR TI Nucleic acid binding properties of the simian immunodeficiency virus nucleocapsid protein NCp8 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DETECTED MAGNETIC-RESONANCE; SINGLE-STRANDED POLYNUCLEOTIDES; MURINE LEUKEMIA-VIRUS; AROMATIC-AMINO-ACIDS; TRYPTOPHAN RESIDUES; ZINC FINGERS; STACKING INTERACTIONS; TYPE-1; FLUORESCENCE; TYROSINE AB The nucleocapsid protein of simian immunodeficiency virus (SIV) NCp8 has two copies of conserved sequences (termed zinc fingers, ZF) of 14 amino acids with 4 invariant residues (CCHC) that coordinate Zn(II), Each of its two ZFs has a Trp residue. A significant quenching of NCp8 Trp fluorescence was seen in nucleic acid complexes, suggesting stacking of the indole ring with nucleobases and the simultaneous involvement of both ZFs in the binding process. Both ZFs contribute to the nucleic acid binding free energy of NCp8, albeit in a not additive manner. NCp8 exhibited a base preference analogous to that of NCp7: G similar to I > T > U > C > A. Alternating base sequences that bind HIV-1 NCp7 in a sequence-specific manner were also bound selectively by NCp8, Specific sequence recognition required at least five bases and the presence of bound Zn(II), The two ZFs account for the net displacement of 3 out of 4 sodium ions upon binding (2 by the first and one by the second finger), and for most (85%) of the hydrophobic stabilization in complex formation. Based on the sequence and functional similarity of SIV NCp8 and HIV-1 NCp7, and using available structural information for free and oligonucleotide bound NCp7, we propose a structural model for NCp8-oligonucleotide complexes. C1 NCI, FCRDC, AIDS Vaccine Program, SAIC Frederick, Ft Detrick, MD 21702 USA. RP Casas-Finet, JR (reprint author), NCI, FCRDC, AIDS Vaccine Program, SAIC Frederick, Bldg 535,POB B, Ft Detrick, MD 21702 USA. NR 49 TC 13 Z9 13 U1 2 U2 6 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 7 PY 2000 VL 275 IS 14 BP 10394 EP 10404 DI 10.1074/jbc.275.14.10394 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 302BT UT WOS:000086345600069 PM 10744728 ER PT J AU Deterding, LJ Prasad, R Mullen, GP Wilson, SH Tomer, KB AF Deterding, LJ Prasad, R Mullen, GP Wilson, SH Tomer, KB TI Mapping of the 5 '-2-deoxyribose-5-phosphate lyase active site in DNA polymerase beta by mass spectrometry SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BASE-EXCISION-REPAIR; N-TERMINAL DOMAIN; DEOXYRIBOSE PHOSPHATE EXCISION; CATALYTIC MECHANISM; IMINO INTERMEDIATE; 8-KDA DOMAIN; PROTEIN; BINDING; IDENTIFICATION; SEQUENCE AB The mechanism of the 5'-2-deoxyribose-5-phosphate lyase reaction catalyzed by mammalian DNA beta-polymerase (beta-pol) was investigated using a cross-linking methodology in combination with mass spectrometric analyses. The approach included proteolysis of the covalently cross-linked protein-DNA complex with trypsin, followed by isolation, peptide mapping, and mass spectrometric and tandem mass spectrometric analyses. The 8-kDa domain of beta-pol was covalently cross-linked to a 5'-2-deoxyribose-5-phosphate-containing DNA substrate by sodium borohydride reduction. Using tandem mass spectrometry, the location of the DNA adduct on the 8-kDa domain was unequivocally determined to be at the Lys(72) as the sole Schiff base nucleophile in the 8-kDa domain of beta-pol. These results provide the first direct evidence in support of a catalytic mechanism involving nucleophilic attack by Lys(72) at the abasic site. C1 NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. Univ Connecticut, Ctr Hlth, Dept Biochem, Farmington, CT 06032 USA. RP Tomer, KB (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233 MD F0-03,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. RI Tomer, Kenneth/E-8018-2013 NR 46 TC 55 Z9 57 U1 0 U2 4 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 7 PY 2000 VL 275 IS 14 BP 10463 EP 10471 DI 10.1074/jbc.275.14.10463 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 302BT UT WOS:000086345600077 PM 10744736 ER PT J AU Lewis, J Devin, A Miller, A Lin, Y Rodriguez, Y Neckers, L Liu, ZG AF Lewis, J Devin, A Miller, A Lin, Y Rodriguez, Y Neckers, L Liu, ZG TI Disruption of Hsp90 function results in degradation of the death domain kinase, receptor-interacting protein (RIP), and blockage of tumor necrosis factor-induced nuclear factor-kappa B activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNALS CELL-DEATH; HEAT-SHOCK-PROTEIN; INDUCED APOPTOSIS; MOLECULAR CHAPERONE; CONTAINS 2; COMPLEX; INHIBITION; ALPHA; IDENTIFICATION; PHOSPHORYLATION AB The death domain kinase, receptor interacting protein (RIP), is one of the major components of the tumor necrosis factor receptor 1 (TNFR1) complex and plays an essential role in tumor necrosis factor (TNF)-mediated nuclear factor kappa B (NF-kappa B) activation. The activation of NF-kappa B protects cells against TNF-induced apoptosis. Heat-shock proteins (Hsps) are chaperone molecules that confer protein stability and help to restore protein native folding following heat shock and other stresses. The most abundant Hsp, Hsp90, is also involved in regulating the stability and function of a number of cell-signaling molecules. Here we report that RTP is a novel Hsp90-associated kinase and that disruption of Hsp90 function by its specific inhibitor, geldanamycin (GA), selectively causes RIP degradation and the subsequent inhibition of TNF-mediated I kappa B kinase and NP-kappa B activation. MG-132, a specific proteasome inhibitor, abrogated GA-induced degradation of RIP but failed to restore the activation of I kappa B kinase by TNF, perhaps because, in the presence of GA and MG-132, RIP accumulated in a detergent-insoluble subcellular fraction. Most importantly, the degradation of RIP sensitizes cells to TNF-induced apoptosis. These data indicate that Hsp90 plays an important role in TNF-mediated NF-kappa B activation by modulating the stability and solubility of RIP. Thus, inhibition of NF-kappa B activation by GA may be a critical component of the anti-tumor activity of this drug. C1 NCI, Dept Cell & Canc Biol, Med Branch, Div Clin Sci,NIH, Bethesda, MD 20892 USA. RP Liu, ZG (reprint author), NCI, Dept Cell & Canc Biol, Med Branch, Div Clin Sci,NIH, Bldg 10,6N105,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 60 TC 233 Z9 250 U1 0 U2 4 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 7 PY 2000 VL 275 IS 14 BP 10519 EP 10526 DI 10.1074/jbc.275.14.10519 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 302BT UT WOS:000086345600085 PM 10744744 ER PT J AU Bae, YS Sung, JY Kim, OS Kim, YJ Hur, KC Kazlauskas, A Rhee, SG AF Bae, YS Sung, JY Kim, OS Kim, YJ Hur, KC Kazlauskas, A Rhee, SG TI Platelet-derived growth factor-induced H2O2 production requires the activation of phosphatidylinositol 3-kinase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FRTL-5 THYROID-CELLS; PROTEIN-KINASE-C; HYDROGEN-PEROXIDE; TYROSINE PHOSPHORYLATION; SIGNAL-TRANSDUCTION; H2O2-GENERATING SYSTEM; RESPIRATORY BURST; PHOSPHOLIPASE-D; ANGIOTENSIN-II; NADPH OXIDASE AB Autophosphorylation of the platelet-derived growth factor (PDGF) receptor triggers intracellular signaling cascades as a result of recruitment of Src homology 2 domain-containing enzymes, including phosphatidylinositol S-kinase (PI3K), the GTPase-activating protein of Pas (GAP), the protein-tyrosine phosphatase SHP-2, and phospholipase C-yl (PLC-gamma 1), to specific phosphotyrosine residues. The roles of these various effecters in PDGF-induced generation of H2O2 have now been investigated in HepG2 cells expressing various PDGF receptor mutants. These mutants included a kinase-deficient receptor and receptors in which various combinations of the tyrosine residues required for the binding of PI3K (Tyr(740) and Tyr(751)), GAP (Tyr(771)), SHP-2 (Tyr(1009)), Or PLC-gamma 1 (Tyr(1021)) were mutated to Phe. PDGF failed to increase H2O2 production in cells expressing either the kinase-deficient mutant or a receptor in which the two Tyr residues required for the binding of PI3K mere replaced by Phe. In contrast, PDGF-induced H2O2, production in cells expressing a receptor in which the binding sites for GAP, SHP-2, and PLC-gamma 1 were all mutated was slightly greater than that in cells expressing the wildtype receptor. Only the PI3K binding site was alone sufficient for PDGF-induced H2O2 production. The effect of PDGF on H2O2 generation was blocked by the PI3K inhibitors LY294002 and wortmannin or by overexpression of a dominant negative mutant of Rad. These results suggest that a product of PI3K is required for PDGF-induced production of H2O2 in nonphagocytic cells, and that Rad mediates signaling between the PI3K product and the putative NADPH oxidase. C1 Ewha Womans Univ, Ctr Cell Signaling Res, Div Mol Life Sci, Seodaemoon Gu, Seoul 120750, South Korea. Ewha Womans Univ, Dept Biol Sci, Seoul 120750, South Korea. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. NHLBI, Int Joint Res Lab, Ctr Cell Signaling Res, NIH, Bethesda, MD 20892 USA. NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. RP Rhee, SG (reprint author), Ewha Womans Univ, Ctr Cell Signaling Res, Div Mol Life Sci, Seodaemoon Gu, 11-1 Daehyun Dong, Seoul 120750, South Korea. NR 48 TC 233 Z9 238 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 7 PY 2000 VL 275 IS 14 BP 10527 EP 10531 DI 10.1074/jbc.275.14.10527 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 302BT UT WOS:000086345600086 PM 10744745 ER PT J AU Yun, CW Ferea, T Rashford, J Ardon, O Brown, PO Botstein, D Kaplan, J Philpott, CC AF Yun, CW Ferea, T Rashford, J Ardon, O Brown, PO Botstein, D Kaplan, J Philpott, CC TI Desferrioxamine-mediated iron uptake in Saccharomyces cerevisiae - Evidence for two pathways of iron uptake SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MAJOR FACILITATOR SUPERFAMILY; TRANSPORT PROTEIN; USTILAGO-MAYDIS; REGULATED GENES; FET3 GENE; YEAST; SIDEROPHORES; EXPRESSION; REDUCTION; MEMBRANE AB In the yeast Saccharomyces cerevisiae, uptake of iron is largely regulated by the transcription factor Aft1. cDNA microarrays were used to identify new iron and AFT1-regulated genes. Four homologous genes regulated as part of the AFT1-regulon (ARN1-4) were predicted to encode members of a subfamily of the major facilitator superfamily of transporters. These genes were predicted to encode proteins with 14 membrane spanning domains and were from 26 to 53% identical at the amino acid level. ARN3 is identical to SIT1, which is reported to encode a ferrioxamine B permease, Deletion of ARN3 did not prevent yeast from using ferrioxamine B as an iron source; however, deletion of ARN3 and FET3, a component of the high affinity ferrous iron transport system, did prevent uptake of ferrioxamine-bound iron and growth on ferrioxamine as an iron source. The siderophore-mediated transport system and the high affinity ferrous iron transport system were localized to separate cellular compartments. Epitope-tagged Arn3p was expressed in intracellular vesicles that co-sediment with the endosomal protein Pep12. In contrast, Fet3p was expressed on the plasma membrane and was digested by extracellular proteases, These data indicate that S. cerevisiae has two pathways for ferrrioxamine-mediated iron uptake, one occurring at the plasma membrane and the other occurring in an intracellular compartment. C1 NIDDK, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT 84132 USA. Stanford Univ, Sch Med, Howard Hughes Med Inst, Dept Biochem, Stanford, CA 94305 USA. RP NIDDK, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. EM carolinep@intra.niddk.nih.gov FU NIDDK NIH HHS [DK-305340] NR 34 TC 145 Z9 150 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD APR 7 PY 2000 VL 275 IS 14 BP 10709 EP 10715 DI 10.1074/jbc.275.14.10709 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 302BT UT WOS:000086345600110 PM 10744769 ER PT J AU Shin, KJ Moon, HR George, C Marquez, VE AF Shin, KJ Moon, HR George, C Marquez, VE TI Construction of the bicyclo[3,1.0]hexane template of a conformationally locked carbocyclic adenosine via an olefin keto-carbene cycloaddition SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID REVERSE-TRANSCRIPTASE; BIOLOGICAL-ACTIVITY; NEPLANOCIN-C; SUGAR RING; NUCLEOSIDES; ANALOGS; THYMIDINE; OLIGONUCLEOTIDES; CRYSTAL AB An intramolecular olefin keto-carbene cycloaddition reaction created the bicyclo[3.1.0]hexane template 10 that was necessary for the synthesis of carbocyclic amine 15. This amine is a direct precursor to a family of rigid nucleosides that are conformationally locked in the Southern hemisphere of the pseudorotational cycle. The synthesis of the conformationally locked adenosine analogue is reported herein as an illustrative example of the methodology. The racemic (South)methanocarba adenosine analogue (+/-)-4 is the first example of a conformationally locked ribonucleoside Version in the Southern hemisphere. C1 NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. USN, Res Lab, Struct Matter Lab, Washington, DC 20375 USA. RP Marquez, VE (reprint author), NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NR 37 TC 53 Z9 53 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD APR 7 PY 2000 VL 65 IS 7 BP 2172 EP 2178 DI 10.1021/jo9917691 PG 7 WC Chemistry, Organic SC Chemistry GA 302CV UT WOS:000086348400036 PM 10774042 ER PT J AU Moody, TW Leyton, J John, C AF Moody, TW Leyton, J John, C TI Sigma ligands inhibit the growth of small cell lung cancer cells SO LIFE SCIENCES LA English DT Article DE sigma ligands; receptors; proliferation; small cell lung cancer ID BREAST-CANCER; RECEPTORS; BINDING; IDENTIFICATION; PROLIFERATION; EXPRESSION; CARCINOMA; LINES; SITES AB The effects of sigma ligands on small cell lung cancer (SCLC) cells were investigated. I-125-N-(2-(piperidino)ethyl)-2-iodobenazmide (2-IBP) bound with high affinity to SCLC cell line NCl-H209 and NCl-N417. Specific I-125-2-IBP binding was inhibited with high affinity by ifendipine, haloperidol, (2-piperidinyl-aminoethyl)-4-iodobenzamide (IPAB) and 1,3-ditolylguanidine (DTG) with IC50 values of 3, 10, 15 and 90 nM respectively. In vitro, 10 mu M 2-IBP, haloperidol or IPAB inhibited NCl-N417 proliferation using a MTT or clonogenic assay. In vivo, 4 mg/kg IPAB or 2-IBP inhibited NCl-N417 xenograft proliferation. I-125-2-IBP localized to the SCLC tumors after subcutaneous injection. These results suggest that sigma ligands may be utilized to localize and inhibit the proliferation of SCLC tumors. C1 NCI, Cell & Canc Biol Dept, Med Branch, Rockville, MD 20850 USA. George Washington Univ, Med Ctr, Dept Radiol, Washington, DC 20037 USA. George Washington Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20037 USA. RP Moody, TW (reprint author), NCI, Cell & Canc Biol Dept, Med Branch, Rockville, MD 20850 USA. FU NCI NIH HHS [CA-58446] NR 26 TC 16 Z9 16 U1 0 U2 2 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 7 PY 2000 VL 66 IS 20 BP 1979 EP 1986 DI 10.1016/S0024-3205(00)00523-3 PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 305XD UT WOS:000086566300009 PM 10821122 ER PT J AU Borlongan, CV Su, TP Wang, Y AF Borlongan, CV Su, TP Wang, Y TI Treatment with delta opioid peptide enhances in vitro and in vivo survival of rat dopaminergic neurons SO NEUROREPORT LA English DT Article DE cell viability; fetal mesencephalic cells; hibernation medium; Parkinson's disease; substantia nigra; 6-hydroxydopamine; tyrosine hydroxylase ID NEURAL TRANSPLANTATION; BEHAVIORAL RECOVERY; NEUROTROPHIC FACTOR; PRESERVATION; INDUCTION; ENADOLINE; ISCHEMIA; PROTECTS; GRAFTS; TIME AB A major problem in neural transplantation therapy is poor survival of grafted cells, which may be due to low cell viability prior to transplantation or scarce trophic factors available to the cells following transplantation. Recently, the delta enkephalin analogue [D-Ala(2),D-Leu(5)]-enkephalin (DADLE) has been demonstrated to protect against, as well as to reverse methamphetamine-induced loss of dopamine transporters. Here, we show that pretreatment with DADLE (0.0025, 0.005, 0.01 g/ml) dose-dependently enhanced cell viability of cultured primary rat fetal mesencephalic cells. in addition, DADLE administration in adult rats (4 mg/kg every 2 h, 4 injections, i.p.) prior to 6-hydroxydopamine lesions of the medial forebrain bundle, significantly reduced the severity of loss of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra I month post-lesion. This is the first report suggesting that DADLE can be used as a supplement factor for improving the cell viability of fetal mesencephalic cells and as a protective agent against neurotoxicity in a Parkinson's disease model. NeuroReport 11:923-926 (C) 2000 Lippincott Williams & Wilkins. C1 NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Borlongan, CV (reprint author), NIDA, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Borlongan, Cesar/0000-0002-2966-9782 NR 25 TC 44 Z9 47 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD APR 7 PY 2000 VL 11 IS 5 BP 923 EP 926 DI 10.1097/00001756-200004070-00005 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 302VA UT WOS:000086385300009 PM 10790856 ER PT J AU Sedelis, M Hofele, K Auburger, GW Morgan, S Huston, JP Schwarting, RKW AF Sedelis, M Hofele, K Auburger, GW Morgan, S Huston, JP Schwarting, RKW TI Evidence for resistance to MPTP in C57BL/6 x BALB/c FI hybrids as compared with their progenitor strains SO NEUROREPORT LA English DT Article DE BALB/c; basal ganglia; C57BL/6; dopamine; FI hybrids; MPTP; neurogenetics; neurotoxicity; Parkinson's disease ID MICE; NEUROTOXICITY; CATECHOLAMINE; GENETICS; NEURONS; TOOL AB The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is capable of producing a syndrome in mice which shares major characteristics with human Parkinson's disease. There is evidence for a genetic influence on the degree of damage exerted by MPTP, since different strains of mice can dramatically differ in their response to MPTP. We produced reciprocal F1 hybrids by crossbreeding the MPTP-susceptible C57BL/6 strain with resistant BALB/c. These hybrids were compared to the parental strains using neural and behavioral measures in order to characterize the genetic transmission of MPTP-susceptibility. The F1 generation as a whole had a lower depletion of neostriatal dopamine levels than even found in BALB/c. Furthermore, there was no significant loss of tyrosine hydroxylase-positive cells in the substantia nigra and quick recovery from deficits in motor behavior in F1, herein resembling BALB/c. We suggest that several loci are involved in susceptibility to MPTP, and that the trait is under control of recessive susceptibility and/or dominant resistance alleles, which interact in F1, leading to extremely low susceptibility. NeuroReport 11:1093-1096 (C) 2000 Lippincott Williams & Wilkins. C1 Univ Dusseldorf, Inst Physiol Psychol 1, D-40225 Dusseldorf, Germany. Univ Dusseldorf, Ctr Biol & Med Res, D-40225 Dusseldorf, Germany. Univ Dusseldorf, Dept Neurol, D-40225 Dusseldorf, Germany. NHGRI, NIH, Bethesda, MD 20892 USA. Univ Marburg, D-35032 Marburg, Germany. RP Sedelis, M (reprint author), Univ Dusseldorf, Inst Physiol Psychol 1, Univ Str 1, D-40225 Dusseldorf, Germany. RI Huston, Joseph/C-8986-2009 NR 14 TC 19 Z9 19 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD APR 7 PY 2000 VL 11 IS 5 BP 1093 EP 1096 DI 10.1097/00001756-200004070-00037 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 302VA UT WOS:000086385300041 PM 10790888 ER PT J AU Kumra, S Wiggs, E Bedwell, J Smith, AK Arling, E Albus, K Hamburger, SD McKenna, K Jacobsen, LK Rapoport, JL Asarnow, RF AF Kumra, S Wiggs, E Bedwell, J Smith, AK Arling, E Albus, K Hamburger, SD McKenna, K Jacobsen, LK Rapoport, JL Asarnow, RF TI Neuropsychological deficits in pediatric patients with childhood-onset schizophrenia and psychotic disorder not otherwise specified SO SCHIZOPHRENIA RESEARCH LA English DT Article DE atypical psychosis; childhood-onset schizophrenia; neuropsychological deficit ID DEVELOPMENTAL DISORDER; CHILDREN; IMPAIRMENT; AGE; PSYCHOPATHOLOGY; DEMENTIA; SEX AB Objective: Children with transient psychotic symptoms and serious emotional disturbances who do not meet current criteria for schizophrenia or other presently recognized diagnostic categories commonly present diagnostic and treatment problems. Clarifying the connections between children with narrowly defined schizophrenia and children with a more broadly defined phenotype (i.e., Psychotic Disorder Not Otherwise Specified, PD-NOS) has implications for understanding the pathophysiology of schizophrenia. In this study, the neuropsychological test performance of a subgroup of children with atypical psychosis was compared with that of patients with childhood-onset schizophrenia (COS). Method: Cognitive function was assessed with neuropsychological test battery regimens in 51 neuroleptic-nonresponsive patients within the first 2 weeks after admission while receiving stable medication. Only those patients who had an IQ > 70 at NIMH testing (24 PD-NOS, 27 COS) were included in this analysis. Seventeen (39%) of 44 COS subjects were unavailable for this study as their IQ tested < 70. The PD-NOS patients were younger than the COS patients at the time of testing (12.0 +/- 2.8 vs 14.4 +/- 1.8 years, respectively, p < 0.004). The test levels of these groups were compared with each other. Results: The neuropsychological test results for the PD-NOS and COS patients were 1-2 standard deviations below normative data across a broad array of cognitive functions. There were no overall differences in the test levels for the six summary scales (F = 2.82, df = 1, 36, p = 0.10) or in the profile shape (F = 1.70, df = 5, 180, p = 0.14) between the PD-NOS and COS groups. For the COS patients, there was a significant difference between their mean full-scale WISC IQ (84.7 +/- 16.2) and their average standard scores for both the spelling (97.7 +/- 16.1, n = 23, t = 4.0, p = 0.001) and reading decoding subtests (97.7 +/- 13.7, n = 23, t = 3.7, p = 0.001) of the Kaufman Test of Educational Achievement. Conclusions: Treatment-refractory PD-NOS and COS patients share a similar pattern of generalized cognitive deficits, including deficits in attention, learning and abstraction which are commonly observed in adult patients with schizophrenia. These data support a hypothesis that at: least some of the PD-NOS cases belong within the schizophrenic spectrum, which is of importance for future genetic studies planned for this cohort. (C) 2000 Elsevier Science B.V. All rights reserved. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. Wellesley Coll, Wellesley, MA 02181 USA. Yale Univ, New Haven, CT 06520 USA. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. RP Kumra, S (reprint author), Clarke Inst Psychiat, Child & Family Study Ctr, 250 Coll St,Suite 132, Toronto, ON M5T 1R8, Canada. NR 54 TC 64 Z9 66 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR 7 PY 2000 VL 42 IS 2 BP 135 EP 144 DI 10.1016/S0920-9964(99)00118-8 PG 10 WC Psychiatry SC Psychiatry GA 301YQ UT WOS:000086338500006 PM 10742651 ER PT J AU Robertson, DL Anderson, JP Bradac, JA Carr, JK Foley, B Funkhouser, RK Gao, F Hahn, BH Kalish, ML Kuiken, C Learn, GH Leitner, T McCutchan, F Osmanov, S Peeters, M Pieniazek, D Salminen, M Sharp, PM Wolinsky, S Korber, B AF Robertson, DL Anderson, JP Bradac, JA Carr, JK Foley, B Funkhouser, RK Gao, F Hahn, BH Kalish, ML Kuiken, C Learn, GH Leitner, T McCutchan, F Osmanov, S Peeters, M Pieniazek, D Salminen, M Sharp, PM Wolinsky, S Korber, B TI HIV-1 nomenclature proposal SO SCIENCE LA English DT Letter ID AFRICAN ORIGIN; SEQUENCE; IDENTIFICATION; THAILAND; ISOLATE C1 Univ Oxford, Oxford, England. Univ Washington, Seattle, WA 98195 USA. NIH, Bethesda, MD 20892 USA. Henry M Jackson Fdn, Rockville, MD USA. Univ Calif Los Alamos Natl Lab, Los Alamos, NM USA. Santa Fe Inst, Santa Fe, NM 87501 USA. Univ Alabama, Birmingham, AL USA. Ctr Dis Control & Prevent, HIV AIDS & Retrovirol Branch, Atlanta, GA USA. Swedish Inst Infect Dis Control, Solna, Sweden. UNAIDS, Geneva, Switzerland. IRD, Montpellier, France. Natl Publ Hlth Inst, Helsinki, Finland. Univ Nottingham, Inst Genet, Nottingham NG7 2RD, England. Northwestern Univ, Sch Med, Chicago, IL USA. RP Robertson, DL (reprint author), Univ Oxford, Oxford, England. RI Wolinsky, Steven/B-2893-2012; Sharp, Paul/F-5783-2010; Learn, Gerald/B-6934-2011; Salminen, Mika/D-8784-2013 OI Sharp, Paul/0000-0001-9771-543X; Salminen, Mika/0000-0003-3020-0866 NR 10 TC 530 Z9 549 U1 5 U2 24 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 7 PY 2000 VL 288 IS 5463 BP 55 EP 57 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 302VT UT WOS:000086387700021 PM 10766634 ER PT J AU Vamecq, J Bac, P Herrenknecht, C Maurois, P Delcourt, P Stables, JP AF Vamecq, J Bac, P Herrenknecht, C Maurois, P Delcourt, P Stables, JP TI Synthesis and anticonvulsant and neurotoxic properties of substituted N-phenyl derivatives of the phthalimide pharmacophore SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PROTOTYPE ANTIEPILEPTIC DRUGS; MICE; RATS; ANALOGS; CHANNEL AB A series of compounds including 4-amino (1), 3-amino (2), 4-nitro (3), 2-methyl-3-amino (4), 2-methyl-3-nitro (5), 2-methyl-4-amino (6), 2-methyl-4-nitro (7), 2-methyl-5-amino (8), 2-methyl-5-nitro (9), 2-methyl-6-amino (10), 2-methyl-6-nitro (11), 2,6-dimethyl (12), 2-methyl-3-carboxy (13), 2-methoxycarbonyl (14), 2-methyl-4-methoxy (15), 2,4-dimethoxy (16), 2-chloro-4-amino (17), and 2-chloro-4-nitro (18) N-phenyl substituents of phthalimide were evaluated along with N-[3-methyl-(2-pyridinyl)]phthalimide (19), N-(3-amino-2-methylphenyl)succinimide (20), and phenytoin for anticonvulsant and neurotoxic properties. Initial screening in the intraperitoneal tip) maximal electroshock-induced seizure (MES) test and the subcutaneous pentylenetetrazol-induced seizure (scPtz) test in mice led to the selection of 1, 2, 4, 10, 12, 17, and 19 for oral MES evaluation in rats. The resultant ED(50) values for 4, 10, 17, and phenytoin were 8.0, 28.3, 5.7 and 29.8 mg/kg, respectively. In the batrachotoxin affinity assay, IC(50) values for 17 and phenytoin were 0.15 and 0.93 mu M, respectively, and in the recently validated magnesium deficiency-dependent audiogenic seizure test, ED(50) values of 5.2 and 23 mg/kg were obtained for 17 and phenytoin, respectively. Electrophysiology studies on compound 17 point out its ability to (i) potentiate GABA-evoked current responses with a failure to directly activate the GABAA receptor and (ii) to affect, at 100 mu M excitatory non NMDA, but not NMDA, receptors with a 25% block of kainate-evoked response. Electrophysiology measurements on voltage-gated sodium channels in N1E-115 neuroblastoma cells confirm voltage-dependent block of these channels by compound 17. In view of its interaction with multiple ion channels, one would predict that compound 17 might be active in a wide range of seizure models. C1 CHU Lille, Hop Roger Salengro, INSERM, Neuropaediat Dept, F-59037 Lille, France. Hop Robert Debre, Dept Prof Philippe Evrard, INSERM, F-75013 Paris, France. Fac Pharm Chatenay Malabry, Pharmacol Lab, Chatenay Malabry, France. SN3 USTL, INSERM, EPI 9938, Lab Physiol Cellulaire, Villeneuve Dascq, France. NINCDS, Preclin Pharmacol Sect, Epilepsy Branch, NIH,Neurosci Ctr, Bethesda, MD 20892 USA. Fac Pharm Chatenay Malabry, Chim Analyt Lab, Chatenay Malabry, France. RP Vamecq, J (reprint author), CHU Lille, Hop Roger Salengro, INSERM, Neuropaediat Dept, 2 Ave Oscar Lembret, F-59037 Lille, France. NR 23 TC 43 Z9 44 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD APR 6 PY 2000 VL 43 IS 7 BP 1311 EP 1319 DI 10.1021/jm990068t PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 302XP UT WOS:000086392000008 PM 10753468 ER PT J AU Phair, RD Misteli, T AF Phair, RD Misteli, T TI High mobility of proteins in the mammalian cell nucleus SO NATURE LA English DT Article ID RNA SPLICING FACTORS; LIVING CELLS; LOCALIZATION; DIFFUSION AB The mammalian cell nucleus contains numerous sub-compartments, which have been implicated in essential processes such as transcription and splicing(1,2). The mechanisms by which nuclear compartments are formed and maintained are unclear. More fundamentally, it is not known how proteins move within the cell nucleus. We have measured the kinetic properties of proteins in the nucleus of living cells using photobleaching techniques. Here we show that proteins involved in diverse nuclear processes move rapidly throughout the entire nucleus. Protein movement is independent of energy, which indicates that proteins may use a passive mechanism of movement. Proteins rapidly associate and dissociate with nuclear compartments. Using kinetic modelling, we determined residence times and steady-state fluxes of molecules in two main nuclear compartments. These data show that many nuclear proteins roam the cell nucleus in vivo and that nuclear compartments are the reflection of the steady-state association/dissociation of its 'residents' with the nucleoplasmic space. Our observations have conceptual implications for understanding nuclear architecture and how nuclear processes are organized in vivo. C1 NCI, NIH, Bethesda, MD 20892 USA. BioInformat Serv, Rockville, MD 20854 USA. RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA. NR 30 TC 796 Z9 809 U1 4 U2 39 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 6 PY 2000 VL 404 IS 6778 BP 604 EP + PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 303BC UT WOS:000086400100054 PM 10766243 ER PT J AU Detre, KM Lombardero, MS Brooks, MM Hardison, RM Holubkov, R Sopko, G Frye, RL Chaitman, BR AF Detre, KM Lombardero, MS Brooks, MM Hardison, RM Holubkov, R Sopko, G Frye, RL Chaitman, BR CA Bypass Angioplasty Revascularizati TI The effect of previous coronary-artery bypass surgery on the prognosis of patients with diabetes who have acute myocardial infarction SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID INSULIN-TREATMENT; CLINICAL COURSE; MORTALITY; MELLITUS; SURVIVAL AB Background: Acute myocardial infarction in patients with diabetes is associated with high mortality. We studied whether previous revascularization by coronary-artery bypass grafting (CABG), as compared with percutaneous transluminal coronary angioplasty (PTCA), influences the prognosis in such patients. Methods: We classified all patients eligible for the Bypass Angioplasty Revascularization Investigation who underwent coronary revascularization within three months after entry into the study according to whether they had diabetes and whether they had undergone CABG, either initially or after PTCA. The protective effect of CABG with regard to mortality in the presence and in the absence of subsequent spontaneous Q-wave myocardial infarction was estimated with the use of Cox regression models. Results: Among the 641 patients with diabetes and the 2962 without diabetes, the cumulative five-year rates of death were 20 percent and 8 percent, respectively (P<0.001), and the five-year rates of spontaneous Q-wave myocardial infarction were 8 percent and 4 percent (P<0.001). CABG greatly reduced the risk of death after spontaneous Q-wave myocardial infarction in the patients with diabetes (relative risk, 0.09; 95 percent confidence interval, 0.03 to 0.29). Among patients with diabetes who had undergone CABG but did not have spontaneous Q-wave myocardial infarction, the corresponding relative risk of death was 0.65 (95 percent confidence interval, 0.45 to 0.94). Among the patients without diabetes, no protective effect of CABG was evident. Conclusions: Among patients with diabetes, previous coronary bypass surgery, as compared with coronary angioplasty, has a highly favorable influence on prognosis after acute myocardial infarction and a smaller beneficial effect among patients who do not have infarction. These findings should influence the type of coronary revascularization procedure selected for patients with diabetes who have multivessel coronary artery disease. (N Engl J Med 2000;342:989-97.) (C) 2000, Massachusetts Medical Society. C1 Univ Pittsburgh, Grad Sch Publ Hlth, BARI Coordinating Ctr, Pittsburgh, PA 15261 USA. NIH, Bethesda, MD 20892 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. St Louis Univ, Hlth Sci Ctr, St Louis, MO 63103 USA. RP Detre, KM (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, BARI Coordinating Ctr, 130 DeSoto St,127 Parran Hall, Pittsburgh, PA 15261 USA. OI Brooks, Maria/0000-0002-2030-7873 NR 29 TC 116 Z9 120 U1 0 U2 2 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 6 PY 2000 VL 342 IS 14 BP 989 EP 997 DI 10.1056/NEJM200004063421401 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 300JB UT WOS:000086248900001 PM 10749960 ER PT J AU Xu, XL Brodie, SG Yang, X Im, YH Parks, WT Chen, L Zhou, YX Weinstein, M Kim, SJ Deng, CX AF Xu, XL Brodie, SG Yang, X Im, YH Parks, WT Chen, L Zhou, YX Weinstein, M Kim, SJ Deng, CX TI Haploid loss of the tumor suppressor Smad4/Dpc4 initiates gastric polyposis and cancer in mice SO ONCOGENE LA English DT Article DE Smad4; Dpc4; juvenile polyposis; gastric cancer; TGF beta 1; cyclin D1 ID GROWTH-FACTOR-BETA; CYCLIN D1; TGF-BETA; JUVENILE POLYPOSIS; COLORECTAL-CANCER; TRANSFORMING GROWTH-FACTOR-BETA-1; HELICOBACTER-FELIS; CHROMOSOME 18Q21.1; MESODERM INDUCTION; EPITHELIAL-CELLS AB The tumor suppressor SMAD4, also known as DPC4, deleted in pancreatic cancer, is a central mediator of TGF-P signaling. It was previously shown that mice homozygous for a null mutation of Smad4 (Smad4(-/-)) died prior to gastrulation displaying impaired extra-embryonic membrane formation and endoderm differentiation. Here we show that Smad4(+/-) mice began to develop polyposis in the fundus and antrum when they were over 6-12 months old, and in the duodenum and cecum in older animals at a lower frequency, With increasing age, polyps in the antrum show sequential changes from hyperplasia, to dysplasia, in-situ carcinoma, and finally invasion. These alterations are initiated by a dramatic expansion of the gastric epithelium where Smad4 is expressed. However, loss of the remaining Smad4 wild-type allele was detected only in later stages of tumor progression, suggesting that haploinsufficiency of Smad4 is sufficient for tumor initiation. Our data also showed that overexpression of TGF-beta 1 and Cyclin D1 was associated with increased proliferation of gastric polyps and tumors. These studies demonstrate that Smad4 functions as a tumor suppressor in the gastrointestinal tract and also provide a valuable model for screening factors that promote or prevent gastric tumorigenesis. C1 NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. NCI, Cell Regulat & Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Deng, CX (reprint author), NIDDKD, Genet Dev & Dis Branch, NIH, 10-9N105, Bethesda, MD 20892 USA. RI deng, chuxia/N-6713-2016 NR 48 TC 160 Z9 178 U1 0 U2 5 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 6 PY 2000 VL 19 IS 15 BP 1868 EP 1874 DI 10.1038/sj.onc.1203504 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 303LX UT WOS:000086424300002 PM 10773876 ER PT J AU Mittur, AV Kaplowitz, N Kempner, ES Ookhtens, M AF Mittur, AV Kaplowitz, N Kempner, ES Ookhtens, M TI Radiation inactivation studies of hepatic sinusoidal reduced glutathione transport system SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Article DE glutathione transport; target size analysis; sinusoidal membrane vesicle ID PERFORMANCE LIQUID-CHROMATOGRAPHY; PLASMA-MEMBRANE VESICLES; ISOLATED RAT HEPATOCYTES; IONIZING-RADIATION; ORGANIC-ANIONS; LIVER; EFFLUX; INHIBITION; KINETICS; IDENTIFICATION AB Sinusoidal transport of reduced glutathione (GSH) is a carrier-mediated process. Perfused liver and isolated hepatocyte models revealed a low-affinity transporter with sigmoidal kinetics (K-m similar to 3.2-12 mM), while studies with sinusoidal membrane vesicles (SMV) revealed a high-affinity unit (K-m similar to 0.34 mM) besides a low-affinity one (K-m similar to 3.5-7 mM). However, in SMV, both the high- and low-affinity units manifested Michaelis-Menten kinetics of GSH transport. We have now established the sigmoidicity of the low-affinity unit (K-m similar to 9) in SMV, consistent with other models, while the high-affinity unit has been retained intact with Michaelis-Menten kinetics (K-m similar to 0.13 mM). We capitalized on the negligible cross-contributions of the two units to total transport at the low and high ends of GSH concentrations and investigated their characteristics separately, using radiation inactivation, as we did in canalicular GSH transport (Am. J. Physiol. 274 (1998) G923-G930). We studied the functional sizes of the proteins that mediate high- and low-affinity GSH transport in SMV by inactivation of transport at low (trace and 0.02 mM) and high (25 and 50 mM) concentrations of GSH. The low-affinity unit in SMV was much less affected by radiation than in canalicular membrane vesicles (CMV). The target size of the low-affinity sinusoidal GSH transporter appeared to be considerably smaller than both the canalicular low- and high-affinity transporters. The high-affinity unit in SMV was markedly inactivated upon irradiation, revealing a single protein structure with a functional size of similar to 70 kDa, This size is indistinguishable from that of the high-affinity GSH transporter in CMV reported earlier. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Univ So Calif, Sch Med, Dept Med, Liver Dis Res Ctr, Los Angeles, CA 90033 USA. NIAMS, Phys Biol Lab, NIH, Bethesda, MD 20892 USA. RP Ookhtens, M (reprint author), Univ So Calif, Sch Med, Dept Med, Liver Dis Res Ctr, 2011 Zonal Ave,HMR-615, Los Angeles, CA 90033 USA. FU NIA NIH HHS [R01 AG-07467]; NIDDK NIH HHS [P30 DK-48522, R37 DK-30312] NR 39 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD APR 5 PY 2000 VL 1464 IS 2 BP 207 EP 218 DI 10.1016/S0005-2736(00)00152-8 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 298FY UT WOS:000086129700004 PM 10727608 ER PT J AU Nourse, A Millar, DB Minton, AP AF Nourse, A Millar, DB Minton, AP TI Physicochemical characterization of generation 5 polyamidoamine dendrimers SO BIOPOLYMERS LA English DT Article DE partial specific volume; sedimentation velocity; sedimentation equilibrium; diffusion ID PROTEINS; VOLUME; CONSEQUENCES AB The dispersity size, and self-interaction of generation 5 polyamidoamine dendrimeric polymers with different terminal groups (surfaces) were characterized using several physicochemical techniques. Amino-surface dendrimers form oligomeric aggregates in aqueous solution, even in the presence of high salt concentrations (0.6M sodium phosphate). In contrast, the hydroxyl-surface polymer G5-OH behaves as a single homogeneous (or paucidisperse) species at low concentration. Measurements of density increment and the sedimentation and diffusion coefficients of G5-OH suggest a more swollen, porous structure than a globular protein of comparable mass. Measurements of the the concentration dependence of sedimentation equilibrium of G5-OH in pH 7.2 phosphate buffer indicate the presence of significant electrostatic repulsion overlaid on,weakly attractive interactions, leading to the formation of nonspecific aggregates at sufficiently high dendrimer concentration. (C) 2000 John Wiley & Sons, Inc.dagger Biopoly 53: 316-328, 2000. C1 NIDDKD, Lab Biochem & Genet, Sect Phys Biochem, NIH, Bethesda, MD 20892 USA. RP Nourse, A (reprint author), NIDDKD, Lab Biochem & Genet, Sect Phys Biochem, NIH, Bethesda, MD 20892 USA. NR 20 TC 34 Z9 35 U1 2 U2 11 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PD APR 5 PY 2000 VL 53 IS 4 BP 316 EP 328 DI 10.1002/(SICI)1097-0282(20000405)53:4<316::AID-BIP4>3.0.CO;2-J PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 304DK UT WOS:000086467400004 PM 10685052 ER PT J AU Tucker, M Goldstein, A Dean, M Knudson, A AF Tucker, M Goldstein, A Dean, M Knudson, A TI National Cancer Institute workshop report: The Phakomatoses Revisited SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NCI, Div Basic Sci, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Knudson, A (reprint author), Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA. RI Tucker, Margaret/B-4297-2015; OI Dean, Michael/0000-0003-2234-0631 NR 0 TC 11 Z9 11 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 5 PY 2000 VL 92 IS 7 BP 530 EP 533 DI 10.1093/jnci/92.7.530 PG 4 WC Oncology SC Oncology GA 300YE UT WOS:000086280700009 PM 10749907 ER PT J AU Grauman, DJ Tarone, RE Devesa, SS Fraumeni, JF AF Grauman, DJ Tarone, RE Devesa, SS Fraumeni, JF TI Alternate ranging methods for cancer mortality maps SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID LUNG-CANCER; UNITED-STATES; EMPLOYMENT; CARCINOMA; PATTERNS; SMOKING AB Background: Mapping techniques can highlight the spatial or temporal variations in rates of cancer mortality. In mapping geographic patterns of cancer mortality, spatial units are grouped into categories defined by specified rate ranges, and then the units in each category are assigned a particular color in the map. We examined the consequences of using different ranging methods when comparing maps over several time intervals. Methods: Maps of mortality rates for cancers of the breast, lung (including the lung, trachea, bronchus, and pleura), and cervix uteri in the United States by county or state economic area are created for different time intervals between 1950 and 1994, Two ranging methods are employed: 1) Ranges are defined for individual time interval by the deciles of rates in that interval (ranging within intervals), and 2) constant ranges for all time intervals are defined by the deciles of rates for the entire 45-year period from 1950 through 1994 (ranging across intervals. The time intervals from 1950 through 1969 and from 1970 through 1991 were chosen to accommodate the availability of detailed county-level population estimates specifically for blacks starting in 1970. Results: The ranging method has little impart on maps for breast cancer mortality, which changed little over time. For lung cancer, which increased over timer and cervix uteri cancer, which decreased over time, ranging within tine intervals shows the geographic variability but does not convey the temporal trends. Trends are evident when ranging across time interval is employed; however, geographic variability is partially obscured by the predominance of spatial units in the highest rate categories in the recent time intervals for lung cancer and in the early time intervals for cervix uteri cancer. Conclusions: Ranging within time intervals displays geographic patterns and changes in geographic patterns, regardless of time trends in rates. Ranging across time intervals shows temporal changes in rates but with some loss of information about geographic variability. C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Grauman, DJ (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,MSC 7244,Rm 8050, Bethesda, MD 20892 USA. NR 30 TC 11 Z9 11 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 5 PY 2000 VL 92 IS 7 BP 534 EP 543 DI 10.1093/jnci/92.7.534 PG 10 WC Oncology SC Oncology GA 300YE UT WOS:000086280700010 PM 10749908 ER PT J AU Loeve, F Brown, ML Boer, R van Ballegooijen, M van Oortmarssen, GJ Habbema, JDF AF Loeve, F Brown, ML Boer, R van Ballegooijen, M van Oortmarssen, GJ Habbema, JDF TI Endoscopic colorectal cancer screening: a cost-saving analysis SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID FECAL-OCCULT-BLOOD; FLEXIBLE SIGMOIDOSCOPY; POLYPS; TRIAL; POPULATION; NEOPLASIA; MORTALITY; SURVEILLANCE; POLYPECTOMY; COLONOSCOPY AB Background: Comprehensive analyses have shown that screening for cancer usually induces net costs. In this study, the possible costs and savings of endoscopic colorectal cancer screening are explored to investigate whether the induced savings may compensate for the costs of screening. Methods: A simulation model for evaluation of colorectal cancer screening, MISCAN-COLON, is used to predict costs and savings for the U.S. population, assuming that screening is performed during a period of 30 years. Plausible baseline parameter values of epidemiology, natural history, screening test characteristics, and unit costs are based on available data and expert opinion. Important parameters are varied to extreme but plausible values. Results: Given the expert opinion-based assumptions, a program based on every 5-year sigmoidoscopy screenings could result in a net savings of direct health care costs due to prevention of cancer treatment costs that compensate for the costs of screening, diagnostic follow-up, and surveillance. This result persists when costs and health effects are discounted at 3%, The "break-even" point, the time required before savings exceed costs, is 35 years for a screening program that terminates after 30 years and 44 years for a screening program that continues on indefinitely. However, net savings increase or turn into net costs when alternative assumptions about natural history of colorectal cancer, costs of screening, surveillance, and diagnostics are considered. Conclusions: Given the present, limited knowledge of the disease process of colorectal cancer, test characteristics, and costs, it may well be that the induced savings by endoscopic colorectal cancer screening completely compensate for the costs. C1 Erasmus Univ, Fac Med, Dept Publ Hlth IMGZ, NL-3000 DR Rotterdam, Netherlands. NCI, Div Canc Control & Populat Sci, Appl Res Branch, Bethesda, MD 20892 USA. RP Loeve, F (reprint author), Erasmus Univ, Fac Med, Dept Publ Hlth IMGZ, POB 1738, NL-3000 DR Rotterdam, Netherlands. RI Boer, Rob/E-6473-2015 OI Boer, Rob/0000-0003-0680-001X FU NCI NIH HHS [N01CN55186] NR 55 TC 123 Z9 125 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 5 PY 2000 VL 92 IS 7 BP 557 EP 563 DI 10.1093/jnci/92.7.557 PG 7 WC Oncology SC Oncology GA 300YE UT WOS:000086280700013 PM 10749911 ER PT J AU Gail, MH Costantino, JP Bryant, J Croyle, R Freedman, L Helzlsouer, K Vogel, V AF Gail, MH Costantino, JP Bryant, J Croyle, R Freedman, L Helzlsouer, K Vogel, V TI Re: Risk/benefit assessment of tamoxifen to prevent breast cancer - Still a work in progress? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Bar Illan Univ, Ramat Gan, Israel. Johns Hopkins Sch Hyg & Publ Hlth, Baltimore, MD USA. Univ Pittsburgh, Inst Canc, Magee Womens Hosp, Pittsburgh, PA 15260 USA. RP Gail, MH (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Execut Plaza S,Rm 8032, Bethesda, MD 20892 USA. NR 3 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 5 PY 2000 VL 92 IS 7 BP 574 EP 574 DI 10.1093/jnci/92.7.574 PG 1 WC Oncology SC Oncology GA 300YE UT WOS:000086280700016 PM 10749915 ER PT J AU Culleton, BF Larson, MG Levy, D AF Culleton, BF Larson, MG Levy, D TI Serum uric acid and cardiovascular disease risk - Response SO ANNALS OF INTERNAL MEDICINE LA English DT Letter ID MORTALITY C1 Univ Calgary, Calgary, AB T2N 2T9, Canada. NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. RP Culleton, BF (reprint author), Univ Calgary, Calgary, AB T2N 2T9, Canada. NR 4 TC 0 Z9 0 U1 0 U2 0 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 4 PY 2000 VL 132 IS 7 BP 592 EP 592 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 298FU UT WOS:000086129300013 ER PT J AU West, FW Seo, HS Bradrick, TD Howell, EE AF West, FW Seo, HS Bradrick, TD Howell, EE TI Effects of single-tryptophan mutations on R67 dihydrofolate reductase SO BIOCHEMISTRY LA English DT Article ID TIME-RESOLVED FLUORESCENCE; N-TERMINAL DOMAIN; ESCHERICHIA-COLI; CIRCULAR-DICHROISM; PROTEIN-STRUCTURE; ANISOTROPY DECAY; TRP APOREPRESSOR; STEADY-STATE; MUTANTS; EQUILIBRIUM AB R67 dihydrofolate reductase (DHFR) is an R-plasmid-encoded enzyme that confers clinical resistance to the ant;bacterial drug trimethoprim. This enzyme shows no sequence or structural homology to the chromosomal DHFRs. The active form of the protein is a homotetramer possessing D-2 symmetry and a single active-site pen. Two tryptophans occur per monomer: W38 and its symmetry-related residues (W138, W238, and W338) occur at the dimer-dimer interfaces, while W45 and its symmetry-related partners (W145, W245, and W345) occur at the monomer-monomer interfaces. Two single-tryptophan mutant genes were constructed to determine the structural and functional consequences of four mutations per tetramer. The W45F mutant retains full enzyme activity and the fluorescence environment of the unmutated W38 residues clearly monitors ligand binding and a pH dependent tetramer reversible arrow 2 dimers equilibrium. In contrast, four simultaneous W38F mutations at the dimer-dimer interfaces result in tetramer destabilization. The ensuing dimer is relatively inactive, as is dimeric wild-type R67 DHFR. A comparison of emission spectra indicates the fluorescent signal of wild-type R67 DHFR is dominated by the contribution from W38. Equilibrium unfolding/folding curves at pH 5.0, where all protein variants are dimeric, indicate the environment monitored by the W38 residue is slightly less stable than the environment monitored by the W45 residue. C1 Univ Tennessee, Dept Biochem Cellular & Mol Biol, Knoxville, TN 37996 USA. NHLBI, Opt Spect Sect, NIH, Bethesda, MD 20892 USA. RP Howell, EE (reprint author), Univ Tennessee, Dept Biochem Cellular & Mol Biol, Knoxville, TN 37996 USA. EM lzh@utk.edu FU NIGMS NIH HHS [GM35308] NR 49 TC 11 Z9 11 U1 1 U2 4 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 4 PY 2000 VL 39 IS 13 BP 3678 EP 3689 DI 10.1021/bi992195x PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 299JF UT WOS:000086194800019 PM 10736167 ER PT J AU Moore-Hoon, ML Turner, RJ AF Moore-Hoon, ML Turner, RJ TI The structural unit of the secretory Na+-K+-2Cl(-) cotransporter (NKCCl) is a homodimer SO BIOCHEMISTRY LA English DT Article ID K-CL COTRANSPORTER; BASOLATERAL MEMBRANE-VESICLES; SHARK RECTAL GLAND; BUMETANIDE-BINDING; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; DIRECT PHOSPHORYLATION; TRANSPORT; RABBIT; RAT AB The oligomeric state of the secretory Na+-K+-2Cl(-) cotransporter (NKCCl) in rat parotid plasma membranes was studied using the reversible chemical cross-linker DTSSP [3,3'-dithiobis-(sulfosuccinimidyl propionate)]. The monomeric apparent molecular mass of NKCCl is similar to 170 kDa. However, we show here that this protein migrates as a similar to 355 kDa complex on SDS-PAGE gels after membrane treatment with DTSSP, indicating that NKCCl exists as an oligomer in the plasma membrane. The stability of this oligomer is such that it is not disrupted by solubilization of the membrane by Low concentrations of the nonionic detergent Triton X-100 (0.3%) or the mild ionic detergent deoxycholate (20 mM); however, higher concentrations of Triton X-100 or treatment with the denaturing detergent SDS do result in destabilization of the NKCCl complex. In additional experiments, we immunoprecipitated the 355 kDa cross-linked complex from biotinylated membranes, then cleaved the cross-linking bends and analyzed the resulting components of the NKCCl oligomer by avidin blotting? silver staining, and 2D electrophoresis. In these studies, we were unable to detect the presence of any proteins other than NKCCl itself in the 355 kDa oligomer, suggesting that this complex is tin NKCCl dimer. Strong evidence for this conclusion was provided by a quantitative analysis of the molecular sizes of oligomers formed by full-length NKCCl and an N-terminally truncated version of NKCCl expressed in HEK293 cells. Taken together, our data provide convincing evidence that the dominant structural unit of NKCCl in the plasma membrane is a homodimer. C1 NIDCR, Membrane Biol Sect, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Turner, RJ (reprint author), NIDCR, Membrane Biol Sect, Gene Therapy & Therapeut Branch, NIH, Bldg 10,Room 1A06,10 Ctr Dr,MSC 1190, Bethesda, MD 20892 USA. NR 36 TC 57 Z9 57 U1 0 U2 2 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 4 PY 2000 VL 39 IS 13 BP 3718 EP 3724 DI 10.1021/bi992301v PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 299JF UT WOS:000086194800023 PM 10736171 ER PT J AU Zeng, GY Nystrom, FH Ravichandran, LV Cong, LN Kirby, M Mostowski, H Quon, MJ AF Zeng, GY Nystrom, FH Ravichandran, LV Cong, LN Kirby, M Mostowski, H Quon, MJ TI Roles for insulin receptor, PI3-kinase, and Akt in insulin-signaling pathways related to production of nitric oxide in human vascular endothelial cells SO CIRCULATION LA English DT Article DE insulin; endothelium; signal transduction; nitric oxide; receptors ID RAT ADIPOSE-CELLS; PROTEIN-KINASE-B; PHOSPHATIDYLINOSITOL 3-KINASE; GENE-TRANSFER; 1-PHOSPHATIDYLINOSITOL 3-KINASE; GLUCOSE-UPTAKE; GROWTH-FACTOR; TRANSLOCATION; GLUT4; ELECTROPORATION AB Background-Previously, we demonstrated that insulin stimulates production of nitric oxide (NO) in endothelial cells. However, specific insulin-signaling pathways mediating production of NO have not been elucidated. Methods and Results-We developed methods for transfection of human umbilical vein endothelial cells (HUVECs) and direct measurement of NO to begin defining insulin-signaling pathways related to NO production. HUVECs were cotransfected with enhanced Green Fluorescent Protein (eGFP) and another gene of interest. Transfection efficiencies >95% were obtained by selecting cells expressing eGFP. Overexpression of insulin receptors in HUVECs resulted in an approximate to 3-fold increase in production of NO in response to insulin. In contrast, HUVECs overexpressing a tyrosine kinase-deficient mutant insulin receptor had a dose-response curve similar to that of control cells. Overexpression of inhibitory mutants of either phosphatidylinositol 3-kinase (PI3K) or Akt resulted in nearly complete inhibition of insulin-stimulated production of NO. Overexpression of an inhibitory mutant of Rns had a much smaller effect. Conclusions-Receptor kinase activity is necessary to mediate production of NO through the insulin receptor. Both PI3K and Akt contribute importantly to this process, whereas the contribution of Ras is small. C1 NHLBI, Hypertens Endocrine Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Expt Res, Bethesda, MD 20014 USA. RP Quon, MJ (reprint author), NHLBI, Hypertens Endocrine Branch, NIH, Bldg 10,Room 8C-218,10 Ctr Dr,MSC 1755, Bethesda, MD 20892 USA. RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Nystrom, Fredrik/0000-0002-1680-1000; Quon , Michael /0000-0002-5289-3707 NR 39 TC 477 Z9 505 U1 1 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 4 PY 2000 VL 101 IS 13 BP 1539 EP 1545 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 300QE UT WOS:000086263000011 PM 10747347 ER PT J AU Philibert, RA Winfield, SL Sandhu, HK Martin, BM Ginns, EI AF Philibert, RA Winfield, SL Sandhu, HK Martin, BM Ginns, EI TI The structure and expression of the human neuroligin-3 gene SO GENE LA English DT Article DE genetics; mental retardation; repetitive DNA ID NEUREXINS; SEQUENCES; BINDING AB The neuroligins are a family of proteins that are thought to mediate cell to cell interactions between neurons. During the sequencing at an Xq13 locus associated with a mental retardation syndrome in some studies, we discovered a portion of the human orthologue of the rat neuroligin-3 gene. We now report the structure and the expression of that gene. The gene spans approximately 30 kb and contains eight exons. Unlike the rat gene, it codes for at least two mRNAs and at least one of which is expressed outside the CNS, Interestingly, the putative promoter for the gene overlaps the last exon of the neighboring HOPA gene and is located less than 1 kb from an OPA element in which a polymorphism associated with mental retardation is found. These findings suggest a possible role for the neuroligin gene in mental retardation and that the role of the gene in humans may differ from its role in rats. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Univ Iowa, Dept Psychiat, MEB, Iowa City, IA 52242 USA. Univ Iowa, Neurosci Program, MEB, Iowa City, IA 52242 USA. NIMH, Clin Neurosci Branch, Bethesda, MD 20892 USA. RP Philibert, RA (reprint author), Univ Iowa, Dept Psychiat, MEB, Rm 2-126B, Iowa City, IA 52242 USA. NR 17 TC 45 Z9 49 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD APR 4 PY 2000 VL 246 IS 1-2 BP 303 EP 310 DI 10.1016/S0378-1119(00)00049-4 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 304NP UT WOS:000086490600031 PM 10767552 ER PT J AU Greenberg, BD Li, Q Lucas, FR Hu, S Sirota, LA Benjamin, J Lesch, KP Hamer, D Murphy, DL AF Greenberg, BD Li, Q Lucas, FR Hu, S Sirota, LA Benjamin, J Lesch, KP Hamer, D Murphy, DL TI Association between the serotonin transporter promoter polymorphism and personality traits in a primarily female population sample SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE neuroticism; genetics; personality traits; serotonin transporter; promoter ID OBSESSIVE-COMPULSIVE DISORDER; GENE REGULATORY REGION; ONSET ALZHEIMERS-DISEASE; ANXIETY-RELATED TRAITS; MESSENGER-RNA LEVELS; FUNCTIONAL POLYMORPHISM; PANIC DISORDER; HARM AVOIDANCE; UNITED-STATES; BINDING-SITES AB The serotonin transporter (5-HTT) regulates serotonergic neurotransmission and is thought to influence emotion. A 5-HTT-linked polymorphic region (5-HTTLPR) has two common variants, short (s) and long (1). We previously found population and within-family associations between the lower-expressing s allele and neuroticism, a trait related to anxiety, hostility, and depression, on a standard measure (the NEO Personality Inventory, Revised [NEO-PI-R]) in a primarily male population (n = 505), and that the s allele was dominant. We investigated this association in a new sample (n = 397, 84% female, primarily sib-pairs). The results robustly replicated the 5-HTTLPR neuroticism association, and the dominance of the s allele. Combined data from the two studies (n = 902) showed a highly significant association between the s allele and higher NEO Neuroticism both across individuals and within families. Association between genotype and a related measure, Anxiety on the 16PF inventory, was replicated in the new population and within families in the combined sample. Association to another trait, estimated TPQ Harm Avoidance, was not replicated in the new sample but found only within the combined sibship group. Another association found in our original study, between the s allele and lower scores on NEO-PI-R Agreeableness, was also replicated and was more robust in the current and the combined samples. Associations between the functional 5-HTTLPR polymorphism were similar in women and men. These results help to define specific personality features reproducibly associated with 5-HTTLPR genotype. Such associations were strongest for traits defined by the NEO, enhancing the attractiveness of the five-factor personality model in genetic research on complex behavioral dimensions. (C) 2000 Wiley-Liss, Inc. C1 NIMH, Clin Sci Lab, NIH, Ctr Clin, Bethesda, MD 20892 USA. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. Ben Gurion Univ Negev, Dept Psychiat, IL-84105 Beer Sheva, Israel. Univ Wurzburg, Dept Psychiat, D-8700 Wurzburg, Germany. RP Greenberg, BD (reprint author), NIMH, Clin Sci Lab, NIH, Ctr Clin, Bldg 10-3D-41, Bethesda, MD 20892 USA. RI Lesch, Klaus-Peter/J-4906-2013 OI Lesch, Klaus-Peter/0000-0001-8348-153X NR 65 TC 223 Z9 234 U1 5 U2 19 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD APR 3 PY 2000 VL 96 IS 2 BP 202 EP 216 DI 10.1002/(SICI)1096-8628(20000403)96:2<202::AID-AJMG16>3.0.CO;2-J PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 299BN UT WOS:000086176100016 PM 10893498 ER PT J AU Nacro, K Bienfait, B Lewin, NE Blumberg, PM Marquez, VE AF Nacro, K Bienfait, B Lewin, NE Blumberg, PM Marquez, VE TI Diacylglycerols with lipophilically equivalent branched acyl chains display high affinity for protein kinase C (PK-C). A direct measure of the effect of constraining the glycerol backbone in DAG lactones SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID 5-DISUBSTITUTED TETRAHYDRO-2-FURANONE TEMPLATE; PHORBOL ESTER; ANALOGS; BINDING AB New synthetic diacylglycerols (DAGs) with equivalent branched acyl chains were compared with commercially available DAGs as PK-C ligands. The results support the view that there is a minimal lipophilic requirement provided by the equivalent acyl groups that results in high binding affinity. Locking the glycerol backbone of the most potent DAG into a five-member lactone resulted in a 10-fold increase in potency. Published by Elsevier Science Ltd. C1 NCI, Div Basic Sci, Labs Med Chem, NIH, Bethesda, MD 20892 USA. NCI, Div Basic Sci, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. RP Marquez, VE (reprint author), NCI, Div Basic Sci, Labs Med Chem, NIH, Bethesda, MD 20892 USA. NR 16 TC 11 Z9 11 U1 0 U2 1 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 3 PY 2000 VL 10 IS 7 BP 653 EP 655 DI 10.1016/S0960-894X(00)00070-6 PG 3 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 299CX UT WOS:000086179200011 PM 10762046 ER PT J AU Dell'Angelica, EC Puertollano, R Mullins, C Aguilar, RC Vargas, JD Hartnell, LM Bonifacino, JS AF Dell'Angelica, EC Puertollano, R Mullins, C Aguilar, RC Vargas, JD Hartnell, LM Bonifacino, JS TI GGAs: A family of ADP ribosylation factor-binding proteins related to adaptors and associated with the Golgi complex SO JOURNAL OF CELL BIOLOGY LA English DT Article DE trans-Golgi network; ADP ribosylation factor; coats; adaptins; VHS ID SACCHAROMYCES-CEREVISIAE; VESICLE FORMATION; COAT PROTEINS; ENDOPLASMIC-RETICULUM; MEMBRANE-PROTEIN; YEAST VACUOLE; GAMMA-ADAPTIN; BREFELDIN-A; CLATHRIN; RECRUITMENT AB Formation of intracellular transport intermediates and selection of cargo molecules are mediated by protein coats associated with the cytosolic face of membranes. Here, we describe a novel family of ubiquitous coat proteins termed GGAs, which includes three members in humans and two in yeast. GGAs have a modular structure consisting of a VHS domain, a region of homology termed GAT, a linker segment, and a region with homology to the ear domain of gamma-adaptins. Immunofluorescence microscopy showed colocalization of GGAs with Golgi markers, whereas immunoelectron microscopy of GGA3 revealed its presence on coated vesicles and buds in the area of the TGN. Treatment with brefeldin A or overexpression of dominant-negative ADP ribosylation factor 1 (ARF1) caused dissociation of GGAs from membranes. The GAT region of GGA3 was found to: target a reporter protein to the Golgi complex; induce dissociation from membranes of ARF-regulated coats such as AP-1, AP-3, AP-4, and COPI upon overexpression; and interact with activated ARF1, Disruption of both GGA genes in yeast resulted in impaired trafficking of carboxypeptidase Y to the vacuole. These observations suggest that GGAs are components of ARF-regulated coats that mediate protein trafficking at the TGN. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP NICHHD, Cell Biol & Metab Branch, NIH, Bldg 18T,Room 101, Bethesda, MD 20892 USA. EM juan@helix.nih.gov OI Bonifacino, Juan S./0000-0002-5673-6370 NR 57 TC 271 Z9 278 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0021-9525 EI 1540-8140 J9 J CELL BIOL JI J. Cell Biol. PD APR 3 PY 2000 VL 149 IS 1 BP 81 EP 93 DI 10.1083/jcb.149.1.81 PG 13 WC Cell Biology SC Cell Biology GA 301HB UT WOS:000086303800011 PM 10747089 ER PT J AU Lucas, PJ Kim, SJ Melby, SJ Gress, RE AF Lucas, PJ Kim, SJ Melby, SJ Gress, RE TI Disruption of T cell homeostasis in mice expressing a T cell-specific dominant negative transforming growth factor beta II receptor SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE lymphoproliferative disorder; T lymphocyte subsets; TCR repertoire; T cell transformation; thymocyte development ID CHORIOMENINGITIS VIRUS-INFECTION; TGF-BETA; IN-VIVO; TRANSGENIC MICE; CTLA-4-DEFICIENT MICE; LYMPHOID HOMEOSTASIS; TARGETED DISRUPTION; IMMUNE-RESPONSE; KNOCKOUT MICE; NITRIC-OXIDE AB The immune system, despite its complexity, is maintained at a relative steady state. Mechanisms involved in maintaining lymphocyte homeostasis are poorly understood; however, recent availability of transgenic (Tg) and knockout mouse models with altered balance of lymphocyte cell populations suggest that cytokines play a major role in maintaining lymphocyte homeostasis. We show here that transforming growth factor (TGF)-beta plays a critical role in maintaining CD8(+) T cell homeostasis in a Tg mouse model that specifically overexpresses a dominant negative TGF-beta II receptor (DNRII) on T cells. DNRII T cell Tg mice develop a CD8(+) T cell lymphoproliferative disorder resulting in the massive expansion of the lymphoid organs. These CD8(+) T cells are phenotypically "naive" except for the upregulation of the cell surface molecule CD44, a molecule usually associated with memory T cells. Despite their dominance in the peripheral lymphoid organs, CD8(+) T cells appear to develop normally in the thymus, suggesting that TGF-beta exerts its homeostatic control in the peripheral immune system. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. RP Gress, RE (reprint author), NCI, Expt Immunol Branch, NIH, 10 Ctr Dr 10-4B-36, Bethesda, MD 20892 USA. NR 61 TC 177 Z9 192 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 3 PY 2000 VL 191 IS 7 BP 1187 EP 1196 DI 10.1084/jem.191.7.1187 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 302KX UT WOS:000086365200010 PM 10748236 ER PT J AU Colella, TA Bullock, TNJ Russell, LB Mullins, DW Overwijk, WW Luckey, CJ Pierce, RA Restifo, NP Engelhard, VH AF Colella, TA Bullock, TNJ Russell, LB Mullins, DW Overwijk, WW Luckey, CJ Pierce, RA Restifo, NP Engelhard, VH TI Self-tolerance to the murine homologue of a tyrosinase-derived melanoma antigen: Implications for tumor immunotherapy SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE tyrosinase; self-tolerance; MHC class I; cytotoxic T lymphocytes; immunotherapy ID CYTOLYTIC T-LYMPHOCYTES; ALTERED PEPTIDE LIGAND; CLASS-I MOLECULES; INFILTRATING LYMPHOCYTES; REJECTION ANTIGEN; HLA-A2 MELANOMAS; TISSUE ANTIGENS; HIGH-AFFINITY; CELL-LINES; IDENTIFICATION AB Thr human tyrosinase-derived peptide YMDGTMSQV is presented on the surface of human histocompatibility leukocyte antigen (HLA)-A*0201(+) melanomas and has been suggested to be a tumor antigen despite the Get that tyrosinase is also expressed in melanocytes. To gain information about immunoreactivity and self-tolerance to this antigen, we established a model using the murine tyrosinase-derived homologue of this peptide FMDGTMSQV, together with transgenic mice expressing the HLA-A*0201 recombinant molecule AAD. The murine peptide was processed and presented by AAD similarly to its human counterpart. After immunization with recombinant vaccinia virus encoding murine tyrosinase, we detected a robust AAD-restricted cytotoxic T lymphocyte (CTL) response to FMDGTMSQV in AAD transgenic mice in which the entire tyrosinase gene had been deleted by a radiation-induced mutation. A residual response was observed in the AAD(+)tyrosinase(+) mice after activation under certain conditions. At least some of these residual CTLs in AAD(+)tyrosinase(+) mice were of high avidity and induced vitiligo upon adoptive transfer into AAD(+)tyrosinase(+) hosts. Collectively, these data suggest that FMDGTMSQV is naturally processed and presented in vivo, and that this presentation leads to substantial but incomplete self-tolerance. The relevance of this model to an understanding of the human immune response to tyrosinase is discussed. C1 Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA. Univ Virginia, Beirne Carter Ctr Immunol Res, Charlottesville, VA 22908 USA. Oak Ridge Natl Lab, Div Life Sci, Oak Ridge, TN 37831 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Engelhard, VH (reprint author), Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z99 CA999999, Z01 BC010763-01]; NCI NIH HHS [CA09109, CA78400, T32 CA009109, R01 CA078400]; NIAID NIH HHS [AI21393, T32 AI007496]; NIGMS NIH HHS [T32 GM007267] NR 66 TC 114 Z9 115 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 3 PY 2000 VL 191 IS 7 BP 1221 EP 1231 DI 10.1084/jem.191.7.1221 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 302KX UT WOS:000086365200013 PM 10748239 ER PT J AU Strey, HH Wang, J Podgornik, R Rupprecht, A Yu, L Parsegian, VA Sirota, EB AF Strey, HH Wang, J Podgornik, R Rupprecht, A Yu, L Parsegian, VA Sirota, EB TI Refusing to twist: Demonstration of a line hexatic phase in DNA liquid crystals SO PHYSICAL REVIEW LETTERS LA English DT Article ID BOND-ORIENTATIONAL ORDER AB We report conclusive high resolution small angle x-ray scattering evidence that long DNA fragments form an untwisted line hexatic phase between the cholesteric and the crystalline phases. The line hexatic phase is a liquid-crystalline phase with long-range hexagonal bond-orientational order, long-range nematic order, but liquidlike, i.e., short-range, positional order. So far, it has not been seen in any other three dimensional system. By line-shape analysis of x-ray scattering data we found that positional order decreases when the line hexatic phase is compressed. We suggest that such anomalous behavior is a result of the chiral nature of DNA molecules. C1 Univ Massachusetts, Dept Polymer Sci & Engn, Amherst, MA 01003 USA. NICHD, LPSB, NIH, Bethesda, MD 20892 USA. Argonne Natl Lab, Adv Photon Source, Argonne, IL 60439 USA. Univ Stockholm, Arrhenius Lab, S-10691 Stockholm, Sweden. NIAMS, LPB, NIH, Bethesda, MD 20892 USA. ExxonMobil Res & Engn Co, Corp Strateg Res, Annandale, NJ 08801 USA. RP Strey, HH (reprint author), Univ Massachusetts, Dept Polymer Sci & Engn, Amherst, MA 01003 USA. RI Sirota, Eric/A-7633-2009; Strey, Helmut/B-5456-2009; Podgornik, Rudolf/C-6209-2008; OI Podgornik, Rudolf/0000-0002-3855-4637; Rupprecht, Allan/0000-0002-2772-1620 NR 18 TC 68 Z9 69 U1 2 U2 13 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD APR 3 PY 2000 VL 84 IS 14 BP 3105 EP 3108 DI 10.1103/PhysRevLett.84.3105 PG 4 WC Physics, Multidisciplinary SC Physics GA 300GD UT WOS:000086243800021 ER PT J AU D'Agostini, F Balansky, R Pesce, C Fiallo, P Lubet, RA Kelloff, GJ De Flora, S AF D'Agostini, F Balansky, R Pesce, C Fiallo, P Lubet, RA Kelloff, GJ De Flora, S TI Induction of alopecia in mice exposed to cigarette smoke SO TOXICOLOGY LETTERS LA English DT Article DE environmental cigarette smoke; alopecia; apoptosis; hair follicle cells; N-acetylcysteine ID CHEMOTHERAPY-INDUCED ALOPECIA; ENVIRONMENTAL TOBACCO-SMOKE; HAIR FOLLICLE CELLS; PEROXYNITRITE CAUSES; RAT THYMOCYTES; CYCLOPHOSPHAMIDE; INHIBITION; APOPTOSIS; CARCINOGENICITY; ACETYLCYSTEINE AB Besides being responsible for a high proportion of those chronic degenerative diseases that are the leading causes of death in the population, tobacco smoking has been associated with skin diseases. Smoke genotoxicants are metabolized in hair follicle cells, where they form DNA adducts and cause DNA damage. The suspicion was raised that, in humans, a link may exist between smoking and both premature grey hair and hair loss. In order to check this hypothesis, we carried out a study in C57BL/6 mice exposed whole-body to a mixture of sidestream and mainstream cigarette smoke. After 3 months exposure, most mice developed areas of alopecia and grey hair, while no such lesions occurred either in sham-exposed mice or in smoke-exposed mice receiving the chemopreventive agent N-acetylcysteine with drinking water. Cell apoptosis occurred massively in the hair bulbs at the edge of alopecia areas. Smoke-exposed mice had extensive atrophy of the epidermis, reduced thickness of the subcutaneous tissue, and scarcity of hair follicles. On the whole, exposure to smoke genotoxic components appears to alter the hair cycle with a dystrophic anagen pattern. Although this mechanism is different from that of genotoxic cytostatic drugs, N-acetylcysteine appears to exert protective effects in both conditions. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Genoa, Dept Hlth Sci, Sect Hyg & Prevent Med, I-16132 Genoa, Italy. Univ Genoa, Dept Biophys Mental & Dent Sci, I-16132 Genoa, Italy. Univ Genoa, Dept Hlth Sci, Sect Social Dermatol, I-16132 Genoa, Italy. NCI, Rockville, MD 20892 USA. RP De Flora, S (reprint author), Univ Genoa, Dept Hlth Sci, Sect Hyg & Prevent Med, Via A Pastore 1, I-16132 Genoa, Italy. FU NCI NIH HHS [N01CN75008] NR 26 TC 26 Z9 26 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD APR 3 PY 2000 VL 114 IS 1-3 BP 117 EP 123 DI 10.1016/S0378-4274(99)00268-4 PG 7 WC Toxicology SC Toxicology GA 300AT UT WOS:000086231200014 PM 10713476 ER PT J AU Okajima, E Thorgeirsson, UP AF Okajima, E Thorgeirsson, UP TI Different regulation of vascular endothelial growth factor expression by the ERK and p38 kinase pathways in v-ras, v-raf, and v-myc transformed cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID LIVER EPITHELIAL-CELLS; TUMOR ANGIOGENESIS; CARCINOMA CELLS; ONCOGENES; TUMORIGENICITY; PROGRESSION; INHIBITION AB Here we show that vascular endothelial growth factor (VEGF) mRNA expression is up-regulated in oncogene transformed rat liver epithelial (RLE) cell lines and that the extracellular signal-regulated kinase (ERK) and p38 kinase differentially regulate the oncogene-mediated stimulation of VEGF. The highest level of VEGF mRNA expression was observed in the v-H-ras transformed RLE cell line, followed by the v-raf and v-myc transformed lines. The PD98059 MEK inhibitor was used to block the ERK pathway and SB203580 inhibitor to block the p38 pathway. The parent and the v-H-ras transformed RLE cell lines showed up-regulation of VEGF RNA expression through the ERK pathway and down-regulation of VEGF through the p38 pathway. VEGF was regulated in a comparable manner in a human breast carcinoma cell line. In the v-raf and v-myc transformed RLE Lines, positive regulation of VEGF was transduced through the p38 pathway. These findings suggest that (1) oncogenic ms differs from raf and myc in the recruitment of the MAPK signaling pathways for VEGF regulation; (2) that VEGF is regulated in ras transformed and human cancer cell Lines in a positive and negative manner by the ERK and p38 signaling pathways. (C) 2000 Academic Press. C1 NCI, Tumor Biol & Carcinogenesis Sect, Cellular Carcinogenesis & Tumor Promot Lab, Div Basic Sci,NIH, Bethesda, MD 20892 USA. RP Thorgeirsson, UP (reprint author), NCI, Tumor Biol & Carcinogenesis Sect, Cellular Carcinogenesis & Tumor Promot Lab, Div Basic Sci,NIH, Bethesda, MD 20892 USA. NR 23 TC 28 Z9 30 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 2 PY 2000 VL 270 IS 1 BP 108 EP 111 DI 10.1006/bbrc.2000.2386 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 302CZ UT WOS:000086348900017 PM 10733912 ER PT J AU Matsunaga, N Virador, V Santis, C Vieira, WD Furumura, M Matsunaga, J Kobayashi, N Hearing, VJ AF Matsunaga, N Virador, V Santis, C Vieira, WD Furumura, M Matsunaga, J Kobayashi, N Hearing, VJ TI In situ localization of agouti signal protein in murine skin using immunohistochemistry with an ASP-specific antibody SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE agouti; pigmentation; melanogenesis; pheomelanin ID YELLOW A(Y) MUTATION; COAT-COLOR MUTANTS; IN-VITRO; GENE; MELANOCYTE; EXPRESSION; TYROSINASE; MODULATION; RECEPTOR; MELANINS AB Switching between production of eumelanin or pheomelanin in follicular melanocytes is responsible for hair color in mammals; in mice, this switch is controlled by the agouti locus, which encodes agouti signal protein (ASP) through the action of melanocortin receptor 1. To study expression and processing patterns of ASP in the skin and its regulation of pigment production in hair follicles, we have generated a rabbit antibody (termed alpha PEP16) against a synthetic peptide that corresponds to the carboxyl terminus of ASP. The specificity of that antibody was measured by ELISA and was confirmed by Western blot analysis. Using immunohistochemistry, we characterized the expression of ASP in the skin of newborn mice at 3, 6, and 9 days postnatally. Expression in nonagouti (a/a) black mouse skin was negative at all times examined, as expected, and high expression of ASP was observed in 6 day newborn agouti (A/+) and in 6 and 9 day newborn lethal yellow (A(y)/a) mouse skin. In lethal yellow (pheomelanogenic) mice, ASP expression increased day by day as the hair color became more yellow. These expression patterns suggest that ASP is delivered quickly and efficiently to melanocytes and to hair matrix cells in the hair bulbs where it regulates melanin production. (C) 2000 Academic Press. C1 NCI, Cell Biol Lab, Pigment Cell Biol Sect, NIH, Bethesda, MD 20892 USA. RP Matsunaga, N (reprint author), NCI, Cell Biol Lab, Pigment Cell Biol Sect, NIH, Bethesda, MD 20892 USA. NR 24 TC 17 Z9 20 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 2 PY 2000 VL 270 IS 1 BP 176 EP 182 DI 10.1006/bbrc.2000.2409 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 302CZ UT WOS:000086348900029 PM 10733924 ER PT J AU Liu, WD Ren, CP Shi, JL Feng, XL He, ZW Xu, LG Lan, K Xie, L Peng, Y Fan, J Kung, HF Yao, KT Xu, RH AF Liu, WD Ren, CP Shi, JL Feng, XL He, ZW Xu, LG Lan, K Xie, L Peng, Y Fan, J Kung, HF Yao, KT Xu, RH TI Characterization of the functionally related sites in the neural inducing gene noggin SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID EPIDERMAL INDUCTION; SPEMANN ORGANIZER; XENOPUS ECTODERM; KUNITZ DOMAIN; INHIBITION; EMBRYOS; RECEPTOR; SIGNALS; BMP-4; NEURALIZATION AB Previously we have shown that blocking bone morphogenetic protein (BMP) receptor signaling by a dominant negative BMP receptor causes neurogenesis in Xenopus animal caps (ACs), whereas the physiological neural inducer noggin acts as a homodimer physically binding to BMP-4 and disrupting its signaling at the ligand level. The present study attempted to elucidate the relationship between the structure and function of noggin. By replacing some cysteine residues with serine residues through a site-directed mutagenesis strategy, we generated three noggin mutants, C145S, C205S, and C(218, 220, 222)S (3CS). Although mRNAs encoded by these mutants were translated as efficiently as wild-type (WT) noggin mRNA, they behaved differently when expressed in vivo. Expression of WT noggin or C205S in Xenopus ACs converted the explants (prospective ectoderm) into neural tissue, indicated by the neural-like morphology and expression of the pan neural marker NCAM in the ACs. In contrast, ACs expressing C145S or 3CS sustained an epidermal fate like the control caps. Similar results were observed in the mesoderm where C205S (but not C145S and 3CS) displayed dorsalizing activity as well as WT noggin. Altogether, our results suggest that Cys145 alone or Cys(218, 220, 222) as a whole in noggin protein is required for the biological activities of noggin, probably participating in the dimerization of noggin with BMP-4 or itself. (C) 2000 Academic Press. C1 Hunan Med Univ, Canc Res Inst, Changsha 410078, Hunan, Peoples R China. NCI, Frederick Canc Res & Dev Ctr, Basic Res Lab, Metab & Canc Susceptibil Sect,NIH, Frederick, MD 21702 USA. NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. Univ Hong Kong, Inst Mol Biol, Hong Kong, Hong Kong, Peoples R China. First Mil Med Univ, Dept Pathol, Guangzhou 510515, Peoples R China. WiCell Res Inst, Madison, WI 53705 USA. RP Yao, KT (reprint author), Hunan Med Univ, Canc Res Inst, Changsha 410078, Hunan, Peoples R China. NR 23 TC 6 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 2 PY 2000 VL 270 IS 1 BP 293 EP 297 DI 10.1006/bbrc.2000.2415 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 302CZ UT WOS:000086348900047 PM 10733942 ER PT J AU Sullivan, DC Menkens, AE AF Sullivan, DC Menkens, AE TI Status of funding programs SO ACADEMIC RADIOLOGY LA English DT Article C1 NCI, Biomed Imaging Program, EPN, Bethesda, MD 20892 USA. RP Sullivan, DC (reprint author), NCI, Biomed Imaging Program, EPN, Room 800,6130 Execut Blvd, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 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 2000 VL 7 IS 4 BP 306 EP 308 DI 10.1016/S1076-6332(00)80519-X PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 315AC UT WOS:000087089600013 PM 10766102 ER PT J AU Hempel, A Camerman, N Dauter, Z Mastropaolo, D Camerman, A AF Hempel, A Camerman, N Dauter, Z Mastropaolo, D Camerman, A TI The antiestrogen [2-(4-benzylphenoxy)ethyl]diethylammonium chloride SO ACTA CRYSTALLOGRAPHICA SECTION C-CRYSTAL STRUCTURE COMMUNICATIONS LA English DT Article ID INTRACELLULAR HISTAMINE ANTAGONIST; BREAST-CANCER; N,N-DIETHYL-2-<4-(PHENYLMETHYL)PHENOXY>ETHANAMINE-HCL; COMBINATION; CELLS AB The crystal structure of the title compound, C19H22NO+. Cl-(common name: N,N-diethyl-2-[(4-phenylmethyl)phenoxy]-ethanamine hydrochloride), contains one molecule in the asymmetric unit. The planes through the two phenyl rings are roughly perpendicular. Protonation occurs at the N atom, to which the Cl- ion is linked via an N-H ... Cl hydrogen bond. The molecule adopts an eclipsed rather than extended conformation. C1 Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada. NCI, Frederick, MD 21701 USA. Brookhaven Natl Lab, NSLS, Upton, NY 11973 USA. Ardono Res, Seattle, WA 98115 USA. RP Hempel, A (reprint author), Univ Toronto, Dept Biochem, Med Sci Bldg, Toronto, ON M5S 1A8, Canada. FU NIAID NIH HHS [AI40392] NR 12 TC 1 Z9 1 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0108-2701 J9 ACTA CRYSTALLOGR C JI Acta Crystallogr. Sect. C-Cryst. Struct. Commun. PD APR PY 2000 VL 56 BP 455 EP 456 PN 4 PG 2 WC Chemistry, Multidisciplinary; Crystallography SC Chemistry; Crystallography GA 311RN UT WOS:000086898800024 PM 10815207 ER PT J AU Boyd, G AF Boyd, G TI The alcoholic family in recovery: a developmental model SO ADDICTION LA English DT Book Review C1 NIAAA, Bethesda, MD USA. RP Boyd, G (reprint author), NIAAA, Bethesda, MD USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU CARFAX PUBLISHING PI BASINGSTOKE PA RANKINE RD, BASINGSTOKE RG24 8PR, HANTS, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD APR PY 2000 VL 95 IS 4 BP 633 EP 633 PG 1 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 307MW UT WOS:000086657900015 ER PT J AU Guralnik, JM Balfour, JL Volpato, S AF Guralnik, JM Balfour, JL Volpato, S TI The ratio of older women to men: Historical perspectives and cross-national comparisons SO AGING-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE mortality; population characteristics; population dynamics; sex distribution; vital statistics ID SEX-DIFFERENCES; GENDER DIFFERENCES; MYOCARDIAL-INFARCTION; SURVIVAL RATES; MORTALITY; REACTIVITY; DISEASE; TRENDS AB In nearly all populations throughout the world there are substantially more older women than men. Although there are many biological explanations for why women have greater longevity than men, the higher proportion of women in the older population appears to be a phenomenon of the twentieth century, Using contemporary data on population size and life expectancy in a large number of countries and historical life table data from a diverse subset of countries, cross-national contrasts and historical trends in the female to male ratio are explored. In the 1990's, only 4 countries had fewer women than men in the age group 75 years and older. The number of women per 100 men aged 75+ in the remainder of the world's countries ranged from 100 to 355. In general, countries with a lower overall life expectancy had a lower number of women per 100 men aged 75+, while countries with higher overall life expectancy had a higher female to male ratio in this age group. A hundred years ago there were nearly equal numbers of women and men aged 75+ in many countries. In all countries studied, the female to male ratio increased as the century progressed. Historical life table data were used to calculate the probability of surviving through 5 stages of life: ages 0 to 5, 5 to 15, 15 to 40, 40 to 65, and 65 to 85. Although the probability of survival through all age intervals increased dramatically during the century, the current disparity in the size of the older populations of men and women can be explained primarily by the divergence in male and female probabilities of survival for the two older age intervals as the century progressed. Thus, with higher life expectancy, whether it be comparing countries or over time within a country, the proportion of the older population that is female is greater. Changes in survival probability in middle and late life, rather than childhood and young adulthood, have been responsible for the increased number of women compared to men in the older population. (C) 2000, Editrice Kurtis. C1 NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. RP Guralnik, JM (reprint author), NIA, Epidemiol Demog & Biometry Program, 7201 Wisconsin Ave,Room 3C-309, Bethesda, MD 20892 USA. RI VOLPATO, STEFANO/H-2977-2014 OI VOLPATO, STEFANO/0000-0003-4335-6034 NR 33 TC 17 Z9 18 U1 0 U2 1 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 0394-9532 J9 AGING-CLIN EXP RES JI Aging-Clin. Exp. Res. PD APR PY 2000 VL 12 IS 2 BP 65 EP 76 PG 12 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 321XY UT WOS:000087481700002 PM 10902048 ER PT J AU Leveille, SG Resnick, HE Balfour, J AF Leveille, SG Resnick, HE Balfour, J TI Gender differences in disability: Evidence and underlying reasons SO AGING-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE aging; disability; epidemiology; men; women ID ACTIVE LIFE EXPECTANCY; BODY-MASS INDEX; OLDER WOMEN; CARDIOVASCULAR HEALTH; MAINTAINING MOBILITY; PHYSICAL FUNCTION; MUSCLE STRENGTH; ALAMEDA COUNTY; WEIGHT CHANGE; RISK-FACTORS AB Women have greater longevity than men and represent a larger proportion of the expanding older population. Several health, disease, behavioral and sociodemographic factors contribute to the higher prevalence of disability in women compared to men. This paper presents a review of methodologic and epidemiologic considerations important to our understanding the gender differences in the prevalence of disability, and discusses underlying causes for these differences. Compared to men, women have a longer duration of life lived with disability, in part due to higher prevalence of non-fatal chronic conditions, constitutional factors such as lower muscle strength and lower bone density, and higher rates of life style factors suck as sedentary behavior and obesity. Several of these factors are modifiable, and provide important targets for researchers, clinicians, and public health practitioners in their efforts to reduce the burden of disability in the older population. (C) 2000. Editrice Kurtis. C1 NIA, Epidemiol Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. RP Leveille, SG (reprint author), Hebrew Rehabil Ctr Aged, Res & Training Inst, 1200 Ctr St, Boston, MA 02131 USA. NR 46 TC 58 Z9 59 U1 3 U2 11 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 0394-9532 J9 AGING-CLIN EXP RES JI Aging-Clin. Exp. Res. PD APR PY 2000 VL 12 IS 2 BP 106 EP 112 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 321XY UT WOS:000087481700006 PM 10902052 ER PT J AU Gentry, RT AF Gentry, RT TI Determinants and analysis of blood alcohol concentrations after social drinking SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Editorial Material C1 NIAAA, Off Collaborat Res, NIH, Bethesda, MD 20892 USA. RP Gentry, RT (reprint author), NIAAA, Off Collaborat Res, NIH, Willco Bldg 400,600 Execut Blvd, Bethesda, MD 20892 USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD APR PY 2000 VL 24 IS 4 BP 399 EP 399 DI 10.1111/j.1530-0277.2000.tb01994.x PG 1 WC Substance Abuse SC Substance Abuse GA 309UV UT WOS:000086788400001 PM 10798563 ER PT J AU Gentry, RT AF Gentry, RT TI Effect of food on the pharmacokinetics of alcohol absorption SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article ID ETHANOL; MODEL C1 NIAAA, Off Collaborat Res, NIH, Bethesda, MD 20892 USA. RP Gentry, RT (reprint author), NIAAA, Off Collaborat Res, NIH, Willco Bldg 400,6000 Execut Blvd, Bethesda, MD 20892 USA. NR 10 TC 26 Z9 29 U1 0 U2 12 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 2000 VL 24 IS 4 BP 403 EP 404 DI 10.1111/j.1530-0277.2000.tb01996.x PG 2 WC Substance Abuse SC Substance Abuse GA 309UV UT WOS:000086788400003 PM 10798565 ER PT J AU Shoaf, SE AF Shoaf, SE TI Pharmacokinetics of intravenous alcohol: Two compartment, dual Michaelis-Menten elimination SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article ID ETHANOL; BLOOD C1 NIAAA, Unit Pharmacokinet Studies, Clin Studies Lab, Bethesda, MD 20892 USA. RP Shoaf, SE (reprint author), Otsuka Amer Pharmaceut Inc, 2440 Res Blvd, Rockville, MD 20850 USA. NR 3 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD APR PY 2000 VL 24 IS 4 BP 424 EP 425 DI 10.1111/j.1530-0277.2000.tb02007.x PG 2 WC Substance Abuse SC Substance Abuse GA 309UV UT WOS:000086788400014 PM 10798576 ER PT J AU Allen, JP Litten, RZ Fertig, JB Sillanaukee, P AF Allen, JP Litten, RZ Fertig, JB Sillanaukee, P TI Carbohydrate-deficient transferrin, gamma-glutamyltransferase, and macrocytic volume as biomarkers of alcohol problems in women SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE carbohydrate-deficient transferrin; gamma-glutamyltranspeptidase; alcohol screening; women alcoholics ID GLUTAMYL-TRANSFERASE; LIVER-DISEASE; HEAVY DRINKERS; SIALIC-ACID; CONSUMPTION; DRINKING; MARKERS; SERUM; ABUSE; ETHANOL AB Background: Early identification of alcohol problems in women is important. Differences in patterns of drinking and in biological function between genders, however, may present unique difficulties in biochemical screening. Methods: Published alcohol-screening studies with female samples and use as biomarkers of carbohydrate-deficient transferrin (CDT), gamma-glutamyltransferase (GGT), and macrocytic volume were reviewed. Results: A wide range of sensitivities and specificities of GGT and CDT have been reported, although, in general, the two markers seem approximately equal in accuracy. As in the case of males, use of them in combination substantially enhances sensitivity and little reduces specificity. Use of macrocytic volume improves the sensitivity of both GGT and CDT as alcohol-screening markers. Conclusions: GGT and CDT have moderate sensitivity in screening for alcohol problems in women. Use of them in concert offers further advantage. C1 NIAAA, Div Clin & Prevent Res, Bethesda, MD 20892 USA. Oy Finnish Immunotechnol Ltd, Tampere, Finland. RP Allen, JP (reprint author), NIAAA, Div Clin & Prevent Res, Willco Bldg,Suite 505,600 Execut Blvd,MSC 7003, Bethesda, MD 20892 USA. NR 36 TC 29 Z9 29 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD APR PY 2000 VL 24 IS 4 BP 492 EP 496 DI 10.1111/j.1530-0277.2000.tb02016.x PG 5 WC Substance Abuse SC Substance Abuse GA 309UV UT WOS:000086788400023 PM 10798585 ER PT J AU Grisham, MB Jourd'Heuil, D Wink, DA AF Grisham, MB Jourd'Heuil, D Wink, DA TI Review article: chronic inflammation and reactive oxygen and nitrogen metabolism - implications in DNA damage and mutagenesis SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article; Proceedings Paper CT 8th Taisho International Symposium on Gastroenterology CY APR 16-17, 1999 CL SHIMODA, JAPAN ID NITRIC-OXIDE SYNTHASE; PEROXYNITRITE IN-VITRO; SUPEROXIDE; CARCINOGENESIS; OXIDATION; RADICALS; CANCER; MECHANISM; HEPATITIS; DISEASE AB It is well known that chronic inflammation of the digestive tract is associated with an increased risk of malignant transformation. Because phagocytic leukocytes and cytokine-activated parachymal cells produce large amounts of reactive metabolites of oxygen and nitrogen, there has been substantial interest in ascertaining whether these reactive intermediates may mediate mutagenesis and malignant transformation in vivo. However, very little information is available regarding the basic chemistry of how these oxygen and nitrogen-derived species may interact to yield potentially carcinogenic agents. This review will discuss our present understanding of the chemical and biochemical interactions between superoxide and nitric oxide and provide a model by which these reactive species may damage DNA and mediate mutagenesis. C1 Louisiana State Univ, Med Ctr, Dept Cellular & Mol Physiol, Shreveport, LA 71130 USA. NCI, Bethesda, MD 20892 USA. RP Grisham, MB (reprint author), Louisiana State Univ, Med Ctr, Dept Cellular & Mol Physiol, POB 33932, Shreveport, LA 71130 USA. FU NIDDK NIH HHS [DK 47663, DK 43785] NR 47 TC 72 Z9 72 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD APR PY 2000 VL 14 SU 1 BP 3 EP 9 DI 10.1046/j.1365-2036.2000.014s1003.x PG 7 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 308NJ UT WOS:000086719200003 PM 10807397 ER PT J AU Picciano, MF AF Picciano, MF TI Is homocysteine a biomarker for identifying women at risk of complications and adverse pregnancy outcomes? SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Editorial Material C1 NIH, Off dietary Supplements, Bethesda, MD 20892 USA. Penn State Univ, University Pk, PA 16802 USA. RP Picciano, MF (reprint author), NIH, Off dietary Supplements, 31 Ctr Dr,Room 1B29, Bethesda, MD 20892 USA. NR 8 TC 15 Z9 16 U1 0 U2 0 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 2000 VL 71 IS 4 BP 857 EP 858 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 297CR UT WOS:000086064400001 PM 10731488 ER PT J AU Reed, E Zerbe, CS Brawley, OW Bicher, A Steinberg, SM AF Reed, E Zerbe, CS Brawley, OW Bicher, A Steinberg, SM TI Analysis of autopsy evaluations of ovarian cancer patients treated at the National Cancer Institute, 1972-1988 SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE ovarian cancer; autopsy; cisplatin ID IN-VITRO; CISPLATIN; CARCINOMA; PACLITAXEL AB Between 1972 and 1988, more than 500 women were treated for ovarian cancer at the National Cancer Institute in Bethesda, Maryland on approved experimental treatment protocols. Of these, 73 underwent autopsy evaluation on the National Cancer Institute campus. We have analyzed the autopsy reports of those individuals to determine the patterns of disease spread at death. By comparison with the literature, the demographics of the cohort did not differ from previously published reports, other than the extent of chemotherapy received antemortem. Median survival of the cohort was 15.6 months (range, 1.7-108.3 months), and median age at diagnosis was 55 years (range, 24-74 years). The median number of treatments regimens received was two (range, 1-6). The pattern of disease spread at autopsy was different from that in previously published work in that there was a higher proportion of patients with disease found in liver parenchyma, lung pleura, and the pericardium. Patients who received cisplatin as part of their initial treatment regimen had a higher incidence of metastases to the adrenal glands, thoracic nodes, bladder, and liver parenchyma, which was not explained by differences in survival. Median survival for patients who received cisplatin as part of their initial therapy was 15.6 months, compared with a median of 15.4 months for patients who did not, These data suggest a changing pattern of disease spread in patients with ovarian cancer receiving aggressive chemotherapy. This may be caused by some effect of platinum-based therapy on the metastatic potential of the tumor. C1 NCI, Med Branch, Bethesda, MD 20892 USA. NCI, Div Canc Prevent & Control, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Branch, Div Clin Sci, Bethesda, MD 20892 USA. RP Reed, E (reprint author), NCI, Med Branch, Bldg 10,Room 12N226, Bethesda, MD 20892 USA. NR 23 TC 25 Z9 26 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD APR PY 2000 VL 23 IS 2 BP 107 EP 116 DI 10.1097/00000421-200004000-00002 PG 10 WC Oncology SC Oncology GA 304EY UT WOS:000086471200002 PM 10776968 ER PT J AU Chie, WC Hsieh, CC Newcomb, PA Longnecker, MP Mittendorf, R Greenberg, ER Clapp, RW Burke, KP Titus-Ernstoff, L Trentham-Dietz, A MacMahon, B AF Chie, WC Hsieh, CC Newcomb, PA Longnecker, MP Mittendorf, R Greenberg, ER Clapp, RW Burke, KP Titus-Ernstoff, L Trentham-Dietz, A MacMahon, B TI Age at any full-term pregnancy and breast cancer risk SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE breast neoplasms; reproductive history; risk factors ID REPRODUCTIVE FACTORS; UNITED-STATES; FIRST BIRTH; LAST BIRTH; 1ST BIRTH; PARITY; WOMEN; PROLACTIN; DISEASE; ASSOCIATION AB The authors analyzed data from two multistate, population-based case-control studies to investigate the association between age at any full-term pregnancy (FP) and breast cancer risk. Study subjects included breast cancer cases aged 20-79 years identified from four statewide cancer registries and randomly selected controls interviewed from 1988 to 1996. Complete information on a comprehensive set of risk factors for breast cancer was available for 9,891 cases and 12,271 controls. The large number of subjects enabled simultaneous adjustment of the covariates and efficient application of various modeling approaches. Overall, each 5-year increase in age at first FP was associated with an odds ratio of 1.07 (95% confidence interval (CI): 1.01, 1.13) for breast cancer. The corresponding estimates were odds ratio = 1.02 (95% CI: 1.00, 1.05) for age at second through ninth FPs. For age at last FP, the effect estimate (odds ratio = 1.01, 95% CI: 0.97, 1.06) was indistinguishable from that for other FPs after the first. In this analysis, a modest and transient increase in breast cancer risk after childbirth was also observed. The relatively greater effect of age at first FP is consistent with the existence of a long-term effect of early first FP on the differentiation of mammary cells, causing them to become less susceptible to carcinogenesis. C1 UMass Mem Hlth Care, Mem Canc Ctr, Worcester, MA 01605 USA. Natl Taiwan Univ, Coll Publ Hlth, Grad Inst Epidemiol, Taipei 10764, Taiwan. Natl Taiwan Univ, Sch Publ Hlth, Taipei 10764, Taiwan. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Wisconsin, Ctr Comprehens Canc, Madison, WI 53706 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. Dartmouth Hitchcock Med Ctr, Dept Community & Family Med, Lebanon, NH 03766 USA. Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Lebanon, NH 03766 USA. Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. Univ Vermont, Med Ctr, Dept Med, Burlington, VT 05405 USA. Maine Bur Hlth, Div Dis Control, Augusta, ME USA. RP Hsieh, CC (reprint author), UMass Mem Hlth Care, Mem Canc Ctr, 373 Plantat St,Suite 211, Worcester, MA 01605 USA. OI Clapp, Richard/0000-0001-8174-0825; Chie, Wei-Chu/0000-0001-5584-6554; Longnecker, Matthew/0000-0001-6073-5322 FU NCI NIH HHS [CA 47305, CA 47147] NR 46 TC 84 Z9 86 U1 1 U2 1 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD APR 1 PY 2000 VL 151 IS 7 BP 715 EP 722 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 300JZ UT WOS:000086251000011 PM 10752799 ER PT J AU Speckman, RA Garg, A Du, FH Bennett, L Veile, R Arioglu, E Taylor, SI Lovett, M Bowcock, AM AF Speckman, RA Garg, A Du, FH Bennett, L Veile, R Arioglu, E Taylor, SI Lovett, M Bowcock, AM TI Mutational and haplotype analyses of families with familial partial lipodystrophy (Dunnigan variety) reveal recurrent missense mutations in the globular C-terminal domain of lamin A/C SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID INTERMEDIATE FILAMENT PROTEINS; NUCLEAR-ENVELOPE; CHROMOSOME 1Q21-22; ROD DOMAIN; GENE; MEMBRANE; BINDING; DNA AB Familial partial lipodystrophy (FPLD), Dunnigan variety, is an autosomal dominant disorder characterized by marked loss of subcutaneous adipose tissue from the extremities and trunk but by excess fat deposition in the head and neck. The disease is frequently associated with profound insulin resistance, dyslipidemia, and diabetes. We have localized a gene for FPLD to chromosome 1q21-q23, and it has recently been proposed that nuclear lamin A/C is altered in FPLD, on the basis of a novel missense mutation (R482Q) in five Canadian probands. This gene had previously been shown to be altered in autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD-AD) and in dilated cardiomyopathy and conduction-system disease. We examined 15 families with FPLD for mutations in lamin A/C. Five families harbored the R482Q alteration that segregated with the disease phenotype. Seven families harbored an R482W alteration, and one family harbored a G465D alteration. All these mutations lie within exon 8 of the lamin A/C gene-an exon that has also been shown to harbor different missense mutations that are responsible for EDMD-AD. Mutations could not be detected in lamin A/C in one FPLD family in which there was linkage to chromosome 1q21-q23. One family with atypical FPLD harbored an R582H alteration in exon 11 of lamin A. This exon does not comprise part of the lamin C coding region. All mutations in FPLD affect the globular C-terminal domain of the lamin A/C protein. In contrast, mutations responsible for dilated cardiomyopathy and conduction-system disease are observed in the rod domain of the protein. The FPLD mutations R482Q and R482W occurred on different haplotypes, indicating that they are likely to have arisen more than once. C1 Washington Univ, Sch Med, Div Human Genet, Dept Genet, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Pediat, Dept Genet, St Louis, MO 63110 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX USA. NIDDK, Diabet Branch, Bethesda, MD USA. RP Speckman, RA (reprint author), Washington Univ, Sch Med, Div Human Genet, Dept Genet, Box 8232,4566 Scott Ave, St Louis, MO 63110 USA. OI Bowcock, Anne/0000-0001-8691-9090 FU NCRR NIH HHS [M01 RR000633, MO1-RR00633]; NIDDK NIH HHS [R01-DK54387, R01 DK054387] NR 26 TC 180 Z9 189 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 2000 VL 66 IS 4 BP 1192 EP 1198 DI 10.1086/302836 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 337QP UT WOS:000088373400003 PM 10739751 ER PT J AU Doody, MM Mandel, JS Linet, MS Ron, E Lubin, JH Boice, JD Fraumeni, JF AF Doody, MM Mandel, JS Linet, MS Ron, E Lubin, JH Boice, JD Fraumeni, JF TI Mortality among Catholic nuns certified as radiologic technologists SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE Catholicism; nuns; mortality; neoplasms; cohort study; epidemiology ID HELICOBACTER-PYLORI INFECTION; BREAST-CANCER; PREVALENCE AB Background Several studies have shown that Catholic nuns have a different mortality experience than women of similar age in the general population. We had a unique opportunity to evaluate mortality patterns of nuns identified in an occupational study of nearly 145,000 radiologic technologists (73% female). Methods A total of 1,103 women were classified as nuns based on their titles of "Sister" or "SR". Their mortality experience was compared to other female radiologic technologists and to U.S. white females. Results Five hundred eighty-three nuns (53%) were deceased as of January 1, 1995. Compared to other technologists, nuns were at significantly increased risk of dying from all causes (Standardized mortality ratio (SMR) = 1.1; 95% Confidence interval (CI) = 1.0-1.2, stomach cancer (SMR = 2.7; 95% CI = 1.2-5.4), diabetes (SMR = 2.2; 95% CI = 1.0-4.1) ischemic heart disease (SMR = 1.2; 95% CI = 1.1-1.4), all digestive diseases (SMR = 2.0; 95% CI = 1.3-3.0), and gastric and duodenal ulcers (SMR = 8.3, 95% CI = 2.3-21.3). In contrast we observed a significant deficit in lung cancer (SMR = 0.5; 95% CI = 0.2-09), no deaths from cervical cancer and a breast cancer risk 10% lower than expected (SMR = 0.9; 95% CI = 0.6-1.3). When compared to U.S. females, nuns experienced significantly reduced mortality from all causes (SMR = 0.8; 95% CI = 0.7-0.9), cervical cancer (SMR = 0.0; 95% CI = 0.0-0.7), all endocrine, metabolic and nutritional diseases (SMR = 0.5; 95% CI = 0.3-0.9), all circulatory diseases (SMR = 0.7; 95% CI = 0.7-0.8) including ischemic heart disease and cerebrovascular disease, and all respiratory diseases (SMR = 0.5; 95% CI = 0.3-0.8), and a nearly significant deficit of diabetes (SMR = 0.6; 95% CI = 0.3-1.0). In contrast, nuns had an almost 3-fold greater risk of tuberculosis (SMR = 2.9; 95% CI = 1.4-5.3) and a 20% excess of breast cancer (SMR = 1.2; 95% CI = 0.8-1.7). The breast cancer excess was concentrated among nuns first certified before 1940 (SMR = 2.0; CI = 1.3-3.0), when radiation doses were possibly the highest, but the risk did not increase with increasing length of certification. Conclusions Compared with the general population, the mortality experience of nuns was favorable and reflected the "healthy worker effect" commonly seen in occupational studies. Patterns observed for breast and cervical cancer-possibly indicate differences in reproductive and sexual activities associated with belonging to a religious order The possibility of a radiation-related excess for breast cancer among nuns certified before 1940 cannot be completely discounted, although there was no dose-response relationship with a surrogate measure of exposure (number of years certified). When their mortality experience was compared with other radiologic technologists, the influence of lifestyle factors was not apparent. Am. J. Ind. Med. 37:339-348, 2000. Published 2000 Wiley-Liss, Inc.(dagger) C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Sch Publ Hlth, Div Environm & Occupat Hlth, Minneapolis, MN USA. RP Doody, MM (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Execut Plaza S,Room 7088,MSC 7362, Bethesda, MD 20892 USA. FU NCI NIH HHS [N0-CP21015, N01-CP61006, N01-CP81058] NR 35 TC 9 Z9 9 U1 2 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0271-3586 EI 1097-0274 J9 AM J IND MED JI Am. J. Ind. Med. PD APR PY 2000 VL 37 IS 4 BP 339 EP 348 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 289NT UT WOS:000085629400003 PM 10706745 ER PT J AU Kimmel, PL AF Kimmel, PL TI Psychosocial factors in adult end-stage renal disease patients treated with hemodialysis: Correlates and outcomes SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE depression; social support; illness effects; quality of life; hemodialysis ID QUALITY-OF-LIFE; AMBULATORY PERITONEAL-DIALYSIS; FUNCTIONAL HEALTH-STATUS; BEHAVIORAL COMPLIANCE; SOCIOECONOMIC-STATUS; SOCIAL SUPPORT; FAMILY SUPPORT; SURVIVAL; DEPRESSION; MORTALITY AB The first three decades of the ESRD program were devoted to extending patient survival. Few data have been generated regarding the factors associated with successful patient adjustment. Depression and perception of the effects of illness are important responses to the experience of ESRD and may be associated with differential survival. Perception and extent of social support can moderate these factors. The association of psychosocial factors and assessments of quality of life are incompletely understood and are topics of research interest. The role of variation in socioeconomic status in association with these factors has not been extensively studied. The challenges for the next 30 years include understanding the relationship of psychosocial factors to demographic and medical factors in large ESRD patient populations and the refinement of associations between psychosocial factors and patient outcomes, including adjustment, compliance, morbidity, and mortality. (C) 2000 by the National Kidney Foundation, Inc. C1 NIDDKD, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. George Washington Univ, Med Ctr, Dept Med, Div Renal Dis & Hypertens, Washington, DC 20037 USA. RP Kimmel, PL (reprint author), NIDDKD, Div Kidney Urol & Hematol Dis, NIH, Room 6AS19B,Bldg 45, Bethesda, MD 20892 USA. NR 66 TC 75 Z9 88 U1 3 U2 15 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2000 VL 35 IS 4 SU 1 BP S132 EP S140 DI 10.1016/S0272-6386(00)70240-X PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 300VV UT WOS:000086274600016 PM 10766011 ER PT J AU Shotelersuk, V Dell'Angelica, EC Hartnell, L Bonifacino, JS Gahl, WA AF Shotelersuk, V Dell'Angelica, EC Hartnell, L Bonifacino, JS Gahl, WA TI A new variant of Hermansky-Pudlak syndrome due to mutations in a gene responsible for vesicle formation SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID CHEDIAK-HIGASHI-SYNDROME; PALE EAR EP; LOCUS HETEROGENEITY; PARTIAL ALBINISM; PROTEIN COMPLEX; HPS GENE; AP-3; IMMUNODEFICIENCY; MELANOCYTES; MELANOSOMES C1 NICHHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Gahl, WA (reprint author), NICHD, NIH, 10 Ctr Dr,MSC 1830,Bldg 10,Room 9S-241, Bethesda, MD 20892 USA. OI Bonifacino, Juan S./0000-0002-5673-6370 NR 39 TC 77 Z9 77 U1 3 U2 6 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD APR 1 PY 2000 VL 108 IS 5 BP 423 EP 427 DI 10.1016/S0002-9343(99)00436-2 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 300ZX UT WOS:000086284600011 PM 10759101 ER PT J AU Stavrou, T Dubovsky, EC Reaman, GH Goldstein, AM Vezina, G AF Stavrou, T Dubovsky, EC Reaman, GH Goldstein, AM Vezina, G TI Intracranial calcifications in childhood medulloblastoma: Relation to nevoid basal cell carcinoma syndrome SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Neuroradiology CY MAY 23-28, 1999 CL SAN DIEGO, CALIFORNIA SP Amer Soc Neuroradiol ID RADIATION-THERAPY; BRAIN-TUMORS; MANIFESTATIONS; CHEMOTHERAPY; VINCRISTINE; CHILDREN; TRIAL; CCNU AB BACKGROUND AND PURPOSE: Medulloblastoma is one of the most common posterior fossa tumors to occur in children, Our purpose was to document the frequency, location, and time of occurrence of intracranial calcifications in cranial CT studies of children with medulloblastoma, METHODS: We retrospectively reviewed cranial CT studies of 56 patients diagnosed with medulloblastoma from 1983 through 1997 for the presence of intracranial calcifications, The findings were compared with 159 cranial CT studies of patients who were evaluated in the emergency department (control group), Thirty-two patients with medulloblastoma without shunts were compared with 118 patients from the control group without shunts, Similarly, 24 patients with medulloblastoma with shunts were compared with 41 patients from the control group with shunts, RESULTS: Overall, three (9%) patients with medulloblastoma without shunts, four (16%) patients with medulloblastoma with shunts, and four (10%) patients from the control group with shunts had fair calcification, Only the two children carrying the diagnoses of medulloblastoma and nevoid basal cell carcinoma syndrome, however, had calcification of the fair cerebri shown on the cranial CT scans obtained during the peridiagnostic period, Both were diagnosed with medulloblastoma before the age of 3 years and later developed jaw cysts and multiple basal cell carcinomas in the radiation field, CONCLUSION: Previous studies have shown that fair calcification is a major component of nevoid basal cell carcinoma syndrome, Our two cases illustrate the importance of considering the diagnosis of nevoid basal cell carcinoma syndrome when fair calcification is present in young patients with medulloblastoma. if the concomitant diagnosis of nevoid basal cell carcinoma syndrome is made, alternative types of therapy should be sought to minimize radiation therapy sequelae. C1 NCI, Genet Epidemiol Branch, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Hematol Oncol, Washington, DC 20010 USA. Childrens Natl Med Ctr, Dept Radiol, Washington, DC 20010 USA. RP Goldstein, AM (reprint author), NCI, Genet Epidemiol Branch, NIH, Execut Plaza S MSC 7236,6120 Execut Blvd, Bethesda, MD 20892 USA. NR 16 TC 10 Z9 10 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD APR PY 2000 VL 21 IS 4 BP 790 EP 794 PG 5 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 305EP UT WOS:000086526700034 PM 10782799 ER PT J AU Berga, SL Loucks-Daniels, TL Adler, LJ Chrousos, GP Cameron, JL Matthews, KA Marcus, MD AF Berga, SL Loucks-Daniels, TL Adler, LJ Chrousos, GP Cameron, JL Matthews, KA Marcus, MD TI Cerebrospinal fluid levels of corticotropin-releasing hormone in women with functional hypothalamic amenorrhea SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 18th Annual Meeting of the American-Gynecological-and-Obstetrical-Society CY SEP 16-18, 1999 CL CARLSBAD, CALIFORNIA SP Amer Gynecolog & Obstetr Soc DE hypothalamic amenorrhea; corticotropin-releasing hormone; vasopressin beta-endorphin ID GENE-EXPRESSION; VASOPRESSIN; NEURONS; ADRENOCORTICOTROPIN; DEPRESSION; SECRETION; RESPONSES; PATTERNS; BLOCKADE AB OBJECTIVE: Women with functional hypothalamic amenorrhea are anovulatory because of reduced gonadotropin-releasing hormone drive. Several studies have documented hypercortisolemia, which suggests that functional hypothalamic amenorrhea is stress-induced. Further, with recovery (resumption of ovulation), cortisol decreased and gonadotropin-releasing hormone drive increased. Corticotropin-releasing hormone can increase cortisol and decrease gonadotropin-releasing hormone. To determine its role in functional hypothalamic amenorrhea, we measured corticotropin-releasing hormone in cerebrospinal fluid along with arginine vasopressin, another potent adrenocorticotropic hormone secretagog, and beta-endorphin, which is released by corticotropin-releasing hormone and can inhibit gonadotropin-releasing hormone. STUDY DESIGN: Corticotropin-releasing hormone, vasopressin, and beta-endorphin levels were measured in cerebrospinal fluid from 14 women with eumenorrhea and 15 women with functional hypothalamic amenorrhea. RESULTS: Levels of corticotropin-releasing hormone in cerebrospinal fluid and of vasopressin were comparable and beta-endorphin levels were lower in women with functional hypothalamic amenorrhea. CONCLUSIONS: in women with established functional hypothalamic amenorrhea, increased cortisol and reduced gonadotropin-releasing hormone are not sustained by elevated cerebrospinal-fluid corticotropin-releasing hormone, vasopressin, or beta-endorphin. These data do not exclude a role for these factors in the initiation of functional hypothalamic amenorrhea. C1 Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Anesthesiol & Crit Care Med, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Neurosci, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Psychol, Pittsburgh, PA USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Magee Womens Res Inst, Pittsburgh, PA USA. RP Berga, SL (reprint author), Univ Pittsburgh, Magee Womens Hosp, Sch Med,Div Reprod Endocrinol, Dept Obstet Gynecol & Reprod Sci, 300 Halket St, Pittsburgh, PA 15213 USA. RI Cameron, Judy/J-6682-2013 FU NCRR NIH HHS [RR-00056]; NIMH NIH HHS [R01MH-50748] NR 25 TC 21 Z9 22 U1 0 U2 0 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 2000 VL 182 IS 4 BP 776 EP 781 DI 10.1016/S0002-9378(00)70326-7 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 305YA UT WOS:000086568300004 PM 10764453 ER PT J AU Negrel, AD Maul, E Pokharel, GP Zhao, JL Ellwein, LB AF Negrel, AD Maul, E Pokharel, GP Zhao, JL Ellwein, LB TI Refractive Error Study in Children: Sampling and measurement methods for a multi-country survey SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID MYOPIA AB PURPOSE: The Refractive Error Study in Children was designed to assess the prevalence of refractive error and vision impairment in children of different ethnic origins and cultural settings. METHODS: Population based cross-sectional samples of children 5 to 15 years of age were obtained through cluster sampling. Presenting, uncorrected, and best-corrected visual acuity, along with refractive error under cycloplegia, were the main outcome measures. Amblyopia and other causes of uncorrectable vision impairment were determined, RESULTS: Study design and sample size calculations, survey enumeration and ophthalmic examination meth ods, quality assurance monitoring, and data analyses and statistical methods are described. CONCLUSIONS: The study design, sample size, and measurement methods ensure that the prevalence of age-specific and sex-specific refractive error can be estimated with reasonable accuracy in the target populations. With commonality of methods, a comparison of findings between studies in different ethic origins and cultural settings is possible. (Am J Ophthalmol 2000;129:421-426. (C) 2000 by Elsevier Science Inc. All rights reserved.). C1 NEI, NIH, Bethesda, MD 20892 USA. WHO, Programme Prevent Blindness & Deafness, CH-1211 Geneva, Switzerland. Pontificia Univ Catolica Chile, Santiago, Chile. Fdn Eye Care Himalaya, Kathmandu, Nepal. Peking Union Med Coll Hosp, Beijing, Peoples R China. RP Ellwein, LB (reprint author), NEI, NIH, 31 Ctr Dr, Bethesda, MD 20892 USA. FU NEI NIH HHS [N01-EY-2103] NR 17 TC 135 Z9 147 U1 2 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD APR PY 2000 VL 129 IS 4 BP 421 EP 426 DI 10.1016/S0002-9394(99)00455-9 PG 6 WC Ophthalmology SC Ophthalmology GA 304FD UT WOS:000086471800001 PM 10764848 ER PT J AU Zhao, JL Pan, XJ Sui, RF Munoz, SR Sperduto, RD Ellwein, LB AF Zhao, JL Pan, XJ Sui, RF Munoz, SR Sperduto, RD Ellwein, LB TI Refractive Error Study in Children: Results from Shunyi District, China SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT 17th Congress of the Asia-Pacific-Academy-of-Ophthalmology CY MAR 07-12, 1999 CL MANILA, PHILIPPINES SP Asia Pacific Acad Ophthalmol AB PURPOSE: To assess the prevalence of refractive errors and vision impairment in school-age children in Shunyi District, northeast of Beijing, the Peoples Republic of China. METHODS: Random selection of village-based clusters was used to identify a sample of children 5 to 15 years of age. Resident registration books were used to enumerate eligible children in the selected villages and identify their current school. Ophthalmic examinations were conducted in 132 schools on children from 29 clusters during May 1988 to July 1998, including visual acuity measurements, cycloplegic retinoscopy, cycloplegic autorefraction, ocular motility evaluation, and examination of the external eye, anterior segment, media, and fundus. Independent replicate measurements of all children with reduced vision and a sample of those with normal vision were done for quality assurance monitoring in three schools. RESULTS: A total of 6,134 children from 4,338 households were enumerated, and 5,884 children (95.9%) were examined. The prevalence of uncorrected, presenting, and best visual acuity 0.5 (20/40) or worse in at least one eye was 12.8%, 10.9%, and 1.8%, respectively; 0.4% had best visual acuity 0.5 or worse in both eyes. Refractive error was the cause in 89.5% of the 1,236 eyes with reduced vision, amblyopia in 5%, other causes in 1.5%, with unexplained causes in the remaining 4%. Myopia -0.5 diopter or less in either eye was essentially absent in 5-year-old children, but increased to 36.7% in males and 55.0% in females by age 15. Over this same age range, hyperopia 2 diopters or greater decreased from 8.8% in males and 19.6% in females to less than 2% in both. Females had a significantly higher risk of both myopia and hyperopia. CONCLUSIONS: Reduced vision because of myopia is an important public health problem in school-age children in Shunyi District. More than 9% of children could benefit from prescription glasses. Further studies are needed to determine whether the upward trend in the prevalence of myopia continues far beyond age 15 and whether the development of myopia is changing for more recent birth cohorts. (Am J Ophthalmol 2000;129:427-435. (C) 2000 by Elsevier Science Inc, All rights reserved.). C1 NEI, NIH, Bethesda, MD 20892 USA. Peking Union Med Coll Hosp, Beijing, Peoples R China. Univ La Frontera, Unidad Epidemiol Clin, Temuco, Chile. RP Ellwein, LB (reprint author), NEI, NIH, 31 Ctr Dr, Bethesda, MD 20892 USA. FU NEI NIH HHS [R01-EY-2103] NR 5 TC 266 Z9 299 U1 6 U2 30 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD APR PY 2000 VL 129 IS 4 BP 427 EP 435 DI 10.1016/S0002-9394(99)00452-3 PG 9 WC Ophthalmology SC Ophthalmology GA 304FD UT WOS:000086471800002 PM 10764849 ER PT J AU Pokharel, GP Negrel, AD Munoz, SR Ellwein, LB AF Pokharel, GP Negrel, AD Munoz, SR Ellwein, LB TI Refractive Error Study in Children: Results from Mechi zone, Nepal SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT 17th Congress of the Asia-Pacific-Academy-of-Ophthalmology CY MAR 07-12, 1999 CL MANILA, PHILIPPINES SP Asia Pacific Acad Ophthalmol AB PURPOSE: To assess the prevalence of refractive error and vision impairment in school age children in the terai area of the Mechi zone in Eastern Nepal. METHODS: Random selection of village-based clusters was used to identify a sample of children 5 to 15 years of age. Children in the 25 selected clusters were enumerated through a door-to door household survey and invited to village sites for examination. Visual acuity measurements, cycloplegic retinoscopy, cycloplegic autorefraction, ocular motility evaluation, and anterior segment, media, and fundus examinations were done from May 1998 through July 1998, Independent replicate examinations for quality assurance monitoring took place in all children with reduced vision and in a sample of those with normal vision in seven villages. RESULTS: A total of 5,526 children from 3,724 households were enumerated, and 5,067 children (91.7%) were examined, The prevalence of uncorrected, presenting, and best visual acuity 0.5 (20/40) or worse in at least one eye was 2.9%, 2.8%, and 1.4%, respectively; 0.4% had best visual acuity 0.5 or worse in both eyes. Refractive error was the cause in 56% of the 200 eyes with reduced uncorrected vision, amblyopia in 9%, other causes in 19%, with unexplained causes in the remaining 16%, Myopia -0.5 diopter or less in either eye or hyperopia 2 diopters or greater was observed in less than 3% of children. Hyperopia risk was associated with female gender and myopia risk with older age. CONCLUSIONS: The prevalence of reduced vision is very low in school age children in Nepal, most of it because of correctable refractive error. Further studies are needed to determine whether the prevalence of myopia will be higher for more recent birth cohorts. (Am J Ophthalmol 2000;129:436-444. (C) 2000 by Elsevier Science Inc, All rights reserved.). C1 NEI, NIH, Bethesda, MD 20892 USA. Fdn Eye Care Himalaya, Kathmandu, Nepal. WHO, Programme Prevent Blindness & Deafness, Geneva, Switzerland. Univ La Frontera, Unidad Epidemiol Clin, Temuco, Chile. RP Ellwein, LB (reprint author), NEI, NIH, 31 Ctr Dr, Bethesda, MD 20892 USA. FU NEI NIH HHS [R01-EY-2103] NR 6 TC 175 Z9 183 U1 2 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD APR PY 2000 VL 129 IS 4 BP 436 EP 444 DI 10.1016/S0002-9394(99)00453-5 PG 9 WC Ophthalmology SC Ophthalmology GA 304FD UT WOS:000086471800003 PM 10764850 ER PT J AU Maul, E Barroso, S Munoz, SR Sperduto, RD Ellwein, LB AF Maul, E Barroso, S Munoz, SR Sperduto, RD Ellwein, LB TI Refractive Error Study in Children: Results from La Florida, Chile SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID VISUAL IMPAIRMENT; EYE; PREVALENCE; POPULATION; AUSTRALIA; ACUITY AB PURPOSE: To assess the prevalence of refractive errors and vision impairment in school-age children in a suburban area (La Florida) of Santiago, Chile. METHODS: Random selection of geographically defined clusters was used to identify a representative sample of children 5 to 15 years of age. Children in the 26 selected clusters were enumerated through a door to-door survey and invited to report to a community health clinic for examination. Visual acuity measurements, cycloplegic retinoscopy, cycloplegic autorefraction, ocular motility evaluation, and examination of the external eye, anterior segment, media, and fundus were done from April through August 1998. Independent replicate examinations of all children with reduced vision and a sample of those with normal vision were done for quality assurance monitoring in six clusters. RESULTS: A total of 6,998 children from 3,830 households were enumerated, and 5,303 children (75.8%) were examined, The prevalence of uncorrected, presenting, and best visual acuity 0.50 (20/40) or worse in at least one eye was 15.8%, 14.7%, and 7.4%, respectively; 3.3% had best visual acuity 0.50 or worse in both eyes. Refractive error was the cause in 56.3% of the 1,285 eyes with reduced vision, amblyopia in 6.5%, other causes in 4.3%, with unexplained causes in the remaining 32.9%. Myopia -0.50 diopter or less in either eye was present in 3.4% of 5-year-old children, increasing to 19.4% in males and 14.7% in females by age 15. Over this same age range, hyperopia 2.00 diopters or greater decreased from 22.7% to 7.1% in males and from 26.3% to 8.9% in females. Females had a significantly higher risk of hyperopia than males. CONCLUSIONS: Refractive error, associated primarily with myopia, is a major cause of reduced vision in school-age children in La Florida. More than 7% of children could benefit from the provision of proper spectacles. Efforts are needed to make existing programs that provide free spectacles for school children more effective. Further studies are needed to determine whether the upward trend in myopia continues far beyond 15 years of age. (Am J Ophthalmol 2000;129:445-454. (C) 2000 by Elsevier Science Inc. All rights reserved.). C1 NEI, NIH, Bethesda, MD 20892 USA. Pontificia Univ Catolica Chile, Santiago, Chile. Univ La Frontera, Unidad Epidemiol Clin, Temuco, Chile. RP Ellwein, LB (reprint author), NEI, NIH, 31 Ctr Dr, Bethesda, MD 20892 USA. FU NEI NIH HHS [R01-EY-2103] NR 12 TC 199 Z9 208 U1 1 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD APR PY 2000 VL 129 IS 4 BP 445 EP 454 DI 10.1016/S0002-9394(99)00454-7 PG 10 WC Ophthalmology SC Ophthalmology GA 304FD UT WOS:000086471800004 PM 10764851 ER PT J AU Emmert-Buck, MR Strausberg, RL Krizman, DB Bonaldo, MF Bonner, RF Bostwick, DG Brown, MR Buetow, KH Chuaqui, RF Cole, DA Duray, PH Englert, CR Gillespie, JW Greenhut, S Grouse, L Hillier, LW Katz, KS Klausner, RD Kuznetzov, V Lash, AE Lennon, G Linehan, WM Liotta, LA Marra, MA Munson, PJ Ornstein, DK Prabhu, VV Prange, C Schuler, GD Soares, MB Tolstoshev, CM Vocke, CD Waterston, RH AF Emmert-Buck, MR Strausberg, RL Krizman, DB Bonaldo, MF Bonner, RF Bostwick, DG Brown, MR Buetow, KH Chuaqui, RF Cole, DA Duray, PH Englert, CR Gillespie, JW Greenhut, S Grouse, L Hillier, LW Katz, KS Klausner, RD Kuznetzov, V Lash, AE Lennon, G Linehan, WM Liotta, LA Marra, MA Munson, PJ Ornstein, DK Prabhu, VV Prange, C Schuler, GD Soares, MB Tolstoshev, CM Vocke, CD Waterston, RH TI Molecular profiling of clinical tissue specimens - Feasibility and applications SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID PROSTATIC INTRAEPITHELIAL NEOPLASIA; LASER CAPTURE MICRODISSECTION; GENE-EXPRESSION PATTERNS; MEN1 GENE; SUSCEPTIBILITY LOCUS; SEQUENCE TAGS; ALLELIC LOSS; HUMAN BRAIN; CANCER; IDENTIFICATION C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Pathogenet Unit, NIH, Bethesda, MD 20892 USA. NCI, Canc Genome Anat Project, Off Director, Bethesda, MD 20892 USA. Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. Univ Iowa, Dept Physiol & Biophys, Iowa City, IA 52242 USA. NICHD, Lab Integrat & Med Biophys, Bethesda, MD USA. Bostwick Labs, Richmond, VA USA. NCI, Lab Populat Genet, Bethesda, MD 20892 USA. Washington Univ, Genome Sequencing Ctr, St Louis, MO USA. Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Univ Calif Lawrence Livermore Natl Lab, Integrated Mol Anal Genomes & Express Consortium, Biol & Biotechnol Res Program, Livermore, CA USA. NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. British Columbia Canc Res Ctr, Genome Sequence Ctr, Vancouver, BC V5Z 1L3, Canada. NIH, Ctr Informat Technol, Math & Stat Comp Lab, Bethesda, MD 20892 USA. RP Emmert-Buck, MR (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2A33,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Bonner, Robert/C-6783-2015; OI Lash, Alex/0000-0003-3787-1590 NR 52 TC 51 Z9 54 U1 0 U2 2 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 2000 VL 156 IS 4 BP 1109 EP 1115 DI 10.1016/S0002-9440(10)64979-6 PG 7 WC Pathology SC Pathology GA 303GJ UT WOS:000086413900001 PM 10751334 ER PT J AU Feng, SLY Guo, Y Factor, VM Thorgeirsson, SS Bell, DW Testa, JR Peifley, KA Winkles, JA AF Feng, SLY Guo, Y Factor, VM Thorgeirsson, SS Bell, DW Testa, JR Peifley, KA Winkles, JA TI The Fn14 immediate-early response gene is induced during liver regeneration and highly expressed in both human and murine hepatocellular carcinomas SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID GROWTH-FACTOR-ALPHA; C-MYC; TRANSGENIC MICE; CELL-LINE; DIFFERENTIAL DISPLAY; DNA-SEQUENCES; CANCER; HEPATECTOMY; ONCOGENES; MUTATION AB Polypeptide growth factors stimulate mammalian cell proliferation by binding to specific cell surface receptors, This interaction triggers numerous biochemical responses including the activation of protein phosphorylation cascades and the enhanced expression of specific genes. We have identified several fibroblast growth factor (FGF)-inducible genes in murine MH 3T3 cells and recently reported that one of them, the FGF-inducible 14 (Fn14) immediate-early response gene, is predicted to encode a novel, cell surface-localized type Ia transmembrane protein. Here, we report that the human Fn14 homolog is located on chromosome 16p13.3 and encodes a 129-amino acid protein with similar to 82% sequence identity to the murine protein. The human Fn14 gene, like the murine Fn14 gene, is expressed at elevated levels after FGF, calf serum or phorbol ester treatment of fibroblasts in vitro and is expressed at relatively high levels in heart and kidney in vivo. We also report that the human Fn14 gene is expressed at relatively low levels in normal liver tissue but at high levels in liver cancer cell lines and in hepatocellular carcinoma specimens. Furthermore, the murine Fn14 gene is rapidly induced during liver regeneration in vivo and is expressed at high levels in the hepatocellular carcinoma nodules that develop in the c-myc/transforming growth factor-alpha-driven and the hepatitis B virus X protein-driven transgenic mouse models of hepatocarcinogenesis. These results indicate that Fn14 may play a role in hepatocyte growth control and Liver neoplasia. C1 Amer Red Cross, Dept Vasc Biol, Holland Lab, Rockville, MD 20855 USA. George Washington Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20037 USA. George Washington Univ, Med Ctr, Inst Biomed Sci, Washington, DC 20037 USA. NCI, Expt Carcinogenesis Lab, Div Basic Sci, Bethesda, MD 20892 USA. Fox Chase Canc Ctr, Human Genet Program, Philadelphia, PA 19111 USA. RP Winkles, JA (reprint author), Amer Red Cross, Dept Vasc Biol, Holland Lab, 15601 Crabbs Branch Way, Rockville, MD 20855 USA. FU NCI NIH HHS [CA-06927, P30 CA006927]; NHLBI NIH HHS [HL-39727, R01 HL039727] NR 44 TC 142 Z9 150 U1 1 U2 4 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 2000 VL 156 IS 4 BP 1253 EP 1261 DI 10.1016/S0002-9440(10)64996-6 PG 9 WC Pathology SC Pathology GA 303GJ UT WOS:000086413900018 PM 10751351 ER PT J AU Albrecht, FE Xu, J Moe, OW Hopfer, U Simonds, WF Orlowski, J Jose, PA AF Albrecht, FE Xu, J Moe, OW Hopfer, U Simonds, WF Orlowski, J Jose, PA TI Regulation of NHE3 activity by G protein subunits in renal brush-border membranes SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE sodium/hydrogen exchanger isoforms; proximal tubule; kidney ID NA+-H+ EXCHANGE; NUCLEOTIDE-BINDING-PROTEIN; BETA-GAMMA-SUBUNITS; RAT-KIDNEY; SODIUM-TRANSPORT; ADENYLYL CYCLASE; NA/H ANTIPORTER; PROXIMAL TUBULE; ALPHA-SUBUNITS; CYCLIC-AMP AB NHE3 activity is regulated by phosphorylation/ dephosphorylation processes and membrane recycling in intact cells. However, the Na+/H+ exchanger (NHE) can also be regulated by G proteins independent of cytoplasmic second messengers, but the G protein subunits involved in this regulation are not known. Therefore, we studied G protein subunit regulation of NHE3 activity in renal brush-border membrane vesicles (BBMV) in a system devoid of cytoplasmic components and second messengers. Basal NHE3 activity was not regulated by G(s)alpha or G(i)alpha, because antibodies to these G proteins by themselves were without effect. The inhibitory effect of D-1-like agonists on NHE3 activity was mediated, in part, by G(s)alpha, because it was partially reversed by anti-G(s)alpha antibodies. Moreover, the amount of G(s)alpha that coimmunoprecipitated with NHE3 was increased by fenoldopam in both brush-border membranes and renal proximal tubule cells. Furthermore, guanosine 5'-O-(3-thiotriphosphate) but not guanosine 5'-O-(2-thiodiphosphate), the inactive analog of GDP, increased the amount of G(s)alpha that coimmunoprecipitated with NHE3. The alpha(2)-adrenergic agonist, UK-14304 or pertussis toxin (PTX) alone had no effect on NHE3 activity, but UK-14304 and PTX treatment attenuated the D-1-like receptor-mediated NHE3 inhibition. The ability of UK-14304 to attenuate the D-1-like agonist effect was not due to G(i)alpha, because the attenuation was not blocked by anti-G(i)alpha antibodies or by PTX. Anti-G beta(common) antibodies, by themselves, slightly inhibited NHE3 activity but had little effect on D-1-like receptor-mediated NHES inhibition. However, anti-G beta(common) antibodies reversed the effects of UK-14304 and PTX on D-1-like agonist-mediated NHE3 inhibition. These studies provide concrete evidence of a direct regulatory role for G(s)alpha, independent of second messengers, in the D-1-like-mediated inhibition of NHES activity in rat renal BBMV. In addition, beta/gamma dimers of heterotrimeric G proteins appear to have a stimulatory effect on NHE3 activity in BBMV. C1 Georgetown Univ, Med Ctr, Dept Pediat, Div Pediat Nephrol, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Physiol & Biophys, Washington, DC 20007 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75235 USA. Case Western Reserve Univ, Sch Med, Dept Physiol, Cleveland, OH 44106 USA. NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. McGill Univ, Sch Med, Dept Physiol, Montreal, PQ H3G 1Y6, Canada. RP Albrecht, FE (reprint author), Georgetown Univ, Med Ctr, Dept Pediat, Div Pediat Nephrol, 3800 Reservoir Rd NW, Washington, DC 20007 USA. RI Hopfer, Ulrich`/B-5463-2009 FU NHLBI NIH HHS [HL23081]; NIDDK NIH HHS [DK39308, DK52612] NR 43 TC 50 Z9 53 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD APR PY 2000 VL 278 IS 4 BP R1064 EP R1073 PG 10 WC Physiology SC Physiology GA 304JA UT WOS:000086478900032 PM 10749796 ER PT J AU Loffing, J Loffing-Cueni, D Macher, A Hebert, SC Olson, B Knepper, MA Rossier, BC Kaissling, B AF Loffing, J Loffing-Cueni, D Macher, A Hebert, SC Olson, B Knepper, MA Rossier, BC Kaissling, B TI Localization of epithelial sodium channel and aquaporin-2 in rabbit kidney cortex SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE immunohistochemistry; morphology; intercalated cells; bumetamide-sensitive sodium-potassium chloride cotransporter; thiazide-sensitive sodium chloride cotransporter; diuretics ID NA-CL COTRANSPORTER; DISTAL NEPHRON SEGMENTS; REGULATED WATER CHANNEL; THICK ASCENDING LIMBS; K-ATPASE ACTIVITY; RAT-KIDNEY; TUBULAR SEGMENTS; COLLECTING DUCT; H-ATPASE; EXPRESSION AB The amiloride-sensitive epithelial sodium channel (ENaC) and the vasopressin-dependent water channel aquaporin-2 (AQP2) mediate mineralocorticoid-regulated sodium- and vasopressin-regulated water reabsorption, respectively. Distributions of ENaC and AQP2 have been shown by immunohistochemistry in rats. Functional data from rabbits suggest a different distribution pattern of these channels than in rats. We studied, by immunohistochemistry in the rabbit kidney cortex, the distributions of ENaC and AQP2, in conjunction with marker proteins for distal segments. In rabbit cortex ENaC is restricted to the connecting tubule (CNT) cells and cortical collecting duct (CCD) cells. The intracellular distribution of ENaC shifts from the apical membrane in the most upstream CNT cells to a cytoplasmic location further downstream in the CNT and in the CCD cells. AQP2 is detected in the CCD cells exclusively. The anatomic subdivisions in the rabbit distal nephron coincide exactly with distributions of apical transport systems. The differences between rabbits and rats in the distribution patterns of ENaC and AQP2 may explain functional differences in renal salt and water handling between these species. C1 Univ Zurich, Inst Anat, CH-8057 Zurich, Switzerland. Vanderbilt Univ, Div Nephrol, Nashville, TN 37232 USA. NHLBI, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. Univ Lausanne, Inst Pharmacol & Toxicol, CH-1005 Lausanne, Switzerland. RP Kaissling, B (reprint author), Univ Zurich, Inst Anat, Winterthurerstr 190, CH-8057 Zurich, Switzerland. EM bkaissl@anatom.unizh.ch FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 54 TC 51 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 2000 VL 278 IS 4 BP F530 EP F539 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 303ZJ UT WOS:000086457800003 PM 10751213 ER PT J AU Portilla, D Dai, GH Peters, JM Gonzalez, FJ Crew, MD Proia, AD AF Portilla, D Dai, GH Peters, JM Gonzalez, FJ Crew, MD Proia, AD TI Etomoxir-induced PPAR alpha-modulated enzymes protect during acute renal failure SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE carnitine palmitoyltransferase; fatty acid oxidation; ischemia/reperfusion ID CARNITINE PALMITOYLTRANSFERASE-I; ACTIVATED RECEPTOR-ALPHA; ACYL-COA OXIDASE; ISCHEMIA-REPERFUSION INJURY; FATTY-ACID OXIDATION; DIFFERENTIAL EXPRESSION; RAT-KIDNEY; PROLIFERATOR; GENE; HEPATOCYTES AB Regulation of fatty acid beta-oxidation (FAO) represents an important mechanism for a sustained balance of energy production/utilization in kidney tissue. To examine the role of stimulated FAO during ischemia, Etomoxir (Eto), clofibrate, and WY-14,643 compounds were given 5 days prior to the induction of ischemia/reperfusion (I/R) injury. Compared with rats administered vehicle, Eto-, clofibrate-, and WY-treated rats had lower blood urea nitrogen and serum creatinines following I/R injury. Histological analysis confirmed a significant amelioration of acute tubular necrosis. YR injury led to a threefold reduction of mRNA and protein levels of acyl CoA oxidase (AOX) and cytochrome P4A1, as well as twofold inhibition of their enzymatic activities. Eto treatment prevented the reduction of mRNA and protein levels and the inhibition of the enzymatic activities of these two peroxisome proliferator-activated receptor-alpha (PPAR alpha) target genes during IIR injury. PPAR alpha null mice subjected to I/R injury demonstrated significantly enhanced cortical necrosis and worse kidney function compared with wild-type controls. These results suggest that upregulation of PPAR alpha-modulated FAO genes has an important role in the observed cytoprotection during I/R injury. C1 Univ Arkansas Med Sci, Dept Internal Med, Div Nephrol, Little Rock, AR 72205 USA. John L McClellan Mem Vet Hosp, Little Rock, AR 72205 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. NCI, Lab Metab, Bethesda, MD 20892 USA. Univ Arkansas Med Sci, Dept Geriatr, Little Rock, AR 72205 USA. RP Portilla, D (reprint author), Univ Arkansas Med Sci, Dept Med, Div Nephrol, 4301 W Markham,Slot 501, Little Rock, AR 72205 USA. EM portilladicier@exchange.vams.edu RI Peters, Jeffrey/D-8847-2011 FU NIDDK NIH HHS [R01-DK-52926] NR 39 TC 102 Z9 103 U1 1 U2 2 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 2000 VL 278 IS 4 BP F667 EP F675 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 303ZJ UT WOS:000086457800019 PM 10751229 ER PT J AU Weinstein, LS Yu, SH Ecelbarger, CA AF Weinstein, LS Yu, SH Ecelbarger, CA TI Variable imprinting of the heterotrimeric G protein G(s) alpha-subunit within different segments of the nephron SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Review DE genomic imprinting; Albright hereditary osteodystrophy; adenosine 3 ',5 '-cyclic monophosphate; pseudohypoparathyroidism; parathyroid hormone ID ALBRIGHT-HEREDITARY-OSTEODYSTROPHY; PSEUDOHYPOPARATHYROIDISM TYPE-IB; STIMULATORY-G-PROTEIN; CYCLASE COUPLING PROTEIN; NUCLEOTIDE REGULATORY PROTEIN; GRADIENT GEL-ELECTROPHORESIS; PEPTIDE RECEPTOR GENE; THICK ASCENDING LIMBS; HUMAN GNAS1 GENE; PARATHYROID-HORMONE AB The heterotrimeric G protein G(s) is required for hormone-stimulated intracellular cAMP generation because it couples hormone receptors to the enzyme adenylyl cyclase. Hormones that activate G(s) in the kidney include parathyroid hormone, glucagon, calcitonin, and vasopressin. Recently, it has been demonstrated that the G(s)alpha gene is imprinted in a tissue-specific manner, leading to preferential expression of G(s)alpha from the maternal allele in some tissues. In the kidney, G(s)alpha is imprinted in the proximal tubule but not in more distal nephron segments, such as the thick ascending limb or collecting duct. This most likely explains why in both humans and mice heterozygous mutations in the maternal allele lead to parathyroid hormone resistance in the proximal tubule whereas mutations in the paternal allele do not. In contrast, heterozygous mutations have little effect on vasopressin action in the collecting ducts. In mice with heterozygous null G(s)alpha mutations (both those with mutations on the maternal or paternal allele), expression of the Na-K-2Cl cotransporter was decreased in the thick ascending limb, suggesting that its expression is regulated by cAMP. The G,cli genes also generate alternative, oppositely imprinted transcripts encoding XL alpha s, a G(s)alpha isoform with a long NH(2)-terminal extension, and NESP55, a chromogranin-like neurosecretory protein. The role, if any, of these proteins in renal physiology is unknown. C1 NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Dept Med, Div Endocrinol & Metab, Washington, DC 20007 USA. RP Weinstein, LS (reprint author), NIDDK, Metab Dis Branch, NIH, Bld 10,Rm 8C101, Bethesda, MD 20892 USA. EM leew@amb.niddk.nih.gov RI Weinstein, Lee/I-5575-2015 NR 75 TC 31 Z9 32 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 2000 VL 278 IS 4 BP F507 EP F514 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 303ZJ UT WOS:000086457800001 PM 10751211 ER PT J AU Halverson, PK Mays, GP Rimer, BK Lerman, C Audrain, J Kaluzny, AD AF Halverson, PK Mays, GP Rimer, BK Lerman, C Audrain, J Kaluzny, AD TI Adoption of a health education intervention for family members of breast cancer patients SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article DE breast neoplasms; counseling; family; health education ID RISK; PREVENTION; TRIAL AB Background: Relatives of breast cancer patients often face substantial uncertainty and psychological stress regarding their own health risks and optimal strategies for prevention and early detection. Efficacious educational and counseling interventions are rarely evaluated for their potential adoption and use in medical practice settings. This study evaluates a health education program for first-degree relatives of breast cancer patients based on the program's potential for being adopted and used by medical practices affiliated with cancer centers. Methods: A randomized, controlled trial was implemented in four community hospital-based medical practices. After 9 months, clinical and administrative staff at each practice were given self-administered surveys. Of 90 staff members recruited to respond, useable responses were received from 60 (67%), including 13 physicians (31%), 43 nurses (98%), and four program managers (100%). Participants made self-reports of program awareness, program support, perceived program performance, likelihood of program adoption and use, and barriers to adoption. Results: A strong majority of respondents (80%) reported that all or most staff agreed with the need for the program. Perceived program performance in meeting goals was generally favorable but varied across sites and across staff types. Overall, 56% of respondents indicated that their practices were likely or highly likely to adopt the program in full. The likelihood of adoption varied substantially across sites and across program components. Conclusions: Evaluating the potential for program adoption offers insight for tailoring preventive health interventions and their implementation strategies to improve diffusion in the field of practice. C1 Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Univ N Carolina, Sch Publ Hlth, Dept Hlth Policy & Adm, Chapel Hill, NC USA. Ctr Dis Control & Prevent, Publ Hlth Practice Program Off, Atlanta, GA USA. NCI, Civ Canc Control & Populat Sci, Rockville, MD USA. Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Washington, DC 20007 USA. Univ N Carolina, Cecil G Sheps Ctr Hlth Serv Res, Sch Publ Hlth, Chapel Hill, NC USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Publ Hlth, Chapel Hill, NC USA. RP Mays, GP (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Dr, Boston, MA 02115 USA. NR 23 TC 6 Z9 6 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD APR PY 2000 VL 18 IS 3 BP 189 EP 198 DI 10.1016/S0749-3797(99)00163-4 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 296UL UT WOS:000086044700001 PM 10722984 ER PT J AU Albright, CL Cohen, S Gibbons, L Miller, S Marcus, B Sallis, J Imai, K Jernick, J Simons-Morton, DG AF Albright, CL Cohen, S Gibbons, L Miller, S Marcus, B Sallis, J Imai, K Jernick, J Simons-Morton, DG TI Incorporating physical activity advice into primary care - Physician-delivered advice within the Activity Counseling Trial SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article DE leisure activity; counseling; behavior; primary health care ID HEALTH PROMOTION; GENERAL-PRACTITIONERS; TRAINING PHYSICIANS; SMOKING CESSATION; INSULIN-SECRETION; PROJECT; ACCEPTABILITY; PRODUCTIVITY; FEASIBILITY; INTERNISTS AB Introduction: The Activity Counseling Trial (ACT) was designed to compare the effectiveness of physician advice alone with physician advice plus behavioral counseling, provided by ACT-trained health educators, to increase levels of physical activity in healthy, sedentary patients. The objective was to determine health care providers' adherence to the ACT protocol for delivering initial "physician" advice on physical activity and to determine providers' satisfaction with the protocol. Methods: Fifty-four physicians or physician assistants from 11 primary care practices located in California, Texas, and Tennessee volunteered to participate as ACT-trained physicians. Providers were trained to integrate 3 to 4 minutes of initial physical activity advice into the routine office visits of sedentary patients, aged 35 to 75 years, with no acute or serious chronic conditions. This advice included assessment of current physical activities, advising the patient about an appropriate physical activity goal, and referring the patient to the health educator. Providers initialed forms to document delivery of advice, and ACT health educators recorded their advice on a computerized tracking system. A provider survey measured length of time spent advising patients about physical activity and provider satisfaction with the program. Results: Ninety-nine percent of patients received the initial physician advice about physical activity. Eighty-three percent of the providers spent less than 5 to 6 minutes, and 46% spent the recommended 3 to 4 minutes providing advice. Sixty-three percent said the advice resulted in little or no increase in the length of an office visit, and 83% said participation was an asset to their clinics. Conclusions: Providers incorporated brief physical activity advice into routine primary care visits with little disruption. Their response to the ACT advice protocol was positive and participation in the study was viewed as beneficial. C1 Stanford Univ, Sch Med, Stanford Ctr Res Dis Prevent, Palo Alto, CA 94304 USA. Univ Arizona, Arizona Prevent Ctr, Tucson, AZ USA. Univ Texas, SW Med Ctr, Cooper Inst Aerob Res, Dallas, TX USA. Univ Tennessee, Memphis, TN USA. Miriam Hosp, Providence, RI 02906 USA. Brown Univ, Sch Med, Providence, RI 02912 USA. San Diego State Univ, San Diego, CA 92182 USA. Santa Clara Valley Med Ctr, Moorpk Clin, San Jose, CA 95128 USA. NHLBI, Bethesda, MD 20892 USA. RP Albright, CL (reprint author), Stanford Univ, Sch Med, Stanford Ctr Res Dis Prevent, 1000 Welch Rd, Palo Alto, CA 94304 USA. FU NHLBI NIH HHS [N01HC45135, N01HC45136, N01HC45137] NR 64 TC 60 Z9 62 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD APR PY 2000 VL 18 IS 3 BP 225 EP 234 DI 10.1016/S0749-3797(99)00155-5 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 296UL UT WOS:000086044700006 PM 10722989 ER PT J AU Cohen, M Deamant, C Barkan, S Richardson, J Young, M Holman, S Anastos, K Cohen, J Melnick, S AF Cohen, M Deamant, C Barkan, S Richardson, J Young, M Holman, S Anastos, K Cohen, J Melnick, S TI Domestic violence and childhood sexual abuse in HIV-infected women and women at risk for HIV SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID CLINICAL CHARACTERISTICS; SUBSTANCE USE; PREVALENCE; PREGNANCY; HEALTH; POPULATION; EMERGENCY; SURVIVORS; BEHAVIORS; INJURIES AB Objectives. The purpose of this study was to determine the prevalence and effect of domestic violence and childhood sexual abuse in women with HIV or at risk for HIV infection. Methods. Participants with HIV or at risk for HIV infection enrolled in the Women's Interagency HIV Study. Childhood sexual abuse; all physical, sexual. and coercive violence by a partner HIV serostatus, demographic data; and substance use and sexual habits were assessed. Results. The lifetime prevalence of domestic violence was 66% and 67%, respectively, in 1288 women with HIV and 357 uninfected women. One quarter of the women reported recent abuse, and 31% of the HIV-seropositive women and 27% of the HIV-seronegative women reported childhood sexual abuse. Childhood sexual abuse was strongly associated with a lifetime history of domestic violence and high-risk behaviors, including using drugs, having more than 10 male sexual partners and having male partners at risk for HIV infection and exchanging sex for drugs, money, or shelter. Conclusions, Our data support the hypothesis of a continuum of risk, with early childhood abuse leading to later domestic violence. which may increase the risk of behaviors leading to HIV infection. C1 Cook Cty Hosp, CORE Ctr, Chicago, IL 60612 USA. Seattle King Cty Dept Publ Hlth, Seattle, WA USA. Univ So Calif, Dept Med, Los Angeles, CA 90089 USA. Georgetown Univ, Dept Med, Washington, DC 20057 USA. SUNY Downstate, Dept Obstet & Gynecol, Brooklyn, NY USA. Catholic Med Ctr Brooklyn & Queens, New York, NY USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. NCI, Bethesda, MD 20892 USA. RP Cohen, M (reprint author), Cook Cty Hosp, CORE Ctr, 2020 W Harrison, Chicago, IL 60612 USA. FU NIAID NIH HHS [U01-AI-31834, U01-AI-34994, U01-AI-35004] NR 32 TC 201 Z9 205 U1 2 U2 5 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD APR PY 2000 VL 90 IS 4 BP 560 EP 565 DI 10.2105/AJPH.90.4.560 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 297WW UT WOS:000086106500009 PM 10754970 ER PT J AU Jackson, SA Anderson, RT Johnson, NJ Sorlie, PD AF Jackson, SA Anderson, RT Johnson, NJ Sorlie, PD TI The relation of residential segregation to all-cause mortality: A study in black and white SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID UNITED-STATES; METROPOLITAN-AREAS; HEALTH; INCOME; DIFFERENTIALS; INEQUALITY; POVERTY AB Objectives. This study investigated the influence of an aggregate measure of the social environment on racial differences in all-cause mortality. Methods. Data from the National Longitudinal Mortality Study were analyzed. Results. After adjustment for family income, age-adjusted mortality risk increased with increasing minority residential segregation among Blacks aged 25 to 44 years and non-Blacks aged 45 to 64 years. In most age/race/gender groups, the highest and lowest mortality risks occurred in the highest and lowest categories of residential segregation, respectively. Conclusions. These results suggest that minority residential segregation may influence mortality risk and underscore the traditional emphasis on the social underpinnings of disease and death. C1 Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Epidemiol Sect, Winston Salem, NC 27157 USA. US Bur Census, Washington, DC 20233 USA. NHLBI, Epidemiol & Biometry Program, Bethesda, MD 20892 USA. RP Jackson, SA (reprint author), Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Epidemiol Sect, 300 S Hawthorne Rd, Winston Salem, NC 27157 USA. NR 19 TC 77 Z9 77 U1 0 U2 4 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD APR PY 2000 VL 90 IS 4 BP 615 EP 617 DI 10.2105/AJPH.90.4.615 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 297WW UT WOS:000086106500017 PM 10754978 ER PT J AU Fix, AD Abdel-Hamid, M Purcell, RH Shehata, MH Abdel-Aziz, F Mikhail, N El Sebai, H Nafeh, M Habib, M Arthur, RR Emerson, SU Strickland, GT AF Fix, AD Abdel-Hamid, M Purcell, RH Shehata, MH Abdel-Aziz, F Mikhail, N El Sebai, H Nafeh, M Habib, M Arthur, RR Emerson, SU Strickland, GT TI Prevalence of antibodies to hepatitis E in two rural Egyptian communities SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID ACUTE SPORADIC HEPATITIS; E VIRUS-INFECTION; WEST KALIMANTAN BORNEO; OPEN-READING FRAME-2; HEV INFECTION; NILE DELTA; CHILDREN; ADULTS; ETIOLOGY; INDIA AB A population-based serosurvey in two rural Egyptian communities was used to assess age-specific prevalence of antibody to hepatitis E virus (anti-HEV). One community is in the Nile Delta (11,182 inhabitants; 3,997 participants) and the other in Upper Egypt (10,970 inhabitants; 6,029 participants). Samples were tested for anti-HEV with a commercial enzyme linked immunoassay (ELISA) based on antigens derived from open reading frame (ORF)2 and ORF3. Although there was a clear difference in sensitivity among the lots of the commercial test used, it was still possible to determine the seroprevalence. The seroprevalence of anti-HEV exceeded 60% in the first decade of life, peaked at 76% in the second decade and remained above 60% until the eighth decade. Prevalence of this magnitude is among the highest reported in the world, with an age-specific pattern more similar to hyperendemic hepatitis A virus transmission than generally described. Lot-to-lot variation in the sensitivity of the commercial ELISA kit highlights a problem when comparing seroepidemiologic studies of different populations. C1 Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. Minia Univ, Fac Med, Menia, Egypt. NIAID, Hepatitis Viruses Sect, NIH, Bethesda, MD 20892 USA. NIAID, Mol Hepatitis Sect, NIH, Bethesda, MD 20892 USA. Assiut Univ, Fac Med, Dept Trop Med, Assiut 71516, Egypt. Minist Hlth & Populat, Ctr Field & Appl Res, Qalyub, Egypt. Menoufia Univ, Liver Inst, Shebeen El Koom, Egypt. WHO, Dept Communicable Dis Surveillance & Response, CH-1211 Geneva, Switzerland. RP Fix, AD (reprint author), Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, 660 W Redwood St, Baltimore, MD 21201 USA. NR 28 TC 60 Z9 64 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD APR PY 2000 VL 62 IS 4 BP 519 EP 523 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 401TX UT WOS:000166945300018 PM 11220771 ER PT J AU Oka, H Ito, Y AF Oka, H Ito, Y TI Separation of lac dye components using high-speed countercurrent chromatography SO AMERICAN LABORATORY LA English DT Article AB Lac dye is a natural food dye that is widely used in food processing. Being extracted from an insect secretion, lac is not a simple material and hitherto has been difficult to separate. This article shows how the use of countercurrent chromatography provides an effective solution to this problem. C1 Aichi Prefectural Inst Publ Hlth, Div Food Related Chem, Kita Ku, Nagoya, Aichi 462, Japan. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Oka, H (reprint author), Aichi Prefectural Inst Publ Hlth, Div Food Related Chem, Kita Ku, Nagoya, Aichi 462, Japan. NR 18 TC 1 Z9 1 U1 0 U2 2 PU INT SCIENTIFIC COMMUN INC PI SHELTON PA PO BOX 870, 30 CONTROLS DRIVE, SHELTON, CT 06484-0870 USA SN 0044-7749 J9 AM LAB JI Am. Lab. PD APR PY 2000 VL 32 IS 8 BP 24 EP + PG 6 WC Chemistry, Analytical; Instruments & Instrumentation SC Chemistry; Instruments & Instrumentation GA 305YC UT WOS:000086568500002 ER PT J AU Oka, H Iwaya, M Harada, K Suzuki, M Ito, Y AF Oka, H Iwaya, M Harada, K Suzuki, M Ito, Y TI Recycling foam countercurrent chromatography SO ANALYTICAL CHEMISTRY LA English DT Article ID WATER FREE; BACITRACIN; COMPONENTS; ADDITIVES; NITROGEN AB A new sample injection method for foam countercurrent chromatography (CCC), named the "recycle injection system", has been developed. In this system, the effluent from the liquid outlet is directly returned into the column through the sample feed line so that the sample solution is continuously recycled for repetitive foam fractionation, The utility of this system was demonstrated in the separations of microcystin ex-tract and bacitracin complex from large volumes of sample solution. Microcystins were separated and enriched in decreasing order of hydrophobicity, Bacitracin A, a hydrophobic major component, in the bacitracin complex was highly enriched in the foam fraction and almost completely isolated from other components. This recycling foam CCC method may be effectively applied for separation and enrichment of various foam-active components from crude natural products. C1 Aichi Prefectural Inst Publ Hlth, Kita Ku, Nagoya, Aichi 4628576, Japan. Meijo Univ, Fac Pharm, Tempa Ku, Nagoya, Aichi 4688503, Japan. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Oka, H (reprint author), Aichi Prefectural Inst Publ Hlth, Kita Ku, Tsuji Machi, Nagoya, Aichi 4628576, Japan. NR 6 TC 6 Z9 8 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD APR 1 PY 2000 VL 72 IS 7 BP 1490 EP 1494 DI 10.1021/ac990974d PG 5 WC Chemistry, Analytical SC Chemistry GA 299YF UT WOS:000086225500026 ER PT J AU Baker, SG AF Baker, SG TI Randomized and nonrandomized clinical studies - Statistical considerations SO ANESTHESIOLOGY LA English DT Editorial Material DE anesthesia; general; observational studies; paired availability design; regional ID VASCULAR-SURGERY; EPIDURAL ANALGESIA; GENERAL-ANESTHESIA; TRIALS C1 NCI, Div Canc Prevent, Biometry Res Gr, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Anesthesiol Crit Care Med, Baltimore, MD USA. RP Baker, SG (reprint author), NCI, Div Canc Prevent, Biometry Res Gr, Bethesda, MD 20892 USA. NR 18 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD APR PY 2000 VL 92 IS 4 BP 928 EP 930 DI 10.1097/00000542-200004000-00006 PG 3 WC Anesthesiology SC Anesthesiology GA 299AB UT WOS:000086172700002 PM 10754608 ER PT J AU Baker, SG Lindeman, KS AF Baker, SG Lindeman, KS TI Epidural analgesia and cesarean section: Two meta-analyses adjusting for utilization of labor analgesia SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 NIH, Rockville, MD USA. Johns Hopkins Univ, Baltimore, MD 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 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD APR PY 2000 SU S MA A31 BP U10 EP U10 PG 1 WC Anesthesiology SC Anesthesiology GA 300VR UT WOS:000086274300031 ER PT J AU Toro, C Deuschl, G Hallett, M AF Toro, C Deuschl, G Hallett, M TI Movement-related electroencephalographic desynchronization in patients with hand cramps: Evidence for motor cortical involvement in focal dystonia SO ANNALS OF NEUROLOGY LA English DT Article ID FIELD POTENTIAL OSCILLATIONS; PACED FINGER MOVEMENTS; VOLUNTARY MOVEMENT; BETA-SYNCHRONIZATION; SENSORIMOTOR CORTEX; WRITERS CRAMP; AWAKE MONKEYS; MU-RHYTHM; EEG; BRISK AB We studied the dynamic changes in the amplitude of scalp electroencephalographic (EEG) oscillations to self-paced simple index finger abduction movements in patients with writer's cramp and compared them with those of normal aged-matched controls. The changes in EEG oscillations were measured in predefined frequency bands (8-10, 10-12, 12-20, and 20-30 Hz) by using the event-related desynchronization technique. Movements of the affected and unaffected hand in patients with writer's cramp showed significantly less reduction in 20- to 30-Hz power compared with controls. The differences in movement-related EEG power decline were apparent over the contralateral central and midline regions before and after electromyographic onset. Because EEG beta rhythm in the sensorimotor region likely emanates from the motor cortex and is related to ongoing muscle activity, this abnormality could be a manifestation of the abnormal motor command at the cortical level. C1 NINCDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. Univ Kiel, Dept Neurol, D-2300 Kiel, Germany. RP Hallett, M (reprint author), NINCDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 10,Room 5n226,10 Ctr Dr MSC 1428, Bethesda, MD 20892 USA. RI Deuschl, Gunther/A-7986-2010 NR 35 TC 50 Z9 50 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 2000 VL 47 IS 4 BP 456 EP 461 DI 10.1002/1531-8249(200004)47:4<456::AID-ANA8>3.0.CO;2-Q PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 300XF UT WOS:000086278500008 PM 10762156 ER PT J AU Chase, TN Oh, JD AF Chase, TN Oh, JD TI Striatal mechanisms and pathogenesis of parkinsonian signs and motor complications SO ANNALS OF NEUROLOGY LA English DT Article; Proceedings Paper CT Meeting of the Levodopa-Induged Dyskinesias CY NOV 20-22, 1998 CL BERMUDA SP Levodopa Induged Dyskinesias ID LEVODOPA-INDUCED DYSKINESIAS; NMDA RECEPTOR SUBUNITS; CENTRAL PATHOPHYSIOLOGICAL MECHANISMS; PROTEIN-KINASE-II; L-DOPA; BASAL GANGLIA; RAT STRIATUM; TYROSINE PHOSPHORYLATION; RESPONSE COMPLICATIONS; SYNAPTIC PLASTICITY AB Recent studies suggest that motor dysfunction associated with the chronic nonphysiologic stimulation of dopaminergic receptors on striatal spiny neurons alters the sensitivity of nearby glutamatergic receptors, especially those of the N-methyl-D-aspartate (NMDA) subtype. Lesioning the nigrostriatal dopamine system of rats or nonhuman primates induces parkinsonian signs; subsequent once- or twice-daily treatment with levodopa produces many of the features of the human motor complication syndrome. Some drugs that block NMDA receptors palliate parkinsonian signs in these animal models, as well as in patients with Parkinson's disease. Certain NMDA receptor antagonists injected into the striatum or given systemically also have the ability to act palliatively or prophylactically to alleviate levodopa-induced response alterations. These observations support the view that sensitization of striatal NMDA receptors contributes to the pathogenesis of motor dysfunction in Parkinson's disease. Since protein phosphorylation serves as an important regulatory mechanism for NMDA receptors, differential increases in the phosphorylation state of tyrosine and serine residues, observed as a result of nigrostriatal system destruction as well as response alteration induction, could account for the apparent augmentation in synaptic efficacy. Current evidence thus suggests that the intermittent stimulation of dopaminergic receptors activates signal transduction pathways in striatal neurons, which augment phosphorylation of NMDA receptors and thus their sensitivity to cortical glutamatergic input. As a result, striatal output changes in ways that favor the appearance of parkinsonian signs and motor complications. C1 NINCDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Chase, TN (reprint author), NINCDS, Expt Therapeut Branch, NIH, Bldg 10,Room 5C103,90900 Rockville Pike, Bethesda, MD 20892 USA. NR 91 TC 82 Z9 87 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 2000 VL 47 IS 4 SU 1 BP S122 EP S130 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 302RN UT WOS:000086379600014 PM 10762139 ER PT J AU Gerfen, CR AF Gerfen, CR TI Dopamine-mediated gene regulation in models of Parkinson's disease SO ANNALS OF NEUROLOGY LA English DT Article; Proceedings Paper CT Meeting of the Levodopa-Induged Dyskinesias CY NOV 20-22, 1998 CL BERMUDA SP Levodopa Induged Dyskinesias ID IMMEDIATE-EARLY GENES; C-FOS; TRANSCRIPTION FACTORS; SUBSTANTIA-NIGRA; GROWTH-FACTOR; NEURONS; EXPRESSION; STRIATUM; RAT; RECEPTORS AB The normal functioning of the basal ganglia is dependent on dopamine maintaining a balance between the two major output pathways of the striatum, through the D1 and D2 dopamine receptors, which have opposing effects on these pathways. Lesions of the dopamine system, such as occur in Parkinson's disease (PD). disrupt this balance. Gene regulation studies provide a measure of the cellular and molecular effects of dopamine on striatal neurons in animal models of PD. Dopamine agonists, involving selective or mixed D1 and D2 agonists, such as levodopa, are able to reverse many of the homeostatic changes induced by striatal dopamine depletion. However, following dopamine depletion, a supersensitive responsiveness of D1 striatal neurons to dopamine agonists develops, indicated by the induction of immediate early genes. The molecular and cellular mechanisms underlying the irreversibility of this supersensitive response with long-term dopamine agonist treatments may provider insights into dyskinesias that develop with long-term levodopa therapy in the treatment of PD. C1 NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. RP Gerfen, CR (reprint author), NIMH, Lab Syst Neurosci, 36 Convent Dr,MSC 4075, Bethesda, MD 20892 USA. NR 34 TC 36 Z9 38 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 2000 VL 47 IS 4 SU 1 BP S42 EP S52 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 302RN UT WOS:000086379600006 PM 10762131 ER PT J AU Hallett, M AF Hallett, M TI Clinical physiology of dopa dyskinesia SO ANNALS OF NEUROLOGY LA English DT Article; Proceedings Paper CT Meeting of the Levodopa-Induged Dyskinesias CY NOV 20-22, 1998 CL BERMUDA SP Levodopa Induged Dyskinesias DE Clinical physiology of dopa dyskinesia ID LEVODOPA-INDUCED DYSKINESIAS; PARKINSONS-DISEASE; REFLEX; CHOREA AB Levodopa-induced dyskinesias are clinically heterogeneous, both in appearance and timing with respect to dose. Electromyogram observations indicate that levodopa-induced dyskinesias are comprised of irregular bursts of either synchronous or asynchronous neuronal firing in antagonist muscles. Studies of the blink reflex and spontaneous blinking have provided useful neurophysiologic information on brainstem function that is sensitive to changes in brain dopamine concentrations. The blink rate is reduced in Parkinson's disease (PD) and increased with dopamine treatment. The blink rate in patients with levodopa-induced dyskinesias, however, has been shown to be faster than that in optimally treated PD patients and normal individuals. These results suggest that dyskinesias are associated with a relative hyperdopaminergic state. However, there appears to be no correlation of dopaminergic benefit to the parkinsonian symptoms, indicating perhaps that there are several dopaminergic systems, including one responsible for motor function and one for dyskinesia. Alternatively it may be that the pattern of neural Bring influences dyskinesias, while the average firing rate may be responsible for motor benefits. C1 NINCDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINCDS, Human Motor Control Sect, NIH, Bldg 10,Room 5N226,10 Ctr Dr MSC 1428, Bethesda, MD 20892 USA. NR 13 TC 10 Z9 11 U1 0 U2 2 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 2000 VL 47 IS 4 SU 1 BP S147 EP S153 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 302RN UT WOS:000086379600017 PM 10762142 ER PT J AU Grillo-Lopez, AJ Cheson, BD Horning, SJ Peterson, BA Carter, WD Varns, CL Klippenstein, DL Shen, CD AF Grillo-Lopez, AJ Cheson, BD Horning, SJ Peterson, BA Carter, WD Varns, CL Klippenstein, DL Shen, CD TI Response criteria for NHL: Importance of 'normal' lymph node size and correlations with response rates SO ANNALS OF ONCOLOGY LA English DT Article DE clinical trials; non-Hodgkin's lymphoma; response criteria ID NON-HODGKINS-LYMPHOMA; LOW-GRADE LYMPHOMA; PHASE-II TRIAL; ANTI-CD20 MONOCLONAL-ANTIBODY; COOPERATIVE-ONCOLOGY-GROUP; LARGE CELL LYMPHOMA; LEUKEMIA-GROUP-B; COMBINATION CHEMOTHERAPY; FLUDARABINE PHOSPHATE; AGGRESSIVE LYMPHOMA AB Background: Oncologic literature cites many different definitions of critical response measurements. Patients and methods: Response criteria (RC) for non-Hodgkin's lymphoma (NHL) were developed by lymphoma experts, endorsed by international lymphoma clinicians, and applied to a 166-patient rituximab (Rituxan(R), MabThera(R)) trial by a third-party, blinded panel of NHL experts (LEXCOR). Retrospectively, we analyzed this data using variations of the original RC and comparing with recently published RC. Results: The definition of a 'normal' lymph node affected the complete response (CR) rate (less than or equal to 1.0 x 1.0 cm, 6%; less than or equal to 1.5 x 1.5 cm, 18%; less than or equal to 2.0 x 2.0 cm, 28%); overall response rate (ORR) was not affected. CR rates increased progressively without greater than or equal to 28 days response confirmation: 12% vs. 6% (less than or equal to 1.0 x 1.0 cm), 26% vs. 18% (less than or equal to 1.5 x 1.5 cm), and 36% vs. 28% (less than or equal to 2.0 x 2.0 cm). CR rate and duration of response (DR) were unaffected when only the six largest, rather than all lesions, were measured. When the new RC were applied, CR rate (32%) was higher and DR (13.9 months) and time to progression (15.6 months) were shorter in complete responders. Conclusions: Standard RC must be consistently and rigorously applied for accurate comparisons between studies. C1 Idec Pharmaceut Corp, San Diego, CA 92121 USA. NCI, CTEP, Rockville, MD USA. Stanford Univ, Palo Alto, CA 94304 USA. Univ Minnesota, Minneapolis, MN USA. San Diego Diagnost Radiol, San Diego, CA USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. RP Grillo-Lopez, AJ (reprint author), Idec Pharmaceut Corp, 303 Callan Rd, San Diego, CA 92121 USA. NR 42 TC 53 Z9 57 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD APR PY 2000 VL 11 IS 4 BP 399 EP 408 DI 10.1023/A:1008332713631 PG 10 WC Oncology SC Oncology GA 312LZ UT WOS:000086945900011 PM 10847457 ER PT J AU Nerurkar, AY Vijayan, P Srinivas, V Soman, CS Dinshaw, KA Advani, SH Magrath, I Bhatia, K Naresh, KN AF Nerurkar, AY Vijayan, P Srinivas, V Soman, CS Dinshaw, KA Advani, SH Magrath, I Bhatia, K Naresh, KN TI Discrepancies in Epstein-Barr virus association at presentation and relapse of classical Hodgkin's disease: Impact on pathogenesis SO ANNALS OF ONCOLOGY LA English DT Article DE EBER-1; EBNA3C; Epstein-Barr virus; Hodgkin's disease; LMP-1 ID REED-STERNBERG CELLS; INSITU HYBRIDIZATION; LYMPHOMA; PERSISTENCE; PROTEIN; PROBES; EBV AB Background: Though Epstein-Barr virus (EBV) has been linked to classical Hodgkin's disease (cHD), only a proportion of cHD cases show EBV-association. While there has been evidence to suggest a crucial role for EBV in the early phase of cHD evolution, we are unclear whether continued presence of EBV is essential for the maintenance of the neoplasm. We have addressed this issue by investigating the EBV-association in paired samples of cHD obtained at presentation and relapse. Materials and methods: We have analysed lymph node biopsy samples from 23 cases of cHD at presentation and relapse. In situhybridization with EBER-1 probe and immunostaining with anti latent membrane protein-1 (LMP-1) antibody was performed on the paraffin sections. PCR for EBNA 3C gene was performed for EBV subtype analysis on the DNA extracted from paraffin sections. Results: EBV-association was documented in both the presentation and relapse samples of 14 cases. One case showed loss of EBV-association at relapse. PCR analysable DNA was obtained from both presentation and relapse samples in four of the EBV-associated cases. The EBNA 3C amplimer corresponded to type A strain of EBV in all the samples. Conclusion: Loss of EBV-association between presentation and relapse seen in one case implies a hit and run mechanism in EBV-induced lymphomagenesis. Though EBV may be essential early in the evolution of cHD, it may not be required for maintenance of the neoplastic clone. Our study also brings out a speculation that a proportion of EBV-negative cHD could represent loss of EBV in the tumour prior to clinical presentation. Alternatively, an unidentified lymphotropic virus other than EBV might play a pathogenetic role in EBV-negative cHD. C1 Tata Mem Hosp, Dept Pathol, Parel 400012, Mumbai, India. Tata Mem Hosp, Dept Radiotherapy, Parel 400012, Mumbai, India. Tata Mem Hosp, Dept Med Oncol, Parel 400012, Mumbai, India. NCI, Lymphoma Biol Sect, Bethesda, MD 20892 USA. RP Naresh, KN (reprint author), Tata Mem Hosp, Dept Pathol, Parel 400012, Mumbai, India. NR 17 TC 18 Z9 20 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD APR PY 2000 VL 11 IS 4 BP 475 EP 478 DI 10.1023/A:1008363805242 PG 4 WC Oncology SC Oncology GA 312LZ UT WOS:000086945900023 PM 10847469 ER PT J AU Bertario, L Russo, A Radice, P Varesco, L Eboli, M Spinelli, P Reyna, A Sala, P AF Bertario, L Russo, A Radice, P Varesco, L Eboli, M Spinelli, P Reyna, A Sala, P CA Hereditary Colorectal Tumors Regis TI Genotype and phenotype factors as determinants for rectal stump cancer in patients with familial adenomatous polyposis SO ANNALS OF SURGERY LA English DT Article ID ILEORECTAL ANASTOMOSIS; CELL-PROLIFERATION; SUBTOTAL COLECTOMY; APC MUTATIONS; RISK; COLI; NUMBER AB Objective To identify factors influencing the occurrence of cancer in the rectal remnant in patients with familial adenomatous polyposis (FAP) after colectomy and ileorectal anastomosis (IRA). Summary Background Data The risk for rectal cancer in patients with FAP after colectomy and IRA remains a major concern, Methods Between 1955 and 1997, 371 patients (206 men, 165 women) from the Registry of Hereditary Colorectal Tumors underwent colectomy and IRA as a primary surgical procedure. Survival was estimated using the Kaplan-Meier method. Cox proportional hazard models were fitted to assess the relative excess risk of rectal cancer and to control for confounding factors. A multivariate analysis was performed to assess the relation between cancer risk in the rectum and sex, age, number of rectal polyps, colon cancer, and APC germline mutation. Results Median follow-up was 81 months. Eighty-nine patients (24%) had colon cancer at the time of surgery. The APC mutation was found in 200 patients. In 27 patients, cancer developed in the retained rectum 1 to 26 years after surgery. The incidence of rectal carcinoma appears to increase with time: at 10, 15, and 20 years after surgery, the cumulative risk was 7.7%, 13.1%, and 23.0%, respectively. Multivariate analysis identified as independent predictors the presence of colon cancer at IRA and a mutation occurring between codons 1250 and 1464; both factors increased the risk nine times. Conclusions The presence of cancer at IRA and APC mutation type are the most important risk factors for the future development of cancer in the rectal remnant in patients with FAP. C1 Natl Canc Inst, Div Surg, I-20133 Milan, Italy. AO Careggi, CSPO, Analyt Epidemiol Sect, Epidemiol Unit, Florence, Italy. Natl Canc Inst, Hereditary Colorectal Tumors Registry, I-20133 Milan, Italy. Natl Canc Inst, Div Expt Oncol, Genoa, Italy. Natl Canc Inst, Div Diagnost & Endoscop Surg, I-20133 Milan, Italy. Natl Canc Inst, Dept Expt Oncol, I-20133 Milan, Italy. RP Bertario, L (reprint author), Ist Nazl Tumori, Via Venezian 1, I-20133 Milan, Italy. RI Radice, Paolo/O-3119-2013; OI Russo, Antonio Giampiero/0000-0002-5681-5861 NR 27 TC 47 Z9 50 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD APR PY 2000 VL 231 IS 4 BP 538 EP 543 DI 10.1097/00000658-200004000-00013 PG 6 WC Surgery SC Surgery GA 300WU UT WOS:000086277400013 PM 10749615 ER PT J AU Keskin, O Bahar, I Jernigan, RL Beutler, JA Shoemaker, RH Sausville, EA Covell, DG AF Keskin, O Bahar, I Jernigan, RL Beutler, JA Shoemaker, RH Sausville, EA Covell, DG TI Characterization of anticancer agents by their growth inhibitory activity and relationships to mechanism of action and structure SO ANTI-CANCER DRUG DESIGN LA English DT Article DE clustering behavior; SVD; tumor cell-line screen ID NATIONAL-CANCER-INSTITUTE; TUMOR-CELL-LINES; DRUG DISCOVERY; COMBINATORIAL LIBRARIES; ELLIPTICINE ANALOGS; SCREEN; INFORMATION; PATTERNS; IDENTIFICATION; INTERFACE AB An analysis of the growth inhibitory potency of 122 anticancer agents available from the National Cancer Institute anticancer drug screen is presented. Methods of singular value decomposition (SVD) were applied to determine the matrix of distances between all compounds. These SVD-derived dissimilarity distances were used to cluster compounds that exhibit similar tumor growth inhibitory activity patterns against 60 human cancer cell lines. Cluster analysis divides the 122 standard agents into 25 statistically distinct groups. The first eight groups include structurally diverse compounds with reactive functionalities that act as DNA-damaging agents while the remaining 17 groups include compounds that inhibit nucleic acid biosynthesis and mitosis. Examination of the average activity patterns across the 60 tumor cell lines reveals unique 'fingerprints' associated with each group. A diverse set of structural features are observed for compounds within these groups, with frequent occurrences of strong within-group structural similarities. Clustering of cell types by their response to the 122 anticancer agents divides the 60 cell types into 21 groups. The strongest within-panel groupings were found for the renal, leukemia and ovarian cell panels. These results contribute to the basis for comparisons between log(GI(50)) screening patterns of the 122 anticancer agents and additional tested compounds. C1 NCI, SAIC, Lab Expt & Computat Biol, Mol Struct Sect,NIH, Frederick, MD 21702 USA. Bogazici Univ, TUBITAK Adv Polymer Mat Res Ctr, Dept Chem Engn, TR-80815 Bebek, Turkey. Bogazici Univ, TUBITAK Adv Polymer Mat Res Ctr, Ctr Polymer Res, TR-80815 Bebek, Turkey. NCI, SAIC, DCTDC,DTP, Lab Drug Discovery Res & Dev, Frederick, MD 21702 USA. NCI, Div Canc Treatment & Diag, Dev Therapeut Program, NIH, Frederick, MD 21702 USA. RP Covell, DG (reprint author), NCI, SAIC, Lab Expt & Computat Biol, Mol Struct Sect,NIH, Frederick, MD 21702 USA. RI Jernigan, Robert/A-5421-2012; Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 NR 64 TC 30 Z9 31 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0266-9536 J9 ANTI-CANCER DRUG DES JI Anti-Cancer Drug Des. PD APR PY 2000 VL 15 IS 2 BP 79 EP 98 PG 20 WC Biochemistry & Molecular Biology; Oncology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Oncology; Pharmacology & Pharmacy GA 331HM UT WOS:000088012900001 PM 10901296 ER PT J AU Groll, AH Mickiene, D Werner, K Petraitiene, R Petraitis, V Calendario, M Field-Ridley, A Crisp, J Piscitelli, SC Walsh, TJ AF Groll, AH Mickiene, D Werner, K Petraitiene, R Petraitis, V Calendario, M Field-Ridley, A Crisp, J Piscitelli, SC Walsh, TJ TI Compartmental pharmacokinetics and tissue distribution of multilamellar liposomal nystatin in rabbits SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID AMPHOTERICIN-B; ENCAPSULATED NYSTATIN; CANDIDA-ALBICANS; ANTIFUNGAL ACTIVITY; TOXICITY; MICE; FORMULATIONS AB The plasma pharmacokinetics of multilamellar liposomal nystatin were studied in normal, catheterized rabbits after single and multiple daily intravenous administration of dosages of 2, 4, and 6 mg/kg of body weight, and drug levels in tissues were assessed after multiple dosing. Concentrations of liposomal nystatin were measured as those of nystatin by a validated high-performance liquid chromatography method, and plasma concentration data were fitted into a two-compartment open model. Across the investigated dosage range, liposomal nystatin demonstrated nonlinear kinetics with more than proportional increases in the AUC(0-24) and decreasing clearance, consistent with dose-dependent tissue distribution and/or a dose-dependent elimination process. After single-dose administration, the mean C-max increased from 13.07 mu g/ml at 2 mg/kg to 41.91 mu g/ml at 6 mg/kg (P < 0.001); the AUC(0-24) changed from 11.65 to 67.34 mu g.h/ml (P < 0.001), the V-d changed from 0.205 to 0.184 liters/kg (not significant), the CLt from 0.173 to 0.101 liters/kg.h (P < 0.05), and terminal half-life from 0.96 to 1.51 h (P < 0.05). There were no significant changes in pharmacokinetic parameters after multiple dosing over 14 days. Assessment of tissue concentrations of nystatin near peak plasma levels after multiple dosing over 15 days revealed preferential distribution to the lungs, liver, and spleen at that time point. Substantial levels were also found in the urine, raising the possibility that renal excretion may play a significant role in drug elimination. Liposomal nystatin administered to rabbits was well tolerated and displayed nonlinear pharmacokinetics, potentially therapeutic peak plasma concentrations, and substantial penetration into tissues. Pharmacokinetic parameters were very similar to those observed in patients, thus validating results derived from infection models in the rabbit and allowing inferences to be made about the treatment of invasive fungal infections in humans. C1 NCI, NIH, Pediat Oncol Branch, Immunocompromised Host Sect, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Pharm, Pharmacokinet Res Lab, Bethesda, MD 20892 USA. RP Walsh, TJ (reprint author), NCI, NIH, Pediat Oncol Branch, Immunocompromised Host Sect, Bldg 10,Rm 13N240,10 Ctr Dr, Bethesda, MD 20892 USA. NR 27 TC 20 Z9 21 U1 0 U2 2 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 2000 VL 44 IS 4 BP 950 EP 957 DI 10.1128/AAC.44.4.950-957.2000 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 295YX UT WOS:000085997200023 PM 10722496 ER PT J AU Hughes, WT Shenep, JL Rodman, JH Fridland, A Willoughby, R Blanchard, S Purdue, L Coakley, DF Cundy, KC Culnane, M Zimmer, B Burchett, S Read, JS AF Hughes, WT Shenep, JL Rodman, JH Fridland, A Willoughby, R Blanchard, S Purdue, L Coakley, DF Cundy, KC Culnane, M Zimmer, B Burchett, S Read, JS CA Pediat AIDS Clin Trials Grp TI Single-dose pharmacokinetics and safety of the oral antiviral compound adefovir dipivoxil in children infected with human immunodeficiency virus type 1 SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID 9-(2-PHOSPHONYLMETHOXYETHYL)ADENINE PMEA; REPLICATION INVITRO; CYNOMOLGUS MONKEYS; METABOLISM; BIOAVAILABILITY; PRODRUGS; ANALOGS; AGENT AB The acyclic phosphonate analog adefovir is a potent inhibitor of retroviruses, including human immunodeficiency virus (HIV) type 1, and, unlike some antiviral nucleosides, does not require the initial phosphorylation step for its activity. Two oral dosages of the adefovir prodrug adefovir dipivoxil were evaluated in a phase I study with children with HIV infection. A total of 14 patients were stratified into age groups ranging from 6 months to 18 years of age. Eight patients received 1.5 mg of adefovir dipivoxil per kg of body weight, and six patients received 3.0 mg of adefovir dipivoxil per kg. Serum samples were obtained at intervals during the 8 h postdosing and were analyzed for adefovir concentrations. Patients were monitored for adverse effects. All samples collected resulted in quantifiable levels of adefovir (lower limit of quantitation, 25 ng/ml) from each patient. The areas under the concentration-versus-time curves (AUCs) were similar (P = 0.85) for the 1.5- and 3.0-mg/kg doses, while the apparent oral clearance (CL/F) was significantly higher (P = 0.05) for the 3-mg/kg dose. Pharmacokinetic parameters differed by patient age. In comparing those children older and younger than the median age of 5.1 years, AUC (P = 0.03), maximum concentration of drug in serum (P = 0.004), and the concentration at 8 h postdosing (P = 0.02) were significantly lower for the younger children. There were no significant differences for apparent volume of distribution and CL/F normalized to body surface area, but there was a suggestive difference in half-life (P = 0.07) among the subjects in the older and younger age groups. No significant adverse events were encountered. These data provide the basis for a multidose phase II study of adefovir dipivoxil in HIV-infected infants and children. C1 St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. NIH, Bethesda, MD 20892 USA. Gilead Sci Inc, Foster City, CA 94404 USA. Frontier Sci & Technol Res Fdn Inc, Chestnut Hill, MA USA. Childrens Hosp, Boston, MA 02115 USA. RP Hughes, WT (reprint author), St Jude Childrens Res Hosp, 332 N Lauderdale St, Memphis, TN 38105 USA. EM walter.hughes@stjude.org NR 24 TC 12 Z9 15 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD APR PY 2000 VL 44 IS 4 BP 1041 EP 1046 DI 10.1128/AAC.44.4.1041-1046.2000 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 295YX UT WOS:000085997200036 PM 10722509 ER PT J AU Warren, KE McCully, CM Walsh, TJ Balis, FM AF Warren, KE McCully, CM Walsh, TJ Balis, FM TI Effect of fluconazole on the pharmacokinetics of doxorubicin in nonhuman primates SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID FUNGAL-INFECTIONS; CLINICAL PHARMACOKINETICS; ADRIAMYCIN AB Antifungal prophylaxis in cancer patients who are undergoing chemotherapy is associated with prolonged neutropenia. We measured the effect of fluconazole on doxorubicin pharmacokinetics in nonhuman primates to determine if neutropenia is related to a pharmacokinetic interaction that delays the clearance of the chemotherapeutic agent. Fluconazole pretreatment had no effect on doxorubicin pharmacokinetics. C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Warren, KE (reprint author), NCI, Pediat Oncol Branch, Bldg 10,Rm 13N240,10 Ctr Dr,MSC 1928, Bethesda, MD 20892 USA. NR 15 TC 4 Z9 4 U1 0 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 2000 VL 44 IS 4 BP 1100 EP 1101 DI 10.1128/AAC.44.4.1100-1101.2000 PG 2 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 295YX UT WOS:000085997200050 PM 10722523 ER PT J AU Gabrielsen, B Carroll, K Stackhouse, T Symonds, H Amoroso, S Maurey, K Sybert, K AF Gabrielsen, B Carroll, K Stackhouse, T Symonds, H Amoroso, S Maurey, K Sybert, K TI National Cancer Institute: Connections with commercial partners for technology development. SO ANTIVIRAL RESEARCH LA English DT Meeting Abstract C1 NCI, Technol Dev & Commercializat Branch, Frederick Canc Res & Dev Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD APR PY 2000 VL 46 IS 1 MA 55 BP A51 EP A51 DI 10.1016/S0166-3542(00)90386-3 PG 1 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 305EZ UT WOS:000086527600056 ER PT J AU Nair, V Taktakishvili, M Neamati, N Pommier, Y AF Nair, V Taktakishvili, M Neamati, N Pommier, Y TI Recognition and inhibition of HIV integrase by novel dinucleotides SO ANTIVIRAL RESEARCH LA English DT Meeting Abstract C1 NCI, Pharmacol Lab, Bethesda, MD 20892 USA. Univ Iowa, Dept Chem, Iowa City, IA 52242 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD APR PY 2000 VL 46 IS 1 MA 30 BP A44 EP A44 PG 1 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 305EZ UT WOS:000086527600031 ER PT J AU Pannecouque, C Pluymers, W Fikkert, V Neamati, N Marchand, C Burke, TR Pommier, Y De Clercq, E Debyser, Z Witvrouw, M AF Pannecouque, C Pluymers, W Fikkert, V Neamati, N Marchand, C Burke, TR Pommier, Y De Clercq, E Debyser, Z Witvrouw, M TI Viral entry as the primary target of anti-HIV activity of chicoric acid and its tetra-acetyl eaters SO ANTIVIRAL RESEARCH LA English DT Meeting Abstract C1 Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium. NCI, Mol Pharmacol Lab, Div Basic Sci, Bethesda, MD 20892 USA. RI Burke, Terrence/N-2601-2014; Marchand, Christophe/D-8559-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD APR PY 2000 VL 46 IS 1 MA 4 BP A36 EP A36 DI 10.1016/S0166-3542(00)90335-8 PG 1 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 305EZ UT WOS:000086527600006 ER PT J AU Turpin, JA Pallansch, L Michejda, C Chlody, WC Rice, WG Buckheit, RW AF Turpin, JA Pallansch, L Michejda, C Chlody, WC Rice, WG Buckheit, RW TI Temacrazine inhibits initiation of HIV-1 transcription SO ANTIVIRAL RESEARCH LA English DT Meeting Abstract C1 So Res Inst, Frederick, MD 21701 USA. Achillion Pharmaceut, Frederick, MD 21701 USA. NCI, ABL Basic Res, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD APR PY 2000 VL 46 IS 1 MA 33 BP A45 EP A45 PG 1 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 305EZ UT WOS:000086527600033 ER PT J AU Gerstenberger, SL Heimler, I Smies, R Hutz, RJ Dasmahapatra, AK Tripoli, V Dellinger, JA AF Gerstenberger, SL Heimler, I Smies, R Hutz, RJ Dasmahapatra, AK Tripoli, V Dellinger, JA TI Minimal endocrine alterations in rodents after consumption of lake trout (Salvelinus namaycush) SO ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY LA English DT Article ID THYROID-HORMONE; AROMATASE-ACTIVITY; POLYCHLORINATED BIPHENYL; PCBS; FISH; RAT; EXPRESSION; SUPPRESSION; PROLACTIN; MERCURY AB Polychlorinated biphenyls (PCBs) and dioxins are known to cause disruptions in circulating hormone concentraions, which may influence fertility and normal fetal development. Structure activity relationships have been determined for individual congeners, but it is unclear what impacts occur due to exposure to complex mixtures of chemicals found in the environment. Most laboratory studies of PCB exposure have used commercial mixtures in high doses, which may not be representative of environmental concentrations of individual congeners, nor accurately represent complex interactions of multiple contaminants. The present study investigated endocrine alterations in rats associated with the consumption of lake trout collected from three specific locations in the Great Lakes. Composite fish samples were analyzed for PCBs, organochlorines, and mercury and ranged from 415 ppb to 1,275 ppb for individual contaminants. Fillet composites were fed to timed-pregnant Long-Evans rats as 30% of their diet. Concentrations of total thyroxine and estrogen were not significantly different in offspring of dosed darns from that of controls. However, aromatase activity was lowered in all dosed groups as compared with controls. This may represent a lowered expression of the CYP 19 gene in exposed rats or may be due to the presence of one or more substances in the contaminants that are capable of altering the affinity of the aromatase enzyme for its normal endogenous substrate. It is also possible that the number of maturing follicles in the lake trout-fed rats may be fewer than controls, which would result in an overall reduction in the enzyme activity. Data regarding the endocrine effects of environmental contaminant mixtures found in fish from the Great Lakes Basin are still controversial. Additionally, information is scarce with respect to the F1 generation of laboratory animals following environmental maternal exposures, therefore, we investigated the reproductive-endocrine alterations in rat offspring associated with the consumption of lake trout (Salvelinus namaycush) collected from three areas in the Great Lakes. C1 Univ Nevada, Dept Environm Studies, Las Vegas, NV 89154 USA. Rush Presbyterian St Lukes Med Ctr, Dept Obstet & Gynecol, Chicago, IL 60612 USA. Univ N Dakota, Grand Forks, ND 58203 USA. Univ Wisconsin, Dept Biol Sci, Milwaukee, WI 53211 USA. NIEHS, Marine & Freshwater Biomed Sci Ctr, Milwaukee, WI 53211 USA. Illinois Poison Ctr, Chicago, IL 60606 USA. RP Gerstenberger, SL (reprint author), Univ Nevada, Dept Environm Studies, 4505 Maryland Pkwy, Las Vegas, NV 89154 USA. NR 40 TC 16 Z9 16 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0090-4341 J9 ARCH ENVIRON CON TOX JI Arch. Environ. Contam. Toxicol. PD APR PY 2000 VL 38 IS 3 BP 371 EP 376 PG 6 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA 285PC UT WOS:000085396600015 PM 10667936 ER PT J AU Judd, LL Akiskal, HS Zeller, PJ Paulus, M Leon, AC Maser, JD Endicott, J Coryell, W Kunovac, JL Mueller, TI Ricc, JP Keller, MB AF Judd, LL Akiskal, HS Zeller, PJ Paulus, M Leon, AC Maser, JD Endicott, J Coryell, W Kunovac, JL Mueller, TI Ricc, JP Keller, MB TI Psychosocial disability during the long-term course of unipolar major depressive disorder SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID FOLLOW-UP EVALUATION; REGRESSION-ANALYSIS; COMPUTER-PROGRAM; SYMPTOMS; WORK; LIFE AB Background: The goal of this study was to investigate psychosocial disability in relation to depressive symptom severity during the long-term course of unipolar major depressive disorder (MDD). Methods: Monthly ratings of impairment in major life functions and social relationships were obtained during an average of 10 years' systematic follow-up of 371 patients with unipolar MDD in the National Institute of Mental Health Collaborative Depression Study. Random regression models were used to examine variations in psychosocial functioning associated with 3 levels of depressive symptom severity and the asymptomatic status. Results: A progressive gradient of psychosocial impairment was associated with a parallel gradient in the level of depressive symptom severity which ranges from asymptomatic to subthreshold depressive symptoms to symptoms at the minor depression/dysthymia level to symptoms at the MDD level. Significant increases in disability occurred with each stepwise increment in depressive symptom severity. Conclusions: During the long-term course, disability is pervasive and chronic but disappears when patients become asymptomatic. Depressive symptoms at levels of subthreshold depressive symptoms, minor depression/dysthymia, and MDD represent a continuum of depressive symptom severity in unipolar MDD, each level of which is associated with a significant stepwise increment in psychosocial disability. C1 Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. NIMH, Collaborat Program Psychobiol Depress, Rockville, MD 20857 USA. Vet Affairs Med Ctr, Psychiat Serv, San Diego, CA 92161 USA. RP Judd, LL (reprint author), Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr, La Jolla, CA 92093 USA. FU NIMH NIH HHS [5 P30 MH49671-06, R01 MH025478]; PHPPO CDC HHS [PHSMH30914] NR 32 TC 358 Z9 361 U1 0 U2 13 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 2000 VL 57 IS 4 BP 375 EP 380 DI 10.1001/archpsyc.57.4.375 PG 6 WC Psychiatry SC Psychiatry GA 302LG UT WOS:000086366100014 PM 10768699 ER PT J AU Preston, KL Umbricht, A Epstein, DH AF Preston, KL Umbricht, A Epstein, DH TI Methadone dose increase and abstinence reinforcement for treatment of continued heroin use during methadone maintenance SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Scientific Meeting of the College-on-problems-of-Drug-Dependence CY JUN 15, 1998 CL PHOENIX, ARIZONA SP Coll Problems Drug Dependence ID COCAINE ABSTINENCE; OPIOID DEPENDENCE; BEHAVIORAL-APPROACH; FOLLOW-UP; DRUG-USE; ADDICTS; ABUSE; BUPRENORPHINE; RETENTION; THERAPY AB Background: Although methadone maintenance is an effective therapy for heroin dependence, some patients continue to use heroin and may benefit from therapeutic modifications. This study evaluated a behavioral intervention, a pharmacological intervention, and a combination of both interventions. Methods: Throughout the study all patients received daily methadone hydrochloride maintenance (initially 50 mg/d orally) and weekly counseling. Following baseline treatment patients who continued to use heroin were randomly assigned to 1 of 4 interventions: (1) contingent vouchers for opiate-negative urine specimens (n = 29 patients); (2) methadone hydrochloride dose increase to 70 mg/d (n = 31 patients); (3) combined contingent vouchers and methadone dose increase (n = 32 patients); and (4) neither intervention (comparison standard; n = 28 patients). Methadone dose increases were double blind. Vouchers had monetary value and were exchangeable for goods and services. Groups not receiving contingent vouchers received matching vouchers independent of urine rest results. Primary outcome measure was opiate-negative urine specimens (thrice weekly urinalysis). Results: Contingent vouchers and a methadone dose increase each significantly increased the percentage of opiate-negative urine specimens during intervention. Contingent vouchers, with or without a methadone dose increase, increased the duration of sustained abstinence as assessed by urine screenings. Methadone dose increase, with or without contingent vouchers, reduced self-reported frequency of use and self-reported craving. Conclusions: In patients enrolled in a methadone-maintainence program who continued to use heroin, abstinence reinforcement and a methadone dose increase were each effective in reducing use. When combined, they did not dramatically enhance each other's effects on any 1 outcome measure, but they did seem to have complementary benefits. C1 NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Preston, KL (reprint author), NIDA, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 NR 47 TC 90 Z9 96 U1 0 U2 3 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 2000 VL 57 IS 4 BP 395 EP 404 DI 10.1001/archpsyc.57.4.395 PG 10 WC Psychiatry SC Psychiatry GA 302LG UT WOS:000086366100017 PM 10768702 ER PT J AU Shen, DF Chang, MA Matteson, DM Buggage, R Kozhich, AT Chan, CC AF Shen, DF Chang, MA Matteson, DM Buggage, R Kozhich, AT Chan, CC TI Biphasic ocular inflammatory response to endotoxin-induced uveitis in the mouse SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; STIMULATING FACTOR; GENE-EXPRESSION; FACTOR-ALPHA; INTERLEUKIN-6; RAT; CYTOKINE; MACROPHAGE; MICE; INDUCTION AB Objective: To examine the kinetics and mechanisms of endotoxin-induced uveitis in the mouse. Methods: C3H/HeN mice were injected subcutaneously with 0.3 mg of Salmonella typhimurium lipopolysaccharide (LPS) in 0.1 mt of phosphate-buffered saline solution or phosphate-buffered saline solution alone in 3 separate experiments; mice were killed after 1, 3, 5, and 7 days. In 2 other separate experiments, mice were killed 1, 3, 6, and 24 hours after LPS injection. All eyes were collected for histological examination, immunohistochemical analyses, aqueous protein level determination, and reverse transcriptase-polymerase chain reaction for ocular interleukin (IL)1 alpha, IL-6, tumor necrosis factor or, and granulocyte-macrophage colony-stimulating factor messenger RNA (mRNA). Enzyme-linked immunosorbent assay was used to measure tumor necrosis factor or and IL-6 levels in aqueous and serum samples. Results: Results were consistent for all experiments. Numbers of ocular inflammatory cells and levels of aqueous protein peaked 1 and 5 days after LPS injection. Control mice did not develop inflammation. Serum and aqueous IL-6 and ocular IL-6 mRNA levels peaked at 1 day and subsided at 3 days. However, ocular IL-1 alpha, tumor necrosis factor or, and granulocyte-macrophage colony-stimulating factor mRNA appeared, peaked, and sub-sided at 3, 5, and 7 days, respectively. Predominant infiltrating cells were neutrophils at 1 day and macrophages at 5 days. Although no ocular inflammatory cells were detected before 24 hours after LPS injection, tumor necrosis factor or mRNA was noticed at 1 hour, peaked at 3 hours, and disappeared at 6 hours and granulocyte-macrophage colony-stimulating factor mRNA was spotted only at 3 hours after LPS injection. Conclusions: The ocular inflammatory response to C3H/ HeN mouse endotoxin-induced uveitis is biphasic for 7 days. The first wave appears at day 1 and subsides by day 3. A second, higher peak appears at day 5. The 2 inflammatory waves are related to the kinetics of the different cytokines released in the eye. This is in contrast to the rat monophasic endotoxin-induced uveitis model, which has only one peak of intense inflammation associated with cytokine release. Clinical Relevance: A biphasic inflammatory response associated with cytokine release lasting several days is observed in C3H/HeN mice with endotoxin-induced uveitis. Because human anterior uveitis has a tendency to be recurrent in nature, this might be a better experimental model. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. RP Chan, CC (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N103,10 Ctr Dr, Bethesda, MD 20892 USA. NR 36 TC 23 Z9 24 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD APR PY 2000 VL 118 IS 4 BP 521 EP 527 PG 7 WC Ophthalmology SC Ophthalmology GA 302ZZ UT WOS:000086397500010 PM 10766138 ER PT J AU Katsetos, CD Kontogeorgos, G Geddes, JF Herman, MM Tsimara-Papastamatiou, H Yu, YX Sakkas, LI Tsokos, M Patchefsky, AS Ehya, H Cooper, HS Provencio, J Spano, AJ Frankfurter, A AF Katsetos, CD Kontogeorgos, G Geddes, JF Herman, MM Tsimara-Papastamatiou, H Yu, YX Sakkas, LI Tsokos, M Patchefsky, AS Ehya, H Cooper, HS Provencio, J Spano, AJ Frankfurter, A TI Differential distribution of the neuron-associated class III beta-tubulin in neuroendocrine lung tumors SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID ATYPICAL CARCINOID-TUMOR; CALCIUM-BINDING PROTEIN; CANCER CELL-LINES; ENDOCRINE-CELLS; IMMUNOHISTOCHEMICAL CHARACTERIZATION; POSTTRANSLATIONAL MODIFICATION; ADRENAL-MEDULLA; MARKERS; ISOTYPE; EXPRESSION AB Objective.-To study the immunoreactivity profile of the neuron-associated class III beta-tubulin isotype (beta III) in epithelial lung tumors. Design.-One hundred four formalin-fixed, paraffin-embedded primary and metastatic lung cancer specimens were immunostained with an anti-beta III mouse monoclonal antibody (TuJ1) and an anti-beta III affinity-purified rabbit antiserum. Paraffin sections from fetal, infantile, and adult nonneoplastic lung tissues were also examined. Results;-In the fetal airway epithelium, beta III staining is detected transiently in rare Kulchitsky-like cells from lung tissues corresponding to the pseudoglandular and canalicular but not the saccular or alveolar stages of development. beta III is absent in healthy, hyperplastic, metaplastic, and dysplastic airway epithelium of the adult lung. In contrast, beta III is highly expressed in small cell lung cancer, large cell neuroendocrine carcinoma, and in some non-small cell lung cancers, particularly adenocarcinomas. There is no correlation between expression of beta III and generic neuroendocrine markers, such as chromogranin A and/or synaptophysin, in pulmonary adenocarcinomas. Also, focal beta III staining is present in primary and metastatic adenocarcinomas (to the lung) originating in the colon, prostate, and ovary, beta III is expressed to a much lesser extent atypical carcinoids and is rarely detectable in typical carcinoids and squamous cell carcinomas of the lung. The distribution of beta III in small cell lung cancer and adenocarcinoma metastases to regional lymph nodes and brain approaches 100% of tumor cells, which is substantially greater than in the primary tumors. Conclusions.-In the context of neuroendocrine lung tumors, beta III immunoreactivity is a molecular signature of high-grade malignant neoplasms (small cell lung cancer and large cell neuroendocrine carcinoma) although its importance in atypical carcinoids must be evaluated further. In addition, beta III may be a useful diagnostic marker in distinguishing between small cell lung cancers and certain non-small cell lung cancers (poorly differentiated squamous cell carcinomas), especially in small biopsy specimens. To our knowledge, beta III is the only tumor biomarker that exhibits a substantially more widespread distribution in poorly differentiated than in better differentiated pulmonary neuroendocrine tumors. However, the significance of beta III phenotypes in non-small cell lung cancer, particularly adenocarcinoma, with respect to neuroendocrine differentiation and prognostic value, requires further evaluation. C1 St Christophers Hosp Children, Neurol Sect, Res Labs, Philadelphia, PA 19134 USA. St Christophers Hosp Children, Dept Pathol & Lab Med, Philadelphia, PA 19134 USA. Med Coll Penn & Hahnemann Univ, Dept Pathol & Lab Med, Philadelphia, PA 19129 USA. Med Coll Penn & Hahnemann Univ, Dept Pediat, Sch Med, Philadelphia, PA 19129 USA. Temple Univ, Sch Med, Dept Microbiol & Immunol, Philadelphia, PA 19122 USA. G Gennimatas Gen Hosp Athens, Dept Pathol, Athens, Greece. St Bartholomews & Royal London Sch Med & Dent, Dept Morbid Anat & Histopathol, London, England. NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. Sotiria Thorac Hosp, Dept Pathol, Athens, Greece. NCI, Pathol Lab, Bethesda, MD 20892 USA. Fox Chase Canc Ctr, Dept Pathol, Philadelphia, PA 19111 USA. Univ Virginia, Dept Neurol, Charlottesville, VA USA. Univ Virginia, Dept Biol, Charlottesville, VA USA. RP Katsetos, CD (reprint author), St Christophers Hosp Children, Neurol Sect, Res Labs, Erie Ave & Front St, Philadelphia, PA 19134 USA. FU NCI NIH HHS [3R01CA64945-02S1]; NINDS NIH HHS [NS21142] NR 62 TC 48 Z9 50 U1 0 U2 3 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 2000 VL 124 IS 4 BP 535 EP 544 PG 10 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 304XG UT WOS:000086508900012 PM 10747310 ER PT J AU Garber, SL Rintala, DH Hart, KA Fuhrer, MJ AF Garber, SL Rintala, DH Hart, KA Fuhrer, MJ TI Pressure ulcer risk in spinal cord injury: Predictors of ulcer status over 3 years SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT 73rd Annual Meeting of the American-Congress-of-Rehabilitation-Medicine CY OCT 15, 1996 CL CHICAGO, ILLINOIS SP Amer Congress Rehabil Med DE pressure ulcers; spinal cord injury ID SORES; COMMUNITY; MANAGEMENT AB Objective: To identify predictors of pressure ulcers in men with spinal cord injury over a 3-year period. Design: Longitudinal, two-panel, cohort. Setting: Community. Participants: One hundred eighteen men with spinal cord injury. Measures: Interviews, questionnaires, and physical examinations were completed in two phases, 3 years apart. Information obtained included demographic and spinal cord injury characteristics; ulcer history; health beliefs and practices; measures of impairment, disability, and handicap; and skin integrity. Results: Thirty-one percent of the participants reported having a pressure ulcer in the 12 months before Phase 2. Some Phase 1 predictors of self-reported ulcers in the year before Phase 2 were a younger age at onset of spinal cord injury, previous pressure ulcer surgery, and the presence of a pressure ulcer in the year before Phase 1. On examination at Phase 2, 59% presented with an ulcer. Phase 1 predictors of ulcer presence at Phase 2 examination were similar to predictors for self-reported ulcers. Conclusion: Individuals with the identified predictive characteristics are at greater risk for developing pressure ulcers. These individuals should receive additional interventions to reduce that risk. Potential interventions include more systematic and frequent follow-up, frequent review of pressure ulcer prevention and management strategies, and provision of needed personal assistance and relevant equipment. C1 Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. Inst Rehabil & Res, Houston, TX USA. Vet Affairs Med Ctr, Ctr Excellence Hlth Aging Disabil, Houston, TX 77030 USA. NIH, Bethesda, MD 20892 USA. RP Garber, SL (reprint author), Houston VA Med Ctr, 580-128,2002 Holcombe Blvd, Houston, TX 77030 USA. NR 36 TC 68 Z9 69 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD APR PY 2000 VL 81 IS 4 BP 465 EP 471 DI 10.1053/mr.2000.3889 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 300WW UT WOS:000086277600014 PM 10768537 ER PT J AU Cheung, ME Craik, RL AF Cheung, ME Craik, RL TI The National Center for Medical Rehabilitation Research Institutional Training Program, 1992 to 1997 SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article C1 NICHHD, Natl Ctr Med Rehabil Res, NIH, Bethesda, MD 20892 USA. Beaver Coll, Dept Phys Therapy, Glenside, PA USA. RP Cheung, ME (reprint author), NICHHD, Natl Ctr Med Rehabil Res, NIH, Bethesda, MD 20892 USA. NR 9 TC 1 Z9 1 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 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD APR PY 2000 VL 81 IS 4 BP 529 EP 534 DI 10.1053/mr.2000.3836 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 300WW UT WOS:000086277600026 PM 10768549 ER PT J AU Manal, K McClay, I Richards, J Stanhope, S AF Manal, K McClay, I Richards, J Stanhope, S TI The effect of shank soft tissue movement on knee moment profiles during natural cadence walking SO ARCHIVES OF PHYSIOLOGY AND BIOCHEMISTRY LA English DT Article; Proceedings Paper CT XXVth Congress of the Societe-de-Biomecanique and XIth Congress of the Societe-Canadienne-de-Biomecanique CY AUG 23-26, 2000 CL MONTREAL, CANADA SP Soc Biomecan, Soc Canadienne Biomecan C1 Univ Delaware, Biomed Engn Res Ctr, Newark, DE 19716 USA. Joyner Sports Med Inst, Harrisburg, PA USA. NIH, Biomech Lab, Bethesda, MD USA. RP Manal, K (reprint author), Univ Delaware, Biomed Engn Res Ctr, Newark, DE 19716 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1381-3455 J9 ARCH PHYSIOL BIOCHEM JI Arch. Physiol. Biochem. PD APR PY 2000 VL 108 IS 1-2 BP 118 EP 118 PG 1 WC Biochemistry & Molecular Biology; Biophysics; Endocrinology & Metabolism; Physiology SC Biochemistry & Molecular Biology; Biophysics; Endocrinology & Metabolism; Physiology GA 364FX UT WOS:000089882600118 ER PT J AU Torpy, DJ Papanicolaou, DA Lotsikas, AJ Wilder, RL Chrousos, GP Pillemer, SR AF Torpy, DJ Papanicolaou, DA Lotsikas, AJ Wilder, RL Chrousos, GP Pillemer, SR TI Responses of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis to interleukin-6 - A pilot study in fibromyalgia SO ARTHRITIS AND RHEUMATISM LA English DT Article ID CORTICOTROPIN-RELEASING FACTOR; SUBSTANCE-P; NONTHYROIDAL ILLNESS; SERUM INTERLEUKIN-6; FIBROSITIS SYNDROME; THYROID-FUNCTION; PAIN THRESHOLD; PLASMA; CATECHOLAMINES; 3,4-DIHYDROXYPHENYLALANINE AB Objective. To determine whether deficient activity of the hypothalamic corticotropin-releasing hormone (CRH) neuron, which stimulates the hypothalamic-pituitary-adrenal (HPA) axis and the central control nuclei of the sympathetic nervous system and inhibits ascending pain pathways, may be pathogenic in patients with fibromyalgia (FM). Methods. We administered interleukin-6 (IL-6; 3 mu g/kg of body weight subcutaneously), a cytokine capable of stimulating hypothalamic CRH release, and measured plasma levels of adrenocorticotropic hormone (ACTH), cortisol, and catecholamines and their metabolites and precursors. Thirteen female FM patients and 8 age- and body mass index-matched female controls were studied. The diagnosis of FM was made according to American College of Rheumatology criteria. Tender points were quantitated by pressure algometry. All subjects had HPA axis studies. Seven FM patients and 7 controls also had catecholamine measurements. Results. After IL-6 injection, delayed ACTH release was evident in the FM patients, with peak levels at 96.9 +/- 6.0 minutes (mean +/- SEM; control peak 68.6 +/- 10.3 minutes; P = 0.02). Plasma cortisol responses to IL-6 did not differ significantly between patients and controls, Basal norepinephrine (NE) levels were higher in the FM patients than in the controls, While a small, although not significant, rise in NE levels occurred after IL-6 injection in the controls, NE levels dramatically increased over basal levels in the FM patients between 60 and 180 minutes after IL-6 injection. Both peak NE levels (mean +/- SEM 537.6 +/- 82.3 versus 254.3 +/- 41.6 pg/ml; P = 0.0001) and time-integrated NE responses (93.2 +/- 16.6 pg/ml x minutes(-3) versus 52.2 +/- 5.7 pg/ml x minutes(-3); P = 0.038) were greater in FM patients than in controls. Heart rate was increased by IL-6 injection in FM patients and controls, but rose to significantly higher levels in the FM patients from 30 minutes to 180 minutes after IL-6 injection (P < 0.03). Conclusion. Exaggerated NE responses and heart rate increases, as well as delayed ACTH release, were observed among female FM patients compared with age-matched female controls. Delayed ACTH release after IL-6 administration in FM is consistent with a defect in hypothalamic CRH neuronal function. Exaggerated NE release may reflect abnormal regulation of the sympathetic nervous system, perhaps secondary to chronically deficient hypothalamic CRH. The excessive heart rate response after IL-6 injection in FM patients may be unrelated to the increase in NE, or it may reflect an alteration in the sensitivity of cardiac beta-adrenoceptors to NE. These responses to a physiologic stressor support the notion that FM may represent a primary disorder of the stress system. C1 NICHHD, NIH, Bethesda, MD 20892 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Torpy, DJ (reprint author), Univ Queensland, Dept Med, Greenslopes Hosp, Newdegate St, Brisbane, Qld 4120, Australia. NR 46 TC 130 Z9 135 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD APR PY 2000 VL 43 IS 4 BP 872 EP 880 DI 10.1002/1529-0131(200004)43:4<872::AID-ANR19>3.0.CO;2-T PG 9 WC Rheumatology SC Rheumatology GA 303AE UT WOS:000086398000019 PM 10765933 ER PT J AU Gorman, JD Danning, C Schumacher, HR Klippel, JH Davis, JC AF Gorman, JD Danning, C Schumacher, HR Klippel, JH Davis, JC TI Multicentric reticulohistiocytosis - Case report with immunohistochemical analysis and literature review SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SYNOVIAL-FLUID; METHOTREXATE; INVOLVEMENT; TUMOR; HISTIOCYTOSIS; PREGNANCY; DISORDER; MARKER; CELLS AB This report describes the case of a patient with multicentric reticulohistiocytosis. Immunohistochemical analysis revealed prominent markers of monocyte/macrophage origin, as well as the presence of tumor necrosis factor alpha, interleukin-1 beta (IL-1 beta), and IL-12; the occurrence of the latter in this disease has not previously been reported. Clinical, laboratory, radiographic, and histologic findings in multicentric reticulohistiocytosis are reviewed. In addition, all published cases of multicentric reticulohistiocytosis which included reports of cytokine and immunohistochemical analysis are reviewed, and evidence fur a monocyte/macrophage origin and role in disease pathogenesis is provided. C1 Univ Calif San Francisco, Dept Rheumatol, San Francisco, CA 94143 USA. NIAMSD, Bethesda, MD 20892 USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. RP Davis, JC (reprint author), Univ Calif San Francisco, Dept Rheumatol, 533 Parnassus Ave,Room U-383, San Francisco, CA 94143 USA. FU NIAMS NIH HHS [AR-07304] NR 33 TC 67 Z9 68 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD APR PY 2000 VL 43 IS 4 BP 930 EP 938 DI 10.1002/1529-0131(200004)43:4<930::AID-ANR27>3.0.CO;2-A PG 9 WC Rheumatology SC Rheumatology GA 303AE UT WOS:000086398000029 PM 10765941 ER PT J AU Li, RL Boerwinkle, E Olshan, AF Chambless, LE Pankow, JS Tyroler, HA Bray, M Pittman, GS Bell, DA Heiss, G AF Li, RL Boerwinkle, E Olshan, AF Chambless, LE Pankow, JS Tyroler, HA Bray, M Pittman, GS Bell, DA Heiss, G TI Glutathione S-transferase genotype as a susceptibility factor in smoking-related coronary heart disease SO ATHEROSCLEROSIS LA English DT Article DE GSTM1; GSTT1; gene-smoking interaction; CHD; case-cohort study; additive interaction ID HUMAN ATHEROSCLEROTIC PLAQUES; TRANS-STILBENE OXIDE; CASE-COHORT DESIGN; GENETIC-POLYMORPHISM; MONOCLONAL ORIGIN; BLADDER-CANCER; RISK-FACTORS; LUNG-CANCER; M1 GSTM1; CLASS-MU AB Cancer studies suggest that the null polymorphisms of glutathione S-transferase M1 or T1 (GSTM1/GSTT1) may affect the ability to detoxify or activate chemicals in cigarette smoke. The potential modification of the association between smoking and coronary heart disease (CHD) by GSTM1 and GSTT1 has not been studied in humans. A case-cohort study was conducted to test the hypotheses that specific genotypes of GSTM1 or GSTT1 affect susceptibility to smoking-related CHD. CHD cases (n = 400) accrued during 1987-1993 and a cohort-representative sample (n = 924) were selected from a biracial cohort of 15 792 middle-aged men and women in four US communities. A significantly higher frequency of GSTM1-0 and a lower frequency of GSTT1-0 were found in whites (GSTM1-0 = 47.1%, GSTT1-0 = 16.4%) than in African-Americans (AAs) (GSTM1-0 = 17.5%, GSTT1-0 = 25.9%). A smoking-GSTM1-0 interaction for the risk of CHD was statistically significant on an additive scale, with ever-smokers with GSTM1-0 at a approximate to 1.5-fold higher risk relative to ever-smokers with GSTM1-1 and a approximate to 2-fold higher risk relative to never-smokers with GSTM1-0, after adjustment for other CHD risk factors. The interaction between having smoked greater than or equal to 20 pack-years and GSTT1-1 was statistically significant on both multiplicative and additive scales. The risk of CHD given both GSTT1-1 and greater than or equal to 20 pack-years of smoking was approximate to three times greater than the risk given exposure to greater than or equal to 20 pack-years of smoking alone, and approximate to four times greater than the risk given exposure to GSTT1-1 alone. The modification of the smoking-CHD association by GSTM1 or GSTT1 suggests that chemicals in cigarette smoke that are substrates for glutathione S-transferases may be involved in the etiology of CHD. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA. Univ Texas, Hlth Sci Ctr, Ctr Human Genet, Houston, TX 77225 USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. Collaborat Studies Coordinat Ctr, Chapel Hill, NC 27514 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Heiss, G (reprint author), Univ N Carolina, Dept Epidemiol, Suite 306,Nations Bank Plaza,137 E Franklin St, Chapel Hill, NC 27514 USA. EM rongling_li@unc.edu; eboerwin@gsbs.gs.uth.tmc.edu; andy_olshan@unc.edu; clec@mail.cscc.unc.edu; jim_pankow@unc.edu; htyroler@aol.com; mbray@imm2.imm.uth.tmc.edu; pittman1@niehs.nih.gov; beill1@niehs.nih.gov; gerardo_heiss@unc.edu OI Pankow, James/0000-0001-7076-483X FU NHLBI NIH HHS [N01HC55015, N01HC55016, N01HC55018] NR 60 TC 95 Z9 98 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD APR PY 2000 VL 149 IS 2 BP 451 EP 462 DI 10.1016/S0021-9150(99)00483-9 PG 12 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 302BK UT WOS:000086344900023 PM 10729397 ER PT J AU Grafman, J AF Grafman, J TI Structuring an emotional world SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material ID LOBE LESIONS; STORY AB Rolls emphasizes the role of emotion in behavior. My commentary provides some balance to that position by arguing that stored social knowledge dominates our behavior and controls emotional states, thereby reducing emotions to a subservient role in behavior. C1 NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, MSC 1440, Bethesda, MD 20892 USA. OI Grafman, Jordan H./0000-0001-8645-4457 NR 13 TC 1 Z9 1 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD APR PY 2000 VL 23 IS 2 BP 200 EP + DI 10.1017/S0140525X00312420 PG 8 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA 344KW UT WOS:000088758300011 ER PT J AU Burgdorf, J Knutson, B Panksepp, J AF Burgdorf, J Knutson, B Panksepp, J TI Anticipation of rewarding electrical brain stimulation evokes ultrasonic vocalization in rats SO BEHAVIORAL NEUROSCIENCE LA English DT Article ID AGGRESSIVE ENCOUNTERS; RATTUS-NORVEGICUS; SEXUAL-BEHAVIOR; WITHDRAWAL; CALLS; COCAINE; STARTLE AB Adult rats emit increased rates of 50-kHz ultrasonic vocalizations (USVs) before receiving social and pharmacological rewards. This study sought to determine whether anticipation of rewarding electrical stimulation of the brain (ESB) would also elicit these vocalizations. In Experiments 1 and 2, rats showed increased 50-kHz USVs before receiving experimenter-delivered ventral tegmental area (VTA) and lateral hypothalamic (LH) ESB on a fixed time 20-s schedule. In Experiments 3 and 4, rats increased their rate of 50-kHz USVs in response to cues that predicted the opportunity to self-stimulate the VTA or LH. Interestingly, unexpected termination of either type of ESB evoked 20-kHz, rather than 50-kHz, USVs. In Experiment 5, a cue that predicted daily 1-hr feeding sessions increased 50-kHz USVs, whereas a cue that predicted footshock decreased 50-kHz USVs. These effects could not be explained simply by changes in locomotor activity or general arousal. Together, these findings support the hypothesis that short 50-kHz USVs may selectively index a state of reward anticipation in rats. C1 NIAAA, Clin Studies Lab, Sect Brain Imaging & Electrophysiol, Bethesda, MD 20892 USA. Bowling Green State Univ, Dept Psychol, Bowling Green, OH 43403 USA. RP Knutson, B (reprint author), NIAAA, Clin Sci Lab, 10 Ctr Dr,Bldg 10,R00m 6S420,Mail Stop 1610, Bethesda, MD 20892 USA. EM knutson@odin.niaaa.nih.gov OI Knutson, Brian/0000-0002-7669-426X FU NICHD NIH HHS [HD30387] NR 31 TC 129 Z9 132 U1 0 U2 11 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 2000 VL 114 IS 2 BP 320 EP 327 DI 10.1037//0735-7044.114.2.320 PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 322CG UT WOS:000087492200010 PM 10832793 ER PT J AU Zimmerberg, J Blank, PS Kolosova, I Cho, MS Tahara, M Coorssen, JR AF Zimmerberg, J Blank, PS Kolosova, I Cho, MS Tahara, M Coorssen, JR TI A stage-specific preparation to study the Ca2+-triggered fusion steps of exocytosis: Rationale and perspectives SO BIOCHIMIE LA English DT Review DE calcium; sea urchin; secretion; SNARE proteins; vesicles ID SEA-URCHIN EGG; ADRENAL CHROMAFFIN CELLS; CORTICAL-GRANULE EXOCYTOSIS; INDIVIDUAL SECRETORY VESICLES; CALCIUM-TRIGGERED FUSION; BOTULINUM TOXIN-A; PROTEIN-KINASE-C; MEMBRANE-FUSION; SNARE COMPLEX; PLASMA-MEMBRANE AB Despite groundbreaking work to identify numerous proteins and to focus attention on molecular interactions, the mechanism of calcium-triggered membrane fusion remains unresolved. A major difficulty in such research has been the many overlapping and interacting membrane trafficking steps in the secretory pathway, including those of membrane retrieval. Identifying the specific role(s) of a given protein, beyond its general involvement in exocytosis, has therefore proven problematic. Furthermore, the power of time-resolved optical and electrophysiological assays can be best applied to testing the function of known proteins rather than to the identification of unknown, critical membrane components. The identification of essential membrane constituents requires combined biochemical (molecular) and functional (physiological) analyses. A fully functional, stage-specific physiological membrane preparation would be one direct approach to dissecting the calcium-triggered fusion steps of regulated exocytosis. Herein we review our use of specific minimal membrane preparations consisting of fully primed and docked secretory vesicles, or the isolated vesicles themselves, and characterize the late events of exocytosis, with an aim towards identification of essential molecular components. We have established a functional definition of the fusion complex and its activation by calcium, based on our kinetic analyses. Together with a variety of biochemical and alternate functional assays, we have tested whether the SNARE core complex that is present in our vesicle membranes satisfies the criteria of the Functionally defined fusion complex. Rather than a direct fusogenic role, the SNARE complex may promote the calcium sensitivity of Fusion, possibly by defining or delimiting a localized, focal membrane fusion site that ensures rapid and efficient exocytosis in vivo. (C) 2000 Society francaise de biochimie et biologie moleculaire / Editions scientifiques et medicales Elsevier SAS. C1 NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. Univ Calgary, Fac Med, Neurosci Res Grp, Dept Physiol & Biophys, Calgary, AB T2N 4N1, Canada. RP Coorssen, JR (reprint author), NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. NR 124 TC 25 Z9 25 U1 1 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 2000 VL 82 IS 4 BP 303 EP 314 DI 10.1016/S0300-9084(00)00215-7 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 326BH UT WOS:000087711700004 PM 10865119 ER PT J AU Kaune, WT Miller, MC Linet, MS Hatch, EE Kleinerman, RA Wacholder, S Mohr, AH Tarone, RE Hianes, C AF Kaune, WT Miller, MC Linet, MS Hatch, EE Kleinerman, RA Wacholder, S Mohr, AH Tarone, RE Hianes, C TI Children's exposure to magnetic fields produced by US television sets used for viewing programs and playing video games SO BIOELECTROMAGNETICS LA English DT Article DE ELF; VLF; appliances; residential; exposure assessment ID EXTREMELY-LOW-FREQUENCY; 60-HZ ELECTRIC-FIELDS; DISPLAY TERMINALS; ELECTROMAGNETIC EMISSIONS; APPLIANCES; UNITS AB Two epidemiologic studies have reported increased risk of childhood leukemia associated with the length of time children watched television (TV) programs or played video games connected to TV sets. To evaluate magnetic field exposures resulting from these activities, the static, ELF, and VLF magnetic fields produced by 72 TV sets used by children to watch TV programs and 34 TV sets used to play video games were characterized in a field study conducted in Washington DC and its Maryland suburbs. The resulting TV-specific magnetic field data were combined with information collected through questionnaires to estimate the magnetic field exposure levels associated with TV watching and video game playing. The geometric means of the ELF and VLF exposure levels so calculated were 0.0091 and 0.0016 mu T, respectively, for children watching TV programs and 0.023 and 0.0038 mu T, respectively, for children playing video games. Geometric means of ambient ELF and VLF levels with TV sets turned off were 0.10 and 0.0027 mu T, respectively. Summed over the ELF frequency range (6-3066 Hz), the exposure levels were small compared to ambient levels. However, in restricted ELF frequency ranges (120 Hz and 606-3066 Hz) and in the VLF band, TV exposure levels were comparable to or larger than normal ambient levels. Even so, the strengths of the 120 Hz or 606-3066 Hz components of TV fields were small relative to the overall ambient levels. Consequently, our results provide little support for a linkage between childhood leukemia and exposure to the ELF magnetic fields produced by TV sets. Our results do suggest that any future research on possible health effects of magnetic fields from television sets might focus on the VLF electric and magnetic fields produced by TV sets because of their enhanced ability relative to ELF fields to induce electric currents. (C) 2000 Wiley-Liss. Inc. C1 EM Factors, Richland, WA 99352 USA. NCI, Rockville, MD USA. WESTAT Corp, Rockville, MD 20850 USA. RP Kaune, WT (reprint author), EM Factors, 640 Jadwin Ave,Ste F, Richland, WA 99352 USA. OI Kleinerman, Ruth/0000-0001-7415-2478 NR 31 TC 14 Z9 14 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0197-8462 J9 BIOELECTROMAGNETICS JI Bioelectromagnetics PD APR PY 2000 VL 21 IS 3 BP 214 EP 227 DI 10.1002/(SICI)1521-186X(200004)21:3<214::AID-BEM8>3.0.CO;2-Y PG 14 WC Biology; Biophysics SC Life Sciences & Biomedicine - Other Topics; Biophysics GA 298GG UT WOS:000086130500008 PM 10723021 ER PT J AU Heinz, A Jones, DW Mazzanti, C Goldman, D Ragan, P Hommer, D Linnoila, M Weinberger, DR AF Heinz, A Jones, DW Mazzanti, C Goldman, D Ragan, P Hommer, D Linnoila, M Weinberger, DR TI A relationship between serotonin transporter genotype and in vivo protein expression and alcohol neurotoxicity SO BIOLOGICAL PSYCHIATRY LA English DT Article DE alcoholism; gene expression; SLC6A4; serotonin transporters; SPECT; beta-CIT ID HEALTHY-HUMAN SUBJECTS; MESSENGER-RNA LEVELS; BETA-CIT BINDING; HUMAN BRAIN; IN-VIVO; DOPAMINE TRANSPORTERS; NONHUMAN-PRIMATES; COCAINE; AVAILABILITY; SENSITIVITY AB Background: Genetic variation of the promoter for the serotonin transporter (5-HTT) gene has been associated with its functional capacity, In vitro, carriers of a short allele (s-carriers) of the 5-HTT promoter display significant reduction? in 5-HTT capacity. Dysfunction of 5-HTT has been observed in alcoholic individuals. We assessed whether the allelic constitution of the 5-HTT gene is associated with reduced serotonin transporter availability among alcoholic individuals, Methods: We genotyped the 5-HTT promoter region and measured the availability of serotonin transporter protein with [I-123]beta-CIT SPECT in the raphe area in 14 abstinent male alcoholic subjects and 8 age-matched control subjects of European American descent. Results: Among control subjects, the ratio of in vivo 5-HTT availability for 11-homozygous individuals relative to s-carriers was comparable to serotonin uptake ratios measured in vitro. There was a significant interaction of diagnosis and 5-HTT promoter genotype on 5-HTT availability (p < .01), Among controls, 11-homozygous individuals displayed a significant increase as compared with s-carriers. The availability of raphe 5-HTT was significantly reduced in 11-homozygous alcoholic individuals and was negatively correlated with their amount of alcohol consumption. Among s-carriers, 5-HTT availability did nor differ significantly between control and alcoholic subjects. Conclusions: Our preliminary findings suggest an association between 5-HTT allelic constitution and in vivo measurements of human serotonin transporter availability, and a potentially selective susceptibility of 11-homozygous individuals to the neurotoxic effects of chronic excessive alcohol consumption. C1 NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. NIAAA, Clin Studies Lab, Intramural Res Program, Bethesda, MD 20892 USA. RP Weinberger, DR (reprint author), NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, 10 Ctr Dr,4S-235,MSC 1379, Bethesda, MD 20892 USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 38 TC 331 Z9 337 U1 2 U2 15 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 2000 VL 47 IS 7 BP 643 EP 649 DI 10.1016/S0006-3223(99)00171-7 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 299HY UT WOS:000086194000009 PM 10745057 ER PT J AU Negrao, AB Deuster, PA Gold, PW Singh, A Chrousos, GP AF Negrao, AB Deuster, PA Gold, PW Singh, A Chrousos, GP TI Individual reactivity and physiology of the stress response SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Article DE catecholamines; cortisol; exercise test ID PITUITARY-ADRENAL AXIS; HEART-RATE REACTIVITY; CELLULAR IMMUNE-RESPONSE; PSYCHOLOGICAL STRESS; CORTISOL RESPONSES; MARKED DIFFERENCES; EXERCISE; NEUROENDOCRINE; SYSTEM; SUSCEPTIBILITY AB The biological response to stress involves the activation of two main neuroendocrine components, the hypnthalamic-pituitary-adrenal axis and the sympathoadrenal medullary systems. Looking at the respones to stressors in a laboratory setting, e.g., cortisol production after exercising on a treadmill, is a valid and controlled way to study how people react to psychological and physical stressors. A common finding in such studies is that individuals respond bimodally to stress, More recently, researchers have been interested in the possible reasons why healthy individuals exhibit differential reactivity to stressors. The literature on the neuroendocrine responses to stress, with a particular focus on investigations of individual reactivity to psychological and physical stressors, is reviewed. (C) 2000 Editions scientifques et medicales Elsevier SAS. C1 NIMH, Clin Neuroendocrinol Branch, DIRP, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Mil & Emergency Med, Bethesda, MD 20814 USA. USDA, Food & Nutr Serv, Off Anal, Alexandria, VA 22302 USA. NICHHD, Pediat & Reporduct Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP NIMH, Clin Neuroendocrinol Branch, DIRP, NIH, Bldg 10,Rm 2D46,10 Ctr Dr,MSC 1284, Bethesda, MD 20892 USA. RI Negrao, Andre Brooking/C-9526-2014; Deuster, Patricia/G-3838-2015 OI Negrao, Andre Brooking/0000-0002-8133-6723; Deuster, Patricia/0000-0002-7895-0888 NR 22 TC 55 Z9 56 U1 1 U2 6 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0753-3322 EI 1950-6007 J9 BIOMED PHARMACOTHER JI Biomed. Pharmacother. PD APR PY 2000 VL 54 IS 3 BP 122 EP 128 DI 10.1016/S0753-3322(00)89044-7 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 316VG UT WOS:000087188300002 PM 10840588 ER PT J AU Osborne, JC Miller, JH Kempner, ES AF Osborne, JC Miller, JH Kempner, ES TI Molecular mass and volume in radiation target theory SO BIOPHYSICAL JOURNAL LA English DT Article ID SIZE DETERMINATION; INACTIVATION; PROTEINS; ENZYMES AB Radiation target analysis is based on the action of ionizing radiation directly on macromolecules. Interactions of this radiation with the molecules leads to considerable structural damage and consequent loss of biological activity. The radiation sensitivity is dependent on the size of the macromolecules. There has been confusion and discrepancy as to whether the molecular mass or the molecular volume was the determinant factor in the sensitivity. Some proteins are known to change their hydrodynamic volume at low pH, and this characteristic can be utilized to compare the radiation sensitivities of these proteins in the two stales. The results show that the radiation sensitivity of proteins depends on the mass of the molecule and is independent of the molecular volume/shape. C1 NIAMSD, Phys Biol Lab, NIH, Bethesda, MD 20892 USA. Beckman Coulter, Fullerton, CA USA. RP NIAMSD, Phys Biol Lab, NIH, Bldg 6,Room 140, Bethesda, MD 20892 USA. NR 23 TC 17 Z9 17 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD APR PY 2000 VL 78 IS 4 BP 1698 EP 1702 PG 5 WC Biophysics SC Biophysics GA 302DE UT WOS:000086349500005 PM 10733952 ER PT J AU Keskin, O Jernigan, RL Bahar, I AF Keskin, O Jernigan, RL Bahar, I TI Proteins with similar architecture exhibit similar large-scale dynamic behavior SO BIOPHYSICAL JOURNAL LA English DT Article ID BINDING-PROTEIN; ESCHERICHIA-COLI; VIBRATIONAL DYNAMICS; FOLDED PROTEINS; CLASSIFICATION; FLUCTUATIONS; CHEMOTAXIS; DATABASE; LEUCINE AB We have investigated the similarities and differences in the computed dynamic fluctuations exhibited by six members of a protein fold family with a coarse-grained Gaussian network model. Specifically, we consider the cofactor binding fragment of CysB; the lysine/arginine/ornithine-binding protein (LAO); the enzyme porphobilinogen deaminase (PBGD); the ribose-binding protein (RBP); the N-terminal lobe of ovotransferrin in ape-form (apo-OVOT); and the leucine/ isoleucine/valine-binding protein (LIVBP). All have domains that resemble a Rossmann fold, but there are also some significant differences. Results indicate that similar global dynamic behavior is preserved for the members of a fold family, and that differences usually occur in regions only where specific function is localized. The present work is a computational demonstration that the scaffold of a protein fold may be utilized for diverse purposes. LAO requires a bound ligand before it conforms to the large-scale fluctuation behavior of the three other members of the family, CysB, PBGD, and REP, ail of which contain a substrate (cofactor) at the active site cleft. The dynamics of the ligand-free enzymes LIVBP and apo-OVOT, on the other hand, concur with that of unliganded LAG. The present results suggest that it is possible to construct structure alignments based on dynamic fluctuation behavior. C1 NCI, Lab Expt & Computat Biol, Div Basic Sci, NIH,Mol Struct Sect, Bethesda, MD 20892 USA. Bogazici Univ, Dept Chem Engn, TR-80815 Bebek, Turkey. Bogazici Univ, Polymer Res Ctr, TR-80815 Bebek, Turkey. TUBITAK, Adv Polymer Mat Res Ctr, TR-80815 Bebek, Turkey. RP Jernigan, RL (reprint author), NCI, Lab Expt & Computat Biol, Div Basic Sci, NIH,Mol Struct Sect, MSC 5677,Rm B-116,Bldg 12B, Bethesda, MD 20892 USA. RI Jernigan, Robert/A-5421-2012 NR 27 TC 132 Z9 133 U1 0 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD APR PY 2000 VL 78 IS 4 BP 2093 EP 2106 PG 14 WC Biophysics SC Biophysics GA 302DE UT WOS:000086349500040 PM 10733987 ER PT J AU Kato, H Okubo, Y Matsumura, Y Roberts, CT Sugahara, K LeRoith, D AF Kato, H Okubo, Y Matsumura, Y Roberts, CT Sugahara, K LeRoith, D TI The tyrosine kinase activity of the chicken insulin receptor is similar to that of the human insulin receptor SO BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY LA English DT Article DE insulin receptor; chicken; tyrosine kinase; IRS-1 ID IGF-I RECEPTOR; BETA-SUBUNIT; DOMAIN; GENE AB The tyrosine kinase activity of a chimeric insulin receptor composed of the extracellular domain of the human insulin receptor (IR) and the intracellular domain of the chicken IR was compared with wild-type human IR. The degrees of autophosphorylation, phosphorylation of IRS-1, and in vitro phosphorylation of an exogenous substrate after stimulation by human insulin were similar to that seen with the human IR. We conclude that the insulin resistance of chickens is not attributable to a lower level of intrinsic tyrosine kinase activity of IR. C1 Univ Tokyo, Grad Sch Agr & Life Sci, Dept Appl Biol Chem, Bunkyo Ku, Tokyo 1138657, Japan. NIDDKD, Clin Endocrine Branch, NIH, Bethesda, MD 20892 USA. Utsunomiya Univ, Fac Agr, Dept Anim Sci, Utsunomiya, Tochigi 3218505, Japan. Oregon Hlth Sci Univ, Dept Pediat, Portland, OR 97201 USA. RP Kato, H (reprint author), Univ Tokyo, Grad Sch Agr & Life Sci, Dept Appl Biol Chem, Bunkyo Ku, Tokyo 1138657, Japan. EM akatoq@mail.ecc.u-tokyo.ac.jp OI Roberts, Charles/0000-0003-1756-5772 NR 17 TC 10 Z9 10 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0916-8451 EI 1347-6947 J9 BIOSCI BIOTECH BIOCH JI Biosci. Biotechnol. Biochem. PD APR PY 2000 VL 64 IS 4 BP 903 EP 906 DI 10.1271/bbb.64.903 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry, Applied; Food Science & Technology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry; Food Science & Technology GA 310DX UT WOS:000086812200042 PM 10830518 ER PT J AU Schriml, LM Peterson, RJ Gerrard, B Dean, M AF Schriml, LM Peterson, RJ Gerrard, B Dean, M TI Use of denaturing HPLC to map human and murine genes and to validate single-nucleotide polymorphisms SO BIOTECHNIQUES LA English DT Article ID LIQUID-CHROMATOGRAPHY; HUMAN GENOME; PROGRAM AB Linkage mapping has been extensively applied ill the murine and human genomes. It remains a powerful approach to mapping genes and identifying genetic variants. As genome efforts identify large numbers of single-nucleotide polymorphisms, it will be critical to validate these polymorphisms and confirm their gene assignment and chromosomal location. The presence of pseudogenes can confuse such efforts. We have used denaturing HPLC to identify polymorphisms in human genes and to genotype individuals in selected CEPH pedigrees. The same approach has been applied to the mapping of murine genes in interspecies backcross animals. This strategy is rapid, accurate and superior in several respects to other technologies. C1 NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Dean, M (reprint author), NCI, Frederick Canc Res & Dev Ctr, Bldg 560,Rm 21-18, Frederick, MD 21702 USA. RI Dean, Michael/G-8172-2012; OI Dean, Michael/0000-0003-2234-0631; Schriml, Lynn/0000-0001-8910-9851 FU NCI NIH HHS [N01-CO-56000] NR 20 TC 17 Z9 17 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD APR PY 2000 VL 28 IS 4 BP 740 EP + PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 302ZF UT WOS:000086395800018 PM 10769753 ER PT J AU Fujio, K Nosaka, T Kojima, T Kawashima, T Yahata, T Copeland, NG Gilbert, DJ Jenkins, NA Yamamoto, K Nishimura, T Kitamura, T AF Fujio, K Nosaka, T Kojima, T Kawashima, T Yahata, T Copeland, NG Gilbert, DJ Jenkins, NA Yamamoto, K Nishimura, T Kitamura, T TI Molecular cloning of a novel type 1 cytokine receptor similar to the common gamma chain SO BLOOD LA English DT Article ID COLONY-STIMULATING-FACTOR; ERYTHROPOIETIN RECEPTOR; BETA-CHAIN; SIGNAL-TRANSDUCTION; CELL-LINES; SECRETED PROTEINS; ACTIVATION; FAMILY; GROWTH; DOMAIN AB In a complementary DNA (cDNA) screening of murine Th2-skewed lymphocytes with our recently developed signal sequence trap method termed SST-REX, a novel type 1 cytokine receptor, Delta1 (delta 1), was identified. Although delta 1 is ubiquitously expressed in multiple tissues, the expression level is higher in Th2-skewed lymphocytes than in Th1-skewed ones. The delta 1 cDNA encodes a 359-amino acid type I membrane protein. The extracellular domain of 206 amino acids showed 24% identity with the murine common gamma receptor that is shared among the receptors for interleukin(IL)-2, IL-4, IL-7, IL-9, and IL-15. The membrane-proximal region of delta 1 includes a box1 motif, which is important for association with Janus kinases (JAKs), and showed a significant homology with that of the mouse erythropoietin receptor (EPOR). A box2 motif was also found in close proximity to the box1 region. Dimerization of the cytoplasmic region of delta 1 alone did not transduce proliferative signals in IL-3-dependent cell lines, However, the membrane-proximal region of delta 1 could substitute for that of human EPOR in transmitting proliferative signals and activating JAK2. These results suggest that delta 1 is a subunit of cytokine receptor that may be involved in multiple receptor systems and play a regulatory role in the immune system and hematopoiesis, (Blood, 2000; 95:2204-2211) (C) 2000 by The American Society of Hematology. C1 Univ Tokyo, Inst Med Sci, Dept Hematopoiet Factors, Minato Ku, Tokyo 1088639, Japan. Tokai Univ, Sch Med, Dept Immunol, Isehara, Kanagawa 25911, Japan. NCI, Mammalian Genet Lab, ABL, Basic Res Program,Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. Univ Tokyo, Grad Sch Med, Dept Allergy & Rheumatol, Tokyo, Japan. RP Kitamura, T (reprint author), Univ Tokyo, Inst Med Sci, Dept Hematopoiet Factors, Minato Ku, 4-6-1 Shirokanedai, Tokyo 1088639, Japan. RI Yamamoto, Kazuhiko/N-5096-2015 NR 54 TC 39 Z9 42 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 2000 VL 95 IS 7 BP 2204 EP 2211 PG 8 WC Hematology SC Hematology GA 298GC UT WOS:000086130100005 PM 10733486 ER PT J AU Sloand, EM Kim, S Maciejewski, JP Van Rhee, F Chaudhuri, A Barrett, J Young, NS AF Sloand, EM Kim, S Maciejewski, JP Van Rhee, F Chaudhuri, A Barrett, J Young, NS TI Pharmacologic doses of granulocyte colony-stimulating factor affect cytokine production by lymphocytes in vitro and in vivo SO BLOOD LA English DT Article ID VERSUS-HOST DISEASE; BONE-MARROW TRANSPLANTATION; NECROSIS-FACTOR-ALPHA; PERIPHERAL-BLOOD; T-CELLS; INTERFERON-GAMMA; APLASTIC-ANEMIA; EXPRESSION; TH1; AUTOIMMUNITY AB Peripheral blood stem cell (PBSC) transplantation is successful in improving engraftment without increasing acute graft-versus-host disease (GVHD), despite much larger numbers of T cells in unmanipulated PBSCs than in bone marrow grafts. In mouse models and retrospective human studies, granulocyte colony-stimulating factor (G-CSF) therapy has been associated with less acute GVHD. We studied the effect of G-CSF on interferon (IFN)-gamma and IL-4 expression in CD4(+) lymphocytes. CD4(+) cells co-cultivated with G-CSF and stimulated with PHA or CD3 monoclonal antibodies showed significant decreases in IFN-gamma and increases in IL-4 expression (n = 13; P <.01), G-CSF appeared to have a direct effect on CD4(+) cells independent of monocytes present in the culture because purified CD4(+) bells exposed to G-CSF, washed, and cocultivated with untreated monocytes demonstrated similar changes in IFN-gamma and IL-4 expression, whereas untreated CD4(+) cells cocultured with G-CSF-stimulated monocytes behaved as controls. We then studied peripheral blood mononuclear cells (PBMCs) from G-CSF-mobilized PBSC donors. When their PBMCs were cultured with PHA or CD3 monoclonal antibody, the percent of IFN-gamma-expressing cells decreased by a mean of 55% and 42%, respectively, whereas the percent of IL-4-containing cells increased by a mean of 39% and 58%, respectively, following G-CSF stimulation. Increased apoptosis of IFN-gamma-producing CD4(+) cells was not responsible for the shift in TH1/TH2 subsets. G-CSF-R mRNA was present in both CD4(+) and CD8(+) cells. These results suggest that G-CSF decreases IFN-gamma and increases IL-4 production in vitro and in vivo and likely modulates a balance between TH1 and TH2 cells, an effect that may be important in PBSC transplantation. (Blood. 2000;95:2269-2274) (C) 2000 by The American Society of Hematology. C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Sloand, EM (reprint author), NHLBI, NIH, 31 Ctr Dr,MSC 2490,Bldg 31,Room 4A11, Bethesda, MD 20892 USA. NR 28 TC 161 Z9 167 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 2000 VL 95 IS 7 BP 2269 EP 2274 PG 6 WC Hematology SC Hematology GA 298GC UT WOS:000086130100015 PM 10733495 ER PT J AU Lehrnbecher, T Foster, CB Zhu, SX Venzon, D Steinberg, SM Wyvill, K Metcalf, JA Cohen, SS Kovacs, J Yarchoan, R Blauvelt, A Chanock, SJ AF Lehrnbecher, T Foster, CB Zhu, SX Venzon, D Steinberg, SM Wyvill, K Metcalf, JA Cohen, SS Kovacs, J Yarchoan, R Blauvelt, A Chanock, SJ TI Variant genotypes of Fc gamma RIIIA influence the development of Kaposi's sarcoma in HIV-infected men SO BLOOD LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; RECEPTOR IIA POLYMORPHISM; NATURAL-KILLER-CELLS; GROWTH-FACTOR; GENETIC RESTRICTION; DISEASE PROGRESSION; HUMAN-NEUTROPHILS; INTERFERON-GAMMA; ONCOSTATIN-M; HUMAN IGG2 AB Disturbances In inflammatory cytokine production and immune regulation coupled with human herpesvirus-8 (HHV-8) infection underlie the current understanding of the pathogenesis of Kaposi's sarcoma (KS), the most common HIV-associated malignancy. The low affinity Fc gamma receptors (Fc gamma R) for IgG link humoral and cellular immunity by mediating interaction between antibodies and effector cells, such as phagocytes and natural killer cells. We examined the frequency of polymorphic forms of the low affinity Fc gamma Rs, FcRIIA, Fc gamma RIIIA, and Fc gamma RIIIB in 2 cohorts of HIV-infected men with KS and found that the Fc gamma RIIIA genotype exerts a significant influence on susceptibility to or protection from KS. The FF genotype was underrepresented in patients with KS, whereas the VF genotype was associated with development of KS. A similar association was observed between Fc gamma RIIIA genotypes and HHV-8 seropositivity. These observations suggest a possible role for Fc gamma RIIIA in the development of KS during HIV infection. (Blood.2000;95:2386-2390) (C) 2000 by The American Society of Hematology. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Ctr Adv Technol, Gaithersburg, MD 20877 USA. NCI, Biostat & Data Management Sect, Gaithersburg, MD 20877 USA. NCI, HIV & AIDS Malignancy Branch, Gaithersburg, MD 20877 USA. NCI, Dermatol Branch, Gaithersburg, MD 20877 USA. NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Chanock, SJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Ctr Adv Technol, 8717 Grovemont Circle, Gaithersburg, MD 20877 USA. RI Venzon, David/B-3078-2008 NR 61 TC 37 Z9 39 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 2000 VL 95 IS 7 BP 2386 EP 2390 PG 5 WC Hematology SC Hematology GA 298GC UT WOS:000086130100031 PM 10733511 ER PT J AU Mattson, MP AF Mattson, MP TI Apoptotic and anti-apoptotic synaptic signaling mechanisms SO BRAIN PATHOLOGY LA English DT Article ID AMYLOID BETA-PEPTIDE; NF-KAPPA-B; MANGANESE SUPEROXIDE-DISMUTASE; PROTECTS HIPPOCAMPAL-NEURONS; NECROSIS-FACTOR-ALPHA; PRECURSOR PROTEIN; CELL-DEATH; MITOCHONDRIAL DYSFUNCTION; CALCIUM HOMEOSTASIS; NEUROTROPHIC FACTOR AB Although several prominent morphological features of apoptosis are evident in the cell body (e.g., cell shrinkage, membrane blebbing, and nuclear DNA condensation and fragmentation) the biochemical and molecular cascades that constitute the cell death machinery can be engaged in synaptic terminals and neurites. Initiating events such as oxyradical production and calcium influx, and effector processes such as Par-4 production, mitochondrial alterations and caspase activation, can be induced in synapses and neurites, Several prominent signal transduction pathways in synaptic terminals play important roles in either promoting or preventing neuronal death in physiological and pathological conditions. For example, activation of glutamate receptors in postsynaptic spines can induce neuronal apoptosis, whereas local activation of neurotrophic factor receptors in presynaptic terminals can prevent neuronal death. Factors capable of inducing nuclear chromatin condensation and fragmentation can be produced locally in synaptic terminals and neurites, and may propogate to the cell body. Recent findings suggest that, beyond their roles in inducing or preventing cell death, apoptotic and anti-apoptotic cascades play roles in synaptic plasticity (structural remodelling and long-term functional changes). For example, caspase activation results in proteolysis of glutamate receptor (AMPA) subunits, which results in altered neuronal responsivity to glutamate. Activation of neurotrophic factor receptors in synaptic terminals can result in local changes in energy metabolism and calcium homeostasis, and can induce long-term changes in synaptic transmission. The emerging data therefore suggest that synapses can be considered as autonomous compartments in which both pro- and anti-apoptotic signaling pathways are activated resulting in structural and functional changes in neuronal circuits. A better understanding of such synaptic signaling mechanisms may reveal novel approaches for preventing and treating an array of neurodegenerative conditions that are initiated by perturbed synaptic homeostasis. C1 NIA, Neurosci Lab, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 98 TC 72 Z9 75 U1 0 U2 3 PU INT SOC NEUROPATHOLOGY PI PITTSBURGH PA 200 LOTHROP ST A506, PITTSBURGH, PA 15213 USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD APR PY 2000 VL 10 IS 2 BP 300 EP 312 PG 13 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 300EX UT WOS:000086241100012 PM 10764050 ER PT J AU Roerig, B Feller, MB AF Roerig, B Feller, MB TI Neurotransmitters and gap junctions in developing neural circuits SO BRAIN RESEARCH REVIEWS LA English DT Article; Proceedings Paper CT Workshop on Gap Junctions in the Nervous and Cardiovascular Systems: Clinical Implications CY JUN 06-11, 1998 CL RIO JANEIRO, BRAZIL DE neurotransmitter; gap junction; neural circuit ID LONG-TERM POTENTIATION; RAT VISUAL-CORTEX; DEVELOPING MAMMALIAN RETINA; SEROTONIN 5-HT3 RECEPTORS; OCULAR DOMINANCE COLUMNS; STARBURST AMACRINE CELLS; POSTNATAL-DEVELOPMENT; HORIZONTAL CELLS; CEREBRAL-CORTEX; GANGLION-CELLS AB A growing body of evidence suggests that highly correlated, spontaneous neural activity plays an important role in shaping connections in the developing nervous system prior to the maturation of sensory afferents. In this article we discuss the mechanisms involved in the generation and the regulation of spontaneous activity patterns in the developing retina and the developing neocortex. Spontaneous activity in the developing retina propagates across the ganglion cell layer as waves of action potentials and drives rhythmic increases in intracellular calcium in retinal neurons. Retinal waves are mediated by a combination of chemical synaptic transmission and gap junctions, and the circuitry responsible for generating retinal waves changes with age and between species. In the developing cortex, spontaneous calcium elevations propagate across clusters of cortical neurons called domains. Cortical domains are generated by a regenerative mechanism involving second messenger diffusion through gap junctions and subsequent calcium release from internal stores. The neocortical gap junction system is regulated by glutamate-triggered second messenger systems as well as neuromodulatory transmitters, suggesting extensive interactions between synaptic transmission and information flow through gap junctions. The interaction between gap junctions and chemical synaptic transmission observed in these developing networks represent a powerful mechanism by which activity across large groups of neurons can be correlated. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Roerig, B (reprint author), Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA. NR 163 TC 95 Z9 100 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0173 J9 BRAIN RES REV JI Brain Res. Rev. PD APR PY 2000 VL 32 IS 1 SI SI BP 86 EP 114 DI 10.1016/S0165-0173(99)00069-7 PG 29 WC Neurosciences SC Neurosciences & Neurology GA 315UK UT WOS:000087131200012 PM 10751659 ER PT J AU Wen, WQ Shu, XO Linet, MS Neglia, JP Potter, JD Trigg, ME Robison, LL AF Wen, WQ Shu, XO Linet, MS Neglia, JP Potter, JD Trigg, ME Robison, LL TI Allergic disorders and the risk of childhood acute lymphoblastic leukemia (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE allergy; leukemia; sibling ID CANCER; DISEASES; HISTORY AB Objectives: To test the hypothesis that childhood acute lymphoblastic leukemia (ALL) is associated with allergic disorders. Methods: We compared the histories of selected allergic disorders (asthma, hay fever, food or drug allergies, eczema, and hives) of 1842 cases of ALL with those of 1986 individually matched controls. The histories of the allergic disorders among siblings of cases and controls were also compared. Results: The combined history of any one or more of the five allergic disorders evaluated was associated with a significant reduced risk of ALL (adjusted OR = 0.7, 95% CI 0.6-0.8), as were hhistories of four specific allergic disorders (asthma, hay fever, food or drug allergies, and eczema). The combined history of any one or more of the five allergic disorders among any of the siblings of the study subjects also revealed a significantly inverse association (adjusted OR = 0.9, 95% CI 0.8-1.0). Conclusion: The results from this study, in agreement with most previous studies on adult cancer, suggest that allergic disorders may be associated with a reduced risk of childhood ALL. C1 Univ S Carolina, Columbia, SC 29208 USA. NCI, Bethesda, MD 20892 USA. Univ Minnesota, Minneapolis, MN USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. AI DuPont Hosp Children, Wilmington, DE USA. RP Shu, XO (reprint author), Childrens Canc Grp, POB 60012, Arcadia, CA 91066 USA. OI Potter, John/0000-0001-5439-1500 FU NCI NIH HHS [CA 13539] NR 22 TC 56 Z9 56 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD APR PY 2000 VL 11 IS 4 BP 303 EP 307 DI 10.1023/A:1008958724739 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 323VY UT WOS:000087586700003 PM 10843442 ER PT J AU Figgs, LW Holland, NT Rothman, N Zahm, SH Tarone, RE Hill, R Vogt, RF Smith, MT Boysen, CD Holmes, FF VanDyck, K Blair, A AF Figgs, LW Holland, NT Rothman, N Zahm, SH Tarone, RE Hill, R Vogt, RF Smith, MT Boysen, CD Holmes, FF VanDyck, K Blair, A TI Increased lymphocyte replicative index following 2,4-dichlorophenoxyacetic acid herbicide exposure SO CANCER CAUSES & CONTROL LA English DT Article DE herbicide; lymphocytes; micronucleus; occupation; 2,4-D ID NON-HODGKINS-LYMPHOMA; SISTER-CHROMATID EXCHANGES; CELL-CYCLE KINETICS; SOFT-TISSUE SARCOMA; IN-VIVO; 2,4-D; MICRONUCLEI; INDIVIDUALS; METABOLITES; MORTALITY AB Objective: Evaluate peripheral blood lymphocyte proliferation (replicative index:RI) and micronuclei frequency (MF) among 2,4-D herbicide applicators. Methods: Twelve applicators spraying only 2,4-D provided a blood and urine specimen upon enrollment, several urine samples during the spraying season, and a blood specimen at the study's end. Nine controls provided blood and urine specimens upon enrollment and at the study's end. Gas chromatography/tandem mass spectroscopy determined urinary 2,4-D levels and standard in-vitro assays determined RI and MF scores. Applicator RI and MF were compared before and after spraying and with controls. Results: Applicators contributed 45 urine specimens with concentrations ranging from 1.0 to 1700 (mu g 2,4-D/g creatinine/L urine) that logarithmically (ln) increased as spraying time increased. Applicator RI increased after spraying (p = 0.016), independent of tobacco and alcohol use, and demonstrated a weak dose-response with increasing urinary 2,4-D levels (p = 0.15). Among 2,4-D applicators, pre-exposure complete blood counts and lymphocyte immunophenotypes were not significantly different from post-exposure measurements. Conclusion: Urinary 2,4-D concentration, an exposure biomarker, may be associated with lymphocyte replicative index, a cell proliferation biomarker. C1 St Louis Univ, Sch Publ Hlth, St Louis, MO 63108 USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. NCI, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Atlanta, GA 30341 USA. Univ Kansas, Med Ctr, Kansas City, KS 66160 USA. Battelle Survey Res Associates, Baltimore, MD 21209 USA. RP Figgs, LW (reprint author), St Louis Univ, Sch Publ Hlth, 3663 Lindell Blvd, St Louis, MO 63108 USA. FU BHP HRSA HHS [OMB NO. 0925-0422] NR 44 TC 28 Z9 31 U1 1 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD APR PY 2000 VL 11 IS 4 BP 373 EP 380 DI 10.1023/A:1008925824242 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 323VY UT WOS:000087586700009 PM 10843448 ER PT J AU Herman, EH Zhang, J Chadwick, DP Ferrans, VJ AF Herman, EH Zhang, J Chadwick, DP Ferrans, VJ TI Comparison of the protective effects of amifostine and dexrazoxane against the toxicity of doxorubicin in spontaneously hypertensive rats SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE doxorubicin; cardiomyopathy; nephrotoxicity; amifostine; dexrazoxane ID PARATHYROID-HORMONE SECRETION; ADRIAMYCIN CARDIOTOXICITY; INDUCED CARDIOMYOPATHY; NORMAL-TISSUES; WR-2721; INHIBITION; ICRF-187; RADIOPROTECTOR; CHEMOTHERAPY; WR-1065 AB Purpose: To compare the protective effects of amifostine and dexrazoxane against the chronic toxicity induced by doxorubicin in spontaneously hypertensive rats (SHR). Methods: The animals were pretreated with amifostine (200 mg/kg, i.p.), dexrazoxane (25 mg/kg, i.p.) or saline 30 min before the administration of doxorubicin (1 mg/kg, i.v.), once-weekly for 12 weeks. Control animals received similar amounts of amifostine or saline. The SHR underwent necropsy examination 1 week after the last dosing, and cardiac, renal, and gastrointestinal lesions were graded semiquantitatively. Results: Amifostine and dexrazoxane provided equal degrees of protection against the renal toxicity of doxorubicin. However, dexrazoxane was more cardioprotective than amifostine, and prevented the mortality induced by doxorubicin. This mortality was not decreased by pretreatment with amifostine. The loss of body weight caused by doxorubicin was actually worsened by coadministration of amifostine. Conclusions: Compared to dexrazoxane, amifostine provided a comparable degree of protection against the nephrotoxicity of doxorubicin, but was less cardioprotective and did not prevent the mortality and loss of body weight produced by doxorubicin. These differences may be related to the fact that amifostine may act as a scavenger of reactive oxygen species, whereas dexrazoxane may prevent their formation. C1 US FDA, Div Appl Pharmacol Res HFD910, Ctr Drug Evaluat & Res, Laurel, MD 20708 USA. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. RP Herman, EH (reprint author), US FDA, Div Appl Pharmacol Res HFD910, Ctr Drug Evaluat & Res, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 39 TC 66 Z9 66 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD APR PY 2000 VL 45 IS 4 BP 329 EP 334 DI 10.1007/s002800050048 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 298VE UT WOS:000086159200010 PM 10755322 ER PT J AU Chow, HHS Earnest, DL Clark, D Mason-Liddil, N Kramer, CB Einspahr, JG Guillen-Rodriguez, JM Roe, DJ Malone, W Crowell, JA Alberts, DS AF Chow, HHS Earnest, DL Clark, D Mason-Liddil, N Kramer, CB Einspahr, JG Guillen-Rodriguez, JM Roe, DJ Malone, W Crowell, JA Alberts, DS TI Effect of subacute ibuprofen dosing on rectal mucosal prostaglandin E-2 levels in healthy subjects with a history of resected polyps SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; FAMILIAL ADENOMATOUS POLYPOSIS; INDUCED COLON CARCINOGENESIS; ABERRANT CRYPT FOCI; COLORECTAL-CANCER; ASPIRIN USE; LARGE-BOWEL; SULINDAC; RISK; INDOMETHACIN AB Nonsteroidal antiinflammatory drugs are among the most promising chemopreventive agents for colorectal cancer. Although the mechanism by which nonsteroidal antiinflammatory drugs exert such effects remains to be further characterized, their best known pharmacological effect is inhibition of prostaglandin synthetase, which leads to decreases in tissue prostaglandin levels. We conducted a randomized, double-blind, controlled study to examine the effect of daily ibuprofen treatment on the rectal mucosal prostaglandin E-2 (PGE(2)) levels in healthy subjects with a history of resected polyps. Study participants (n = 27) completed a 2-week run-in period and were then randomized to take a single, daily dose of ibuprofen (300 or 600 mg) or of a placebo for 4 weeks. Rectal biopsy specimens were taken before and after the run-in period and at 2 and 4 weeks after the ibuprofen/ placebo treatment. Notably large between- and within-subject variability in the rectal mucosal PGE(2) content was seen. The changes in PGE(2) levels after ibuprofen/ placebo treatment correlated with the baseline PGE, content. After adjustment of the baseline values, 2 weeks of 300 mg/day of ibuprofen treatment resulted in significantly more suppression of PGE(2) levels than that observed after the placebo treatment (55% versus 22% suppression from baseline; P = 0.033). Although other ibuprofen treatment schedules and doses appeared to result in suppression in the PGE(2) levels, the suppression was not statistically significant because of the large variability in this measurement. Because lower doses are associated with fewer adverse effects, a dose of 300 mg of ibuprofen/day should be considered for future Phase n chemoprevention studies. Stratifying study participants, based on their baseline PGE(2) levels and inclusion of a larger number of study subjects, are recommended for future trials where the rectal mucosal PGE(2) level is to be used as a surrogate end point biomarker. C1 Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Alberts, DS (reprint author), Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA. FU NCI NIH HHS [N01-CN-85106-02] NR 47 TC 8 Z9 9 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 2000 VL 9 IS 4 BP 351 EP 356 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 307YV UT WOS:000086682500002 PM 10794478 ER PT J AU Fears, TR Ziegler, RG Donaldson, JL Falk, RT Hoover, RN Stanczyk, FZ Vaught, JB Gail, MH AF Fears, TR Ziegler, RG Donaldson, JL Falk, RT Hoover, RN Stanczyk, FZ Vaught, JB Gail, MH TI Reproducibility studies and interlaboratory concordance for androgen assays in female plasma SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BREAST-CANCER RISK; DEHYDROEPIANDROSTERONE SULFATE; HIRSUTE WOMEN; RADIOIMMUNOASSAY; TESTOSTERONE; ESTROGENS; GLUCURONIDE; METABOLISM; SECRETION; BIRTH AB We conducted studies to determine the magnitude and sources of variability in androgen assay results and to identify laboratories capable of performing such assays for large epidemiological studies. We studied androstanediol (ADIOL), androstanediol glucuronide (ADIOL G), androstenedione (ADION), androsterone glucuronide (ANDRO G), androsterone sulfate (ANDRO S), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA S), dihydrotestosterone (DHT), and testosterone (TESTO), A single sample of plasma was obtained from five postmenopausal women, five premenopausal women in the midfollicular phase of the menstrual cycle, and five women in the midluteal phase, divided into aliquots, and stored at -70 degrees. Four sets of two coded aliquots from each woman were then sent to participating labs for analysis at monthly intervals over 4 months. Using the logarithm of assay measurements, we estimated the components of variance and three measures of reproducibility. The usual coefficient of variation is a function of the components that are under the control of the laboratory. The intraclass correlation between measurements for a given individual is the proportion of the total variability that is associated with individuals. The minimum detectable relative difference is important to evaluate study feasibility, Results suggest that a single sample of ADIOL G, DHEA, DHEA S, and ANDRO G (with two lab replicates per sample) can be used to discriminate reliably among women in a given menstrual phase or menopausal status. The results for DHT, TESTO, ADION, and ANDRO S are more problematic and suggest that the present measurement techniques should be used with care, especially with midluteal phase women, The results for ADIOL suggest that this assay is not yet ready for use in epidemiological studies. C1 NCI, Biostat Branch, Bethesda, MD 20892 USA. NCI, Environm Epidemiol Branch, Bethesda, MD 20892 USA. NCI, Epidemiol & Biostat Program, Bethesda, MD 20892 USA. NCI, Nutr Epidemiol Branch, Bethesda, MD 20892 USA. Womens & Childrens Hosp, Los Angeles, CA 90033 USA. MA Bioserv, Rockville, MD 20850 USA. RP Fears, TR (reprint author), NCI, Biostat Branch, Execut Plaza S,Room 8040,MSC 7368,6120 Execut Blv, Bethesda, MD 20892 USA. NR 32 TC 38 Z9 39 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 2000 VL 9 IS 4 BP 403 EP 412 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 307YV UT WOS:000086682500009 PM 10794485 ER PT J AU Candotti, F Agbaria, R Mullen, CA Touraine, R Balzarini, J Johns, DG Blaese, RM AF Candotti, F Agbaria, R Mullen, CA Touraine, R Balzarini, J Johns, DG Blaese, RM TI Use of a herpes thymidine kinase/neomycin phosphotransferase chimeric gene for metabolic suicide gene transfer SO CANCER GENE THERAPY LA English DT Article DE retroviral vector; gene therapy; suicide gene; ganciclovir; (E)-5-(2-bromovinyl)-2 ' -deoxyuridine ID SIMPLEX VIRUS TYPE-1; KINASE GENE; RETROVIRAL VECTORS; ANTIHERPETIC DRUGS; MAMMALIAN-CELLS; TUMOR-CELLS; FUSION GENE; THERAPY; CARCINOMA; 9-(1,3-DIHYDROXY-2-PROPOXYMETHYL)GUANINE AB Metabolic suicide gene transfer is widely applied for gene therapy of cancer, and retroviral vectors expressing the herpes simplex virus thymidine kinase (HSV-tk) gene are commonly used in clinical trials. Most of these vectors contain positive selectable markers that undoubtedly facilitate the determination of viral titer and the identification of high-titer producer clones. However, the presence of additional transcriptional units may result in reduced expression of the gene of interest. The use of fusion genes expressing bifunctional proteins may help to overcome this problem. We have constructed a retroviral vector carrying the TNFUS69 chimeric gene, which originates From the fusion of the HSV-tk and neomycin phosphotransferase II genes, and evaluated the functional expression of the encoded fusion protein. In vitro, expression of the fusion gene conferred to target cells both resistance to neomycin and selective sensitivity to the antiherpetic drugs ganciclovir and (E)-5-(2-bromovinyl)-2'-deoxyuridine. Cells transduced with the fusion gene, however, showed reduced ability to phosphorylate ganciclovir compared with cells expressing the native HSV-tk. Therefore, although the fusion gene may be used as a constituent of retroviral cassettes for positive and negative selection in vitro, its usefulness for suicide gene transfer applications in vivo may depend upon the possibility of using (E)-5-(2-bromovinyl)-2'-deoxyuridine in a clinical context. C1 Natl Human Genome Res Inst, Clin Gene Therapy Branch, NIH, Bethesda, MD 20892 USA. NCI, Med Chem Lab, NIH, Bethesda, MD 20892 USA. Katholieke Univ Leuven, Rega Inst Med Res, Louvain, Belgium. RP Candotti, F (reprint author), Natl Human Genome Res Inst, Clin Gene Therapy Branch, NIH, Bldg10,Room 10C103,10 Ctr Dr,MSC 1851, Bethesda, MD 20892 USA. NR 31 TC 10 Z9 11 U1 1 U2 1 PU STOCKTON PRESS PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD APR PY 2000 VL 7 IS 4 BP 574 EP 580 DI 10.1038/sj.cgt.7700153 PG 7 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 311GQ UT WOS:000086876700009 PM 10811475 ER PT J AU Parshad, R Ning, Y Sanford, KK AF Parshad, R Ning, Y Sanford, KK TI Suppression of x-ray-induced chromatid breaks in human tumor cells by introduction of normal chromosome 4 SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID DEFICIENT DNA-REPAIR; NEOPLASTIC TRANSFORMATION; RADIOSENSITIVITY; KERATINOCYTES; CANCER; PREDISPOSITION; CULTURE; LINES AB Human turner cells in culture frequently short an infinite lifespan and are characterized by an abnormally high frequency of chromatid breaks after x-irradiation during G(2) phase of the cell cycle. This abnormally high frequency of persistent chromatid breaks results from deficient repair of the radiation-induced DNA damage. In three of four tumor cell lines, addition qi a single human chromosome 4 from normal cells by microcell fusion resulted in efficient repair as evidenced by suppression of radiation-induced chromatid breaks to the level in normal cells. With respect to senescence-related gene Isl, two of these four tumor cell lines belonged to complementation group A and one each to groups C and D. Chromosome 4 restored DNA repair efficiency in only one of the two tumor cell lines of complementation group A. These results suggest that chromosome 4 carries a DNA repair gene or gene(s) that complement the repair deficiency in three of these four tumor lines. Furthermore, the gene(s) involved in cellular senescence on chromosome 4 appear to differ from the gene(s) for repair of radiation-induced DNA damage during G(2). (C) Elsevier Science Inc., 2000, All rights reserved. C1 Howard Univ, Coll Med, Dept Pathol, Washington, DC 20059 USA. Gene Care Wilson Genet Ctr, Washington, DC USA. NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Parshad, R (reprint author), Howard Univ, Coll Med, Dept Pathol, 520 West St NW, Washington, DC 20059 USA. NR 24 TC 2 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD APR 1 PY 2000 VL 118 IS 1 BP 72 EP 75 DI 10.1016/S0165-4608(99)00177-6 PG 4 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 298DL UT WOS:000086124000015 PM 10731596 ER PT J AU Bartlett, DL AF Bartlett, DL TI Treatment of patients with hepatic metastases SO CANCER JOURNAL LA English DT Article ID PERCUTANEOUS ETHANOL INJECTION; COLORECTAL LIVER METASTASES; SMALL HEPATOCELLULAR-CARCINOMA; PROSPECTIVE RANDOMIZED TRIAL; INTRAARTERIAL FLOXURIDINE; RADIOFREQUENCY ABLATION; NEUROENDOCRINE TUMORS; THERMAL ABLATION; RESECTION; CANCER C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Bartlett, DL (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B-17,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 53 TC 6 Z9 6 U1 0 U2 0 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PONE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. Sci. Am. PD APR PY 2000 VL 6 SU 2 BP S169 EP S176 PG 8 WC Oncology SC Oncology GA 343GW UT WOS:000088694200010 PM 10803832 ER PT J AU Rosenberg, SA AF Rosenberg, SA TI The identification of cancer antigens: Impact on the development of cancer vaccines SO CANCER JOURNAL LA English DT Review ID TUMOR-INFILTRATING LYMPHOCYTES; CYTOLYTIC T-LYMPHOCYTES; HUMAN-MELANOMA; HLA-A2 MELANOMAS; SYNTHETIC PEPTIDES; TYROSINASE GENE; CELL RESPONSE; EPITOPES; IMMUNOTHERAPY; CARCINOMA C1 NCI, Dept Surg, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Dept Surg, Surg Branch, NIH, Bethesda, MD 20892 USA. NR 45 TC 10 Z9 10 U1 0 U2 1 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PONE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. Sci. Am. PD APR PY 2000 VL 6 SU 2 BP S142 EP S149 PG 8 WC Oncology SC Oncology GA 343GW UT WOS:000088694200007 PM 10803829 ER PT J AU Jacoby, RF Cole, CE Tutsch, K Newton, MA Kelloff, G Hawk, ET Lubet, RA AF Jacoby, RF Cole, CE Tutsch, K Newton, MA Kelloff, G Hawk, ET Lubet, RA TI Chemopreventive efficacy of combined piroxicam and difluoromethylornithine treatment of Apc mutant Min mouse adenomas, and selective toxicity against Apc mutant embryos SO CANCER RESEARCH LA English DT Article ID MULTIPLE INTESTINAL NEOPLASIA; ALPHA-DIFLUOROMETHYLORNITHINE; ORNITHINE DECARBOXYLASE; COLORECTAL-CANCER; LIQUID-CHROMATOGRAPHY; COLON CARCINOGENESIS; POLYPOSIS; CYCLOOXYGENASE-2; INHIBITION; SULINDAC AB Genetic knockout or pharmacological inhibition of cyclooxygenase-2? decreases the number and size of adenomas in mouse models of familial adenomatous polyposis. Epidemiological and clinical studies in humans indicate that the entire class of nonsteroidal anti-inflammatory drugs (NSAIDs! that inhibit both COX-I and COX-2 enzymes are promising colon cancer chemopreventive agents. We used the Ape mutant Min mouse model to test combinations of agents that might maximize preventive benefit with minimal toxicity because they act via different mechanisms, Min mice (n = 144) were exposed to low doses of the nonselective COX inhibitor piroxicam and the ornithine decarboxylase (ODC) inhibitor difluoromethylornithine (DFMO), beginning at the time they were weaned and continuing throughout the duration of the experiment. Piroxicam at 12, 25, and 50 ppm in the diet caused dose-dependent decreases in the number of tumors in the middle and distal portions of the small intestine. This decrease in tumor multiplicity was associated with a striking decrease in the size of those tumors that did grow out, In contrast, none of the doses of piroxicam alone decreased tumor multiplicity in the proximal portion of the intestine (duodenum). Exposure to DEMO (0.5 or 1.0% in water) caused a dose-dependent decrease in tumor multiplicity in the middle and distal portions of the small intestine. However, this decreased multiplicity was not associated with a striking decrease in the size of the tumors. Combined treatment of mice with piroxicam plus DEMO was much more effective than either agent alone and resulted in a significant number of mice totally free of any intestinal adenomas (P < 0.001), in contrast to the 100% incidence and high multiplicity in control Min mice, In addition to this profound effectiveness in reducing tumor number, the few residual tumors in mice treated with the combined drugs were markedly smaller in size than tumors that arose from control Min mice, These experiments suggest that selective COX-2 inhibition combined with ODC inhibition is a very promising approach for colon cancer prevention, These COX-2 and ODC inhibitor drugs were not overtly toxic at the doses used when administered to mice after weaning. However, when treatment was begun in utero, the Mendelian expected progeny ratio of 1:I that we routinely obtained in untreated control litters was no longer observed. Apc(Min/+) progeny of pregnant dams treated with piroxicam and/or DEMO were reduced in number and their ratio to Apc(+/+) progeny was decreased to approximate to 0.28:1. Thus, these agents are effective against adenomas that have homozygous mutation of the APC gene and also select against fetuses bearing a heterozygous mutation in the APC gene. C1 Univ Wisconsin, Ctr Comprehens Canc, Madison, WI 53792 USA. Natl Canc Inst, Chemoprevent Branch, Div Canc Prevent, Bethesda, MD 20892 USA. RP Jacoby, RF (reprint author), H6 516 Ctr Clin Sci 5124, 600 Highland Ave, Madison, WI 53792 USA. FU NCI NIH HHS [N01 CN 65122] NR 37 TC 119 Z9 122 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2000 VL 60 IS 7 BP 1864 EP 1870 PG 7 WC Oncology SC Oncology GA 301YK UT WOS:000086338000017 PM 10766173 ER PT J AU Brauch, H Weirich, G Brieger, J Glavac, D Rodl, H Eichinger, M Feurer, M Weidt, E Puranakanitstha, C Neuhaus, C Pomer, S Brenner, W Schirmacher, P Storkel, S Rotter, M Masera, A Gugeler, N Decker, HJ AF Brauch, H Weirich, G Brieger, J Glavac, D Rodl, H Eichinger, M Feurer, M Weidt, E Puranakanitstha, C Neuhaus, C Pomer, S Brenner, W Schirmacher, P Storkel, S Rotter, M Masera, A Gugeler, N Decker, HJ TI VHL alterations in human clear cell renal cell carcinoma: Association with advanced tumor stage and a novel hot spot mutation SO CANCER RESEARCH LA English DT Article ID HIPPEL-LINDAU-DISEASE; SUPPRESSOR GENE; GERMLINE MUTATIONS; SOMATIC MUTATIONS; PROTEIN; DNA; CARCINOGENESIS; CLASSIFICATION; CHROMOSOME-3; METHYLATION AB To elucidate the role of somatic alterations for renal cancer etiology and prognosis, we analyzed 227 sporadic renal epithelial tumors for mutations and hypermethylations in the von Hippel-Lindau tumor suppressor gene VHL. Tumors were classified according to the recommendations of the Union Internationale Contre fe Cancer (UICC) and the American Joint Committee on Cancer (AJCC), Somatic VHL mutations were identified by PCR, single-strand conformation polymorphism analysis, and sequencing, and hypermethylations were identified by restriction enzyme digestion and Southern blotting, Frequencies of VHL alterations were established, and an association with tumor type or tumor type and tumor stage was evaluated, VHL mutations and hypermethylations were identified in 45% of clear cell renal cell carcinomas (CCRCCs) and occasionally (3 of 28) in papillary (chromophilic) renal cell carcinomas (RCCs), Lack of VHL mutations and hypermethylations in chromophobe RCCs and oncocytomas was statistically significant (P = 0.0001 and P = 0.0004, respectively), RCCs carrying VHL alterations showed, in nine cases (12%), mutations at a hot spot involving a thymine repeat (ATT.TTT) in exon 2, Tumor staging was critical to the VHL mutation/hypermethylation detection rate in CCRCCs shown by separate evaluation of patients from medical centers in Munich, Heidelberg, and Mainz. The spectrum of pT(1), pT(2), and pT(3) CCRCCs and the VHL mutation/hypermethylation detection rate varied among these three groups, Altogether, VHL alterations were significantly associated with pT(3) CCRCCs (P = 0.009), This is the first evidence of frequent somatic VHL mutations at a particular site within exon 2 and an association of VHL mutations/hypermethylations with a standard prognostic factor. C1 Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70376 Stuttgart, Germany. TUM, Inst Pathol, Lab Mol Pathol, D-81675 Munich, Germany. NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Ft Detrick, MD 21702 USA. Univ Mainz, Dept Med 3, D-55131 Mainz, Germany. Univ Ljubljana, Inst Pathol, Mol Genet Lab, Ljubljana 1000, Slovenia. Univ Heidelberg, Dept Urol, D-69120 Heidelberg, Germany. Univ Mainz, Dept Urol, D-55131 Mainz, Germany. Univ Mainz, Inst Pathol, D-55131 Mainz, Germany. Univ Witten Herdecke, Inst Pathol, D-42283 Wuppertal, Germany. Bioscientia Inst, Dept Mol Genet, D-55218 Ingelheim, Germany. RP Brauch, H (reprint author), Dr Margarete Fischer Bosch Inst Clin Pharmacol, Auerbachstr 112, D-70376 Stuttgart, Germany. NR 41 TC 146 Z9 153 U1 2 U2 5 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 2000 VL 60 IS 7 BP 1942 EP 1948 PG 7 WC Oncology SC Oncology GA 301YK UT WOS:000086338000028 PM 10766184 ER PT J AU Wistuba, II Behrens, C Virmani, AK Mele, G Milchgrub, S Girard, L Fondon, JW Garner, HR McKay, B Latif, F Lerman, MI Lam, S Gazdar, AF Minna, JD AF Wistuba, II Behrens, C Virmani, AK Mele, G Milchgrub, S Girard, L Fondon, JW Garner, HR McKay, B Latif, F Lerman, MI Lam, S Gazdar, AF Minna, JD TI High resolution chromosome 3p allelotyping of human lung cancer and preneoplastic/preinvasive bronchial epithelium reveals multiple, discontinuous sites of 3p allele loss and three regions of frequent breakpoints SO CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR GENE; SQUAMOUS-CELL CARCINOMA; HOMOZYGOUS DELETION; FHIT GENE; HUMAN SEMAPHORIN; FORMER SMOKERS; LINE U2020; SHORT ARM; 3P21.3; LESIONS AB Allele loss involving chromosome arm 3p is one of the most frequent and earliest known genetic events in lung cancer pathogenesis and may affect several potential tumor suppressor gene regions. To Further study the role of chromosome 3p allele loss in the pathogenesis of lung cancer, we performed high resolution toss of heterozygosity (LOH) studies on 97 lung cancer and 54 preneoplastic/preinvasive microdissected respiratory epithelial samples using a panel of 28 3p markers. Allelic losses of 3p were detected in 96% of the lung cancers and in 78% of the preneoplastic/ preinvasive lesions. The allele losses were often multiple and discontinuous, with areas of LOH interspersed with areas of retention of heterozygosity, Most small cell lung carcinomas (91%) and squamous cell carcinomas (95%) demonstrated larger 3p segments of allele loss, whereas most (71%) of the adenocarcinomas and preneoplastic/preinvasive lesions had smaller chromosome areas of 3p allele loss. There was a progressive increase in the frequency and size of 3p allele loss regions with increasing severity of histopathological preneoplastic/preinvasive changes. In analyses of the specific parental allele lost comparing 42 preneoplastic/preinvasive foci with those lost in the lung cancer in the same patient (n = 10), the same parental allele was lost in 88% of 244 comparisons for 28 3p markers (P = 1.2 x 10(-36) for this occurring by chance). This indicates the occurrence of allele-specific loss in these foci similar to that seen in the tumor by a currently unknown mechanism. Analysis of all of the data indicated multiple regions of localized 3p allele loss including telomere-D3S1597, D3S1111-D3S2432, D3S2432-D3S1537, D3S1537, D3S1537-D3S1612, D3S4604/Luca19.1-D3S4622/Luca4.1, D3S4624/Luca2.1, D3S4624/ Luca2.1-D3S1582, D3S1766, D3S1234-D3S1300 (FHIT/FRA3B region centered on D3S1300), D3S1284-D3S1577 (U2020/DUTT1 region centered on D351274), and D3S1511-centromere. A panel of six markers in the 600-kb 3p21.3 deletion region showed loss in 77% of the lung cancers, 70% of normal or preneoplastic/preinvasive lesions associated with lung cancer, and 49% of 47 normal, mildly abnormal, or preneoplastic/preinvasive lesions found in smokers without lung cancer; however, loss was seen in 0% of 18 epithelial samples from seven never smokers. The 600-kh 3p21.3 region and the 3p14.2 (FHIT/FRA3B) and 3p12 (U2020/DUTT1) regions were common, independent sites of breakpoints (retention of heterozygosity by some markers and LOH by other markers in the immediate region), We conclude that 3p allele loss Is nearly universal in lung cancer pathogenesis; involves multiple, discrete, 3p LOH sites that often show a "discontinuous LOH" pattern in individual tumors; occurs in preneoplastic/preinvasive lesions in smokers with and without lung cancer (multiple lesions often Lose the same parental allele); frequently involves breakpoints in at least three very small defined genomic regions; and appears to have allele Loss and breakpoints first occurring in the 600-kb 3p21.3 region. These findings are consistent with previously reported LOH studies in a variety of tumors showing allele loss occurring by mitotic recombination and induced by oxidative damage. C1 Univ Texas, SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75390 USA. Dept Pathol, Dallas, TX 75390 USA. Dept Internal Med & Pharmacol, Dallas, TX 75390 USA. McDermott Ctr Human Growth & Dev, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Ctr Biomed Invent, Dallas, TX 75390 USA. Pontificia Univ Catolica Chile, Dept Pathol, Santiago, Chile. British Columbia Canc Agcy, Vancouver, BC V5Z 355, Canada. Univ Birmingham, Dept Paediat, Birmingham B15 2TT, W Midlands, England. Univ Birmingham, Dept Child Hlth, Birmingham B15 2TT, W Midlands, England. NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Frederick, MD 21702 USA. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. RP Minna, JD (reprint author), Univ Texas, SW Med Ctr, Hamon Ctr Therapeut Oncol Res, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. FU NCI NIH HHS [CA71618, N01CN45580, P50-CA70907] NR 70 TC 304 Z9 325 U1 4 U2 11 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 2000 VL 60 IS 7 BP 1949 EP 1960 PG 12 WC Oncology SC Oncology GA 301YK UT WOS:000086338000029 PM 10766185 ER PT J AU Iordanov, MS Ryabinina, OP Wong, J Dinh, TH Newton, DL Rybak, SM Magun, BE AF Iordanov, MS Ryabinina, OP Wong, J Dinh, TH Newton, DL Rybak, SM Magun, BE TI Molecular determinants of apoptosis induced by the cytotoxic ribonuclease onconase: Evidence for cytotoxic mechanisms different from inhibition of protein synthesis SO CANCER RESEARCH LA English DT Article ID CYTOCHROME-C RELEASE; PERMEABILITY TRANSITION PORE; RIBOTOXIC STRESS-RESPONSE; POLY(ADP-RIBOSE) POLYMERASE; ANTITUMOR RIBONUCLEASE; ISOLATED-MITOCHONDRIA; CASPASE ACTIVATION; DEATH RECEPTORS; CANCER-THERAPY; MICE DEFICIENT AB Cytotoxic endoribonucleases (RNases) possess a potential for use in cancer therapy. However, the molecular determinants of RNase-induced cell death are not well understood. In this work, we identify such determinants of the cytotoxicity induced by onconase, an amphibian cytotoxic RNase. Onconase displayed a remarkable specificity for tRNA in vivo, leaving rRNA and mRNA apparently undamaged. Onconase-treated cells displayed apoptosis-associated cell blebbing, nuclear pyknosis and fragmentation (karyorrhexis), DNA fragmentation, and activation of caspase-3-like activity. The cytotoxic action of onconase correlated with inhibition of protein synthesis. However, we present evidence for the existence of a mechanism of onconase-induced apoptosis that is independent of inhibition of protein synthesis. The caspase inhibitor benzyloxycarbonyl-VaI-Ala-Asp(OMe) fluoromethyl ketone (zVADfmk), at concentrations that completely prevent apoptosis and caspase activation induced by ligation of the death receptor Fas, had only a partial protective effect on onconase-induced cell death. The proapoptotic activity of the p53 tumor suppressor protein and the Fas ligand/Fas/Fas-associating protein with death domain (FADD)/caspase-8 proapoptotic cascade were not required for onconase-induced apoptosis. Procaspases-9, -3, and -7 were processed in onconase-treated cells, suggesting the involvement of the mitochondrial apoptotic machinery in onconase-induced apoptosis. However, the onconase-induced activation of the caspase-9/caspase-3 cascade correlated with atypically little release of cytochrome c from mitochondria. In turn, the low levels of cytochrome c released from mitochondria correlated with a lack of detectable translocation of proapoptotic Bax from the cytosol onto mitochondria in response to onconase. This suggests the possibility of involvement of a different, potentially Bax- and cytochrome c-independent mechanism of caspase-9 activation in onconase-treated tells. As one possible mechanism, we demonstrate that procaspase-9 is released from mitochondria in onconase-treated cells. A detailed understanding of the molecular determinants of the cytotoxic action of onconase could provide means of positive or negative therapeutic modulation of the activity of this potent anticancer agent. C1 Oregon Hlth Sci Univ, Dept Cell & Dev Biol, Portland, OR 97201 USA. Sci Applicat Int Corp, Intramural Res Support Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Discovery Res & Dev, Dev Therapeut Program,Div Canc Treatment & Diag, Frederick, MD 21702 USA. RP Magun, BE (reprint author), Oregon Hlth Sci Univ, Dept Cell & Dev Biol, 3181 SW Sam Jackson Pk Rd,Mail Code L215, Portland, OR 97201 USA. FU NCI NIH HHS [CA-39360]; NIEHS NIH HHS [ES-08456] NR 68 TC 108 Z9 119 U1 0 U2 5 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 2000 VL 60 IS 7 BP 1983 EP 1994 PG 12 WC Oncology SC Oncology GA 301YK UT WOS:000086338000033 PM 10766189 ER PT J AU Lunn, RM Helzlsouer, KJ Parshad, R Umbach, DM Harris, EL Sanford, KK Bell, DA AF Lunn, RM Helzlsouer, KJ Parshad, R Umbach, DM Harris, EL Sanford, KK Bell, DA TI XPD polymorphisms: effects on DNA repair proficiency SO CARCINOGENESIS LA English DT Article ID PIGMENTOSUM GROUP-D; PHASE-X-IRRADIATION; XERODERMA-PIGMENTOSUM; COCKAYNE-SYNDROME; CHROMATID DAMAGE; EXCISION-REPAIR; REPAIR/TRANSCRIPTION GENE; CLINICAL-FEATURES; BREAST-CANCER; TRICHOTHIODYSTROPHY AB XPD codes for a DNA helicase involved in transcription and nucleotide excision repair. Rare XPD mutations diminish nucleotide excision repair resulting in hypersensitivity to UV light and increased risk of skin cancer. Several polymorphisms in this gene have been identified but their impact on DNA repair is not known. We compared XPD genotypes at codons 312 and 751 with DNA repair proficiency in 31 women. XPD genotypes were measured by PCR-RFLP, DNA repair proficiency was assessed using a cytogenetic assay that detects X-ray induced chromatid aberrations (breaks and gaps). Chromatid aberrations were scored per 100 metaphase cells following incubation at 37 degrees C (1.5 h after irradiation) to allow for repair of DNA damage. Individuals with the Lys/Lys codon 751 XPD genotype had a higher number of chromatid aberrations (132/100 metaphase cells) than those having a 751Gln allele (34/100 metaphase cells). Individuals having greater than 60 chromatid breaks plus gaps were categorized as having sub-optimal repair. Possessing a Lys/Lys751 genotype increased the risk of sub-optimal DNA repair (odds ratio 7.2, 95% confidence interval = 1.01-87.7). The Asp312Asn XPD polymorphism did not appear to affect DNA repair proficiency. These results suggest that the Lys751 (common) allele may alter the XPD protein product resulting in suboptimal repair of X-ray -induced DNA damage. C1 NIEHS, Lab Computat Biol & Risk Anal, NIH, Res Triangle Pk, NC 27709 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Howard Univ, Coll Med, Dept Pathol, Washington, DC 20059 USA. NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. NCI, Cellular & Mol Biol Lab, Div Canc Etiol, NIH, Bethesda, MD 20892 USA. RP Bell, DA (reprint author), NIEHS, Lab Computat Biol & Risk Anal, NIH, POB 12233,MD C3-03, Res Triangle Pk, NC 27709 USA. FU NCI NIH HHS [CA36390] NR 27 TC 338 Z9 369 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 2000 VL 21 IS 4 BP 551 EP 555 DI 10.1093/carcin/21.4.551 PG 5 WC Oncology SC Oncology GA 308ZH UT WOS:000086742400003 PM 10753184 ER PT J AU Delfino, RJ Sinha, R Smith, C West, J White, E Lin, HJ Liao, SY Gim, JSY Ma, HL Butler, J Anton-Culver, H AF Delfino, RJ Sinha, R Smith, C West, J White, E Lin, HJ Liao, SY Gim, JSY Ma, HL Butler, J Anton-Culver, H TI Breast cancer, heterocyclic aromatic amines from meat and N-acetyltransferase 2 genotype SO CARCINOGENESIS LA English DT Article ID SLOW ACETYLATOR MUTATIONS; METABOLIC-ACTIVATION; GENETIC POLYMORPHISMS; CIGARETTE-SMOKING; MAMMARY-GLAND; HISTORY QUESTIONNAIRE; VARYING DEGREES; COOKING METHOD; COOKED FOODS; RISK AB Breast cancer risk has been hypothesized to increase with exposure to heterocyclic aromatic amines (HAAs) formed from cooking meat at high temperature. HAAs require enzymatic activation to bind to DNA and initiate carcinogenesis. N-acetyltransferase 2 (NAT2) enzyme activity may play a role, its rate determined by a polymorphic gene. We examined the effect of NAT2 genetic polymorphisms on breast cancer risk from exposure to meat by cooking method, doneness and estimated HAA [2-amino-l-methyl-6-phenylimidazole[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5 -f]quinoxaline (MeIQx)) and 2-amino-3,4,8-trimethylimidazo[4,5-f] quinoxaline (DiMeIQx)] intake. Women were recruited with suspicious breast masses and questionnaire data were collected prior to biopsy to blind subjects and interviewers to diagnoses. For 114 cases with breast cancer and 280 controls with benign breast disease, NAT2 genotype was determined using allele-specific PCR amplification to detect slow acetylator mutations, HAAs were estimated from interview data on meat type, cooking method and doneness, combined with a quantitative HAA database, Logistic regression models controlled for known risk factors, first including all controls, then 108 with no or low risk (normal breast or no hyperplasia) and finally 149 with high risk (hyperplasia, atypical hyperplasia, complex fibroadenomas). Meat effects were examined within NAT2 strata to assess interactions. We found no association between NAT2 and breast cancer, These Californian women ate more white than red meat (control median 46 versus 8 g/day), There were no significant associations of breast cancer with red meat for any doneness, White meat was significantly protective (>67 versus <26 g/day, OR 0.46, 95% CI 0.23-0.94, P for trend = 0.02), as was chicken, including well done, pan fried and barbecued chicken, MeIQx and DiMeIQx were not associated with breast cancer. A protective effect of PhIP was confounded after controlling for well done chicken. Results were unchanged using low or high risk controls or dropping 30 in situ cases. There was no interaction between NAT2 and HAAs. These findings do not support a role for HAAs from meat or NAT2 in the etiology of breast cancer. Further research is needed to explain the white meat association. C1 Univ Calif Irvine, Coll Med, Dept Med, Div Epidemiol, Irvine, CA 92697 USA. NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. Breast Care Ctr Orange, Orange, CA USA. Saddleback Breast Ctr, Laguna Hills, CA USA. Univ Calif Los Angeles, Harbor Med Ctr, Div Med Genet, Torrance, CA 90509 USA. Univ Calif Irvine, Coll Med, Dept Pathol, Irvine, CA 92697 USA. Univ Calif Irvine, Coll Med, Dept Surg, Irvine, CA 92697 USA. RP Delfino, RJ (reprint author), Univ Calif Irvine, Coll Med, Dept Med, Div Epidemiol, 224 Irvine Hall, Irvine, CA 92697 USA. RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 FU NCI NIH HHS [1R01CA66782, 1R01CA73403] NR 65 TC 75 Z9 78 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 2000 VL 21 IS 4 BP 607 EP 615 DI 10.1093/carcin/21.4.607 PG 9 WC Oncology SC Oncology GA 308ZH UT WOS:000086742400012 PM 10753193 ER PT J AU Nakajima, T Kamijo, Y Usuda, N Liang, Y Fukushima, Y Kametani, K Gonzalez, FJ Aoyama, T AF Nakajima, T Kamijo, Y Usuda, N Liang, Y Fukushima, Y Kametani, K Gonzalez, FJ Aoyama, T TI Sex-dependent regulation of hepatic peroxisome proliferation in mice by trichloroethylene via peroxisome proliferator-activated receptor alpha (PPAR alpha) SO CARCINOGENESIS LA English DT Article ID RAT-LIVER; SPECIES-DIFFERENCES; FATTY-ACIDS; PURIFICATION; PROTEIN; DEHYDROGENASE; MITOCHONDRIAL; EXPRESSION; WY-14,643; ENZYMES AB The mechanism of trichloroethylene-induced liver peroxisome proliferation and the sex difference in response was investigated using wild-type Sv/129 and peroxisome proliferator-activated receptor alpha (PPAR alpha)-null mice. Trichloroethylene treatment (0.75 g/kg for 2 weeks by gavage) resulted in liver peroxisome proliferation in wild-type mice, but not in PPAR alpha-null mice, suggesting that trichloroethylene-induced peroxisome proliferation is primarily mediated by PPAR alpha. No remarkable sex difference was observed in induction of peroxisome proliferation, as measured morphologically, but a markedly higher induction of several enzymes and PPAR alpha protein and mRNA was found in males. On the other hand, trichloroethylene induced liver cytochrome P450 2E1, the principal enzyme responsible for metabolizing trichloroethylene to chloral hydrate, only in males, which resulted in similar expression levels in both sexes after the treatment. Trichloroethylene influenced neither the level of catalase, an enzyme involved in the reduction of oxidative stress, nor aldehyde dehydrogenase, the main enzyme catalyzing the conversion to trichloroacetic acid. These results suggest that trichloroethylene treatment causes a male-specific PPAR alpha-dependent increase in cellular oxidative stress. C1 Shinshu Univ, Sch Med, Dept Hyg, Matsumoto, Nagano 3908621, Japan. Shinshu Univ, Sch Med, Dept Internal Med 2, Matsumoto, Nagano 3908621, Japan. Shinshu Univ, Sch Med, Dept Anat 1, Matsumoto, Nagano 3908621, Japan. Shinshu Univ, Sch Med, Dept Aging Biochem, Matsumoto, Nagano 3908621, Japan. Shinshu Univ, Sch Med, Gen Res Lab, Matsumoto, Nagano 3908621, Japan. NCI, Lab Metab, Bethesda, MD 20892 USA. RP Nakajima, T (reprint author), Shinshu Univ, Sch Med, Dept Hyg, Matsumoto, Nagano 3908621, Japan. NR 33 TC 40 Z9 42 U1 1 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 2000 VL 21 IS 4 BP 677 EP 682 DI 10.1093/carcin/21.4.677 PG 6 WC Oncology SC Oncology GA 308ZH UT WOS:000086742400022 PM 10753203 ER PT J AU Shane, BS de Boer, J Watson, DE Haseman, JK Glickman, BW Tindall, KR AF Shane, BS de Boer, J Watson, DE Haseman, JK Glickman, BW Tindall, KR TI LacI mutation spectra following benzo[a]pyrene treatment of Big Blue (R) mice SO CARCINOGENESIS LA English DT Article ID DOSE-DEPENDENT DIFFERENCES; (+)-ANTI-BENZOPYRENE DIOL EPOXIDE; AROMATIC HYDROCARBON CARCINOGENESIS; MOUSE SKIN PAPILLOMAS; ENDOGENOUS APRT GENE; HAMSTER OVARY CELLS; HA-RAS GENE; TRANSGENIC MICE; ESCHERICHIA-COLI; DNA-ADDUCTS AB The mutation spectrum of the lad gene from the liver of C57B16 Big Blue(R) transgenic mice treated with benzo[a]pyrene (B[a]P) has been compared with the spectrum of spontaneous mutations observed in the liver of untreated Big Blue(R) mice, Mice were treated with B[a]P for 3 days followed by a partial hepatectomy one day after the last injection. Liver tissue was removed for analysis at hepatectomy and, again, 3 days later at the time of sacrifice. Earlier, we reported that the lacI mutant frequency in these B[a]P-treated mice was elevated in the liver both at the time of hepatectomy and at sacrifice; however, a statistically significant increase in the mutant frequency was observed only at sacrifice. In this study, the DNA sequence spectra of lad mutations observed in the liver of B[a]P-treated Big Blue(R) mice at hepatectomy and at time of sacrifice were compared with each other and with the spectrum of spontaneous liver mutations. No differences were observed between the two B[a]P-treatment spectra, However, mutation frequencies of both GC->TA and GC->CG at the time of hepatectomy and at sacrifice were significantly elevated compared with the spontaneous frequency of these same transversions, Also, the frequency of AT->TA transversions was significantly higher than the spontaneous frequency at the time of hepatectomy but not at sacrifice. The frequency of all other classes of mutations scored was not significantly different from the frequency of these same events in the spontaneous spectra, These data support the view that B[a]P treatment results in the induction of GC->TA and GC->CG transversions within 1 day of the last injection and they provide insights regarding the relative roles of benzo[a]pyrene-7,8-diol-9,10-epoxide and radical cations of B[a]P in B[a]P-induced mutagenesis in vivo. Finally, these data provide evidence for B[a]P-induced mutagenesis under conditions where no statistical increase in mutant frequency could be shown. C1 NIEHS, Mol Mutagenesis Grp, Lab Environm Carcinogenesis & Mutagenesis, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. Univ Victoria, Ctr Environm Hlth, Victoria, BC V8W 2Y2, Canada. Louisiana State Univ, Inst Environm Studies, Baton Rouge, LA 70803 USA. RP Tindall, KR (reprint author), NIEHS, Mol Mutagenesis Grp, Lab Environm Carcinogenesis & Mutagenesis, POB 12233, Res Triangle Pk, NC 27709 USA. FU NCRR NIH HHS [RR 10230-01] NR 87 TC 33 Z9 35 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 2000 VL 21 IS 4 BP 715 EP 725 DI 10.1093/carcin/21.4.715 PG 11 WC Oncology SC Oncology GA 308ZH UT WOS:000086742400027 PM 10753208 ER PT J AU Tsutsui, T Tamura, Y Hagiwara, M Miyachi, T Hikiba, H Kubo, C Barrett, JC AF Tsutsui, T Tamura, Y Hagiwara, M Miyachi, T Hikiba, H Kubo, C Barrett, JC TI Induction of mammalian cell transformation and genotoxicity by 2-methoxyestradiol, an endogenous metabolite of estrogen SO CARCINOGENESIS LA English DT Article ID HAMSTER-EMBRYO CELLS; CATECHOL ESTROGENS; NEOPLASTIC TRANSFORMATION; ANEUPLOIDY INDUCTION; DIETHYLSTILBESTROL; CARCINOGENESIS; TUBULIN; CULTURE; GROWTH AB 2-Methoxyestradiol (2-MeOE2) is an endogenous metabolite of 17 beta-estradiol and a proposed inhibitor of tumor growth and angiogenesis. However, 2-MeOE2 is also an inhibitor of microtubule assembly and other microtubule inhibitors, e.g, colcemid and diethylstilbestrol, induce aneuploidy and cell transformation in cultured mammalian cells. To assess the in vitro carcinogenicity and related activity of 2-MeOE2, the abilities of this metabolite to induce cell transformation and genetic effects were studied simultaneously using Syrian hamster embryo (SHE) fibroblasts, Growth of these cells was reduced by treatment with 2-MeOE2 at 0.1-1.0 mu g/ml in a concentration-dependent manner. Treatment of SHE cells with 2-MeOE2 at 0.3 or 1.0 mu g/ml for 2-48 h also resulted in a concentration- and treatment time-related increase in the mitotic index and the percentage of multinucleated cells, Treatment with 2-MeOE2 at 0.1-1.0 mu g/ml for 48 h induced a statistically significant increase in the frequencies of morphological transformation of SHE cells in a concentration-dependent manner. A statistically significant increase in the frequencies of somatic mutations at the Na+/K+ ATPase or hprt locus was also observed in cells treated with 2-MeOE2 for 48 h at 0.1 or 0.3 mu g/ml, respectively. Treatment of SHE cells with 2-MeOE2 at 0.3 or 1.0 mu g/ml for 24 h induced chromosome aberrations, mainly breaks, exchanges and chromosome pulverization, The incidence of chromosome aberrations was not affected by co-treatment with alpha-naphthoflavone, an inhibitor of 2-hydroxylase that inhibits oxidative conversion of 2-MeOE2 to 2-hydroxyestradiol, but the incidence was slightly increased by co-treatment with L-ascorbic acid. Numerical chromosomal changes in the near diploid range and in the tetraploid and near tetraploid ranges were also detected in 2-MeOE2-treated cells. These findings indicate that 2-MeOE2 has cell transforming and genotoxic activities in cultured mammalian cells and potential carcinogenic activity. C1 NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. Nippon Dent Univ, Sch Dent Tokyo, Dept Pharmacol, Tokyo 1028159, Japan. RP Barrett, JC (reprint author), NIEHS, Mol Carcinogenesis Lab, POB 12233, Res Triangle Pk, NC 27709 USA. NR 30 TC 32 Z9 33 U1 1 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 2000 VL 21 IS 4 BP 735 EP 740 DI 10.1093/carcin/21.4.735 PG 6 WC Oncology SC Oncology GA 308ZH UT WOS:000086742400029 PM 10753210 ER PT J AU Peters, JM Rusyn, I Rose, ML Gonzalez, FJ Thurman, RG AF Peters, JM Rusyn, I Rose, ML Gonzalez, FJ Thurman, RG TI Peroxisome proliferator-activated receptor alpha is restricted to hepatic parenchymal cells, not Kupffer cells: implications for the mechanism of action of peroxisome proliferators in hepatocarcinogenesis SO CARCINOGENESIS LA English DT Article ID RAT-LIVER; HEPATOCYTE PROLIFERATION; HYPOLIPIDEMIC DRUG; WY-14,643; CLOFIBRATE; APOPTOSIS; NAFENOPIN; INCREASES; GENE AB Peroxisome proliferators increase hepatocyte proliferation and cause liver tumors in rodents, yet the mechanism of action is not understood. Based on studies with null mice it is known that peroxisome proliferator-activated receptor-alpha (PPAR alpha) is involved. There is also evidence that Kupffer cells play a central role in peroxisome proliferator-induced carcinogenesis, most likely via mechanisms involving increases in superoxide, activation of nuclear factor kappa B and production of tumor necrosis factor-alpha (TNF alpha), However, it is not known whether PPAR alpha is constitutively expressed in Kupffer cells. Therefore, the expression of PPAR isoforms in rat Kupffer and parenchymal cells was examined. Kupffer cells and hepatocytes of >99 % purity mere isolated from rats fed either a control diet or one containing 0.1% WY-14,643 for 1 week. Protein and RNA were obtained and PPAR expression was analyzed using northern and western blots. PPAR alpha, PPAR beta and PPAR gamma mRNA was detected in purified hepatocytes, In Kupffer cells, mRNA encoding PPAR gamma was present while transcripts for PPAR alpha and PPAR beta were not detected, Immunoblots were consistent with the results found by northern analysis. Moreover, when Kupffer cells from wild-type or PPAR alpha-null mice were treated with WY-14,643 in vitro, superoxide production was similar. Combined, these results show that PPAR alpha is expressed in rat parenchymal cells but not in Kupffer cells. These data are consistent with the hypothesis that parenchymal cells respond to Kupffer cell-derived TNF alpha via mechanisms dependent on PPARa within the parenchymal cells. C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Dept Pharmacol, Hepatobiol & Toxicol Lab, Chapel Hill, NC 27599 USA. RP Peters, JM (reprint author), Penn State Univ, Ctr Mol Toxicol, Fenske Lab 226, University Pk, PA 16802 USA. RI Peters, Jeffrey/D-8847-2011; Rusyn, Ivan/S-2426-2016 NR 23 TC 94 Z9 95 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 2000 VL 21 IS 4 BP 823 EP 826 DI 10.1093/carcin/21.4.823 PG 4 WC Oncology SC Oncology GA 308ZH UT WOS:000086742400041 PM 10753222 ER PT J AU Brightman, MW Kaya, M AF Brightman, MW Kaya, M TI Permeable endothelium and the interstitial space of brain SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Article DE fenestrated vessel induction; brain interstitial clefts; extracellular solute flow in brain ID CENTRAL-NERVOUS-SYSTEM; GAP JUNCTION COMMUNICATION; RAT-BRAIN; GROWTH-FACTOR; PLASMINOGEN-ACTIVATOR; MICROVASCULAR PERMEABILITY; EXTRACELLULAR-MATRIX; CEREBROSPINAL-FLUID; BASEMENT-MEMBRANES; SUBARACHNOID SPACE AB 1. Fenestrated vessels can be reversibly induced in brain by agents that stimulate urokinase production. This plasminogen activator, like vascular endothelial growth factor and metalloproteinases, is secreted by tumor cells and may account for induction of fenestrated vessels. Why only some of the brain's barrier vessels are converted to fenestrated vessels is unknown. 2. The structures responsible for the filtering of solutes by fenestrated vessels may be the same as those of continuous, less permeable vessels: the glycocalyx on the surfaces of the endothelial cells and the subendothelial basal lamina. 3. Solutes leaving the cerebral ventricles immediately enter the interstitial clefts between the cells lining the ventricles. A fraction of a variety of solutes, injected into CSF compartments, is retained by subendothelial basal lamina, from which the solutes may be released in a regulated way. 4. The brain's CSF and interstitial clefts are the conduits for nonsynaptic volume transmission of diffusible signals, e.g., ions, neurotransmitters, and hormones. This type of transmission could be abetted by a parallel, cell-to-cell volume transmission mediated by gap junctions between astrocytes bordering CSF compartments and parenchymal astrocytes. 5. The width and contents of the interstitial clefts in fetal brain permit cell migration and outgrowth of neurites. The contents of the narrower and different interstitial clefts of mature brain permit solute convection but must be enzymatically degraded in order for cells to migrate through it. C1 NIH, Neurobiol Lab, Bethesda, MD 20892 USA. RP Brightman, MW (reprint author), NIH, Neurobiol Lab, Bldg 36,Room 2A-21, Bethesda, MD 20892 USA. NR 70 TC 20 Z9 20 U1 1 U2 4 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 2000 VL 20 IS 2 BP 111 EP 130 DI 10.1023/A:1006944203934 PG 20 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA 283ET UT WOS:000085263700001 PM 10696505 ER PT J AU Rapoport, SI AF Rapoport, SI TI Osmotic opening of the blood-brain barrier: Principles, mechanism, and therapeutic applications SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Article DE arabinose; mannitol; blood-brain barrier; brain; drug; chemotherapy; osmosis; shrinkage; permeability; tumor; bulk flow; tight junctions; capillary ID POSITRON EMISSION TOMOGRAPHY; CENTRAL-NERVOUS-SYSTEM; RAT-BRAIN; INTRACAROTID INJECTION; HYPEROSMOLAR MANNITOL; CEREBRAL ENDOTHELIUM; TIGHT JUNCTIONS; CELL-ADHESION; IN-VITRO; DISRUPTION AB 1. Osmotic opening of the blood-brain barrier by intracarotid infusion of a hypertonic arabinose or mannitol solution is mediated by vasodilatation and shrinkage of cerebrovas cular endothelial cells, with widening of the interendothelial tight junctions to an estimated radius of 200 Angstrom. The effect may be facilitated by calcium-mediated contraction of the endothelial cytoskeleton. 2. The marked increase in apparent blood-brain barrier permeability to intravascular substances (10-fold for small molecules) following the osmotic procedure is due to both increased diffusion and bulk fluid how across the tight junctions. The permeability effect is largely reversed within 10 min. 3. In experimental animals, the osmotic method has been used to grant wide access to the brain of water-soluble drugs, peptides, antibodies, boron compounds for neutron capture therapy, and viral vectors for gene therapy. The method also has been used together with anticancer drugs to treat patients with metastatic or primary brain tumors, with some success and minimal morbidity. C1 NIA, Sect Brain Physiol & Metab, NIH, Bethesda, MD 20892 USA. RP Rapoport, SI (reprint author), NIA, Sect Brain Physiol & Metab, NIH, Bethesda, MD 20892 USA. EM sir@helix.nih.gov NR 97 TC 190 Z9 199 U1 4 U2 30 PU SPRINGER/PLENUM PUBLISHERS 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 2000 VL 20 IS 2 BP 217 EP 230 DI 10.1023/A:1007049806660 PG 14 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA 283ET UT WOS:000085263700007 PM 10696511 ER PT J AU Okayama, Y AF Okayama, Y TI Mast cell matrix interactions SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Editorial Material ID ADHESION MOLECULES; FIBRONECTIN; INTEGRINS; VITRONECTIN; EXPRESSION C1 NIH, Lab Allerg Dis, Bethesda, MD 20892 USA. RP Okayama, Y (reprint author), NIH, Lab Allerg Dis, Bldg 10,Room 11C206,10 Ctr Dr MSC 1881, Bethesda, MD 20892 USA. NR 20 TC 6 Z9 6 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0954-7894 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD APR PY 2000 VL 30 IS 4 BP 455 EP 457 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA 312EP UT WOS:000086930500001 PM 10718840 ER PT J AU Goldstein, DS AF Goldstein, DS TI A new sign of sympathetic neurocirculatory failure: premature ventricular contraction as a "one-beat Valsalva maneuver" SO CLINICAL AUTONOMIC RESEARCH LA English DT Article DE sympathetic nervous system; premature ventricular contraction; extrasystole; dysautonomia; autonomic nervous system; trimethaphan ID HUMANS AB Sympathetic neurocirculatory failure (SNF) features orthostatic hypotension and abnormal beat-to-beat blood pressure (BP) responses to the Valsalva maneuver. This article describes a new sign of SNF, based on changes in BP after premature ventricular contractions (PVCs), Records of supine beat-to-beat BP at rest were reviewed from 22 patients with SNF and 52 control subjects, Records were also taken during intravenous infusion of the ganglion blocker trimethaphan from 38 control subjects. In all 10 control subjects who had PVCs, after the postextrasystolic beat, mean arterial pressure increased progressively to levels higher than before the PVC, peaking at about the eighth beat. In contrast, in all 13 patients with SNF who had PVCs, after the postextrasystolic beat, BP decreased to less than baseline and then increased gradually back to baseline. In all 3 control subjects who had at least one PVC before trimethaphan infusion and another during trimethaphan infusion, the post-PVC pressure pattern during trimethaphan infusion resembled that in SNF patients. Because of a brief increase in sympathetic cardiovascular outflows, after a PVC, BP increases progressively to greater than pre-PVC values, mimicking the pressure overshoot after release of the Valsalva maneuver. Just as the absence of the overshoot of BP after release of the Valsalva maneuver supports a diagnosis of SNF, so does the absence of the overshoot after a PVC. C1 NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, NIH, 10 Ctr Dr,MSC-1620,Bldg 10,Room 6N252, Bethesda, MD 20892 USA. NR 11 TC 8 Z9 8 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-9851 J9 CLIN AUTON RES JI Clin. Auton. Res. PD APR PY 2000 VL 10 IS 2 BP 63 EP 67 DI 10.1007/BF02279893 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 304BG UT WOS:000086462200004 PM 10823337 ER PT J AU Madden, T Tran, HT Beck, D Huie, R Newman, RA Pusztai, L Wright, JJ Abbruzzese, JL AF Madden, T Tran, HT Beck, D Huie, R Newman, RA Pusztai, L Wright, JJ Abbruzzese, JL TI Novel marine-derived anticancer agents: A phase I clinical, pharmacological, and pharmacodynamic study of dolastatin 10 (NSC 376128) in patients with advanced solid tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID ANTINEOPLASTIC AGENTS; CELL-LINES; INHIBITION; LYMPHOMA; GROWTH AB Dolastatin (DOLA)-10 is a pentapeptide isolated from the mollusc Dolabella auricularia with clinically promising antitumor activity documented in various in vitro and in vivo tumor models. The objectives of this Phase I study were to determine the maximum tolerated dose, evaluate toxic effects, and document any antitumor activity of this novel agent. Using an electrospray ionization mass spectroscopy system, we also characterized the clinical pharmacokinetics, pharmacodynamics, and metabolism of DOLA-10, The maximum tolerated dose was reached at 300 mu g/m(2), Granulocytopenia, the dose-limiting toxicity, was documented in 33% of the patients treated at that dose level. There were no episodes of thrombocytopenia or severe anemia (Hgb < 8), and no major nonhematological toxicity was observed. Stabilization of tumor growth was observed in four patients, but no objective responses were seen. Whereas a two-compartment model described the DOLA-10 plasma concentration-time data reasonably well, a three-compartment model consistently performed better. After a rapid distribution phase, DOLA-10 plasma levels declined with mean beta and gamma half-lives of 0.99 and 18.9 h, respectively. Significant interpatient and intrapatient variability in DOLA-10 plasma clearances was observed. The mean area under the concentration-time curve increased proportionally as the dose was escalated, but there was significant overlap between dose levels. The area under the concentration-time curve and the percentage of decline in neutrophils were correlated. A single DOLA-10 metabolite was detected in five patients. Unlike the in vitro studies of DOLA-10, the principal metabolite detected was an N-demethyl derivative, confirmed by mass spectroscopy. In all five subjects, the concentration of this metabolite never exceeded 2% of the simultaneously measured parent drug concentration. The available preclinical, pharmacological, and clinical data suggest that further study of escalated DOLA-10 dosing with cytokine support is warranted. C1 Univ Texas, MD Anderson Canc Ctr, Div Pharm, Houston, TX 77030 USA. NCI, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. RP Abbruzzese, JL (reprint author), Univ Texas, MD Anderson Canc Ctr, Div Pharm, Box 90,1515 Holcombe Blvd, Houston, TX 77030 USA. FU NCI NIH HHS [U01 CA62461] NR 17 TC 59 Z9 66 U1 1 U2 5 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 2000 VL 6 IS 4 BP 1293 EP 1301 PG 9 WC Oncology SC Oncology GA 307BL UT WOS:000086633500013 PM 10778954 ER PT J AU Messmann, RA Vitetta, ES Headlee, D Senderowicz, AM Figg, WD Schindler, J Michiel, DF Creekmore, S Steinberg, SM Kohler, D Jaffe, ES Stetler-Stevenson, M Chen, HC Ghetie, V Sausville, EA AF Messmann, RA Vitetta, ES Headlee, D Senderowicz, AM Figg, WD Schindler, J Michiel, DF Creekmore, S Steinberg, SM Kohler, D Jaffe, ES Stetler-Stevenson, M Chen, HC Ghetie, V Sausville, EA TI A phase I study of combination therapy with immunotoxins IgG-HD37-deglycosylated ricin A chain (dgA) and IgG-RFB4-dgA (Combotox) in patients with refractory CD19(+), CD22(+) B cell lymphoma SO CLINICAL CANCER RESEARCH LA English DT Article ID VASCULAR LEAK SYNDROME; FUSION TOXIN DAB486IL-2; HUMAN ENDOTHELIAL-CELLS; LARGE-SCALE PREPARATION; A-CHAIN; ANTI-CD22 IMMUNOTOXIN; MONOCLONAL-ANTIBODIES; PSEUDOMONAS EXOTOXIN; CONTINUOUS-INFUSION; SCID MICE AB This study used an 8-day continuous infusion regimen of a 1:1 mixture of two immunotoxins (ITs) prepared from deglycosylated ricin A chain (dgA) conjugated to monoclonal antibodies directed against CD22 (RFB4-dgA) and CD19 (HD37-dgA; Combotox) in a Phase I trial involving 22 patients dth refractory B cell lymphoma to determine the maximum tolerated dose, clinical pharmacology, and toxicity profile and to characterize any clinical responses. Adult patients received a continuous infusion of Combotox at 10, 20, or 30 mg/m(2)/192 h. No intrapatient dose escalation,vas permitted. Patients with greater than or equal to 50 circulating tumor cells (CTCs)/mm(3) in peripheral blood tolerated all doses without major toxicity. The maximum level of serum IT (C-max) achieved in this group was 345 ng/ml of RFB4-dgA and 660 ng/ml of HD37-dgA (1005 ng/ml of Combotox), In contrast, patients without CTCs (<50/mm(3)) had unpredictable clinical courses that included two deaths probably related to the IT. Additionally, patients exhibited a significant potential for association between mortality and a history of either autologous bone marrow or peripheral blood stem cell transplants (P-2 = 0.003) and between mortality and a history of radiation therapy (P-2 = 0.036). In patients with CTCs, prior therapies appeared to have little impact on toxicity. Subsequent evaluation of the ITs revealed biochemical heterogeneity between two lots of HD37-dgA. In addition, BD37-dgA thawed at the study site tended to contain significant particulates, which were not apparent in matched controls stored at the originating site. This suggests that a tendency to aggregate may hare resulted from shipping, storage, and handling of the IT that occurred prior to preparation for administration. It is not clear to what extent, if any, the aggregation of HD37-dgA IT was related to the encountered clinical toxicities: however, the potential to aggregate does suggest one possible basis for problems in our clinical experience with HD37-dgA and leads us to the conclusion that non-aggregate-forming formulations for these ITs should be pursued prior to future clinical trials. C1 NCI, Dev Therapeut Program, Clin Trials Unit, Med Branch, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. NCI, Dept Pharm, Bethesda, MD 20892 USA. NCI, Med Branch, Bethesda, MD 20892 USA. NCI, Biol Resources Branch, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Ctr Canc Immunobiol, Dallas, TX 75235 USA. NCI, Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, NIH, Frederick, MD 21702 USA. RP Messmann, RA (reprint author), NCI, Dev Therapeut Program, Clin Trials Unit, Med Branch, 10 Ctr Dr Bldg 10,Room 12N226, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 FU FDA HHS [FDR 001124-03] NR 43 TC 92 Z9 96 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 2000 VL 6 IS 4 BP 1302 EP 1313 PG 12 WC Oncology SC Oncology GA 307BL UT WOS:000086633500014 PM 10778955 ER PT J AU Kreitman, RJ Margulies, I Stetler-Stevenson, M Wang, QC FitzGerald, DJP Pastan, I AF Kreitman, RJ Margulies, I Stetler-Stevenson, M Wang, QC FitzGerald, DJP Pastan, I TI Cytotoxic activity of disulfide-stabilized recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) toward fresh malignant cells from patients with B-cell leukemias SO CLINICAL CANCER RESEARCH LA English DT Article ID PSEUDOMONAS EXOTOXIN-A; CHRONIC LYMPHOCYTIC-LEUKEMIA; HUMAN ENDOTHELIAL-CELLS; VASCULAR LEAK SYNDROME; PHASE-I; CONTINUOUS-INFUSION; ANTITUMOR-ACTIVITY; SINGLE-CHAIN; ANTI-TAC; DIPHTHERIA-TOXIN AB Chemical conjugates of anti-CD22 monoclonal antibodies and toxins have been used to treat CD22+ hematological malignancies. A. new anti-CD22 recombinant immunotoxin RFB4(dsFv)-PE38, composed of the Fv portion of the monoclonal antibody RFB4 fused to a truncated form of Pseudomonas exotoxin A, is being developed to target CD22+ tumor cells. To explore the potential clinical utility of this recombinant toxin in treating patients with B-cell malignancies, the fresh cells of patients were incubated ex vivo with RFB4(dsFv)-PE38. Specific cytotoxicity was demonstrated in the malignant cells of 25 of 28 patients with a variety of B-cell malignancies, including acute and chronic lymphocytic leukemias and large cell, mantle cell, and follicular lymphomas. The IC(50)s, the concentrations necessary for 50% inhibition of protein synthesis, were 3-10 ng/ml in five patients and 10-50 ng/ml in seven patients. Cytotoxicity correlated with cell death upon direct examination of the malignant cells. Significant cytotoxicity was observed with cells containing as few as 350 CD22 sites/cell. A more active derivative of RFB4(dsFv)-PE38, RFB4(dsFv)-PE38KDEL, was produced and was slightly to more than 10-fold more cytotoxic toward patient cells and about twice as toxic to mice. Thus, RFB4(dsFv)-PE38 was specifically cytotoxic toward malignant cells from patients with B-cell leukemias, These data support the testing of RFB4(dsFv)-PE38 in patients with CD22+ leukemias and lymphomas, which is presently under way. C1 NCI, Mol Biol Lab, Div Canc Biol, NIH, Bethesda, MD 20892 USA. NCI, Clin Pathol Lab, Div Canc Therapy, NIH, Bethesda, MD 20892 USA. RP Kreitman, RJ (reprint author), NCI, Mol Biol Lab, Div Canc Biol, NIH, 37-4E16,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 37 TC 78 Z9 82 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 2000 VL 6 IS 4 BP 1476 EP 1487 PG 12 WC Oncology SC Oncology GA 307BL UT WOS:000086633500039 PM 10778980 ER PT J AU Rehak, NN Cecco, SA Csako, G AF Rehak, NN Cecco, SA Csako, G TI Biochemical composition and electrolyte balance of "unstimulated" whole human saliva SO CLINICAL CHEMISTRY AND LABORATORY MEDICINE LA English DT Article DE whole human saliva; ionized calcium; electrolyte balance; anion gap; lactate dehydrogenase isoenzymes ID HUMAN-PAROTID SALIVA; ION-SELECTIVE ELECTRODES; IONIZED CALCIUM; SERUM AB The biochemical composition of "unstimulated" whole saliva was determined in healthy adult subjects. Based on their relative concentration, salivary analytes could be classified into three arbitrary categories: concentration lower than in serum (saliva/serum ratio < 0.5; 12 analytes), similar to serum (ratio = 0.5-1.5; five analytes), and higher than in serum (ratio > 1.5; five analytes). Consistent with local production, an elevated lactate dehydrogenase (LDH) activity in the saliva was associated with a non-serum like LDH isoenzyme pattern: LDH5 much greater than LDH4 > LDH3 much greater than LDH2 > LDH1. Compared with serum, the concentrations of hydrogen (as reflected in the pH), potassium and inorganic phosphorus were much higher (saliva/serum ratio greater than or equal to 3), whereas that of sodium, total magnesium, chloride, and total carbon dioxide were lower (saliva/serum ratio less than or equal to 0.3). The concentration of ionized calcium was similar in saliva and serum (saliva/serum ratio = 0.8), while ionized magnesium was unmeasurable in saliva. The salivary ionized calcium fraction was higher (0.76) than previously suggested (0.51). The difference between the main salivary cations (potassium, sodium), and anions (phosphate, chloride) was similar to serum (anion gap: 4 vs. 11 meq/l). Highly significant (p less than or equal to 0.012) correlations occured among salivary pH, dihydrophosphate, total calcium, and potassium. Our data suggest that calcium, potassium, chloride and phosphates are the major salivary complex-forming ions. The major compositional differences between serum and saliva show that saliva is not a passive "ultrafiltrate" of serum and salivary constituents may play a distinct physiological role. C1 Warren Grant Magnuson Clin Ctr, Clin Chem Serv, Dept Clin Pathol, NIH, Bethesda, MD 20892 USA. RP Rehak, NN (reprint author), Warren Grant Magnuson Clin Ctr, Clin Chem Serv, Dept Clin Pathol, NIH, Bethesda, MD 20892 USA. NR 33 TC 36 Z9 37 U1 3 U2 19 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 2000 VL 38 IS 4 BP 335 EP 343 DI 10.1515/CCLM.2000.049 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 344HR UT WOS:000088753600010 PM 10928655 ER PT J AU Lazarova, Z Hsu, R Briggaman, RA Yancey, KB AF Lazarova, Z Hsu, R Briggaman, RA Yancey, KB TI Fab fragments directed against laminin 5 induce subepidermal blisters in neonatal mice SO CLINICAL IMMUNOLOGY LA English DT Article DE autoimmunity; bullous disease; basement membrane; animal model ID EPIDERMAL BASEMENT-MEMBRANE; ANCHORING FILAMENTS; ALPHA-3 CHAIN; AUTOANTIBODIES; EPILIGRIN; ADHESION; INTEGRIN; LIGAND; HEMIDESMOSOMES; ACANTHOLYSIS AB Patients with one form of cicatricial pemphigoid have IgG autoantibodies directed against laminin 5 (alpha 3 beta 3 gamma 2), an adhesion protein in epidermal basement membrane. Anti-laminin 5 autoantibodies are not found in patients with other skin or mucosal diseases and hence serve as a specific marker for this autoimmune blistering disorder, The demonstration that experimental and patient anti-laminin 5 IgG are pathogenic in animal models indicated that such autoantibodies are central to disease pathophysiology, To investigate further the role of antibody valence and complement in triggering lesion formation in vivo rabbit anti-laminin 5 (or normal, control) Fab fragments were passively transferred to neonatal BALB/c mice. Mice receiving anti-laminin 5 Fab fragments developed, in a dose-related fashion, circulating anti-basement membrane antibodies, deposits of immunoreactive rabbit IgG (but not murine C3) in epidermal basement membranes, and subepithelial blisters of skin and mucous membranes, Such alterations were not observed in mice treated with equivalent concentrations of normal rabbit Fab fragments. These studies demonstrated that neither complement activation nor cross-Linking of laminin 5 in epidermal basement membranes was required for induction of subepidermal blister formation in this animal model of a human autoimmune bullous disease. (C) 2000 Academic Press. C1 NCI, Dermatol Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Sch Med, Dept Dermatol, Chapel Hill, NC 27599 USA. RP Lazarova, Z (reprint author), NCI, Dermatol Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NR 31 TC 29 Z9 29 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD APR PY 2000 VL 95 IS 1 BP 26 EP 32 DI 10.1006/clim.2000.4845 PN 1 PG 7 WC Immunology SC Immunology GA 302EG UT WOS:000086352000004 PM 10794429 ER PT J AU Niemela, JE Puck, JM Fischer, RE Fleisher, TA Hsu, AP AF Niemela, JE Puck, JM Fischer, RE Fleisher, TA Hsu, AP TI Efficient detection of thirty-seven new IL2RG mutations in human X-linked severe combined immunodeficiency SO CLINICAL IMMUNOLOGY LA English DT Article DE X-linked severe combined immunodeficiency; (XSCID); interleukin-2 (IL-2) receptor gamma chain; common gamma chain (gamma(c)); DNA mutation analysis; protein sequence; X-linked inheritance; primary immunodeficiency ID RECEPTOR-GAMMA-CHAIN; IL-2 RECEPTOR; B-CELLS; GENE; SCIDX1; INTERLEUKIN-4; SUPERFAMILY; SEQUENCES; PROTEINS; BINDING AB X-linked severe combined immunodeficiency (XSCID) is a rare and potentially fatal disease caused by mutations of IL2RG, the gene encoding the interleukin-2 receptor gamma chain, a component of multiple cytokine receptors that are essential for lymphocyte development and function. To date, over 100 different mutations of IL2RG resulting in XSCID have been published. Using nonradioactive, direct DNA sequencing of a single PCR amplicon containing the whole IL2RG gene, we found IL2RG mutations in 78 previously unpublished unrelated cases of XSCID, We report 37 newly identified mutations of IL2RG, including 23 point mutations, 10 small deletions, 3 instances of the same single nucleotide insertion, 1 large deletion, and 2 complex mutations. More than half of the mutations (22 of 37) were predicted to result in unstable IL2RG mRNA. The remaining 14 mutations disrupted conserved functional motifs common to all cytokine receptor family members; changed protein conformation, charge, or hydrophobicity; or altered the intracellular portion of the protein, which is critical for proper interaction with signal-transducing molecules including Janus family tyrosine kinase 3. C1 NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Sect Mol Diagnost, Dept Clin Pathol, Clin Ctr,NIH, Bethesda, MD 20892 USA. RP Puck, JM (reprint author), NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. OI Niemela, Julie/0000-0003-4197-3792 NR 40 TC 18 Z9 18 U1 0 U2 4 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 2000 VL 95 IS 1 BP 33 EP 38 DI 10.1006/clim.2000.4846 PN 1 PG 6 WC Immunology SC Immunology GA 302EG UT WOS:000086352000005 PM 10794430 ER PT J AU Cooper, PJ Beck, LA Espinel, I Deyampert, NM Hartnell, A Jose, PJ Paredes, W Guderian, RH Nutman, TB AF Cooper, PJ Beck, LA Espinel, I Deyampert, NM Hartnell, A Jose, PJ Paredes, W Guderian, RH Nutman, TB TI Eotaxin and RANTES expression by the dermal endothelium is associated with eosinophil infiltration after ivermectin treatment of onchocerciasis SO CLINICAL IMMUNOLOGY LA English DT Article DE chemokines; filarial; helminth; posttreatment reactions ID AIRWAY HYPERRESPONSIVENESS; TISSUE EOSINOPHILIA; MAZZOTTI REACTION; MESSENGER-RNA; LYMPH-NODES; CELLS; CHEMOKINES; INFLAMMATION; MACROPHAGES; RECRUITMENT AB The roles of eotaxin, RANTES, and MCP-3 expression in eosinophil recruitment to the site of parasite killing that occurs following ivermectin treatment of onchocerciasis were assessed in the skin of 13 Onchocerca volvulus-infected subjects and two noninfected controls before and after ivermectin treatment. Adverse reactions in infected subjects were associated with the appearance of eosinophils in the dermis as part of a perivascular inflammatory infiltrate. Although no expression of RANTES and eotaxin was seen in dermal vascular endothelial cells in biopsies taken before treatment (nor at any time in the skin of uninfected controls), endothelial expression of both eotaxin and RANTES was noted by 24 h following treatment. While RANTES expression was transient, eotaxin expression increased in parallel with increasing eosinophil recruitment up to 60 h posttreatment. These observations indicate that endothelial expression of eotaxin and RANTES may have an important role in eosinophil recruitment into the skin during helminth-killing reactions. (C) 2000 Academic Press. C1 NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. Johns Hopkins Univ, Ctr Asthma & Allergy, Baltimore, MD 21224 USA. Hosp Vozandes, Dept Clin Invest, Quito, Ecuador. Natl Heart & Lung Inst, London, England. RP Cooper, PJ (reprint author), NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. FU NIAID NIH HHS [R01 AI045839] NR 49 TC 21 Z9 24 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD APR PY 2000 VL 95 IS 1 BP 51 EP 61 DI 10.1006/clim.1999.4829 PN 1 PG 11 WC Immunology SC Immunology GA 302EG UT WOS:000086352000007 PM 10794432 ER PT J AU Rex, JH Walsh, TJ Sobel, JD Filler, SG Pappas, PG Dismukes, WE Edwards, JE AF Rex, JH Walsh, TJ Sobel, JD Filler, SG Pappas, PG Dismukes, WE Edwards, JE TI Practice guidelines for the treatment of candidiasis SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; ITRACONAZOLE ORAL SOLUTION; INVASIVE FUNGAL-INFECTIONS; LIPOSOMAL AMPHOTERICIN-B; IN-VITRO SUSCEPTIBILITY; CHRONIC MUCOCUTANEOUS CANDIDIASIS; ORTHOTOPIC LIVER-TRANSPLANTATION; PROSTHETIC VALVE ENDOCARDITIS; HOSPITAL-ACQUIRED CANDIDEMIA; TRIAL COMPARING FLUCONAZOLE AB Infections due to Candida species are the most common of the fungal infections. Candida species produce a broad range of infections, ranging from non-life-threatening mucocutaneous illnesses to invasive process that may involve virtually any organ. Such a broad range of infections requires an equally broad range of diagnostic and therapeutic strategies. This document summarizes current knowledge about treatment of multiple forms of candidiasis and is the guideline of the Infectious Diseases Society of America (IDSA) for the treatment of candidiasis. Throughout this document, treatment recommendations are scored according to the standard scoring scheme used in other IDSA guidelines to illustrate the strength of the underlying data. The document covers 4 major topical areas. The role of the microbiology laboratory. To a greater extent than for other fungi, treatment of candidiasis can now be guided by in vitro susceptibility testing. The guidelines review the available information supporting current testing procedures and interpretive breakpoints and place these data into clinical context. Susceptibility testing is most helpful in dealing with infection due to non-albicans species of Candida. In this setting, especially if the patient has been treated previously with an azole antifungal agent, the possibility of microbiological resistance must be considered. Treatment of invasive candidiasis. In addition to acute hematogenous candidiasis, the guidelines review strategies for treatment of 15 other forms of invasive candidiasis. Extensive data from randomized trials are really available only for therapy of acute hematogenous candidiasis in the nonneutropenic adult. Choice of therapy for other forms of candidiasis is based on case series and anecdotal reports. In general, both amphotericin B and the azoles have a role to play in treatment. Choice of therapy is guided by weighing the greater activity of amphotericin B for some non-albicans species (e.g., Candida krusei) against the lesser toxicity and ease of administration of the azole antifungal agents. Flucytosine has activity against many isolates of Candida but is not often used. Treatment of mucocutaneous candidiasis. Therapy for mucosal infections is dominated by the azole antifungal agents. These drugs may be used topically or systemically and have been proven safe and efficacious. A significant problem with mucosal disease is the is the propensity for a small proportion of patients to suffer repealed relapses. in some situations. the explanation for such a relapse is obvious (e.g., relapsing oropharyngeal candidiasis in an individual with advanced and uncontrolled HIV infection), but in other patients the cause is cryptic (e.g., relapsing vaginitis in a healthy woman). Rational strategies for these situations are discussed in the guidelines and must consider the possibility of induction of resistance over time. Prevention of invasive candidiasis. Prophylactic strategies are useful if the risk of a target disease is sharply elevated in a readily identified group of patients. Selected patient groups undergoing therapy that produces prolonged neutropenia (e.g., some bone-marrow transplant recipients) or who receive a solid-organ transplant (e.g., some liver transplant recipients) have a sufficient risk of invasive candidiasis to warrant prophylaxis. C1 Univ Texas, Sch Med, Ctr Study Emerging & Reemerging Pathogens, Dept Internal Med,Div Infect Dis, Houston, TX 77030 USA. Natl Canc Inst, Infect Dis Sect, Pediat Branch, Bethesda, MD USA. Wayne State Univ, Sch Med, Detroit, MI USA. Harbor UCLA Med Ctr, Torrance, CA 90509 USA. Univ Alabama, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA. RP Rex, JH (reprint author), Univ Texas, Sch Med, Ctr Study Emerging & Reemerging Pathogens, Dept Internal Med,Div Infect Dis, 6431 Fannin,1728 JFB, Houston, TX 77030 USA. RI Filler, Scott/A-2779-2009 NR 184 TC 512 Z9 544 U1 2 U2 24 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR PY 2000 VL 30 IS 4 BP 662 EP 678 DI 10.1086/313749 PG 17 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 313PX UT WOS:000087009000011 PM 10770728 ER PT J AU Stevens, DA Kan, VL Judson, MA Morrison, VA Dummer, S Denning, DW Bennett, JE Walsh, TJ Patterson, TF Pankey, GA AF Stevens, DA Kan, VL Judson, MA Morrison, VA Dummer, S Denning, DW Bennett, JE Walsh, TJ Patterson, TF Pankey, GA TI Practice guidelines for diseases caused by Aspergillus SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS; INVASIVE PULMONARY ASPERGILLOSIS; BONE-MARROW TRANSPLANTATION; LIPOSOMAL AMPHOTERICIN-B; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; CHRONIC GRANULOMATOUS-DISEASE; CENTRAL-NERVOUS-SYSTEM; SUCCESSFUL CONSERVATIVE TREATMENT; LINKED-IMMUNOSORBENT-ASSAY; COLONY-STIMULATING FACTOR AB Aspergillosis comprises a variety of manifestations of infection. These guidelines are directed to 3 principal entities: invasive aspergillosis, involving several organ systems (particularly pulmonary disease); pulmonary aspergilloma; and allergic bronchopulmonary aspergillosis. The recommendations are distilled in this summary, but the reader is encouraged to review the more extensive discussions in subsequent sections, which show the strength of the recommendations and the quality of the evidence, and the original publications cited in detail. Invasive aspergillosis. Because it is highly lethal in the immunocompromised host. even in the face of therapy, work-up must be prompt and aggressive, and therapy may need to be initiated upon suspicion of the diagnosis, without definitive proof (BIII). Intravenous therapy should be: used initially in rapidly progressing disease (BIII). The largest therapeutic experience is with amphotericin B deoxycholate, which should be given at maximum tolerated doses (e.g., 1-1.5 mg/kg/d) and should be continued. despite modest increases in serum creatinine levels (BIII). Lipid formulations of amphotericin are indicated for the patient who has impaired renal Function or who develops nephrotoxicity while receiving deoxycholate amphotericin (AII). Oral itraconazole is an alternative for patients who can take oral medication. are likely to be adherent, can be demonstrated (by serum level monitoring) to absorb the drug, and lack the potential for interaction with other drugs (BII). Oral itraconazole is attractive for continuing therapy in the patient who responds to initial iv therapy (CIII). Therapy should be prolonged beyond resolution of disease and reversible underlying predispositions (BIII). Adjunctive therapy (particularly surgery and combination chemotherapy. also immunotherapy), may be useful in certain situations (CIII). Aspergilloma. The optimal treatment strategy for aspergilloma is unknown. Therapy is predominantly directed at preventing life-threatening hemoptysis. Surgical removal of aspergilloma is definitive treatment, but because of significant morbidity and mortality it should be reserved for high-risk patients such its those with episodes of life-threatening hemoptysis, and considered for patients with underlying sarcoidosis, immunocompromised patients, and those with increasing Asper Aspergillus-specific IgG titers (CIII). Surgical candidates would need to have adequate pulmonary function to undergo the operation. Bronchial artery embolization rarely produces a permanent success. but may be useful as a temporizing procedure in patients with life-threatening hemoptysis. Endobronchial and intracavitary instillation of antifungals or oral itraconazole may be useful for this condition. Since the majority of aspergillomas do not cause life-threatening hemoptysis, the morbidity and cost of treatment must be weighed against the clinical benefit. Allergic bronchopulmonary aspergillosis (APBA). Although no well-designed studies have been carried out, the available data support the use of corticosteroids for acute exacerbations of ABPA (AII). Neither the optimal corticosteroid dose nor the duration of therapy has been standardized, but limited data suggest the starting dose should be similar to 0.5 mg/kg/d of prednisone. The decision to taper corticosteroids should be made on an individual basis, depending on the clinical course (BIII). The available data suggest that clinical symptoms alone are inadequate to make such decisions. since significant lung damage may occur in asymptomatic patients. Increasing serum IgE levels, new or worsening infiltrate on chest radiograph. and worsening spirometry suggest that corticosteroids should be used (BII). Multiple asthmatic exacerbations in a patient with ABPA suggest that chronic corticosteroid therapy should be used (BIII). Itraconazole appears useful as a corticosteroid sparing agent (BII). Although the frequency of these diseases is on the rise, there is a paucity of randomized comparative trials involving these entities; therefore, the recommendations represent a compromise and consensus among students of these diseases (i.e., the authors). They have synthesized the recommendations from published and personal experience, including case series, open trials, and any comparative trials, as indicated. C1 Santa Clara Valley Med Ctr, Dept Med, San Jose, CA 95128 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Dept Vet Affairs Med Ctr, Washington, DC USA. Georgetown Univ, Sch Med, Washington, DC USA. Dept Vet Affairs Med Ctr, Minneapolis, MN USA. Univ Minnesota, Minneapolis, MN USA. Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. NIAID, Mycoses Study Grp, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Ochsner Clin, New Orleans, LA USA. Cancer & Leukemia Grp B, Chicago, IL USA. N Manchester Gen Hosp, Manchester, Lancs, England. Univ Manchester, Sch Med, Manchester M13 9PT, Lancs, England. RP Stevens, DA (reprint author), Santa Clara Valley Med Ctr, Dept Med, 751 S Bascom Ave, San Jose, CA 95128 USA. OI Denning, David/0000-0001-5626-2251; Judson, Marc/0000-0002-4663-7985 NR 202 TC 473 Z9 512 U1 1 U2 26 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR PY 2000 VL 30 IS 4 BP 696 EP 709 DI 10.1086/313756 PG 14 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 313PX UT WOS:000087009000015 PM 10770732 ER PT J AU Gaydos, CA Quinn, TC Gaydos, JC AF Gaydos, CA Quinn, TC Gaydos, JC TI The challenge of sexually transmitted diseases for the military: What has changed? SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID LIGASE CHAIN-REACTION; CHLAMYDIA-TRACHOMATIS INFECTION; PELVIC INFLAMMATORY DISEASE; FAMILY-PLANNING CLINICS; NEISSERIA-GONORRHOEAE; COST-EFFECTIVENESS; UNITED-STATES; WOMEN; URINE; DIAGNOSIS C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NIAID, NIH, Bethesda, MD 20892 USA. Walter Reed Army Inst Res, Dept Def Global Emerging Infect Surveillance & Re, Washington, DC USA. RP Gaydos, CA (reprint author), 1159 Ross Res Bldg,720 Rutland Ave, Baltimore, MD 21205 USA. RI Gaydos, Charlotte/E-9937-2010 NR 32 TC 17 Z9 18 U1 2 U2 7 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR PY 2000 VL 30 IS 4 BP 719 EP 722 DI 10.1086/313758 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 313PX UT WOS:000087009000017 PM 10770734 ER PT J AU Kaplan, JE Masur, H Holmes, KK Freedberg, KA Holtgrave, D Piscitelli, SC Van Dyke, R Watts, H AF Kaplan, JE Masur, H Holmes, KK Freedberg, KA Holtgrave, D Piscitelli, SC Van Dyke, R Watts, H CA US Public Hlth Service Infect Dis TI An overview of the 1999 US Public Health Service/Infectious Diseases Society of America guidelines for preventing opportunistic infections in human immunodeficiency virus-infected persons SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID PNEUMOCYSTIS-CARINII PNEUMONIA; COST-EFFECTIVENESS ANALYSIS; DRUG-INTERACTIONS; ORAL GANCICLOVIR; UNITED-STATES; HIV; AIDS; ADHERENCE; INTERVENTION; WOMEN C1 Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Atlanta, GA 30333 USA. NIH, Bethesda, MD 20892 USA. Univ Washington, Seattle, WA 98195 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Tulane Univ, Sch Med, New Orleans, LA 70112 USA. RP Kaplan, JE (reprint author), Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Mailstop G-29, Atlanta, GA 30333 USA. NR 65 TC 8 Z9 8 U1 2 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR PY 2000 VL 30 SU 1 BP S15 EP S28 DI 10.1086/313844 PG 14 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 314QQ UT WOS:000087067600003 PM 10770912 ER PT J AU Masur, H Holmes, KK Kaplan, JE AF Masur, H Holmes, KK Kaplan, JE TI Introduction to the 1999 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus SO CLINICAL INFECTIOUS DISEASES LA English DT Article AB Opportunistic infections (OIs) are well recognized to produce substantial morbidity and mortality among patients with HIV infection. Since measures are available for reducing the incidence and the impact of these processes for patients, the United States Public Health Service and the Infectious Diseases Society of America, with endorsing professional societies, have developed guidelines for implementing a comprehensive strategy to prevent these OIs, These guidelines have been developed by a diverse working group of expert health care providers and patient representatives in order to synthesize available data and to provide practical advice for health care practitioners and patients. C1 NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. Univ Washington, Seattle, WA 98195 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Masur, H (reprint author), NIH, Dept Crit Care Med, Bldg 10,Rm 7D43,10 Ctr Dr,MSC 1662, Bethesda, MD 20892 USA. NR 2 TC 4 Z9 5 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR PY 2000 VL 30 SU 1 BP S1 EP S4 DI 10.1086/313847 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 314QQ UT WOS:000087067600001 PM 10770910 ER PT J AU Sulkowski, MS Mast, EE Seeff, LB Thomas, DL AF Sulkowski, MS Mast, EE Seeff, LB Thomas, DL TI Hepatitis C virus infection as an opportunistic disease in persons infected with human immunodeficiency virus SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID INJECTION-DRUG USERS; CHRONIC LIVER-DISEASE; INTERFERON-ALPHA THERAPY; NON-B-HEPATITIS; FOLLOW-UP; NON-A; NATURAL-HISTORY; HOMOSEXUAL MEN; UNITED-STATES; RISK-FACTORS AB Hepatitis C virus (HCV) is an RNA virus of the Flaviviridae family and is a major cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Owing to shared routes of transmission, HCV and human immunodeficiency virus (HIV) coinfection are common, affecting approximately one-third of all HIV-infected persons in the United States. In addition, HIV coinfection is associated with higher HCV RNA level and a more rapid progression of HCV-related liver disease, which leads to an increased risk of cirrhosis, HCV infection may also impact the course and management of HIV disease, particularly by increasing the risk of antiretroviral drug-induced hepatotoxicity. Thus, chronic HCV infection acts as an opportunistic disease in HIV-infected persons, because the incidence of infection is increased and the natural history of HCV infection is accelerated in coinfected persons. Strategies to prevent primary HCV infection and to modify the progression of HCV-related liver disease are urgently needed for HIV-HCV-coinfected individuals. C1 Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD 21218 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Hepatitis Branch, Div Viral & Rickettsial Dis, Atlanta, GA USA. RP Sulkowski, MS (reprint author), Johns Hopkins Univ, Sch Med, Div Infect Dis, 1830 E Monument St,Room 450C, Baltimore, MD 21287 USA. NR 89 TC 120 Z9 126 U1 2 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR PY 2000 VL 30 SU 1 BP S77 EP S84 DI 10.1086/313842 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 314QQ UT WOS:000087067600007 PM 10770916 ER PT J AU Mackall, C Berzofsky, J Helman, LJ AF Mackall, C Berzofsky, J Helman, LJ TI Targeting tumor specific translocations in sarcomas in pediatric patients for immunotherapy SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT 4th Combined Meeting of the American-and-European-Musculoskeletal-Tumor-Societies CY MAY 06-10, 1998 CL WASHINGTON, D.C. SP Amer & European Musculoskeletal Tumor Soc ID EWS/FLI-1 FUSION GENE; EWINGS-SARCOMA; GROWTH-FACTOR; REGENERATION AB In an effort to develop more effective therapies for various sarcomas in pediatric patients, the authors have focused on using recurrent tumor-specific translocations as potential novel tumor antigens, In general, these translocations generate fusion transcription factors. Because cytotoxic T cell lymphocyte receptors recognize peptide fragments bound to major histocompatibility complex Class 1 molecules, it is possible that unique peptides spanning the translocation breakpoint region may be processed, bound to major histocompatibility complex Class I molecules and displayed on the tumor cell surface where they could be susceptible to cytotoxic T cell lymphocyte killing. The authors have investigated the PAX-3-FKHR fusion product seen in alveolar rhabdomyosarcoma, and the EWS-FLI-1 fusion product seen in Ewing's sarcoma, Peptides spanning these fusion regions contain potential major histocompatibility complex Class 1 and Class II binding moths suggesting they may serve as novel T cell antigens. Preliminary mouse experiments suggest that cytotoxic T cell lymphocytes specific for the PAX-3-FKHR fusion peptide can be generated and can recognize and kill tumor cells bearing the PAX-3-FKHR fusion protein. Clinical trials are ongoing to determine whether this approach will be useful. C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Helman, LJ (reprint author), NCI, Pediat Oncol Branch, 10 Ctr Dr,MSC 1928,Bldg 10,Room 13N240, Bethesda, MD 20892 USA. NR 15 TC 39 Z9 40 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD APR PY 2000 IS 373 BP 25 EP 31 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 303RJ UT WOS:000086437400006 PM 10810459 ER PT J AU Bhattacharyya, U Dasmahapatra, AK Medda, AK AF Bhattacharyya, U Dasmahapatra, AK Medda, AK TI Vitamin B-12-induced alterations in activities of alpha-glycerophosphate dehydrogenase and malic enzyme in brain of singi fish, Heteropneustes fossilis (Bloch) SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY LA English DT Article DE brain metabolism; cycloheximide; enzyme induction; alpha-glycerophosphate dehydrogenase; fish brain; Heteropneustes fossilis; malic enzyme; neural enzyme; vitamin B-12 ID ENDOCYTOSIS; DEFICIENCY; RECEPTOR; TISSUE; GENE AB Different doses of vitamin B-12 (0.25, 0.5, 1, 2 and 4 mu g/g, injected intraperitoneally for three consecutive days) altered the activities of mitochondrial-alpha-glycerophosphate dehydrogenase (alpha-GPD) and NADP-dependent cytosolic malic enzyme (ME) in the brain of singi fish. The alpha-GPD activity increased at doses of 0.5, 1, 2 and 4 mu g/g vitamin B-12. A dose of 0.5 mu g/g vitamin B-12 induced less activity than higher doses. ME activity increased with 1, 2 and 4 mu g/g of vitamin B-12/g. The mitochondrial and cytosolic protein content remained unchanged after vitamin B-12 administration. Cycloheximide treatment inhibited the vitamin B-12-induced increase in alpha-GPD and ME activity. Thus, vitamin B-12 is involved in the induction of some enzymes in fish brain. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Bose Inst, Dept Anim Physiol, Calcutta 700009, W Bengal, India. Vidyasagar Coll Women, Dept Zool, Calcutta, W Bengal, India. Univ Wisconsin, NIEHS, Marine & Freshwater Biomed Sci Ctr, Milwaukee, WI 53204 USA. RP Dasmahapatra, AK (reprint author), Bose Inst, Dept Anim Physiol, Calcutta 700009, W Bengal, India. NR 29 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0305-0491 J9 COMP BIOCHEM PHYS B JI Comp. Biochem. Physiol. B-Biochem. Mol. Biol. PD APR PY 2000 VL 125 IS 4 BP 451 EP 456 DI 10.1016/S0305-0491(00)00160-7 PG 6 WC Biochemistry & Molecular Biology; Zoology SC Biochemistry & Molecular Biology; Zoology GA 322YU UT WOS:000087537800002 PM 10904858 ER PT J AU Champoux, M Norcross, J Suomi, SJ AF Champoux, M Norcross, J Suomi, SJ TI Rhesus monkeys with late-onset hydrocephalus differ from non-impaired animals during neonatal neurobehavioral assessments: Six-year retrospective analysis SO COMPARATIVE MEDICINE LA English DT Article ID MACACA-MULATTA; INFANTS; BRAIN; MOVEMENTS AB Background and Purpose: A recent case study indicated that a hydrocephalic rhesus monkey had abnormal response patterns in a standardized neonatal primate assessment, We conducted a retrospective study to determine whether this assessment could also differentiate neonatal rhesus monkeys that appeared normal but developed signs of hydrocephalus later in life from neonates with normal development and no evidence of hydrocephalus. Methods: One-hundred eighty-two rhesus monkeys were assessed on postnatal days 7, 14, 21, and 30, As neonates, clinical signs of hydrocephalus or other illnesses were not evident in any animal. Six monkeys developed signs of hydrocephalus between 5 months and 5 years of age, and each received confirmed diagnoses of hydrocephalus at necropsy. Results: Compared with colony norms, the monkeys that developed hydrocephalus had diminished orientation abilities, more muscle tension, less behavioral evidence of distress, and more pronounced responses to some reflex-evoking stimuli, and difficulty in self-righting (day 7 only). Discriminant function analysis comparing the hydrocephalic animals with a matched control group provided a high probability of correct group assignment at days 7, 14, and 21. Conclusions: Some as yet undetermined factor may predispose some monkeys to develop hydrocephalus, which may also be reflected in different scores on neurodevelopmental test items during early infancy. C1 NICHD, Comparat Ethol Lab, Poolesville, MD 20837 USA. RP Champoux, M (reprint author), Anim Ctr, NIH, POB 529, Poolesville, MD 20837 USA. NR 34 TC 2 Z9 2 U1 1 U2 2 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1058-2401 J9 COMPARATIVE MED JI Comparative Med. PD APR PY 2000 VL 50 IS 2 BP 218 EP 224 PG 7 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 317CA UT WOS:000087206900017 PM 10857014 ER PT J AU Zalla, T Sirigu, A Pillon, B Dubois, B Agid, Y Grafman, J AF Zalla, T Sirigu, A Pillon, B Dubois, B Agid, Y Grafman, J TI How patients with Parkinson's disease retrieve and manage cognitive event knowledge SO CORTEX LA English DT Article DE scripts; frontal lobe; basal ganglia; reward; motivation ID FRONTAL-LOBE; BASAL GANGLIA; MEMORY; LESIONS; REWARD; SCRIPTS; DEFICITS; NEURONS; CORTEX AB Several studies have pointed out that basal ganglia are involved in adaptive control of action at both motor and cognitive level. This study aimed to investigate how basal ganglia retrieve and manage script event knowledge required in planning behavior. Script event knowledge was investigated in patients with Parkinson's Disease using three kinds of activity that differed in familiarity. Unlike patients with prefrontal lesions, patients with Parkinson's Disease were able to order events in a typical sequence and obeyed the boundaries and hierarchies between events. In contrast, patients with Parkinson's Disease were impaired in evaluating how important each script event was within the context of goal-oriented planning activity. Our findings indicate that the prefrontal cortex and the basal ganglia are differentially involved in planning. The role of the basal ganglia might consist in providing a feedback about the goodness of each action while building up meaningful sequences of events during learning. C1 Hop La Pitie Salpetriere, INSERM, U289, Paris, France. NINDS, NIH, Cognit Neurosci Sect, Bethesda, MD 20892 USA. RP Zalla, T (reprint author), Inst Cognit Sci, 67 Blvd Pinel, F-69675 Bron, France. EM zalla@isc.cnrs.fr OI Grafman, Jordan H./0000-0001-8645-4457 NR 42 TC 19 Z9 19 U1 0 U2 4 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 0010-9452 J9 CORTEX JI Cortex PD APR PY 2000 VL 36 IS 2 BP 163 EP 179 DI 10.1016/S0010-9452(08)70522-7 PG 17 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 308XW UT WOS:000086739000002 PM 10815704 ER PT J AU Quezado, ZMN Eichacker, PQ AF Quezado, ZMN Eichacker, PQ TI Inhaled nitric oxide: Move than a selective pulmonary vasodilator SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE inhaled nitric oxide; vasodilator; systemic effects; sepsis; leukocyte; inflammation ID RESPIRATORY-DISTRESS SYNDROME; ACUTE LUNG INJURY; HYPERTENSION; THERAPY; SEPSIS; NO C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NIH, Bethesda, MD 20892 USA. RP Quezado, ZMN (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Quezado, Zenaide/O-4860-2016 OI Quezado, Zenaide/0000-0001-9793-4368 NR 16 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD APR PY 2000 VL 28 IS 4 BP 1235 EP 1236 DI 10.1097/00003246-200004000-00063 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 311AV UT WOS:000086862800063 PM 10809320 ER PT J AU Hewlett, BS Lamb, ME Leyendecker, B Scholmerich, A AF Hewlett, BS Lamb, ME Leyendecker, B Scholmerich, A TI Internal working models, trust, and sharing among foragers SO CURRENT ANTHROPOLOGY LA English DT Article ID MATERNAL RESPONSIVENESS; ATTACHMENT ORGANIZATION; INFANT CARE; CHILDHOOD; CULTURE C1 Washington State Univ, Dept Anthropol, Vancouver, WA 98686 USA. NICHHD, Sect Social & Emot Dev, Washington, DC USA. Univ Halle Wittenberg, D-4010 Halle, Germany. Ruhr Univ Bochum, Bochum, Germany. RP Hewlett, BS (reprint author), Washington State Univ, Dept Anthropol, Vancouver, WA 98686 USA. RI Schoelmerich, Axel/C-9039-2009 OI Schoelmerich, Axel/0000-0002-9844-3920 NR 50 TC 25 Z9 25 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0011-3204 J9 CURR ANTHROPOL JI Curr. Anthropol. PD APR PY 2000 VL 41 IS 2 BP 287 EP 297 DI 10.1086/300135 PG 11 WC Anthropology SC Anthropology GA 304WV UT WOS:000086507800015 ER PT J AU Eddington, ND Cox, DS Roberts, RR Stables, JP Powell, CB Scott, KR AF Eddington, ND Cox, DS Roberts, RR Stables, JP Powell, CB Scott, KR TI Enaminones-versatile therapeutic pharmacophores. Further advances SO CURRENT MEDICINAL CHEMISTRY LA English DT Review ID BLOOD-BRAIN-BARRIER; ENDOTHELIAL-CELL MONOLAYERS; DEPENDENT SODIUM-CHANNEL; ANTICONVULSANT ACTIVITY; LOCAL-ANESTHETICS; MODEL SYSTEM; BINDING; AGENTS; INVITRO; TRANSPORT AB Enaminones, enamines of beta-dicarbonyl compounds, have been know for many years. In our initial account (Current Med. Chem. 1994, 1, 159-175), we reported on the anticonvulsant activity of a series of enaminones, notably methyl 4-[(p-chlorophenyl)amino]-6-methyl-2-oxo-cyclohex-3-en-1-oate, 9a (R=CH3, R-1=4-Cl), which, in animal tests, compared favorably to phenytoin and carbamazepine. Since that time, further research in our laboratory and other laboratories have expanded the therapeutic potential of these compounds. In addition to new anticonvulsant derivatives, we have uncovered a novel brain transport mechanism for the enaminones and developed a preliminary regression model for further synthetic direction. These topics will each be presented and elaborated. C1 Howard Univ, Sch Pharm, Dept Pharmaceut Sci, Washington, DC 20059 USA. Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. 3M Co, Corp Res, Sci Res Lab, 3M Ctr, St Paul, MN 55144 USA. NINDS, Epilepsy Branch, Div Convuls Dev & Neuromuscular Disorders, Bethesda, MD 20892 USA. Emory Univ, Dept Chem, Atlanta, GA 30054 USA. RP Scott, KR (reprint author), Howard Univ, Sch Pharm, Dept Pharmaceut Sci, Washington, DC 20059 USA. FU NIGMS NIH HHS [GM08244-08] NR 75 TC 90 Z9 91 U1 1 U2 4 PU BENTHAM SCIENCE PUBL BV PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PD APR PY 2000 VL 7 IS 4 BP 417 EP 436 PG 20 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 292WG UT WOS:000085817800003 PM 10702617 ER PT J AU Staudt, LM AF Staudt, LM TI Immunological techniques - The expression of the genome during immune responses - Editorial overview SO CURRENT OPINION IN IMMUNOLOGY LA English DT Editorial Material C1 NCI, Metab Branch, Div Clin Sci, Bethesda, MD 20892 USA. RP Staudt, LM (reprint author), NCI, Metab Branch, Div Clin Sci, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2000 VL 12 IS 2 BP 199 EP 200 DI 10.1016/S0952-7915(99)00073-4 PG 2 WC Immunology SC Immunology GA 292GQ UT WOS:000085786300011 ER PT J AU Alizadeh, AA Staudt, LM AF Alizadeh, AA Staudt, LM TI Genomic-scale gene expression profiling of normal and malignant immune cells SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID GERMINAL-CENTER FORMATION; NF-KAPPA-B; IDENTIFICATION; HYBRIDIZATION; INFLAMMATION; MICROARRAY; PATTERNS; CYCLE; YEAST; BCL-6 AB Gene expression variation is critical for the normal development and physiology of immune cells. Using cDNA microarrays, a systematic, genomic-scale view of gene expression in immune cells at many stages of differentiation and activation can be obtained. From the high vantagepoint provided by this technology, the gene expression physiology of immune cells appears remarkably ordered and logical. Each stage of lymphocyte differentiation can be defined by a characteristic gene expression signature. Genes that are coregulated over hundreds of experimental conditions often encode functionally related proteins. Gene expression profiles also provide unprecedented ability to define the molecular and functional relationships between normal and malignant lymphocyte cell populations. C1 NCI, Metab Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA. RP Staudt, LM (reprint author), NCI, Metab Branch, Div Clin Sci, NIH, Bldg 10,Room 4N114,9000 Rockville Pike, Bethesda, MD 20892 USA. OI Alizadeh, Arash Ash/0000-0002-5153-5625 NR 27 TC 91 Z9 93 U1 2 U2 5 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 2000 VL 12 IS 2 BP 219 EP 225 DI 10.1016/S0952-7915(99)00078-3 PG 7 WC Immunology SC Immunology GA 292GQ UT WOS:000085786300016 PM 10712950 ER PT J AU Gottesman, S Morris, NR AF Gottesman, S Morris, NR TI Cell regulation - Variations on every theme SO CURRENT OPINION IN MICROBIOLOGY LA English DT Review C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Piscataway, NJ 08876 USA. RP Gottesman, S (reprint author), NCI, Mol Biol Lab, Bldg 37,Room 2E18, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 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 2000 VL 3 IS 2 BP 115 EP 117 DI 10.1016/S1369-5274(00)00061-8 PG 3 WC Microbiology SC Microbiology GA 299QD UT WOS:000086208600001 ER PT J AU Yarmolinsky, M AF Yarmolinsky, M TI Transcriptional silencing in bacteria SO CURRENT OPINION IN MICROBIOLOGY LA English DT Review ID PROTEIN H-NS; COLI NUCLEOID PROTEIN; POSITION-EFFECT VARIEGATION; F-PLASMID PARTITION; ESCHERICHIA-COLI; BGL OPERON; GENE-EXPRESSION; CURVED DNA; MINI-F; ANTITERMINATOR PROTEIN AB Transcriptional silencing and repression are modes of negative control of gene expression that differ in specificity. Repressors, when present at promoter-specific binding sites, interfere locally with RNA polymerase function. Silencing proteins act by covering a continuous region of DNA, compete with a broader spectrum of proteins and are non-specific with respect to the promoters affected. Studies of transcriptional silencing promise an entree to relatively unexplored areas of prokaryotic biology. C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Yarmolinsky, M (reprint author), NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NR 78 TC 25 Z9 26 U1 0 U2 2 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 2000 VL 3 IS 2 BP 138 EP 143 DI 10.1016/S1369-5274(00)00065-5 PG 6 WC Microbiology SC Microbiology GA 299QD UT WOS:000086208600005 PM 10744994 ER PT J AU Bernstein, HD AF Bernstein, HD TI The biogenesis and assembly of bacterial membrane proteins SO CURRENT OPINION IN MICROBIOLOGY LA English DT Review ID SIGNAL RECOGNITION PARTICLE; MALTOSE-BINDING PROTEIN; ESCHERICHIA-COLI K-12; AMINO-ACID-RESIDUES; LACTOSE PERMEASE; INNER MEMBRANE; ENDOPLASMIC-RETICULUM; NASCENT POLYPEPTIDES; SEQUENCE RECOGNITION; PERIPLASMIC PROTEIN AB Bacterial proteins in the inner and outer membranes differ dramatically in their architecture. Although both types of proteins are transported across the inner membrane through a common pore, recent studies have identified distinct factors that target them to transport sites and catalyze proper folding. C1 NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Bernstein, HD (reprint author), NIDDKD, Genet & Biochem Branch, NIH, Bldg 10,Room 9D-20,10 Ctr Dr, Bethesda, MD 20892 USA. NR 68 TC 41 Z9 42 U1 0 U2 1 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 2000 VL 3 IS 2 BP 203 EP 209 DI 10.1016/S1369-5274(00)00076-X PG 7 WC Microbiology SC Microbiology GA 299QD UT WOS:000086208600016 PM 10744997 ER PT J AU Zwickl, P Baumeister, W Steven, A AF Zwickl, P Baumeister, W Steven, A TI Dis-assembly lines: the proteasome and related ATPase-assisted proteases SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Review ID 20S PROTEASOME; ESCHERICHIA-COLI; ELECTRON-MICROSCOPY; CRYSTAL-STRUCTURE; BETA-SUBUNITS; THERMOPLASMA-ACIDOPHILUM; PROTEIN; DEGRADATION; RESOLUTION; COMPLEXES AB Self-compartmentalizing proteases, such as the proteasome and several prokaryotic energy-dependent proteases, are designed to act in the crowded environment of the cell. Proteins destined for degradation are recognized and unfolded by regulatory subcomplexes that invariably contain ATPase modules, before being translocated into another subcomplex, the proteolytic core, for degradation. The sequential actions effected on substrates are reflected in the linear arrangement of these subcomplexes; thus, the holocomplexes are organized as molecular disassembly and degradation lines. C1 Max Planck Inst Biochem, Dept Mol Struct Biol, D-82152 Martinsried, Germany. NIAMS, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. RP Zwickl, P (reprint author), Max Planck Inst Biochem, Dept Mol Struct Biol, Klopferspitz 18A, D-82152 Martinsried, Germany. NR 94 TC 64 Z9 64 U1 0 U2 1 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 2000 VL 10 IS 2 BP 242 EP 250 DI 10.1016/S0959-440X(00)00075-0 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 306DW UT WOS:000086582900017 PM 10753810 ER PT J AU Gnant, MFX Turner, EM Alexander, HR AF Gnant, MFX Turner, EM Alexander, HR TI Effects of hyperthermia and tumour necrosis factor on inflammatory cytokine secretion and procoagulant activity in endothelial cells SO CYTOKINE LA English DT Article DE hyperthermia; tumour necrosis factor; endothelial cells; tissue factor; cytokines ID ISOLATED LIMB PERFUSION; ISOLATED HEPATIC PERFUSION; CHINESE-HAMSTER CELLS; FACTOR-ALPHA; MALIGNANT-MELANOMA; LEUKOCYTE ADHESION; TNF-ALPHA; EXPRESSION; INVITRO; MELPHALAN AB The application of hyperthermia (HT) and tumour necrosis factor alpha (TNF) in isolation perfusion of the limb or liver results in regression of advanced cancers confined to these regions of the body in most patients and are thought to exert anti-tumour effects primarily on tumour neovasculature. However, the individual contribution of either treatment factor on endothelial cells (EC) are not known. In this study, we investigated the in vitro effects of moderate and severe HT on human umbilical vein EC (HUVEC) with and without TNF in clinically relevant doses. HUVEC mere exposed to normothermia (37 degrees C) or moderate (39 degrees C) and severe (41 degrees C) HT for 90 or 180 min with or without TNF (1 mu g/ml). Cell viability, cytokine secretion (IL-6, IL-8, VEGF, ICAM-1, VCAM-1, RANTES, E-selectin, P-selectin, L-selectin, and PECAM-1), and induction of procoagulant activity as reflected in tissue factor (TF) production were assessed at the end of the treatment period and at several time points thereafter. Neither HT nor TNF exerted significant cytotoxic effects on EC at the doses and temperatures used, HT resulted in increased production of PECAM-1 with little or no additional effect when combined with TNF. TNF caused increased secretion of IL-6, IL-8, ICAM-1, and VCAM-1 with little or no additional effect from HT. Increased E-selectin and RANTES levels mere observed with TNF and HT only at 24 h after treatment. HT and TNF had mainly antagonistic effects on VEGF secretion with HT causing primarily decreased production and TNF causing increased VEGF secretion under all temperatures. Most notably, there was a rapid, prolonged and synergistic peak increase in procoagulant activity when TNF and HT mere used in combination compared to TNF or HT treatment alone. These results indicate that TNF and HT exert primarily independent effects on inflammatory cytokine production in EC but synergistically increase procoagulant activity as reflected in TF production. These data provide a possible mechanism for the thrombotic effects in tumour neovasculature seen following isolation perfusion with these agents and provide a rationale for their combined use in this treatment setting. (C) 2000 Academic Press. C1 NCI, Surg Branch, Surg Metab Sect, NIH, Bethesda, MD 20892 USA. RP Alexander, HR (reprint author), NCI, Surg Branch, Surg Metab Sect, NIH, Bldg 10,Room 2B07,9000 Rockville Pike, Bethesda, MD 20892 USA. OI Gnant, Michael/0000-0003-1002-2118 NR 46 TC 31 Z9 34 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1043-4666 J9 CYTOKINE JI Cytokine PD APR PY 2000 VL 12 IS 4 BP 339 EP 347 DI 10.1006/cyto.1999.0568 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 301AD UT WOS:000086285200006 PM 10805214 ER PT J AU Roilides, E Katsifa, H Tsaparidou, S Stergiopoulou, T Panteliadis, C Walsh, TJ AF Roilides, E Katsifa, H Tsaparidou, S Stergiopoulou, T Panteliadis, C Walsh, TJ TI Interleukin 10 suppresses phagocytic and antihyphal activities of human neutrophils SO CYTOKINE LA English DT Article DE Candida albicans; interleukin 10; neutrophil; Staphylococcus aureus ID TUMOR-NECROSIS-FACTOR; HUMAN POLYMORPHONUCLEAR LEUKOCYTES; COLONY-STIMULATING FACTOR; T-CELL PROLIFERATION; CANDIDA-ALBICANS; PROTECTS MICE; ATTRIBUTABLE MORTALITY; BACTERICIDAL ACTIVITY; RECEPTOR ANTAGONIST; CYTOKINE PRODUCTION AB We investigated the effects of human interleukin 10 (IL-10) on the antibacterial and antifungal activities of human neutrophils (PMNs) against Staphylococcus aureus and Candida albicans, Incubation of PMNs from healthy volunteers with 20-100 ng/ml of IL-10 at 37 degrees C for 1 h suppressed phagocytosis of serum-opsonized S. aureus (P=0.02) and blastoconidia of C. albicans (P<0.01). In contrast, 2-100 ng/ml of IL-10 had no effect on superoxide anion production upon stimulation with phorbol myristate acetate, N-formylmethionyl leucyl phenylalanine, C. albicans blastoconidia or pseudohyphae; neither did it significantly affect conidiocidal or bactericidal activities of PMNs. However, 20-100 ng/ml of IL-10 significantly decreased PMN-induced damage of C, albicans pseudohyphae (P=0.008). The suppression of phagocytic activity of PMNs against S. am eas and blastoconidia of C, albicans as well as the impairment of PMN-induced hyphal damage may have important implications for understanding the immunosuppressive profile of IL-10 in clinical usage. C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. Univ Thessaloniki, Dept Pediat 3, GR-54006 Salonika, Greece. RP Walsh, TJ (reprint author), NCI, Pediat Oncol Branch, Bldg 10,Rm 13N240, Bethesda, MD 20892 USA. NR 58 TC 31 Z9 32 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 2000 VL 12 IS 4 BP 379 EP 387 DI 10.1006/cyto.1999.0567 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 301AD UT WOS:000086285200012 PM 10805220 ER PT J AU Pazman, C Mayes, CA Fanto, M Haynes, SR Mlodzik, M AF Pazman, C Mayes, CA Fanto, M Haynes, SR Mlodzik, M TI Rasputin, the Drosophila homologue of the RasGAP SH3 binding protein, functions in Ras- and Rho-mediated signaling SO DEVELOPMENT LA English DT Article DE RasGAP; development; ommatidial polarity; Ras; Rho; Drosophila ID GTPASE-ACTIVATING PROTEIN; RECEPTOR TYROSINE KINASE; GUANINE-NUCLEOTIDE EXCHANGE; RNA-RECOGNITION MOTIF; CELL-FATE; PLANAR POLARITY; MAP KINASE; FUNCTIONS DOWNSTREAM; RIBONUCLEOPROTEIN-K; TISSUE POLARITY AB The small GTPase Ras plays an important role in many cellular signaling processes. Ras activity is negatively regulated by GTPase activating proteins (GAPs). It has been proposed that RasGAP may also function as an effector of Ras activity. We have identified and characterized the Drosophila homologue of the RasGAP-binding protein G3BP encoded by rasputin (rin), ria mutants are viable and display defects in photoreceptor recruitment and ommatidial polarity in the eye. Mutations in rin/G3BP genetically interact with components of the Ras signaling pathway that function at the level of Ras and above, but not with Raf/MAPK pathway components. These interactions suggest that Rin is required as an effector in Ras signaling during eye development, supporting an effector role for RasGAP. The ommatidial polarity phenotypes of rin are similar to those of RhoA and the polarity genes, e.g. fz and dsh. Although rin/G3BP interacts genetically with RhoA, affecting both photoreceptor differentiation and polarity, it does not interact with the gain-of-function genotypes of fz and dsh, These data suggest that Rin is not a general component of polarity generation, but serves a function specific to Ras and RhoA signaling pathways. C1 EMBL, Dev Biol Programme, D-69117 Heidelberg, Germany. NICHHD, LMG, NIH, Bethesda, MD 20892 USA. RP Mlodzik, M (reprint author), EMBL, Dev Biol Programme, Meyerhofstr 1, D-69117 Heidelberg, Germany. RI Fanto, Manolis/C-5618-2009 NR 68 TC 34 Z9 35 U1 0 U2 3 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 2000 VL 127 IS 8 BP 1715 EP 1725 PG 11 WC Developmental Biology SC Developmental Biology GA 313TQ UT WOS:000087015700016 PM 10725247 ER PT J AU Ko, MSH Kitchen, JR Wang, XH Threat, TA Wang, XQ Hasegawa, A Sun, T Grahovac, MJ Kargul, GJ Lim, MK Cui, YS Sano, Y Tanaka, T Liang, YL Mason, S Paonessa, PD Sauls, AD DePalma, GE Sharara, R Rowe, LB Eppig, J Morrell, C Doi, H AF Ko, MSH Kitchen, JR Wang, XH Threat, TA Wang, XQ Hasegawa, A Sun, T Grahovac, MJ Kargul, GJ Lim, MK Cui, YS Sano, Y Tanaka, T Liang, YL Mason, S Paonessa, PD Sauls, AD DePalma, GE Sharara, R Rowe, LB Eppig, J Morrell, C Doi, H TI Large-scale cDNA analysis reveals phased gene expression patterns during preimplantation mouse development SO DEVELOPMENT LA English DT Article DE mouse development; preimplantation; cDNA analysis; EST; stage-specific gene; gene mapping ID RNA DIFFERENTIAL DISPLAY; SEQUENCE TAGS; MAMMALIAN DEVELOPMENT; MOLECULAR-CLONING; PROTEIN-SYNTHESIS; EMBRYOS; GENOME; TRANSCRIPTION; IDENTIFICATION; CONSTRUCTION AB Little is known about gene action in the preimplantation events that initiate mammalian development. Based on cDNA collections made from each stage from egg to blastocyst, 25438 3'-ESTs were derived, and represent 9718 genes, half of them novel. Thus, a considerable fraction of mammalian genes is dedicated to embryonic expression. This study reveals profound changes in gene expression that include the transient induction of transcripts at each stage. These results raise the possibility that development is driven by the action of a series of stage-specific expressed genes. The new genes, 798 of them placed on the mouse genetic map, provide entry points for analyses of human and mouse developmental disorders. C1 Wayne State Univ, Ctr Mol Med & Genet, JST, ERATO Doi Bioasymmetry Project, Detroit, MI 48202 USA. NIA, Genet Lab, Dev Genom & Aging Sect, NIH, Baltimore, MD 21224 USA. JST, ERATO Doi Bioasymmetry Project, Mihama Ku, Chiba 2617112, Japan. Jackson Lab, Bar Harbor, ME 04609 USA. NIA, Res Resources Branch, Stat & Expt Design Sect, Baltimore, MD 21224 USA. Fujitsu Labs Ltd, Mihama Ku, Chiba 2610023, Japan. RP Ko, MSH (reprint author), Wayne State Univ, Ctr Mol Med & Genet, JST, ERATO Doi Bioasymmetry Project, Detroit, MI 48202 USA. RI Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 FU NICHD NIH HHS [R01HD32243] NR 49 TC 172 Z9 178 U1 0 U2 6 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 2000 VL 127 IS 8 BP 1737 EP 1749 PG 13 WC Developmental Biology SC Developmental Biology GA 313TQ UT WOS:000087015700018 PM 10725249 ER PT J AU Semba, I Nonaka, K Takahashi, I Takahashi, K Dashner, R Shum, L Nuckolls, GH Slavkin, HC AF Semba, I Nonaka, K Takahashi, I Takahashi, K Dashner, R Shum, L Nuckolls, GH Slavkin, HC TI Positionally-dependent chondrogenesis induced by BMP4 is co-regulated by Sox9 and Msx2 SO DEVELOPMENTAL DYNAMICS LA English DT Review DE BMP4; Sox9; Msx2; type II collagen; Meckel's cartilage; chondrogenesis; mouse embryo; mandibular process; bead implantation; organ culture; whole-mount in situ hybridization; Alcian Blue staining; competitive RT-PCR; adenovirus gene delivery ID BONE MORPHOGENETIC PROTEIN-2; II COLLAGEN GENE; SRY-RELATED GENE; CHICK LIMB BUD; MOUSE MANDIBULAR MORPHOGENESIS; AUTOSOMAL SEX REVERSAL; PROGRAMMED CELL-DEATH; NEURAL CREST CELLS; CAMPOMELIC DYSPLASIA; SIGNALING PATHWAYS AB Cranial neural crest cells emigrate from the posterior midbrain and anterior hindbrain to populate the first branchial arch and eventually differentiate into multiple cell lineages in the maxilla and mandible during craniofacial morphogenesis. In the developing mouse mandibular process, the expression profiles of BMP4, Msx2, Sox9, and type II collagen demonstrate temporally and spatially restrictive localization patterns suggestive of their functions in the patterning and differentiation of cartilage, Under serumless culture conditions, beads soaked in BMP4 and implanted into embryonic day 10 (E10) mouse mandibular explants induced ectopic cartilage formation in the proximal position of the explant. However, BMP4-soaked beads implanted at the rostral position did not have an inductive effect. Ectopic chondrogenesis was associated with the up-regulation of Sox9 and Msx2 expression in the immediate vicinity of the BMP4 beads 24 hours after implantation. Control beads had no effect on cartilage induction or Msx2 and Sox9 expression. SoxS was induced at all sites of BMP4 bead implantation In contrast, Msx2 expression was induced more intensely at the rostral position when compared with the proximal position, and suggested that Msx2 expression was inhibitory to chondrogenesis. To test the hypothesis that over-expression of Msx2 inhibits chondrogenesis, we ectopically expressed Msx2 in the mandibular process organ culture system using adenovirus gene delivery strategy. Microinjection of the Msx2-adenovirus to the proximal position inhibited BMP4-induced chondrogenesis, Over-expression of Msx2 also resulted in the abrogation of endogenous cartilage and the down-regulation of type II collagen expression, Taken together, these results suggest that BMP4 induces chondrogenesis, the pattern of which is positively regulated by SoxS and negatively by Msx2, Chondrogenesis only occurs at sites where SoxS expression is high relative to that of Msx2. The combinatorial action of these transcription factors appear to establish a threshold for SoxS function and thereby restricts the position of chondrogenesis, Published 2000 Wiley-Liss, Inc.(dagger). C1 NIAMSD, Craniofacial Dev Sect, NIH, Bethesda, MD 20892 USA. RP Slavkin, HC (reprint author), NIAMSD, Craniofacial Dev Sect, NIH, 6 Ctr Dr,Bldg 6,Room 324,MSC-2745, Bethesda, MD 20892 USA. FU NIAMS NIH HHS [Z01AR41114] NR 103 TC 73 Z9 74 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD APR PY 2000 VL 217 IS 4 BP 401 EP 414 DI 10.1002/(SICI)1097-0177(200004)217:4<401::AID-DVDY7>3.0.CO;2-D PG 14 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 299TZ UT WOS:000086215100007 PM 10767084 ER PT J AU Westergaard, GC Byrne, G Suomi, SJ AF Westergaard, GC Byrne, G Suomi, SJ TI Handedness and cortisol in tufted capuchin monkey infants SO DEVELOPMENTAL PSYCHOBIOLOGY LA English DT Article DE cortisol; capuchin; handedness; laterality; stress; hormones ID CEBUS-APELLA; HAND PREFERENCE; LATERAL BIAS; PRENATAL STRESS; TOOL-USE; BEHAVIOR; ASYMMETRIES; HEMISPHERE; AGE AB In this research, we examined the relationship between handedness and levels of plasma cortisol in infant monkeys (Cebus apella). Specifically, we sought to test the hypothesis that stress functioning is related to hemispheric specialization and is manifested in a positive correlation between cortisol levels ann the frequency of right- versus left-hand use. We found a significant relationship between str ess cortisol at age 6 months and lateral bias towards greater rise of the light versus left hand at ages 6 and 12 months. These data suggest art early developmental influence of stress reactivity on the emergence of hemispheric specialization for manual control in infant monkeys through the 1st year of postnatal life. (C) 2000 John Wiley & Sons, Inc. C1 Labs Virginia Inc, Div Res, Yemassee, SC USA. NICHHD, Comparat Ethol Lab, Poolesville, MD USA. RP Westergaard, GC (reprint author), Labs Virginia Inc, Div Res, Yemassee, SC USA. FU NCRR NIH HHS [R24 RR09983] NR 26 TC 15 Z9 15 U1 0 U2 3 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0012-1630 J9 DEV PSYCHOBIOL JI Dev. Psychobiol. PD APR PY 2000 VL 36 IS 3 BP 213 EP 217 DI 10.1002/(SICI)1098-2302(200004)36:3<213::AID-DEV4>3.0.CO;2-1 PG 5 WC Developmental Biology; Psychology SC Developmental Biology; Psychology GA 298ZV UT WOS:000086172100004 PM 10737866 ER PT J AU Bornstein, SR Abu-Asab, M Glasow, A Path, G Hauner, H Tsokos, M Chrousos, GP Scherbaum, WA AF Bornstein, SR Abu-Asab, M Glasow, A Path, G Hauner, H Tsokos, M Chrousos, GP Scherbaum, WA TI Immnohistochemical and ultrastructural localization of leptin and leptin receptor in human white adipose tissue and differentiating human adipose cells in primary culture SO DIABETES LA English DT Article ID TUMOR-NECROSIS-FACTOR; GENE-PRODUCT LEPTIN; 3T3-L1 ADIPOCYTES; OBESE GENE; OB GENE; EXPRESSION; CORTISOL; INSULIN; PLASMA; FAT AB Leptin is mainly produced in white adipose tissue and acts both at distant sites and locally at the tissue from which it originates. The cellular and subcellular localization of leptin and its receptor (Ob-receptor [Ob-R]) and their relationship to various stages of fat cell maturation have not been characterized as Set. Therefore, we analyzed leptin and Ob-R by using reverse transcriptase-polymerase chain reaction, immunohistochemistry, and ultrastructural immunogold labeling in human white adipose tissue and in human adipocyte cell cultures at early and late stages of differentiation. Both leptin and its receptor were present in mature unilocular fat cells. The thin cytoplasmic rim of the adipocytes exhibited the strongest expression of both leptin and Ob-R. At early stages of differentiating human adipocytes, leptin was mainly expressed in multilocular preadipocytes, whereas the Ob-R was found predominantly on fibroblast-like cells. Other cellular components of human white adipose tissue were characterized by anti-CD31 for endothelial cells, anti-CD68 for macrophages, and antibodies specifically labeling B-cells and T-cells. In addition to fat cells, endothelial cells were immunopositive for the full-length leptin receptor. On the ultrastructural level, leptin was mainly found attached to cellular membranes and in small alveolate vesicle-like structures in the cytoplasm of adipocytes. Leptin was also present on the cell membranes of endothelial cells and macrophages. We conclude that the expression of the Ob-R in human white adipose tissue is not restricted to adipocytes but is present in resident endothelial and immune cells. Ultrastructural localization studies revealed an association of leptin with cell membranes and small vesicles. The cellular and subcellular distribution of leptin and its receptor suggests an important autocrine and paracrine role for leptin in human adipose tissue. C1 NINCDS, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Univ Leipzig, Dept Pediat, D-7010 Leipzig, Germany. Univ Dusseldorf, Diabet Res Inst, D-4000 Dusseldorf, Germany. RP Bornstein, SR (reprint author), NINCDS, Pediat & Reprod Endocrinol Branch, NIH, Bldg 10,Room 10N262,9000 Rockville Pike, Bethesda, MD 20892 USA. OI Abu-Asab, Mones/0000-0002-4047-1232 NR 50 TC 122 Z9 132 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD APR PY 2000 VL 49 IS 4 BP 532 EP 538 DI 10.2337/diabetes.49.4.532 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 300YR UT WOS:000086281800002 PM 10871189 ER PT J AU Kido, Y Philippe, N Schaffer, AA Accili, D AF Kido, Y Philippe, N Schaffer, AA Accili, D TI Genetic modifiers of the insulin resistance phenotype in mice SO DIABETES LA English DT Article ID DEPENDENT DIABETES-MELLITUS; RECEPTOR SUBSTRATE-1; INTESTINAL NEOPLASIA; QUANTITATIVE TRAITS; COMPLEX TRAITS; KNOCKOUT MICE; EGF RECEPTOR; GK RAT; MOUSE; NIDDM AB Insulin resistance can result from genetic interactions among susceptibility alleles. To identify genetic loci predisposing to insulin resistance, we used crosses between different strains of mice with a targeted null allele of the insulin receptor gene. On the genetic background of B6 mice, the insulin receptor gene mutation causes mild hyperinsulinemia. In contrast, on the genetic background of 129/Sv mice, the same mutation causes severe hyperinsulinemia, suggesting that the 129/Sv strain harbors alleles that interact with the insulin receptor mutation and predispose to insulin resistance. As a first step to identify these alleles, we generated an F-2 intercross between insulin receptor heterozygous mutant mice on B6 and 129/Sv backgrounds (B6(IR) x 129(IR)) and performed a genome-wide scan with polymorphic markers at a 20-cM resolution. me report the identification of loci on chromosomes 2 (logarithm of odds [LOD] 5.58) and 10 (LOD 5.58) that show significant evidence for linkage to plasma insulin levels as a quantitative trait. These findings indicate that targeted mutations in knockout mice can be used to unravel the complex genetic interactions underlying insulin resistance. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Accili, D (reprint author), Berrie Res Pavil,1150 St Nicolas Ave,Room 238A, New York, NY 10032 USA. RI Schaffer, Alejandro/F-2902-2012 NR 52 TC 59 Z9 60 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 2000 VL 49 IS 4 BP 589 EP 596 DI 10.2337/diabetes.49.4.589 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 300YR UT WOS:000086281800009 PM 10871196 ER PT J AU Lievre, M Gueyffier, F Ekbom, T Fagard, R Cutler, J Schron, E Marre, M Boissel, JP AF Lievre, M Gueyffier, F Ekbom, T Fagard, R Cutler, J Schron, E Marre, M Boissel, JP CA The INDANA Steering Comm TI Efficacy of diuretics and beta-blockers in diabetic hypertensive patients - Results from a meta-analysis SO DIABETES CARE LA English DT Article; Proceedings Paper CT Symposium on Data, Results, and Consequences of Major Trials with focus on Type 2 Diabetes CY SEP 07-08, 1998 CL BARCELONA, SPAIN ID RANDOMIZED CLINICAL-TRIALS; ISOLATED SYSTOLIC HYPERTENSION; CORONARY HEART-DISEASE; HIGH BLOOD-PRESSURE; ANTIHYPERTENSIVE THERAPY; CARDIOVASCULAR EVENTS; INTERVENTION TRIAL; MILD HYPERTENSION; METAANALYSIS; MORTALITY AB OBJECTIVE - To review the effectiveness of diuretic or beta-blocker-based treatment of hypertension in diabetic patients. RESEARCH DESIGN AND METHODS - A meta-analysis on individual patient data was performed on four trials of the treatment of hypertension in which diabetic patients were included and treated with first-line diuretics or beta-blockers. The main outcomes were the relative risk of death, fatal or nonfatal stroke, fatal or nonfatal coronary events, and major cardiovascular events. RESULTS - There were 92 diabetic patients who received first-line beta-blockers and 1,008 who received diuretics. In the control groups, diabetic patients had nearly twice the risk of any outcome when compared with nondiabetic patients. The same blood pressure reduction was achieved under treatment in the diabetic and nondiabetic patients, except for systolic pressure, which decreased more in the nondiabetic patients at 1 year. In the 15,843 nondiabetic patients, the risk of all four outcomes was reduced significantly in the treated group. In the 2,254 diabetic patients, the risk reduction was significant only for fatal and nonfatal stroke (36%, P = 0.011) and major cardiovascular events (20%, P = 0.032),but not for death (5%, P = 0.65) and fatal or nonfatal coronary events (15%, P = 0.23). However, no heterogeneity was detected between diabetic patients and nondiabetic patients for any outcome. The numbers of outcomes avoided for 1,000 patients treated for 5 years were higher in diabetic patients (e.g., 38 major cardiovascular events) than with nondiabetic patients (e.g., 28 major cardiovascular events). CONCLUSIONS - These results show that hypertensive diabetic patients benefit from first-line treatment with diuretics. No conclusion can be drawn for beta-blockers, owing to the small sample size. C1 Univ Lyon 1, Lyon Hosp, Dept Clin Pharmacol, Equipe Accueil 643, Lyon, France. Dept Community Hlth Sci, Dalby Lund, Sweden. Hypertens & Cardiovasc Rehabil Unit, Louvain, Belgium. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Hosp Angers, Angers, France. RP Lievre, M (reprint author), Fac Med HRT Laennec, Serv Pharmacol Clin, Rue Guillaume Paradin,BP 8071, F-69376 Lyon 08, France. RI Gueyffier, Francois/B-8545-2008 OI Gueyffier, Francois/0000-0002-9921-0977 NR 43 TC 35 Z9 35 U1 0 U2 1 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 2000 VL 23 SU 2 BP B65 EP B71 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 300VJ UT WOS:000086273600011 PM 10860193 ER PT J AU Brown, SG King, BF Kim, YC Jang, SY Burnstock, G Jacobson, KA AF Brown, SG King, BF Kim, YC Jang, SY Burnstock, G Jacobson, KA TI Activity of novel adenine nucleotide derivatives as agonists and antagonists at recombinant rat P2X receptors SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE ion channel; oocytes; purines; ATP derivatives; bisphosphates; deoxyadenosine derivatives ID P-2Y-PURINOCEPTOR AGONISTS; P2Y(1) RECEPTORS; POTENT; IDENTIFICATION; PURINOCEPTORS; PLATELETS AB The effects of structural modifications of adenine nucleotides previously shown to enhance either agonist (2-thioether groups) or antagonist (additional phosphate moieties at the 3'- or 2'-position) properties at P2Y(1) receptors were examined at recombinant rat P2X(1), P2X(2), P2X(3), and P2X(4) receptors exp pressed in Xenopus oocytes. The potency of P2Y(1) agonists HT-AMP (2-(hexylthio)adenosine-5'-monophosphate) and PAPET (2-[2-(4-aminophenyl)ethylthio]adenosine was examined at P2X receptors. Both nucleotides showed a preference for the Group I (alpha,beta-meATP-sensitive, fast-inactivating) P2X subunits. HT-AMP was 5-fold more potent than ATP at P2X(3) receptors and a partial agonist at all except P2X(2) receptors, at which it was a full agonist. The efficacy of HT-AMP was as low as 23% at P2X(4) receptors. PAPET was a weak partial agonist at rat P2X(4) receptors and a nearly full agonist at the other subtypes. At rat P2X(3) receptors, PAPET was more potent than any other known agonist (EC(50) = 17 +/- 3 nM). MRS 2179 (N(6)- methyl-2'-deoxyadenosine 3', 5-bisphosphate, a potent P2Y(1) receptor antagonist) inhibited ATP-evoked responses at rat P2X(1) receptors with an IC(50) value of 1.15 +/- 0.21 mu M. MRS 2179 was a weak antagonist at rat P2X(3) receptors, with an IC(50) value of 12.9 +/- 0.1 mu M, and was inactive at rat P2X(2) and P2X(4) receptors. Thus, MRS 2179 was 11-fold and 130-fold selective for P2Y(1) receptors vs. P2X(1) and P2X(3) receptors, respectively. MRS 2209, the corresponding 3'-deoxy-2'-phosphate isomer, was inactive at rat P2X(1) receptors, thus demonstrating its greater selectivity as a P2Y(1) receptor antagonist. Various adenine bisphosphates in the family of MRS 2179 containing modifications of either the adenine (P2Y(1) antagonists with 2- and 6-substitutions), the phosphate (a 3',5'-cyclic diphosphate, inactive at P2Y(1) receptors), or the ribose moieties (antagonist carbocyclic analogue), were inactive at both rat P2X(1) and P2X(3) receptors. An anhydrohexitol derivative (MRS 2269) and an acyclic derivative (MRS 2286), proved to be selective antagonists at P2Y(1) receptors, since they were inactive as agonist or antagonist at P2X(1) and P2X(3) receptors. Published 2000 Wiley-Liss, Inc.dagger C1 NIDDK, LBC, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. UCL, Sch Med, Auton Neurosci Inst, London W1N 8AA, England. RP Jacobson, KA (reprint author), NIDDK, LBC, Mol Recognit Sect, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031116-20, Z99 DK999999] NR 26 TC 54 Z9 54 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD APR PY 2000 VL 49 IS 4 BP 253 EP 259 PG 7 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 325MQ UT WOS:000087679900004 PM 22791931 ER PT J AU LeRoith, D AF LeRoith, D TI Editorial: Insulin-like growth factor I receptor signalling - Overlapping or redundant pathways? SO ENDOCRINOLOGY LA English DT Editorial Material ID PHOSPHATIDYLINOSITOL 3-KINASE; REGULATED KINASES; DOMAINS; AKT; SUBSTRATE-1; ACTIVATION; APOPTOSIS; SURVIVAL; SHC C1 NIH, Bethesda, MD 20892 USA. RP LeRoith, D (reprint author), NIH, MSC 1758,Bldg 10,Room 8D12,10 Ctr Dr, Bethesda, MD 20892 USA. NR 20 TC 87 Z9 89 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 2000 VL 141 IS 4 BP 1287 EP 1288 DI 10.1210/en.141.4.1287 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 337WJ UT WOS:000088385800001 PM 10746630 ER PT J AU Draznin, B Miles, P Kruszynska, Y Olefsky, J Friedman, J Golovchenko, I Stjernholm, R Wall, K Reitman, M Accili, D Cooksey, R McClain, D Goalstone, M AF Draznin, B Miles, P Kruszynska, Y Olefsky, J Friedman, J Golovchenko, I Stjernholm, R Wall, K Reitman, M Accili, D Cooksey, R McClain, D Goalstone, M TI Effects of insulin on prenylation as a mechanism of potentially detrimental influence of hyperinsulinemia SO ENDOCRINOLOGY LA English DT Article ID GERANYLGERANYL TRANSFERASE; MOLECULAR-MECHANISMS; GLUCOSAMINE INFUSION; GROWTH-FACTOR; RESISTANCE; MICE; PROTEIN; FARNESYLTRANSFERASE; ACTIVATION; MUSCLE AB To investigate the cause and effect relationship between hyperinsulinemia and the increased amounts of farnesylated p21Ras, we performed hyperinsulinemic euglycemic clamps in normal weight volunteers as well as in normal mice and dogs. Insulin infusions significantly raised the amounts of farnesylated p21Ras in the white blood cells of humans, in liver samples of mice and dogs, and in aorta samples of mice. Obese hyperinsulinemic individuals and dogs (made hyperinsulinemic by surgical diversion of the pancreatic outflow from the portal vein into the vena cava) displayed increased amounts of farnesylated p21Ras before the hyperinsulinemic clamps. Infusions of insulin did not alter the already increased levels of farnesylated p21Ras in these experimental models. To further investigate the role of acquired insulin resistance in modulating insulin's effect on p21Ras prenylation, we induced insulin resistance in rats by glucosamine infusion. Insulin-resistant glucosamine-treated animals displayed significantly increased farnesylated p21Ras in response to insulin infusion compared to that in control saline-treated animals. Transgenic models of insulin resistance (heterozygous insulin receptor substrate-1 knockout mice, A-ZIP/F-1 fatless mice, and animals overexpressing glutamine:fructose-6-phosphate amidotransferase) contained increased amounts of farnesylated pa21Ras. We conclude that hyperinsulinemia, either endogenous (a prominent feature of insulin resistance) or produced by infusions of insulin, increases the amounts of farnesylated p21Ras in humans, mice, and dogs. This aspect of insulin action may represent one facet of the molecular mechanism of the potentially detrimental influence of hyperinsulinemia. C1 Univ Colorado, Hlth Sci Ctr, Denver Affairs Med Ctr,Dept Med, Dept Vet Affairs,Res Serv, Denver, CO 80220 USA. Univ Calif San Diego, San Diego Vet Affairs Med Ctr, San Diego, CA 92161 USA. Univ Calif San Diego, Dept Med, San Diego, CA 92161 USA. Case Western Reserve Univ, Sch Med, Dept Nutr, Cleveland, OH 44106 USA. NICHHD, Diabet Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Mississippi, Med Ctr, Vet Affairs Med Ctr, Jackson, MS 39216 USA. Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA. RP Draznin, B (reprint author), Vet Affairs Med Ctr 151, 1055 Clermont St, Denver, CO 80220 USA. EM drazninb@den-res.org RI Reitman, Marc/B-4448-2013 OI Reitman, Marc/0000-0002-0426-9475 NR 36 TC 36 Z9 39 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 2000 VL 141 IS 4 BP 1310 EP 1316 DI 10.1210/en.141.4.1310 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 337WJ UT WOS:000088385800004 PM 10746633 ER PT J AU Sharp, RR Barrett, JC AF Sharp, RR Barrett, JC TI The Environmental Genome Project: Ethical, legal, and social implications SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material DE environmental genome project; environmental genomics; ethics; genetic susceptibility; human subjects research; informed consent ID INFORMED CONSENT; GENETIC RESEARCH; TISSUE SAMPLES; PUBLIC-HEALTH; HUMAN-DISEASE; INSTITUTE AB The National Institute of Environmental Health Sciences is supporting a multiyear research initiative examining genetic influences on environmental response. Proponents of this new initiative, known as the Environmental Genome Project, hope that the information learned will improve our understanding of environmentally associated diseases and allow clinicians and public health officials to target disease-prevention strategies to those who are at increased risk Despite these potential benefits, the project presents several ethical and social challenges. Of immediate concern is the protection of individual research participants. Other ethical issues relate to the application of research results and how study findings could affect social priorities. Clarifying these emerging areas of concern, many of which have nor received adequate attention in the existing bioethics literature, is an important step toward minimizing potential research-related risks and defining research needs. C1 NIEHS, Off Sci Director, Res Triangle Pk, NC 27709 USA. RP Sharp, RR (reprint author), NIEHS, Off Sci Director, POB 12233,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 48 TC 17 Z9 20 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 2000 VL 108 IS 4 BP 279 EP 281 DI 10.2307/3454343 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 306KT UT WOS:000086596400021 PM 10753083 ER PT J AU Barr, DB Barr, JR Bailey, SL Lapeza, CR Beeson, MD Caudill, SP Maggio, VL Schecter, A Masten, SA Lucier, GW Needham, LL Sampson, EJ AF Barr, DB Barr, JR Bailey, SL Lapeza, CR Beeson, MD Caudill, SP Maggio, VL Schecter, A Masten, SA Lucier, GW Needham, LL Sampson, EJ TI Levels of methyleugenol in a subset of adults in the general US population as determined by high resolution mass spectrometry SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE mass spectrometry; methyleugenol; reference range; serum ID CHROMATOGRAPHY; EXPOSURE AB We developed a sensitive and accurate analytical method for quantifying methyleugenol (ME) in human serum. Our method uses a simple solid-phase extraction followed by a highly specific analysis using isotope dilution gas chromarography-high resolution mass spectrometry. Our method is very accurate; its limit of detection is 3.1 pg/g and its average coefficient of variation is 14% over a 200-pg/g range. We applied this method to measure serum ME concentrations in adults in the general U.S. population. ME was detected in 98% of our samples, with a mean ME concentration of 24 pg/g (range < 3.1-390 pg/g). Lipid adjustment of the data did not alter the distribution. Bivariate and multivariate analyses using selected demographic variables showed only marginal relationships between race/ethnicity and sex/fasting status with serum ME concentrations. Although no demographic variable was a good predictor of ME exposure or dose, our data indicate prevalent exposure of U.S. adults to ME. Detailed pharmacokinetic studies are required to determine the relationship between ME intake and human serum ME concentrations. C1 Ctr Dis Control & Prevent, CDC, Div Sci Lab, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA. NIEHS, Environm Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. RP Barr, DB (reprint author), Ctr Dis Control & Prevent, CDC, Div Sci Lab, Natl Ctr Environm Hlth, 4770 Buford Highway NE,Mailstop F17, Atlanta, GA 30341 USA. RI Needham, Larry/E-4930-2011; Barr, Dana/E-2276-2013; Barr, Dana/E-6369-2011; masten, scott/R-1403-2016 OI masten, scott/0000-0002-7847-181X NR 12 TC 8 Z9 8 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 2000 VL 108 IS 4 BP 323 EP 328 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 306KT UT WOS:000086596400028 PM 10753090 ER PT J AU Peluso, M Vineis, P AF Peluso, M Vineis, P TI 'Mediterranean diet' and DNA adducts SO EUROPEAN JOURNAL OF CANCER PREVENTION LA English DT Editorial Material ID BLADDER-CANCER; SMOKERS; FRUIT C1 Natl Canc Inst, Unit Expt Oncol, I-16132 Genoa, Italy. Biomed Sci & Human Oncol Dept, Canc Epidemiol Unit, I-10126 Turin, Italy. RP Peluso, M (reprint author), Natl Canc Inst, Unit Expt Oncol, Largo R Benzi 10, I-16132 Genoa, Italy. NR 14 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-8278 J9 EUR J CANCER PREV JI Eur. J. Cancer Prev. PD APR PY 2000 VL 9 IS 2 BP 71 EP 72 DI 10.1097/00008469-200004000-00001 PG 2 WC Oncology SC Oncology GA 313WL UT WOS:000087022600001 PM 10830572 ER PT J AU Krebs-Smith, SM Graubard, BI Kahle, LL Subar, AF Cleveland, LE Ballard-Barbash, R AF Krebs-Smith, SM Graubard, BI Kahle, LL Subar, AF Cleveland, LE Ballard-Barbash, R TI Low energy reporters vs others: a comparison of reported food intakes SO EUROPEAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE diet surveys; dietary underreporting; energy intake; dietary assessment; diet recalls ID FUNDAMENTAL PRINCIPLES; DIETARY; PHYSIOLOGY; WEIGHT; ADULTS AB Objective: To partition the food reports of low energy reporters (LERs) and non-LERs into four aspects-tendency to report a given food, frequency of reports per user, portion sizes per mention, and the qualitative (low-fat? low-sugar, low-energy) differences of the reports - in order to determine what differentiates them from one another. Assessment method: Two non-consecutive 24h dietary recalls. Low energy reporting was defined as energy intake lower than 80% of estimated basal metabolic rate. Setting:In-home personal interviews. Subjects: 8334 adults from a stratified, multi-stage area probability sample designed to be representative of noninstitutionlized persons residing in households in the United States. Results: Across all different types of foods, there are those food groups which LERs are less likely to report (28 of 44 food groups), those which they report less frequently when they do report them (15 of 44 groups), and those for which they report smaller quantities per mention (26 of 44). Qualitative differences in the food choices - that is, differences in fat, sugar, and/or energy content-were not so widespread (4 of 24 food groups). Conclusions: The practical application of analyses such as these is to improve the methods of gathering dietary data so that this kind of bias can be reduced. Further methodological research is needed to reduce the likelihood of respondents neglecting to mention foods and underestimating portion sizes. C1 NCI, NIH, Bethesda, MD 20892 USA. Informat Management Serv Inc, Silver Spring, MD USA. USDA ARS, Riverdale, MD USA. RP Krebs-Smith, SM (reprint author), NCI, NIH, 6130 Execut Blvd MSC 7344,EPN 313, Bethesda, MD 20892 USA. NR 25 TC 138 Z9 142 U1 3 U2 14 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0954-3007 J9 EUR J CLIN NUTR JI Eur. J. Clin. Nutr. PD APR PY 2000 VL 54 IS 4 BP 281 EP 287 DI 10.1038/sj.ejcn.1600936 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 323GP UT WOS:000087558000002 PM 10745278 ER PT J AU Bullmann, C Faust, M Hoffmann, A Heppner, C Jockenhovel, F Muller-Wieland, D Krone, W AF Bullmann, C Faust, M Hoffmann, A Heppner, C Jockenhovel, F Muller-Wieland, D Krone, W TI Five cases with central diabetes insipidus and hypogonadism as first presentation of neurosarcoidosis SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID SERUM LEVEL; SARCOIDOSIS; PITUITARY; MANIFESTATIONS; HYPOPHYSITIS; PROGRESS; PATIENT; MARKERS AB Objectives: We retrospectively reviewed 5 patients with neurosarcoidosis, who all presented with central diabetes insipidus and hypogonadism. Design: This was a single-centre, retrospective analysis of 5 cases with a minimum follow-up of 2 years. Methods: Case analysis included clinical, biochemical, and endocrinological evaluation and frequent CT/MRI scans of involved organs as primary evaluation and in response to immunosuppressive therapy. Result: Neurosarcoidosis was diagnosed in all patients. Two patients had no proven extracerebral manifestation and had a stable disease over 3 and 5 years. One patient showed deterioration with corticosteroids alone but partial remission after additional cyclophosphamide. Pituitary dysfunction remained unchanged in all patients, despite total clinical and radiological remission in two patients. However, one of these patients died of acute granulomatous meningoencephalitis after two years of follow-up. Conclusion: Although the presenting symptoms of neurosarcoidosis may vary, the occurrence of central diabetes insipidus associated with typical radiological features is suggestive of neurosarcoidosis. However, there is an increasing number of case reports on lymphocytic hypophysitis. Without the bioptic diagnosis, the differentiation between potentially lethal isolated neurosarcoidosis and lymphocytic hypophysitis is difficult. These cases demonstrate the difficulties in diagnosing neurosarcoidosis and reflect experiences with follow-up parameters. C1 Univ Cologne, Klin & Poliklin Innere Med 2, D-50924 Cologne, Germany. NIDDK, NIH, Bethesda, MD USA. RP Bullmann, C (reprint author), Univ Cologne, Klin & Poliklin Innere Med 2, Joseph Stelzmann Str 9, D-50924 Cologne, Germany. NR 31 TC 58 Z9 61 U1 0 U2 0 PU BIO SCIENTIFICA LTD PI BRISTOL PA 16 THE COURTYARD, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4NQ, ENGLAND SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD APR PY 2000 VL 142 IS 4 BP 365 EP 372 DI 10.1530/eje.0.1420365 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 309NZ UT WOS:000086775500010 PM 10754478 ER PT J AU Boehlk, S Fessele, S Mojaat, A Miyamoto, NG Werner, T Nelson, EL Schlondorff, D Nelson, PJ AF Boehlk, S Fessele, S Mojaat, A Miyamoto, NG Werner, T Nelson, EL Schlondorff, D Nelson, PJ TI ATF and Jun transcription factors, acting through an Ets/CRE promoter module, mediate lipopolysaccharide inducibility of the chemokine RANTES in monocytic Mono Mac 6 cells SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE lipopolysaccharide; RANTES; transcriptional regulation; CRE element; monocyte ID CASEIN KINASE-II; NUCLEAR FACTOR; T-LYMPHOCYTES; IN-VIVO; C-JUN; GENE; MACROPHAGES; ACTIVATION; EXPRESSION; IDENTIFICATION AB The chemokine RANTES is produced by a variety of tissues, including cells of the monocyte/ macrophage lineage. RANTES expression is rapidly and transiently up-regulated in primary monocytes and the monocytic cell line Mono Mac 6 in response to stimulation by the bacterial product lipopolysaccharide (LPS). Transient transfection of Mono Mac 6 cells with RANTES reporter-promoter deletion constructs, in conjunction with DNase I footprinting and heterologous reporter gene assays, allowed identification of an LPS-responsive region within the RANTES promoter Electrophoretic mobility shift assays (EMSA), methylation interference and EMSA supershift experiments were used to characterize sequences and transcription factors responsible for this LPS inducibility. The region, termed RANTES site G [R(G)], contains consensus sites for Ets and CRE/AP-1-like elements. Site-directed mutagenesis of the Ets site resulted in a loss of only 15 % of promoter activity, while mutation of the CRE/ AP-1 site led to a loss of 40 % of LPS-induced promoter activity. The Ets site constitutively binds the Ets family member PU.1. LPS stimulation leads to an induction of ATF-3 and JunD factor binding to the CRE/AP-1 site. Thus, LPS induction of RANTES transcription is mediated, in part, through the activation and selective binding of ATF and Jun nuclear factors to the R(G) promoter module. C1 Univ Munich, AG Med Poliklin, Munich, Germany. Berlex Biosci Inc, Dept Immunol, Richmond, CA USA. GSF, Natl Res Ctr Environm & Hlth, Inst Mammalian Genet, Neuherberg, Germany. Genomatix Software GmbH, Munich, Germany. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. RP Nelson, PJ (reprint author), Univ Munich, Med Poliklin, Schillerstr 42, D-80336 Munich, Germany. OI Fessele, Sabine/0000-0002-5399-3574 NR 42 TC 52 Z9 54 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD APR PY 2000 VL 30 IS 4 BP 1102 EP 1112 DI 10.1002/(SICI)1521-4141(200004)30:4<1102::AID-IMMU1102>3.0.CO;2-X PG 11 WC Immunology SC Immunology GA 305MK UT WOS:000086543700016 PM 10760799 ER PT J AU Chang, JT Segal, BM Nakanishi, K Okamura, H Shevach, EM AF Chang, JT Segal, BM Nakanishi, K Okamura, H Shevach, EM TI The costimulatory effect of IL-18 on the induction of antigen-specific IFN-gamma production by resting T cells is IL-12 dependent and is mediated by up-regulation of the IL-12 receptor beta 2 subunit SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE Th1 lymphocyte; experimental allergic encephalomyelitis autoimmunity; IFN-gamma; IL-12 receptor ID TH2 CELLS; AUTOIMMUNE-DISEASE; MICE; EXPRESSION; RESPONSES; CYTOKINE; ACTIVATION; SYNERGISM; TYPE-1; IGIF AB IL-18 was originally described as a cytokine which induced lFN-gamma production by established Th1 cells in an IL-12-independent manner. However, subsequent studies demonstrated that exogenous IL-18 in the absence of IL-12 failed to drive Th1 differentiation of naive cells and induced IFN-gamma from established Th1 cells only in combination with IL-12. We have examined the role of endogenous IL-18 in controlling Th1 lineage commitment. When naive TCR-transgenic T cells were stimulated with antigen, anti-IL-18 antibodies resulted in partial inhibition of IFN-gamma production, but did not inhibit Th1 differentiation. To distinguish whether the inhibitory effect of anti-IL-18 antibodies was mediated directly by blocking IFN-gamma production or indirectly by blocking IL-12R beta 2 up-regulation, naive T cells from IL-12-/-mice were stimulated with anti-CD3 and IL-18, These cells failed to produce IFN-gamma, but markedly upregulated IL-12R beta 2 expression. We propose that the major effect of IL-18 on Th1 development is mediated by up-regulation of IL-12R beta 2 expression, thereby enhancing IL-12-mediated signaling. The enhancement of IL-12R beta 2 expression by IL-18 may be particularly important for the differentiation of foreign antigen- or autoantigen-specific Th1 cells when the stimulatory concentration of IL-12 in the microenvironment is just below the threshold required for Th1 development. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. HHMI NIH Res Scholars Program, Bethesda, MD USA. RP Shevach, EM (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N315, Bethesda, MD 20892 USA. NR 22 TC 112 Z9 113 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 2000 VL 30 IS 4 BP 1113 EP 1119 DI 10.1002/(SICI)1521-4141(200004)30:4<1113::AID-IMMU1113>3.0.CO;2-P PG 7 WC Immunology SC Immunology GA 305MK UT WOS:000086543700017 PM 10760800 ER PT J AU Sodora, DL Douek, DC Silvestri, G Montgomery, L Rosenzweig, M Igarashi, T Bernacky, B Johnson, RP Feinberg, MB Martin, MA Koup, RA AF Sodora, DL Douek, DC Silvestri, G Montgomery, L Rosenzweig, M Igarashi, T Bernacky, B Johnson, RP Feinberg, MB Martin, MA Koup, RA TI Quantification of thymic function by measuring T cell receptor excision circles within peripheral blood and lymphoid tissues in monkeys SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE thymus; T lymphocyte; monkey ID SIMIAN IMMUNODEFICIENCY VIRUS; BONE-MARROW TRANSPLANTATION; V(D)J RECOMBINATION; SOOTY MANGABEYS; GENE-EXPRESSION; INFECTION; NAIVE; MEMORY; DISEASE; LOCUS AB The thymus is the primary organ responsible for the production of mature TCR alpha/beta T cells. Quantification of a DNA excision circle that is produced during TCR rearrangement, termed a signal joint TCR rearrangement excision circle (sjTREC) can be used as a measure of thymic function. Here sjTREC measurement has been applied to two monkey species used as animal models of human disease, rhesus macaques (Asian origin) and sooty mangabeys (African origin). Initial PCR analysis determined that the TCR delta Rec-psi J alpha rearrangement leading to sjTREC formation occurs in both species. Primers to a DNA sequence conserved in macaques, mangabeys and humans were used in a quantitative competitive PCR assay to quantify sjTREC. We found that as in humans, sjTREC in these two monkey species decline with age, sjTREC are first generated in thymocytes during the early stages of TCR rearrangement. Lymph node CD4(+) and CD8(+) T cells contain more sjTREC than peripheral blood T cell populations, suggesting that recent thymic emigrants home to the lymphoid tissues. The sjTREC level is significantly higher within the peripheral blood CD4(+) and CD8(+) T cells of mangabeys compared to macaques. Removal of the thymus in four macaques led to a profound decrease in peripheral blood sjTREC level by 1 year post-thymectomy, indicating the lack of a significant extra-thymic source of peripheral naive T cells in macaques. Our results indicate that production, trafficking, and proliferation of recent thymic emigrants in these two monkey species represents a useful animal model system for understanding human immunological disorders. C1 Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75235 USA. Emory Univ, Emory Vaccine Res Ctr, Atlanta, GA 30322 USA. Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Immunol, Southborough, MA 01772 USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Dept Vet Sci Bastrop, Houston, TX 77030 USA. RP Sodora, DL (reprint author), Univ Texas, SW Med Ctr, Dept Internal Med, 5323 Harry Hines Blvd,Room Y9-204, Dallas, TX 75235 USA. FU NIAID NIH HHS [AI35522, AI44758]; NIDCR NIH HHS [DE12926] NR 36 TC 63 Z9 63 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 2000 VL 30 IS 4 BP 1145 EP 1153 DI 10.1002/(SICI)1521-4141(200004)30:4<1145::AID-IMMU1145>3.0.CO;2-7 PG 9 WC Immunology SC Immunology GA 305MK UT WOS:000086543700021 PM 10760804 ER PT J AU Ma, W Maric, D Li, BS Hu, Q Andreadis, JD Grant, GM Liu, QY Shaffer, KM Chang, YH Zhang, L Pancrazio, JJ Pant, HC Stenger, DA Barker, JL AF Ma, W Maric, D Li, BS Hu, Q Andreadis, JD Grant, GM Liu, QY Shaffer, KM Chang, YH Zhang, L Pancrazio, JJ Pant, HC Stenger, DA Barker, JL TI Acetylcholine stimulates cortical precursor cell proliferation in vitro via muscarinic receptor activation and MAP kinase phosphorylation SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE Ca2+ imaging; neural stem cell; neurogenesis; rat; signal transduction ID STEM-CELLS; OLIGODENDROCYTE PROGENITORS; CHOLINERGIC NEURONS; PROTEIN-KINASE; GROWTH-FACTORS; RAT-BRAIN; EXPRESSION; MITOGEN; NEUROTRANSMITTERS; SUBUNITS AB Increasing evidence has shown that some neurotransmitters act as growth-regulatory signals during brain development. Here we report a role for the classical neurotransmitter acetylcholine (ACh) to stimulate proliferation of neural stem cells and stem cell-derived progenitor cells during neural cell lineage progression in vitro. Neuroepithelial cells in the ventricular zone of the embryonic rat cortex were found to express the m2 subtype of the muscarinic receptor. Neural precursor cells dissociated from the embryonic rat cortical neuroepithelium were expanded in culture with basic fibroblast growth factor (bFGF). reverse transcriptase-polymerase chain reaction (RT-PCR) revealed the presence of m2, m3 and m4 muscarinic receptor subtype transcripts, while immunocytochemistry demonstrated m2 protein. ACh and carbachol induced an increase in cytosolic Ca2+ and membrane currents in proliferating (BrdU(+)) cells, both of which were abolished by atropine. Exposure of bFGF-deprived precursor cells to muscarinic agonists not only increased both cell number and DNA synthesis, but also enhanced differentiation of neurons. These effects were blocked by atropine, indicating the involvement of muscarinic ACh receptors. The growth-stimulating effects were also antagonized by a panel of inhibitors of second messengers, including 1,2-bis-(O-aminophenoxy)-ethane-N, N, N',N'-tetraacetic acid (BAPTA-AM) to chelate cytosolic Ca2+, EGTA to complex extracellular Ca2+, pertussis toxin, which uncouples certain G-proteins, the protein kinase C inhibitor H7 and the mitogen-activated protein kinase (MAPK) inhibitor PD98059. Muscarinic agonists activated MARK, which was significantly inhibited by atropine and the same panel of inhibitors. Thus, muscarinic receptors expressed by neural precursors transduce a growth-regulatory signal during neurogenesis via pathways involving pertussis toxin-sensitive G-proteins, Ca2+ signalling, protein kinase C activation, MAPK phosphorylation and DNA synthesis. C1 USN, Ctr Biomol Sci & Engn, Res Lab, Washington, DC 20375 USA. NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Ma, W (reprint author), USN, Ctr Biomol Sci & Engn, Res Lab, Washington, DC 20375 USA. RI Pancrazio, Joseph/M-3206-2015 OI Pancrazio, Joseph/0000-0001-8276-3690 FU NIAAA NIH HHS [R21AA12237-02] NR 38 TC 115 Z9 119 U1 1 U2 6 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD APR PY 2000 VL 12 IS 4 BP 1227 EP 1240 DI 10.1046/j.1460-9568.2000.00010.x PG 14 WC Neurosciences SC Neurosciences & Neurology GA 311UM UT WOS:000086904100008 PM 10762352 ER PT J AU Skaleric, U Manthey, CM Mergenhagen, SE Gaspirc, B Wahl, SM AF Skaleric, U Manthey, CM Mergenhagen, SE Gaspirc, B Wahl, SM TI Superoxide release and superoxide dismutase expression by human gingival fibroblasts SO EUROPEAN JOURNAL OF ORAL SCIENCES LA English DT Article DE gingival fibroblasts; lipopolysaccharide; TNF-alpha; superoxide; superoxide dismutase ID TUMOR NECROSIS FACTOR; GROWTH-FACTOR-BETA; FREE-RADICALS; HYDROGEN-PEROXIDE; OXYGEN RADICALS; TISSUE-INJURY; INFLAMMATION; CYTOKINES; PROLIFERATION; INTERLEUKIN-1 AB Oxygen reactive intermediates released from phagocytic cells are important for microbicidal activity, but they may also be harmful to surrounding cells and matrix components at the inflammation site. In different forms of inflammatory periodontal disease, peripheral and crevicular polymorphonuclear leukocytes, as well-as mononuclear phagocytes and gingival fibroblasts, are exposed to bacterial cell wall components and cytokines. The aim of this study was to evaluate if some bacterial components and cytokines induce superoxide release and superoxide dismutase (SOD) expression in gingival fibroblasts. Lipopolysaccharide (LPS), streptococcal cell walls (SCW), and formyl-methionyl-leucyl-phenylalanine were found to stimulate O-2(-) release from gingival fibroblasts, which increased when Ca2+ was added. Phorbol myristate acetate, a potent activator of respiratory burst in phagocytes, was found to be a weak stimulator of O-2(-) release in gingival fibroblasts. Of the cytokines tested, tumor necrosis factor (TNF)-alpha was found to activate superoxide release in gingival fibroblasts. Gene expression for manganese superoxide dismutase (MnSOD), but not for copper/zinc superoxide dismutase (CuZnSOD), was demonstrated in fibroblasts exposed to LPS, SCW and TNF-alpha using Northern blot analysis. The production of MnSOD may be protective for these cells. We conclude that bacterial cell wall components and cytokines modulate O-2(-) release by gingival fibroblasts which may contribute to periodontal pathology. C1 Univ Ljubljana, Fac Med, Dept Oral Med & Periodontol, Ljubljana 1000, Slovenia. NIDCR, Oral Infect & Immun branch, NIH, Bethesda, MD USA. RP Skaleric, U (reprint author), Univ Ljubljana, Fac Med, Dept Oral Med & Periodontol, Ljubljana 1000, Slovenia. EM skaleric@ibmi.mf.uni-lj.si RI Gaspirc, Boris/A-6110-2008 NR 44 TC 29 Z9 31 U1 1 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0909-8836 J9 EUR J ORAL SCI JI Eur. J. Oral Sci. PD APR PY 2000 VL 108 IS 2 BP 130 EP 135 DI 10.1034/j.1600-0722.2000.90771.x PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 300YZ UT WOS:000086282500008 PM 10768726 ER PT J AU Rand, MK Hikosaka, O Miyachi, S Lu, XF Nakamura, K Kitaguchi, K Shimo, Y AF Rand, MK Hikosaka, O Miyachi, S Lu, XF Nakamura, K Kitaguchi, K Shimo, Y TI Characteristics of sequential movements during early learning period in monkeys SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE procedural memory; sequential movements; memory transfer; monkey ID INTERMANUAL TRANSFER; FUNCTIONAL-ANATOMY; MOTOR; SKILL; TASK; ACQUISITION; PERFORMANCE; ACTIVATION; FREQUENCY; KNOWLEDGE AB We previously demonstrated that the organization of a learned sequential movement, after long-term practice, is based on the entire sequence and that the information pertaining to the sequence is largely specific to the hand used for practice. However, it remained unknown whether these characteristics are present from the beginning of learning. To answer the question, we examined the performance of four monkeys for the same sequential procedure in the early stage of learning. The monkeys' task was to press five consecutive pairs of buttons (which were illuminated), in a correct order for every pair, which they had to find by trial-and-error during a block of trials. We first examined whether the memory of a sequential procedure that was learned once was specific to the hand used for practice. The second time that the monkeys attempted to learn a novel sequence, they were required to use either the same hand they used the first time or the opposite hand. The number of errors decreased to a similar degree in the same-hand condition and in the opposite-hand condition. The performance time decreased in the same-hand condition, but not in the opposite-hand condition. The results suggest that, in the early stage of learning, memory of the correct performance of a sequential procedure is not specific to the hand originally used to perform the sequence (unlike the well-learned stage, where the transfer was incomplete), whereas memory of the fast performance of a sequential procedure is relatively specific to the hand used for practice (like the well-learned stage). We then examined whether memory of a sequential procedure depends on the entire sequence, not individual stimulus sets. For the second learning block, we had the monkey learn the sequence in the same or reversed order. In the reversed order, the order within each set was identical, but the order of sets was reversed. The number of errors decreased in both the same-order and reversed-order conditions to a similar degree for two out of four monkeys; the decrease was larger in the same-order condition for the other two monkeys. For all monkeys, the performance time decreased in the same-order condition, but not in the reversed-order condition. The results suggest that the memory structure for correct performance varies among monkeys in the early stage of learning (unlike the well-learned stage, where the memory of individual sets was consistently absent). On the other hand, memory of the fast performance of a sequential procedure is relatively specific to the learned order used for practice (like the well-learned stage). (C) Springer-Verlag 2000. C1 Arizona State Univ, Dept Exercise Sci & Phys Educ, Tempe, AZ 85287 USA. Juntendo Univ, Sch Med, Dept Physiol, Bunkyo Ku, Tokyo 1138421, Japan. NIMH, Lab Syst Neurosci, NIH, Bethesda, MD 20892 USA. VAMC, Brain Sci Ctr, Minneapolis, MN 55417 USA. Ctr Neural Basis Cognit, Mellon Inst 115, Pittsburgh, PA 15213 USA. RP Rand, MK (reprint author), Arizona State Univ, Dept Exercise Sci & Phys Educ, Box 870404, Tempe, AZ 85287 USA. NR 44 TC 39 Z9 39 U1 3 U2 7 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD APR PY 2000 VL 131 IS 3 BP 293 EP 304 DI 10.1007/s002219900283 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 303ZD UT WOS:000086457300005 PM 10789945 ER PT J AU Sun, B Sun, SH Chan, CC Caspi, RR AF Sun, B Sun, SH Chan, CC Caspi, RR TI Evaluation of in vivo cytokine expression in EAU-susceptible and resistant rats: a role for IL-10 in resistance? SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE experimental autoimmune uveitis; cytokines; IL-10; T-cells; rat ID EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; GENETIC SUSCEPTIBILITY; RETINAL ANTIGENS; UVEITIS; DISEASE AB Messenger RNAs for six cytokines (IL-12p40, IFN-gamma, IL-10, IL-4, TNF-alpha and TGF-beta 1) expressed in vivo during development of experimental autoimmune uveitis (EAU) were quantitated by PCR in (uncultured) peripheral lymphoid cells and in the eyes of EAU-susceptible Lewis and EAU resistant F344 rats. Disease was induced by immunization with the R16 peptide of IRBP (in RT1B(1) haplotype rats) or with whole IRBP (in all haplotypes). In the periphery, both Lewis and F344 expressed similar cytokine patterns. In ocular tissues, however, only Lewis expressed elevated type 1 and inflammatory cytokines (IL-12p40, IFN-gamma and TNF-alpha), coincident with onset and peak of disease. Interestingly, naive F344 rats expressed higher basal levels of IL-10 mRNA in the eyes, To examine the possible involvement of this phenomenon in resistance, basal levels of IL-10 vs susceptibility to IRBP were compared in Lewis, BN, DA, F344 and ACI strains. Lewis, BN and DA were susceptible and had low levels of IL-10 mRNA in eyes. F344 and ACI were resistant and expressed high basal levels of IL-10 mRNA. In an in vitro study, recombinant rat IL-10 (but not human or mouse IL-10) suppressed lymphocyte proliferation and IFN-gamma production by primed lymph node cells of R16 immunized rats, but did not suppress uveitogenic long-term T-cell lines polarized to the Th1 phenotype, suggesting that mature effector lymphocytes in the rat may lose their ability to be suppressed by IL-10, We propose that higher expression of the IL-10 gene in ocular tissues in some rat strains may represent a mechanism that contributes to a higher threshold of resistance to EAU, but this threshold may be overcome by a more mature Th1 effector with a reduced sensitivity to IL-10. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Caspi, RR (reprint author), NEI, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 15 TC 42 Z9 43 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD APR PY 2000 VL 70 IS 4 BP 493 EP 502 DI 10.1006/exer.1999.0808 PG 10 WC Ophthalmology SC Ophthalmology GA 315WQ UT WOS:000087136300012 PM 10865998 ER PT J AU Krupp, E Heynen, T Li, XL Post, RM Weiss, SRB AF Krupp, E Heynen, T Li, XL Post, RM Weiss, SRB TI Tolerance to the anticonvulsant effects of lamotrigine on amygdala kindled seizures: Cross-tolerance to carbamazepine but not valproate or diazepam SO EXPERIMENTAL NEUROLOGY LA English DT Article DE epilepsy; kindling; amygdala; lamotrigine; carbamazepine; tolerance; rats; valproate; diazepam ID CONTINGENT TOLERANCE; ANTIEPILEPTIC DRUGS; SYNAPTIC REORGANIZATION; BIPOLAR DISORDER; RECEPTOR-BINDING; CALCIUM CURRENTS; RATS; EPILEPSY; MECHANISMS; GABA(A) AB Using an amygdala-kindled seizure paradigm, we evaluated the acute and chronic anticonvulsant effects of lamotrigine (LTG). Lamotrigine produced dose-dependent inhibitory effects on seizure stage, afterdischarge (AD), and seizure duration. Lamotrigine (15 mg/kg) also increased the afterdischarge and seizure thresholds. Following repeated LTG administration and stimulation at 48-h intervals, tolerance developed to LTG's (15 mg/kg) anticonvulsant effects, and cross-tolerance was observed to the anticonvulsant effects of carbamazepine (CBZ, 15 mg/kg). In a separate group of kindled rats, CBZ (15 mg/kg) was repeatedly administered to induce tolerance. This led to a partial cross-tolerance to LTG, manifesting as an increased rate of tolerance development to LTG, and seizures following the first injection in some animals, which were not observed in CBZ-nontolerant controls. When these rats were made fully tolerant to LTG and then exposed to higher doses of LTG (30 and 50 mg/kg), no anticonvulsant effects were observed. In contrast, higher doses of CBZ (30 mg/kg) did restore efficacy in CBZ-tolerant animals. Cross-tolerance from LTG to valproate and diazepam was not observed, although cross-tolerance from CBZ to valproate has been reported previously. These data suggest that LTG has both shared and distinct anticonvulsant mechanisms from those of CBZ on amygdala-kindled seizures. The implications of these results for clinical therapeutics remain to be evaluated. (C) 2000 Academic Press. C1 NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. RP Krupp, E (reprint author), BASF LYNX Biosci AG, Dept Neurosci, INF 515, D-69120 Heidelberg, Germany. NR 58 TC 27 Z9 27 U1 0 U2 6 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD APR PY 2000 VL 162 IS 2 BP 278 EP 289 DI 10.1006/exnr.1999.7343 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 305EH UT WOS:000086526100005 PM 10739634 ER PT J AU Albensi, BC Sullivan, PG Thompson, MB Scheff, SW Mattson, MP AF Albensi, BC Sullivan, PG Thompson, MB Scheff, SW Mattson, MP TI Cyclosporin ameliorates traumatic brain-injury-induced alterations of hippocampal synaptic plasticity SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Alzheimer's disease; apoptosis; learning and memory; long-term depression; long-term potentiation; mitochondrial permeability transition ID LONG-TERM POTENTIATION; PERMEABILITY TRANSITION PORE; EXCITATORY AMINO-ACIDS; MITOCHONDRIAL DYSFUNCTION; RAT HIPPOCAMPUS; COGNITIVE DEFICITS; LIPID-PEROXIDATION; CORTICAL IMPACT; CYTOCHROME-C; CELL-DEATH AB Although traumatic brain injury (TBI) often results in impaired learning and memory functions, the underlying mechanisms are unknown and there are currently no treatments that can preserve such functions. We studied plasticity at CA3-CA1 synapses in hippocampal slices from rats subjected to controlled cortical impact TBI. Long-term potentiation (LTP) of synaptic transmission was markedly impaired, whereas long-term depression (LTD) was enhanced, 48 h following TBI when compared to unoperated and sham control rats. Post-TBI administration of cyclosporin A, a compound that stabilizes mitochondrial function, resulted in a highly significant amelioration of the impairment of LTP and completely prevented the enhancement of LTD. Our data suggest that alterations in hippocampal synaptic plasticity may be responsible for learning and memory deficits resulting from TBI and that agents such as cyclosporin A that stabilize mitochondrial function may be effective treatments for TBI. (C) 2000 Academic Press. C1 Univ Kentucky, Sanders Brown Res Ctr Aging, Lexington, KY 40536 USA. Univ Kentucky, Dept Anat & Neurobiol, Lexington, KY 40536 USA. NIA, Neurosci Lab, Baltimore, MD 21224 USA. RP Albensi, BC (reprint author), Univ Kentucky, Sanders Brown Res Ctr Aging, Lexington, KY 40536 USA. RI Albensi, Benedict/F-7304-2010; Mattson, Mark/F-6038-2012 NR 56 TC 66 Z9 68 U1 1 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD APR PY 2000 VL 162 IS 2 BP 385 EP 389 DI 10.1006/exnr.1999.7338 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 305EH UT WOS:000086526100014 PM 10739643 ER PT J AU Shakarian, AM Dwyer, DM AF Shakarian, AM Dwyer, DM TI Pathogenic Leishmania secrete antigenically related chitinases which are encoded by a highly conserved gene locus SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE chromosome; trypanosomatid protozoan; human parasite; chitinolytic activity; normal rabbit serum (NRS). ID SANDFLY VECTOR; DONOVANI; PROMASTIGOTES AB Recently, we identified and characterized a single-copy chitinase gene (LdCht1) from Leishmania donovani, a protozoan pathogen of humans. It has been hypothesized that this parasite enzyme plays a critical role in the survival of all Leishmania species within their sandfly vectors and for their transmission to humans. Thus, in the current study, pulse-field gel electrophoresis and Southern hybridization with the LdCht1 gene probe were used to demonstrate that this chitinase gene has been conserved across species lines of various pathogenic Leishmania. Further, immunoprecipitation and enzyme activity assays using an anti-LdCht1-peptide serum were used to show that the chitinases produced and released by this group of parasites possessed both highly conserved antigenic epitopes and enzyme activities. Results of these studies demonstrate that the chitinase gene locus and enzyme activity have been conserved across species lines among this group of human pathogens. C1 NIAID, Cell Biol Sect, Parasit Dis Lab, Div Intramural Res,NIH, Bethesda, MD 20892 USA. RP Dwyer, DM (reprint author), NIAID, Cell Biol Sect, Parasit Dis Lab, Div Intramural Res,NIH, 9000 Rockville Pike,Bldg 4,Room 126, Bethesda, MD 20892 USA. NR 7 TC 14 Z9 15 U1 0 U2 2 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 2000 VL 94 IS 4 BP 238 EP 242 DI 10.1006/expr.2000.4493 PG 5 WC Parasitology SC Parasitology GA 323LG UT WOS:000087566400004 PM 10831391 ER PT J AU Su, XZ Carlton, JMR AF Su, XZ Carlton, JMR TI Genome display and typing of Plasmodium parasites using anchored PolyA and PolyT oligonucleotides SO EXPERIMENTAL PARASITOLOGY LA English DT Article ID MALARIA PARASITES; CHLOROQUINE RESISTANCE; DNA POLYMORPHISMS; LINKAGE MAP; FALCIPARUM; CHABAUDI; MARKERS; RECOMBINATION C1 NIAID, NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. Univ Florida, Coll Vet Med, Dept Pathobiol, Gainesville, FL 32610 USA. RP Su, XZ (reprint author), NIAID, NIH, Parasit Dis Lab, Room 126,Bldg 4,4 Ctr Dr MSC 0425, Bethesda, MD 20892 USA. OI Su, Xinzhuan/0000-0003-3246-3248 NR 23 TC 3 Z9 3 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 2000 VL 94 IS 4 BP 273 EP 278 DI 10.1006/expr.2000.4492 PG 6 WC Parasitology SC Parasitology GA 323LG UT WOS:000087566400010 PM 10831397 ER PT J AU Tavel, JA AF Tavel, JA TI Ongoing trials in HIV protease inhibitors SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Article DE AIDS; antiretrovirals; HIV; protease inhibitors ID RITONAVIR PLUS SAQUINAVIR; RANDOMIZED TRIAL; INDINAVIR; INFECTION; THERAPY; DISEASE AB The development of antiretrovirals has led to a revolution in the care of patients infected with HIV. What was once a uniformly fatal syndrome has become a more creatable, chronic, infectious disease. Central to this revolution have been the protease inhibitors, a class of drugs with potent antiretroviral activity. The first member of this class was approved for use in 1995 and there are now five protease inhibitors approved by the US Food and Drug Administration (FDA): amprenavir, indinavir, nelfinavir, ritonavir and saquinavir. As a result of the magnitude of the HIV pandemic coupled with the clinically proven efficacy of protease inhibitors, there are currently hundreds of ongoing clinical trials with these agents. Trial designs include comparisons between the various licensed protease inhibitors, comparisons of protease inhibitors to other classes of potent antiretroviral drugs, investigations with new protease inhibitors, investigations of protease inhibitor-related toxicities and attempts at simplifying current dosing regimens. C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Tavel, JA (reprint author), NIAID, NIH, 9000 Rockville Pike,Bldg 10,Room 11C-103, Bethesda, MD 20892 USA. NR 32 TC 10 Z9 11 U1 0 U2 1 PU ASHLEY PUBL LTD PI LONDON PA 1ST FL, THE LIBRARY, 1 SHEPHERDS HILL HIGHGATE, LONDON N6 5QJ, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD APR PY 2000 VL 9 IS 4 BP 917 EP 928 DI 10.1517/13543784.9.4.917 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 344VP UT WOS:000088780400020 PM 11060719 ER PT J AU Lin, ZC Itokawa, M Uhl, GR AF Lin, ZC Itokawa, M Uhl, GR TI Dopamine transporter proline mutations influence dopamine uptake, cocaine analog recognition, and expression SO FASEB JOURNAL LA English DT Article DE affinity; translocation; ion gradients; turnover rate; plasma membrane targeting ID NOREPINEPHRINE TRANSPORTERS; STRUCTURAL DOMAINS; PROTEINS; RESIDUES; 1-METHYL-4-PHENYLPYRIDINIUM; INHIBITION; SUBSTRATE; CLONING; HELICES AB Analyses of mutation effects can aid in understanding how large proteins act, The dopamine transporter (DAT) mediates complex actions in recognizing cocaine and in recognizing and translocating dopamine, sodium, and chloride. DAT proline residues, especially those in transmembrane (TM) domains, are good candidates for involvement in these DAT actions. We now report production of mutants substituting alanine and/or glycine residues for 16 prolines located in or near putative DAT TM domains. We examine effects of these modifications on DAT expression, dopamine uptake, and cocaine analog binding. Mutants in prolines located in five DAT TM domains and four connecting loops alter apparent DAT membrane targeting, Five mutations decrease dopamine affinities more than threefold without significantly decreasing cocaine analog affinities. One decreases cocaine analog affinity without decreasing dopamine affinity. Two mutations decrease affinities for both dopamine and cocaine analog. P101 is especially implicated in dopamine uptake. Alanine substitution for this proline yields dopamine V-max values of less than 3% of wild-type values despite dopamine affinities more than fourfold higher than wild-type and normal Na+ and Cl- dependence. These DAT proline mutants identify DAT regions likely for dopamine translocation and for recognition of dopamine and cocaine.-Lin, Z., Itokawa, M., Uhl, G, R. Dopamine transporter proline mutations influence dopamine uptake, cocaine analog recognition, and expression. C1 NIDA, Mol Neurobiol Branch, IRP, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21224 USA. RP Uhl, GR (reprint author), NIDA, Mol Neurobiol Branch, IRP, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 33 TC 49 Z9 49 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2000 VL 14 IS 5 BP 715 EP 728 PG 14 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 301DH UT WOS:000086292700009 PM 10744628 ER PT J AU van Birgelen, APJM van den Berg, M AF van Birgelen, APJM van den Berg, M TI Toxicokinetics SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article; Proceedings Paper CT Meeting on the Assement of the Health Risk of Dioxins: Re-Evaluation of the Tolerable Daily Intake (TDI) CY MAY 25-29, 1998 CL GENEVA, SWITZERLAND SP WHO, European Ctr Environm & Hlth, Int Programme Chem Safety DE body burden; lipophilicity; metabolism; receptor binding; species difference ID DIBENZO-P-DIOXINS; CHLORINATED AROMATIC-HYDROCARBONS; NEONATAL NEUROLOGICAL DEVELOPMENT; POLYCHLORINATED-BIPHENYLS PCBS; SPRAGUE-DAWLEY RATS; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TCDD; BODY BURDEN; HEPATIC SEQUESTRATION; INCLUDING HUMANS; LIVER-MICROSOMES AB The toxicokinetic determinants of dioxin and related chemicals depend on three major properties: lipophilicity, metabolism, and binding to CYP1A2 in the liver. The induction of CYP1A2 is partially, under the control of the aryl hydrocarbon receptor (AhR). Lipophilicity increases with more chlorination and controls absorption and tissue partitioning. Metabolism is the rate-limiting step for elimination. Induction of CYP1A2 leads to hepatic sequestration of TCDD. Binding to this inducible hepatic protein results in non-linear dose-dependent tissue distribution. with increasing doses, the relative concentration in extra-hepatic tissues decreases while that in liver increases. The induction of this protein occurs in both animals and humans and results in an increase in the liver to fat ratio of these compounds. Humans have similar sensitivities to rodents for dioxin-like compounds when using tissue concentration (from in vitro studies), body burden, average lifetime serum lipid concentration, or lifetime area-under-the-curve concentration based on both low dose (biochemical) and high dose (cancer) driven endpoints. To reach the same tissue concentration in humans as rodents however, humans need a lower daily intake than rodents based on differences in pharmacokinetic behaviour. This clearly indicates that physiologically based pharmacokinetic models should be explored for the estimation of the daily intake of dioxin-like compounds in humans based on tissue dose levels or derivatives of those. C1 NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. Univ Utrecht, Toxicol Res Inst, NL-3508 TD Utrecht, Netherlands. RP van Birgelen, APJM (reprint author), Hoffmann La Roche Inc, 340 Kingsland St, Nutley, NJ 07110 USA. NR 63 TC 11 Z9 11 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PD APR PY 2000 VL 17 IS 4 BP 267 EP 273 DI 10.1080/026520300283342 PG 7 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 325WP UT WOS:000087699700004 PM 10912241 ER PT J AU Portier, C AF Portier, C TI Risk ranges for various endpoints following exposure to 2,3,7,8-TCDD SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article; Proceedings Paper CT Meeting on the Assement of the Health Risk of Dioxins: Re-Evaluation of the Tolerable Daily Intake (TDI) CY MAY 25-29, 1998 CL GENEVA, SWITZERLAND SP WHO, European Ctr Environm & Hlth, Int Programme Chem Safety DE cancer endpoints; curve fitting; dose-response; mechanistic models; non-cancer endpoints; (non-)linearity ID ETHOXYRESORUFIN-O-DEETHYLASE; ARYL-HYDROCARBON HYDROXYLASE; DOSE-RESPONSE RELATIONSHIPS; POLYCHLORINATED-BIPHENYLS; CANCER MORTALITY; GENE-EXPRESSION; CHLOROPHENOXY HERBICIDES; TISSUE DISTRIBUTION; PHENOXY HERBICIDES; CELL-PROLIFERATION AB Conducting a dose-response analysis for an environmental contaminant requires a careful evaluation of most of the available data focusing on both the magnitude of the effect and the possible ranges of dose-response shapes which fit the data. This paper calculates potency values (1% response exposures) for human and animal data on cancer, non-cancer and biological effect endpoints for TCDD and finds that a reasonable estimate for 1% excess cancer would be between 1 and 50 pg/kg/day. The paper also evaluates the adequacy of linear and non-linear models for fitting these data and concludes that the assumption of a threshold dose-response is not fully supported by these data. C1 NIEHS, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. RP Portier, C (reprint author), NIEHS, Lab Computat Biol & Risk Anal, POB 12233, Res Triangle Pk, NC 27709 USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 61 TC 5 Z9 5 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PD APR PY 2000 VL 17 IS 4 BP 335 EP 346 DI 10.1080/026520300283405 PG 12 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 325WP UT WOS:000087699700010 PM 10912247 ER PT J AU Kadiiska, MB Mason, RP AF Kadiiska, MB Mason, RP TI Acute methanol intoxication generates free radicals in rats: An ESR spin trapping investigation SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE methanol; free radicals; rat ID 1-HYDROXYETHYL RADICALS; HYDROXYL RADICALS; LIVER-MICROSOMES; ONE-ELECTRON; ALCOHOL-DEHYDROGENASE; CARBON-TETRACHLORIDE; AQUEOUS-SOLUTION; NITROUS-OXIDE; ETHANOL; METABOLISM AB Electron spin resonance (ESR) spectroscopy has been used to investigate free radical generation in rats with acute methanol poisoning. The spin trapping technique was used where a spin trapping agent, alpha-(4-pyridyl 1-oxide)N-tert-butylnitrone (POBN), reacted with the corresponding alcohol-derived or alcohol-dependent radical to from radical adducts. One radical adduct was detected in both bile and urine samples 2 h after acute methanol poisoning in male Sprague Dawley rats. The hyperfine coupling constants for the radical adduct from [C-13]-labeled methanol detected in the bile were a(N) = 15.58, a(beta)(H) = 2.81 G, and a(beta)(13C) = 4.53 G, which unambiguously identified this species as POBN/(CH2OH)-C-.. The same radical adduct was detected in urine. The identification of a methanol-derived radical adduct in samples from bile and urine provided strong direct evidence for the generation of the alcohol-derived radicals during acute intoxication by methanol. Simultaneous administration of the alcohol dehydrogenase inhibitor 4-methylpyrazole and methanol resulted in an increase in the generation of the free radical metabolite detected in the bile. This is the first ESR evidence of methanol-derived free radical generation in an animal model of acute methanol intoxication. (C) 2000 Elsevier Science Inc. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Kadiiska, MB (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 56 TC 30 Z9 31 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 1 PY 2000 VL 28 IS 7 BP 1106 EP 1114 DI 10.1016/S0891-5849(00)00203-3 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 323EE UT WOS:000087551200011 PM 10832072 ER PT J AU Abou-Saif, A Gibril, F Shojamanesh, H Jensen, RT AF Abou-Saif, A Gibril, F Shojamanesh, H Jensen, RT TI Does a change in serum chromogranin A or gastrin levels predict clinically important changes in gastrinoma size? 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 PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 3266 BP A641 EP A641 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702630 ER PT J AU Allison, JE Levin, TR Ackerson, LM Hurley, LB Lieu, TA Libran, DL Hiatt, RA AF Allison, JE Levin, TR Ackerson, LM Hurley, LB Lieu, TA Libran, DL Hiatt, RA TI Test and treat for H.pylori clinical outcomes in an HMO population on chronic acid suppression therapy for physician diagnosed peptic ulcer disease. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Pilgrim Hlth Care, Boston, MA USA. Kaiser Permanente, Oakland, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 1 Z9 1 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 2391 BP A438 EP A439 PN 1 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783701793 ER PT J AU Andreolotti, AG Tapia, JA Bragado, MJ Jensen, RT Garcia-Marin, LJ AF Andreolotti, AG Tapia, JA Bragado, MJ Jensen, RT Garcia-Marin, LJ TI CCK stmulates tyrosine phosphorylation of Crk by a PKC-independent, Ca2(+) dependent mechanisim in pancreatic acini. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Extremadura, E-06071 Badajoz, Spain. UEX, Dpto Fisiol, Caceres, Spain. UAH, Dept Fisiol, Alcala De Henares, Spain. NIDDK, 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 PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 624 BP A88 EP A88 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783700358 ER PT J AU Ashktorab, H Bancroft, C Neapolitano, M Allen, CR Dubois, A Elghazi, Y Smoot, DT AF Ashktorab, H Bancroft, C Neapolitano, M Allen, CR Dubois, A Elghazi, Y Smoot, DT TI Helicobacter pylori alters AP1, OCT1, and NF-KB DNA binding activity and pERK expression in gastric epithelial cells. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Howard Univ, Washington, DC 20059 USA. NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NR 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 4828 BP A868 EP A868 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783703538 ER PT J AU Bhatia, M Brady, M Shokuhi, S Zagorski, J Neoptolemos, JP Slavin, J AF Bhatia, M Brady, M Shokuhi, S Zagorski, J Neoptolemos, JP Slavin, J TI Treatment with neutralizing antibody against cytokine-induced neutrophil chemoattractant protects rats against acute pancreatitis-associated lung injury. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Liverpool, Dept Surg, Liverpool, Merseyside, England. NIDR, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 2190 BP A425 EP A425 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783701738 ER PT J AU Boirivant, M Fuss, IJ Ferroni, L De Pascale, M Strober, W AF Boirivant, M Fuss, IJ Ferroni, L De Pascale, M Strober, W TI Oral administration of recombinant cholera toxin subunit B inhibits IL-12 mediated murine experimental colitis. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Inst Super Sanita, Rome, Italy. NIH, Lci, Mis, Bethesda, MD 20892 USA. ISS, Immunol Lab, Rome, Italy. RI BOIRIVANT, MONICA/B-9977-2016 NR 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 2982 BP A571 EP A571 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702346 ER PT J AU Bonelli, L Senore, C Sciallero, S Ferraris, R Malfitana, G Penna, A Andreoni, B Crosta, C Zappa, M Gasperoni, S Bartolini, S Segnan, N AF Bonelli, L Senore, C Sciallero, S Ferraris, R Malfitana, G Penna, A Andreoni, B Crosta, C Zappa, M Gasperoni, S Bartolini, S Segnan, N TI Absolute risk of rectosigmoid neoplasms at screening flexible sigmoidoscopy and history of negative colorectal endoscopy (SCORE trial-Italy). SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Infirm Hosp, Rimini, Italy. Cspo, Florence, Italy. Ieo, Milan, Italy. Fondo E Tempia, Biella, Italy. Infirm Hosp, Biella, Italy. Mauriziano Umberto I Hosp, Turin, Italy. CPO Piemonte, Turin, Italy. Natl Canc Inst, Genoa, Italy. NR 0 TC 1 Z9 1 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 2426 BP A441 EP A441 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783701804 ER PT J AU Brant, SR Panhuysen, C Bailey-Wilson, J Lee, S Mann, J Rohal, PM Picco, MF Kirschner, BS Hanauer, SB Cho, JH Bayless, TM AF Brant, SR Panhuysen, C Bailey-Wilson, J Lee, S Mann, J Rohal, PM Picco, MF Kirschner, BS Hanauer, SB Cho, JH Bayless, TM TI Crohn's disease diagnosis before age 22 and with greater severity of disease identifies multiplex pedigrees at greater risk for locus IBD1. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Johns Hopkins Univ, Baltimore, MD USA. Boston Univ, Boston, MA 02215 USA. NIH, Baltimore, MD USA. Univ Chicago, Chicago, IL 60637 USA. Mayo Clin, Jacksonville, FL 32224 USA. NR 0 TC 1 Z9 1 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 3865 BP A708 EP A708 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702889 ER PT J AU Carroll, RE Matkowskyj, KA Battey, JF Benya, RV AF Carroll, RE Matkowskyj, KA Battey, JF Benya, RV TI Gastrin-releasing peptide (GRP) with its receptor (GRP-R) is a mitogen and morphogen in colon cancer. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Illinois, Chicago, IL USA. NIDCD, NIH, Bethesda, MD USA. NR 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 2926 BP A558 EP A558 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702290 ER PT J AU Carroll, RE Matkowskyj, KA Battey, JF Benya, RV AF Carroll, RE Matkowskyj, KA Battey, JF Benya, RV TI Gastrin-releasing peptide (GRP) with its receptor (GRP-R) is an autocrine growth factor important for villous development. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDCD, NIH, Bethesda, MD USA. Univ Illinois, Chicago, IL USA. NR 0 TC 1 Z9 1 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 2382 BP A436 EP A436 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783701785 ER PT J AU Deng, CX Mishra, L AF Deng, CX Mishra, L TI TGF-beta signaling by Smads in gastrointestinal development and cancer. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD USA. VAMC, Washington, DC USA. Temple Univ, Fels Canc Inst, Philadelphia, PA 19122 USA. NR 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 1203 BP A187 EP A187 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783700753 ER PT J AU Di Bisceglie, AM Bonkovsky, HL Dienstag, JL Everson, GT Lindsay, KL Gretch, DR Hoefs, JC Lee, WH Lok, AS Tralka, TS Shiffman, ML Wright, EC AF Di Bisceglie, AM Bonkovsky, HL Dienstag, JL Everson, GT Lindsay, KL Gretch, DR Hoefs, JC Lee, WH Lok, AS Tralka, TS Shiffman, ML Wright, EC TI Design of the halt-c trial (hepatitis C antiviral long-term treatment to prevent cirrhosis). SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 St Louis Univ, Sch Med, St Louis, MO USA. Univ Massachusetts, Sch Med, Worcester, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Colorado, Hlth Sci Ctr, Boulder, CO 80309 USA. USC, Sch Med, Los Angeles, CA USA. Univ Washington, Seattle, WA 98195 USA. Univ Calif Irvine, Med Ctr, Orange, CA USA. Univ Texas, Dallas, TX 75230 USA. Univ Michigan, Med Ctr, Ann Arbor, MI USA. NIDDK, NIH, Bethesda, MD USA. Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. New England Res Inst, Waltham, MA USA. RI Lok, Anna /B-8292-2009 NR 0 TC 3 Z9 3 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 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 6515 BP A1435 EP A1435 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RY UT WOS:000086784101588 ER PT J AU El-Omar, EM Wang, CD McColl, KE Rabkin, CS AF El-Omar, EM Wang, CD McColl, KE Rabkin, CS TI Interleukin-10 promoter polymorphisms influence risk of chronic H-pylori infection. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NCI, Rockville, MD USA. Univ Glasgow, Glasgow, Lanark, Scotland. NR 0 TC 3 Z9 3 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 4922 BP A889 EP A889 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783703618 ER PT J AU El-Omar, EM Chow, WHM McColl, KE Fraumeni, JF Rabkin, CS AF El-Omar, EM Chow, WHM McColl, KE Fraumeni, JF Rabkin, CS TI Interleukin-1 beta-enhancing genotypes are associated with increased risk of gastric cancer and its precursors. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Univ Glasgow, Glasgow, Lanark, Scotland. NR 0 TC 0 Z9 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 1022 BP A181 EP A181 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783700729 ER PT J AU El-Serag, HB Everhart, JE AF El-Serag, HB Everhart, JE TI Improved survival following esophageal variceal hemorrhage in the department of veterans affairs (VA). SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Houston VAMC, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. NIDDKD, Bethesda, MD 20892 USA. NR 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 1220 BP A192 EP A192 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783700770 ER PT J AU Ferrin, LJ Lee, HC AF Ferrin, LJ Lee, HC TI Structure of the fibroblast growth factor receptor 2 (FGFR2) amplicon in a gastric cancer cell line. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Univ Minnesota, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 2818 BP A532 EP A532 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702183 ER PT J AU Franchimont, DP Galon, J Gadina, M Visconti, R Chrousos, GP O'Shea, JJ AF Franchimont, DP Galon, J Gadina, M Visconti, R Chrousos, GP O'Shea, JJ TI Inhibition of Th1 immune response by glucocorticoids: Dexamethasone inhibits IL-12-induced Stat4 phosphorylation in T lymphocytes. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIAMS, NIH, Bethesda, MD USA. NIH, DEB, Bethesda, MD USA. NR 0 TC 1 Z9 1 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 4216 BP A790 EP A791 PN 1 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783703229 ER PT J AU Franchimont, DP Bouma, G Galon, J Wolkersdorfer, GW Haidan, A Chrousos, GP Bornstein, SR AF Franchimont, DP Bouma, G Galon, J Wolkersdorfer, GW Haidan, A Chrousos, GP Bornstein, SR TI Functional and morphological adrenal changes in TNBS-induced colitis. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, DEB, Bethesda, MD 20892 USA. NR 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 1852 BP A343 EP A343 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783701400 ER PT J AU Gaspard, JP Warshaw, AL Jensen, RT Chung, DC AF Gaspard, JP Warshaw, AL Jensen, RT Chung, DC TI Mapping of a novel pancreatic endocrine tumor suppressor gene locus to a 0.5 cm region on chromosome 3p. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NIH, Bethesda, MD 20892 USA. NR 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 3274 BP A643 EP A643 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702638 ER PT J AU Gershon, MD Li, S Chen, JX Weihems, C Murphy, DL AF Gershon, MD Li, S Chen, JX Weihems, C Murphy, DL TI Abnormal intestinal function in mice lacking the serotonin reuptake transporter (SERT). SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Columbia Univ, New York, NY 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 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 5395 BP A1173 EP A1173 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RY UT WOS:000086784100469 ER PT J AU Gershon, MD Li, S Chen, JX Murphy, DL AF Gershon, MD Li, S Chen, JX Murphy, DL TI Abnormal intestinal function in mice lacking the serotonin reuptake transporter (SERT). SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Columbia Univ, New York, NY USA. NIH, Bethesda, MD 20892 USA. NR 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 2096 BP A402 EP A402 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783701644 ER PT J AU Gibril, F Doppman, JL Chang, R Abou-Saif, A Peghini, P Roy, PK Shojamanish, H Jensen, RT AF Gibril, F Doppman, JL Chang, R Abou-Saif, A Peghini, P Roy, PK Shojamanish, H Jensen, RT TI Is selective intra-arterial secretin (IAS) during angiography useful in patients suspected of Zollinger-Ellison syndrome (ZES) with a negative intravenous secretin? A prospective study. 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 PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 3690 BP A674 EP A675 PN 1 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702760 ER PT J AU Gibril, F Doppman, JL Alexander, RH Abou-Saif, A Norton, JA Jensen, RT AF Gibril, F Doppman, JL Alexander, RH Abou-Saif, A Norton, JA Jensen, RT TI Are all pancreatic gastrinomas in different locations equally aggressive? A prospective study. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. NIH, Bethesda, MD 20892 USA. NR 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 2728 BP A510 EP A511 PN 1 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702094 ER PT J AU Goebel, SU Roy, PK Peghini, PL Jensen, RT Serrano, J AF Goebel, SU Roy, PK Peghini, PL Jensen, RT Serrano, J TI Amplification of the HER2/neu oncogene in 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 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 5278 BP A1146 EP A1146 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RY UT WOS:000086784100352 ER PT J AU Goebel, SU Vortmeyer, AO Zhuang, Z Serrano, J Jensen, RT Lubensky, IA AF Goebel, SU Vortmeyer, AO Zhuang, Z Serrano, J Jensen, RT Lubensky, IA TI Monoclonality of sporadic gastrinomas at multiple sites. 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 PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 2387 BP A437 EP A437 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783701789 ER PT J AU Goebel, SU Peghini, PL Goldsmith, P Spiegel, AM Gibril, F Raffeld, M Serrano, J Jensen, RT AF Goebel, SU Peghini, PL Goldsmith, P Spiegel, AM Gibril, F Raffeld, M Serrano, J Jensen, RT TI Expression and function of the calcium sensing receptor (CAR) in 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 PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 1656 BP A297 EP A297 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783701204 ER PT J AU Gonsky, R Deem, RL Young, HA Targan, SR AF Gonsky, R Deem, RL Young, HA Targan, SR TI CD2-mediated activation of STAT: Transactivation of the IFN-Gamma intronic STAT cis-element is unique for LPMC and independent of IL-12. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NCI, Ferde, Frederick, MD 21701 USA. NR 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 3628 BP A663 EP A663 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702716 ER PT J AU Gonsky, R Deem, RL Bream, J Young, HA Targan, SR AF Gonsky, R Deem, RL Bream, J Young, HA Targan, SR TI A dual role for the-204 to-172 bp region of the IFN-gamma promoter: An activator of expression in LPL while a silencer of expression in PBL. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NCI, Ferde, Frederick, MD USA. NR 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 709 BP A109 EP A109 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783700443 ER PT J AU Holt, PR Arber, N O'Connor, J Halmos, B McGlynn, C Moss, SF Pou, R Yang, K Fan, KH Newmark, H Lipkin, M AF Holt, PR Arber, N O'Connor, J Halmos, B McGlynn, C Moss, SF Pou, R Yang, K Fan, KH Newmark, H Lipkin, M TI Serum 25 hydroxy vitamin D-3 inhibits proliferation of colonic epithelial cells in subjects at high risk for colon neoplasia. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Strang Canc Res Lab, New York, NY USA. NCI, Bethesda, MD 20892 USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. Columbia Univ, New York, NY USA. Tel Aviv Sourasky Med Ctr, Tel Aviv, Israel. St Lukes Roosevelt Hosp Ctr, New York, NY USA. NR 0 TC 5 Z9 5 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 1565 BP A276 EP A276 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783701113 ER PT J AU Igarashi, H Ito, T Hou, W Mantey, SA Pradhan, TK Coy, DH Jensen, RT AF Igarashi, H Ito, T Hou, W Mantey, SA Pradhan, TK Coy, DH Jensen, RT TI Identification of a simplified polyalaninated VIP analogue with high affinity for human VIP1 receptors. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD USA. Tulane Med Sch, New Orleans, LA USA. NR 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 2150 BP A415 EP A415 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783701698 ER PT J AU Igarashi, H Ito, T Pradhan, TK Mantey, SA Taylor, JE Murphy, WA Coy, DH Jensen, RT AF Igarashi, H Ito, T Pradhan, TK Mantey, SA Taylor, JE Murphy, WA Coy, DH Jensen, RT TI Toxicity of a possible therapeutic GRF analogue in vivo in monkeys but in rats is likely due to VIP receptor agonist activity. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD USA. Biomeasure Inc, Milford, MA USA. Tulane Med Sch, New Orleans, LA USA. NR 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 1689 BP A305 EP A305 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783701237 ER PT J AU Levin, TR Allison, JE Ackerson, LM Hurley, LB Libran, DL Lieu, TA Hiatt, RA AF Levin, TR Allison, JE Ackerson, LM Hurley, LB Libran, DL Lieu, TA Hiatt, RA TI Health care costs of a test and treat intervention for H-pylori in chronic peptic ulcer disease: A randomized controlled trial in a large health maintenance organization. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NCI, Rockville, MD USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Pilgrim Hlth Care, Boston, MA USA. Kaiser Permanente, Oakland, CA USA. NR 0 TC 1 Z9 1 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 2392 BP A439 EP A439 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783701794 ER PT J AU Limburg, PJ Dawsey, SM Qiao, YL Wang, GQ Perez-Perez, GI Blaser, MJ Mark, SD Dong, ZW Taylor, PR AF Limburg, PJ Dawsey, SM Qiao, YL Wang, GQ Perez-Perez, GI Blaser, MJ Mark, SD Dong, ZW Taylor, PR TI Helicobacter pylori seropositivity and esophageal squamous cancer risk in 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 37212 USA. RI Qiao, You-Lin/B-4139-2012 OI Qiao, You-Lin/0000-0001-6380-0871 NR 0 TC 2 Z9 2 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 3940 BP A724 EP A724 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702953 ER PT J AU Mantey, SA Coy, DH Hocart, S Jensen, RT AF Mantey, SA Coy, DH Hocart, S Jensen, RT TI Discovery of a selective agonist for the novel bombesin (Bn) receptor subtype 3. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Tulane Univ, Sch Med, New Orleans, LA 70112 USA. NR 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 1694 BP A307 EP A307 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783701242 ER PT J AU Matkowskyj, RA Mantey, S Schonfeld, D Jensen, RT Danilkovich, LV Benya, RV AF Matkowskyj, RA Mantey, S Schonfeld, D Jensen, RT Danilkovich, LV Benya, RV TI Quantitive immunohistochemistry (Q-IHC) by measuring cumulative signal strength can be used to determine GRP receptor number on archived tissues. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Illinois, Chicago, IL USA. NIDDK, NIH, Bethesda, MD USA. NR 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 2935 BP A560 EP A560 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702299 ER PT J AU Mishra, L Tran, PT Bhanumathy, CD Tang, Y Rashid, A Danovitch, S Fleury, T Mishra, B Deng, C AF Mishra, L Tran, PT Bhanumathy, CD Tang, Y Rashid, A Danovitch, S Fleury, T Mishra, B Deng, C TI TGF Beta signaling by SMAD2/3 and ELF spectrins results in bile duct formation and is disrupted in primary biliary cirrhosis. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 DVAMC & Fels Canc Inst, Washington, DC USA. DVAMC & Fels Canc Inst, Philadelphia, PA USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Johns Hopkins Univ, Baltimore, MD USA. Sibley Hosp, Washington, DC USA. NIDDK, NIH, Bethesda, MD USA. NIH, NHGRI, CGTB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 270 BP A2 EP A2 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783700005 ER PT J AU Pavan, WJ AF Pavan, WJ TI "Neural crest mutants: Microarrays, gut manifestations - A moving story". SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Natl Human Genome Res, 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 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 4974 BP A1072 EP A1072 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RY UT WOS:000086784100039 ER PT J AU Peghini, PL Goebel, SU Gibril, F Raffeld, M Jensen, RT Serrano, J AF Peghini, PL Goebel, SU Gibril, F Raffeld, M Jensen, RT Serrano, J TI Is the epidermal growth factor receptor (EGFR) overexpressed in 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 PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 3283 BP A646 EP A646 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702647 ER PT J AU Phillips, RK Wallace, M Lynch, PM Hawk, E Gordon, GB Saunders, BP Godio, L Rodriguez-Bigas, MA Sherman, JW Kelloff, G Levin, B Steinbach, G AF Phillips, RK Wallace, M Lynch, PM Hawk, E Gordon, GB Saunders, BP Godio, L Rodriguez-Bigas, MA Sherman, JW Kelloff, G Levin, B Steinbach, G TI The effect of celecoxib on duodenal polyposis in familial adenomatous polyposis (FAP). SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, Bethesda, MD 20892 USA. GD Searle & Co, Skokie, IL 60077 USA. St Marks Hosp, London EC1V 2PS, England. Roswell Pk Canc Inst, Roswell Pk, NY USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 1464 BP A252 EP A252 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783701012 ER PT J AU Pisegna, JR Tarasova, NI Kopp, JA Asico, LD Li, XX Stalter, J Michejda, CJ Jose, PA Wank, SA AF Pisegna, JR Tarasova, NI Kopp, JA Asico, LD Li, XX Stalter, J Michejda, CJ Jose, PA Wank, SA TI Cholecystokinin type B receptors (CCKBRs) in the rat kidney mediate gastrin-stimulated urinary sodium excretion through inositol phosphate turnover (IP) and inhibition of Na+/K+ ATPase. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Cure, Ddrc, VAMC, Los Angeles, CA USA. NCI, Frederick, MD 21701 USA. NIH, Bethesda, MD 20892 USA. Georgetown Univ, Washington, DC USA. NIDDK, NIH, Ddb, Bethesda, MD USA. NR 0 TC 1 Z9 1 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 1672 BP A301 EP A301 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783701220 ER PT J AU Roy, PK Feigenbaum, KM Koviack, PD Abou-Saif, A Shojamanesh, H Gibril, F Jensen, RT AF Roy, PK Feigenbaum, KM Koviack, PD Abou-Saif, A Shojamanesh, H Gibril, F Jensen, RT TI Prospective evaluation of proposed gastric acid secretory criteria for diagnosis of Zollinger-Ellison syndrome (ZES). 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 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 5940 BP A1301 EP A1301 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RY UT WOS:000086784101014 ER PT J AU Roy, PK Abou-Saif, A Shojamanesh, H Gibril, F Jensen, RT AF Roy, PK Abou-Saif, A Shojamanesh, H Gibril, F Jensen, RT TI Presenting clinical features in Zollinger-Ellison syndrome (ZES): Results from a prospective study of 261 cases. 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 PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 3285 BP A646 EP A646 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702649 ER PT J AU Ruhl, CE Everhart, JE AF Ruhl, CE Everhart, JE TI Esophagitis and hiatal hernia increased the risk of iron-deficiency anemia in a national, prospective study. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Social & Sci Syst Inc, Bethesda, MD USA. NIDDK, Bethesda, MD USA. NR 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 3791 BP A693 EP A693 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702828 ER PT J AU Sarosiek, J Jensen, RT Maton, PM Peura, DA Harlow, D Feng, T McCallum, RW Pisegna, JR AF Sarosiek, J Jensen, RT Maton, PM Peura, DA Harlow, D Feng, T McCallum, RW Pisegna, JR TI Salivary and gastric epidermal growth factor in patients with Zollinger-Ellison Syndrome: Its protective potential in the esophagus. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. NIH, Bethesda, MD 20892 USA. Univ Oklahoma, Oklahoma City, OK USA. Univ Virginia, Hlth Sci Ctr, Charlottesville, VA USA. Cure Ddrc, Los Angeles, CA USA. VAMC, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 1420 BP A241 EP A241 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783700968 ER PT J AU Schneider, R Breidert, MG Bornstein, SR Chrousos, GP Ehninger, G AF Schneider, R Breidert, MG Bornstein, SR Chrousos, GP Ehninger, G TI Leptin is a contributing factor to the integrity of gastric mucosa. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Tech Univ Hosp, Dept Med 1, Dresden, Germany. 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 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 5950 BP A1303 EP A1303 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RY UT WOS:000086784101024 ER PT J AU Shaoyong, Y Long, JM Nass, PH Ingram, DK Crowell, MD AF Shaoyong, Y Long, JM Nass, PH Ingram, DK Crowell, MD TI Cns processing of noxious colorectal distention: A murine model using immediate early gene transcription of c-Fos. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sch Med, MM Schuster Ctr, Baltimore, MD USA. NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 4419 BP A841 EP A841 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783703431 ER PT J AU Shojamanesh, H Abou-Saif, A Venzon, DJ Jensen, RT Gibril, F AF Shojamanesh, H Abou-Saif, A Venzon, DJ Jensen, RT Gibril, F TI Prospective study of the effectiveness of chemotherapy in patients with metastatic gastrinoma to the liver. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008 NR 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 1007 BP A177 EP A177 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783700714 ER PT J AU Tapia, JA Andreolotti, AG Garcia-Marin, LJ Jensen, RT AF Tapia, JA Andreolotti, AG Garcia-Marin, LJ Jensen, RT TI Is CCK-mediated PKC-Delta tyrosine phosphorylation or translocation necessary for its activation in pancreatic acini? SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Extremadura, Caceres, Spain. NIDDK, 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 PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 639 BP A91 EP A91 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783700373 ER PT J AU Tokita, M Katsuno, T Llinares, M Martinez, J Jensen, RT AF Tokita, M Katsuno, T Llinares, M Martinez, J Jensen, RT TI Different highly selective gastrin-releasing peptide receptor (GRPR) peptide antagonists interact with different receptor domains. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD USA. Univ Montpellier, F-34059 Montpellier, France. NR 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 1708 BP A310 EP A310 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783701256 ER PT J AU Vaquero, E Gukovskaya, AS Brennan, ML Lusis, AJ Holland, SM Pandol, SJ AF Vaquero, E Gukovskaya, AS Brennan, ML Lusis, AJ Holland, SM Pandol, SJ TI Leukocyte NADPH oxidase but not myeloperoxidase regulates pancreatic trypsin activation in cerulein induced pancreatitis. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 956 BP A170 EP A170 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783700688 ER PT J AU Weber, HC Walters, J Leyton, J Casibang, M Purdom, S Jensen, RT Ellis, C Clark, G Moody, TW AF Weber, HC Walters, J Leyton, J Casibang, M Purdom, S Jensen, RT Ellis, C Clark, G Moody, TW TI Ligand activation of the human bombesin receptor subtype-3 induces phosphorylation of MAP kinase, ELK-1 activation, and increases c-fos mRNA expression in lung cancer cells. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Boston Univ, Boston, MA 02215 USA. NIH, Rockville, MD USA. NIH, Bethesda, MD 20892 USA. NR 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 643 BP A92 EP A92 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783700377 ER PT J AU Younes, M Hensen, DE Ertan, A Miller, CC AF Younes, M Hensen, DE Ertan, A Miller, CC TI Incidence and survival trends of esophageal carcinoma in the United States. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. NCI, NIH, Bethesda, MD 20892 USA. Univ Texas, Sch Med, Houston, TX USA. NR 0 TC 1 Z9 1 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 3850 BP A705 EP A705 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702874 ER PT J AU Younossi, ZM Kleiner, DE Gramlich, TL Boparai, N AF Younossi, ZM Kleiner, DE Gramlich, TL Boparai, N TI Application of NIDDK NASH pathologic protocol to patients with non-alcoholic fatty liver disease. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 1066 BP A974 EP A974 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783703963 ER PT J AU Boonpongmanee, S Tio, TL Zubarick, RS Mayoral, W Nwakwakwawa, V Levy, H Clare, A AF Boonpongmanee, S Tio, TL Zubarick, RS Mayoral, W Nwakwakwawa, V Levy, H Clare, A TI Gastrointestinal manifestations in patients with classical and hypermobile Ehlers-Danlos syndrome. SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Georgetown Univ, Med Ctr, Washington, DC 20007 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, 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 2000 VL 51 IS 4 MA 1743 BP AB278 EP AB278 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 313PD UT WOS:000087007300808 ER PT J AU Fleischer, DE Wang, GQ Wang, GQ Nishioka, NS Bouma, B Farahvash, M Liu, BN Tse, T Dong, Z Dawsey, SM AF Fleischer, DE Wang, GQ Wang, GQ Nishioka, NS Bouma, B Farahvash, M Liu, BN Tse, T Dong, Z Dawsey, SM TI Endoscopic mucosal resection using a cap method (EMR-C) provides safe and effective treatment for early esophageal cancer. SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Georgetown Univ, Med Ctr, Washington, DC 20007 USA. CICAMS, Inst Canc, Beijing, Peoples R China. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Boston, MA 02115 USA. Univ Tehran, Tehran 14174, Iran. VAMC, Washington, DC USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2000 VL 51 IS 4 MA 7046 BP AB253 EP AB253 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 313PD UT WOS:000087007300711 ER PT J AU Tio, TL Benjamin, SB Gibril, F Abou-Saif, A Roy, PK Shojamanesh, H Alexander, RA Jensen, RT AF Tio, TL Benjamin, SB Gibril, F Abou-Saif, A Roy, PK Shojamanesh, H Alexander, RA Jensen, RT TI Prospective study of the ability of endoscopic ultrasound to localize duodenal gastrinomas. SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Georgetown Univ, Med Ctr, Washington, DC 20007 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, 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 2000 VL 51 IS 4 MA 3894 BP AB139 EP AB139 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 313PD UT WOS:000087007300298 ER PT J AU Tonon, G Roschke, A Stover, K Shou, YP Kuehl, WM Kirsch, IR AF Tonon, G Roschke, A Stover, K Shou, YP Kuehl, WM Kirsch, IR TI Spectral karyotyping combined with locus-specific FISH simultaneously defines genes and chromosomes involved in chromosomal translocations SO GENES CHROMOSOMES & CANCER LA English DT Article ID HYBRIDIZATION; ABNORMALITIES AB Genes that play roles in malignant transformation have often been found proximate to cancer-associated chromosomal breakpoints. Identifying genes that flank chromosomal reconfigurations is thus essential for cancer cytogenetics. To simplify and expedite this identification, we have developed a novel approach, based on simultaneous spectral karyotyping and fluorescence in situ hybridization (FISH) which, in a single step, can identify gross chromosomal aberrations as well as detect the involvement of specific loci in these rearrangements. Signals for specifically queried genes (FISH probe) were easily detectable in metaphase cells, together with the signals from painted chromosomes (spectral karyotyping probes). The concentration and size of the FISH probes could cover a wide range and still be used successfully. Some of the nucleotide-bound dyes used for the labeling, as Cy3, Spectrum Orange, Alexa 594, Texas Red, and Rhodamine 110, were particularly efficient. More than one gene can be queried in the same metaphase, because multiple FISH probes could be hybridized simultaneously. To demonstrate this technique, we applied it to the myeloma cell line Karpas 620, which has numerous chromosomal rearrangements. The approach that we present here will be particularly useful for the analysis of complex karyotypes and for testing hypotheses arising from cancer gene expression studies. Published 2000 Wiley-Liss, Inc. C1 NCI, Med Branch, Dept Genet, NNMC, Bethesda, MD 20889 USA. RP Kirsch, IR (reprint author), NCI, Med Branch, Dept Genet, NNMC, 8901 Wisconsin Ave,Bldg 8,Room 5101, Bethesda, MD 20889 USA. NR 19 TC 11 Z9 11 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD APR PY 2000 VL 27 IS 4 BP 418 EP 423 DI 10.1002/(SICI)1098-2264(200004)27:4<418::AID-GCC12>3.0.CO;2-O PG 6 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 288GU UT WOS:000085555000012 PM 10719373 ER PT J AU Carroll, RJ Gail, MH Benichou, J Pee, D AF Carroll, RJ Gail, MH Benichou, J Pee, D TI Score tests for familial correlation in genotyped-proband designs SO GENETIC EPIDEMIOLOGY LA English DT Article DE asymptotics; epidemiology; genetics; generalized linear mixed models; kin-cohort design; proband; random effects; retrospective studies; score tests ID HOMOGENEITY; PENETRANCE; CANCER; MODELS; COHORT AB In the genotyped-proband design, a proband is selected based on an observed phenotype, the genotype of the proband is observed, and then the phenotypes of all first-degree relatives are obtained. The genotypes of these first-degree relatives are not observed. call et al. [(1999) Genet Epidemiol] discuss likelihood analysis of this design under the assumption that the phenotypes are conditionally independent of one another given the observed and unobserved genotypes. Li and Thompson [(1997) Biometrics 53:282-293] give an example where this assumption is suspect, thus suggesting that it is important to develop tests for conditional independence. In this paper, we develop a score test for the conditional independence assumption in models that might include covariates or observation of genotypes for some of the first degree relatives. The problem can be cast more generally as one of score testing in the presence of missing covariates. A standard analysis would require specifying a distribution for the covariates, which is not convenient and could lead to a lack of model-robustness. We show that by considering a natural conditional likelihood, and basing the score test on it, a simple analysis results. The methods are applied to a study of the penetrance for breast cancer of BRCA1 and BRCA2 mutations among Ashkenazi Jews. (C) 2000 Wiley-Liss, Inc. C1 Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Rouen, CHU Rouen, Sch Med, Biostat Unit, Rouen, France. Informat Mangement Syst, Rockville, MD USA. RP Carroll, RJ (reprint author), Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. FU NCI NIH HHS [CA57030]; NIEHS NIH HHS [P30ESO9106] NR 13 TC 1 Z9 1 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD APR PY 2000 VL 18 IS 4 BP 293 EP 306 DI 10.1002/(SICI)1098-2272(200004)18:4<293::AID-GEPI3>3.0.CO;2-L PG 14 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 310NP UT WOS:000086834500002 PM 10797590 ER PT J AU Pickeral, OK Makalowski, W Boguski, MS Boeke, JD AF Pickeral, OK Makalowski, W Boguski, MS Boeke, JD TI Frequent human genomic DNA transduction driven by LINE-1 retrotransposition SO GENOME RESEARCH LA English DT Article ID INSERTION; SEQUENCES; PROTEIN; TRANSCRIPTION; ELEMENT; CELLS; GENE AB Human L1 retrotransposons can produce DNA transduction events in which unique DNA segments downstream of L1 elements are mobilized as part of aberrant retrotransposition events. That L1s are capable of carrying out such a reaction in tissue culture cells was elegantly demonstrated. Using bioinformatic approaches to analyze the structures of L1 element target site duplications and Ranking sequence features, we provide evidence suggesting that similar to 15% of full-length L1 elements bear evidence of flanking DNA segment transduction. Extrapolating these findings to the 600,000 copies of LI in the genome, we predict that the amount of DNA transduced by L1 represents similar to 1% of the genome, a fraction comparable with that occupied by exons. C1 Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Boeke, JD (reprint author), Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. RI Makalowski, Wojciech/I-2843-2016 FU NCI NIH HHS [CA16519, P01 CA016519] NR 22 TC 160 Z9 163 U1 1 U2 5 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD APR PY 2000 VL 10 IS 4 BP 411 EP 415 DI 10.1101/gr.10.4.411 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 309AD UT WOS:000086744300005 PM 10779482 ER PT J AU Iwamoto, H Nishino, K Magone, TM Whitcup, SM Yoshida, O Yoshida, H Ozaki, A Fukushima, A Ueno, H AF Iwamoto, H Nishino, K Magone, TM Whitcup, SM Yoshida, O Yoshida, H Ozaki, A Fukushima, A Ueno, H TI Experimental immune-mediated blepharoconjunctivitis in rats induced by immunization with ragweed pollen SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article ID ALLERGIC CONJUNCTIVITIS; ADOPTIVE TRANSFER; MURINE MODEL; LEWIS RATS; TH2 CELLS; T-CELLS; RESPONSES; MICE; INFLAMMATION; IL-4 AB Background: A study was performed to compare the effects of immunization with ragweed pollen (RW) in two different adjuvants on the characteristics of a previously described model of experimental immune-mediated blepharoconjunctivitis (EC) in rats. Methods: Lewis or Brown Norway (BN) rats were immunized with 100 mu g of RW in emulsion with aluminum hydroxide [Al(OH)(3)] or complete Freund's adjuvant (CFA). Three weeks later, the animals were challenged with eye drops containing RW in PBS. Twenty-four hours after topical challenge, eyes, blood, and lymph nodes were obtained for histology, measurement of antigen-specific antibodies, and proliferation or cytokine assays, respectively. In addition to active immunization, recipients of RW-primed lymph node cells were challenged and evaluated as above. Results: RW in both adjuvants induced infiltration with predominantly mononuclear cells in Lewis rats and eosinophils in BN rats. As well as active immunization, eosinophils were detected only in BN rats by adoptive transfer of cells. Lymphocyte proliferative responses to RW were high in immunized Lewis rats when CFA was used as an adjuvant. In contrast, proliferative responses in BN rats were higher when Al(OH)(3) was used, RW-specific IgE was detected only in BN rats. There were no significant differences in RW-specific IgG1/gCr2a ratio among the four groups. Lewis rats had higher level of RW-specific interferon-gamma in the culture supernatant. Conclusions: The characteristics of EC are different in Lewis and BN rats, dependent on the genetic background of the rat strains. The response to RW was similar to other previously used antigens, such as ovalbumin. C1 Kochi Med Sch, Dept Ophthalmol, Immunol Lab, Nankoku, Kochi 7838505, Japan. NEI, Clin Branch, NIH, Bethesda, MD 20892 USA. RP Fukushima, A (reprint author), Kochi Med Sch, Dept Ophthalmol, Immunol Lab, Nankoku, Kochi 7838505, Japan. NR 21 TC 18 Z9 19 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD APR PY 2000 VL 238 IS 4 BP 346 EP 351 DI 10.1007/s004170050363 PG 6 WC Ophthalmology SC Ophthalmology GA 316YL UT WOS:000087195800009 PM 10853935 ER PT J AU Dunn, SE AF Dunn, SE TI Insulin-like growth factor I stimulates angiogenesis and the production of vascular endothelial growth factor SO GROWTH HORMONE & IGF RESEARCH LA English DT Article; Proceedings Paper CT 1st International Workshop on Growth Hormone, Insulin-like Growth Factors and Neoplasia CY OCT 24-25, 1999 CL BOSTON, MASSACHUSETTS ID CANCER RISK; BREAST-CANCER; PLASMA-LEVELS C1 NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Dunn, SE (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. NR 7 TC 28 Z9 28 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1096-6374 J9 GROWTH HORM IGF RES JI Growth Horm. IGF Res. PD APR PY 2000 VL 10 SU A BP S41 EP S42 DI 10.1016/S1096-6374(00)90020-0 PG 2 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 346YK UT WOS:000088898600021 PM 10984289 ER PT J AU Le Roith, D AF Le Roith, D TI Regulation of proliferation and apoptosis by the insulin-like growth factor I receptor SO GROWTH HORMONE & IGF RESEARCH LA English DT Article; Proceedings Paper CT 1st International Workshop on Growth Hormone, Insulin-like Growth Factors and Neoplasia CY OCT 24-25, 1999 CL BOSTON, MASSACHUSETTS ID EXPRESSION; PRODUCT; IGF C1 NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Le Roith, D (reprint author), NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NR 6 TC 20 Z9 21 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1096-6374 J9 GROWTH HORM IGF RES JI Growth Horm. IGF Res. PD APR PY 2000 VL 10 SU A BP S12 EP S13 DI 10.1016/S1096-6374(00)90005-4 PG 2 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 346YK UT WOS:000088898600006 PM 10984274 ER PT J AU Doo, E Hoofnagle, JH AF Doo, E Hoofnagle, JH TI Combination therapy of hepatitis B SO GUT LA English DT Editorial Material ID TERM FOLLOW-UP; INTERFERON-ALFA; INFECTION; LAMIVUDINE; TRIAL C1 NIDDKD, Liver Dis Sect, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Doo, E (reprint author), NIDDKD, Liver Dis Sect, Digest Dis Branch, NIH, Bldg 10,Room 9B06, Bethesda, MD 20892 USA. NR 10 TC 4 Z9 4 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD APR PY 2000 VL 46 IS 4 BP 450 EP 451 DI 10.1136/gut.46.4.450 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 298MB UT WOS:000086142300005 PM 10716669 ER PT J AU Van Dam, GM Afeworki, M Subramanian, S Krishna, MC Hoekstra, HJ Cook, JA Russo, A Mitchell, JB AF Van Dam, GM Afeworki, M Subramanian, S Krishna, MC Hoekstra, HJ Cook, JA Russo, A Mitchell, JB TI A new functional in vivo imaging technique of normal and ischemic liver using electron paramagnetic resonance imaging (EPRI) SO GUT LA English DT Meeting Abstract C1 Univ Groningen Hosp, Dept Surg, Groningen, Netherlands. NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. Deventer Hosp, Dept Surg, NL-7400 GC Deventer, Netherlands. NR 0 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 0017-5749 J9 GUT JI Gut PD APR PY 2000 VL 46 SU 2 MA W51 BP A45 EP A45 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 298YZ UT WOS:000086170200178 ER PT J AU Furlong, MT Morin, PJ AF Furlong, MT Morin, PJ TI Rare activation of the TCF/beta-catenin pathway in ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT 90th Annual Meeting of the American-Association-for-Cancer-Research CY APR 10-14, 1999 CL PHILADELPHIA, PENNSYLVANIA SP Amer Assoc Canc Res DE beta-catenin; TCF; APC; ovarian cancer; transcription ID BETA-CATENIN; COLORECTAL-CANCER; CELL-LINES; APC; MUTATIONS; CARCINOMA; COMPLEX; GENE; XENOPUS; TCF AB Objective. The activation of the T cell factor/beta-catenin pathway is a crucial event in colon cancer initiation. A recent report describing the presence of beta-catenin mutations in endometrioid ovarian cancer suggested that the TCF/beta-catenin pathway may be generally activated in ovarian cancer. We therefore undertook to determine the frequency of activation of this pathway in ovarian cancer cell lines using a functional screen, Methods. We functionally screened a series of ovarian cancer cell lines for the presence of constitutive TCF/beta-catenin-mediated transcriptional activity using a reporter assay. Lines possessing such activity were subjected to mutational and gel-shift analysis, as well as sensitivity to the introduction of dominant-negative TCF or APC alleles. A cDNA harboring a beta-catenin point mutation found in an ovarian cancer line was incorporated into an expression plasmid for functional analysis. Results. Constitutive TCF/beta-catenin transcriptional activity was detected in 21% (4 of 19) of ovarian lines studied, while 32% (6 of 19) exhibited greater than twofold repression. One of the constitutively active lines, UCI107, harbored an activating beta-catenin point mutation, which was shown to be capable of inducing TCF/beta-catenin transcriptional activity in transiently transfected 293 cells. A second active line, SW626, was shown to harbor an inactivating APC mutation and may in fact be of colonic origin. The third and fourth lines harbored neither an APC nor a beta-catenin mutation. Gel-shift analysis, together with the absence of sensitivity to dominant-negative TCF, indicated that the reporter activity exhibited by the latter two cell lines may not be due to a TCF/beta-catenin transcriptional complex. Conclusions. These results indicate that genuine constitutive activation of the TCF/beta-catenin pathway is infrequent in ovarian cancer, but that constitutive transcriptional repression from TCF sites is more common in this tumor type. C1 NIA, Biol Chem Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Morin, PJ (reprint author), NIA, Biol Chem Lab, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 39 TC 23 Z9 23 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD APR PY 2000 VL 77 IS 1 BP 97 EP 104 DI 10.1006/gyno.1999.5718 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 304NW UT WOS:000086491200015 PM 10739697 ER PT J AU Annab, LA Terry, L Cable, PL Brady, J Stampfer, MR Barrett, JC Afshari, CA AF Annab, LA Terry, L Cable, PL Brady, J Stampfer, MR Barrett, JC Afshari, CA TI Establishment and characterization of a breast cell strain containing a BRCA1 185delAG mutation SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT Keystone Symposia 99 CY MAR 15-20, 1999 CL TAOS, NEW MEXICO DE BRCA1; breast cell line; breast cancer; germline mutation ID OVARIAN-CANCER FAMILIES; ASHKENAZI JEWISH WOMEN; TUMOR-SUPPRESSOR GENE; DNA-DAMAGING AGENTS; ESTROGEN-RECEPTOR; CYCLE REGULATION; EXPRESSION; CARCINOMA; LINES; P53 AB Objective. The aim of this study was to examine whether cells containing the heterozygous form of a BRCA1 185delAG mutation would exhibit abnormal growth or an altered response to DNA damage. Methods. A primary culture of human mammary epithelial cells (90P) was obtained from the nontumor breast tissue of a 35-year-old patient who had undergone a mastectomy for removal of a breast tumor. These cells were immortalized (90PE6E7) following retroviral infection with HPV-16 viral E6/E7. genes. Both the 90P cell strain and the cell line were characterized for their ability to grow in culture, form colonies in soft agar, and produce tumors in athymic nude mice compared to normal breast epithelial cells containing wild-type BRCA1. 90P cells were also analyzed for cellular response to gamma radiation and H2O2. Results. These cells were confirmed to contain a frameshift mutation, 185delAG, of the BRCA1 gene. Despite being heterozygous for wild-type BRCA1, the 220-kDa full-size BRCA1 protein was abundantly expressed. 90P and 90PE6E7 cells grew at a similar rate and were anchorage dependent. 90PE6E7 also failed to form tumors in athymic nude mice, Finally, 90P cells exhibited a survival response similar to that of normal mammary epithelial cells to radiation damage and exposure to oxidative stress. Conclusion. To our knowledge the 90P cells and the 90PE6E7 cells are the first characterized, non-tumor-derived breast epithelial cells that are heterozygous for the BRCA1 germline mutation 185delAG. Our conclusion is that these BRCA1 mutant cells appear to have growth and stress response characteristics similar to those of normal human breast cells, which is consistent with the hypothesis that loss of heterozygosity must occur to impair putative BRCA1 function. (C) 2000 Academic Press. C1 NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94704 USA. RP Annab, LA (reprint author), NIEHS, Mol Carcinogenesis Lab, POB 12233,MD2-04, Res Triangle Pk, NC 27709 USA. FU NCI NIH HHS [CA-24844] NR 49 TC 8 Z9 8 U1 1 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD APR PY 2000 VL 77 IS 1 BP 121 EP 128 DI 10.1006/gyno.2000.5734 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 304NW UT WOS:000086491200019 PM 10739701 ER PT J AU Lacey, JV Brinton, LA Barnes, WA Gravitt, PE Greenberg, MD Hadjimichael, OC McGowan, L Mortel, R Schwartz, PE Kurman, RJ Hildesheim, A AF Lacey, JV Brinton, LA Barnes, WA Gravitt, PE Greenberg, MD Hadjimichael, OC McGowan, L Mortel, R Schwartz, PE Kurman, RJ Hildesheim, A TI Use of hormone replacement therapy and adenocarcinomas and squamous cell carcinomas of the uterine cervix SO GYNECOLOGIC ONCOLOGY LA English DT Article DE cervical carcinomas; hormone replacement therapy; human papillomavirus; HPV; cervical adenocarcinomas ID PROGESTERONE RECEPTORS; ESTROGEN; EPIDEMIOLOGY; CANCER; RISK; TRANSFORMATION AB Introduction. Exogenous hormones may influence the development of cervical adenocarcinomas. Incidence rates of adenocarcinomas and use of noncontraceptive hormones have increased since the 1970s, but few studies have investigated this potential relationship. Methods. We conducted a multicenter case-control study of 124 women with adenocarcinomas, 139 women with squamous eel carcinomas matched on age, diagnosis date, clinic, and stage of disease (in situ or invasive) to adenocarcinoma cases, and 307 healthy community controls who were also matched on age, ethnicity, and residence to adenocarcinoma cases. Participants completed in-person interviews regarding exogenous hormone use before diagnosis and other risk factors and volunteered cervical samples for human papillomavirus (HPV) testing via a PCR-based method. Odds ratios (ORs) with 95% confidence intervals (CIs) estimated relative risks. Results. Only 13 adenocarcinoma cases (10.5%), 7 squamous carcinoma cases (5%), and 20 controls (6.5%) had used noncontraceptive hormones for menopausal symptoms, irregular periods, or disease prevention; most use was short-term, former use. Ever-use was associated with adenocarcinomas (OR = 2.1, 95% CI 0.95-4.6) but not squamous carcinomas (OR = 0.85, 95% CI 0.34-2.1), No trends were seen with duration of use or ages at first use, but unopposed estrogens were positively associated with adenocarcinomas (OR = 2.7). Unopposed estrogens remained associated with adenocarcinomas (OR = 2.0) when analyses were restricted to the HPV-positive controls. Menopausal status was not associated with adenocarcinomas or squamous carcinomas and did not modify the other associations. Conclusion. Although small numbers warrant tentative conclusions, exogenous estrogens, especially unopposed estrogens, were positively associated with adenocarcinomas. Noncontraceptive hormones were negatively but weakly associated with squamous carcinomas. (C) 2000 Academic Press. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Georgetown Univ, Vincent T Lombardi Canc Res Ctr, Washington, DC USA. Roche Mol Syst Inc, Alameda, CA USA. Grad Hosp, Philadelphia, PA USA. Yale Univ, Sch Med, New Haven, CT USA. George Washington Univ, Div Gynecol Oncol, Washington, DC USA. Milton S Hershey Med Ctr, Hershey, PA USA. Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. RP Lacey, JV (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 23 TC 49 Z9 55 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD APR PY 2000 VL 77 IS 1 BP 149 EP 154 DI 10.1006/gyno.2000.5731 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 304NW UT WOS:000086491200022 PM 10739704 ER PT J AU Baranowski, T Stables, G AF Baranowski, T Stables, G TI Process evaluations of the 5-a-Day projects SO HEALTH EDUCATION & BEHAVIOR LA English DT Article ID HEALTH; PROGRAMS AB Process evaluation is an important, but infrequently conducted, component of evaluating the impact of health promotion interventions. The process evaluation results from the nine 5-a-Day projects were overviewed. Process evaluation helped explain some of the weaker aspects of program performance, process indicators occasionally declined over time and varied by demographic characteristics, and some process measures were related to mediating variables and program outcomes. Future development of process evaluation must include further development of concepts, more consistent and thorough conduct of process evaluation, appropriate methodological work, and assessment of the relations among the process evaluation components and the program mediators and outcomes. Further development in this area promises refinement in understanding how and why interventions achieve their effects, how best to conduct intervention programs to maximize effects, and enhancement of the internal and external validity of the studies. C1 Baylor Coll Med, Dept Pediat, Childrens Nutr Res Ctr, Houston, TX 77030 USA. NCI, Rockville, MD USA. RP Baranowski, T (reprint author), Baylor Coll Med, Dept Pediat, Childrens Nutr Res Ctr, Houston, TX 77030 USA. FU NCI NIH HHS [CA75614, CA73503] NR 20 TC 109 Z9 110 U1 2 U2 17 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-1981 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD APR PY 2000 VL 27 IS 2 BP 157 EP 166 DI 10.1177/109019810002700202 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 298WK UT WOS:000086162300001 PM 10768797 ER PT J AU Thio, CL Thomas, DL Carrington, M AF Thio, CL Thomas, DL Carrington, M TI Chronic viral hepatitis and the human genome SO HEPATOLOGY LA English DT Review ID B VIRUS-INFECTION; MANNOSE-BINDING PROTEIN; CHRONIC ACTIVE HEPATITIS; NECROSIS-FACTOR-ALPHA; HUMAN-LEUKOCYTE ANTIGENS; CYTOTOXIC T-LYMPHOCYTES; CLASS-II GENES; C VIRUS; HLA ANTIGENS; HEREDITARY HEMOCHROMATOSIS C1 Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. NCI, Lab Genom Divers, Frederick, MD 21701 USA. RP Thio, CL (reprint author), Johns Hopkins Univ, Sch Med, Div Infect Dis, 720 Rutland Ave,Ross 1156, Baltimore, MD 21205 USA. FU NIAID NIH HHS [U19AI40035]; NIDA NIH HHS [F32DA05887, R01DA13324] NR 71 TC 95 Z9 104 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 2000 VL 31 IS 4 BP 819 EP 827 DI 10.1053/he.2000.4316 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 299JH UT WOS:000086195000001 PM 10733534 ER PT J AU Sanz-Ortega, J Steinberg, SM Moro, E Saez, M Lopez, JA Sierra, E Sanz-Esponera, J Merino, MJ AF Sanz-Ortega, J Steinberg, SM Moro, E Saez, M Lopez, JA Sierra, E Sanz-Esponera, J Merino, MJ TI Comparative study of tumor angiogenesis and immunohistochemistry for p53, c-ErbB2, c-myc and EGFr as prognostic factors in gastric cancer SO HISTOLOGY AND HISTOPATHOLOGY LA English DT Article DE angiogenesis; p53; gastric cancer; prognosis ID INVASIVE BREAST-CARCINOMA; SQUAMOUS-CELL CARCINOMA; GROWTH-FACTOR RECEPTOR; MICROVESSEL DENSITY; INHIBITS ANGIOGENESIS; EXPRESSION; METASTASIS; STAGE; GENE; INDICATOR AB Gastric cancer (GC) continues to be a highly aggressive malignancy with poor prognosis and low survival rates. The survival of patients with GC depends mainly on the stage of the disease, with early GC having a 5 year survival of 90-100% and advanced tumors a 5 year survival of 15-25%. The role of other prognostic factors in these tumors is still under investigation. 28 gastric dysplasia, 45 Early GC and 98 Advanced Gastric Cancers were evaluated for expression of the oncogenes p53, c-ErbB2, c-myc and the EGFr in paraffin-embedded material utilizing Avidin-Biotin immunohistochemistry techniques. In 34 cases of GC microvessel density (MVD) was determined in CD34 stained sections. Statistical correlations with stage, histologic type, differentiation degree, location, size, ploidy patterns and overall survival were done. The Mantel-Cox test was performed to evaluate which factors had an independent prognostic value. Both, tumor angiogenesis and p53 protein expression were statistically associated (95% confidence intervals) with overall survival in patients with GC. p53 protein expression was also correlated with cardial location, nodal involvement and tumor stage. c-ErbB2 may recognize a group of highly aggressive well differentiated adenocarcinomas with worse prognosis. c-myc was also significantly enhanced in well differentiated tumors. EGFr showed no significant associations. Mantel-Cox was performed to compare the prognostic value of tumor stage, p53 protein expression and tumor angiogenesis. Tumor angiogenesis was the most important prognostic indicator to predict overall survival in our series. p53 expression was not independent and did not provide additional prognostic information to tumor stage. Our study suggests that angiogenesis as demonstrated by microvessel counts in CD34 stained sections is a significantly important prognostic factor for predicting survival in gastric cancer. C1 Hosp Univ San Carlos, Dept Pathol Anat, Madrid, Spain. NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Sanz-Ortega, J (reprint author), Hosp Univ San Carlos, Dept Pathol Anat, Martin Lagos S-N, Madrid, Spain. RI Moro-Rodriguez, Ernesto/B-6788-2008; Sanz, Julian/G-5276-2013 OI Moro-Rodriguez, Ernesto/0000-0003-1574-6852; NR 41 TC 69 Z9 79 U1 0 U2 2 PU F HERNANDEZ PI MURCIA PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN SN 0213-3911 J9 HISTOL HISTOPATHOL JI Histol. Histopath. PD APR PY 2000 VL 15 IS 2 BP 455 EP 462 PG 8 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 305ZJ UT WOS:000086571400014 PM 10809364 ER PT J AU Pistillo, MP Nicolo, G Salvi, S Capanni, P Perdelli, L Pasciucco, G Ferrara, GB AF Pistillo, MP Nicolo, G Salvi, S Capanni, P Perdelli, L Pasciucco, G Ferrara, GB TI Biochemical analysis of HLA class I subunits expression in breast cancer tissues SO HUMAN IMMUNOLOGY LA English DT Article DE HLA-class I subunits; Western blot; densitometry; immunohistochemistry; monoclonal antibodies ID ANTIGEN EXPRESSION; GENE-EXPRESSION; DOWN-REGULATION; PRIMARY TUMORS; CELL-LINES; MHC; CARCINOMAS; MOLECULES; HETEROGENEITY; TRANSPORTER AB The expression of HLA class 1 alpha-chain and beta(2)-m subunits was studied at the protein level by a semiquantitative Western blot (WB) approach, in 25 primary breast rumors. The results indicated three pathways of alterations defined comparing the tumor WB gel band with the corresponding PBL gel band: (i) high downregulation pattern (the tumor WE gel band was less than or equal to 50% relative to the PBL band), which was found in 44% and 36% of tumors for alpha-chain and beta(2)-m, respectively; (ii) low downregulation pattern (the tumor gel band was between 51% and 75%), which was found in 24% and 20% of tumors for alpha-chain and beta(2)-m, respectively; and (iii) absent downregulation pattern (the tumor gel band was >75%), which was found in 32% and 44% of tumors for alpha-chain and beta(2)-m, respectively. The concordance rate with immunohistochemistry (IHC) performed on the same tissue samples was 72% for alpha-chain and 64% for beta(2)-m This study shows that the use of a semiquantitative WE technique ran well define the levels of HLA class I antigens in an autologous setting allowing the biochemical analysis of HLA class I downregulation directly in solid tumor tissues. In addition, the WE technique can be a valuable tool to objectively support the IHC method. (C) American Society for Histocompatibility and Immunogenetics, 2000. Published by Elsevier Science Inc. C1 Ctr Biotecnol Avanzate, Immunogenet Lab, Natl Canc Inst, I-16132 Genoa, Italy. Natl Canc Inst, Pathol Lab, I-16132 Genoa, Italy. Univ Genoa, Dept Oncol Biol & Genet, Genoa, Italy. RP Pistillo, MP (reprint author), Ctr Biotecnol Avanzate, Immunogenet Lab, Natl Canc Inst, Largo Rosanna Benzi 10, I-16132 Genoa, Italy. NR 38 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 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD APR PY 2000 VL 61 IS 4 BP 397 EP 407 DI 10.1016/S0198-8859(99)00179-2 PG 11 WC Immunology SC Immunology GA 296AG UT WOS:000086000400005 PM 10715517 ER PT J AU Hild, SA Reel, JR Hoffman, LH Blye, RP AF Hild, SA Reel, JR Hoffman, LH Blye, RP TI CDB-2914: Anti-progestational/anti-glucocorticoid profile and post-coital anti-fertility activity in rats and rabbits SO HUMAN REPRODUCTION LA English DT Article DE agonist; antagonist; anti-fertility; glucocorticoid; progestin ID HUMAN PROGESTERONE-RECEPTOR; RHESUS-MONKEYS; ANTIPROGESTIN ZK-137-316; ENDOMETRIAL MATURATION; AGONIST ACTIVITY; EARLY-PREGNANCY; LUTEAL-PHASE; RU-486; RU486; ANTAGONIST AB Our goal was to determine the endocrine and post-coital anti-fertility activity of CDB-2914, Concurrent administration of progesterone to rats on day 4 post-mating blocked the anti-fertility activity of a single oral 2 mg dose of CDB-2914, CDB-2914 did not exhibit progestational activity in the oestradiol-primed immature female rabbit, at doses that exhibited anti-progestational activity. CDB-2914 antagonized exogenous and endogenous progesterone-stimulated uterine haptoglobin synthesis and secretion in immature and adult mated rabbits respectively. Neither CDB-2914 nor mifepristone exhibited glucocorticoid activity as determined by thymus involution in rats; mifepristone was twice as potent as CDB-2914 in antagonizing glucocorticoid action. Post-coital CDB-2914 treatment resulted in a dose-dependent reduction in implantation sites and, pregnancy rates in rabbits. CDB-2914-induced inhibition of uterine weight increase, endometrial glandular arborization and uterine haptoglobin synthesis/secretion correlated with inhibition of pregnancy in mated rabbits. A single oral dose of 64 mg CDB-2914/rabbit was effective at blocking pregnancy when administered on day 4, 5, or 6 post-mating, whereas 32 mg/rabbit was only partially effective in this regard, These data demonstrate that CDB-2914 is a potent, orally active anti-progestin with weak antiglucocorticoid activity. CDB-2914 inhibited implantation in adult rats and rabbits demonstrating its potential as a post-coital contraceptive drug. C1 BIOQUAL Inc, Rockville, MD 20850 USA. Vanderbilt Univ, Sch Med, Dept Cell Biol, Nashville, TN 37212 USA. NICHHD, Contracept & Reprod Hlth Branch, Rockville, MD USA. RP Hild, SA (reprint author), BIOQUAL Inc, 9600 Med Ctr Dr, Rockville, MD 20850 USA. FU NICHD NIH HHS [HD29969, N01-HD-1-3130, N01-HD-6-3259] NR 49 TC 33 Z9 33 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 EI 1460-2350 J9 HUM REPROD JI Hum. Reprod. PD APR PY 2000 VL 15 IS 4 BP 822 EP 829 DI 10.1093/humrep/15.4.822 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 302TM UT WOS:000086381800017 PM 10739827 ER PT J AU Chobanian, AV Hill, M AF Chobanian, AV Hill, M TI National Heart, Lung, and Blood Institute workshop on sodium and blood pressure - A critical review of current scientific evidence SO HYPERTENSION LA English DT Review DE blood pressure; cardiovascular diseases; sodium ID RANDOMIZED CONTROLLED TRIALS; DIETARY-SODIUM; MILD HYPERTENSION; POSTMENOPAUSAL WOMEN; CLINICAL-TRIALS; URINARY SODIUM; SALT INTAKE; WEIGHT-LOSS; METAANALYSIS; CALCIUM C1 NHLBI, Natl High Blood Pressure Educ Program, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Nursing, Ctr Nursing Res, Baltimore, MD USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Chobanian, AV (reprint author), NHLBI, Natl High Blood Pressure Educ Program, NIH, 31 Ctr Dr,MSC 2480, Bethesda, MD 20892 USA. NR 56 TC 108 Z9 117 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X EI 1524-4563 J9 HYPERTENSION JI Hypertension PD APR PY 2000 VL 35 IS 4 BP 858 EP 863 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 306TD UT WOS:000086611700002 PM 10775551 ER PT J AU Johnson, CA Seidel, J Sofer, A AF Johnson, CA Seidel, J Sofer, A TI Interior-point methodology for 3-D PET reconstruction SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE image reconstruction; iterative methods; nonlinear optimization; PET ID POSITRON-EMISSION TOMOGRAPHY; PENALIZED LIKELIHOOD ESTIMATION; EXPECTATION MAXIMIZATION ALGORITHM; TRUNCATED-NEWTON METHODS; IMAGE-RECONSTRUCTION; EM ALGORITHM; MAXIMUM-LIKELIHOOD; BAYESIAN RECONSTRUCTION; 3D RECONSTRUCTION; NOISE PROPERTIES AB Interior-point methods have been successfully applied to a wide variety of linear and nonlinear programming applications. This paper presents a class of algorithms, based on path-following interior-point methodology, for performing regularized maximum-likelihood (ML) reconstructions on three-dimensional (3-D) emission tomography data. The algorithms solve a sequence of subproblems that converge to the regularized maximum likelihood solution from the interior of the feasible region (the nonnegative orthant), We propose two methods, a primal method which updates only the primal image variables and a primal-dual method which simultaneously updates the primal variables and the Lagrange multipliers, A parallel implementation permits the interior-point methods to scale to very large reconstruction problems. Termination is based on well-defined convergence measures, namely, the Karush-Kuhn-Tucker first-order necessary conditions for optimality, We demonstrate the rapid convergence of the path-following interior-point methods using both data from a small animal scanner and Monte Carlo simulated data. The proposed methods can readily be applied to solve the regularized, weighted least squares reconstruction problem. C1 NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. NIH, Dept Nucl Med, Bethesda, MD 20892 USA. George Mason Univ, Syst Engn & Operat Res Dept, Fairfax, VA 22030 USA. RP Johnson, CA (reprint author), NIH, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. NR 56 TC 22 Z9 24 U1 1 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD APR PY 2000 VL 19 IS 4 BP 271 EP 285 DI 10.1109/42.848179 PG 15 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 333AP UT WOS:000088106800003 PM 10909923 ER PT J AU Bosselut, R Kubo, S Guinter, T Kopacz, JL Altman, JD Feigenbaum, L Singer, A AF Bosselut, R Kubo, S Guinter, T Kopacz, JL Altman, JD Feigenbaum, L Singer, A TI Role of CD8 beta domains in CD8 coreceptor function: Importance for MHC I binding, signaling, and positive selection of CD8(+) T cells in the thymus SO IMMUNITY LA English DT Article ID COMPLEX CLASS-I; TYROSINE-PROTEIN-KINASE; BETA-CHAIN; TRANSGENIC MICE; NEGATIVE SELECTION; LYMPHOCYTES-T; INTRAEPITHELIAL LYMPHOCYTES; CD4(+)CD8(+) THYMOCYTES; CYTOPLASMIC DOMAINS; SURFACE EXPRESSION AB The contribution of the CDB beta subunit to CD8 coreceptor function is poorly understood. We now demonstrate that the CD8 beta extracellular domain increases the avidity of CD8 binding to MHC I, and that the intracellular domain of CD8 beta enhances association with two intracellular molecules required for TCR signal transduction, Lck and LAT. By assessing CD8(+) T cell differentiation in CD8 beta-deficient mice reconstituted with various transgenic CD8 beta chimeric molecules, we also demonstrate that the intracellular and extracellular domains of CD8 beta can contribute independently to CD8(+) T cell development, but that both CD8 beta domains together are most efficient. Thus, this study identifies the molecular functions of the CD8 beta intracellular and extracellular domains and documents their contributions to CD8(+) T cell development. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Emory Univ, Vaccine Ctr Yerkes, Atlanta, GA 30329 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick, MD 21702 USA. RP Singer, A (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 69 TC 80 Z9 81 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD APR PY 2000 VL 12 IS 4 BP 409 EP 418 DI 10.1016/S1074-7613(00)80193-4 PG 10 WC Immunology SC Immunology GA 309FH UT WOS:000086757300006 PM 10795739 ER PT J AU Devin, A Cook, A Lin, Y Rodriguez, Y Kelliher, M Liu, ZG AF Devin, A Cook, A Lin, Y Rodriguez, Y Kelliher, M Liu, ZG TI The distinct roles of TRAF2 and RIP in IKK activation by TNF-R1: TRAF2 recruits IKK to TNF-R1 while RIP mediates IKK activation SO IMMUNITY LA English DT Article ID NF-KAPPA-B; TUMOR-NECROSIS-FACTOR; SIGNAL-TRANSDUCTION PATHWAYS; DOMAIN KINASE RIP; DEATH DOMAIN; CELL-DEATH; FACTOR RECEPTORS; TERMINAL KINASE; FACTOR-ALPHA; PROTEIN AB The death domain kinase RIP and the TNF receptor-associated factor 2 (TRAF2) are essential effecters in TNF signaling. To understand the mechanism by which RIP and TRAF2 regulate TNF-induced activation of the transcription factor NF-KB, we investigated their respective roles in TNF-R1-mediated IKK activation using both RIP-/- and TRAF2(-/-) fibroblasts. We found that TNF-R1-mediated IKK activation requires both RIP and TRAF2 proteins. Although TRAF2 or RIP can be independently recruited to the TNF-R1 complex, neither one of them alone is capable of transducing the TNF signal that leads to IKK activation. Moreover, we demonstrated that IKK is recruited to the TNF-R1 complex through TRAF2 upon TNF treatment and that IKK activation requires the presence of RIP in the same complex. C1 NCI, Dept Cell & Canc Biol, Med Branch, Div Clin Sci,NIH, Bethesda, MD 20892 USA. Univ Massachusetts, Med Ctr, Worcester, MA 01605 USA. RP Liu, ZG (reprint author), NCI, Dept Cell & Canc Biol, Med Branch, Div Clin Sci,NIH, Bethesda, MD 20892 USA. FU NIGMS NIH HHS [R01 GM061298] NR 52 TC 304 Z9 320 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD APR PY 2000 VL 12 IS 4 BP 419 EP 429 DI 10.1016/S1074-7613(00)80194-6 PG 11 WC Immunology SC Immunology GA 309FH UT WOS:000086757300007 PM 10795740 ER PT J AU Gosselin, P Makrigiannis, AP Nalewaik, R Anderson, SK AF Gosselin, P Makrigiannis, AP Nalewaik, R Anderson, SK TI Characterization of the Ly491 promoter SO IMMUNOGENETICS LA English DT Article DE mouse; natural killer cells; major histocompatibility complex receptor; Ly49; promoter ID NATURAL-KILLER-CELLS; RECEPTOR REPERTOIRE; NK CELLS; EXPRESSION; FAMILY; LY-49; GENES; PHOSPHORYLATION; RECRUITMENT; PHOSPHATASE AB Fourteen potential Ly49 genes have been identified in the C57Bl/6 mouse strain. and cDNAs containing a complete coding region have been isolated for 10 members of this gene family. Ly49 proteins are primarily expressed in natural killer (NK) cells. Although the sequence of the Ly49a promoter region has been published, no study of the cell-specific activity of the promoter has been reported. A 12-kb genomic fragment of the Ly49I gene was isolated and characterized by DNA sequencing. Approximately 5 kb of DNA sequence upstream of the first Ly49I exon was determined and this region was used to perform promoter analysis using luciferase reporter plasmid constructs. A core promoter was identified that was preferentially transcribed in a Ly49-expressing cell line, EL-4. Electrophoretic mobility shift assays using oligonucleotide probes from the core Ly49i promoter and comparable regions from the Ly49a promoter demonstrated the importance of TATA-related elements in generating EL-4 and NK cell-specific DNA/protein complexes. C1 NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, SAIC Frederick, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Expt Immunol Lab, Div Basic Sci, Frederick, MD 21702 USA. RP Anderson, SK (reprint author), NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, SAIC Frederick, Bldg 560,Room 31-93, Frederick, MD 21702 USA. RI Anderson, Stephen/B-1727-2012 OI Anderson, Stephen/0000-0002-7856-4266 FU NCI NIH HHS [N01-CO-56000] NR 29 TC 18 Z9 18 U1 0 U2 1 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 2000 VL 51 IS 4-5 BP 326 EP 331 DI 10.1007/s002510050626 PG 6 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 312BV UT WOS:000086924100009 PM 10803845 ER PT J AU Wiltrout, RH AF Wiltrout, RH TI Regulation and antimetastatic functions of liver-associated natural killer cells SO IMMUNOLOGICAL REVIEWS LA English DT Review ID LARGE GRANULAR LYMPHOCYTES; BETA T-CELLS; BIOLOGICAL RESPONSE MODIFIERS; MURINE RENAL-CANCER; NK CELLS; RECOMBINANT INTERLEUKIN-2; HEPATIC METASTASES; PERIPHERAL-BLOOD; KUPFFER-CELLS; BONE-MARROW AB The liver is a complex organ composed of hepatic parenchymal cells and a variety of non-parenchymal cells that consist of endothelial cells, Kupffer cells, and several subsets of resident lymphocytes, including natural killer (NK), T and NK1.1(+)/CD3(+) (NI(/T) cells. The regulation of these various lymphoid subpopulations and their relative contributions to antiviral, antitumor and pathogenic inflammatory responses in the liver remain topics of much interest. Studies from our laboratory have shown that various immune stimulants and cytokines can augment liver-associated NK activity at least partially through the mobilization of NK cells from the bone marrow to the liver. The mobilization process can be dependent on the induction of interferon (IFN)-gamma and/or tumor necrosis factor-a and on very late activation antigen-4/vascular cell adhesion molecule-1 interaction. The induction of IFN-gamma by cytokines such as interleukin (IL)-12 also rapidly triggers the induction of chemokine genes in parenchymal cells that may contribute to the localization of NK and T cells. Both IL-2 and IL-12 trigger changes in the number and functions of liver-associated leukocyte subsets, and induce antimetastatic effects that are likely mediated through several direct and indirect mechanisms. The overall goal of these studies is to understand the interactions and functions of liver-associated NK1.1(+) cells in the context of innate and adaptive immune responses to neoplasia. C1 NCI, Frederick Canc Res & Dev Ctr, Expt Immunol Lab, Div Basic Sci, Frederick, MD 21702 USA. RP Wiltrout, RH (reprint author), NCI, Frederick Canc Res & Dev Ctr, Expt Immunol Lab, Div Basic Sci, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 79 TC 46 Z9 49 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD APR PY 2000 VL 174 BP 63 EP 76 DI 10.1034/j.1600-0528.2002.00014h.x PG 14 WC Immunology SC Immunology GA 305HK UT WOS:000086533200005 PM 10807507 ER PT J AU Higginbottom, A Wilkinson, I McCullough, B Lanza, F Azorsa, DO Partridge, LJ Monk, PN AF Higginbottom, A Wilkinson, I McCullough, B Lanza, F Azorsa, DO Partridge, LJ Monk, PN TI Antibody cross-linking of human CD9 and the high-affinity immunoglobulin E receptor stimulates secretion from transfected rat basophilic leukaemia cells SO IMMUNOLOGY LA English DT Article ID ANTI-CD9 MONOCLONAL-ANTIBODY; FC-EPSILON-RI; LEUKEMIA RBL-2H3 CELLS; IGE-RECEPTOR; MAST-CELLS; HUMAN PLATELETS; IIIA COMPLEX; GAMMA-CHAIN; GLYCOPROTEIN; ASSOCIATION AB Previous studies have shown that antibody cross-linking of the tetraspanin protein CD9 stimulates the degranulation of platelets and eosinophils, although the mechanism of activation is unclear. In this work we transfected human CD9 into the rat basophilic leukaemia (RBL-2H3) cell line and studied the stimulation of secretion from these cells in response to a panel of anti-CD9 antibodies. Intact immunoglobulin G1 (IgG1) antibodies activated transfected cells whereas F(ab')(2) fragments of antibody and an intact IgG2a did not. Stimulation of secretion was inhibited by co-incubation with monomer murine immunoglobulin E (IgE) but not with an IgG1 isotype control, indicating that the response involves the endogenous high-affinity IgE receptor (Fc epsilon RI). The anti-CD9 antibody activation curve was biphasic, and supraoptimal antibody concentrations stimulated little or no degranulation, indicating that multivalent binding of human CD9 molecules is necessary for the formation of an active complex with rat Fc epsilon RI. Immunoprecipitation of Fc epsilon RI under mild detergent conditions co-precipitated CD9, suggesting the presence of pre-existing complexes of CD9 and Fc epsilon RI that could be activated by antibody cross-linking. These data are further evidence that tetraspanins are involved in Fc epsilon RI signalling and may reflect the participation of tetraspanins in the formation of complexes with other membrane proteins that use components of Fc receptors for signal transduction. C1 Univ Sheffield, Dept Mol Biol & Biotechnol, Sheffield S10 2UH, S Yorkshire, England. INSERM, U311, Etablissement Transfus, Strasbourg, France. NIH, Natl Human Genome Res Inst, Canc Genet Branch, Bethesda, MD USA. RP Monk, PN (reprint author), Univ Sheffield, Dept Mol Biol & Biotechnol, Firth Court,Western Bank, Sheffield S10 2UH, S Yorkshire, England. RI Monk, Peter/C-6155-2008; Lanza, Francois/H-9252-2016 OI Monk, Peter/0000-0003-4637-3059; Lanza, Francois/0000-0002-5802-4748 NR 40 TC 6 Z9 6 U1 2 U2 4 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD APR PY 2000 VL 99 IS 4 BP 546 EP 552 DI 10.1046/j.1365-2567.2000.00992.x PG 7 WC Immunology SC Immunology GA 308GC UT WOS:000086701300009 PM 10792502 ER PT J AU Miyagi, T Chuang, LF Lam, KM Kung, HF Wang, JM Osburn, BI Chuang, RY AF Miyagi, T Chuang, LF Lam, KM Kung, HF Wang, JM Osburn, BI Chuang, RY TI Opioids suppress chemokine-mediated migration of monkey neutrophils and monocytes - an instant response SO IMMUNOPHARMACOLOGY LA English DT Article DE opioids; interleukin-8 (IL-8); RANTES; chemotaxis; monkey leukocytes ID SIMIAN-IMMUNODEFICIENCY-VIRUS; RECEPTOR GENE-EXPRESSION; MU-OPIATE RECEPTOR; MORPHINE-SULFATE; T-CELL; LYMPHOCYTES; INFECTION; COFACTOR; PROTEIN; 7-TRANSMEMBRANE AB Opioid users having acquired human immunodeficiency syndrome (AIDS) are at a greater risk than non-users of contracting opportunistic infections. Opioid-administered and simian immunodeficiency virus (SIV)-infected rhesus monkeys have been an excellent model for studying AIDS and drug abuse in humans. In this study, chemotaxis of monkey leukocytes was evaluated using the chemokines interleukin-8 (IL-8) and regulated upon activation, normal T cell expressed (RANTES) as the chemoattractants, and the effects of various opioid agonists and antagonists on the efficiency of chemotaxis were examined. Opioids were either incubated with monkey leukocytes or added directly to chemokines, and the number of cells migrating toward IL-8 (for neutrophils) or RANTES (for monocytes) was scored. Inhibition of chemotaxis was seen with both assay conditions, and the inhibition was mediated by opioids binding to mu or kappa receptors. Binding to delta opiod receptors was rarely, if ever, observed. Although opioids themselves may act as weak chemoattractants for monkey leukocytes, addition of opioid agonists to chemokines would reduce the chemoattractant ability of the chemokines. Opioids did not cause the same inhibitory effect on the chemotactic migration of neutrophils when the complement component C5a or the chemotactic peptide N-formyl-MET-LEU-PHE (fMLP) was used as chemoattractant. These studies suggest that the presence of opioids during SIV infection immediately alters cheomkine-mediated immune functions. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Univ Calif Davis, Sch Med, Dept Med Pharmacol & Toxicol, Davis, CA 95616 USA. Univ Calif Davis, Dept Populat Hlth & Reprod, Davis, CA 95616 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. Univ Calif Davis, Dept Vet Pathol Microbiol & Immunol, Davis, CA 95616 USA. RP Chuang, RY (reprint author), Univ Calif Davis, Sch Med, Dept Med Pharmacol & Toxicol, Davis, CA 95616 USA. FU NIDA NIH HHS [DA 05901, DA 10433] NR 21 TC 46 Z9 48 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0162-3109 J9 IMMUNOPHARMACOLOGY JI Immunopharmacology PD APR PY 2000 VL 47 IS 1 BP 53 EP 62 DI 10.1016/S0162-3109(99)00188-5 PG 10 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 296EN UT WOS:000086010200006 PM 10708810 ER PT J AU Pavliakova, D Moncrief, JS Lyerly, DM Schiffman, G Bryla, DA Robbins, JB Schneerson, R AF Pavliakova, D Moncrief, JS Lyerly, DM Schiffman, G Bryla, DA Robbins, JB Schneerson, R TI Clostridium difficile recombinant toxin A repeating units as a carrier protein for conjugate vaccines: Studies of pneumococcal type 14, Escherichia coli K1, and Shigella flexneri type 2a polysaccharides in mice SO INFECTION AND IMMUNITY LA English DT Article ID INFLUENZAE TYPE-B; PSEUDOMEMBRANOUS COLITIS; A GENE; ANTIBODY-RESPONSE; IMMUNIZATION; PROTECTION; HAMSTERS; ANTIGENS; DISEASE; TETANUS AB Unlike the native protein, a nontoxic peptide (repeating unit of the native toxin designated rARU) from Clostridium difficile toxin A (CDTA) afforded an antigen that could be bound covalently to the surface polysaccharides of pneumococcus type 14, Shigella flexneri type 2a, and Escherichia coli K1. The yields of these polysaccharide-protein conjugates were significantly increased by prior treatment of rARU with succinic anhydride. Conjugates, prepared with rARU or succinylated (rARUsucc), were administered to mice by a clinically relevant dosage and immunization scheme. All conjugates elicited high levels of serum immunoglobulin G both to the polysaccharides and to CDTA. Conjugate-induced anti-CDTA had neutralizing activity in vitro and protected mice challenged with CDTA, similar to the rARU alone. Conjugates prepared with succinylated rARU, therefore, have potential for serving both as effective carrier proteins for polysaccharides and for preventing enteric disease caused by C. difficile. C1 NICHHD, NIH, Bethesda, MD 20892 USA. Techlab Inc, Blacksburg, VA USA. Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. RP Schneerson, R (reprint author), NICHHD, NIH, Bldg 6,Room 424, Bethesda, MD 20892 USA. NR 43 TC 19 Z9 23 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 2000 VL 68 IS 4 BP 2161 EP 2166 DI 10.1128/IAI.68.4.2161-2166.2000 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 296EP UT WOS:000086010300056 PM 10722615 ER PT J AU Kumar, S Collins, W Egan, A Yadava, A Garraud, O Blackman, MJ Guevara-Patino, JA Diggs, C Kaslow, DC AF Kumar, S Collins, W Egan, A Yadava, A Garraud, O Blackman, MJ Guevara-Patino, JA Diggs, C Kaslow, DC TI Immunogenicity and efficacy in Aotus monkeys of four recombinant Plasmodium falciparum vaccines in multiple adjuvant formulations based on the 19-kilodalton C terminus of merozoite surface protein 1 SO INFECTION AND IMMUNITY LA English DT Article ID PROTECTIVE IMMUNE-RESPONSE; SACCHAROMYCES-CEREVISIAE; ERYTHROCYTE INVASION; MALARIA; FRAGMENT; IMMUNIZATION; ANTIBODIES; YOELII; PURIFICATION; EXPRESSION AB The immunogenicity and protective efficacy of four versions of recombinant C-terminal 19-kDa epidermal growth factor-like region of the major surface protein 1 (rMSP1(19)) of Plasmodium falciparum was studied in Aotus monkeys. Vaccination with each of the four rMSP1(19) constructs elicited high levels of antibodies to MSP1(19) but only one construct, the 19-kDa fragment expressed as a secreted fusion protein from Saccharomyces cerevisiae (yP30P2MSP1(19)), induced a high degree of protective immunity in Aotus nancymai against lethal P. falciparum challenge. Protective formulation required Freund's adjuvant; vaccination with yP30P2MSP1(19) in six other adjuvants that are suitable for human use induced lower levels of antibody response and no protection. These results emphasize the need to continue the search for an adjuvant that is comparable to Freund's adjuvant in potency and is safe for use in humans. C1 NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Div Parasit Dis, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Sci Resources Program, Atlanta, GA 30333 USA. Natl Inst Med Res, Div Parasitol, London NW7 1AA, England. US Agcy Int Dev, Malad Vaccine Dev Program, Washington, DC 20523 USA. RP Kumar, S (reprint author), USN, Med Res Ctr, Malaria Program, 503 Robert Grant Ave, Silver Spring, MD 20910 USA. NR 25 TC 87 Z9 91 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 2000 VL 68 IS 4 BP 2215 EP 2223 DI 10.1128/IAI.68.4.2215-2223.2000 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 296EP UT WOS:000086010300063 PM 10722622 ER PT J AU Johnson, A Leke, R Harun, L Ginsberg, C Ngogang, J Stowers, A Saul, A Quakyi, IA AF Johnson, A Leke, R Harun, L Ginsberg, C Ngogang, J Stowers, A Saul, A Quakyi, IA TI Interaction of HLA and age on levels of antibody to Plasmodium falciparum rhoptry-associated proteins 1 and 2 SO INFECTION AND IMMUNITY LA English DT Article ID INHIBITORY MONOCLONAL-ANTIBODIES; ERYTHROCYTE SURFACE-ANTIGEN; HUMORAL IMMUNE-RESPONSE; RECOMBINANT PROTEINS; MALARIA SPOROZOITE; HOLOENDEMIC AREA; CELL EPITOPE; CHILDREN; SEQUENCE; MONKEYS AB The Plasmodium falciparum rhoptry-associated proteins 1 and 2 (RAP1 and RAP2) are candidate antigens for a subunit malaria vaccine. The design of the study, which looks at the acquisition of immunity to malaria from childhood to old age, has allowed us to document the interaction of HLA and age on levels of antibody to specific malarial antigens. Antibodies reach maximum levels to RAP1 after the age of 15 but to RAP2 only after the age of 30. The effect of HLA-DRB1 and -DQB1 and age on levels of antibody to rRAP1 and rRAP2 was analyzed with a multiple regression model in which all HLA alleles and age were independent variables. DQB1*0301 and -*03032 showed an age-dependent association with levels of antibody to rRAP1, being significant in children 5 to 15 years (P < 0.001) but not in individuals over 15 years of age. DRB1*03011 showed an age-dependent association with antibody levels to rRAP2; however, this association was in adults over the age of 30 years (P < 0.01) but not in individuals under the age of 30 years. No associations were detected between DRB1 alleles and RAP1 antibody levels or between DQB1 alleles and RAP2 antibody levels. Thus, not only the HLA allele but also the age at which an interaction is manifested varies for different malarial antigens. The interaction may influence either the rate of acquisition of antibody or the final level of antibody acquired by adults. C1 Georgetown Univ, Sch Med, Dept Pediat, Washington, DC 20007 USA. Georgetown Univ, Sch Med, Dept Biol, Washington, DC 20007 USA. Univ Yaounde 1, Ctr Biotechnol, Yaounde, Cameroon. NIAID, Malaria Vaccine Dev Unit, NIH, Bethesda, MD 20892 USA. Univ Queensland, Brisbane, Qld, Australia. Queensland Inst Med Res, Brisbane, Qld 4006, Australia. RP Johnson, A (reprint author), Georgetown Univ, Sch Med, Dept Pediat, PCS Bldg LD8D,3900 Reservoir Rd NW, Washington, DC 20007 USA. RI Saul, Allan/I-6968-2013 OI Saul, Allan/0000-0003-0665-4091 FU NIAID NIH HHS [UO1-AI-35839] NR 47 TC 14 Z9 16 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 2000 VL 68 IS 4 BP 2231 EP 2236 DI 10.1128/IAI.68.4.2231-2236.2000 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 296EP UT WOS:000086010300065 PM 10722624 ER PT J AU Segal, BH Sakamoto, N Patel, M Maemura, K Klein, AS Holland, SM Bulkley, GB AF Segal, BH Sakamoto, N Patel, M Maemura, K Klein, AS Holland, SM Bulkley, GB TI Xanthine oxidase contributes to host defense against Burkholderia cepacia in the p47(phox-/-) mouse model of chronic granulomatous disease SO INFECTION AND IMMUNITY LA English DT Article ID RECOMBINANT INTERFERON-GAMMA; ENDOTHELIAL-CELLS; GENE-EXPRESSION; RETICULOENDOTHELIAL FUNCTION; ASPERGILLUS-NIDULANS; PSEUDOMONAS-CEPACIA; NITRIC-OXIDE; INFECTION; MICE; DEHYDROGENASE AB Chronic granulomatous disease (CGD) is an inherited disorder of the NADPH oxidase in which phagocytes are defective in generating superoxide and downstream microbicidal reactive oxidants, leading to recurrent life-threatening bacterial and fungal infections. Xanthine oxidase (XO) is another enzyme known to produce superoxide in many tissues. Using the p47(phox-/-) mouse model of CGD, we evaluated the residual antibacterial activity of SO. Clearance of Burkholderia cepacia? a major pathogen in CGD, was reduced in p47(phox-/-) mice compared to that in wild-type mice and was further inhibited in p47(phox-/-) mice by pretreatment with the specific XO inhibitor allopurinol. Hepatic B. cepacia burden aas similar in the two genotypes, but allopurinol significantly reduced net hepatic killing and killing efficiency only in p47(phox-/-) mice. Clearance and killing of intravenous Escherichia coli was intact in p47(phox-/-) mice and nas unaffected by pretreatment with allopurinol. Ln CGD, XO mag. contribute to host defense against a subset of reactive oxidant-sensitive pathogens. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21287 USA. RP Bulkley, GB (reprint author), Johns Hopkins Hosp, 600 N Wolfe St,Blalock 685, Baltimore, MD 21287 USA. RI Patel, Mayur/K-2363-2013 FU NIDDK NIH HHS [DK31764, R01 DK031764] NR 41 TC 33 Z9 33 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 2000 VL 68 IS 4 BP 2374 EP 2378 DI 10.1128/IAI.68.4.2374-2378.2000 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 296EP UT WOS:000086010300089 PM 10722648 ER PT J AU Wolf, K Fischer, E Hackstadt, T AF Wolf, K Fischer, E Hackstadt, T TI Ultrastructural analysis of developmental events in Chlamydia pneumoniae-infected cells SO INFECTION AND IMMUNITY LA English DT Article ID SP STRAIN TWAR; TRACHOMATIS; PENICILLIN; MORPHOLOGY; MEMBRANE; PSITTACI; ENTRY AB Chlamydia pneumoniae is an obligate intracellular parasite with a developmental cycle believed to be common to all members of the genus Chlamydia. We present a detailed description based on transmission and scanning electron microscopy of temporal events and inclusion structures throughout the C. pneumoniae AR-39 developmental cycle. C1 NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, NIH,Rocky Mt Labs, Hamilton, MT 59840 USA. NIAID, Med Branch, NIH, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Hackstadt, T (reprint author), NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, NIH,Rocky Mt Labs, Hamilton, MT 59840 USA. NR 25 TC 73 Z9 79 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 2000 VL 68 IS 4 BP 2379 EP 2385 DI 10.1128/IAI.68.4.2379-2385.2000 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 296EP UT WOS:000086010300090 PM 10722649 ER PT J AU Ribeiro, JMC Rowton, ED Charlab, R AF Ribeiro, JMC Rowton, ED Charlab, R TI Salivary amylase activity of the phlebotomine sand fly, Lutzomyia longipalpis SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE saliva; amylase; salivary glands; glucosidase; hematophagy; sugar feeding; starch; sandfly ID YELLOW-FEVER MOSQUITO; AEDES-AEGYPTI; ALPHA-GLUCOSIDASE; PAPATASI DIPTERA; PSYCHODIDAE; GLANDS; DIGESTION; MIDGUT AB Both male and female adult stages of the sand fly Lutzomyia longipalpis have detectable amylase activity in their salivary glands, as indicated by formation of p-nitrophenyl-alpha-D-maltoside from p-nitrophenyl-alpha-D-octoside and by hydrolysis of 4-nitrophenyl-alpha-D-maltoheptaoside-4, 6,-O-ethylidene. No salivary alpha-glucosidase was detected. Amylase activity was also found in the crop and midgut of female flies, although in a smaller amount. Salivary amylase is significantly reduced from the salivary glands immediately after a blood meal, as is the case with salivary alpha-glucosidases in mosquitoes. Presence of salivary gland amylase in these sand flies, and absence of salivary alpha-glucosidase, indicates that in nature these insects may have a significant intake of carbohydrates in the form of starch, as suggested by their plant-feeding behavior, previously demonstrated by Schlein and Warburg (Schlein, Y., Warburg, A., 1986. Phytophagy and the feeding cycle of Phlebotomus papatasi (Diptera: Psychodidae) under experimental conditions. Journal of Medical Entomology 23, 11-15), and Alexander and Usma (Alexander, B., Usma, M.C., 1994. Potential sources of sugar for the phlebotomine sandfly Lutzomyia youngi (Diptera: Psychodidae) in a Columbia coffee plantation. Ann. Trop. Med. Parasitol. 88, 543-549). Published by Elsevier Science Ltd. C1 NIAID, Sect Med Entomol, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Dept Entomol, Washington, DC 20307 USA. RP Ribeiro, JMC (reprint author), NIAID, Sect Med Entomol, Parasit Dis Lab, NIH, Bldg 4,Room 126,4 Ctr Dr,MSC-0425, Bethesda, MD 20892 USA. RI Rowton, Edgar/A-4474-2012; Rowton, Edgar/A-1975-2011; OI Rowton, Edgar/0000-0002-1979-1485; Ribeiro, Jose/0000-0002-9107-0818 NR 28 TC 22 Z9 22 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0965-1748 J9 INSECT BIOCHEM MOLEC JI Insect Biochem. Mol. Biol. PD APR PY 2000 VL 30 IS 4 BP 271 EP 277 DI 10.1016/S0965-1748(99)00119-8 PG 7 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA 302HA UT WOS:000086358600001 PM 10727893 ER PT J AU Ribeiro, JMC Rowton, ED Charlab, R AF Ribeiro, JMC Rowton, ED Charlab, R TI The salivary 5 '-nucleotidase/phosphodiesterase of the hematophagus sand lutzomyia fly, Lutzomyia longipalpis SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE saliva; sand fly; nucleotidase; apyrase; hematophagy; purinergic; platelet; adenosine; UDPG; bis-p-nitrophenylphosphate; ADP ID AEDES-AEGYPTI; 5'-NUCLEOTIDASE; ARTHROPODS; ADENOSINE; APYRASE AB Salivary gland homogenates from adult female Lutzomyia longipalpis sand flies contain large amounts of 5'-nucleotidase and phosphodiesterase activities. Phosphodiesterase activity was found to be associated with 5'-nucleotidase in several independent experiments: (i) it coelutes with 5'-nucleotidase on a molecular sieving column, (ii) it coelutes with 5'-nucleotidase on a chromatofocusing column, and (iii) it has the same thermal inactivation kinetics as the 5'-nucleotidase activity. Additionally, both activities are independent of divalent cations, and both are decreased following a blood meal, suggesting that they reside in the same molecule. The role of salivary nucleotidases and purine nucleotides in blood-feeding by sand flies is discussed. Published by Elsevier Science Ltd. C1 NIAID, Sect Med Entomol, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Dept Entomol, Washington, DC 20307 USA. RP Ribeiro, JMC (reprint author), NIAID, Sect Med Entomol, Parasit Dis Lab, NIH, Bldg 4,Room 126,4 Ctr Dr,MSC-0425, Bethesda, MD 20892 USA. RI Rowton, Edgar/A-4474-2012; Rowton, Edgar/A-1975-2011; OI Rowton, Edgar/0000-0002-1979-1485; Ribeiro, Jose/0000-0002-9107-0818 NR 21 TC 18 Z9 19 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0965-1748 J9 INSECT BIOCHEM MOLEC JI Insect Biochem. Mol. Biol. PD APR PY 2000 VL 30 IS 4 BP 279 EP 285 DI 10.1016/S0965-1748(99)00123-X PG 7 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA 302HA UT WOS:000086358600002 PM 10727894 ER PT J AU Tsutsui, T Tamura, Y Yagi, E Barrett, JC AF Tsutsui, T Tamura, Y Yagi, E Barrett, JC TI Involvement of genotoxic effects in the initiation of estrogen-induced cellular transformation: Studies using Syrian hamster embryo cells treated with 17 beta-estradiol and eight of its metabolites SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID SISTER CHROMATID EXCHANGES; NEOPLASTIC TRANSFORMATION; CHROMOSOME-ABERRATIONS; MAMMALIAN-CELLS; PROLIFERATION; CHEMICALS; HORMONES AB To examine a direct involvement of genotoxic effects of estrogens in the initiation of hormonal carcinogenesis, the abilities of 17 beta-estradiol (E-2) and 8 of its metabolites to induce cellular transformation and genetic effects were studied using the Syrian hamster embryo (SHE) cell model. Treatment with E-2, estrone (E-1), 2-hydroxyestrone (2-OHE1), 4-hydroxyestrone (4-OHE1), 2-methoxyestrone (2-MeOE1), 16 alpha-hydroxyestrone (16 alpha-OHE1), 2-hydroxyestradiol (2-OHE2), 4-hydroxyestradiol (4-OHE2) or estriol (E-3) for 1 to 3 days inhibited SHE cell growth in a concentration-dependent manner. Concentration-dependent increases in the frequency of morphological transformation in SHE cells were exhibited by treatment for 48 hr with each of all estrogens examined, except for E-3. The transforming activities of the estrogens, determined by the induced transformation frequencies, were ranked as follows: 4-OHE1 > 2-OHE1 > 4-OHE2 > 2-OHE2 greater than or equal to E-2 or E-1 > 2-MeOE1 or 16 alpha-OHE1 > E-3. Somatic mutations in SHE cells at the Na+/K(+)ATPase and /or hprt loci were induced only when the cells were treated with 4-OHE1, 2-MeOE1 or 4-OHE2 for 48 hr. Some estrogen metabolites induced chromosome aberrations in SHE cells following treatment for 24 hr. The rank order of the clastogenic activities of the estrogens that induced chromosome aberrations was 4-OHE1 > 2-OHE1 or 4-OHE2 > 2-OHE2 > E-1. Significant increases in the percentage of aneuploid cells in the near diploid range were exhibited in SHE cells treated for 48 hr or 72 hr with each of the estrogens, except for 4-OHE, and E-3. Our results indicate that the transforming activities of all estrogens tested correspond to at least one of the genotoxic effects by each estrogen, i.e., chromosome aberrations, aneuploidy or gene mutations, suggesting the possible involvement of genotoxicity in the initiation of estrogen-induced carcinogenesis. Int. J. Cancer 86:8-14, 2000. (C) 2000 Wiley-Liss, Inc. C1 NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. Nippon Dent Univ, Dept Pharmacol, Tokyo, Japan. RP Barrett, JC (reprint author), NIEHS, Mol Carcinogenesis Lab, MD C2-15, Res Triangle Pk, NC 27709 USA. NR 20 TC 41 Z9 41 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD APR 1 PY 2000 VL 86 IS 1 BP 8 EP 14 DI 10.1002/(SICI)1097-0215(20000401)86:1<8::AID-IJC2>3.0.CO;2-V PG 7 WC Oncology SC Oncology GA 289UM UT WOS:000085640400002 PM 10728588 ER PT J AU Merrill, RM Capocaccia, R Feuer, EJ Mariotto, A AF Merrill, RM Capocaccia, R Feuer, EJ Mariotto, A TI Cancer prevalence estimates based on tumour registry data in the Surveillance, Epidemiology, and End Results (SEER) Program SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cancer; prevalence; burden; cohort; cross-sectional; life table ID MEDICARE CLAIMS DATA; SURVIVAL; MORTALITY AB Background The Connecticut Tumor Registry (CTR) has collected cancer data for a sufficiently long period of time to capture essentially all prevalent cases of cancer, and to provide unbiased estimates of cancer prevalence. However, prevalence proportions estimated from Connecticut data may not be representative of the total US, particularly for racial/ethnic subgroups. The purpose of this study is to apply the modelling approach developed by Capocaccia and De Angelis to cancer data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute to obtain more representative US site-specific cancer prevalence proportion estimates for white and black patients. Methods Incidence and relative survival were modelled and used to obtain estimated completeness indices of SEER prevalence proportions for ail cancer sites combined, stomach, cervix uteri, skin melanomas, non-Hodgkin's lymphomas, lung and bronchus, colon/rectum, female breast, and prostate. For validation purposes, modelled completeness indices were computed for Connecticut and compared with empirical completeness indices (the ratio of Connecticut based prevalence proportion estimates using 1973-1993 data to 1940-1993 data). The SEER-based modelled completeness indices were used to adjust SEER prevalence proportion estimates for white and black patients. Results Model validation showed that the adjusted SEER cancer prevalence proportions provided reasonably unbiased prevalence proportion estimates in general, although more complex modelling of the completeness indices is necessary for female cancers of the colon, melanoma, breast, cervix, and all cancers combined. The SEER-based cancer prevalence proportions are incomplete for most cancer sites, more so for women, whites, and at older ages. For all cancers combined, prevalence proportions tended to he higher for whites than blacks. For the site-specific cancers this was true for stomach, prostate, cervix uteri, and lung and bronchus (men only). For colon/rectal cancers the prevalence proportions were higher for blacks through ages 59 (men) and 64 (women), and then for the remaining ages they were higher for whites. Prevalence proportions were lowest for stomach cancer and highest for prostate and female breast cancers. Men experienced higher prevalence proportions than women for skin melanomas, non-Hodgkin's lymphomas, lung and bronchus, and colon/rectal cancers. Conclusion The modelling approach applied to SEER data generally provided reasonable estimates of cancer prevalence. These estimates are useful because they are more representative of cancer prevalence than previously obtained and reported in the US. C1 Brigham Young Univ, Dept Hlth Sci, Coll Hlth & Humn Performance, Provo, UT 84602 USA. Univ Utah, Coll Med, Div Epidemiol, Dept Family & Prevent Med, Salt Lake City, UT 84132 USA. Ist Super Sanita, Epidemiol & Biostat Lab, I-00161 Rome, Italy. NCI, Appl Res Branch, Canc Control Res Program, Div Canc Control & Populat Sci,EPN, Bethesda, MD 20892 USA. RP Merrill, RM (reprint author), Brigham Young Univ, Dept Hlth Sci, Coll Hlth & Humn Performance, 213 Richards Bldg, Provo, UT 84602 USA. NR 25 TC 71 Z9 75 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD APR PY 2000 VL 29 IS 2 BP 197 EP 207 DI 10.1093/ije/29.2.197 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 323XE UT WOS:000087589600001 PM 10817114 ER PT J AU Reddy, BS Hirose, Y Lubet, RA Steele, VE Kelloff, GJ Rao, CV AF Reddy, BS Hirose, Y Lubet, RA Steele, VE Kelloff, GJ Rao, CV TI Lack of chemopreventive efficacy of DL-selenomethionine in colon carcinogenesis SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE chemoprevention; colon cancer; selenomethionine ID SYNTHETIC ORGANOSELENIUM COMPOUND; CANCER CHEMOPREVENTION; DIETARY SELENIUM; 1,4-PHENYLENEBIS(METHYLENE)SELENOCYANATE; INHIBITION; AGENT AB Epidemiologic observations and laboratory research have suggested that dietary selenium reduces the risk of colon cancer. Selenium-enriched brewer's yeast as a dietary supplement reduces the incidence of and mortality from cancer of the colon in humans. It is not clear whether the observed inhibitory effect is due to selenomethionine, or to other forms of selenium, or to a mixture of the selenium compounds present in selenium-enriched brewer's yeast. Therefore, bioassay described in this study examined the chemopreventive efficacy of 10 and 15 ppm selenomethionine, equivalent to 3.6 and 5.4 ppm as selenium, against azoxymethane (AOM)-induced colon carcinogenesis. At five weeks of age, groups of male F344 rats were fed diets containing 0 (control diet), 10 or 15 ppm selenomethionine. At seven and eight weeks of age, all rats except those in vehicle-treated groups received s.c. injections of AOM at a dose rate of 15 mg/kg body wt. The rats were maintained on their respective diets for 52 weeks and were then sacrificed. Colon tumors were processed and evaluated histopathologically. Colon tumor incidence and multiplicity were analyzed statistically. No obvious toxic effects were observed following dietary administration of 10 or 15 ppm selenomethionine as indicated by body weight gain. Administration of 10 or 15 ppm selenomethionine had no significant effect on colon tumor incidence and multiplicity. This study suggests that i) selenomethionine lacks chemopreventive efficacy against AOM-induced colon carcinogenesis and ii) other forms of selenium or a mixture of selenium compounds present in selenium-enriched brewer's yeast need to be evaluated for their chemopreventive efficacy. C1 Amer Hlth Fdn, Div Nutr Carcinogenesis, Chemoprevent Program, Valhalla, NY 10595 USA. NCI, Chemoprevent Agent Dev Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. RP Reddy, BS (reprint author), Amer Hlth Fdn, Div Nutr Carcinogenesis, Chemoprevent Program, 1 Dana Rd, Valhalla, NY 10595 USA. RI Chinthalapally, Rao/B-3633-2010 FU NCI NIH HHS [CA17613, CA46589, CN65119] NR 25 TC 17 Z9 17 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD APR PY 2000 VL 5 IS 4 BP 327 EP 330 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 294VD UT WOS:000085930300001 PM 10719045 ER PT J AU Walder, K Morris, C Ravussin, E AF Walder, K Morris, C Ravussin, E TI A polymorphism in the gene encoding CART is not associated with obesity in Pima Indians SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE CART; polymorphism; obesity; Pima Indians ID AMPHETAMINE-REGULATED TRANSCRIPT; COCAINE AB Cocaine- and amphetamine-regulated transcript (CART) is a hypothalamic peptide that may be involved in the regulation of food intake. We screened the human CART gene and identified a novel C-->G substitution in the 3'-untranslated region of exon 3. This polymorphism was genotyped in a total of 68 Pima Indians with extremes of BMI. The frequencies for alleles C and G were 0.76 and 0.24, respectively. There was no evidence of an association between the genotype frequency at this variant and extremes of BMI in this group of Pima Indians. The results of this study do neat suggest a significant role for this variant in exon 3 of CART as a determinant of obesity in Pima Indians. C1 NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. RP Walder, K (reprint author), Deakin Univ, Sch Hlth Sci, Metab Res Unit, Geelong Campus, Geelong, Vic 3217, Australia. NR 6 TC 21 Z9 21 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD APR PY 2000 VL 24 IS 4 BP 520 EP 521 DI 10.1038/sj.ijo.0801196 PG 2 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 300RR UT WOS:000086266400019 PM 10805512 ER PT J AU Yamano, S Baum, BJ AF Yamano, S Baum, BJ TI Prospects for gene-based immunopharmacology in salivary glands SO JAPANESE JOURNAL OF PHARMACOLOGY LA English DT Review DE gene therapeutics; salivary gland; autoimmune disease; cytokine; adeno-associated virus ID AUTOIMMUNE-DISEASE; SJOGRENS-SYNDROME; IN-VIVO; THERAPY APPROACH; GROWTH-HORMONE; NOD MICE; SECRETION; EXPRESSION; LYMPHOCYTES; CIRCULATION AB The clinical potential of gene transfer is increasing. One likely major application of this emerging biotechnology will be for gene therapeutics, the use of a gene as a drug. Salivary glands provide an unusual but increasingly valuable target site for gene transfer. Studies in animal salivary glands from several laboratories, including our own, have provided proof of this concept. In this review, we provide a background and perspective on possible strategies for gene-based immunopharmacology in salivary glands. We use as a target disease model the autoimmune exocrinopathy Sjogren's syndrome. C1 Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Baum, BJ (reprint author), Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, Bldg 10,Room 1N113,10 Ctr Dr,MSC 1190, Bethesda, MD 20892 USA. OI Yamano, Seiichi/0000-0003-2056-4359 NR 50 TC 10 Z9 10 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 0021-5198 J9 JPN J PHARMACOL JI Jpn. J. Pharmacol. PD APR PY 2000 VL 82 IS 4 BP 281 EP 286 DI 10.1254/jjp.82.281 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 307AG UT WOS:000086630700002 PM 10875746 ER PT J AU Engels, EA Whitby, D Goebel, PB Stossel, A Waters, D Pintus, A Contu, L Biggar, RJ Goedert, JJ AF Engels, EA Whitby, D Goebel, PB Stossel, A Waters, D Pintus, A Contu, L Biggar, RJ Goedert, JJ TI Identifying human herpesvirus 8 infection: Performance characteristics of serologic assays SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE human herpesvirus 8; Kaposi's sarcoma; diagnostic tests; receiver operator curves; serology; sensitivity; specificity ID SARCOMA-ASSOCIATED HERPESVIRUS; KAPOSIS-SARCOMA; PERIPHERAL-BLOOD; HUMAN-HERPESVIRUS-8; ANTIBODIES; TRANSMISSION; AIDS; SEROEPIDEMIOLOGY; PREVALENCE; LYMPHOMA AB Epidemiologic studies of infection with the oncogenic human herpesvirus 8 (HHV-8) depend on serologic methods to diagnose infection. However, optimal strategies for identifying HHV-8 infection remain undefined. We therefore evaluated four enzyme-linked immunoassays (EIAs) and one immunofluorescence assay (IFA) using sera from 87 individuals with the prototype HHV-8 disease, Kaposi's sarcoma (KS), and 210 participants in a hemophilia study (who were presumed not to be infected with HHV-8). Assays performed reasonably well in distinguishing between infected and uninfected persons, with receiver operator curve areas between 0.86 and 0.96. Nonetheless, IFA had only 86% sensitivity and 88% specificity, and no EIA simultaneously had sensitivity and specificity above 90% for any of the optical density (OD) cutpoints used to define seropositivity. Some assays were markedly less sensitive with diluted KS sera, suggesting that they poorly identify low-titer antibodies present in asymptomatic infection. We also developed a classification tree that categorized individuals as seropositive if they had OD > 2.00 on recombinant K8.1 protein EIA or if they had both K8.1 OD between 0.51 and 2.00 and positive IFA results; this strategy had between 80% and 90% sensitivity and 95% and 100% specificity. Overall, assays performed adequately for use in most epidemiologic investigations, but wider applications will require improved tests. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Sci Applicat Int Corp, Frederick, MD USA. Univ Cagliari, Cattedra Genet Med, Cagliari, Italy. RP Engels, EA (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8005, Rockville, MD 20852 USA. FU NCI NIH HHS [N01-CO-56000] NR 27 TC 66 Z9 72 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD APR 1 PY 2000 VL 23 IS 4 BP 346 EP 354 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 313PQ UT WOS:000087008400009 PM 10836758 ER PT J AU Hauk, PJ Hamid, QA Chrousos, GP Leung, DYM AF Hauk, PJ Hamid, QA Chrousos, GP Leung, DYM TI Induction of corticosteroid insensitivity in human PBMCs by microbial superantigens SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE superantigens; dexamethasone; glucocorticoid resistance; glucocorticoid receptor beta; inflammation; human PBMCs ID GLUCOCORTICOID RECEPTOR-BETA; STEROID-RESISTANT ASTHMA; INTRAVENOUS IMMUNOGLOBULIN; T-CELLS; EXPRESSION; ACTIVATION; DISEASE; PSORIASIS; ISOFORM AB Background: Microbial superantigens have been described to contribute to the pathogenesis of chronic inflammatory diseases often complicated by insensitivity to glucocorticoid therapy. In bronchial asthma glucocorticoid insensitivity has been associated with increased expression of glucocorticoid receptor beta, an endogenous inhibitor of the classic glucocorticoid receptor beta. Objective: To study a potential mechanism by which superantigens could contribute to poor disease control, we examined their capacity to alter steroid sensitivity and expression of glucocorticoid receptor beta. Methods: The capacity of dexamethasone to inhibit stimulation of PBMCs from 7 healthy subjects with the prototypic superantigens, staphylococcal enterotoxin (SE) beta, toxic shock syndrome toxin (TSST)-1 and SEE, versus PHA, was tested. The expression of glucocorticoid receptor beta in normal PBMCs after stimulation with SEE, versus PHA, was assessed by immunocytochemistry. Results: Dexamethasone 10(-6) mol/L caused a 99% inhibition of PNA-induced PBMC proliferation but only a 19% inhibition of the SEE-induced, 26% inhibition of the TSST-1, and 29% inhibition of the SEE-induced PBMC proliferation (P < .01 for all superantigens versus PHA) demonstrating that superantigens can induce steroid insensitivity. Stimulation of normal PBMCs with SEE induced a significant increase of glucocorticoid receptor (beta compared with PHA and unstimulated cells (P < .01). Conclusion: We have demonstrated the capacity of microbial superantigens to induce glucocorticoid insensitivity, which should be considered in the diagnosis and treatment of patients with superantigen-triggered diseases. These data suggest that superantigens may contribute to glucocorticoid insensitivity through induction of glucocorticoid receptor beta. C1 Natl Jewish Med & Res Ctr, Dept Pediat, Denver, CO 80206 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. McGill Univ, Dept Pathol, Montreal, PQ, Canada. NICHHD, NIH, Dev Endocrinol Branch, Bethesda, MD 20892 USA. McGill Univ, Meakins Christie Labs, Montreal, PQ, Canada. RP Leung, DYM (reprint author), Natl Jewish Med & Res Ctr, Dept Pediat, Room K926,1400 Jackson St, Denver, CO 80206 USA. FU NHLBI NIH HHS [HL36577, HL37260]; NIAMS NIH HHS [AR41256] NR 26 TC 138 Z9 146 U1 2 U2 6 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 2000 VL 105 IS 4 BP 782 EP 787 DI 10.1067/mai.2000.105807 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 306PB UT WOS:000086604100018 PM 10756230 ER PT J AU Bromley, CM Snowder, GD Van Vleck, LD AF Bromley, CM Snowder, GD Van Vleck, LD TI Genetic parameters among weight, prolificacy, and wool traits of Columbia, Polypay, Rambouillet, and Targhee sheep SO JOURNAL OF ANIMAL SCIENCE LA English DT Article DE genetic correlation; growth; heritability; reproduction ID VARIANCE-COMPONENTS; GROWTH TRAITS; LAMB WEIGHTS; BEEF-CATTLE; SELECTION; REPRODUCTION; PERFORMANCE; EFFICIENCY; BREEDS; EWES AB Genetic parameters for Columbia, Polypay, Rambouillet, and Targhee sheep were estimated using REML with animal models for prolificacy, weight, and wool traits. All bivariate analyses included a covariance between additive genetic effects for the two traits plus appropriate additional covariances. Number of observations by breed ranged from 5,140 to 7,095 for prolificacy traits, from 7,750 to 9,530 for weight traits, and from 4,603 to 34,746 for wool traits. Heritability estimates ranged from .03 to .11 for prolificacy traits (litter size at birth and litter size at weaning), from .09 to .26 for weight traits (birth weight and average daily gain), and from .25 to .53 for wool traits (fleece weight, fleece grade and staple length). Estimates of direct genetic correlations among prolificacy and among weight traits were positive and ranged from .58 to 1.00 and .18 to 1.00, respectively. Estimates of direct genetic correlation between fleece weight and staple length were positive (.50 to .70) but were negative between fleece weight and fleece grade (-.60 to -.34) and between staple length and fleece grade (-.72 and -.40). Prolificacy and wool traits were essentially uncorrelated. Weight and prolificacy traits were slightly positively correlated. Weight traits had a moderate positive direct genetic correlation with fleece weight and staple length, but were uncorrelated with fleece grade. These estimates of genetic parameters between prolificacy, weight, and wool traits can be used to construct multiple-trait selection indexes for dual-purpose sheep. C1 Univ Nebraska, Dept Anim Sci, Lincoln, NE 68583 USA. ARS, USDA, US Sheep Expt Stn, Dubois, ID 83423 USA. Roman L Hruska US Meat Anim Res Ctr, Lincoln, NE 68583 USA. RP Bromley, CM (reprint author), NCI, Genet Epidemiol Branch, 6120 Execut Blvd, Bethesda, MD 20892 USA. NR 37 TC 63 Z9 67 U1 0 U2 4 PU AMER SOC ANIMAL SCIENCE PI SAVOY PA 1111 NORTH DUNLAP AVE, SAVOY, IL 61874 USA SN 0021-8812 J9 J ANIM SCI JI J. Anim. Sci. PD APR PY 2000 VL 78 IS 4 BP 846 EP 858 PG 13 WC Agriculture, Dairy & Animal Science SC Agriculture GA 334ZX UT WOS:000088217900008 PM 10784173 ER PT J AU Kalnin, K Stegalkina, S Yarmolinsky, M AF Kalnin, K Stegalkina, S Yarmolinsky, M TI pTAR-encoded proteins in plasmid partitioning SO JOURNAL OF BACTERIOLOGY LA English DT Article ID P1 PLASMID; F-PLASMID; NUCLEOTIDE-SEQUENCE; BACTERIAL PLASMIDS; BACILLUS-SUBTILIS; STABILITY OPERON; DNA-REPLICATION; ATPASE ACTIVITY; CHROMOSOME; REGION AB Partition cassettes, essential for the segregational stability of low-copy-number bacterial plasmids, typically encode two autoregulated proteins and an adjacent cis-acting centromere analog to which one or perhaps both proteins bind. The diminutive partition region of pTAR of Agrobacterium spp, was reported to be exceptional, encoding only a single protein, ParA (D, R. Gallie and C, I. Kado, J, Mol. Biol, 193:465-478, 1987), However, resequencing of the region revealed two small downstream genes, parB and orf-84, of which only parB was found to be essential for partitioning in A. tumefaciens. Purified ParA exhibited a weak ATPase activity that was modestly increased by nonspecific DNA. ParB bound in vitro to repeated sequences present in a region, parS, that possesses centromere and operator functions and within which we identified the primary transcription start site by primer extension. In certain respects the Par proteins behave normally in the foreign host Escherichia coli, In E. call, as in A. tumefaciens, ParB repressed the partition operon; ParA, inactive alone, augmented this repression. Functional similarities between the partition system of pTAR and those of other plasmids and bacteria are prominent, despite differences in size, organization, and amino acid sequence. C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Yarmolinsky, M (reprint author), NCI, Biochem Lab, NIH, 37 Convent Dr, Bethesda, MD 20892 USA. EM myarmo@helix.nih.gov NR 41 TC 34 Z9 34 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 2000 VL 182 IS 7 BP 1889 EP 1894 DI 10.1128/JB.182.7.1889-1894.2000 PG 6 WC Microbiology SC Microbiology GA 295EE UT WOS:000085953100014 PM 10714993 ER PT J AU Kajava, AV Zolov, SN Kalinin, AE Nesmeyanova, MA AF Kajava, AV Zolov, SN Kalinin, AE Nesmeyanova, MA TI The net charge of the first 18 residues of the mature sequence affects protein translocation across the cytoplasmic membrane of gram-negative bacteria SO JOURNAL OF BACTERIOLOGY LA English DT Article ID COLI ALKALINE-PHOSPHATASE; MALTOSE-BINDING PROTEIN; ESCHERICHIA-COLI; SIGNAL PEPTIDE; BETA-LACTAMASE; N-TERMINUS; INNER MEMBRANE; CLEAVAGE SITE; MUTANT FORMS; SECRETION AB This statistical study shows that in proteins of gram-negative bacteria exported by the Sec-dependent pathway, the first 14 to 18 residues of the mature sequences have the highest deviation between the observed and expected net charge distributions. Moreover, almost all sequences have either neutral or negative net charge in this region. This rule is restricted to gram-negative bacteria, since neither eukaryotic nor grampositive bacterial exported proteins have this charge bias. Subsequent experiments performed with a series of Escherichia coli alkaline phosphatase mutants confirmed that this charge bias is associated with protein translocation across the cytoplasmic membrane. Two consecutive basic residues inhibit translocation effectively when placed within the first 14 residues of the mature protein but not when placed in positions 19 and 20. The sensitivity to arginine partially reappeared again 30 residues away from the signal sequence. These data provide new insight into the mechanism of protein export in gram-negative bacteria and lead to practical recommendations for successful secretion of hybrid proteins. C1 NIH, Ctr Mol Modeling, CIT, Bethesda, MD 20892 USA. Russian Acad Sci, Skryabin Inst Biochem & Physiol Microorganisms, Lab Prot Secret Bacteria, Pushchino 142292, Moscow Region, Russia. RP Kajava, AV (reprint author), NIH, Ctr Mol Modeling, CIT, Bldg 12A Room 2011, Bethesda, MD 20892 USA. RI Zolov, Sergey/C-4017-2008; Zolov, Sergey/D-9761-2011; Kajava, Andrey/E-1107-2014 OI Kajava, Andrey/0000-0002-2342-6886 NR 54 TC 43 Z9 47 U1 0 U2 7 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 2000 VL 182 IS 8 BP 2163 EP 2169 DI 10.1128/JB.182.8.2163-2169.2000 PG 7 WC Microbiology SC Microbiology GA 299NU UT WOS:000086205400013 PM 10735858 ER PT J AU O'Grady, PI Borden, A Vandewiele, D Ozgenc, A Woodgate, R Lawrence, CW AF O'Grady, PI Borden, A Vandewiele, D Ozgenc, A Woodgate, R Lawrence, CW TI Intrinsic polymerase activities of UmuD ' C-2 and MucA ' B-2 are responsible for their different mutagenic properties during bypass of a T-T cis-syn cyclobutane dimer SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI; DNA-REPAIR; ULTRAVIOLET-LIGHT; UV-MUTAGENESIS; RECA PROTEIN; MUTATIONS; UMUC; REQUIREMENTS; SUBSTITUTION; LESION AB In wild-type Escherichia coli, translesion replication is largely dependent upon the UmuD'C-2 complex (DNA polymerase V [polV]) or its plasmid-encoded homologs, such as MucA'B-2. Interestingly, both the efficiency of translesion replication of a T-T cis-syn dimer and the spectra of mutations observed are different in Umu- and Muc-expressing strains, We have investigated whether the polIII core is responsible for these differences by measuring the frequency of dimer bypass, the error rate of bypass, and the resulting mutation spectrum in mutants carrying a deletion of dnaQ (epsilon subunit) or holE (theta subunit) or carrying the dnaQ allele mutD5, which is deficient in proofreading but is competent in the structural function of epsilon, or the dnaE antimutator allele spq-2. The chromosomal copy of the umuDC operon was deleted in each strain, and the UmuDC, UmuD'C, MucAB, or MucA'B proteins were expressed from a low-copy-number plasmid. With only few exceptions, we found that the characteristically different mutation spectra resulting from Umu- and Muc-mediated bypass are maintained in all of the strains investigated, indicating that differences in the activity or structure of the polIII core are not responsible for the observed phenotype. We also demonstrate that the MucA'B-2 complex is more efficient in promoting translesion replication than the UmuD'C-2 proteins and show that, contrary to expectation, the T-T dimer is bypassed more accurately by MucA'B-2 than by UmuD'C-2. These results are consistent with the view that in a wild-type cell, the polV-like enzymes are responsible for the spectra of mutations generated during translesion replication and that polIII may simply be required to fix the misincorporations as mutations by completing chromosomal replication. Our observations also show that the mutagenic properties of a lesion can depend strongly on the particular enzyme employed in bypass. C1 Univ Rochester, Med Ctr, Sch Med & Dent, Dept Biochem & Biophys, Rochester, NY 14642 USA. NICHHD, Sect DNA Replicat Repair & Mutagenesis, Bethesda, MD 20892 USA. RP Lawrence, CW (reprint author), Univ Rochester, Med Ctr, Sch Med & Dent, Dept Biochem & Biophys, Rochester, NY 14642 USA. FU NIGMS NIH HHS [GM31858] NR 40 TC 15 Z9 15 U1 0 U2 2 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 2000 VL 182 IS 8 BP 2285 EP 2291 DI 10.1128/JB.182.8.2285-2291.2000 PG 7 WC Microbiology SC Microbiology GA 299NU UT WOS:000086205400028 PM 10735873 ER PT J AU Balbach, JJ Yang, J Weliky, DP Steinbach, PJ Tugarinov, V Anglister, J Tycko, R AF Balbach, JJ Yang, J Weliky, DP Steinbach, PJ Tugarinov, V Anglister, J Tycko, R TI Probing hydrogen bonds in the antibody-bound HIV-1 gp120 V3 loop by solid state NMR REDOR measurements SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE HIV-1; peptide; antibody complex; solid state NMR; V3 loop ID PRINCIPAL NEUTRALIZING DETERMINANT; IMMUNODEFICIENCY-VIRUS TYPE-1; DOUBLE-RESONANCE NMR; ENVELOPE GLYCOPROTEIN GP120; ROTATIONAL-ECHO; CONFORMATIONAL PREFERENCES; EXCHANGE SPECTROSCOPY; IMMUNOGENIC PEPTIDE; DISTANCE GEOMETRY; CRYSTAL-STRUCTURE AB We describe solid state NMR measurements on frozen solutions of the complex of the 24-residue HIV-1 gp120 V3 loop peptide RP135 with the Fab fragment of the anti-gp120 antibody 0.5 beta, using rotational echo double resonance (REDOR). In order to probe possible hydrogen bonding between arginine side chains and glycine backbone carbonyls in the region of the conserved Gly-Pro-Gly-Arg (GPGR) motif of the V3 loop, RP135 samples were prepared with N-15 labels at the eta nitrogen positions of arginine side chains and C-13 labels at glycine carbonyl positions and C-13-detected C-13-N-15 REDOR measurements were performed on peptide/antibody complexes of these labeled samples. Such hydrogen bonding was previously observed in a crystal structure of the V3 loop peptide/antibody complex RP142/59.1 [Ghiara et al. (1994) Science, 264, 82-85], but is shown by the REDOR measurements to be absent in the RP135/0.5 beta complex. These results confirm the antibody-dependent conformational differences in the GPGR motif suggested by previously reported solid state NMR measurements of phi and Psi backbone dihedral angles in the RP135/0.5 beta complex. In addition, we describe REDOR measurements on the helical synthetic peptide MB(i+4)EK in frozen solution that establish our ability to detect C-13-N-15 dipole-dipole couplings in the distance range appropriate to these hydrogen bonding studies. We also report the results of molecular modeling calculations on the central portion RP135, using a combination of the solid state NMR restraints of Weliky et al. [Nat. Struct. Biol., 6, 141-145, 1999] and the liquid state NMR restraints of Tugarinov et al. (Nat. Struct. Biol., 6, 331-335, 1999]. The dynamics calculations demonstrate the mutual compatibility of the two sets of experimental structural restraints and reduce ambiguities in the solid state NMR restraints that result from symmetry and signal-to-noise considerations. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Michigan State Univ, Dept Chem, E Lansing, MI 48824 USA. NIH, Ctr Mol Modeling, Ctr Informat Technol, Bethesda, MD 20892 USA. Weizmann Inst Sci, Dept Biol Struct, IL-76100 Rehovot, Israel. RP Tycko, R (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5,Room 112, Bethesda, MD 20892 USA. FU NIGMS NIH HHS [GM53329] NR 66 TC 27 Z9 28 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD APR PY 2000 VL 16 IS 4 BP 313 EP 327 DI 10.1023/A:1008343623240 PG 15 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 306XA UT WOS:000086622900004 PM 10826883 ER PT J AU Barrientos, LG Dolan, C Gronenborn, AM AF Barrientos, LG Dolan, C Gronenborn, AM TI Characterization of surfactant liquid crystal phases suitable for molecular alignment and measurement of dipolar couplings SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE lamellar phase; liquid crystal; molecular alignment; residual dipolar coupling; surfactant ID CETYLPYRIDINIUM BROMIDE MICELLES; MAGNETIC-FIELD DEPENDENCE; HIGH-RESOLUTION NMR; TERNARY-SYSTEMS; HUMAN UBIQUITIN; ALCOHOL BRINE; MACROMOLECULES; PROTEINS; DISTANCES; BEHAVIOR AB Media employed for imparting partial alignment onto solute molecules have recently attracted considerable attention, since they permit the measurement of NMR parameters for solute biomolecules commonly associated with solid state NMR. Here we characterize a medium which is based on a quasi-ternary surfactant system comprising cetylpyridinium bromide/hexanol/sodium bromide. We demonstrate that dilute solutions of this system can exist in liquid crystalline phases which orient in the magnetic field and allow the measurement of residual dipolar couplings under a variety of conditions. The present system is extremely versatile and robust, tolerating different buffer conditions, temperature ranges and concentrations. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Barrientos, LG (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. NR 38 TC 72 Z9 73 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD APR PY 2000 VL 16 IS 4 BP 329 EP 337 DI 10.1023/A:1008356618658 PG 9 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 306XA UT WOS:000086622900005 PM 10826884 ER PT J AU Horita, DA Farnsworth, DW Byrd, RA AF Horita, DA Farnsworth, DW Byrd, RA TI A simple and inexpensive preparation of perdeuterated sorbitol for use as a biomacromolecule stabilization agent in NMR studies SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE deuteration; excipient; protein stabilization; sorbitol ID STABILITY; PROTEIN AB Sorbitol is an excellent protein-stabilization agent, but it is typically used at high concentrations where the H-1 signals can interfere with NMR data collection and analysis. Deuteration of sorbitol can ameliorate this problem; however, perdeuterated sorbitol is not commercially available. We describe a simple and inexpensive method for preparation of perdeuterated sorbitol from perdeuterated glucose. The method is described explicitly and examples are given where the use of perdeuterated sorbitol has allowed the extraction of information, from NMR spectra, that is otherwise unobtainable. C1 NCI, Frederick Canc Res & Dev Ctr, Macromol NMR Sect, Struct Biophys Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Mol Aspects Drug Design Sect, Struct Biophys Lab, Frederick, MD 21702 USA. RP Byrd, RA (reprint author), NCI, Frederick Canc Res & Dev Ctr, Macromol NMR Sect, Struct Biophys Lab, POB B,Bldg 538, Frederick, MD 21702 USA. RI Byrd, R. Andrew/F-8042-2015; OI Byrd, R. Andrew/0000-0003-3625-4232; Horita, David/0000-0002-9563-107X NR 12 TC 2 Z9 2 U1 1 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD APR PY 2000 VL 16 IS 4 BP 339 EP 342 DI 10.1023/A:1008339715488 PG 4 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 306XA UT WOS:000086622900006 PM 10826885 ER PT J AU Tolstorukov, MY Maleev, VY AF Tolstorukov, MY Maleev, VY TI Conformational transitions of DNA induced by changing water content of the sample: A theoretical study SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Article ID HYDRATION; DYNAMICS AB A semi-phenomenological model with spatially distributed parameters is suggested to describe the processes of conformational transitions induced with change of water content of wet DNA samples. It allows describing conformational dynamics of DNA molecules with heterogeneous primary structures. It has been shown that the process of cooperative conformational transition can be simulated as propagating front of a new conformation. The evolution of a conformational perturbation of DNA molecule has been described. It can collapse for finite time or occupy the whole molecule depending on the water content of the sample. C1 Kharkov State Univ, Chair Mol & Appl Biophys, UA-310077 Kharkov, Ukraine. RP Tolstorukov, MY (reprint author), NCI, Lab Expt & Computat Biol, NIH, Bldg 12B,Room B116,MSC 5677,12 South Drive, Bethesda, MD 20892 USA. NR 17 TC 2 Z9 2 U1 0 U2 2 PU ADENINE PRESS INC PI GUILDERLAND PA PO BOX 355/340, GUILDERLAND, NY 12084 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD APR PY 2000 VL 17 IS 5 BP 913 EP 920 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 306HA UT WOS:000086590200014 PM 10798535 ER PT J AU Hannan, MT Felson, DT Dawson-Hughes, B Tucker, KL Cupples, LA Wilson, PWF Kiel, DP AF Hannan, MT Felson, DT Dawson-Hughes, B Tucker, KL Cupples, LA Wilson, PWF Kiel, DP TI Risk factors for longitudinal bone loss in elderly men and women: The Framingham Osteoporosis Study SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE bone density; elderly; osteoporosis; longitudinal study; risk factors ID HEALTHY POSTMENOPAUSAL WOMEN; DUAL-PHOTON ABSORPTIOMETRY; X-RAY ABSORPTIOMETRY; MINERAL DENSITY; PHYSICAL-ACTIVITY; VITAMIN-D; FRACTURE PREDICTION; POST-MENOPAUSAL; PROXIMAL FEMUR; HIP-FRACTURES AB Few studies have evaluated risk factors for bone loss in elderly 7 women and men. Thus, we examined risk factors for 4-year longitudinal change in bone mineral density (BMD) at the hip, radius, and spine in elders. Eight hundred elderly women and men from the population-based Framingham Osteoporosis Study had BMD assessed in 1988-1989 and again in 1992-1993. BMD was measured at femoral neck, trochanter, Ward's area, radial shaft, ultradistal radius, and lumbar spine using Lunar densitometers. We examined the relation of the following factors at baseline to percent BMD loss: age, weight, change in weight, height, smoking, caffeine, alcohol use, physical activity, serum 25-OH vitamin D, calcium intake, and current estrogen replacement in women. Multivariate regression analyses were conducted with simultaneous adjustment for all variables. Mean age at baseline was 74 years +/- 4.5 years (range, 67-90 years). Average 4-year BMD loss for women (range, 3.4-4.8%) was greater than the loss for men (range, 0.2-3.6%) at all sites; however, BMD fell with age in both elderly women and elderly men. For women, lower baseline weight, weight loss in interim, and greater alcohol use were associated with BMD loss. Women who gained weight during the interim gained BMD or had little change in BMD. For women, current estrogen users had less bone loss than nonusers; at: the femoral neck, nonusers lost up to 2.7% more BMD. For men, lower baseline weight and weight loss also were associated with BMD loss. Men who smoked cigarettes at baseline lost more BMD at the trochanter site. Surprisingly, bone loss was not affected by caffeine, physical activity, serum 25-OH vitamin D, or calcium intake. Risk factors consistently associated with bone loss in elders include female sex, thinness, and weight loss, while weight gain appears to protect against bone loss for both men and women. This population-based study suggests that current estrogen use may help to maintain bone in women, whereas current smoking was associated with bone loss in men. Even in the elderly years, potentially modifiable risk factors, such as weight, estrogen use, and cigarette smoking are important components of bone health. C1 Hebrew Rehabil Ctr Aged, Res & Training Inst, Boston, MA 02131 USA. Harvard Univ, Sch Med, Div Aging, Boston, MA 02115 USA. Boston Univ, Ctr Arthritis, Boston, MA 02215 USA. Tufts Univ, JeanMayer Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. Framingham Heart Study, NHLBI, Framingham, MA USA. RP Hannan, MT (reprint author), Hebrew Rehabil Ctr Aged, Res & Training Inst, 1200 Ctr St, Boston, MA 02131 USA. RI Tucker, Katherine/A-4545-2010; OI Hannan, Marian/0000-0002-9586-6928; Kiel, Douglas/0000-0001-8474-0310; Tucker, Katherine/0000-0001-7640-662X FU NIAMS NIH HHS [R01-AR/AG41398, R01-AR20613]; PHS HHS [N01-38038] NR 66 TC 385 Z9 413 U1 5 U2 40 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD APR PY 2000 VL 15 IS 4 BP 710 EP 720 DI 10.1359/jbmr.2000.15.4.710 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 296VM UT WOS:000086047500012 PM 10780863 ER PT J AU Tomatis, L Huff, J AF Tomatis, L Huff, J TI Evidence of carcinogenicity of DDT in nonhuman primates SO JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY LA English DT Letter C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Tomatis, L (reprint author), Natl Inst Environm Hlth Sci, POB 12233, Res Triangle Pk, NC 27709 USA. NR 2 TC 6 Z9 6 U1 7 U2 7 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0171-5216 J9 J CANCER RES CLIN JI J. Cancer Res. Clin. Oncol. PD APR PY 2000 VL 126 IS 4 BP 246 EP 246 DI 10.1007/s004320050040 PG 1 WC Oncology SC Oncology GA 304FX UT WOS:000086473900010 PM 10782899 ER PT J AU Sazer, S Dasso, M AF Sazer, S Dasso, M TI The Ran decathlon: multiple roles of Ran SO JOURNAL OF CELL SCIENCE LA English DT Article DE RanGTPase; nucleus; mitosis; spindle; septum ID CELL-CYCLE PROGRESSION; XENOPUS EGG EXTRACTS; GTP-BOUND RAN; DNA-REPLICATION; SCHIZOSACCHAROMYCES-POMBE; NUCLEAR-ENVELOPE; BINDING PROTEIN; FISSION YEAST; RCC1-RELATED PROTEIN; SELF-ORGANIZATION AB The Ran GTPase system affects many cellular processes, including the regulation of cell cycle progression, nuclear envelope structure and function, and nucleocytoplasmic transport. The biochemical basis for the involvement of Ran in nuclear import and export has been well documented, but the direct targets of Ran in other cellular processes have not yet been identified. There is, however, mounting evidence that Ran directly affects at least some of these other cellular processes by mechanisms independent of its role in transport. In this Commentary we discuss evidence linking Ran to different aspects of cell function, and how these multiple facets of Ran's activity may relate to each other. C1 Baylor Coll Med, Verna & Marrs Mclean Dept Biochem & Mol Biol, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RP Sazer, S (reprint author), Baylor Coll Med, Verna & Marrs Mclean Dept Biochem & Mol Biol, 1 Baylor Plaza, Houston, TX 77030 USA. OI Dasso, Mary/0000-0002-5410-1371 NR 56 TC 106 Z9 109 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 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD APR PY 2000 VL 113 IS 7 BP 1111 EP 1118 PG 8 WC Cell Biology SC Cell Biology GA 310XT UT WOS:000086855400002 PM 10704362 ER PT J AU Shen, DW Goldenberg, S Pastan, I Gottesman, MM AF Shen, DW Goldenberg, S Pastan, I Gottesman, MM TI Decreased accumulation of [C-14]carboplatin in human cisplatin-resistant cells results from reduced energy-dependent uptake SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID HUMAN OVARIAN-CARCINOMA; TRANSFERRIN-BOUND IRON; ACTIVE EFFLUX SYSTEM; LUNG-CANCER CELLS; HUMAN KB CELLS; MULTIDRUG-RESISTANCE; CROSS-RESISTANCE; IN-VIVO; CELLULAR ACCUMULATION; ACQUIRED-RESISTANCE AB We have isolated cisplatin-resistant human liver carcinoma (7404-CP20) cells with reduced accumulation of cisplatin and other drugs (methotrexate, arsenate, and arsenite) to which these cells are cross-resistant. To determine whether the reduction of drug accumulation in cisplatin-resistant cells results from impaired uptake or from active efflux, [C-14]carboplatin was used for kinetic analysis of drug uptake and efflux. We demonstrate here that the uptake of [C-14]carboplatin in 7404 parental cells is time, temperature, and energy dependent, and that the rate of uptake is reduced in 7404-CP20 cells. Efflux of [C-14]carboplatin in cisplatin-resistant cells was comparable to efflux in the parental cisplatin-sensitive cells. There was little effect of temperature (between 37 degrees C and 4 degrees C) on efflux in cisplatin-resistant cells. Immunoblotting with specific antibodies directed to MRP1 and MRP2 (cMOAT) also showed that expression of these two ABC transporter genes was considerably reduced in 7404-CP20 cells and another cisplatin-resistant cell line KB-CP20, in contradistinction to previous studies suggesting that MRP might be responsible for cisplatin efflux. To rule out a generalized defect in uptake of small molecules, Fluorescence-activated cell sorter (FACS) analysis of rhodamine 123 uptake showed that there was no difference between cisplatin-sensitive and -resistant cells. The presence of a pleiotropic defect in uptake of [C-14]carboplatin, [H-3]methotrexate, [As-73]arsenate, and [As-73]arsenite in cisplatin-resistant cells, in association with reduced expression of related cell surface proteins as demonstrated in our previous work, suggests a novel mechanism for acquisition of resistance to cisplatin associated with reduced activity of many different specific uptake systems. Published 2000 Wiley-Liss. Inc. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 1A09,37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. NR 58 TC 68 Z9 71 U1 1 U2 9 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 2000 VL 183 IS 1 BP 108 EP 116 DI 10.1002/(SICI)1097-4652(200004)183:1<108::AID-JCP13>3.0.CO;2-4 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 289FF UT WOS:000085609300013 PM 10699972 ER PT J AU Blum, MS Fales, HM Morse, RA Underwood, BA AF Blum, MS Fales, HM Morse, RA Underwood, BA TI Chemical characters of two related species of giant honeybees (Apis dorsata and A-laboriosa): Possible ecological significance SO JOURNAL OF CHEMICAL ECOLOGY LA English DT Article DE Apis laboriosa; Apis dorsata; sting-shaft volatiles; cephalic compounds; gamma-octanoic lactone; A-dorsata esters; A-laboriosa specific status ID DRONE AB The Himalyan honeybee, Apis laboriosa, is sometimes considered to be a form of the rock honeybee, A. dorsata, rather than a separate species. Analyses of potential exocrine compounds produced by both forms revealed that the cephalic and abdominal natural products of these two honeybees shared no common denominators. The sting shaft of workers of A. dorsata is the source of a large series of esters dominated by 1-acetoxy-2-decene. Other major constituents include isopentyl acetate, accompanied by isopentyl propionate, farnesyl acetate, and several other esters. On the other hand, nothing but presumed structural lipids (e.g., ethyl palmitoleate) were identified from sting shafts of workers of A. laboriosa. By contrast, cephalic (including mandibular glands) extracts from workers of A, laboriosa contained gamma-octanoic lactone, whereas comparable extracts of A. dorsata workers contained only structural lipids. The major qualitative differences in the chemical characters between A. laboriosa and A. dorsata are consistent with the designation of these two forms as distinct species. C1 Univ Georgia, Dept Entomol, Athens, GA 30602 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Cornell Univ, Dept Entomol, Ithaca, NY 14853 USA. RP Blum, MS (reprint author), Univ Georgia, Dept Entomol, Athens, GA 30602 USA. NR 14 TC 12 Z9 14 U1 0 U2 4 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0098-0331 J9 J CHEM ECOL JI J. Chem. Ecol. PD APR PY 2000 VL 26 IS 4 BP 801 EP 807 DI 10.1023/A:1005476405192 PG 7 WC Biochemistry & Molecular Biology; Ecology SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology GA 306ZC UT WOS:000086627700001 ER PT J AU Kanik, KS Chrousos, GP Schumacher, HR Crane, ML Yarboro, CH Wilder, RL AF Kanik, KS Chrousos, GP Schumacher, HR Crane, ML Yarboro, CH Wilder, RL TI Adrenocorticotropin, glucocorticoid, and androgen secretion in patients with new onset synovitis/rheumatoid arthritis: Relations with indices of inflammation SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PITUITARY-ADRENAL AXIS; RHEUMATOID-ARTHRITIS; DEHYDROEPIANDROSTERONE DHEA; MICROVASCULAR SYSTEMS; SEX-HORMONES; INTERLEUKIN-6; IMMUNE; PREGNANCY; IL-6; MECHANISMS AB To determine whether alterations in adrenocortical function occur early in the development of inflammatory joint disease, we examined patients with new onset synovitis (<1 yr) prior to treatment with corticosteroids or other disease-modifying antirheumatic drugs. Thirty-two patients with new onset synovitis, including 15 fitting criteria for rheumatoid arthritis (RA), taking no medications, were referred for study by local rheumatologists; 32 age- and sex-matched healthy individuals were recruited as controls. Patients and controls had blood drawn under identical conditions between 0900 and 1100 h. Plasma ACTH, cortisol, dehydroepiandrosterone (DHEA), DHEA sulfate, free and total testosterone, erythrocyte sedimentation rate, C-reactive protein, and rheumatoid factor were measured. Compared with controls, patients had higher inflammatory indices (erythrocyte sedimentation rate, C-reactive protein) and lower basal morning levels of free testosterone (lower in males age greater than or equal to 45 yr), but similar levels of ACTH, cortisol, DHEA, DHEA sulfate, and total testosterone. In addition, the positive correlations between ACTH-cortisol, ACTH-DHEA, and cortisol-DHEA, observed in the normal controls, were weakened or abolished in the patients (both total and RA subset). No positive relations between inflammatory indices and ACTH or cortisol were noted, yet an inverse correlation between these indices and DHEA and testosterone was observed. Moreover, a steeper age-associated decline in DHEA was observed in our cross-sectional sample of patients with new onset synovitis. We conclude that patients with synovitis (including those fitting criteria for RA) have adrenocortical hormone alterations within a year of disease onset. Paradoxically, these patients have no positive relation between indices of inflammation and ACTH or cortisol, but rather serum androgen levels are inversely correlated with these indices. In addition, the relations between ACTH, the classic stimulus of cortisol and adrenal androgens, and these hormones are weakened or abolished, whereas the negative relation between age and zona reticularis function is steeper than that of controls. C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NIAMSD, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Kanik, KS (reprint author), Univ S Florida, Coll Med, Div Rheumatol, Tampa, FL 33612 USA. EM kkanik@com1.med.usf.edu NR 41 TC 64 Z9 67 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2000 VL 85 IS 4 BP 1461 EP 1466 DI 10.1210/jc.85.4.1461 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 337WY UT WOS:000088387200018 PM 10770182 ER PT J AU Mauras, N O'Brien, KO Welch, S Rini, A Helgeson, K Vieira, NE Yergey, AL AF Mauras, N O'Brien, KO Welch, S Rini, A Helgeson, K Vieira, NE Yergey, AL TI Insulin-like growth factor I and growth hormone (GH) treatment in GH-deficient humans: Differential effects on protein, glucose, lipid, and calcium metabolism SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID WHOLE-BODY PROTEIN; BONE TURNOVER; LEUCINE METABOLISM; BINDING-PROTEINS; DOSE-RESPONSE; MEN; KINETICS; ADULTS; SENSITIVITY; CHILDREN AB We examined the effects of recombinant human (rh) insulin-like growth factor I(IGF-I) vs. rhGH in a variety of metabolic paths in a group of eight severely GH-deficient young adults using an array of contemporary tools. Protein, glucose, and calcium metabolism were studied using stable labeled tracer infusions of L-[1-C-13]leucine, [6,6-H-2(2)]glucose, and Ca-42 and Ca-44; substrate oxidation rates were assessed using indirect calorimetry; muscle strength was determined by isokinetic and isometric dynamometry of the anterior quadriceps, as well as growth factors, hormones, glucose, and lipid concentrations in plasma before and alter 8 weeks of rhIGF-I(60 mu g/kg, sc, twice daily), followed by 4 weeks of washout, then 8 weeks of rhGH(12.5 mu g/kg day, sc); the treatment order was randomized. In the doses administered, rhIGF-I and rhGH both increased fat-free mass and decreased the percent fat mass, with a more robust decrease in the percent fat mass after rhGH; both were associated with an increase in whole body protein synthesis rates and a decrease in protein oxidation. Neither hormone affected isokinetic or isometric measures of skeletal muscle strength. However, rhGH was more potent than rhIGF-I at increasing lipid oxidation rates and improving plasma lipid profiles. Both hormones increased hepatic glucose output, but rhGH treatment was also associated with decreased carbohydrate oxidation and increased glucose and insulin concentrations, indicating subtle insulin resistance. Neither hormone significantly affected hone calcium fluxes, supporting the concept that these hormones, by themselves, are not pivotal in bone calcium metabolism. In conclusion, rhIGF-I and rhGH share common effects on protein, muscle, and calcium metabolism, yet have divergent effects on lipid and carbohydrate metabolism in the GH-deficient state. These differences may allow for better selection of treatment modalities depending on the choice of desired effects in hypopituitarism. C1 Nemours Childrens Clin, Div Endocrinol, Jacksonville, FL 32207 USA. Nemours Res Programs, Jacksonville, FL 32207 USA. Baptist Med Ctr, Phys Therapy Dept, Jacksonville, FL 32207 USA. Johns Hopkins Sch Publ Hlth & Hyg, Baltimore, MD 21205 USA. NIH, Bethesda, MD 20892 USA. RP Mauras, N (reprint author), Nemours Childrens Clin, Div Endocrinol, 807 Nira St, Jacksonville, FL 32207 USA. EM nmauras@nemours.org FU NCRR NIH HHS [RR-00585]; NIDDK NIH HHS [R01-DK-51360] NR 51 TC 70 Z9 73 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2000 VL 85 IS 4 BP 1686 EP 1694 DI 10.1210/jc.85.4.1686 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 337WY UT WOS:000088387200053 PM 10770216 ER PT J AU Hahm, KB Im, YH Lee, C Parks, WT Bang, YJ Green, JE Kim, SJ AF Hahm, KB Im, YH Lee, C Parks, WT Bang, YJ Green, JE Kim, SJ TI Loss of TGF-beta signaling contributes to autoimmune pancreatitis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID IDIOPATHIC CHRONIC-PANCREATITIS; SJOGRENS-SYNDROME; NECROTIZING PANCREATITIS; ANTIGEN EXPRESSION; TRANSGENIC MICE; GROWTH-FACTOR; RAT; AUTOANTIBODIES; PATHOGENESIS; MECHANISM AB Recent observations suggest that immune response is involved in the development of pancreatitis. However, the exact pathogenesis underlying this immune-mediated response is still under debate. TGF-beta has been known to be an important regulating factor in maintaining immune homeostasis. To determine the role of TGF-beta in the initiation or progression of pancreatitis, TGF-beta signaling was inactivated in mouse pancreata by overexpressing a dominant-negative mutant form of TGF-beta type II receptor in the pancreas, under control of the pS2 mouse trefoil peptide promoter. Transgenic mice showed marked increases in MHC class II molecules and matrix metalloproteinase expression in pancreatic acinar cells. These mice also showed increased susceptibility to cerulein-induced pancreatitis. This pancreatitis was characterized by severe pancreatic edema, inflammatory cell infiltration, T- and B-cell hyperactivation, IgG-type autoantibodies against pancreatic acinar cells, and IgM-type autoantibodies against pancreatic ductal epithelial cells. Therefore, TGF-beta signaling seems to be essential either in maintaining the normal immune homeostasis and suppressing autoimmunity or in preserving the integrity of pancreatic acinar cells. C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. Seoul Natl Univ, Coll Med, Canc Res Ctr, Seoul 110744, South Korea. RP Kim, SJ (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Bldg 41,Room B1106, Bethesda, MD 20892 USA. RI Bang, Yung Jue/J-2759-2012 NR 41 TC 55 Z9 62 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 2000 VL 105 IS 8 BP 1057 EP 1065 DI 10.1172/JCI8337 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 305KG UT WOS:000086538400008 PM 10772650 ER PT J AU Leclercq, IA Farrell, GC Field, J Bell, DR Gonzalez, FJ Robertson, GR AF Leclercq, IA Farrell, GC Field, J Bell, DR Gonzalez, FJ Robertson, GR TI CYP2E1 and CYP4A as microsomal catalysts of lipid peroxides in murine nonalcoholic steatohepatitis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID LIVER-INJURY; CYTOCHROME-P450 2E1; HEPATIC STEATOSIS; ARACHIDONIC-ACID; OXIDATIVE STRESS; NATURAL-HISTORY; FATTY LIVER; INDUCTION; DISEASE; METABOLISM AB Nonalcoholic steatohepatitis (NASH) and alcoholic liver disease have similar pathological features. Because CYP2E1 plays a key role in alcoholic Liver disease with its ability to stimulate lipid peroxidation, we tested the proposal that CYP2E1 could also be a factor in the development of NASH. In a dietary model - mice fed a methionine- and choline-deficient (MCD) diet - liver injury was associated with both induction of CYP2E1 and a 100-fold increase in hepatic content of lipid peroxides. Microsomal NADPH-dependent lipid oxidases contributed to the formation of these lipid peroxides, and in vitro inhibition studies demonstrated that: CYP2E1 was the major catalyst. To further define the role of CYP2E1 as an initiator of oxidative stress in NASH, Cyp2e1(-/-)mice were administered the MCD diet. CYP2E1 deficiency neither prevented the development of NASH nor abrogated the increased microsomal NADPH-dependent: lipid peroxidation, indicating the operation of a non-CYP2E1 peroxidase pathway. In Cyp2e1(-/-) mice with NASH (but not in wild-type mice), CYP4A10 and CYP4A14 were upregulated. Furthermore, hepatic microsomal lipid peroxidation was substantially inhibited by anti-mouse CYP4A10 antibody in vitro. These results show that experimental NASH is strongly associated with hepatic microsomal lipid peroxidation. CYP2E1, the main enzyme associated with that process in wildtype mice, is not unique among P450 proteins in catalyzing peroxidation of endogenous Lipids. We have now identified CYP4A enzymes as alternative initiators of oxidative stress in the liver. C1 Univ Sydney, Westmead Hosp, Dept Med, Storr Liver Unit, Westmead, NSW 2145, Australia. Univ Sydney, Westmead Hosp, Westmead Millennium Inst, Westmead, NSW 2145, Australia. Univ Nottingham, Sch Biol, Nottingham NG7 2DR, England. NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Robertson, GR (reprint author), Univ Sydney, Westmead Hosp, Dept Med, Storr Liver Unit, Westmead, NSW 2145, Australia. NR 48 TC 465 Z9 486 U1 1 U2 23 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 2000 VL 105 IS 8 BP 1067 EP 1075 DI 10.1172/JCI8814 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 305KG UT WOS:000086538400010 PM 10772651 ER PT J AU Pelletier, R Peter, J Antin, C Gonzalez, C Wood, L Walsh, TJ AF Pelletier, R Peter, J Antin, C Gonzalez, C Wood, L Walsh, TJ TI Emergence of resistance of Candida albicans to clotrimazole in human immunodeficiency virus-infected children: In vitro and clinical correlations SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID ORAL CANDIDIASIS; IN-VITRO; AMPHOTERICIN-B; FLUCONAZOLE; SUSCEPTIBILITY; INVITRO; AGENTS; YEASTS AB Oropharyngeal candidiasis (OPC) is a common opportunistic infection in human immunodeficiency virus (HIV)-infected patients and other immunocompromised hosts. Clotrimazole troches are widely used in the treatment of mucosal candidiasis, However, little is known about the potential contribution of clotrimazole resistance to the development of refractory mucosal candidiasis, We therefore investigated the potential emergence of resistance to clotrimazole in a prospectively monitored HIV-infected pediatric population receiving this azole. Adapting the National Committee for Clinical Laboratory Standards M27-A reference method for broth antifungal susceptibility testing of yeasts to clotrimazole, we compared MICs in macrodilution and microdilution assays, We further analyzed the correlation between these in vitro findings and the clinical response to antifungal therapy. One isolate from each of 87 HIV-infected children was studied by the macrodilution and microdilution methods. Two inoculum sizes were tested by the macrodilution method (10(3) and 10(4) CFU/ml) in order to assess the effect of inoculum size on clotrimazole MICs, The same isolates also were tested using a noncolorimetric microdilution method. Clotrimazole concentrations ranged from 0.03 to 16 mu g/ml. Readings were performed after incubation for 24 and 48 h at 35 degrees C, For 62 (71.2%) of 87 clinical isolates, the MICs were low (less than or equal to 0.06 mu g/ml). The MIC for 90% of the strains tested was 0.5 mu g/ml, and the highest MIC was 8 mu g/ml. There was no significant difference between MICs at the two inoculum sizes. There was 89% agreement (CI tube) between the microdilution method at 24 h and the macrodilution method at 48 h. If the MIC of clotrimazole for an isolate of C. albicans was greater than or equal to 0.5 mu g/ml, there was a significant risk (P < 0.001) of cross-resistance to other azoles: fluconazole, greater than or equal to 64 mu g/ml (relative risk [RR] = 8.9); itraconazole, greater than or equal to 1 mu g/ml (RR = 10), Resistance to clotrimazole was highly associated with clinically overt failure of antifungal azole therapy. Six (40%) of 15 patients for whom the clotrimazole MIC was greater than or equal to 0.5 (mu g/ml required amphotericin B for refractory mucosal candidiasis versus 4 (5.5%) of 72 for whom the MIC was <0.5 mu g/ml (P = 0.001; 95% confidence interval = 2.3 to 22; RR = 7.2). These findings suggest that an interpretive breakpoint of 0.5 mu g/ml may be useful in defining clotrimazole resistance in C. albicans, The clinical laboratory's ability to determine MICs of clotrimazole may help to distinguish microbiologic resistance from the other causes of refractory OPC, possibly reducing the usage of systemic antifungal agents. We conclude that resistance to clotrimazole develops in isolates of C. albicans from HIV-infected children, that cross-resistance to other azoles may develop concomitantly, and that this resistance correlates with refractory mucosal candidiasis. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. Ctr Hosp Univ Quebec, Quebec City, PQ, Canada. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bldg 10,Rm 13N240, Bethesda, MD 20892 USA. NR 31 TC 39 Z9 43 U1 0 U2 2 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 2000 VL 38 IS 4 BP 1563 EP 1568 PG 6 WC Microbiology SC Microbiology GA 301GN UT WOS:000086302500045 PM 10747144 ER PT J AU Kreitman, RJ Wilson, WH White, JD Stetler-Stevenson, M Jaffe, ES Giardina, S Waldmann, TA Pastan, I AF Kreitman, RJ Wilson, WH White, JD Stetler-Stevenson, M Jaffe, ES Giardina, S Waldmann, TA Pastan, I TI Phase I trial of recombinant immunotoxin anti-Tac(Fv)PE38 (LMB-2) in patients with hematologic malignancies SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HAIRY-CELL LEUKEMIA; VASCULAR LEAK SYNDROME; A-CHAIN IMMUNOTOXIN; FUSION TOXIN DAB486IL-2; NON-HODGKINS-LYMPHOMAS; AERUGINOSA EXOTOXIN-A; PSEUDOMONAS-EXOTOXIN; INTERLEUKIN-2 RECEPTOR; CONTINUOUS-INFUSION; DIPHTHERIA-TOXIN AB Purpose: To evaluate the toxicity, pharmacokinetics, immunogenicity, and antitumor activity of anti-Tac(Fv)-PE38 (LMB-2), an anti-CD25 recombinant immunotoxin that contains an antibody Fv fragment fused to truncated Pseudomonas exotoxin, Patients and Methods: Patients with CB25(+) hematologic malignancies for whom standard and salvage therapies failed were treated with LMB-2 at dose levels that ranged from 2 to 63 mu g/kg administered intravenously over 30 minutes on alternate days for three doses (QOD x 3), Results: LMB-2 was administered to 35 patients for a total of 59 cycles. Dose-limiting toxicity at the 63 mu g/kg level was reversible and included transaminase elevations in one patient and diarrhea and cardiomyopathy in another. LMB-2 was well tolerated in nine patients at the maximum-tolerated dose (40 mu g/kg QOD x 3); toxicity was transient and most commonly included transaminase elevations (eight patients) and fever (seven patients). Only six of 35 patients developed significant neutralizing antibodies after the first cycle, The median half-life was 4 hours. One hairy cell leukemia (HCL) patient achieved a complete remission, which is ongoing at 20 months. Seven partial responses were observed in cutaneous T-cell lymphoma (one patient), HCL (three patients), chronic lymphocytic leukemia (one patient), Hodgkin's disease (one patient), and adult T-cell leukemia (one patient), Responding patients had 2 to 5 log reductions of circulating malignant cells, improvement in skin lesions, and regression of lymphomatous masses and splenomegaly. All four patients with HCL responded to treatment. Conclusion: LMB-2 has clinical activity in CD25(+) hematologic malignancies and is relatively nonimmunogenic. It is the first recombinant immunotoxin to induce major responses in cancer. MB-2 and similar agents that target other cancer antigens merit further clinical development, J Clin Oncol 18:1622-1636. (C) 2000 by American Society of Clinical Oncology. C1 NCI, Mol Biol Lab,Lab Clin Pathol, Metab Branch,Med Branch, NIH, Bethesda, MD 20892 USA. NCI, Biopharmaceut Dev Program, Sci Applicat Int Cor Frederick, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab,Lab Clin Pathol, Metab Branch,Med Branch, NIH, Bldg 37-4E16,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 75 TC 262 Z9 273 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR PY 2000 VL 18 IS 8 BP 1622 EP 1636 PG 15 WC Oncology SC Oncology GA 307LV UT WOS:000086655500004 PM 10764422 ER PT J AU Grothe, DR Calis, KA Jacobsen, L Kumra, S DeVane, CL Rapoport, JL Bergstrom, RF Kurtz, DL AF Grothe, DR Calis, KA Jacobsen, L Kumra, S DeVane, CL Rapoport, JL Bergstrom, RF Kurtz, DL TI Olanzapine pharmacokinetics in pediatric and adolescent inpatients with childhood-onset schizophrenia SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID ANTIPSYCHOTIC AGENT OLANZAPINE; ELECTROCHEMICAL DETECTION; HALOPERIDOL; TRIAL; METABOLITES; DISPOSITION; CHILDREN AB Well-designed studies investigating how pediatric or adolescent patients with mental disorders respond to and metabolize the newer antipsychotic drugs are practically nonexistent. Without such data, clinicians have difficulty designing appropriate dosage regimens for patients in these age groups. The results from a study of olanzapine pharmacokinetics in children and adolescents are described. Eight inpatients (ages 10-18 years) with treatment-resistant childhood-onset schizophrenia received olanzapine (2.5-20 mg/day) over 8 weeks. Blood samples, collected during dose titration and at a steady state provided pharmacokinetic data. The final evaluation (week 8) included extensive sampling for 36 hours after a 20-mg dose. Olanzapine concentrations in these eight pediatric patients were of the same magnitude as those for nonsmoking adult patients with schizophrenia but may be as much as twice the typical olanzapine concentrations in patients with Schizophrenia who smoke. Olanzapine pharmacokinetic evaluation gave an apparent mean oral clearance of 9.6 +/- 2.4 L/hr and a mean elimination half-life of 37.2 +/- 5.1 hours in these young patients. The determination of the initial olanzapine dose for adolescent patients should take into consideration factors such as the patient's size. In general, however, the usual dose recommendation of 5 to 10 mg once daily with a target: dose of 10 mg/day is Likely a good clinical guideline for most adolescent patients on the basis of our pharmacokinetics results. C1 NIMH, Ctr Clin, Dept Pharm, NIH, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. Eli Lilly & Co, Lilly Lab Clin Res, Indianapolis, IN 46285 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. RP Calis, KA (reprint author), NIMH, Ctr Clin, Dept Pharm, NIH, Bethesda, MD 20892 USA. NR 26 TC 43 Z9 44 U1 0 U2 3 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 2000 VL 20 IS 2 BP 220 EP 225 DI 10.1097/00004714-200004000-00015 PG 6 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 301GR UT WOS:000086302800015 PM 10770461 ER PT J AU DelCarmen-Wiggins, R Huffman, LC Pedersen, FA Bryan, YE AF DelCarmen-Wiggins, R Huffman, LC Pedersen, FA Bryan, YE TI Mothers' and fathers' perceptions of three year olds' attachment behavior SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE attachment; mother-child; father-child; predictors ID CHILD RELATIONSHIPS; INFANT TEMPERAMENT; SECURITY; QUALITY; FAMILY; REPRESENTATION; METAANALYSIS; ASSOCIATIONS; ORGANIZATION; ANTECEDENTS AB This investigation reports on the antecedents and cross-sectional predictors of young children's attachment security based on Q-sort methodology, with particular consideration of the convergence of parental reports. Mothers' and fathers' ratings of child temperament and child behavior problems, as well as each parent's construction of the marital relationship and his/her affective state, were examined in relation to Q-sort assessments of mother-child and father-child attachment security. Generally, a moderate degree of convergence between maternal and paternal perceptions of attachment security was found; this association was stronger than the correlations reported based on studies using the Strange Situation procedure at 12 to 18 months of age, Antecedent relationships between ratings of parental affective symptoms, as well as ratings of marital quality and security of attachment, were stronger for fathers than for mothers. These findings may suggest closer links for fathers than for mothers between parental nurturing responses and psychological state, or they may reveal a stronger subjective bias for fathers inherent in the Q-sort method. C1 Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. NICHHD, Bethesda, MD 20892 USA. RP Huffman, LC (reprint author), Stanford Univ, Sch Med, 700 Sand Hill Rd,1134, Palo Alto, CA 94304 USA. NR 50 TC 1 Z9 1 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD APR PY 2000 VL 21 IS 2 BP 97 EP 106 DI 10.1097/00004703-200004000-00003 PG 10 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 305KC UT WOS:000086537900003 PM 10791477 ER PT J AU Schreurs, BG Shi, T Pineda, S Buck, DL AF Schreurs, BG Shi, T Pineda, S Buck, DL TI Conditioning the unconditioned response: Modification of the rabbit's (Oryctolagus cuniculus) unconditioned nictitating membrane response SO JOURNAL OF EXPERIMENTAL PSYCHOLOGY-ANIMAL BEHAVIOR PROCESSES LA English DT Article ID CROSS-MODAL TRANSFER; CS-US CONTIGUITY; REFLEX FACILITATION; SENSORY MODALITIES; STIMULUS; EYEBLINK; CONNECTIONS; DIMINUTION; INTERVALS; ABDUCENS AB Conditioning-specific reflex modification (CRM) occurs when classical conditioning modifies responding to an unconditioned stimulus (US) in the absence of a conditioned stimulus (CS). Three experiments monitored rabbit nictitating (Oryctolagus cuniculus) membrane unconditioned responses to 5 intensities and 4 durations of periorbital electrical stimulation before and after CS or US manipulation. CRM occurred after 12 days of CS-US pairings but not following unpaired CS/US presentations or restraint. CRM survived CS-alone and CS/US-unpaired extinction of the conditioned response (CR) but not presentations of the US alone, although CRs remained intact. Thus, CRs could be weakened without eliminating CRM and CRM could be weakened without eliminating CRs. Data indicate CRM is a reliable, associative effect that is more than a generalized CR and may not be explained by habituation, stimulus generalization, contextual conditioning, or bidirectional conditioning. C1 NINDS, Behav Neurosci Unit, Lab Adapt Syst, NIH, Bethesda, MD 20892 USA. RP Schreurs, BG (reprint author), NINDS, Behav Neurosci Unit, Lab Adapt Syst, NIH, Bldg 36,Room B205, Bethesda, MD 20892 USA. OI Schreurs, Bernard/0000-0002-5776-0807 NR 44 TC 30 Z9 30 U1 0 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0097-7403 J9 J EXP PSYCHOL ANIM B JI J. Exp. Psychol.-Anim. Behav. Process. PD APR PY 2000 VL 26 IS 2 BP 144 EP 156 DI 10.1037//0097-7403.26.2.144 PG 13 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental; Zoology SC Psychology; Behavioral Sciences; Zoology GA 328XH UT WOS:000087876700003 PM 10782430 ER PT J AU Bautista, AP AF Bautista, AP TI Impact of alcohol on the ability of Kupffer cells to produce chemokines and its role in alcoholic liver disease SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Review DE alcoholic hepatitis; glycoprotein 120; hepatic dysfunction; human immunodeficiency virus-1; inflammation; lymphocytes; macrophages; nuclear transcription factors; signal transduction ID SUPEROXIDE ANION RELEASE; CHEMOTACTIC FACTOR; HEPATIC-INJURY; ETHANOL; EXPRESSION; PROTEIN; INTOXICATION; MACROPHAGES; LIPOPOLYSACCHARIDE; HEPATOCYTES AB Chemokines are implicated in the pathogenesis of alcoholic liver disease in humans and in experimental models of alcohol intoxication. The major sources of these chemokines are Kupffer cells which represent more than 80% of tissue macrophages in the body. Kupffer cells are highly responsive to the effects of ethanol, endotoxin and human immunodeficiency virus (HIV)-1 glycoprotein120. These agents, either independently or in combination, may exacerbate the production of chemokines. Chemokines are agents that are highly chemotactic to mononuclear cells and granulocytes. The levels of these chemokines in sera and tissue are elevated in patients with alcoholic hepatitis, alcoholic cirrhosis, diseased livers, viral hepatitis, and in experimental models of chronic alcohol intoxication. Alcohol-induced influx of endotoxin from the gut into the portal circulation is suggested to play an important role in the activation of Kupffer cells which leads to enhanced chemokine release. The up-regulation of chemokines during alcohol consumption is selective. During the early phase of alcoholic liver disease, C-X-C or alpha- chemokines predominate. This is also associated with neutrophilic infiltration of the liver. In the later stage, up-regulation of C-C or beta-chemokine production and migration of mononuclear cells into the liver are observed, and this may lead to liver cirrhosis. Selective up-regulation of chemokine synthesis and release may involve differential modulation of the transcription factors required for chemokine gene expression. Increased cytokine release following alcohol consumption may also regulate chemokine secretion in Kupffer cells via paracrine and autocrine mechanisms and vice versa. In addition, infection with HIV-1 may further compromise the liver to more damage. During HIV-1 infection, a pre-existing liver disease superimposed on chronic alcohol consumption may also exacerbate HIV-1 replication and lymphocytic infiltration in the liver, because of the ability of HIV-1 gp120 to stimulate chemokine production by Kupffer cells and stimulate migration of inflammatory leucocytes in the liver. (C) 2000 Blackwell Science Asia Pty Ltd. C1 Louisiana State Univ, Med Ctr, Dept Physiol, New Orleans, LA 70112 USA. Louisiana State Univ, Med Ctr, NIAAA, Sponsored Alcohol Res Ctr, New Orleans, LA 70112 USA. RP Bautista, AP (reprint author), Louisiana State Univ, Med Ctr, Dept Physiol, 1901 Perdido St MEB Room 7272, New Orleans, LA 70112 USA. EM abauti@lsumc.edu FU NIAAA NIH HHS [R01 AA 08846, R01 AA 10746, R01 AA 10466] NR 50 TC 45 Z9 47 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD APR PY 2000 VL 15 IS 4 BP 349 EP 356 DI 10.1046/j.1440-1746.2000.02174.x PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 301XL UT WOS:000086335800005 PM 10824877 ER PT J AU Goold, SD Biddle, AK Klipp, G Danis, M AF Goold, SD Biddle, AK Klipp, G Danis, M TI "Choosing healthplans all together" a game to assess consumer values and preferences for health insurance. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Michigan, Ann Arbor, MI 48109 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 2 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 68 EP 69 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400196 ER PT J AU Murabito, JM Larson, MG Evans, JC Freund, KM Kreger, BE Splansky, GL Wilson, PWF Moskowitz, MA AF Murabito, JM Larson, MG Evans, JC Freund, KM Kreger, BE Splansky, GL Wilson, PWF Moskowitz, MA TI Regular mammography use in women in the Framingham Offspring Study. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Boston Med Ctr, Gen Internal Med Sect, Boston, MA USA. NHLBI, Framingham Heart Study, Boston, MA 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 86 EP 86 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400269 ER PT J AU Danis, M Biddle, AJ Goold, SD AF Danis, M Biddle, AJ Goold, SD TI Insurance preferences of the uninsured. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Natl Inst Hlth, Bethesda, MD USA. Univ N Carolina, Chapel Hill, NC USA. Univ Michigan, Ann Arbor, MI 48109 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 107 EP 107 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400358 ER PT J AU Ziebuhr, J Snijder, EJ Gorbalenya, AE AF Ziebuhr, J Snijder, EJ Gorbalenya, AE TI Virus-encoded proteinases and proteolytic processing in the Nidovirales SO JOURNAL OF GENERAL VIROLOGY LA English DT Review ID INFECTIOUS-BRONCHITIS VIRUS; MOUSE HEPATITIS-VIRUS; HUMAN CORONAVIRUS 229E; EQUINE ARTERITIS VIRUS; PAPAIN-LIKE PROTEINASE; STRAND RNA VIRUSES; OPEN READING FRAME; DEHYDROGENASE-ELEVATING VIRUS; REPLICASE ORF1A PROTEIN; P-28 CLEAVAGE SITE C1 Univ Wurzburg, Inst Immunol & Virol, D-97078 Wurzburg, Germany. Leiden Univ, Med Ctr, Dept Virol, NL-2300 RC Leiden, Netherlands. NCI, Frederick Canc Res & Dev Ctr, SAIC, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. RP Ziebuhr, J (reprint author), Univ Wurzburg, Inst Immunol & Virol, Versbacher Str 7, D-97078 Wurzburg, Germany. RI Gorbalenya, Alexander/J-4818-2012 OI Gorbalenya, Alexander/0000-0002-4967-7341 FU NCI NIH HHS [N01-CO-56000] NR 126 TC 413 Z9 447 U1 1 U2 19 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AE, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD APR PY 2000 VL 81 BP 853 EP 879 PN 4 PG 27 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 301ZX UT WOS:000086341400001 PM 10725411 ER PT J AU Romeo, R Hegerich, P Emerson, SU Colombo, M Purcell, RH Bukh, J AF Romeo, R Hegerich, P Emerson, SU Colombo, M Purcell, RH Bukh, J TI High prevalence of TT virus (TTV) in naive chimpanzees and in hepatitis C virus-infected humans: frequent mixed infections and identification of new TTV genotypes in chimpanzees SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID DNA VIRUS; POSTTRANSFUSION HEPATITIS; UNKNOWN ETIOLOGY; BLOOD-DONORS; NON-A; SEQUENCES AB A recently discovered DNA virus, TT virus (TTV), is prevalent in humans. In the present study, the genetic heterogeneity of TTV was evaluated in hepatitis C virus (HCV)-infected patients and in chimpanzees. rm DNA was detected by PCR in serum samples from all ten HCV-infected patients studied; at least five major TTV genotypes, all previously identified in humans, were recovered. Eight patients were infected with multiple variants of Till. TTV DNA was detected by PCR in serum samples from 11 (65%) of 17 naive chimpanzees bred in captivity; a persistent infection was present in three of six animals. At least five chimpanzees were infected with more than one TTV variant. Detection of TTV DNA in chimpanzee faecal samples suggests the possibility of faecal-oral transmission. Phylogenetic analysis of ORF1 sequences amplified from chimpanzees identified three major genotypes which had not previously been recognized in humans. C1 NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Mol Hepatitis Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Milan, Dept Internal Med, IRCCS, Maggiore Hosp, Milan, Italy. 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 [N01-CO-56000]; NIAID NIH HHS [N01-AI-52705] NR 30 TC 24 Z9 25 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AE, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD APR PY 2000 VL 81 BP 1001 EP 1007 PN 4 PG 7 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 301ZX UT WOS:000086341400016 PM 10725426 ER PT J AU Rimer, BK AF Rimer, BK TI Use of multiple media and breast cancer screening: An introduction SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID HEALTH COMMUNICATION C1 NCI, Off Dis Prevent & Populat Sci, NIH, Bethesda, MD 20892 USA. RP Rimer, BK (reprint author), NCI, Off Dis Prevent & Populat Sci, NIH, Execut Plaza N,Room 242, Bethesda, MD 20892 USA. NR 11 TC 7 Z9 7 U1 2 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PD APR-JUN PY 2000 VL 5 IS 2 BP 113 EP 116 DI 10.1080/108107300406848 PG 4 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 334TM UT WOS:000088201800002 PM 11010344 ER PT J AU Burton, SL AF Burton, SL TI Asking to die: Inside the Dutch debate about euthanasia. SO JOURNAL OF HEALTH POLITICS POLICY AND LAW LA English DT Book Review C1 Natl Inst Hlth, Bethesda, MD 20892 USA. RP Burton, SL (reprint author), Natl Inst Hlth, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 0361-6878 J9 J HEALTH POLIT POLIC JI J. Health Polit. Policy Law PD APR PY 2000 VL 25 IS 2 BP 378 EP 381 DI 10.1215/03616878-25-2-378 PG 4 WC Health Care Sciences & Services; Health Policy & Services; Medicine, Legal; Social Issues; Social Sciences, Biomedical SC Health Care Sciences & Services; Legal Medicine; Social Issues; Biomedical Social Sciences GA 308NX UT WOS:000086720700005 ER PT J AU Emanuel, EJ AF Emanuel, EJ TI A time to die: The place for physician assistance. SO JOURNAL OF HEALTH POLITICS POLICY AND LAW LA English DT Book Review C1 Natl Inst Hlth, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Emanuel, EJ (reprint author), Natl Inst Hlth, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 0361-6878 J9 J HEALTH POLIT POLIC JI J. Health Polit. Policy Law PD APR PY 2000 VL 25 IS 2 BP 382 EP 387 DI 10.1215/03616878-25-2-382 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Medicine, Legal; Social Issues; Social Sciences, Biomedical SC Health Care Sciences & Services; Legal Medicine; Social Issues; Biomedical Social Sciences GA 308NX UT WOS:000086720700006 ER PT J AU Aoki, Y Jones, KD Tosato, G AF Aoki, Y Jones, KD Tosato, G TI Kaposi's sarcoma-associated herpesvirus-encoded interleukin-6 SO JOURNAL OF HEMATOTHERAPY & STEM CELL RESEARCH LA English DT Review ID PRIMARY EFFUSION LYMPHOMA; MULTICENTRIC CASTLEMANS-DISEASE; ENDOTHELIAL GROWTH-FACTOR; MULTIPLE-MYELOMA PATIENTS; SPINDLE CELLS; IN-VIVO; TRANSPLANT RECIPIENTS; PERMEABILITY FACTOR; INHIBITORY FACTOR; TRANSGENIC MICE AB Since the discovery of the virus in 1994, the rapid pace with which Karposi's sarcoma-associated herpesvirus (KSHV) research has progressed has quickly led to a broad understanding of the structure of the virus and its biology and pathology in humans, Molecular piracy of potentially useful cellular genes has emerged as a characteristic feature of this virus, The viral homolog of human IL-6, vIL-6 is an example in kind, Studies in vitro and in vivo have shown that vIL-6 can stimulate the growth of KSHV-infected primary infusion lymphoma (PEL) cells, can promote hematopoiesis, and act as an angiogenic factor through the induction of vascular endothelial growth factor (VEGF), It is not difficult to envision how vIL-6, through these properties and perhaps others yet to be identified, can contribute to KSHV survival and spread in the human population. C1 NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Aoki, Y (reprint author), NCI, Med Branch, NIH, Bldg 29A,Room 2D06,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 76 TC 34 Z9 34 U1 1 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1525-8165 J9 J HEMATOTH STEM CELL JI J. hematother. Stem Cell Res. PD APR PY 2000 VL 9 IS 2 BP 137 EP 145 DI 10.1089/152581600319351 PG 9 WC Hematology; Medicine, Research & Experimental; Transplantation SC Hematology; Research & Experimental Medicine; Transplantation GA 312CY UT WOS:000086926700005 PM 10813527 ER PT J AU Touloukian, CE Leitner, WW Topalian, SL Li, YF Robbins, PF Rosenberg, SA Restifo, NP AF Touloukian, CE Leitner, WW Topalian, SL Li, YF Robbins, PF Rosenberg, SA Restifo, NP TI Identification of a MHC class II-restricted human gp100 epitope using DR4-IE transgenic mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; TUMOR-INFILTRATING LYMPHOCYTES; MELANOMA ANTIGEN GP100; CELL RESPONSES; IN-VIVO; METASTATIC MELANOMA; DENDRITIC CELLS; HIGH-AFFINITY; CD4(+); PEPTIDE AB CD4(+) T cells play a central role in the induction and persistence of CD8(+) T cells in several models of autoimmune and infectious disease. To improve the efficacy of a synthetic peptide vaccine based on the self-Ag, gp100, we sought to provide Ag-specific T cell help. To identify a gp100 epitope restricted by the MHC class II allele with the highest prevalence in patients with malignant melanoma (HLA-DRB1*0401), we immunized mice transgenic for a chimeric human-mouse class II molecule (DR4-IE) with recombinant human gp100 protein. We then searched for the induction of CD4(+) T cell reactivity using candidate epitopes predicted to bind to DRB1*0401 by a computer-assisted algorithm. Of the 21 peptides forecasted to bind most avidly, murine CD4(+) T cells recognized the epitope (human gp100(44-59), WNRQLYPEWTEAQRLD) that was predicted to bind best. Interestingly, the mouse helper T tells also recognized human melanoma cells expressing DRB1*0401. To evaluate whether human CD4(+) T cells could be generated from the peripheral blood of patients with melanoma, we used the synthetic peptide h-gp100(44-59) to sensitize lymphocytes ex vivo. Resultant human CD4(+) T cells specifically recognized melanoma, as measured by tumor cytolysis and the specific release of cytokines and chemokines. NI,A class II transgenic mice may be useful in the identification of helper epitopes derived from Ags of potentially great clinical utility. C1 NCI, Surg Branch, Bethesda, MD 20892 USA. RP Restifo, NP (reprint author), NCI, Surg Branch, Bldg 10,Room 2B42, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008; Leitner, Wolfgang/F-5741-2011; OI Leitner, Wolfgang/0000-0003-3125-5922; Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z99 CA999999, Z01 BC010763-01] NR 60 TC 102 Z9 103 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2000 VL 164 IS 7 BP 3535 EP 3542 PG 8 WC Immunology SC Immunology GA 296JF UT WOS:000086020700014 PM 10725708 ER PT J AU Yu, X Fournier, S Allison, JP Sharpe, AH Hodes, RJ AF Yu, X Fournier, S Allison, JP Sharpe, AH Hodes, RJ TI The role of B7 costimulation in CD4/CD8 T cell homeostasis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NEGATIVE SELECTION; TRANSGENIC MICE; CD4(+)CD8(+) THYMOCYTES; CD28-DEFICIENT MICE; APOPTOSIS; BCL-2; ACTIVATION; EXPRESSION; CD28; LYMPHOCYTE AB The effect of B7-mediated costimulation on T cell homeostasis was examined in studies of B7-1 (CD80) and B7-2 (CD86) transgenic as well as B7-defieient mice. B7 overexpression in transgenic mice resulted in marked polyclonal peripheral T cell hyperplasia accompanied by skewing toward an increased proportion of CD8 single-positive cells and a decreased proportion of CD4 single-positive cells in thymus and more markedly in peripheral T cells. B7-induced T cell expansion was dependent on both CD28 and TCR expression. Transgenic overexpression of B7-1 or B7-2 resulted in down-regulation of cell surface CD28 on thymocytes and peripheral T cells through a mechanism mediated by intercellular interaction. Mice deficient in B7-1 and B7-2 exhibited changes that were the reciprocal of those observed in B7-overexpressing transgenics: a marked increase in the CD4/CD8 ratio in peripheral T cells and an increase in cell surface CD28 in thymus and peripheral T cells, These reciprocal effects of genetically engineered increase or decrease in B7 expression indicate that B7 costimulation plays a physiological role in the regulation of CD4(+) and CD8(+) T cell homeostasis. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NIA, NIH, Bethesda, MD USA. Univ Calif Berkeley, Dept Mol & Cellular Biol, Berkeley, CA 94720 USA. Brigham & Womens Hosp, Dept Pathol, Div Immunol Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Yu, X (reprint author), NCI, Expt Immunol Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. NR 36 TC 48 Z9 49 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 2000 VL 164 IS 7 BP 3543 EP 3553 PG 11 WC Immunology SC Immunology GA 296JF UT WOS:000086020700015 PM 10725709 ER PT J AU Hwu, P Du, MX Lapointe, R Do, M Taylor, MW Young, HA AF Hwu, P Du, MX Lapointe, R Do, M Taylor, MW Young, HA TI Indoleamine 2,3-dioxygenase production by human dendritic cells results in the inhibition of T cell proliferation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TRYPTOPHAN CATABOLISM; GM-CSF; GAMMA; PHENOTYPE; PHASE; IL-4 AB Dendritic cells (DCs) play a key role in the activation and regulation of B and T lymphocytes, Production of indoleamine 2,3-dioxygenase (IDO) by macrophages has recently been described to result in inhibition of T cell proliferation through tryptophan degradation. Since DCs can be derived from monocytes, we sought to determine whether DCs could produce IDO which could potentially regulate T cell proliferation. Northern blot analysis of RNA from cultured monocyte-derived human DC revealed that IDO mRNA was induced upon activation with CD40 ligand and IFN-gamma. IDO produced from activated DCs was functionally active and capable of metabolizing tryptophan to kynurenine. Activated T cells were also capable of inducing IDO production by DCs, which was inhibited by a neutralizing Ab against IFN-gamma, DC production of IDO resulted in inhibition of T cell proliferation, which could be prevented using the IDO inhibitor 1-methyl-DL-tryptophan. These results suggest that activation of DCs induces the production of functional IDO, which causes depletion of tryptophan and subsequent inhibition of T cell proliferation. This may represent a potential mechanism for DCs to regulate the immune response. C1 NCI, Surg Branch, Div Clin Sci, Bethesda, MD 20892 USA. Indiana Univ, Dept Biol, Bloomington, IN 47405 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Hwu, P (reprint author), NCI, Surg Branch, Div Clin Sci, Bldg 10,Room 2B42,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 13 TC 420 Z9 440 U1 2 U2 20 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 2000 VL 164 IS 7 BP 3596 EP 3599 PG 4 WC Immunology SC Immunology GA 296JF UT WOS:000086020700021 PM 10725715 ER PT J AU Dybul, M Chun, TW Ward, DJ Hertogs, K Larder, B Fox, CH Orenstein, JM Baird, BF Li, YX Green, LG Engel, D Liu, SY Mican, JM Fauci, AS AF Dybul, M Chun, TW Ward, DJ Hertogs, K Larder, B Fox, CH Orenstein, JM Baird, BF Li, YX Green, LG Engel, D Liu, SY Mican, JM Fauci, AS TI Evaluation of lymph node virus burden in human immunodeficiency virus-infected patients receiving efavirenz-based protease inhibitor-sparing highly active antiretroviral therapy SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 39th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) CY SEP 27, 1999 CL SAN FRANCISCO, CALIFORNIA ID HIV-1 REPLICATION; T-CELLS; TISSUE; BLOOD; COMBINATION; PLASMA; RNA; RESISTANCE; INDINAVIR; DISEASE AB Although efavirenz-containing regimens effectively suppress plasma levels of human immunodeficiency virus (HIV) RNA, it is now clear that undetectable plasma viremia may not reflect a lack of viral replication. Because lymphoid tissue is an active site of HIV replication, the lymph node virus burden was analyzed in persons who received highly active antiretroviral therapy (HAART) containing either efavirenz or a protease inhibitor (PI). Testing with in situ hybridization revealed no detectable follicular dendritic cell-associated HIV RNA in either group, and only 2 of 8 persons in the efavirenz group and 1 of 4 in the PI group had detectable RNA in lymph node mononuclear cells (LNMC) when tested by use of nucleic acid sequence-based amplification. Low levels of replication-competent HIV were identified in both groups by use of quantitative coculture assays. There was no evidence of development of resistance to either regimen in virus isolated from LNMC. These data support the use of efavirenz as an alternative to a PI in initial HAART regimens. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. Mol Histol Labs Inc, Rockville, MD USA. Adv BioSci Inc, Rockville, MD USA. Dupont Circle Phys Grp, Washington, DC USA. George Washington Univ, Dept Pathol, Washington, DC USA. Virco, Mechelen, Belgium. Virco UK Ltd, Cambridge, England. RP Dybul, M (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Rm 11N204, Bethesda, MD 20892 USA. NR 30 TC 20 Z9 20 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 2000 VL 181 IS 4 BP 1273 EP 1279 DI 10.1086/315407 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 311KT UT WOS:000086883900006 PM 10836864 ER PT J AU Benson, CA Williams, PL Cohn, DL Becker, S Hojczyk, P Nevin, T Korvick, JA Heifets, L Child, CC Lederman, MM Reichman, RC Powderly, WG Notario, GF Wynne, BA Hafner, R AF Benson, CA Williams, PL Cohn, DL Becker, S Hojczyk, P Nevin, T Korvick, JA Heifets, L Child, CC Lederman, MM Reichman, RC Powderly, WG Notario, GF Wynne, BA Hafner, R CA AIDS Clin Trials Grp 196 T Beirn Comm Programs Clin Res AIDS TI Clarithromycin or rifabutin alone or in combination for primary prophylaxis of Mycobacterium avium complex disease in patients with AIDS: A randomized, double-blind, placebo-controlled trial SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT XIth International Conference on AIDS CY JUL 07-13, 1996 CL VANCOUVER, CANADA ID IMMUNODEFICIENCY-VIRUS INFECTION; 2 CONTROLLED TRIALS; OPPORTUNISTIC INFECTIONS; INTRACELLULARE COMPLEX; WEEKLY AZITHROMYCIN; BACTEREMIA; THERAPY; RISK; EPIDEMIOLOGY; ETHAMBUTOL AB The efficacy and safety of clarithromycin and rifabutin alone and in combination for prevention of Mycobacterium avium complex (MAC) disease were compared in 1178 patients with AIDS who had less than or equal to 100 CD4 T cells/mu L in a randomized, double-blind, placebo-controlled trial. MAC disease occurred in 9%, 15%, and 7% of those randomized to clarithromycin or rifabutin alone or in combination, respectively; time-adjusted event rates per 100 patient-years (95% confidence interval [CI]) were 6.3 (4.2-8.3), 10.5 (7.8-13.2), and 4.7 (2.9-6.5). Risk of MAC disease was reduced by 44% with clarithromycin (risk ratio [RR], 0.56; 95% CI, 0.37-0.84; P = .005) and by 57% with combination therapy (RR, 0.43; 95% CI, 0.27-0.69; P =.0003), versus rifabutin. Combination therapy was not more effective than clarithromycin (RR, 0.79; 95% CI, 0.48-1.31; P = .36). Of those in whom clarithromycin or combination therapy failed, 29% and 27% of MAC isolates, respectively, were resistant to clarithromycin. There were no survival differences. Clarithromycin and combination therapy were more effective than rifabutin for prevention of MAC disease, but combination therapy was associated with more adverse effects (31%; P < .001). C1 Univ Colorado, Hlth Sci Ctr, Div Infect Dis, Denver, CO 80262 USA. Rush Med Coll, Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Abbott Labs, Macrolide Venture, Abbott Pk, IL USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. Denver Publ Hlth, Denver, CO USA. Natl Jewish Med & Res Ctr, Denver, CO USA. Frontier Sci & Technol Res Fdn, Amherst, NY USA. Univ Rochester, Sch Med, Div Infect Dis, Rochester, NY USA. Adult AIDS Clin Trials Grp, Operat Ctr, Rockville, MD USA. NIAID, Opportunist Infect Res Branch, Treatment Res Programs, Div Aids, Bethesda, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco Gen Hosp, San Francisco, CA 94110 USA. Case Western Reserve Univ, Sch Med, Div Infect Dis, Cleveland, OH 44106 USA. Adria Labs, Div Erbamont Inc, Dublin, OH USA. Washington Univ, Sch Med, Div Infect Dis, St Louis, MO 63110 USA. RP Benson, CA (reprint author), Univ Colorado, Hlth Sci Ctr, Div Infect Dis, 4200 E 9th Ave,B-168, Denver, CO 80262 USA. NR 32 TC 49 Z9 55 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 2000 VL 181 IS 4 BP 1289 EP 1297 DI 10.1086/315380 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 311KT UT WOS:000086883900008 PM 10762562 ER PT J AU Everhart, JE Kruszon-Moran, D Perez-Perez, GI Tralka, TS McQuillan, G AF Everhart, JE Kruszon-Moran, D Perez-Perez, GI Tralka, TS McQuillan, G TI Seroprevalence and ethnic differences in Helicobacter pylori infection among adults in the United States SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Epidemiological-Research CY JUN, 1998 CL BOSTON, MASSACHUSETTS SP Soc Epidemiol Res ID POPULATION; PREVALENCE; CHILDREN; DISEASE; COHORT; AGE AB The seroprevalence of Helicobacter pylori infection was examined in the adult US population and among different ethnic groups. Stored sera from 7465 adult participants in the first phase of the third National Health and Nutritional Examination Survey (1988-1991) were tested with a sensitive and specific IgG ELISA, to diagnose infection. Seroprevalence of H. pylori among all participants was 32.5%. This increased with age, from 16.7% for persons 20-29 years old to 56.9% for those greater than or equal to 70 years old. Age-adjusted prevalence was substantially higher among non-Hispanic blacks (52.7%) and Mexican Americans (61.6%) than among non-Hispanic whites (26.2%). After controlling for age and other associated factors, the odds ratios relative to non-Hispanic whites decreased for non-Hispanic blacks, from 3.9 (95% confidence interval [CI], 3.1-4.9) to 3.3 (95% CI, 2.6-4.2), and for Mexican Americans, from 6.3 (95% CI, 4.8-8.3) to 2.3 (95% CI, 1.6-3.5). The high prevalence of H. pylori infection among non-Hispanic blacks and Mexican Americans is partially explained by other factors associated with infection. C1 NIDDK, Epidemiol & Clin Trials Branch, Div Digest Dis & Nutr, Bethesda, MD 20892 USA. Natl Ctr Hlth Stat, Div Hlth Examinat Stat, Hyattsville, MD 20782 USA. Vanderbilt Univ, Sch Med, Div Infect Dis, Nashville, TN 37212 USA. RP Everhart, JE (reprint author), NIDDK, Epidemiol & Clin Trials Branch, Div Digest Dis & Nutr, Natcher Bldg,Room 6AN-12J,45 Ctr Dr MSC 6600, Bethesda, MD 20892 USA. FU NIDDK NIH HHS [DK-6-2202] NR 19 TC 171 Z9 177 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR PY 2000 VL 181 IS 4 BP 1359 EP 1363 DI 10.1086/315384 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 311KT UT WOS:000086883900016 PM 10762567 ER PT J AU Hisada, M O'Brien, TR Rosenberg, PS Goedert, JJ AF Hisada, M O'Brien, TR Rosenberg, PS Goedert, JJ CA Multicenter Hemophilia Cohort Stud TI Virus load and risk of heterosexual transmission of human immunodeficiency virus and hepatitis C virus by men with hemophilia SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID VIRAL LOAD; TRANSFUSION RECIPIENTS; RNA LEVELS; HIV RNA; INFECTION; PLASMA; TYPE-1 AB A high human immunodeficiency virus (HIV) load may increase the probability of HIV transmission by sexual contact, but the association of virus load of hepatitis C virus (HCV) with risk of HCV transmission is uncertain. HIV and HCV virus loads were examined in hemophilic men, as were risks of HIV and HCV transmission to their female partners in a hemophilia cohort in which most subjects are dually infected. A higher HIV load was associated with an increased risk of HIV transmission (odds ratio [OR], 1.31 per log(10) increase in virus load). A higher HCV load was associated, although not significantly, with an increased risk of HCV transmission (OR, 1.42 per log(10)). HCV load was higher among dually infected men than in those infected with HCV alone (P = .001). However, much larger studies are needed to clearly show whether HIV/HCV coinfection significantly increases the risk of HCV transmission to female partners. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RP Hisada, M (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS-8007, Rockville, MD 20852 USA. NR 15 TC 56 Z9 57 U1 1 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 2000 VL 181 IS 4 BP 1475 EP 1478 DI 10.1086/315396 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 311KT UT WOS:000086883900035 PM 10753732 ER PT J AU Singer, SM Nash, TE AF Singer, SM Nash, TE TI The role of normal flora in Giardia lamblia infections in mice SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CRYPTOSPORIDIUM-PARVUM AB The presence of normal bacterial flora in the intestinal tract is thought to protect against colonization by pathogens. Only a few specific examples of this protection have been demonstrated for bacterial pathogens and protozoan infections. Mice from one commercial breeding farm were found to be less susceptible to infection with Giardia lamblia than were isogenic mice from another facility. When mice were housed together, resistance to infection was readily transferred to normally susceptible mice. After resistant mice were treated with neomycin, differences in susceptibility to infection were shown to be due to differences in the resident Bora present in these mice. These results suggest the possible use of probiotic therapy for prevention of G. lamblia infections and may help explain some of the variability of outcomes seen in G. lamblia infections in humans. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Singer, SM (reprint author), Georgetown Univ, Dept Biol, Reiss Sci Bldg,Room 306A,37th & O St NW, Washington, DC 20057 USA. NR 13 TC 58 Z9 60 U1 1 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR PY 2000 VL 181 IS 4 BP 1510 EP 1512 DI 10.1086/315409 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 311KT UT WOS:000086883900043 PM 10751141 ER PT J AU LeBlanc, RA Straus, SE AF LeBlanc, RA Straus, SE TI Effects of famciclovir and valacyclovir on herpes simplex virus type 1 infection, latency, and reactivation in mice: How dissimilar are study results? Reply SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter ID VALACICLOVIR; MODEL C1 NIH, Med Virol Sect, Clin Invest Lab, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP LeBlanc, RA (reprint author), NIH, Med Virol Sect, Clin Invest Lab, Natl Ctr Complementary & Alternat Med, 31 Ctr Dr,Room 5B41, 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 2000 VL 181 IS 4 BP 1518 EP 1518 DI 10.1086/315410 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 311KT UT WOS:000086883900046 ER PT J AU Bal, W Kozlowski, H Kasprzak, KS AF Bal, W Kozlowski, H Kasprzak, KS TI Molecular models in nickel carcinogenesis SO JOURNAL OF INORGANIC BIOCHEMISTRY LA English DT Article; Proceedings Paper CT 5th International Symposium on Applied Bioinorganic Chemistry (5 ISABC) CY APR 13-17, 1999 CL CORFU, GREECE SP European Cooperat Field Sci & Tech Res, Greek Minist Culture, Greek Minist Educ, Univ Ioannina, Minist Ind, Gen Secretariat Res & Technol DE nickel(II); nickel(II)-peptide interactions; histone H1; histone H2A; histone H3; histone H4; core histone tetramer; peptide bond hydrolysis; 2'-deoxyguanosine oxidation; speciation ID METAL-BINDING SEQUENCE; L-HISTIDINE; 2'-DEOXYGUANOSINE OXIDATION; CRYSTAL-STRUCTURE; HISTONE OCTAMER; LINKER HISTONES; DNA; NUCLEOSOME; COMPLEXES; PROTEIN AB Nickel compounds are known human carcinogens, but the exact molecular mechanisms of nickel carcinogenesis are not known. Due to their abundance, histones are likely targets for Ni(II) ions among nuclear macromolecules. This paper reviews our recent studies of peptide and protein models of Ni(II) binding to histones. The results allowed us to propose several mechanisms of Ni(II)-inflicted damage, including nucleobase oxidation and sequence-specific histone hydrolysis. Quantitative estimations of Ni(II) speciation, based on these studies, support the likelihood of Ni(II) binding to histones in vivo, and the protective role of high levels of glutathione. These calculations indicate the importance of histidine in the intracellular Ni(II) speciation. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Univ Wroclaw, Fac Chem, PL-50138 Wroclaw, Poland. NCI, Comparat Carcinogenesis Lab, FCRDC, Frederick, MD 21702 USA. RP Bal, W (reprint author), Univ Wroclaw, Fac Chem, PL-50138 Wroclaw, Poland. NR 56 TC 76 Z9 78 U1 2 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0162-0134 J9 J INORG BIOCHEM JI J. Inorg. Biochem. PD APR PY 2000 VL 79 IS 1-4 BP 213 EP 218 DI 10.1016/S0162-0134(99)00169-5 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA 313EZ UT WOS:000086988500031 PM 10830868 ER PT J AU Kasprzak, KS Bialkowski, K AF Kasprzak, KS Bialkowski, K TI Inhibition of antimutagenic enzymes, 8-oxo-dGTPases, by carcinogenic metals. Recent developments SO JOURNAL OF INORGANIC BIOCHEMISTRY LA English DT Article; Proceedings Paper CT 5th International Symposium on Applied Bioinorganic Chemistry (5 ISABC) CY APR 13-17, 1999 CL CORFU, GREECE SP European Cooperat Field Sci & Tech Res, Greek Minist Culture, Greek Minist Educ, Univ Ioannina, Minist Ind, Gen Secretariat Res & Technol DE cadmium; cobalt; copper; nickel; 8-oxo-dGTPase ID DNA-BASE DAMAGE; MALE F344 RATS; ESCHERICHIA-COLI; REPLICATION FIDELITY; MUTAGENIC SUBSTRATE; HUMAN-CELLS; MUTT; NICKEL; MICE; CADMIUM AB Nickel, cadmium, cobalt, and copper are carcinogenic to humans and/or animals, but the underlying mechanisms are poorly understood. Our studies have been focused on one such mechanism involving mediation by the metals of promutagenic oxidative damage to DNA bases. The damage may be inflicted directly in DNA or in the deoxynucleotide pool, from which the damaged bases are incorporated into DNA. Such incorporation is prevented in cells by 8-oxo-2'-deoxyguanosine 5'-triphosphate pyrophosphatases (8-oxo-dGTPases). Thus, inhibition of these enzymes should enhance carcinogenesis. We have studied effects of Cd(II), Cu(II), Co(II), and Ni(II) on the activity of isolated bacterial and human 8oxo-dGTPases. Cd(II) and Cu(II) were strongly inhibitory, while Ni(II) and Co(II) were much less suppressive. After developing an assay for 8-oxo-dGTPase activity, we confirmed the inhibition by Cd(II) in cultured cells and in the rat testis, the target organ for cadmium carcinogenesis. 8Oxo-dGTPase inhibition was accompanied by an increase in the g-oxo-dG level in testicular DNA. (C) 2000 Elsevier Science Inc. All rights reserved. C1 NCI, Comparat Carcinogenesis Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Univ Med Sch, Dept Clin Biochem, Bydgoszcz, Poland. RP Kasprzak, KS (reprint author), NCI, Comparat Carcinogenesis Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. EM kasorkaz@mail.ncifcrf.gov RI Bialkowski, Karol/E-2328-2014 NR 46 TC 34 Z9 35 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0162-0134 J9 J INORG BIOCHEM JI J. Inorg. Biochem. PD APR PY 2000 VL 79 IS 1-4 BP 231 EP 236 DI 10.1016/S0162-0134(99)00240-8 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA 313EZ UT WOS:000086988500034 PM 10830871 ER PT J AU Miranda, KM Espey, MG Wink, DA AF Miranda, KM Espey, MG Wink, DA TI A discussion of the chemistry of oxidative and nitrosative stress in cytotoxicity SO JOURNAL OF INORGANIC BIOCHEMISTRY LA English DT Article; Proceedings Paper CT 5th International Symposium on Applied Bioinorganic Chemistry (5 ISABC) CY APR 13-17, 1999 CL CORFU, GREECE SP European Cooperat Field Sci & Tech Res, Greek Minist Culture, Greek Minist Educ, Univ Ioannina, Minist Ind, Gen Secretariat Res & Technol DE nitric oxide; oxidative stress; nitrosative stress; cytotoxicity ID LOW-DENSITY-LIPOPROTEIN; WOODCHUCK HEPATITIS-VIRUS; NITRIC-OXIDE PROTECTS; HYDROGEN-PEROXIDE; MARMOTA-MONAX; INHIBITION; SUPEROXIDE; INSIGHTS; METALLOTHIONEIN; PEROXYNITRITE AB Nitric oxide (NO) has been shown to be a key bioregulatory agent in a wide variety of biological processes, yet cytotoxic properties have been reported as well. This dichotomy has raised the question of how this potentially toxic species can be involved in so many fundamental physiological processes. We have investigated the effects of NO on a variety of toxic agents and correlated how its chemistry might pertain to the observed biology. The results generate a scheme termed the chemical biology of NO in which the pertinent reactions can be categorized into direct and indirect effects. The former involves the direct reaction of NO with its biological targets generally at low fluxes of NO. Indirect effects are reactions mediated by reactive nitrogen oxide species, such as those generated from the NO/O-2 and NO/O-2(-) reactions, which can lead to cellular damage via nitrosation or oxidation of biological components. This report discusses several examples of cytotoxicity involved with these stresses. (C) 2000 Elsevier Science Inc. All rights reserved. C1 NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. RP Miranda, KM (reprint author), NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. RI Miranda, Katrina/B-7823-2009 NR 33 TC 21 Z9 21 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0162-0134 J9 J INORG BIOCHEM JI J. Inorg. Biochem. PD APR PY 2000 VL 79 IS 1-4 BP 237 EP 240 DI 10.1016/S0162-0134(99)00241-X PG 4 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA 313EZ UT WOS:000086988500035 PM 10830872 ER PT J AU Waalkes, MP AF Waalkes, MP TI Cadmium carcinogenesis in review SO JOURNAL OF INORGANIC BIOCHEMISTRY LA English DT Article; Proceedings Paper CT 5th International Symposium on Applied Bioinorganic Chemistry (5 ISABC) CY APR 13-17, 1999 CL CORFU, GREECE SP European Cooperat Field Sci & Tech Res, Greek Minist Culture, Greek Minist Educ, Univ Ioannina, Minist Ind, Gen Secretariat Res & Technol DE cadmium; carcinogenesis; humans; rodents; zinc ID DIETARY ZINC-DEFICIENCY; WISTAR CRL-(WI)BR RATS; DOSE-RESPONSE ANALYSIS; INJECTION SITE; TUMOR-INDUCTION; OXIDE FUMES; C-JUN; METALLOTHIONEIN; PROSTATE; MICE AB Cadmium is an inorganic toxicant of great environmental and occupational concern which was classified as a human carcinogen in 1993. Occupational cadmium exposure is associated with lung cancer in humans. Cadmium exposure has also, on occasion, been linked to human prostate cancer. The epidemiological data linking cadmium and pulmonary cancer are much stronger than for prostatic cancer. Other target sites for cadmium carcinogenesis in humans (liver, kidney, stomach) are considered equivocal. In rodents, cadmium causes tumors at several sites and by various routes. Cadmium inhalation in rats results in pulmonary adenocarcinomas, supporting a role in human lung cancer. Prostate tumors and preneoplastic proliferative lesions can be induced in rats after cadmium ingestion or injection. Prostatic carcinogenesis in rats occurs only at cadmium doses below those that induce chronic degeneration and dysfunction of the testes, a well-known effect of cadmium, confirming the androgen dependency of prostate tumors. Other targets of cadmium in rodents include the testes, adrenals, injection sites, and hematopoietic system. Various treatments can modify cadmium carcinogenesis including supplemental zinc, which prevents cadmium-induced injection site and testicular tumors while facilitating prostatic tumors. Cadmium is poorly mutagenic and probably acts through indirect mechanisms, although the precise mechanisms remain unknown. (C) 2000 Elsevier Science Inc. All rights reserved. C1 NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC 27706 USA. RP Waalkes, MP (reprint author), NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC 27706 USA. NR 32 TC 436 Z9 463 U1 6 U2 58 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0162-0134 J9 J INORG BIOCHEM JI J. Inorg. Biochem. PD APR PY 2000 VL 79 IS 1-4 BP 241 EP 244 DI 10.1016/S0162-0134(00)00009-X PG 4 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA 313EZ UT WOS:000086988500036 PM 10830873 ER PT J AU Sprecher, E Bale, SJ DiGiovanna, JJ Uitto, J Richard, G AF Sprecher, E Bale, SJ DiGiovanna, JJ Uitto, J Richard, G TI Netherton syndrome is not linked to 18q12, a region homologous to the murine Lanceolate Hair (lah) locus SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Letter C1 Thomas Jefferson Univ, Dept Dermatol & Cutaneous Biol, Philadelphia, PA 19107 USA. NIAMSD, Genet Studies Sect, NIH, Bethesda, MD USA. Brown Univ, Rhode Isl Hosp, Dept Dermatol, Div Dermatopharmacol, Providence, RI 02903 USA. RP Richard, G (reprint author), Thomas Jefferson Univ, Dept Dermatol & Cutaneous Biol, 233 S 10th St,BLSB,Suite 409, Philadelphia, PA 19107 USA. FU NIAMS NIH HHS [P01-AR38923] NR 9 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 2000 VL 114 IS 4 BP 741 EP 742 DI 10.1046/j.1523-1747.2000.00932-3.x PG 2 WC Dermatology SC Dermatology GA 302CA UT WOS:000086346300024 PM 10745035 ER PT J AU Koren, AO Horti, AG Mukhin, AG Gundisch, D Dannals, RF London, ED AF Koren, AO Horti, AG Mukhin, AG Gundisch, D Dannals, RF London, ED TI Synthesis and initial in vitro characterization of 6-[F-18]fluoro-3-(2(S)-azetidinylmethoxy)pyridine, a high-affinity radioligand for central nicotinic acetylcholine receptors SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE nicotinic acetylcholine receptors; A-85380; nucleophilic heteroaromatic substitution; fluorine-18; radioligand; receptor binding ID IN-VIVO; RADIOIODINATED ANALOG; HUMAN BRAIN; EPIBATIDINE; PET; THERAPEUTICS; RADIOTRACER; BINDING; A-85380; RAT AB 6-[F-18]Fluora-3-(2(S)-azetidinylmethoxy)pyridine ([F-18](1) under bar), a novel analogue of the high-affinity nicotinic acetylcholine receptor ligand, A-85380, was prepared by a two-step procedure from an appropriate nitro precursor. In the first step, a Kryptofix 222-assisted F-18 nucleophilic heteroaromatic substitution in 6-nitro-3-((1-tert-butoxycarbonyl-2(S)-azetidinyl)methoxy)pyridine provided a radio-fluorinated Boc-protected intermediate. Subsequent acidic deprotection of the intermediate gave [F-18](1) under bar with an overall radiochemical yield of 8 to 12% (non-decay-corrected). The typical synthesis time was ca. 110 min. Specific radioactivity of the final product ranged from 1000 to 4500 mCi/mu mol, as calculated at the end-of-synthesis. III vitro studies demonstrated that the novel radioligand bound to a single population of sites in rat brain membranes, presumably, to the alpha 4 beta 2 subtype of nicotinic acetylcholine receptor. This binding was characterized by a K-d value of 28 pM, consistent with the K-i value of 25 pM, derived previously for unlabeled (1) under bar in competition assays with (+/-)-[H-3]epibatidine. C1 NIDA, Brain Imaging Ctr, Intramural Res Program, Baltimore, MD 21224 USA. Johns Hopkins Med Inst, Dept Radiol, Div Nucl Med, Baltimore, MD 21287 USA. RP Horti, AG (reprint author), NIDA, Brain Imaging Ctr, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 28 TC 16 Z9 16 U1 1 U2 5 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD APR PY 2000 VL 43 IS 5 BP 413 EP 423 DI 10.1002/(SICI)1099-1344(200004)43:5<413::AID-JLCR326>3.0.CO;2-1 PG 11 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 307NY UT WOS:000086660500001 ER PT J AU Markey, SP Dudding, T Wang, TCL AF Markey, SP Dudding, T Wang, TCL TI Base- and acid-catalyzed interconversions of O-acyl- and N-acyl-ethanolamines: a cautionary note for lipid analyses SO JOURNAL OF LIPID RESEARCH LA English DT Article DE anandamide; arachidonoylethanolamide; palmitoylethanolamide; mass spectrometry ID CANNABINOID RECEPTOR; ENZYMATIC-SYNTHESIS; ENDOGENOUS LIGAND; RAT-BRAIN; ANANDAMIDE; BIOSYNTHESIS AB The isolation and quantification of ethanolamine containing lipids from animal tissues may expose neutral lipid extracts to acidic or basic conditions during chromatographic separations or derivatization chemistry While investigating the acid- and base-catalyzed production of anandamide in chromatographic fractions of rat brain extracts not containing anandamide, we observed that O,N-acyl migrations are facile. O,N-acyl migrations are well documented in synthetic organic chemistry literature, but are not well described or recognized with regard to methods in lipid isolation or lipid enzyme studies. We report here the synthesis and characterization of O- and N-acyl (palmitoylor arachidonoyl-)ethanolamines. Their rearrangements in base and acid are quantified by liquid chromatography-electrospray ionization mass spectrometry. The rearrangements proceed through a cyclic intermediate that is also formed during chemical reactions commonly used for derivatization of acylethanolamines for gas chromatography-mass spectrometry. The isolation and characterization of N- or O-acylethanolamines and their enzymatic formation requires awareness and consideration of the proclivity of these compounds to chemically rearrange. C1 NIMH, Lab Neurotoxicol, Bethesda, MD 20892 USA. RP Markey, SP (reprint author), NIMH, Lab Neurotoxicol, Bethesda, MD 20892 USA. NR 23 TC 23 Z9 23 U1 2 U2 4 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD APR PY 2000 VL 41 IS 4 BP 657 EP 662 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 304WT UT WOS:000086507600018 PM 10744787 ER PT J AU Cardiff, RD Wagner, U Henninghausen, L AF Cardiff, RD Wagner, U Henninghausen, L TI Mammary cancer in humans and mice: A tutorial for comparative pathology. The CD-ROM SO JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA LA English DT Article DE mouse mammary gland; human breast; oncogenes; breast cancer; CD-ROM; histopathology; mammary development AB This article introduces a CD-ROM containing whole-mount and histological images of normal growth and development of both the mouse mammary gland and the human breast. It also covers nonneoplastic lesions and neoplasias in both species including a catalog of lesions in genetically engineered mice. Instructions, with examples, on techniques such as whole-mount preparation, immunohistochemistry, in situ hybridization, and common histological stains are provided. The images are based on full-scale 1996 X 1640 pixel images at 300 pixels/inch and are annotated. Every genetically engineered model has one or more accompanying citations. Tables are provided for orientation and organization. The CD includes zoom capabilities, a search engine, and a help mode. C1 Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA. Univ Calif Davis, Dept Pathol, Davis, CA 95616 USA. NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. RP Cardiff, RD (reprint author), Univ Calif Davis, Ctr Comparat Med, Cty Rd 98n & Hutchison Dr, Davis, CA 95616 USA. RI Wagner, Ulrike/B-6039-2009 NR 1 TC 8 Z9 8 U1 0 U2 0 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 2000 VL 5 IS 2 BP 243 EP 244 DI 10.1023/A:1026451607575 PG 2 WC Oncology; Endocrinology & Metabolism; Physiology SC Oncology; Endocrinology & Metabolism; Physiology GA 385MV UT WOS:000166009000009 PM 11149576 ER PT J AU Mortier, GR Weis, M Nuytinck, L King, LM Wilkin, DJ De Paepe, A Lachman, RS Rimoin, D Eyre, DR Cohn, DH AF Mortier, GR Weis, M Nuytinck, L King, LM Wilkin, DJ De Paepe, A Lachman, RS Rimoin, D Eyre, DR Cohn, DH TI Report of five novel and one recurrent COL2A1 mutations with analysis of genotype-phenotype correlation in patients with a lethal type II collagen disorder SO JOURNAL OF MEDICAL GENETICS LA English DT Article DE type II collagen disorders; achondrogenesis II-hypochondrogenesis; spondyloepiphyseal dysplasia congenita; COL2A1 ID SPONDYLOEPIPHYSEAL DYSPLASIA CONGENITA; ACHONDROGENESIS-HYPOCHONDROGENESIS; SERINE SUBSTITUTION; ALPHA-1(II) CHAIN; KNIEST-DYSPLASIA; GENE; CARTILAGE; GLYCINE; FAMILY; IDENTIFICATION AB Achondrogenesis II-hypochondrogenesis and severe spondyloepiphyseal dysplasia congenita (SEDC) are lethal forms of dwarfism caused by dominant mutations in the type II collagen gene (COL2A1). To identify the underlying defect in seven cases with this group of conditions, we used the combined strategy of cartilage protein analysis and COL2A1 mutation analysis. Overmodified type II collagen and the presence of type I collagen was found in the cartilage matrix of all seven cases. Five patients were heterozygous for a nucleotide change that predicted a glycine substitution in the triple helical domain (G313S, G517V, G571A, G910C, G943S). In an five cases, analysis of cartilage type II collagen suggested incorporation of the abnormal al(II) chain in the extracellular collagen trimers. The G943S mutation has been reported previously in another unrelated patient with a strikingly similar phenotype, illustrating the possible specific effect of the mutation. The radiographically less severely affected patient was heterozygous for a 4 bp deletion in the splice donor site of intron 35, likely to result in aberrant splicing. One case was shown to be heterozygous for a single nucleotide change predicted to result in a T1191N substitution in the carboxy-propeptide of the proal(II) collagen chain. Study of the clinical, radiographic, and morphological features of the seven cases supports evidence for a phenotypic continuum between achondrogenesis II-hypochondrogenesis and lethal SEDC and suggests a relationship between the amount of type I collagen in the cartilage and the severity of the phenotype. C1 State Univ Ghent Hosp, Dept Med Genet, B-9000 Ghent, Belgium. Univ Washington, Dept Orthoped, Seattle, WA 98195 USA. Univ Calif Los Angeles, Steven Spielberg Pediat Res Ctr, Burns & Allen Cedars Sinai Res Inst, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Pediat, Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Radiol, Sch Med, Los Angeles, CA 90024 USA. Natl Human Genome Res Inst, Med Genet Branch, NIH, Bethesda, MD USA. RP Mortier, GR (reprint author), State Univ Ghent Hosp, Dept Med Genet, Pintelaan 185, B-9000 Ghent, Belgium. RI Mortier, Geert/D-2542-2012 FU NIAMS NIH HHS [AR37318, R01 AR036794, R37 AR037318]; NICHD NIH HHS [HD22657] NR 32 TC 41 Z9 42 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD APR PY 2000 VL 37 IS 4 BP 263 EP 271 DI 10.1136/jmg.37.4.263 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 303XN UT WOS:000086453000005 PM 10745044 ER PT J AU Aravind, L Wolf, YI Koonin, EV AF Aravind, L Wolf, YI Koonin, EV TI The ATP-Cone: An evolutionarily mobile, ATP-binding regulatory domain SO JOURNAL OF MOLECULAR MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article ID PROTEIN SECONDARY STRUCTURE; RIBONUCLEOTIDE REDUCTASE; 2-PHOSPHOGLYCERATE KINASE; METHANOTHERMUS-FERVIDUS; PREDICTION; SITE C1 Natl Ctr Biotechnol Informat, Natl Lib Med, NIH, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), Natl Ctr Biotechnol Informat, Natl Lib Med, NIH, Bethesda, MD 20894 USA. NR 19 TC 35 Z9 37 U1 0 U2 5 PU HORIZON SCIENTIFIC PRESS PI WYMONDHAM PA PO BOX 1, NORFOLK, WYMONDHAM NR18 0JA, ENGLAND SN 1464-1801 J9 J MOL MICROB BIOTECH JI J. Mol. Microbiol. Biotechnol. PD APR PY 2000 VL 2 IS 2 BP 191 EP 194 PG 4 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 404JE UT WOS:000167093000005 PM 10939243 ER PT J AU Rashid, MA Gustafson, KR Boyd, MR AF Rashid, MA Gustafson, KR Boyd, MR TI HIV-inhibitory cembrane derivatives from a Philippines collection of the soft coral Lobophytum species SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID MARINE NATURAL-PRODUCTS; GENUS LOBOPHYTUM; DITERPENES AB Bioassay-guided fractionation of an aqueous extract of a Philippine Islands collection of the soft coral Lobophytum sp, concentrated its HIV-inhibitory activity into fractions rich in cembranoid diterpenes. Lobohedleolide (1), (7Z)-lobohedleolide (2), and a new compound, 17-dimethylaminolobohedleolide (3), were purified from these fractions by HPLC. The structures of compounds 1-3 were elucidated by spectroscopic analyses and by comparison of their spectral data with previously reported values. The relative stereochemistry of the gamma-lactone ring substituents of 3 was determined by 1D NOESY experiments. While several other cembranoids that contain a dimethylamino functional group have been reported from the soft coral Sinularia sp., compound 3 represents the first cembrane diterpene with this functional group isolated from a Lobophytum species. Diterpenoids 1-3 exhibited moderate HIV-inhibitory activity (EC50 approximately 3-5 mu g/mL) in a cell-based in vitro anti-HIV assay. C1 NCI, Frederick Canc Res & Dev Ctr, Div Canc Treatment & Diag, Dev Therapeut Program,Lab Drug Discovery Res & De, Frederick, MD 21702 USA. SAIC, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Boyd, MR (reprint author), NCI, Frederick Canc Res & Dev Ctr, Div Canc Treatment & Diag, Dev Therapeut Program,Lab Drug Discovery Res & De, Bldg 1052,Room 121, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 23 TC 64 Z9 72 U1 0 U2 9 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 2000 VL 63 IS 4 BP 531 EP 533 DI 10.1021/np990372p PG 3 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 310HP UT WOS:000086820700026 PM 10785433 ER PT J AU Gotoh, J Itoh, Y Kuang, TY Cook, M Law, MJ Sokoloff, L AF Gotoh, J Itoh, Y Kuang, TY Cook, M Law, MJ Sokoloff, L TI Negligible glucose-6-phosphatase activity in cultured astroglia SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE 2-deoxyglucose; glucose metabolism; astrocytes ID CEREBRAL GLUCOSE-UTILIZATION; DEOXYGLUCOSE-6-PHOSPHATE STABILITY INVIVO; RAT-BRAIN; CYTOCHEMICAL-LOCALIZATION; ASTROCYTES; METABOLISM; MECHANISM; GLYCOGEN; SYSTEM; SODIUM AB 2-Deoxy[C-14]glucose-6-phosphate (2-[C-14]DG-6-P) dephosphorylation and glucose-6-phosphatase (G-6-Pase) activity were examined in cultured rat astrocytes under conditions similar to those generally used in assays of glucose utilization. Astrocytes were loaded with 2-[C-14]DG-6-P by preincubation for 15 min in medium containing 2 mM glucose and 50 mu M 2-deoxy[C-14]glucose (2-[C-14]DG). The medium was then replaced with identical medium including 2 mM glucose but lacking 2-[C-14]DG, and incubation was resumed for 5 min to diminish residual free 2-[C-14]DG levels in the cells by either efflux or phosphorylation. The medium was again replaced with fresh 2-[C-14]DG-free medium, and the incubation was continued for 5, 15, or 30 min. Intracellular and extracellular C-14 contents were measured at each time point, and the distribution of C-14 between 2-[C-14]DG and 2-[C-14]DG-6-P was characterized by paper chromatography. The results showed little if any hydrolysis of 2-[C-14]DG-6-P or export of free 2-[C-14]DG from cells to medium; there were slightly increasing losses of 2-[C-14]DG and 2-[C-14]DG-6-P into the medium with increasing incubation time, but they were in the same proportions found in the cells, suggesting they were derived from nonadherent or broken cells. Experiments carried out with medium lacking glucose during the assay for 2-deoxyglucose-6-phosphatase activity yielded similar results. Evidence for G-6-Pase activity was also sought by following the selective detritiation of glucose from the 2-C position when astrocytes were incubated with [2-H-3]glucose and [U-C-14]glucose in the medium. No change in the H-3/C-14 ratio was found in incubations for as long as 15 min. These results indicate negligible G-6-Pase activity in cultured astrocytes. C1 NIMH, Cerebral Metab Lab, Bethesda, MD 20892 USA. RP Sokoloff, L (reprint author), NIMH, Cerebral Metab Lab, Bldg 36,1A 05,36 Convent Dr MSC 4030, Bethesda, MD 20892 USA. NR 42 TC 19 Z9 19 U1 1 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 2000 VL 74 IS 4 BP 1400 EP 1408 DI 10.1046/j.1471-4159.2000.0741400.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 295DL UT WOS:000085951400008 PM 10737595 ER PT J AU Pedersen, WA Chan, SL Mattson, MP AF Pedersen, WA Chan, SL Mattson, MP TI A mechanism for the neuroprotective effect of apolipoprotein E: Isoform-specific modification by the lipid peroxidation product 4-hydroxynonenal SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Alzheimer's disease; amyotrophic lateral sclerosis; apoptosis; oxidative stress; spinal cord; transgenic mice ID AMYOTROPHIC-LATERAL-SCLEROSIS; AMYLOID BETA-PEPTIDE; E MESSENGER-RNA; ALZHEIMERS-DISEASE; IMMUNOHISTOCHEMICAL DETECTION; 4-HYDROXY-2-NONENAL ADDUCTS; SUPEROXIDE-DISMUTASE; GLUTAMATE TRANSPORT; PRECURSOR PROTEIN; ALDEHYDIC PRODUCT AB Inheritance of the apolipoprotein E (apoE) epsilon 4 allele increases the risk for Alzheimer's disease and may also influence the pathogenesis of other neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). The influence of apoE genotype on disease susceptibility must ultimately be explained by the fact that apoE proteins differ in only two amino acids: apoE2 has two cysteine residues, apoE3 has one cysteine residue, and apoE4 has none. We previously reported increased protein modification by the lipid peroxidation product 4-hydroxynonenal (HNE), which covalently binds to proteins on cysteine residues, in human ALS lumbar spinal cord, We now report increased levels of HNE-modified apoE in lumbar spinal cord samples from mice expressing an ALS-linked mutation in Cu/Zn-superoxide dismutase relative to controls. Studies of interactions of pure apoE proteins with HNE showed that the isoforms differ in the amount of HNE they can bind, with the order E2 > E3 > E4. This correlated with the differential ability of apoE isoforms to protect against apoptosis induced by HNE in cultures of mouse spinal cord motor neurons and by the amyloid beta-peptide in cultures of rat hippocampal neurons. These data suggest that apoE plays a major role in detoxifying HNE, and the differential neuroprotective effect of its isoforms may help explain the relationship between apoE genotype and the susceptibility to neurodegenerative diseases. C1 Univ Kentucky, Sanders Brown Res Ctr Aging, Lexington, KY USA. Univ Kentucky, Dept Anat & Neurobiol, Lexington, KY 40536 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, GRC 4F01,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 51 TC 93 Z9 96 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD APR PY 2000 VL 74 IS 4 BP 1426 EP 1433 DI 10.1046/j.1471-4159.2000.0741426.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 295DL UT WOS:000085951400011 PM 10737598 ER PT J AU El Daly, E Chefer, V Sandill, S Shippenberg, TS AF El Daly, E Chefer, V Sandill, S Shippenberg, TS TI Modulation of the neurotoxic effects of methamphetamine by the selective kappa-opioid receptor agonist U69593 SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE methamphetamine; dopamine; microdialysis; kappa-opioid receptors; U69593 ID RAT STRIATUM; DOPAMINE TRANSPORTER; GLUTAMATE RELEASE; BEHAVIORAL SENSITIZATION; NUCLEUS-ACCUMBENS; REVERSE TRANSPORT; MICE LACKING; UPTAKE SITES; AMINO-ACIDS; AMPHETAMINE AB kappa-Opioid receptor agonists prevent alterations in dopamine neurotransmission that occur in response to repeated cocaine administration. The present microdialysis study examined whether administration of the selective kappa-opioid receptor agonist U69593 with methamphetamine prevents alterations in dopamine levels produced by neurotoxic doses of methamphetamine. Swiss Webster mice were injected intraperitoneally with methamphetamine (10.0 mg/kg) or saline, four times in 1 day, at 2-h intervals. Prior to the first and third injection, they received U69593 (0.32 mg/kg s.c,) or vehicle. Microdialysis was conducted 3, 7, or 21 days later. Basal and K+ evoked (60 and 100 mM) dopamine overflow were reduced 3 days after methamphetamine administration. These effects were long-lasting in that they were still apparent 7 and 21 days after methamphetamine treatment. Intrastriatal (5.0 and 50 mu M) or systemic (1.0-10.0 mg/kg) administration of methamphetamine increased dopamine concentrations in control animals. In mice preexposed to methamphetamine, methamphetamine-evoked dopamine overflow was reduced. In animals that had received methamphetamine with U69593, basal dopamine levels did not differ from those of vehicle-treated controls. U69593 treatment attenuated the decrease in K+-evoked dopamine produced by prior methamphetamine exposure. The reduction in methamphetamine-evoked dopamine levels was also attenuated, The administration of U69593 alone did not modify basal or stimulus-evoked dopamine levels. These data demonstrate that repeated methamphetamine administration reduces presynaptic dopamine neuronal function in mouse striatum and that co-administration of a selective kappa-opioid receptor agonist with methamphetamine attenuates these effects. U69593 treatment did not modify the hyperthermic effects of methamphetamine, indicating that this kappa-opioid receptor agonist selectively attenuates methamphetamine-induced alterations in dopamine neurotransmission. C1 NIDA, Integrated Neurosci Unit, Behav Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. Suez Canal Univ, Fac Educ, Dept Biol, Suez, Egypt. RP Shippenberg, TS (reprint author), NIDA, Integrated Neurosci Unit, Behav Neurosci Lab, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. FU NIDA NIH HHS [DA10084] NR 60 TC 16 Z9 16 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD APR PY 2000 VL 74 IS 4 BP 1553 EP 1562 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 295DL UT WOS:000085951400025 PM 10737612 ER PT J AU Liow, K Asmar, P Liow, M Spanaki, M Townsend, JJ Buys, S Baringer, JR Osborn, A AF Liow, K Asmar, P Liow, M Spanaki, M Townsend, JJ Buys, S Baringer, JR Osborn, A TI Intravascular lymphomatosis: Contribution of cerebral MRI findings to diagnosis SO JOURNAL OF NEUROIMAGING LA English DT Article DE MRI; lymphomatosis AB Intravascular lymphomatosis (It) is a rare variant of non-Hodgkin's lymphoma with an unusual predilection for the central nervous system (CNS). Most cases are not diagnosed until postmortem because of variable clinical presentation and nonspecific laboratory findings. Neuroimaging findings vary widely and range from diffuse involvement of the deep while matter to infarct-like lesions. Cerebral magnetic resonance imaging (MRI) may show parenchymal and meningeal gadolinium enhancement. The authors describe brain MRI findings of linear, punctate, and patchy enhancement suggestive of CNS IL in two patients confirmed by brain biopsy/histologic studies. High index of clinical suspicion and careful interpretation of MRI (including gadolinium contrast studies) may contribute to premortem diagnosis and early intervention of this often-missed disease. C1 NINDS, NIH, Bethesda, MD 20892 USA. Univ Utah, Sch Med, Dept Radiol, Salt Lake City, UT USA. Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT USA. Univ Utah, Sch Med, Dept Hematol & Oncol, Salt Lake City, UT USA. Univ Utah, Sch Med, Dept Neurol, Salt Lake City, UT USA. NIA, NIH, Bethesda, MD 20892 USA. RP Liow, K (reprint author), NINDS, NIH, Bldg 10,Room 5N-250,10 Ctr Dr MSC 1402, Bethesda, MD 20892 USA. NR 5 TC 19 Z9 21 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-2284 J9 J NEUROIMAGING JI J. Neuroimaging PD APR PY 2000 VL 10 IS 2 BP 116 EP 118 PG 3 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 306LY UT WOS:000086599200008 PM 10800265 ER PT J AU Chase, TN Oh, JD Konitsiotis, S AF Chase, TN Oh, JD Konitsiotis, S TI Antiparkinsonian and antidyskinetic activity of drugs targeting central glutamatergic mechanisms SO JOURNAL OF NEUROLOGY LA English DT Article; Proceedings Paper CT Symposium on Non-Dopaminergic Treatment of Parkinsons Disease CY MAY, 1999 CL TAORMINA, ITALY DE AMPA receptor; medium spiny neuron; NMDA receptor; phosphorylation; signal transduction ID LEVODOPA-INDUCED DYSKINESIAS; MOTOR RESPONSE ALTERATIONS; NMDA RECEPTOR SUBUNITS; MPTP-TREATED MONKEYS; MESSENGER-RNA EXPRESSION; PARKINSONS-DISEASE; L-DOPA; BASAL GANGLIA; GENE-EXPRESSION; RAT STRIATUM AB Motor dysfunction produced by the chronic non-physiological stimulation of dopaminergic receptors on striatal medium spiny neurons is associated with alterations in the sensitivity of glutamatergic receptors, including those of the N-methyl-D-aspartate (NMDA) subtype. Functional characteristics of these ionotropic receptors are regulated by their phosphorylation state. Lesioning the nigrostriatal dopamine system of rats induces parkinsonian signs and increases the phosphorylation of striatal NMDA receptor subunits on serine and tyrosine residues. The intrastriatal administration of certain inhibitors of the kinases capable of phosphorylating NMDA receptors produces a dopaminomimetic motor response in these animals. Treating parkinsonian rats twice daily with levodopa induces many of the characteristic features of the human motor complication syndrome and further increases the serine and tyrosine phosphorylation of specific NMDA receptor subunits. Again, the intrastriatal administration of selective inhibitors of certain serine and tyrosine kinases alleviates the motor complications. NMDA receptor antagonists, including some non-competitive chan-nel blockers, act both palliatively and prophylactically in rodent and primate models to reverse these levodopa-induced response alterations. Similarly, in clinical studies dextrorphan, dextromethorphan, and amantadine have been found to be efficacious against motor complications. Recent observations in animal models further indicate that certain amino3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) antagonists alleviate, while others exacerbate, these complications. Thus, it appears that the denervation or intermittent stimulation of striatal dopaminergic receptors differentially activates signal transduction pathways in medium spiny neurons. These in turn modify the phosphorylation state of ionotropic glutamate receptors and consequently their sensitivity to cortical input. These striatal changes contribute to symptom production in Parkinson's disease, and their prevention or reversal could prove useful in the treatment of this disorder. C1 NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Chase, TN (reprint author), NINDS, Expt Therapeut Branch, NIH, Bldg 10,Rrom 5C211,10 Ctr Dr,MSC-406, Bethesda, MD 20892 USA. NR 88 TC 71 Z9 73 U1 0 U2 0 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PLATZ DER DEUTSCHEN EINHEIT 25, D-64293 DARMSTADT, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD APR PY 2000 VL 247 SU 2 BP 36 EP 42 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 315GM UT WOS:000087104300006 ER PT J AU Sommer, MA Wurtz, RH AF Sommer, MA Wurtz, RH TI Composition and topographic organization of signals sent from the frontal eye field to the superior colliculus SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Review ID DORSOLATERAL PREFRONTAL CORTEX; ALERT RHESUS-MONKEY; UNIT-ACTIVITY; HORSERADISH-PEROXIDASE; DELAYED-RESPONSE; ELECTRICAL-STIMULATION; CORTICOTECTAL NEURONS; CONDUCTION-VELOCITY; SUBSTANTIA-NIGRA; MACAQUE MONKEYS AB The frontal eye held (FEF) and superior colliculus (SC) contribute to saccadic eye movement generation, and much of the FEF's oculomotor influence may be mediated through the SC. The present study examined the composition and topographic organization of signals flowing from FEF to SC by recording from FEF neurons that were antidromically activated from rostral or caudal SC. The first and most general result was that, in a sample of 88 corticotectal neurons, the types of signals relayed from FEF to SC were highly diverse, reflecting the general population of signals within FEF rather than any specific subset of signals. Second, many neurons projecting from FEF to SC carried signals thought to reflect cognitive operations, namely tonic discharges during the delay period of a delayed-saccade task (delay signals), elevated discharges during the gap period of a gap task (gap increase signals), or both. Third, FEF neurons discharging during fixation were found to project to the SC, although they did not project preferentially to rostral SC, where similar fixation neurons are found. Neurons that did project preferentially to the rostral SC were those with foveal visual responses and those pausing during the gap period of the gap task. Many of the latter neurons also had foveal visual responses, presaccadic pauses in activity, and postsaccadic increases in activity. These two types of rostral-projecting neurons therefore may contribute to the activity of rostral SC fixation neurons. Fourth, conduction velocity was used as an indicator of cell size to correct for sampling bias. The outcome of this correction procedure suggested that among the most prevalent neurons in the FEF corticotectal population are those carrying putative cognitive-related signals, i.e., delay and gap increase signals, and among the least prevalent are those carrying presaccadic burst discharges but lacking peripheral visual responses. Fifth, corticotectal neurons carrying various signals were biased topographically across the FEF. Neurons with peripheral visual responses but lacking presaccadic burst discharges were biased laterally, neurons with presaccadic burst discharges but lacking peripheral visual responses were biased medially, and neurons carrying delay or gap increase signals were biased dorsally. Finally, corticotectal neurons were distributed within the FEF as a function of their visual or movement field eccentricity and projected to the SC such that eccentricity maps in both structures were closely aligned. We conclude that the FEF most likely influences the activity of SC neurons continuously from the start of fixation, through visual analysis and cognitive manipulations, until a saccade is generated and fixation begins anew. Furthermore, the projection from FEF to SC is highly topographically organized in terms of function at both its source and its termination. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Sommer, MA (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,Rm 2A50,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 113 TC 212 Z9 212 U1 0 U2 9 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 2000 VL 83 IS 4 BP 1979 EP 2001 PG 23 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 306LV UT WOS:000086598900020 PM 10758109 ER PT J AU Kastner, S De Weerd, P Ungerleider, LG AF Kastner, S De Weerd, P Ungerleider, LG TI Texture segregation in the human visual cortex: A functional MRI study SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID ILLUSORY CONTOURS; ORIENTATION DISCRIMINATION; PERCEPTION; LESIONS; FIGURE; AREAS; CAT; SENSITIVITY; MECHANISMS; ATTENTION AB Texture segregation in the human visual cortex: a functional MRI study. J. Neurophysiol. 83: 2453-2457, 2000. The segregation of visual scenes based on contour information is a fundamental process of early vision. Contours can be defined by simple cues, such as luminance, as well as by more complex cues, such as texture. Single-cell recording studies in monkeys suggest that the neural processing of complex contours starts as early as primary visual cortex. Additionally, lesion studies in monkeys indicate an important contribution of higher order areas to these processes. Using functional MRI, we have investigated the level at which neural correlates of texture segregation can be found in the human visual cortex. Activity evoked by line textures, with and without texture-defined boundaries, was compared in five healthy subjects. Areas V1, V2/VP, V4, TEO, and V3A were activated by both kinds of line textures as compared with blank presentations. Textures with boundaries forming a checkerboard pattern, relative to uniform textures, evoked significantly more activity in areas V4, TEO, less reliably in V3A, but not in V1 or V2/VP. These results provide evidence that higher order areas with large receptive fields play an important role in the segregation of visual scenes based on texture-defined boundaries. C1 NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. Univ Arizona, Coll Social & Behav Sci, Dept Psychol, Tucson, AZ 85721 USA. RP Kastner, S (reprint author), NIMH, Lab Brain & Cognit, NIH, Bldg 49,Rm 1B80, Bethesda, MD 20892 USA. NR 44 TC 110 Z9 110 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD APR PY 2000 VL 83 IS 4 BP 2453 EP 2457 PG 5 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 306LV UT WOS:000086598900057 PM 10758146 ER PT J AU Fleck, MW Hirotsune, S Gambello, MJ Phillips-Tansey, E Suares, G Mervis, RF Wynshaw-Boris, A McBain, CJ AF Fleck, MW Hirotsune, S Gambello, MJ Phillips-Tansey, E Suares, G Mervis, RF Wynshaw-Boris, A McBain, CJ TI Hippocampal abnormalities and enhanced excitability in a murine model of human lissencephaly SO JOURNAL OF NEUROSCIENCE LA English DT Article DE lissencephaly; platelet-activating factor acetylhydrolase; knockout mouse; hippocampus; bromodeoxyuridine; Golgi; epilepsy; potassium ID PLATELET-ACTIVATING-FACTOR; NEURONAL MIGRATION; NEOCORTICAL NEURONS; BASAL DENDRITES; DENTATE-GYRUS; GRANULE CELLS; IN-VITRO; GENE; LIS1; EXPRESSION AB Human cortical heterotopia and neuronal migration disorders result in epilepsy; however, the precise mechanisms remain elusive. Here we demonstrate severe neuronal dysplasia and heterotopia throughout the granule cell and pyramidal cell layers of mice containing a heterozygous deletion of Lis1, a mouse model of human 17p13.3-linked lissencephaly. Birth-dating analysis using bromodeoxyuridine revealed that neurons in Lis1+/- murine hippocampus are born at the appropriate time but fail in migration to form a defined cell layer. Heterotopic pyramidal neurons in Lis1+/- mice were stunted and possessed fewer dendritic branches, whereas dentate granule cells were hypertrophic and formed spiny basilar dendrites from which the principal axon emerged. Both somatostatin- and parvalbumin-containing inhibitory neurons were heterotopic and displaced into both stratum radiatum and stratum lacunosum-moleculare. Mechanisms of synaptic transmission were severely disrupted, revealing hyperexcitability at Schaffer collateral-CA1 synapses and depression of mossy fiber-CA3 transmission. In addition, the dynamic range of frequency-dependent facilitation of Lis1+/- mossy fiber transmission was less than that of wild type. Consequently, Lis1+/- hippocampi are prone to interictal electrographic seizure activity in an elevated [K+](o) model of epilepsy. In Lis1+/- hippocampus, intense interictal bursting was observed on elevation of extracellular potassium to 6.5 mM, a condition that resulted in only minimal bursting in wild type. These anatomical and physiological hippocampal defects may provide a neuronal basis for seizures associated with lissencephaly. C1 NICHHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. Neurocognit Res Labs, Columbus, OH 43212 USA. RP McBain, CJ (reprint author), NICHHD, Lab Cellular & Mol Neurophysiol, NIH, Bldg 49-5A72,49 Convent Dr, Bethesda, MD 20892 USA. NR 42 TC 93 Z9 97 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 1 PY 2000 VL 20 IS 7 BP 2439 EP 2450 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 298JY UT WOS:000086136600005 PM 10729324 ER PT J AU Hoffman, AF Lupica, CR AF Hoffman, AF Lupica, CR TI Mechanisms of cannabinoid inhibition of GABA(A) synaptic transmission in the hippocampus SO JOURNAL OF NEUROSCIENCE LA English DT Article DE brain slice; calcium channels; cannabis; electrophysiology; GABA(A) receptors; GABA(B) receptors; hippocampal; marijuana; potassium channels; presynaptic; ruthenium red ID PRESYNAPTIC INHIBITION; RAT HIPPOCAMPUS; PYRAMIDAL CELLS; POSTSYNAPTIC CURRENTS; CALCIUM CHANNELS; RUTHENIUM RED; RECEPTOR; NEURONS; RELEASE; INTERNEURONS AB The localization of cannabinoid (CB) receptors to GABAergic interneurons in the hippocampus indicates that CBs may modulate GABAergic function and thereby mediate some of the disruptive effects of marijuana on spatial memory and sensory processing. To investigate the possible mechanisms through which CB receptors may modulate GABAergic neurotransmission in the hippocampus, whole-cell voltage-clamp recordings were performed on CA1 pyramidal neurons in rat brain slices. Stimulus-evoked GABA(A) receptor-mediated IPSCs were reduced in a concentration-dependent manner by the CB receptor agonist WIN 55,212-2 (EC50 of 138 nM). This effect was blocked by the CB1 receptor antagonist SR141716A (1 mu M) but not by the opioid antagonist naloxone. In contrast, evoked GABA(B)-mediated IPSCs were insensitive to the CB agonist. WIN 55,212-2 also reduced the frequency of spontaneous, action potential-dependent IPSCs (sIPSCs), without altering action potential-independent miniature IPSCs (mIPSCs), measured while sodium channels were blocked by tetrodotoxin (TTX). Blockade of voltage-dependent calcium channels (VDCCs) by cadmium also eliminated the effect of WIN 55,212-2 on sIPSCs. Depolarization of inhibitory terminals with elevated extracellular potassium caused a large increase in the frequency of mIPSCs that was inhibited by both cadmium and WIN 55,212-2. The presynaptic effect of WIN 55,212-2 was also investigated using the potassium channel blockers barium and 4-aminopyridine. Neither of these agents significantly altered the effect of WIN 55,212-2 on evoked IPSCs. Together, these data suggest that presynaptic CB1 receptors reduce GABA(A)- but not GABA(B)-mediated synaptic inhibition of CA1 pyramidal neurons by inhibiting VDCCs located on inhibitory nerve terminals. C1 Natl Inst Drug Abuse, Cellular Neurobiol Branch, Intramural Res Program, Baltimore, MD 21224 USA. RP Lupica, CR (reprint author), Natl Inst Drug Abuse, Cellular Neurobiol Branch, Intramural Res Program, Bldg C,Room 267,5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Hoffman, Alexander/H-3035-2012 OI Hoffman, Alexander/0000-0002-2676-0628 NR 66 TC 277 Z9 283 U1 0 U2 9 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 1 PY 2000 VL 20 IS 7 BP 2470 EP 2479 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 298JY UT WOS:000086136600008 PM 10729327 ER PT J AU Racca, C Stephenson, FA Streit, P Roberts, JDB Somogyi, P AF Racca, C Stephenson, FA Streit, P Roberts, JDB Somogyi, P TI NMDA receptor content of synapses in stratum radiatum of the hippocampal CA1 area SO JOURNAL OF NEUROSCIENCE LA English DT Article DE hippocampus; spine; immunocytochemistry; electron microscopy; NMDA receptor; AMPA receptor; glutamate receptor; spine apparatus ID LONG-TERM POTENTIATION; DENDRITIC SPINES; ENDOPLASMIC-RETICULUM; SILENT SYNAPSES; MOLECULAR-CLONING; RAT HIPPOCAMPUS; PYRAMIDAL CELLS; AMPA RECEPTORS; MESSENGER-RNAS; NEURONS AB Glutamate receptors activated by NMDA (NMDARs) or AMPA (AMPARs) are clustered on dendritic spines of pyramidal cells. Both the AMPAR-mediated postsynaptic responses and the synaptic AMPAR immunoreactivity show a large intersynapse variability. Postsynaptic responses mediated by NMDARs show less variability. To assess the variability in NMDAR content and the extent of their coexistence with AMPARs in Schaffer collateral-commissural synapses of adult rat CA1 pyramidal cells, electron microscopic immunogold localization of receptors has been used. Immunoreactivity of NMDARs was detected in virtually all synapses on spines, but AMPARs were undetectable, on average, in 12% of synapses. A proportion of synapses had a very high AMPAR content relative to the mean content, resulting in a distribution more skewed toward larger values than that of NMDARs. The variability of synaptic NMDAR content [coefficient of variation (CV), 0.64-0.70] was much lower than that of the AMPAR content (CV, 1.17-1.45). Unlike the AMPAR content, the NMDAR content showed only a weak correlation with synapse size. As reported previously for AMPARs, the immunoreactivity of NMDARs was also associated with the spine apparatus within spines. The results demonstrate that the majority of the synapses made by CA3 pyramidal cells onto spines of CA1 pyramids express both NMDARs and AMPARs, but with variable ratios. A less-variable NMDAR content is accompanied by a wide variability of AMPAR content, indicating that the regulation of expression of the two receptors is not closely linked. These findings support reports that fast excitatory transmission at some of these synapses is mediated by activation mainly of NMDARs. C1 Univ Oxford, MRC, Anat Neuropharmacol Unit, Oxford OX1 3TH, England. Univ London, Sch Pharm, London WC1N 1AX, England. Univ Zurich, Inst Hirnforsch, CH-8057 Zurich, Switzerland. RP Racca, C (reprint author), Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, Bldg 36,Room 5D08,36 Convent Dr, Bethesda, MD 20892 USA. NR 58 TC 186 Z9 194 U1 0 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 1 PY 2000 VL 20 IS 7 BP 2512 EP 2522 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 298JY UT WOS:000086136600012 PM 10729331 ER PT J AU Weeks, R Horwitz, B Aziz-Sultan, A Tian, B Wessinger, CM Cohen, LG Hallett, M Rauschecker, JP AF Weeks, R Horwitz, B Aziz-Sultan, A Tian, B Wessinger, CM Cohen, LG Hallett, M Rauschecker, JP TI A positron emission tomographic study of auditory localization in the congenitally blind SO JOURNAL OF NEUROSCIENCE LA English DT Article DE blindness; cross-modal plasticity; extrastriate; parietal cortex; positron emission tomography; sound localization ID VISUAL-CORTEX; SIGHTED SUBJECTS; CEREBRAL-CORTEX; COMPLEX SOUNDS; ACTIVATION; ORGANIZATION; ATTENTION; LOCATIONS; DEAF AB We have used positron emission tomography (PET) to measure regional cerebral blood flow (rCBF) in sighted and congenitally blind subjects performing auditory localization tasks. During scanning, the spectral and binaural cues of localized sound were reproduced by a sound system and delivered via headphones. During tasks that required auditory localization both the sighted and blind subjects strongly activated posterior parietal areas. In addition, the blind subjects activated association areas in the right occipital cortex, the foci of which were similar to areas previously identified in visual location and motion detection experiments in sighted subjects. The blind subjects, therefore, demonstrated visual to auditory crossmodal plasticity with auditory localization activating occipital association areas originally intended for dorsal-stream visual processing. To determine the functional connectivity of pre-selected brain regions in primary and non-primary auditory and posterior parietal cortex in the two cohorts, we performed an inter-regional correlation analysis on the rCBF data set. During auditory localization in the blind subjects, rCBF activity in the right posterior parietal cortex was positively correlated with that in the right occipital region, whereas in sighted subjects correlations were generally negative. There were no significant positive occipital correlations in either cohort when reference regions in temporal or left parietal cortex were chosen. This indicates that in congenitally blind subjects the right occipital cortex participates in a functional network for auditory localization and that occipital activity is more likely to arise from connections with posterior parietal cortex. C1 Georgetown Univ, Med Ctr, Georgetown Inst Cognit & Computat Sci, Washington, DC 20007 USA. NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Human Cort Physiol Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, Language Sect, Voice Speech & Language Branch, NIH, Bethesda, MD 20892 USA. RP Rauschecker, JP (reprint author), Georgetown Univ, Med Ctr, Georgetown Inst Cognit & Computat Sci, WP15 NRB,3970 Reservoir Rd NW, Washington, DC 20007 USA. EM rauscheckerj@giccs.georgetown.edu RI Rauschecker, Josef/A-4120-2013 FU NIDCD NIH HHS [R01-DC03489] NR 45 TC 294 Z9 303 U1 1 U2 15 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 1 PY 2000 VL 20 IS 7 BP 2664 EP 2672 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 298JY UT WOS:000086136600028 PM 10729347 ER PT J AU Rak, R Chao, DL Pluta, RM Mitchell, JB Oldfield, EH Watson, JC AF Rak, R Chao, DL Pluta, RM Mitchell, JB Oldfield, EH Watson, JC TI Neuroprotection by the stable nitroxide Tempol during reperfusion in a fat model of transient focal ischemia SO JOURNAL OF NEUROSURGERY LA English DT Article DE free radical; Tempol; transient focal ischemia; reperfusion injury; neuroprotection; stroke ID SUPEROXIDE-DISMUTASE; FREE-RADICALS; INJURY; DAMAGE; PATHOPHYSIOLOGY; MODULATION; INFARCT; MIMICS; CELLS; RATS AB Object. The use of thrombolytic agents in the treatment of stroke has yielded surprisingly modest success, possibly because of reperfusion injury mediated by reactive oxygen species (ROS). Therefore, scavenging ROS may be of therapeutic value in the treatment of stroke. Nitroxides an low-weight superoxide dismutase mimics, which allows them to act as cell-permeable antioxidants. In this study the nitroxide 4-hydroxy-2,2,6,6,-tetramethylpiperidine-1-oxyl (Tempol) is investigated to determine its ability to reduce reperfusion injury. Methods. Male Sprague-Dawley rats weighing between 280 g and 350 g underwent middle cerebral artery occlusion with an intraluminal suture for 60 minutes. Regional cerebral blood flow, blood pressure, cerebral temperature, and rectal temperature were monitored during the procedure. After reperfusion, the animals were randomized to groups receiving blinded intravenous administration of either Tempol (10 mg/kg; eight animals) or vehicle (eight animals) over the first 20 minutes of reperfusion (Study I). In a second study to determine dose dependency, animals were randomized to groups receiving Tempol (20 mg/kg; eight animals), low-dose Tempol (5 mg/kg: eight animals), or vehicle (eight animals; Study II). The rats were killed after 4 hours of reperfusion, and brain sections were stained with 2,3,5 triphenyltetrazolium chloride. Infarct volumes were measured using digital imaging. Animals receiving Tempol had significantly reduced infarct volumes at doses of 20 mg/kg and 10 mg/kg compared with controls(49.01 +/- 18.22% reduction [p = 0.003] and 47.47 +/- 34.57 [p = 0.02], respectively). No significant differences in the physiological variables measured were observed between groups. Conclusions. Tempol provides significant neuroprotection after reperfusion in a rat model of transient focal ischemia. These results support the importance of ROS in reperfusion injury and encourage further study of this molecule as a therapeutic agent following thrombolysis. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. RP Oldfield, EH (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Room 5D37-1414, Bethesda, MD 20892 USA. NR 24 TC 77 Z9 83 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD APR PY 2000 VL 92 IS 4 BP 646 EP 651 DI 10.3171/jns.2000.92.4.0646 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 299DH UT WOS:000086180200010 PM 10761655 ER PT J AU Thakur, ML McAfee, JG AF Thakur, ML McAfee, JG TI Gopal (Mani) Subramanian, PhD - In Memoriam SO JOURNAL OF NUCLEAR MEDICINE LA English DT Biographical-Item C1 Thomas Jefferson Univ, Philadelphia, PA 19107 USA. NIH, Bethesda, MD 20892 USA. RP Thakur, ML (reprint author), Thomas Jefferson Univ, Philadelphia, PA 19107 USA. NR 0 TC 0 Z9 0 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 2000 VL 41 IS 4 BP 26N EP 26N PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 302YE UT WOS:000086393400007 ER PT J AU Pietrini, P Alexander, GE Furey, ML Dani, A Mentis, MJ Horwitz, B Guazzelli, M Schapiro, MB Rapoport, SI AF Pietrini, P Alexander, GE Furey, ML Dani, A Mentis, MJ Horwitz, B Guazzelli, M Schapiro, MB Rapoport, SI TI Cerebral metabolic response to passive audiovisual stimulation in patients with Alzheimer's disease and healthy volunteers assessed by PET SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE PET; FDG; dementia; brain; activation; cognition ID POSITRON-EMISSION TOMOGRAPHY; GLUCOSE-METABOLISM; BLOOD-FLOW; NEUROFIBRILLARY TANGLES; NEURONAL-ACTIVITY; APOLIPOPROTEIN-E; SYNAPSE LOSS; ACTIVATION; DEMENTIA; RISK AB Alzheimer's disease is associated with reductions in resting-state brain metabolism, as measured by PET, progressing with dementia severity. The purpose of this study was to see to what extent brain regions with reduced resting-state metabolic rates in Alzheimer patients could be activated by a passive audiovisual stimulation test and to compare the result with activation in age-matched healthy volunteers. The extent of activation in Alzheimer's disease is considered to reflect the integrity of synaptic function, or inherent viability, and the potential responsiveness of the Alzheimer brain to drug therapy. Methods: Regional cerebral metabolic rates for glucose (rCMR(glc), in mg/100 g tissue/min) were measured in the resting state (eyes and ears covered) and during passive audiovisual stimulation (watching a movie) in 15 otherwise healthy Alzheimer patients of differing dementia severity (Mattis Dementia Rating Scale score, 23-128) and in 14 age-matched healthy volunteers (score, 141 +/- 3) using PET with 2 sequential injections of FDG. Results: In the volunteers, audiovisual stimulation caused significant rCMR(glc) increases in visual and auditory cortical areas but significant decreases in frontal areas. In the mildly demented patients, rCMR(glc) responses were within 2 SDs of the mean in volunteers. However, the magnitude of the rCMR(glc) responses during stimulation declined significantly with dementia severity in the right occipitotemporal, right and left occipital association, and left calcarine cortical regions. Conclusion: Functional brain responsiveness, evaluated by a passive audiovisual stimulation paradigm with PET, is within normal limits in mildly demented Alzheimer patients but fails with worsening dementia severity. Declining responsiveness may account for the limited success of neurotransmitter replacement therapy in Alzheimer patients with moderate-to-severe dementia, C1 NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. Univ Pisa, Dept Human & Environm Sci, Pisa, Italy. Univ Pisa, Dept Psychiat Neurobiol Pharmacol & Biotechnol, Pisa, Italy. RP Pietrini, P (reprint author), NIA, Neurosci Lab, NIH, Bldg 10,Rm 6C414,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Furey, Maura/H-5273-2013 NR 38 TC 27 Z9 29 U1 3 U2 3 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 2000 VL 41 IS 4 BP 575 EP 583 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 302YE UT WOS:000086393400013 PM 10768555 ER PT J AU Bonson, KR Grant, SJ Links, JM London, ED AF Bonson, KR Grant, SJ Links, JM London, ED TI Validation of an analytic method of calculating cerebral glucose metabolism using PET SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE plasma integral; FDG PET; analytic method AB Quantitative modeling of cerebral metabolic rate for glucose (CMRglc) using PET with the FDG method requires calculation of the integral of the time course of radioactivity in arterial plasma. Numeric integration has typically been used but requires 30 or more blood samples taken between 15 s and 100 min after injection of the radiotracer. Our laboratory has developed an alternative integration method that fits the values of the plasma samples to an analytically integrable function using only 4-6 samples taken between 40 and 110 min after radiotracer injection. Methods: The plasma integrals were calculated by both the analytic and the numeric methods with data from FDG PET studies that were not used in the development of the analytic method, In 39 PET studies from 22 healthy volunteers, 30 plasma samples were taken over 110 min. Results: The plasma integrals determined by the analytic and numeric methods yielded a within-subject correlation coefficient of >0.95 and differences of <10%. Conclusion: Because the analytic method requires less blood sampling and does not require sampling immediately after radiotracer injection, the experimental procedure is simplified without loss of accuracy in CRRglc computation, and the effect of missing or incorrect samples is reduced. C1 NIDA, Brain Imaging Ctr, Intramural Res Program, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA. RP London, ED (reprint author), NIDA, Brain Imaging Ctr, Intramural Res Program, POB 5180, Baltimore, MD 21224 USA. NR 5 TC 3 Z9 3 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 2000 VL 41 IS 4 BP 658 EP 660 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 302YE UT WOS:000086393400026 PM 10768567 ER PT J AU Surova-Trojanova, H Barker, WC Carrasquillo, JA Bacharach, SL AF Surova-Trojanova, H Barker, WC Carrasquillo, JA Bacharach, SL TI Registration of planar emission images with reprojected CT data SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE planar radionuclide scintigraphy; CT; multimodality registration ID 3-DIMENSIONAL REGISTRATION; TOMOGRAPHY; ANTIBODY; FUSION; BRAIN; PET AB Planar gamma-camera imaging is still widely used clinically. Alignment of planar images with images from tomographic modalities, such as CT, or with other planar images would be desirable. Here, we present and evaluate a method for such an alignment, using planar transmission images acquired with the emission images and reprojection of the 3-dimensional CT data. This method permits determination of which CT slice corresponds to a particular row of pixels in the gamma-camera image and which column of pixels in that CT slice corresponds to a particular pixel in the emission data. Methods: A method based on maximization of the correlation coefficient, previously used for 3-dimensional datasets, was modified to permit 2-dimensional registrations. Planar transmission measurements were obtained using a collimated Tc-99m flood source in conjunction with planar emission studies. The CT data were first reprojected to permit the 2-dimensional registration. The registration method was evaluated for its accuracy and reproducibility. Results: For phantom data, the registration errors were -0.1 +/- 1.0 mm for x-translations, 1.0 +/- 1.3 mm for gamma-translations, and -0.2 +/- 0.3 degrees for rotations. For patient data, the errors were 1.6 +/- 0.8 mm for x-translations, 1.3 +/- 1.0 mm for gamma-translations, and 0.5 +/- 0.5 degrees for rotations. An examination of the need for rescaling of the attenuation data (to compensate for the different photon energies used in the respective attenuation measurements) showed no significant impact on registration error. When 5 different regions of interest were used for the correlation coefficient calculation, the mean errors attributable to region-of-interest choice alone were 1.0 mm for x-translations, 2.0 mm for gamma-translations, and 1.2 degrees for rotations. Conclusion: In almost all instances, translational registration errors were kept to subpixel levels (pixel size, 2.6 mm) and rotational errors to 1 degrees or less. The 1 exception was in the easily avoidable case of "pitch" rotations of the patient of 2 degrees or more. The modified registration method provides a simple yet reliable way to provide cross-modality evaluation of planar emission data. C1 NIH, Dept Nucl Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Barker, WC (reprint author), NIH, Dept Nucl Med, Warren Grant Magnuson Clin Ctr, Bldg 10,Rm 1C-401,10 Ctr Dr,MSC 1180, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 17 TC 3 Z9 3 U1 0 U2 2 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 2000 VL 41 IS 4 BP 700 EP 705 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 302YE UT WOS:000086393400031 PM 10768572 ER PT J AU Kobayashi, H Kao, CHK Kreitman, RJ Le, N Kim, MK Brechbiel, MW Paik, CH Pastan, I Carrasquillo, JA AF Kobayashi, H Kao, CHK Kreitman, RJ Le, N Kim, MK Brechbiel, MW Paik, CH Pastan, I Carrasquillo, JA TI Pharmacokinetics of In-111- and I-125-labeled antiTac single-chain Fv recombinant immunotoxin SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE interleukin-2 receptor alpha subunit; immunotoxin; In-111; I-125; monoclonal antibody ID B-CELL LYMPHOMA; IN-VIVO BIODISTRIBUTION; PSEUDOMONAS-EXOTOXIN; PHASE-I; MONOCLONAL-ANTIBODY; INTERLEUKIN-2 RECEPTOR; CONTINUOUS-INFUSION; MEDIATED CLEAVAGE; DIPHTHERIA-TOXIN; ZME-GELONIN AB The use of immunotoxins for cancer therapy is an attractive strategy that exploits the targeting specificity of monoclonal antibodies and their fragments as well as the exquisite toxicity of the toxins. However, few studies of immunotoxins have evaluated their biodistribution in vivo. Previous studies have used I-125 for tracing immunotoxin biodistribution in mice. Because the immunotoxin works only when it is internalized and because of known problems with quick dehalogenation after internalization of antibodies, we decided to use In-111, which has greater intracellular retention than iodine. Methods: To trace the in vivo pharmacokinetics of the immunotoxin in mice, we labeled the antiTac(Fv)-PE38 with In-111 and compared it with I-125-labeled antiTac(Fv)-PE38. We successfully labeled antiTac(Fv)-PE38 with In-111 at up to 2.96 GBq/mg. A 3- to 4-fold decrease in cytotoxicity was observed for both radiolabeled preparations. We evaluated the internalization of In-111- and I-125-labeled antiTac(Fv)-PE38 into ATAC4 cells (Tac-positive) as well as their biodistribution and pharmacokinetics in vivo in mice. In addition, some mice receiving these reagents were co-infused with 30 mg L-lysine to inhibit renal accumulation. Results: Significantly more In-111- than I-125-labeled antiTac(Fv)-PE38 accumulated in the ATAC4 cells (20% versus 5% of initial surface-bound radioactivity; P < 0.001). In vivo, significantly more In-111- than I-125-labeled antiTac(Fv)-PE38 accumulated in the kidney (119 versus 31 percentage injected dose per gram [%ID/g]; P < 0.001). The tumor accumulation of In-111-labeled antiTac(Fv)-PE38 at 96 h was 13-fold greater than that of I-125-labeled antiTac(fv)-PE38 (1.4 versus 0.1 %ID/g; P < 0.001). No antiTac(Fv)-PE38 was excreted into the urine in its intact form unless lysine was co-infused. Go-injected lysine reduced the renal accumulation of In-111-labeled antiTac(Fv)-PE38 by 62%. Conclusion: We evaluated the biodistribution, pharmacokinetics, and catabolism of In-111-labeled antiTac(Fv)-PE38 and found that it differed from I-125-labeled antiTac(Fv)-PE38. These studies suggest that In-111-labeled antiTac(Fv)-PE38 can be used to trace the fate of antiTac(Fv)-PE38 in humans. C1 NIH, Dept Nucl Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Chem Sect, Radiat Oncol Branch, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Carrasquillo, JA (reprint author), NIH, Dept Nucl Med, Warren G Magnuson Clin Ctr, Bldg 10,Rm 1C496,10 Ctr Dr,MSC 1180, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 40 TC 34 Z9 35 U1 1 U2 2 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 2000 VL 41 IS 4 BP 755 EP 762 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 302YE UT WOS:000086393400038 PM 10768579 ER PT J AU Robison, WG Jacot, JL Katz, ML Glover, JP AF Robison, WG Jacot, JL Katz, ML Glover, JP TI Retinal vascular changes induced by the oxidative stress of alpha-tocopherol deficiency contrasted with diabetic microangiopathy SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID VITAMIN-E-DEFICIENCY; ALDOSE REDUCTASE; RAT RETINA; ISCHEMIA-REPERFUSION; PIGMENT EPITHELIUM; OUTER SEGMENT; CAPILLARIES; RETINOPATHY; PREVENTION; METABOLISM AB It has been proposed that oxidative tissue damage is involved in the development of diabetic angiopathies. To evaluate this hypothesis, experiments were conducted to identify the retinal vessel changes induced by the oxidative stress related to alpha-tocopherol deficiency and examine possible similarities with the lesions characteristic of diabetic retinopathy. Twenty-one-day-old male Fisher 344 albino rats were divided randomly to receive a basal, chemically defined diet either with (adequate group) or without (deficient group) alpha-tocopherol. After 6 and 8 months, some rats (n = 3 per group) were killed and the eves removed. In order to evaluate cell integrity and localization of lipofuscin-specific autofluorescence by light and fluorescence microscopy, some of the retinas were prepared for cryostat-sections while others were digested by elastase to isolate intact retinal vasculatures. After 8 and 14 months, the central retina of one eye per rat (n = 6 to 8 per group) was examined by electron microscopy for retinal capillary basement membrane (RCBM) thickening and other ultrastructural changes. At 6 and 8 months, the deficient rats exhibited extensive shortening and disarray of rod outer segments (ROS), marked loss of photoreceptor cells, and pronounced increases in the numbers of granules with lipofuscin-specific autofluorescence in the retinal pigment epithelium (RPE) and retinal vessels. At 14 months, the ultrastructure revealed that the damage to ROS involved disruption of membranes and that the capillary lipofuscin was contained mainly within the endothelial cells. Membrane remnants were found in the lipofuscin granules of both the RPE and retinal vessels. In addition, there was an increase in RCBM thickness (98.7 +/- 2.6 nm vs. 86.9 +/- 2.9 nm). RCBM thickening was the only finding common with diabetic retinopathy, and the thickening was 13.6%, significantly less than that reported in diabetic rat models with 8 and 14 months durations (34% and 53.1%, respectively). Capillary lipofuscin accumulation, which was prominent in the deficient rats, is not notable in diabetes. Both the moderate RCBM thickening and marked lipofuscin accumulations seen in alpha-tocopherol-deficient rats were similar to changes occurring in the aging process, though more pronounced. The spectrum of microangiopathies characteristic of diabetic retinopathy did not develop in alpha-tocopherol-deficient rats. These findings suggest that oxidative damage, though probably involved, is unlikely to play a predominant role in the development of diabetic retinal microangiopathies. C1 NEI, NIH, Bethesda, MD 20892 USA. RP Robison, WG (reprint author), NEI, NIH, Bldg 6,Rm 316, Bethesda, MD 20892 USA. FU NEI NIH HHS [EY08813] NR 45 TC 29 Z9 31 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1080-7683 J9 J OCUL PHARMACOL TH JI J. Ocular Pharmacol. Ther. PD APR PY 2000 VL 16 IS 2 BP 109 EP 120 DI 10.1089/jop.2000.16.109 PG 12 WC Ophthalmology; Pharmacology & Pharmacy SC Ophthalmology; Pharmacology & Pharmacy GA 306FX UT WOS:000086587600002 PM 10803422 ER PT J AU Kador, PF Lee, JW Fujisawa, S Blessing, K Lou, MF AF Kador, PF Lee, JW Fujisawa, S Blessing, K Lou, MF TI Relative importance of aldose reductase versus nonenzymatic glycosylation on sugar cataract formation in diabetic rats SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID LENS PROTEIN GLYCATION; GLUTATHIONE; INHIBITION; PATHWAY AB The relative importance of sorbitol formation versus nonenzymatic glycosylation and advanced glycosylation end products (AGEs) on sugar cataract formation was examined in diabetic rats. Diabetes was experimentally induced in young, 50 g rats with streptozotocin, and aldose reductase inhibitors were administered in the diet for up to 8 weeks at concentrations of 0.06% for tolrestat or ponalrestat and 0.0125% for AL-1576. Cataract formation was monitored by hand-held slit lamp for up to 11 weeks. Lens polyol levels were monitored by GLC, glycosylated protein levels were spectrophotometrically determined, and AGE products were estimated by fluorescence measurements and ELISA. Sugar cataract formation was observed in all untreated diabetic rats while cataract formation was inhibited in all diabetic rats treated with the AR inhibitors. Lens sorbitol levels were reduced in all ARI-treated rats. Glycosylated lens protein levels were elevated in the diabetic rats, and these levels were not significantly lower in the non-cataractous lenses from ARI-treated diabetic rats. Fluorescence measurements of the lens proteins revealed increased lens AGE levels in all diabetic rats, and these were slightly reduced in the aldose reductase inhibitor treated diabetics. With ELISA, immunoreactive AGEs were only detected in cataractous lenses from the untreated diabetic rats. Immunoreactive AGEs were not detected in the clear lenses of the aldose reductase inhibitor treated diabetics or in the non-diabetic controls. These results support the concept that sugar cataract formation is initiated by the aldose reductase catalyzed intracellular accumulation of polyols and that these sugar cataracts can be prevented through inhibition of aldose reductase. C1 NEI, Lab Ocular Therapeut, NIH, Bethesda, MD 20892 USA. RP Kador, PF (reprint author), NEI, Lab Ocular Therapeut, NIH, 10 Ctr Dr MSC 1850,Bldg 10,Room 10B11, Bethesda, MD 20892 USA. NR 33 TC 25 Z9 25 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1080-7683 J9 J OCUL PHARMACOL TH JI J. Ocular Pharmacol. Ther. PD APR PY 2000 VL 16 IS 2 BP 149 EP 160 DI 10.1089/jop.2000.16.149 PG 12 WC Ophthalmology; Pharmacology & Pharmacy SC Ophthalmology; Pharmacology & Pharmacy GA 306FX UT WOS:000086587600005 PM 10803425 ER PT J AU Glover, JP Jacot, JL Basso, MD Hohman, TC Robison, WG AF Glover, JP Jacot, JL Basso, MD Hohman, TC Robison, WG TI Retinal capillary dilation: Early diabetic-like retinopathy in the galactose-fed rat model SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID ALDOSE REDUCTASE INHIBITOR; INTERVENTION; PREVENTION AB The purpose of this study was to determine whether capillary dilation is one of the earliest structural changes in the diabetic-like retinopathy of the galactose-fed rat model and thus may represent a stage where intervention treatment might still be effective. Weanling female Sprague-Dawley rats were randomized into 3 groups and fed Purina laboratory chow plus one of the following for 4 months: 50% starch (Control); 50% D-galactose (Galactose); or 50% D-galactose with ARI-509 (25 mg/kg body wt/day) (lnhibitor). One eye from each of 5 rats per treatment group was processed for retinal vasculature wholemounts using elastase digestion, stained with a standard periodic-acid-Schiff reaction and counterstained with hematoxylin. Average capillary width, overall capillary density and total capillary length were measured, using computerized image analysis, within an are-shaped area (4.4 mm(2)) of each vasculature surrounding, but separated from, the optic disc margin by approximately 0.7 mm. Galactose rats exhibited significant (p < 0.001) increases in capillary width (Mean +/- SEM: 7.56 +/- 0.07 mu m) and density (42.78 +/- 0.37%) compared with Control rats (6.68 +/- 0.11 mu m and 37.18 +/- 0.30%, respectively). These increases were prevented with inhibitor treatment (6.58 +/- 0.16 mu m and 35.88 +/- 0.97%, respectively). Capillary length remained unchanged at 4 months (Control: 246.66 +/- 2.46 mm; Galactose: 250.75 +/- 1.26 mm;Inhibitor: 242.25 +/- 8.43 mm). Retinal capillary dilation, expressed as increased width and density, is one of the earliest detectable lesions in galactose-fed rats. In these rats, the lesion occurs as early as retinal capillary basement membrane thickening (RCBMT), one of the earliest reported changes in human diabetic retinopathy. Like RCBMT, capillary dilation can be prevented in rats with aldose reductase inhibitor treatment. Unlike RCBMT, capillary dilation could be clinically detectable and may be useful for the diagnosis of early retinopathy and for determining the timing of therapeutic intervention. C1 NEI, NIH, Bethesda, MD 20892 USA. RP Robison, WG (reprint author), NEI, NIH, Bldg 6,Room 316, Bethesda, MD 20892 USA. NR 13 TC 5 Z9 5 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1080-7683 J9 J OCUL PHARMACOL TH JI J. Ocular Pharmacol. Ther. PD APR PY 2000 VL 16 IS 2 BP 167 EP 172 DI 10.1089/jop.2000.16.167 PG 6 WC Ophthalmology; Pharmacology & Pharmacy SC Ophthalmology; Pharmacology & Pharmacy GA 306FX UT WOS:000086587600007 PM 10803427 ER PT J AU Piatigorsky, J AF Piatigorsky, J TI Review: A case for corneal crystallins SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID MAJOR SOLUBLE-PROTEIN; ALDEHYDE DEHYDROGENASE; LENS CRYSTALLINS; BOVINE CORNEA; ALPHA-CRYSTALLIN; GENE; IDENTIFICATION; EXPRESSION; EYE; TRANSKETOLASE AB It is established that the diverse, multifunctional crystallins are responsible for the optical properties of the cellular, transparent lens of the complex eyes of vertebrates and invertebrates. Lens crystallins often differ among species and may be enzymes or stress proteins. I present here the idea that abundant water-soluble enzymes and other proteins may also be used for cellular transparency in the epithelial cells and, possibly, stromal keratocytes of the cornea. Aldehyde dehydrogenases and transketolase are among the putative "corneal crystallins" in mammals, and gelsolin may be a corneal crystallin in the zebrafish. In invertebrates, the glutathione S-transferase-related S-crystallins of the lens appear to be used also as corneal crystallins in the squid, and an aldehyde dehydrogenase-related protein is the crystallin in the lens and, possibly, cornea of the scallop. The use of abundant, taxonspecific water-soluble proteins as crystallins for cellular transparency in the cornea would provide a new conceptual link between this tissue and the lens. C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Piatigorsky, J (reprint author), NEI, Mol & Dev Biol Lab, NIH, 6 Ctr Dr,Room 201, Bethesda, MD 20892 USA. NR 43 TC 43 Z9 44 U1 1 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1080-7683 J9 J OCUL PHARMACOL TH JI J. Ocular Pharmacol. Ther. PD APR PY 2000 VL 16 IS 2 BP 173 EP 180 DI 10.1089/jop.2000.16.173 PG 8 WC Ophthalmology; Pharmacology & Pharmacy SC Ophthalmology; Pharmacology & Pharmacy GA 306FX UT WOS:000086587600008 PM 10803428 ER PT J AU Raff, SB Carney, JA Krugman, D Doppman, JL Stratakis, CA AF Raff, SB Carney, JA Krugman, D Doppman, JL Stratakis, CA TI Prolactin secretion abnormalities in patients with the "syndrome of spotty skin pigmentation, myxomas, endocrine overactivity and schwannomas" (Carney complex) SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 80th Annual Meeting of the Endocrine-Society CY JUN 21-27, 1998 CL NEW ORLEANS, LOUISIANA SP Endocrine Soc DE prolactin; Carney complex; somatomedin C; insulin-like growth factor I; multiple endocrine neoplasia syndromes; McCune Albright syndrome ID MCCUNE-ALBRIGHT SYNDROME; HUMAN PITUITARY-TUMORS; GROWTH-HORMONE GH; ACTIVATING MUTATIONS; SPECIAL ASSOCIATIONS; CUTANEOUS MYXOMAS; CARDIAC MYXOMAS; GENETIC-LOCUS; IGF-I; HYPERPROLACTINEMIA AB Carney complex is a multiple neoplasia and lentiginosis syndrome. Acromegaly due to growth hormone (GH)-producing adenomas has been considered the only pituitary-related manifestation of the complex. In the present study, seven patients with Carney complex, who belonged to three unrelated kindreds and had relatives with acromegaly, were investigated for the presence of GH and prolactin (PRL) secretion abnormalities (familial cases). In addition, four patients with the complex and no family history of the complex were studied (sporadic cases). Seven of the patients were female and four were male; their mean age was 24.27 +/- 4.34 years, Sampling every 20 min for one hour in the morning and under fasting and unstimulated conditions was performed in all patients, for determination of serum PRL levels. Insulin-like growth factor-I (IGF-I) levels and magnetic resonance imaging (MRI) of the pituitary were also obtained. Patients who had elevated IGF-I levels underwent investigation for acromegaly by oral glucose tolerance test and thyrotropin-releasing hormone. Seven of the 11 patients (63.6%) had moderately high PRL levels (mean Z score value 2.12 +/- 0.66); three of these patients also had elevated IGF-I levels but a negative investigation for acromegaly, All patients had negative pituitary MRI, The patient with the highest PRL levels underwent 24-hour sampling every 20 min, which demonstrated a higher baseline secretion of this hormone with preservation of its circadian pulsatility, Hyperprolactinemia was present in two siblings and a parent-child pair. We conclude that prolactin hypersecretion, albeit mild, appears to be frequent in patients with Carney complex, is inherited in an autosomal dominant manner in kindreds with the syndrome, and may be associated with elevated IGF-I levels in some, but not all, patients. C1 NICHD, Unit Genet & Endocrinol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NICHD, Dept Diagnost Radiol, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. Univ Connecticut, New Britain Gen Hosp, Sch Med, New Britain, CT USA. Mayo Clin & Mayo Fdn, Dept Lab Med & Pathol, Rochester, MN 55905 USA. RP Stratakis, CA (reprint author), NICHD, Unit Genet & Endocrinol, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262,10 Ctr Dr MSC 1862, Bethesda, MD 20892 USA. NR 32 TC 29 Z9 29 U1 0 U2 1 PU FREUND PUBLISHING HOUSE LTD PI LONDON PA STE 500, CHESHAM HOUSE, 150 REGENT ST, LONDON W1R 5FA, ENGLAND SN 0334-018X J9 J PEDIATR ENDOCR MET JI J. Pediatr. Endocrinol. Metab. PD APR PY 2000 VL 13 IS 4 BP 373 EP 379 PG 7 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 303CD UT WOS:000086402500004 PM 10776991 ER PT J AU Gladen, BC Ragan, NB Rogan, WJ AF Gladen, BC Ragan, NB Rogan, WJ TI Pubertal growth and development and prenatal and lactational exposure to polychlorinated biphenyls and dichlorodiphenyl dichloroethene SO JOURNAL OF PEDIATRICS LA English DT Article ID FEMALE RATS; DDT HOMOLOGS; SELF-REPORT; HUMAN-MILK; IN-UTERO; PCBS; REPRODUCTION; ADOLESCENTS; MATURATION; TOXICITY AB Objectives: Polychlorinated biphenyls (PCBs) and dichlorodiphenyl dichloroethene (DDE) are ubiquitous toxic environmental contaminants. Prenatal and early life exposures affect pubertal events in experimental animals. We studied whether prenatal or lactational exposures to background levels of PCBs or DDE were associated with altered pubertal grow th and development in humans. Study design: Follow-up of 594 children from an existing North Carolina cohort whose prenatal and lactational exposures had previous been measured. Height, weight, and stage of pubertal development were assessed through annual mail questionnaires. Results: Height of boys at puberty increased with transplacental exposure to DDE, as did weight adjusted for height; adjusted means for those with the highest exposures (maternal concentration 4+ ppm fat) were 6.3 cm taller and 6.9 kg larger than those with the lowest (0 to 1 ppm). There was no effect on the ages at which pubertal stages were attained. Lactational exposures to DDE had no apparent effects; neither did transplacental or lactational exposure to PCBs. Girls with the highest transplacental PCB exposures were heavier for their heights than other girls by 5.4 kg, but differences were significant only if the analysis was restricted to white girls. Conclusions: Prenatal exposures at background levels mag affect body size at puberty. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Gladen, BC (reprint author), NIEHS, Biostat Branch, Mail Drop A3-03,POB 12233, Res Triangle Pk, NC 27709 USA. RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 NR 30 TC 160 Z9 161 U1 2 U2 13 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD APR PY 2000 VL 136 IS 4 BP 490 EP 496 DI 10.1016/S0022-3476(00)90012-X PG 7 WC Pediatrics SC Pediatrics GA 302LU UT WOS:000086367200013 PM 10753247 ER PT J AU He, JY Cheung, AP Wang, E Struble, E Fang, KX Nguyen, N Liu, P AF He, JY Cheung, AP Wang, E Struble, E Fang, KX Nguyen, N Liu, P TI Stability-indicating LC assay of and impurity identification in homoharringtonine samples SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article; Proceedings Paper CT 10th International Symposium on Pharmaceutical and Biomedical Analysis (PBA 99) CY MAY 09-12, 1999 CL WASHINGTON, D.C. DE homoharringtonine; new congeners; decomposition products; identity; validated stability-indicating HPLC assay ID HARRINGTONIA VAR DRUPACEA; CEPHALOTAXUS-HARRINGTONIA; PHASE-II; MYELOGENOUS LEUKEMIA; ALKALOIDS AB Homoharringtonine (HHT) is a potent myelosuppressive agent and has antitumor activity. Recent studies suggest that it inhibits tumor growth by inducing apoptosis. HHT is an ester of the alkaloid cephalotaxine. It is isolated from genus Cephalotaxus. At least ten HHT analogs have been identified from cephalotaxus extracts. High performance liquid chromatography (HPLC) separations of the cephalotaxine alkaloids in plant extracts have been reported, they have not been validated as specific and stability-indicating for HHT. Due to the complexity of the alkaloid extracts, it is conceivable that additional analogs may still be unresolved from HHT. This paper presents an improved and validated HPLC assay for HHT. The assay is stability-indicating, precise (R.S.D. < 1%), linear (r(2) = 0.9999), and accurate (error < 1%). The assay reveals three congeners present as impurities in HHT samples. Two are new and have not been previously reported. Identities of the impurities and forced decomposition products, elucidated with their HPLC retention and spectral data, are also presented. (C) 2000 Elsevier Science B.V. All rights reserved. C1 SRI Int, Biopharmaceut Dev Div, Menlo Park, CA 94025 USA. NCI, Pharmaceut Resources Branch, DCTD, NIH, Bethesda, MD 20892 USA. RP He, JY (reprint author), SRI Int, Biopharmaceut Dev Div, 333 Ravenswood Ave, Menlo Park, CA 94025 USA. FU NCI NIH HHS [N01-CM-77104] NR 21 TC 10 Z9 10 U1 1 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD APR PY 2000 VL 22 IS 3 BP 541 EP 554 DI 10.1016/S0731-7085(99)00314-3 PG 14 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 301BK UT WOS:000086288100015 PM 10766371 ER PT J AU He, JY Cheung, AP Struble, E Wang, E Liu, P AF He, JY Cheung, AP Struble, E Wang, E Liu, P TI Enantiomeric separation of an aryloxyphenoxypropanoic acid by CE and LC SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article; Proceedings Paper CT 10th International Symposium on Pharmaceutical and Biomedical Analysis (PBA 99) CY MAY 09-12, 1999 CL WASHINGTON, D.C. DE aryloxyphenoxypropanoic acid; chloroquinoxalinyloxyphenoxypropanoic acid; chiral separation; capillary electrophoresis; high-performance liquid chromatography; hydroxypropyl cyclodextrin; teicoplanin ID CAPILLARY-ZONE-ELECTROPHORESIS; PERFORMANCE LIQUID-CHROMATOGRAPHY; CYCLODEXTRIN INCLUSION COMPLEXES; CHIRAL STATIONARY-PHASE; BETA-CYCLODEXTRIN; CYCLOHEXANEDIONE HERBICIDES; MASS-SPECTROMETRY; RESOLUTION; RESISTANCE; FLUAZIFOP AB A capillary electrophoresis (CE) and an high performance liquid chromatography (HPLC) chiral separation have been developed for an aryloxyphenoxypropanoic acid, 2-{4-[(7-chloro-2-quinoxalinyl)oxy]phenoxy} propanoic acid, a new antitumor agent. The racemic mixture is analyzed, without derivatization, as the free acids. The CE assay is based on inclusion complexation with hydroxypropyl-beta-cyclodextrin. HPLC separation is achieved with a CSP column with the glycopeptide, teicoplanin, as the chiral selector. Both methods give baseline resolution to the R-and S-isomers. The methods were validated for assay and for optical purity assessment of the R-isomer. For assay, the HPLC method is precise (RSD < 0.6%), accurate (error, 0.5%) and linear (r(2) = 0.9998). It is able to precisely (RSD = 0.5%) and accurately (error, 0.9%) detect 0.3-6.0% of one isomer (S) in the other (R). The CE assay is much less precise and accurate than HPLC. It is a good alternative to separate and detect the enantiomers, however. (C) 2000 Elsevier Science B.V. All rights reserved. C1 SRI Int, Biopharmaceut Dev Div, Menlo Park, CA 94025 USA. NCI, Pharmaceut Resources Branch, DCTD, NIH, Bethesda, MD 20892 USA. RP He, JY (reprint author), SRI Int, Biopharmaceut Dev Div, 333 Ravenswood Ave, Menlo Park, CA 94025 USA. FU NCI NIH HHS [N01-CM-77104] NR 35 TC 5 Z9 5 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD APR PY 2000 VL 22 IS 3 BP 583 EP 595 DI 10.1016/S0731-7085(00)00231-4 PG 13 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 301BK UT WOS:000086288100019 PM 10766375 ER PT J AU He, M Shippenberg, TS AF He, M Shippenberg, TS TI Strain differences in basal and cocaine-evoked dopamine dynamics in mouse striatum SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID LOCOMOTOR-ACTIVITY; NUCLEUS-ACCUMBENS; IN-VIVO; QUANTITATIVE MICRODIALYSIS; EXTRACELLULAR DOPAMINE; INBRED STRAINS; DBA MICE; AMPHETAMINE; C57BL/6J; INVIVO AB In vivo microdialysis was used to characterize basal dopamine (DA) dynamics and cocaine-evoked DA levels in the striatum of 129/Sv-ter, C57BL/6J, DBA/2J, and Swiss-Webster mice. Basal dialysate levels of DA did not differ in the four strains tested. Similarly, the no net flux method of quantitative microdialysis revealed no difference in extracellular levels between strains. However, the in vivo extraction fraction of DA was significantly less in 129/Sv-ter (53%) mice compared with C57BL/6J (68%), DBA/2J (69%), and Swiss-Webster (67%) mice, indicating a lower rate of basal DA uptake in the 129/Sv-ter strain. Perfusion of K+ (60 and 100 mM) through the microdialysis probe significantly increased dialysate DA levels and there was no difference between strains in the magnitude of this effect. The acute administration of cocaine (5-20 mg/kg i.p.) increased DA levels in the four strains tested. Cocaine-evoked DA levels (in nanomoles) were significantly greater in 129/Sv-ter compared with C57BL/6J, DBA/2J, or Swiss-Webster mice after administration of either 5, 10, or 20 mg/kg cocaine. However, the percentage increase in DA did not differ across strains. These data demonstrate that there are strain-related differences in basal DA dynamics in the striatum of the mouse. Basal DA uptake was reduced in striatum of 129/Sv-ter mice compared with C57BL/6J, DBA/2J, or Swiss-Webster mice. In addition, the response of DA levels to cocaine may be enhanced in 129/Sv-ter compared with C57BL/6J, DBA/2J, or Swiss-Webster mice. C1 NIDA, Integrat Neurosci Unit, Behav Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Shippenberg, TS (reprint author), NIDA, Integrat Neurosci Unit, Behav Neurosci Lab, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 42 TC 43 Z9 43 U1 1 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD APR PY 2000 VL 293 IS 1 BP 121 EP 127 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 307QQ UT WOS:000086664800016 PM 10734161 ER PT J AU Kono, H Rusyn, I Bradford, BU Connor, HD Mason, RP Thurman, RG AF Kono, H Rusyn, I Bradford, BU Connor, HD Mason, RP Thurman, RG TI Allopurinol prevents early alcohol-induced liver injury in rats SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID TUMOR-NECROSIS-FACTOR; INTRAGASTRIC ETHANOL INFUSION; NF-KAPPA-B; KUPFFER CELLS; XANTHINE-OXIDASE; DIETARY-FAT; DISEASE; MACROPHAGES; REPERFUSION; INHIBITION AB Free radical formation caused by chronic ethanol administration could activate transcription factors such as nuclear factor-kappa B (NF-kappa B), which regulates production of inflammatory cytokines. Xanthine oxidase is one potential source of reactive oxygen species. Therefore, the purpose of this study is to determine whether allopurinol, a xanthine oxidase inhibitor and scavenger of free radicals, would affect free radical formation, NF-kappa B activation, and early alcohol-induced liver injury in rats. Male Wistar rats were fed a high-fat diet with or without ethanol (10-16 g/kg/day) continuously for up to 4 weeks with the Tsukamoto-French enteral protocol. Either allopurinol or saline vehicle was administered daily. Allopurinol had no effect on body weight or the cyclic pattern of ethanol in urine. Mean urine ethanol concentrations were 271 +/- 38 and 252 +/- 33 mg/dl in ethanol- and ethanol + allopurinol-treated rats, respectively. In the control group, serum aspartate aminotransferase and alanine aminotransferase levels were similar to 40 I.U./I and 25 U/I, respectively. Administration of enteral ethanol for 4 weeks increased serum transaminases similar to 5-fold. Allopurinol blunted these increases significantly by similar to 50%. Ethanol treatment also caused severe fatty infiltration, mild inflammation, and necrosis. These pathological changes also were blunted significantly by allopurinol. Furthermore, enteral ethanol caused free radical adduct formation, values that were reduced by similar to 40% by allopurinol. NF-kappa B binding was minimal in the control group but was increased significantly nearly 2.5-fold by ethanol. This increase was blunted to similar values as control by allopurinol. These results indicate that allopurinol prevents early alcohol-induced liver injury, most likely lay preventing oxidant-dependent activation of NF-kappa B. C1 Univ N Carolina, Dept Pharmacol, Hepatobiol & Toxicol Lab, Chapel Hill, NC 27599 USA. Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC 27599 USA. Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, Res Triangle Pk, NC USA. RP Rusyn, I (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 NR 45 TC 67 Z9 68 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD APR PY 2000 VL 293 IS 1 BP 296 EP 303 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 307QQ UT WOS:000086664800037 PM 10734182 ER PT J AU McBain, CJ AF McBain, CJ TI Multiple forms of feedback inhibition by str. oriens inhibitory interneurons? SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Editorial Material ID STRATUM-ORIENS; HIPPOCAMPUS; INPUT C1 NICHD, LCMN, Bethesda, MD 20892 USA. RP McBain, CJ (reprint author), NICHD, LCMN, Rm 5A72,Bldg 49,49 Convent Dr, Bethesda, MD 20892 USA. NR 7 TC 4 Z9 4 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD APR 1 PY 2000 VL 524 IS 1 BP 2 EP 2 DI 10.1111/j.1469-7793.2000.t01-3-00002.x PG 1 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 305ZP UT WOS:000086571900002 PM 10747179 ER PT J AU Connaughton, VP Nelson, R AF Connaughton, VP Nelson, R TI Axonal stratification patterns and glutamate-gated conductance mechanisms in zebrafish retinal bipolar cells SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID CARP RETINA; ON-CENTER; 2-AMINO-4-PHOSPHONOBUTYRIC ACID; CENTRAL ILLUMINATION; INDUCED RESPONSES; GANGLION-CELLS; RAT RETINA; CAT RETINA; RECEPTORS; GOLDFISH AB 1. Whole-cell patch recording and puff pipette techniques were used to identify glutamate receptor mechanisms on bipolar cell (BC) dendrites in the zebrafish retinal slice. Recorded neurons were stained with Lucifer Yellow, to correlate glutamate responses with BC morphology. 2. BC axon terminals (ATs) consisted of swellings or varicosities along the axon, as well as at its end. AT stratification patterns identified three regions in the inner plexiform layer (IPL): a thick sublamina a, with three bands of ATs, a narrow terminal-free zone in the mid-IPL, and a thin sublamina b, with two bands of ATs. BCs occurred with ATs restricted to sublamina a (Group a), sublamina b (Group b) or with ATs in both sublaminae (Group a/b). 3. OFF-BCs belonged to Group a or Group alb. These cells responded to glutamate or kainate with a CNQX-sensitive conductance increase. Reversal potential (E-rev) ranged from -0.6 to +18 mV. Bipolar cells stimulated sequentially with both kainate and glutamate revealed a population of glutamate-insensitive, kainate-sensitive cells in addition to cells sensitive to both agonists. 4. ON-BCs responded to glutamate via one of three mechanisms: (a) a conductance decrease with E-rev approximate to 0 mV, mimicked by L-(+)-2-amino-4-phosphonobutyric acid (APB) or trans-1-amino-1,3-cyclopentanedicarboxylic acid (trans-ACPD), (b) a glutamate-gated chloride conductance increase (I-Glu-like) characterized by E-rev greater than or equal to E-cl (where E-cl is the chloride equilibrium potential) and partial blockade by extracellular Li+/Na+ substitution or (c) the activation of both APE and chloride mechanisms simultaneously to produce a response with outward currents at all holding potentials. APE-like responses were found only among BCs in Group b, with a single AT ramifying deep within sublamina b; whereas, cells expressing I-Glu-like currents had one or more ATs, and occurred within Groups b or a/b. 5. Multistratified cells (Group alb) were common and occurred with either ON- or OFF-BC physiology. OFF-BCs typically had one or more ATs in sublamina a and only one AT in sublamina b. In contrast, multistratified ON-BCs had one or more ATs in sublamina b and a single AT ramifying deep in sublamina a. Multistratified ON-BCs expressed the I-Glu-like mechanism only. 6. Visual processing in the zebrafish retina involves at least 13 BC types. Some of these BCs have ATs in both the ON- and OFF-sublaminae, suggesting a significant role for ON- and OFF-inputs throughout the IPL. C1 NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Connaughton, VP (reprint author), American Univ, Dept Biol, 4400 Massachusetts Ave NW, Washington, DC 20016 USA. NR 44 TC 52 Z9 53 U1 1 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD APR 1 PY 2000 VL 524 IS 1 BP 135 EP 146 DI 10.1111/j.1469-7793.2000.t01-1-00135.x PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 305ZP UT WOS:000086571900011 PM 10747188 ER PT J AU Gerin, W Pickering, TG Glynn, L Christenfeld, N Schwartz, A Carroll, D Davidson, K AF Gerin, W Pickering, TG Glynn, L Christenfeld, N Schwartz, A Carroll, D Davidson, K TI An historical context for behavioral models of hypertension SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Review DE cardiovascular reactivity; blood pressure; heart rate; hypertension; individual differences ID BLOOD-PRESSURE REACTIVITY; CARDIOVASCULAR REACTIVITY; SOCIAL SUPPORT; MENTAL STRESS AB Objective: The pul pose of this study is provide an historical context for current behavioral models of hypertension. Methods: A selective sample of the cardiovascular reactivity literature was reviewed, from 1932 to present. Results: In the earliest model, cardiovascular reactivity was regarded as a marker of disease risk; however, in later models, reactivity came to be viewed as a causal influence in the development of hypertension. As the models evolved, the underlying assumptions changed. Thus, the risk marker model assumed that cardiovascular responses to stress were a stable, generalized characteristic of the individual, and therefore the eliciting stimuli were arbitrary. The later models, however, assume that the nature of the eliciting stimulus is a determinant of the cardiovascular response, We describe the increasing complexity of the four models, and contrast their underlying assumptions and the implications of these assumptions. Conclusion: We provide an overview of study designs and variables that should be incorporated into studies seeking to understand the ways in which cardiovascular responses to stress may influence the development of hypertension. (C) 2000 Elsevier Science Inc. All rights reserved. C1 NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. Cornell Univ, New York Hosp, Med Ctr, Hypertens Ctr, New York, NY 10021 USA. Univ Calif Irvine, Irvine, CA 92717 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Univ Birmingham, Birmingham, W Midlands, England. Univ Alabama, Tuscaloosa, AL 35401 USA. RP Gerin, W (reprint author), NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [P01 HL 47540] NR 43 TC 48 Z9 49 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD APR-MAY PY 2000 VL 48 IS 4-5 BP 369 EP 377 DI 10.1016/S0022-3999(99)00095-1 PG 9 WC Psychiatry SC Psychiatry GA 329HA UT WOS:000087900500009 PM 10880659 ER PT J AU Henderson, CE Ownby, DR Trumble, A DerSimonian, R Kellner, LH AF Henderson, CE Ownby, DR Trumble, A DerSimonian, R Kellner, LH TI Predicting asthma severity from allergic sensitivity to cockroaches in pregnant inner city women SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE asthma; cockroaches; IgE; pregnancy complications ID SKIN-TEST REACTIVITY; SERUM IGE; AIRWAY RESPONSIVENESS; ASSOCIATION; CHILDREN; ATOPY AB OBJECTIVE: To measure and compare cockroach (CR)-specific immunoglobin E (IgE) in sera from pregnant women with mild, moderate and severe asthma. STUDY DESIGN: CR IgE Levels were measured in stored sera collected during the Collaborative Perinatal Project. Three matched groups of 93 women were formed: group I (mild), history of asthma but no acute exacerbation; group II (moderate), acute asthma exacerbation; group III (severe), required hospitalization for a diagnosis of status asthmaticus. ANOVA was used to compare the three means. RESULTS: Mean CR IgE paralleled prenatal asthma severity. Mean values were 6.50, 13.12 and 28.99 kU/L for groups I, II and III, respectively (P =.06). High allergen sensitivity, defined as CR IgE > 60 kU/L, was identified in 8 of the 93 study samples. The prevalence of high allergen sensitivity increased as clinical asthma became more severe. Sixty-two per cent (5/8) of the high allergen sensitivity occurred in group III. CONCLUSION: There appears to be a positive correlation between sensitivity to CR allergens and asthma severity during pregnancy, and these findings support further evaluation of CR allergen sensitivity as a predictor of asthma severity in pregnancy. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Obstet & Gynecol & Womens Hlth, Bronx, NY 10461 USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Med Coll Georgia, Dept Pediat, Sect Allergy Immunol, Augusta, GA 30912 USA. NICHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA. RP Henderson, CE (reprint author), Jack D Weiler Hosp, Room 703,1825 Eastchester Rd, Bronx, NY 10461 USA. NR 22 TC 10 Z9 10 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA P.O. DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD APR PY 2000 VL 45 IS 4 BP 341 EP 344 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 308DB UT WOS:000086694300011 PM 10804493 ER PT J AU Zhang, YQ Hannan, MT Chaisson, CE McAlindon, TE Evans, SR Aliabadi, P Levy, D Felson, DT AF Zhang, YQ Hannan, MT Chaisson, CE McAlindon, TE Evans, SR Aliabadi, P Levy, D Felson, DT TI Bone mineral density and risk of incident and progressive radiographic knee osteoarthritis in women: the Framingham Study SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE bone mineral density; osteoarthritis; longitudinal studies ID REPLACEMENT-THERAPY; OSTEO-ARTHRITIS; OSTEOPOROSIS; HIP; ASSOCIATION; THICKNESS; CHINGFORD; HAND; AGE; MEN AB Objective. To examine the relations of bone mineral density (BMD) and change in BMD to risk of incident and progressive radiographic knee osteoarthritis COA) in a longitudinal cohort study. Methods. Female participants aged 63 to 91 years (mean age 71) in the Framingham Study received anteroposterior weight bearing knee radiographs at biennial examinations 18 (1983-85) and 22 (1992-93). Knee radiographs were given scores for global severity of OA (Kellgren-Lawrence scale: range 0 to 4) add for the presence of osteophytes and joint space narrowing (range 0 to 3). Femoral neck BMD was assessed using dual photon absorptiometry at examination 20 and dual x-ray absorptiometry at examination 22. We examined the relations of BMD at examination 20 and its change between examination 20 and examination 22 to incident and progressive knee OA, as well as to worsening of individual radiographic features adjusting for age, body mass index, and other potential confounding factors. Results. In total, 473 women (ages 63 to 91 yrs) had complete assessments. Over 8 years of Followup, risk of incident radiographic knee OA increased from 5.6% among women in the lowest age-specific quartile of BMD to 14.2, 10.3, and 11.8% among women in the 2nd, 3rd, and highest; quartiles, respectively, Multivariate adjusted OR of incident OA for each increase quartile of BMD were 1.0, 2.5, 2.0, and 2.3, respectively (p for trend = 0.222). This was mainly reflected in an increased risk of osteophyte: development. However, risk of progressive OA decreased from 34.4 to 22,0, 20.3, and 18.9% as BMD increased. Compared to those in the lowest quartile of BMD, adjusted OR for progressive disease were 0.3, 0.2, and 0.1 among women in the 2nd, 3rd, and highest quartiles (p for trend < 0.001), respectively, mainly due to its effect on lowering the risk of joint space lass. Compared to those who lost BMD > 0.04 g/cm(2) over the followup period, women who gained BMD were at increased risk of incident but at a significantly decreased risk of progressive knee OA. BMD change was not associated with osteophyte development, but gain in BMD lowered the risk of joint space loss. Conclusion. High BMD and BMD gain decreased the risk of progression of radiographic knee OA, but may be associated with an increased risk of incident knee Ok The protective effect was mainly through its influence on reducing the risk of joint space loss. Our results offer insights into how bone may affect the course of the most common joint disease, and thus may have potential therapeutic implications. C1 Boston Univ, Med Ctr, Arthrit Ctr, Boston, MA 02115 USA. Hebrew Rehabil Ctr Aged, Res & Training Inst, Boston, MA 02131 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Aging, Boston, MA 02115 USA. NHLBI, Framingham Heart Study, NIH, Boston, MA USA. RP Felson, DT (reprint author), Boston Univ, Med Ctr, Arthrit Ctr, Room A-203,80 E Concord St, Boston, MA 02115 USA. FU NHLBI NIH HHS [N01-HC-38038]; NIA NIH HHS [AG09300]; NIAMS NIH HHS [AR20613] NR 30 TC 130 Z9 136 U1 0 U2 233 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 2000 VL 27 IS 4 BP 1032 EP 1037 PG 6 WC Rheumatology SC Rheumatology GA 305KD UT WOS:000086538100033 PM 10782833 ER PT J AU Barrios, LC Baer, K Bennett, G Bergan, A Bryn, S Callaway, S Davis, D Downs, R Dressler, K Ho, T Karp, N Mathews-Younes, A MacMurray, N O'Brien, E Overpeck, M Reed, W Small, M Tuma, F AF Barrios, LC Baer, K Bennett, G Bergan, A Bryn, S Callaway, S Davis, D Downs, R Dressler, K Ho, T Karp, N Mathews-Younes, A MacMurray, N O'Brien, E Overpeck, M Reed, W Small, M Tuma, F TI Federal activities addressing violence in schools SO JOURNAL OF SCHOOL HEALTH LA English DT Article C1 Ctr Dis Control & Prevent, Div Adolescent & Sch Hlth, Atlanta, GA 30341 USA. Subst Abuse & Mental Hlth Serv Adm, Rockville, MD USA. US Dept Justice, Washington, DC 20530 USA. US Hlth Resources & Serv Adm, Rockville, MD 20857 USA. US Dept Housing & Urban Dev, Washington, DC 20410 USA. Off Natl Drug Control Policy, Washington, DC 20006 USA. NIH, Bethesda, MD 20892 USA. RP Barrios, LC (reprint author), Ctr Dis Control & Prevent, Div Adolescent & Sch Hlth, 4770 Buford Highway NE,Mailstop K-33, Atlanta, GA 30341 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SCHOOL HEALTH ASSOC PI KENT PA PO BOX 708, KENT, OH 44240 USA SN 0022-4391 J9 J SCHOOL HEALTH JI J. Sch. Health PD APR PY 2000 VL 70 IS 4 BP 119 EP 140 PG 22 WC Education & Educational Research; Education, Scientific Disciplines; Health Care Sciences & Services; Public, Environmental & Occupational Health SC Education & Educational Research; Health Care Sciences & Services; Public, Environmental & Occupational Health GA 305MV UT WOS:000086544700001 ER PT J AU Wolffe, AP Guschin, D AF Wolffe, AP Guschin, D TI Chromatin structural features and targets that regulate transcription SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Review ID THYROID-HORMONE RECEPTOR; RIBOSOMAL-RNA GENE; NUCLEOSOME CORE STRUCTURE; MITOTIC CHROMOSOME CONDENSATION; MAMMALIAN HISTONE DEACETYLASE; ACIDIC ACTIVATION DOMAINS; XENOPUS-LAEVIS OOCYTE; YEAST SWI/SNF COMPLEX; TATA-BINDING PROTEIN; DNA METHYLATION AB The nucleosome and chromatin fiber provide the common structural framework for transcriptional control in eukaryotes. The folding of DNA within these structures can both promote and impede transcription dependent on structural context. Importantly, neither the nucleosome nor the chromatin fiber is a static structure. Histone dissociation, histone modification, nucleosome mobility, and assorted allosteric transitions contribute to transcriptional control. Chromatin remodeling is associated with gene activation and repression. Energy-dependent processes mediate the assembly of both activating and repressive proteins into the nucleosomal infrastructure. Recent progress allows the structural consequences of these processes to be visualized at the chromosomal level. DNA and RNA polymerase, SWI/SNF complexes, histone deacetylases, and acetyltransferases are targeted by gene-specific regulators to mediate these structural transitions. The mistargeting of these enzymes contributes to human developmental abnormalities and tumorigenesis. These observations illuminate the roles of chromatin and chromosomal structural biology in human disease. C1 NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RP Wolffe, AP (reprint author), NICHHD, Mol Embryol Lab, NIH, Bldg 18T,Room 106, Bethesda, MD 20892 USA. NR 193 TC 245 Z9 251 U1 1 U2 10 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 PY 2000 VL 129 IS 2-3 BP 102 EP 122 DI 10.1006/jsbi.2000.4217 PG 21 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 316EP UT WOS:000087154900002 PM 10806063 ER PT J AU DePamphilis, ML AF DePamphilis, ML TI Nuclear structure and DNA replication SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Review DE eukaryotic DNA replication; nucleus; nuclear structure; nuclear matrix; nucleoskeleton; origin recognition complex; cell cycle ID ORIGIN RECOGNITION COMPLEX; XENOPUS EGG EXTRACT; CELL-FREE-EXTRACTS; CHORION GENE AMPLIFICATION; MATRIX ATTACHMENT REGIONS; CHICKEN LYSOZYME GENE; BETA-GLOBIN LOCUS; S-PHASE; LICENSING SYSTEM; MAMMALIAN-CELLS AB DNA replication is a highly conserved process among eukaryotes where it occurs within a unique organelle-the nucleus. The importance of this structure is indicated by the fact that assembly of prereplication complexes on cellular chromatin is delayed until mitosis is completed and a nuclear structure has formed. Although nuclear structure is dispensable for DNA replication in vitro, it does appear to play a role in vivo by regulating the concentration of proteins required to initiate DNA replication, by facilitating the assembly or activity of DNA replication forks, and by determining where in the genome initiation of DNA replication occurs. C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP DePamphilis, ML (reprint author), NICHHD, NIH, Bldg 6,Room 416, Bethesda, MD 20892 USA. NR 105 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 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD APR PY 2000 VL 129 IS 2-3 BP 186 EP 197 DI 10.1006/jsbi.2000.4219 PG 12 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 316EP UT WOS:000087154900007 PM 10806068 ER PT J AU Allen, JP AF Allen, JP TI Measuring treatment process variables in Alcoholics Anonymous SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE Alcoholics Anonymous; 12 steps; alcoholism treatment process; Brown-Peterson recovery progress inventory; Alcoholics Anonymous involvement; Alcoholics Anonymous affiliation ID AFFILIATION; RECOVERY; PURPOSE; GOALS; SCALE; LIFE AB Alcoholism treatment research has traditionally focused on direct questions of efficacy, such as is a particular intervention better than no treatment or is one treatment more effective than another. Recent projects, however, have also attempted to identify variables explaining why treatments vary in their effects. Many of these variables relate to the process of treatment itself or changes that may occur within the patients. Clinicians also need to continuously monitor progress of patients in engaging in behaviors supportive of long-term sobriety and how well the values and behaviors fostered by the particular treatment regimen are being incorporated into daily life. Measurement of process variables may assist in both regards. In the last decade several psychometric instruments have been developed to elucidate the processes involved in Alcoholic Anonymous (AA), a key adjunct of most formal alcoholism programs in the United States. These instruments measure dimensions such as involvement in AA, completion of steps, and adoption of values encouraged by AA. Sh such measures are summarized here and several fruitful topics for future research on the measures are suggested. (C) 2000 Elsevier Science Inc. All rights reserved. C1 NIAAA, Div Clin & Prevent Res, Bethesda, MD 20892 USA. RP Allen, JP (reprint author), NIAAA, Div Clin & Prevent Res, Willco Bldg,Suite 505,6000 Execut Blvd,MSC 7003, Bethesda, MD 20892 USA. NR 18 TC 7 Z9 8 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD APR PY 2000 VL 18 IS 3 BP 227 EP 230 DI 10.1016/S0740-5472(99)00071-9 PG 4 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 305GT UT WOS:000086531600003 PM 10742635 ER PT J AU Rothman, RB Gorelick, DA Heishman, SJ Eichmiller, PR Hill, BH Norbeck, J Liberto, JG AF Rothman, RB Gorelick, DA Heishman, SJ Eichmiller, PR Hill, BH Norbeck, J Liberto, JG TI An open-label study of a functional opioid kappa antagonist in the treatment of opioid dependence SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE naltrexone; buprenorphine; opioid dependence; opioid receptors ID BUPRENORPHINE; MORPHINE; DYNORPHIN; RECEPTOR; COCAINE; SYSTEMS; OPIATE; NALTREXONE; ADDICTION; TOLERANCE AB Several lines of evidence, including the well-established observation that kappa opiate agonists produce dysphoria and psychotomimetic effects in humans, suggest that dysfunction of the endogenous kappa opioid system may contribute to opioid and cocaine addiction. The objective of this open-label study was to determine the effectiveness of a functional K antagonist as a treatment for opioid dependence. This was accomplished by combining a partial mu agonist/kappa antagonist (buprenorphine. 4 mg, sublingual) with a mu antagonist (naltrexone, 50 mg by mouth), theoretically leaving kappa antagonism as the major medication effect. Subjects were treatment-seeking heroin-dependent las per Diagnostic and Statistical Manual of Mental Disorders, 4th ed.) men (41 +/- 7 years old; 19 +/- 8 years heroin use) eligible for methadone maintenance. After inpatient detoxification and a naloxone-challenge test to verify that they were not physically dependent on opioids, subjects received naltrexone. Starting on the fourth day, patients also received liquid buprenorphine. All patients received medication at the clinic 6 days per week and a full program of psychosocial treatment. The major endpoints of the study were: pupil diameter to determine if the mu agonist effects of buprenorphine were blocked by naltrexone, urine toxicology, and retention in treatment. Five patients (33%) completed the 3-month study. Four were abstinent from opioids and cocaine for the entire study, and one was abstinent from opioids and cocaine for the last 9 weeks. Six subjects dropped out due to either minor side effects or disliking the sensation of sublingual buprenorphine. There were no significant changes in pupillary diameter. The positive response to treatment exceeds that expected from naltrexone alone (90% dropout). These promising results suggest that controlled studies of this medication combination should be conducted. (C) 2000 Elsevier Science Inc. All rights reserved. C1 NIDA, NIH, Baltimore, MD 21224 USA. Vet Affairs Med Ctr, Baltimore, MD 21201 USA. RP Rothman, RB (reprint author), NIDA, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 33 TC 66 Z9 67 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD APR PY 2000 VL 18 IS 3 BP 277 EP 281 DI 10.1016/S0740-5472(99)00074-4 PG 5 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 305GT UT WOS:000086531600010 PM 10742642 ER PT J AU Gruber, R Sadeh, A Raviv, A AF Gruber, R Sadeh, A Raviv, A TI Instability of sleep patterns in children with attention-deficit/hyperactivity disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit/hyperactivity disorder; sleep; actigraph; instability ID DEFICIT DISORDER; PARENTAL REPORTS; NIGHT WAKING; INFANTS; HYPERACTIVITY; DISTURBANCES; PERFORMANCE; TEMPERAMENT; ACTIGRAPHY; SYMPTOMS AB Objective: To compare the stability of the sleep-wake system of children with attention-deficit/hyperactivity disorder (ADHD) and controls by objective and subjective measures. Method: Thirty-eight school-age boys with diagnosed ADHD and 64 control school-age boys were examined using actigraphic monitoring and sleep diaries. over 5 consecutive nights. Results: Increased instability in sleep onset, sleep duration, and true sleep were found in the ADHD group compared with the control group. Discriminant analysis revealed that children's classification (ADHD versus control) could be significantly predicted on the basis of their sleep measures. Conclusions: The findings support the hypothesis that instability of the sleep-wake system is a characteristic of children with ADHD. Given the potential negative effects of disturbed or unstable sleep on daytime functioning, it is recommended that a thorough sleep assessment be conducted when a sleep disturbance is suspected or when symptoms associated with daytime sleepiness or decreased arousal level are present. C1 Tel Aviv Univ, Dept Psychol, Lab Childrens Sleep & Arousal Disorders, IL-69978 Tel Aviv, Israel. RP Gruber, R (reprint author), NIMH, Sect Dev Psychopathol, Bldg 15-K,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Sadeh, Avi/K-5392-2012 NR 51 TC 155 Z9 155 U1 2 U2 20 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 2000 VL 39 IS 4 BP 495 EP 501 DI 10.1097/00004583-200004000-00019 PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 299GG UT WOS:000086190000019 PM 10761352 ER PT J AU Alderman, EL Brooks, MM Bourassa, M Califf, RM Chaitman, BR Detre, K Faxon, D Frye, R Hardison, RM Hlatky, M Holubkov, R Jones, RH Kelsey, SF Schaff, H Shemin, RJ Sopko, G Sutton-Tyrrell, K Williams, DO AF Alderman, EL Brooks, MM Bourassa, M Califf, RM Chaitman, BR Detre, K Faxon, D Frye, R Hardison, RM Hlatky, M Holubkov, R Jones, RH Kelsey, SF Schaff, H Shemin, RJ Sopko, G Sutton-Tyrrell, K Williams, DO CA BARI Investigators TI Seven-year outcome in the Bypass Angioplasty Revascularization Investigation (BARI) by treatment and diabetic status SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CORONARY ANGIOPLASTY; SURGERY; DISEASE AB OBJECTIVES To compare seven-year survival in the Bypass Angioplasty Revascularization Investigation (BARI) patients randomly assigned to percutaneous transluminal coronary angioplasty (PTCA) Versus coronary artery bypass grafting (CABG). BACKGROUND The primary results of BARI reported no significant difference in five-year survival between CABG and PTCA groups. However, among patients with treated diabetes mellitus, a subgroup not specified a priori, a striking difference was seen in favor of CABG. METHODS Symptomatic patients with multivessel disease (n = 1,829) were randomly assigned to initial treatment strategy of CABG or PTCA and followed for an average of 7.8 years. The intention-to-treat principle was used to extend the initial five-year BARI treatment comparisons. RESULTS Kaplan-Meier estimates of seven-year survival for the total population were 84.4% for CABG and 80.9% for PTCA (p = 0.043). This difference could be explained by the 353 patients with treated diabetes mellitus for whom estimates of seven year survival were 76.4% CABG and 55.7% PTCA (p = 0.0011). Among the remaining 1,476 patients without treated diabetes, survival was virtually identical by assigned treatment (86.4% CABG, 86.8% PTCA, p = 0.72). The PTCA group had substantially higher subsequent revascularization rates than the CABG group (59.7% vs. 13,1%, p < 0.001); however, the changes between the five- and seven-year rates were similar for the two groups. CONCLUSIONS At seven years, there was a statistically significant survival advantage for patients randomized to CABG compared with PTCA. Among patients with treated diabetes mellitus, the benefit of CABG over PTCA seen at five years was more pronounced at seven years; among nondiabetic patients, there was essentially no treatment difference. (J Am Coll Cardiol 2000; 35:1122-9) (C) 2000 by the American College of Cardiology. C1 NHLBI, Bethesda, MD 20892 USA. Univ Pittsburgh, Grad Sch Publ Hlth, BARI Coordinating Ctr, Pittsburgh, PA 15261 USA. RP Detre, K (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, BARI Coordinating Ctr, Room 127 Parran Hall,130 DeSoto St, Pittsburgh, PA 15261 USA. NR 28 TC 247 Z9 262 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR PY 2000 VL 35 IS 5 BP 1122 EP 1129 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 300RL UT WOS:000086265900003 ER PT J AU White, LR Petrovitch, H Ross, GW Masaki, K Hardman, J Nelson, J Davis, D Markesbery, W AF White, LR Petrovitch, H Ross, GW Masaki, K Hardman, J Nelson, J Davis, D Markesbery, W TI Brain aging and midlife tofu consumption SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION LA English DT Article DE brain; aging; nutrition; soy; cognition ID TYROSINE KINASE INHIBITOR; LONG-TERM POTENTIATION; POSTMENOPAUSAL WOMEN; ESTROGEN-RECEPTOR; ISOFLAVONOID EXCRETION; PREMENOPAUSAL WOMEN; SYNAPTIC PLASTICITY; DIETARY SOY; JAPANESE; PHYTOESTROGENS AB Objective: To examine associations of midlife tofu consumption with brain function and structural changes in late Life. Methods: The design utilized surviving participants of a longitudinal study established in 1965 for research on heart disease, stroke, and cancer. Information on consumption of selected foods was available from standardized interviews conducted 1965-1967 and 1971-1974. A 4-level composite intake index defined "low-low" consumption as fewer than two servings of tofu pr week in 1965 and no tofu in the prior week in 1971. Men who reported two or more servings per week at both interviews were defined as "high-high" consumers. intermediate or less consistent "low" and "high" consumption levels were also defined. Cognitive functioning was tested at the 1991-1993 examination, when participants were aged 71 to 93 years (n = 3734). Brain atrophy was assessed using neuroimage (n = 574) and autopsy (n = 290) information. Cognitive function data were also analyzed for wives of a sample of study participants (n = 502) who had been living with the participants at the time of their dietary interviews. Results: Poor cognitive test performance, enlargement of ventricles and low brain weight were each significantly and independently associated with higher midlife tofu consumption. A similar association of midlife tofu intake with poor late Life cognitive test scores was also observed among wives of cohort members. using the husband's answers to food frequency questions as proxy for the wife's consumption. Statistically significant associations were consistently demonstrated in linear and logistic multivariate regression models. Odds ratios comparing endpoints among "high-high" with "low-low" consumers were mostly in the range of 1.6 to 2.0. Conclusions: In this population, higher midlife tofu consumption was independently associated with indicators of cognitive impairment and brain atrophy in late life. C1 Univ Hawaii Manoa, Honolulu, HI 96822 USA. NIA, NIH, Bethesda, MD 20892 USA. Dept Vet Affairs, Honolulu, HI USA. Kuakini Med Ctr, Honolulu, HI USA. Louisiana State Univ, Baton Rouge, LA 70803 USA. Univ Kentucky, Lexington, KY USA. RP White, LR (reprint author), Hawaii Ctr Hlth Res, 846 S Hotel St,Suite 306, Honolulu, HI 96813 USA. FU NIA NIH HHS [N01-AG-4-2149] NR 56 TC 104 Z9 110 U1 0 U2 11 PU AMER COLL NUTRITION PI NEW YORK PA C/O HOSP. JOINT DIS. 301 E. 17TH ST., NEW YORK, NY 10003 USA SN 0731-5724 J9 J AM COLL NUTR JI J. Am. Coll. Nutr. PD APR PY 2000 VL 19 IS 2 BP 242 EP 255 PG 14 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 299PY UT WOS:000086208100006 PM 10763906 ER PT J AU Horowitz, AM Drury, TF Goodman, HS Yellowitz, JA AF Horowitz, AM Drury, TF Goodman, HS Yellowitz, JA TI Oral pharyngeal cancer prevention and early detection - Dentists' opinions and practices SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID UNITED-STATES; KNOWLEDGE; RISK AB Background. The five-year survival rate for patients in the United States diagnosed with oral pharyngeal cancer is 52 percent, which suggests that these cancers are diagnosed at late stages. The authors conducted this study to determine U.S. dentists' opinions and practices regarding oral cancer prevention and early detection. Methods. The authors mailed a pretested survey to 7,000 randomly selected general practitioners. A total of 3,200 dentists provided information on how they conduct oral cancer examinations, their use of health history questions to assess patients' oral cancer risks and their oral cancer training and practices. The authors carried out analyses using unweighted data; both bivariate and logistic analytical techniques at a P less than or equal to .01 level of significance were used. Results. On average, dentists assessed about five of the eight health history items on the survey. Eighty-six percent indicated that they did not conduct oral cancer examinations on edentulous patients 18 years of age or older; 81 percent, however, reported that they conducted oral cancer examinations for 100 percent of their patients 40 years of age or older on their initial appointment. Conclusions. The reported practices of these dentists regarding oral cancer, in conjunction with their opinions about key aspects of these practices and their training, point to a need for systematic educational updates in oral cancer prevention and early detection. Clinical Implications. Dentists need to determine their patients' risks for oral cancers and provide routine and comprehensive oral cancer examinations. C1 Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. Maryland Dept Hlth & Mental Hyg, Off Oral Hlth, Baltimore, MD USA. Univ Maryland, Sch Dent, Dept Oral Hlth Care, Baltimore, MD 21201 USA. RP Horowitz, AM (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Bldg 45,Room 3AN 44B, Bethesda, MD 20892 USA. NR 28 TC 65 Z9 67 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 2000 VL 131 IS 4 BP 453 EP 462 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 302LN UT WOS:000086366700012 PM 10770007 ER PT J AU Slavkin, HC AF Slavkin, HC TI Compassion, communication and craniofacial orodental trauma: Opportunities abound SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID INJURIES; ETIOLOGY; SWEDEN 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 25 TC 2 Z9 2 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD APR PY 2000 VL 131 IS 4 BP 507 EP 510 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 302LN UT WOS:000086366700020 PM 10770015 ER PT J AU Radimer, KL Subar, AF Thompson, FE AF Radimer, KL Subar, AF Thompson, FE TI Nonvitamin, nonmineral dietary supplements: Issues and findings from NHANES III SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID ALTERNATIVE MEDICINE AB The Commission on Dietary Supplement Labels encourages nutrition professionals to become knowledgeable about all dietary supplements. The Dietary Supplement Health and Education Act of 1995 (DSHEA) expanded the definition of dietary supplements beyond essential nutrients while distinguishing them from drugs or food additives. In order to give practical advice to consumers and policymakers, dietetics professionals need to understand the implications resulting from this less-restrictive regulatory environment for supplements. Dietetics professionals must also become familiar with claims made by manufacturers, retailers, and others regarding popular nonvitamin, nonmineral (NVNM) supplements, as well as usage prevalence and trends. However, NVNM supplements currently are classified inconsistently, and information on the prevalence of use is limited. Sales data suggest that total intake is increasing, and garlic and ginseng are consistently among the most popular supplements. Reported use of NVNM supplements in the third National Health and Nutrition Examination Survey was highest for garlic and lecithin. The data suggest associations of NVNM supplement use with age and more healthful lifestyles; however, there is also a reported link with higher alcohol consumption and obesity. Associations with education, income, region, and urbanization are not evident from the sales data. Standardized survey procedures regarding question phraseology, referent time period, and supplement categorization-along with use of representative samples-will improve our ability to assess supplement use, prevalence, and trends. C1 NCI, Appl Res Program, Bethesda, MD 20892 USA. NR 45 TC 95 Z9 99 U1 3 U2 5 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD APR PY 2000 VL 100 IS 4 BP 447 EP 454 DI 10.1016/S0002-8223(00)00137-1 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 460ME UT WOS:000170310700015 PM 10767902 ER PT J AU Visser, M Deeg, DJH Lips, P Harris, TB Bouter, LM AF Visser, M Deeg, DJH Lips, P Harris, TB Bouter, LM TI Skeletal muscle mass and muscle strength in relation to lower-extremity performance in elder men and women SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE aged; cross-sectional studies; epidemiology; geriatric assessment; hand strength; human; leg physiology; skeletal muscle; walking ID SELF-REPORTED DISABILITY; X-RAY ABSORPTIOMETRY; PHYSICAL PERFORMANCE; MUSCULAR STRENGTH; RISK-FACTORS; OLDER WOMEN; BODY-FAT; ASSOCIATION; DETERMINANTS; PROFILES AB OBJECTIVE: Low muscle strength is associated with poorer physical function, but limited empirical evidence is available to prove the relationship between muscle mass and physical function. We tested the hypothesis that persons with lower muscle mass or muscle strength have poorer lower-extremity performance (LEP). DESIGN: A cross-sectional, population-based study. PARTICIPANTS: A cohort of 449 men and women aged 65 years and older living in Amsterdam and its surroundings participating in the second examination (1995-1996) of the Longitudinal Aging Study Amsterdam. MEASUREMENTS: Leg skeletal muscle mass was measured using dual-energy X-rap absorptiometry (DXA). Grip strength was used as an indicator of muscle strength. Timed functional performance tests, including walking and repeated chair stands, were used to assess LEP. RESULTS: After adjustment for body height and age, leg muscle mass was positively associated with LEP in men (regression coefficient 0.178 [95% confidence interval 0.013-0.343], P =.035). In women an inverse association was observed, which became positive after additional adjustment for body mass index (BMI) (0.202 [-0.001-0.405], P = .052). Grip strength was positively associated with LEP in men and women. After additional adjustment for behavioral, physiological, and psychological variables, the associations between leg muscle mass and LEP disappeared, whereas grip strength remained to be independently associated with LEP in men (0.079 [0.042-0.116], P = .0001), with a tendency in women (0.046 [-0.009-0.101], P = .11). Results were similar when quartiles of leg muscle mass or grip strength were used. CONCLUSIONS: These results suggest that low muscle strength, but not low muscle mass, is associated with poor physical function in older men and women. However, prospective studies are needed to investigate the association between loss of muscle mass and physical function. C1 Free Univ Amsterdam, Fac Med, Inst Res Extramural Med, NL-1081 BT Amsterdam, Netherlands. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD USA. Vrije Univ Amsterdam, Dept Psychiat, Amsterdam, Netherlands. Vrije Univ Amsterdam, Acad Hosp, Dept Endocrinol, Amsterdam, Netherlands. RP Visser, M (reprint author), Free Univ Amsterdam, Fac Med, Inst Res Extramural Med, Van Boechorststr 7, NL-1081 BT Amsterdam, Netherlands. OI Bouter, Lex/0000-0002-2659-5482 NR 38 TC 138 Z9 141 U1 0 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2000 VL 48 IS 4 BP 381 EP 386 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 302LJ UT WOS:000086366300005 PM 10798463 ER PT J AU Humphrey, SM AF Humphrey, SM TI Incremental benefit of human indexing SO JOURNAL OF THE AMERICAN SOCIETY FOR INFORMATION SCIENCE LA English DT Letter ID RETRIEVAL C1 Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. RP Humphrey, SM (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0002-8231 J9 J AM SOC INFORM SCI JI J. Am. Soc. Inf. Sci. PD APR PY 2000 VL 51 IS 6 BP 582 EP 582 PG 1 WC Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA 295WD UT WOS:000085990100010 ER PT J AU Zhou, W Merrick, BA Khaledi, MG Tomer, KB AF Zhou, W Merrick, BA Khaledi, MG Tomer, KB TI Detection and sequencing of phosphopeptides affinity bound to immobilized metal ion beads by matrix-assisted laser desorption/ionization mass spectrometry SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID 2-DIMENSIONAL GEL-ELECTROPHORESIS; PHOSPHORYLATION SITES; PROTEIN-PHOSPHORYLATION; POSTTRANSLATIONAL MODIFICATIONS; IDENTIFICATION; CHROMATOGRAPHY; PEPTIDES; PHOSPHOPROTEINS; THREONINE; RESIDUES AB Consecutive enzymatic: reactions of analytes which are affinity bound to immobilized metal ion beads with subsequent direct analysis of the products by matrix-assisted laser desorption/ ionization mass spectrometry have been used for detecting phosphorylation sites. The usefulness of this method was demonstrated by analyzing two commercially available phosphoproteins, beta-casein and alpha-casein, as well as one phosphopeptide from a kinase reaction mixture. Agarose loaded with either Fe3+ or Ca3+ was used to isolate phosphopeptides from the protein digest. Results from using either metal ion were complementary. Less overall suppression effect was achieved when Ga3+-loaded agarose was used rn isolate phosphopeptides. The selectivity for monophosphorylated peptides, however, was better with Fe3+ loaded agarose. This technique is easy to use and has the ability to analyze extremely complicated phosphopeptide mixtures. Moreover, it eliminates the need for prior high-performance liquid chromatography separation or radiolabeling, thus greatly simplifying the sample preparation. (J Am Soc Mass Spectrom 2000, 11, 273-282) (C) 2000 American Society for Mass Spectrometry. C1 NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Chem, Raleigh, NC 27695 USA. RP Tomer, KB (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233,MD F0-03, Res Triangle Pk, NC 27709 USA. RI Tomer, Kenneth/E-8018-2013 NR 39 TC 137 Z9 140 U1 0 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD APR PY 2000 VL 11 IS 4 BP 273 EP 282 DI 10.1016/S1044-0305(00)00100-8 PG 10 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 298RA UT WOS:000086151900001 PM 10757163 ER PT J AU Schafer, JA Patlak, CS Andreoli, TE AF Schafer, JA Patlak, CS Andreoli, TE TI Fluid absorption and active and passive ion flows in the rabbit superficial pars recta (Reprinted from Am. J. Physiol, vol 233, pg F154-F167, 1977) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Reprint DE proximal straight tubule; net volume absorption; sodium transport; chloride transport; bicarbonate transport; mathematical model ID PROXIMAL STRAIGHT TUBULE; COLLECTING TUBULES; RAT-KIDNEY; WATER; REABSORPTION; MEMBRANES; TRANSPORT; NA+ AB Isolated rabbit proximal straight tubules were perfused with Krebs-Ringer buffers containing 127.8 mM NaCl and 3.8 mM NaHCO3 (pH 6.6), and bathed with Krebs-Ringer buffers containing 105 mM NaCl and 25 mM NaHCO3 (pH 7.4). Na isethionate replaced Na acetate in both mediums; acetate omission had no effect on net volume absorption (J(v), nl min(-1) mm(-1)). In acetate-free mediums, J(v) was 0.41 +/- 0.04 (SE) at 37 degrees C and 0.16 +/- 0.01 at 21 degrees C. J(v) at 21 degrees C was referable to passive driving forces. The transepithelial voltage was +2.7 mV (lumen positive) at 37 degrees C and rose to +3.7 mV at 21 degrees C. At 37 degrees C, net Cl- absorption accounted for 85 +/- 3% of net cation absorption. The data were analyzed in terms of model calculations with flow-diffusion equations for lateral intercellular spaces. Approximately one-third of the Na+ absorption at 37 degrees C could be accounted for by dissipative transport processes; the remainder was active. The computed ionic concentrations along the entire length of intercellular spaces were nearly identical to the ionic concentrations in the bathing solutions, and passive ion transport across the epithelium was accurately predicted from bulk phase ion concentrations. With intercellular spaces isosomotic to the external solutions, fluid absorption could be accounted for in terms of the oppositely directed gradients of Cl- and HCO3- across junctional complexes, because the junctional complexes were more permeable to Cl- than HCO3-. C1 Univ Alabama, Dept Med, Div Nephrol, Birmingham, AL 35294 USA. Univ Alabama, Dept Physiol & Biophys, Birmingham, AL 35294 USA. NIMH, Theoret Stat & Math Branch, Bethesda, MD 20014 USA. RP Schafer, JA (reprint author), Univ Alabama, Dept Med, Div Nephrol, Birmingham, AL 35294 USA. FU NIADDK NIH HHS [5-R01-AM 14873] NR 41 TC 0 Z9 0 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 2000 VL 11 IS 4 BP 784 EP 800 PG 17 WC Urology & Nephrology SC Urology & Nephrology GA 296VF UT WOS:000086046900023 PM 10752539 ER PT J AU Teigen, PM AF Teigen, PM TI In memoriam: Richard J. Durling SO JOURNAL OF THE HISTORY OF MEDICINE AND ALLIED SCIENCES LA English DT Biographical-Item C1 Natl Lib Med, Hist Med Div, Bethesda, MD 20894 USA. RP Teigen, PM (reprint author), Natl Lib Med, Hist Med Div, Bethesda, MD 20894 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-5045 J9 J HIST MED ALL SCI JI J. Hist. Med. Allied Sci. PD APR PY 2000 VL 55 IS 2 BP 179 EP 181 DI 10.1093/jhmas/55.2.179 PG 3 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA 304WD UT WOS:000086506400004 ER PT J AU Albertsen, PC Hanley, JA Harlan, LC Gilliland, FD Hamilton, A Liff, JM Stanford, JL Stephenson, RA AF Albertsen, PC Hanley, JA Harlan, LC Gilliland, FD Hamilton, A Liff, JM Stanford, JL Stephenson, RA TI The positive yield of imaging studies in the evaluation of men with newly diagnosed prostate cancer: A population based analysis SO JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms; neoplasm staging; tomography; magnetic resonance imaging; prostate ID UNITED-STATES; BONE-SCAN; TRENDS; UROLOGISTS; MANAGEMENT AB Purpose: We determine the positive yield of imaging studies performed on men with newly diagnosed prostate cancer. Materials and Methods: A prospective, population based survey was conducted on 3,690 men with prostate cancer diagnosed between October 1, 1994, and October 31, 1995. Cases were identified by the rapid case ascertainment systems used in 6 geographic regions participating in the Surveillance, Epidemiology and End Results Program. Based on information captured in primary medical record reviews we estimated the positive yield of bone scans, computerized tomography (CT) and magnetic resonance imaging. Results: The positive yield of bone scan and CT was less than 5% and 12%, respectively, for all men with prostate specific antigen (PSA) 4 to 20 ng./ml., and less than 2% and 9%, respectively, for those who also had a Gleason score of 6 or less. Only men with PSA greater than 50 ng./ml. and those with Gleason scores 8 to 10 and PSA greater than 20 ng./ml. had positive yields greater than 10% and 20% for bone scan and CT, respectively. Conclusions: Imaging studies designed to identify metastases and/or extracapsular extension in men with newly diagnosed prostate cancer frequently have a low positive yield. Wide variations exist in the use of imaging studies and are associated with tumor factors, such as Gleason score and serum PSA, and nontumor factors, such as state of residence. More extensive cost-effectiveness analyses are needed to define appropriate guidelines for ordering imaging studies to optimize the positive yield among men with newly diagnosed prostate cancer. C1 Univ Connecticut, Ctr Hlth, Div Urol, Farmington, CT 06032 USA. NCI, Appl Res Branch, Bethesda, MD 20892 USA. Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. Univ Utah, Div Urol, Salt Lake City, UT USA. McGill Univ, Dept Epidemiol & Biostat, Montreal, PQ, Canada. RP Albertsen, PC (reprint author), Univ Connecticut, Ctr Hlth, Div Urol, Farmington, CT 06032 USA. FU NCI NIH HHS [N01-PC-67000, N01-PC-67005, N01-PC-67006] NR 12 TC 36 Z9 40 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD APR PY 2000 VL 163 IS 4 BP 1138 EP 1143 DI 10.1016/S0022-5347(05)67710-5 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 295NE UT WOS:000085974000018 PM 10737483 ER PT J AU Nishigaki, K Hanson, C Ohashi, T Thompson, D Muszynski, K Ruscetti, S AF Nishigaki, K Hanson, C Ohashi, T Thompson, D Muszynski, K Ruscetti, S TI Erythroid cells rendered erythropoietin independent by infection with friend spleen focus-forming virus show constitutive activation of phosphatidylinositol 3-kinase and Akt kinase: Involvement of insulin receptor substrate-related adapter proteins SO JOURNAL OF VIROLOGY LA English DT Article ID TYROSINE-PHOSPHORYLATED PROTEIN; SIGNAL-TRANSDUCTION; DNA-BINDING; PROTOONCOGENE PRODUCT; STAT5 ACTIVATION; RESPONSIVE CELLS; HOMOLOGY DOMAIN; GROWTH-HORMONE; ASSOCIATION; PATHWAY AB The erythroleukemia-inducing Friend spleen focus-forming virus (SFFV) encodes a unique envelope glycoprotein which allows erythroid cells to proliferate and differentiate in the absence of erythropoietin (Epo), In an effort to understand how SFFV causes Epo independence, we have been examining erythroid cells rendered factor independent by SFFV infection for constitutive activation of signal-transducing molecules. Previous studies from our laboratory showed that various signal-transducing molecules known to be activated by Epo, including Stat proteins and components of the Raf-1/MAP kinase pathway, are constitutively activated in SFFV-infected erythroid cells in the absence of Epo. Since another signal transduction pathway involving activation of phosphatidylinositol 3-kinase (PI 3-kinase) after Epo stimulation plays an important role in erythroid cell proliferation and differentiation, we carried out studies to determine if this pathway was also activated in SFFV-infected cells in the absence of Epo. Our studies show that PI 3-kinase is constitutively activated in erythroid cells rendered factor independent by infection with SFFV and that PI 3-kinase activity, but not Epo receptor tyrosine phosphorylation, is required for the proliferation of these cells in the absence of Epo. We further show that in SFFV-infected erythroid cells grown in the absence of Epo, PI 3-kinase associates with the insulin receptor substrate (IRS)-related adapter molecules IRS-2, Gab1, and Gab2, which are constitutively tyrosine phosphorylated in SFFV-infected cells. Finally, Akt, a protein kinase that is one of the downstream effecters of PI 3-kinase, and SHIP, a lipid phosphatase that is important for Akt activation through PI 3-kinase, are both tyrosine phosphorylated in SFFV-infected cells grown in the absence of Epo, Our results indicate that induction of Epo independence by SFFV requires the activation of PI 3-kinase and suggest that constitutive activation of this kinase in SFFV-infected cells may occur primarily through interaction of PI 3-kinase with constitutively phosphorylated IRS-related adapter molecules. C1 NCI, Frederick Canc Res & Dev Ctr, Basic Res Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick, MD 21702 USA. Tokyo Med & Dent Univ, Tokyo, Japan. RP Ruscetti, S (reprint author), NCI, Frederick Canc Res & Dev Ctr, Basic Res Lab, Bldg 469,Room 205, Frederick, MD 21702 USA. RI Ohashi, Takashi/C-4671-2012 OI Ohashi, Takashi/0000-0002-3769-4224 NR 70 TC 46 Z9 49 U1 1 U2 4 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 2000 VL 74 IS 7 BP 3037 EP 3045 DI 10.1128/JVI.74.7.3037-3045.2000 PG 9 WC Virology SC Virology GA 295NH UT WOS:000085974400009 PM 10708418 ER PT J AU Smith, RH Kotin, RM AF Smith, RH Kotin, RM TI An adeno-associated virus (AAV) initiator protein, Rep78, catalyzes the cleavage and ligation of single-stranded AAV ori DNA SO JOURNAL OF VIROLOGY LA English DT Article ID SITE-SPECIFIC INTEGRATION; ROLLING-CIRCLE REPLICATION; ADENOASSOCIATED VIRUS; MINUTE VIRUS; IN-VITRO; HAIRPIN MODEL; SEQUENCE; PARVOVIRUS; HELICASE; GENOME AB The Rep78 protein of adeno-associated virus (AAV) contains amino acid sequence motifs common to rolling-circle replication (RCR) initiator proteins, In this report, we describe RCR initiator-like activities of Rep78. We demonstrate that a maltose-binding protein (MBP)-Rep78 fusion protein can catalyze the cleavage and ligation of single-stranded DNA substrates derived from the AAV origin of replication, Rep-mediated single-stranded DNA cleavage was strictly dependent on the presence of certain divalent cations (e.g., Mn2+ or Mg2+) but did not require the presence of a nucleoside triphosphate cofactor. Electrophoretic mobility shift assays demonstrated that binding of single-stranded DNA by MBP-Rep78 was influenced by the length of the substrate as well as the presence of potential single-stranded cis-acting sequence elements. Site-directed mutagenesis was used to examine the role of specific tyrosine residues within a conserved RCR motif (motif 3) of Rep78. Replacement of Tyr-156 with phenylalanine abolished the ability of MBP-Rep78 to mediate the cleavage and ligation of single-stranded DNA substrates but not the ability to stably bind single-stranded DNA. The cleaving-joining activity of Rep78 is consistent with the mechanism of replicative intermediate dimer resolution proposed for the autonomous parvoviruses and may have implications for targeted integration of recombinant AAV vectors. C1 NHLBI, LMH, Bethesda, MD 20892 USA. RP Kotin, RM (reprint author), NHLBI, LMH, Bldg 10,Rm 7D18, Bethesda, MD 20892 USA. RI kotin, robert/B-8954-2008 NR 39 TC 44 Z9 44 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 2000 VL 74 IS 7 BP 3122 EP 3129 DI 10.1128/JVI.74.7.3122-3129.2000 PG 8 WC Virology SC Virology GA 295NH UT WOS:000085974400018 PM 10708427 ER PT J AU Bailly, JE McAuliffe, JM Durbin, AP Elkins, WR Collins, PL Murphy, BR AF Bailly, JE McAuliffe, JM Durbin, AP Elkins, WR Collins, PL Murphy, BR TI A recombinant human parainfluenza virus type 3 (PIV3) in which the nucleocapsid N protein has been replaced by that of bovine PIV3 is at attenuated in primates SO JOURNAL OF VIROLOGY LA English DT Article ID ADULT VOLUNTEERS; HEMAGGLUTININ-NEURAMINIDASE; NUCLEOTIDE-SEQUENCE; REASSORTANT VIRUS; RHESUS-MONKEYS; INFLUENZA; VACCINE; INFANTS; GENE; REPLICATION AB The shipping fever (SF) and Kansas (Ka) strains of bovine parainfluenza virus type 3 (BPIV3) are restricted in their replication in rhesus monkeys 100- to 1,000-fold compared to human parainfluenza virus type 3 (HPIV3), and the Ba strain also was shown to be attenuated in humans. To initiate an investigation of the genetic basis of the attenuation of BPIV3 in primates, we produced viable chimeric HPIV3 recombinants containing the nucleoprotein (N) open reading frame (ORF) from either BPIV3 Ka or SF in place of the HPIV3 N ORF. These chimeric recombinants mere designated cKa-N and cSF-N, respectively. Remarkably, cKa-N and cSF-N grew to titers comparable to those of their HPIV3 and BPIV3 parents in LLC-MK2 monkey kidney and Madin-Darby bovine kidney cells, Thus, the heterologous nature of the N protein did not impede replication in vitro, However, cKa-N and cSF-N were each restricted in replication in rhesus monkeys to a similar extent as Iia and SF, respectively. This identified the BPIV3 N protein as a determinant of;the host range restriction of BPIV3 in primates. These chimeras thus combine the antigenic determinants of BPIV3 with the host range restriction and attenuation phenotype of BPIV3, Despite their restricted replication in rhesus monkeys, the chimeric viruses induced a level of resistance to HPIV3 challenge in these animals which was indistinguishable from that conferred by immunization with HPIV3. The infectivity, attenuation, and immunogenicity of these BPIV3/HPIV3 chimeras suggest that the modified Jennerian approach described in the present report represents a novel method to design vaccines to protect against HPIV3-induced disease in humans. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Murphy, BR (reprint author), NIAID, Infect Dis Lab, NIH, Bldg 7, Bethesda, MD 20892 USA. NR 31 TC 27 Z9 28 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 2000 VL 74 IS 7 BP 3188 EP 3195 DI 10.1128/JVI.74.7.3188-3195.2000 PG 8 WC Virology SC Virology GA 295NH UT WOS:000085974400026 PM 10708435 ER PT J AU Murakami, T Freed, EO AF Murakami, T Freed, EO TI Genetic evidence for an interaction between human immunodeficiency virus type 1 matrix and alpha-helix 2 of the gp41 cytoplasmic tail SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 ENVELOPE GLYCOPROTEIN; LEUCINE ZIPPER; MATURE VIRIONS; HOST-RANGE; CELL-LINE; PROTEIN; DOMAIN; ASSOCIATION; INFECTIVITY; SEGMENTS AB The incorporation of envelope (Env) glycoproteins into virions is an essential step in the retroviral replication cycle. Lentiviruses, including human immunodeficiency virus type 1 (HTV-1), encode Env glycoproteins with unusually long cytoplasmic tails, the functions of which have not been fully elucidated. In this study, we examine the effects on virus replication of a number of mutations in a helical motif (alpha-helix 2) located near the center of the HIV-1 gp41 cytoplasmic tail. We find that, in T-cell lines, small deletions in this domain disrupt the incorporation of Env glycoproteins into virions and markedly impair virus infectivity. Through the analysis of viral revertants, we demonstrate that a single amino acid change (34VI) in the matrix domain of Gag reverses the Env incorporation and infectivity defect imposed by a small deletion near the C terminus of a-helix 2. These results provide genetic evidence, in the context of infected T cells, for an interaction between HIV-1 matrix and the gp41 cytoplasmic tail and identify domains of both proteins involved in this putative interaction. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Freed, EO (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Rm 307, Bethesda, MD 20892 USA. NR 46 TC 150 Z9 150 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2000 VL 74 IS 8 BP 3548 EP 3554 DI 10.1128/JVI.74.8.3548-3554.2000 PG 7 WC Virology SC Virology GA 296VT UT WOS:000086048000014 PM 10729129 ER PT J AU Ward, BM Moss, B AF Ward, BM Moss, B TI Golgi network targeting and plasma membrane internalization signals in vaccinia virus B5R envelope protein SO JOURNAL OF VIROLOGY LA English DT Article ID ACTIN-CONTAINING MICROVILLI; VESICULAR STOMATITIS-VIRUS; TO-CELL SPREAD; EXTRACELLULAR VIRUS; OUTER ENVELOPE; ENDOPLASMIC-RETICULUM; CYTOPLASMIC DOMAIN; TAIL FORMATION; A33R GENE; GLYCOPROTEIN AB The vaccinia virus B5R type I integral membrane protein accumulates in the Golgi network, from where it becomes incorporated into the envelope of extracellular virions. Our objective was to determine the domains of B5R responsible for Golgi membrane targeting in the absence of other viral components. Fusion of an enhanced green fluorescent protein to the C terminus of B5R allowed imaging of the chimeric protein without altering intracellular trafficking and Golgi network localization in transfected cells. Deletion or swapping of B5R domains with corresponding regions of the vesicular stomatitis virus G protein, which is targeted to the plasma membrane, indicated that (i) the N-terminal extracellular domain of B5R had no specific role in Golgi apparatus localization, (ii) the transmembrane domain of B5R was sufficient for exiting the endoplasmic reticulum, and (iii) removal of the cytoplasmic tail impaired Golgi network localization and increased the accumulation of B5R in the plasma membrane. Further experiments demonstrated that the cytoplasmic tail mediated internalization of B5R from the plasma membrane, suggesting a retrieval mechanism. Mutagenesis revealed residues required for Golgi membrane localization and efficient plasma membrane retrieval of the B5R protein: a tyrosine at residue 310 and two adjacent leucines at residues 315 and 316. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 4 Ctr Dr,MSC 0445, Bethesda, MD 20892 USA. NR 54 TC 46 Z9 47 U1 0 U2 6 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 2000 VL 74 IS 8 BP 3771 EP 3780 DI 10.1128/JVI.74.8.3771-3780.2000 PG 10 WC Virology SC Virology GA 296VT UT WOS:000086048000037 PM 10729152 ER PT J AU Zabner, J Seiler, M Walters, R Kotin, RM Fulgeras, W Davidson, BL Chiorini, JA AF Zabner, J Seiler, M Walters, R Kotin, RM Fulgeras, W Davidson, BL Chiorini, JA TI Adeno-associated virus type 5 (AAV5) but not AAV2 binds to the apical surfaces of airway epithelia and facilitates gene transfer SO JOURNAL OF VIROLOGY LA English DT Article ID RECOMBINANT ADENOASSOCIATED VIRUS; CYSTIC-FIBROSIS; TRACHEAL EPITHELIUM; VECTORS; CELLS; TRANSDUCTION; THERAPY; EXPRESSION; PERSISTENT; EFFICIENT AB In the genetic disease cystic fibrosis, recombinant adeno-associated virus type 2 (AAV2) is being investigated as a vector to transfer CFTR cDNA to airway epithelia. However, earlier work has shown that the apical surface of human airway epithelia is resistant to infection by AAV2, presumably as a result of a lack of heparan sulfate proteoglycans on the apical surface. This inefficiency can be overcome by increasing the amount of vector or by increasing the incubation time. However, these interventions are not very practical for translation into a therapeutic airway-directed vector. Therefore,,ve examined the efficiency of other AAV serotypes at infecting human airway epithelia. When applied at low multiplicity of infection to the apical surface of differentiated airway epithelia we found that a recombinant AAV5 bound and mediated gene transfer 50-fold more efficiently than AAV2. Furthermore, in contrast to AAV2, AAV5-mediated gene transfer was not inhibited by soluble heparin. Recombinant AAV5 was also more efficient than AAV2 in transferring beta-galactosidase cDNA to murine airway and alveolar epithelia in vivo. These data suggest that AAV5-derived vectors bind and mediate gene transfer to human and murine airway epithelia, and the tropism of AAV5 may be useful to target cells that are not permissive for AAV2. C1 Univ Iowa, Coll Med, Dept Internal Med, Iowa City, IA 52242 USA. Univ Iowa, Coll Med, Dept Physiol & Biophys, Iowa City, IA 52242 USA. NHLBI, NIH, Lab Mol Hematol, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, NIH, Gene Therapeut Branch, Bethesda, MD 20892 USA. RP Zabner, J (reprint author), Univ Iowa, Coll Med, Dept Internal Med, 500 EMRB, Iowa City, IA 52242 USA. RI kotin, robert/B-8954-2008 FU NHLBI NIH HHS [HL58340, R01 HL058340] NR 43 TC 226 Z9 236 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2000 VL 74 IS 8 BP 3852 EP 3858 DI 10.1128/JVI.74.8.3852-3858.2000 PG 7 WC Virology SC Virology GA 296VT UT WOS:000086048000044 PM 10729159 ER PT J AU Beer, BE Bailes, E Dapolito, G Campbell, BJ Goeken, RM Axthelm, MK Markham, PD Bernard, J Zagury, D Franchini, G Sharp, PM Hirsch, VM AF Beer, BE Bailes, E Dapolito, G Campbell, BJ Goeken, RM Axthelm, MK Markham, PD Bernard, J Zagury, D Franchini, G Sharp, PM Hirsch, VM TI Patterns of genomic sequence diversity among their simian immunodeficiency viruses suggest that L'Hoest monkeys (Cercopithecus lhoesti) are a natural lentivirus reservoir SO JOURNAL OF VIROLOGY LA English DT Article ID AFRICAN-GREEN MONKEYS; WILD-CAPTURED CHIMPANZEE; CROSS-SPECIES TRANSMISSION; HIGHLY DIVERGENT; SOOTY MANGABEY; SEROEPIDEMIOLOGIC SURVEY; CERCOCEBUS-ATYS; SYKES MONKEYS; WEST-AFRICA; INFECTION AB Recently, we described a novel simian immunodeficiency virus (SIVlhoest) from a wild-caught L'Hoest monkey (Cercopithecus lhoesti) from a North American zoo. To investigate whether L'Hoest monkeys are the natural host for these viruses, we have screened blood samples from 14 wild animals from the Democratic Republic of Congo. Eight (57%) were found to be seropositive for SIV. Nearly full-length genome sequences were obtained for SIV isolates from three of these monkeys and compared to the original isolate and to other SIVs. The four samples of SIVlhoest formed a distinct cluster in phylogenetic trees. Two of these isolates differed on average at only about 5% of nucleotides, suggesting that they were epidemiologically linked; otherwise, the SIVlhoest isolates differed on average by 18%. Both the level of diversity and the pattern of its variation along the genome were very similar to those seen among isolates of SIVagm from vervet monkeys, pointing to similarities in the nature of, and constraints on, SIV evolution in these two species. Discordant phylogenetic relationships among the SIVlhoest isolates for different genomic regions indicated that mosaic viruses have been generated by recombination, implying that individual monkeys have been coinfected by more than one strain of SIV. Taken together, these observations provide strong evidence that L'Hoest monkeys constitute a natural reservoir for SIV. C1 NIAID, NIH, Mol Microbiol Lab, Rockville, MD 20852 USA. Univ Nottingham, Queens Med Ctr, Inst Genet, Nottingham NG7 2UH, England. Oregon Hlth Sci Univ, Div Pathobiol & Immunol, Beaverton, OR 97006 USA. Adv BioSci Labs Inc, Kensington, MD USA. Inst Jean Godinot, F-51100 Reims, France. Univ Paris 06, Paris, France. NCI, NIH, Basic Res Lab, Bethesda, MD 20892 USA. RP Hirsch, VM (reprint author), NIAID, NIH, Mol Microbiol Lab, Rockville, MD 20852 USA. RI Sharp, Paul/F-5783-2010 OI Sharp, Paul/0000-0001-9771-543X NR 51 TC 34 Z9 34 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 2000 VL 74 IS 8 BP 3892 EP 3898 DI 10.1128/JVI.74.8.3892-3898.2000 PG 7 WC Virology SC Virology GA 296VT UT WOS:000086048000050 PM 10729165 ER PT J AU Poon, DTK Coren, LV Ott, DE AF Poon, DTK Coren, LV Ott, DE TI Efficient incorporation of HLA class II onto human immunodeficiency virus type 1 requires envelope glycoprotein packaging SO JOURNAL OF VIROLOGY LA English DT Article ID MHC CLASS-II; CYTOPLASMIC DOMAIN; CELLULAR PROTEINS; VIRAL INFECTIVITY; HIV-1; PATHOGENESIS; CELLS; VIRIONS; SIGNAL; GP41 AB HLA class II DR is one of the most abundant cell surface proteins incorporated onto human immunodeficiency virus type 1 (HIV-1) during budding. The mechanism for HLA class II protein incorporation is not known and may involve a viral protein. To determine whether Env affects HLA class II protein incorporation, HIV-1 virions, either with or without Env on their surface, were produced from HLA class II expressing cells and analyzed by whole-virus immunoprecipitation with antisera against HLA class II proteins. HLA class II proteins were detected on virions only when wild-type Env was incorporated, while similar experiments showed that HLA class I proteins were incorporated independent of Env packaging. Therefore, the packaging of HIV-1 Env protein is required for the efficient incorporation of HLA class II but not class I proteins into the virion. Analysis of two Env mutants revealed that the presence of a 43-amino-acid sequence between amino acids 708 and 750 in the gp41(TM) cytoplasmic tail was required for efficient incorporation of HLA class II proteins. These data show that HIV-1 actively incorporates HLA class II proteins in a process that, either directly or indirectly, requires Env. C1 NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, AIDS Vaccine Program, Frederick, MD 21702 USA. RP Ott, DE (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, AIDS Vaccine Program, POB B,Bldg 535,Rm 433, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 38 TC 19 Z9 20 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 2000 VL 74 IS 8 BP 3918 EP 3923 DI 10.1128/JVI.74.8.3918-3923.2000 PG 6 WC Virology SC Virology GA 296VT UT WOS:000086048000054 PM 10729169 ER PT J AU Kim, V Yewdell, JW Green, WR AF Kim, V Yewdell, JW Green, WR TI Naturally occurring TAP-dependent specific T-cell tolerance for a variant of an immunodominant retroviral cytotoxic T-lymphocyte epitope SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA VIRUSES; MHC CLASS-I; ANTIGEN PRESENTATION; POSITIVE SELECTION; MICE; SEQUENCES; PEPTIDE; GENERATION; CTL; SUSCEPTIBILITY AB Upon immunization and restimulation with tumors induced by the endogenous AKR/Gross murine leukemia virus (MuLV), C57BL/6 mice generate vigorous H-2K(b)-restricted cytotoxic T-lymphocyte (CTL) responses to a determinant (KSPWFTTL) derived from the p15E transmembrane portion of the viral envelope glycoprotein. By contrast, the highly homologous determinant RSPWFTTL, expressed by tumor cells induced by Friend/Moloney/Rauscher (FMR) MuLV, is not immunogenic, even when presented to the immune system as vaccinia virus-encoded cytosolic or endoplasmic reticulum (ER)-targeted minigene products. Such minigene products are usually highly immunogenic since they bypass the need for cells to liberate the peptide or transport the peptide into the ER by the transporter associated with antigen processing (TAP). Using KSPWFTTL-specific CTLs that cross-react with RSPWFTTL, we previously demonstrated that presentation of RSPWFTTL from its natural viral gene product is TAP dependent. Here, we show first that C57BL/6 mice express mRNA encoding RSPWFTTL but not KSPWFTTL and second that the ER-targeted RSPWFTTL minigene product is highly immunogenic in C57BL/6 mice with a targeted deletion in TAP1. These findings provide the initial demonstration of TAP-dependent tolerance induction to a specific self peptide and demonstrate that this contributes to the differential recognition of RSPWFTTL and KSPWFTTL by C57BL/6 mice. C1 Dartmouth Med Sch, Dept Microbiol, Lebanon, NH 03756 USA. Norris Cotton Canc Ctr, Lebanon, NH 03756 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Green, WR (reprint author), Dartmouth Med Sch, Dept Microbiol, Borwell Bldg,1 Med Ctr Dr, Lebanon, NH 03756 USA. RI yewdell, jyewdell@nih.gov/A-1702-2012 FU NCI NIH HHS [CA-23108, CA-69525, P30 CA023108]; NIAID NIH HHS [AI-07363, T32 AI007363] NR 31 TC 4 Z9 4 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 2000 VL 74 IS 8 BP 3924 EP 3928 DI 10.1128/JVI.74.8.3924-3928.2000 PG 5 WC Virology SC Virology GA 296VT UT WOS:000086048000055 PM 10729170 ER PT J AU Haynes, SG Lynch, BS Biegel, R Malliou, E Rudick, J Sassaman, AP AF Haynes, SG Lynch, BS Biegel, R Malliou, E Rudick, J Sassaman, AP TI Women's health and the environment: Innovations in science and policy SO JOURNAL OF WOMENS HEALTH & GENDER-BASED MEDICINE LA English DT Review ID BREAST-CANCER RISK; CIGARETTE-SMOKING; HORMONE METABOLISM; EXPOSURES; POLYMORPHISMS; ENDOMETRIOSIS; EPIDEMIOLOGY; PREGNANCY; FERTILITY; WORKSHOP AB Current scientific findings indicate that environmental factors affect women's health. Specifically, evidence has accumulated on the effects of the environment on reproductive health, cancer, injury, respiratory problems, autoimmune diseases, and other health problems. To review the current state of the science and policies related to women's health and the environment, the Federal Interagency Working Group on Women's Health and the Environment of the Department of Health and Human Services and the Society for Women's Health Research jointly sponsored a conference in 1998 entitled Women's Health and the Environment: Innovations in Science and Policy. The aim of the conference was to provide a forum for scientists to share recent findings, promising avenues of research, methodological barriers, and data gaps about women's susceptibility to environmental agents. The conference generated 22 recommendations for policy, 17 recommendations for communication and training, and 48 recommendations for research to be considered by the federal government. The purpose of this review is to bring to the attention of the scientific community and policymakers the breadth of the women's health implications associated with environmental factors by highlighting key research findings presented at the conference. This review summarizes the current status of science in women's health, it describes relevant activities by the federal government, and it suggests recommendations for future research and policy initiatives in the context of women's health and the environment. C1 US Dept HHS, Publ Hlth Serv, Off Womens Hlth, Washington, DC 20201 USA. Prospect Associates Ltd, Silver Spring, MD USA. Soc Womens Hlth Res, Washington, DC USA. NIH, Off Res Womens Hlth, Bethesda, MD 20892 USA. NIEHS, Div Extramural Res & Training, NIH, Res Triangle Pk, NC 27709 USA. RP Haynes, SG (reprint author), US Dept HHS, Publ Hlth Serv, Off Womens Hlth, Room 712-E,Hubert H Humphrey Bldg,200 Independenc, Washington, DC 20201 USA. NR 65 TC 1 Z9 1 U1 1 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1524-6094 J9 J WOMEN HEALTH GEN-B JI J. WOMENS HEALTH GENDER-BASED MED. PD APR PY 2000 VL 9 IS 3 BP 245 EP 273 DI 10.1089/152460900318452 PG 29 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 306PK UT WOS:000086604900005 PM 10787222 ER PT J AU Guralnik, JM Ferrucci, L Pieper, CF Leveille, SG Markides, KS Ostir, GV Studenski, S Berkman, LF Wallace, RB AF Guralnik, JM Ferrucci, L Pieper, CF Leveille, SG Markides, KS Ostir, GV Studenski, S Berkman, LF Wallace, RB TI Lower extremity function and subsequent disability: Consistency across studies, predictive models, and value of gait speed alone compared with the short physical performance battery SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID DEPRESSIVE SYMPTOMS; OLDER PERSONS; WOMENS HEALTH; POPULATION; ADULTS; RISK; AGE AB Background. Although it has been demonstrated that physical performance measures predict incident disability in previously nondisabled older persons, the available data have not been fully developed to create usable methods for determining risk profiles in community-dwelling populations. Using several populations and different follow-up periods, this study replicates previous findings by using the Established Populations for the Epidemiologic Study of the Elderly (EPESE) performance battery and provides equations for the prediction of disability risk according to age, sex, and level of performance. Methods. Tests of balance, time to walk 8 ft, and time to rise from a chair 5 times were administered to 4,588 initially nondisabled persons in the four sites of the EPESE and to 1,946 initially nondisabled persons in the Hispanic EPESE. Follow-up assessment for activity of daily living (ADL) and mobility-related disability occurred from 1 to 6 years later. Results. In the EPESE, compared with those with the best performance (EPESE summary performance score of 10-12), the relative risks of mobility-related disability for those with scores of 4-6 ranged from 2.9 to 4.9 and the relative risk of disability for those with scores of 7-9 ranged from 1.5 to 2.1, with similar consistent results for ADL disability. The observed rates of incident disability according to performance level in the Hispanic EPESE agreed closely with rates predicted from models developed from the EPESE sites. Receiver operating characteristic curves showed that gait speed alone performed almost as well as the full battery in predicting incident disability. Conclusions. Performance tests of lower extremity function accurately predict disability across diverse populations. Equations derived from models using both the summary score and the gait speed alone allow for the estimation of risk of disability in community-dwelling populations and provide valuable information for estimating sample size for clinical trials of disability prevention. C1 NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Natl Inst Res & Care Elderly, INRCA, Dept Geriatr, Florence, Italy. Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Durham, NC 27710 USA. Ctr Aging, Dept Prevent Med & Community Hlth, Galveston, TX USA. Univ Kansas, Med Ctr, Ctr Aging, Kansas City, KS 66103 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Iowa, Dept Prevent Med & Environm Hlth, Iowa City, IA 52242 USA. RP Guralnik, JM (reprint author), NIA, Epidemiol Demog & Biometry Program, Gateway Bldg,Suite 3C-309,7201 Wisconsin Ave, Bethesda, MD 20892 USA. FU NIA NIH HHS [N01-AG-0-2105, N01-AG-0-2106, N01-AG-0-2107] NR 27 TC 925 Z9 937 U1 4 U2 67 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 2000 VL 55 IS 4 BP M221 EP M231 PG 11 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 331XT UT WOS:000088044500013 PM 10811152 ER PT J AU Kopple, JD Greene, T Chumlea, WC Hollinger, D Maroni, BJ Merrill, D Scherch, LK Schulman, G Wang, SR Zimmer, GS AF Kopple, JD Greene, T Chumlea, WC Hollinger, D Maroni, BJ Merrill, D Scherch, LK Schulman, G Wang, SR Zimmer, GS CA Modification Diet Renal Dis Study TI Relationship between nutritional status and the glomerular filtration rate: Results from the MDRD Study SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT Conference on Forefronts in Nephrology - News in Aldosterone Action CY AUG 15-18, 1999 CL CHANTILLY, FRANCE SP Int Soc Nephrol DE malnutrition; nutrition; chronic renal failure; dietary intake; anthropometry; serum albumin; transferrin ID CHRONIC-RENAL-FAILURE; MAINTENANCE HEMODIALYSIS-PATIENTS; AMBULATORY PERITONEAL-DIALYSIS; DIETARY-PROTEIN RESTRICTION; ENERGY-INTAKE; NUTRIENT INTAKE; DISEASE; MALNUTRITION; VARIABILITY; RISK AB Background. The relationship between the protein-energy nutritional status and renal function was assessed in 1785 clinically stable patients with moderate to advanced chronic renal failure who were evaluated during the baseline phase of the Modification of Diet in Renal Disease Study. Their mean +/- SD glomerular filtration rate (GFR) was 39.8 +/- 21.1 mL/min/ 1.73 m(2). Methods. The GFR was determined by I-121-iothalamate clearance and was correlated with dietary and nutritional parameters estimated from diet records. biochemistry measurements, and anthropometry. Results. The following parameters correlated directly with the GFR in both men and women: dietary protein intake estimated from the urea nitrogen appearance, dietary protein and energy intake estimated from dietary diaries, serum albumin, transferrin. percentage body fat, skinfold thickness, and urine creatinine excretion. Serum total cholesterol, actual and relative body weights, body mass index, and arm muscle area also correlated with the GFR in men. The relationships generally persisted after statistically controlling for reported efforts to restrict diets. Compared with patients with GFR > 37 mL/min/ 1.73 m(2), the means of several nutritional parameters were significantly lower for GFR between 21 and 37 mL/min/1.73 m(2), and lower still for GFRs under 21 mL/min/1.73 m(2). In multivariable regression analyses, the association of GFR with several of the anthropometric and biochemical nutritional parameters was either attenuated or eliminated completely after controlling for protein and energy intakes. which were themselves strongly associated with many of the nutritional parameters. On the other hand, few patients showed evidence for actual protein-energy malnutrition. Conclusions. These cross-sectional findings suggest that in patients with chronic renal disease, dietary protein and energy intakes and serum and anthropometric measures of protein-energy nutritional status progressively decline as the GFR decreases. The reduced protein and energy intakes, as GFR falls, may contribute to the decline in many of the nutritional measures. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Kopple, JD (reprint author), Univ Calif Los Angeles, Los Angeles Cty Harbor Med Ctr, Div Nephrol & Hypertens, 1000 W Carson St, Torrance, CA 90509 USA. NR 51 TC 223 Z9 228 U1 1 U2 6 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 2000 VL 57 IS 4 BP 1688 EP 1703 DI 10.1046/j.1523-1755.2000.00014.x PG 16 WC Urology & Nephrology SC Urology & Nephrology GA 300TU UT WOS:000086269300058 PM 10760105 ER PT J AU Zhu, WH Guo, XD Villaschi, S Nicosia, RF AF Zhu, WH Guo, XD Villaschi, S Nicosia, RF TI Regulation of vascular growth and regression by matrix metalloproteinases in the rat aorta model of angiogenesis SO LABORATORY INVESTIGATION LA English DT Article ID MICROVASCULAR ENDOTHELIAL-CELLS; IN-VITRO; EXPRESSION; INVITRO; LOCALIZATION; PROLIFERATION; ORGANIZATION; MICROVESSELS; PROGRESSION; COLLAGENASE AB Matrix metalloproteinases (MMPs) have been implicated in the formation of microvessels during angiogenesis, but their role in vascular regression is poorly understood. The rat aorta model of angiogenesis was used to study the function of MMPs at different stages of the angiogenic process. Gelatin zymography and Western analysis demonstrated production of MMP-2 and MMP-9 by aortic outgrowths in serum-free collagen gel culture. MMP-2 was found in both culture medium and collagen gel, whereas MMP-9 was predominantly associated with the gel. MMP expression increased gradually during the angiogenic growth phase and stayed high when vessels regressed and collagen lysed around the aortic rings. The MMP inhibitors, batimastat and marimastat, blocked formation of microvessels when added to the culture medium at the beginning of the experiment. They, however, stabilized the microvessels and prevented vascular regression after the angiogenic growth phase. This effect was observed also under conditions of angiogenic stimulation by basic fibroblast growth factor. MMP inhibitor-mediated stabilization of microvessels was associated with inhibition of collagen lysis and accumulation of collagen fibrils in the subendothelial space. This study demonstrates that MMPs promote microvessel formation during the early stages of angiogenesis, but also contribute to the reabsorption of the neovasculature in the later stages of this process. The time-dependent divergent effects of MMPs on microvessel growth and survival may influence the in vivo activity of MMP inhibitors used to treat angiogenesis-dependent disorders. C1 VA Puget Sound Hlth Care Syst, Pathol & Lab Med S113 Lab, Seattle, WA 98108 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. NCI, Dept Pathol, Bethesda, MD 20892 USA. Univ Roma Tor Vergata, Dipartimento Biopatol, Rome, Italy. RP Nicosia, RF (reprint author), VA Puget Sound Hlth Care Syst, Pathol & Lab Med S113 Lab, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NHLBI NIH HHS [HL52585] NR 41 TC 78 Z9 83 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD APR PY 2000 VL 80 IS 4 BP 545 EP 555 PG 11 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 307DP UT WOS:000086638200011 PM 10780671 ER PT J AU Babiker, A Darby, S De Angelis, D Kwart, D Porter, K Beral, V Darbyshire, J Day, N Gill, N Coutinho, R Prins, M van Benthem, B Coutinho, R Dabis, F Marimoutou, C Ruiz, I Tusell, J Altisent, C Evatt, B Jaffe, H Kirk, O Pedersen, C Rosenberg, P Goedert, J Biggar, R Melbye, M Brettie, R Downs, A Hamouda, O Touloumi, G Karafoulidou, A Katsarou, O Donfield, S Gomperts, E Hilgartner, M Hoots, K Schoenbaum, E Beral, V Zangerle, R Del Amo, J Pezzotti, P Rezza, G Hutchinson, S Day, N De Angelis, D Gore, S Kingsley, L Schrager, L Rosenberg, P Goedert, J Melnick, S Koblin, B Eskild, A Bruun, J Sannes, M Evans, B Lepri, AC Sabin, C Buchbinder, S Vittinghoff, E Moss, A Osmond, D Winkelstein, W Goldberg, D Boufassa, F Meyer, L Egger, M Francioli, P Rickenbach, M Cooper, D Tindall, B Sharkey, T Vizzard, J Kaldor, J Cunningham, P Vanhems, P Vizzard, J Kaldor, J Learmont, J Farewell, V Berglund, O Mosley, J Operskalski, E van den Berg, M Metzger, D Tobin, D Woody, G Rusnak, J Hendrix, C Garner, R Hawkes, C Renzullo, P Garland, F Darby, S Ewart, D Giangrande, P Lee, C Phillips, A Spooner, R Wilde, J Winter, M Babiker, A Darbyshire, J Evans, B Gill, N Johnson, A Phillips, A Porter, K Lorenzo, JI Schechter, M AF Babiker, A Darby, S De Angelis, D Kwart, D Porter, K Beral, V Darbyshire, J Day, N Gill, N Coutinho, R Prins, M van Benthem, B Coutinho, R Dabis, F Marimoutou, C Ruiz, I Tusell, J Altisent, C Evatt, B Jaffe, H Kirk, O Pedersen, C Rosenberg, P Goedert, J Biggar, R Melbye, M Brettie, R Downs, A Hamouda, O Touloumi, G Karafoulidou, A Katsarou, O Donfield, S Gomperts, E Hilgartner, M Hoots, K Schoenbaum, E Beral, V Zangerle, R Del Amo, J Pezzotti, P Rezza, G Hutchinson, S Day, N De Angelis, D Gore, S Kingsley, L Schrager, L Rosenberg, P Goedert, J Melnick, S Koblin, B Eskild, A Bruun, J Sannes, M Evans, B Lepri, AC Sabin, C Buchbinder, S Vittinghoff, E Moss, A Osmond, D Winkelstein, W Goldberg, D Boufassa, F Meyer, L Egger, M Francioli, P Rickenbach, M Cooper, D Tindall, B Sharkey, T Vizzard, J Kaldor, J Cunningham, P Vanhems, P Vizzard, J Kaldor, J Learmont, J Farewell, V Berglund, O Mosley, J Operskalski, E van den Berg, M Metzger, D Tobin, D Woody, G Rusnak, J Hendrix, C Garner, R Hawkes, C Renzullo, P Garland, F Darby, S Ewart, D Giangrande, P Lee, C Phillips, A Spooner, R Wilde, J Winter, M Babiker, A Darbyshire, J Evans, B Gill, N Johnson, A Phillips, A Porter, K Lorenzo, JI Schechter, M CA Collaborative Grp AIDS Incubation TI Time from HIV-1 seroconversion to AIDS and death before widespread use of highly-active antiretroviral therapy: a collaborative re-analysis SO LANCET LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INJECTING DRUG-USERS; HOMOSEXUAL MEN; HEPATITIS-C; DISEASE PROGRESSION; TYPE-1 INFECTION; NATURAL-HISTORY; AGE; HEMOPHILIA; SURVIVAL AB Background We used data from Europe, North America, and Australia to assess the effect of exposure category on the AIDS incubation period and HIV-1 survival and whether the effect of age at seroconversion varies with exposure category and with time since seroconversion. Methods 38 studies of HIV-1-infected individuals whose dates of seroconversion could be reliably estimated were included in the analysis. Individual data on 13 030 HIV-1-infected individuals from 15 countries were collated, checked, and analysed centrally. We calculated estimates of mortality and AIDS incidence rates and estimated the proportions of individuals surviving and developing AIDS at each year after seroconversion from the numbers of observed deaths or cases of AIDS and the corresponding person-years at risk. Analyses were adjusted for age at seroconversion, time since seroconversion, and other factors as appropriate. Findings Mortality and AIDS incidence increased strongly with time since seroconversion and age at seroconversion. Median survival varied from 12.5 years (95% CI 12.1-12.9) for those aged 15-24 years at seroconversion to 7.9 years (7.4-8.5) for those aged 45-54 years at seroconversion, whereas for development of AIDS the corresponding values were 11.0 years (10.7-11.7) and 7.7 years (7.1-8.6). There was no appreciable effect of exposure category on survival. For AIDS incidence, the exposure category effect that we noted was explained by the high incidence of Kaposi's sarcoma in those infected through sex between men. We estimated that among people aged 25-29 years at seroconversion 90% (89-91) and 60% (57-62) survived to 5 years and 10 years, respectively, after seroconversion, whereas 13% (12-15) and 46% (44-49), respectively, developed AIDS (excluding Kaposi's sarcoma). Interpretation Before widespread use of highly-active antiretroviral therapy (before 1996), time since seroconversion and age at seroconversion were the major determinants of survival and development of AIDS in Europe, North America, and Australia. C1 Radcliffe Infirm, Imperial Canc Res Fund, Canc Epidemiol Unit, Oxford OX2 6HE, England. Amsterdam Cohort Study Drug Users, Amsterdam, Netherlands. Amsterdam Cohort Study Homosexual Men, Amsterdam, Netherlands. Barcelona Haemophillia Cohort, Barcelona, Spain. Ctr Dis Control & Prevent, Atlanta, GA USA. Copenhagen Cohort, Copenhagen, Denmark. Aquitaine Cohort, Aquitaine, France. Edinburgh City Hosp Cohort, Edinburgh, Midlothian, Scotland. European Ctr Epidemiol Monitoring AIDS, St Maurice, France. HERO Study, Birmingham, AL USA. Imperial Canc Res Fund, Canc Epidemiol Unit, Oxford, England. Innsbruck AIDS Study, Innsbruck, Austria. Inst Salud Carlos III, Madrid, Spain. MRC BIAS, Edinburgh, Midlothian, Scotland. MRC, Biostat Unit, Cambridge CB2 2BW, England. NCI, Bethesda, MD 20892 USA. New York Blood Ctr, New York Prospect AIDS Study, New York, NY 10021 USA. Publ Hlth Lab Serv, Ctr Communicable Dis Surveillance, London NW9 5EQ, England. Royal Free Hosp, Sch Med, London, England. San Francisco City Clin Cohort, San Francisco, CA USA. San Francisco Gen Hosp Cohort, San Francisco, CA USA. San Francisco Mens Hlth Study, San Francisco, CA USA. Scottish Ctr Infect & Environm Hlth, Glasgow, Lanark, Scotland. Swiss HIV Cohort Study, Lausanne, Switzerland. Sydney AIDS Prospect Study, Sydney, NSW, Australia. Sydney Primary HIV Infect Cohort, Sydney, NSW, Australia. Sydney Primary HIV Infect Working Party, Sydney, NSW, Australia. Sydney Red Cross Cohort, Sydney, NSW, Australia. Toronto Sexual Hlth Study, Toronto, ON, Canada. Univ Utrecht Hosp, Utrecht, Netherlands. Univ Penn, Risk Assessment Project, Philadelphia, PA 19104 USA. USAF, HIV Nat Hist Study, Washington, DC 20330 USA. USA, Data Syst Cohort, Washington, DC 20310 USA. USN, HIV Cohort, Washington, DC 20350 USA. Valencia Haemophilia Cohort, Valencia, Spain. Vancouver Lymphadenopathy AIDS Study, Vancouver, BC, Canada. RP Beral, V (reprint author), Radcliffe Infirm, Imperial Canc Res Fund, Canc Epidemiol Unit, Gibson Bldg, Oxford OX2 6HE, England. RI Sabin, Caroline/C-2464-2008; Phillips, Andrew/B-4427-2008; Beral, Valerie/B-2979-2013; Kaldor, John /D-4545-2011; SHCS, int. coll. B/G-4090-2011; SHCS, all/G-4072-2011; Metzger, David/D-9499-2012; Hendrix, Craig/G-4182-2014; REZZA, GIOVANNI/D-4393-2016; DEL AMO VALERO, JULIA/M-7020-2015 OI Phillips, Andrew/0000-0003-2384-4807; Hendrix, Craig/0000-0002-5696-8665; REZZA, GIOVANNI/0000-0003-0268-6790; DEL AMO VALERO, JULIA/0000-0002-3104-540X NR 26 TC 261 Z9 266 U1 2 U2 16 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD APR 1 PY 2000 VL 355 IS 9210 BP 1131 EP 1137 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 302TC UT WOS:000086380900010 ER PT J AU Frankel, AE McCubrey, JA Miller, MS Delatte, S Ramage, J Kiser, M Kucera, GL Alexander, RL Beran, M Tagge, EP Kreitman, RJ Hogge, DE AF Frankel, AE McCubrey, JA Miller, MS Delatte, S Ramage, J Kiser, M Kucera, GL Alexander, RL Beran, M Tagge, EP Kreitman, RJ Hogge, DE TI Diphtheria toxin fused to human interleukin-3 is toxic to blasts from patients with myeloid leukemias SO LEUKEMIA LA English DT Article DE diphtheria fusion toxin; interleukin-3; acute myeloid leukemia; chronic myeloid leukemia ID COLONY-STIMULATING FACTOR; ACUTE MYELOGENOUS LEUKEMIA; FACTOR FUSION PROTEIN; CELL-LINE; GM-CSF; PSEUDOMONAS EXOTOXIN; MULTIDRUG-RESISTANCE; RECEPTOR EXPRESSION; FUNCTIONAL DOMAINS; PROGENITOR CELLS AB Leukemic blasts from patients with acute phase chronic myeloid leukemic and refractory acute myeloid leukemia are highly resistant to a number of cytotoxic drugs. To overcome multi-drug resistance, we engineered a diphtheria fusion protein by fusing human interleukin-3 (IL3) to a truncated form of diphtheria toxin (DT) with a (G(4)S)(2) linker (L), expressed and purified the recombinant protein, and tested the cytotoxicity of the DTLIL3 molecule on human leukemias and normal progenitors. The DTLIL3 construct was more cytotoxic to interleukin-3 receptor (IL3R) bearing human myeloid leukemia cell lines than receptor-negative cell lines based on assays of cytotoxicity using thymidine incorporation, growth in semi-solid medium and induction of apoptosis. Exposure of mononuclear cells to 680 pM DTLIL3 for 48 h in culture reduced the number of cells capable of forming colonies in semi-solid medium (colony-forming units leukemia) greater than or equal to 10-fold in 4/11 (36%) patients with myeloid acute phase chronic myeloid leukemia (CML) and 3/9 (33%) patients with acute myeloid leukemia (AML). Normal myeloid progenitors (colony-forming unit granulocyte-macrophage) from five different donors treated and assayed under identical conditions showed intermediate sensitivity with three- to five-fold reductions in colonies. The sensitivity to DTLIL3 of leukemic progenitors from a number of acute phase CML patients suggests that this agent could have therapeutic potential for some patients with this disease. C1 Wake Forest Univ, Bowman Gray Sch Med, Dept Canc Biol, Winston Salem, NC 27157 USA. E Carolina Univ, Dept Microbiol, Greenville, NC USA. Med Univ S Carolina, Dept Surg, Charleston, SC 29425 USA. Univ Texas, MD Anderson Canc Ctr, Dept Med, Houston, TX 77030 USA. NCI, Mol Biol Lab, Bethesda, MD 20892 USA. British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. RP Frankel, AE (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Canc Biol, Med Ctr Blvd, Winston Salem, NC 27157 USA. OI McCubrey, James/0000-0001-6027-3156 FU NCI NIH HHS [R01CA51025, R01CA54116, R01CA76178] NR 54 TC 76 Z9 79 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD APR PY 2000 VL 14 IS 4 BP 576 EP 585 DI 10.1038/sj.leu.2401743 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 303DU UT WOS:000086406200004 PM 10764142 ER PT J AU Selleri, C Maciejewski, JP AF Selleri, C Maciejewski, JP TI The role of FAS-mediated apoptosis in chronic myelogenous leukemia SO LEUKEMIA & LYMPHOMA LA English DT Review DE Fas; Fas-mediated apoptosis; chronic myelogenous leukemia ID CHRONIC MYELOID-LEUKEMIA; ABL TYROSINE KINASE; TUMOR-NECROSIS-FACTOR; BCR-ABL; INTERFERON-ALPHA; PROGENITOR CELLS; HEMATOPOIETIC-CELLS; IN-VITRO; POSITIVE CELLS; DNA-DAMAGE AB Clinical observation and laboratory evidence suggest that immune mechanisms play an important role in the natural control of evolution of the Ph+ clone in chronic phase as well as during progression of chronic myelogenous leukemia (CML), The understanding of these mechanisms could facilitate development of innovative therapeutic approaches. Due to bcr-abl translocation, CML cells carry an intrinsic resistance to apoptotic signals. However, resistance to apoptosis is not absolute and can be overcome through enhancement of immune-mediated pathways, e.g., during graft vs, leukemia reaction after allogeneic bone marrow transplantation or during interferon-alpha (IFN-alpha) therapy. Among the effector mechanisms, T-lymphocyte-mediated killing of target cells via Fas-receptor (Fas-R) triggering plays an important role in the elimination of malignant cells, including CML cells. Although CML Ph+ progenitor cells express Fas-R, the expression levels are variable and do not correlate with clinical parameters. In addition, CML progenitor cells also express functional Fas-ligand (Fas-L), which may be an important immune surveillance escape factor. IFN-alpha can greatly upmodulate Fas-R expression, an effect that seems to be more pronounced in CML compared to normal cells, while Fas-L expression levels are not affected by IFN-alpha, thereby improving their susceptibility to elimination by the immune system. Responsiveness to Fas-induced apoptosis following stimulation with IFN-alpha correlates with the clinical effects of IFN-alpha therapy. This effect seems to be associated with decreased bcr-ablprotein levels, which are influenced by Fas via posttranscriptional modulation. In comparison to the chronic phase, CML cells derived from patients in blast crisis are refractory to Fas-mediated apoptosis, regardless of the expression levels of Fas, suggesting that an immune-mediated selection pressure could result in aquisition of Fas-resistance. In the future, enhancement of immunological recognition and elimination of CML cells may prove to be an effective therapeutic approach directed towards the cure of CML. C1 Univ Naples Federico II, Div Hematol, Naples, Italy. RP Maciejewski, JP (reprint author), NHLBI, Hematol Branch, Natl Inst Hlth, Bldg 10,Room 7C108, Bethesda, MD 20892 USA. NR 98 TC 8 Z9 8 U1 0 U2 1 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD APR PY 2000 VL 37 IS 3-4 BP 283 EP 297 PG 15 WC Oncology; Hematology SC Oncology; Hematology GA 297KL UT WOS:000086081900004 PM 10752980 ER PT J AU Gutierrez, MI Kingma, DW Sorbara, L Tran, M Raffeld, M Jaffe, ES Magrath, I Bhatia, K AF Gutierrez, MI Kingma, DW Sorbara, L Tran, M Raffeld, M Jaffe, ES Magrath, I Bhatia, K TI Association of EBV strains, defined by multiple loci analyses, in non-Hodgkin lymphomas and reactive tissues from HIV positive and HIV negative patients SO LEUKEMIA & LYMPHOMA LA English DT Article DE EBV; EBNA-1; mutations; strains; HIV-associated NHL ID EPSTEIN-BARR-VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; BURKITTS-LYMPHOMAS; SEQUENCE VARIATION; NUCLEAR ANTIGEN; EBNA-1; GENE AB Epstein-Barr virus (EBV) associated with lymphoid neoplasms demonstrates preferential association with certain viral strains. Previous subtyping studies have however been confined to analysis of sequence variability within a single locus in EBV. Variations have now been reported for several latently expressed EBV genes, including, EBNAs-1, 2 and LMP-1. Variant EBNA-1 strains have been identified in Burkitt's lymphomas and clustering of subtypes for LMP and EBNA-2 have been associated with either malignancy and/or clinical disease. To investigate the linkage between the variability in these three loci in EBV associated with lymphoid malignancies, we subclassified EBV-associated lymphoproliferations (9 reactive and 24 malignant) from HIV-negative and HIV-positive patients by analysis of the EBNA-1, LMP1, and EBNA-2 genes. Our results demonstrate that (1) EBV identical to the prototype B95.8 strain (Type 1 EBNA-2, wild type EBNA-1 and LMP-I) is very rarely associated with turners. (2) The EBNA-1 variant V-leucine, restricted to malignant lymphomas in immunocompetent patients, was readily identified in non-malignant lesions in HIV infected patients. (3) Variations of EBNA-1 occur independent of variations at other loci. C1 NCI, Pediat Branch, Lymphoma Biol Sect, NIH, Bethesda, MD 20892 USA. RP Bhatia, K (reprint author), NCI, Pediat Branch, Lymphoma Biol Sect, NIH, Bldg 10,Room 13N240,10 Ctr Dr,MSC-1928, Bethesda, MD 20892 USA. NR 18 TC 10 Z9 11 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD APR PY 2000 VL 37 IS 3-4 BP 425 EP 429 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 297KL UT WOS:000086081900018 PM 10752994 ER PT J AU Ciminale, V Hatziyanni, M Felber, BK Bear, J Hatzakis, A Pavlakis, GN AF Ciminale, V Hatziyanni, M Felber, BK Bear, J Hatzakis, A Pavlakis, GN TI Unusual CD4+CD8+phenotype in a Greek patient diagnosed with adult T-cell leukemia positive for human T-cell leukemia virus type I (HTLV-I) SO LEUKEMIA RESEARCH LA English DT Article DE HTLV-I; ATL; leukemia ID LYMPHOMA; INFECTION AB We describe the first Greek patient diagnosed with Adult T cell leukemia (ATL) characterized by an expansion of CD4 + CD8 + double positive lymphocytes. Low levels of plasma antibodies against HTLV-I Env and Gag proteins were detected. Analysis of the the patient's DNA revealed that she was infected by a cosmopolitan strain of HTLV-I. Since HTLV-I usually leads to the expansion of CD4 + cells, this patient illustrates a rare immunophenotype, which suggests that the HTLV-I-induced proliferative response may occur in a pre-T cell stage. (C) 2000 Published by Elsevier Science Ltd. All rights reserved. C1 NCI, ABL Basic Res Program, Human Retrovirus Sect, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Metaxa Canc Hosp Piraeus, Dept Hematol, Piraeus 18537, Greece. NCI, Human Retrovirus Pathogenesis Sect, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. Univ Athens, Sch Med, Dept Hyg & Epidemiol, Athens 11572, Greece. RP Pavlakis, GN (reprint author), NCI, ABL Basic Res Program, Human Retrovirus Sect, Frederick Canc Res & Dev Ctr, Room 210,Bldg 535,Sultan St, Frederick, MD 21702 USA. NR 14 TC 11 Z9 11 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD APR PY 2000 VL 24 IS 4 BP 353 EP 358 DI 10.1016/S0145-2126(99)00193-9 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 295TQ UT WOS:000085984300009 PM 10713333 ER PT J AU Said, B McCart, JA Libutti, SK Choyke, PL AF Said, B McCart, JA Libutti, SK Choyke, PL TI Ferumoxide-enhanced MRI in patients with colorectal cancer and rising CEA: surgical correlation in early recurrence SO MAGNETIC RESONANCE IMAGING LA English DT Article DE liver; metastases; ferumoxide ID SUPERPARAMAGNETIC IRON-OXIDE; FOCAL LIVER-LESIONS; ARTERIAL PORTOGRAPHY; HEPATIC METASTASES; FIELD-STRENGTH; CT; SEQUENCES AB The purpose of this study was to evaluate the value of Ferumoxide-enhanced magnetic resonance (MR) imaging in the detection of hepatic metastases in high-risk patients treated for colorectal cancer that have rising CEA. We used 19 patients treated previously for colorectal cancer with rising CEA levels underwent an unenhanced T-1-weighted (T1W), T-2-weighted (T2W), STIR, and Ferumoxide-enhanced hepatic MRI. Following these studies, a laparotomy was performed and the liver was evaluated by palpation and intraoperative ultrasound. Two observers who were blinded to surgical results evaluated each MR sequence separately. The number of lesions considered highly suspicious for metastatic lesions were determined for each sequence and were compared to the results of surgery. The McNemar test was used to compare the outcomes of the different sequences. MR Imaging was unable to detect small (<5 mm) metastases discovered at surgery. The best non-contrast sequences for detecting metastases were the STIR with 42% sensitivity, 83% specificity and an overall accuracy of 56% and the T1W sequence (sensitivity 38%, specificity 100%, accuracy 57%), which were not significantly different (p > 0.4). The noncontrast T2W sequence had a sensitivity of 29% and a specificity of 77% with an overall accuracy of 46%. When all pre contrast scans were grouped together the common sensitivity was 42%, specificity was 77% and accuracy was 54%. The post-ferumoxide T2W scans had a sensitivity of 42%, specificity of 85%, and accuracy of 57%, but did not detect any additional lesions. There was no statistical difference between the pre- and post-contrast studies with regard to identifying patients with metastatic disease (p > 0.1). In conclusion, we found small hepatic metastases in patients with early signs of recurrent colorectal cancer are difficult to detect on MRI. Ferumoxide-enhanced MRI was unable to detect additional hepatic metastases and performed no better than unenhanced MRI in detecting small hepatic metastasis. (C) 2000 Elsevier Science Inc. All rights reserved. C1 NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Choyke, PL (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NR 18 TC 8 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 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD APR PY 2000 VL 18 IS 3 BP 305 EP 309 DI 10.1016/S0730-725X(99)00134-4 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 306EV UT WOS:000086585100011 PM 10745140 ER PT J AU Bandettini, PA Cox, RW AF Bandettini, PA Cox, RW TI Event-related fMRI contrast when using constant interstimulus interval: Theory and experiment SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE human brain mapping; fMRI; BOLD; event-related ID HUMAN BRAIN-FUNCTION; HUMAN VISUAL-CORTEX; SENSORY STIMULATION; ACTIVATION; MRI; OXYGENATION; TASK; RESPONSES; DYNAMICS; TRIALS AB Event-related functional magnetic resonance imaging (ER-fMRI) involves the mapping of averaged hemodynamic changes resulting from repeated, brief (<3 sec) brain activation episodes. In this paper, two issues regarding constant-interstimulus interval ER-fMRI were addressed. First, the optimal interstimulus interval (ISI), given a stimulus duration (SD), was determined. Second, the statistical power of ER-fMRI relative to that of a blocked-design paradigm was determined. Experimentally, it was found that with a 2-sec SD, the optimal ISI is 12 to 14 sec. Theoretically, the optimal repetition interval (T-opt = ISI + SD) is 12 to 14 sec for stimuli of 2 sec or less, for longer stimuli, T-opt is 8 + 2 SD. At the optimal ISI for SD = 2 sec, the experimentally determined functional contrast of ER-fMRI was only -35% lower than that of blocked-design fMRI. Simulations that assumed a linear system demonstrated an event-related functional contrast that was -65% lower than that of the blocked design. These differences between simulated and experimental contrast suggest that the ER-fMRI amplitude is greater than that predicted by a linear shift-invariant system. (C) 2000 Wiley-Liss, Inc. C1 Med Coll Wisconsin, Biophys Res Inst, Milwaukee, WI 53226 USA. RP Bandettini, PA (reprint author), NIMH, Lab Brain & Cognit, NIH, Bldg 10,Room 4C104,10 Ctr Dr,MSC 1366, Bethesda, MD 20892 USA. RI Bandettini, Peter/F-5871-2012 FU NIMH NIH HHS [MH51358] NR 46 TC 137 Z9 139 U1 4 U2 13 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 2000 VL 43 IS 4 BP 540 EP 548 DI 10.1002/(SICI)1522-2594(200004)43:4<540::AID-MRM8>3.0.CO;2-R PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 299TR UT WOS:000086214400008 PM 10748429 ER PT J AU Tong, ZB Nelson, LM Dean, J AF Tong, ZB Nelson, LM Dean, J TI Mater encodes a maternal protein in mice with a leucine-rich repeat domain homologous to porcine ribonuclease inhibitor SO MAMMALIAN GENOME LA English DT Article ID GLUTAMIC-ACID DECARBOXYLASE; AUTOIMMUNE OOPHORITIS; MESSENGER-RNA; POLYADENYLATED RNA; OOCYTE MATURATION; MOUSE OOCYTES; EXPRESSION; EMBRYO; CELLS; GENE AB MATER (Maternal Antigen That Embryos Require) is an ooplasm-specific protein first identified as an antigen (OP1) associated with ovarian autoimmunity in mice. Its primary structure has been deduced from full-length cDNA that encodes a 125-kDa protein required for progression of the mouse embryo beyond two cells. Expression of the gene encoding MATER is restricted to the oocyte, which makes it one of a growing, but still limited, number of maternal-effect genes in mammals. To further investigate the function of MATER during oogenesis and early development, we have characterized the gene and resultant protein. Mater is a single-copy gene in the genome of 129/Sv mice and is located at the proximal end of Chromosome (Chr) 7. The gene, spanning approximately 32 kbp, contains 15 exons ranging in size from 48 to 1576 bp, which together encode the 1111 amino acid MATER protein. The first five exons encode 26-27 amino acid hydrophilic repeats, and exons 8-14 encode 14 leucine-rich repeats. The three-dimensional structure of the latter domain can be closely modeled on the previously determined X-ray crystallographic coordinates of porcine ribonuclease inhibitor. These characterizations of the gene and protein provide the basis for genetic investigations of MATER function in early mammalian development. C1 NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20007 USA. NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Tong, ZB (reprint author), NICHD, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262, Bethesda, MD 20892 USA. NR 41 TC 53 Z9 57 U1 1 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 2000 VL 11 IS 4 BP 281 EP 287 DI 10.1007/s003350010053 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 305LQ UT WOS:000086541900005 PM 10754103 ER PT J AU Gopal-Srivastava, R Kays, WT Piatigorsky, J AF Gopal-Srivastava, R Kays, WT Piatigorsky, J TI Enhancer-independent promoter activity of the mouse alpha B-crystallin/small heat shock protein gene in the lens and cornea of transgenic mice SO MECHANISMS OF DEVELOPMENT LA English DT Article DE lens; cornea; crystallin; small heat shock protein; gene expression; promoter activity; enhancer ID NON-LENTICULAR TISSUES; MAJOR SOLUBLE-PROTEIN; ALDEHYDE DEHYDROGENASE; BOVINE CORNEA; A-CRYSTALLIN; EXPRESSION; PAX-6; IDENTIFICATION; EVOLUTION; MUSCLE AB The alpha B-crystallin/small heat shock protein gene is expressed very highly in the mouse eye lens and to a lesser extent in many other nonocular tissues, including the heart, skeletal muscle and brain. Previously we showed in transgenic mice that lens-specific alpha B-crystallin promoter activity is directed by a proximal promoter fragment (-164/+44) and that non-lens promoter activity depends on an upstream enhancer (-427/-259) composed of at least 5 cis-control elements. Here we have used truncated alpha B-crystallin promoter-CAT transgenes to test by biphasic CAT assays and/or histochemistry for specific expression in the cornea and lens. Deletion either of 87 bp (-427/-340) from the 5' end of the alpha B-crystallin enhancer or of the whole enhancer (-427/-258) abolished alpha B-crystallin promoter activity in all tissues except the lens and corneal epithelium when examined by the biphasic CAT assay in 4-5-week-old transgenic mice. These truncations also lowered promoter strength in the lens. The -426/+444-CAT, - 339/+44-CAT and - 164/+44-CAT (previously thought to be lens-specific in transgenic mice) transgenes were all expressed in the 4-6-week-old corneal epithelium when examined histochemically. Immunohistochemical staining confirmed the presence of endogenous alpha B-crystallin in the mature corneal epithelial cells. CAT gene expression driven by the alpha B-crystallin promoter with or without the enhancer was evident in the embryonic and 4-6-week-old lens. By contrast, activity of the alpha B-crystallin promoter/enhancer-CAT transgene was not detectable in the corneal epithelium before birth. Taken together, these results indicate that the intact enhancer of the alpha B-crystallin/small heat shock protein gene is required for promoter activity in all tissues tested except the lens and cornea. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. EM joramp@intra.nei.nih.gov NR 55 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 EI 1872-6356 J9 MECH DEVELOP JI Mech. Dev. PD APR PY 2000 VL 92 IS 2 BP 125 EP 134 DI 10.1016/S0925-4773(99)00341-X PG 10 WC Developmental Biology SC Developmental Biology GA 303BA UT WOS:000086399900002 PM 10727852 ER PT J AU Roilides, E Lyman, CA Sein, T Gonzalez, C Walsh, TJ AF Roilides, E Lyman, CA Sein, T Gonzalez, C Walsh, TJ TI Antifungal activity of splenic, liver and pulmonary macrophages against Candida albicans and effects of macrophage colony-stimulating factor SO MEDICAL MYCOLOGY LA English DT Article DE Candida; M-CSF; tissue macrophages ID FACTOR M-CSF; PHASE-I TRIAL; PERITONEAL-MACROPHAGES; ALVEOLAR MACROPHAGES; MURINE MACROPHAGES; FUNGAL-INFECTIONS; INTERFERON-GAMMA; RABBIT ALVEOLAR; RECOMBINANT; EXPRESSION AB Disseminated infections due to Candida albicans are frequently encountered in immunocompromised patients. We compared the antifungal activities of macrophages residing in spleen, liver and lungs of rabbits against blastoconidia and pseudohyphae of C, albicans, Splenic adherent cells (SAC), Kupffer cells (KC) and pulmonary alveolar macrophages (PAM) all ingested blastoconidia efficiently. SAC caused significantly more damage to unopsonized pseudohyphae compared with KC (P < 0.01) or PAM (P <0.001). Incubation of SAC with 15 ng ml(-1) of recombinant human macrophage colony-stimulating factor (M-CSF) at 37 degrees C for 2 days significantly enhanced phagocytosis (P = 0.02) and killing (P = 0.05) of blastoconidia. In contrast, M-CSF had no effect on phagocytic activities of KC or PAM against blastoconidia or on damage caused by any of the macrophages to pseudohyphae of C. albicans. Thus, although all three resident macrophage types ingest blastoconidia efficiently, they differ in their capacity to cause damage to pseudohyphae and in their responsiveness to M-CSF for antifungal activation. M-CSF augments the capacity of SAC to ingest and kill blastoconidia and may therefore have a role in the treatment and prevention of hematogenously disseminated candidiasis. C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. Aristotelian Univ Salonika, Hippokrat Hosp, Dept Pediat 3, GR-54006 Salonika, Greece. RP Walsh, TJ (reprint author), NCI, Pediat Oncol Branch, Bldg 10,Rm 13N240, Bethesda, MD 20892 USA. NR 41 TC 13 Z9 14 U1 1 U2 2 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 2000 VL 38 IS 2 BP 161 EP 168 PG 8 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 313TY UT WOS:000087016400009 PM 10817233 ER PT J AU Daniels, MP Lowe, BT Shah, S Ma, JX Samuelson, SJ Lugo, B Parakh, T Uhm, CS AF Daniels, MP Lowe, BT Shah, S Ma, JX Samuelson, SJ Lugo, B Parakh, T Uhm, CS TI Rodent nerve-muscle cell culture system for studies of neuromuscular junction development: Refinements and applications SO MICROSCOPY RESEARCH AND TECHNIQUE LA English DT Article DE motoneuron; myotube; synapse; rat; acetylcholine receptor; agrin; axon; growth cone ID ACETYLCHOLINE-RECEPTOR AGGREGATION; CHICK CILIARY GANGLION; NEWLY FORMED SYNAPSES; AGRIN MESSENGER-RNA; RAT SPINAL-CORD; EMBRYONIC NEURONS; SKELETAL-MUSCLE; GROWTH-FACTOR; NGF RECEPTOR; INDUCTION AB Understanding of vertebrate neuromuscular junction (NMJ) development has been advanced by experimentation with cultures of dissociated embryonic nerve and skeletal muscle cells, particularly those derived from Xenopus and chick embryos. We previously developed a rodent (rat) nerve-muscle coculture system that is characterized by extensive induction of acetylcholine receptor (AChR) aggregation at sites of axonal contact with myotubes (Dutton et al., 1995). In this article, we report modifications of this culture system and examples of its application to the study of NMJ development: (1) We describe improved methods for the enrichment; of myoblasts to give higher yields of myotubes with equal or greater purity. (2) We demonstrate lipophilic dye labeling of axons in cocultures by injection of dye into neuron aggregates and show the feasibility of studying the growth of living axons on myotubes during synapse formation. (3) We describe the preparation of a better-defined coculture system containing myotubes with purified rat motoneurons and characterize the system with respect to axon-induced AChR aggregation. (4) We demonstrate dependence of the pattern of axon-induced AChR aggregation on muscle cell species, by the use of chick-rat chimeric co-cultures. (5) We provide evidence for the role of alternatively-spliced agrin isoforms in synapse formation by using single cell RT-PCR with neurons collected from co-cultures after observation of axon-induced AChR aggregation, Microsc. Res. Tech. 49:26-37, 2000. Published 2000. Wiley-Liss, Inc. C1 NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. RP Daniels, MP (reprint author), NHLBI, Lab Biochem Genet, NIH, Bldg 36,Rm 1C06,36 Convent Dr,MSC 4036, Bethesda, MD 20892 USA. NR 54 TC 31 Z9 32 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1059-910X J9 MICROSC RES TECHNIQ JI Microsc. Res. Tech. PD APR 1 PY 2000 VL 49 IS 1 BP 26 EP 37 DI 10.1002/(SICI)1097-0029(20000401)49:1<26::AID-JEMT4>3.0.CO;2-8 PG 12 WC Anatomy & Morphology; Biology; Microscopy SC Anatomy & Morphology; Life Sciences & Biomedicine - Other Topics; Microscopy GA 300ZK UT WOS:000086283500004 PM 10757876 ER PT J AU Pozner, A Goldenberg, D Negreanu, V Le, SY Elroy-Stein, O Levanon, D Groner, Y AF Pozner, A Goldenberg, D Negreanu, V Le, SY Elroy-Stein, O Levanon, D Groner, Y TI Transcription-coupled translation control of AML1/RUNX1 is mediated by cap- and internal ribosome entry site-dependent mechanisms SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; FACTOR MESSENGER-RNA; HUMAN FIBROBLAST GROWTH-FACTOR-2; CENTRAL-NERVOUS-SYSTEM; BINDING PROTEIN; POLIOVIRUS RNA; DEFINITIVE HEMATOPOIESIS; ALTERNATIVE TRANSLATION; 5'-UNTRANSLATED REGION; PICORNAVIRUS RNA AB AML1/RUNX1 belongs to the runt domain transcription factors that are important regulators of hematopoiesis and osteogenesis. Expression of AML1 is regulated at the level of transcription by two promoters, distal (D) and proximal (P), that give rise to mRNAs bearing two distinct 5' untranslated regions (5'UTRs) (D-UTR and P-UTR). Here we show that these 5'UTRs act as translation regulators in vivo. AML1 mRNAs bearing the uncommonly long (1,631-bp) P-UTR are poorly translated, whereas those with the shorter (452-bp) D-UTR are readily translated. The low translational efficiency of the P-UTR is attributed to its length and the cis-acting elements along it. Transfections and in vitro assays with bicistronic constructs demonstrate that the D-UTR mediates cap-dependent translation whereas the P-UTR mediates cap-independent translation and contains a functional internal ribosome entry site (IRES). The IRES-containing bicistronic constructs are more active in hematopoietic cell lines that normally express the P-UTR-containing mRNAs. Furthermore, we show that the IRES-dependent translation increases during megakaryocytic differentiation but not during erythroid differentiation, of K562 cells. These results strongly suggest that the function of the P-UTR IRES-dependent translation in vivo is to tightly regulate the translation of AML1 mRNAs. The data show that AML1 expression is regulated through usage of alternative promoters coupled with IRES-mediated translation control. This IRES-mediated translation regulation adds an important new dimension to the fine-tuned control of AML1 expression. C1 Weizmann Inst Sci, Dept Mol Genet, IL-76000 Rehovot, Israel. Tel Aviv Univ, Dept Cell Re s& Immunol, IL-69978 Tel Aviv, Israel. NCI, Lab Expt & Computat Biol, DBS, Frederick, MD 21702 USA. RP Groner, Y (reprint author), Weizmann Inst Sci, Dept Mol Genet, IL-76000 Rehovot, Israel. NR 70 TC 95 Z9 96 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2000 VL 20 IS 7 BP 2297 EP 2307 DI 10.1128/MCB.20.7.2297-2307.2000 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 292RQ UT WOS:000085809200001 PM 10713153 ER PT J AU Lee, BS Bi, L Garfinkel, DJ Bailis, AM AF Lee, BS Bi, L Garfinkel, DJ Bailis, AM TI Nucleotide excision repair/TFIIH helicases Rad3 and Ssl2 inhibit short-sequence recombination and Ty1 retrotransposition by similar mechanisms SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RNA-POLYMERASE-II; SACCHAROMYCES-CEREVISIAE GENOME; NUCLEAR-LOCALIZATION SIGNAL; MITOTIC RECOMBINATION; DNA HELICASE; HOMOLOGOUS RECOMBINATION; XERODERMA-PIGMENTOSUM; YEAST HOMOLOG; SPT3 GENE; TRANSCRIPTION AB Eukaryotic genomes contain potentially unstable sequences whose rearrangement threatens genome structure and function. Here we show that certain mutant alleles of the nucleotide excision repair (NER)/TFIIH helicase genes RAD3 and SSL2 (RAD25) confer synthetic lethality and destabilize the Saccharomyces cerevisiae genome by increasing both short-sequence recombination and Ty1 retrotransposition. The rad3-G595R and ssl1-rtt mutations do not markedly alter Ty1 RNA or protein levels or target site specificity. However, these mutations cause an increase in the physical stability of broken DNA molecules and unincorporated Ty1 cDNA, which leads to higher levels of short-sequence recombination and Ty1 retrotransposition. Our results link components of the core NER/TFIIH complex with genome stability, homologous recombination, and host defense against Ty1 retrotransposition via a mechanism that involves DNA degradation. C1 NCI, Gene Regulat & Chromosome Biol Lab, Frederick Canc Res & Dev Ctr, NIH, Frederick, MD 21702 USA. City Hope Natl Med Ctr, Beckman Res Inst, Dept Mol Biol, Duarte, CA 91010 USA. RP Garfinkel, DJ (reprint author), NCI, Gene Regulat & Chromosome Biol Lab, Frederick Canc Res & Dev Ctr, NIH, POB B, Frederick, MD 21702 USA. OI Bailis, Adam/0000-0001-5628-0468 FU NCI NIH HHS [CA33572, P30 CA033572]; NIGMS NIH HHS [GM57484, R01 GM057484] NR 77 TC 32 Z9 33 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 2000 VL 20 IS 7 BP 2436 EP 2445 DI 10.1128/MCB.20.7.2436-2445.2000 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 292RQ UT WOS:000085809200015 PM 10713167 ER PT J AU Qiu, HF Hu, CH Anderson, J Bjork, GR Sarkar, S Hopper, AK Hinnebusch, AG AF Qiu, HF Hu, CH Anderson, J Bjork, GR Sarkar, S Hopper, AK Hinnebusch, AG TI Defects in tRNA processing and nuclear export induce GCN4 translation independently of phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSFER-RNA-SYNTHETASE; PROTEIN-KINASE GCN2; SACCHAROMYCES-CEREVISIAE GENE; TRANSFER RIBONUCLEIC-ACIDS; PSEUDOURIDINE SYNTHASES; IDENTITY DETERMINANTS; CELL VIABILITY; RIBOSOMAL-RNA; MESSENGER-RNA; YEAST AB Induction of GCN4 translation in amino acid-starved cells involves the inhibition of initiator tRNA(Met) binding to eukaryotic translation initiation factor 2 (eIF2) in response to eIF2 phosphorylation by protein kinase GCN2, It was shown previously that GCN4 translation could be induced independently of GCN2 by overexpressing a mutant tRNA(AAC)(Val), (tRNA(Val*)) or the RNA component of RNase MRP encoded by NME1, Here we show that overexpression of the tRNA pseudouridine 55 synthase encoded by PUS4 also leads to translational derepression of GCN4 (Gcd(-) phenotype) independently of eIF2 phosphorylation, Surprisingly, the Gcd(-) phenotype of high-copy-number PUS4 (hcPUS4) did not require PUS4 enzymatic activity, and several lines of evidence indicate that PUS4 overexpression did not diminish functional initiator tRNA(Met) levels. The presence of hcPUS4 or hcNME1 led to the accumulation of certain tRNA precursors, and their Gcd(-) phenotypes were reversed by overexpressing the RNA component of RNase P (RPR1), responsible for 5'-end processing of all tRNAs, Consistently, overexpression of a mutant pre-tRNA(Tyr) that cannot be processed by RNase P had a Gcd(-) phenotype, Interestingly, the Gcd- phenotype of hcPUS4 also was reversed by overexpressing LOS1, required for efficient nuclear export of tRNA, and los1 Delta cells have a Gcd- phenotype, Overproduced PUS4 appears to impede 5'-end processing or export of certain tRNAs in the nucleus in a manner remedied by increased expression of RNase P or LOS1, respectively, The mutant tRNA(Val*) showed nuclear accumulation in otherwise wild-type cells, suggesting a defect in export to the cytoplasm, We propose that yeast contains a nuclear surveillance system that perceives defects in processing or export of tRNA and evokes a reduction in translation initiation at the step of initiator tRNA(Met) binding to the ribosome. C1 NICHHD, Lab Eukaryot Gene Regulat, Bethesda, MD 20892 USA. Umea Univ, Dept Microbiol, S-90187 Umea, Sweden. Penn State Univ, Coll Med, Dept Biochem & Mol Biol, Hershey, PA 17033 USA. RP Hinnebusch, AG (reprint author), NICHHD, Lab Eukaryot Gene Regulat, Bldg 6A,Rm B1A-13A, Bethesda, MD 20892 USA. FU NIGMS NIH HHS [GM27930, R01 GM027930] NR 60 TC 46 Z9 50 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 2000 VL 20 IS 7 BP 2505 EP 2516 DI 10.1128/MCB.20.7.2505-2516.2000 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 292RQ UT WOS:000085809200022 PM 10713174 ER PT J AU Zhu, XG Park, KS Kaneshige, M Bhat, MK Zhu, QH Mariash, CN McPhie, P Cheng, SY AF Zhu, XG Park, KS Kaneshige, M Bhat, MK Zhu, QH Mariash, CN McPhie, P Cheng, SY TI The orphan nuclear receptor Ear-2 is a negative coregulator for thyroid hormone nuclear receptor function SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID OXYTOCIN GENE PROMOTER; RETINOID-X RECEPTOR; TRANSCRIPTIONAL ACTIVATION; RESPONSE ELEMENT; COUP-TFII; COACTIVATOR; PHOSPHORYLATION; BINDING; BETA; DNA AB Thyroid hormone (T3) nuclear receptors (TR) are ligand-dependent transcription factors which regulate growth, differentiation, and development. One emerging hypothesis suggests that TR mediate these diverse effects via a large network of coregulators. Recently, we found that TR-mediated transcriptional responses varied in six cell lines derived from different tissues. We therefore used human TR subtype beta 1 (TR beta 1) as bait to search for coregulators in human colon carcinoma RKO cells with a yeast two-hybrid system. RKO cells exhibited T3-dependent and -independent transcriptional activation. One of the three positive clones was identified as Ear-2, which is a distant member of the chick ovalbumin upstream promoter-transcription factors of the orphan nuclear receptor family. The physical interaction between Ear-2 and TR beta 1 was further confirmed by specific binding of Ear-2 to glutathione S-transferase-TR beta 1, In addition, Ear-2 was found to associate with TR beta 1 in cells. As a result of this physical interaction, binding of TR beta 1 to the T3 response elements was inhibited. Using reporter systems, we found that both the basal activation and the T3-dependent activation mediated by TP beta 1 were repressed by Ear-2 in CV1 cells. In RKO cells, however, the T3-independent transcriptional activity was more sensitive to the repression effect of Ear-2 than the T3-dependent transcriptional activity. The repression effect of Ear-2 was reversed by steroid hormone receptor coactivator I. These results suggest that TR-mediated responses reflect a balance of corepressors and coactivators in cells. These findings further strengthen the hypothesis that the diverse activities of TR are achieved via a large network of coregulators that includes Ear-2. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Biochem Pharmacol Lab, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Dept Med, Div Endocrinol & Diabet, Minneapolis, MN 55455 USA. RP Cheng, SY (reprint author), Bldg 37,Room 2D24,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. FU NIDDK NIH HHS [P30 DK050456, P30 DK50456] NR 36 TC 21 Z9 23 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2000 VL 20 IS 7 BP 2604 EP 2618 DI 10.1128/MCB.20.7.2604-2618.2000 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 292RQ UT WOS:000085809200030 PM 10713182 ER PT J AU Bera, TK Pastan, I AF Bera, TK Pastan, I TI Mesothelin is not required for normal mouse development or reproduction SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MOLECULAR-CLONING; SURFACE AB Mesothelin is a glycosylphosphatidylinositol-linked glycoprotein highly expressed in mesothelial cells, mesotheliomas, and ovarian cancer, but the biological function(s) of the protein is not known. We have analyzed the expression of the mouse mesothelin gene in different developmental stages and in various adult tissues by Northern hybridization, The 2.5-kb mesothelin transcript was detected in the mRNA of E 7.0, E 15.0, and E 17.0 stages of mouse development. In adult tissues the mesothelin gene was expressed in lung, heart, spleen, liver, kidney, and testis, To directly assess the function of the mesothelin in vivo, we generated mutant mice in which the mesothelin gene was inactivated by replacing it with the neomycin resistance gene. In homozygous mutant mice neither mesothelin mRNA nor the protein product was detected, Null mutant mice were obtained in accordance with Mendelian laws, and both males and females produced offspring normally. No anatomical or histological abnormalities were detected in any tissues where mesothelin was reportedly expressed in wild-type mice. Our results demonstrate that mesothelin function is not essential for growth or reproduction in mice. 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 9 TC 94 Z9 100 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2000 VL 20 IS 8 BP 2902 EP 2906 DI 10.1128/MCB.20.8.2902-2906.2000 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 299VJ UT WOS:000086218300029 PM 10733593 ER PT J AU Ugur, O Jones, TLZ AF Ugur, O Jones, TLZ TI A proline-rich region and nearby cysteine residues target XL alpha s to the Golgi complex region SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID HETEROTRIMERIC-G-PROTEINS; TRIMERIC G-PROTEINS; ENDOPLASMIC-RETICULUM; MEMBRANE ATTACHMENT; MOLECULAR CHARACTERIZATION; DIFFERENTIAL DISTRIBUTION; MAMMALIAN-CELLS; CHOLERA-TOXIN; AMINO-ACIDS; SH3 DOMAINS AB XL alpha s is a splice variant of the heterotrimeric G protein, G alpha(s), found on Golgi membranes in cells with regulated and constitutive secretion. We examined the role of the alternatively spliced amino terminus of XL alpha s for Golgi targeting with the use of subcellular fractionation and fluorescence microscopy. XL alpha s incorporated [H-3]palmitate, and mutation of cysteines in a cysteine-rich region inhibited this incorporation and lessened membrane attachment. Deletion of a proline-rich region abolished Golgi localization of XL alpha s without changing its membrane attachment. The proline-rich and cysteine-rich regions together were sufficient to target the green fluorescent protein, a cytosolic protein, to Golgi membranes. The membrane attachment and Golgi targeting of the fusion protein required the putative palmitoylation sites, the cysteine residues in the cysteine-rich region. Several peripheral membrane proteins found at the Golgi have proline-rich regions, including a G alpha(i2) splice variant, dynamin II, beta III spectrin, comitin, and a Golgi SNARE, GS32. Our results suggest that proline-rich regions can be a Golgi-targeting signal for G protein alpha subunits and possibly for other peripheral membrane proteins as well. C1 Ankara Univ, Fac Med, Dept Pharmacol & Clin Pharmacol, TR-06100 Ankara, Turkey. NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Jones, TLZ (reprint author), Ankara Univ, Fac Med, Dept Pharmacol & Clin Pharmacol, TR-06100 Ankara, Turkey. NR 61 TC 32 Z9 32 U1 0 U2 4 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD APR PY 2000 VL 11 IS 4 BP 1421 EP 1432 PG 12 WC Cell Biology SC Cell Biology GA 304WZ UT WOS:000086508200022 PM 10749939 ER PT J AU Rehman, I Lowry, DT Adams, C Abdel-Fattah, R Holly, A Yuspa, SH Hennings, H AF Rehman, I Lowry, DT Adams, C Abdel-Fattah, R Holly, A Yuspa, SH Hennings, H TI Frequent codon 12 Ki-ras mutations in mouse skin tumors initiated by N-methyl-N '-nitro-N-nitrosoguanidine and promoted by mezerein SO MOLECULAR CARCINOGENESIS LA English DT Article DE papilloma; keratoacanthoma; squamous cell carcinoma; promotion; progression ID N-RAS; HA-RAS; PROTO-ONCOGENE; LIVER-TUMORS; GENE; MICE; CANCER; LUNG; ACTIVATION; PAPILLOMAS AB (DMBA) differ in effectiveness when tumor formation is promoted by 12-O-tetradecanoylphorbol-13-acetate (TPA). Even at high doses, MNNG is less effective, producing fewer benign and malignant tumors with a longer latent period. In DMBA-initiated skin, 10 wk of TPA promotion produced a maximal tumor response. With MNNG, 20 wk of TPA promotion was required, producing nearly four times as many papillomas as 10 wk of promotion. Promotion of MNNG-initiated skin with mezerein induced the appearance of very rapidly-growing papillomas within 5 wk, 3 wk earlier than the first TPA-promoted papillomas. Thus, MNNG may induce a novel mutation resulting in a population of initiated cells that respond especially well to mezerein. Since ras mutations are common in experimental tumors in many tissues, we determined the frequency of activating mutations in the Ha-ras, Ki-ras, and N-ras oncogenes. Activating Ha-ras mutations were present in essentially all DMBA-initiated tumor; and about 70% of MNNG-initiated tumors. No N-ras mutations were found in tumors lacking other ras mutations. Surprisingly, 41% of the papillomas arising in the first 11 wk in MNNG-initiated, mezerein-promoted mice bore mutations in codon 12 of the Ki-ras oncogene. Activating Ki-ras mutations were also found in more than 60% of squamous cell carcinomas and 40% of keratoacanthomas. Although mutations in Ha-ras are frequently detected in mouse skin tumors, mutations in Ki-ras are rare. This is the first report of mutated Ki-ras in skin tumors from mice initiated by MNNG. Published 2000 Wiley-Liss. Inc.(1) C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. RP Hennings, H (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bldg 37,Room 3B12,37 Convent Dr,MSC4255, Bethesda, MD 20892 USA. NR 44 TC 19 Z9 19 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD APR PY 2000 VL 27 IS 4 BP 298 EP 307 DI 10.1002/(SICI)1098-2744(200004)27:4<298::AID-MC8>3.0.CO;2-4 PG 10 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 301BH UT WOS:000086287900007 PM 10747294 ER PT J AU Napolitano, G Montani, V Giuliani, C Di Vincenzo, S Bucci, I Todisco, V Laglia, G Coppa, A Singer, DS Nakazato, M Kohn, LD Colletta, G Monaco, F AF Napolitano, G Montani, V Giuliani, C Di Vincenzo, S Bucci, I Todisco, V Laglia, G Coppa, A Singer, DS Nakazato, M Kohn, LD Colletta, G Monaco, F TI Transforming growth factor-beta 1 down-regulation of major histocompatibility complex class I in thyrocytes: Coordinate regulation of two separate elements by thyroid-specific as well as ubiquitous transcription factors SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; NF-KAPPA-B; DEOXYRIBONUCLEIC-ACID SYNTHESIS; THYROTROPIN RECEPTOR PROMOTER; SYSTEMIC-LUPUS-ERYTHEMATOSUS; AMP-RESPONSIVE ELEMENT; GENE-EXPRESSION; TGF-BETA; FRTL-5 CELLS; ANTIGEN-EXPRESSION AB Transforming growth factor (TGF)-beta 1-decreased major histocompatibility complex (MHC) class I gene expression in thyrocytes is transcriptional; it involves trans factors and cis elements important for hormone- as well as iodide-regulated thyroid growth and function. Thus, in rat FRTL-5 thyrocytes, TGF-beta 1 regulates two elements within -203 bp of the transcription start site of the MHC class I 5'-flanking region: Enhancer A, -180 to -170 bp, and a downstream regulatory element (DRE), -129 to -90 bp, that contains a cAMP response element (CRE)-like sequence. TGF-beta 1 reduces the interaction of a NF-kappa B p50/fra-2 heterodimer (MOD-1) with Enhancer A while increasing its interaction with a NF-kappa B p50/p65 heterodimer. Both reduced MOD-1 and increased p50/p65 suppresses class I expression. Decreased MOD-1 and increased p50/p65 have been separately associated with the ability of autoregulatory (high) concentrations of iodide to suppress thyrocyte growth and function, as well as MHC class I expression. TGF-beta 1 has two effects on the downstream regulatory element (DRE). It increases DRE binding of a ubiquitously expressed Y-box protein, termed TSEP-1 (TSHR suppressor element binding protein-1) in rat thyroid cells; TSEP-1 has been shown separately to be an important suppressor of the TSH receptor (TSHR) in addition to MHC class I and class II expression. It also decreases the binding of a thyroid-specific trans factor, thyroid transcription factor-1 (TTF-l), to the DRE, reflecting the ability of TGF-beta 1 to decrease TTF-1 RNA levels. TGF-beta 1-decreased TTF-l expression accounts in part for TGF-beta 1-decreased thyroid growth and function, since decreased TTF-l has been shown to decrease thyroglobulin, thyroperoxidase, sodium iodide symporter, and TSHR gene expression, coincident with decreased MHC class I. Finally, we show that TGF-beta 1 increases c-jun RNA levels and induces the formation of new complexes involving c-jun, fra-2, ATF-1, and c-fos, which react with Enhancer A and the DRE. TGF-beta 1 effects on c-jun may be a pivotal fulcrum in the hitherto unrecognized coordinate regulation of Enhancer A and the DRE. C1 Univ G dAnnunzio, Chair Endocrinol, Dept Med, I-66100 Chieti, Italy. Univ G dAnnunzio, Chair Endocrinol, Dept Oncol & Neurosci, I-66100 Chieti, Italy. Univ Roma La Sapienza, Dept Expt Med & Pathol, I-00161 Rome, Italy. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Monaco, F (reprint author), Univ G dAnnunzio, Chair Endocrinol, Dept Med, Palazzina Scuole Specializzazione,Via Dei Vestini, I-66100 Chieti, Italy. EM lenk@bdg10.niddk.nih.gov RI coppa, anna/N-3274-2016 NR 70 TC 17 Z9 18 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD APR PY 2000 VL 14 IS 4 BP 486 EP 505 DI 10.1210/me.14.4.486 PG 20 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 301JW UT WOS:000086307900003 PM 10770487 ER EF