FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Sloand, EM Fuhrer, M Maciejewski, JP Johnson, S Keyvonafar, K Barrett, J Young, NS AF Sloand, EM Fuhrer, M Maciejewski, JP Johnson, S Keyvonafar, K Barrett, J Young, NS TI When cytogenetic abnormalities occur in patients with paroxysmal nocturnal hemoglobinuia (PNH), they primarily affect the glyocphosphatydlinositol (GPI)-positive cell clones. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Div Intramural Res, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 864 BP 229A EP 229A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700865 ER PT J AU Plasilova, M O'Keefe, CL Rodriguez, A Risitano, AM Kalaycio, M Young, NS Maciejewski, JP AF Plasilova, M O'Keefe, CL Rodriguez, A Risitano, AM Kalaycio, M Young, NS Maciejewski, JP TI Paroxysmal nocturnal hemoglobinuria-IN the search for disease-specific T-cell clones. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Cleveland Clin Fdn, Hematopoiesis & Leukemia Program, Cleveland, OH 44195 USA. NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 867 BP 230A EP 230A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700868 ER PT J AU Zeng, WH Chen, GB Kajigaya, S Nunez, O Charrowa, A Billings, E Young, NS AF Zeng, WH Chen, GB Kajigaya, S Nunez, O Charrowa, A Billings, E Young, NS TI Genes expression profiling in CD34 cells identifies significant differences between aplastic anemia patients and normal individuals. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA. NHLBI, NIH, Bioinformat Core Facil, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 875 BP 232A EP 232A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700876 ER PT J AU Maciejewski, JP Nunez, O Sloand, EM Young, NS AF Maciejewski, JP Nunez, O Sloand, EM Young, NS TI Recombinant-humanized-anti-IL2-receptor antibody (Daclizumab) produces responses in patients with moderate aplastic anemia. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Div Intramural Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 878 BP 233A EP 233A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700879 ER PT J AU Jie, W Rogers, H Noguchi, CT AF Jie, W Rogers, H Noguchi, CT TI SATB1 activates early globin gene expression by histone modification of the beta-globin gene cluster. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NIDDK, NIH, Biol Chem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 897 BP 238A EP 238A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700898 ER PT J AU Erdmann, A Gao, ZG Jung, U Foley, JE Jacobson, KA Fowler, DH AF Erdmann, A Gao, ZG Jung, U Foley, JE Jacobson, KA Fowler, DH TI Differential regulation of Tc1 and Tc2 cell function by the A(2A) adenosine receptor. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NCI, NIH, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NIDDK, Bioorgan Chem Lab, NIH, Mol Recognit Sect, Bethesda, MD 20892 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 940 BP 248A EP 248A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700941 ER PT J AU Hou, JW Levine, B June, C Fowler, D AF Hou, JW Levine, B June, C Fowler, D TI Naive (CD45RA+) vs memory (CD45RO+) status of human CD4 cells greatly influences Th1/Th2 polarization potential. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NCI, Bethesda, MD 20892 USA. Abramson Family Canc Res Inst, Philadelphia, PA USA. RI Levine, Bruce/D-1688-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 944 BP 249A EP 249A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700945 ER PT J AU Czapiga, M Kirk, A Lekstrom-Himes, J AF Czapiga, M Kirk, A Lekstrom-Himes, J TI Human platelets exhibit chemotaxis using functional N-formyl peptide receptors. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NIAID, NIH, Bethesda, MD 20892 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 951 BP 251A EP 251A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184700952 ER PT J AU Eyster, ME Sanders, JC Goedert, JJ AF Eyster, ME Sanders, JC Goedert, JJ TI Viral clearance occurs very early during the natural resolution of transfusion-acquired hepatitis C virus infections. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Penn State Univ, Coll Med, Hershey, PA USA. NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1086 BP 283A EP 283A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184701086 ER PT J AU Griffith, LM McCoy, JP Bolan, CD Stroncek, DF Pickett, A Linton, GF Leitman, SF Childs, RW AF Griffith, LM McCoy, JP Bolan, CD Stroncek, DF Pickett, A Linton, GF Leitman, SF Childs, RW TI Persistent recipient plasma cells and antidonor isohemagglutinin production in patients with delayed donor erythroid engraftment following major ABO incompatible nonmyeloablative stem cell transplantation (NST). SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NHLBI, NIH, Flow Cytometry Core Facil, Bethesda, MD 20892 USA. NIAID, NIH, Host Def Lab, Bethesda, MD 20892 USA. NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1087 BP 283A EP 284A PN 1 PG 2 WC Hematology SC Hematology GA 614JK UT WOS:000179184701087 ER PT J AU Griffith, LM Wesley, RA Childs, RW Conley, B Carter, CS Read, EJ Stroncek, DF Barrett, AJ Bolan, CD Leitman, SF AF Griffith, LM Wesley, RA Childs, RW Conley, B Carter, CS Read, EJ Stroncek, DF Barrett, AJ Bolan, CD Leitman, SF TI Transfusion support following nonmyeloablative or myeloablative allogeneic hematopoietic cell transplantation - CD34 cell dose and red cells transfused pretransplant predict intensity of support and time to transfusion independence. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NIH, Warren G Magnuson Clin Ctr, Biostat Branch, Off Director, Bethesda, MD 20892 USA. NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1088 BP 284A EP 284A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184701088 ER PT J AU Leitman, SF Browning, JN Yu, YY Mason, G Conry-Cantilena, C Klein, HG Bolan, C AF Leitman, SF Browning, JN Yu, YY Mason, G Conry-Cantilena, C Klein, HG Bolan, C TI Impact of using hemochromatosis subjects as allogeneic blood donors: A prospective study. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1090 BP 284A EP 284A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184701090 ER PT J AU Lazo, A Tassello, J Ohagen, A Aytay, S Wong, S Brown, K AF Lazo, A Tassello, J Ohagen, A Aytay, S Wong, S Brown, K TI INACTINE (TM) technology inactivates clinical isolates of parvovirus B19 in RBC concentrates as demonstrated by PCR and infectivity assays. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 VI Technol Inc, Watertown, MA USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1094 BP 285A EP 285A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184701094 ER PT J AU Nemeth, MJ Curtis, DJ Cline, AP Kirby, MR Bodine, DM AF Nemeth, MJ Curtis, DJ Cline, AP Kirby, MR Bodine, DM TI Decreased numbers of hematopoietic stem cells in HMG-4 knock-out mice. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. Royal Melbourne Hosp, Rotary Bone Marrow Res Lab, Melbourne, Vic, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1114 BP 290A EP 290A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184701114 ER PT J AU Laukkanen, MO Kuramoto, K Takatoku, M von Kalle, C Dunbar, CE AF Laukkanen, MO Kuramoto, K Takatoku, M von Kalle, C Dunbar, CE TI The effect of total body irradiation on stem cell dynamics in non-human primate rhesus macaques. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Univ Freiburg, Dept Internal Med, D-7800 Freiburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1119 BP 291A EP 292A PN 1 PG 2 WC Hematology SC Hematology GA 614JK UT WOS:000179184701119 ER PT J AU Garvey, TL Khanna-Gupta, A Casanova, JL Berliner, N Lekstrom-Himes, JA AF Garvey, TL Khanna-Gupta, A Casanova, JL Berliner, N Lekstrom-Himes, JA TI Functional analysis of the alpha and beta promoters of C/EBP epsilon. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NIAID, NIH, Host Def Lab, Bethesda, MD 20892 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. Necker Enfants Malad Med Sch, Pediat Immunol Hematol Unit, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1149 BP 298A EP 298A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184701149 ER PT J AU Aerbajinai, W Giattina, M Bhanu, NV Lee, YWT Raffeld, M Miller, JL AF Aerbajinai, W Giattina, M Bhanu, NV Lee, YWT Raffeld, M Miller, JL TI The pro-apoptotic factor Nix is co-expressed with Bcl-xL during terminal human erythroid differentiation. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NIH, Biol Chem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1182 BP 306A EP 306A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184701182 ER PT J AU Lin, YW Zhang, ZH Aplan, PD AF Lin, YW Zhang, ZH Aplan, PD TI Genomic instability in leukemic cell lines. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NCI, Genet Branch, Rockville, MD USA. RI Aplan, Peter/K-9064-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1198 BP 309A EP 309A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184701198 ER PT J AU Hu, J Magnusson, MK Robyn, J Dunbar, CE AF Hu, J Magnusson, MK Robyn, J Dunbar, CE TI Analysis of gene expression patterns in hematopoietic cells transformed with leukemogenic fusion genes activating Abl versus PDGF receptor tyrosine kinases. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1210 BP 312A EP 313A PN 1 PG 2 WC Hematology SC Hematology GA 614JK UT WOS:000179184701210 ER PT J AU Davies, A Rosenwald, A Wright, G Henrickson, SE Hong, Z Fitzgibbon, J Last, K Norton, A Staudt, LM Lister, TA AF Davies, A Rosenwald, A Wright, G Henrickson, SE Hong, Z Fitzgibbon, J Last, K Norton, A Staudt, LM Lister, TA TI Gene expression profiling in paired follicular lymphoma samples pre- and post-transformation to large B cell lymphoma. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 St Bartholomews Hosp, Canc Res UK Med Oncol Unit, Dept Med Oncol, London, England. NCI, NIH, Ctr Canc Res, Metab Branch, Bethesda, MD 20892 USA. NCI, NIH, Div Canc Treatment & Diagnosis, Biometr Res Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1221 BP 315A EP 316A PN 1 PG 2 WC Hematology SC Hematology GA 614JK UT WOS:000179184701221 ER PT J AU Marcucci, G Stock, W Klisovic, MI Guimond, M Sher, DA Moran, M Zwiebel, JA Cataland, SR Kefauver, C Chan, KK Frankel, SR Grever, MR Byrd, JC AF Marcucci, G Stock, W Klisovic, MI Guimond, M Sher, DA Moran, M Zwiebel, JA Cataland, SR Kefauver, C Chan, KK Frankel, SR Grever, MR Byrd, JC TI In vivo activity of Genasense (TM) (G3139) (GS), a bcl-2 antisense oligonucleotide in previously untreated patients (pts) > 60 years with acute myeloid leukemia (AML): Initial report of a phase I study in combination with daunorubicin and cytarabine. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. Ohio State Univ, Dept Med, Columbus, OH 43210 USA. Univ Chicago, Chicago, IL 60637 USA. NCI, Bethesda, MD 20892 USA. Genta Inc, Berkeley Hts, NJ USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1307 BP 337A EP 337A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184701307 ER PT J AU Islam, A Bielat, K Smith, G AF Islam, A Bielat, K Smith, G TI Does thalidomide have an effect other than anti-angiogenesis. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Buffalo Gen Hosp, Dept Med, Div Hematol Oncol, Buffalo, NY 14203 USA. NCI, Bethesda, MD 20892 USA. Sheehan Mem Hosp, Dept Med, Buffalo, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 4918 BP 341B EP 341B PN 2 PG 1 WC Hematology SC Hematology GA 614JL UT WOS:000179184801460 ER PT J AU Miller, TP LeBlanc, M Grogan, TM Braziel, RM Staudt, LM Fisher, RL AF Miller, TP LeBlanc, M Grogan, TM Braziel, RM Staudt, LM Fisher, RL TI Major histocompatibility complex (MHC) class II antigen HLA-DR gene expression levels in diffuse large B-cell lymphoma correlate with survival. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85721 USA. SW Oncol Grp, Ctr Stat, Seattle, WA USA. Oregon Hlth Sci Univ, Dept Pathol, Portland, OR 97201 USA. NCI, Metab Branch, Bethesda, MD 20892 USA. Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY 14627 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1341 BP 346A EP 346A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184701341 ER PT J AU Grube, M Rezvani, K Sconocchia, G Fujiwara, H Melenhorst, JJ Hensel, N Barrett, AJ AF Grube, M Rezvani, K Sconocchia, G Fujiwara, H Melenhorst, JJ Hensel, N Barrett, AJ TI Are normally expressed B-cell differentiation antigens possible target antigens for cellular immunotherapy in B-cell malignancies? SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHLBI, NIH, Hematol Branch, Stem Cell Allogene Transplantat Unit, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1375 BP 354A EP 355A PN 1 PG 2 WC Hematology SC Hematology GA 614JK UT WOS:000179184701375 ER PT J AU Jamroziak, K Smolewski, P Robey, RW Cebula, B Balcerczak, E Mirowski, M Szmigielska-Kaplon, A Bates, SE Robak, T AF Jamroziak, K Smolewski, P Robey, RW Cebula, B Balcerczak, E Mirowski, M Szmigielska-Kaplon, A Bates, SE Robak, T TI Activity of breast cancer resistance protein (BCRP/ABCG2) in B-cell chronic lymphocytic leukemia (B-CLL). SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Med Univ Lodz, Dept Hematol, Lodz, Poland. NCI, Dev Therapeut Dept, NIH, Bethesda, MD 20892 USA. Med Univ Lodz, Mol Biol Lab, Dept Pharmaceut Biochem, Lodz, Poland. RI Szmigielska, Katarzyna/S-9216-2016; Balcerczak, Ewa/S-9838-2016 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 4980 BP 356B EP 356B PN 2 PG 1 WC Hematology SC Hematology GA 614JL UT WOS:000179184801522 ER PT J AU Hegde, U White, T Stetler-Stevenson, M Marti, G Janik, J Pittaluga, S Kingma, D Steinberg, S Cheson, B Jaffe, ES Wilson, WH AF Hegde, U White, T Stetler-Stevenson, M Marti, G Janik, J Pittaluga, S Kingma, D Steinberg, S Cheson, B Jaffe, ES Wilson, WH TI Phase I study of combination rituximab (CD20) and apolizumab (Hu1D10) monoclonal antibody therapy in previously treated B-cell lymphoma and chronic lymphocytic leukemia. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA. US FDA, Bethesda, MD 20014 USA. Georgetown Univ Hosp, Div Hematol Oncol, Washington, DC 20007 USA. NR 0 TC 6 Z9 6 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1389 BP 358A EP 358A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184701390 ER PT J AU Xiang, S Lee, CH Pack, S Vatolin, S Chernukin, I Klenova, E Doquier, F Loukinov, D Furuta, M Hardin, J Kuehl, M Barlogie, B Shaughnessy, J Lobanenkov, V Morse, H AF Xiang, S Lee, CH Pack, S Vatolin, S Chernukin, I Klenova, E Doquier, F Loukinov, D Furuta, M Hardin, J Kuehl, M Barlogie, B Shaughnessy, J Lobanenkov, V Morse, H TI BORIS, an unusual cancer/testic gene at 20q13 which shares the same 11 zinc-finger domain with the ubiquitous tumor suppressor gene, CTCF, at 16q22 is aberrantly expressed in multiple myeloma: Implications for pathogenesis and treatment. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NIAID, Immunopathol Lab, NIH, Rockville, MD USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Univ Essex, Dept Biol Sci, Colchester CO4 3SQ, Essex, England. Fred Hutchinson Canc Res Ctr, SW Oncol Grp, Seattle, WA 98104 USA. NCI, Dept Genet, Med Branch, NIH, Bethesda, MD 20892 USA. Univ Arkansas Med Sci, Myeloma & Transplantat Res Ctr, Little Rock, AR 72205 USA. RI Pack, Svetlana/C-2020-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 5024 BP 366B EP 366B PN 2 PG 1 WC Hematology SC Hematology GA 614JL UT WOS:000179184801566 ER PT J AU Schechter, GP Buskell, ZL Haynes, R Talastas, M Dufour, DR Seeff, LB AF Schechter, GP Buskell, ZL Haynes, R Talastas, M Dufour, DR Seeff, LB TI Monoclonal Gammopathy and hepatitis C exposure in hospitalized patients at an urban VA medical center. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Vet Affairs Med Ctr, Washington, DC 20422 USA. George Washington Univ, Washington, DC USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 5055 BP 373B EP 373B PN 2 PG 1 WC Hematology SC Hematology GA 614JL UT WOS:000179184801597 ER PT J AU Lucas, DM Baird, ME Byrd, JC Tschumper, RC Jelinek, DF Kitada, S Reed, JC Rosenwald, A Staudt, LM Neuberg, DS Tallman, MS Flinn, IW Grever, MR AF Lucas, DM Baird, ME Byrd, JC Tschumper, RC Jelinek, DF Kitada, S Reed, JC Rosenwald, A Staudt, LM Neuberg, DS Tallman, MS Flinn, IW Grever, MR TI ZAP70 and caspase-3 protein expression independently associate with immunoglobulin VH gene mutational status in patients with B-cell chronic lymphocytic leukemia (B-CLL). SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Ohio State Univ, Columbus, OH 43210 USA. Mayo Clin, Rochester, MN USA. Burnham Inst, La Jolla, CA 92037 USA. NIH, Div Clin Sci, Bethesda, MD 20892 USA. Eastern Cooperat Oncol Grp, Boston, MA USA. Johns Hopkins Univ, Med Ctr, Baltimore, MD 21218 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1478 BP 381A EP 381A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184701479 ER PT J AU Chen, JC Lipovsky, K Young, NS AF Chen, JC Lipovsky, K Young, NS TI Immune-mediated bone marrow failure mouse model reveals T cell infiltration and indiscriminant bone marrow cell destruction. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 5150 BP 396B EP 396B PN 2 PG 1 WC Hematology SC Hematology GA 614JL UT WOS:000179184801692 ER PT J AU Sun, K Murphy, WJ AF Sun, K Murphy, WJ TI Role of NK cells in allogeneic bone marrow resistance under non-myeloablative conditions: Depletion of host NK subsets in SCID mice increases donor engraftment and results in long-term subacute GVHD. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NCI, SAIC, IRSP, Frederick, MD 21701 USA. Univ Nevada, Dept Microbiol, Reno, NV 89557 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 5203 BP 409B EP 409B PN 2 PG 1 WC Hematology SC Hematology GA 614JL UT WOS:000179184801745 ER PT J AU Rezvani, K Grube, M Hensel, N Fujiwara, H Sconocchia, G Barrett, J AF Rezvani, K Grube, M Hensel, N Fujiwara, H Sconocchia, G Barrett, J TI A highly sensitive RT-PCR assay for interferon-gamma identifies multiple circulating low frequency CD8+ T cells recognizing tumor peptides PR1, WT1 and BCR-ABL in normal individuals, CML patients and stem cell transplant (SCT) recipients. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 5208 BP 410B EP 410B PN 2 PG 1 WC Hematology SC Hematology GA 614JL UT WOS:000179184801750 ER PT J AU Michalek, J Collins, RH Durrani, HP Douek, DC Vitetta, ES AF Michalek, J Collins, RH Durrani, HP Douek, DC Vitetta, ES TI Donor-derived alloreactive T cell clones and anti-leukemia T cell clones can be different. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Univ Texas, SW Med Ctr, Ctr Canc Immunobiol, Dallas, TX 75230 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 5212 BP 411B EP 411B PN 2 PG 1 WC Hematology SC Hematology GA 614JL UT WOS:000179184801754 ER PT J AU Oh, H Zhang, MJ Akiyama, H Asai, T Barrett, AJ Loberiza, FR Miyawaki, S Okamoto, S Ringden, O Horowitz, MM AF Oh, H Zhang, MJ Akiyama, H Asai, T Barrett, AJ Loberiza, FR Miyawaki, S Okamoto, S Ringden, O Horowitz, MM TI Comparison of graft-versus-host disease (GVHD) and survival in different ethnic populations: Collaborative study by the Japan Adult Leukemia Study Group (JALSG) and the International Bone Marrow Transplant Registry (IBMTR). SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 INOUE Mem Hosp, Dept Med, Chiba, Japan. Med Coll Wisconsin, Int Bone Marrow Transplant Registry, Milwaukee, WI 53226 USA. Tokyo Metropolitan Komagome Hosp, Dept Internal Med, Tokyo, Japan. Chiba Univ Hosp, Div Transfus, Chiba, Japan. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Saiseikai Maebashi Hosp, Dept Internal Med, Maebashi, Gumma, Japan. Keio Univ Hosp, Div Hematol, Tokyo, Japan. Huddinge Univ Hosp, S-14186 Huddinge, Sweden. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1621 BP 418A EP 418A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184701622 ER PT J AU Chakrabarti, S Srinivasan, R Geller, N Abo-Zena, RA Marquesen, M Goodwin, R Donohue, T Dunbar, C Young, NS Leitman, SF Read, EJ Bolan, CD Barrett, AJ Childs, R AF Chakrabarti, S Srinivasan, R Geller, N Abo-Zena, RA Marquesen, M Goodwin, R Donohue, T Dunbar, C Young, NS Leitman, SF Read, EJ Bolan, CD Barrett, AJ Childs, R TI Impact of adding mycophenolate mofetil (MMF) to cyclosporine (CSA) as prophylaxis for acute graft versus host disease (GVHD) following nonmyeloablative allogeneic peripheral blood stem cell (PBSC) transplantation. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHLBI, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1626 BP 419A EP 420A PN 1 PG 2 WC Hematology SC Hematology GA 614JK UT WOS:000179184701627 ER PT J AU Childs, R Bradstock, K Gottlieb, D Blaise, D Leifer, E Geller, N Mohty, M Faucher, C Srinivasan, R Kefford, R Hegenbart, U Niederwieser, D Barrett, AJ AF Childs, R Bradstock, K Gottlieb, D Blaise, D Leifer, E Geller, N Mohty, M Faucher, C Srinivasan, R Kefford, R Hegenbart, U Niederwieser, D Barrett, AJ TI Non-myeloablative allogeneic stem cell transplantation (NST) for metastatic melanoma: Nondurable chemotherapy responses without clinically meaningful graft-vs-tumor (GVT) effects. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHLBI, Bethesda, MD 20892 USA. Westmead Hosp, Sydney, NSW, Australia. Inst J Paoli I Calmettes, F-13009 Marseille, France. Univ Leipzig, Leipzig, Germany. NR 0 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1661 BP 429A EP 429A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184701662 ER PT J AU Choi, U Malech, HL AF Choi, U Malech, HL TI Efficient selective enrichment of hematopoietic stem cells transduced with MFGS retrovirus encoding benzyl guanine resistant methylguanine methyltransferase linked to therapeutic X-linked chronic granulomatous disease gene. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NIAID, NIH, Host Def Lab, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1696 BP 438A EP 438A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184701697 ER PT J AU Hematti, P Tuchman, SA Agricola, BA Metzger, ME Donahue, RE Dunbar, CE Tisdale, JF AF Hematti, P Tuchman, SA Agricola, BA Metzger, ME Donahue, RE Dunbar, CE Tisdale, JF TI Comparison of retroviral transduction efficiency of rhesus macaque bone marrow CD34+cells versus G-CSF or G-CSF plus SCF moblized peripheral blood CD34+cells. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA. NIDDKD, NIH, Mol & Clin Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1699 BP 439A EP 439A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184701700 ER PT J AU Kang, EM Metzger, M Krouse, A Donahue, RE Tisdale, JF AF Kang, EM Metzger, M Krouse, A Donahue, RE Tisdale, JF TI Nonmyeloablative conditioning for autologous transplantation of gene modified cells in the large animal model. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NIDDK, NIH, MCHB, Bethesda, MD USA. NHLBI, NIH, HN, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1705 BP 440A EP 440A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184701706 ER PT J AU McLaren, GD Barton, JC Gordeuk, VR McLaren, CE Adams, PC Reboussin, DM Acton, R Harris, EL Dawkins, FW Mellen, BG Sholinsky, P Speechley, M Eckfeldt, JH AF McLaren, GD Barton, JC Gordeuk, VR McLaren, CE Adams, PC Reboussin, DM Acton, R Harris, EL Dawkins, FW Mellen, BG Sholinsky, P Speechley, M Eckfeldt, JH TI High HFE C282Y homozygote frequency in Caucasians but not in Hispanics, African Americans, or Asians: An analysis of 50,290 primary care patients in the hemochromatosis and iron overload screening (HEIRS) Study. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA. VA Long Beach Healthcare Syst, Med Hlth Care Grp, Long Beach, CA USA. Southern Iron Disorders Ctr, Birmingham, AL USA. Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20059 USA. London Hlth Sci Ctr, Dept Med, London, ON, Canada. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Epidemiol, Birmingham, AL 35294 USA. Univ Alabama, Dept Int Hlth, Birmingham, AL 35294 USA. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. NHLBI, Genet Epidemiol SRG, Bethesda, MD 20892 USA. Univ Western Ontario, Dept Biostat & Epidemiol, London, ON N6A 3K7, Canada. Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1733 BP 447A EP 447A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184701734 ER PT J AU Ataga, KI Kelly, EA Santucci, S Strayhorn, D Amamoo, AM Rodgers, G Orringer, EP AF Ataga, KI Kelly, EA Santucci, S Strayhorn, D Amamoo, AM Rodgers, G Orringer, EP TI Prevalence of pulmonary hypertension (PHT) in sickle cell disease (SCD). SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Univ N Carolina, Dept Med, Chapel Hill, NC 27515 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. NIH, Mol & Clin Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1749 BP 451A EP 451A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184701750 ER PT J AU Coates, T Dampier, C Evans, G Kalinyak, K Lail, A Mentzer, W Piomelli, S Rader, E Space, S Howard, T AF Coates, T Dampier, C Evans, G Kalinyak, K Lail, A Mentzer, W Piomelli, S Rader, E Space, S Howard, T TI Prevalence of parvovirus B19 infection in a cohort of children and adolescents with sickle cell disease. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Univ So Calif, Childrens Hosp Los Angeles, Los Angeles, CA 90089 USA. Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. NHLBI, Rockville, MD USA. Univ Cincinnati, Sch Med, Cincinnati, OH 45221 USA. Rho Inc, Chapel Hill, NC USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Columbia Univ, New York, NY USA. Albert Einstein Coll Med, Bronx, NY USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Univ Alabama, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1766 BP 455A EP 456A PN 1 PG 2 WC Hematology SC Hematology GA 614JK UT WOS:000179184701767 ER PT J AU Howard, T Dampier, C Evans, G Kalinyak, K Lail, A Mentzer, W Piomeli, S Radel, E Space, S Coates, T AF Howard, T Dampier, C Evans, G Kalinyak, K Lail, A Mentzer, W Piomeli, S Radel, E Space, S Coates, T TI Hydroxyurea use in children: Preliminary results from the Comprehensive Sickle Cell Centers common database. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Univ Alabama, Birmingham, AL USA. Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. Univ Cincinnati, Cincinnati, OH 45221 USA. Rho Inc, Chapel Hill, NC USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Columbia Univ, New York, NY 10027 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Univ So Calif, Childrens Hosp Los Angeles, Los Angeles, CA 90089 USA. NHLBI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1764 BP 455A EP 455A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184701765 ER PT J AU Rogers, HM Yu, XB Smith, R Noguchi, CT AF Rogers, HM Yu, XB Smith, R Noguchi, CT TI Hypoxia alters expression of transcription factors in erythroid progenitor cells and induces gamma-globin gene expression. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NIDDK, NIH, Biol Chem Lab, Bethesda, MD USA. Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Div Immunol & Hematopoiesis, Baltimore, MD 21218 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1769 BP 456A EP 456A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184701770 ER PT J AU Nakamura, R Akin, C Bahceci, E Chakrabarti, S Greene, A Eniafe, R Dunbar, CE Young, NS Leitman, SF Read, EJ Metcalfe, D Childs, R Barrett, J AF Nakamura, R Akin, C Bahceci, E Chakrabarti, S Greene, A Eniafe, R Dunbar, CE Young, NS Leitman, SF Read, EJ Metcalfe, D Childs, R Barrett, J TI Allogeneic no myeloablative peripheral, blood, stem cell transplantation for advanced systemic mastocytosis: Clinical evidence for a graft-versus-mastocyiosis effect. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Natl Inst Immunol & Infect Dis, Lab Allerg Dis, Bethesda, MD USA. Yale Univ, Sect Med Oncol, New Haven, CT USA. NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 5405 BP 457B EP 457B PN 2 PG 1 WC Hematology SC Hematology GA 614JL UT WOS:000179184801947 ER PT J AU Hay, BN Puck, JM Uzel, G Davis, J Hsu, AP Linton, G Woltz, P Malech, HL AF Hay, BN Puck, JM Uzel, G Davis, J Hsu, AP Linton, G Woltz, P Malech, HL TI Absence of B-cell, NK-cell, myeloid or CD34+cell engraftment in some X-linked severe combined immunodeficiency (XSCID) patients following haploidentical transplant. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHGRI, NIH, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. NIAID, NIH, Host Def Lab, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1800 BP 464A EP 464A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184701801 ER PT J AU Otsu, M Candotti, F AF Otsu, M Candotti, F TI Analysis of competitive engraftment of murine X-SCID and gamma c-expressing bone marrow progenitor cells. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NIH, MHGRI, GMBB, Disorders Immun Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1798 BP 464A EP 464A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184701799 ER PT J AU Wada, T Schurman, SH Konno, A Garabedian, EK Anderson, SM Nelson, DL Candotti, F AF Wada, T Schurman, SH Konno, A Garabedian, EK Anderson, SM Nelson, DL Candotti, F TI Second-site mutation in Wiskott-Aldrich syndrome protein gene causes somatic mosaicism in two WAS siblings. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHGRI, NIH, Disorders Immun Sect, Bethesda, MD 20892 USA. NCI, NIH, Metab Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1803 BP 465A EP 465A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184701804 ER PT J AU Kasten-Sportes, C McCarthy, N Gea-Banacloche, J Chow, C Steinberg, S Marchigiani, D Castro, KM Bishop, MR Fowler, DH Gress, RE AF Kasten-Sportes, C McCarthy, N Gea-Banacloche, J Chow, C Steinberg, S Marchigiani, D Castro, KM Bishop, MR Fowler, DH Gress, RE TI High-dose chemotherapy and autologous transplant for stage IIIB inflammatory breast cancer. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 5469 BP 473B EP 473B PN 2 PG 1 WC Hematology SC Hematology GA 614JL UT WOS:000179184802011 ER PT J AU Czapiga, M Kirk, A Lekstrom-Mines, J AF Czapiga, M Kirk, A Lekstrom-Mines, J TI Endogenous N-formyl peptides attract activated platelets and provide a mechanism for the delivery of costimulatory molecules to sites of injury. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NIAID, NIH, Bethesda, MD 20892 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1846 BP 476A EP 476A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184701847 ER PT J AU Sekiya, F Kim, YJ Rhee, SG Kunapuli, SP AF Sekiya, F Kim, YJ Rhee, SG Kunapuli, SP TI PLC-gamma2 activation in platelets requires dual phosphorylation at Tyr753 and Tyr759. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Temple Univ, Sch Med, Thrombosis Res Ctr, Philadelphia, PA 19122 USA. NHLBI, NIH, Lab Cell Signalling, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1852 BP 477A EP 477A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184701853 ER PT J AU Fogarty, PF Rick, ME Zeng, WH Risitano, AM Dunbar, CE Bussel, JB AF Fogarty, PF Rick, ME Zeng, WH Risitano, AM Dunbar, CE Bussel, JB TI T cell repertoire characteristics are associated with response to splenectomy in patients with immune thrombocytopenia. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. New York Presbyterian Hosp, Dept Pediat Hematol Oncol, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1856 BP 478A EP 478A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184701857 ER PT J AU Adler, RL Hematti, P Keyvanfar, K Kuramoto, K Sellers, SE von Kalle, C Dunbar, CE AF Adler, RL Hematti, P Keyvanfar, K Kuramoto, K Sellers, SE von Kalle, C Dunbar, CE TI Analysis of clonal contributions to T lymphoid and myeloid lineages during recovery from autologous transplantation in the rhesus macaque. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA. Univ Freiburg, Dept Internal Med, D-7800 Freiburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1979 BP 507A EP 507A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184701980 ER PT J AU Zhang, JW Chao, N Huang, HY Xi, H Johnson, T Haug, J Feng, J Mishina, Y Li, LH AF Zhang, JW Chao, N Huang, HY Xi, H Johnson, T Haug, J Feng, J Mishina, Y Li, LH TI Blocking of the signaling through BMPR1A leads to an increase in the hematopoietic stem cell number via the regulation of the niche size. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Univ Missouri, Sch Dent, Dept Oral Biol, Kansas City, MO USA. Stowers Inst Med Res, Kansas City, MO USA. NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1977 BP 507A EP 507A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184701978 ER PT J AU Orlic, D Cline, A Clevenger, R Sheikh, FH Chimenti, S Kajstura, J Dutra, A Pak, E Hoyt, RF Anversa, P Bodine, DM AF Orlic, D Cline, A Clevenger, R Sheikh, FH Chimenti, S Kajstura, J Dutra, A Pak, E Hoyt, RF Anversa, P Bodine, DM TI Clonal analysis of mobilized bone marrow stem cell regeneration of acute myocardial infarctions in mice. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHGRI, NIH, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. NHLBI, NIH, Lab Anim Med & Surg, Bethesda, MD 20892 USA. NHGRI, NIH, Genet Dis Res Branch, Bethesda, MD 20892 USA. New York Med Coll, Dept Med, Valhalla, NY 10595 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 1998 BP 512A EP 512A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184701999 ER PT J AU Teal, HE Finkelstein, LD Cheng, A Paulson, RF Correll, PH AF Teal, HE Finkelstein, LD Cheng, A Paulson, RF Correll, PH TI Grb2 is essential for STK receptor signaling in erythroid cells upon MSP stimulation and following infection with Friend erythroleukemia virus. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Penn State Univ, University Pk, PA 16802 USA. Washington Univ, St Louis, MO 63130 USA. NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 2029 BP 519A EP 519A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184702030 ER PT J AU Xin, C Cheung, JY Qin, T Barber, DL Conrad, K Abrasonis, V Zhang, WY Birnbaumer, L Miller, BA AF Xin, C Cheung, JY Qin, T Barber, DL Conrad, K Abrasonis, V Zhang, WY Birnbaumer, L Miller, BA TI Erythropoietin modulation, of calcium influx through TRPC in primary splenic erythroblasts. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Weis Ctr Res, Geisinger Clin, Danville, PA 17822 USA. Ontario Canc Inst, Div Cellular & Mol Biol, Toronto, ON M4X 1K9, Canada. NIEHS, Div Intramural Res, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 2035 BP 520A EP 521A PN 1 PG 2 WC Hematology SC Hematology GA 614JK UT WOS:000179184702036 ER PT J AU Akel, SM Bertolette, DC Ruscetti, FW AF Akel, SM Bertolette, DC Ruscetti, FW TI Overexpression of Smad7 prevents TGF-beta and activin signaling and function in erythroleukemic cells but increases endomitosis during megakaryocytic differentiation. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NCI, Frederick Canc Res & Dev Ctr, Basic Res Lab, CCR, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 2040 BP 522A EP 522A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184702041 ER PT J AU Whitmarsh, R Saginario, C Ya, Z Hilgenfeld, E Rappaport, EF Megonigal, MD Carroll, M Liu, ML Osheroff, N Helman, LJ Cheung, NKV Ried, T Blair, IA Felix, CA AF Whitmarsh, R Saginario, C Ya, Z Hilgenfeld, E Rappaport, EF Megonigal, MD Carroll, M Liu, ML Osheroff, N Helman, LJ Cheung, NKV Ried, T Blair, IA Felix, CA TI Reciprocal DNA topoisomerase II cleavage events at 5 '-TATTA-3 ' sequence in MLL and AF-9 create homologous single-stranded overhangs that anneal to form der(11) and der(9) genomic breakpoint junctions in treatment-related AML without further processing. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. NCI, Div Genet, Bethesda, MD 20892 USA. Childrens Hosp Philadelphia, Joseph Stokes Jr Res Inst, Philadelphia, PA 19104 USA. Hosp Univ Penn, Sch Med, Div Hematol Oncol, Philadelphia, PA 19104 USA. Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. Univ Penn, Sch Med, Ctr Canc Pharmacol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 2077 BP 530A EP 531A PN 1 PG 2 WC Hematology SC Hematology GA 614JK UT WOS:000179184702078 ER PT J AU Gang, H Osato, M Shigesada, K Liu, PP Ito, Y AF Gang, H Osato, M Shigesada, K Liu, PP Ito, Y TI Molecular basis for a dominant inactivation of RUNX1/AML1 by the leukemogenic inversion 16 chimera. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PA SP Amer Soc Hematol C1 Kyoto Univ, Inst Virus Res, Dept Viral Oncol, Kyoto 606, Japan. Kyoto Univ, Inst Virus Res, Dept Mol Genet, Kyoto 606, Japan. Harvard Univ, Sch Med, Harvard Inst Med, Boston, MA USA. Natl Univ Singapore, Inst Mol & Cell Biol, RUNX Res Grp, Singapore 117548, Singapore. NHGRI, NIH, Bethesda, MD 20892 USA. RI Liu, Paul/A-7976-2012; Osato, Motomi/N-5056-2014 OI Liu, Paul/0000-0002-6779-025X; Osato, Motomi/0000-0003-3982-9054 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 2093 BP 534A EP 534A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184702094 ER PT J AU Peterson, T Tian, EM Dib, A Turabi, A Zhan, FH Barlogie, B Shaughnessy, J Kuehl, M AF Peterson, T Tian, EM Dib, A Turabi, A Zhan, FH Barlogie, B Shaughnessy, J Kuehl, M TI Bi-allelic deletion of p18INK4c in a subset of myeloma cell lines and tumors. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NCI, Genet Branch, Bethesda, MD 20892 USA. Univ Arkansas Med Sci, Lambert Lab Myeloma Genet, Little Rock, AR 72205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 2101 BP 536A EP 536A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184702102 ER PT J AU Xu, K Chung, D Glasow, A Guidez, F Monks, A Stegmaier, K Golub, TR Zelent, A Waxman, S AF Xu, K Chung, D Glasow, A Guidez, F Monks, A Stegmaier, K Golub, TR Zelent, A Waxman, S TI Specific dithiophene analogs potentiate ATRA induction of acute promyelocytic leukemia cell differentiation and gene expression in vivo. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Inst Canc Res, Leukaemia Res Fund Ctr, London SW3 6JB, England. NCI, SAIC Frederick, Frederick, MD USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Mt Sinai Sch Med, Dept Med, New York, NY USA. RI Guidez, Fabien/B-3750-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 2125 BP 541A EP 541A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184702126 ER PT J AU Gojo, I Karp, JE Mann, D Rollins, S Greer, J Tidwell, ML Zhai, SP Figg, WD Trepel, J Ryan, Q Sausville, E AF Gojo, I Karp, JE Mann, D Rollins, S Greer, J Tidwell, ML Zhai, SP Figg, WD Trepel, J Ryan, Q Sausville, E TI Phase I study of histone deacetylase inhibitor (HDI) MS-275 in adults with refractory or relapsed hematologic malignancies. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. NCI, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 2198 BP 559A EP 559A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184702199 ER PT J AU Cortes, JE Estey, E Giles, F O'Brien, S Keating, M McConkey, D Wright, J Schenkein, D Kantarjian, H AF Cortes, JE Estey, E Giles, F O'Brien, S Keating, M McConkey, D Wright, J Schenkein, D Kantarjian, H TI Phase I study of Bortezomib (PS-341, VELCADETM), a proteasome inhibitor, in patients with refractory or relapsed acute leukemias and myelodysplastic syndromes. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, CTEP, Bethesda, MD 20892 USA. Millenium Pharmaceut Inc, Cambridge, MA USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 2201 BP 560A EP 560A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184702202 ER PT J AU Lancet, JE Karp, JE Gotlib, J Liesveld, JL Kaufmann, SH Gojo, I Greenberg, PL Meschinchi, S Adjei, A Tidwell, M Messina, P Greer, J Dugan, K Bruzek, L Radich, JP Wright, JJ AF Lancet, JE Karp, JE Gotlib, J Liesveld, JL Kaufmann, SH Gojo, I Greenberg, PL Meschinchi, S Adjei, A Tidwell, M Messina, P Greer, J Dugan, K Bruzek, L Radich, JP Wright, JJ TI Zarnestra (TM) (R115777) in previously untreated poor-risk AML and MDS: Preliminary results of a phase II trial. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY 14627 USA. Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Stanford Univ, Div Hematol, Stanford, CA 94305 USA. Mayo Clin, Rochester, MN USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. NCI, CTEP, IDB, Rockville, MD USA. NR 0 TC 15 Z9 15 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 2200 BP 560A EP 560A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184702201 ER PT J AU Shami, P Saavedra, JE Wang, LY Keefer, LK AF Shami, P Saavedra, JE Wang, LY Keefer, LK TI JS-K, a novel nitric oxide (NO) generator, induces leukemia cell apoptosis by a caspase dependent mechanism and inhibits their growth in vivo. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Univ Utah, Salt Lake City, UT 84112 USA. Salt Lake City VA Med Ctr, Salt Lake City, UT USA. NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 2212 BP 563A EP 563A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184702213 ER PT J AU O'Keefe, CL Plasilova, M Risitano, A Lichtin, A Hsi, E Maciejewski, JP AF O'Keefe, CL Plasilova, M Risitano, A Lichtin, A Hsi, E Maciejewski, JP TI Molecular analysis of the T-cell receptor repertoire in large granular lymphocytic leukemia. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Cleveland Clin Fdn, Expt Hematol & Hematopoiesis Sect, Cleveland, OH 44195 USA. NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 2236 BP 569A EP 569A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184702237 ER PT J AU Sattler, M Pride, YB Gramlich, JL Quinnan, LR Salgia, R Lipkowitz, S Griffin, JD AF Sattler, M Pride, YB Gramlich, JL Quinnan, LR Salgia, R Lipkowitz, S Griffin, JD TI CBL-B is a negative regulator of transformation by BCR/ABL. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NCI, Dept Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 2290 BP 583A EP 583A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184702291 ER PT J AU Ptasznik, A Urbanowska, E Chinta, S Costa, MA Katz, BA Stanislaus, MA Demir, G Pan, ZK Linnekin, D Gewirtz, AM AF Ptasznik, A Urbanowska, E Chinta, S Costa, MA Katz, BA Stanislaus, MA Demir, G Pan, ZK Linnekin, D Gewirtz, AM TI A novel molecular mechanism explaining dysfunctional migration properties of leukemia cells. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Univ Penn, Div Hematol Oncol, Philadelphia, PA 19104 USA. Med Univ Warsaw, Dept Hematol Oncol & Internal Med, Warsaw, Poland. Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. NCI, Basic Res Lab, Div Basic Sci, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 23025 BP 586A EP 586A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184702304 ER PT J AU Carvallo, C Kurlander, R Geller, N Griffith, L Linehan, WM Childs, R AF Carvallo, C Kurlander, R Geller, N Griffith, L Linehan, WM Childs, R TI Prior chemotherapy (chemo) facilitates donor engraftment following nonmyeloablative allogeneic stem cell transplantation (NST). SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NCI, NIH, UOB, Bethesda, MD 20892 USA. NIH, DLM, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NIH, DTM, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 2442 BP 620A EP 620A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184702444 ER PT J AU Bishop, MR Marchigiani, D Odom, J Castro, K Dean, R Kasten-Sportes, C Carter, C Read, E Leitman, S Gress, R Fowler, D AF Bishop, MR Marchigiani, D Odom, J Castro, K Dean, R Kasten-Sportes, C Carter, C Read, E Leitman, S Gress, R Fowler, D TI Contribution of T cells to engraftment: A comparison of T cell depleted vs. T cell replete allografts after reduced-intensity conditioning. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 2447 BP 621A EP 621A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184702449 ER PT J AU Battiwalla, M Cavet, J Hensel, N Cullup, H Dickinson, A Nakamura, R Follman, D Childs, R Middleton, P Barrett, AJ AF Battiwalla, M Cavet, J Hensel, N Cullup, H Dickinson, A Nakamura, R Follman, D Childs, R Middleton, P Barrett, AJ TI Donor IL-1 Ra gene polymorphisms affect in vitro and in vivo responses to CMV antigen. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA. Univ Newcastle Upon Tyne, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 2465 BP 626A EP 626A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184702467 ER PT J AU Baxter-Lowe, LA Kim, Y Carter, S Fernandez-Vina, M Wagner, L Jensen, L Fraser, J Kernan, N Kurtzberg, J AF Baxter-Lowe, LA Kim, Y Carter, S Fernandez-Vina, M Wagner, L Jensen, L Fraser, J Kernan, N Kurtzberg, J TI Ability of minority patients to find donors from an ethnically diverse cord blood bank. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. Emmes Corp, Rockville, MD USA. Natl Naval Med Res Inst, Kensington, MD USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 2521 BP 640A EP 641A PN 1 PG 2 WC Hematology SC Hematology GA 614JK UT WOS:000179184702523 ER PT J AU Jison, ML Munson, PJ Schechter, AN Barb, J Logun, C Pease-Fye, M Nichols, J Danner, RL Gladwin, MT AF Jison, ML Munson, PJ Schechter, AN Barb, J Logun, C Pease-Fye, M Nichols, J Danner, RL Gladwin, MT TI Peripheral blood mononuclear cell gene expression in patients with sickle cell disease. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. NIDDKD, Biol Chem Lab, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 2603 BP 661A EP 662A PN 1 PG 2 WC Hematology SC Hematology GA 614JK UT WOS:000179184702605 ER PT J AU Chen, JC Lipovsky, K Bennett, L Young, NS AF Chen, JC Lipovsky, K Bennett, L Young, NS TI Biased lineage commitment and advanced senescence in hematopoietic stem cells from hemoglobin-deficient mice. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 2625 BP 667A EP 667A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184702627 ER PT J AU Battiwalla, M Sauntharajah, Y Nakamura, R Wisch, L Melenhorst, J Molldrem, J Barrett, AJ AF Battiwalla, M Sauntharajah, Y Nakamura, R Wisch, L Melenhorst, J Molldrem, J Barrett, AJ TI Treatment of T-LGL (large granular lymphocytic disease) with cyclosporine A - Long term follow-up. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA. Univ Illinois, Chicago, IL 60680 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 2635 BP 669A EP 670A PN 1 PG 2 WC Hematology SC Hematology GA 614JK UT WOS:000179184702637 ER PT J AU Melchionda, F Fry, TJ Mackall, CL AF Melchionda, F Fry, TJ Mackall, CL TI IL7 and IL15 but not IL2 increase Ag specific effector T cells following dendritic cell based vaccination. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 2653 BP 674A EP 674A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184702655 ER PT J AU Re, F Srinivasan, R Igarashi, T Marincola, F Marquesen, M Childs, R AF Re, F Srinivasan, R Igarashi, T Marincola, F Marquesen, M Childs, R TI Green fluorescent protein (GFP) expression in dendritic cells enhances their immunogenicity and elicits GFP-specific cytotoxic T-cell (CTL) responses in humans. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 2663 BP 676A EP 676A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184702665 ER PT J AU Fujiwara, H El Ouriaghli, F Sconocchia, G Rezvani, K Grube, M Melenhorst, J Hensel, N Barrett, AJ AF Fujiwara, H El Ouriaghli, F Sconocchia, G Rezvani, K Grube, M Melenhorst, J Hensel, N Barrett, AJ TI Neutrophil elastase: A candidate antigen for adoptive T cell therapy for myeloid leukemia? SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHLBI, NIH, Hematol Branch, Stem Cell Allogene Transplantat Unit, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 2666 BP 677A EP 677A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184702668 ER PT J AU Sconocchia, G Fujiwara, H Rezvani, K Adams, M El Ouiriaghli, F Grube, M Hensel, N Barrett, AJ AF Sconocchia, G Fujiwara, H Rezvani, K Adams, M El Ouiriaghli, F Grube, M Hensel, N Barrett, AJ TI CD34-derived CD56+ cells from 21 day cultures exibit powerful anti-proliferative effects with low cell mediated cytotoxicity against tumor cell lines. A new functional property of early NK cells. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHLBI, NIH, Hematol Branch, Stem Cell Allotransplantat Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 2669 BP 678A EP 678A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184702671 ER PT J AU Ahmad, A Aggarwal, A Sharma, D Kinsella, V Dave, HP Schechter, GP Rick, ME AF Ahmad, A Aggarwal, A Sharma, D Kinsella, V Dave, HP Schechter, GP Rick, ME TI Rituximab for the treatment of relapsing/refractory thrombotic thrombocytopenic purpura (TTP). SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Washington Hosp Ctr, Washington, DC 20010 USA. George Washington Univ, Dept Hematol, Washington, DC 20052 USA. VA Hosp, Washington, DC 20052 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 2703 BP 686A EP 686A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184702705 ER PT J AU Ling, C Ying, S Chin, K Tang, DC Rodgers, GP AF Ling, C Ying, S Chin, K Tang, DC Rodgers, GP TI Analysis of the molecular regulation of hematopoietic stem cell fate using rapid analysis of gene expression (RAGE) and proteomic profiling. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NIDDK, NIH, Mol & Clin Hematol Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 2819 BP 715A EP 715A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184702821 ER PT J AU Jie, W Kohwi-Shigematsu, T Noguchi, CT AF Jie, W Kohwi-Shigematsu, T Noguchi, CT TI Tal1 exhibits transcriptional repression and modifies RAR beta gene expression by targeting satellite DNA. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NIDDK, NIH, Biol Chem Lab, Bethesda, MD USA. Lawrence Berkeley Natl Lab, Dept Cell & Mol Biol, Berkeley, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 2848 BP 722A EP 722A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184702850 ER PT J AU Chu, YW Memon, S Sharrow, SO Hakim, FT Gress, RE AF Chu, YW Memon, S Sharrow, SO Hakim, FT Gress, RE TI TCR rearrangement excision circle assessment to determine the effect of exogenous interleukin-7 on recent thymic emigrants in mice. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. RI Memon, Sarfraz/E-1198-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 2857 BP 724A EP 724A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184702859 ER PT J AU El Kassar, N Lucas, P Sharrow, S Klug, D Bare, CV Merchant, M Mackall, C Gress, RE AF El Kassar, N Lucas, P Sharrow, S Klug, D Bare, CV Merchant, M Mackall, C Gress, RE TI Dose effect of IL-7 on thymic development. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NCI, NIH, Expt Immunol Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 2858 BP 724A EP 724A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184702860 ER PT J AU Bradley, HL Hawley, TS Ramezani, A Stetler-Stevenson, WG Stetler-Stevenson, M Hawley, RG Bunting, KD AF Bradley, HL Hawley, TS Ramezani, A Stetler-Stevenson, WG Stetler-Stevenson, M Hawley, RG Bunting, KD TI Autocrine inhibition of M1 myeloid differentiation by constitutive expression of tissue inhibitor of matrix metalloproteinase-1. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Amer Red Cross, Holland Lab, Hematopoiesis Dept, Rockville, MD USA. George Washington Univ, Dept Anat & Cell Biol, Washington, DC 20052 USA. Amer Red Cross, Holland Lab, Flow Cytometry Facil, Rockville, MD USA. NIH, Div Clin Sci, Bethesda, MD 20892 USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 2902 BP 734A EP 735A PN 1 PG 2 WC Hematology SC Hematology GA 614JK UT WOS:000179184702904 ER PT J AU Kreitman, RJ Wilson, WH Margulies, A Pastan, I Matsushita, K AF Kreitman, RJ Wilson, WH Margulies, A Pastan, I Matsushita, K TI Soluble CD22, a new test which correlates with disease status in B-cell leukemia and lymphoma. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. NCI, Med Oncol Clin Res Unit, Bethesda, MD 20892 USA. Kagoshima Univ, Dept Internal Med 1, Kagoshima 890, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 2996 BP 757A EP 757A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184702998 ER PT J AU Zhuo, Z Zhang, ML Mandler, R Goldman, C Morris, JC Janick, JE Waldmann, TA AF Zhuo, Z Zhang, ML Mandler, R Goldman, C Morris, JC Janick, JE Waldmann, TA TI Effective therapy for murine model of adult T-cell leukemia with anti-CD2 monoclonal antibody, MEDI-507. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NCI, NIH, Metab Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 3021 BP 763A EP 763A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184703023 ER PT J AU Lew, G Gu, LB Zhou, MX Kreitman, RJ FitzGerald, DJ Pastan, I Woods, WG Findley, HW AF Lew, G Gu, LB Zhou, MX Kreitman, RJ FitzGerald, DJ Pastan, I Woods, WG Findley, HW TI BL22, an anti-CD22 recombinant immunotoxin, is active in vitro and in vivo against B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells from pediatric patients. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Emory Univ, Sch Med, Atlanta, GA 30322 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 3024 BP 764A EP 764A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184703026 ER PT J AU O'Connor, OA Moskowitz, CH Wright, JJ MacGregor-Cortelli, B Straus, D Furst, D Horse-Grant, D Schenkein, DP Zelenetz, AD AF O'Connor, OA Moskowitz, CH Wright, JJ MacGregor-Cortelli, B Straus, D Furst, D Horse-Grant, D Schenkein, DP Zelenetz, AD TI Phase II clinical experience with the proteasome inhibitor PS-341 in patients with indolent lymphomas. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NCI, DCTD, CTEP, Invest Drug Branch, Bethesda, MD 20892 USA. Millennium Pharmaceut, Oncol Clin Dev, Cambridge, England. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 3063 BP 774A EP 774A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184703065 ER PT J AU Gotlib, J Loh, M Vattikuti, S Dugan, K Quesada, S Katamneni, U Sridhar, K Wright, J Thibault, A Rybak, ME Shannon, K Greenberg, PL AF Gotlib, J Loh, M Vattikuti, S Dugan, K Quesada, S Katamneni, U Sridhar, K Wright, J Thibault, A Rybak, ME Shannon, K Greenberg, PL TI Phase I/II study of ZARNESTRA (TM) (farnesyltransferase inhibitor [FTI] R115777, tipifarnib) in patients with myeloproliferative disorders (MPDs): Preliminary results. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Univ Calif San Francisco, Med Ctr, San Francisco, CA 94143 USA. VA Palo Alto Hosp, Palo Alto, CA USA. NCI, CTEP, Bethesda, MD 20892 USA. Johnson & Johnson Pharmaceut Res & Dev, Titusville, NJ USA. NR 0 TC 10 Z9 11 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 3153 BP 798A EP 799A PN 1 PG 2 WC Hematology SC Hematology GA 614JK UT WOS:000179184703155 ER PT J AU Drobyski, WR Hecht, T Gendelman, M AF Drobyski, WR Hecht, T Gendelman, M TI Effect of interleukin 7 administration on murine graft versus host disease and allogeneic marrow engraftment. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Med Coll Wisconsin, Bone Marrow Transplant Program, Milwaukee, WI 53226 USA. NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 3237 BP 819A EP 819A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184703239 ER PT J AU Murphy, WJ Koh, CY AF Murphy, WJ Koh, CY TI Allogeneic NK cells as a means to purge residual tumor in syngeneic bone marrow transplantation. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Univ Nevada, Dept Microbiol, Reno, NV 89557 USA. NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Frederick, MD 21702 USA. RI Koh, Crystal/D-9986-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 3252 BP 823A EP 823A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184703254 ER PT J AU Yamashita, K Song, GZ Horwitz, DA Malech, HL Horwitz, ME AF Yamashita, K Song, GZ Horwitz, DA Malech, HL Horwitz, ME TI Ex vivo generation of potent murine regulatory CD4 T-cells using TGF-beta. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NIAID, Host Def Lab, Bethesda, MD 20892 USA. Univ So Calif, Sch Med, Dept Med, Div Rheumatol & Immunol, Los Angeles, CA 90033 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 3250 BP 823A EP 823A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184703252 ER PT J AU Stroncek, DF Shawker, T Follmann, D Leitman, SF AF Stroncek, DF Shawker, T Follmann, D Leitman, SF TI Spleen size transiently increases in G-CSF-mobilized peripheral blood stem cell donors. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 3263 BP 826A EP 826A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184703265 ER PT J AU Lim, JB Bettinotti, M Caruccio, L Nagorsen, D Stroncek, D Provenzano, M AF Lim, JB Bettinotti, M Caruccio, L Nagorsen, D Stroncek, D Provenzano, M TI Identification of two different CMV epitopes as common target antigens for HLA-A*0301 restricted CMV-specific cytotoxic T lymphocytes. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA. Univ Milan, NIH, Ist Nazl Tumori, Bone Marrow Transplant Unit, I-20122 Milan, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 3293 BP 834A EP 834A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184703295 ER PT J AU Provenzano, M Lim, JB Stroncek, DF AF Provenzano, M Lim, JB Stroncek, DF TI The simultaneous stimulation of PBMCs from CMV-seropositive individuals using cross-reactive HLA class I restricted pp65 peptides can be a valid strategy for selection and expansion of CMV specific CTLs for any HLA class I donor. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 Univ Milan, Ist Nazl Tumori, BMT Unit, I-20122 Milan, Italy. NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 3294 BP 834A EP 834A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184703296 ER PT J AU Hakim, FT Memon, SA Gress, RE AF Hakim, FT Memon, SA Gress, RE TI Recovery of CD8(+) T cell populations post transplant. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. RI Memon, Sarfraz/E-1198-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 3320 BP 841A EP 841A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184703322 ER PT J AU Nakamura, R Battiwalla, M Solomon, S Follmann, D Chakrabarti, S Cortez, K Hensel, N Childs, R Barrett, J AF Nakamura, R Battiwalla, M Solomon, S Follmann, D Chakrabarti, S Cortez, K Hensel, N Childs, R Barrett, J TI Persisting CMV antigenemia early post-transplant predicts for increased relapse and treatment failure beyond 100 days post-transplant and correlates with poor lymphocyte proliferation to CMV antigen. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 3322 BP 842A EP 842A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184703324 ER PT J AU Brenner, S Choi, U Whiting-Theobald, NL Linton, GF Malech, HL AF Brenner, S Choi, U Whiting-Theobald, NL Linton, GF Malech, HL TI 3(rd) generation lentivector that co-expresses gp91(phox) and P140K mutant MGMT achieves high selection survival of gp91(phox) corrected X-CGD patient CD34(+) stem cells. SO BLOOD LA English DT Meeting Abstract CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol C1 NIAID, NIH, Host Def Lab, Bethesda, MD 20892 USA. RI Brenner, Sebastian/D-7456-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2002 VL 100 IS 11 MA 3422 BP 868A EP 868A PN 1 PG 1 WC Hematology SC Hematology GA 614JK UT WOS:000179184703424 ER PT J AU Kalmijn, S van Boxtel, MPJ Verschuren, MWM Jolles, J Launer, LJ AF Kalmijn, S van Boxtel, MPJ Verschuren, MWM Jolles, J Launer, LJ TI Cigarette smoking and alcohol consumption in relation to cognitive performance in middle age SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE age factors; age groups; alcohol drinking; cognition; cohort studies; middle age; psychomotor performance; smoking ID CEREBRAL BLOOD-FLOW; HIGH-DENSITY-LIPOPROTEIN; CHOLESTEROL DETERMINATION; PLASMINOGEN-ACTIVATOR; SEX-DIFFERENCES; NATIONAL HEART; POPULATION; COHORT; DRINKING; DISEASE AB In the elderly, cigarette smoking has been related to reduced cognitive performance and moderate alcohol consumption to increased cognitive performance. It is not clear whether these associations also exist in middle age. The authors examined these relations in a population-based cohort study of 1,927 randomly selected, predominantly middle-aged subjects aged 45-70 years at the time of cognitive testing and living in the Netherlands. From 1995 until 2000, an extensive cognitive battery was administered, and compound scores were calculated. Risk factors had been assessed approximately 5 years previously. Multiple linear regression analyses (in which one unit of the cognitive score = one standard deviation) showed that, after the authors adjusted for age, sex, education, alcohol consumption, and cardiovascular risk factors, current smokers had reduced psychomotor speed (beta = -0.159, 95% confidence interval: -0.071, -0.244; p = 0.0003) and reduced cognitive flexibility (beta = -0.133, 95% confidence interval: -0.035,-0.230; p = 0.008) compared with never smokers. This effect was similar to that of being approximately 4 years older. Alcohol consumption was related to increased speed and better flexibility, especially among women who drank 1-4 alcoholic beverages a day. In conclusion, among middle-aged subjects, current smoking was inversely and alcohol consumption positively related to psychomotor speed and cognitive flexibility. This finding suggests that actions to prevent cognitive decline can be taken in middle age. C1 Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, NL-3508 GA Utrecht, Netherlands. Natl Inst Publ Hlth & Environm, Dept Chron Dis Epidemiol, NL-3720 BA Bilthoven, Netherlands. Univ Maastricht, Dept Psychiat & Neuropsychol, Maastricht, Netherlands. NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. RP Kalmijn, S (reprint author), Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, D01-335,POB 85500, NL-3508 GA Utrecht, Netherlands. EM s.kalmijn@jc.azu.nl NR 57 TC 154 Z9 155 U1 0 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 15 PY 2002 VL 156 IS 10 BP 936 EP 944 DI 10.1093/aje/kwf135 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 616LW UT WOS:000179306100006 PM 12419766 ER PT J AU Wong, LJC Liang, MH Kwon, H Bai, RK Alper, O Gropman, A AF Wong, LJC Liang, MH Kwon, H Bai, RK Alper, O Gropman, A TI A cystic fibrosis patient with two novel mutations in mitochondrial DNA: Mild disease led to delayed diagnosis of both disorders SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE mtDNA mutation; cystic fibrosis; TTGE screening of the entire mitochondrial genome AB A 21-year-old woman who has been suspected of mitochondrial cytopathy, but negative for common mitochondrial DNA (mtDNA) point mutations and deletions, was screened for unknown mutations in the entire mitochondrial genome by temporal temperature gradient gel electrophoresis (TTGE). Her asymptomatic mother's blood DNA was also analyzed and used as a reference. Two tRNA regions showing different TTGE patterns between the proband and her mother were sequenced. Two novel mutations, G15995A in tRNA(pro) and A8326G in tRNA(lys), were revealed. These mutations are present in heteroplasmic states. They both occurred at a nucleotide position that is highly conserved throughout evolution. This patient is also a compound heterozygote for the cystic fibrosis (CF) mutations, DeltaF508 and R347P. The phenotype for R347P has been associated with mild disease. Due to the mild features of the R347P mutation in the CF transmembrane conductance regulator (CFTR) gene and the heterogeneous clinical presentation of the mtDNA disease, the patient was not definitively diagnosed until age 21. This case underscores the importance of a complete mutational analysis of the entire mitochondrial genome when a patient suspected of mitochondrial disorder is negative for common mtDNA mutations. (C) 2002 Wiley-Liss, Inc. C1 Georgetown Univ, Med Ctr, Inst Mol & Human Genet, Washington, DC 20007 USA. NINDS, Neurogenet Branch, NIH, Bethesda, MD USA. Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. RP Wong, LJC (reprint author), Georgetown Univ, Med Ctr, Inst Mol & Human Genet, 3800 Reservoir Rd NW, Washington, DC 20007 USA. NR 17 TC 26 Z9 26 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 15 PY 2002 VL 113 IS 1 BP 59 EP 64 DI 10.1002/ajmg.10767 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 607QQ UT WOS:000178802600011 PM 12400067 ER PT J AU Li, W Boykins, RA Backlund, PS Wang, GY Chen, HC AF Li, W Boykins, RA Backlund, PS Wang, GY Chen, HC TI Identification of phosphoserine and phosphothreonine as cysteic acid and beta-methylcysteic acid residues in peptides by tandem mass spectrometric sequencing SO ANALYTICAL CHEMISTRY LA English DT Article ID AFFINITY-CHROMATOGRAPHY; PHOSPHORYLATION SITES; PROTEIN-PHOSPHORYLATION; SELECTIVE DETECTION; SUBSTITUTED SERYL; THREONYL RESIDUES; COMPLEX-MIXTURES; PHOSPHOPEPTIDES; PHOSPHOPROTEINS; ELIMINATION AB Tandem mass spectrometry has long been an intrinsic tool to determine phosphorylation sites in proteins. However, loss of the phosphate moiety from both phosphoserine and phosphothreonine residues in low-energy collision-induced dissociation is a common phenomenon, which makes identification of P-Ser and P-Thr residues complicated. A method for direct sequencing of the Ser and Thr phosphorylation sites by ESI tandem mass spectrometry followingbeta-elimination/sulfite addition to convert -HPO4 to SO3 has been studied. Five model phosphopeptides, including three synthetic P-Ser-, P-Thr-, or P-Ser- and P-Thr-containing peptides; a protein kinases C-phosphorylated peptide; and a phosphopeptide derived from,beta-casein trypsin digests were modified and then sequenced using an ESI-quadrupole ion trap mass spectrometer. Following incubation of P-Ser- or P-Thr-containing peptides with Na2SO3/NaOH, 90% P-Ser and 80% P-Thr was converted to cysteic acid and beta-methylcysteic acid, respectively, as revealed by amino acid analysis. The conversion can be carried out at I muM concentration of the peptide. Both cysteic acid and beta-methylcysteic acid residues in the sequence were shown to be stable and easily identifiable under general conditions for tandem mass spectrometric sequencing applicable to common peptides. C1 NICHHD, Endocrinol & Reprod Res Branch, Lab Cell & Mol Biophys, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Biophys Lab, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20892 USA. RP Chen, HC (reprint author), NICHD, NIH, Bldg 49,Room 6A36,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 30 TC 27 Z9 28 U1 0 U2 3 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 NOV 15 PY 2002 VL 74 IS 22 BP 5701 EP 5710 DI 10.1021/ac020259v PG 10 WC Chemistry, Analytical SC Chemistry GA 616VH UT WOS:000179323700002 PM 12463352 ER PT J AU Koffler, LD Fernstrom, MJ Akiyama, TE Gonzalez, FJ Ruch, RJ AF Koffler, LD Fernstrom, MJ Akiyama, TE Gonzalez, FJ Ruch, RJ TI Positive regulation of connexin32 transcription by hepatocyte nuclear factor-1 alpha SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE cell communication; connexin; gap junction; gene regulation; liver; transcription ID GAP JUNCTION PROTEIN; RAT-LIVER; HEPATOCELLULAR-CARCINOMA; INTERCELLULAR COMMUNICATION; MOLECULAR-CLONING; GENE; EXPRESSION; CELLS; MOUSE; HNF-1-ALPHA AB Connexin32 (Cx32) encodes the predominant gap junction protein expressed by hepatocytes. We investigated the transcriptional control of Cx32 in expressing and nonexpressing rat liver cell lines and hypothesized that a putative hepatocyte nuclear factor-1 (HNF-1) binding site (centered at mp -187) in the liver-active, P1 promoter is essential for transcription of Cx32. HNF-1alpha was expressed by Cx32-expressing rat liver cell lines and bound the promoter at the -187 site, but was not expressed by non-Cx32-expressing hepatic lines. Stable transfection of non-Cx32-expressing WB-F344 rat liver epithelial cells with HNF-1alpha stimulated a transfected Cx32 promoter element (mp -244 to -33), binding of HNF-1alpha to the -187 site, and expression of endogenous Cx32. Site-directed mutagenesis of this HNF-1 binding site abolished HNF-1alpha binding and proximal promoter activity. Hepatic Cx32 expression was also significantly decreased in HNF-1alpha(-/-) mice. These data indicate that HNF-1alpha is a positive regulator of Cx32 expression in hepatic cells. (C) 2002 Elsevier Science (USA). All rights reserved. C1 Med Coll Ohio, Dept Pathol, Toledo, OH 43614 USA. NIH, Metab Lab, Bethesda, MD 20892 USA. RP Ruch, RJ (reprint author), Med Coll Ohio, Dept Pathol, 3055 Arlington Ave, Toledo, OH 43614 USA. FU NCI NIH HHS [CA57612] NR 42 TC 21 Z9 23 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD NOV 15 PY 2002 VL 407 IS 2 BP 160 EP 167 AR PII S0003-9861(02)00488-5 DI 10.1016/S0003-9861(02)00488-5 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 617MY UT WOS:000179366500003 PM 12413486 ER PT J AU Crombag, HS Jedynak, JP Redmond, K Robinson, TE Hope, BT AF Crombag, HS Jedynak, JP Redmond, K Robinson, TE Hope, BT TI Locomotor sensitization to cocaine is associated with increased Fos expression in the accumbens, but not in the caudate SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE striatum; neuroplasticity; immunohistochemistry; psychomotor activity; dose-effect; dopamine; glutamate; rat ID TIME-DEPENDENT SENSITIZATION; MESSENGER-RNA EXPRESSION; C-FOS; BEHAVIORAL SENSITIZATION; NUCLEUS-ACCUMBENS; RAT STRIATUM; AMPHETAMINE SENSITIZATION; EXTRACELLULAR DOPAMINE; PROTEINS; INDUCTION AB Behavioral sensitization following repeated intermittent cocaine administrations is thought to involve alterations in cocaine regulation of neural activity within the accumbens and caudate brain regions. Although Fos immunohistochemistry and c-fos in situ hybridization have frequently been used to assess changes in cocaine-induced neural activity following prior cocaine exposure, these techniques have rarely been used to examine neural activity in the accumbens of behaviorally sensitized animals. In the present experiment, we compared the ability of increasing doses of cocaine to induce Fos in the accumbens and caudate of rats following a treatment procedure (7 once daily injections of 15 mg/kg of cocaine or the saline vehicle) shown to produce robust and persistent (I week) locomotor sensitization. In sensitized animals, there was a leftward shift in the dose-response curve for cocaine induction of Fos in the accumbens, but not in the caudate. These results provide the first parametric evidence for sensitization of cocaine-induced Fos expression in the accumbens. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, Baltimore, MD 21224 USA. Univ Michigan, Biopsychol Program, Dept Psychol, Ann Arbor, MI 48109 USA. RP Hope, BT (reprint author), Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Hope, Bruce/A-9223-2010; OI Hope, Bruce/0000-0001-5804-7061; Jedynak, Jakub/0000-0001-7291-3632 NR 41 TC 53 Z9 54 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD NOV 15 PY 2002 VL 136 IS 2 BP 455 EP 462 AR PII S0166-4328(02)00196-1 DI 10.1016/S0166-4328(02)00196-1 PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 620GC UT WOS:000179524800015 PM 12429408 ER PT J AU Ma, JX Bradbury, JA King, L Maronpot, R Davis, LS Breyer, MD Zeldin, DC AF Ma, JX Bradbury, JA King, L Maronpot, R Davis, LS Breyer, MD Zeldin, DC TI Molecular cloning and characterization of mouse CYP2J6, an unstable cytochrome P450 isoform SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE cytochrome P450; benzphetamine; gastrointestinal tract; epithelial cells; in situ hybridization; baculovirus ID ARACHIDONIC-ACID; EXTRAHEPATIC TISSUES; INTESTINAL-MUCOSA; IMMUNOHISTOCHEMICAL LOCALIZATION; EPOXYEICOSATRIENOIC ACIDS; FUNCTIONAL-SIGNIFICANCE; CELLULAR-LOCALIZATION; ACCESSION NUMBERS; CDNA CLONING; EXPRESSION AB A cDNA encoding a new cytochrome P450 was cloned from a mouse liver library. Sequence analysis revealed that this 2046-bp cDNA encodes a 501-amino acid polypeptide that is 72-94% identical to other CYP2J subfamily P450s and is designated CYP2J6. Northern analysis demonstrated that CYP2J6 transcripts are abundant in the small intestine and present at lower levels in other mouse tissues. In situ hybridization revealed that CYP2J6 mRNAs are present in luminal epithelial cells of the gastrointestinal mucosa. The CYP2J6 cDNA was expressed in Sf9 cells using baculovirus. The heterologously expressed CYP2J6 protein displayed a typical P450 CO-difference spectrum; however, the protein was unstable as evidenced by the loss of the Soret maxima at 450 nm and the appearance of a 420 nm peak when CYP2J6-expressing cells were disrupted by mechanical homogenization, sonication, or freeze-thaw. Immunoblotting of mouse microsomes with the anti-human CYP2J2 IgG, which cross-reacts with rodent CYP2Js, demonstrated the presence of multiple distinct murine CYP2J immunoreactive proteins in various tissues. Immunoblotting with an antibody to a CYP2J6-specific peptide detected a prominent 55-57 kDa protein in Sf9 cell extracts expressing recombinant CYP2J6 but did not detect a protein of similar molecular mass in mouse small intestinal microsomes. Mixing experiments demonstrated that recombinant CYP2J6 is degraded rapidly in the presence of small intestinal microsomes consistent with proteolysis at highly sensitive sites. Sf9 cells, which express both CYP2J6 and NADPH-P450 oxidoreductase, metabolized benzphetamine but not arachidonic acid. We conclude that CYP2J6 is an unstable P450 that is active in the metabolism of benzphetamine, but not arachidonic acid. Published by Elsevier Science Inc. C1 NIEHS, Div Intramural Res, Res Triangle Pk, NC 27709 USA. Vanderbilt Univ, Dept Med, Nashville, TN 37232 USA. RP Zeldin, DC (reprint author), NIEHS, Div Intramural Res, 111 TW Alexander Dr,Bldg 101, Res Triangle Pk, NC 27709 USA. FU NIDDK NIH HHS [2P01 DK 38266] NR 46 TC 15 Z9 17 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD NOV 15 PY 2002 VL 64 IS 10 BP 1447 EP 1460 AR PII S0006-2952(02)01393-X DI 10.1016/S0006-2952(02)01393-X PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 617RL UT WOS:000179374600004 PM 12417258 ER PT J AU Payne, JL Quiroz, JA Zarate, CA Manji, HK AF Payne, JL Quiroz, JA Zarate, CA Manji, HK TI Timing is everything: Does the robust upregulation of noradrenergically regulated plasticity genes underlie the rapid antidepressant effects of sleep deprivation? SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Learning and Unlearning Fears CY MAR 21, 2002 CL AUSTIN, TEXAS DE antidepressant; circadian rhythm; rapid-eye-movement sleep; locus coeruleus; CREB; BDNF ID RAT-BRAIN; MECHANISMS; EXPRESSION; DEPRESSION; WAKING AB The mechanisms by which sleep deprivation brings about rapid antidepressant effects remain to be elucidated. Biological rhythms have the capacity to temporally dissociate biochemical processes, and imposing a temporal coincidence on normally dissociated events can have striking and unexpected effects. In this context, it is noteworthy that the locus coeruleus (LC) noradrenergic projection is quiescent only during rapid-eye-movement (REM) sleep, when the target tissues display their greatest sensitivity; indeed, the temporal dissociation between the firing of the LC noradrenergic neurons and the sensitivity of its postsynaptic targets in the cortex may have considerable relevance for the antidepressant effects of sleep deprivation. Sleep deprivation rapidly upregulates several plasticity-related genes, effects that are noradrenergically mediated; these are the very same genes that are upregulated by chronic antidepressants. Thus, activating the norepinephrine system during REM sleep (by infusing an alpha(2) antagonist) may allow an interaction with a primed, sensitized postsynaptic milieu, thereby rapidly increasing the expression of plasticity genes and consequently a rapid antidepressant response. (C) 2002 Society of Biological Psychiatry. C1 NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. RP Payne, JL (reprint author), NIMH, Mol Pathophysiol Lab, 9000 Rockville Pike,Bldg 10,Room 3s242, Bethesda, MD 20892 USA. NR 23 TC 27 Z9 27 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 15 PY 2002 VL 52 IS 10 BP 921 EP 926 AR PII S0002-3223(02)01676-1 DI 10.1016/S0006-3223(02)01676-1 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 615GW UT WOS:000179238300002 PM 12437933 ER PT J AU Grillon, C AF Grillon, C TI Startle reactivity and anxiety disorders: Aversive conditioning, context, and neurobiology SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Learning and Unlearning Fears CY MAR 21, 2002 CL AUSTIN, TEXAS DE fear conditioning; associative learning; context conditioning; startle; psychophysiology; anxiety ID FEAR-POTENTIATED STARTLE; POSTTRAUMATIC-STRESS-DISORDER; CORTICOTROPIN-RELEASING FACTOR; ACOUSTIC STARTLE; STRIA TERMINALIS; BED NUCLEUS; BASE-LINE; ANTICIPATORY ANXIETY; DOUBLE DISSOCIATION; HIPPOCAMPAL VOLUME AB The aim of this article is to review studies on human anxiety using the startle reflex methodology and to apply the literature on context conditioning in rats to interpret the results. A distinction is made between cued fear (as in specific phobia), a phasic response to an explicit threat cue, and anxiety, a more sustained and future-oriented response not linked to a specific discrete cue. Experimentally, contextual fear, as opposed to cued fear, may best reflect the feeling of aversive expectation about potential future dangers that characterizes anxiety. Following a brief description of the neurobiology of cued fear and context conditioning, evidence is presented showing that anxious patients are overly sensitive to threatening contexts. It is then argued that the degree to which contextual fear is prompted by threat depends on whether the danger is predictable or unpredictable. Consistent with animal data, unpredictable shocks in humans result in greater context conditioning compared to predictable shocks. Because conditioning promotes predictability, it is proposed to use conditioning procedures to study the development of appropriate and inappropriate aversive expectations. Cued fear learning is seen as an adaptive process by which undifferentiated fear becomes cue-specific. Deficits in cued fear learning lead to the development of nonadaptive aversive expectancies and an attentional bias toward generalized threat. Lacking a cue for threat, the organism cannot identify periods of danger and safety and remains in a chronic state of anxiety. Factors that may affect conditioning are discussed. (C) 2002 Society of Biological Psychiatry. C1 NIMH, DHHS, MAP, NIH, Bethesda, MD 20892 USA. RP Grillon, C (reprint author), NIMH, DHHS, MAP, NIH, 15K North Dr,Bldg 15K,Room 113,MSC2670, Bethesda, MD 20892 USA. FU NIMH NIH HHS [5R01 MH53618] NR 123 TC 277 Z9 280 U1 21 U2 56 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 15 PY 2002 VL 52 IS 10 BP 958 EP 975 AR PII S0006-3223(02)01665-7 DI 10.1016/S0006-3223(02)01665-7 PG 18 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 615GW UT WOS:000179238300006 PM 12437937 ER PT J AU Kimbrell, TA Ketter, TA George, MS Little, JT Benson, BE Willis, MW Herscovitch, P Post, RM AF Kimbrell, TA Ketter, TA George, MS Little, JT Benson, BE Willis, MW Herscovitch, P Post, RM TI Comment on "Regional cerebral glucose utilization in patients with a range of severities of unipolar depression" - Reply SO BIOLOGICAL PSYCHIATRY LA English DT Letter C1 NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP Kimbrell, TA (reprint author), NIMH, Biol Psychiat Branch, NIH, Bldg 10,Room 3S239,10 Ctr Dr,MSC 1272, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 15 PY 2002 VL 52 IS 10 BP 1031 EP 1032 AR PII S0006-3223(02)01481-6 DI 10.1016/S0006-3223(02)01481-6 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 615GW UT WOS:000179238300012 ER PT J AU Washington, AV Quigley, L McVicar, DW AF Washington, AV Quigley, L McVicar, DW TI Initial characterization of TREM-like transcript (TLT)-1: a putative inhibitory receptor within the TREM cluster SO BLOOD LA English DT Article ID EXPRESSION; MONOCYTES; SEPSIS AB The TREMs (triggering receptors expressed on myeloid cells) represent a family of 5 receptors clustered on murine chromosome 17. TREMs 1 and 2 affect various aspects of myeloid cell activation and development, including responsiveness to lipopolysaccharide and regulation of dendritic cell maturation, yet no inhibitory receptor has been demonstrated within this cluster. Here we characterize TLT-1 (TREM-like transcript-1), a putative Inhibitory receptor within the TREM cluster that contains an extracellular V-set Ig domain, a proline-rich region, and an immune receptor tyrosine-based inhibitory motif (ITIM) in its cytoplasmic tail. To our knowledge, TLT-1 is the first ITIM-containing receptor carrying a potential Src homology 3 domain ligand. TLT-1 transcripts are abundant in bone marrow cells, but not in lymphocytes, and phosphorylated TLT-1 associates with SHP-1, suggesting that It is indeed an Inhibitory receptor. Based on these characteristics, it is likely that TLT-1 regulates the signaling of the TREM family receptors. C1 NCI, Expt Immunol Lab, Frederick, MD 21701 USA. RP McVicar, DW (reprint author), NCI-FCRDC Bldg 560 Room 31-93, Frederick, MD 21702 USA. RI McVicar, Daniel/G-1970-2015 NR 11 TC 32 Z9 38 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2002 VL 100 IS 10 BP 3822 EP 3824 DI 10.1182/blood-2002-02-0523 PG 3 WC Hematology SC Hematology GA 613YE UT WOS:000179158500052 PM 12393607 ER PT J AU Castle, PE Wacholder, S Sherman, ME Lorincz, AT Glass, AG Scott, DR Rush, BB Demuth, F Schiffman, M AF Castle, PE Wacholder, S Sherman, ME Lorincz, AT Glass, AG Scott, DR Rush, BB Demuth, F Schiffman, M TI Absolute risk of a subsequent abnormal pap among oncogenic human papillomavirus DNA-Positive, cytologically negative women SO CANCER LA English DT Article DE Pap; ASC; LSIL; HSIL; HPV; absolute risk ID INTRAEPITHELIAL NEOPLASIA; EPIDEMIOLOGIC EVIDENCE; CERVICAL-CANCER; WORLDWIDE; PREGNANCY; INFECTION AB BACKGROUND. The addition of human papillomavirus (HPV) DNA testing to cytologic screening for cervical carcinoma is now being considered. The majority of women in screening cohorts who test positive for oncogenic types of HPV DNA have concurrent negative Pap tests. The absolute risk of a subsequent abnormal Pap test for these women is uncertain. Therefore, the proper counseling and clinical management of these women is also uncertain. METHODS. A subcohort of 2020 women with a negative Pap test who tested positive at enrollment for oncogenic HPV DNA types using the Hybrid Capture 2 Test were followed for 57 months at Kaiser Permanente (Portland, OR). Absolute risks of new abnormal cytologic interpretations were computed using Kaplan-Meier methods. Logistic regression models were used to evaluate determinants of a new abnormal Pap test. RESULTS. The cumulative incidence for a Pap test interpreted as atypical squamous cells or more severe (greater than or equal to ASC) was 16.8% (95% confidence interval [CI] = 15.0-18.6%), 6.4% (95% CI = 5.2-7.6%) for low-grade squamous intraepithelial lesions or more severe, and 2.2% (95% CI = 1.5-2.9%) for high-grade squamous intraepithelial lesions or more severe. By comparison, the cumulative incidence of greater than or equal to ASC among HPV-negative women was 4.2% (95% CI = 3.9-4.6%). The highest viral load (100 relative light units per the positive control or greater) was associated with a greater risk of an abnormal Pap test (odds ratio= 2.7, 95% CI = 1.7-4.1) than lower viral loads. CONCLUSIONS. These results suggest that about 15% of women in annual screening programs who concurrently have a negative Pap test and a positive oncogenic HPV test will have a subsequent abnormal Pap test within 5 years. This risk estimate will be useful to the many clinicians and patients likely to be diagnosed with an HPV infection and negative cytology if HPV DNA is added to general screening. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Digene Corp, Gaithersburg, MD USA. Kaiser Permanente, Portland, OR USA. Informat Management Serv Inc, Silver Spring, MD USA. RP Castle, PE (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 7074,EPS MSC 7234, Bethesda, MD 20892 USA. NR 15 TC 58 Z9 64 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 15 PY 2002 VL 95 IS 10 BP 2145 EP 2151 DI 10.1002/cncr.10927 PG 7 WC Oncology SC Oncology GA 611HH UT WOS:000179010200014 PM 12412168 ER PT J AU Herzog, CR Devereux, TR Pittman, B You, M AF Herzog, CR Devereux, TR Pittman, B You, M TI Carcinogenic induction directs the selection of allelic losses in mouse lung tumorigenesis SO CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; TUMOR-SUPPRESSOR GENE; GENOMIC INSTABILITY; HUMAN CANCERS; DNA; CHROMOSOME-4; IMBALANCES; ADENOCARCINOMAS; HETEROZYGOSITY; METABOLITES AB Recent evidence suggests that genome-wide allelic imbalances are inducible by carcinogens and may occur as cells adapt to carcinogenic exposure during tumorigenesis. We investigated the role of carcinogenic exposure on global and selected loss of heterozygosity (LOH) during mouse lung adenocareinogenesis. Tumor induction by 4-(methyinitrosamino)-1-(3-pyridyl)-1-butanone (NNK) or vinyl carbamate (VC) resulted in a significant overall increase in the number of chromosomes affected by LOH per tumor when compared with spontaneous lung tumors. Allelic loss on chromosome 12 occurred at a frequency of 35% and 40% in NNK- and VC-induced tumors, respectively, compared with 8.3% in spontaneous tumors (P < 0.01). In contrast, spontaneous lung adenocarcinomas displayed LOH on chromosome 4 at a frequency of 77%, whereas a frequency of only 36% (P < 0.001) was observed in tumors induced by NNK. Sixty-four percent of the VC-induced tumors displayed LOH on chromosome 4. In addition, allelic losses on chromosomes 12 and 14 were significantly associated with an increase in chromosomal instability, suggesting that genes inactivated on these chromosomes may contribute to this effect. The results from this study demonstrate that geno-toxic carcinogens increase chromosome instability, as evidenced by a significant increase in global LOH frequency, and significantly alter the selection of chromosomal alterations during lung tumor development. C1 Amer Hlth Fdn, Valhalla, NY 10595 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Herzog, CR (reprint author), Amer Hlth Fdn, 1 Dana Rd, Valhalla, NY 10595 USA. FU NCI NIH HHS [CA17613] NR 36 TC 7 Z9 7 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2002 VL 62 IS 22 BP 6424 EP 6429 PG 6 WC Oncology SC Oncology GA 616QV UT WOS:000179315200015 PM 12438228 ER PT J AU Steele, VE Boone, CW Dauzonne, D Rao, CV Bensasson, RV AF Steele, VE Boone, CW Dauzonne, D Rao, CV Bensasson, RV TI Correlation between electron-donating ability of a series of 3-nitroflavones and their efficacy to inhibit the onset and progression of aberrant crypt foci in the rat colon SO CANCER RESEARCH LA English DT Article ID TRANSCRIPTION FACTORS; REDOX PROPERTIES; CHEMOPREVENTION; CANCER; FLAVONOIDS; INDUCTION; ENZYMES; DRUGS AB A series of five 3-nitroflavones were tested for their ability to inhibit the formation of colon aberrant crypt foci (ACF) induced by a s.c. injection of azoxymethane (C2H6N2O) in rats. Our aim was to relate the electrondonating effects of the 3-nitroflavones as characterized by their Hammett substitution constants with their efficacy in inhibiting ACE In a first assay (initiation, protocol A) the 3-nitroflavone as well as the 4'-substituted nitro-, methoxy-, fluoro-, and hydroxy-3-nitroflavones were continuously present in the diet. In a second assay (postinitiation, protocol B) they were given for a period of 4 weeks after the last azoxymethane injection. The different substituents of the 3-nitroflavones at the 4'-position spanned a spectrum of Hammett constants (sigma(p)(+)), going from +0.79 for the electron-withdrawing group, NO2, to -0.92 for the electron-donating group, OH. For both protocols the percentages of inhibition plotted versus the Hammett substitution constants showed a linear correlation, the most efficacious ACF inhibition being produced by the molecules with the most electron-donating substituents. Moreover, the nitroflavones were not only chemoprotective during initiation of the ACF, but also therapeutic in the postinitiation progression assay. The above correlations may be of predictive value in the search for new chemoprotective agents. The overall molecular mechanism of the inhibition of ACF by the 3-nitroflavones under study appears to involve redox reactions. C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. CNRS, UMR 176, Inst Curie, Lab Pharmacochim, F-75248 Paris, France. Amer Hlth Fdn, Valhalla, NY 10595 USA. CNRS UMR 8646, Museum Natl Hist Nat, Lab Biophys, F-75005 Paris, France. CNRS ESA 8041, F-75005 Paris, France. RP Steele, VE (reprint author), NCI, Div Canc Prevent, EPN 2108,MSC 7322,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Chinthalapally, Rao/B-3633-2010 FU NCI NIH HHS [N01-CN-65108] NR 28 TC 14 Z9 15 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2002 VL 62 IS 22 BP 6506 EP 6509 PG 4 WC Oncology SC Oncology GA 616QV UT WOS:000179315200031 PM 12438244 ER PT J AU Pennisi, PA Barr, V Nunez, NP Stannard, B Le Roith, D AF Pennisi, PA Barr, V Nunez, NP Stannard, B Le Roith, D TI Reduced expression of insulin-like growth factor I receptors in MCF-7 breast cancer cells leads to a more metastatic phenotype SO CANCER RESEARCH LA English DT Article ID BETA-CATENIN COMPLEX; RHO-FAMILY GTPASES; E-CADHERIN; IGF-I; TYROSINE PHOSPHORYLATION; ACTIN CYTOSKELETON; BASEMENT-MEMBRANE; COLON-CARCINOMA; ADHESION; INTEGRIN AB Several lines of evidence support an important role for the insulin-like growth factor system in breast cancer. Alterations in insulin-like growth factor I receptor (IGF-IR) have been associated with breast cancer metastasis; however, the specific role played by the IGF-IR in this process remains unclear. To address this issue, we evaluated MCF-7 breast cancer cells stably transfected either with an antisense construct to the IGF-IR, which reduced the expression of the IGF-IRs by similar to50% (SX13 cells), or with the empty vector as control (NEO cells). Using functional assays for motility, attachment, and aggregation, we found a 3-fold increase in migration using both the wounding assay and the Boyden chamber migration assay. In addition, the SX13 cells attached less, and there was a reduction in cellular aggregation. These functional changes were accompanied by similar to50% decrease in expression of E-cadherin and similar to80% increase in p120 protein levels. Moreover, there was a significant reduction in p120 present in the E-cadherin-catenin-p120 complex. There was a 2-fold increase in active Rac1 and Cdc42 and a 35% decrease in active Rho in the SX13 cells. Our findings strongly suggest that the IGF-IR plays a role in the stabilization of the E-cadherin-catenin complex, thereby providing one possible explanation for the association between low levels of IGF-IR and a higher risk of mammary tumor metastasis. C1 NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Barr, V (reprint author), NIDDKD, Clin Endocrinol Branch, NIH, Room 8D12,Bldg 10, Bethesda, MD 20892 USA. NR 54 TC 52 Z9 56 U1 0 U2 4 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 NOV 15 PY 2002 VL 62 IS 22 BP 6529 EP 6537 PG 9 WC Oncology SC Oncology GA 616QV UT WOS:000179315200034 PM 12438247 ER PT J AU Recio, JA Noonan, FP Takayama, H Anver, MR Duray, P Rush, WL Lindner, G De Fabo, EC DePinho, RA Merlino, G AF Recio, JA Noonan, FP Takayama, H Anver, MR Duray, P Rush, WL Lindner, G De Fabo, EC DePinho, RA Merlino, G TI Ink4a/Arf deficiency promotes ultraviolet radiation-induced melanomagenesis SO CANCER RESEARCH LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; FACTOR SCATTER FACTOR; COMPARATIVE GENOMIC HYBRIDIZATION; MALIGNANT-MELANOMA; CUTANEOUS MELANOMA; FACTOR/SCATTER FACTOR; SPORADIC MELANOMA; TUMOR-SUPPRESSOR; TRANSGENIC MICE; MET RECEPTOR AB Cutaneous malignant melanoma (CMM), already known for its highly aggressive behavior and resistance to conventional therapy, has evolved into a health crisis by virtue of a dramatic elevation in incidence. The underlying genetic basis for CMM, as well as the fundamental role for UV radiation in its etiology, is now widely accepted. However, the only bona fide genetic locus to emerge from extensive analysis of CMM suppressor candidates is INK4a/ARF at 9p21, which is lost frequently in familial and occasionally in somatic CMM. The functional relationship between INK4a/ARF and UV radiation in the pathogenesis of CMM is largely unknown. Recently, we reported that hepatocyte growth factor/scatter factor (HGF/SF)-transgenic mice develop melanomas after a single erythemal dose of neonatal UV radiation, supporting epidemiological data implicating childhood sunburn in CMM. Here we show that neonatal UV irradiation induces a full spectrum of melanocyte pathology from early premalignant lesions through distant metastases. Cutaneous melanomas arise with histopathological and molecular pathogenetic features remarkably similar to CMM, including loss of ink4a/arf. A role for ink4a/arf in UV-induced melanomagenesis was directly assessed by placing the HGF/SF transgene on a genetic background devoid of ink4a/arf. Median time to melanoma development induced by UV radiation was only 50 days in HGF/SF ink4a/arf(-/-) mice, compared with 152 and 238 days in HGF/SF ink4a/arf(+/-) and HGF/SF ink4a/arf(+/+) mice, respectively. These studies provide experimental evidence that ink4a/arf plays a critical role in UV-induced melanomagenesis and strongly suggest that sunburn is a highly significant risk factor, particularly in families harboring germ-line mutations in INK4a/ARF. C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. George Washington Univ, Sch Med, Dept Immunol & Dermatol, Washington, DC 20037 USA. Sci Applicat Int Corp, Pathol Histotechnol Lab, NCI, Frederick, MD 21702 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Dept Dermatopathol, Washington, DC 20306 USA. Univ Hamburg, Hosp Eppendorf, Dept Dermatol, D-20246 Hamburg, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol Med & Genet, Boston, MA 02115 USA. RP Merlino, G (reprint author), NCI, Mol Biol Lab, Bldg 37,Room 5002, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA-92258, N0I-CO-56000] NR 62 TC 70 Z9 72 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2002 VL 62 IS 22 BP 6724 EP 6730 PG 7 WC Oncology SC Oncology GA 616QV UT WOS:000179315200060 PM 12438273 ER PT J AU Wulfkuhle, JD Sgroi, DC Krutzsch, H McLean, K McGarvey, K Knowlton, M Chen, S Shu, HJ Sahin, A Kurek, R Wallwiener, D Merino, MJ Petricoin, EF Zhao, YM Steeg, PS AF Wulfkuhle, JD Sgroi, DC Krutzsch, H McLean, K McGarvey, K Knowlton, M Chen, S Shu, HJ Sahin, A Kurek, R Wallwiener, D Merino, MJ Petricoin, EF Zhao, YM Steeg, PS TI Proteomics of human breast ductal carcinoma in situ SO CANCER RESEARCH LA English DT Article ID SURGICAL-ADJUVANT-BREAST; TRANS-GOLGI NETWORK; IN-SITU; LOCAL RECURRENCE; HYDROGEN-PEROXIDE; FOLLOW-UP; CONSERVING THERAPY; ESTROGEN-RECEPTOR; HORMONE RECEPTORS; TUMOR PROGRESSION AB We report the first proteomic analysis of matched normal ductal/ lobular units and ductal carcinoma in situ (DCIS) of the human breast. An understanding of the transition from normal epithelium to the first definable stage of cancer at the functional level of protein expression is hypothesized to contribute to improved detection, prevention, and treatment. Ten sets of two-dimensional gels were evaluated, containing either matched normal ductal/lobular units or DCIS from either whole tissue sections or up to 100,000 laser capture microdissected epithelial cells. Differential protein expression was confirmed by image analysis. Protein spots (315) were excised and subjected to mass spectrometry sequencing. Fifty-seven proteins were differentially expressed between normal ductal/ lobular units and DCIS. Differences in overall protein expression levels and posttranslational processing were evident. Ten differentially expressed proteins were validated in independent DCIS specimens, and 14 of 15 proteomic trends from two-dimensional gel analyses were confirmed by standard inummohistochemical analysis using a limited independent tumor cohort. Many of the proteins identified were previously unconnected with breast cancer, including proteins regulating the intracellular trafficking of membranes, vesicles, cancer preventative agents, proteins, ions, and fatty acids. Other proteomic identifications related to cytoskeletal architecture, chaperone function, the microenvironment, apoptosis, and genomic instability. Proteomic analysis of DCIS revealed differential expression patterns distinct from previous nucleic acid-based studies and identified new facets of the earliest stage of breast cancer progression. C1 NCI, Womens Canc Sect, Pathol Lab, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02129 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX 75390 USA. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Univ Tubingen, Dept Obstet & Gynecol, D-72076 Tubingen, Germany. US FDA, Ctr Biol Evaluat & Res, NCI, Clin Proteom Program,Div Therapeut Prot, Bethesda, MD 20892 USA. RP Steeg, PS (reprint author), NCI, Womens Canc Sect, Pathol Lab, Bldg 10,Room 2A33, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA 85146] NR 69 TC 188 Z9 200 U1 2 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 NOV 15 PY 2002 VL 62 IS 22 BP 6740 EP 6749 PG 10 WC Oncology SC Oncology GA 616QV UT WOS:000179315200062 PM 12438275 ER PT J AU Jaboin, J Kim, CJ Kaplan, DR Thiele, CJ AF Jaboin, J Kim, CJ Kaplan, DR Thiele, CJ TI Brain-derived neurotrophic factor activation of TrkB protects neuroblastoma cells from chemotherapy-induced apoptosis via phosphatidylinositol 3 '-kinase pathway SO CANCER RESEARCH LA English DT Article ID CEREBELLAR GRANULE NEURONS; GLUTAMATE-INDUCED NEUROTOXICITY; SIGNAL-TRANSDUCTION; IN-VIVO; CORTICAL-NEURONS; SURVIVAL; BDNF; EXPRESSION; GROWTH; DIFFERENTIATION AB Neuroblastoma (NB) tumors expressing high levels of brain-derived neurotrophic factor (BDNF) and TrkB are associated with poor 5-year survival outcomes. Our previous studies indicated that BDNF blocked the cytotoxic effects of vinblastine on NB cells. Here we evaluated the ability of BDNF to decrease the chemosensitivity of NB cells to a number of common chemotherapeutic agents. Two SH-SY5Y NB cell lines (TB3 and TB8) expressing TrkB under the control of a tetracycline (Tet)-repressible promoter element were generated, and used to assess apoptosis resulting from treatment with cisplatin, doxorubicin, etoposide, and vinblastine. BDNF treatment of high TrkB-expressing TB8 (Tet-) and TB3 (Tet-) cells blocked drug-induced cell death in a dose-dependent manner. Only high-dose BDNF (100 ng/ml) could block the effects of chemotherapy in low TrkB-expressing cells. The ability of BDNF to rescue the cells from chemotherapeutic agent-induced cell death was inhibited by treatment with the Trk tyrosine kinase inhibitor K252a or the phosphatidylinositol 3'-kinase (PI3K) inhibitor LY294002, but not by the mitogen-activated protein kinase kinase inhibitor PD98059 or the peritoneal lymphocyte gamma inhibitor U73122, indicating that both TrkB and PI3K activities are required for the survival-promoting effects of BDNF. BDNF also protected TrkB-expressing NGP and KCNR NB cells from chemotherapeutic agent-induced cell death, and LY294002 inhibited this protection. These results suggest that TrkB and BDNF can contribute to the chemoresistance of poor prognosis tumors, and that suppression of PI3K activity might improve the ability of these agents to induce the death of NB tumors. C1 NCI, Cell & Mol Biol Sect, Pediat Oncol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. Seoul Natl Univ, Coll Med, Dept Pathol, Seoul 100799, South Korea. Montreal Neurol Inst, Brain Tumor Res Ctr, Montreal, PQ H3A 2B4, Canada. RP Thiele, CJ (reprint author), NCI, Cell & Mol Biol Sect, Pediat Oncol Branch, Canc Res Ctr, 10 Ctr Dr,MSC 1928, Bethesda, MD 20892 USA. EM ct47a@nih.gov RI Seoul National University, Pathology/B-6702-2012 NR 40 TC 127 Z9 130 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 NOV 15 PY 2002 VL 62 IS 22 BP 6756 EP 6763 PG 8 WC Oncology SC Oncology GA 616QV UT WOS:000179315200064 PM 12438277 ER PT J AU Feinberg, AP Oshimura, M Barrett, JC AF Feinberg, AP Oshimura, M Barrett, JC TI Epigenetic mechanisms in human disease SO CANCER RESEARCH LA English DT Editorial Material ID MUTATIONS; METHYLATION; GENE; DNA; INSTABILITY; ANGELMAN; PROTEIN; CANCER; CTCF C1 Johns Hopkins Univ, Sch Med, Dept Med Oncol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. Tottori Univ, Sch Life Sci, Dept Mol & Cellular Genet, Yonago, Tottori 683, Japan. NCI, Canc Res Ctr, Bethesda, MD 20892 USA. RP Feinberg, AP (reprint author), Johns Hopkins Univ, Sch Med, Dept Med Oncol, 720 Ruland Ave,Ross 1064, Baltimore, MD 21205 USA. FU NCI NIH HHS [R37 CA054358, R37 CA054358-12] NR 23 TC 35 Z9 37 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2002 VL 62 IS 22 BP 6784 EP 6787 PG 4 WC Oncology SC Oncology GA 616QV UT WOS:000179315200068 PM 12438281 ER PT J AU Cohen, JI Davenport, DS Stewart, JA Deitchman, S Hilliard, JK Chapman, LE AF Cohen, JI Davenport, DS Stewart, JA Deitchman, S Hilliard, JK Chapman, LE CA B Virus Working Grp TI Recommendations for prevention of and therapy for exposure to B virus (Cercopithecine herpesvirus 1) SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID CYTOMEGALOVIRUS DISEASE; SIMIAE INFECTION; RHESUS MACAQUES; PROPHYLAXIS; TRIAL AB B virus (Cercopithecine herpesvirus 1) is a zoonotic agent that can cause fatal encephalomyelitis in humans. The virus naturally infects macaque monkeys, resulting in disease that is similar to herpes simplex virus infection in humans. Although B virus infection generally is asymptomatic or mild in macaques, it can be fatal in humans. Previously reported cases of B virus disease in humans usually have been attributed to animal bites, scratches, or percutaneous inoculation with infected materials; however, the first fatal case of B virus infection due to mucosal splash exposure was reported in 1998. This case prompted the Centers for Disease Control and Prevention (Atlanta, Georgia) to convene a working group in 1999 to reconsider the prior recommendations for prevention and treatment of B virus exposure. The present report updates previous recommendations for the prevention, evaluation, and treatment of B virus infection in humans and considers the role of newer antiviral agents in postexposure prophylaxis. C1 NIH, Med Virol Sect, Clin Invest Lab, Bethesda, MD 20892 USA. Michigan State Univ, Kalamazoo Ctr Med Studies, Div Infect Dis, Kalamazoo, MI USA. Georgia State Univ, Ctr Dis Control & Prevent, Atlanta, GA 30303 USA. Georgia State Univ, Virol Immunol Ctr, Atlanta, GA 30303 USA. RP Cohen, JI (reprint author), NIH, Med Virol Sect, Clin Invest Lab, Bldg 10,Rm 11N228,10 Ctr Dr,MSC 1888, Bethesda, MD 20892 USA. NR 39 TC 64 Z9 75 U1 1 U2 8 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV 15 PY 2002 VL 35 IS 10 BP 1191 EP 1203 DI 10.1086/344754 PG 13 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 611PM UT WOS:000179027000008 PM 12410479 ER PT J AU Doan, NM Keiser, PB Bates, RA Fedorko, DP Weina, PJ Lucey, DR AF Doan, NM Keiser, PB Bates, RA Fedorko, DP Weina, PJ Lucey, DR TI A 33-year-old woman from Nigeria with eosinophilia - Loiasis SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID DOUBLE-BLIND; DIETHYLCARBAMAZINE C1 Washington Hosp Ctr, Washington, DC 20010 USA. NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. NIH, Microbiol Serv, Bethesda, MD 20892 USA. Walter Reed Army Inst Res, Silver Spring, MD USA. RP Doan, NM (reprint author), Washington Hosp Ctr, Rm 2A-56, Washington, DC 20010 USA. RI Weina, Peter/A-2120-2011 NR 7 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV 15 PY 2002 VL 35 IS 10 BP 1204 EP + PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 611PM UT WOS:000179027000009 PM 12420728 ER PT J AU Cai, JL Wu, YY Mirua, T Pierce, JL Lucero, MT Albertine, KH Spangrude, GJ Rao, MS AF Cai, JL Wu, YY Mirua, T Pierce, JL Lucero, MT Albertine, KH Spangrude, GJ Rao, MS TI Properties of a fetal multipotent neural stem cell (NEP cell) SO DEVELOPMENTAL BIOLOGY LA English DT Article DE NSC; NEP; NRP; GRP; differentiation; precursor ID GROWTH-FACTOR RECEPTOR; CENTRAL-NERVOUS-SYSTEM; FOCAL CEREBRAL-ISCHEMIA; ADULT-MOUSE BRAIN; SPINAL-CORD; PROGENITOR CELLS; PRECURSOR CELLS; RAT-BRAIN; NEURONAL DIFFERENTIATION; DEVELOPMENTAL EXPRESSION AB Multipotent neural stem cells (NSCs) present in the developing neural tube (E10.5, neuroepithelial cells; NEP) were examined for the expression of candidate stem cell markers, and the expression of these markers was compared with later appearing precursor cells (E14.5) that can be distinguished by the expression of embryonic neural cell adhesion molecule (E-NCAM) and A2B5. NEP cells possess gap junctions, express connexins, and appear to lack long cilia. Most candidate markers, including Nestin, Presenilin, Notch, and Numb, were expressed by both NEP cells as well as other cell populations. Fibroblast growth factor receptor 4 (FGFR4), Frizzled 9 (Fz9), and SRY box-containing gene 2 (Sox2) as assessed by immunocytochemistry and in situ hybridization are markers that appear to distinguish NSCs from other precursor cells. Neither Hoechst 33342 nor rhodamine- 123 staining, telomerase (Tert) expression, telomerase activity, or breakpoint cluster region protein I (Bcrp1) transporter expression could be used to distinguish NEP stem cells from other dividing cells. NEP cells, however, lacked expression of several lineage markers that are expressed by later appearing cells. These included absence of expression of CD44, E-NCAM, A2B5, epidermal growth factor receptor (EGFR), and platelet-derived growth factor receptor-alpha (PDGFRalpha), suggesting that negative selection using cell surface epitopes could be used to isolate stem cell populations from mixed cultures of cells. Using mixed cultures of cells isolated from E14.5 stage embryos, we show that NEP cells can be enriched by depleting differentiating cells that express E-NCAM or A2B5 immunoreactivity. Overall, our results show that a spectrum of markers used in combination can reliably distinguish multipotent NSCs from other precursor cells as well as differentiated cells present in the CNS. (C) 2002 Elsevier Science (USA) C1 NIA, Neurosci Lab, Baltimore, MD 21224 USA. Univ Utah, Dept Neurobiol & Anat, Salt Lake City, UT 84132 USA. Univ Utah, Dept Oncol Sci, Salt Lake City, UT 84132 USA. Univ Utah, Dept Physiol, Salt Lake City, UT 84132 USA. RP Rao, MS (reprint author), NIA, Neurosci Lab, Baltimore, MD 21224 USA. FU NCRR NIH HHS [S10-RR-10489]; NIDCD NIH HHS [R01DC02994]; NIDDK NIH HHS [R01DK57899] NR 88 TC 136 Z9 151 U1 1 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD NOV 15 PY 2002 VL 251 IS 2 BP 221 EP 240 DI 10.1006/dbio.2002.0828 PG 20 WC Developmental Biology SC Developmental Biology GA 617TX UT WOS:000179377900003 PM 12435354 ER PT J AU Chang, W ten Dijke, P Wu, DK AF Chang, W ten Dijke, P Wu, DK TI BMP pathways are involved in otic capsule formation and epithelial-mesenchymal signaling in the developing chicken inner ear SO DEVELOPMENTAL BIOLOGY LA English DT Article ID BONE MORPHOGENETIC PROTEINS; SENSORY ORGAN GENERATION; MOUSE EMBRYOGENESIS; GROWTH-FACTOR; II RECEPTOR; IN-VITRO; NOGGIN; EXPRESSION; LIMB; CHONDROGENESIS AB The vertebrate inner ear consists of a complex labyrinth of epithelial cells that is surrounded by a bony capsule. The molecular mechanisms coordinating the development of the membranous and bony labyrinths are largely unknown. Previously, using avian retrovirus encoding Noggin (RCAS-Noggin) or beads soaked with Noggin protein, we have shown that bone morphogenetic proteins (BMPs) are important for the development of the otic epithelium in the chicken inner ear. Here, using two additional recombinant avian retroviruses, dominant negative and constitutively active forms of BMP receptors IB (BMPRIB), we show that BMPs, possibly acting through BMPRIB, are important for otic capsule formation. We also show that Bmp2 is strongly expressed in the prospective semicircular canals starting from the canal outpouch stage, suggesting that BMP2 plays an important role in canal formation. In addition, by correlating expression patterns of Bmps, their receptors, and localization of phosphorylated R-Smad (phospho R-Smad) immunoreactivity, an indicator of BMP activation, we show that BMPs emanating from the otic epithelium influence chondrogenesis of the otic capsule including the cartilage surrounding the semicircular canals. (C) 2002 Elsevier Science (USA) C1 Natl Inst Deafness & Other Commun Disorders, Rockville, MD 20850 USA. Netherlands Canc Inst, Div Cellular Biochem, NL-1066 CX Amsterdam, Netherlands. RP Wu, DK (reprint author), Natl Inst Deafness & Other Commun Disorders, 5 Res Court,Rm 2B34, Rockville, MD 20850 USA. NR 46 TC 58 Z9 64 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD NOV 15 PY 2002 VL 251 IS 2 BP 380 EP 394 DI 10.1006/dbio.2002.0822 PG 15 WC Developmental Biology SC Developmental Biology GA 617TX UT WOS:000179377900014 PM 12435365 ER PT J AU Tonkin, LA Saccomanno, L Morse, DP Brodigan, T Krause, M Bass, BL AF Tonkin, LA Saccomanno, L Morse, DP Brodigan, T Krause, M Bass, BL TI RNA editing by ADARs is important for normal behavior in Caenorhabditis elegans SO EMBO JOURNAL LA English DT Article DE chemotaxis; double-stranded RNA; inosine; neuronal; vulva ID C-ELEGANS; ADENOSINE-DEAMINASE; CANDIDATE ENZYME; NERVOUS-SYSTEM; MESSENGER-RNAS; PROTEIN; GENE; VULVA; REQUIREMENTS; CHROMOSOME AB Here we take advantage of the well-characterized and simple nervous system of Caenorhabditis elegans to further our understanding of the functions of RNA editing. We describe the two C.elegans ADAR genes, adr-1 and adr-2, and characterize strains containing homozygous deletions in each, or both, of these genes. We find that adr-1 is expressed in most, if not all, cells of the C.elegans nervous system and also in the developing vulva. Using chemotaxis assays, we show that both ADARs are important for normal behavior. Biochemical, molecular and phenotypic analyses indicate that ADR-1 and ADR-2 have distinct roles in C.elegans, but sometimes act together. C1 Univ Utah, Dept Biochem, Salt Lake City, UT 84132 USA. Univ Utah, Howard Hughes Med Inst, Salt Lake City, UT 84132 USA. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Bass, BL (reprint author), Univ Utah, Dept Biochem, 20 N 1900 E, Salt Lake City, UT 84132 USA. OI Krause, Michael/0000-0001-6127-3940 FU NCI NIH HHS [CA 42014]; NIGMS NIH HHS [GM 44073, R01 GM044073, R01 GM044073-11] NR 43 TC 128 Z9 137 U1 3 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD NOV 15 PY 2002 VL 21 IS 22 BP 6025 EP 6035 DI 10.1093/emboj/cdf607 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 618YZ UT WOS:000179446900009 PM 12426375 ER PT J AU Ito, A Kawaguchi, Y Lai, CH Kovacs, JJ Higashimoto, Y Appella, E Yao, TP AF Ito, A Kawaguchi, Y Lai, CH Kovacs, JJ Higashimoto, Y Appella, E Yao, TP TI MDM2-HDAC1-mediated deacetylation of p53 is required for its degradation SO EMBO JOURNAL LA English DT Article DE acetylation; HDAC1; MDM2; p53; ubiquitylation ID TUMOR-SUPPRESSOR P53; RING-FINGER DOMAIN; C-TERMINAL DOMAIN; DNA-DAMAGE; NUCLEAR EXPORT; MDM2; ACETYLATION; ACTIVATION; PHOSPHORYLATION; UBIQUITINATION AB The tumor suppressor p53 is stabilized and activated in response to cellular stress through post-translational modifications including acetylation. p300/CBP-mediated acetylation of p53 is negatively regulated by MDM2. Here we show that MDM2 can promote p53 deacetylation by recruiting a complex containing HDAC1. The HDAC1 complex binds MDM2 in a p53-independent manner and deacetylates p53 at all known acetylated lysines in vivo. Ectopic expression of a dominant-negative HDAC1 mutant restores p53 acetylation in the presence of MDM2, whereas wildtype HDAC1 and MDM2 deacetylate p53 synergistically. Fibroblasts overexpressing a dominant negative HDAC1 mutant display enhanced DNA damage-induced p53 acetylation, increased levels of p53 and a more pronounced induction of p21 and MDM2. These results indicate that acetylation promotes p53 stability and function. As the acetylated p53 lysine residues overlap with those that are ubiquitylated, our results suggest that one major function of p53 acetylation is to promote p53 stability by preventing MDM2-dependent ubiquitylation, while recruitment of HDAC1 by MDM2 promotes p53 degradation by removing these acetyl groups. C1 Duke Univ, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Yao, TP (reprint author), Duke Univ, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. RI Ito, Akihiro/A-6100-2015 FU NCI NIH HHS [CA 85676-01A1, R01 CA085676] NR 33 TC 334 Z9 347 U1 1 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD NOV 15 PY 2002 VL 21 IS 22 BP 6236 EP 6245 DI 10.1093/emboj/cdf616 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 618YZ UT WOS:000179446900029 PM 12426395 ER PT J AU Kannouche, P de Henestrosa, ARF Coull, B Vidal, AE Gray, C Zicha, D Woodgate, R Lehmann, AR AF Kannouche, P de Henestrosa, ARF Coull, B Vidal, AE Gray, C Zicha, D Woodgate, R Lehmann, AR TI Localization of DNA polymerases eta and iota to the replication machinery is tightly co-ordinated in human cells SO EMBO JOURNAL LA English DT Article DE DNA polymerase; replication foci; UV light; xeroderma pigmentosum variants ID XERODERMA-PIGMENTOSUM VARIANT; PRONE LESION BYPASS; ERROR-PRONE; SACCHAROMYCES-CEREVISIAE; ULTRAVIOLET-RADIATION; TRANSLESION SYNTHESIS; EXCISION-REPAIR; GENE ENCODES; Y-FAMILY; POL-IOTA AB Y-family DNA polymerases can replicate past a variety of damaged bases in vitro but, with the exception of DNA polymerise eta (poleta), which is defective in xeroderma pigmentosum variants, there is little information on the functions of these polymerases in vivo. Here, we show that DNA polymerase iota (poliota), like poleta, associates with the replication machinery and accumulates at stalled replication forks following DNA-damaging treatment. We show that poleta and poliota foci form with identical kinetics and spatial distributions, suggesting that localization of these two polymerases is tightly co-ordinated within the nucleus. Furthermore, localization of poll in replication foci is largely dependent on the presence of poleta. Using several different approaches, we demonstrate that poleta and poliota interact with each other physically and that the C-terminal 224 amino acids of poliota are sufficient for both the interaction with poleta and accumulation in replication foci. Our results provide strong evidence that poleta targets poliota to the replication machinery, where it may play a general role in maintaining genome integrity as well as participating in translesion DNA synthesis. C1 Univ Sussex, Genome Damage & Stabil Ctr, Brighton BN1 9RQ, E Sussex, England. Canc Res UK London Res Inst, London WC2A 3PX, England. NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. RP Lehmann, AR (reprint author), Univ Sussex, Genome Damage & Stabil Ctr, Brighton BN1 9RQ, E Sussex, England. RI Zicha, Daniel/H-9310-2016 NR 37 TC 64 Z9 68 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD NOV 15 PY 2002 VL 21 IS 22 BP 6246 EP 6256 DI 10.1093/emboj/cdf618 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 618YZ UT WOS:000179446900030 PM 12426396 ER PT J AU Tekirian, TL AF Tekirian, TL TI The central role of the trans-golgi network as a gateway of the early secretory pathway: Physiologic vs nonphysiologic protein transit SO EXPERIMENTAL CELL RESEARCH LA English DT Review DE aging; protein trafficking; Alzheimer's Disease; trans-Golgi network; TGN; endoplasmic reticulum; ER; ubiquitin; amyloid; precursor protein; beta-amyloid; presenilin; notch; furin; tau; axonal; somatodendritic; glycosyltransferase; adaptor; vesicle; trafficking; protein transit; protein sorting phosphoinositides ID AMYLOID PRECURSOR PROTEIN; CLATHRIN-COATED VESICLES; ALZHEIMERS-DISEASE; ENDOPLASMIC-RETICULUM; MAMMALIAN-CELLS; BETA-SECRETASE; TRANSFECTED CELLS; CYTOPLASMIC TAIL; PLASMA-MEMBRANE; DISTINCT SITES AB The current review focuses upon recent advances concerning the interrelationship between the ER and the trans-Golgi network (ER-TGN), the ER and the nucleus (ER-nucleus), and the ER-ubiquitin-proteasomal pathways at the level of basic cell biology. The overall emphasis of this paper centers upon the high likelihood that measurements of ER-associated protein or gene expression levels are not representative of a strict ER alone phenotype. Rather, that ER phenotype reflects a synthesis of phenotypes derived from intracellular compartments and phosphorylated messengers in rapport with the ER. The ER-TGN, ER-nuclear, and ER-ubiquitin-proteasomal transit paths share the ability to feed into the decision of whether TGN vesicles can interact with specific phosphorylated residues in order to drive physiologic, constitutive, anterograde traffic, retrograde traffic, and degradation. TGN vesicles can: (a) traffic to endosomes versus plasma membrane phosphodomains depending upon the presence or the absence of select Golgi-localized gamma-ear containing ADP ribosylation factor-binding proteins and/or protein kinase D; (b) be maintained within the TGN in the presence of a phosphosorting acidic cluster motif adaptor, (c) transit back to the ER via specialized TGN/ER glycosyltransferases (which modulate phosphorylated proteins); (d) transit to the nucleus via phosphatidylinositol-4-kinase-associated phosphodomains; and/or (e) retrotranslocate to the ubiquitin-proteasome pathway, which is equipped with E3 ligase potential, in order to further regulate endosomal versus plasma membrane traffic. The TGN is also a critical gateway for protein transit in the sense that, as a function of sorting within this compartment, proteins are sent to the axon, cell body, or dendrites. As the decision to sort to the axon versus the somatodendritic compartment is intimately tied to TGN function, future understanding of TGN biology at the levels of neurogenesis and protein sorting is predicted to also effectively increase our understanding of synaptic sorting/regulation. (C) 2002 Elsevier Science (USA). C1 NCI, Regulat Cellular Groth Div, Frederick, MD 21702 USA. RP Tekirian, TL (reprint author), NCI, Regulat Cellular Groth Div, Bldg 560,POB B,Room 22-12, Frederick, MD 21702 USA. NR 67 TC 12 Z9 12 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE 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 NOV 15 PY 2002 VL 281 IS 1 BP 9 EP 18 DI 10.1006/excr.2002.5656 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 617TY UT WOS:000179378000002 PM 12441125 ER PT J AU Nava, VE Hobson, JP Murthy, S Milstien, S Spiegel, S AF Nava, VE Hobson, JP Murthy, S Milstien, S Spiegel, S TI Sphingosine kinase type 1 promotes estrogen-dependent tumorigenesis of breast cancer MCF-7 cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE breast cancer; MCF-7 cells; sphingosine-1-phosphate; sphingosine kinase; tumorigenesis; angiogenesis; nude mice ID LYSOPHOSPHATIDIC ACID; INTRACELLULAR SPHINGOSINE-1-PHOSPHATE; SIGNALING PATHWAYS; SURFACE RECEPTORS; INDUCED APOPTOSIS; CARCINOMA CELLS; CYTOCHROME-C; NUDE-MICE; 1-PHOSPHATE; GROWTH AB The sphingolipid metabolite, sphingosine-1-phosphate (SIP), formed by phosphorylation of sphingosine, has been implicated in cell growth, suppression of apoptosis, and angiogenesis. In this study, we have examined the contribution of intracellular SIP to tumorigenesis of breast adenocarcinoma MCF-7 cells. Enforced expression of sphingosine kinase type 1 (SPHK1) increased S1P levels and blocked MCF-7 cell death induced by anti-cancer drugs, sphingosine, and TNF-alpha. SPHK1. also conferred a growth advantage, as determined by proliferation and growth in soft agar, which was estrogen dependent. While both ERK and Akt have been implicated in MCF-7 cell growth, SPHK1. stimulated ERK1/2 but had no effect on Akt. Surprisingly, parental growth of MCF-7 cells was only weakly stimulated by S1P or dihydro-S1P, ligands for the S1P receptors which usually mediate growth effects. When injected into mammary fat pads of ovariectomized nude mice implanted with estrogen pellets, MCF-7/SPHK1 cells formed more and larger tumors than vector transfectants with higher microvessel density in their periphery. Collectively, our results suggest that SPHK1 may play an important role in breast cancer progression by regulating tumor cell growth and survival. (C) 2002 Elsevier Science (USA). C1 Georgetown Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20007 USA. NIMH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Dept Biochem, Richmond, VA 23298 USA. RP Spiegel, S (reprint author), Georgetown Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20007 USA. FU NCI NIH HHS [CA61774] NR 54 TC 148 Z9 154 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD NOV 15 PY 2002 VL 281 IS 1 BP 115 EP 127 DI 10.1006/excr.2002.5658 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 617TY UT WOS:000179378000012 PM 12441135 ER PT J AU Gottesman, S AF Gottesman, S TI Stealth regulation: biological circuits with small RNA switches SO GENES & DEVELOPMENT LA English DT Review ID PROGRAMMED CELL-DEATH; BINDING PROTEIN CSRA; ESCHERICHIA-COLI; ANTISENSE RNA; PLASMID REPLICATION; MESSENGER-RNA; C-ELEGANS; CAENORHABDITIS-ELEGANS; COMPARATIVE GENOMICS; CONTROLS EXPRESSION C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. RP Gottesman, S (reprint author), NCI, Mol Biol Lab, Bethesda, MD 20892 USA. NR 90 TC 88 Z9 88 U1 0 U2 5 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 NOV 15 PY 2002 VL 16 IS 22 BP 2829 EP 2842 DI 10.1101/gad.1030302 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 616CE UT WOS:000179283500001 PM 12435626 ER PT J AU Loftus, SK Erickson, RP Walkley, SU Bryant, MA Incao, A Heidenreich, RA Pavan, WJ AF Loftus, SK Erickson, RP Walkley, SU Bryant, MA Incao, A Heidenreich, RA Pavan, WJ TI Rescue of neurodegeneration in Niemann-Pick C mice by a prion-promoter-driven Npc1 cDNA transgene SO HUMAN MOLECULAR GENETICS LA English DT Article ID DISEASE TYPE-C; CHOLESTEROL HOMEOSTASIS; STORAGE DISORDER; MESSENGER-RNA; PROTEIN GENE; BALB/C MICE; MOUSE; EXPRESSION; SCRAPIE; PRP AB Niemann-Pick disease type C (NPC) is a neurodegenerative disorder with major visceral complications, including liver disease that can be fatal before onset of neurodegeneration. We have sought to determine the extent to which visceral disease contributes to neurodegeneration by making transgenic mice in which the wild-type NPC1 protein is expressed primarily in the CNS using the prion promoter. When the transgene was introduced into the npc1(-/-) animals neurodegeneration was prevented, a 'normal' lifespan occurred and the sterility of npc1(-/-) mice was corrected. The rescue did not provide complete neurological correction in the CNS as GM2 and GM3 gangliosides were observed to accumulate in some neurons and glia of transgenic animals. Two of three transgenic lines demonstrated some low-level ectopic expression resulting in correction of visceral phenotypes in liver and spleen. Interestingly, the third transgenic line continued to have moderate histocytosis in liver and spleen, yet had no detectable neurodegeneration. Thus, it is primarily the lack of NPC1 in the CNS and not the secondary effects of the visceral involvement that causes the neurological decline in NPC disease. In addition, the expression levels of NPC1 found in the CNS of transgenic animals were much greater than in normal littermates, demonstrating that overexpression of NPC1 is not harmful and allowing possibilities for genetic therapy interventions that utilize overexpression. C1 NHGRI, NIH, Genet Dis Res Branch, Bethesda, MD 20892 USA. Univ Arizona, Dept Pediat, Steele Mem Childrens Res Ctr, Angel Char Children, Tucson, AZ 85721 USA. Univ Arizona, Dept Mol & Cellular Biol, Tucson, AZ 85721 USA. Univ Arizona, Genet Comm, Tucson, AZ USA. Albert Einstein Coll Med, Dept Neurosci, Sidney Weisner Lab Genet Neurol Dis, Bronx, NY 10467 USA. NIH, Diagnost & Res Serv Branch, Vet Resources Program, Off Res Serv, Bethesda, MD 20892 USA. RP Pavan, WJ (reprint author), NHGRI, NIH, Genet Dis Res Branch, 49 Convent Dr,Bldg 49,Room 4A67, Bethesda, MD 20892 USA. NR 34 TC 49 Z9 49 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 NOV 15 PY 2002 VL 11 IS 24 BP 3107 EP 3114 DI 10.1093/hmg/11.24.3107 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 613EW UT WOS:000179120100012 PM 12417532 ER PT J AU Cumberlin, RL AF Cumberlin, RL CA Natl Canc Inst Radation Res Prog TI Clinical research in neutron capture therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article C1 NCI, Radiat Oncol Sci Program, Radiat Res Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Cumberlin, RL (reprint author), NCI, Radiat Oncol Sci Program, Radiat Res Program, Div Canc Treatment & Diag, 6130 Execut Blvd,EPN-6000, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 15 PY 2002 VL 54 IS 4 BP 992 EP 998 AR PII S0360-3016(02)03041-9 DI 10.1016/S0360-3016(02)03041-9 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 613FR UT WOS:000179122400002 PM 12419424 ER PT J AU Notkins, AL AF Notkins, AL TI Immunologic and genetic factors in type 1 diabetes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID PROTEIN-TYROSINE-PHOSPHATASE; GLUTAMIC-ACID DECARBOXYLASE; BETA-CELL; TRANSMEMBRANE PROTEIN; AUTOANTIGEN; DISEASE; MELLITUS; VIRUS; IDENTIFICATION; AUTOANTIBODIES C1 NIDCR, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Notkins, AL (reprint author), NIDCR, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bldg 30,Rm 121,30 Convent Dr,MSC 4322, Bethesda, MD 20892 USA. NR 28 TC 65 Z9 71 U1 0 U2 4 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 NOV 15 PY 2002 VL 277 IS 46 BP 43545 EP 43548 DI 10.1074/jbc.R200012200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 615XE UT WOS:000179272000001 PM 12270944 ER PT J AU Grzesik, WJ Frazier, CR Shapiro, JR Sponseller, PD Robey, PG Fedarko, NS AF Grzesik, WJ Frazier, CR Shapiro, JR Sponseller, PD Robey, PG Fedarko, NS TI Age-related changes in human bone proteoglycan structure - Impact of osteogenesis imperfecta SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH-FACTOR-BETA; PERFORMANCE LIQUID-CHROMATOGRAPHY; COLLAGEN-MUTATION-DATABASE; TRANSFORMING GROWTH-FACTOR-BETA-1; DERMATAN SULFATE; HYALURONIC-ACID; CELLS-INVITRO; NITROUS-ACID; OSTEOBLASTS; BIOSYNTHESIS AB Proteoglycans (PGs) are a family of molecules that undergo extensive post-translational modifications that include addition of glycosaminoglycan (GAG) chains as well as N- and O-linked oligosaccharides to the protein core. PG composition and structure have been reported to alter with age. To test whether the post-translational modifications to PGs can serve as in vitro surrogate end point markers for chronological age, the extent of GAG modifications was determined for PGs derived from normal human bone cells of 14 donors (age range, fetal to 60 years). Isolated cells were steady state radiolabeled with (SO42-)-S-35 and [H-3]GlcN. For biglycan and decorin, iduronate content was linearly correlated with age (increased 1.5X between fetal and age 60 years). For the syndecan-like heparan sulfate PG, the N-sulfation of post-natal cells increased over 3.5-fold until reaching a plateau during the 4th decade of life. The amount of O-linked oligosaccharides was also found to decrease as a function of increasing normal donor age, whereas the specific activity of the metabolic precursor pool remained constant regardless of donor age. These age-related changes in post-translational modifications were then used to demonstrate that osteoblasts derived from patients with osteogenesis imperfecta did not exhibit facets of a pre-mature aging, but rather were arrested in a fetal-like phenotypic state. A growth matrix rich in thrombospondin altered PG metabolism in osteoblastic cells, resulting in the production and secretion of the fetal-like (rich in O-linked oligosaccharides) forms of decorin and biglycan. This effect was qualitatively different from the effect of transforming growth factor-beta, which predominantly altered GAGs rather than O-linked oligosaccharides. No other Arg-Gly-Asp protein (fibronectin, vitronectin, type I collagen, osteopontin, and bone sialoprotein) showed any detectable effect on PG metabolism in bone cells. These results indicate that a proper matrix stoichiometry is critical for metabolism of PGs. C1 Johns Hopkins Univ, Sch Med, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD 21224 USA. Univ N Carolina, Dent Res Ctr, Sch Dent, Chapel Hill, NC 27599 USA. Johns Hopkins Univ, Kennedy Krieger Inst, Osteogenesis Imperfecta Program, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Orthoped, Baltimore, MD 21205 USA. NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. RP Fedarko, NS (reprint author), Rm 5A-64 JHAAC,5501 Hopkins Bayview Circle, Baltimore, MD 21224 USA. EM ndarko@jhmi.edu RI Robey, Pamela/H-1429-2011; OI Robey, Pamela/0000-0002-5316-5576; Fedarko, Neal/0000-0001-6055-6279 FU NIAMS NIH HHS [AR 42358] NR 58 TC 43 Z9 44 U1 0 U2 3 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 NOV 15 PY 2002 VL 277 IS 46 BP 43638 EP 43647 DI 10.1074/jbc.M202124200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 615XE UT WOS:000179272000015 PM 12221073 ER PT J AU Scheinfeld, MH Ghersi, E Laky, K Fowlkes, BJ D'Adamio, L AF Scheinfeld, MH Ghersi, E Laky, K Fowlkes, BJ D'Adamio, L TI Processing of beta-amyloid precursor-like protein-1 and-2 by gamma-secretase regulates transcription SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INTRACELLULAR DOMAIN; ALZHEIMERS-DISEASE; INTRAMEMBRANE CLEAVAGE; FE65 PROTEIN; FAMILY; NOTCH; APLP2; GENE; PRESENILIN-1; INHIBITORS AB The familial Alzheimer's disease gene product beta-amyloid (Abeta) precursor protein (APP) is processed by the beta-and gamma-secretases to produce Abeta as well as AID (APP Intracellular Domain) which is derived from the extreme carboxyl terminus of APP. AID was originally shown to lower the cellular threshold to apoptosis and more recently has been shown to modulate gene expression such that it represses Notch-dependent gene expression while in combination with Fe65 it enhances gene activation. Here we report that the two other members of the APP family, beta-amyloid precursor-like protein-1 and -2 (APLP1 and APLP2), are also processed by the gamma-secretase in a Presenilin 1-dependent manner. Furthermore, the extreme carboxyl-terminal fragments produced by this processing (here termed APP-like Intracellular Domain or ALID1 and ALID2) are able to enhance Fe65-dependent gene activation, similar to what has been reported for AID. Considering that only APP and not the APLPs have been linked to familial Alzheimer's disease (AD), this data should help in understanding the physiologic roles of the APP family members and in differentiating these functions from the pathologic role of APP in Alzheimer's disease. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. RP D'Adamio, L (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM ldadamio@aecom.yu.edu OI D'Adamio, Luciano/0000-0002-9820-4882; Scheinfeld, Meir H/0000-0001-8880-4318 FU NIGMS NIH HHS [T32GM07288] NR 41 TC 117 Z9 123 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 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 15 PY 2002 VL 277 IS 46 BP 44195 EP 44201 DI 10.1074/jbc.M208110200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 615XE UT WOS:000179272000086 PM 12228233 ER PT J AU Zang, XX Taylor, P Wang, JM Meyer, DJ Scott, AL Walkinshaw, MD Maizels, RM AF Zang, XX Taylor, P Wang, JM Meyer, DJ Scott, AL Walkinshaw, MD Maizels, RM TI Homologues of human macrophage migration inhibitory factor from a parasitic nematode - Gene cloning, protein activity, and crystal structure SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN LYMPHATIC FILARIASIS; BRUGIA-MALAYI; FACTOR MIF; IMMUNE EVASION; PHENYLPYRUVATE TAUTOMERASE; CYTOKINE MIF; MODULATION; RESPONSES; MICROFILARIAE; PURIFICATION AB Cytokines are the molecular messengers of the vertebrate immune system, coordinating the local and systemic immune responses to infective organisms. We report here functional and structural data on cytokine-like proteins from a eukaryotic pathogen. Two homologues of the human cytokine macrophage migration inhibitory factor (MIF) have been isolated from the parasitic nematode Brugia malayi. Both molecules (Bm-MIF-1 and Bm-MIF-2) show parallel functions to human MIF. They are chemotactic for human monocytes and activate them to produce IL-8, TNF-alpha, and endogenous MIF. The human and nematode MIF homologues share a tautomerase enzyme activity, which is in each case abolished by the mutation of the N-terminal proline residue. The crystal structure of Bm-MIF-2 at 1.8-Angstrom resolution has been determined, revealing a trimeric assembly with an inner pore created by beta-stranded sheets from each subunit. Both biological activity and crystal structure reveal remarkable conservation between a human cytokine and its parasite counterpart despite the considerable phylogenetic divide among these organisms. The strength of the similarity implies that MIF-mediated pathways play an important role in nematode immune evasion strategies. C1 Univ Edinburgh, Inst Cell Anim & Populat Biol, Edinburgh EH9 3JT, Midlothian, Scotland. Univ Edinburgh, Inst Cell & Mol Biol, Edinburgh EH9 3JT, Midlothian, Scotland. NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Frederick, MD 21702 USA. Univ London London Sch Hyg & Trop Med, Dept Infect & Trop Dis, London WC1E 7HT, England. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. RP Zang, XX (reprint author), Univ Edinburgh, Inst Cell Anim & Populat Biol, W Mains Rd, Edinburgh EH9 3JT, Midlothian, Scotland. OI walkinshaw, malcolm/0000-0001-5955-9325 NR 56 TC 67 Z9 73 U1 1 U2 7 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 NOV 15 PY 2002 VL 277 IS 46 BP 44261 EP 44267 DI 10.1074/jbc.M204655200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 615XE UT WOS:000179272000095 PM 12221083 ER PT J AU Hall, JM Korach, KS AF Hall, JM Korach, KS TI Analysis of the molecular mechanisms of human estrogen receptors alpha and beta reveals differential specificity in target promoter regulation by xenoestrogens SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTIONAL ACTIVITY; RESPONSE ELEMENTS; ER-ALPHA; ANTIESTROGENS; PHYTOESTROGENS; COREGULATORS; CONFORMATION; RECRUITMENT; XENOBIOTICS; CONTEXT AB Most of the currently available information on the transcriptional activities of endocrine-disrupting chemicals (xenoestrogens) through estrogen receptors a (ERalpha) and beta (ERbeta) has been derived from transactivation studies on synthetic estrogen-responsive reporters. Thus, the ability of the xenoestrogen-liganded ERs to regulate endogenous estrogen-responsive gene expression has not been well characterized. Here, we have evaluated the activities of xenoestrogens through ERalpha and ERbeta on the vitellogenin A2 estrogen-response element (ERE) and the human pS2, lactoferrin, and complement 3 physiological target gene promoters. Using mammalian cell transient transfection assays, we found that the activities of xenoestrogens were mediated in a promoter-specific manner. For example, when bound to all ligands examined, ERa displayed high levels of transcription on the vitellogenin ERE and the lactoferrin promoter, but substantially lower activity on the complement 3 and pS2 promoters. However, one of the most important observations was that there were significant differences in the relative transcriptional activities of xenoestrogen-bound ERalpha and ERbeta on different promoters, suggesting that ERalpha and ERbeta make unique contributions to xenoestrogen action in target cells. When probing the molecular mechanism of the promoter-specific activities observed, we found that the transcriptional activity of the ERs correlated with the ability of each receptor to assume an active conformation on specific promoters. Taken together, the results indicate that the transcriptional activities of xenoestrogens are mediated in a promoter-specific manner and that estrogen-responsive promoters communicate differently with ERalpha and ERbeta by influencing their structures in a distinct manner that leads to diversity in their transcriptional responses. C1 NIEHS, Receptor Biol Sect, Res Triangle Pk, NC 27709 USA. RP Hall, JM (reprint author), NIEHS, Receptor Biol Sect, Bldg 101,Rm E460,MD E4-01,111 TW Alexander Dr,POB, Res Triangle Pk, NC 27709 USA. OI Korach, Kenneth/0000-0002-7765-418X NR 33 TC 66 Z9 67 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 15 PY 2002 VL 277 IS 46 BP 44455 EP 44461 DI 10.1074/jbc.M200849200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 615XE UT WOS:000179272000117 PM 12200415 ER PT J AU Day, KC McCabe, MT Zhao, X Wang, YH Davis, JN Phillips, J Von Geldern, M Ried, T KuKuruga, MA Cunha, GR Hayward, SW Day, ML AF Day, KC McCabe, MT Zhao, X Wang, YH Davis, JN Phillips, J Von Geldern, M Ried, T KuKuruga, MA Cunha, GR Hayward, SW Day, ML TI Rescue of embryonic epithelium reveals that the homozygous deletion of the retinoblastoma gene confers growth factor independence and immortality but does not influence epithelial differentiation or tissue morphogenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-SUPPRESSOR; CELL-CYCLE; MALIGNANT TRANSFORMATION; CHROMOSOMAL-ABERRATIONS; TARGETED DISRUPTION; PROSTATE-CANCER; CARCINOMA-CELLS; VIRAL ONCOGENES; KINASE-ACTIVITY; G(1) CONTROL AB The ability to rescue viable prostate precursor tissue from retinoblastoma-deficient (Rb-/-) fetal mice has allowed for the isolation and characterization of the first Rb-/- prostate epithelial cell line. This cell line, designated Rb-/-PrE, was utilized for experiments examining the consequences of Rb loss on an epithelial population. These findings demonstrated that Rb deletion has no discernible effect on prostatic histodifferentiation in Rb-/-PrE cultures. When Rb-/-PrE cells were recombined with embryonic rat urogenital mesenchyme and implanted into athymic male, nude mouse hosts, the recombinants developed into fully differentiated and morphologically normal prostate tissue. The Rb-/-PrE phenotype was characterized by serum independence in culture and immortality in vivo, when compared with wild type controls. Cell cycle analysis revealed elevated S phase DNA content accompanied by increased expression of cyclin El and proliferating cell nuclear antigen. Rb-/-PrE cultures also exhibited a diminished ability to growth arrest under high density culture conditions. We believe that the development of Rb-/- prostate tissue and cell lines has provided a unique experimental platform with which to investigate the consequences of Rb deletion in epithelial cells under various physiological conditions. Additionally, the development of this technology will allow similar studies in other tissues and cell populations rescued from Rb-/- fetuses. C1 Univ Michigan, Dept Urol, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. NCI, Urol Oncol Branch, Genet Sect, NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Med Ctr, Dept Canc Biol, Vanderbilt Ingram Comprehens Canc Ctr, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Urol Surg, Vanderbilt Ingram Comprehens Canc Ctr, Nashville, TN 37232 USA. RP Day, ML (reprint author), Univ Michigan, Dept Urol, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. FU NCI NIH HHS [CA96403, P50 CA69568]; NIDDK NIH HHS [DK56137]; PHS HHS [F005952, F005192] NR 61 TC 21 Z9 21 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 15 PY 2002 VL 277 IS 46 BP 44475 EP 44484 DI 10.1074/jbc.M205361200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 615XE UT WOS:000179272000119 PM 12191999 ER PT J AU Shu, S Liu, XN Parent, CA Uyeda, TQP Korn, ED AF Shu, S Liu, XN Parent, CA Uyeda, TQP Korn, ED TI Tail chimeras of Dictyostelium myosin II support cytokinesis and other myosin II activities but not full development SO JOURNAL OF CELL SCIENCE LA English DT Article DE myosin II; cytokinesis; chemotaxis; development; ConA capping ID HEAVY-CHAIN PHOSPHORYLATION; CHEMOATTRACTANT-ELICITED INCREASES; CLEAVAGE FURROW; MOTOR DOMAIN; NULL-CELLS; IN-VIVO; LOCALIZATION; DISCOIDEUM; EXPRESSION; LACKING AB Dictyostelium lacking myosin 11 cannot grow in suspension culture, develop beyond the mound stage or cap concanavalin A receptors and chemotaxis is impaired. Recently, we showed that the actin-activated MgATPase activity of myosin chimeras in which the tail domain of Dictyostelium myosin 11 heavy chain is replaced by the tail domain of either Acanthamoeba or chicken smooth muscle myosin 11 is unregulated and about 20 times higher than wild-type myosin. The Acanthamoeba chimera forms short bipolar filaments similar to, but shorter than, filaments of Dictyostelium myosin and the smooth muscle chimera forms much larger side-polar filaments. We now find that the Acanthamoeba chimera expressed in myosin null cells localizes to the periphery of vegetative amoeba similarly to wild-type myosin but the smooth muscle chimera is heavily concentrated in a single cortical patch. Despite their different tail sequences and filament structures and different localization of the smooth muscle chimera in interphase cells, both chimeras support growth in suspension culture and concanavalin A capping and colocalize with the ConA cap but the Acanthamoeba chimera subsequently disperses more slowly than wild-type myosin and the smooth muscle chimera apparently not at all. Both chimeras also partially rescue chemotaxis. However, neither supports full development. Thus, neither regulation of myosin activity, nor regulation of myosin polymerization nor bipolar filaments is required for many functions of Dictyostelium myosin 11 and there may be no specific sequence required for localization of myosin to the cleavage furrow. C1 NHLBI, Cell Biol Lab, Nihon Univ, Bethesda, MD 20892 USA. NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Natl Inst Adv Ind Sci & Technol, Gene Funct Res Ctr, Tsukuba, Ibaraki 3058562, Japan. RP Korn, ED (reprint author), NHLBI, Cell Biol Lab, Nihon Univ, Bethesda, MD 20892 USA. RI Korn, Edward/F-9929-2012 NR 62 TC 10 Z9 10 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD NOV 15 PY 2002 VL 115 IS 22 BP 4237 EP 4249 DI 10.1242/jcs.00112 PG 13 WC Cell Biology SC Cell Biology GA 622TC UT WOS:000179662300004 PM 12376556 ER PT J AU Ma, Y Lang, LX Kiesewetter, DO Eckelman, WC AF Ma, Y Lang, LX Kiesewetter, DO Eckelman, WC TI Liquid chromatography-tandem mass spectrometry identification of metabolites of three phenylcarboxyl derivatives of the 5-HT1A antagonist, N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridyl) trans-4-fluorocyclohexanecarboxamide (FCWAY), produced by human and rat hepatocytes SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE FCWAY analogues; 5-HT antagonists ID RECEPTOR ANTAGONIST; P-MPPI; PET; WAY-100635; RADIOLIGAND AB We have previously described fluorine-18 radiolabeled FCWAY [N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridyl) trans-4-fluorocyclohexanecarboxamide] as a high affinity ligand for imaging the S-HT1A receptor in vivo. In a search for radiopharmaceuticals with unique imaging applications using positron emission tomography (PET), we have also developed three new phenylcarboxamide analogues of FCWAY Two of these analogues were generated by replacing the fluorocyclohexane carboxylic acid with fluorobenzoic acid (FBWAY) or with 3-methyl-4-fluorobenzoic acid (MeFBWAY). The final analogue was generated by replacing the pyridyl group with a pyrimidyl group and the fluorocyclohexane carboxylate with fluorobenzoic acid (FPWAY). We evaluated the metabolic profile of these compounds using either human or rat hepatocytes to produce metabolites and LC-MS/MS to identify these metabolites. We also compared the metabolic rate of these compounds in human or rat hepatocytes. These in vitro metabolism studies indicate that hydrolysis of the amide linkage was the major metabolic pathway for FPWAY and FBWAY in human hepatocytes, whereas aromatic oxidation is the major metabolic pathway for MeFBWAY The comparative metabolic rate in human hepatocytes was FPWAY>FBWAY> MeFBWAY In rat hepatocytes, aromatic oxidation was the major metabolic pathway for all three analogs and the rate of this process was similar for all of the analogues. These in vitro metabolic studies demonstrated species differences prior to the acquisition and interpretation of in vivo results. Published by Elsevier Science B.V. C1 NIH, PET Dept, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Ma, Y (reprint author), NIH, PET Dept, Warren G Magnuson Clin Ctr, Bldg 10 Rm 1C401,10 Ctr Dr MSC 1180, Bethesda, MD 20892 USA. NR 16 TC 11 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD NOV 15 PY 2002 VL 780 IS 1 BP 99 EP 110 AR PII S1570-0232(02)00434-8 DI 10.1016/S1570-0232(02)00434-8 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 613BF UT WOS:000179110200012 PM 12383485 ER PT J AU Knoetig, SM Torrey, TA Naghashfar, Z McCarty, T Morse, HC AF Knoetig, SM Torrey, TA Naghashfar, Z McCarty, T Morse, HC TI CD19 signaling pathways play a major role for murine AIDS induction and progression SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RETROVIRUS-INDUCED IMMUNODEFICIENCY; LYMPHOCYTE ANTIGEN RECEPTOR; TYROSINE-PHOSPHATASE 1C; EXCHANGE FACTOR VAV; B-CELL RESPONSES; CD4+ T-CELLS; LEUKEMIA-VIRUS; C57BL/6 MICE; TRANSDUCTION MOLECULE; KINASE ACTIVATION AB Infection of genetically susceptible mice with the LP-BM5 mixture of murine leukemia viruses including an etiologic defective virus (BM5def) causes an immunodeficiency syndrome called murine AIDS (MAIDS). The disease is characterized by interactions between B cells and CD4(+) T cells resulting in polyclonal activation of both cell types. It is known that BM5def is expressed at highest levels in B cells and that B cells serve as viral APC. The CD19-CD21 complex and CD22 on the surface of B cells play critical roles as regulators of B cell responses to a variety of stimuli, influencing cell activation, differentiation, and survival. CD19 integrates positive signals induced by B cell receptor ligation by interacting with the protooncogene Vav, which leads to subsequent tyrosine phosphorylation of this molecule. In contrast, CD22 negatively regulates Vav phosphorylation. To analyze the role of CD19, CD21, Vav, and CD22 in MAIDS, we infected mice deficient in CD19, CD21 (CR2), Vav-1, or CD22 with LP-BM5 murine leukemia viruses. Infected CR2(-/-) mice developed MAIDS with a time course and severity indistinguishable from that of wildtype mice. In contrast, CD19 as well as Vav-1 deficiency restricted viral replication and suppressed the development of typical signs of MAIDS including splenomegaly, lymphadenopathy, and hypergammaglobulinemia. Finally, CD22 deficiency was found to accelerate MAIDS development. These results provide novel insights into the B cell signaling pathways required for normal induction and progression of MAIDS. C1 NIAID, Immunopathol Lab, NIH, Rockville, MD 20852 USA. RP Morse, HC (reprint author), NIAID, Immunopathol Lab, NIH, Twinbrook 1,5640 Fishers Lane, Rockville, MD 20852 USA. OI Morse, Herbert/0000-0002-9331-3705 NR 69 TC 8 Z9 8 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 NOV 15 PY 2002 VL 169 IS 10 BP 5607 EP 5614 PG 8 WC Immunology SC Immunology GA 614CG UT WOS:000179170300032 PM 12421939 ER PT J AU Rubio-Godoy, V Dutoit, V Zhao, YD Simon, R Guillaume, P Houghten, R Romero, P Cerottini, JC Pinilla, C Valmori, D AF Rubio-Godoy, V Dutoit, V Zhao, YD Simon, R Guillaume, P Houghten, R Romero, P Cerottini, JC Pinilla, C Valmori, D TI Positional scanning-synthetic peptide library-based analysis of self- and pathogen-derived peptide cross-reactivity with tumor-reactive Melan-A-specific CTL SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL-RECEPTOR; MELAN-A/MART-1 ANTIGENIC PEPTIDE; RECOGNITION; TCR; LYMPHOCYTES; IDENTIFICATION; VITILIGO; LIGANDS; HLA-A2; REPERTOIRE AB Synthetic combinatorial peptide libraries in positional scanning format (PS-SCL) have recently emerged as a useful tool for the analysis of T cell recognition. This includes identification of potentially cross-reactive sequences of self or pathogen origin that could be relevant for the understanding of TCR repertoire selection and maintenance, as well as of the cross-reactive potential of Ag-specific immune responses. In this study, we have analyzed the recognition of sequences retrieved by using a biometric analysis of the data generated by screening a PS-SCL with a tumor-reactive CTL clone specific for an immunodominant peptide from the melanocyte differentiation and tumor-associated Ag Melan-A. We found that 39% of the retrieved peptides were recognized,by the CTL clone used for PS-SCL screening. The proportion of peptides recognized was higher among those with both high predicted affinity for the HLA-A2 molecule and high predicted stimulatory score. Interestingly, up to 94% of the retrieved peptides were cross-recognized by other Melan-A-specific CTL. Cross-recognition was at least partially focused, as some peptides were cross-recognized by the majority of CTL. Importantly, stimulation of PBMC from melanoma patients with the most frequently recognized peptides elicited the expansion of heterogeneous CD8(+) T cell populations, one fraction of which cross-recognized Melan-A. Together, these results underline the high predictive value of PS-SCL for the identification of sequences cross-recognized by Ag-specific T cells. C1 Torrey Pines Inst Mol Studies & Mixture Sci, San Diego, CA 92121 USA. Univ Lausanne Hosp, Lausanne Branch, Ludwig Inst Canc Res, Div Clin Onco Immunol, Lausanne, Switzerland. NCI, Mol Stat & Bioinformat Sect, Biometrie Res Branch, NIH, Bethesda, MD 20892 USA. Lausanne Branch, Ludwig Inst Canc Res, Lausanne, Switzerland. RP Pinilla, C (reprint author), Torrey Pines Inst Mol Studies & Mixture Sci, 3550 Gen Atom Court, San Diego, CA 92121 USA. RI Valmori, Danila/K-2439-2015 NR 35 TC 31 Z9 32 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 NOV 15 PY 2002 VL 169 IS 10 BP 5696 EP 5707 PG 12 WC Immunology SC Immunology GA 614CG UT WOS:000179170300042 PM 12421949 ER PT J AU Ostrand-Rosenberg, S Clements, VK Terabe, M Park, JM Berzofsky, JA Dissanayake, SK AF Ostrand-Rosenberg, S Clements, VK Terabe, M Park, JM Berzofsky, JA Dissanayake, SK TI Resistance to metastatic disease in STAT6-Deficient mice requires hemopoietic and nonhemopoietic cells and is IFN-gamma Dependent(1) SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MOUSE MAMMARY-TUMOR; COMPLEX CLASS-II; T-CELLS; INTERFERON-GAMMA; CUTTING EDGE; IMMUNOTHERAPY; RESPONSES; IMMUNITY; CANCER; IL-4 AB Mice deficient for the STAT6 gene (STAT6-/- mice) have enhanced immunosurveillance against primary and metastatic tumors. Because STAT6 is a downstream effector of the IL-4R, and IL-13 binds to the type 2 IL-4R, IL-13 has been proposed as an inhibitor that blocks differentiation of tumor-specific CD8(+) T cells. Immunity in STAT6(-/-) mice is unusually effective in that 45-80% of STAT6(-/-) mice with established, spontaneous metastatic 4T1 mammary carcinoma, whose primary tumors are surgically excised, survive indefinitely, as compared with <10% of STAT(+/+) (BALB/c) mice. Surprisingly, STAT6(-/-) and BALB/c reciprocal bone marrow chimeras do not have increased immunosurveillance, demonstrating that immunity requires STAT6-/- hemopoietic and nonhemopoietic components. Likewise, CD1(-/-) mice that are NKT deficient and therefore IL-13 deficient also have heightened tumor immunity. However, STAT6(-/-) and CD1(-/-) reciprocal bone marrow chimeras do not have increased survival, suggesting that immunity in STAT6(-/-) and CD1(-/-) mice is via noncomplementing mechanisms. Metastatic disease is not reduced in BALB/c mice treated with an IL-13 inhibitor, indicating that IL-13 alone is insufficient for negative regulation of 4T1 immunity. Likewise, in vivo depletion of CD4(+)CD25(+) T cells in BALB/c mice does not increase survival, demonstrating that CD4(+)CD25(+) cells do not regulate immunity. Cytokine production and tumor challenges into STAT6(-/-)IFN-gamma(-/-) mice indicate that IFN-gamma is essential for immunity. Therefore, immunosurveillance in STAT6(-/-) mice facilitates survival against metastatic cancer via an IFN-gamma-dependent mechanism involving hemopoietic. and nonhemopoietic derived cells, and is not exclusively dependent on counteracting IL-13 or CD4(+)CD25(+) T cells. C1 Univ Maryland, Dept Biol Sci, Baltimore, MD 21250 USA. NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Ostrand-Rosenberg, S (reprint author), Univ Maryland, Dept Biol Sci, 1000 Hilltop Circle, Baltimore, MD 21250 USA. FU NCI NIH HHS [R01 CA 52527, R01 CA 84232] NR 30 TC 75 Z9 79 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 NOV 15 PY 2002 VL 169 IS 10 BP 5796 EP 5804 PG 9 WC Immunology SC Immunology GA 614CG UT WOS:000179170300053 PM 12421960 ER PT J AU McCartney-Francis, NL Wahl, SM AF McCartney-Francis, NL Wahl, SM TI Dysregulation of IFN-gamma signaling pathways in the absence of TGF-beta 1 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NITRIC-OXIDE SYNTHASE; REGULATORY FACTOR-I; GROWTH-FACTOR-BETA; KNOCKOUT MICE; SELECTIVE-INHIBITION; AUTOIMMUNE-DISEASE; INDUCED ARTHRITIS; CARDIAC MYOCYTES; SALIVARY-GLANDS; NULL MOUSE AB Deficiency of TGF-beta1 is associated with immune dysregulation and autoimmunity as exemplified by the multifocal inflammatory lesions and early demise of the TGF-beta1 null mice. Elevated NO metabolites (nitrite and nitrate) in the plasma of these mice suggest a participatory role of NO in the pathogenic inflammatory response. To determine the mechanism for this dysregulation, we examined upstream elements that could contribute to the overexpression of NO, including inducible NO synthase (MOS) and transcription factors Stat1alpha and IFN-regulatory factor-1 (IRF-1). The coincident up-regulation of IFN-gamma, an iNOS inducer, and iNOS, before the appearance of inflammatory lesions, suggests that failed regulation of the IFN-gamma signaling pathway may underlie the immunological disorder in TGF-beta1 null mice. In fact, IFN-gamma-driven transcription factors IRF-1 and Stat1alpha, both of which act as transcriptional activators of iNOS, were elevated in the null mice. Treatment of mice with a polyclonal anti-IFN-gamma Ab reduced expression and activity not only of transcription factors Stat1alpha and IRF-1 but also of iNOS. Furthermore, anti-IFN-gamma treatment delayed the cachexia normally seen in TGF-beta1 null mice and increased their longevity. The global nature of immune dysregulation in TGF-beta1 null mice documents TGF-beta1 as an essential immunoregulatory molecule. C1 Natl Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP McCartney-Francis, NL (reprint author), Natl Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bldg 30,Room 326,30 Convent Dr, Bethesda, MD 20892 USA. NR 46 TC 29 Z9 30 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 NOV 15 PY 2002 VL 169 IS 10 BP 5941 EP 5947 PG 7 WC Immunology SC Immunology GA 614CG UT WOS:000179170300072 PM 12421979 ER PT J AU Choudhury, BK Wild, JS Alam, R Klinman, DM Boldogh, I Dharajiya, N Mileski, WJ Sur, S AF Choudhury, BK Wild, JS Alam, R Klinman, DM Boldogh, I Dharajiya, N Mileski, WJ Sur, S TI In vivo role of p38 mitogen-activated protein kinase in mediating the anti-inflammatory effects of CpG oligodeoxynucleotide in murine asthma SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INDUCED AIRWAY HYPERRESPONSIVENESS; INDUCED EOSINOPHIL RECRUITMENT; ALLERGIC LUNG INFLAMMATION; CD4+ T-CELLS; INTERFERON-GAMMA; PRESENTING CELLS; BACTERIAL-DNA; MUCOSAL IL-12; CUTTING EDGE; INTERLEUKIN-12 AB DNA containing unmethylated CpG motifs is intrinsically immunostimulatory, inducing the production of a variety of cytokines and chemokines by immune cells. The strong Th1 response triggered by CpG oligodeoxynucleotide (ODN) inhibits the development of Th2-mediated allergic asthma in mice. This work documents that CpG ODN-induced IL-12 production plays a critical role in this process, because intrapulmonary CpG ODN inhibits allergic inflammation in wild-type but not IL-12(-/-) mice. CpG ODN rapidly localized to alveolar macrophages (AM), thereby triggering the phosphorylation of p38 mitogen-activated protein kinase (MAP kinase). AM cultured with CpG but not control ODN up-regulated IL-12 p40 expression and release, and these effects were blocked by the highly specific p38 MAP kinase inhibitor SB202190. Intrapulmonary administration of this inhibitor blocked the ability of CpG ODN to produce IL-12 in the lungs and reversed the anti-inflammatory effects of CpG ODN on allergic lung inflammation. These findings indicate that IL-12 production by AM is stimulated by intrapulmonary CpG ODN administration through a p38 MAP kinase-dependent process, and IL-12 is a key cytokine that mediates CpG ODN-induced protection against allergic lung inflammation. C1 Univ Texas, Med Branch, Dept Internal Med, Div Allergy & Immunol, Galveston, TX 77555 USA. Univ Texas, Med Branch, NIH, Asthma & Allerg Dis Res Ctr, Galveston, TX 77555 USA. Univ Texas, Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA. Univ Texas, Med Branch, Dept Surg, Galveston, TX 77555 USA. US FDA, Sect Retroviral Res, Bethesda, MD 20014 USA. RP Sur, S (reprint author), Univ Texas, Med Branch, Dept Internal Med, Div Allergy & Immunol, Med Res Bldg 8-104, Galveston, TX 77555 USA. FU NIAID NIH HHS [K08 AI 01539, P01 AI 46004]; NIEHS NIH HHS [ES 06676] NR 38 TC 37 Z9 40 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 NOV 15 PY 2002 VL 169 IS 10 BP 5955 EP 5961 PG 7 WC Immunology SC Immunology GA 614CG UT WOS:000179170300074 PM 12421981 ER PT J AU Robbins, PF El-Gamil, M Li, YF Zeng, G Dudley, M Rosenberg, SA AF Robbins, PF El-Gamil, M Li, YF Zeng, G Dudley, M Rosenberg, SA TI Multiple HLA class II-restricted melanocyte differentiation antigens are recognized by tumor-infiltrating lymphocytes from a patient with melanoma SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD4(+) T-CELLS; IN-VITRO; IDENTIFICATION; EPITOPES; GP100; SELF; TYROSINASE; REJECTION; INDUCTION; PROTEIN AB Dramatic clinical responses were observed in patient 888 following the adoptive transfer of autologous tumor-infiltrating lymphocytes (TIL). Previously, extensive analysis of the specificity of class I-restricted T cells from patient 888, TIL has revealed that these T cells recognize a mutated, as well as several nonmutated tumor Ags. Additional studies that were conducted on TIL from patient 888 indicated that they contained CD4-positive T cells that recognized the autologous tumor that had been induced to express HLA class II molecules. Tumor-reactive CD4-positive T cell clones were isolated from TIL and tested for their ability to react with Ags that are recognized by HLA class I-restricted, melanoma-reactive T cells. Using this approach, T cell clones were identified that recognized an epitope expressed in both the tyrosinase-related protein I and tyrosinase-related protein 2 Ags in the context of the HLA-DRbeta1*1502 class II gene product. Additional clones were found to recognize an epitope of gp100 in the context of the same HLA-DR restriction element. These observations provide an impetus to develop strategies directed toward generating HLA class II-restricted tumor-reactive T cells. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Robbins, PF (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B42, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 SC003811-33] NR 43 TC 53 Z9 55 U1 1 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 NOV 15 PY 2002 VL 169 IS 10 BP 6036 EP 6047 PG 12 WC Immunology SC Immunology GA 614CG UT WOS:000179170300084 PM 12421991 ER PT J AU Levin, MC Lee, SM Morcos, Y Brady, J Stuart, J AF Levin, MC Lee, SM Morcos, Y Brady, J Stuart, J TI Cross-reactivity between immunodominant human T lymphotropic virus type I tax and neurons: Implications for molecular mimicry SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 3rd International Symposium on NeuroVirology CY SEP 14-16, 2000 CL SAN FRANCISCO, CALIFORNIA SP NINDS, NIMH, Penn State Univ, Life Sci Consortium, Integrat Biosci Grad Program, Temple Univ, Coll Sci & Technol, Ctr Neurovirol & Canc Biol, Adv Biosci Resources, Inc, Pharmacia & Upjohn Inc ID HTLV-I; MONOCLONAL-ANTIBODIES; NEUROLOGIC DISEASE; EXPRESSION; MYELOPATHY; PROTEINS; EPITOPES; HAM/TSP AB Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is associated with immunoreactivity to HTLV-I tax. Antibodies isolated from patients with HAM/TSP and monoclonal antibodies (MAbs) to HTLV-I tax stained neurons. In neuronal extracts, HAM/TSP immunoglobulin G identified heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) as the autoantigen. Importantly, tax MAbs reacted with hnRNP A1. To identify the epitope recognized by the tax MAbs, the fine epitope specificity of the antibodies was determined using overlapping peptides. This analysis identified an epitope at the C-terminus (tax(346-353)), which overlaps a human immunodominant domain. Preincubation of this peptide with tax MAbs inhibited antibody binding to tax, hnRNP A1, and neurons. This indicates that a cross-reactive immune response between HTLV-I tax and neuronal hnRNP A1 is contained within the human immunodominant epitope of tax and suggests that molecular mimicry plays a role in the pathogenesis of HAM/TSP. C1 Univ Tennessee, Dept Neurol, Lab Viral & Demyelinating Dis, Memphis, TN 38163 USA. Vet Affairs Med Ctr, Div Res, Memphis, TN USA. NCI, Virus Tumor Biol Sect, NIH, Bethesda, MD 20892 USA. RP Levin, MC (reprint author), Univ Tennessee, Dept Neurol, Lab Viral & Demyelinating Dis, Link Bldg 415,855 Monroe Ave, Memphis, TN 38163 USA. FU NINDS NIH HHS [R01 NS-38876-01] NR 15 TC 29 Z9 31 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2002 VL 186 IS 10 BP 1514 EP 1517 DI 10.1086/344734 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 609EQ UT WOS:000178891000021 PM 12404172 ER PT J AU Gomes, RB Brodskyn, U de Oliveira, CI Costa, J Miranda, JC Caldas, A Valenzuela, JG Barral-Netto, M Barral, A AF Gomes, RB Brodskyn, U de Oliveira, CI Costa, J Miranda, JC Caldas, A Valenzuela, JG Barral-Netto, M Barral, A TI Seroconversion against Lutzomyia longipalpis saliva concurrent with the development of anti-Leishmania chagasi delayed-type hypersensitivity SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID SAND FLY SALIVA; CUTANEOUS LEISHMANIASIS; MAJOR INFECTION; VECTOR SALIVA; MAXADILAN; MICE AB Antibody responses to salivary gland sonicate (SGS) from Lutzomyia longipalpis were investigated using serum samples from individuals living in an area where visceral leishmaniasis is endemic. Individuals were classified into 2 groups, according to the alteration of their responses to Leishmania chagasi antigen over the course of 6 months. Group 1 included children who experienced anti-L. chagasi seroconversion from negative to positive; group 2 included children who experienced delayed-type hypersensitivity (DTH) response to L. chagasi antigen conversion from negative to positive. Individuals who experienced seroconversion against L. chagasi antigens did not have increased anti-saliva antibody response, whereas those who developed a positive anti-L. chagasi DTH response had increased immunoglobulin (Ig) G, IgG1 and IgE anti-SGS antibody levels. Despite wide variation, serum samples from individuals in group 2 recognized more bands in SGS than did those from individuals in group 1. This simultaneous appearance of anti-saliva humoral response and anti-L. chagasi cell-mediated immunity supports the hypothesis that induction of immune response against SGS can facilitate induction of a protective response against leishmaniasis. C1 Fdn Oswaldo Cruz, Ctr Pesquisa Goncalo Moniz, Lab Imunoparasitol, BR-40295001 Salvador, BA, Brazil. Univ Fed Bahia, Inst Ciencias Saude, Lab Imunol, Salvador, BA, Brazil. Univ Fed Maranhao, Dept Patol, Sao Luis, Maranhao, Brazil. Immunol Invest Inst, Sao Paulo, Brazil. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Barral, A (reprint author), Fdn Oswaldo Cruz, Ctr Pesquisa Goncalo Moniz, Lab Imunoparasitol, Rua Valdemar Falcao 121, BR-40295001 Salvador, BA, Brazil. RI Barral Netto, Manoel/B-3904-2009; Barral, Aldina/B-4191-2009; de Oliveira, Camila/B-4358-2009 OI Barral Netto, Manoel/0000-0002-5823-7903; Barral, Aldina/0000-0002-7177-464X; de Oliveira, Camila/0000-0002-7868-5164 FU NIAID NIH HHS [AI-30639] NR 15 TC 85 Z9 87 U1 1 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2002 VL 186 IS 10 BP 1530 EP 1534 DI 10.1086/344733 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 609EQ UT WOS:000178891000025 PM 12404176 ER PT J AU Gorbalenya, AE Pringle, FM Zeddam, JL Luke, BT Cameron, CE Kalmakoff, J Hanzlik, TN Gordon, KHJ Ward, VK AF Gorbalenya, AE Pringle, FM Zeddam, JL Luke, BT Cameron, CE Kalmakoff, J Hanzlik, TN Gordon, KHJ Ward, VK TI The palm subdomain-based active site is internally permuted in viral RNA-dependent RNA polymerases of an ancient lineage SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE RNA viruses; RNA polymerases; evolution; protein permutation; ancient palm subdomain ID SECONDARY STRUCTURE PREDICTION; MULTIPLE SEQUENCE ALIGNMENT; PANCREATIC NECROSIS VIRUS; HEPATITIS-C VIRUS; POSITIVE-STRAND; CRYSTAL-STRUCTURE; CIRCULAR PERMUTATIONS; DNA-POLYMERASE; FUNCTIONAL DOMAINS; DISEASE VIRUS AB Template-dependent polynucleotide synthesis is catalyzed by enzymes whose core component includes a ubiquitous alphabeta palm subdomain comprising A, B and C sequence motifs crucial for catalysis. Due to its unique, universal conservation in all RNA viruses, the palm subdomain of RNA-dependent RNA polymerases (RdRps) is widely used for evolutionary and taxonomic inferences. We report here the results of elaborated computer-assisted analysis of newly sequenced replicases from Thosea asigna virus (TaV) and the closely related Euprosterna elaeasa virus (EeV), insect-specific ssRNA + viruses, which revise a capsid-based classification of these viruses with tetraviruses, an Alphavirus-like family. The replicases of TaV and EeV do not have characteristic methyltransferase and helicase domains, and include a putative RdRp with a unique C-AB motif arrangement in the palm subdomain that is also found in two dsRNA birnaviruses. This circular motif rearrangement is a result of migration of similar to22 amino acid (aa) residues encompassing motif C between two internal positions, separated by similar to110 aa, in a conserved region of similar to550 aa. Protein modeling shows that the canonical palm subdomain architecture of poliovirus (ssRNA +) RdRp could accommodate the identified sequence permutation through changes in backbone connectivity of the major structural elements in three loop regions underlying the active site. This permutation transforms the ferredoxin-like beta1alphaAbeta2beta3alphaBbeta4 fold of the palm subdomain into the beta2beta3beta1alphaAalphaBbeta4 structure and brings beta-strands carrying two principal catalytic Asp residues into sequential proximity such that unique structural properties and, ultimately, unique functionality of the permuted RdRps. may result. The permuted enzymes show unprecedented interclass sequence conservation between RdRps of true ssRNA + and dsRNA viruses and form a minor, deeply separated cluster in the RdRp tree, implying that other, as yet unidentified, viruses may employ this type of RdRp. The structural diversification of the palm subdomain might be a major event in the evolution of template-dependent polynucleotide polymerases in the RNA-protein world. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 NCI, Sci Applicat Int Corp, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. Leiden Univ, Med Ctr, Ctr Infect Dis, Dept Med Microbiol, NL-2300 RC Leiden, Netherlands. Univ Otago, Dept Microbiol, Dunedin, New Zealand. CSIRO, Div Entomol, Canberra, ACT 2601, Australia. Penn State Univ, Dept Biochem & Mol Biol, Althouse Lab 201, University Pk, PA 16802 USA. RP Gorbalenya, AE (reprint author), NCI, Sci Applicat Int Corp, Adv Biomed Comp Ctr, POB B, Frederick, MD 21702 USA. RI Gordon, Karl/A-1976-2008; Gorbalenya, Alexander/J-4818-2012 OI Gordon, Karl/0000-0002-4371-0454; Gorbalenya, Alexander/0000-0002-4967-7341 FU PHS HHS [N01-C0-12400, N01-C0-56000] NR 78 TC 96 Z9 100 U1 0 U2 4 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD NOV 15 PY 2002 VL 324 IS 1 BP 47 EP 62 DI 10.1016/S0022-2836(02)01033-1 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 620JP UT WOS:000179530500004 PM 12421558 ER PT J AU Ikemoto, S Wise, RA AF Ikemoto, S Wise, RA TI Rewarding effects of the cholinergic agents carbachol and neostigmine in the posterior ventral tegmental area SO JOURNAL OF NEUROSCIENCE LA English DT Article DE reinforcement; self-administration; acetylcholine; nicotinic; muscarinic receptors; D-1 receptors; mesocorticolimbic dopamine neurons ID MIDBRAIN DOPAMINE NEURONS; NUCLEUS-ACCUMBENS; BRAIN-STIMULATION; MUSCARINIC RECEPTORS; RAT; NICOTINE; ACTIVATION; ACETYLCHOLINE; REGIONS; SYSTEM AB Rats learned to lever-press for microinjections of the cholinergic agonist carbachol (30-500 pmol per infusion) or the acetylcholinesterase inhibitor neostigmine (7.5-75 pmol per infusion) into the posterior ventral tegmental area (VTA) of the brain. Intracranial carbachol self-administration was site-specific. Carbachol was not reliably self-administered into a site just dorsal to the VTA or into the adjacent substantia nigra and was self-administered only weakly into the adjacent anterior VTA or interpeduncular nucleus. Carbachol produced conditioned place preferences when injected into the posterior but not into the anterior VTA or sites dorsal to the posterior VTA. Rats self-administered carbachol less when it was co-infused with the muscarinic cholinergic receptor antagonist scopolamine or the nicotinic cholinergic receptor antagonist dihydro-beta-erythroidine, and also when the rats were pretreated with the D-1 dopamine antagonist SCH 23390. These findings implicate both nicotinic and muscarinic cholinergic neurotransmission in ventral tegmental reward function and suggest special involvement of the posterior portion of the VTA in cholinergic reward function. C1 NIDA, Behav Neurosci Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Ikemoto, S (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Ikemoto, Satoshi/0000-0002-0732-7386 NR 43 TC 79 Z9 81 U1 1 U2 3 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 NOV 15 PY 2002 VL 22 IS 22 BP 9895 EP 9904 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 613TF UT WOS:000179147000028 PM 12427846 ER PT J AU Rocha, BA Goulding, EH O'Dell, LE Mead, AN Coufal, NG Parsons, LH Tecott, LH AF Rocha, BA Goulding, EH O'Dell, LE Mead, AN Coufal, NG Parsons, LH Tecott, LH TI Enhanced locomotor, reinforcing, and neurochemical effects of cocaine in serotonin 5-hydroxytryptamine 2C receptor mutant mice SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cocaine; serotonin; serotonin 2c receptor; behavior; reinforcement; mice ID VENTRAL TEGMENTAL AREA; MIDBRAIN DOPAMINE NEURONS; MEDIAN RAPHE NUCLEI; INTRAVENOUS COCAINE; 5-HT2C RECEPTORS; EXTRACELLULAR DOPAMINE; SUBSTANTIA-NIGRA; RAT; ACCUMBENS; DORSAL AB Brain serotonin [5-hydroxytryptamine (5-HT)] systems substantially influence the effects of cocaine; however, the contributions of individual 5-HT receptor subtypes to the regulation of cocaine responses are unclear. A line of mutant mice devoid of 5-HT2C receptors was used to examine the contribution of this receptor subtype to the serotonergic modulation of cocaine responses. Mutants display enhanced exploration of a novel environment and increased sensitivity to the locomotor stimulant effects of cocaine. In an operant intravenous self-administration model under a progressive ratio schedule of reinforcement, mutants display elevated levels of lever pressing for cocaine injections, indicating that the drug is more reinforcing in these mice. Moreover, mutants exhibit enhanced cocaine-induced elevations of dopamine (DA) levels in the nucleus accumbens, a brain region implicated in the stimulant and rewarding properties of cocaine. In contrast, phenotypic differences in dorsal striatal DA levels were not produced by cocaine treatment. These findings strongly implicate 5-HT2C receptors in the serotonergic suppression of DA-mediated behavioral responses to cocaine and as a potential therapeutic target for cocaine abuse. C1 NIDA, Intramural Res Program, Baltimore, MD 21224 USA. Univ Maryland, Maryland Psychiat Res Ctr, Baltimore, MD 21247 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Ctr Neurobiol & Psychiat, San Francisco, CA 94143 USA. The Scripps Res Inst, Res Inst, Dept Neuropharmacol, La Jolla, CA 92037 USA. RP Tecott, LH (reprint author), 401 Parnassus Ave,IRE-0984, San Francisco, CA 94143 USA. FU NIDA NIH HHS [R29 DA 12579, DA 11177] NR 67 TC 113 Z9 116 U1 0 U2 3 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 NOV 15 PY 2002 VL 22 IS 22 BP 10039 EP 10045 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 613TF UT WOS:000179147000043 PM 12427861 ER PT J AU Yuan, XQ Chittajallu, R Belachew, S Anderson, S McBain, CJ Gallo, V AF Yuan, XQ Chittajallu, R Belachew, S Anderson, S McBain, CJ Gallo, V TI Expression of the green fluorescent protein in the oligodendrocyte lineage: A transgenic mouse for developmental and physiological studies SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE glia; potassium channels; 2 '-3 '-cyclic nucleotide 3 '-phosphodiesterase promoter; Schwann cells ID ION CHANNEL EXPRESSION; CENTRAL-NERVOUS-SYSTEM; WHITE MATTER GLIA; PRECURSOR CELLS; MEMBRANE DEPOLARIZATION; RECEPTOR ACTIVATION; PROGENITOR CELLS; K+ CHANNELS; MICE; DIFFERENTIATION AB We generated a transgenic mouse expressing the enhanced green fluorescent protein (EGFP) under the control of the 2'-3'-cyclic nucleotide T-phosphodiesterase (CNP) promoter. EGFP(+) cells were visualized in live tissue throughout embryonic and postnatal development. Immunohistochemical analysis in brain tissue and in sciatic nerve demonstrated that EGFP expression was restricted to cells of the oligodendrocyte and Schwann cell lineages. EGFP was also strongly expressed in "adult" oligodendrocyte progenitors (OPs) and in gray matter oligodendrocytes. Fluorescence-activated cell sorting allowed high-yield purification of EGFP(+) oligodendrocyte-lineage cells from transgenic brains. Electrophysiological patch clamp recordings of EGFP(+) cells in situ demonstrated that OP cells displayed large outward tetraethylammonium (TEA)-sensitive K+ currents and very small inward currents, whereas mature oligodendrocytes were characterized by expression of large inward currents and small outward K+ currents. The proliferation rate of EGFP(+) cells in developing white matter decreased with the age of the animals and was strongly inhibited by TEA. Oligodendrocyte development and physiology can be studied in live tissue of CNP-EGFP transgenic mice, which represent a source of pure EGFP(+) oligodendrocyte-lineage cells throughout development. (C) 2002 Wiley-Liss, Inc. C1 Childrens Natl Med Ctr, Childrens Res Inst, Ctr Res Neurosci, Washington, DC 20010 USA. NHGRI, Gene Transfer Lab, Hematopoiesis Sect, Flow Cytometry Core Unit, Bethesda, MD 20892 USA. NICHHD, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD USA. RP Gallo, V (reprint author), Childrens Natl Med Ctr, Childrens Res Inst, Ctr Res Neurosci, 111 Michigan Ave NW, Washington, DC 20010 USA. NR 47 TC 118 Z9 119 U1 0 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD NOV 15 PY 2002 VL 70 IS 4 BP 529 EP 545 DI 10.1002/jnr.10368 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 610RX UT WOS:000178975500001 PM 12404507 ER PT J AU Bell, MJ Hallenbeck, JM AF Bell, MJ Hallenbeck, JM TI Effects of intrauterine inflammation on developing rat brain SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE cerebral palsy; oligodendrocytes; astrocytes; apoptosis; periventricular leukomalacia ID NECROSIS-FACTOR-ALPHA; WHITE-MATTER LESIONS; CEREBRAL-PALSY; PERIVENTRICULAR LEUKOMALACIA; RISK-FACTORS; PREMATURE-INFANT; LIFE EXPECTANCY; AMNIOTIC-FLUID; FISCHER RATS; CELL-DEATH AB Damage to the white matter in the brain during development can lead to cerebral palsy (CP), a heterogeneous group of clinical syndromes that results in life-long disorders of movement and posture. Periventricular leukomalacia (PVL) is a pathological process within the white matter characterized by oligodendrocyte loss and is associated with the development of CP. Clinically, CP and PVL are associated with intrauterine infection and inflammation, but mechanisms involved are not well understood. We developed a model of intrauterine inflammation in Lewis and Fischer 344 rats to study the effects of intrauterine inflammation on developing glia. Pregnant rats were intracervically injected with lipopolysaccharide (LPS) at 15 days of gestation (E15) and a dose of LPS that caused low fetal mortality was determined. At E20, treated fetuses had increased TUNEL+ nuclei and tumor necrosis factor (TNF)-alpha-immunoreactive areas within the brains. In a second series of animals allowed to survive until postnatal day 21 (PND 21), immunostaining was performed against several glial markers. Staining for the oligodendrocyte-specific proteins 2', 3'-cyclic nucleotide phosphodiesterase (CNP) and myelin proteolipid protein (PLP) was decreased in treated pups compared to shams within the corpus callosum, a white matter structure used as a representative area of developing white matter. Treated pups had activated astrocytes lining cerebral blood vessels, as observed by glial fibrillary acidic protein (GFAP) staining, while sham pups did not. Activated microglia were not detected using OX42 as a cell marker. Our model of intrauterine inflammation causes increased TUNEL and TNF-alpha staining early after injury, suggesting increased apoptotic cell death, possibly by cytokine-related mechanisms. (C) 2002 Wiley-Liss, Inc. C1 George Washington Univ, Childrens Res Inst, Ctr Res Neurosci, Childrens Natl Med Ctr,Sch Med, Washington, DC 20010 USA. NINDS, Stroke Branch, NIH, Bethesda, MD USA. RP Bell, MJ (reprint author), George Washington Univ, Childrens Res Inst, Ctr Res Neurosci, Childrens Natl Med Ctr,Sch Med, 111 Michigan Ave NW, Washington, DC 20010 USA. NR 47 TC 116 Z9 121 U1 2 U2 6 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 NOV 15 PY 2002 VL 70 IS 4 BP 570 EP 579 DI 10.1002/jnr.10423 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 610RX UT WOS:000178975500005 PM 12404511 ER PT J AU Chong, HS Torti, FM Torti, SV Brechbiel, MW AF Chong, HS Torti, FM Torti, SV Brechbiel, MW TI Synthesis of 1,3,5-cis,cis-triaminocyclohexane N-pyridyl derivatives as potential antitumor agents SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID TRANSFERRIN RECEPTOR; IRON CHELATOR; MONOCLONAL-ANTIBODIES; CELL-LINES; GROWTH; PROLIFERATION; APOPTOSIS; CARCINOMA; DEFEROXAMINE; INHIBITION AB Iron deprivation has been previously proven to be a promising strategy in treating tumor cells. A series of cis,cis-1,3,5-triaminocyclohexane N-pyridyl derivatives as iron-depleting antitumor agents were prepared. Cytotoxic activity of these derivatives was evaluated in the HeLa cancer cell line. Among the tested derivatives, N-ethyl-N,N',N"-tris(2-pyridylmethyl)-cis,cis-1,3,5-triaminocyclohexane (17) exhibited potent cytotoxicity against this cancer cell line. On the basis of the structure of 17, a bifunctional iron chelator 24 was designed and prepared. Bifunctional agent 24 possessing a maleimide linker that is functional for conjugation to thiolated monoclonal antibodies is a promising lead compound for development of antitumor conjugates for antibody-targeted therapies. C1 NCI, Chem Sect, NIH, Bethesda, MD 20892 USA. Wake Forest Univ, Dept Canc Biol, Winston Salem, NC 27157 USA. Wake Forest Univ, Dept Biochem, Winston Salem, NC 27157 USA. Wake Forest Univ, Ctr Comprehens Canc, Winston Salem, NC 27157 USA. RP Chong, HS (reprint author), NCI, Chem Sect, NIH, Bethesda, MD 20892 USA. EM chongjoy@mail.nih.gov FU NIDDK NIH HHS [DK 57781] NR 29 TC 13 Z9 13 U1 0 U2 1 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 NOV 15 PY 2002 VL 67 IS 23 BP 8072 EP 8078 DI 10.1021/jo0204911 PG 7 WC Chemistry, Organic SC Chemistry GA 613BH UT WOS:000179110400016 PM 12423134 ER PT J AU Lane, MA Mattison, J Ingram, DK Roth, GS AF Lane, MA Mattison, J Ingram, DK Roth, GS TI Caloric restriction and aging in primates: Relevance to humans and possible CR mimetics SO MICROSCOPY RESEARCH AND TECHNIQUE LA English DT Article DE rhesus monkeys; dietary restriction; 2-deoxyglucose; squirrel monkeys ID MONKEYS MACACA-MULATTA; MALE RHESUS-MONKEYS; PROTECTS HIPPOCAMPAL-NEURONS; TERM DIETARY RESTRICTION; OXIDATIVE INJURY; BRAIN-DAMAGE; 2-DEOXY-D-GLUCOSE; INVOLVEMENT; METABOLISM; MECHANISM AB For nearly 70 years it has been recognized that reduction in caloric intake by 30-40% from ad libitum levels leads to a significant extension of mean and maximal lifespan in a variety of short-lived species. This effect of caloric restriction (CR) on lifespan has been reported in nearly all species tested and has been reproduced hundreds of times under a variety of different laboratory conditions. In addition to prolonging lifespan, CR also prevents or delays the onset of age-related disease and maintains many physiological functions at more youthful levels. Studies in longer-lived species, specifically rhesus and squirrel monkeys, have been underway since the late 1980s. The studies in nonhuman primates are beginning to yield valuable information suggesting that the effect of CR on aging is universal across species and that this nutritional paradigm will have similar effects in humans. Even if CR can be shown to impact upon human aging, it is unlikely that most people will be able to maintain the strict dietary control required for this regimen. Thus, elucidation of the biological mechanisms of CR and development of alternative strategies to yield similar benefits is of primary importance. CR mimetics, or interventions that "mimic" certain protective effects of CR, may represent one such alternative strategy. Published 2002 Wiley-Liss. Inc. C1 NIA, Neurosci Lab, Baltimore, MD 21224 USA. RP Lane, MA (reprint author), NIA, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 45 TC 56 Z9 58 U1 0 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1059-910X J9 MICROSC RES TECHNIQ JI Microsc. Res. Tech. PD NOV 15 PY 2002 VL 59 IS 4 BP 335 EP 338 DI 10.1002/jemt.10214 PG 4 WC Anatomy & Morphology; Biology; Microscopy SC Anatomy & Morphology; Life Sciences & Biomedicine - Other Topics; Microscopy GA 615CZ UT WOS:000179229400013 PM 12424798 ER PT J AU Kirmani, BF Jacobowitz, DM Kallarakal, AT Namboodiri, MAA AF Kirmani, BF Jacobowitz, DM Kallarakal, AT Namboodiri, MAA TI Aspartoacylase is restricted primarily to myelin synthesizing cells in the CNS: therapeutic implications for Canavan disease SO MOLECULAR BRAIN RESEARCH LA English DT Article DE N-acetylaspartate; oligodendroglia; in situ hybridization; acetate deficiency hypothesis; acetate supplementation therapy ID N-ACETYL-ASPARTATE; RAT-BRAIN; LIPID-SYNTHESIS; NERVOUS-SYSTEM; BOVINE BRAIN; EXPRESSION; OLIGODENDROCYTES; ACETYLASPARTATE; GENE; LOCALIZATION AB Canavan disease is a devastating neurodegenerative childhood disease caused by mutation,, in aspartoacylase, an enzyme that deacetylates N-acetylaspartate to generate free acetate in the brain. Localization of aspartoacylase in different cell types in the rat brain was examined in an attempt to understand the pathogenesis of Canavan disease, In situ hybridization histochemistry with a riboprobe based on murine aspartoacylase cDNA was used in this study. The hybridization signal was detectable primarily in the myelin-synthesizing cells, namely oligodendroglia. These findings provide strong additional support for insufficient myelin synthesis as the pathogenic basis of Canavan disease and make a compelling case for acetate supplementation as a simple and noninvasive therapy for this fatal disease with no treatment. Published by Elsevier Science B.V. C1 Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. RP Namboodiri, MAA (reprint author), Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bldg C,Room 2116,4301 Jones Bridge Rd, Bethesda, MD 20814 USA. NR 31 TC 22 Z9 23 U1 0 U2 1 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 NOV 15 PY 2002 VL 107 IS 2 BP 176 EP 182 AR PII S0169-328X(02)00490-4 DI 10.1016/S0169-328X(02)00490-4 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 620GN UT WOS:000179525800010 ER PT J AU Oliveira, L Volchan, E Pessoa, L Pantoja, JH Joffily, M Souza-Neto, D Marques, RF Rocha-Miranda, CE AF Oliveira, L Volchan, E Pessoa, L Pantoja, JH Joffily, M Souza-Neto, D Marques, RF Rocha-Miranda, CE TI Contour integration in the primary visual cortex of the opossum SO NEUROREPORT LA English DT Article DE contour integration; Didelphis; receptive field; striate cortex ID PERCEPTUAL COMPLETION; ILLUSORY CONTOURS; STRIATE CORTEX; REPRESENTATION; CONNECTIONS; MECHANISMS; RESPONSES; AREAS AB To investigate whether contour integration is a generalized mammalian feature we studied single cells in VI on the South-America opossum (Didelphis aurita), a plesiomorphic animal believed to retain basic characteristics of early mammals. We observed that when a cell's receptive field (RF) was masked (i.e. an artificial scotoma was produced), sweeping a long bar (several times the length of the RF) at the cell's preferred orientation elicited robust responses in many cells (28/103, or 27%). Therefore, some cells in the primary visual cortex of the opossum interpolate under conditions consistent with physical occlusion. The present results indicate that the property of contour integration appears to be a basic property of the mammalian visual system. C1 Univ Fed Rio de Janeiro, Inst Biophys Carlos Chagas Filho, CCS BL G, BR-21949900 Rio De Janeiro, Brazil. NIMH, Lab Brain & Cognit, NIH, Bethesda, MD USA. RP Oliveira, L (reprint author), Univ Fed Rio de Janeiro, Inst Biophys Carlos Chagas Filho, CCS BL G, Ilha Fondao, BR-21949900 Rio De Janeiro, Brazil. RI Volchan, Eliane/C-5792-2013 NR 24 TC 5 Z9 5 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 NOV 15 PY 2002 VL 13 IS 16 BP 2001 EP 2004 DI 10.1097/00001756-200211150-00002 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 625NB UT WOS:000179821600002 PM 12438914 ER PT J AU Liang, HL Bressler, SL Ding, MZ Truccolo, WA Nakamura, R AF Liang, HL Bressler, SL Ding, MZ Truccolo, WA Nakamura, R TI Synchronized activity in prefrontal cortex during anticipation of visuomotor processing SO NEUROREPORT LA English DT Article DE anticipation; event-related potential; local field potential; oscillation; response time; prefrontal cortex; synchronization; top-down control ID VISUAL-ATTENTION; PARIETAL RHYTHMS; CONNECTIONS; MACAQUE; AREAS; IMMOBILITY; MODULATION; MECHANISMS; TOPOGRAPHY; EEG AB It is commonly presumed, though not well established, that the prefrontal cortex exerts top-down control of sensory processing. One aspect of this control is thought to be a facilitation of sensory pathways in anticipation of such processing. To investigate the possible involvement of prefrontal cortex in anticipatory top-down control, we studied the statistical relations between prefrontal activity, recorded while a macaque monkey waited for presentation of a visual stimulus, and subsequent sensory and motor events. Local field potentials were simultaneously recorded from prefrontal, motor, occipital and temporal cortical sites in the left cerebral hemisphere. Spectral power and coherence analysis revealed that during stimulus anticipation three of five prefrontal sites participated in a coherent oscillatory network synchronized in the P-frequency range. Pre-stimulus network power and coherence were highly correlated with the amplitude and latency of early visual evoked potential components in visual cortical areas, and with response time. The results suggest that synchronized oscillatory networks in prefrontal cortex are involved in top-down anticipatory mechanisms that facilitate subsequent sensory processing in visual cortex. They further imply that stronger top-down control leads to larger and faster sensory responses, and a subsequently faster motor response. C1 Univ Texas, Houston, TX 77030 USA. Florida Atlantic Univ, Ctr Complex Syst & Brain Sci, Boca Raton, FL 33431 USA. Brown Univ, Dept Neurosci, Providence, RI 02912 USA. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Bressler, SL (reprint author), Univ Texas, Houston, TX 77030 USA. FU NIMH NIH HHS [MH42900, MH58190] NR 28 TC 71 Z9 73 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD NOV 15 PY 2002 VL 13 IS 16 BP 2011 EP 2015 DI 10.1097/00001756-200211150-00004 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 625NB UT WOS:000179821600004 PM 12438916 ER PT J AU Watanabe, K Imada, T Nihei, K Shimojo, S AF Watanabe, K Imada, T Nihei, K Shimojo, S TI Neuromagnetic responses to chromatic flicker: implications for photosensitivity SO NEUROREPORT LA English DT Article DE chromatic flicker; chromatic sensitivity; magnetoencephalography (MEG); parieto-occipital sulcus; photosensitive epilepsy ID SENSITIVE EPILEPSY; COLOR; CONTRAST; BRAIN AB Excessive cortical excitation due to visual stimulation often leads to photosensitive epilepsy. Here we demonstrate that even in normal subjects, prolonged stimulation with low-luminance chromatic (equiluminant) flicker evokes neuromagnetic activity in the primary visual cortex, which develops slowly (up to 1000 ms) and depends on the color combination of flicker. This result suggests that chromatic sensitivity is a critical factor of cortical excitation, which can be amplified over time by a flickering stimulus. We further show that transient activity occurs in the parieto-occipital sulcus as early as 100-400 ms after flicker onset, which is negatively correlated with the later occipital activity. The early parieto-occipital activity may reflect a defensive mechanism that suppresses cortical hyperactivity due to chromatic flicker. C1 CALTECH, Div Biol, Pasadena, CA 91125 USA. NTT Corp, Human & Informat Sci Lab, Commun Sci Labs, Atsugi, Kanagawa 2430198, Japan. Natl Childrens Hosp, Dept Neurol, Setagaya Ku, Tokyo 1548509, Japan. RP Watanabe, K (reprint author), NEI, Lab Sensorimotor Res, NIH, Bldg 49,Room 2A50,49 Convent Dr, Bethesda, MD 20892 USA. NR 14 TC 8 Z9 8 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 EI 1473-558X J9 NEUROREPORT JI Neuroreport PD NOV 15 PY 2002 VL 13 IS 16 BP 2161 EP 2165 DI 10.1097/00001756-200211150-00034 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 625NB UT WOS:000179821600034 PM 12438946 ER PT J AU Wernicke, C Smolka, M Gallinat, J Winterer, G Schmidt, LG Rommelspacher, H AF Wernicke, C Smolka, M Gallinat, J Winterer, G Schmidt, LG Rommelspacher, H TI Evidence for the importance of the human dopamine transporter gene for withdrawal symptomatology of alcoholics in a German population SO NEUROSCIENCE LETTERS LA English DT Article DE alcoholism; dopamine transporter; 3 ' untranslated region; withdrawal ID POLYMORPHISM; ASSOCIATION; DAT1; DNA AB Two new polymorphisms in the 3' untranslated region (3'UTR) of the dopamine transporter (DAT1) gene, adjacent to the known variable number of tandem repeats (VNTR) polymorphism, have been investigated in the present population-based association study including 351 alcoholics and 336 controls. The Dral restriction site was not polymorphic in our population. The G2319A polymorphism was not significantly different with respect to genotype or allele distribution between alcoholics and controls. Subsequently, in individuals with VNTR homozygosity for the ten repeat allele, we found a higher prevalence of A/A homozygosity in patients with seizure history (P = 0.001, odds ratio (OR) = 7.913), with delirium history (P = 0.032, OR = 4.707), and with an alcoholic mother (P = 0.021, OR = 5.250), compared to homozygote 10/10 controls. Our findings provide further evidence that the 3'UTR of the DAT1 gene affects vulnerability to severe alcohol withdrawal. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Free Univ Berlin, Benjamin Franklin Med Sch, Dept Clin Neurobiol, D-14050 Berlin, Germany. Univ Mainz, Dept Psychiat, D-55131 Mainz, Germany. NIMH, Clin Brain Disorder Branch, Bethesda, MD 20892 USA. Free Univ Berlin, Benjamin Franklin Med Sch, Dept Psychiat, D-14050 Berlin, Germany. RP Wernicke, C (reprint author), Free Univ Berlin, Benjamin Franklin Med Sch, Dept Clin Neurobiol, Ulmenallee 32, D-14050 Berlin, Germany. RI Smolka, Michael/B-4865-2011 OI Smolka, Michael/0000-0001-5398-5569 NR 12 TC 26 Z9 29 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD NOV 15 PY 2002 VL 333 IS 1 BP 45 EP 48 AR PII S0304-3940(02)00985-0 DI 10.1016/S0304-3940(02)00985-0 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 611XP UT WOS:000179043400012 PM 12401557 ER PT J AU Gaidamakova, EK Neumann, RD Panyutin, IG AF Gaidamakova, EK Neumann, RD Panyutin, IG TI Site-specific strand breaks in RNA produced by I-125 radiodecay SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SYNTHETIC OLIGODEOXYNUCLEOTIDE; DNA; DECAY; LYMPHOMA; COMPLEX; TRIPLEX AB Decay of I-125 produces a shower of low energy electrons (Auger electrons) that cause strand breaks in DNA in a distance-dependent manner with 90% of the breaks located within 10 bp from the decay site. We studied strand breaks in RNA molecules produced by decay of I-125 incorporated into complementary DNA oligonucleotides forming RNA/DNA duplexes with the target RNA. The frequencies and distribution of the breaks were unaffected by the presence of the free radical scavenger dimethyl sulfoxide (DMSO) or by freezing of the samples. Therefore, as was the case with DNA, most of the breaks in RNA were direct rather than caused by diffusible free radicals produced in water. The distribution of break frequencies at individual bases in RNA molecules is narrower, with a maximum shifted to the 3'-end with respect to the distribution of breaks in DNA molecules of the same sequence. This correlates with the distances from the radioiodine to the sugars of the corresponding bases in A-form (RNA/DNA duplex) and B-form (DNA/DNA duplex) DNA. Interestingly, when I-125 was located close to the end of the antisense DNA oligonucleotide, we observed breaks in RNA beyond the RNA/DNA duplex region. This was not the case for a control DNA/DNA hybrid of the same sequence. We assume that for the RNA there is an interaction between the RNA/DNA duplex region and the single-stranded RNA tail, and we propose a model for such an interaction. This report demonstrates that I-125 radioprobing of RNA could be a powerful method to study both local conformation and global folding of RNA molecules. C1 NIH, Dept Nucl Med, Bethesda, MD 20892 USA. Inst Mol Biol & Biophys, Novosibirsk 630117, Russia. RP Panyutin, IG (reprint author), NIH, Dept Nucl Med, Bldg 10, Bethesda, MD 20892 USA. NR 24 TC 8 Z9 8 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV 15 PY 2002 VL 30 IS 22 BP 4960 EP 4965 DI 10.1093/nar/gkf622 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 615NZ UT WOS:000179253800018 PM 12434000 ER PT J AU Moody, TW Leyton, J Casibang, M Pisegna, J Jensen, RT AF Moody, TW Leyton, J Casibang, M Pisegna, J Jensen, RT TI PACAP-27 tyrosine phosphorylates mitogen activated protein kinase and increases VEGF mRNAs in human lung cancer cells SO REGULATORY PEPTIDES LA English DT Article DE PACAP; lung cancer; mitogen activated protein kinase; VEGF ID VASOACTIVE INTESTINAL POLYPEPTIDE; ENDOTHELIAL GROWTH-FACTOR; ADENYLATE-CYCLASE; SIGNAL-TRANSDUCTION; LIVER METASTASIS; SPLICE VARIANTS; MESSENGER-RNAS; RECEPTOR; THERAPY; CLONING AB The effects of pituitary adenylate cyclase activating polypeptide (PACAP) on human lung cancer cell line NC1-1299 mitogen activated protein kinase (MAPK) tyrosine phosphorylation and vascular endothelial cell growth factor (VEGF) expression were investigated. PACAP-27 (100 nM) increased MAPK tyrosine phosphorylation 3-fold, 5 min after addition to NC1-H1299 cells. PACAP caused tyrosine phosphorylation in a concentration-dependent manner being half-maximal at 10 nM PACAP-27. PACAP-27 or PACAP-38 (100 nM) but not PACAP28-38 or VIP caused increased MAPK tyrosine phosphorylation using NC1-H1299 cells. Also, the increase in MAPK tyrosine phosphorylation caused by PACAP-27 was totally inhibited by 10 muM PACAP(6-38), a PAC(1) receptor antagonist or 10 muM PD98059, a MAPKK inhibitor. These results suggest that PAC(1) receptors regulate tyrosine phosphorylation of MAPK in a MAPKK-dependent manner. PACAP-27 (100 nM) caused increased VEGF mRNA in NC1-H1299 cells after 8 h. The increase in VEGF mRNA caused by PACAP-27 was partially inhibited by PACAP(6-38), PD98059 and H-89. Addition of VIP to NC1-H1299 cells caused increased VEGF mRNA, which was totally inhibited by H89, a PKA inhibitor. These results suggest that PAC(1) and VPAC(1) receptors regulate VEGF expression in lung cancer cells. Published by Elsevier Science B.V. C1 NCI, Off Director, Ctr Canc Res, Bethesda, MD 20892 USA. Univ Calif Los Angeles, VAGLAHS, Gastrointestinal Div, Los Angeles, CA 90073 USA. NIDDKD, Gastroenterol Sect, Bethesda, MD 20892 USA. RP Moody, TW (reprint author), NCI, Off Director, Ctr Canc Res, Bldg 31,Rm 3A34,31 Ctr Dr, Bethesda, MD 20892 USA. NR 28 TC 19 Z9 19 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD NOV 15 PY 2002 VL 109 IS 1-3 BP 135 EP 140 AR PII S0167-0115(02)00196-9 DI 10.1016/S0167-0115(02)00196-9 PG 6 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 614WA UT WOS:000179213400019 PM 12409225 ER PT J AU Kim, K Lee, SH Seo, YR Perkins, SN Kasprzak, KS AF Kim, K Lee, SH Seo, YR Perkins, SN Kasprzak, KS TI Nickel(II)-induced apoptosis in murine T cell hybridoma cells is associated with increased Fas ligand expression SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE nickel(II); apoptosis; T cell hybridoma cells; Fas ligand; caspases; caspase inhibitors; reactive oxygen species ID FACTOR-KAPPA-B; DNA-DAMAGE; NICKEL CARCINOGENESIS; MEDIATED APOPTOSIS; DEATH RECEPTORS; ACTIVATION; LYMPHOCYTES; INDUCTION; SUPPRESSION; MECHANISM AB Nickel(II) exposure has multiple effects on the immune system, including thymic involution, decreased T cell number in the spleen, and decreased natural killer cell activity. Using a murine T cell hybridoma cell line (KMIs 8.3.5.1) to model nickel-induced cell death in immune cells, we found that nickel(II) acetate treatment rapidly induced apoptosis in these cells, as signified by membrane blebbing, chromatin condensation, increased annexin V staining, and an increased proportion of cells with hypodiploid DNA. Preceding these morphological changes, nickel(II) treatment increased expression of Fas ligand (FasL) mRNA and protein levels and also increased caspase-3-like protease activity. Coincubation with caspase inhibitors markedly inhibited nickel(II)-induced apoptosis, with Z-IETD-FMK, an inhibitor of caspase-8 and granzyme B, nearly as, effective as less selective caspase inhibitors. Agents that generate reactive oxygen species (ROS) cause apoptosis in a variety of cells by inducing expression of FasL. Given that nickel(II) can directly generate ROS, exposure to nickel(II) may lead to apoptosis through a similar mechanism. (C) 2002 Elsevier Science (USA). C1 NCI, Basic Res Lab, Ctr Canc Res, Frederick, MD 21701 USA. NCI, Comparat Carcinogenesis Lab, Ctr Canc Res, Frederick, MD 21701 USA. Korea Univ, Grad Sch Biotechnol, Cell Biol Lab, Seoul 136701, South Korea. NCI, Off Prevent Oncol, Div Canc Prevent, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Lab Biosyst & Canc, Ctr Canc Res, Bethesda, MD 20892 USA. RP Perkins, SN (reprint author), NCI, Basic Res Lab, Ctr Canc Res, Bldg 538,Room 205-E, Frederick, MD 21701 USA. NR 36 TC 35 Z9 39 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV 15 PY 2002 VL 185 IS 1 BP 41 EP 47 DI 10.1006/taap.2002.9513 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 620KR UT WOS:000179533000005 PM 12460735 ER PT J AU Hu, JJ Mohrenweiser, HW Bell, DA Leadon, SA Miller, MS AF Hu, JJ Mohrenweiser, HW Bell, DA Leadon, SA Miller, MS TI Symposium overview: Genetic polymorphisms in DNA repair and cancer risk SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE DNA repair; SNPs; cancer risk ID TRANSCRIPTION-COUPLED REPAIR; NUCLEOTIDE EXCISION-REPAIR; IONIZING-RADIATION SENSITIVITY; ACID SUBSTITUTION VARIANTS; SQUAMOUS-CELL CARCINOMA; DOUBLE-STRAND BREAKS; LUNG-CANCER; ENVIRONMENT INTERACTION; XPD POLYMORPHISMS; COCKAYNE-SYNDROME AB A symposium, Genetic Polymorphisms in DNA Repair and Cancer Risk, was presented at the 40th Annual Meeting of the Society of Toxicology, held in San Francisco, California, in March 2001. A brief report of the symposium was published (Kaiser, Science 292, 837-838, 2001). Molecular epidemiological studies have shown that polymorphic variants of genes involved in the metabolism and repair of carcinogens can act as cancer susceptibility genes. These variants of drug metabolic and DNA-repair enzymes either increase the activation of chemical carcinogens or decrease the cells' ability to detoxify/repair mutagenic damages. Although on an individual basis these variant alleles may only slightly change catalytic activity and increase cancer risk, their polymorphic frequency in the human population may contribute to a high proportion of cancer cases. Studies conducted over the past few years have identified variant alleles for a number of DNA-repair genes, some of which have been shown to change DNA-repair capacity. Identifying these genotypic alterations in DNA-repair enzymes and their association with cancer may help to elucidate the mechanisms of cancer etiology and to predict both disease risk and response to cancer therapy, since most antineoplastic treatments mediate their effects through DNA damage. (C) 2002 Elsevier Science (USA). C1 Wake Forest Univ, Sch Med, Dept Canc Biol, Winston Salem, NC 27157 USA. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27157 USA. Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, Livermore, CA 94550 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Radiat Oncol, Chapel Hill, NC 27514 USA. RP Hu, JJ (reprint author), Wake Forest Univ, Sch Med, Dept Canc Biol, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM jenhu@wfubmc.edu NR 85 TC 64 Z9 67 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV 15 PY 2002 VL 185 IS 1 BP 64 EP 73 DI 10.1006/taap.2002.9518 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 620KR UT WOS:000179533000008 PM 12460738 ER PT J AU Xavier, S Yamada, K Samuni, AM Samuni, A DeGraff, W Krishna, MC Mitchell, JB AF Xavier, S Yamada, K Samuni, AM Samuni, A DeGraff, W Krishna, MC Mitchell, JB TI Differential protection by nitroxides and hydroxylamines to radiation-induced and metal ion-catalyzed oxidative damage SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article DE radiation; nitroxide; DNA damage; protection ID DOUBLE-STRAND BREAKS; SINGLE-STRAND; MAMMALIAN-CELLS; IONIZING-RADIATION; FREE-RADICALS; DNA-DAMAGE; SV40 DNA; SUPEROXIDE; INHIBITION; RADIOPROTECTION AB Modulation of radiation- and metal ion-catalyzed oxidative-induced damage using plasmid DNA, genomic DNA, and cell survival, by three nitroxides and their corresponding hydroxylamines, were examined. The antioxidant property of each compound was independently determined by reacting supercoiled DNA with copper II/1,10-phenanthroline complex fueled by the products of hypoxanthine/xanthine oxidase (HX/XO) and noting the protective effect as assessed by agarose gel electrophoresis. The nitroxides and their corresponding hydroxylamines protected approximately to the same degree (33-47% relaxed form) when compared to 76.7% relaxed form in the absence of protectors. Likewise, protection by both the nitroxide and corresponding hydroxylamine were observed for Chinese hamster V79 cells exposed to hydrogen peroxide. In contrast, when plasmid DNA damage was induced by ionizing radiation (100 Gy), only nitroxides (10 mM) provide protection (32.4-38.5% relaxed form) when compared to radiation alone or in the presence of hydroxylamines (10 mM) (79.8% relaxed form). Nitroxide protection was concentration dependent. Radiation cell survival studies and DNA double-strand break (DBS) assessment (pulse field electrophoresis) showed that only the nitroxide protected or prevented damage, respectively. Collectively, the results show that nitroxides and hydroxylamines protect equally against the damage, mediated by oxidants generated by the metal ion-catalyzed Haber-Weiss reaction, but only nitroxides protect against radiation damage, suggesting that nitroxides may more readily react with intermediate radical species produced by radiation than hydroxylamines. Published by Elsevier Science B.V. C1 NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Hadassah Med Sch, IL-91120 Jerusalem, Israel. RP Mitchell, JB (reprint author), NCI, Radiat Biol Branch, Bldg 10,Room B3-B69,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Yamada, Ken-ichi/E-6318-2012 NR 40 TC 43 Z9 43 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD NOV 14 PY 2002 VL 1573 IS 2 BP 109 EP 120 AR PII S0304-4165(02)00339-2 DI 10.1016/S0304-4165(02)00339-2 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 609QL UT WOS:000178916400002 PM 12399020 ER PT J AU Koonin, EV Wolf, YI Karev, GP AF Koonin, EV Wolf, YI Karev, GP TI The structure of the protein universe and genome evolution SO NATURE LA English DT Review ID GENE-TRANSFER; METABOLIC NETWORKS; ATP-BINDING; FOLDS; CLASSIFICATION; FAMILIES; SUPERFAMILIES; SEQUENCES; DATABASE; DOMAINS AB Despite the practically unlimited number of possible protein sequences, the number of basic shapes in which proteins fold seems not only to be finite, but also to be relatively small, with probably no more than 10,000 folds in existence. Moreover, the distribution of proteins among these folds is highly non-homogeneous some folds and superfamilies are extremely abundant, but most are rare. Protein folds and families encoded in diverse genomes show similar size distributions with notable mathematical properties, which also extend to the number of connections between domains in multidomain proteins. All these distributions follow asymptotic power laws, such as have been identified in a wide variety of biological and physical systems, and which are typically associated with scale-free networks. These findings suggest that genome evolution is driven by extremely general mechanisms based on the preferential attachment principle. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov NR 76 TC 343 Z9 348 U1 4 U2 29 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 14 PY 2002 VL 420 IS 6912 BP 218 EP 223 DI 10.1038/nature01256 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 614QM UT WOS:000179200900058 PM 12432406 ER PT J AU Menard, C Hein, P Paquin, A Savelson, A Yang, XM Lederfein, D Barnabe-Heider, F Mir, AA Sterneck, E Peterson, AC Johnson, PF Vinson, C Miller, FD AF Menard, C Hein, P Paquin, A Savelson, A Yang, XM Lederfein, D Barnabe-Heider, F Mir, AA Sterneck, E Peterson, AC Johnson, PF Vinson, C Miller, FD TI An essential role for a MEK-C/EBP pathway during growth factor-regulated cortical neurogenesis SO NEURON LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; ALPHA-TUBULIN; TRANSCRIPTIONAL REGULATION; BINDING PROTEINS; PROGENITOR CELLS; TUMOR-SUPPRESSOR; GENE-EXPRESSION; CEREBRAL-CORTEX; DNA-BINDING; STEM-CELLS AB Mammalian neurogenesis is determined by an interplay between intrinsic genetic mechanisms and extrinsic cues such as growth factors. Here, we have defined a signaling cascade, 6 MEK-C/EBP pathway, that is essential for cortical progenitor cells to become post-mitotic neurons. Inhibition of MEK or of the C/EBP family of transcription factors inhibits neurogenesis while expression of a C/EBPbeta mutant that is a phosphorylation-mimic at a MEK-Rsk site enhances neurogenesis. C/EBP mediates this positive effect by direct transcriptional I activation of neuron-specific genes such as Talpha1 alpha-tubulin. Conversely, inhibition of C/EBP-dependent transcription enhances CNTF-mediated generation of astrocytes from the same progenitor cells. Thus, activation of a MEK-C/EBP pathway enhances neurogenesis and inhibits gliogenesis, thereby providing a mechanism whereby growth factors can selectively bias progenitors to become neurons during development. C1 Univ Toronto, Inst Res, Hosp Sick Children, Toronto, ON M5G 1X8, Canada. McGill Univ, Ctr Neuronal Survival, Montreal Neurol Inst, Royal Victoria Hosp, Montreal, PQ, Canada. McGill Univ, Brain Tumor Res Ctr, Montreal Neurol Inst, Royal Victoria Hosp, Montreal, PQ, Canada. Natl Canc Inst, Frederick, MD 21702 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Miller, FD (reprint author), Univ Toronto, Inst Res, Hosp Sick Children, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. RI Johnson, Peter/A-1940-2012 OI Johnson, Peter/0000-0002-4145-4725 NR 40 TC 140 Z9 144 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD NOV 14 PY 2002 VL 36 IS 4 BP 597 EP 610 DI 10.1016/S0896-6273(02)01026-7 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 616PX UT WOS:000179313100008 PM 12441050 ER PT J AU Kirch, HC Ruschen, S Brockmann, D Esche, H Horikawa, I Barrett, JC Opalka, B Hengge, UR AF Kirch, HC Ruschen, S Brockmann, D Esche, H Horikawa, I Barrett, JC Opalka, B Hengge, UR TI Tumor-specific activation of hTERT-derived promoters by tumor suppressive E1A-mutants involves recruitment of p300/CBP/HAT and suppression of HDAC-1 and defines a combined tumor targeting and suppression system SO ONCOGENE LA English DT Article DE E1A; tumor suppressor; hTERT promoter; tumor-specific expression; histone deacetylase ID REVERSE-TRANSCRIPTASE GENE; ADENOVIRUS-5 E1A GENE; HISTONE DEACETYLASE; ONCOPROTEIN E1A; MELANOMA-CELLS; C-MYC; TELOMERASE; TRANSFORMATION; PROTEIN; REPRESSION AB Adenovirus (Ad) E1A proteins are transcriptional regulators with antioncogenic but also transforming properties. We have previously shown that transformation-defective Ad5 E1A-derivatives are excellent tumor suppressors. For tumor-specific expression of the E1A-derivatives we intend to use tumor specific human telomerase reverse transcriptase (hTER7) core promoters. Here, we show that Spm2 and other E1A proteins with an intact amino terminus activated all hTERT constructs 10-20-fold in malignant tumor cells but not in primary fibroblasts, without affecting the activity of endogenous telomerase. The transcription rate in tumor cells was in the range of transcription from the SV40 promoter, which qualifies an E1A-hTERT system as a putative tumor targeting/expression system. The activation of the hTERT promoter by E1A was enhanced upon deletion of the Wilms' tumor I negative regulatory element and maintained high after deletion of the adjacent c-Myc-responsive E-box, demonstrating an important role of the remaining sequences that contain several Sp1-motifs. E1A-mediated hTERT activation was independent from the presence of the conserved region 3 (CR3) of E1A but dependent on E1A's binding to p300/CBP and recruitment of its histone acetyltransferase activity. Moreover, E1A-Spm2 and histone deacetylase-1 behaved as antagonists with respect to the regulation of transcription from the hTERT promoter. Overall, hTERT promoter/E1A-Spm2 systems may turn out to be excellent tools for transcriptionally targeted anticancer gene therapy. C1 Univ Essen Gesamthsch, Dept Internal Med Canc Res, D-45147 Essen, Germany. Univ Essen Gesamthsch, Inst Mol Biol Canc Res, D-45147 Essen, Germany. NCI, Canc Res Ctr, Lab Biosyst & Canc Res, NIH, Bethesda, MD 20892 USA. Univ Essen Gesamthsch, Dept Dermatol, D-45147 Essen, Germany. RP Kirch, HC (reprint author), Univ Essen Gesamthsch, Dept Internal Med Canc Res, Hufelandstr 55, D-45147 Essen, Germany. NR 39 TC 16 Z9 22 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 14 PY 2002 VL 21 IS 52 BP 7991 EP 8000 DI 10.1038/sj.onc.1205965 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 612VY UT WOS:000179097200008 PM 12439749 ER PT J AU Denis, PA Kieninger, M Ventura, ON Cachau, RE Diercksen, GHF AF Denis, PA Kieninger, M Ventura, ON Cachau, RE Diercksen, GHF TI Complete basis set and density functional determination of the enthalpy of formation of the controversial HO3 radical: a discrepancy between theory and experiment SO CHEMICAL PHYSICS LETTERS LA English DT Article ID POTENTIAL-ENERGY SURFACE; AB-INITIO; HYDROGEN TRIOXIDE; THERMOCHEMISTRY; KINETICS; SINGLET; ATOMS; WATER; HOOO AB Enthalpies of formation of the HOOOH molecule and HOOO radical were determined accurately employing density functional (DFT), coupled-clusters (CC) and complete basis set (CBS) extrapolation methods. The enthalpy of formation of the HO3 radical was determined as 7.1 +/- 2 kcal/mol at 298 K through a series of calculations employing the isodesmic reaction HOOOH + OH - HOH + HOOO. This value is in disagreement with the experimental one of Speranza, -1 +/- 5 kcal/mol. The enthalpy of formation of HOOOH, calculated at the extrapolated CBS/CCSD(T) and CBS-APNO levels, amounts to -21.1 +/- 1 kcal/mol, also in disagreement with the experimentally determined upper limit of -26.0 kcal/mol. Further examination of the procedure used to determine this value from the raw experimental data, suggests that this value is not as reliable as originally thought (by Speranza). The data should be reexamined and perhaps supplemented with additional experiments. (C) 2002 Published by Elsevier Science B.V. C1 Univ Republica, Fac Quim, UDELAR, CCPG DEQUIFIM, Montevideo 11800, Uruguay. SAIC, Adv Biomed Comp Ctr, NCI, Ft Detrick, MD 21702 USA. Max Planck Inst Astrophys, D-85741 Garching, Germany. RP Ventura, ON (reprint author), Univ Republica, Fac Quim, UDELAR, CCPG DEQUIFIM, CC 1157, Montevideo 11800, Uruguay. OI Denis, Pablo/0000-0003-3739-5061 NR 35 TC 38 Z9 38 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-2614 J9 CHEM PHYS LETT JI Chem. Phys. Lett. PD NOV 13 PY 2002 VL 365 IS 5-6 BP 440 EP 449 AR PII S0009-2614(02)01432-X DI 10.1016/S0009-2614(02)01432-X PG 10 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 614HE UT WOS:000179181600011 ER PT J AU Laurin, D Foley, DJ Masaki, KH White, LR Launer, LJ AF Laurin, D Foley, DJ Masaki, KH White, LR Launer, LJ TI Vitamin E and C supplements and risk of dementia SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID MEN C1 NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. Pacific Hlth Res Inst, Honolulu, HI USA. RP Laurin, D (reprint author), NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [N01-HC-05102]; NIA NIH HHS [N01-AG-4-2149] NR 6 TC 22 Z9 24 U1 2 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 13 PY 2002 VL 288 IS 18 BP 2266 EP 2268 DI 10.1001/jama.288.18.2266 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 614JZ UT WOS:000179186400024 PM 12425703 ER PT J AU Ball, K Berch, DB Helmers, KF Jobe, JB Leveck, MD Marsiske, M Morris, JN Rebok, GW Smith, DM Tennstedt, SL Unverzagt, FW Willis, SL AF Ball, K Berch, DB Helmers, KF Jobe, JB Leveck, MD Marsiske, M Morris, JN Rebok, GW Smith, DM Tennstedt, SL Unverzagt, FW Willis, SL CA ACTIVE Study Grp TI Effects of cognitive training interventions with older adults - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID MINI-MENTAL-STATE; AGE; DRIVERS; MEMORY; PERFORMANCE; YOUNG; IMPAIRMENT; HEALTH; RECALL; NORMS AB Context Cognitive function in older adults is related to independent living and need for care. However, few studies have addressed whether improving cognitive functions might have short- or long-term effects on activities related to living independently: Objective To evaluate whether 3 cognitive training interventions improve mental abilities and daily functioning in older, independent-living adults. Design Randomized, controlled, single-blind trial with recruitment conducted from March 1998 to October 1999 and 2-year follow-up through December 2001. Setting and Participants Volunteer sample of 2832 persons aged 65 to 94 years recruited from senior housing, community centers, and hospital/clinics in 6 metropolitan areas in the United States. Interventions Participants were randomly assigned to 1 of 4 groups: 10-session group training for memory (verbal episodic memory; n=711), or reasoning (ability to solve problems that follow a serial pattern; n=705), or speed of processing (visual search and identification; n=712); or a no-contact control group (n=704). For the 3 treatment groups, 4-session booster training was offered to a 60% random sample 11 months later. Main Outcome Measures Cognitive function and cognitively demanding everyday functioning. Results Thirty participants were incorrectly randomized and were excluded from the analysis. Each intervention improved the targeted cognitive ability compared with baseline, durable to 2 years (P<.001 for all). Eighty-seven percent of speed-, 74% of reasoning-, and 26% of memory-trained participants demonstrated reliable cognitive improvement immediately after the intervention period. Booster training enhanced training gains in speed (P<.001) and reasoning (P<.001) interventions (speed booster, 92%; no booster, 68%; reasoning booster, 72%;. no booster, 49%), which were maintained at 2-year follow-up (P<.001 for both). No training effects on everyday functioning were detected at -2 years. Conclusions Results support the effectiveness and durability of the cognitive training interventions in improving targeted cognitive abilities: Training effects were of a magnitude equivalent to the amount of decline expected in elderly persons without dementia over 7- to 14-year intervals. Because of minimal functional decline across all groups, longer follow-up is likely required to observe training effects on everyday function. C1 Univ Alabama, Dept Psychol, Ctr Res Appl Gerontol, Birmingham, AL 35294 USA. NIA, NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Florida, Inst Aging, Gainesville, FL USA. Univ Florida, Dept Hlth Policy & Epidemiol, Gainesville, FL USA. Univ Florida, Dept Clin & Hlth Psychol, Gainesville, FL USA. Hebrew Rehabil Ctr Aged, Roslindale, MA USA. Johns Hopkins Univ, Dept Mental Hyg, Baltimore, MD USA. Indiana Univ, Sch Med, Dept Psychiat, Bloomington, IN USA. New England Res Inst, Watertown, MA 02172 USA. Penn State Univ, Dept Human Dev & Family Studies, University Pk, PA 16802 USA. RP Ball, K (reprint author), Univ Alabama, Dept Psychol, Ctr Res Appl Gerontol, 924 19th St S,101 Holley Mears Bldg, Birmingham, AL 35294 USA. OI Marsiske, Michael/0000-0001-5973-2116 FU NIA NIH HHS [U01 AG14260, U01 AG014260, U01 AG014263, U01 AG014276, U01 AG014276-04, U01 AG014276-05, U01 AG014276-05S1, U01 AG014276-05S2, U01 AG014276-05S3, U01 AG014276-06A1, U01 AG014276-07, U01 AG014276-07S1, U01 AG014276-08, U01 AG014276-08S1, U01 AG014282, U01 AG014289, U01 AG14263, U01 AG14282, U01 AG14289]; NINR NIH HHS [U01 NR004507, U01 NR004508, U01 NR04507, U01NR04508] NR 57 TC 798 Z9 827 U1 12 U2 123 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 13 PY 2002 VL 288 IS 18 BP 2271 EP 2281 DI 10.1001/jama.288.18.2271 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 614JZ UT WOS:000179186400026 PM 12425704 ER PT J AU Blackman, MB Sorkin, JD Munzer, T Bellantoni, MF Busby-Whitehead, J Stevens, TE Jayme, J O'Connor, KG Christmas, C Tobin, JD Stewart, KJ Cottrell, E St Clair, C Pabst, KM Harman, SM AF Blackman, MB Sorkin, JD Munzer, T Bellantoni, MF Busby-Whitehead, J Stevens, TE Jayme, J O'Connor, KG Christmas, C Tobin, JD Stewart, KJ Cottrell, E St Clair, C Pabst, KM Harman, SM TI Growth hormone and sex steroid administration in healthy aged women and men - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY; MUSCLE STRENGTH; FACTOR-I; TESTOSTERONE REPLACEMENT; BODY-COMPOSITION; HYPOGONADAL MEN; OLDER MEN; ESTROGEN REPLACEMENT; RESISTANCE EXERCISE AB Context Hormone administration to elderly individuals can increase lean body mass (LBM) and decrease fat, but interactive effects of growth hormone (GH) and sex steroids and their influence on strength and endurance are unknown. Objective To evaluate the effects of recombinant human GH and/or sex steroids on body composition, strength, endurance, and adverse outcomes in aged persons. Design, Setting, and Participants A 26-week randomized, double-blind, placebo-controlled parallel-group trial in healthy, ambulatory, community-dwelling US women (n=57) and men (n=74) aged 65 to 88 years recruited between June 1992 and July 1998. Interventions Participants were randomized to receive GH (starting dose, 30 mug/kg reduced to 20 mug/kg, subcutaneously 3 times/wk) + sex steroids (women: transdermal estradiol,100 mug/d, plus oral medroxyprogesterone acetate, 10 mg/d, during the last 10 days of each 28-day cycle [HRT]; men: testosterone enanthate, biweekly intramuscular injections of 100 mg) (n=35); GH + placebo sex steroid (n=30); sex steroid + placebo GH (n=35); or placebo GH + placebo sex steroid (n=31) in a 2 x 2 factorial design. Main Outcome Measures Lean body mass, fat mass, muscle strength, maximum oxygen uptake ((V) over doto(2)max) during treadmill test, and adverse effects. Results In women, LBM increased by 0.4 kg with placebo, 1.2 kg with HRT (P=.09), 1.0 kg with GH (P=.001), and 2.1 kg with GH+HRT (P<.001). Fat mass decreased significantly in the GH and GH+HRT groups. In men, LBM increased by 0.1 kg with placebo, 1.4 kg with testosterone (P=.06), 3.1 kg with GH (P<.001), and 4.3 kg with GH+testosterone (P<.001). Fat mass decreased significantly with GH and GH+testosterone. Women's strength decreased in the placebo group and increased's strength nonsignificantly with HRT (P=.09), GH (P=.29), and GH+HRT (P=.14). Men also did not increase significantly except for a marginally significant increase of 13.5 kg with GH+testosterone (P=.05). Women's (V) over dot o(2)max declined by 0.4 mL/min/kg in the placebo and HRT groups but increased with GH (P=.07) and GH+HRT (P=.06). 3 Men's (V) over dot o(2)max declined by 1.2 mL/min/kg with placebo and by 0.4 mL/min/kg with testosterone (P=.49) but increased with GH (P=.11) and with GH+testosterone (P<.001). Changes in strength (r=0.355; P<.001) and in (V) over dot o(2)max (r=0.320; P=.002) were directly related to changes in LBM. Edema was significantly more common in women taking GH (39% vs 0%) and GH+HRT (38% vs 0%). Carpal tunnel symptoms were more common in men taking GH+testosterone (32% vs 0%) and arthralgias were more common in men taking GH (41% vs 0%). Diabetes or glucose intolerance occurred in 18 GH-treated men vs 7 not receiving GH (P=.006). Conclusions In this study, GH with or without sex steroids in healthy, aged women and men increased LBM and decreased fat mass. Sex steroid + GH increased muscle strength marginally and (V) over dot o(2)max in men, but women had no significant change in strength or cardiovascular endurance. Because adverse effects were frequent (importantly, diabetes and glucose intolerance), GH interventions; in the elderly should be confined to controlled studies. C1 Natl Ctr Complementary & Alternat Med, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Endocrinol & Metab, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD 21205 USA. NIA, Endocrine Sect, NIH, Lab Clin Invest,Intramural Res Program, Bethesda, MD 20892 USA. NIA, Metab Sect, NIH, Lab Clin Invest,Intramural Res Program, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. Burgerspital, St Gallen, Switzerland. Univ N Carolina, Sch Med, Div Geriatr Med, Chapel Hill, NC USA. Univ S Alabama, Sch Med, Div Geriatr Med, Mobile, AL USA. Louth Hosp, Louth, Ireland. Kronos Res Inst, Phoenix, AZ USA. RP Blackman, MB (reprint author), Natl Ctr Complementary & Alternat Med, NIH, 8 West Dr,Bldg 15 B-1, Bethesda, MD 20892 USA. OI Bellantoni, Michele/0000-0001-8525-2247 FU NCRR NIH HHS [M0-1-RR-02719]; NIA NIH HHS [R0-1 AG11005] NR 62 TC 257 Z9 264 U1 2 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 13 PY 2002 VL 288 IS 18 BP 2282 EP 2292 DI 10.1001/jama.288.18.2282 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 614JZ UT WOS:000179186400027 PM 12425705 ER PT J AU Gawley, RE Pinet, S Cardona, CM Datta, PK Ren, T Guida, WC Nydick, J Leblanc, RM AF Gawley, RE Pinet, S Cardona, CM Datta, PK Ren, T Guida, WC Nydick, J Leblanc, RM TI Chemosensors for the marine toxin saxitoxin SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID PARALYTIC SHELLFISH TOXINS; ELECTRON-TRANSFER SENSORS; COUMARYL CROWN-ETHER; NEUTRAL MOLECULES; CRYSTAL-STRUCTURE; ION RECOGNITION; MOUSE BIOASSAY; ASSAY; COMPLEXES; RECEPTOR AB Eleven anthracylmethyl crown ethers have been synthesized and evaluated as fluorescence sensors for the marine toxin saxitoxin. Fluorescence enhancement data are consistent with a 1:1 binding complex for all crowns. The binding constants are in the range of 10(4) M-1 in ammonium phosphate buffer (pH 7.1) in 80% ethanol solvent. Selectivity for sensing saxitoxin versus several organic analytes has been demonstrated for the first time. Possible modes of binding are presented, and relevance to saxitoxin monitoring programs are discussed. C1 Univ Miami, Dept Chem, Coral Gables, FL 33124 USA. Univ Miami, NIEHS, Marine & Freshwater Biomed Sci Ctr, Coral Gables, FL 33124 USA. Eckerd Coll, Dept Chem, Petersburg, FL 33711 USA. RP Gawley, RE (reprint author), Univ Miami, Dept Chem, POB 249118, Coral Gables, FL 33124 USA. EM rgawley@miami.edu; rml@miami.edu FU NIEHS NIH HHS [ES05931, ES05705, ES07320] NR 58 TC 42 Z9 42 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD NOV 13 PY 2002 VL 124 IS 45 BP 13448 EP 13453 DI 10.1021/ja027507p PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA 613FW UT WOS:000179122900039 PM 12418897 ER PT J AU Bittner, V Hardison, R Kelsey, SF Weiner, BH Jacobs, AK Sopko, G AF Bittner, V Hardison, R Kelsey, SF Weiner, BH Jacobs, AK Sopko, G TI Non-high-density lipoprotein cholesterol levels predict five-year outcome in the Bypass Angioplasty Revascularization Investigation (BARI) SO CIRCULATION LA English DT Article DE lipids; cholesterol; coronary disease; prognosis ID CORONARY HEART-DISEASE; MORTALITY; MEN; FINLAND; RISK AB Background-Current National Cholesterol Education Program guidelines recommend that non-high-density lipoprotein cholesterol (non-HDL-C) be considered a secondary target of therapy among individuals with triglycerides >2.26 mmol/L. It is not known whether non-HDL-C relates to prognosis among patients with coronary heart disease. Methods and Results-Lipid levels were available at baseline among 1514 patients (73% men; mean age, 61 years) enrolled in the Bypass Angioplasty Revascularization Investigation (BARI); all had multivessel coronary artery disease. Patients were followed for 5 years. Outcomes of death, nonfatal myocardial infarction, and death or myocardial infarction were modeled using univariate and multivariate time-dependent proportional hazards methods; angina pectoris at 5 years was modeled using univariate and multivariate logistic regression. Non-HDL-C was a strong and independent predictor of nonfatal myocardial infarction (multivariate relative risk, 1.049 [95% confidence intervals, 1.006 to 1.093] for every 0.26 mmol/L increase) and angina pectoris (multivariate odds ratio, 1.049 [95% confidence intervals, 1.004 to 1.096] for every 0.26 mmol/L increase), but it did not relate to mortality. HDL-C and LDL-C did not predict events during follow-up. Conclusions-Among patients with lipid values in BARI, non-HDL-C is a strong and independent predictor of nonfatal myocardial infarction and angina pectoris at 5 years, even after consideration of powerful clinical variables. Our data suggest that non-HDL-C is an appropriate treatment target among patients with coronary heart disease. C1 Univ Alabama, Birmingham, AL 35294 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Massachusetts, Worcester, MA USA. Boston Univ, Boston, MA 02215 USA. NHLBI, Bethesda, MD 20892 USA. RP Bittner, V (reprint author), Univ Alabama, LHRB 310,700 19th St S, Birmingham, AL 35294 USA. OI Bittner, Vera/0000-0001-9456-850X FU NHLBI NIH HHS [HL38504, HL42145, HL38524, HL38509, HL38556, HL38493, HL 38512, HL38514-6, HL38532, HL38642, HL38529, HL38518, HL38610] NR 15 TC 93 Z9 101 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 NOV 12 PY 2002 VL 106 IS 20 BP 2537 EP 2542 DI 10.1161/01.CIR.0000038496.57570.06 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 617BH UT WOS:000179339300020 PM 12427648 ER PT J AU Hallett, M AF Hallett, M TI Blepharospasm - Recent advances SO NEUROLOGY LA English DT Review ID BENIGN ESSENTIAL BLEPHAROSPASM; TRANSCRANIAL MAGNETIC STIMULATION; PRIMARY SOMATOSENSORY CORTEX; IDIOPATHIC FOCAL DYSTONIA; REPETITIVE STRAIN INJURY; REGIONAL PAIN SYNDROME; DISORDERS STUDY-GROUP; BLINK REFLEX; MOVEMENT-DISORDERS; WRITERS CRAMP AB Benign essential blepharospasm is a common focal dystonia characterized by involuntary eyelid closure. Its etiology, supported by animal models, appears to be multifactorial, representing the influence of a genetic background and an environmental trigger. The genetic background could be responsible for the reduced brain inhibition, identified with physiologic studies that would set up a permissive condition for increased brain plasticity. Reduced D, receptors identified with PET might be an indicator of this reduced inhibition. The trigger could be repetitive use or local ocular disease. Although symptomatic therapy is available, better approaches are needed and will likely become available as the genetics and pathophysiology become well understood. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 5N226,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. NR 71 TC 78 Z9 87 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV 12 PY 2002 VL 59 IS 9 BP 1306 EP 1312 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 613LT UT WOS:000179134300005 PM 12434791 ER PT J AU Bolla, KI Brown, K Eldreth, D Tate, K Cadet, JL AF Bolla, KI Brown, K Eldreth, D Tate, K Cadet, JL TI Dose-related neurocognitive effects of marijuana use SO NEUROLOGY LA English DT Article ID COGNITIVE DEFICITS; CANNABIS; ECSTASY; PERFORMANCE; IMPAIRMENT; MEMORY; ABUSE; MDMA; MEN; RAT AB Background: Although about 7 million people in the US population use marijuana at least weekly, there is a paucity of scientific data on persistent neurocognitive effects of marijuana use. Objective: To determine if neurocognitive deficits persist in 28-day abstinent heavy marijuana users and if these deficits are dose-related to the number of marijuana joints smoked per week. Methods: A battery of neurocognitive tests was given to 28-day abstinent heavy marijuana abusers. Results: As joints smoked per week increased, performance decreased on tests measuring memory, executive functioning, psychomotor speed, and manual dexterity. When dividing the group into light, middle, and heavy user groups, the heavy group performed significantly below the light group on 5 of 35 measures and the size of the effect ranged from 3.00 to 4.20 SD units. Duration of use had little effect on neurocognitive performance. Conclusions: Very heavy use of marijuana is associated with persistent decrements in neurocognitive performance even after 28 days of abstinence. It is unclear if these decrements will resolve with continued abstinence or become progressively worse with continued heavy marijuana use. C1 Johns Hopkins Univ, Bayview Med Ctr, Dept Neurol, Sch Med, Baltimore, MD 21224 USA. NIDA, IRP, Mol Neuropsychiat Sect, NIH, Baltimore, MD USA. RP Bolla, KI (reprint author), Johns Hopkins Univ, Bayview Med Ctr, Dept Neurol, Sch Med, 4940 Eastern Ave,Hopkins Bayview Res Campus, Baltimore, MD 21224 USA. NR 43 TC 297 Z9 305 U1 7 U2 47 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV 12 PY 2002 VL 59 IS 9 BP 1337 EP 1343 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 613LT UT WOS:000179134300010 PM 12427880 ER PT J AU Sumner, CJ Fischbeck, KH AF Sumner, CJ Fischbeck, KH TI Jaw drop in Kennedy's disease SO NEUROLOGY LA English DT Article ID RECESSIVE BULBOSPINAL NEURONOPATHY C1 NINDS, Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Sumner, CJ (reprint author), Bldg 10,Room 3B11,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 7 TC 3 Z9 4 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 NOV 12 PY 2002 VL 59 IS 9 BP 1471 EP 1472 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 613LT UT WOS:000179134300044 PM 12427914 ER PT J AU Kondrashov, AS Sunyaev, S Kondrashov, FA AF Kondrashov, AS Sunyaev, S Kondrashov, FA TI Dobzhansky-Muller incompatibilities in protein evolution SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MULTIPLE SEQUENCE ALIGNMENT; CORRELATED MUTATIONS; SUPPRESSOR MUTATION; EPISODIC EVOLUTION; STRUCTURAL BASIS; GENE; SPECIATION; DROSOPHILA; RECEPTOR; DISEASE AB We study fitness landscape in the space of protein sequences by relating sets of human pathogenic missense mutations in 32 proteins to amino acid substitutions that occurred in the course of evolution of these proteins. On average, approximate to10% of deviations of a nonhuman protein from its human ortholog are compensated pathogenic deviations (CPDs), i.e., are caused by an amino acid substitution that, at this site, would be pathogenic to humans. Normal functioning of a CPD-containing protein must be caused by other, compensatory deviations of the nonhuman species from humans. Together, a CPD and the corresponding compensatory deviation form a Dobzhansky-Muller incompatibility that can be visualized as the corner on a fitness ridge. Thus, proteins evolve along fitness ridges which contain only approximate to10 steps between successive corners. The fraction of CPDs among all deviations of a protein from its human ortholog does not increase with the evolutionary distance between the proteins, indicating that substitutions that carry evolving proteins around these corners occur in rapid succession, driven by positive selection. Data on fitness of interspecies hybrids suggest that the compensatory change that makes a CPD fit usually occurs within the same protein. Data on protein structures and on cooccurrence of amino acids at different sites of multiple orthologous proteins often make it possible to provisionally identify the substitution that compensates a particular CPD. C1 NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. European Mol Biol Lab, D-69117 Heidelberg, Germany. RP Kondrashov, FA (reprint author), NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RI Kondrashov, Fyodor Alexeevich/H-6331-2015 OI Kondrashov, Fyodor Alexeevich/0000-0001-8243-4694 NR 52 TC 169 Z9 172 U1 1 U2 12 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 NOV 12 PY 2002 VL 99 IS 23 BP 14878 EP 14883 DI 10.1073/pnas.232565499 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 615AZ UT WOS:000179224800049 PM 12403824 ER PT J AU Kobiler, O Koby, S Teff, D Court, D Oppenheim, AB AF Kobiler, O Koby, S Teff, D Court, D Oppenheim, AB TI The phage lambda CII transcriptional activator carries a C-terminal domain signaling for rapid proteolysis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ATP-DEPENDENT PROTEASE; ESCHERICHIA-COLI FTSH; BACTERIOPHAGE-LAMBDA; IN-VIVO; DEGRADATION; STABILITY; SIGMA(32); RNA; PURIFICATION; MUTAGENESIS AB ATP-dependent proteases, like FtsH (HfIB), recognize specific protein substrates. One of these is the lambda CII protein, which plays a key role in the phage lysis-lysogeny decision. Here we provide evidence that the conserved C-terminal end of CII acts as a necessary and sufficient cis-acting target for rapid proteolysis. Deletions of this conserved tag, or a mutation that confers two aspartic residues at its C terminus do not affect the structure or activity of CII. However, the mutations abrogate CII degradation by FtsH. We have established an in vitro assay for the lambda CIII protein and demonstrated that CIII directly inhibits proteolysis by FtsH to protect CII and CII mutants from degradation. Phage A carrying mutations in the C terminus of CII show increased frequency of lysogenization, which indicates that this segment of CII may itself be sensitive to regulation that affects the lysis-lysogeny development. In addition, the region coding for the C-terminal end of CII overlaps with a gene that encodes a small antisense RNA called OOP. We show that deletion of the end of the cII gene can prevent OOP RNA, supplied in trans, interfering with CII activity. These findings provide an example of a gene that carries a region that modulates stability at the level of mRNA and protein. C1 NCI, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Mol Genet & Biotechnol, IL-91120 Jerusalem, Israel. RP Oppenheim, AB (reprint author), NCI, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. RI Kobiler, Oren/J-2268-2012 OI Kobiler, Oren/0000-0001-9914-3770 NR 36 TC 46 Z9 47 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 NOV 12 PY 2002 VL 99 IS 23 BP 14964 EP 14969 DI 10.1073/pnas.222172499 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 615AZ UT WOS:000179224800065 PM 12397182 ER PT J AU Liu, CY Pouliot, JJ Nash, HA AF Liu, CY Pouliot, JJ Nash, HA TI Repair of topoisomerase I covalent complexes in the absence of the tyrosyl-DNA phosphodiesterase Tdp1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SACCHAROMYCES-CEREVISIAE; APURINIC ENDONUCLEASE; STRAND BREAKS; YEAST; GENE; RECOMBINATION; MUTANTS; DAMAGE; IDENTIFICATION; RESISTANCE AB Accidental or drug-induced interruption of the breakage and reunion cycle of eukaryotic topoisomerase I (Top1) yields complexes in which the active site tyrosine of the enzyme is covalently linked to the 3' end of broken DNA. The enzyme tyrosyl-DNA phosphodiesterase (Tdp1) hydrolyzes this protein-DNA link and thus functions in the repair of covalent complexes, but genetic studies in yeast show that alternative pathways of repair exist. Here, we have evaluated candidate genes for enzymes that might act in parallel to Tdp1 so as to generate free ends of DNA. Despite finding that the yeast April protein has a Tdp1-like biochemical activity, genetic inactivation of all known yeast apurinic endonucleases does not increase the sensitivity of a tdp1 mutant to direct induction of Top1 damage. In contrast, assays of growth in the presence of the Top1 poison camptothecin (CPT) indicate that the structure-specific nucleases dependent on RAD1 and MUS81 can contribute independently of TDP1 to repair, presumably by cutting off a segment of DNA along with the topoisomerase. However, cells in which all three enzymes are genetically inactivated are not as sensitive to the lethal effects of CPT as are cells defective in double-strand break repair. We show that the MRE11 gene is even more critical than the RAD52 gene for double-strand break repair of CPT lesions, and comparison of an mre11 mutant with a tdp1 rad1 mus81 triple mutant demonstrates that other enzymes complementary to Tdp1 remain to be discovered. C1 NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. RP NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. EM nash@codon.nih.gov NR 45 TC 110 Z9 112 U1 0 U2 2 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 NOV 12 PY 2002 VL 99 IS 23 BP 14970 EP 14975 DI 10.1073/pnas.182557199 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 615AZ UT WOS:000179224800066 PM 12397185 ER PT J AU Di Palma, F Belyantseva, IA Kim, HJ Vogt, TF Kachar, B Noben-Trauth, K AF Di Palma, F Belyantseva, IA Kim, HJ Vogt, TF Kachar, B Noben-Trauth, K TI Mutations in Mcoln3 associated with deafness and pigmentation defects in varitint-waddler (Va) mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MUCOLIPIDOSIS TYPE-IV; NONSELECTIVE CATION CHANNEL; W-LOCUS; C-KIT; CAENORHABDITIS-ELEGANS; PROTO-ONCOGENE; ION CHANNELS; SI-LOCUS; MOUSE; GENE AB Deafness in spontaneously occurring mouse mutants is often associated with defects in cochlea sensory hair cells, opening an avenue to systematically identify genes critical for hair cell structure and function. The classical semidominant mouse mutant varitint-waddler (Va) exhibits early-onset hearing loss, vestibular defects, pigmentation abnormalities, and perinatal lethality. A second allele, Va(J), which arose in a cross segregating for Va, shows a less severe phenotype. By using a positional cloning strategy, we identify two additional members of the mucolipin gene family (Mcoln2 and Mcoln3) in the 350-kb Va(J) minimal interval and provide evidence for Mcoln3 as the gene mutated in varitint-waddler. Mcoln3 encodes a putative six-transmembrane-domain protein with sequence and motif similarities to the family of nonselective transient-receptor-potential (TRP) ion channels. In the Va allele an Ala419Pro substitution occurs in the fifth transmembrane domain of Mcoln3, and in Va(J), a second sequence alteration (IIe362Thr) occurring in cis partially rescues the Va allele. Mcoln3 localizes to cytoplasmic compartments of hair cells and plasma membrane of stereocilia. Hair cell defects are apparent by embryonic day 17.5, assigning Mcoln3 an essential role during early hair cell maturation. Our data suggest that Mcoln3 is involved in ion homeostasis and acts cell-autonomously. Hence, we identify a molecular link between hair cell physiology and melanocyte function. Last, MCOLN2 and MCOLN3 are candidate genes for hereditary and/or sporadic forms of neurosensory disorders in humans. C1 Natl Inst Deafness & Other Commun Disorders, Neurogenet Sect, Mol Biol Lab, NIH, Rockville, MD 20850 USA. Natl Inst Deafness & Other Commun Disorders, Sect Struct Cell Biol, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA. RP Noben-Trauth, K (reprint author), Natl Inst Deafness & Other Commun Disorders, Neurogenet Sect, Mol Biol Lab, NIH, 5 Res Court, Rockville, MD 20850 USA. NR 41 TC 137 Z9 146 U1 1 U2 2 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 NOV 12 PY 2002 VL 99 IS 23 BP 14994 EP 14999 DI 10.1073/pnas.222425399 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 615AZ UT WOS:000179224800070 PM 12403827 ER PT J AU Silva, AC Koretsky, AP AF Silva, AC Koretsky, AP TI Laminar specificity of functional MRI onset times during somatosensory stimulation in rat SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN AUDITORY-CORTEX; OCULAR DOMINANCE COLUMNS; CORTICAL BLOOD-FLOW; EVENT-RELATED FMRI; FOREPAW STIMULATION; WHISKER STIMULATION; CEREBRAL-CORTEX; VISUAL-CORTEX; INITIAL DIP; HUMAN BRAIN AB The blood oxygenation level-dependent (BOLD) response to somatosensory stimulation was measured in alpha-chloralose-anesthetized rats. BOLD fMRI was obtained at 40-ms temporal resolution and spatial resolution of 200 x 200 x 2,000 mum(3) by using a gated activation paradigm in an 11.7 T MRI. Results show a consistent heterogeneity of fMRI onset times and amplitudes. The earliest onset time (0.59 +/- 0.17 s, n = 9) corresponded anatomically to layer IV, with superficial and deeper layers starting significantly later (1.27 +/- 0.43 s in layers I-III, and 1.11 +/- 0.45 s in layer VI). The amplitude of BOLD signal changes also varied with the cortical depth from the pial surface. Changes in the supragranular layers (8.3%) were 44% bigger than changes in the intermediate layers (5.5%), located only approximate to700 mum below, and 144% larger than the bottom layer (3.5%), located approximate to1.4 mm below the pial surface. The data presented demonstrate that BOLD signal changes have distinct amplitude and temporal characteristics, which vary spatially across cortical layers. C1 NINDS, Lab Funct & Mol Imaging, Bethesda, MD 20892 USA. RP Silva, AC (reprint author), NINDS, Lab Funct & Mol Imaging, 10 Ctr Dr,Bldg 10-B1D118, Bethesda, MD 20892 USA. RI Silva, Afonso/A-7129-2009; Koretsky, Alan/C-7940-2015 OI Koretsky, Alan/0000-0002-8085-4756 NR 56 TC 138 Z9 141 U1 0 U2 2 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 NOV 12 PY 2002 VL 99 IS 23 BP 15182 EP 15187 DI 10.1073/pnas.222561899 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 615AZ UT WOS:000179224800102 PM 12407177 ER PT J AU Psaty, BM Manolio, TA Smith, NL Heckbert, SR Gottdiener, JS Burke, GL Weissfeld, J Enright, P Lumley, T Powe, N Furberg, CD AF Psaty, BM Manolio, TA Smith, NL Heckbert, SR Gottdiener, JS Burke, GL Weissfeld, J Enright, P Lumley, T Powe, N Furberg, CD TI Time trends in high blood pressure control and the use of antihypertensive medicationsin older adults - The cardiovascular health study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID PRACTICE GUIDELINES COMMITTEE; ASSOCIATION TASK-FORCE; ISOLATED SYSTOLIC HYPERTENSION; ACUTE MYOCARDIAL-INFARCTION; OF-VETERANS-AFFAIRS; UNITED-STATES; PHARMACOLOGICAL TREATMENT; CALCIUM-ANTAGONISTS; ACC/AHA GUIDELINES; TEMPORAL PATTERNS AB Background: Control of high blood pressure (BP) in older adults is an important part of public health efforts at prevention. Objective: To assess recent time trends in the awareness, treatment, and control of high BP and in the use of medications to treat high BP. Methods: In the Cardiovascular Health Study, 5888 adults 65 years and older were recruited from 4 US centers. At baseline, participants underwent an extensive examination that included the measurement of BP, use of medications, and other risk factors. Participants were followed up with annual visits that assessed BP and medication use from baseline,in 1989-1990 through the examination in 1998-1999. The primary outcome measures were control of BP to levels lower than than 140/90 mm Hg and the prevalence of use of various classes of antihypertensive medications. Results: The awareness, treatment, and control of high BP improved during the 1990s. The proportions aware and treated were higher among blacks than whites, though control prevalences were similar. For both groups combined, the control of high BP to lower than 140/90 mm Hg increased from 37% at baseline to 49% in 1999. The 51% whose BP was not controlled generally had isolated mild to moderate elevations in systolic BP. Among treated persons, the improvement in control was achieved in part by a mean increase of 0.2 antihypertensive medications per person over the course of 9 years. Improved control was also achieved by increasing the proportion of the entire Cardiovascular Health Study population that was treated for hypertension, from 34.5% in 1990 to 51.1% in 1999. Time trends in antihypertensive drug use were pronounced. Among those without coronary disease, the use of low-dose diuretics and beta-blockers decreased, while the use of newer agents, such as calcium channel blockers, angiotensin-converting enzyme inhibitors, and alpha-blockers increased. Conclusions: While control of high BP improved in the 1990s, about half the participants with hypertension had uncontrolled BP, primarily mild to moderate elevations in systolic BP. Low-dose diuretics and beta-blockers-the preferred agents since 1993 according to the recommendations of the joint National Committee on the Detection, Evaluation and Treatment of High Blood Pressure-remained underused. More widespread use of these agents will be an important intervention to prevent the devastating complications of hypertension, including stroke, myocardial infarction, and heart failure. C1 Univ Washington, Cardiovasc Hlth Res Unit, Dept Med Epidemiol & Hlth Serv, Seattle, WA 98101 USA. Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98101 USA. Univ Washington, Cardiovasc Hlth Res Unit, Dept Biostat, Seattle, WA 98101 USA. NHLBI, Epidemiol & Biometry Program, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. St Francis Hosp, Roslyn, NY USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27103 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Resp Sci, Tucson, AZ USA. Johns Hopkins Univ, Dept Med, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. RP Psaty, BM (reprint author), Univ Washington, Cardiovasc Hlth Res Unit, Dept Med Epidemiol & Hlth Serv, 1730 Minor Ave,Suite 1360, Seattle, WA 98101 USA. FU CCR NIH HHS [RC-HL35129, RC-HL15103]; NHLBI NIH HHS [N01-HC-85081, N01-HC-85085, N01-HC-85079, N01-HC-85086, N01-HC-85082, N01-HC-85083, HL43201, N01-HC-85084, N01-HC-85080]; NIA NIH HHS [AG09556] NR 61 TC 95 Z9 99 U1 0 U2 3 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 NOV 11 PY 2002 VL 162 IS 20 BP 2325 EP 2332 DI 10.1001/archinte.162.20.2325 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 613TV UT WOS:000179148300006 PM 12418946 ER PT J AU Hartman, NR Cysyk, RL Bruneau-Wack, C Thenot, JP Parker, RJ Strong, JM AF Hartman, NR Cysyk, RL Bruneau-Wack, C Thenot, JP Parker, RJ Strong, JM TI Production of intracellular S-35-glutathione by rat and human hepatocytes for the quantification of xenobiotic reactive intermediates SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article DE adducts; glutathione; hepatocytes; acetaminophen; reactive intermediates; metabolism ID LIQUID-CHROMATOGRAPHY; COVALENT BINDING; GLUTATHIONE; PARACETAMOL; ACETAMINOPHEN; SPECTROMETRY; METABOLISM; TOXICITY; LIVER; DNA AB The quantification and identification of xenobiotic reactive intermediates is difficult in the absence of highly radiolabeled drug. We have developed a method for identifying these intermediates by measuring the formation of adducts to intracellularly generated radiolabeled glutathione (GSH). Freshly isolated adherent rat and human hepatocytes were incubated overnight in methionine and cystine-free ('thio-free') medium. They were then exposed to 100 muM methionine and 10 muCi S-35-labeled methionine in otherwise thio-free medium to replete Cellular GSH pools with intracellularly generated S-35-labeled GSH. After 3 h, acetaminophen was added as a test compound and the cells were incubated for an additional 24 h. Intracellular GSH and its specific activity were quantified after reaction with monobromobimane followed by HPLC analysis with fluorescence and radiochemical detection. Radiolabeled GSH as detectable at 3 h and maintained high specific activity and physiological concentrations for up to 24 h. Incubation medium from acetaminophen treated and nontreated hepatocytes were analyzed for radiolabeled peaks by HPLC using radiochemical detection, Radiolabeled peaks not present in nontreated hepatocytes were identified as acetaminophen GSH adducts by LC-MS. Formation of acetaminophen S-35-GSH adducts by rat hepatocytes containing endogenously synthesized S-35-GSH was increased with acetaminophen concentrations ranging from 500 to 2 mM. Published by Elsevier Science Ireland Ltd. C1 US FDA, Ctr Drug Evaluat & Res, Off Testing & Res, Lab Clin Pharmacol, Laurel, MD USA. NCI, Basic Res Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Sanofi Synthelabo Rech, Pharmacokinet & Metab, F-91380 Chilly Mazarin, France. RP Strong, JM (reprint author), Room 2017,Mod-1,8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 18 TC 14 Z9 14 U1 0 U2 2 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 NOV 10 PY 2002 VL 142 IS 1-2 BP 43 EP 55 AR PII S0009-2797(02)00053-4 DI 10.1016/S0009-2797(02)00053-4 PG 13 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 616QJ UT WOS:000179314200005 PM 12399154 ER PT J AU Kapetanovic, IM Torchin, CD Strong, JM Yonekawa, WD Lu, C Li, AP Dieckhaus, CM Santos, WL Macdonald, TL Sofia, RD Kupferberg, HJ AF Kapetanovic, IM Torchin, CD Strong, JM Yonekawa, WD Lu, C Li, AP Dieckhaus, CM Santos, WL Macdonald, TL Sofia, RD Kupferberg, HJ TI Reactivity of atropaldehyde, a felbamate metabolite in human liver tissue in vitro SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article DE reactive metabolites; aldehyde dehydrogenase; glutathione transferase; atropaldehyde; glutathione; hepatocytes ID GLUTATHIONE S-TRANSFERASES; IN-VITRO; MERCAPTURIC ACIDS; OXIDATIVE STRESS; HUMAN URINE; RAT; TOXICITY; IDENTIFICATION; ACROLEIN; DETOXIFICATION AB Antiepileptic therapy with a broad spectrum drug felbamate (FBM) has been limited due to reports of hepatotoxicity and aplastic anemia associated with its use. It was proposed that a bioactivation of FBM leading to formation of alpha,beta-unsaturated aldehyde, atropaldehyde (ATPAL) could be responsible for toxicities associated with the parent drug. Other members of this class of compounds, acrolein and 4-hydroxynonenal (HNE), are known for their reactivity and toxicity. It has been proposed that the bioactivation of FBM to ATPAL proceeds though a more stable cyclized product, 4-hydroxy-5-phenyltetrahydro-1.3-oxazin-2-one (CCMF) whose formation has been shown recently. Aldehyde dehydrogenase (ALDH) and glutathione transferase (GST) are detoxifying enzymes and targets for reactive aldehydes. This study examined effects of ATPAL and its precursor, CCMF on ALDH, GST and cell viability in liver, the target tissue for its metabolism and toxicity. A known toxin, HNE, which is also a substrate for ALDH and GST, was used for comparison. Interspecies difference in metabolism of FBM is well documented, therefore, human tissue was deemed most relevant and used for these studies. ATPAL inhibited ALDH and GST activities and led to a loss of hepatocyte viability. Several fold greater concentrations of CCMF were necessary to demonstrate a similar degree of ALDH inhibition or cytotoxicity as observed with ATPAL. This is consistent with CCMF requiring prior conversion to the more proximate toxin, ATPAL. GSH was shown to protect against ALDH inhibition by ATPAL. In this context. ALDH and GST are detoxifying pathways and their inhibition would lead to an accumulation of reactive species from FBM metabolism and/or metabolism of other endogenous or exogenous compounds and predisposing to or causing toxicity. Therefore, mechanisms of reactive aldehydes toxicity could include direct interaction with critical cellular macromolecules or indirect interference with cellular detoxification mechanisms. Published by Elsevier Science Ireland Ltd. C1 US FDA, CDER, Lab Clin Pharmacol, MOD1, Laurel, MD 20708 USA. NINDS, NIH, Bethesda, MD 20892 USA. In Vitro Technol, Baltimore, MD 21227 USA. Univ Virginia, Dept Chem, Charlottesville, VA 22901 USA. Wallace Labs, Cranbury, NJ 08512 USA. RP Kapetanovic, IM (reprint author), NCI, Div Canc Prevent, Chemoprevent Agent Dev Res Grp, NIH, 6130 Execut Blvd,Suite 2116,MSC 7322, Bethesda, MD 20892 USA. OI Santos, Webster/0000-0002-4731-8548; Li, Albert/0000-0001-5772-6265 NR 30 TC 18 Z9 18 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD NOV 10 PY 2002 VL 142 IS 1-2 BP 119 EP 134 AR PII S0009-2797(02)00058-3 DI 10.1016/S0009-2797(02)00058-3 PG 16 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 616QJ UT WOS:000179314200010 PM 12399159 ER PT J AU Garcia-Closas, M Herbstman, J Schiffman, M Glass, A Dorgan, JF AF Garcia-Closas, M Herbstman, J Schiffman, M Glass, A Dorgan, JF TI Relationship between serum hormone concentrations, reproductive history, alcohol consumption and genetic polymorphisms in pre-menopausal women SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE sex hormones; pre-menopausal women; genetic polymorphisms; alcohol; reproductive history ID BREAST-CANCER RISK; CATECHOL-O-METHYLTRANSFERASE; POLYCYSTIC-OVARY-SYNDROME; POSTMENOPAUSAL WOMEN; PREMENOPAUSAL WOMEN; CYTOCHROME-P450 1B1; LUTEINIZING-HORMONE; CYP17 POLYMORPHISM; BINDING GLOBULIN; SEX-HORMONES AB Reproductive characteristics, alcohol intake and polymorphisms in genes encoding sex-steroid metabolizing enzymes might influence the risk of hormone-related cancers by changing circulating concentrations of sex hormones. The relationship between these factors and serum concentrations of estradiol, progesterone, androstenedione, testosterone and DHEA was evaluated in a cross-sectional study of 218 pre-menopausal women from Kaiser Permanente Health Plan in Portland, Oregon. Risk factor information was obtained from questionnaires and hormone serum concentrations were determined by radioimmunoassays. Genotypes for CYP11A 5'UTR(tttta)n, CYP17 5'-UTR -34 T>C, CYP19 IVS4(ttta)n, CYP1B1 (L432V and S453N) and COMT(VI58M) were determined from genomic DNA samples. Increasing number of full-term pregnancies was associated with a significant decrease in late-follicular progesterone levels (p-trend = 0.03). Increasing alcohol consumption was associated with higher estradiol levels averaged through the menstrual cycle (p-trend = 0.009) and higher progesterone levels during luteal phase (p-trend = 0.04). Androstenedione and testosterone levels were higher among light to moderate drinkers compared to non-drinkers, although we only observe a significant trend with increasing levels of alcohol consumption for androstenedione. Women heterozygous or homozygous for the CYP1B1 L432V or the S453N polymorphisms had increased luteal estradiol levels (p-value = 0.04 for L432V and 0.04 for S453N). None of the other factors evaluated was significantly associated with serum concentration of hormones. In conclusion, results from this cross-sectional study of pre-menopausal women provide support for an association between light to moderate alcohol intake and elevated levels of estrogen and androgen levels. Our data suggest that circulating levels of progesterone might be related to parity and alcohol consumption, however the biological plausibility of the observed associations is unclear. We found little support for an influence of the evaluated genetic polymorphisms in the steroid synthesis and metabolism pathway on serum hormone levels, except for a possible effect of the CYP1B1 L432V and S453N polymorphisms on serum estradiol levels. (C) 2002 Wiley-Liss, Inc. C1 NCI, Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. Kaiser Permanente, Hlth Plan, Portland, OR USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RP Garcia-Closas, M (reprint author), NCI, Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 7076, Rockville, MD 20852 USA. RI Garcia-Closas, Montserrat /F-3871-2015 OI Garcia-Closas, Montserrat /0000-0003-1033-2650 NR 62 TC 80 Z9 82 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 NOV 10 PY 2002 VL 102 IS 2 BP 172 EP 178 DI 10.1002/ijc.10651 PG 7 WC Oncology SC Oncology GA 603QF UT WOS:000178570600011 PM 12385014 ER PT J AU Rabkin, M El-Sadr, W Katzenstein, DA Mukherjee, J Masur, H Mugyenyi, P Munderi, P Darbyshire, J AF Rabkin, M El-Sadr, W Katzenstein, DA Mukherjee, J Masur, H Mugyenyi, P Munderi, P Darbyshire, J TI Antiretroviral treatment in resource-poor settings: clinical research priorities SO LANCET LA English DT Editorial Material ID IMMUNODEFICIENCY-VIRUS INFECTION; CD4 CELL COUNT; VIRAL LOAD; DISEASE PROGRESSION; CONTROLLED TRIAL; THERAPY; ADHERENCE; INDINAVIR; AIDS C1 Columbia Univ, Dept Med, New York, NY 10027 USA. Columbia Univ, Harlem Hosp, Mailman Sch Publ Hlth, New York, NY USA. Columbia Univ, Harlem Hosp, Div Infect Dis, New York, NY USA. Stanford Univ, Dept Med, Stanford, CA 94305 USA. Harvard Univ, Sch Med, Dept Social Med, Boston, MA 02115 USA. NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. Joint Clin Res Ctr, Kampala, Uganda. WHO, Dept Essential Drugs & Med, CH-1211 Geneva, Switzerland. Med Res Ctr, Clin Trials Unit, London, England. RP Rabkin, M (reprint author), Columbia Univ, Dept Med, New York, NY 10027 USA. NR 26 TC 38 Z9 39 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD NOV 9 PY 2002 VL 360 IS 9344 BP 1503 EP 1505 DI 10.1016/S0140-6736(02)11478-4 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 614JV UT WOS:000179186000031 PM 12433534 ER PT J AU Barrientos, LG Gronenborn, AM AF Barrientos, LG Gronenborn, AM TI The domain-swapped dimer of cyanovirin-N contains two sets of oligosaccharide binding sites in solution SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE cyanovirin-N; domain-swapped dimer; high-mannose sugars; protein-carbohydrate interaction; HIV inactivation ID HIV-INACTIVATING PROTEIN; GP120; GLYCOPROTEINS AB The binding of high-mannose oligosaccharides to the domain-swapped dimeric form of the potent HIV-inactivating protein cyanovirin-N (CV-N) was investigated in solution by NMR, complementing recent structural studies by X-ray crystallography on similar complexes [J. Biol. Chem. 277 (2002) 34336]. The crystal structures of CV-N dimer complexed with Man-9 and hexamannoside revealed two carbohydrate binding sites on opposite ends of the molecule. No binding was observed at site 1, previously identified on the solution monomer of CV-N [Structure 9 (2001) 931; Shenoy et al., Chem. Biol. 9 (2002) 1109]. Here, we report the presence of four sugar binding sites on the CV-N dimer in solution, identified by chemical shift mapping with hexamannoside and nonamannoside, synthetic substructures of Man-9. Our results demonstrate that in solution the domain-swapped CV-N dimer, like the CV-N monomer, contains two types of sites that are available for carbohydrate binding, suggesting that the occlusion of the primary sites in the crystal is due to specific features of the solid state. (C) 2002 Elsevier Science (USA). All rights reserved. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Gronenborn, AM (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NR 15 TC 25 Z9 25 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE 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 NOV 8 PY 2002 VL 298 IS 4 BP 598 EP 602 AR PII S0006-291X(02)02489-0 DI 10.1016/S0006-291X(02)02489-0 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 616AR UT WOS:000179280000022 PM 12408994 ER PT J AU Barazi, HO Li, ZQ Cashel, JA Krutzsch, HC Annis, DS Mosher, DF Roberts, DD AF Barazi, HO Li, ZQ Cashel, JA Krutzsch, HC Annis, DS Mosher, DF Roberts, DD TI Regulation of integrin function by CD47 ligands - Differential effects on alpha(v)beta(3) and alpha(4)beta(1) integrin-mediated adhesion SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-BINDING DOMAIN; PROTEIN CD47; T-CELLS; ALPHA(3)BETA(1) INTEGRIN; SIGNALING PATHWAY; PLASMA-MEMBRANE; RECEPTOR; THROMBOSPONDIN-1; ACTIVATION; IDENTIFICATION AB We examined the regulation of alpha(4)beta(1) integrin function in melanoma cells and T cells by ligands of CD47. A CD47 antibody (B6H12) that inhibited alpha(v)beta(3)-mediated adhesion of melanoma cells induced by CD47-binding peptides from thrombospondin-1 directly stimulated alpha(4)beta(1)-mediated adhesion of the same cells to vascular cell adhesion molecule-1 and N-terminal regions of thrombospondin-1 or thrombospondin-2. B6H12 also stimulated alpha(4)beta(1)- as well as alpha(2)beta(1)- and alpha(5)beta(1)-mediated adhesion of CD47-expressing T cells but not of CD47-deficient T cells. alpha(4)beta(1) and CD47 co-purified as a detergent-stable complex on a CD47 antibody affinity column. CD47-binding peptides based on C-terminal sequences of thrombospondin-1 also, specifically enhanced adhesion of melanoma cells and T cells to alpha(4)beta(1) ligands. Unexpectedly, activation of alpha(4)beta(1) function by the thrombospondin-1 CD47-hinding peptides also occurred in CD47-deficient T cells. CD47-independent activation of alpha(4)beta(1), required the Val-Val-Met (VVM) motif of the peptides and was sensitive to inhibition by pertussis toxin. These results indicate that activation of alpha(4)beta(1), by the CD47 antibody B6H12 and by VVM peptides occurs by different mechanisms. The antibody directly activates a CD47-alpha(4)beta(1) complex, whereas VVM peptides may target an unidentified G(i)-linked receptor that regulates alpha(4)beta(1). C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Univ Wisconsin, Dept Med, Madison, WI 53706 USA. RP Roberts, DD (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Rm 2A33,10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 52 TC 46 Z9 46 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 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 8 PY 2002 VL 277 IS 45 BP 42859 EP 42866 DI 10.1074/jbc.M206849200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 612MZ UT WOS:000179081200058 PM 12218055 ER PT J AU Perrot, V Vazquez-Prado, J Gutkind, JS AF Perrot, V Vazquez-Prado, J Gutkind, JS TI Plexin B regulates Rho through the guanine nucleotide exchange factors leukemia-associated rho GEF (LARG) and PDZ-RhoGEF SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HETEROTRIMERIC G-PROTEINS; AXON GUIDANCE; ACTIVE RAC; SEMAPHORIN RECEPTORS; MOLECULAR-BASIS; P115 RHOGEF; BINDING; CYTOSKELETON; GTPASES; FAMILY AB Plexins represent a novel family of transmembrane receptors that transduce attractive and repulsive signals mediated by the axon-guiding molecules semaphorins. Emerging evidence implicates Rho GTPases in these biological events. However, Plexins lack any known catalytic activity in their conserved cytoplasmic tails, and how they transduce signals from semaphorins to Rho is still unknown. Here we show that Plexin B2 associates directly with two members of a recently identified family of Dbl homology/pleckstrin homology containing guanine nucleotide exchange factors for Rho, PDZ-RhoGEF, and Leukemia-associated Rho GEF (LARG). This physical interaction is mediated by their PDZ domains and a PDZ-binding motif found only in Plexins of the B family. In addition, we show that ligand-induced dimerization of Plexin B is sufficient to stimulate endogenous RhoA potently and to induce the reorganization of the cytoskeleton. Moreover, overexpression of the PDZ domain of PDZ-RhoGEF but not its regulator of G protein signaling domain prevents cell rounding and neurite retraction of differentiated PC12 cells induced by activation of endogenous Plexin 131 by semaphorin 4D. The association of Plexins with LARG and PDZ-RhoGEF thus provides a direct molecular mechanism by which semaphorins acting on Plexin B can control Rho, thereby regulating the actin-cytoskeleton during axonal guidance and cell migration. C1 Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Gutkind, JS (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, 9000 Rockville Pike,Bldg 30,Rm 211, Bethesda, MD 20892 USA. RI Gutkind, J. Silvio/A-1053-2009; VAZQUEZ-PRADO, JOSE/C-1630-2017 NR 29 TC 158 Z9 164 U1 0 U2 3 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 NOV 8 PY 2002 VL 277 IS 45 BP 43115 EP 43120 DI 10.1074/jbc.M206005200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 612MZ UT WOS:000179081200091 PM 12183458 ER PT J AU Goldschmidt, V Rigourd, M Ehresmann, C Le Grice, SFJ Ehresmann, B Marquet, R AF Goldschmidt, V Rigourd, M Ehresmann, C Le Grice, SFJ Ehresmann, B Marquet, R TI Direct and indirect contributions of RNA secondary structure elements to the initiation of HIV-1 reverse transcription SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PRIMER-BINDING-SITE; DEPENDENT DNA-POLYMERASE; YEAST TY1 RETROTRANSPOSON; EFFICIENT INITIATION; TYPE-1 RNA; ANTISENSE OLIGONUCLEOTIDES; MUTATIONAL ANALYSIS; GENETIC-ANALYSIS; TEMPLATE-PRIMER AB Initiation of human immunodeficiency virus type 1 (HIV-1) reverse transcription requires specific recognition between the viral RNA (vRNA), tRNA(3)(Lys), which acts as primer, and reverse transcriptase (RT). The specificity of this ternary complex is mediated by intricate interactions between the HIV-1 RNA and tRNA(3)(Lys). Here, we compared the relative importance of the secondary structure elements of this complex in the initiation process. To this aim, we used the previously published three-dimensional model of the initiation complex to rationally introduce a series of deletions and substitutions in the vRNA. When necessary, we used chemical probing to check the structure of the tRNA(3)(Lys)-mutant vRNA complexes. For each of them, we measured the binding affinity of RT and the kinetics of initial extension of tRNA(3)(Lys) and of synthesis of the (-) strand strong stop DNA. Our results were overall in keeping with the three-dimensional model of the initiation complex. Surprisingly, we found that disruption of the intermolecular template-primer interactions, which are not directly recognized by RT, more severely affected reverse transcription than deletions or disruption of one of the intramolecular helices to which RT directly binds. Perturbations of the highly constrained junction between the intermolecular helix formed by the primer binding site and the 3' end of tRNA(3)(Lys) and the helix immediately upstream also had dramatic effects on the initiation of reverse transcription. Taken together, our results demonstrate the overwhelming importance of the overall three-dimensional structure of the initiation complex and identify structural elements that constitute promising targets for anti-initiation-specific drugs. C1 Univ Strasbourg 1, Inst Biol Mol & Cellulaire, CNRS, UPR 9002, F-67084 Strasbourg, France. NCI, Resistance Mech Lab, NIH, Frederick, MD 21702 USA. RP Marquet, R (reprint author), Univ Strasbourg 1, Inst Biol Mol & Cellulaire, CNRS, UPR 9002, 15 Rue Rene Descartes, F-67084 Strasbourg, France. OI Marquet, Roland/0000-0002-4209-3976 NR 65 TC 23 Z9 23 U1 0 U2 0 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 NOV 8 PY 2002 VL 277 IS 45 BP 43233 EP 43242 DI 10.1074/jbc.M205295200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 612MZ UT WOS:000179081200105 PM 12194974 ER PT J AU Du, J Stankiewicz, MJ Liu, Y Xi, Q Schmitz, JE Lekstrom-Himes, JA Ackerman, SJ AF Du, J Stankiewicz, MJ Liu, Y Xi, Q Schmitz, JE Lekstrom-Himes, JA Ackerman, SJ TI Novel combinatorial interactions of GATA-1, PU.1, and C/EBP epsilon isoforms regulate transcription of the gene encoding eosinophil granule major basic protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID ENHANCER-BINDING-PROTEIN; MULTIPOTENT HEMATOPOIETIC PROGENITORS; FACTOR-RECEPTOR PROMOTER; SERUM-ALBUMIN GENE; DNA-BINDING; LINEAGE COMMITMENT; GRANULOCYTIC DIFFERENTIATION; ERYTHROID-DIFFERENTIATION; RESTRICTED EXPRESSION; TARGETED DISRUPTION AB GATA-1 and the ets factor PU.1 have been reported to functionally antagonize one another in the regulation of erythroid versus myeloid gene transcription and development. The CCAAT enhancer binding protein epsilon (C/EBPepsilon) is expressed as multiple isoforms and has been shown to be essential to myeloid (granulocyte) terminal differentiation. We have defined a novel synergistic, as opposed to antagonistic, combinatorial interaction between GATA-1 and PU.1, and a unique repressor role for certain C/EBPepsilon isoforms in the transcriptional regulation of a model eosinophil granulocyte gene, the major basic protein (MBP). The eosinophil-specific P2 promoter of the MBP gene contains GATA-1, C/EBP, and PU.1 consensus sites that bind these factors in nuclear extracts of the eosinophil myelocyte cell line, AML14.3D10. The promoter is transactivated by GATA-1 alone but is synergistically transactivated by low levels of PU.1 in the context of optimal levels of GATA-1. The C/EBPepsilon(27) isoform strongly represses GATA-1 activity and completely blocks GATA-1/PU.1 synergy. In vitro mutational analyses of the MBP-P2 promoter showed that both the GATA-1/PU.1 synergy, and repressor activity of C/EBPepsilon(27) are mediated via protein-protein interactions through the C/EBP and/or GATA-binding sites but not the PU.1 sites. Co-immunoprecipitations using lysates of AML14.3D10 eosinophils show that both C/EBPepsilon(32/30) and epsilon(27) physically interact in vivo with PU.1 and GATA-1, demonstrating functional interactions among these factors in eosinophil progenitors. Our findings identify novel combinatorial protein-protein interactions for GATA-1, PU.1, and C/EBPepsilon isoforms in eosinophil gene transcription that include GATA-1/PU.1 synergy and repressor activity for C/EBPepsilon(27). C1 Univ Illinois, Coll Med, Dept Biochem & Mol Biol, Chicago, IL 60612 USA. NIH, Host Def Lab, Bethesda, MD 20892 USA. RP Ackerman, SJ (reprint author), Univ Illinois, Coll Med W, Dept Biochem & Mol Biol, MC536,A-312,1819 W Polk St, Chicago, IL 60612 USA. FU NIAID NIH HHS [AI33043] NR 106 TC 67 Z9 68 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 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 8 PY 2002 VL 277 IS 45 BP 43481 EP 43494 DI 10.1074/jbc.M204777200 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 612MZ UT WOS:000179081200133 PM 12202480 ER PT J AU Lee, HC Bernstein, HD AF Lee, HC Bernstein, HD TI Trigger factor retards protein export in Escherichia coli SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL RECOGNITION PARTICLE; INNER MEMBRANE-PROTEINS; NASCENT CHAINS; SELECTIVE BINDING; BACTERIAL PROTEIN; CHAPERONE SECB; SRP; TRANSLOCATION; DNAK; SPECIFICITY AB Trigger factor (TF) is a ribosome-associated protein that interacts with a wide variety of nascent polypeptides in Escherichia coli. Previous studies have indicated that TF cooperates with DnaK to facilitate protein folding, but the basis of this cooperation is unclear. In this study we monitored protein export in E. coli that lack or overproduce TF to obtain further insights into its function. Whereas inactivation of genes encoding most molecular chaperones (including dnaK) impairs protein export, inactivation of the TF gene accelerated protein export and suppressed the need for targeting factors to maintain the translocation competence of pre-secretory proteins. Furthermore, overproduction of TF (but not DnaK) markedly retarded protein export. Manipulation of TF levels produced similar effects on the export of a cytosolic enzyme fused to a signal peptide. The data strongly suggest that TF has a unique ability to sequester nascent polypeptides for a relatively prolonged period. Based on our results, we propose that TF and DnaK promote protein folding by distinct (but complementary) mechanisms. C1 NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Bernstein, HD (reprint author), NIDDK, Genet & Biochem Branch, NIH, Bldg 10,Rm 9D-20, Bethesda, MD 20892 USA. NR 43 TC 55 Z9 55 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 8 PY 2002 VL 277 IS 45 BP 43527 EP 43535 DI 10.1074/jbc.M205950200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 612MZ UT WOS:000179081200138 PM 12205085 ER PT J AU Zhu, XX Yu, QS Cutler, RG Culmsee, CW Holloway, HW Lahiri, DK Mattson, MP Greig, NH AF Zhu, XX Yu, QS Cutler, RG Culmsee, CW Holloway, HW Lahiri, DK Mattson, MP Greig, NH TI Novel p53 inactivators with neuroprotective action: Syntheses and pharmacological evaluation of 2-imino-2,3,4,5,6,7-hexahydrobenzothiazole and 2-imino-2,3,4,5,6,7-hexahydrobenzoxazole derivatives SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID TUMOR-SUPPRESSOR GENE; CELL-DEATH; OLIGOMERIZATION DOMAIN; CRYSTAL-STRUCTURE; PROTECTS NEURONS; BRAIN INJURY; APOPTOSIS; MICE; EXPRESSION; INDUCTION AB Tumor suppressor protein, p53, is an intracellular protein that is critical within the biochemical cascade that leads to cell death via apoptosis. Recent studies identified the tetrahydrobenzothiazole analogue, pifithrin-alpha (2), as a p53 inhibitor that was effective in protecting neuronal cells against a variety of lethal insults and reducing the side effects of anticancer drugs. As up-regulation of p53 has been described as a common feature of several neurodegenerative disorders, including Alzheimer's disease, 2 and novel analogues (3-16) were synthesized to W assess the value of tetrahydrobenzothiazole analogues as neuroprotective agents and (ii) define the structural requirements for p53 inactivation. Not only did 2 exhibit neuroprotective activity in both tissue culture and in vivo stroke models but also compounds 6, 7, 10, 13, 15, and 16 proved to be highly potent in protecting PC12 cells and compounds 3, 4, and 6 were highly potent in protecting primary hippocampal. cells against death induced by the DNA-damaging agent, camptothecin. C1 NIA, Neurosci Lab, Gerontol Res Ctr, Intramural Res Program,NIH, Baltimore, MD 21224 USA. Indiana Univ, Sch Med, Dept Psychiat, Inst Psychiat Res, Indianapolis, IN 46202 USA. RP Greig, NH (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr, Intramural Res Program,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM GreigN@vax.grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 NR 42 TC 72 Z9 76 U1 1 U2 4 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 NOV 7 PY 2002 VL 45 IS 23 BP 5090 EP 5097 DI 10.1021/jm020044d PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 611XH UT WOS:000179042800018 PM 12408720 ER PT J AU Grigorenko, BL Nemukhin, AV Topol, IA Burt, SK AF Grigorenko, BL Nemukhin, AV Topol, IA Burt, SK TI Modeling of biomolecular systems with the quantum mechanical and molecular mechanical method based on the effective fragment potential technique: Proposal of flexible fragments SO JOURNAL OF PHYSICAL CHEMISTRY A LA English DT Article ID AB-INITIO; SERINE PROTEASES; PROTON-TRANSFER; ENERGY MINIMIZATION; QM/MM CALCULATIONS; CHORISMATE MUTASE; CLAISEN REARRANGEMENT; DYNAMICS SIMULATIONS; H+ TRANSLOCATION; EXTENDED SYSTEMS AB Development and applications of a new approach to hybrid quantum mechanical and molecular mechanical (QM/MM) theory based on the effective fragment potential (EFP) technique for modeling properties and reactivity of large molecular systems of biochemical significance are described. It is shown that a restriction of frozen internal coordinates of effective fragments in the original formulation of the theory (Gordon, M.. S.; Freitag, M. A.; Bandyopadhyay, P.; Jensen, J. H.; Kairys, V.; Stevens, W. J. J. Phys. Chem. A 2001, 105, 293) can be removed by introducing a set of small EFs and replacing the EFP-EFP interactions by the customary MM force fields. The concept of effective fragments is also utilized to solve the QM/MM boundary problem across covalent bonds. The buffer fragment, which is common for both subsystems, is introduced and treated specially when energy and. energy gradients are computed. An analysis of conformations of dipeptide-water complexes, as well as of dipepties with His and Lys residues, confirms the reliability of the theory. By using the Hartree-Fock and MP2 quantum chemistry methods with the OPLS-AA molecular mechanical force fields, we calculated the energy difference between the enzyme-substrate complex and the first tetrahedral intermediate for the model active site of the serine protease catalytic system. In another example, the multiconfigurational complete active space self-consistent field (CASSCF) method was used to model the homolytic dissociation of the peptide helix over the central C-N bonds. Finally, the potentials of internal rotation of the water dimer considered as a part of the water wire inside a polyglycine analogue of the ion channel gramicidin A were computed. In all cases, an importance of the peptide environment from MM subsystems on the computed properties of the quantum parts is demonstrated. C1 NCI, SAIC Frederick, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119899, Russia. RP Topol, IA (reprint author), NCI, SAIC Frederick, Adv Biomed Comp Ctr, POB B, Frederick, MD 21702 USA. RI Nemukhin, Alexander/P-9662-2015 NR 73 TC 45 Z9 48 U1 1 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5639 J9 J PHYS CHEM A JI J. Phys. Chem. A PD NOV 7 PY 2002 VL 106 IS 44 BP 10663 EP 10672 DI 10.1021/jp026464w PG 10 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 611HU UT WOS:000179011300024 ER PT J AU Lapidus, LJ Steinbach, PJ Eaton, WA Szabo, A Hofrichter, J AF Lapidus, LJ Steinbach, PJ Eaton, WA Szabo, A Hofrichter, J TI Effects of chain stiffness on the dynamics of loop formation in polypeptides. Appendix: Testing a 1-dimensional diffusion model for peptide dynamics SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID UNFOLDED CYTOCHROME-C; WORMLIKE CHAINS; CONTACT FORMATION; ENERGY-TRANSFER; PROTEINS; KINETICS; POLYMERS; RATES AB Quenching of the triplet state of tryptophan by cysteine provides an important new tool for measuring the rate at which a specific intramolecular contact is formed in disordered polypeptides. By measuring the viscosity dependence of the quenching rate, both the reaction-limited and the diffusion-limited quenching rates can be determined. The diffusion-limited rate corresponds to the rate of forming a short-range contact. The reaction-limited rate, which depends solely on the equilibrium end-to-end distribution, becomes essentially length-independent for short chains, providing clear-cut evidence that the chain is stiff. The length dependence of the reaction-limited rate can be accurately calculated using the distance dependence of the quenching rate determined at room temperature in a rigid glass, together with the end-to-end distance distribution for a wormlike chain having a persistence length of 0.6-0.7 nm. In addition, the length dependence of the diffusion-limited rate can also be reproduced by treating the dynamics as diffusion on the 1D potential of mean force obtained from this distribution. The diffusion coefficient for the chain ends required to fit the diffusion-influenced rates is about 1.7 x 10(-6) cm(2) s(-1) at a viscosity of 1 cp and 293 K, almost 10 times smaller than the value expected for free diffusion of the contacting residues. Molecular dynamics simulations performed using a Ramachandran-like potential provide justification for this analysis. Diffusion-limited rates calculated from-the trajectories are in excellent agreement with those calculated with the ID diffusion model using the simulated end-to-end distance distributions. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NIH, Ctr Mol Modeling, Bethesda, MD 20892 USA. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Hofrichter, J (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. RI Szabo, Attila/H-3867-2012 NR 37 TC 133 Z9 134 U1 3 U2 22 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD NOV 7 PY 2002 VL 106 IS 44 BP 11628 EP 11640 DI 10.1021/jp020829v PG 13 WC Chemistry, Physical SC Chemistry GA 611HW UT WOS:000179011500032 ER PT J AU Guttmacher, AE Collins, FS AF Guttmacher, AE Collins, FS TI Genomic medicine - A primer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID APOLIPOPROTEIN-E; LINKAGE DISEQUILIBRIUM; ALZHEIMERS-DISEASE; MOLECULAR-GENETICS; BREAST-CANCER; PATHOGENESIS; MUTATION; RISK C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Guttmacher, AE (reprint author), NHGRI, NIH, Bldg 31,Rm 4B09, Bethesda, MD 20892 USA. EM guttmach@mail.nih.gov NR 40 TC 322 Z9 342 U1 0 U2 12 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 NOV 7 PY 2002 VL 347 IS 19 BP 1512 EP 1520 DI 10.1056/NEJMra012240 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 611XG UT WOS:000179042700009 PM 12421895 ER PT J AU Wu, KJ Mattioli, M Morse, HC Dalla-Favera, R AF Wu, KJ Mattioli, M Morse, HC Dalla-Favera, R TI c-MYC activates protein kinase A (PKA) by direct transcriptional activation of the PKA catalytic subunit beta (PKA-C beta) gene SO ONCOGENE LA English DT Article DE c-MYC; PKA; transcriptional activation ID CYCLIC-AMP; CELL-PROLIFERATION; DIFFERENTIAL EXPRESSION; MYC/MAX/MAD NETWORK; ESTROGEN-RECEPTOR; 3T3 CELLS; BINDING; GROWTH; TRANSFORMATION; MAX AB The c-MYC proto-oncogene encodes a ubiquitous transcription factor involved in the control of cell growth and differentiation and broadly implicated in tumorigenesis. Understanding the function of c-MYC and its role in cancer depends upon the identification of c-MYC target genes. Here we show that c-MYC induces the activity of Protein Kinase A (PKA), a key effector of cAMP-mediated signal transduction, by inducing the transcription of the gene encoding the PKA catalytic subunit beta (PKA-Cbeta). c-MYC-mediated induction of PKA-Cbeta gene transcription occurs in multiple tissues, is independent of cell proliferation and is mediated by direct binding of cMYC to the PKA-Cbeta gene promoter sequences. Constitutive expression of PKA-Cbeta in Rat1A cells induces their transformation, and c-MYC-induced transformation can be reverted by pharmacological inhibition of PKA, suggesting that up-regulation of PKA is critical for cMYC-associated tumorigenesis. These results indicate that, by activating PKA, c-MYC can provide endogenous activation of the cAMP signal transduction pathway independently of extracellular signals. C1 Columbia Univ, Inst Canc Genet, New York, NY 10032 USA. Columbia Univ, Dept Pathol, New York, NY 10032 USA. Columbia Univ, Dept Genet & Dev, New York, NY 10032 USA. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. RP Dalla-Favera, R (reprint author), Columbia Univ, Inst Canc Genet, New York, NY 10032 USA. RI Mattioli, Michela/K-3951-2013; Wu, Kou-Juey/P-4654-2015; OI Mattioli, Michela/0000-0002-1692-9178; Morse, Herbert/0000-0002-9331-3705 FU NCI NIH HHS [CA 37165] NR 45 TC 32 Z9 34 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 7 PY 2002 VL 21 IS 51 BP 7872 EP 7882 DI 10.1038/sj.onc.1205986 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 610DT UT WOS:000178946000012 PM 12420224 ER PT J AU Milligan, R Wingrove, BK Richards, L Rodan, M Monroe-Lord, L Jackson, V Hatcher, B Harris, C Henderson, C Johnson, AA AF Milligan, R Wingrove, BK Richards, L Rodan, M Monroe-Lord, L Jackson, V Hatcher, B Harris, C Henderson, C Johnson, AA TI Perceptions about prenatal care: views of urban vulnerable groups SO BMC PUBLIC HEALTH LA English DT Article ID LOW-INCOME; WOMEN; BARRIERS; BIRTH; CITY; CHILDBEARING; PREGNANCY; RISK AB Background: In the United States, infant mortality rates remain more than twice as high for African Americans as compared to other racial groups. Lack of adherence to prenatal care schedules in vulnerable, hard to reach, urban, poor women is associated with high infant mortality, particularly for women who abuse substances, are homeless, or live in communities having high poverty and high infant mortality. This issue is of concern to the women, their partners, and members of their communities. Because they are not part of the system, these womens' views are often not included in other studies. Methods: This qualitative study used focus groups with four distinct categories of people, to collect observations about prenatal care from various perspectives. The 169 subjects included homeless women; women with current or history of substance abuse; significant others of homeless women; and residents of a community with high infant mortality and poverty indices, and low incidence of adequate prenatal care. A process of coding and recoding using Ethnograph and counting ensured reliability and validity of the process of theme identification. Results: Barriers and motivators to prenatal care were identified in focus groups. Pervasive issues identified were drug lifestyle, negative attitudes of health care providers and staff, and non-inclusion of male partners in the prenatal experience. Conclusions: Designing prenatal care relevant to vulnerable women in urban communities takes creativity, thoughtfulness, and sensitivity. System changes recommended include increased attention to substance abuse treatment/prenatal care interaction, focus on provider/staff attitudes, and commitment to inclusion of male partners. C1 NICHHD, Div Epidemiol Stat & Prevent Res, Rockville, MD USA. Georgetown Univ, Sch Nursing & Hlth Studies, Washington, DC USA. Univ Dist Columbia, Dept Sociol, Washington, DC USA. Georgetown Univ, Dept Family Med, Washington, DC USA. Univ Dist Columbia, Community Extens Serv, Washington, DC USA. Georgetown Univ, Dept Obstet & Gynecol, Washington, DC USA. Amer Publ Hlth Assoc, Washington, DC USA. Howard Univ, Allied Sch Nutr, Washington, DC 20059 USA. RP Wingrove, BK (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, Rockville, MD USA. FU NICHD NIH HHS [U18-HD30450, U18 HD030445, U18 HD030447, U18 HD031206, U18 HD031919, U18-HD30445, U18-HD30447, U18-HD30454, U18-HD30458, U18-HD31206, U18-HD31919] NR 50 TC 29 Z9 29 U1 1 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2458 J9 BMC PUBLIC HEALTH JI BMC Public Health PD NOV 6 PY 2002 VL 2 AR 25 DI 10.1186/1471-2458-2-25 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 632XD UT WOS:000180249400001 PM 12421466 ER PT J AU Masumi, A Tamaoki, S Wang, IM Ozato, K Komuro, K AF Masumi, A Tamaoki, S Wang, IM Ozato, K Komuro, K TI IRF-8/ICSBP and IRF-1 cooperatively stimulate mouse IL-12 promoter activity in macrophages SO FEBS LETTERS LA English DT Article DE interleukin-12; ICSBP; IRF-1; mouse macrophage; ISRE; IFN-gamma ID SEQUENCE-BINDING-PROTEIN; REGULATORY FACTOR FAMILY; P40 GENE PROMOTER; NF-KAPPA-B; IMMUNE-RESPONSES; TRANSCRIPTION FACTOR; IFN-GAMMA; INTRACELLULAR INFECTION; INTERLEUKIN-12 IL-12; IN-VIVO AB IRF-8/ICSBP and IRF-1 are IRF family members whose expression is induced in response to IFN-gamma in macrophages. IL-12 is a cytokine produced in macrophages that plays a critical role in host defense. IFN-gamma and bacterial lipopolysaccharide (LPS) induce IL-12p40 transcription, which is necessary for the production of IL-12. We have previously shown that IL-12p40 expression is impaired in ICSBP-deficient mice and that transfection of ICSBP together with IRF-1 can activate IL-12p40 expression in mouse macrophage cells. To further study the role of ICSBP and IRF-1, we investigated murine IL-12p40 promoter activity in the macrophage cell line RAW 264.7. We show here that co-transfection of ICSBP and IRF-1 synergistically stimulates IL-12 promoter activity to a level comparable to that induced by IFN-gamma/LPS. Mutation of the Ets or NFkappaB site previously shown to be important for IL-12p40 transcription did not abolish the activation by ICSBP and IRF-1. However, mutation of the ISRE-like site found downstream from the NFkappaB and C/EBP sites abrogated the activation by ICSBP and IRF-1. Together, these results indicate that ICSBP and IRF-1 cooperatively stimulate murine IL-12 transcription through a novel regulatory element in the murine promoter. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved. C1 Natl Inst Infect Dis, Dept Safety Res Biol, Tokyo 2080011, Japan. Showa Univ, Sch Med, Dept Biochem, Shinagawa Ku, Hatanodia, Japan. Wyeth Res, Resp Dis, Cambridge, MA 02140 USA. NICHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Masumi, A (reprint author), Natl Inst Infect Dis, Dept Safety Res Biol, Gakuen 4-7-1,Musashimurayama Shi, Tokyo 2080011, Japan. NR 27 TC 55 Z9 58 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 6 PY 2002 VL 531 IS 2 BP 348 EP 353 AR PII S0014-5793(02)03556-1 DI 10.1016/S0014-5793(02)03556-1 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 613HY UT WOS:000179127900045 PM 12417340 ER PT J AU Resnick, SM Henderson, VW AF Resnick, SM Henderson, VW TI Hormone therapy and risk of Alzheimer disease SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID ESTROGEN REPLACEMENT THERAPY; CONTROLLED TRIAL; DEMENTIA; WOMEN; AD; COGNITION; MEMORY; AGE C1 NIA, Lab Personal & Cognit, Baltimore, MD 21224 USA. Univ Arkansas Med Sci, Dept Geriatr, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Neurol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Epidemiol, Little Rock, AR 72205 USA. RP Resnick, SM (reprint author), NIA, Lab Personal & Cognit, Box 03,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 29 TC 171 Z9 175 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 6 PY 2002 VL 288 IS 17 BP 2170 EP 2172 DI 10.1001/jama.288.17.2170 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 611ZJ UT WOS:000179048100029 PM 12413378 ER PT J AU Gius, D Coleman, CN AF Gius, D Coleman, CN TI Treatment of nasopharyngeal cancer: Raising the "Barr" SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID VIRUS DNA; QUANTITATIVE-ANALYSIS; CARCINOMA; PLASMA; CELLS C1 NCI, DCRT, Radiat Oncol Branch, Ctr Canc Res,Radiat Oncol Sci Program, Bethesda, MD 20892 USA. RP Gius, D (reprint author), NCI, DCRT, Radiat Oncol Branch, Ctr Canc Res,Radiat Oncol Sci Program, Bldg 10,Rm B3B69,MSC 1002, Bethesda, MD 20892 USA. NR 19 TC 3 Z9 3 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 6 PY 2002 VL 94 IS 21 BP 1594 EP 1595 PG 2 WC Oncology SC Oncology GA 611YG UT WOS:000179045100002 PM 12419779 ER PT J AU Mariotto, A Feuer, EJ Harlan, LC Wun, LM Johnson, KA Abrams, J AF Mariotto, A Feuer, EJ Harlan, LC Wun, LM Johnson, KA Abrams, J TI Trends in use of adjuvant multi-agent chemotherapy and tamoxifen for breast cancer in the United States: 1975-1999 SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID TUMORS AB Background: Understanding trends in the dissemination of findings from clinical research can help in estimating their population-level benefits. We evaluated trends in the use of adjuvant multi-agent chemotherapy, tamoxifen, and the combination of both treatments for early-stage breast cancer in the United States from 1975 through 1999. Methods: Data on treatment of 217508 patients diagnosed from 1975 through 1999 with stages 1, 11, and IIIA breast cancer were obtained from eight registries of the Surveillance, Epidemiology, and End Results (SEER) Program. Models of dissemination were developed from these data after adjustment based on information from a series of population-based Patterns of Care (POC) studies that randomly selected case patients from the SEER registries. The POC studies included 7116 patients diagnosed from 1987 through 1991 and in 1995 who were eliminated from the SEER data used in this analysis. Results: The modeled disseminations were generally compatible with the POC-observed proportions of each treatment. The use of multi-agent chemotherapy was higher among premenopausal women, and the use of tamoxifen was higher among postmenopausal women. The use of multi-agent chemotherapy for postmenopausal women diagnosed with lymph node-positive stage II+ or stage IIIA cancer reached a peak in 1983 and then decreased through 1986, indicating its substitution with tamoxifen. After 1986, the combined use of multi-agent chemotherapy and tamoxifen increased for almost all stages and ages. After the early 1990s, tamoxifen use in postmenopausal women with stage II+ or stage III breast cancer declined. Conclusions: The observed dissemination patterns suggest that the results of clinical trials are disseminated fairly rapidly to community-based physicians and their patients. C1 NCI, NIH, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, NIH, Div Canc Prevent, Bethesda, MD 20892 USA. NCI, NIH, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Mariotto, A (reprint author), NCI, NIH, Div Canc Control & Populat Sci, 6116 Execut Blvd,Suite 504 MSC 8317, Bethesda, MD 20892 USA. NR 27 TC 91 Z9 94 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 6 PY 2002 VL 94 IS 21 BP 1626 EP 1634 PG 9 WC Oncology SC Oncology GA 611YG UT WOS:000179045100010 PM 12419789 ER PT J AU Hsing, AW Chokkalingam, AP Gao, YT Madigan, M Deng, J Gridley, G Fraumeni, JF AF Hsing, AW Chokkalingam, AP Gao, YT Madigan, M Deng, J Gridley, G Fraumeni, JF TI Allium vegetables and risk of prostate cancer: A population-based study SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID STOMACH-CANCER; REDUCED RISK; CONSUMPTION; CARCINOMA; CHINA; ONIONS; FRUITS; CELLS; GENE AB Epidemiologic and laboratory studies suggest that allium vegetables and garlic constituents have antitumor effects. In a population-based, case-control study conducted in Shanghai, China, we investigated the association between intake of allium, vegetables, including garlic, scallions, onions, chives, and leeks, and the risk of prostate cancer. We administered in-person interviews and collected information on 122 food items from 238 case subjects with incident, histologically confirmed prostate cancer and from 471 male population control subjects. Men in the highest of three intake categories of total allium vegetables (>10.0 g/day) had a statistically significantly lower risk (odds ratio [OR] = 0.51, 95% confidence interval [CI] = 0.34 to 0.76; P-trend<.001) of prostate cancer than those in the lowest category (<2.2 g/day). Similar comparisons between categories showed reductions in risk for men in the highest intake categories for garlic (OR = 0.47, 95% CI = 0.31 to 0.71; P-trend<.001) and scallions (OR = 0.30, 95% CI = 0.18 to 0.51; P-trend<.001). The reduced risk of prostate cancer associated with allium vegetables was independent of body size, intake of other foods, and total calorie intake and was more pronounced for men with localized than with advanced prostate cancer. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Shanghai Canc Inst, Shanghai, Peoples R China. RP Hsing, AW (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Plaza Blvd,EPS 7058,MSC 7234, Bethesda, MD 20892 USA. NR 29 TC 165 Z9 175 U1 0 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 6 PY 2002 VL 94 IS 21 BP 1648 EP 1651 PG 4 WC Oncology SC Oncology GA 611YG UT WOS:000179045100013 PM 12419792 ER PT J AU Bartunek, J Kong, SW Vanderheyden, M Brown, J Riggi, L Chen, IB Nimgaonkar, A Butte, A Tack, W De Bruyne, B Goethals, M Izumo, S Schinke, M AF Bartunek, J Kong, SW Vanderheyden, M Brown, J Riggi, L Chen, IB Nimgaonkar, A Butte, A Tack, W De Bruyne, B Goethals, M Izumo, S Schinke, M TI Tissue expression profiling in human pressure overload hypertrophy due to aortic stenosis SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 CV Ctr, Aalst, Belgium. Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02215 USA. Childrens Hosp, Boston, MA 02115 USA. NHLBI, USA Cardiogenom PGA, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 24 BP 5 EP 5 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142700066 ER PT J AU Cappola, TP Cope, L Cernetich, A Barouch, LA Lavoie, T Ye, SQ Irizarry, R Durrani, S Hoffman, E Garcia, JGN Hare, J AF Cappola, TP Cope, L Cernetich, A Barouch, LA Lavoie, T Ye, SQ Irizarry, R Durrani, S Hoffman, E Garcia, JGN Hare, J TI Deficiency of different NOS isoforms activates distinct cardiac hypertrophy transcriptional programs SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 Johns Hopkins Univ, NHLBI, Program Genom Applicat HOPGENE, Baltimore, MD USA. Childrens Natl Med Ctr, Ctr Genet Med, Washington, DC 20010 USA. RI Garcia, Joe/E-8862-2010 NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 42 BP 9 EP 9 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142700084 ER PT J AU Sorger, JM Despres, D Hill, J Schimel, D Martin, B McVeigh, ER AF Sorger, JM Despres, D Hill, J Schimel, D Martin, B McVeigh, ER TI MRI tracking of intravenous magnetically-labeled mesenchymal stem cells following myocardial infarction in rats SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Osiris Therapeut Inc, Baltimore, MD USA. NR 0 TC 1 Z9 1 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 NOV 5 PY 2002 VL 106 IS 19 SU S MA 76 BP 16 EP 16 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142700118 ER PT J AU Holmes, BB Myers, CR Weng, BY Moss, J Li, PL Campbell, WB AF Holmes, BB Myers, CR Weng, BY Moss, J Li, PL Campbell, WB TI Identification of two ADP-ribosyltransferases, ART-3 and ART-5 in coronary arterial, smooth muscle cells: Potential role in EET-induced relaxation SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 Med Coll Wisconsin, Milwaukee, WI 53226 USA. NIH, Bethesda, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 181 BP 36 EP 36 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142700223 ER PT J AU Kim, MP Wahl, LM AF Kim, MP Wahl, LM TI Angiotensin II mediates production of matrix metalloproteinases-1 and-9 by monocytes: Implication for atherosclerotic plaque rupture SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 NIDCR, Immunopathol Sect, NIH, Bethesda, 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 213 BP 43 EP 43 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142700255 ER PT J AU Foster, WAA Joshua, J Genovese, DJ Curry, CL Vega, GL Boston, RC Sumner, AE AF Foster, WAA Joshua, J Genovese, DJ Curry, CL Vega, GL Boston, RC Sumner, AE TI The Framingham Risk Score (FRS) in African Americans is associated with dyslipidemia of insulin resistance SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 Howard Univ Hosp, Washington, DC USA. Univ Maryland, Baltimore, MD 21201 USA. NIDDK, NIH, Bethesda, MD USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 221 BP 45 EP 45 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142700263 ER PT J AU Bose, S French, S Joubert, F Balaban, RS AF Bose, S French, S Joubert, F Balaban, RS TI Regulation of cardiac oxidative phosphorylation by phosphate SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 277 BP 56 EP 56 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142700319 ER PT J AU Wright, G Steenbergen, C Murphy, E AF Wright, G Steenbergen, C Murphy, E TI Inhibition of the prolyl hydroxylase oxygen sensor mimics hypoxia in heart cells and induces nitric oxide synthase-2 and heme oxygenase-1 protein SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 NIEHS, Res Triangle Pk, NC 27709 USA. Duke Univ, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 279 BP 56 EP 56 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142700321 ER PT J AU Cross, HR Murphy, E Steenbergen, C AF Cross, HR Murphy, E Steenbergen, C TI Adrenergic stimulation reveals male/female differences in ischemic injury SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 Duke Univ, Med Ctr, Durham, NC USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 285 BP 57 EP 57 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142700327 ER PT J AU Ahmet, I Krawczyk, M Moon, C Lakatta, EG Talan, MI AF Ahmet, I Krawczyk, M Moon, C Lakatta, EG Talan, MI TI Chronic treatment with beta 2-adrenoceptor (AR) agonist, fenoterol, arrests the functional decline following experimental myocardial infarction in rats SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 NIA, Lab CV Sci, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 290 BP 58 EP 58 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142700332 ER PT J AU Jha, S Mohiddin, SA Fananapazir, L Keating, MT AF Jha, S Mohiddin, SA Fananapazir, L Keating, MT TI Autosomal dominant dilated cardiomyopathy: Clinical characterization and genetic linkage to a novel locus on chromosome 10q26 SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 Childrens Hosp, Boston, MA 02115 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 305 BP 61 EP 61 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142700347 ER PT J AU Remaley, AT Stonik, J Thomas, F Bark, S Demosky, S Neufeld, E Brewer, B AF Remaley, AT Stonik, J Thomas, F Bark, S Demosky, S Neufeld, E Brewer, B TI Structural features of synthetic peptides that promote lipid efflux SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 383 BP 76 EP 76 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142700425 ER PT J AU Hill, JM Hinds, KA Dick, AJ Thompson, RB Shapiro, E Raman, VK Dunbar, CE Lederman, RJ AF Hill, JM Hinds, KA Dick, AJ Thompson, RB Shapiro, E Raman, VK Dunbar, CE Lederman, RJ TI Dual magnetic/fluorescent contrast labeling for magnetic resonance imaging of cardiovascular stem and progenitor cells SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 418 BP 83 EP 83 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142700460 ER PT J AU Bocharov, AV Baranova, IN Vishnyakova, TG Chen, ZG Remaley, AT Csako, G Patterson, AP Eggerman, TL AF Bocharov, AV Baranova, IN Vishnyakova, TG Chen, ZG Remaley, AT Csako, G Patterson, AP Eggerman, TL TI Synthetic amphipathic alpha-helical peptides, mimics of exchangeable apolipoproteins, block LPS uptake and the lipopolysaccharide-induced proinflammatory cytokine response in THP-1 monocyte cells SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 NIH, CC, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 425 BP 84 EP 85 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142700467 ER PT J AU Skavdahl, M Petranka, J Steenbergen, C Murphy, E AF Skavdahl, M Petranka, J Steenbergen, C Murphy, E TI Decreased phospho-BAD in failing human hearts: A role for calcineurin SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 NIEHS, Res Triangle Pk, NC 27709 USA. Duke Univ, Sch Med, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 473 BP 94 EP 94 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142700515 ER PT J AU Gabel, SA London, RE Steenbergen, C Murphy, E AF Gabel, SA London, RE Steenbergen, C Murphy, E TI Inhibition of phosphatidylinositol 3-kinase blocks protection in females and induces a positive inotropic effect in female but not male mouse hearts SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 NIEHS, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 972 BP 194 EP 194 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142701014 ER PT J AU Mammen, PPA Kanatous, SB Shaul, PW Balaban, RS Garry, DJ AF Mammen, PPA Kanatous, SB Shaul, PW Balaban, RS Garry, DJ TI Myoglobin is a regulator of nitric oxide homeostasis in the heart SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 Univ Texas, SW Med Ctr, Dallas, TX USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 1026 BP 204 EP 204 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142701067 ER PT J AU Volkova, M Morrell, C Margulies, KB Lakatta, EG Boheler, KR AF Volkova, M Morrell, C Margulies, KB Lakatta, EG Boheler, KR TI Complex interactions of age and gender on gene expression in patients with heart failure SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 NIA, NIH, Baltimore, MD 21224 USA. Temple Univ, Sch Med, Philadelphia, PA 19122 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 1045 BP 208 EP 208 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142701086 ER PT J AU Zhu, WZ Yang, DM Zhang, SJ Cheng, HP Bouvier, M Hebert, TE Lakatta, EG Xiao, RP AF Zhu, WZ Yang, DM Zhang, SJ Cheng, HP Bouvier, M Hebert, TE Lakatta, EG Xiao, RP TI Heterodimerization of beta 1- and beta 2-adrenergic receptors in cardiac myocytes SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 NIH, Baltimore, MD USA. Univ Montreal, Dept Biochem, Montreal, PQ H3C 3J7, Canada. RI Bouvier, Michel/H-2758-2014 OI Bouvier, Michel/0000-0003-1128-0100 NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 1124 BP 223 EP 223 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142701165 ER PT J AU Vindgradova, TM Spurgeon, HA Ziman, B Lakatta, EG AF Vindgradova, TM Spurgeon, HA Ziman, B Lakatta, EG TI The trigger for Ca2+ release via ryanodine receptors during diastolic depolarization in cardiac pacemaker cells is not voltage dependent SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 1144 BP 227 EP 227 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142701185 ER PT J AU Zhang, YM Boheler, KR Narlow, M Dudley, SC AF Zhang, YM Boheler, KR Narlow, M Dudley, SC TI Sarcoplasmic reticulum Ca2+ release significantly shortens the cardiac action potential and reduces arrhythmic risk SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 Emory Univ, Atlanta VA Med Ctr, Decatur, GA 30033 USA. NIH NIA GRC LCS, Mol Cardiol Unit, 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 1147 BP 228 EP 228 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142701188 ER PT J AU Wang, SQ Stern, MD Cheng, HP AF Wang, SQ Stern, MD Cheng, HP TI Nanoscopic interactions between ryanodine receptors during local Ca2+release in cardiac myocytes SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 1152 BP 229 EP 229 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142701193 ER PT J AU Landmesser, U McCann, L Hwang, J Cai, H Dikalov, S Holland, SM Harrison, DG AF Landmesser, U McCann, L Hwang, J Cai, H Dikalov, S Holland, SM Harrison, DG TI Critical role of the NADPH oxidase subunit p47(phox) for endothelial superoxide production and hypertension in response to angiotensin II SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 Emory Univ, Atlanta, GA 30322 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 1176 BP 233 EP 233 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142701217 ER PT J AU Gaussin, V Liu, J Mishina, Y Hanks, MC Burch, JB AF Gaussin, V Liu, J Mishina, Y Hanks, MC Burch, JB TI Atrioventricular valves and conduction defects following conditional deletion of ALK3, the type Ia receptor for bone morphogenetic proteins, in cardiac myocytes of the atrioventricular SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 UMNDJ, New Jersey Med Sch, Newark, NJ USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Procter & Gamble Pharmaceut, Mason, OH USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 1200 BP 238 EP 238 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142701241 ER PT J AU Vishnyakova, TG Bocharov, AV Baranova, IN Chen, ZG Remaley, AT Eggerman, TL Patterson, AP AF Vishnyakova, TG Bocharov, AV Baranova, IN Chen, ZG Remaley, AT Eggerman, TL Patterson, AP TI Binding and internalization of lipopolysaccharide by Cla-1, a human homologue of rodent scavenger receptor B1 SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 NHLBI, NIH, Bethesda, MD 20892 USA. NIH, CC, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 1225 BP 243 EP 243 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142701266 ER PT J AU Amar, MJA Joyce, C Shamburek, RD Fruchart-Najib, J Santamarina-Fojo, S Brewer, HB AF Amar, MJA Joyce, C Shamburek, RD Fruchart-Najib, J Santamarina-Fojo, S Brewer, HB TI Kinetic analysis in ABCA1 transgenic mice reveals delayed HDL and enhanced ApoB-lipoprotein catabolism resulting in a protective lipoprotein profile and reduced atherosclerosis SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 NIH, Bethesda, MD 20892 USA. Inst Pasteur, F-59019 Lille, France. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 1258 BP 251 EP 251 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142701298 ER PT J AU Basso, FP Amar, MJA Duverger, N Chimini, G Knapper, CL Brewer, HB Santamarina-Fojo, S AF Basso, FP Amar, MJA Duverger, N Chimini, G Knapper, CL Brewer, HB Santamarina-Fojo, S TI Adenovirus-mediated overexpression of ABCA1 in C57BL/6 and ABCA1-K0 mice establishes the liver as an important source of HDL-C SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 NHLBI, NIH, Bethesda, MD 20892 USA. CNRS ENSCP Aventis, Evry, France. INSERM CNRS, Marseille, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 1257 BP 251 EP 251 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142701297 ER PT J AU Joyce, CW Tansey, TR Vaisman, B Fruchart-Najib, J Hoyt, R Brewer, HB Silvia, SF AF Joyce, CW Tansey, TR Vaisman, B Fruchart-Najib, J Hoyt, R Brewer, HB Silvia, SF TI Overexpression of ABCA1 leads to the development of a proatherogenic lipoprotein profile in LDL receptor knockout mice SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 NHLBI, NIH, Bethesda, MD 20892 USA. Inst Pasteur, F-59019 Lille, France. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 1259 BP 251 EP 251 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142701299 ER PT J AU Lambert, G Sinal, CJ Amar, MJA Santamarina-Fojo, S Gonzalez, FJ Brewer, HB AF Lambert, G Sinal, CJ Amar, MJA Santamarina-Fojo, S Gonzalez, FJ Brewer, HB TI The nuclear hormone receptor FXR is an important regulator of the entero-hepatic circulation of cholesterol SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 NHLBI, NIH, Bethesda, MD 20892 USA. Dalhousie Univ, Halifax, NS, Canada. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 1265 BP 252 EP 252 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142701305 ER PT J AU Kobayashi, K Yokote, K Fujimoto, M Kawamura, H Maezawa, Y Roberts, AB Deng, CX Mori, S Saito, Y AF Kobayashi, K Yokote, K Fujimoto, M Kawamura, H Maezawa, Y Roberts, AB Deng, CX Mori, S Saito, Y TI Targeted disruption of Smad3 results in enhanced neointimal hyperplasia through alteration of smooth muscle cell response to TGF-beta SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 Chiba Univ Hosp, Chiba, Japan. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 1380 BP 274 EP 274 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142701419 ER PT J AU Campia, U Sullivan, G Bryant, MB Quon, MJ Panza, JA AF Campia, U Sullivan, G Bryant, MB Quon, MJ Panza, JA TI Acute hyperinsulinemia impairs flow-mediated dilation independent of insulin sensitivity or lipid profile SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 Washington Hosp Ctr, Washington, DC 20010 USA. NIH, Bethesda, MD 20892 USA. RI Quon, Michael/B-1970-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 1486 BP 295 EP 295 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142701525 ER PT J AU Liu, XK Katchman, A Whitfield, B Wan, G Woosley, R Ebert, S AF Liu, XK Katchman, A Whitfield, B Wan, G Woosley, R Ebert, S TI In vivo androgen treatment shortens the QT interval and increases the densities of I-Kr and I-K1 repolarizing potassium currents in orchiectomized male rabbits SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 Mayo Clin, Rochester, MN USA. Georgetown Univ, Washington, DC USA. NIH, Washington, DC USA. Univ Arizona, Tucson, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 1521 BP 303 EP 303 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142701560 ER PT J AU Hill, JM Zalos, G Halcox, JPJ Schenke, WH Finkel, T Quyyumi, AA AF Hill, JM Zalos, G Halcox, JPJ Schenke, WH Finkel, T Quyyumi, AA TI Endothelial progenitor cells and endothelial dysfunction SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 Emory Univ Hosp, Atlanta, GA 30322 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 1597 BP 319 EP 319 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142701636 ER PT J AU Mohiddin, SA Antaramian, A Farrell, EF Gomez, AM Lin, JP Yu, ZX Valdivia, H Fananapazir, L AF Mohiddin, SA Antaramian, A Farrell, EF Gomez, AM Lin, JP Yu, ZX Valdivia, H Fananapazir, L TI A naturally-occurring sorcin missense mutation (F112L) is associated with hypertrophic cardiomyopathy, hypertension, and impaired modulation of cardiac ryanodine receptor SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 Univ Wisconsin, Madison, WI USA. NHLBI, NIH, Bethesda, MD 20892 USA. RI Gomez, Ana Maria/B-5376-2013 OI Gomez, Ana Maria/0000-0003-0009-2884 NR 0 TC 4 Z9 4 U1 0 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 NOV 5 PY 2002 VL 106 IS 19 SU S MA 1598 BP 319 EP 319 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142701637 ER PT J AU Hodges, M Bailey, JJ Church, TR AF Hodges, M Bailey, JJ Church, TR TI A post-MI Holter has significant predictive power for the post-MADIT-II era SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 NIH, Bethesda, MD 20892 USA. Univ Minnesota, Minneapolis, MN USA. Minneapolis Heart Inst, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 1851 BP 372 EP 372 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142701889 ER PT J AU Faris, OP Leclercq, C Kato, R Evans, F Spinelli, J Halperin, HR McVeigh, ER Kass, DA AF Faris, OP Leclercq, C Kato, R Evans, F Spinelli, J Halperin, HR McVeigh, ER Kass, DA TI Systolic improvement and mechanical resynchronization do not require electrical synchrony in the dilated failing heart with LBBB SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. Guidant Corp, St Paul, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 1901 BP 382 EP 382 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142701939 ER PT J AU Arai, AE Ingkanisom, WP Rhoads, KL Aletras, AH Kellman, P AF Arai, AE Ingkanisom, WP Rhoads, KL Aletras, AH Kellman, P TI User dependent parameters can markedly influence apparent infarat size an MRI SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 1929 BP 388 EP 388 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142701967 ER PT J AU Ingkanisom, WP Rhoads, KL Kellman, P Aletras, AH Arai, AE AF Ingkanisom, WP Rhoads, KL Kellman, P Aletras, AH Arai, AE TI MRI delayed hyperenhancement overestimates acute myocardial infarction size in humans SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 1936 BP 389 EP 389 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142701974 ER PT J AU Li, XK Wang, HF Jones, M Davies, CH Hashimoto, I Schindera, ST Rusk, RA AF Li, XK Wang, HF Jones, M Davies, CH Hashimoto, I Schindera, ST Rusk, RA TI Strain rate slopes during isovolumic systole are better than tissue velocity acceleration for evaluating left ventricular contractile function: In vivo study SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 Oregon Hlth & Sci Univ, Portland, OR 97201 USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 2108 BP 424 EP 424 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142702146 ER PT J AU Hill, JM Dick, AJ Raman, VK Thompson, RB Herzka, DA Hinds, KA Dunbar, CE Lederman, RJ AF Hill, JM Dick, AJ Raman, VK Thompson, RB Herzka, DA Hinds, KA Dunbar, CE Lederman, RJ TI In vivo MRI tracking of magnetically-labeled mesenchymal stem cells injected after myocardial infarction in swine SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 2167 BP 436 EP 436 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142702205 ER PT J AU Fleg, J Hougaku, H Zonderman, A Evans, M Metter, EJ AF Fleg, J Hougaku, H Zonderman, A Evans, M Metter, EJ TI Lower socioeconomic status predicts higher carotid intimal-medial thickness in African Americans SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 2200 BP 442 EP 442 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142702238 ER PT J AU Keaney, JF Larson, MG Vasan, RS Wilson, PWF Lipinska, I Corey, D Massaro, JM Sutherland, P Vita, JA Benjamin, EJ AF Keaney, JF Larson, MG Vasan, RS Wilson, PWF Lipinska, I Corey, D Massaro, JM Sutherland, P Vita, JA Benjamin, EJ TI Obesity as a source of systemic oxidative stress: Clinical correlates of oxidative stress in the Framingham Study SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 Boston Univ, Sch Med, Boston, MA 02118 USA. NHLBI, Framingham Heart Study, Boston, MA USA. NR 0 TC 3 Z9 3 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 2311 BP 467 EP 467 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142702349 ER PT J AU Mathew, J McSherry, F Wittes, J Garg, R Probstfield, J Williford, W Yusuf, S AF Mathew, J McSherry, F Wittes, J Garg, R Probstfield, J Williford, W Yusuf, S TI Racial differences in outcome and treatment effect in heart failure (HF) in Digitalis Investigation Group (DIG) trial SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 Baystate Med Ctr, Galesburg, IL USA. Perry Point VA Med Ctr, Perry Point, MD USA. Stat Collaborat, Washington, DC USA. Univ Washington, Seattle, WA 98195 USA. McMaster Univ, Hamilton, ON, Canada. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 2339 BP 473 EP 473 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142702377 ER PT J AU Najjar, SS Scuteri, A O'Connor, FE Muller, DC Andres, R Fleg, JL Lakatta, EG AF Najjar, SS Scuteri, A O'Connor, FE Muller, DC Andres, R Fleg, JL Lakatta, EG TI Modifiable cardiovascular risk factors are independent determinants of arterial stiffness SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 NIA, NIH, Baltimore, MD 21224 USA. INRCA, Unita Operat Geriatria, Rome, Italy. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 2350 BP 475 EP 475 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142702388 ER PT J AU Cushman, WC Ford, CE Cutler, JA Margolis, KL Davis, BR Grimm, RH AF Cushman, WC Ford, CE Cutler, JA Margolis, KL Davis, BR Grimm, RH TI Blood pressure control in the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT) SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 VA Med Ctr, Memphis, TN USA. Univ Texas, Hlth Sci Ctr SPH, Houston, TX USA. NHLBI DECA CAPP OD, Bethesda, MD USA. Berman Ctr Outcomes & Clin Res, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 2355 BP 476 EP 476 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142702393 ER PT J AU Detrano, R Anderson, M Nelson, J Wong, N Carr, J Bild, D AF Detrano, R Anderson, M Nelson, J Wong, N Carr, J Bild, D TI Effect of scanner type and calcium measure on the re-scan variability of calcium quantity by computed tomography SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 Univ Calif Los Angeles, Harbor Med Ctr, Torrance, CA 90509 USA. Univ Washington, Seattle, WA 98195 USA. Univ Calif Irvine, Irvine, CA USA. Wake Forest Univ, Winston Salem, NC 27109 USA. NHLBI, Bethesda, MD 20892 USA. RI Carr, John/A-1938-2012 OI Carr, John/0000-0002-4398-8237 NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 2367 BP 479 EP 479 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142702405 ER PT J AU Moak, J McAreavey, D Tripodi, D Mohiddin, S Fananapazir, L AF Moak, J McAreavey, D Tripodi, D Mohiddin, S Fananapazir, L TI Programmed ventricular stimulation in a large cohort of children with hypertrophic cardiomyopathy - A predictor of clinical outcome SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 Childrens Natl Med Ctr, Washington, DC 20010 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 2411 BP 488 EP 488 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142702449 ER PT J AU Merz, NB Johnson, BD Bittner, V Berga, S Braunstein, G Hodgson, TK Shaw, L Smith, K Kelsey, SF Sopko, G AF Merz, NB Johnson, BD Bittner, V Berga, S Braunstein, G Hodgson, TK Shaw, L Smith, K Kelsey, SF Sopko, G TI Diabetes and estrogen deficiency in premenopausal women: The NHLBI-sponsored WISE study SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Alabama, Birmingham, AL USA. Atlanta CV Res Inst, Atlanta, GA USA. Univ Florida, Gainesville, FL USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 2512 BP 508 EP 509 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142702550 ER PT J AU Merz, NB Johnson, BD Bittner, V Matthews, KA Sharaf, B Kelsey, SF Sopko, G AF Merz, NB Johnson, BD Bittner, V Matthews, KA Sharaf, B Kelsey, SF Sopko, G TI Reproductive hormones and chest pain in women: The NHLBI-sponsored WISE study SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Alabama, Birmingham, AL USA. Brown Univ, Providence, RI 02912 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 2664 BP 540 EP 540 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142702702 ER PT J AU Chinali, M de Simone, G Roman, MJ Bella, JN Liu, JE Lee, ET Best, LG Fabsitz, RR Howard, BV Devereux, RB AF Chinali, M de Simone, G Roman, MJ Bella, JN Liu, JE Lee, ET Best, LG Fabsitz, RR Howard, BV Devereux, RB TI Elevated left atrial ejection force is a predictor of cardiovascular events: The strong heart study SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 Cornell Univ, Weill Med Coll, New York, NY USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Missouri Breaks Ind Res, Timber Lake, SD USA. NIH NHLBI DECA, Bethesda, MD USA. MedStar Res Inst, Washington, DC USA. RI Chinali, Marcello/H-5794-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 2762 BP 559 EP 559 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142702800 ER PT J AU Fox, CS Parise, H Vasan, RS Levy, D O'Donnell, CJ D'Agostino, RB Benjamin, EJ AF Fox, CS Parise, H Vasan, RS Levy, D O'Donnell, CJ D'Agostino, RB Benjamin, EJ TI Mitral annular calcification is associated with incident atrial fibrillation and all-cause mortality: The Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Sch Med, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 2763 BP 559 EP 559 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142702801 ER PT J AU Shapiro, PA Park, SJ Gupta, L Flannery, M Seemuth, K Zheng, W Saniuk, C Willerson, JT Watson, JT Burton, N Foy, B Heitjan, DF Oren, R AF Shapiro, PA Park, SJ Gupta, L Flannery, M Seemuth, K Zheng, W Saniuk, C Willerson, JT Watson, JT Burton, N Foy, B Heitjan, DF Oren, R TI Quality of life outcomes in heart failure patients treated with optimal medical management vs. long-term mechanical assist device therapy: Results from the REMATCH trial SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 Columbia Univ, New York, NY USA. Univ Iowa, Iowa City, IA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Texas Heart Inst, Houston, TX 77025 USA. NHLBI, Bethesda, MD 20892 USA. Inova Fairfax Hosp, Annandale, VA USA. Loyola Univ, Coll Med, Maywood, IL 60153 USA. Univ Minnesota, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 2997 BP 606 EP 607 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142703035 ER PT J AU Olshansky, B Warner, A Solomon, A Sharma, A Platia, E O'Neill, G Feld, G Rosenfeld, L Akiyama, T Brodsky, M Ingalls, S Greene, HL AF Olshansky, B Warner, A Solomon, A Sharma, A Platia, E O'Neill, G Feld, G Rosenfeld, L Akiyama, T Brodsky, M Ingalls, S Greene, HL CA NHLBI AFFIRM Investigators TI Rate control in atrial fibrillation: A substudy of the AFFIRM trial SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 Univ Iowa, Iowa City, IA USA. VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Reg Cardiol Assoc, Med Grp, Sacramento, CA USA. Washington Hosp Ctr, Washington, DC 20010 USA. Univ Calif Davis, Sacramento, CA 95817 USA. Univ Calif Davis, Sacramento, CA 95817 USA. Mercy Gen Hosp, Sacramento, CA USA. Univ Calif San Diego, Med Ctr, San Diego, CA 92103 USA. Yale Univ, Sch Med, New Haven, CT USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Univ Calif Irvine, Irvine Med Ctr, Orange, CA 92668 USA. Axio Res Corp, Seattle, WA USA. NHLBI, AFFIRM Investigators, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 3125 BP 633 EP 634 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142703164 ER PT J AU Cook, JR Nappi, J Baessler, C Duquette, M Salunkhe, K Gardner, M Mickel, M Dalquist, J AF Cook, JR Nappi, J Baessler, C Duquette, M Salunkhe, K Gardner, M Mickel, M Dalquist, J CA NHLBI AFFIRM Investigators TI Hormone therapy increases atrial fibrillation recurrence rates: Results from the AFFIRM study SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 Baystate Med Ctr, Springfield, MA USA. Med Univ S Carolina, Charleston, SC 29425 USA. Med Coll Penn & Hahnemann Univ, Philadelphia, PA USA. Intermountain Hlth Care, Salt Lake City, UT USA. Axio Res Corp, Seattle, WA USA. NHLBI, AFFIRM Investigators, Bethesda, 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 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 3127 BP 634 EP 634 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142703166 ER PT J AU Johnson, BD Kip, K Sharaf, BL Ridker, PM Merz, CNB Kelsey, SF Tjandrawan, T Pepine, CJ Stylianou, MP Rogers, WJ Mankad, S Reis, SE AF Johnson, BD Kip, K Sharaf, BL Ridker, PM Merz, CNB Kelsey, SF Tjandrawan, T Pepine, CJ Stylianou, MP Rogers, WJ Mankad, S Reis, SE TI Relationship between IL-6/CRP and coronary artery disease (CAD) severity in women. The NHLBI-sponsored women's ischemia syndrome evaluation (WISE) study SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 Univ Pittsburgh, Pittsburgh, PA USA. Rhode Isl Hosp, Providence, RI USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Univ Florida, Gainesville, FL USA. NHLBI, Bethesda, MD 20892 USA. Univ Alabama, Med Ctr, Birmingham, AL 35294 USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. RI Reis, Steven/J-3957-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 3141 BP 637 EP 637 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142703180 ER PT J AU Mohiddin, SA Kent, K Begley, DA Leifer, E Shawl, F Goldstein, S Sachdev, V Ageyman, K Arai, A Fananapazir, L AF Mohiddin, SA Kent, K Begley, DA Leifer, E Shawl, F Goldstein, S Sachdev, V Ageyman, K Arai, A Fananapazir, L TI A Randomized prospective comparison of alcohol septal ablation and dual chamber pacemaker therapy in obstructive hypertrophic cardiomyopathy associated with drug-refractory symptoms SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 NHLBI, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Washington, DC USA. Washington Adventist Hosp, Washington, DC USA. Washington Hosp Ctr, Washington, DC 20010 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 3228 BP 654 EP 654 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142703267 ER PT J AU Mancini, DM Ronan, N Ascheim, DD Renlund, D Bourge, R Massin, E Eisen, H Lawless, C Hosenpud, J Foss, J Nickens, P Johnson, W Aaronson, KD AF Mancini, DM Ronan, N Ascheim, DD Renlund, D Bourge, R Massin, E Eisen, H Lawless, C Hosenpud, J Foss, J Nickens, P Johnson, W Aaronson, KD TI Predictors of survival in patients with end stage heart failure SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 Columbia Univ, New York, NY USA. Univ Utah, Salt Lake City, UT USA. Univ Alabama, Birmingham, AL USA. Texas Heart Inst, Houston, TX 77025 USA. Temple Univ, Philadelphia, PA 19122 USA. Loyola Univ, Chicago, IL 60611 USA. St Lukes Hosp, Milwaukee, WI USA. Thoratec Corp, Pleasanton, CA USA. NHLBI, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 3354 BP 680 EP 680 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142703392 ER PT J AU Hees, PS Fleg, JL Mirza, Z Ahmed, S Lakatta, EG Shapiro, EP AF Hees, PS Fleg, JL Mirza, Z Ahmed, S Lakatta, EG Shapiro, EP TI Left ventricular diastolic functional reserve declines with age despite preserved relaxation reserve SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 NHLBI, NIH, Rockville, MD USA. Johns Hopkins Univ, Baltimore, MD USA. NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 1 Z9 1 U1 0 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 NOV 5 PY 2002 VL 106 IS 19 SU S MA 3493 BP 708 EP 709 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142703530 ER PT J AU Holvoet, P Kritchevsky, SB Tracy, RP Mertens, A Cummings, S Goodpaster, B Harris, TB AF Holvoet, P Kritchevsky, SB Tracy, RP Mertens, A Cummings, S Goodpaster, B Harris, TB TI The metabolic syndrome is associated with elevated circulating oxidized LDL in the health, aging and body composition cohort SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 Katholieke Univ Leuven, Ctr Expt Surg & Anesthesiol, Louvain, Belgium. Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. NIA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 3594 BP 730 EP 730 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142703630 ER PT J AU Cao, J Peterson, D Psaty, B Kuller, L Barzilay, J Bleyer, A Manolio, T Waxler, J Blaum, C Cushman, M AF Cao, J Peterson, D Psaty, B Kuller, L Barzilay, J Bleyer, A Manolio, T Waxler, J Blaum, C Cushman, M TI Association of microalbuminuria with clinical and subclinical cardiovascular disease in the presence or absence of diabetes and hypertension SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 Henry Ford Hlth Syst, Detroit, MI USA. Univ Washington, Seattle, WA 98195 USA. Univ Pittsburgh, Pittsburgh, PA USA. Kaiser Permanente, Atlanta, GA USA. Wake Forest Univ, Winston Salem, NC 27109 USA. NHLBI, Bethesda, MD 20892 USA. Univ Calif Davis, Davis, CA 95616 USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Vermont, Burlington, VT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 3655 BP 744 EP 744 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142703691 ER PT J AU Vigilance, CP Furberg, CD O'Meara, E Kuller, L Powe, N Psaty, B Manolio, T AF Vigilance, CP Furberg, CD O'Meara, E Kuller, L Powe, N Psaty, B Manolio, T TI Subclinical disease measures identify older adults with known coronary disease at high risk of subsequent mortality: The cardiovascular health study (CHS) SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 NHLBI, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Wake Forest Univ, Wakeforest, NC USA. Univ Washington, Seattle, WA 98195 USA. Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 3658 BP 744 EP 744 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142703694 ER PT J AU Mozaffarian, D Longstreth, WT Lemaitre, RN Burke, GL Manolio, TA Siscovick, DS AF Mozaffarian, D Longstreth, WT Lemaitre, RN Burke, GL Manolio, TA Siscovick, DS TI Fish consumption and stroke risk among older adults SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 VA Puget Sound Hlth Care Ctr, CV Hlth Res Unit, Seattle, WA USA. Univ Washington, CV Hlth Res Unit, Seattle, WA 98195 USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. NHLBI, NIH, DECA, Bethesda, MD 20892 USA. RI Mozaffarian, Dariush/B-2276-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S MA 3726 BP 759 EP 759 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142703762 ER PT J AU Wang, SQ Stern, MD Cheng, HP AF Wang, SQ Stern, MD Cheng, HP TI Nanoscopic interactions between ryanodine receptors during local Ca2+ release in cardiac myocytes SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S BP H EP H PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142700002 ER PT J AU Hill, JM Zalos, G Halcox, JP Schenke, WH Finkel, T Quyyumi, AA AF Hill, JM Zalos, G Halcox, JP Schenke, WH Finkel, T Quyyumi, AA TI Endothelial progenitor cells and endothelial dysfunction SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 NHLBI, NIH, Bethesda, MD 20892 USA. Emory Univ Hosp, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S BP T EP T PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142700033 ER PT J AU Mohiddin, SA Antaramian, A Farrell, EF Gomez, AM Lin, JP Yu, ZX Valdivia, H Fananapazir, L AF Mohiddin, SA Antaramian, A Farrell, EF Gomez, AM Lin, JP Yu, ZX Valdivia, H Fananapazir, L TI A naturally occurring sorcin missense mutation (F112L) is associated, with hypertrophic cardiomyopathy, hypertension, and impaired modulation of cardiac ryanodine receptor SO CIRCULATION LA English DT Meeting Abstract CT American-Heart-Association Abstracts From Scientific Sessions CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc C1 NHLBI, NIH, Bethesda, MD 20892 USA. Univ Wisconsin, Madison, WI USA. RI Gomez, Ana Maria/B-5376-2013 OI Gomez, Ana Maria/0000-0003-0009-2884 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 5 PY 2002 VL 106 IS 19 SU S BP T EP U PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613QJ UT WOS:000179142700034 ER PT J AU Cummings, L Riley, L Black, L Souvorov, A Resenchuk, S Dondoshansky, I Tatusova, T AF Cummings, L Riley, L Black, L Souvorov, A Resenchuk, S Dondoshansky, I Tatusova, T TI Genomic BLAST: custom-defined virtual databases for complete and unfinished genomes SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE genome analysis; sequence analysis; unfinished genome; bacterium; archaeon; eukaryote ID SEARCH AB BLAST (Basic Local Alignment Search Tool) searches against DNA and protein sequence databases have become an indispensable tool for biomedical research. The proliferation of the genome sequencing projects is steadily increasing the fraction of genome-derived sequences in the public databases and their importance as a public resource. We report here the availability of Genomic BLAST, a novel graphical tool for simplifying BLAST searches against complete and unfinished genome sequences. This tool allows the user to compare the query sequence against a virtual database of DNA and/or protein sequences from a selected group of organisms with finished or unfinished genomes. The organisms for such a database can be selected using either a graphic taxonomy-based tree or an alphabetical list of organism-specific sequences. The first option is designed to help explore the evolutionary relationships among organisms within a certain taxonomy group when performing BLAST searches. The use of an alphabetical list allows the user to perform a more elaborate set of selections, assembling any given number of organism-specific databases from unfinished or complete genomes. This tool, available at the NCBI web site http://www.ncbi.nlm.nih.gov/cgi-bin/Entrez/genom_table_cgi, currently provides access to over 170 bacterial and archaeal genomes and over 40 eukaryotic genomes. (C) 2002 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Tatusova, T (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NR 6 TC 75 Z9 76 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD NOV 5 PY 2002 VL 216 IS 2 BP 133 EP 138 AR PII S0378-1097(02)00955-2 DI 10.1016/S0378-1097(02)00955-2 PG 6 WC Microbiology SC Microbiology GA 618QP UT WOS:000179429000002 PM 12435493 ER PT J AU Denton, TT Seib, T Bridges, RJ Thompson, CM AF Denton, TT Seib, T Bridges, RJ Thompson, CM TI Synthesis and preliminary evaluation of trans-3,4-conformationally-restricted glutamate and pyroglutamate analogues as novel EAAT2 inhibitors SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID AMINO-ACID TRANSPORTERS; SYNAPTIC VESICLES; HIGH-AFFINITY; SODIUM; DERIVATIVES; SUBTYPES; CELLS AB Select trans-4,5-[bi]cyclohexenylglutamic and pyroglutamic acids (3,4-substituted glutamates) were synthesized in three steps and were screened as potential inhibitors of the sodium dependent excitatory amino acid transporters 2 (EAAT2) and 3 (EAAT3), the chloride dependent glial cystine/glutamate exchanger system x(c)(-), and the glutamate vesicular transport system (VGLUT). Two glutamate analogues and one pyroglutamate analogue were found to inhibit EAAT2 with activity comparable to dihydrokainate. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Univ Montana, Dept Chem, Missoula, MT 59812 USA. Univ Montana, COBRE Ctr Struct & Funct Neurosci, Dept Pharmaceut Sci, Missoula, MT 59812 USA. RP Thompson, CM (reprint author), Univ Montana, Dept Chem, Missoula, MT 59812 USA. EM cmthomp@selway.umt.edu FU NCRR NIH HHS [RR15583]; NINDS NIH HHS [NS38248, NS30570] NR 24 TC 9 Z9 9 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X EI 1464-3405 J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD NOV 4 PY 2002 VL 12 IS 21 BP 3209 EP 3213 AR PII S0960-894X(02)00520-6 DI 10.1016/S0960-894X(02)00520-6 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 605TL UT WOS:000178693100043 PM 12372536 ER PT J AU Aliberti, J Serhan, C Sher, A AF Aliberti, J Serhan, C Sher, A TI Parasite-induced lipoxin A(4) is an endogenous regulator of IL-12 production and immunopathology in Toxoplasma gondii infection SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE Toxoplasma gondii; interleukin-12; eicosanoid; lipoxygenase; lipoxin A(4) ID INTRACELLULAR PATHOGEN; IMMUNE-RESPONSE; STABLE ANALOGS; CUTTING EDGE; IFN-GAMMA; T-CELLS; MICE; TRAFFICKING; PREVENTION; INHIBITION AB The production of interleukin (IL)-12 is critical for the development of interferon (IFN)-gamma-dependent resistance to Toxoplasma gondii. Nevertheless, when this response is dysregulated, such as occurs in the absence of IL-10, the uncontrolled inflammation that results can have lethal consequences for the host. Recently, we demonstrated that lipoxin (LX)A(4), an eicosanoid mediator that depends on 5-lipoxygenase (LO) for its biosynthesis, exerts a regulatory role on dendritic cell IL-12 production triggered artificially by a T. gondii extract. We now formally establish the physiological relevance of this pathway in the systemic control of IL-12 production induced by live T. gondii infection and demonstrate its function to be distinct from that of IL-10. Thus, T. gondii-exposed wild-type, but not 5-LO-deficient animals, produced high levels of serum LXA(4) beginning at the onset of chronic infection. Moreover, 5-LO-/-, in contrast to wild-type mice, succumbed during the same period displaying a marked encephalitis. The increased mortality of the 5-LO-/- animals was also associated with significant elevations of IL-12 and IFN-gamma and was completely prevented by the administration of a stable LXA(4) analogue. Together, these findings demonstrate a new pathway involving the induction of host LXs for the in vivo regulation of proinflammatory responses during microbial infection. C1 NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesiol Perioperat & Pain Res,Sch Med, Boston, MA 02115 USA. RP Aliberti, J (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, 50 S Dr,MSC 8003, Bethesda, MD 20892 USA. RI Aliberti, Julio/G-4565-2012; Aliberti, Julio/I-7354-2013 OI Aliberti, Julio/0000-0003-3420-8478 FU NIDCR NIH HHS [P01-DE 13499, P01 DE013499]; NIGMS NIH HHS [GM 38765, R01 GM038765, R37 GM038765] NR 27 TC 135 Z9 144 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 4 PY 2002 VL 196 IS 9 BP 1253 EP 1262 DI 10.1084/jem.20021183 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 613VC UT WOS:000179151300012 PM 12417634 ER PT J AU Okada, Y Fujisawa, Y Morishita, A Shiotani, K Miyazaki, A Fujita, Y Li, T Tsuda, Y Yokoi, T Bryant, SD Lazarus, LH AF Okada, Y Fujisawa, Y Morishita, A Shiotani, K Miyazaki, A Fujita, Y Li, T Tsuda, Y Yokoi, T Bryant, SD Lazarus, LH TI Immediate deamination from the aminomethyl group attached to 1,2-dihydropyrazin-2-one derivative during catalytic hydrogenation SO TETRAHEDRON LETTERS LA English DT Article ID AMINO-ACIDS; PEPTIDES; PYRAZINONE AB The catalytic hydrogenation of 3,6-bis(benzyloxycarbonylaminomethyl)-5-methyl-1,2-dihydropyrazin-2-one to remove benzyloxycarbonyl (Z) groups resulted ill a side reaction. Purification by reverse-phase HPLC and analysis by proton unclear magnetic resonance (H-1 NMR) spectroscopy identified the product as 3-aminomethyl-5,6-dimethyl-1,2-dihydropyrazin-2-one. It was determined through the synthesis of two 1,2-dihydropyrazin-2-one derivatives, composed of alanine and 2,3-diaminopropionic acid that deamination occurred specifically and easily (under atmospheric pressure and at the room temperature) Only in the case of 6-benzyloxycarbonylaminomethyl-3,5-dimethyl-1,2-dihydropyrazin-2-one. The catalytic hydrogenation of 3,6-bis(benzyloxycarbonylaminomethyl)-5-methyl-1,2-dihydropyrazin-2-one specifically yields the deaminated product, 3-aminomethyl-5,6-dimethyl-1,2-dihydropyrazin-2-one. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Kobe Gakuin Univ, Fac Pharmaceut Sci, Nishi Ku, Kobe, Hyogo 6512180, Japan. Kobe Gakuin Univ, High Technol Res Ctr, Nishi Ku, Kobe, Hyogo 6512180, Japan. NIEHS, LCBRA, Res Triangle Pk, NC 27709 USA. RP Okada, Y (reprint author), Kobe Gakuin Univ, Fac Pharmaceut Sci, Nishi Ku, Kobe, Hyogo 6512180, Japan. EM okada@pharm.kobegakuin.ac.jp NR 11 TC 3 Z9 3 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD NOV 4 PY 2002 VL 43 IS 45 BP 8137 EP 8139 AR PII S0040-4039(02)01944-5 DI 10.1016/S0040-4039(02)01944-5 PG 3 WC Chemistry, Organic SC Chemistry GA 607CX UT WOS:000178774600032 ER PT J AU Tuo, JS Chen, C Zeng, XM Christiansen, M Bohr, VA AF Tuo, JS Chen, C Zeng, XM Christiansen, M Bohr, VA TI Functional crosstalk between hOgg1 and the helicase domain of Cockayne syndrome group B protein SO DNA REPAIR LA English DT Article DE Cockayne syndrome group B gene; motif VI; base excision repair; glycosylase/apurinic lyase; 8-hydroxyguanine ID RNA-POLYMERASE-II; BASE EXCISION-REPAIR; DNA-REPAIR; HUMAN-CELLS; XERODERMA-PIGMENTOSUM; PUTATIVE HELICASES; COUPLING FACTOR; ACTIVE GENES; OGG1 GENE; TRANSCRIPTION AB We have previously reported that the Cockayne syndrome group B gene product (CSB) contributes to base excision repair (BER) of 8-hydroxyguanine (8-OH-Gua) and the importance of motifs V and VI of the putative helicase domains of CSB in BER of 8-OH-Gua. To further elucidate the function of CSB in BER, we investigated its role in the pathway involving human 8-OH-Gua glycosylase/apurinic lyase (hOgg1). Depletion of CSB protein with anti-CSB antibody reduced the 8-OH-Gua incision rate of wild type cell extracts but not of CSB null and motif VI mutant cell extracts, suggesting a direct contribution of CSB to the catalytic process of 8-OH-Gua incision and the importance of its motif VI in this pathway. Introduction of recombinant purified CSB partially complemented the depletion of CSB as shown by the recovery of the incision activity. This complementation could not fully recover the deficiency of the incision activity in WCE from CS-B null and mutant cell lines, suggesting that some additional factor(s) are necessary for the full activity. Electrophoretic mobility shift assays (EMSAs) showed a defect in binding of CSB null and motif VI mutant cell extracts to 8-OH-Gua-containing oligonucleotides. We detected less hOgg1 transcript and protein in the cell extracts from CS-B null and mutant cells, suggesting hOgg1 may be the missing component. Pull-down of hOgg1 by histidine-tagged CSB and co-localization of those two proteins after gamma-radiation indicated their co-existence in vivo, particularly under cellular stress. However, we did not detect any functional and physical interaction between purified CSB and hOgg1 by incision, gel shift and yeast two-hybrid assays, suggesting that even though hOgg1 and CSB might be in a common protein complex, they may not interact directly. We conclude that CSB functions in the catalysis of 8-OH-Gua BER and in the maintenance of efficient hOgg1 expression, and that motif VI of the putative helicase domain of CSB is crucial in these functions. Published by Elsevier Science B.V. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Aarhus Univ, Danish Ctr Mol Gerontol, Dept Biol Mol, DK-8000 Aarhus C, Denmark. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 50 TC 59 Z9 60 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD NOV 3 PY 2002 VL 1 IS 11 BP 913 EP 927 AR PII S1568-7864(02)00116-7 DI 10.1016/S1568-7864(02)00116-7 PG 15 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 608CZ UT WOS:000178828700004 PM 12531019 ER PT J AU Marietta, C Gulam, H Brooks, PJ AF Marietta, C Gulam, H Brooks, PJ TI A single 8,5 '-cyclo-2 '-deoxyadenosine lesion in a TATA box prevents binding of the TATA binding protein and strongly reduces transcription in vivo SO DNA REPAIR LA English DT Article DE aging; neurodegeneration; xeroderma pigmentosum; DNA repair; oxidative stress ID BENZOPYRENE DIOL EPOXIDE; INDUCED PYRIMIDINE DIMERS; XERODERMA-PIGMENTOSUM; DNA-REPAIR; FACTOR SP1; GC BOX; SEQUENCE; GENE; CISPLATIN; PROMOTER AB 8,5'-Cyclo-2'-deoxypurine (cPu) lesions result from the action of the hydroxyl radical on DNA. These lesions represent a unique class of oxidative DNA lesions in that they are repaired by the nucleotide excision repair (NER) pathway but not by base excision repair (BER) or direct repair. Previous work has shown that cyclopurines can block mammalian DNA and RNA polymerases. Thus, these lesions are of interest because of their potential role in the neurodegeneration as well as internal cancers observed in patients with xeroderma pigmentosum (XP) who lack the capacity to carry out NER. In the present work, we found that the S-isomer of 8,5'-cyclo-2'-deoxyadenosine (M) can prevent binding of the TATA binding protein (TBP) to the TATA box from the CMV promoter. To assess the functional importance of this effect in living cells, we transfected constructs containing a single cA in the CMV TATA box into XP cells to determine the effect of the lesion on gene expression in vivo. Using this approach, we found that the lesion reduced gene expression by approximately 75%. This effect was comparable to the effect of an inactivating mutation of the TATA box in the same promoter. These findings identify an additional biological effect of cyclopurine lesions in mammalian cells, which is the ability to interfere with transcription by preventing transcription factor binding to cognate recognition sequences. In addition, the approach we used in this study represents a novel method for assessing the effects of DNA lesions in non-transcribed sequences on gene expression in living cells. Published by Elsevier Science B.V. C1 NIAAA, Mol Neurobiol Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Brooks, PJ (reprint author), NIAAA, Mol Neurobiol Sect, Neurogenet Lab, NIH, 12420 Parklawn Dr,MSC 8110, Bethesda, MD 20892 USA. NR 42 TC 45 Z9 45 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD NOV 3 PY 2002 VL 1 IS 11 BP 967 EP 975 AR PII S1568-7864(02)00148-9 DI 10.1016/S1568-7864(02)00148-9 PG 9 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 608CZ UT WOS:000178828700009 PM 12531024 ER PT J AU Cebral, JR Yim, PJ Lohner, R Soto, O Choyke, PL AF Cebral, JR Yim, PJ Lohner, R Soto, O Choyke, PL TI Blood flow modeling in carotid arteries with computational fluid dynamics and MR imaging SO ACADEMIC RADIOLOGY LA English DT Article DE carotid arteries, flow dynamics; carotid arteries, MR; carotid arteries, stenosis or obstruction; magnetic resonance (MR), vascular studies ID SHEAR-STRESS; BIFURCATION; ATHEROSCLEROSIS; TRIANGULATIONS; HEMODYNAMICS; VELOCITY; STENOSIS AB Rationale and Objectives. The authors' goal was to develop a noninvasive method for detailed assessment of blood flow patterns from direct in vivo measurements of vessel anatomy and flow rates. Materials and Methods. The authors developed a method to construct realistic patient-specific finite element models of blood flow in carotid arteries. Anatomic models are reconstructed from contrast material-enhanced magnetic resonance (MR) angiographic images with a tubular deformable model along each arterial branch. A surface-merging algorithm is used to create a watertight model of the carotid bifurcation for subsequent finite element grid generation, and a fully implicit scheme is used to solve the incompressible Navier-Stokes equations on unstructured grids. Physiologic boundary conditions are derived from cine phase-contrast MR flow velocity measurements at two locations below and above the bifurcation. Vessel wall compliance is incorporated by means of fluid-solid interaction algorithms. Results. The method was tested on imaging data from a healthy subject and a patient with mild stenosis. Finite element grids were successfully generated, and pulsatile blood flow calculations were performed. Computed and measured velocity profiles show good agreement. Flow patterns and wall shear stress distributions were visualized. Conclusions. Patient-specific computational fluid dynamics modeling based on MR images can be performed robustly and efficiently. Preliminary validation studies in a physical flow-through model suggest that the model is accurate. This method can be used to characterize blood flow patterns in healthy and diseased arteries and may eventually help physicians to supplement imaging-based diagnosis and predict and evaluate the outcome of interventional procedures. C1 George Mason Univ, Sch Computat Sci, Fairfax, VA 22030 USA. NIH, Imaging Sci Program, Bethesda, MD 20892 USA. RP George Mason Univ, Sch Computat Sci, 4400 Univ Dr,MSN 4C7, Fairfax, VA 22030 USA. NR 33 TC 83 Z9 86 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 EI 1878-4046 J9 ACAD RADIOL JI Acad. Radiol. PD NOV PY 2002 VL 9 IS 11 BP 1286 EP 1299 DI 10.1016/S1076-6332(03)80562-7 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 611NB UT WOS:000179023000007 PM 12449361 ER PT J AU Dauter, Z AF Dauter, Z TI One-and-a-half wavelength approach SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID ANOMALOUS DIFFRACTION; MACROMOLECULAR STRUCTURES; ISOMORPHOUS REPLACEMENT; SCATTERING; CRYSTALLOGRAPHY; DISPERSION; PHASES AB In many cases single-wavelength anomalous diffraction (SAD) phasing leads to a successful structure solution, but it is impossible to predict beforehand if single-wavelength data with a certain amount of anomalous signal resulting will be sufficient. It is therefore safer to continue collecting data at different wavelengths according to a MAD protocol, but to simultaneously attempt to phase the first data set by the SAD method. If this is successful, then further data collection can be abandoned. This '1.5-wavelength' approach may save a substantial amount of time and effort and diminishes the effects of crystal radiation damage. The principles of SAD phasing are illustrated using vector diagrams in the Argand plane. C1 Brookhaven Natl Lab, NSLS, Natl Canc Inst, Synchrotron Radiat Res Sect, Upton, NY 11973 USA. RP Dauter, Z (reprint author), Brookhaven Natl Lab, NSLS, Natl Canc Inst, Synchrotron Radiat Res Sect, Bldg 725A-X9, Upton, NY 11973 USA. EM dauter@bnl.gov NR 33 TC 21 Z9 22 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD NOV PY 2002 VL 58 BP 1958 EP 1967 DI 10.1107/S0907444902016645 PN 11 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 606QQ UT WOS:000178745000011 PM 12393929 ER PT J AU Goebel, HH Goldfarb, L Laing, N AF Goebel, HH Goldfarb, L Laing, N TI Protein aggregate myopathies SO ACTA NEUROPATHOLOGICA LA English DT Meeting Abstract CT Joint Meeting of the Belgian-Dutch-and-German-Societies/47th Annual Meeting of the Deutsche-Gesellschaft-fur-Neuropathologie CY OCT 09-12, 2002 CL AACHEN, GERMANY SP Belgian Dutch & German Soc, Deutsch Gesell Neuropathol C1 Univ Mainz, Dept Neuropathol, D-6500 Mainz, Germany. NIH, Bethesda, MD 20892 USA. Australian Neuromuscular Res Inst, Nedlands, WA, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD NOV PY 2002 VL 104 IS 5 BP 552 EP 552 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 606TX UT WOS:000178750700056 ER PT J AU Mehendale, SM Bollinger, RC Kulkarni, SS Stallings, RY Brookmeyer, RS Kulkarni, SV Divekar, AD Gangakhedkar, RR Joshi, SN Risbud, AR Thakar, MA Mahajan, BA Kale, VA Ghate, MV Gadkari, DA Quinn, TC Paranjape, RS AF Mehendale, SM Bollinger, RC Kulkarni, SS Stallings, RY Brookmeyer, RS Kulkarni, SV Divekar, AD Gangakhedkar, RR Joshi, SN Risbud, AR Thakar, MA Mahajan, BA Kale, VA Ghate, MV Gadkari, DA Quinn, TC Paranjape, RS TI Rapid disease progression in human immunodeficiency virus type 1-infected seroconverters in India SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID PLASMA VIRAL LOAD; HIV-1 INFECTION; NATURAL-HISTORY; CELL COUNT; AIDS; COHORT; POPULATION; SURVIVAL; AFRICA; TUBERCULOSIS AB To determine if the early immunological and virological events of HIV infection are unique in a setting with limited access to health care and HIV-1 subtype C infection, we undertook a prospective cohort study to characterize the early natural history of HIV viral load and CD4(+) T lymphocyte counts in individuals with recent HIV seroconversion in India. CD4(+) T lymphocyte counts were prospectively measured for up to 720 days in 46 antiviral drug-naive persons with very early HIV infection, documented by HIV antibody seroconversion. HIV viral RNA levels were measured subsequently on reposited plasma samples from these same time points. The median viral load "set point" for Indian seroconverters was 28,729 RNA copies/ml. The median CD4(+) cell count following acute primary HIV infection was 644 cells/mm(3). Over the first 2 years since primary infection, the annual rate of increase in HIV viral load was +8274 RNA copies/ml/year and the annual decline in CD4 cell count was -120 cells/year. Although the viral "set point" was similar, the median trajectory of increasing viral load in Indian seroconverters was greater than what has been reported in untreated HIV seroconverters in the United States. These data suggest that the more rapid HIV disease progression described in resource-poor settings may be due to very early virological and host events following primary HIV infection. A rapid increase in viral load within the first 2 years after primary infection may have to be considered when applying treatment guidelines for antiretroviral therapy and opportunistic infection prophylaxis. C1 Natl AIDS Res Inst, Pune 411026, Maharashtra, India. Johns Hopkins Univ, Baltimore, MD USA. Natl Inst Virol, Pune, Maharashtra, India. NIAID, NIH, Bethesda, MD 20892 USA. RP Mehendale, SM (reprint author), Natl AIDS Res Inst, Plot 73 G Block MIDC, Pune 411026, Maharashtra, India. FU FIC NIH HHS [D43TW0000]; NCRR NIH HHS [5M01 RR00722]; NIAID NIH HHS [AI 33879-02] NR 27 TC 32 Z9 33 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV 1 PY 2002 VL 18 IS 16 BP 1175 EP 1179 DI 10.1089/08892220260387913 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 612FD UT WOS:000179063100002 PM 12487823 ER PT J AU Farr, SA Banks, WA Uezu, K Freed, EO Kumar, VB Morley, JE AF Farr, SA Banks, WA Uezu, K Freed, EO Kumar, VB Morley, JE TI Mechanisms of HIV type 1-induced cognitive impairment: Evidence for hippocampal cholinergic involvement with overstimulation of the VIPergic system by the viral coat protein core SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; VASOACTIVE INTESTINAL POLYPEPTIDE; ACTIVE ANTIRETROVIRAL THERAPY; ENVELOPE GLYCOPROTEIN GP120; BLOOD-BRAIN-BARRIER; NITRIC-OXIDE; ADSORPTIVE ENDOCYTOSIS; CEREBROSPINAL-FLUID; PEPTIDE VIP; IN-VIVO AB HIV-1 is associated with a neuroAIDS syndrome that includes cognitive impairment. Several components of HIV-1 are capable of affecting cognition, but which of these is the major mediator is unknown. We injected into the lateral cerebral ventricle of mice HIV-1 pseudoviruses expressing the full viral genome with or without the viral coat glycoproteins, gp120/gp41. Only virus possessing gp120/gp41 induced defects in memory as assessed in an active avoidance T-maze footshock paradigm. By itself, gp120 also induced impairments that were reversed by hippocampal cholinergic stimulation. Paradoxically, low doses of gp120 could improve memory. Such low-dose, paradoxic improvement is a characteristic of substances that impair memory by overstimulating pathways that normally sustain memory. Consistent with this, a low, but not a high, dose of gp120 reversed memory impairment induced by overstimulation of the VIPergic system, a memory-sustaining pathway. Further characterization showed that two strains of gp120 (SF and MN) were equally effective at improving memory and that, unlike other actions of gp120, glycation was not required. We conclude that (1) the predominant cognitive-impairing component of HIV-1 is its viral coat glycoproteins, (2) gp120 impairs memory by overstimulating pathways that normally sustain memory, (3) the cognitive effect of gp120 is mediated by its protein core, and (4) gp120 likely impairs memory by affecting the cholinergic/VIPergic system. C1 Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, St Louis, MO 63125 USA. St Louis Univ, Sch Med, Dept Internal Med, Div Geriatr Med, St Louis, MO 63106 USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Cochran VAMC, 915 N Grand Blvd, St Louis, MO 63106 USA. EM bankswa@slu.edu RI morley, john/F-9177-2011 OI morley, john/0000-0001-6444-2965 FU NINDS NIH HHS [R01 NS41863] NR 44 TC 11 Z9 11 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV 1 PY 2002 VL 18 IS 16 BP 1189 EP 1195 DI 10.1089/08892220260387931 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 612FD UT WOS:000179063100004 PM 12487825 ER PT J AU Archer, JD Cooper, GS Reist, PC Storm, JF Nylander-French, LA AF Archer, JD Cooper, GS Reist, PC Storm, JF Nylander-French, LA TI Exposure to respirable crystalline silica in eastern North Carolina farm workers SO AIHA JOURNAL LA English DT Article DE agriculture; dust; farming; occupational exposure; silica; respirable ID CALIFORNIA AGRICULTURE; OCCUPATIONAL EXPOSURE; RHEUMATOID-ARTHRITIS; QUARTZ EXPOSURE; DUST AB Occupational exposure to crystalline silica has been linked to silicosis, some forms of cancer, and certain autoimmune diseases. Little information exists on exposure levels of respirable silica in the agricultural industry. This study assessed respirable silica exposure of farm workers in eastern North Carolina. Sandy soils in this region have been shown to contain high levels of respirable silica. Personal breathing zone samples (n = 37) were collected from 27 workers at seven farms during various agricultural activities. The highest respirable silica concentrations were measured during sweet potato transplanting (3.91 +/- 2.07 mg/ml). Respirable silica exposure was observed to be associated with agricultural activity, soil moisture, relative humidity, and wind speed. Most of the variation in exposure (79%) was explained by agricultural activity and soil moisture. The observed percentage of silica levels (mean 34.7%) were almost twice as high as was reported in studies of California agriculture. This may be due to the loamy sand and sandy loam soil types in the regions in this study. In agriculture, respirable silica exposure is highly variable, but the potential for exposures above the threshold limit value of 0.05 mg/m(3) exists during particular agricultural activities. C1 Univ N Carolina, Sch Publ Hlth, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27695 USA. RP Nylander-French, LA (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Environm Sci & Engn, CB 7400,Rosenau Hall, Chapel Hill, NC 27599 USA. NR 23 TC 18 Z9 18 U1 0 U2 3 PU AMER INDUSTRIAL HYGIENE ASSOC PI FAIRFAX PA 2700 PROSPERITY AVE #250, FAIRFAX, VA 22031-4307 USA SN 1529-8663 J9 AIHA J JI AIHA J. PD NOV-DEC PY 2002 VL 63 IS 6 BP 750 EP 755 DI 10.1202/0002-8894(2002)063<0750:ETRCSI>2.0.CO;2 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 636CK UT WOS:000180436800016 PM 12570084 ER PT J AU Umhau, JC Petrulis, SG Diaz, R Riggs, PA Biddison, JR George, DT AF Umhau, JC Petrulis, SG Diaz, R Riggs, PA Biddison, JR George, DT TI Long-term abstinent alcoholics have a blunted blood glucose response to 2-deoxy-D-glucose SO ALCOHOL AND ALCOHOLISM LA English DT Article ID SUPRACHIASMATIC NUCLEUS; INSULIN SENSITIVITY; FOOD-INTAKE; CONSUMPTION; WITHDRAWAL; REDUCTION; RATS; HYPERGLYCEMIA; ANGIOTENSIN; MECHANISMS AB Aims: In this study we explored the relationship between alcohol and carbohydrate consumption in long-term abstinent alcoholics. Methods: We employed an established laboratory paradigm which allowed us to stimulate and measure dietary intake. 2-Deoxy-d-glucose (2-DG) is a glucose analogue that causes an intracellular energy deprivation resulting in exaggerated food consumption and a compensatory metabolic response to raise blood glucose. Using a double-blind design, we gave an infusion of 25 mg/kg 2-DG or placebo to 20 long-term abstinent alcoholics and 19 healthy volunteers. Results: There were no baseline differences in any dietary, behavioural or biochemical variables. As expected, 2-DG increased caloric consumption and blood glucose levels in a time-dependent fashion. There were no differences in food consumption between the alcoholics and the healthy volunteers following the 2-DG stimulus. However, the alcoholic group had a significantly blunted response in blood glucose. Conclusions: The origin of this atypical blood glucose response may antedate the onset of alcoholism, or it may be secondary to alcohol-related damage that persists beyond 6 months. Previous accounts of increased sweet consumption in alcoholics were not substantiated, although they may be present in the peri-withdrawal period. C1 NIAAA, Clin Studies Lab, Bethesda, MD 20892 USA. RP Umhau, JC (reprint author), NIAAA, Clin Studies Lab, 10 Ctr Dr,MSC-1610,Bldg 10,Room 6S-240, Bethesda, MD 20892 USA. NR 41 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0735-0414 J9 ALCOHOL ALCOHOLISM JI Alcohol Alcohol. PD NOV-DEC PY 2002 VL 37 IS 6 BP 586 EP 590 DI 10.1093/alcalc/37.6.586 PG 5 WC Substance Abuse SC Substance Abuse GA 622UW UT WOS:000179666300012 PM 12414552 ER PT J AU Grimbacher, B Belohradsky, BH Holland, SM AF Grimbacher, B Belohradsky, BH Holland, SM TI Immunoglobulin E in primary immunodeficiency diseases SO ALLERGY LA English DT Review DE hyper-IgE syndrome; immunoglobulin E; Netherton Comel syndrome; Omenn syndrome; primary immunodeficiency; Wiskott Aldrich syndrome ID WISKOTT-ALDRICH-SYNDROME; HYPER-IGE-SYNDROME; INFECTION JOBS SYNDROME; HYPERIMMUNOGLOBULIN-E SYNDROME; SYSTEMIC LUPUS-ERYTHEMATOSUS; BONE-MARROW TRANSPLANTATION; X-LINKED AGAMMAGLOBULINEMIA; INTERFERON-GAMMA PRODUCTION; RECURRENT-INFECTION; STAPHYLOCOCCUS-AUREUS C1 Univ Freiburg, Med Ctr, Dept Rheumatol & Clin Immunol, D-79106 Freiburg, Germany. Dr Von Haunerschen Kinderspital, Univ Childrens Hosp, Dept Infect Dis & Clin Immunol, Munich, Germany. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Grimbacher, B (reprint author), Univ Freiburg, Med Ctr, Dept Rheumatol & Clin Immunol, Hugstetter Str 55, D-79106 Freiburg, Germany. NR 139 TC 21 Z9 22 U1 2 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-4538 J9 ALLERGY JI Allergy PD NOV PY 2002 VL 57 IS 11 BP 995 EP 1007 DI 10.1034/j.1398-9995.2002.02168.x PG 13 WC Allergy; Immunology SC Allergy; Immunology GA 599PC UT WOS:000178343400004 PM 12358995 ER PT J AU Black, S AF Black, S TI Why we have death SO AMERICAN BIOLOGY TEACHER LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Black, S (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 11 TC 1 Z9 1 U1 0 U2 0 PU NATL ASSOC BIOLOGY TEACHERS INC PI RESTON PA 12030 SUNRISE VALLEY DR, #110, RESTON, VA 20191 USA SN 0002-7685 J9 AM BIOL TEACH JI Am. Biol. Teach. PD NOV-DEC PY 2002 VL 64 IS 9 BP 648 EP 648 PG 1 WC Biology; Education, Scientific Disciplines SC Life Sciences & Biomedicine - Other Topics; Education & Educational Research GA 618EN UT WOS:000179405800005 ER PT J AU Penninx, BWJH Kritchevsky, S Tracy, RP Newman, AB Harris, T Pahor, M AF Penninx, BWJH Kritchevsky, S Tracy, RP Newman, AB Harris, T Pahor, M TI Inflammation, cardiovascular disease, and disability in older persons SO AMERICAN HEART JOURNAL LA English DT Meeting Abstract CT 3rd Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY SEP 30-OCT 01, 2001 CL WASHINGTON, D.C. C1 Wake Forest Univ, Winston Salem, NC 27109 USA. Univ Tennessee, Memphis, TN USA. Univ Vermont, Burlington, VT USA. Univ Pittsburgh, Pittsburgh, PA USA. NIA, 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 0002-8703 J9 AM HEART J JI Am. Heart J. PD NOV PY 2002 VL 144 IS 5 MA 78 BP 914 EP 914 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 615NJ UT WOS:000179252400100 ER PT J AU Boland, LL Folsom, AR Sorlie, PD Taylor, HA Rosamond, WD Chambless, LE Cooper, LS AF Boland, LL Folsom, AR Sorlie, PD Taylor, HA Rosamond, WD Chambless, LE Cooper, LS TI Occurrence of unrecognized myocardial infarction in subjects aged 45 to 65 years (The ARIC study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY HEART-DISEASE; PREVALENCE; PROGNOSIS; RISK; EXPERIENCE; REYKJAVIK; MORTALITY; TRENDS AB Previous observational studies conducted predominantly in white men before 1988 estimated that 20% to 40% of myocardial infarctions (MIs) are unrecognized. Recent data on the proportion of MIs that are unrecognized, especially in women and African-Americans, are largely unavailable. Participants in the Atherosclerosis Risk in Communities (ARIC)study were men and women, aged 45 to 65 years, who were free of clinically recognized coronary heart disease and electrocardiographic evidence of MI at baseline (n = 12,843). Three follow-up clinic examinations were conducted approximately 3, 6, and 9 years after baseline, and included a 12-lead electrocardiogram at rest. Electrocardiographic evidence of infarction was defined as the appearance between the baseline and subsequent examinations of a major Q wave or a minor Q wave with ischemic ST-T changes. Clinically recognized (hospitalized) MI events were also identified and validated. Incident unrecognized MI was defined as electrocardiographic evidence of MI before, or in the absence of, a clinically recognized MI during the follow-up period. Of 508 Mis, 20% were unrecognized (95% confidence interval 16% to 23%), with African-Americans having a slightly higher percentage (23%) than whites (19%). The percentage of unrecognized Mis in men and women was similar. The percentage of unrecognized Mis in the ARIC sample between 1987 and 1998 was slightly lower than previous estimates from other populations. (C) 2002 by Excerpta Medica, Inc. C1 Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55454 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA. Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC USA. RP Folsom, AR (reprint author), Univ Minnesota, Sch Publ Hlth, Div Epidemiol, 1300 S 2nd St,Suite 300, Minneapolis, MN 55454 USA. FU NHLBI NIH HHS [N01-HC-55016, N01-HC-55015, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022] NR 20 TC 43 Z9 47 U1 0 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 1 PY 2002 VL 90 IS 9 BP 927 EP 931 AR PII S0002-9149(02)02655-3 DI 10.1016/S0002-9149(02)02655-3 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 610ZC UT WOS:000178991100004 PM 12398956 ER PT J AU Manolio, TA Gottdiener, JS Tsang, TSM Gardin, JM AF Manolio, TA Gottdiener, JS Tsang, TSM Gardin, JM CA Cardiovasc Hlth Study Collaborativ TI Left atrial dimensions determined by M-mode echocardiography in black and white older (>= 65 years) adults (The Cardiovascular Health Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID BLOOD-PRESSURE; RISK-FACTORS; DISEASE; HYPERTENSION; POPULATION AB Stroke and atrial fibrillation are common and serious illnesses in the elderly, the risks of which are substantially increased by left atrial (LA) enlargement. Despite growing recognition of the importance of LA-enlargement, the distribution and correlates of LA dimension in the elderly have not been well defined. A total of 3,882 women and men aged >65 years were studied. Increased LA dimension was independently associated with increased weight, mitral annular calcium, regional wall motion abnormalities, mitral early peak inflow velocity, and left ventricular (LV) fractional shortening. Increased LA dimension was' negatively associated with aortic leaflet thickening. The relation with LV fractional shortening was curvilinear With a nadir at 35% to 40%. LA dimension in black men was approximately 1.9 mm less than in white men in multivariate analyses. Adjustment for spirometric lung volumes and chest dimensions appeared to diminish the race-LA dimension relation. Thus, LA dimension is strongly associated with weight and with several echocardiographic valvular abnormalities; its relation with LV fractional shortening is U-shaped with a nadir at the borderline of LV functional impairment. (C) 2002 by Excerpta Medica, Inc. C1 NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. St Francis Hosp, Div Cardiol, Roslyn, NY USA. Mayo Clin, Div Cardiovasc Dis & Internal Med, Rochester, MN USA. St John Hosp & Med Ctr, Div Cardiol, Detroit, MI USA. RP Manolio, TA (reprint author), NHLBI, Div Epidemiol & Clin Applicat, 6701 Rockledge Dr,Room 8160, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [HC-35129, HC-95103, N01-HC-85079, HC-85085] NR 23 TC 26 Z9 27 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 1 PY 2002 VL 90 IS 9 BP 983 EP 987 AR PII S0002-9149(02)02665-6 DI 10.1016/S0002-9149(02)02665-6 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 610ZC UT WOS:000178991100014 PM 12398966 ER PT J AU Sumner, AE Farmer, NM Tulloch-Reid, MK Sebring, NG Yanovski, JA Reynolds, JC Boston, RC Premkumar, A AF Sumner, AE Farmer, NM Tulloch-Reid, MK Sebring, NG Yanovski, JA Reynolds, JC Boston, RC Premkumar, A TI Sex differences in visceral adipose tissue volume among African Americans SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE African Americans; visceral adipose tissue; fat distribution; percentage body fat; total body fat content; fat mass ID INSULIN-MEDIATED SUPPRESSION; NONESTERIFIED FATTY-ACIDS; COMPUTED-TOMOGRAPHY; PREDICTIVE EQUATIONS; WOMEN; TRIGLYCERIDE; SENSITIVITY; SECRETION; WHITE; MEN AB Background: Men are believed to have more visceral adipose tissue (VAT) than women have, but studies in African Americans that measured VAT from a single computed tomography (CT) slice found no sex difference. Objective: We used a serial-slice CT scan to investigate whether there is a sex difference in VAT volume among African Americans. Design: Single-slice CT measurements of VAT area at lumbar spine L2-3 and L4-5 levels were taken in 110 African Americans (44 men, 66 women). In 59 subjects (24 men, 35 women), VAT volume was also measured with contiguous CT slices from the diaphragm to the iliac crest. Fat mass was determined by dual-energy X-ray absorptiometry. Results: Men and women had similar ages ((x) over bar +/- SD: 36.1 +/- 7.8 and 35.6 +/- 7.8 y, respectively) and body mass indexes in kg/m(2) (29.5 +/- 6.9 and 32.0 +/- 8.9). The percentage of body fat was lower (P < 0.0001) in men (21.8 +/- 7.3%) than in women (37.4 +/- 7.9%). The VAT volume was greater (P = 0.01) in men (1443 +/- 931 cm(3)) than in women (940 +/- 821 cm(3)). There was no sex difference in unadjusted VAT area at L2-3 (men, 88.6 +/- 63.5 cm(2); women, 57.2 +/- 45.4 cm(2)) or L4-5 (men, 65.6 +/- 53.3 cm(2); women, 55.0 +/- 38.3 cm(2)). After adjustment for percentage of body fat or fat mass, men had larger VAT area at both levels (P < 0.01). After adjustment for body mass index, the sex difference in VAT area was detectable at L2-3 (P < 0.001) but not at L4-5 (P = 0.22). Conclusions: VAT volume is greater in men than in women. Detection of sex differences in VAT area among African Americans on single-slice CT requires adjustment for body fat content. At L2-3, adjustment for body mass index alone is adequate to detect sex differences in VAT. C1 NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. NICHD, Dev Endocrinol Branch, Bethesda, MD USA. NIH, Dept Nutr, Bethesda, MD 20892 USA. NIH, Dept Nucl Med, Bethesda, MD 20892 USA. NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. Univ Penn, New Bolton Ctr, Dept Clin Studies, Philadelphia, PA 19104 USA. RP Sumner, AE (reprint author), NIDDK, Diabet Branch, NIH, Bldg 10,Room 8S235D, Bethesda, MD 20892 USA. RI Tulloch-Reid, Marshall/E-4383-2012 NR 17 TC 23 Z9 23 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 NOV PY 2002 VL 76 IS 5 BP 975 EP 979 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 609PE UT WOS:000178913500010 PM 12399268 ER PT J AU Horlick, M Arpadi, SM Bethel, J Wang, J Moye, J Cuff, P Pierson, RN Kotler, D AF Horlick, M Arpadi, SM Bethel, J Wang, J Moye, J Cuff, P Pierson, RN Kotler, D TI Bioelectrical impedance analysis models for prediction of total body water and fat-free mass in healthy and HIV-infected children and adolescents SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE bioelectrical impedance analysis; pediatrics; ethnicity; puberty; HIV infection ID X-RAY ABSORPTIOMETRY; PREPUBERTAL CHILDREN; BIOIMPEDANCE ANALYSIS; GROWTH DISORDERS; CROSS-VALIDATION; DILUTION; YOUNG; POPULATION; AGREEMENT; POTASSIUM AB Background: Bioelectrical impedance analysis (BIA) is an attractive method of measuring pediatric body composition in the field, but the applicability of existing equations to diverse populations has been questioned. Objective: The objectives were to evaluate the performance of 13 published pediatric BIA-based predictive equations for total body water (TBW) and fat-free mass (FFM) and to refit the best-performing models. Design: We used TBW by deuterium dilution, FFM by dual-energy X-ray absorptiometry, and BIA-derived variables to evaluate BIA models in a cross-sectional study of 1291 pediatric subjects aged 4-18 y, from several ethnic backgrounds, including 54 children with HIV infection and 627 females. The best-performing models were refitted according to criterion values from this population, cross-validated, and assessed for performance. Additional variables were added to improve the predictive accuracy of the equations. Results: The correlation between predicted and criterion values was high for all models tested, but bias and precision improved with the refitted models. The 95% limits of agreement between predicted and criterion values were 16% and 11% for TBW and FFM, respectively. Bias was significant for some subgroups, and there was greater loss of precision in specific age groups and pubertal stages. The models with additional variables eliminated bias, but the limits of agreement and the loss of precision persisted. Conclusion: This study confirms that BIA prediction models may not be appropriate for individual evaluation but are suitable for population studies. Additional variables may be necessary to eliminate bias for specific subgroups. C1 Childrens Hosp New York, New York, NY USA. Columbia Univ, St Lukes Roosevelt Hosp, Dept Pediat, New York, NY USA. Columbia Univ, St Lukes Roosevelt Hosp, Dept Med, New York, NY USA. Columbia Univ, St Lukes Roosevelt Hosp, Body Composit Unit, New York, NY USA. WESTAT Corp, Rockville, MD 20850 USA. NICHHD, Bethesda, MD 20892 USA. RP Horlick, M (reprint author), St Lukes Roosevelt Hosp, Body Composit Unit, Plant Basement,1111 Amsterdam Ave, New York, NY 10025 USA. OI moye, john/0000-0001-9976-8586 FU NICHD NIH HHS [N01-HD-3-3162]; NIDDK NIH HHS [DK37352] NR 48 TC 73 Z9 79 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 NOV PY 2002 VL 76 IS 5 BP 991 EP 999 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 609PE UT WOS:000178913500012 PM 12399270 ER PT J AU Bloedon, LT Jeffcoat, AR Lopaczynski, W Schell, MJ Black, TM Dix, KJ Thomas, BF Albright, C Busby, MG Crowell, JA Zeisel, SH AF Bloedon, LT Jeffcoat, AR Lopaczynski, W Schell, MJ Black, TM Dix, KJ Thomas, BF Albright, C Busby, MG Crowell, JA Zeisel, SH TI Safety and pharmacokinetics of purified soy isoflavones: single-dose administration to postmenopausal women SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE genistein; daidzein; glycitein; soy isoflavones; cancer; toxicity; pharmacokinetics; postmenopausal women ID BREAST-CANCER CELLS; PHYTO-ESTROGENS; KINASE-ACTIVITY; POTENT INHIBITORS; MAMMARY-CANCER; BLOOD-PRESSURE; GROWTH-FACTOR; DIETARY SOY; GENISTEIN; APOPTOSIS AB Background: Soy isoflavones are being evaluated as chemopreventive agents for breast and other cancers. Objective: The objective was to perform safety and pharmacokinetic studies of purified unconjugated isoflavone preparations containing genistein, daidzein, and glycitein in postmenopausal women. Design: Twenty-four healthy postmenopausal women ingested a single dose of 1 of 2 purified (from soybeans) isoflavone preparations that delivered a genistein dose of 2, 4, 8, or 16 mg/kg body wt. These doses were higher than those previously administered to human females. Toxicity studies were performed 24 h and 3, 6, 14, and 30 d after isoflavone administration. Kinetic studies were performed during the first 24 h. Results: We observed a 7% decrease in systolic and diastolic blood pressure and a 32% decrease in the neutrophil count 24 h after treatment with formulation A. Isolated episodes of nausea, pedal edema, and breast tenderness were judged to be possibly related to the study treatment. The terminal plasma half-lives for free genistein, daidzein, and glycitein averaged 3.8, 7.7, and 3.4 h, respectively. The terminal pseudo half-lives for total genistein and total daidzein in plasma averaged 10.1 and 10.8 h, respectively. The estimated bioavailabilities of both total genistein and total daidzein from each of the 2 formulations were not significantly different. Conclusions: A single-dose administration of purified unconjugated isoflavones at amounts that exceed normal dietary intakes had minimal clinical toxicity in healthy postmenopausal women. The pharmacokinetic data suggest that chronic dosing at 12-24-h intervals would not lead to progressive accumulation of these isoflavones. C1 Univ N Carolina, Sch Med, Dept Nutr, Sch Publ Hlth, Chapel Hill, NC 27599 USA. Natl Canc Inst, Chemoprevent Agent Dev Res Grp, Div Canc Prevent, Rockville, MD USA. RP Zeisel, SH (reprint author), Univ N Carolina, Sch Med, Dept Nutr, Sch Publ Hlth, CB 7400,McGavran Greenberg Bldg, Chapel Hill, NC 27599 USA. OI Thomas, Brian/0000-0002-0097-4804 FU NCI NIH HHS [CA16086, N01-CN-75035]; NCRR NIH HHS [RR00046]; NIDDK NIH HHS [DK56350] NR 62 TC 105 Z9 111 U1 0 U2 6 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 NOV PY 2002 VL 76 IS 5 BP 1126 EP 1137 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 609PE UT WOS:000178913500031 PM 12399289 ER PT J AU Bild, DE Bluemke, DA Burke, GL Detrano, R Roux, AVD Folsom, AR Greenland, P Jacobs, DR Kronmal, R Liu, K Nelson, JC O'Leary, D Saad, MF Shea, S Szklo, M Tracy, RP AF Bild, DE Bluemke, DA Burke, GL Detrano, R Roux, AVD Folsom, AR Greenland, P Jacobs, DR Kronmal, R Liu, K Nelson, JC O'Leary, D Saad, MF Shea, S Szklo, M Tracy, RP TI Multi-ethnic study of atherosclerosis: Objectives and design SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cardiovascular diseases; cardiovascular system; cohort studies; coronary disease; epidemiologic methods; prospective studies ID CORONARY-HEART-DISEASE; BEAM COMPUTED-TOMOGRAPHY; CAROTID-ARTERY ATHEROSCLEROSIS; LEFT-VENTRICULAR MASS; MYOCARDIAL-INFARCTION; CARDIOVASCULAR HEALTH; BLOOD-PRESSURE; GENDER DIFFERENCES; MEDIA THICKNESS; YOUNG-ADULTS AB The Multi-Ethnic Study of Atherosclerosis was initiated in July 2000 to investigate the prevalence, correlates, and progression of subclinical cardiovascular disease (CVD) in a population-based sample of 6,500 men and women aged 45-84 years. The cohort will be selected from six US field centers. Approximately 38% of the cohort will be White, 28% African-American, 23% Hispanic, and 11% Asian (of Chinese descent). Baseline measurements will include measurement of coronary calcium using computed tomography; measurement of ventricular mass and function using cardiac magnetic resonance imaging; measurement of flow-mediated brachial artery endothelial vasodilation, carotid intimal-medial wall thickness, and distensibility of the carotid arteries using ultrasonography; measurement of peripheral vascular disease using ankle and brachial blood pressures; electrocardiography; and assessments of microalbuminuria, standard CVD risk factors, sociodemographic factors, life habits, and psychosocial factors. Blood samples will be assayed for putative biochemical risk factors and stored for use in nested case-control studies. DNA will be extracted and lymphocytes will be immortalized for genetic studies. Measurement of selected subclinical disease indicators and risk factors will be repeated for the study of progression over 7 years. Participants will be followed through 2008 for identification and characterization of CVD events, including acute myocardial infarction and other coronary heart disease, stroke, peripheral vascular disease, and congestive heart failure; therapeutic interventions for CVD; and mortality. C1 NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Radiol & Radiol Sci, Baltimore, MD USA. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. Harbor UCLA Res & Educ Inst, Los Angeles, CA USA. Columbia Univ, Dept Med, Sch Med, New York, NY USA. Columbia Univ, Dept Epidemiol, Sch Med, New York, NY USA. Columbia Univ, Dept Epidemiol, Sch Publ Hlth, New York, NY USA. Columbia Univ, Dept Med, Sch Publ Hlth, New York, NY USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA. Univ Washington, Dept Biostat, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. Tufts Univ New England Med Ctr, Dept Radiol, Boston, MA 02111 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. Univ Vermont, Coll Med, Dept Pathol, Lab Clin Biochem Res, Burlington, VT 05405 USA. Univ Vermont, Coll Med, Dept Biochem, Lab Clin Biochem Res, Burlington, VT 05405 USA. RP Bild, DE (reprint author), MESA Coordinating Ctr, Bldg 29,Suite 310,6200 NE 74th St, Seattle, WA 98115 USA. OI Bluemke, David/0000-0002-8323-8086 FU NHLBI NIH HHS [N01-HC-95159, N01-HC-95169] NR 83 TC 1370 Z9 1383 U1 4 U2 49 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 1 PY 2002 VL 156 IS 9 BP 871 EP 881 DI 10.1093/aje/kwf113 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 611UA UT WOS:000179035100012 PM 12397006 ER PT J AU Downing, GJ AF Downing, GJ TI Enhancing pathways to therapeutic development with clinical biomarkers SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Editorial Material C1 NIH, Off Sci Policy & Planning, Off Sci Policy, Off Director, Bethesda, MD 20892 USA. RP Downing, GJ (reprint author), NIH, Off Sci Policy & Planning, Off Sci Policy, Off Director, Bldg 1,Rm 218,1 Ctr Dr, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD NOV-DEC PY 2002 VL 10 IS 6 BP 646 EP 648 DI 10.1176/appi.ajgp.10.6.646 PG 3 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 614DC UT WOS:000179172200002 PM 12427572 ER PT J AU Ming, JE Muenke, M AF Ming, JE Muenke, M TI Multiple hits during early embryonic development: Digenic diseases and holoprosencephaly SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Review ID BARDET-BIEDL-SYNDROME; PRIMARY CONGENITAL GLAUCOMA; LEMLI-OPITZ-SYNDROME; SONIC-HEDGEHOG GENE; JUNCTIONAL EPIDERMOLYSIS-BULLOSA; SIMPLE MENDELIAN DISORDERS; POLYCYSTIC KIDNEY-DISEASE; VENTRAL MIDLINE CELLS; OPEN-ANGLE GLAUCOMA; ONE-EYED PINHEAD C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Dept Pediat, Div Human Genet & Mol Biol, Philadelphia, PA 19104 USA. RP Muenke, M (reprint author), NHGRI, Med Genet Branch, NIH, 10 Ctr Dr MSC 1852,Bldg 10 Room 10C103, Bethesda, MD 20892 USA. FU NICHD NIH HHS [HD01218] NR 123 TC 197 Z9 202 U1 2 U2 15 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2002 VL 71 IS 5 BP 1017 EP 1032 DI 10.1086/344412 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 609CD UT WOS:000178884300002 PM 12395298 ER PT J AU Atwood, LD Heard-Costa, NL Cupples, LA Jaquish, CE Wilson, PWF D'Agostino, RB AF Atwood, LD Heard-Costa, NL Cupples, LA Jaquish, CE Wilson, PWF D'Agostino, RB TI Genomewide linkage analysis of body mass index across 28 years of the Framingham Heart Study SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID VARIANCE-COMPONENTS; PEDIGREES; LOCUS AB We performed a genomewide linkage analysis of six separate measurements of body mass index (BMI) taken over a span of 28 years, from 1971 to 1998, in the Framingham Heart Study. Variance-components linkage analysis was performed on 330 families, using 401 polymorphic markers. The number of individuals with data at each exam ranged from 1,930, in 1971, to 1,401, in 1998. Sex, age, and age squared were included as covariates in the model. There was substantial evidence for linkage on chromosome 6q23-25, in the area of D6S1009, GATA184A08, D6S2436, and D6S305. The six measurements had maximum LOD scores of 4.64, 2.29, 2.41, 1.40, 0.99, and 3.08, respectively, all in the chromosome 6q23-25 region. There was also evidence for linkage of multiple measures on chromosome 11q14 in the area of D11S1998, D11S4464, and D11S912. The six measurements had maximum LOD scores of 0.61, 3.27, 1.30, 0.68, 1.30, and 2.29, respectively, all in the chromosome 11q14 region. Both of these regions have been reported in previous studies. Evidence in the same regions from multiple measurements does not constitute replication; however, it does indicate that linkage studies of BMI are robust with respect to measurement error. It is unclear whether the variation in LOD scores in these regions is due to age effects, varying sample size, or other confounding factors. C1 Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. Boston Univ, Dept Math & Stat, Boston, MA 02118 USA. NHLBI, Bethesda, MD 20892 USA. RP Atwood, LD (reprint author), Boston Univ, Sch Med, Dept Neurol, 715 Albany St,B-609, Boston, MA 02118 USA. FU NHLBI NIH HHS [HC-25195, N01HC25195] NR 19 TC 114 Z9 117 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2002 VL 71 IS 5 BP 1044 EP 1050 DI 10.1086/343822 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 609CD UT WOS:000178884300004 PM 12355400 ER PT J AU Brody, LC Conley, M Cox, C Kirke, PN McKeever, MP Mills, JL Molloy, AM O'Leary, VB Parle-McDermott, A Scott, JM Swanson, DA AF Brody, LC Conley, M Cox, C Kirke, PN McKeever, MP Mills, JL Molloy, AM O'Leary, VB Parle-McDermott, A Scott, JM Swanson, DA TI A polymorphism, R653Q, in the trifunctional enzyme methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase/formyltetrahydrofolate synthetase is a maternal genetic risk factor for neural tube defects: Report of the birth defects research group SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DEHYDROGENASE-METHENYLTETRAHYDROFOLATE-CYCLOHYDROLASE; 5,10-METHYLENETETRAHYDROFOLATE REDUCTASE GENE; SPINA-BIFIDA; FORMYLTETRAHYDROFOLATE SYNTHETASE; THERMOLABILE VARIANT; SACCHAROMYCES-CEREVISIAE; TURKISH PATIENTS; C677T MUTATION; FOLATE LEVELS; MTHFR GENE AB Women who take folic acid periconceptionally reduce their risk of having a child with a neural tube defect (NTD) by >50%. A variant form of methylenetetrahydrofolate reductase (MTHFR) (677C-->T) is a known risk factor for NTDs, but the prevalence of the risk genotype explains only a small portion of the protective effect of folic acid. This has prompted the search for additional NTD-associated variants in folate-metabolism enzymes. We have analyzed five potential single-nucleotide polymorphisms (SNPs) in the cytoplasmic, nicotinamide adenine dinucleotide phosphate-dependent, trifunctional enzyme methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase/formyltetrahydrofolate synthetase (MTHFD1) for an association with NTDs in the Irish population. One SNP, R653Q, in this gene appears to be associated with NTD risk. We observed an excess of the MTHFD1 "Q" allele in the mothers of children with NTD, compared with control individuals. This excess was driven by the overrepresentation of QQ homozygotes in the mothers of children with NTD compared with control individuals (odds ratio 1.52 [95% confidence interval 1.16-1.99], P=.003). We conclude that genetic variation in the MTHFD1 gene is associated with an increase in the genetically determined risk that a woman will bear a child with NTD and that the gene may be associated with decreased embryo survival. C1 Univ Dublin Trinity Coll, Dept Biochem, Dublin 2, Ireland. Univ Dublin Trinity Coll, Dept Clin Med, Dublin 2, Ireland. Univ Dublin Trinity Coll, Child Hlth Epidemiol Div, Hlth Res Board, Dublin 2, Ireland. NICHHD, Genome Technol Branch, NHGRI, NIH, Bethesda, MD 20892 USA. NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. RP Parle-McDermott, A (reprint author), Univ Dublin Trinity Coll, Dept Biochem, Dublin 2, Ireland. NR 39 TC 161 Z9 168 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2002 VL 71 IS 5 BP 1207 EP 1215 DI 10.1086/344213 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 609CD UT WOS:000178884300020 PM 12384833 ER PT J AU Huizing, M Anikster, Y Gahl, WA AF Huizing, M Anikster, Y Gahl, WA TI Griscelli syndrome types 1 and 2 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Letter C1 NHGRI, NIH, Sect Human Biochem Genet, Med Genet Branch, Bethesda, MD 20892 USA. Chaim Sheba Med Ctr, Metab Unit, IL-52621 Tel Hashomer, Israel. RP Huizing, M (reprint author), NHGRI, NIH, Sect Human Biochem Genet, Med Genet Branch, 10 Ctr Dr,MSC 1851,Bldg 10,Room 10C-103, Bethesda, MD 20892 USA. NR 3 TC 1 Z9 1 U1 1 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2002 VL 71 IS 5 BP 1238 EP 1238 DI 10.1086/344141 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 609CD UT WOS:000178884300026 ER PT J AU Weinberg, CR Mitchell, L AF Weinberg, CR Mitchell, L TI Regarding "Parental genotypes in the risk of a complex disease" SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Letter ID LINKAGE DISEQUILIBRIUM; SUBJECT; TRIADS; GENES C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. RP Weinberg, CR (reprint author), Natl Inst Environm Hlth Sci, MD A3-03,POB 12233, Res Triangle Pk, NC 27709 USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2002 VL 71 IS 5 BP 1239 EP 1240 DI 10.1086/344143 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 609CD UT WOS:000178884300028 PM 12452178 ER PT J AU Sarnak, MJ Wang, SR Beck, GJ Kusek, JW Selhub, J Greene, T Levey, AS AF Sarnak, MJ Wang, SR Beck, GJ Kusek, JW Selhub, J Greene, T Levey, AS TI Homocysteine, cysteine, and B vitamins as predictors of kidney disease progression SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE homocysteine; B vitamins; progression of kidney disease; glomerular filtration rate (GFR) ID STAGE RENAL-DISEASE; RISK FACTOR; PLASMA HOMOCYSTEINE; CARDIOVASCULAR-DISEASE; VASCULAR-DISEASE; SERUM; HYPERHOMOCYSTEINEMIA; MORTALITY; ATHEROSCLEROSIS; CHROMATOGRAPHY AB Background: Pathological similarities between atherosclerosis and glomerulosclerosis suggest that risk factors for the two processes may be similar. Elevated total homocysteine (tHcy) levels and low B vitamin levels are risk factors for atherosclerosis, but have not been evaluated sufficiently as risk factors for the progression of kidney disease. Methods: Frozen samples from the Modification of Diet in Renal Disease Study were assayed for serum tHcy, cysteine, pyridoxal 5-phosphate (PLP), folate, and vitamin B-12 levels in 804 participants. These factors were evaluated in both continuous and categorical analyses as risk factors for glomerular filtration rate (GFR) decline by using univariate and multivariable analyses. Results: At baseline, mean tHcy levels in study A (GFR, 25 to 55 mL/min/1.73 m(2)) and study B (GFR, 13 to 24 mL/min/1.73 m(2)) were 16.9 mumol/L (median, 15.6 mumol/L) and 23.0 mumol/L (median, 20.5 mumol/L), respectively. Mean follow-up was 2.2 years. Mean GFR declines were -4.35 and -3.65 mL/min/y in studies A and B, respectively. There was no significant association between change in GFR with baseline level of tHcy in univariate (-0.26 mL/min/y per 1-SD unit increase in tHcy level; 95% confidence interval [CI], -0.67 to 0.15) or multivariable (-0.18 mL/min/y per 1-SD unit increase in tHcy level; 95% CI, -0.53 to 0.17) analysis in study A or univariate (0.07 mL/min/y per 1-SD unit increase in tHcy level; 95% CI, -0.36 to 0.51) or multivariable (0.24 mL/min/y per 1-SD unit increase in tHcy level; 95% CI, -0.16 to 0.64) analysis in study B. Similarly, higher cysteine levels and lower B vitamin levels were not associated with faster rates of GFR decline in multivariable analysis in either study. Conclusion: Higher tHcy or cysteine levels and lower folate, PLP, and vitamin Bit levels are not independent risk factors for progression of nondiabetic kidney disease. C1 Tufts Univ New England Med Ctr, Boston, MA 02111 USA. Tufts Univ, Sch Med, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. NIH, Bethesda, MD 20892 USA. RP Sarnak, MJ (reprint author), Tufts Univ New England Med Ctr, Box 391,750 Washington St, Boston, MA 02111 USA. FU NIDDK NIH HHS [U01 DK35073, K23 DK02904-02] NR 39 TC 26 Z9 27 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD NOV PY 2002 VL 40 IS 5 BP 932 EP 939 DI 10.1053/ajkd.2002.36323 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 611ZA UT WOS:000179047100007 PM 12407637 ER PT J AU Cusumano, AM Bodkin, NL Hansen, BC Iotti, R Owens, J Klotman, PE Kopp, JB AF Cusumano, AM Bodkin, NL Hansen, BC Iotti, R Owens, J Klotman, PE Kopp, JB TI Glomerular hypertrophy is associated with hyperinsulinemia and precedes overt diabetes in aging rhesus monkeys SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE diabetes; glomerulosclerosis; glomerular basement membrane (GBM); electron microscopy (EM); insulin ID PANCREAS TRANSPLANTATION; MESANGIAL MATRIX; MASSIVE OBESITY; RENAL-DISEASE; INSULIN; MELLITUS; KIDNEY; LESIONS; MORPHOLOGY; SCLEROSIS AB Background. Rhesus monkeys have a high prevalence of obesity and spontaneous type 2 diabetes mellitus after the age of 10 years. These monkeys go through a defined, sequential set of metabolic phases, including fasting hyperinsulinemia, impaired glucose tolerance, and fasting hyperglycemia. Using these monkeys, we addressed the hypothesis that renal structural features characteristic of diabetic nephropathy might precede the appearance of overt diabetes. Methods: We carried out a quantitative analysis of renal tissue, using light microscopy and electron microscopy, from 6 metabolically normal young monkeys, 7 metabolically normal aged monkeys, 7 hyperinsulinemic monkeys, and 18 diabetic monkeys. Results: Glomerular volume was increased significantly in hyperinsulinemic monkeys and diabetic monkeys compared with aged normal monkeys. In the normal monkey, glomerular basement membrane (GBM) width rises with age but reaches a plateau at about 20 years of age; the presence of diabetes was associated with markedly increased GBM width. Glomerular tuft volume and GBM width were correlated most closely with age and with glucose tolerance. Conclusion: Diabetic monkey kidneys are characterized by glomerular enlargement, glomerulosclerosis, and thickening of the GBM. Glomerular hypertrophy begins in the prediabetic hyperinsulinemic phase. This finding suggests that early intervention may be required in human patients to preserve normal glomerular structure. C1 NIDDKD, Vet Resources Program, Off Res Serv, NIH, Bethesda, MD 20892 USA. Ctr Med Educ & Clin Invest, Nephrol Sect, CEMIC, Buenos Aires, DF, Argentina. Ctr Med Educ & Clin Invest, Dept Pathol, Buenos Aires, DF, Argentina. Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. CUNY Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. NIDDKD, Kidney Dis Sect, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Kopp, JB (reprint author), NIDDKD, Vet Resources Program, Off Res Serv, NIH, Bldg 10,Room 3N116, Bethesda, MD 20892 USA. RI Hansen, Barbara/J-8723-2012; OI Hansen, Barbara/0000-0001-9646-3525; Kopp, Jeffrey/0000-0001-9052-186X NR 33 TC 55 Z9 63 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD NOV PY 2002 VL 40 IS 5 BP 1075 EP 1085 DI 10.1053/ajkd.2002.36348 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 611ZA UT WOS:000179047100024 PM 12407654 ER PT J AU Redlinger-Grosse, K Bernhardt, BA Berg, K Muenke, M Biesecker, BB AF Redlinger-Grosse, K Bernhardt, BA Berg, K Muenke, M Biesecker, BB TI The decision to continue: The experiences and needs of parents who receive a prenatal diagnosis of holoprosencephaly SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE holoprosencephaly; prenatal diagnosis; pregnancy continues on; decision making ID FETAL ANOMALIES; ABNORMALITY; PREGNANCY; ABORTION AB Holoprosencephaly (HPE) is a condition characterized by a defect in the development of the midline embryonic forebrain. When detected prenatally, the diagnosis of HPE offers parents a poor but often uncertain prognosis. Since the majority of parents receiving a prenatal diagnosis of an abnormality terminate their pregnancies, few studies have examined parents' experiences and needs surrounding the decision to continue a pregnancy. We present a descriptive study of in-depth interviews with 24 parents who chose to continue their pregnancy after receiving a prenatal diagnosis of HPE. Parents were asked about their decision-making process to continue the pregnancy. Qualitative analysis was used to identify common themes that emerged from these parents' experiences. The results suggest that most parents did not make an active decision about continuing the pregnancy. Rather, they described a more subtle decision-making process that evolved over time and consisted of several factors. These factors included the parents' religious and personal beliefs, past experiences, and the uncertainty involved in the diagnosis of HPE. Throughout the decision-making process, they described informational, emotional, and supportive needs from family, friends, and health professionals. All of these factors contributed to the evolution of the parents' decision to continue the pregnancy and the acceptance of their decision. Results of this exploratory study suggest health care professionals need to work with parents as they make their decision to continue an affected pregnancy. The results also provide the groundwork for prospective investigation into parents' decision-making process as they receive and adjust to prenatal diagnoses of an abnormality. Published (C) 2002 Wiley-Liss, Inc. C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Obstet Gynecol, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD USA. Johns Hopkins Univ, Dept Hlth Policy & Management, Bloomberg Sch Publ Hlth, Baltimore, MD 21218 USA. RP Redlinger-Grosse, K (reprint author), Johns Hopkins Univ Hosp, Prenatal Diagnost Ctr, 600 N Wolfe St,CMSC 1004, Baltimore, MD 21287 USA. NR 36 TC 33 Z9 34 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 1 PY 2002 VL 112 IS 4 BP 369 EP 378 DI 10.1002/ajmg.10657 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 603PN UT WOS:000178568700010 PM 12376939 ER PT J AU Romero, R Chaiworapongsa, T Espinoza, J Gomez, R Yoon, BH Edwin, S Mazor, M Maymon, E Berry, S AF Romero, R Chaiworapongsa, T Espinoza, J Gomez, R Yoon, BH Edwin, S Mazor, M Maymon, E Berry, S TI Fetal plasma MMP-9 concentrations are elevated in preterm premature rupture of the membranes SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 22nd Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 14-19, 2002 CL NEW ORLEANS, LOUISIANA SP Soc Maternal Fetal Med DE premature rupture of membranes; fetal plasma; matrix metalloproteinase-9; preterm labor; interleukin-1 beta; soluble tumor necrosis factor receptors ID TUMOR-NECROSIS-FACTOR; INFLAMMATORY RESPONSE SYNDROME; MATRIX METALLOPROTEINASE-9; SOLUBLE RECEPTORS; FACTOR-ALPHA; PARTURITION; LABOR; MATRIX-METALLOPROTEINASE-9; INFECTION AB OBJECTIVE: The objective of this study was to determine whether the concentrations of matrix metalloproteinase-9 (MMP-9) in the fetal (fetal plasma and amniotic fluid) and maternal compartments (plasma) are different in patients presenting with preterm premature rupture of membranes (PROM) than in those with preterm labor and intact membranes. STUDY DESIGN: Fetal plasma MMP-9, interleukin-1beta (IL-1beta) IL-6, soluble tumor necrosis factor receptors 1 (sTNF-R1) and 2 (sTNF-R2) were measured in fetuses with preterm labor and intact membranes (n = 96) and preterm PROM (n = 43). The concentrations of analytes were determined with sensitive and specific immunoassays. A P value <.05 was considered significant. RESULTS: (1) The median fetal plasma MMP-9 concentration was significantly higher in fetuses with preterm PROM than in those with preterm labor (P =.035). (2) In contrast, fetal plasma IL-1beta, sTNF-R1, and sTNF-R2 were significantly higher in patients with preterm labor than in those with preterm PROM (IL-1beta, P =.01; sTNF-R1, P =.003; and sTNF-R2, P =.02). (3) The median amniotic fluid concentration of MMP-9 was higher in patients with preterm PROM than in those with preterm labor (P <.001). CONCLUSION: Fetuses with preterm PROM have increased concentrations of an enzyme (MMP-9) implicated in the mechanism of membrane rupture but lower concentrations of IL-1beta, sTNF-R1, and sTNF-R2 than fetuses with preterm labor and intact membranes. A role for the fetus in the genesis of preterm PROM deserves consideration. C1 Wayne State Univ, Hutzel Hosp, NICHD, Perinatol Res Branch,Dept OB GYN, Detroit, MI 48201 USA. NICHHD, Perinatal Res Branch, Bethesda, MD 20892 USA. Seoul Natl Univ, Dept Obstet & Gynecol, Seoul 151742, South Korea. Soroka Univ, Med Ctr, Dept Obstet & Gynecol, Beer Sheva, Israel. RP Romero, R (reprint author), Wayne State Univ, Hutzel Hosp, NICHD, Perinatol Res Branch,Dept OB GYN, 4707 St Antoine Blvd, Detroit, MI 48201 USA. RI Yoon, Bo Hyun/H-6344-2011 NR 23 TC 68 Z9 72 U1 0 U2 2 PU MOSBY, 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 NOV PY 2002 VL 187 IS 5 BP 1125 EP 1130 DI 10.1067/mob.2002.127312 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 619BZ UT WOS:000179454600001 PM 12439489 ER PT J AU Kim, YM Chaiworapongsa, T Gomez, R Bujold, E Yoon, BH Rotmensch, S Thaler, HT Romero, R AF Kim, YM Chaiworapongsa, T Gomez, R Bujold, E Yoon, BH Rotmensch, S Thaler, HT Romero, R TI Failure of physiologic transformation of the spiral arteries in the placental bed in preterm premature rupture of membranes SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 22nd Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 14-19, 2002 CL NEW ORLEANS, LOUISIANA SP Soc Maternal Fetal Med DE placental bed; placenta; physiologic transformation; placentation; preterm premature rupture of membranes; precclampsia; spiral arteries ID FETAL GROWTH-RETARDATION; PRE-ECLAMPSIA; MORPHOLOGICAL-CHANGES; PREGNANCY AB OBJECTIVE: The purpose of this study was to determine whether failure of physiologic transformation of the spiral arteries occurs in patients with preterm premature rupture of membranes (PROM). STUDY DESIGN: A cross-sectional study was designed to examine the histopathologic findings in the placental bed and placenta of patients with preterm PROM, preeclampsia, and normal women at term. Immunohistochemistry with cytokeratin 7 and periodic acid-Schiff (PAS) were used to detect trophoblast and fibrinoid and to diagnose failure of physiologic transformation of the spiral arteries. RESULTS: One hundred thirteen cases met the inclusion criteria, 59 from patients with normal pregnancies, 31 with preterm PROM, and 23 with preeclampsia. The mean number of the spiral arteries with failure of physiologic transformation of the myometrial segment was significantly higher in patients with preterm PROM and preeclampsia than in normal pregnant women at term (P =.006 and P <.0001, respectively). In contrast, the mean number of the spiral arteries with failure of physiologic transformation of the decidual segment of the spiral arteries in the basal plate of the placenta was not significantly different in patients with preterm PROM from that in normal pregnant women (P >.05). Placentas from patients with preterm PROM had a higher frequency of vascular lesions than those from normal pregnant women (P=.02). CONCLUSION: Defective placentation, defined as failure of physiologic transformation of the myometrial segment of the spiral artery, is frequently present in preterm PROM. C1 Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, NICHHD,Perinatol Res Branch, Detroit, MI 48201 USA. NICHHD, Perinatol Res Branch, Bethesda, MD 20892 USA. Seoul Natl Univ, Dept Obstet & Gynecol, Seoul 151742, South Korea. Edith Wolfson Med Ctr, Dept Obstet & Gynecol, Holson, Israel. Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. RP Romero, R (reprint author), Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, NICHHD,Perinatol Res Branch, 4707 St Antoine Blvd, Detroit, MI 48201 USA. RI Yoon, Bo Hyun/H-6344-2011 NR 18 TC 137 Z9 141 U1 0 U2 3 PU MOSBY, 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 NOV PY 2002 VL 187 IS 5 BP 1137 EP 1142 DI 10.1067/mob.2002.127720 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 619BZ UT WOS:000179454600003 PM 12439491 ER PT J AU Berghella, V Klebanoff, M McPherson, C Carey, JC Hauth, JC Ernest, JM Heine, RP Wapner, RJ Trout, W Moawad, A Leveno, KJ Miodovnik, M Sibai, BM Van Dorsten, JP Dombrowski, MP O'Sullivan, MJ Varner, M Langer, O AF Berghella, V Klebanoff, M McPherson, C Carey, JC Hauth, JC Ernest, JM Heine, RP Wapner, RJ Trout, W Moawad, A Leveno, KJ Miodovnik, M Sibai, BM Van Dorsten, JP Dombrowski, MP O'Sullivan, MJ Varner, M Langer, O CA Natl Inst Child Hlth Dev Maternal TI Sexual intercourse association with asymptomatic bacterial vaginosis and Trichomonas vaginalis treatment in relationship to preterm birth SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE bacterial vaginosis; Trichomonas vaginalis; preterm birth; sex ID METRONIDAZOLE THERAPY; RANDOMIZED TRIAL; PREGNANT-WOMEN; DELIVERY; COITUS; INFECTIONS; PARTNERS; WEIGHT AB OBJECTIVE: The purpose of this study was to determine whether sexual intercourse was associated with the treatment efficacy or the incidence of preterm birth in two large randomized trials in which metronidazole treatment of bacterial vaginosis or Trichomonas vaginalis did not reduce preterm birth. STUDY DESIGN: Secondary analysis of two multicenter, double-blind, placebo-controlled trials in which women with asymptomatic bacterial vaginosis on Gram stain or asymptomatic T vaginalis on culture were randomized at 16 to 23 weeks of gestation to metronidazole or placebo. In both studies, women took 2 g of metronidazole or placebo in the presence of a nurse (first dose) and were given a second dose to take 48 hours later. This regimen was repeated (third and fourth doses) at 24 to 29 weeks. At the time of the third dose, bacterial vaginosis and T vaginalis specimens were collected again. Patients who were randomly selected to receive metronidazole were analyzed for bacterial vaginosis and T vaginalis at 24 to 29 weeks and for preterm birth of < 37 weeks of gestation, according to intercourse between first and second doses and between the second and third doses. Continuous variables were compared with the use of the Wilcoxon rank-sum test; categoric variables were compared with the use of the chi(2) test, Fisher exact test, or the Mantel-Haenzel test of trend. RESULTS: Sexual intercourse between the first and second doses or between the second and third doses did not influence the incidence of bacterial vaginosis (18% vs 24%; relative risk, 0.7; 95% Cl, 0.5-1.1; and 23% vs 20%; relative risk, 1.2; 95% Cl, 0.9-1.6, respectively) or T vaginalis (4% vs 8%; relative risk, 0.5; 95% Cl, 0.1-3.6; and 5% vs 10%; relative risk, 0.5; 95% Cl, 0.2-1.1; respectively) at 24 to 29 weeks of gestation compared with no intercourse. In the T vaginalis trial, sexual intercourse between the first and second doses or between the second and third doses did not influence the incidence of preterm birth (13% vs 17%; relative risk, 0.8; 95% Cl, 0.3-2.1; and 16% vs 17%; relative risk, 1.0; 95% Cl, 0.6-1.6; respectively) compared with no intercourse. In the bacterial vaginosis trial, although sexual intercourse between the first and second doses did not influence the incidence of preterm birth (11% vs 12%; relative risk, 0.9; 95% Cl, 0.6-1.5), sexual intercourse between the second and third doses was associated with a reduction in the incidence of preterm birth (10% vs 16%; relative risk, 0.6; 95% Cl, 0.4-0.9) compared with no intercourse. CONCLUSION: Sexual intercourse was associated with neither the efficacy of metronidazole treatment of bacterial vaginosis or T vaginalis nor with the incidence of preterm birth. In the bacterial vaginosis study, intercourse between the second and third doses had a negative association with preterm birth. C1 Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. Univ Utah, Salt Lake City, UT 84112 USA. Univ Miami, Miami, FL 33152 USA. Wayne State Univ, Detroit, MI 48202 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Univ Cincinnati, Cincinnati, OH 45221 USA. Columbia Univ Coll Phys & Surg, St Lukes Roosevelt Hosp, New York, NY 10032 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Univ Chicago, Chicago, IL 60637 USA. Ohio State Univ, Columbus, OH 43210 USA. Med Coll Penn & Hahnemann Univ, Philadelphia, PA USA. Univ Pittsburgh, Pittsburgh, PA USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Univ Alabama, Birmingham, AL USA. Univ Oklahoma, Oklahoma City, OK USA. NICHHD, Bethesda, MD 20892 USA. RP Berghella, V (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. RI Varner, Michael/K-9890-2013; OI Varner, Michael/0000-0001-9455-3973; Berghella, Vincenzo/0000-0003-2854-0239 FU NICHD NIH HHS [U10 HD27917, U10 HD21410, U10 HD21414, U10 HD27860, U10 HD27861, U10 HD27869, U10 HD27883, U10 HD27889, U10 HD27905, U10 HD27915, U10 HD34116, U10 HD34122, U10 HD34136, U10 HD34208, U10 HD34210, U10 HD36801] NR 29 TC 7 Z9 7 U1 0 U2 2 PU MOSBY, 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 NOV PY 2002 VL 187 IS 5 BP 1277 EP 1282 DI 10.1067/mob.2002.127134 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 619BZ UT WOS:000179454600032 PM 12439520 ER PT J AU Bernstein, HB Jackson, RW Anderson, J Kinter, AL AF Bernstein, HB Jackson, RW Anderson, J Kinter, AL TI The effect of elective cesarean delivery and intraparturn infection on fetal lymphocyte activation. and susceptibility to HIV infection SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 22nd Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 14-19, 2002 CL NEW ORLEANS, LOUISIANA SP Soc Maternal Fetal Med DE fetal lymphocyte activation; human immunodeficiency virus infection; mode of delivery; chorioamnionitis; preterm labor ID HUMAN-IMMUNODEFICIENCY-VIRUS; SUBCLINICAL INFECTION; TRANSMISSION; TYPE-1; BLOOD; CORD; INTRAUTERINE; CHILDREN; DISEASE; PRETERM AB OBJECTIVE: Mother-to-child transmission of the human immunodeficiency virus may be reduced with elective cesarean delivery before labor. Because immune activation enhances the human immunodeficiency virus infection, we hypothesized that fetal lymphocytes that are obtained at elective cesarean delivery may be less activated, therefore less susceptible to human immunodeficiency virus infection than cells that are obtained after normal spontaneous vaginal delivery at term. A second hypothesis was that intrapartum infection correlates with increased lymphocyte activation and susceptibility to human immunodeficiency virus infection. STUDY DESIGN: Samples were obtained after normal spontaneous vaginal delivery (n = 13), elective cesarean delivery (n = 12), chorioamnionitis (n = 5), and preterm labor (n = 6). Activation markers were measured by flow cytometry, and cord blood mononuclear cells were infected with the human immunodeficiency virus. RESULTS: Cell activation was comparable within the normal spontaneous vaginal delivery and elective cesarean delivery groups; there was no difference in susceptibility to in vitro human immunodeficiency virus infection. Intrapartum infection (chorioamnionitis, preterm labor) was associated with increased cell activation. Chorioamnionitis/preterm labor also tended to increase cord blood mononuclear cell susceptibility to human immunodeficiency virus infection. CONCLUSION: Labor did not activate fetal lymphocytes or alter susceptibility to human immunodeficiency virus infection compared with elective cesarean delivery. Intrapartum infection was associated with cell activation, and there was a trend toward increased susceptibility to human immunodeficiency virus infection. These data suggest that fetal lymphocyte activation correlates with susceptibility to human immunodeficiency virus infection and may account for the increased mother-to-child transmission of the human immunodeficiency virus that has been seen in association with chorioamnionitis and preterm labor. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Obstet & Gynecol, Baltimore, MD 21205 USA. RP Bernstein, HB (reprint author), Univ Calif Los Angeles, Dept Obstet & Gynecol, David Geffen Sch Med, 10833 LeConte Ave,Room 22-150 CHS,Box 951740, Los Angeles, CA 90095 USA. FU NICHD NIH HHS [5K12HD00849] NR 18 TC 4 Z9 5 U1 0 U2 1 PU MOSBY, 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 NOV PY 2002 VL 187 IS 5 BP 1283 EP 1289 DI 10.1067/mob.2002.126978 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 619BZ UT WOS:000179454600033 PM 12439521 ER PT J AU Romero, R Kuivaniemi, H Tromp, G Olson, JM AF Romero, R Kuivaniemi, H Tromp, G Olson, JM TI The design, execution, and interpretation of genetic association studies to decipher complex diseases SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Review DE genetic studies; polymorphisms; single nucleotide polymorphisms; linkage disequilibrium; complex disorders ID FACTOR-V-LEIDEN; TUMOR-NECROSIS-FACTOR; PRETERM PREMATURE RUPTURE; FETAL INHERITED THROMBOPHILIAS; ADVERSE DRUG-REACTIONS; PROTEIN-C RESISTANCE; FACTOR-ALPHA GENE; LINKAGE DISEQUILIBRIUM; BETA(2)-ADRENERGIC RECEPTOR; HUMAN-GENOME AB Genetic association studies are becoming increasingly frequent in the obstetric and gynecologic literature and they are considered central to the deciphering of the genetic basis of complex disease. The purpose, design, execution, analysis, and interpretation of genetic association studies in reproduction are discussed. Frequently used terms are defined (eg, genotype, haplotype, polymorphism, single nucleotide polymorphism, linkage disequilibrium). Guidelines are proposed for the evaluation of reports of genetic association studies (including selection of polymorphisms for study, study design, assay characteristics, sample size, multiple testing, and multivariable analysis). The potential value of this type of investigation in elucidating the mechanisms of disease in reproduction is illustrated. C1 Natl Inst Child & Hlth & Human Dev, Perinatol Res Branch, Detroit, MI 48201 USA. Wayne State Univ, Ctr Mol Med & Genet, Sch Med, Detroit, MI 48202 USA. Wayne State Univ, Dept Surg, Sch Med, Detroit, MI 48202 USA. Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. RP Romero, R (reprint author), Natl Inst Child & Hlth & Human Dev, Perinatol Res Branch, 4707 St Antoine Blvd, Detroit, MI 48201 USA. RI Tromp, Gerard/B-2677-2017; OI Tromp, Gerard/0000-0002-7761-0806; Kuivaniemi, Helena/0000-0001-5753-8766 NR 119 TC 70 Z9 75 U1 1 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD NOV PY 2002 VL 187 IS 5 BP 1299 EP 1312 DI 10.1067/mob.2002.128319 PG 14 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 619BZ UT WOS:000179454600036 PM 12439524 ER PT J AU Zhao, JL Mao, J Luo, R Li, FR Munoz, SR Ellwein, LB AF Zhao, JL Mao, J Luo, R Li, FR Munoz, SR Ellwein, LB TI The progression of refractive error in school-age children: Shunyi District, China SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID SINGAPOREAN CHILDREN; MYOPIA PROGRESSION; SCHOOLCHILDREN AB . PURPOSE: To assess the progression of refractive error and the incidence of myopia in school,age children in the Shunyi District of Beijing, China. . DESIGN: A longitudinal cohort study. . METHODS: A population-based sample of 4,662 children initially examined in 1998 at ages 5 to 13 years was reexamined between September and November, 2000. Refractive error was measured under cycloplegia with autorefraction. Age, sex, and baseline refractive error were evaluated as risk factors for progression. .RESULTS: In 28.5 months, the average change in refractive error was -0.42 diopters (standard deviation, 0.68) in right eyes. Myopic shift of refractive error was associated with female sex, older age, and higher myopic or hyperopic refractive error at baseline. The average change in astigmatic error was essentially zero, with significant change in both directions more likely among those with higher baseline astigmatism. Findings were similar for left eyes. The cumulative incidence of myopia, defined as a spherical equivalent refractive error of -0.50 diopters or more in either eye, among initial emmetropes and hyperopes was 14.1% (95% confidence interval [CI], 11.8%-16.5%) for male and 23.5% (95% CI, 20.8%-26.1%) for female subjects. Myopia incidence increased sixfold to sevenfold between baseline age 5 and 12, before decreasing at age 13, for both male and female subjects. . CONCLUSIONS: In the design of cost,effective prod grams for the periodic screening and treatment of uncorrected refractive error, children initially found to require refractive correction should be targeted for relatively frequent rescreening, as should girls and older children. Further study is required to better understand environmental and genetic risk factors for myopia development and progression. (C) 2002 by Elsevier Science Inc. All rights reserved. C1 NEI, NIH, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Eye Res Ctr, Beijing 100037, Peoples R China. Beijing Union Med Coll Hosp, Dept Ophthalmol, Beijing, Peoples R China. Univ La Frontera, Unidad Epidemiol Clin, Temuco, Chile. RP Ellwein, LB (reprint author), NEI, NIH, 31 Ctr Dr,MSC 2510, Bethesda, MD 20892 USA. FU NEI NIH HHS [N01-EY-2103] NR 17 TC 69 Z9 80 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD NOV PY 2002 VL 134 IS 5 BP 735 EP 743 AR PII S0002-9394(02)01689-6 DI 10.1016/S0002-9394(02)01689-6 PG 9 WC Ophthalmology SC Ophthalmology GA 614DT UT WOS:000179173600013 PM 12429251 ER PT J AU Allander, SV Illei, PB Chen, YD Antonescu, CR Bittner, M Ladanyi, M Meltzer, PS AF Allander, SV Illei, PB Chen, YD Antonescu, CR Bittner, M Ladanyi, M Meltzer, PS TI Expression profiling of synovial sarcoma by cDNA microarrays - Association of ERBB2, IGFBP2, and ELF3 with epithelial differentiation SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID GROWTH-FACTOR-I; HUMAN CELL-LINE; MOLECULAR CLASSIFICATION; PROGNOSTIC FACTORS; ACUTE-LEUKEMIA; MESSENGER-RNA; SOFT-TISSUE; GENE; FUSION; SYT AB Synovial sarcoma is an aggressive spindle cell sarcoma with two major histological subtypes, biphasic and monophasic, defined respectively by the presence or absence of areas of glandular epithelial differentiation. It is characterized by a specific chromosomal translocation, t(X;18)(p11.2;q11.2), which juxtaposes the SYT gene on chromosome 18 to either the SSX1 or the SSX2 gene on chromosome X. The chimeric SYT-SSX products are thought to function as transcriptional proteins that deregulate gene expression, thereby providing a putative oncogenic stimulus. We investigated the pattern of gene expression in synovial sarcoma using cDNA microarrays containing 6548 sequence-verified human cDNAs. A tissue microarray containing 37 synovial sarcoma samples verified to bear the SYT-SSX fusion was constructed for complementary analyses. Gene expression analyses were performed on individual tumor samples; 14 synovial sarcomas, 4 malignant fibrous histiocytomas, and 1 fibrosarcoma. Statistical analysis showed a distinct expression profile for the group of synovial sarcomas as compared to the other soft tissue sarcomas, which included variably high expression of ERBB2, IGFBP2, and IGF2 in the synovial sarcomas. Immunohistochemical analysis of protein expression in tissue microarrays of 37 synovial. sarcomas demonstrated strong expression of ERBB2 and IGFBP2 in the glandular epithelial component of biphasic tumors and in solid epithelioid areas of some monophasic tumors. Fluorescence in situ hybridization analysis indicated that the ERBB2 overexpression was not because of gene amplification. Differentially expressed genes were also found in a comparison of the expression profiles of the biphasic and monophasic histological subgroups of synovial sarcoma, notably several keratin genes, and ELF3, an epithelial-specific transcription factor gene. Finally, we also noted differential overexpression of several neural- or neuroectodermal-associated genes in synovial sarcomas relative to the comparison sarcoma group, including OLFM1, TLE2, CNTNAP1, and DRPLA. Our high-throughput studies of gene expression patterns, complemented by tissue microarray studies, confirm the distinctive expression profile of synovial sarcoma, provide leads for the study of glandular morphogenesis in this tumor, and identify a new potential therapeutic target, ERBB2, in a subset of cases. C1 Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Ladanyi, M (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA. FU NCI NIH HHS [P01 CA047179, P01 CA47179] NR 68 TC 125 Z9 128 U1 0 U2 3 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 2002 VL 161 IS 5 BP 1587 EP 1595 DI 10.1016/S0002-9440(10)64437-9 PG 9 WC Pathology SC Pathology GA 614NV UT WOS:000179197000009 PM 12414507 ER PT J AU Sedaghat, AR Sherman, A Quon, MJ AF Sedaghat, AR Sherman, A Quon, MJ TI A mathematical model of metabolic insulin signaling pathways SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE signal transduction; metabolism; insulin resistance; GLUT4 ID KINASE C-ZETA; GLUCOSE-TRANSPORT ACTIVITY; RAT ADIPOSE-CELLS; GROWTH-FACTOR-I; PHOSPHATIDYLINOSITOL 3-KINASE; SUBCELLULAR TRAFFICKING; RECEPTOR SUBSTRATE-1; PLASMA-MEMBRANE; PHOSPHOINOSITIDE 3-KINASE; STIMULATED TRANSLOCATION AB We develop a mathematical model that explicitly represents many of the known signaling components mediating translocation of the insulin-responsive glucose transporter GLUT4 to gain insight into the complexities of metabolic insulin signaling pathways. A novel mechanistic model of postreceptor events including phosphorylation of insulin receptor substrate-1, activation of phosphatidylinositol 3-kinase, and subsequent activation of downstream kinases Akt and protein kinase C-zeta is coupled with previously validated subsystem models of insulin receptor binding, receptor recycling, and GLUT4 translocation. A system of differential equations is defined by the structure of the model. Rate constants and model parameters are constrained by published experimental data. Model simulations of insulin dose-response experiments agree with published experimental data and also generate expected qualitative behaviors such as sequential signal amplification and increased sensitivity of downstream components. We examined the consequences of incorporating feedback pathways as well as representing pathological conditions, such as increased levels of protein tyrosine phosphatases, to illustrate the utility of our model for exploring molecular mechanisms. We conclude that mathematical modeling of signal transduction pathways is a useful approach for gaining insight into the complexities of metabolic insulin signaling. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Math Res Branch, NIH, Bethesda, MD 20892 USA. RP Quon, MJ (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10,Rm 8C-218,10 Ctr Dr MSC 1755, Bethesda, MD 20892 USA. RI Quon, Michael/B-1970-2008 NR 59 TC 89 Z9 89 U1 0 U2 10 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD NOV PY 2002 VL 283 IS 5 BP E1084 EP E1101 DI 10.1152/ajpendo.00571.2001 PG 18 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 602PW UT WOS:000178514500026 PM 12376338 ER PT J AU Armando, I Jezova, M Juorio, AV Terron, JA Falcon-Neri, A Semino-Mora, C Imboden, H Saavedra, JM AF Armando, I Jezova, M Juorio, AV Terron, JA Falcon-Neri, A Semino-Mora, C Imboden, H Saavedra, JM TI Estrogen upregulates renal angiotensin II AT(2) receptors SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE renin-angiotensin system; reproductive hormones; kidney function; cyclic nucleotides; prostaglandins ID TISSUE-SPECIFIC EXPRESSION; IN-SITU HYBRIDIZATION; RAT MESANGIAL CELLS; SMOOTH-MUSCLE CELLS; GENE-DISRUPTED MICE; TYPE-2 RECEPTOR; HYPERTENSIVE RATS; QUANTITATIVE AUTORADIOGRAPHY; POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY AB AT(2) receptors may act in opposition to and in balance with AT(1) receptors, their stimulation having beneficial effects. We found renal AT(2) receptor expression in female mice higher than in male mice. We asked the question of whether such expression might be estrogen dependent. In male, female, ovariectomized, and estrogen-treated ovariectomized mice, we studied renal AT(1) and AT(2) receptors by immunocytochemistry and autoradiography, AT(2) receptor mRNA by RT-PCR, and cAMP, cGMP, and PGE(2) by RIA. AT(1) receptors predominated. AT(2) receptors were present in glomeruli, medullary rays, and inner medulla, and in female kidney capsule. AT(1) and AT(2) receptors colocalized in glomeruli. Female mice expressed fewer glomerular AT(1) receptors. Ovariectomy decreased AT(1) receptors in medullary rays and capsular AT(2) receptors. Estrogen administration normalized AT(1) receptors in medullary rays and increased AT(2) receptors predominantly in capsule and inner medulla, and also in glomeruli, medullary rays, and inner stripe of outer medulla. In medullas of estrogen-treated ovariectomized mice there was higher AT(2) receptor mRNA, decreased cGMP, and increased PGE(2) content. We propose that the protective effects of estrogen may be partially mediated through enhancement of AT(2) receptor stimulation. C1 NIMH, Pharmacol Sect, NIH, Bethesda, MD 20892 USA. Univ Bern, Div Neurobiol, Bern, Switzerland. RP NIMH, Pharmacol Sect, NIH, 10 Ctr Dr,MSC 1514,Bldg 10,Rm 2D-57, Bethesda, MD 20892 USA. EM ArmandoI@intra.nimh.nih.gov NR 60 TC 69 Z9 71 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X EI 1522-1466 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD NOV PY 2002 VL 283 IS 5 BP F934 EP F943 DI 10.1152/ajprenal.00145.2002 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 601UA UT WOS:000178465500008 PM 12372768 ER PT J AU Chakravarty, D Cai, Q Ferraris, JD Michea, L Burg, MB Kultz, D AF Chakravarty, D Cai, Q Ferraris, JD Michea, L Burg, MB Kultz, D TI Three GADD45 isoforms contribute to hypertonic stress phenotype of murine renal inner medullary cells SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE cell cycle; hypertonicity; nephrotoxins; kidney inner medulla ID MOLECULAR-CLONING; GENE-EXPRESSION; KIDNEY-CELLS; DNA-DAMAGE; PROTEIN; MYD118; HYPEROSMOLALITY; INDUCTION; APOPTOSIS; STABILITY AB Mammalian renal inner medullary (IM) cells routinely face and resist hypertonic stress. Such stress causes DNA damage to which IM cells respond with cell cycle arrest. We report that three growth arrest and DNA damage-inducible 45 (GADD45) isoforms (GADD45alpha, GADDD45beta, and GADD45gamma) are induced by acute hypertonicity in murine IM cells. Maximum induction occurs 16-18 h after the onset of hypertonicity. GADD45gamma is induced more strongly (7-fold) than GADD45beta (3-fold) and GADD45alpha (2-fold). GADD45alpha and GADD45beta protein induction is more pronounced and stable compared with the corresponding transcripts. Hypertonicity of various forms (NaCl, KCl, sorbitol, or mannitol) always induces GADD45 transcripts, whereas nonhypertonic hyperosmolality (urea) has no effect. Actinomycin D does not prevent hypertonic GADD45 induction, indicating that mRNA stabilization is the mechanism that mediates this induction. GADD45 induction patterns in IM cells exposed to 10 different stresses suggest isoform specificity, but similar functions, of individual isoforms during hypertonicity, heat shock, and heavy metal stress, when GADD45gamma induction is strongest (17-fold). These data associate all known GADD45 isoforms with the hypertonicity phenotype of renal IM cells. C1 Univ Calif Davis, Dept Anim Sci, Davis, CA 95616 USA. Univ Florida, Whitney Lab, St Augustine, FL 32080 USA. NIH, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. RP Kultz, D (reprint author), Univ Calif Davis, Dept Anim Sci, Meyer Hall,1 Shields Ave, Davis, CA 95616 USA. EM dkueltz@ucdavis.edu FU NIDDK NIH HHS [DK-59470] NR 38 TC 20 Z9 22 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 NOV PY 2002 VL 283 IS 5 BP F1020 EP F1029 DI 10.1152/ajprenal.00118.2002 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 601UA UT WOS:000178465500018 PM 12372778 ER PT J AU Karniski, LP Wang, T Everett, LA Green, ED Giebisch, G Aronson, PS AF Karniski, LP Wang, T Everett, LA Green, ED Giebisch, G Aronson, PS TI Formate-stimulated NaCl absorption in the proximal tubule is independent of the pendrin protein SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE chloride/formate exchange; Pendred syndrome; PDS; SLC26A4 ID RENAL MICROVILLUS MEMBRANES; CONVOLUTED TUBULE; PASSIVE COMPONENTS; CHLORIDE TRANSPORT; SYNDROME GENE; RAT; PDS; EXCHANGE; REABSORPTION; MECHANISM AB A significant fraction of active chloride reabsorption across the apical membrane of the proximal tubule is mediated by a chloride/formate exchange process, whereby intracellular formate drives the transport of chloride into the cell. When chloride/formate exchange operates in parallel with Na(+)/H(+) exchange and H(+)-coupled recycling of formate, the net result is electroneutral NaCl reabsorption. Pendrin is the protein product of the PDS gene (SLC26A4) and functions in several different anion exchange modes, including chloride/formate exchange. Pendrin is expressed in the kidney and may serve as the transporter responsible for formate-dependent NaCl reabsorption. In the present study, Pds-knockout mice were used to determine the role of pendrin in proximal tubule chloride reabsorption. We show that formate-dependent NaCl absorption in microperfused proximal tubules is similar between wild-type and pendrin-deficient mice. In addition, there is no difference in the rate of formate-mediated chloride transport in brush-border membrane vesicles isolated from wild-type and pendrin-deficient mice. These studies demonstrate that pendrin is not responsible for formate-dependent NaCl reabsorption in the proximal tubule. C1 Vet Affairs Med Ctr, Dept Internal Med, Iowa City, IA 52242 USA. Univ Iowa, Coll Med, Iowa City, IA 52242 USA. Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Karniski, LP (reprint author), Univ Iowa Hosp & Clin, Dept Internal Med, 200 Hawkins Dr, Iowa City, IA 52242 USA. EM lawrence-karniski@uiowa.edu FU NIDDK NIH HHS [DK-17433, DK-47881] NR 33 TC 14 Z9 14 U1 0 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 NOV PY 2002 VL 283 IS 5 BP F952 EP F956 DI 10.1152/ajprenal.00182.2002 PG 5 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 601UA UT WOS:000178465500010 PM 12372770 ER PT J AU Nielsen, J Kwon, TH Masilamani, S Beutler, K Hager, H Nielsen, S Knepper, MA AF Nielsen, J Kwon, TH Masilamani, S Beutler, K Hager, H Nielsen, S Knepper, MA TI Sodium transporter abundance profiling in kidney: effect of spironolactone SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE aldosterone; collecting duct; distal convoluted tubule ID ALDOSTERONE-INDUCED PROTEIN; THICK ASCENDING LIMB; NA-CL COTRANSPORTER; RAT-KIDNEY; MINERALOCORTICOID RECEPTOR; KINASE SGK; EXPRESSION; ENAC; INCREASES; CHANNELS AB Renal tubule profiling studies were carried out to investigate the long-term effects of administration of spironolactone, a mineralocorticoid receptor antagonist, on abundances of the major Na transporter and Na channel proteins along the rat renal tubule. Oral administration of spironolactone for 7 days to NaCl-restricted rats did not significantly alter abundances of Na transporters expressed proximal to the macula densa, while substantially decreasing the abundances of the thiazide-sensitive Na-Cl cotransporter (NCC), the alpha-subunit of the amiloride-sensitive epithelial Na channel (ENaC), and the 70-kDa form of the alpha-subunit of ENaC. A dependency of NCC expression on aldosterone was confirmed by showing increased NCC expression in response to aldosterone infusion in adrenalectomized rats. Immunoperoxidase labeling of ENaC in renal cortex confirmed that dietary NaCl restriction causes a redistribution of ENaC to the apical domain of connecting tubule cells and showed that high-dose spironolactone administration does not block this apical redistribution. In contrast, spironolactone completely blocked the increase in alpha-ENaC abundance in response to dietary NaCl restriction. We conclude that the protein abundances of NCC, alpha-ENaC, and the 70-kDa form of gamma-ENaC are regulated via the classical mineralocorticoid receptor, but the subcellular redistribution of ENaC in response to dietary NaCl restriction is not prevented by blockade of the mineralocorticoid receptor. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. Aarhus Univ, Water & Salt Res Ctr, DK-8000 Aarhus C, Denmark. RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, Rm 6N260,Bldg 10,10 Ctr Dr MSC 1603, Bethesda, MD 20892 USA. EM knep@helix.nih.gov FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]; NHLBI NIH HHS [Z01-HL-01282-KE, K00-HL66994] NR 38 TC 40 Z9 40 U1 0 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 NOV PY 2002 VL 283 IS 5 BP F923 EP F933 DI 10.1152/ajprenal.00015.2002 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 601UA UT WOS:000178465500007 PM 12372767 ER PT J AU Roca, CA Schmidt, PJ Smith, MJ Danaceau, MA Murphy, DL Rubinow, DR AF Roca, CA Schmidt, PJ Smith, MJ Danaceau, MA Murphy, DL Rubinow, DR TI Effects of metergoline on symptoms in women with premenstrual dysphoric disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; SEROTONIN REUPTAKE INHIBITORS; TRYPTOPHAN DEPLETION; MENSTRUAL-CYCLE; FLUOXETINE; RECEPTORS; INCREASE; PHASE AB Objective: The authors investigated the role of acute serotonergic modulation in the efficacy of selective serotonin re-uptake inhibitors (SSRIs) in women with premenstrual dysphoric disorder. Method: Patients with premenstrual dysphoric disorder (whose symptoms had remitted during treatment with fluoxetine) and a group of unmedicated healthy comparison women received the serotonin receptor antagonist metergoline as part of a double-blind, placebo-controlled crossover study. Results: The patients with premenstrual dysphoric disorder experienced a return of symptoms 24 hours after treatment with metergoline but not diphenhydramine (active placebo). The comparison women experienced no changes in mood. Conclusions: These data support the role of altered serotonergic transmission in the efficacy of SSRI treatment for premenstrual dysphoric disorder. C1 NIMH, Bethesda, MD 20892 USA. RP Roca, CA (reprint author), NIMH, Bldg 10,Room 3N242,10 Ctr Dr, Bethesda, MD 20892 USA. NR 28 TC 23 Z9 24 U1 0 U2 1 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD NOV PY 2002 VL 159 IS 11 BP 1876 EP 1881 DI 10.1176/appi.ajp.159.11.1876 PG 6 WC Psychiatry SC Psychiatry GA 613EY UT WOS:000179120300013 PM 12411222 ER PT J AU Brown, TM Fee, E AF Brown, TM Fee, E TI "Palliatives will no longer do": The deep roots and continuing dynamic of community-oriented primary care SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID MEDICINE C1 Univ Rochester, Dept Hist, Rochester, NY USA. Univ Rochester, Dept Community & Prevent Med, Rochester, NY USA. Natl Lib Med, Hist Med Div, NIH, Bethesda, MD USA. RP Fee, E (reprint author), Bldg 38,Room 1E21,8600 Rockville Pike, Bethesda, MD 20894 USA. NR 13 TC 3 Z9 3 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD NOV PY 2002 VL 92 IS 11 BP 1711 EP 1712 DI 10.2105/AJPH.92.11.1711 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 608VU UT WOS:000178868600008 PM 12406789 ER PT J AU Fee, E Brown, TM Theerman, P AF Fee, E Brown, TM Theerman, P TI Rural health centers in the Americas SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article C1 NIH, Natl Lib Med, Hist Med Div, Bethesda, MD 20892 USA. Univ Rochester, Dept Hist, Rochester, NY USA. Univ Rochester, Dept Community & Prevent Med, Rochester, NY USA. RP Fee, E (reprint author), Bldg 38,Room 1E21,8600 Rockville Pike, Bethesda, MD 20894 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD NOV PY 2002 VL 92 IS 11 BP 1733 EP 1733 DI 10.2105/AJPH.92.11.1733 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 608VU UT WOS:000178868600014 PM 12406795 ER PT J AU Brown, TM Fee, E AF Brown, TM Fee, E TI Sidney Kark and John Cassel: Social medicine pioneers and South African emigres SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 Univ Rochester, Dept Hist, Rochester, NY 14627 USA. Univ Rochester, Dept Community & Prevent Med, Rochester, NY 14627 USA. NIH, Natl Lib Med, Hist Med Div, Bethesda, MD 20892 USA. RP Brown, TM (reprint author), Univ Rochester, Dept Hist, Rochester, NY 14627 USA. NR 6 TC 4 Z9 4 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD NOV PY 2002 VL 92 IS 11 BP 1744 EP 1745 DI 10.2105/AJPH.92.11.1744 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 608VU UT WOS:000178868600018 PM 12406799 ER PT J AU Eichacker, PQ Parent, C Kalil, A Esposito, C Cui, X Banks, SM Gerstenberger, EP Fitz, Y Danner, RL Natanson, C AF Eichacker, PQ Parent, C Kalil, A Esposito, C Cui, X Banks, SM Gerstenberger, EP Fitz, Y Danner, RL Natanson, C TI Risk and the efficacy of antiinflammatory agents - Retrospective and confirmatory studies of sepsis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE septic shock; preclinical and clinical trials; metaregression analysis; antiinflammatory therapies ID TUMOR-NECROSIS-FACTOR; PLATELET-ACTIVATING-FACTOR; INTERLEUKIN-1 RECEPTOR ANTAGONIST; PLACEBO-CONTROLLED TRIAL; CONTROLLED MULTICENTER TRIAL; ESCHERICHIA-COLI ENDOTOXIN; FACTOR MONOCLONAL-ANTIBODY; INDUCED LETHAL TOXICITY; SEPTIC SHOCK; FACTOR-ALPHA AB We investigated whether a relationship between risk of death and treatment effect could explain the disparate results between the preclinical and clinical sepsis trials of antiinflammatory agents over the last decade. A metaregression analysis of cited preclinical studies showed that the treatment effects of these agents were highly dependent on risk of death (p = 0.0001) and that animals were studied at significantly higher control mortality rates than humans (median [25th-75th quartile], 88% [79-96%] versus 39% [32-42%], p = 0.0001). An analysis of the clinical trials showed that antiinflammatory agents were also significantly more efficacious in septic patients with higher risk of death (p = 0.002) and were harmful in those with low risk. To test this relationship prospectively, we studied antiinflammatory agents in models employing differing doses of bacterial challenge to produce the full range of risk of death. We found that the efficacy of these agents, although very beneficial at high control mortality rates, was much reduced (p = 0.0001) and similar to those in human trials at moderate control mortality rates (i.e., 30 to 40%). The efficacy of antiinflammatory agents during sepsis is dependent on the risk of death, an observation that explains the apparent contradiction between preclinical and clinical trial results. Accounting for this relationship may be necessary for the safe and effective development of antiinflammatory therapies for sepsis. C1 NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Eichacker, PQ (reprint author), NIH, Dept Crit Care Med, Bldg 10,Room 7D43,10 Ctr Dr,MSC 1662, Bethesda, MD 20892 USA. NR 87 TC 211 Z9 215 U1 0 U2 6 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV 1 PY 2002 VL 166 IS 9 BP 1197 EP 1205 DI 10.1164/rccm.200204-302OC PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 611EZ UT WOS:000179004600006 PM 12403688 ER PT J AU Neeman, Z Patti, JW Wood, BJ AF Neeman, Z Patti, JW Wood, BJ TI Percutaneous radiofrequency ablation of chordoma SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID TUMOR ABLATION C1 NIH, Imaging Sci Program, Ctr Clin, Bethesda, MD 20892 USA. RP Wood, BJ (reprint author), NIH, Imaging Sci Program, Ctr Clin, Bldg 10,Rm 1C 660,10 Ctr Dr MSC 1182, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 CL999999] NR 7 TC 20 Z9 22 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD NOV PY 2002 VL 179 IS 5 BP 1330 EP 1332 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 606GG UT WOS:000178725800040 PM 12388524 ER PT J AU Lim, MS Beaty, M Sorbara, L Cheng, RZ Pittaluga, S Raffeld, M Jaffe, ES AF Lim, MS Beaty, M Sorbara, L Cheng, RZ Pittaluga, S Raffeld, M Jaffe, ES TI T-cell/histiocyte-rich large B-cell lymphoma - A heterogeneous entity with derivation from germinal center B cells SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE non-Hodgkin's lymphoma; T-cell-rich large B-cell; lymphoma; BCL-6; BCL-2; nodular lymphocyte predominant Hodgkin's lymphoma; Hodgkin's disease; immunophenotype ID NON-HODGKINS-LYMPHOMAS; EPSTEIN-BARR-VIRUS; BCL-6 PROTEIN; CLINICOPATHOLOGICAL ENTITY; GENE-EXPRESSION; DISEASE; DIFFUSE; REARRANGEMENT; NEOPLASMS; REGION AB T-cell/histiocyte-rich large B-cell non-Hodgkin's lymphoma (THRLBCL) is an unusual morphologic variant of diffuse large B-cell lymphoma. We reviewed 30 cases of THRLBCL to evaluate its heterogeneity based on morphologic, immunophenotypic, and genetic features. Cases were classified according to the appearance of the large neoplastic B cells into three morphologic variants: 1) lymphocytic and histiocytic (L&H-like) (resembling the L&H cells of nodular lymphocyte predominance Hodgkin's lymphoma (14 cases); 2) centroblast (or immunoblast)-like (10 cases), and 3) Reed-Sternberg cell-like (resembling the neoplastic cells of classic Hodgkin's lymphoma) (6 cases). We used a panel of immunohistochemical stains, including those with specificity for germinal center B cells: CD20, CD79a, CD30, CD15, epithelial membrane antigen, BCL-2, BCL-6, and CD10. The BCL-2/JH polymerase chain reaction assay was further performed to investigate a relationship to follicular lymphoma. The results were correlated with Epstein-Barr virus status as determined by staining for latent membrane protein and EBER-1 in situ hybridization. All cases were of B-cell immunophenotype with strong surface CD20 reactivity in the neoplastic large lymphoid cells, although CD79a was more inconsistently and weakly expressed (10 of 17). Nuclear positivity for the BCL-6 protein was detected in the tumor cells in 26 of 29 (90%) cases. However, differences in expression of other antigens were encountered in the histologic subtypes. Epithelial membrane antigen positivity, a feature often seen in nodular lymphocyte predominance Hodgkin's lymphoma, was observed in 11 of 30 (37%) cases and was most commonly seen in cases with L&H cell morphology (8 of 14; 57%). CD30 expression was observed in 9 of 30 (30%) cases but was most frequent in cases with Reed-Sternberg-like morphology (3 of 6 [50%]). CD10 expression was infrequent overall (3 of 29; 10%), with 2 of 3 positive cases identified in the centroblastic group. The overall rarity of positivity for CD10, BCL-2 Q of 22; 13%), and BCL-2 JH rearrangement (I of 28; 4%) indicates a lack of connection to follicular lymphoma for all subtypes. The three cases that were negative for BCL-6 protein were LMP-1 positive and EBER-1 positive by in situ hybridization, and 2 of 3 had neoplastic cells with Reed-Sternberg-like morphology. These results demonstrate that although a large proportion of THRLBCL represent tumors of germinal center B cell derivation, they exhibit a diversity of morphologic and immunophenotypic features. A subset of THRLBCL may be related to nodular lymphocyte predominance Hodgkin's lymphoma. A small percentage show features closely resembling classic Hodgkin's lymphoma and could be considered a variant of grey zone lymphoma. C1 NCI, Hematopathol Sect, Pathol Lab, Bethesda, MD USA. RP Jaffe, ES (reprint author), Bldg 10,Room 2N202,10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. NR 46 TC 59 Z9 61 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD NOV PY 2002 VL 26 IS 11 BP 1458 EP 1466 DI 10.1097/00000478-200211000-00008 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 609YQ UT WOS:000178934300008 PM 12409722 ER PT J AU Cole, M Shen, J Hommer, D AF Cole, M Shen, J Hommer, D TI Convulsive syncope associated with acupuncture SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE acupuncture; convulsive syncope AB Syncope is a rare but known reaction to acupuncture; however, convulsive syncope has never been previously documented as a reaction to acupuncture. This case report describes an episode of convulsive syncope, characterized by irregular clonic-tonic movements while the patient was unconscious. The episode occurred immediately after the insertion of acupuncture needles into the bilateral ST-36 acupuncture point. Here we discuss the presentation, possible causes, and prevention of convulsive syncope. C1 NIAAA, Clin Studies Lab, NIH, Bethesda, MD 20892 USA. RP Cole, M (reprint author), NIAAA, Clin Studies Lab, NIH, Room 6S-240,Mail Stop 1610,10 Ctr Dr,Bldg 10, Bethesda, MD 20892 USA. NR 7 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD NOV PY 2002 VL 324 IS 5 BP 288 EP 289 DI 10.1097/00000441-200211000-00011 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 614KY UT WOS:000179189400011 PM 12449453 ER PT J AU Bucci, JR Oglesby, RJ Agodoa, LY Abbott, KC AF Bucci, JR Oglesby, RJ Agodoa, LY Abbott, KC TI Hospitalizations for total hip arthroplasty after renal transplantation in the United States SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE African American; age; avascular necrosis of the hip; body mass index; Caucasian; complications; diabetes; female; gender; mortality; rejection; renal transplant; repeat; revision; risk; total hip arthroplasty; USRDS ID PROSPECTIVE-PAYMENT SYSTEM; AVASCULAR NECROSIS; ASEPTIC NECROSIS; DISEASE; COMPLICATIONS; CHILDREN; FAILURE; RISK AB The national incidence of and factors associated with total hip arthroplasty in renal transplant recipients has not been reported. We conducted an historical cohort study of 42096 renal transplant recipients in the United States between 1 July 1994 and 30 June 1998. Primary outcomes were associations with hospitalizations for a primary discharge code of total hip arthroplasty (ICD9 procedure code 81.51x) within 3 years after renal transplant using Cox regression. Renal transplant recipients had a cumulative incidence of total hip arthroplasty of 5.1 episodes/1000 person-years, which is 5-8 times higher than reported in the general population. Avascular necrosis of the hip was the most frequent primary diagnosis associated with total hip arthroplasty in this population (72% of cases). Repeat surgeries were performed in 27% of patients with avascular necrosis, vs. 15% with other diagnoses. Total hip arthroplasty was more frequent in transplant recipients who were older, African American, or who experienced allograft rejection. Mortality after total hip arthroplasty was 0.21% at 30 days and 15% at 3 years, similar to the mortality of all transplant recipients. The most common indication for total hip arthroplasty after renal transplant is avascular necrosis of the hip, in contrast to the general population. Although repeat surgeries are common, total hip arthroplasty is well tolerated and is not associated with increased mortality in this population. C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Walter Reed Army Med Ctr, Rheumatol Serv, Washington, DC 20307 USA. NIDDK, NIH, Bethesda, MD USA. RP Abbott, KC (reprint author), Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. OI Abbott, Kevin/0000-0003-2111-7112 NR 29 TC 21 Z9 24 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD NOV PY 2002 VL 2 IS 10 BP 999 EP 1004 DI 10.1034/j.1600-6143.2002.21020.x PG 6 WC Surgery; Transplantation SC Surgery; Transplantation GA 620ZM UT WOS:000179564100020 PM 12482155 ER PT J AU Elster, EA Markusic, J Ball, R Soballe, P Henry, M Louie, A Clare, S AF Elster, EA Markusic, J Ball, R Soballe, P Henry, M Louie, A Clare, S TI Primary acinic cell carcinoma of the breast SO AMERICAN SURGEON LA English DT Article; Proceedings Paper CT 67th Annual Meeting of the Southeastern-Surgical-Congress CY FEB 13-17, 1999 CL TAMPA, FLORIDA SP SE Surg Congress AB Acinic cell carcinoma (ACC) is an uncommon neoplasm of the salivary glands with low malignant potential. Even rarer is the occurrence of primary ACC of the breast, there is only one previously documented case. We now describe the second case of a primary carcinoma of the breast with morphological, ultrastructural, and immunohistochemical features consistent with an ACC. In contrast to the previous case report we report the lack of encapsulation of the tumor and a spectrum of cell types within the tumor including cells resembling well-differentiated infiltrating ductal carcinoma. Additionally we did not observe the abundant nuclear abnormalities noted in the previously published case. We report for the first time the mucicarmine-staining pattern of this tumor as well as immunohistochemistry directed against cytokeratin 7, the estrogen receptor, and the progesterone receptor. C1 Natl Naval Med Res Inst, Dept Surg, Bethesda, MD USA. Natl Naval Med Res Inst, Dept Radiol, Bethesda, MD USA. Natl Naval Med Res Inst, Dept Pathol, Bethesda, MD USA. NCI, Dept Surg, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Surg, Washington, DC 20007 USA. RP Elster, EA (reprint author), PSC 475,Box 1817, FPO, AP 96350 USA. NR 4 TC 17 Z9 19 U1 0 U2 0 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 141 WEST WIEUCA RD, STE B100, ATLANTA, GA 30342 USA SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD NOV PY 2002 VL 68 IS 11 BP 993 EP 995 PG 3 WC Surgery SC Surgery GA 614RH UT WOS:000179203900018 PM 12455793 ER PT J AU Gordon, SM Brahim, JS Dubner, R McCullagh, LM Sang, C Dionne, RA AF Gordon, SM Brahim, JS Dubner, R McCullagh, LM Sang, C Dionne, RA TI Attenuation of pain in a randomized trial by suppression of peripheral nociceptive activity in the immediate postoperative period SO ANESTHESIA AND ANALGESIA LA English DT Article ID PLASMA BETA-ENDORPHIN; RAT SPINAL-CORD; DORSAL HORN; PREEMPTIVE ANALGESIA; LOCAL-ANESTHESIA; INFLAMMATION; SURGERY; INFILTRATION; HYPERALGESIA; NEURONS AB Peripheral neuronal barrage from tissue injury produces central nervous system changes that contribute to the maintenance of postoperative pain. The therapeutic approaches to blocking these central changes remain controversial, because previous studies have not differentiated presurgical interventions from those administered after tissue injury, yet before pain onset. In this study, we evaluated the relative contributions of blockade of nociceptive input during surgery or during the immediate postoperative period on pain suppression. Subjects were randomly allocated to one of four groups: preoperative 2% lidocaine, postoperative 0.5% bupivacaine, both, or placebo injections. General anesthesia was induced and third molars extracted. Pain was assessed over 4 h and at 24 and 48 h. The P-endorphin in blood samples increased twofold during surgery, which is indicative of activation of the peripheral nociceptive barrage in response to painful stimuli. Pain was decreased in the immediate postoperative period in the bupivacaine groups, whereas it increased in the lidocaine group over time. Pain intensity was less 48 h after surgery in the groups whose postoperative pain was blocked by the administration of bupivacaine, but no effect was demonstrated for the preoperative administration of lidocaine alone. These results in the oral surgery pain model suggest that minimizing the peripheral nociceptive barrage during the immediate postoperative period decreases pain at later time periods. In contrast, blocking the intraoperative nociceptive barrage does not appear to contribute significantly to the subsequent reduction in pain. C1 Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. NIH, Dept Nursing, Ctr Clin, Bethesda, MD 20892 USA. Univ Maryland, Sch Dent, Baltimore, MD 21201 USA. Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. RP Dionne, RA (reprint author), 10 Ctr Dr,Room 1N-117, Bethesda, MD 20892 USA. EM raymond.dionne@nih.gov NR 39 TC 16 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 EI 1526-7598 J9 ANESTH ANALG JI Anesth. Analg. PD NOV PY 2002 VL 95 IS 5 BP 1351 EP 1357 DI 10.1213/01.ANE.0000033210.87385.AD PG 7 WC Anesthesiology SC Anesthesiology GA 609NV UT WOS:000178912600047 PM 12401625 ER PT J AU Sei, Y Brandom, BW Bina, S Hosoi, E Gallagher, KL Wyre, HW Pudimat, PA Holman, SJ Venzon, DJ Daly, JW Muldoon, S AF Sei, Y Brandom, BW Bina, S Hosoi, E Gallagher, KL Wyre, HW Pudimat, PA Holman, SJ Venzon, DJ Daly, JW Muldoon, S TI Patients with malignant hyperthermia demonstrate an altered calcium control mechanism in B lymphocytes SO ANESTHESIOLOGY LA English DT Article; Proceedings Paper CT 7th Malignant Hyperthermia Biopsy Center Meeting CY MAR 23, 2001 CL PITTSBURGH, PENNSYLVANIA ID RYANODINE RECEPTOR MUTATIONS; CENTRAL CORE DISEASE; CA2+ RELEASE; CONTRACTURE TEST; CAFFEINE; CELLS; IDENTIFICATION; SENSITIVITY; CHANNEL; GENE AB Background: Altered Ca2+ homeostasis in skeletal muscle is a key molecular event triggering malignant hyperthermia (MH) in malignant hyperthermia-susceptible (MHS) individuals. Genetic studies have shown that mutations in the type 1 ryanodine receptor (RYR1) are associated with MH susceptibility. Because human B lymphocytes express the RYR1, it is hypothesized that Ca2+ homeostasis in B lymphocytes is altered in MHS individuals. Methods: This study investigated the Ca2+ response of B cells to caffeine and 4-chloro-m-cresol in 13 MHS and 21 MH-negative (MHN) individuals who had been diagnosed by caffeine halothane contracture test (CHCT) and 18 healthy volunteers. Changes in [Ca2+](i) in B cells were measured directly in fluo-3 loaded cells using a dual-color flow cytometric technique. Further, B cell phenotype was correlated with CHCT results in a family with the Val2168Met (G6502A) mutation. Results: Caffeine-induced (50 mm) increases in [Ca2+](i) in B cells were significantly greater in MHS than in MHN (P = 0.0004), control (P = 0.0001) or non-MHS (MHN and control) individuals (P < 0.0001). The 4-chloro-m-cresol-induced (400 μM) increases in [Ca2+](i) were also significantly different between MHS and controls (P = 0.003) or between MHS and non-MHS (MHN and control) individuals (P = 0.0078). A study of a family with the Val2168Met mutation demonstrated expression of the RYR1 mRNA mutant in B cells from the family members with MHS phenotype and a clear segregation of genotype with B-cell phenotype. Conclusion: The Ca2+ responses to caffeine or 4-chloro-m-cresol in B lymphocytes showed significant differences between MHS and MHN (or control) individuals. Although the molecular mechanisms of these alterations are currently undetermined, the results suggest that the enhanced Ca2+ responses are associated with mutations in the RYR1 gene in some MHS individuals. C1 Uniformed Serv Univ Hlth Sci, Dept Anesthesiol, Bethesda, MD 20814 USA. Childrens Hosp, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ Tokushima, Tokushima 770, Japan. Natl Canc Inst, Biostat & Data Management Sect, Bethesda, MD USA. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Sei, Y (reprint author), Uniformed Serv Univ Hlth Sci, Dept Anesthesiol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. NR 21 TC 30 Z9 30 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD NOV PY 2002 VL 97 IS 5 BP 1052 EP 1058 DI 10.1097/00000542-200211000-00005 PG 7 WC Anesthesiology SC Anesthesiology GA 611TV UT WOS:000179034600004 PM 12411786 ER PT J AU Kurtzman, HS Church, RM Crystal, JD AF Kurtzman, HS Church, RM Crystal, JD TI Data archiving for animal cognition research: Report of an NIMH workshop SO ANIMAL LEARNING & BEHAVIOR LA English DT Article AB In July 2001, the National Institute of Mental Health sponsored 4 workshop titled "Data Archiving for Animal Cognition Research." Participants included scientists as well as experts in archiving, publishing, policy, and law. As is described in this report, the workshop resulted in a set of conclusions and recommendations concerning (A) the impact of data archiving, on research, (B) how to incorporate data archiving into research practice, (C) contents of lata archives, (D) technical and archival standards, And (E) organizational, financing, and-policy issues. The animal cognition research community is encouraged to begin now to establish archives, deposit data and related materials, and make use of archived-materials in: new scientific projects. C1 NIMH, Cognit Sci Program, Bethesda, MD 20892 USA. Brown Univ, Providence, RI 02912 USA. Univ Georgia, Athens, GA 30602 USA. RP Kurtzman, HS (reprint author), NIMH, Cognit Sci Program, 6001 Execut Blvd,Rm 7217, Bethesda, MD 20892 USA. NR 3 TC 9 Z9 9 U1 0 U2 0 PU PSYCHONOMIC SOC INC PI AUSTIN PA 1710 FORTVIEW RD, AUSTIN, TX 78704 USA SN 0090-4996 J9 ANIM LEARN BEHAV JI Anim. Learn. Behav. PD NOV PY 2002 VL 30 IS 4 BP 405 EP 412 DI 10.3758/BF03195965 PG 8 WC Psychology, Biological; Behavioral Sciences; Psychology, Experimental; Zoology SC Psychology; Behavioral Sciences; Zoology GA 633MF UT WOS:000180286500011 PM 12593332 ER PT J AU Crespo, CJ Palmieri, MRG Perdomo, RP McGee, DL Smit, E Sempos, CT Lee, IM Sorlie, PD AF Crespo, CJ Palmieri, MRG Perdomo, RP McGee, DL Smit, E Sempos, CT Lee, IM Sorlie, PD TI The relationship of physical activity and body weight with all-cause mortality: Results from-the Puerto Rico heart health program SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE mortality; obesity; exercise; Puerto Ricans; epidemiology; Puerto Rico Heart Health Program ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; MIDDLE-AGED MEN; CARDIOVASCULAR-DISEASE MORTALITY; 20-YEAR FOLLOW-UP; LEISURE-TIME; MASS INDEX; CARDIORESPIRATORY FITNESS; UNITED-STATES; PUBLIC-HEALTH AB PURPOSE: To study the relationship of physical activity and obesity with all-cause mortality in Puerto Rican Men. METHODS: The Puerto Rico Heart Health Program collected physical activity and anthropometric measurements in 9,824 men between 1962 and 1965. After excluding those with known coronary heart disease at baseline, and those who died within the first three years of the study we analyzed the data for the relationship between physical activity and overweight status to all-cause mortality in 9,136 men. We stratified our participants by quartiles of physical activity. Participants were classified into four categories of body weight: underweight (BMI < 18.5), healthy weight (BMI =18.5-24-9), overweight (BMI = 25-29.9), and obese (BMI = 30+). RESULTS: After adjusting for age, education, smoking status, hypertension status, hypercholesterolemic status., urban/rural residence, and overweight status, physical activity was independently related to all-cause mortality. All-cause mortality was lower in those in quartile 2 (OR = 0.68, CI = 0.58-0-79) than quartile 1 (reference, sedentary group). Mortality among those in quartile 3 and 4 (0.63, CI = 0.54-0.75; and 0.55, CI = 0.46-0.65, respectively) were also significantly lower than those observed in quartile 1, but not significantly lower than those observed in quartile 2. Furthermore, within every category of body weight, those who were most active had significantly lower odds ratio of all-cause mortality. CONCLUSION: Our findings support the current recommendation that some physical activity is better than none, in protecting against all-cause mortality. The benefits of an active lifestyle are independent of body weight and that overweight and obese Puerto Rican men who are physically active experienced significant reductions in all-cause mortality compared with their sedentary counterparts. (C) 2002 Elsevier Science Inc. All rights reserved. C1 SUNY Buffalo, Dept Social & Prevent Med, Sch Med & Biomed Sci, Buffalo, NY 14214 USA. Univ Puerto Rico, Sch Med, San Juan, PR 00936 USA. Univ Puerto Rico, Grad Sch Publ Hlth, San Juan, PR 00936 USA. S Carolina Med Sch, Charleston, SC USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NHLBI, NIH, Rockville, MD USA. RP Crespo, CJ (reprint author), SUNY Buffalo, Dept Social & Prevent Med, Sch Med & Biomed Sci, 270 Farber Hall, Buffalo, NY 14214 USA. FU NIA NIH HHS [1R03AG17296-01] NR 64 TC 68 Z9 69 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD NOV PY 2002 VL 12 IS 8 BP 543 EP 552 AR PII S1047-2797(01)00296-4 DI 10.1016/S1047-2797(01)00296-4 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 619HV UT WOS:000179471300002 PM 12495827 ER PT J AU Duan, WZ Zhu, XX Ladenheim, B Yu, QS Guo, ZH Oyler, J Cutler, RG Cadet, JL Greig, NH Mattson, MP AF Duan, WZ Zhu, XX Ladenheim, B Yu, QS Guo, ZH Oyler, J Cutler, RG Cadet, JL Greig, NH Mattson, MP TI p53 inhibitors preserve dopamine neurons and motor function in experimental parkinsonism SO ANNALS OF NEUROLOGY LA English DT Article ID TUMOR-SUPPRESSOR GENE; COMPLEX-I INHIBITORS; ALPHA-SYNUCLEIN; TRANSGENIC MICE; PC12 CELLS; CASPASE-3 ACTIVATION; DEPENDENT APOPTOSIS; SUBSTANTIA-NIGRA; PROTECTS NEURONS; BAX ACTIVATION AB Drugs currently used for patients with Parkinson's disease provide temporary relief of symptoms but do not halt or slow the underlying neurodegenerative disease process. Increasing evidence suggests that neurons die in Parkinson's disease by a process called apoptosis, which may be triggered by mitochondrial impairment and oxidative stress. We report that two novel synthetic inhibitors of the tumor suppressor protein p53, pifithrin-alpha (PFT-alpha) and Z-1-117, are highly effective in protecting midbrain dopaminergic neurons and improving behavioral outcome in a mouse model of Parkinson's disease. Mice given intraperitoneal injections of PFT-alpha or Z-1-117 exhibited improved motor function, reduced damage to nigrostriatal dopaminergic neurons and reduced depletion of dopamine and its metabolites after exposure to the toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP caused an increase in the level of the proapoptotic protein Bax, which was prevented by giving mice PFT-alpha and Z-1-117. PFT-alpha and Z-1-117 also suppressed Bax production and apoptosis in cultured dopaminergic cells exposed to MPP+. Our findings demonstrate a pivotal role for p53 in experimental parkinsonism and identify a novel class of synthetic p53 inhibitors with clinical potential. C1 NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. Natl Inst Drug Abuse, Mol Neuropsychiat Sect, Intramural Res Program, Baltimore, MD USA. Natl Inst Drug Abuse, Medicat Discovery Branch, Intramural Res Program, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr, 4F01,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 52 TC 147 Z9 148 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 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 2002 VL 52 IS 5 BP 597 EP 606 DI 10.1002/ana.10350 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 609PK UT WOS:000178914000012 PM 12402257 ER PT J AU Murata, T Shimizu, K Narita, M Manganiello, VC Tagawa, T AF Murata, T Shimizu, K Narita, M Manganiello, VC Tagawa, T TI Characterization of phosphodiesterase 3 in human malignant melanoma cell line SO ANTICANCER RESEARCH LA English DT Article DE phosphodiesterase 3; phosphodiesterase 3 inhibitor; human malignant melanoma; human osteosarcoma ID INHIBITED CAMP-PHOSPHODIESTERASE; EXPRESSION; GENE; FAMILY; TARGET; PDE11A; RAT AB Little is known concerning the expression, distribution and function of phosphodiesterase (PDE) A in malignant tumor cells, including human malignant melanoma HMG and osteosarcoma HOSM-1 cells. PDE3 activity was detected in homogenates of HMG cells; however, much less activity was found in HOSM-1 cells. In HMG cells, most of the PDE3 activity was in the particulate fraction. PDE3A and 3B mRNAs were detected by RT-PCR in RNA from HMG cells only. The nucleotide sequences of the fragments were identical to those of human PDE3A and 3B. The PDE3-specific inhibitors, trequinsin and cilostamide, did not inhibit the proliferation of HMG or HOSM-1 cells. Although two PDE3 isoforms may be expressed in human malignant melanoma cells, their functional importance is not known. C1 Mie Univ, Fac Med, Dept Oral & Maxillofacial Surg, Tsu, Mie 5148507, Japan. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Murata, T (reprint author), Mie Univ, Fac Med, Dept Oral & Maxillofacial Surg, 1-174 Edobashi, Tsu, Mie 5148507, Japan. NR 16 TC 12 Z9 13 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD NOV-DEC PY 2002 VL 22 IS 6A BP 3171 EP 3174 PG 4 WC Oncology SC Oncology GA 630WD UT WOS:000180132400008 PM 12530061 ER PT J AU Mahady, GB Pendland, SL Yun, G Lu, Z AF Mahady, GB Pendland, SL Yun, G Lu, Z TI Turmeric (Curcuma longa) and curcumin inhibit the growth of Helicobacter pylori, a group 1 carcinogen SO ANTICANCER RESEARCH LA English DT Article DE Curcuma longa; curcumin; chemoprevention; Helicobacter pylori; turmeric ID DIETARY CURCUMIN; CANCER AB Background: Curcumin, a polyphenolic chemical constituent derived from turmeric (Curcuma longa), has been shown to prevent gastric and colon cancers in rodents. Many mechanisms have been proposed for the chemopreventative effects, although the effect of curcumin on the growth of Helicobacter pylori has not been reported. H. pylori is a Group 1 carcinogen and is associated with the development of gastric and colon cancer. Materials and Methods: A methanol extract of the dried powdered turmeric rhizome and curcumin were., tested against 19 strains of H. pylon, including 5 cagA+ strains. Results: Both the methanol extract and curcumin inhibited the growth of all strains of H. pylori in vitro with a minimum inhibitory concentration range of 625-50 mug/ml. Conclusion: These data demonstrate that curcumin inhibits the growth of H. pylori cagA+ strains in vitro, and this may be one of the mechanisms by which curcumin exerts its chemopreventative effects. C1 Univ Illinois, UIC,NIH, Bot Ctr Dietary Supplements Res,Coll Pharm, WHO Collaborating Ctr Tradit Med,Dept Pharm Pract, Chicago, IL 60612 USA. Univ Illinois, Coll Pharm, WHO Collaborating Ctr Tradit Med, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA. RP Mahady, GB (reprint author), Univ Illinois, UIC,NIH, Bot Ctr Dietary Supplements Res,Coll Pharm, WHO Collaborating Ctr Tradit Med,Dept Pharm Pract, 833 S Wood St,MC 877, Chicago, IL 60612 USA. FU NCCIH NIH HHS [R21 AT000412-01, AT00412-01] NR 16 TC 111 Z9 118 U1 2 U2 13 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD NOV-DEC PY 2002 VL 22 IS 6C BP 4179 EP 4181 PG 3 WC Oncology SC Oncology GA 637MA UT WOS:000180514600055 PM 12553052 ER PT J AU Lai, TJ Liu, XC Leon, YL Guo, NW Yu, ML Hsu, CC Rogan, WJ AF Lai, TJ Liu, XC Leon, YL Guo, NW Yu, ML Hsu, CC Rogan, WJ TI A cohort study of behavioral problems and intelligence in children with high prenatal polychlorinated biphenyl exposure SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID FOLLOW-UP; PCBS; TAIWAN; DIOXINS; OIL AB Background: In 1978, about 2000 persons in Taiwan were poisoned when their cooking oil was contaminated during Manufacture with heat-degraded polychlorinated biphenyls, which are toxic, very widespread pollutant chemicals. The chemicals cannot be metabolized or excreted, and 8 of the first 39 children born to affected women died. When examined in 1985, 117 surviving children were found to have ectodermal defects, developmental delay, and disordered behavior. We have continued to observe the children. Methods: From 1992 through 1995, 118 children born between 1978 and 1985 (during or after their mothers' exposure) and 118 matched neighborhood control children had cognitive function measured yearly with the Wechsler Intelligence Scale for Children-Revised and behavioral problems measured with the Achenbach Child Behavior Checklist and the Rutter Child Behavior Scale A. Results: The exposed children scored 3 points (P=.05) lower than control children for IQ; 3 points (P=.002) higher on the Child Behavior Checklist (an effect size similar to the sex difference); and 6 points (P<.001) higher on the Rutter scale (3 times the sex difference). Birth year x exposure interactions, testing whether children born long after the exposure were as affected as those born soon after, were small and not significant. Age x exposure interactions, testing whether the children improved relative to control children as they got older, were significant only for the Rutter scale. Conclusions: Prenatal exposure to these compounds produces long-lasting cognitive and behavioral damage, but there is some evidence of recovery. C1 Natl Cheng Kung Univ, Ctr Med, Tainan, Taiwan. Chung Shan Med Univ, Dept Psychiat, Taichung, Taiwan. Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. Natl Cheng Kung Univ, Ctr Med, Dept Occupat & Environm Med, Tainan, Taiwan. Natl Cheng Kung Univ, Ctr Med, Dept Publ Hlth, Tainan, Taiwan. Kaohsiung Med Coll, Dept Psychol, Kaohsiung, Taiwan. En Chu Kong Hosp, Dept Psychiat, Taipei, Taiwan. RP Leon, YL (reprint author), Natl Cheng Kung Univ, Ctr Med, 61 Shiao Tong Rd, Tainan, Taiwan. RI Yu, Ming-Lung/C-9540-2009; Rogan, Walter/I-6034-2012; OI Rogan, Walter/0000-0002-9302-0160; GUO, Yue Leon/0000-0002-8530-4809 NR 25 TC 24 Z9 27 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 NOV PY 2002 VL 59 IS 11 BP 1061 EP 1066 DI 10.1001/archpsyc.59.11.1061 PG 6 WC Psychiatry SC Psychiatry GA 614EE UT WOS:000179174700012 PM 12418940 ER PT J AU Petrovitch, H Ross, GW Abbott, RD Sanderson, WT Sharp, DS Tanner, CM Masaki, KH Blanchette, PL Popper, JS Foley, D Launer, L White, LR AF Petrovitch, H Ross, GW Abbott, RD Sanderson, WT Sharp, DS Tanner, CM Masaki, KH Blanchette, PL Popper, JS Foley, D Launer, L White, LR TI Plantation work and risk of Parkinson disease in a population-based longitudinal study SO ARCHIVES OF NEUROLOGY LA English DT Article ID ENVIRONMENTAL-FACTORS; EARLY ONSET; ETIOLOGY; EXPOSURE; MEN; PESTICIDES; PREVALENCE; TOXINS; HAWAII AB Context: Parkinson disease (PD) has an unknown cause; however, convincing evidence is emerging that indicates pesticides can selectively injure the dopaminergic system in laboratory animals. Retrospective studies in humans demonstrate a link between exposure to agricultural lifestyle factors and PD. Objective: To determine whether working on a plantation in Hawaii and exposure to pesticides are associated with an increased risk of PD decades later. Design and Setting: Prospective cohort study based on the island of Oahu, Hawaii, with 30 years of follow-up. Years of work on a plantation were assessed by questionnaire at study enrollment in 1965. Self-reported information on pesticide exposure was collected at a separate examination 6 years later. Participants: Participants were 7986 Japanese American men born between 1900 and 1919 who were enrolled in the longitudinal Honolulu Heart Program. Main Outcome Measures: Incident PD was determined by medical record review or by an examination conducted by a study neurologist at a later date.. Results: During follow-up, 116 men developed PD. Age-adjusted incidence increased significantly among men who worked more than 10 years on a plantation. The relative risk of PD was 1.0 (95% confidence interval, 0.6-1.6), 1.7 (95% confidence interval, 0.8-3.7), and 1.9 (95% confidence interval, 1.0-3.5) for men who worked on a plantation 1 to 10 years, 11 to 20 years, and more than 20 years compared with men who never did plantation work (P=.006, test for trend). Age-adjusted incidence of PD was higher in men exposed to pesticides than in men not exposed to pesticides although this was not statistically significant (P=.10, test for trend). Conclusion: These longitudinal observations regarding plantation work in Hawaii support case-control studies suggesting that exposure to pesticides increases the risk of PD. C1 NIA, NIH, Bethesda, MD 20892 USA. Parkinsons Inst, Sunnyvale, CA USA. Kuakini Med Ctr, Honolulu Asia Aging Study, Honolulu, HI USA. Pacific Hlth Res Inst, Honolulu, HI 96813 USA. NIOSH, Washington, DC USA. Univ Virginia, Sch Med, Dept Hlth Evaluat Sci, Div Biostat & Epidemiol, Charlottesville, VA 22908 USA. Dept Vet Affairs, Honolulu, HI USA. Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. RP Petrovitch, H (reprint author), Pacific Hlth Res Inst, 846 S Hotel St, Honolulu, HI 96813 USA. FU NHLBI NIH HHS [N01-HC-05102]; NIA NIH HHS [N01-AG-4-2149]; PHS HHS [HELD00B0059] NR 54 TC 84 Z9 90 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD NOV PY 2002 VL 59 IS 11 BP 1787 EP 1792 DI 10.1001/archneur.59.11.1787 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 614ER UT WOS:000179175800016 PM 12433267 ER PT J AU SanGiovanni, JP Chew, EY Reed, GF Remaley, NA Bateman, JB Sugimoto, TA Klebanoff, MA AF SanGiovanni, JP Chew, EY Reed, GF Remaley, NA Bateman, JB Sugimoto, TA Klebanoff, MA TI Infantile cataract in the collaborative perinatal project - Prevalence and risk factors SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID CONGENITAL EYE MALFORMATIONS; EPIDEMIOLOGIC ANALYSIS; CONSECUTIVE BIRTHS; UNITED-KINGDOM; CHILDHOOD; CHILDREN AB Objectives: To estimate the prevalence of 4 categories of infantile cataract in subjects surviving the neonatal period in a US cohort, and to investigate risk factors for isolated infantile cataract. Design: Prospective study of 55 908 pregnancies enrolled in the Collaborative Perinatal Project from 1959 to 1965 at 12 university medical centers. Methods: We gathered data on demographic, lifestyle, and prenatal and perinatal obstetrical and postnatal factors using a standardized protocol. Pediatricians and neurologists examined infants at birth, 4 months, 1 year, and 7 years. We used exact logistic regression methods to compare putative risk factors in infants with isolated cataract with those in infants with no history of cataract. Outcome Measures: Infantile cataract as diagnosed using a standardized dilated ophthalmic examination. Results: Infantile cataract occurred in 13.6 per 10000 infants (95% confidence interval [CI], 10.7-17.1). Isolated infantile cataract occurred 3.8 times as often among infants born at weights at or below 2500 g than among those born at or above 2500 g (95% CI, 1.5-8.6; P<.001), after controlling for a set of covariates; we observed similar results for bilateral isolated cataract (odds ratio = 4.4; 95% CI, 1.2-13.9). No risk factor identified in bivariate analyses was independently associated with the odds of developing isolated unilateral infantile cataract. Conclusions: Infantile cataract is a rare disorder occurring during childhood. Prevalence estimates reported here are within the limits of those from large-cohort studies in economically developed nations. Infants born at weights at or below 2500 g have a 3- to 4-fold increased odds of developing infantile cataract. C1 NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. Univ Colorado, Childrens Hosp, Rocky Mt Lions Eye Inst, Dept Ophthalmol, Denver, CO 80202 USA. NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. RP SanGiovanni, JP (reprint author), NEI, Div Epidemiol & Clin Res, NIH, Bldg 31,Room 6A52,31 Ctr Dr,MSC 2510, Bethesda, MD 20892 USA. RI SanGiovanni, John Paul/A-7605-2008; Osman, Sanha/B-4056-2012 FU Intramural NIH HHS [Z99 EY999999] NR 27 TC 28 Z9 33 U1 0 U2 3 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 NOV PY 2002 VL 120 IS 11 BP 1559 EP 1565 PG 7 WC Ophthalmology SC Ophthalmology GA 614RE UT WOS:000179203400018 PM 12427072 ER PT J AU Chen, KH Chang, BHJ Younan, P Shlykov, SG Sanborn, BM Chan, L AF Chen, KH Chang, BHJ Younan, P Shlykov, SG Sanborn, BM Chan, L TI Increased intracellular calcium transients by calmodulin antagonists differentially modulate tumor necrosis factor-alpha-induced E-selectin and ICAM-1 expression SO ATHEROSCLEROSIS LA English DT Article DE endothelial cell; intracellular calcium; tumor necrosis factor-alpha; calmodulin antagonist; adhesion molecule ID LOW-DENSITY-LIPOPROTEIN; VASCULAR ENDOTHELIAL-CELLS; NITRIC-OXIDE SYNTHASE; GENE-EXPRESSION; ATHEROSCLEROSIS; DYSFUNCTION; INHIBITION; DEFICIENT; BINDING; MICE AB We investigated the role of intracellular calcium ([Ca2+](i)) in adhesion molecule expression in human umbilical vascular endothelial cells (HUVECs). Calmodulin (CaM) antagonists, W-7, trifluoperazine and chlorpromazine, triggered a rise in [Ca2+](i) in HUVECs. In the presence of extracellular Ca2+, thapsigargin pretreatment completely prevented W-7-stimulated increase in [Ca2+](i), indicating that increase is attributable to the release of Ca2+ from internal stores. The increased [Ca2+](i) acted as a second messenger to enhance tumor necrosis factor-alpha (TNF-alpha)-induced E-selectin and suppress intercellular cell adhesion molecule (ICAM-1) expression. Preincubation of HUVECs with the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraaceticacetomethyl ester blocked W-7-mediated effects on E-selectin and ICAM-1. The W-7 effects were paralleled by changes in the respective mRNAs, suggesting regulation at a pretranslational level. These findings indicate that CaM-regulated [Ca2+](i) in HUVECs may play an important role in controlling expression of endothelial adhesion molecules involved in atherogenesis. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Univ Texas, Sch Med, Dept Biochem & Mol Biol, Houston, TX 77225 USA. RP Chen, KH (reprint author), NIAID, NIH, Bldg 10,Room 11C304, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [HL-16512]; NICHD NIH HHS [HD-09618] NR 30 TC 10 Z9 12 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD NOV PY 2002 VL 165 IS 1 BP 5 EP 13 AR PII S0021-9150(01)00768-7 DI 10.1016/S0021-9150(01)00768-7 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 599JZ UT WOS:000178332300002 PM 12208465 ER PT J AU Negus, SS Bidlack, JM Mello, NK Furness, MS Rice, KC Brandt, MR AF Negus, SS Bidlack, JM Mello, NK Furness, MS Rice, KC Brandt, MR TI Delta opioid antagonist effects of buprenorphine in rhesus monkeys SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE buprenorphine; delta opioid receptor; rhesus monkey; SNC80; schedule-controlled behaviour; drug discrimination ID MU-AGONIST/DELTA-ANTAGONIST; GAMMA-S BINDING; PHYSICAL-DEPENDENCE; RECEPTOR; MORPHINE; TOLERANCE; SCHEDULE; POTENT; SNC80; ACTIVATION AB Buprenorphine is an opioid with high affinity, for delta, mu and kappa opioid receptors. The delta receptor-mediated effects of buprenorphine in vivo have not been studied. Thus, the present study examined the delta receptor-mediated effects of buprenorphine in rhesus monkeys. In vitro assays of receptor binding and agonist-stimulated GTPgammaS binding confirmed that buprenorphine had high affinity for, and low efficacy at, delta receptors. In an assay of schedule-controlled responding for food presentation in four monkeys, buprenorphine produced little effect alone, but it antagonized the effects of the delta agonist SNC80, the mu agonist morphine and the kappa agonist U50,488. Buprenorphine was approximately 30-fold less potent as a delta antagonist than as a mu or kappa antagonist. In three monkeys trained to discriminate SNC80 from saline, buprenorphine alone produced only saline-appropriate responding, and buprenorphine pretreatment antagonized the discriminative stimulus effects of SNC80. In a fourth monkey, buprenorphine produced a partial substitution for SNC80 that could be blocked by the delta-selective antagonist naltrindole but not by the mu-selective antagonist quadazocine. These results indicate that, in rhesus monkeys, buprenorphine has very low efficacy at delta receptors, and that buprenorphine produces delta receptor-mediated effects with lower potency than it produces mu or kappa receptor-mediated effects. (C) 2002 Lippincott Williams Wilkins. C1 Harvard Univ, Alcohol & Drug Abuse Res Ctr, Sch Med, McLean Hosp, Belmont, MA 02478 USA. Univ Rochester, Dept Physiol & Pharmacol, Rochester, NY USA. NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Negus, SS (reprint author), Harvard Univ, Alcohol & Drug Abuse Res Ctr, Sch Med, McLean Hosp, 115 Mill St, Belmont, MA 02478 USA. FU NIDA NIH HHS [P01-DA14528, R01-DA11460, K05-DA00360, R01-DA02519, K05-DA00101, T32-DA07252, R01-DA03742] NR 47 TC 19 Z9 21 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD NOV PY 2002 VL 13 IS 7 BP 557 EP 570 PG 14 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 620CR UT WOS:000179516200005 PM 12409994 ER PT J AU Tian, ZG Sun, R Wei, HM Gao, B AF Tian, ZG Sun, R Wei, HM Gao, B TI Impaired natural killer (NK) cell activity in leptin receptor deficient mice: leptin as a critical regulator in NK cell development and activation SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE cell differentiation; natural cytotoxicity; hormone; immunoregulation; leptin; NK cells; db/db mice; poly I:C; IL-15 ID OB/OB MICE; DB/DB MICE; OB-R; EXPRESSION; PROLIFERATION; OBESITY; HEMATOPOIESIS; HYPOTHALAMUS; SENSITIVITY; IMMUNITY AB Leptin is an adipocyte-secreted hormone that centrally regulates weight control via targeting the leptin receptor in the central nervous system. Recently, the leptin receptor has also been detected in peripheral systems including immune tissues, suggesting that leptin may play an important role in the regulation of immune function. It has been shown that leptin modulates functions of T lymphocytes, B lymphocytes, and monocytes/macrophage. However, the effect of leptin on NK cells remains unknown. In the present paper, we observed that percentage of NK cells and total amount of NK cells in the liver, spleen, lung, and peripheral blood were declined in leptin receptor deficient mice (db/db B6 mice), indicating that NK cell development was vigorously influenced by leptin receptor deficiency. Both basal and poly I:C-stimulated NK cell activation (CD69 surface marker expression) were retarded in db/db mice. In addition, leptin treatment increased the basal or synergistically enhanced IL-15- and poly I:C-induced specific lysis of splenocytes in normal littermates but not in db/db mice. Taken together, these findings suggest that leptin plays an important role in NK cell development and activation. (C) 2002 Elsevier Science (USA). All rights reserved. C1 Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Anhui, Peoples R China. Shandong Acad Med Sci, Shandong Canc Biotherapy Ctr, Jinan, Peoples R China. NIAAA, Lab Physiol Studies, NIH, Bethesda, MD USA. RP Tian, ZG (reprint author), Univ Sci & Technol China, Sch Life Sci, 443 Huangshan Rd, Hefei 230027, Anhui, Peoples R China. RI Tian, Zhigang/J-3512-2013 NR 31 TC 130 Z9 142 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE 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 NOV 1 PY 2002 VL 298 IS 3 BP 297 EP 302 AR PII S0006-291X(02)02462-2 DI 10.1016/S0006-291X(02)02462-2 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 612PR UT WOS:000179085100001 PM 12413939 ER PT J AU Tsuchiya, K Kirima, K Yoshizumi, M Houchi, H Tamaki, T Mason, RP AF Tsuchiya, K Kirima, K Yoshizumi, M Houchi, H Tamaki, T Mason, RP TI The role of thiol and nitrosothiol compounds in the nitric oxide-forming reactions of the iron-N-methyl-D-glucamine dithiocarbamate complex SO BIOCHEMICAL JOURNAL LA English DT Article DE 5,5-dimethylpyrroline-N-oxide (DMPO); EPR; reactive oxygen species ID PARAMAGNETIC-RESONANCE SPECTROSCOPY; VIVO EPR DETECTION; SEPTIC-SHOCK MICE; IN-VIVO; S-NITROSOTHIOLS; RELAXING FACTOR; AQUEOUS-SOLUTIONS; ONLINE DETECTION; TREATED MICE; L-CYSTEINE AB The object of the present study is to investigate whether the physiologically dominant thiol compounds such as GSH and cysteine or their nitrosothiol compounds affect the formation of the iron-N-methyl-D-glucamine dithiocarbarnate [(MGD)(2)Fe2+]- nitric oxide complex. The present study provided experimental evidence that physiological concentrations of GSH (approx. 5 mM) and L-Cysteine (approx. 0.5 mM) accelerated the formation of the (MGD)(2)Fe2+-NO complex from nitrite by two and three times respectively. The rate constants for the reduction of (MGD),Fell to (MGD)(2)Fe2+ by GSH and cysteine were calculated as 1.3 and 2.0 x 10(2) M(-1.)s(-1) respectively. Furthermore, depletion of GSH was demonstrated in PC12 cells, and thiol compounds enhanced the formation of reactive oxygen species by the (MGD)(2)Fe2+ complex by accelerating its redox turnover. The main effect of the physiological concentration of thiols was the reduction of (MGD)(3)Fe3+. S-nitrosoglutathione spontaneously reacted with (MGD)(2)Fe2+ to produce the (MGD)(2) Fe2+-NO complex with a 1:2 stoichiometry. In fact, (MGD)(2)Fe2+ was as good an indicator of nitrosothiols as it was of NO itself. The present study elucidates the difficulties of utilizing the (MGD)(2)Fe2+ complex for the quantification of NO in biological samples, especially in vivo. C1 Univ Tokushima, Sch Med, Dept Pharmacol, Tokushima 7708503, Japan. Univ Tokushima, Sch Med, Dept Pharm, Tokushima 7708503, Japan. NIEHS, Free Rad Metabolite Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Tsuchiya, K (reprint author), Univ Tokushima, Sch Med, Dept Pharmacol, Tokushima 7708503, Japan. NR 82 TC 18 Z9 18 U1 1 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD NOV 1 PY 2002 VL 367 BP 771 EP 779 DI 10.1042/BJ20020310 PN 3 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 614FP UT WOS:000179177900022 PM 12141947 ER PT J AU Lupi, R Dani, N Dietrich, A Marchegiani, A Turacchio, S Berrie, CP Mossi, J Gierschik, P Corda, D Di Girolamo, M AF Lupi, R Dani, N Dietrich, A Marchegiani, A Turacchio, S Berrie, CP Mossi, J Gierschik, P Corda, D Di Girolamo, M TI Endogenous mono-ADP-ribosylation of the free G beta gamma prevents stimulation of phosphoinositide 3-kinase-gamma and phospholipase C-beta 2 and is activated by G-protein-coupled receptors SO BIOCHEMICAL JOURNAL LA English DT Article DE CHO cell; mono-ADP-ribosyltransferase ID HETEROTRIMERIC G-PROTEIN; ADENOSINE A(1) RECEPTOR; ALPHA-SUBUNITS; CHO CELLS; EXPRESSION SYSTEM; BOVINE BRAIN; BREFELDIN-A; RIBOSYLTRANSFERASE; MEMBRANES; BINDING AB We have recently demonstrated that the beta subunit of the heterotrimeric G-proteins is endogenously mono-ADP-ribosylated in intact cells. The modified betagamma heterodimer loses its ability to inhibit calmodulin-stimulated type I adenylate cyclase and, remarkably, is de-ADP-ribosylated by a cytosolic hydrolase that completes an ADP-/de-ADP-ribosylation cycle of potential physiological relevance. In the present study, we show that this ADP-ribosylation might indeed be a general mechanism for termination of fly signalling, since the ADP-ribosylated fly subunit is also unable to activate both phosphoinositide 3-kinase-gamma and phospholipase C-beta2. Moreover, we show that beta subunit ADP-ribosylation is induced by G-protein-coupled receptor activation, since hormone stimulation of Chinese-hamster ovary plasma membranes leads to increases in beta subunit labelling. This occurs when fly is in its active heterodimeric conformation, since full inhibition of this modification can be achieved by binding of GDP-alphai3 to the betagamma heterodimer. Taken together, these findings delineate a pathway that arises from the activation of a G-protein-coupled receptor and leads to the inhibition of betagamma activity through its reversible mono-ADP-ribosylation. C1 Ist Ric Farmacol Mario Negri, Consorzio Mario Negri Sud, Dept Cell Biol & Oncol, I-66030 Santa Maria Imbaro, Chieti, Italy. Univ Ulm, Dept Pharmacol & Toxicol, D-89081 Ulm, Germany. NIH, Pulm Crit Care Med Branch, Bethesda, MD 20892 USA. RP Di Girolamo, M (reprint author), Ist Ric Farmacol Mario Negri, Consorzio Mario Negri Sud, Dept Cell Biol & Oncol, Via Nazl, I-66030 Santa Maria Imbaro, Chieti, Italy. RI Dietrich, Alexander/G-8619-2013; Corda, Daniela/K-6385-2016 OI Corda, Daniela/0000-0002-3614-751X FU Telethon [E.0841] NR 57 TC 22 Z9 22 U1 0 U2 3 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD NOV 1 PY 2002 VL 367 BP 825 EP 832 DI 10.1042/BJ20020660 PN 3 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 614FP UT WOS:000179177900028 PM 12149126 ER PT J AU Blackshear, PJ AF Blackshear, PJ TI Tristetraprolin and other CCCH tandem zinc-finger proteins in the regulation of mRNA turnover SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT Colloquium on mRNA Degradation - An Important Process in Controlling Gene Expression CY JUL 16-18, 2002 CL CARDIFF UNIV, CARDIFF, WALES SP Molec & Cellular Pharmol Grp HO CARDIFF UNIV DE AU-rich element; cytokine; deadenylation ID TUMOR-NECROSIS-FACTOR; COLONY-STIMULATING FACTOR; MESSENGER-RNA STABILITY; TRANSCRIPTION FACTOR; NUCLEOTIDE-SEQUENCE; DEFICIENCY SYNDROME; MAMMALIAN-CELLS; GENE; EXPRESSION; TIS11 AB The tristetraprolin (TTP) family of CCCH tandem zinc-finger proteins is composed of three known members in mammals, with a fourth member recently identified in frogs and fish. Although TTP was first cloned more than 10 years ago as a growth factor-induced gene, a physiological function for the protein has been discovered only within the last few years. TTP is now known to bind to so-called class 11 AU-rich elements within the mRNAs that encode turnout necrosis factor-alpha and granulocyte/macrophage colony-stimulating factor. In both cases, this binding results in destabilization of the mRNA and decreased secretion of the protein. Recent evidence suggests that TTP can accomplish this accelerated mRNA degradation by first promoting removal of the polyadenylated tail from the mRNA (deadenylation). In functional assays in cells, the other family members have similar activities, but are expressed differently in tissues and in response to stimuli, suggesting that they may control the stability of mRNAs under different circumstances from those in which TTP affects mRNA. All of these proteins are phosphoproteins and nucleocytoplasmic shuttling proteins, suggesting that their activities can be regulated in ways other than regulating gene transcription. Together, the TTP family members should be capable of complex regulation of short-lived mRNAs containing this type of AU-rich instability motif. C1 NIEHS, Off Clin Res, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. RP Blackshear, PJ (reprint author), A2 05 NIEHS, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 30 TC 255 Z9 261 U1 3 U2 11 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD NOV PY 2002 VL 30 BP 945 EP 952 DI 10.1042/BST0300945 PN 6 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 625KX UT WOS:000179816600026 PM 12440952 ER PT J AU Dobbin, K Simon, R AF Dobbin, K Simon, R TI Comparison of microarray designs for class comparison and class discovery SO BIOINFORMATICS LA English DT Article ID GENE-EXPRESSION PROFILES; MOLECULAR CLASSIFICATION; CDNA MICROARRAY; BREAST-CANCER; GENOME; PATTERNS AB Motivation: Two-color microarray experiments in which an aliquot derived from a common RNA sample is placed on each array are called reference designs. Traditionally, microarray experiments have used reference designs, but designs without a reference have recently been proposed as alternatives. Results: We develop a statistical model that distinguishes the different levels of variation typically present in cancer data, including biological variation among RNA samples, experimental error and variation attributable to phenotype. Within the context of this model, we examine the reference design and two designs which do not use a reference, the balanced block design and the loop design, focusing particularly on efficiency of estimates and the performance of cluster analysis. We calculate the relative efficiency of designs when there are a fixed number of arrays available, and when there are a fixed number of samples available. Monte Carlo simulation is used to compare the designs when the objective is class discovery based on cluster analysis of the samples. The number of discrepancies between the estimated clusters and the true clusters were significantly smaller for the reference design than for the loop design. The efficiency of the reference design relative to the loop and block designs depends on the relation between inter- and intra-sample variance. These results suggest that if cluster analysis is a major goal of the experiment, then a reference design is preferable. If identification of differentially expressed genes is the main concern, then design selection may involve a consideration of several factors. C1 NCI, Bethesda, MD 20892 USA. RP Dobbin, K (reprint author), NCI, EPN Mailstop 7434,6130 Execut Blvd, Bethesda, MD 20892 USA. NR 22 TC 85 Z9 87 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD NOV PY 2002 VL 18 IS 11 BP 1438 EP 1445 DI 10.1093/bioinformatics/18.11.1438 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 615MM UT WOS:000179249800006 PM 12424114 ER PT J AU McShane, LM Radmacher, MD Freidlin, B Yu, R Li, MC Simon, R AF McShane, LM Radmacher, MD Freidlin, B Yu, R Li, MC Simon, R TI Methods for assessing reproducibility of clustering patterns observed in analyses of microarray data SO BIOINFORMATICS LA English DT Article ID GENE-EXPRESSION; MOLECULAR CLASSIFICATION; MELANOMA; CANCER AB Motivation: Recent technological advances such as cDNA microarray technology have made it possible to simultaneously interrogate thousands of genes in a biological specimen. A cDNA microarray experiment produces a gene expression 'profile'. Often interest lies in discovering novel subgroupings, or 'clusters', of specimens based on their profiles, for example identification of new tumor taxonomies. Cluster analysis techniques such as hierarchical clustering and self-organizing maps have frequently been used for investigating structure in microarray data. However, clustering algorithms always detect clusters, even on random data, and it is easy to misinterpret the results without some objective measure of the reproducibility of the clusters. Results: We present statistical methods for testing for overall clustering of gene expression profiles, and we define easily interpretable measures of cluster-specific reproducibility that facilitate understanding of the clustering structure. We apply these methods to elucidate structure in cDNA microarray gene expression profiles obtained on melanoma tumors and on prostate specimens. C1 NCI, Biometr Res Branch, DCTD, NIH, Bethesda, MD 20892 USA. Emmes Corp, Rockville, MD 20850 USA. RP McShane, LM (reprint author), NCI, Biometr Res Branch, DCTD, NIH, Bethesda, MD 20892 USA. NR 25 TC 135 Z9 138 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD NOV PY 2002 VL 18 IS 11 BP 1462 EP 1469 DI 10.1093/bioinformatics/18.11.1462 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 615MM UT WOS:000179249800009 PM 12424117 ER PT J AU Teng, CT Beard, C Gladwell, W AF Teng, CT Beard, C Gladwell, W TI Differential expression and estrogen response of lactoferrin gene in the female reproductive tract of mouse, rat, and hamster SO BIOLOGY OF REPRODUCTION LA English DT Article DE estradiol; female reproductive tract; menstrual cycle; uterus; vagina ID MESSENGER-RNA; DEVELOPMENTAL EXPOSURE; PROTEIN LACTOFERRIN; MOLECULAR MECHANISM; COUP-TF; IN-VIVO; RECEPTOR; CELLS; DIETHYLSTILBESTROL; TRANSFERRIN AB Lactoferrin, an iron-binding glycoprotein, kills bacteria and modulates inflammatory and immune responses. Presence of lactoferrin in the female reproductive tract suggests that the protein may be part of the mucosal immune system and act as the first line of defense against pathogenic organisms. We have discovered that lactoferrin is a major estrogen-inducible protein in the uterus of immature mice and is up-regulated by physiological levels of estrogen during proestrous in mature mice. In the present study, we examined lactoferrin gene expression and its response to estrogen stimulation in the female reproductive tract of several strains of immature mouse, rat, and hamster. The lactoferrin expression in the cycling adult female rat was also evaluated. Lactoferrin gene polymorphism exists among the different mouse strains. In the three inbred mouse strains studied, lactoferrin gene expression is stimulated by estrogen in the immature uterus, although it is less robust than in the outbred CD-1 mouse. We found that the lactoferrin gene is constitutively expressed in the epithelium of the vagina and the isthmus oviduct; however, it is estrogen inducible in the uterus of immature mice and rats. Furthermore, lactoferrin is elevated in the uterine epithelium of the mature rat during the proestrous and estrous stages of the estrous cycle. Estrogen stimulation of lactoferrin gene expression in the reproductive tract of an immature hamster is limited to the vaginal epithelium. The present study demonstrates differential expression and estrogen responsiveness of the lactoferrin gene in different regions of the female rodent reproductive tract and variation among the rodent species studied. C1 NIEHS, Gene Regulat Sect, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA. RP Teng, CT (reprint author), NIEHS, Gene Regulat Sect, Lab Reprod & Dev Toxicol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 63 TC 37 Z9 42 U1 1 U2 5 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD NOV PY 2002 VL 67 IS 5 BP 1439 EP 1449 DI 10.1095/biolreprod.101.002089 PG 11 WC Reproductive Biology SC Reproductive Biology GA 607LD UT WOS:000178792300011 PM 12390874 ER PT J AU Han, IS Han, MH Kim, J Lew, S Lee, YJ Horkay, F Magda, JJ AF Han, IS Han, MH Kim, J Lew, S Lee, YJ Horkay, F Magda, JJ TI Constant-volume hydrogel osmometer: A new device concept for miniature biosensors SO BIOMACROMOLECULES LA English DT Article ID GLUCOSE; GELS; KINETICS; PRESSURE; STATE AB A new type of biosensor is proposed that combines the recognition properties of "intelligent" hydrogels with the sensitivity and reliability of microfabricated pressure transducers. In the proposed device, analyte-induced changes in the osmotic swelling pressure of an environmentally responsive hydrogel are measured by confining it within a small implantable enclosure between a rigid semipermeable membrane and the diaphragm of a, miniature pressure transducer. Proof-of-principle tests of this device were performed in vitro using pH-sensitive hydrogels, with osmotic deswelling data for the same hydrogels used as a benchmark for comparison. The swelling pressure of the hydrogel was accurately determined from osmotic deswelling measurements against reservoirs of known osmotic stress. Values of swelling pressure vs salt concentration measured with a preliminary version of the sensor agree well with osmotic deswelling results. Through modification of the hydrogel with various enzymes or pendant binding moieties, the sensor has the potential to detect a wide range of biological analytes with good specificity. C1 MBiotech Inc, Salt Lake City, UT 84119 USA. NICHD, Sect Tissue Biophys & Biomimet, NIH, Bethesda, MD 20892 USA. Univ Utah, Dept Chem & Fuels Engn, Salt Lake City, UT 84112 USA. RP Han, IS (reprint author), MBiotech Inc, 2411 S 1070 W,Suite C, Salt Lake City, UT 84119 USA. RI magda, jules/A-9715-2009; OI Magda, Jules/0000-0002-1063-6526 FU NIDDK NIH HHS [R43DK55959] NR 31 TC 53 Z9 53 U1 7 U2 19 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1525-7797 J9 BIOMACROMOLECULES JI Biomacromolecules PD NOV-DEC PY 2002 VL 3 IS 6 BP 1271 EP 1275 DI 10.1021/bm0255894 PG 5 WC Biochemistry & Molecular Biology; Chemistry, Organic; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA 615GB UT WOS:000179236500018 PM 12425665 ER PT J AU Esslinger, CS Titus, J Koch, HP Bridges, RJ Chamberlin, AR AF Esslinger, CS Titus, J Koch, HP Bridges, RJ Chamberlin, AR TI Methylation of L-trans-2,4-pyrrolidine dicarboxylate converts the glutamate transport inhibitor from a substrate to a non-substrate inhibitor SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID HIGH-AFFINITY; 1,3-DIPOLAR CYCLOADDITION; KAINIC ACID; NEUROTRANSMITTER; SYNAPTOSOMES; FAMILY; BRAIN AB The 4-methyl analogue of the potent inhibitor of CNS L-glutamate neurotransmitter transporters, L-trans-2,4-PDC, was synthesized via a 1,3-dipolar cycloaddition reaction sequence. The bioassays performed not only exhibit increased potency of the methylated derivative over L-trans-2,4-PDC, but also exhibit non-substrate properties at the rat forebrain synaptosomal glutamate transporter while the parent L-trans-2,4-PDC exhibits substrate properties. These results support two hypotheses developed for distinguishing the physiological properties of transport inhibitors based on molecular modeling studies, and are reported here. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Univ Montana, COBRE, Ctr Struct & Funct Neurosci, Dept Pharmaceut Sci, Missoula, MT 59812 USA. Univ Calif Irvine, Dept Chem, Irvine, CA 92717 USA. RP Esslinger, CS (reprint author), Univ Montana, COBRE, Ctr Struct & Funct Neurosci, Dept Pharmaceut Sci, Missoula, MT 59812 USA. FU NCRR NIH HHS [RR15583]; NINDS NIH HHS [R01 NS027600, NS10156, NS27600, NS30570] NR 34 TC 15 Z9 16 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD NOV PY 2002 VL 10 IS 11 BP 3509 EP 3515 AR PII S0968-0896(02)00250-X DI 10.1016/S0968-0896(02)00250-X PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 599UN UT WOS:000178353700015 PM 12213465 ER PT J AU Guy, HR AF Guy, HR TI Computational simulations of peptide binding to proteins: How scorpions sting K+ channels SO BIOPHYSICAL JOURNAL LA English DT Editorial Material C1 NCI, Lab Expt Computat Biol, NIH, Bethesda, MD 20892 USA. RP Guy, HR (reprint author), NCI, Lab Expt Computat Biol, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 2002 VL 83 IS 5 BP 2325 EP 2326 PG 2 WC Biophysics SC Biophysics GA 611NP UT WOS:000179024500001 PM 12414669 ER PT J AU Chen, YD Yan, B Rubin, RJ AF Chen, YD Yan, B Rubin, RJ TI Fluctuations and randomness of movement of the bead powered by a single kinesin molecule in a force-clamped motility assay: Monte Carlo simulations SO BIOPHYSICAL JOURNAL LA English DT Article ID MOTOR PROTEIN KINETICS; MODEL; PROCESSIVITY AB The motility assay of K. Visscher, M. J. Schnitzer, and S. M. Block (Nature, 400:184-189, 1999) in which the movement of a bead powered by a single kinesin motor can be measured is a very useful tool in characterizing the force-dependent steps of the mechanochemical cycle of kinesin motors, because in this assay the external force applied to the bead can be controlled (clamped) arbitrarily. However, because the bead is elastically attached to the motor and the response of the clamp is not fast enough to compensate the Brownian motion of the bead, interpretation or analysis of the data obtained from the assay is not trivial. In a recent paper (Y. Chen and B. Yan, Biophys. Chem. 91:79-91, 2001), we showed how to evaluate the mean velocity of the bead and the motor in the motility assay for a given mechanochemical cycle. In this paper we extend the study to the evaluation of the fluctuation or the randomness of the velocity using a Monte Carlo simulation method. Similar to the mean, we found that the randomness of the velocity of the motor is also influenced by the parameters that affect the dynamic behavior of the bead, such as the viscosity of the medium, the size of the bead, the stiffness of the elastic element connecting the bead and the motor, etc. The method presented in this paper should be useful in modeling the kinetic mechanism of any processive motor (such as conventional kinesin and myosin V) based on measured force-clamp motility data. C1 NIDDKD, Math Res Branch, NIH, Bethesda, MD 20892 USA. RP NIDDK, MRB, NIH, BSA Bldg,Suite 350,9000 Rockville Pike, Bethesda, MD 20892 USA. EM ydchen@helix.nih.gov NR 30 TC 9 Z9 9 U1 0 U2 1 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 NOV PY 2002 VL 83 IS 5 BP 2360 EP 2369 PG 10 WC Biophysics SC Biophysics GA 611NP UT WOS:000179024500005 PM 12414673 ER PT J AU Rengifo, J Rosales, R Gonzalez, A Cheng, HP Stern, MD Rios, E AF Rengifo, J Rosales, R Gonzalez, A Cheng, HP Stern, MD Rios, E TI Intracellular Ca2+ release as irreversible Markov process SO BIOPHYSICAL JOURNAL LA English DT Article ID FROG SKELETAL-MUSCLE; INTRAMEMBRANOUS CHARGE MOVEMENT; RETICULUM CALCIUM DEPLETION; CUT TWITCH FIBERS; 20 MM EGTA; SARCOPLASMIC-RETICULUM; RYANODINE RECEPTORS; VOLTAGE-DEPENDENCE; ANTIPYRYLAZO-III; CHANNEL PORE AB In striated muscles, intracellular Ca2+ release is tightly controlled by the membrane voltage sensor. Ca2+ ions are necessary mediators of this control in cardiac but not in skeletal muscle, where their role is ill-understood. An intrinsic gating oscillation of Ca2+ release-not involving the voltage sensor-is demonstrated in frog skeletal muscle fibers under voltage clamp. A Markov model of the Ca2+ release units is shown to reproduce the oscillations, and it is demonstrated that for Markov processes to have oscillatory transients, its transition rates must violate thermodynamic reversibility. Such irreversibility results in permanent cycling of the units through a ring of states, which requires a source of free energy. Inhibition of the oscillation by 20 to 40 mM EGTA or partial depletion of Ca2+ in the sarcoplasmic reticulum (SR) identifies the SR [Ca2+] gradient as the energy source, and indicates a location of the critical Ca2+-sensing site at distances greater than 35 nm from the open channel. These results, which are consistent with a recent demonstration of irreversibility in gating of cardiac Ca2+ sparks, (Wang, S.-Q., L.-S. Song, L. Xu, G. Meissner, E. G. Lakatta, E. Rios, M. D. Stern, and H. Cheng. 2002. Biophys. J. 83:242-251) exemplify a cell-wide oscillation caused by coupling between ion permeation and channel gating. C1 Rush Univ, Dept Mol Biophys & Physiol, Chicago, IL 60612 USA. Inst Venezolano Invest Cient, Dept Matemat, Caracas 1020A, Venezuela. NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Rios, E (reprint author), Rush Univ, Dept Mol Biophys & Physiol, 1750 W Harrison St,Suite 1279 JS, Chicago, IL 60612 USA. RI Rosales, Rafael/F-6819-2013 NR 43 TC 24 Z9 24 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 NOV PY 2002 VL 83 IS 5 BP 2511 EP 2521 PG 11 WC Biophysics SC Biophysics GA 611NP UT WOS:000179024500017 PM 12414685 ER PT J AU Josephson, IR Guia, A Lakatta, EG Stern, MD AF Josephson, IR Guia, A Lakatta, EG Stern, MD TI Modulation of the gating of unitary cardiac L-type Ca2+ channels by conditioning voltage and divalent ions SO BIOPHYSICAL JOURNAL LA English DT Article ID CALCIUM CHANNELS; DEPENDENT INACTIVATION; CHARGE MOVEMENTS; VENTRICULAR CELLS; BETA-SUBUNIT; CURRENTS; FACILITATION; MECHANISM; COMPONENTS; MYOCYTES AB Although a considerable number of studies have characterized inactivation and facilitation of macroscopic L-type Ca2+ channel currents, the single channel properties underlying these important regulatory processes have only rarely been examined using Ca2+ ions. We have compared unitary L-type Ca2+ channel currents recorded with a low concentration of Ca2+ ions with those recorded with Ba2+ ions to elucidate the ionic dependence of the mechanisms responsible for the prepulse-dependent modulation of Ca2+ channel gating kinetics. Conditioning prepulses were applied across a wide range of voltages to examine their effects on the subsequent Ca2+ channel activity, recorded at a constant test potential. All recordings were made in the absence of any Ca2+ channel agonists. Moderate-depolarizing prepulses resulted in a decrease in the probability of opening of the Ca2+ channels during subsequent test voltage steps (inactivation), the extent of which was more dramatic with Ca2+ ions than Ba2+ ions. Facilitation, or increase of the average probability of opening with strong predepolarization, was due to long-duration mode 2 openings with Ca2+ ions and Ba2+ ions, despite a decrease in Ca2+ channel availability (inactivation) under these conditions. The degree of both prepulse-induced inactivation and facilitation decreased with increasing Ba2+ ion concentration. The time constants (and their proportions) describing the distributions of Ca2+ channel open times (which reflect mode switching) were also prepulse-, and ion-dependent. These results support the hypothesis that both prior depolarization and the nature and concentration of permeant ions modulate the gating properties of cardiac L-type Ca2+ channels. C1 NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Josephson, IR (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 28 TC 14 Z9 14 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 NOV PY 2002 VL 83 IS 5 BP 2575 EP 2586 PG 12 WC Biophysics SC Biophysics GA 611NP UT WOS:000179024500023 PM 12414691 ER PT J AU Josephson, IR Guia, A Lakatta, EG Stern, MD AF Josephson, IR Guia, A Lakatta, EG Stern, MD TI Modulation of the conductance of unitary cardiac L-type Ca2+ channels by conditioning voltage and divalent ions SO BIOPHYSICAL JOURNAL LA English DT Article ID BETA-ADRENERGIC STIMULATION; CALCIUM CHANNELS; GATING BEHAVIOR; CELLS; MUSCLE; MODES AB The accompanying paper (Josephson, I. R., A. Guia, E. G. Lakatta, and M. D. Stern. 2002. Biophys. J. 83:2575-2586) examined the effects of conditioning prepulses on the kinetics of unitary L-type Ca2+ channel currents using Ca2+ and Ba2+ ions to determine the ionic-dependence of gating mechanisms responsible for channel inactivation and facilitation. Here we demonstrate that in addition to alterations in gating kinetics, the conductance of single L-type Ca2+ channels was also dependent on the prior conditioning voltage and permeant ions. All recordings were made in the absence of any Ca2+ channel agonists. Strongly depolarizing prepulses produced an increased frequency of long-duration (mode 2) openings during the test voltage steps. Mode 2 openings also displayed >25% larger single channel current amplitude (at 0 mV) than briefer (but well-resolved) mode 1 openings. The conductance of mode 2 openings was 26 pS for 105 mM Ba2+, 18 pS for 5 mM Ba2+, and 6 pS for 5 mM Ca2+ ions; these values were 70% greater than the conductance of Ca2+ channel openings of all durations (mode 1 and mode 2). Thus, the prepulse-driven shift into mode 2 gating results in a longer-lived Ca2+ channel conformation that, in addition, displays altered permeation properties. These results, and those in the accompanying paper, support the hypothesis that multiple aspects of single L-type Ca2+ channel behavior (gating kinetics, modal transitions, and ion permeation) are interrelated and are modulated by the magnitude of the conditioning depolarization and the nature and concentration of the ions permeating the channel. C1 NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. RP Josephson, IR (reprint author), NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. NR 18 TC 16 Z9 16 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 2002 VL 83 IS 5 BP 2587 EP 2594 PG 8 WC Biophysics SC Biophysics GA 611NP UT WOS:000179024500024 PM 12414692 ER PT J AU Kozlovsky, Y Chernomordik, LV Kozlov, MM AF Kozlovsky, Y Chernomordik, LV Kozlov, MM TI Lipid intermediates in membrane fusion: Formation, structure, and decay of hemifusion diaphragm SO BIOPHYSICAL JOURNAL LA English DT Article ID BROWNIAN DYNAMICS SIMULATION; HEXAGONAL PHASE-TRANSITIONS; INFLUENZA HEMAGGLUTININ; PHOSPHOLIPID-BILAYERS; STALK MECHANISM; BENDING ELASTICITY; MOLECULAR THEORY; PORE FORMATION; VESICLES; EXOCYTOSIS AB Lipid bilayer fusion is thought to involve formation of a local hemifusion connection, referred to as a fusion stalk. The subsequent fusion stages leading to the opening of a fusion pore remain unknown. The earliest fusion pore could represent a bilayer connection between the membranes and could be formed directly from the stalk. Alternatively, fusion pore can form in a single bilayer, referred to as hemifusion diaphragm (HID), generated by stalk expansion. To analyze the plausibility of stalk expansion, we studied the pathway of hemifusion theoretically, using a recently developed elastic model. We show that the stalk has a tendency to expand into an HID for lipids with sufficiently negative spontaneous splay, (J) over tilde (s) < 0. For different experimentally relevant membrane configurations we find two characteristic values of the spontaneous splay. X and (J) over tilde (s)**, determining HD dimension. The HD is predicted to have a finite equilibrium radius provided that the spontaneous splay is in the range (J) over tilde (s)** < (J) over tilde (s) < (J) over tilde (s)*, and to expand infinitely for (J) over tilde (s) < (J) over tilde (s)**. In the case of common lipids, which do not fuse spontaneously, an HID forms only under action of an external force pulling the diaphragm rim apart. We calculate the dependence of the HID radius on this force. To address the mechanism of fusion pore formation, we analyze the distribution of the lateral tension emerging in the HD due to the establishment of lateral equilibrium between the deformed and relaxed portions of lipid monolayers. We show that this tension concentrates along the HID rim and reaches high values sufficient to rupture the bilayer and form the fusion pore. Our analysis supports the hypothesis that transition from a hemifusion to a fusion pore involves radial expansion of the stalk. C1 Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. NICHHD, Sect Membrane Biol, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Kozlov, MM (reprint author), Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. EM michk@post.tau.ac.il NR 75 TC 145 Z9 148 U1 3 U2 24 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 NOV PY 2002 VL 83 IS 5 BP 2634 EP 2651 PG 18 WC Biophysics SC Biophysics GA 611NP UT WOS:000179024500029 PM 12414697 ER PT J AU Tcherkasskaya, O Gronenborn, AM Klushin, L AF Tcherkasskaya, O Gronenborn, AM Klushin, L TI Excluded volume effect within the continuous model for the fluorescence energy transfer SO BIOPHYSICAL JOURNAL LA English DT Article ID BLOCK-COPOLYMER INTERFACES; RESTRICTED GEOMETRY; FILMS; ACCEPTORS AB We consider and discuss the transfer of electronic energy between donor and acceptor molecules, both continuously distributed in an infinite space. In particular, the ensemble-average fluorescence intensity decay for the donor was calculated, taking into account the excluded volume. The latter may be associated either with finite molecular size or any other spatial restrictions, which are imposed on fluorophore distribution by a superstructure. Results show that in a system using excluded volume, the time dependence in donor decay is more complex compared to that predicted by a simplified stretched exponential model. We identify a crossover between two distinct time regimes in the refined decay and demonstrate its correlation with two competing parameters: r(m), which characterizes the minimal distance between interacting molecules, and R-0, which is related to the strength of the molecular interactions. In this context, the "apparent dimensionality" of the energy transfer recovered from the stretched exponential model ignores the crossover, and may be quite misleading. Basic theoretical considerations to that end are provided. C1 Georgetown Univ, Sch Med, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20007 USA. NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. Russian Acad Sci, Inst Macromol Cpds, Lab Theory Polymers, St Petersburg 199004, Russia. Amer Univ Beirut, Dept Phys, Beirut, Lebanon. RP Tcherkasskaya, O (reprint author), Georgetown Univ, Sch Med, Med Ctr, Dept Biochem & Mol Biol, 3900 Reservoir Rd NW, Washington, DC 20007 USA. NR 20 TC 7 Z9 7 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 2002 VL 83 IS 5 BP 2826 EP 2834 PG 9 WC Biophysics SC Biophysics GA 611NP UT WOS:000179024500046 PM 12414714 ER PT J AU Hott, AM Huether, CA McInerney, JD Christianson, C Fowler, R Bender, H Jenkins, J Wysocki, A Markle, G Karp, R AF Hott, AM Huether, CA McInerney, JD Christianson, C Fowler, R Bender, H Jenkins, J Wysocki, A Markle, G Karp, R TI Genetics content in introductory biology courses for non-science majors: Theory and practice SO BIOSCIENCE LA English DT Article C1 Univ Cincinnati, Dept Biol, Cincinnati, OH 45221 USA. Natl Coalit Hlth Profess Educ Genet, Lutherville Timonium, MD 21093 USA. San Jose State Univ, Dept Biol Sci, San Jose, CA 95192 USA. Univ Notre Dame, Human Genet Program, Notre Dame, IN 46556 USA. Swarthmore Coll, Dept Biol, Swarthmore, PA 19081 USA. NIH, Bethesda, MD 20892 USA. RP Hott, AM (reprint author), Univ Cincinnati, Dept Biol, Cincinnati, OH 45221 USA. NR 11 TC 18 Z9 18 U1 1 U2 3 PU AMER INST BIOLOGICAL SCI PI WASHINGTON PA 1444 EYE ST, NW, STE 200, WASHINGTON, DC 20005 USA SN 0006-3568 J9 BIOSCIENCE JI Bioscience PD NOV PY 2002 VL 52 IS 11 BP 1024 EP 1035 DI 10.1641/0006-3568(2002)052[1024:GCIIBC]2.0.CO;2 PG 12 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 613NJ UT WOS:000179138100009 ER PT J AU Erickson, M Morkowski, S Lehar, S Gillard, G Beers, C Dooley, J Rubin, JS Rudensky, A Farr, AG AF Erickson, M Morkowski, S Lehar, S Gillard, G Beers, C Dooley, J Rubin, JS Rudensky, A Farr, AG TI Regulation of thymic epithelium by keratinocyte growth factor SO BLOOD LA English DT Article ID LACKING INVARIANT CHAIN; VERSUS-HOST DISEASE; T-CELL DEVELOPMENT; IN-VITRO; MICE LACKING; DEVELOPMENT SUGGESTS; MONOCLONAL-ANTIBODY; HUMAN THYMOCYTES; FACTOR FAMILY; EXPRESSION AB Here we demonstrate that keratinocyte growth factor (KGF) and FGFR2IIIb signaling can affect development and function of thymic epithelium (TE) and that alphabeta-lineage thymocytes contribute to intrathymic levels of KGF. Thymocyte expression of KGF is developmentally regulated, being undetectable in CD3(-)4(-)8(-) thymocytes and expressed at highest levels by mature CD4 or CD8 thymocytes. Exposure of thymocyte-depleted fetal thymic lobes to KGF resulted in reduced thymic epithelial expression of class II major histocompatibility complex (MHC), invariant chain (li), and cathepsin L (CatL) molecules involved in thymocyte-positive selection and also stimulated expression of the cytokines interleukin 6 (IL-6) and thymic stromal-derived lymphopoietin (TSLP), while having little effect on IL-7 or stem cell factor expression. Within intact fetal thymic organ culture (FTOC), exogenous KGF impairs the generation of CD4 thymocytes. Two lines of evidence point to responsiveness of the medullary TE compartment to KGF and FGFR2IIIb signaling. First, the medullary compartment is expanded in intact FTOC exposed to KGF in vitro. Second, in the RAG-deficient thymus, where the thymocytes do not express detectable levels of KGF message, the hypoplastic medullary TE compartment can be expanded by administration of recombinant KGF in vivo. This expansion is accompanied by restoration of the normal profile of medullary TE-associated chemokine expression in the RAG2(-/-) thymus. Collectively, these findings point to a role for KGF and FGFR signaling in the development and function of thymic epithelium. (C) 2002 by The American Society of Hematology. C1 Univ Washington, Sch Med, Dept Biol Struct, Seattle, WA 98195 USA. Univ Washington, Howard Hughes Med Inst, Dept Immunol, Seattle, WA 98195 USA. NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Farr, AG (reprint author), Univ Washington, Sch Med, Dept Biol Struct, Box 357420, Seattle, WA 98195 USA. FU NIA NIH HHS [AG 04360]; NIAID NIH HHS [AI 24137, AI 24206] NR 62 TC 93 Z9 100 U1 1 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2002 VL 100 IS 9 BP 3269 EP 3278 DI 10.1182/blood-2002-04-1036 PG 10 WC Hematology SC Hematology GA 608AE UT WOS:000178822300030 PM 12384427 ER PT J AU Wiestner, A Cho, HJ Asch, AS Michelis, MA Zeller, JA Peerschke, EIB Weksler, BB Schechter, GP AF Wiestner, A Cho, HJ Asch, AS Michelis, MA Zeller, JA Peerschke, EIB Weksler, BB Schechter, GP TI Rituximab in the treatment of acquired factor VIII inhibitors SO BLOOD LA English DT Article ID RECOMBINANT FACTOR VIIA; IMMUNOSUPPRESSIVE THERAPY; HEMOPHILIA; PATIENT AB Autoantibodies against factor VIII (FVIII) are rare but can cause life-threatening bleeding requiring costly factor replacement and prolonged immunosuppression. We report 4 consecutively treated patients whose acquired FVIII inhibitors responded rapidly to immunosuppressive regimens that included rituximab, a monoclonal antibody against CD20(+) B cells. Three patients had spontaneously occurring inhibitors. The fourth,,a patient with mild hemophilia A, developed both an autoantibody and an alloantibody following recombinant FVIII treatment. Pretreatment FVIII activities ranged from less than 1% to 4% and inhibitor titers from 5 to 60 Bethesda units (BU). One patient with polymyalgia rheumatica who developed the inhibitor while receiving prednisone responded to single agent rituximab. The hemophilia patient had rapid resolution of the autoantibody, whereas the alloantibody persisted for months. Responses continue off treatment from more than 7 to more than 12 months. This report adds to the growing evidence that rituximab has efficacy in immune disorders resulting from autoantibody formation. C1 Vet Affairs Med Ctr, Hematol Sect, Washington, DC 20422 USA. George Washington Univ, Washington, DC 20052 USA. Hackensack Univ, Med Ctr, Hackensack, NJ USA. Cornell Univ, Weill Med Coll, New York, NY USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Schechter, GP (reprint author), Vet Affairs Med Ctr, Hematol Sect, 50 Irving St NW,Room 4D113, Washington, DC 20422 USA. NR 25 TC 153 Z9 158 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2002 VL 100 IS 9 BP 3426 EP 3428 DI 10.1182/blood-2002-03-0765 PG 3 WC Hematology SC Hematology GA 608AE UT WOS:000178822300051 PM 12384448 ER PT J AU Rouault, TA AF Rouault, TA TI Post-transcriptional regulation of human iron metabolism by iron regulatory proteins SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article; Proceedings Paper CT Meeting on Molecular and Clinical Aspects of Human Iron Metabolism CY SEP 28-OCT 02, 2002 CL CHIEMESEE, GERMANY SP Deutsch Forsch Gemeinsch, Vifor Fresenium Med Care, Blood Cells Fdn, Schwarz pharma, Innova Med Biotech ID ELEMENT-BINDING PROTEIN; TISSUE OXYGEN; CELLS; DEGRADATION; HYPOXIA; MUTANT AB In mammalian iron metabolism, ferritin, transferrin receptor and several other iron metabolism genes are post-transcriptionally regulated. Iron regulatory proteins 1 and 2 are cytosolic proteins that bind to RNA stem-loops known as iron-responsive elements in several transcripts. We have studied the role of these proteins in knockout mice and discovered that misregulation of iron metabolism can be a primary cause of neurodegeneration. C1 NICHD, Sect Human Iron Metab, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. RP Rouault, TA (reprint author), NICHD, Sect Human Iron Metab, Cell Biol & Metab Branch, Bldg 18,Room 101, Bethesda, MD 20892 USA. NR 14 TC 35 Z9 38 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD NOV-DEC PY 2002 VL 29 IS 3 BP 309 EP 314 DI 10.1006/bcmd.2002.0571 PG 6 WC Hematology SC Hematology GA 660FC UT WOS:000181822300008 PM 12547221 ER PT J AU Rouault, T AF Rouault, T TI Commentary 2: Iron metabolism and mitochondrial abnormalities in Friedreich ataxia SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Editorial Material ID SULFUR CLUSTER; SACCHAROMYCES-CEREVISIAE; FRATAXIN; PROTEINS C1 NICHD, Sect Human Iron Metab, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. RP Rouault, T (reprint author), NICHD, Sect Human Iron Metab, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD NOV-DEC PY 2002 VL 29 IS 3 BP 551 EP 552 DI 10.1006/bcmd.2002.0594 PG 2 WC Hematology SC Hematology GA 660FC UT WOS:000181822300039 ER PT J AU Lipman, DJ Souvorov, A Koonin, EV Panchenko, AR Tatusova, TA AF Lipman, David J. Souvorov, Alexander Koonin, Eugene V. Panchenko, Anna R. Tatusova, Tatiana A. TI The relationship of protein conservation and sequence length SO BMC EVOLUTIONARY BIOLOGY LA English DT Article AB Background: In general, the length of a protein sequence is determined by its function and the wide variance in the lengths of an organism's proteins reflects the diversity of specific functional roles for these proteins. However, additional evolutionary forces that affect the length of a protein may be revealed by studying the length distributions of proteins evolving under weaker functional constraints. Results: We performed sequence comparisons to distinguish highly conserved and poorly conserved proteins from the bacterium Escherichia coli, the archaeon Archaeoglobus fulgidus, and the eukaryotes Saccharomyces cerevisiae, Drosophila melanogaster, and Homo sapiens. For all organisms studied, the conserved and nonconserved proteins have strikingly different length distributions. The conserved proteins are, on average, longer than the poorly conserved ones, and the length distributions for the poorly conserved proteins have a relatively narrow peak, in contrast to the conserved proteins whose lengths spread over a wider range of values. For the two prokaryotes studied, the poorly conserved proteins approximate the minimal length distribution expected for a diverse range of structural folds. Conclusions: There is a relationship between protein conservation and sequence length. For all the organisms studied, there seems to be a significant evolutionary trend favoring shorter proteins in the absence of other, more specific functional constraints. C1 [Lipman, David J.; Souvorov, Alexander; Koonin, Eugene V.; Panchenko, Anna R.; Tatusova, Tatiana A.] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Lipman, DJ (reprint author), NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM lipman@ncbi.nlm.nih.gov; souvorov@ncbi.nlm.nih.gov; koonin@ncbi.nlm.nih.gov; panch@ncbi.nlm.nih.gov; tatiana@ncbi.nlm.nih.gov NR 18 TC 65 Z9 68 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2148 J9 BMC EVOL BIOL JI BMC Evol. Biol. PD NOV 1 PY 2002 VL 2 AR 20 DI 10.1186/1471-2148-2-20 PG 10 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA V13DH UT WOS:000207647000001 PM 12410938 ER PT J AU Lu, L Zhang, B Liu, ZY Zhang, ZY AF Lu, L Zhang, B Liu, ZY Zhang, ZY TI Reactivation of cocaine conditioned place preference induced by stress is reversed by cholecystokinin-B receptors antagonist in rats SO BRAIN RESEARCH LA English DT Article DE stress ID CORTICOTROPIN-RELEASING FACTOR; INDUCED RELAPSE; BEHAVIORAL SENSITIZATION; NUCLEUS-ACCUMBENS; CCKA RECEPTOR; AUTORADIOGRAPHIC LOCALIZATION; MORPHINE-DEPENDENCE; MESSENGER-RNA; SPINAL-CORD; DOPAMINE AB The effects of different cholecystokinin (CCK) receptor antagonists (devazepide and L365,260) on cocaine or stress-induced reactivation of cocaine conditioned place preference (CPP) were investigated in rats. After receiving alternate injection of cocaine (10 mg/kg) and saline for 8 consecutive days, the rats spent more time in the drug-paired side (cocaine CPP) on day 9. These animals did not show cocaine CPP on day 31 following saline-paired training daily from days 10 to 30 (21-day extinction). However, a single injection of cocaine (10 mg/kg) or 15 min of intermittent footshock could reinstate CPP on day 32 with significant more time spent in the drug-paired side in comparison with that on day 0. Systemic injection of CCK-A receptor antagonists, devazepide (0.1 and 1 mg/kg, i.p.), 30 min before cocaine priming, significantly attenuated cocaine-induced reinstatement of CPP, while CCK-B receptor antagonist, L365,260 (0.1 and 1 mg/kg, i.p.), did not show a similar effect. In contrast, pretreatment with L365,260 (0.1 and 1 mg/kg, i.p.) but not devazepide (0.1 and I mg/kg, i.p.) significantly blocked stress-induced reinstatement of CPP. In another experiment, CCK-A or B receptor antagonists were infused into nucleus accumbens or amygdala to determine which brain area are involved in the role of different CCK receptors in stress or drug-induced relapse to cocaine seeking. The results show that infusion of the devazepide (10 mug) into the nucleus accumbens significantly inhibited the cocaine-induced reinstatement of CPP, while infusion of devazepide (1 and 10 mug) into amygdala did not affect cocaine-induced reactivation of CPP. Interestingly, infusion of L365,260 (1 and 10 mug) into both nucleus accumbens or amygdala significantly attenuated or blocked stress-induced reinstatement of CPP. These findings demonstrate that CCK-A and B receptor have different roles in relapse to drug craving and further suggest that the brain areas involved in the CCK receptors on reinstatement of drug seeking are not identical. CCK-B receptor antagonists might be of some value in the treatment and prevention of relapse to stress-induced to drug craving following long-term detoxification. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Kailuan Mental Hlth Ctr, Tangshan 063001, Peoples R China. W China Univ Med Sci, Inst Mental Hlth, Chengdu 640041, Peoples R China. Fudan Univ, Ctr Med, Shanghai, Peoples R China. RP Lu, L (reprint author), NIDA, IRP, Behav Neurosci Branch, NIH, 5500 NAthan Shock Dr, Baltimore, MD 21224 USA. EM llu@intra.nida.nih.gov NR 60 TC 41 Z9 45 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD NOV 1 PY 2002 VL 954 IS 1 BP 132 EP 140 AR PII S0006-8993(02)03359-0 DI 10.1016/S0006-8993(02)03359-0 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 620FN UT WOS:000179523500017 PM 12393241 ER PT J AU Anderson, WF Chatterjee, N Ershler, WB Brawley, OW AF Anderson, WF Chatterjee, N Ershler, WB Brawley, OW TI Estrogen receptor breast cancer phenotypes in the surveillance, epidemiology, and end results database SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE age-specific rates (or risks); breast cancer model; estrogen receptor alpha; prognostic factors ID PROGESTERONE-RECEPTOR; MUTATION CARRIERS; DNA CONTENT; BRCA1; TAMOXIFEN; AGE; CARCINOMA; MORTALITY; CARCINOGENESIS; OOPHORECTOMY AB Background. Researchers question whether estrogen receptoralpha-negative (ERN) and -positive (ERP) represent different stages of one disease or different breast cancer types. Objective. To further examine ERalpha phenotypes, we stratified incident tumor characteristics in the Surveillance, Epidemiology, and End Results (SEER) Database (n = 82,488) by ERN and ERP. Methods. Study variables included black-white race, age-at-diagnosis, and standard incident tumor characteristics. These characteristics were arbitrarily dichotomized into good versus poor prognostic factor groups, for example, good (tumor size less than or equal to 2.0 cm, negative axillary lymph nodes, and good histologic grade) versus poor (tumor size > 2.0 cm, positive nodes, and poor grade). Age frequency density plots were generated from the corresponding age-at-diagnosis frequency histograms. Average annual age-specific incidence rates (or risks) were adjusted to the 1970 United States standard female population. Results. Age frequency density plots demonstrated bimodal premenopausal and postmenopausal breast cancer populations. ERN was correlated with premenopausal disease, black race, and poor prognostic factor groups, whereas ERP was associated with postmenopausal disease, white race, and favorable tumor characteristics. ERN rates increased premenopausally and then flattened to a nearly constant level after 50 years of age. ERP risk rose for most of a woman's lifetime with the greatest risk occurring between 75 and 79 years. Conclusions. ERalpha exhibited bimodal age frequency distribution with a dichotomous pattern for age-specific rates, racial, and prognostic factor profiles. Menopause had a greater effect on ERN than ERP. Possible implications for breast carcinogenesis and cancer prevention are discussed in the text. C1 NCI, Div Canc Prevent, EPN, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol, Bethesda, MD 20892 USA. Inst Adv Studies Aging & Geriatr Med, Washington, DC USA. Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. NCI, Genet Biostat Branch, Bethesda, MD 20892 USA. RP Anderson, WF (reprint author), NCI, Div Canc Prevent, EPN, Room 2144,6130 Execut Blvd, Bethesda, MD 20892 USA. NR 57 TC 265 Z9 270 U1 0 U2 9 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD NOV PY 2002 VL 76 IS 1 BP 27 EP 36 DI 10.1023/A:1020299707510 PG 10 WC Oncology SC Oncology GA 593FD UT WOS:000177979600004 PM 12408373 ER PT J AU Milner, JA AF Milner, JA TI Functional foods and health: a US perspective SO BRITISH JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT International Symposium on Functional Foods CY OCT 17-19, 2001 CL PARIS, FRANCE SP ILSI Europe DE diet; cancer; polymorphism; genes; phytochemicals ID CANCER PREVENTION; GENE-EXPRESSION; DIETARY FIBER; CARCINOGENESIS; EXPOSURE; POLYMORPHISMS; OLIGOFRUCTOSE; TRANSCRIPTION; COMPONENTS; DEFICIENCY AB Linkages between diet habits and the quality of life continue to surface on numerous fronts. Collectively these epidemiological, pre-clinical and clinical studies provide rather compelling evidence that numerous essential and non-essential dietary components are capable of influencing growth, development and performance and disease prevention. Scientific discoveries and widespread interest in the potential medicinal benefits of foods and food components have fostered a variety of content, health and structure-function claims. Unfortunately, defining the ideal diet is complicated by the numerous and diverse components that may influence biological processes. Inconsistencies in the literature may reflect the multi-factorial nature of these processes and the specificity that individual dietary constituents have in modifying genetic and epigenetic events. New and emerging genomic and proteonomic approaches and technologies offer exciting opportunities for identifying molecular targets for dietary components and thus determining mechanisms by which they influence the quality of life. All cells have unique,signatures' that are characterized by active and inactive genes and cellular products. It is plausible that bridging knowledge about unique cellular characteristics with molecular targets for nutrients can be used to develop strategies to optimize nutrition and minimize disease risk. C1 NCI, Nutr Sci Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. RP Milner, JA (reprint author), NCI, Nutr Sci Res Grp, Div Canc Prevent, 6130 Execut Blvd,Suite 3164, Bethesda, MD 20892 USA. NR 56 TC 18 Z9 19 U1 2 U2 6 PU C A B I PUBLISHING PI WALLINGFORD PA C/O PUBLISHING DIVISION, WALLINGFORD OX10 8DE, OXON, ENGLAND SN 0007-1145 J9 BRIT J NUTR JI Br. J. Nutr. PD NOV PY 2002 VL 88 SU 2 BP S151 EP S158 DI 10.1079/BJN2002680 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 623HV UT WOS:000179698200007 PM 12495457 ER PT J AU Tasaki, I Matsumoto, G AF Tasaki, I Matsumoto, G TI On the cable theory of nerve conduction SO BULLETIN OF MATHEMATICAL BIOLOGY LA English DT Article AB Conduction of an impulse in the nonmyelinated nerve fiber is treated quantitatively by considering it as a direct consequence of the coexistence of two structurally distinct regions, resting and active, in the fiber. The profile of the electrical potential change induced in the vicinity of the boundary between the two regions is analyzed by using the cable equations. Simple mathematical formulae relating the conduction velocity to the electrical parameters of the fiber are derived from the symmetry of the potential profile at the boundary. The factors that determine the conduction velocity in the myelinated nerve fiber are reexamined. Published by Elsevier Science Ltd on behalf of Society for Mathematical Biology. C1 NICHD, LIMB, STBB, NIH, Bethesda, MD 20892 USA. NIMH, LCMR, NIH, Bethesda, MD 20892 USA. RIKEN, Brain Sci Inst, Brainway Grp, Wako, Saitama 3510198, Japan. RP Tasaki, I (reprint author), NICHD, LIMB, STBB, NIH, Bldg 13,Rm 3E-25, Bethesda, MD 20892 USA. NR 22 TC 11 Z9 12 U1 1 U2 8 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0092-8240 J9 B MATH BIOL JI Bull. Math. Biol. PD NOV PY 2002 VL 64 IS 6 BP 1069 EP 1082 DI 10.1006/blum.2002.0310 PG 14 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 620JM UT WOS:000179530300003 PM 12508531 ER PT J AU Saslow, D Runowicz, CD Solomon, D Moscicki, AB Smith, RA Eyre, HJ Cohen, C AF Saslow, D Runowicz, CD Solomon, D Moscicki, AB Smith, RA Eyre, HJ Cohen, C TI American Cancer Society guideline for the early detection of cervical neoplasia and cancer SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Article ID HUMAN-PAPILLOMAVIRUS INFECTION; TERM FOLLOW-UP; LOW-RESOURCE SETTINGS; THINPREP PAP TEST; NATURAL-HISTORY; NEW-ENGLAND; COSTA-RICA; DIAGNOSTIC-ACCURACY; PAPANICOLAOU SMEARS; OLDER WOMEN AB An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical neoplasia and cancer, based on recommendations from a formal review and recent workshop, is presented. The new screening recommendations address when to begin screening, when screening may be discontinued, whether to screen women who have had a hysterectomy, appropriate screening intervals, and new screening technologies, including liquid-based cytology and HPV DNA testing. C1 Amer Canc Soc, Breast & Gynecol Canc, Atlanta, GA 30329 USA. Amer Canc Soc, Canc Screening, Atlanta, GA 30329 USA. Amer Canc Soc, Res & Canc Control, Atlanta, GA 30329 USA. St Lukes Roosevelt Hosp, Dept Obstet & Gynecol, New York, NY 10025 USA. Natl Canc Inst, ASCUS LSIL Triage Study, Rockville, MD USA. Univ Calif San Francisco, Div Adolescent Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Teen Colposcopy Clin, San Francisco, CA 94143 USA. Mt Sinai Med Ctr, Dept Obstet Gynecol & Reprod Sci, New York, NY 10029 USA. RP Saslow, D (reprint author), Amer Canc Soc, Breast & Gynecol Canc, Atlanta, GA 30329 USA. NR 86 TC 530 Z9 575 U1 1 U2 24 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0007-9235 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD NOV-DEC PY 2002 VL 52 IS 6 BP 342 EP 362 PG 21 WC Oncology SC Oncology GA 620XT UT WOS:000179559500004 PM 12469763 ER PT J AU Osyczka, AM Noth, U O'Connor, J Caterson, EJ Yoon, K Danielson, KG Tuan, RS AF Osyczka, AM Noth, U O'Connor, J Caterson, EJ Yoon, K Danielson, KG Tuan, RS TI Multilineage differentiation of adult human bone marrow progenitor cells transduced with human papilloma virus type 16 E6/E7 genes SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE adult human bone marrow; multipotential progenitor cells; osteogenesis; adipogenesis; chondrogenesis ID MESENCHYMAL STEM-CELLS; GROWTH-FACTOR-BETA; BRONCHIAL EPITHELIAL-CELLS; STROMAL CELLS; IN-VITRO; ADIPOCYTE DIFFERENTIATION; TGF-BETA; CHONDROGENIC DIFFERENTIATION; MORPHOGENETIC PROTEIN-2; PRECURSOR CELLS AB We have established a new adult human bone marrow-derived cell line hMPC 32F, stably transduced with human papilloma virus type 16 E6/E7 genes, that displays mesenchymal multilineage differentiation ability in vitro. The hMPC 32F cells exhibited a population doubling time of 22 It and have been maintained in culture for about 20 passages. When cultured in conditions promoting osteogenic, adipogenic, or chondrogenic differentiation, hMPC 32F cells expressed mature differentiated phenotypes. These include (1) osteoblastic phenotype characterized by upregulated alkaline phosphatase (ALP) expression and extracellular matrix mineralization, (2) adipocytic phenotype with the presence of intracellular lipid droplets, and (3) chondrocytic phenotype of round cells surrounded by a sulfated proteoglycanrich matrix. In addition, the hMPC 32F cells expressed differentiation lineage-specific genes, as detected by RTPCR. Furthermore, osteogenic and adipogenic cultures responded to regulatory factors such as transforming growth factor-beta1 (TGF-beta1) and 1alpha, 25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3). Thus, continuous treatment of osteogenic cultures for 2 weeks with TGF-beta1 decreased ALP activity and mRNA expression and inhibited osteocalcin mRNA expression and matrix mineralization, whereas 1,25(OH)(2)D-3 had an additive, stimulatory effect. In adipogenic cultures, treatment with TGF-beta1 for 2 weeks markedly inhibited adipogenesis whereas 1,25(OH)(2)D-3 had no obvious effect. Finally, clonal analysis of hMPC 32F cells revealed a high percentage of multipotent clones, although clones of more restricted differentiation potential were also present. These characteristics of the hMPC 32F cell line suggest their pluripotent, progenitor, and nontransformed nature and indicate their potential application for studying the mechanisms governing developmental potential of adult human bone marrow mesenchymal progenitor cells. C1 Thomas Jefferson Univ, Dept Orthopaed Surg, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Dept Dermatol & Cutaneous Biol, Philadelphia, PA 19107 USA. NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. RP Tuan, RS (reprint author), Thomas Jefferson Univ, Dept Orthopaed Surg, Philadelphia, PA 19107 USA. FU NCI NIH HHS [CA 71602]; NIAMS NIH HHS [AR 45181, AR 39740, AR 47396, AR 44501]; NIDCR NIH HHS [DE 12864, DE 11327] NR 81 TC 29 Z9 29 U1 0 U2 3 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD NOV PY 2002 VL 71 IS 5 BP 447 EP 458 DI 10.1007/s00223-001-1090-2 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 619PF UT WOS:000179484600010 PM 12232673 ER PT J AU Kitazono, M Bates, S Fok, P Fojo, T Blagosklonny, MV AF Kitazono, M Bates, S Fok, P Fojo, T Blagosklonny, MV TI The histone deacetylase inhibitor FR901228 (depsipeptide) restores expression and function of pseudo-null p53 SO CANCER BIOLOGY & THERAPY LA English DT Article DE FR901228; histone deacetylase inhibitors (HDAC inhibitors); p53 ID CELL-DEATH; METHYLATION; CANCER; GENE; MUTATIONS; PROMOTER; PATHWAY; ARREST; GROWTH; LINES AB We have previously described a novel mechanism of p53 dysfunction, characterized by repression of mRNA and protein expression effectively leading to functional inactivation of wt p53 in SW-1736 human anaplastic thyroid cancer cells (pseudo-null p53). Here we demonstrated that treatment of SW-1736 cells with sub-cytotoxic concentrations of FR901228, a histone deacetylase (HDAC) inhibitor, results in marked induction of p53 mRNA and protein. The p53 induced by FR901228 was functional as evidenced by mdm-2 and p21 transactivation, and its further accumulation following DNA damage by doxorubicin. Furthermore, pretreatment with FR901228 sensitized SW-1736 cells to doxorubicin. This study validates the concept of pseudo-null p53, as a mechanism of p53 inactivation, and demonstrates that pseudo-null p53 can be rescued pharmacologically. C1 NCI, CCR, NIH, Bethesda, MD 20892 USA. New York Med Coll, Dept Med, Brander Canc Res Inst, Valhalla, NY 10595 USA. RP Fojo, T (reprint author), NCI, CCR, NIH, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 16 TC 27 Z9 27 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD NOV-DEC PY 2002 VL 1 IS 6 BP 665 EP 668 PG 4 WC Oncology SC Oncology GA 672XT UT WOS:000182549600013 PM 12642691 ER PT J AU Ando, L Price, DK Dahut, WL Cox, MC Reed, E Figg, WD AF Ando, L Price, DK Dahut, WL Cox, MC Reed, E Figg, WD TI Pharmacogenetic associations of CYP2C19 genotype with in vivo metabolisms and pharmacological effects of thalidomide SO CANCER BIOLOGY & THERAPY LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 18-21, 2002 CL ORLANDO, FL SP Amer Soc Clin Oncol DE thalidomide; cytochrome P450; metabolism; pharmacogenetics; prostate cancer ID REFRACTORY MULTIPLE-MYELOMA; INDEPENDENT PROSTATE-CANCER; TERATOGEN METABOLISM; S-MEPHENYTOIN; ANGIOGENESIS; POLYMORPHISM; PHENOTYPE; CYTOCHROME-P-450; POPULATIONS; ACTIVATION AB Thalidomide requires cytochrome P450 (CYP)catalyzed biotransformation for its antiangiogenic property, and CYP2C19 is responsible for 5-hydroxylation and 5'-hydroxylation of thalidomide in human. This study explored a hypothesis that patients with poor metabolizing phenotype of CYP2C19 receive little benefit from thalidomide treatment and that the poor metabolizer genotype is associated with lower ability to form the metabolites. A case-control study was conducted with 63 patients with prostate cancer who had been enrolled in a randomized phase II trial of thalidomide monotherapy (200 to 1,200 mg/day). CYP2C19 polymorphism (CYP2C19*2, CYP2C19*3, CYP2C19*4) was compared with clinical events (prostate-specific antigen (PSA) decline) and formations of the hydroxylated metabolites. Two patients were homozygous for the variant CYP2C19*2 allele (poor metabolizing phenotype). Both of these were included in the 25 patients whose PSA failed to demonstrate a decline. While 32% and 48% of the patients had quantifiable levels of 5-hydroxythalidomide and cis-5'-hydroxythalidomide, respectively, these metabolite were below quantification in both poor metabolizing patients. None had CYP2C19*3 or CYP2C19*4 alleles. Although this study had no power to detect the statistical significance of the CYP2C19 genotype, the findings were consistent with our hypothesis. The role of CYP2C19 polymorphism in thalidomide treatments remains to be elucidated. C1 NCI, Mol Pharmacol Sect, Canc Therapeut Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Med Oncol Clin Res Unit, Canc Therapeut Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Mol Pharmacol Sect, Canc Therapeut Branch, Ctr Canc Res, Bldg 10,Rm 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 29 TC 1 Z9 1 U1 1 U2 4 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4047 EI 1555-8576 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD NOV-DEC PY 2002 VL 1 IS 6 BP 669 EP 673 PG 5 WC Oncology SC Oncology GA 672XT UT WOS:000182549600014 ER PT J AU Honjo, Y Morisaki, K Huff, LM Robey, RW Hung, J Dean, M Bates, SE AF Honjo, Y Morisaki, K Huff, LM Robey, RW Hung, J Dean, M Bates, SE TI Single-nucleotide polymorphism (SNP) analysis in the ABC half-transporter ABCG2 (MXR/BCRP/ABCP1) SO CANCER BIOLOGY & THERAPY LA English DT Article DE drug resistance; single nucleotide polymorphism; ABCG2/MAR/BCRP/ABCP1 ID BREAST-CANCER CELLS; FUNCTIONAL POLYMORPHISMS; RESISTANCE PROTEIN; GENETIC-VARIATION; CARCINOMA CELLS; MITOXANTRONE; OVEREXPRESSION; MUTATIONS; EXPRESSION; LINES AB Variations in the amino acid sequence of ABC transporters have been shown to impact substrate specificity. We identified two acquired mutations in ABCG2, the ABC half-transporter overexpressed in mitoxantrone-resistant cell lines. These mutations confer differences in substrate specificity and suggest that naturally occurring variants could also affect substrate specificity. To search for the existence of single nucleotide polymorphisms (SNPs) in ABCG2, we sequenced 90 ethnically diverse DNAs from the Single Nucleotide Polymorphism Discovery Resource representing the spectrum of human genotypes. We identified 3 noncoding SNPs in the untranslated regions, 3 nonsynonymous and 2 synonymous SNPs in the coding region and 7 SNPs in the intron sequences adjacent to the sixteen ABCG2 exons. Nonsynonymous SNPs at nucleotide 238 (V12M; exon 2) and nucleotide 625 (Q141 K; exon 5) showed a greater frequency of heterozygosity (22.2% and 10%) than the SNP at 2062 (D620N; exon 16). Heterozygous changes at nucleotide 238 are in linkage disequilibrium with an SNP observed 36 bases downstream from the end of exon 2. No polymorphism at amino acid 482 was identified to correspond to the R to G or R to T mutations previously found in two drug resistant cell lines. Among 23 drug resistant sublines for which sequence at position 482 was determined no additional mutations were found. Heterozygosity at amino acid 12 allowed us to identify overexpression of a single allele in a subset of drug resistant cell lines, a feature that could be exploited clinically in evaluating the significance of ABCG2 expression in malignancy. We conclude that ABCG2 is well conserved and that described amino acid polymorphisms seem unlikely to alter transporter stability or function. C1 NCI, Mol Therapeut Sect, Canc Therapeut Branch, Bethesda, MD 20892 USA. NCI, Lab Genom Divers, Ctr Canc Res, Bethesda, MD 20892 USA. RP Bates, SE (reprint author), NCI, Mol Therapeut Sect, Canc Therapeut Branch, Bldg 10 Rm 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 29 TC 81 Z9 85 U1 0 U2 4 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD NOV-DEC PY 2002 VL 1 IS 6 BP 696 EP 702 PG 7 WC Oncology SC Oncology GA 672XT UT WOS:000182549600019 PM 12642696 ER PT J AU Miller, LD Long, PM Wong, L Mukherjee, S McShane, LM Liu, ET AF Miller, LD Long, PM Wong, L Mukherjee, S McShane, LM Liu, ET TI Optimal gene expression analysis by microarrays SO CANCER CELL LA English DT Review ID CDNA; CLASSIFICATION; CARCINOMAS; SUBCLASSES; VALIDATION; PATTERNS AB DNA microarrays make possible the rapid and comprehensive assessment of the transcriptional activity of a cell, and as such have proven valuable in assessing the molecular contributors to biological processes and in the classification of human cancers. The major challenge in using,this technology is the analysis of its massive data output, which requires computational means for interpretation and a heightened need for quality data. The optimal analysis requires an accounting and control of the many sources of variance within the system, an understanding of the limitations of the statistical approaches, and the ability to make sense of the results through intelligent database interrogation. C1 Genome Inst Singapore, Singapore 117528, Singapore. Inst Infocomm Res, Microarray & Express Genomics Lab, Singapore 119613, Singapore. MIT, Whitehead Inst, Cambridge, MA 02138 USA. NCI, Ctr Biol & Computat Learning, NIH, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. RP Miller, LD (reprint author), Genome Inst Singapore, Singapore 117528, Singapore. RI Liu, Edison/C-4141-2008; Miller, Lance/A-5633-2009; Wong, Limsoon/E-5033-2010; OI Wong, Limsoon/0000-0003-1241-5441; Mukherjee, Sayan/0000-0002-6715-3920 NR 36 TC 92 Z9 96 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD NOV PY 2002 VL 2 IS 5 BP 353 EP 361 DI 10.1016/S1535-6108(02)00181-2 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 618JQ UT WOS:000179415300004 PM 12450790 ER PT J AU Staudt, LM Wilson, WH AF Staudt, LM Wilson, WH TI Focus on lymphomas SO CANCER CELL LA English DT Article ID ANTI-CD20 MONOCLONAL-ANTIBODY; MANTLE CELL LYMPHOMAS; NON-HODGKINS-LYMPHOMA; NF-KAPPA-B; THERAPY; GENE; OVEREXPRESSION; CHEMOTHERAPY; BCL-6 C1 NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Staudt, LM (reprint author), NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NR 37 TC 15 Z9 15 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD NOV PY 2002 VL 2 IS 5 BP 363 EP 366 DI 10.1016/S1535-6108(02)00178-2 PG 4 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 618JQ UT WOS:000179415300005 PM 12450791 ER PT J AU Noy, R Ben-Zvi, Z Elezra, M Candotti, F Ford, H Morris, JC Marquez, VE Johns, DG Agbaria, R AF Noy, R Ben-Zvi, Z Elezra, M Candotti, F Ford, H Morris, JC Marquez, VE Johns, DG Agbaria, R TI Pharmacokinetics and organ distribution of N-methanocarbathymidine, a novel thymidine analog, in mice bearing tumors transduced with the herpes simplex thymidine kinase gene SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE N-methanocarbathymidine; (N)-MCT; HSV-tk; gene therapy; cancer ID MALIGNANT BRAIN-TUMORS; CENTRAL-NERVOUS-SYSTEM; DNA POLYMERASE-ALPHA; IN-SITU USE; MOLECULAR NEUROSURGERY; ANTIHERPETIC DRUGS; SUICIDE GENES; THERAPY; CELLS; GANCICLOVIR AB Purpose: The conformationally rigid nucleoside, N-methanocarbathymidine [(N)-MCT] exerts a potent antiproliferative effect both in vitro and in vivo against murine colon cancer cells (MC38) expressing the herpes simplex virus thymidine kinase gene (MC38/HSV-tk). Metabolic studies have revealed that high levels of (N)-MCT triphosphate accumulate in transduced cells and are incorporated into DNA, resulting in cell death. The objective of the present study was to assess the pharmacokinetic profile of (N)-MCT in C57BL/6 mice bearing nontransduced MC38 and MC38/HSV-tk tumors. Methods: Male black C57BL/6 mice bearing subcutaneous tumors derived from wildtype and HSV-tk-transduced MC38 murine colon cancer cells in the left and right flank, respectively, were treated i.p. with radiolabeled (N)-MCT (100 mg/kg). Mice were killed at each of the predetermined times after drug administration. Blood, urine, tumors and various organs and tissues were obtained for measurement of drug levels. Results: Plasma and tissue concentrations of (N)-MCT peaked at 0.25-0.5 h. The major pharmacokinetic parameters calculated for (N)-MCT in plasma were: T(1/2)beta 4.7 h, AUC 147 mug(.)h/ml, CL 0.69 l/kg per h. The penetration of (N)-MCT into brain and testes was slow. Between 4 and 24 h after drug administration, the levels of (N)-MCT measured in HSV-tk-expressing tumors were significantly higher than in wildtype tumors. HPLC analysis of methanolic extracts of plasma and urine obtained at various times after drug administration revealed no (N)-MCT metabolites in the plasma, and the compound was secreted unchanged in the urine. Conclusions: After i.p. injection into mice, (N)-MCT was rapidly absorbed and distributed in all organs examined. No drug metabolites were detectable in plasma and the compound was secreted unchanged in urine. These results are essential for the future development and in postulating the most efficient use of (N)-MCT in the HSV-tk enzyme prodrug system for gene therapy approaches for the treatment of cancer. C1 Ben Gurion Univ Negev, Fac Hlth Sci, Dept Clin Pharmacol, IL-84105 Beer Sheva, Israel. NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Med Chem Lab, Frederick, MD 21701 USA. NCI, Ctr Canc Res, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Agbaria, R (reprint author), Ben Gurion Univ Negev, Fac Hlth Sci, Dept Clin Pharmacol, IL-84105 Beer Sheva, Israel. NR 36 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD NOV PY 2002 VL 50 IS 5 BP 360 EP 366 DI 10.1007/s00280-002-0505-8 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 623DQ UT WOS:000179688400003 PM 12439593 ER PT J AU van Gils, CH Bostick, RM Stern, MC Taylor, JA AF van Gils, CH Bostick, RM Stern, MC Taylor, JA TI Differences in base excision repair capacity may modulate the effect of dietary antioxidant intake on prostate cancer risk: An example of Polymorphisms in the XRCC1 gene SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID S-TRANSFERASE-MU; DNA-REPAIR; BETA-CAROTENE; POLY(ADP-RIBOSE) POLYMERASE; DAMAGED DNA; HUMAN CHROMOSOME-19; PLASMA LYCOPENE; BREAST-CANCER; VITAMIN-C; SMOKING AB We propose a hypothesis that differences in base excision repair capacity modulate the effect of dietary antioxidant intake on prostate cancer risk. As a preliminary test of this hypothesis, we conducted a pilot case-control study to evaluate prostate cancer risk in men with polymorphisms in the XRCC1 gene, a key player in base excision repair, across different strata of antioxidant intake. Seventy-seven prostate cancer patients and 183 community controls, for whom we have detailed dietary information, were frequency matched on age and race. We found a somewhat lower prostate cancer risk for men with one or two copies of the variant alleles at the XRCC1 codons 194 and 399 than for those who were homozygous for the common allele [codon 194: odds ratio (OR) = 0.8; 95% confidence interval (CI), 0.4-1.8 and codon 399: OR 0.8; 95% CI, 0.5-1.3]. The variant at codon 280 was associated with a slightly increased prostate cancer risk (OR = 1.5; 95% CI, 0.7-3.6). Only the codon 399 polymorphism occurred frequently enough to investigate its joint effect with antioxidant intake. Prostate cancer risk was highest among men who were homozygous for the common allele at codon 399 and had low dietary intake of vitamin E (OR = 2.4; 95% CI, 1.0-5.6) or lycopene (OR = 2.0; 95% CI, 0.8-4.9), whereas low intake of these antioxidants in men without this genotype hardly increased prostate cancer risk. The polymorphism did not modulate risk associated with low intake of vitamin C, A, or beta-carotene. The data give some support for our hypothesis but should be regarded as preliminary, because it is limited by small sample size. We discuss what kind of data and what kind of studies are needed for future evaluation of this hypothesis. C1 NIEHS, Mol & Genet Epidemiol Sect, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. Univ S Carolina, S Carolina Canc Ctr, Columbia, SC 29203 USA. RP Taylor, JA (reprint author), NIEHS, Mol & Genet Epidemiol Sect, Mol Carcinogenesis Lab, NIH, MD A3-05, Res Triangle Pk, NC 27709 USA. OI taylor, jack/0000-0001-5303-6398 NR 68 TC 75 Z9 78 U1 1 U2 5 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 NOV PY 2002 VL 11 IS 11 BP 1279 EP 1284 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 615WL UT WOS:000179270300001 PM 12433703 ER PT J AU Castle, PE Schiffman, M Burk, RD Wacholder, S Hildesheim, A Herrero, R Bratti, MC Sherman, ME Lorincz, A AF Castle, PE Schiffman, M Burk, RD Wacholder, S Hildesheim, A Herrero, R Bratti, MC Sherman, ME Lorincz, A TI Restricted cross-reactivity of hybrid capture 2 with nononcogenic human papillomavirus types SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CERVICAL-CANCER; COSTA-RICA; INFECTION; WOMEN; STRATEGIES; WORLDWIDE; SYSTEMS AB Hybrid Capture 2 Test using probe B (HC2-B) is a clinical test for the detection of 13 human papillomavirus (HPV) types associated with cervical cancer (oncogenic types), but the potential clinical significance of HC2-B cross-reactivity with untargeted (nononcogenic) HPV types has not been fully evaluated. Thus, HC2-B test results on 954 clinical cervical specimens from a population-based natural history study of HPV in Costa Rica were compared with the data from testing of the same specimens twice by HPV type-specific MY09/MY11 L1 consensus primer PCR. Specimens positive by PCR for single HPV types not targeted by HC2-B were used for determining type-specific cross-reactivity. Effects of cross-reactivity on clinical performance were estimated by calculating sensitivity and specificity with and without cross-reactivity for the detection of high-grade cervical lesions. HC2-B tested positive for single infections by untargeted (cross-reactive) types 11, 53, 61, 66, 67, 70, 71, and 81. Cross-reactivity was strongly associated with PCR signal strength (P-Trend = 0.0001) and cervical abnormalities (P = 0.0002, Pearson chi(2)). We estimated that HC2-B cross-reactivity resulted in minor changes in screening performance. Clinical sensitivity increased from 84.3% to 87.9%, clinical specificity decreased from 89.6% to 88.1%, and referral rates increased from 11.7% to 13.2% for detection of greater than or equal tocervical intraepithelial neoplasia grade 2. The clinical effect of cross-reactivity varied by cytologic interpretation. Among women with normal cytologic interpretations, cross-reactivity significantly improved the accuracy of identifying cytologically nonevident histology of greater than or equal tocervical intraepithelial neoplasia grade 2 because of increased sensitivity with maintained specificity. However, among women with equivocal or mildly abnormal cytologic interpretations, cross-reactivity decreased the accuracy of HPV testing because of substantial decreases in specificity. In summary, cross-reactivity with nononcogenic HPV types had little effect on the overall clinical performance of HC2-B as a general screening test, but reduction of cross-reactivity might improve the performance of HPV testing for triage of equivocal or mildly abnormal cytologic interpretations. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Bronx, NY 10461 USA. Proyecto Epidemiol Guanacaste, San Jose, Costa Rica. Digene Corp, Gaithersburg, MD 20878 USA. RP Castle, PE (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,MSC 7234, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA78527] NR 16 TC 128 Z9 140 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 NOV PY 2002 VL 11 IS 11 BP 1394 EP 1399 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 615WL UT WOS:000179270300015 PM 12433717 ER PT J AU Hildesheim, A Ryan, RL Rinehart, E Nayak, S Wallace, D Castle, PE Niwa, S Kopp, W AF Hildesheim, A Ryan, RL Rinehart, E Nayak, S Wallace, D Castle, PE Niwa, S Kopp, W TI Simultaneous measurement of several cytokines using small volumes of biospecimens SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID VIRUS AB The role of host immunity in the development of virus-induced cancers has been difficult to elucidate, in part because of our inability to effectively measure multiple immune parameters using available amounts of biological material. The objective of the present study was to validate the use of a newly developed multiplex assay, the LINCOplex assay, for the simultaneous measurement of multiple cytokines [interleukin/(IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IFN-gamma, and tumor necrosis factor-alpha]. Supernatants obtained from peripheral blood mononuclear cell cultures stimulated with various different mitogens and antigens (including phytohemagglutinin, influenza, tetanus, HPV16 E6 and E7 peptides, and media alone) were selected for study. In total, 750 specimens obtained from 26 participants were tested in replicate using the 8-plex LINCOplex assay (25 mul of specimen required per well). Every specimen was included in duplicate in a blinded fashion. For some specimens, multiple 2-fold dilutions of the same specimen were included to evaluate the linearity of results. The availability of independently obtained IL-2 and IFN-gamma results from standard single cytokine (simplex) assays allowed for a direct comparison between the LINCOplex results and those obtained from the simplex assays. Spearman correlation coefficients for continuous results, and exact agreement rates and weighted kappa statistics for quartiled variables, were computed to evaluate intra-and interassay agreement. IL-4 levels were consistently below the detectable level of the assay (3 pg/ml) whereas IL-6 and IL-8 levels were consistently above the highest detectable level of the assay (10,000 pg/ml), and these three cytokines were, therefore, not evaluated further. For the remaining five cytokines, excellent intra-assay reproducibility was observed, with Spearman correlation coefficients consistently above 0.90 for all five cytokines. Exact agreement rates ranging from 77.6-90.3% and weighted kappas ranging from 0.81-0.92 were observed. Similar results were observed when analysis was restricted to supernatants obtained from cultures that had been stimulated with HPV16 peptides and when analysis was restricted to supernatants obtained from cultures containing no antigen or mitogen, suggesting that the LINCOplex assay is applicable under conditions where moderate or weak cytokine responses/levels are expected. Linearity of results was observed when dilutions of a single specimen were blindly tested, with the exception of IL-2 and IL-10, where deviations from linearity were sometimes observed. For IL-2 and IFN-gamma, where results from simplex assays were available for comparison, the LINCOplex assay and the simplex assay results agreed well. Spearman correlation coefficients were 0.86 and 0.93 for IL-2 and IFN-gamma, respectively. Exact agreement and weighted kappa values were 68.5% and 0.72 (95% confidence interval, 0.65-0.79), respectively, for IL-2 and 67.3% and 0.73 (95% confidence interval, 0.67-0.80), respectively, for IFN-gamma. These results indicate the applicability of the LINCOplex assay for the simultaneous measurement of multiple cytokines using small amounts of biological material. C1 NCI, Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Linco Res Inc, St Charles, MO 63304 USA. SAIC, Cell Proc & Immune Monitoring Lab, Frederick, MD 21702 USA. Westat Corp, Rockville, MD 20850 USA. RP Hildesheim, A (reprint author), NCI, Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 7062,MSC 7234, Rockville, MD 20852 USA. FU NCI NIH HHS [N01-CO-56000] NR 13 TC 26 Z9 26 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2002 VL 11 IS 11 BP 1477 EP 1484 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 615WL UT WOS:000179270300028 PM 12433730 ER PT J AU Hayes, RB Smith, CO Huang, WY Read, Y Kopp, WC AF Hayes, RB Smith, CO Huang, WY Read, Y Kopp, WC TI Whole blood cryopreservation in epidemiological studies SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID LYMPHOCYTES; CANCER AB Standardized and cost-effective biological sample collection, processing, and storage procedures are needed in large-scale epidemiological studies to provide material for testing a broad range of etiological hypotheses. One component of sample collection in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial involves shipment of blood in acid-citrate-dextrose anticoagulant to a central processing laboratory, where 10% DMSO is added, and whole blood aliquots are cryopreserved. A single technician is able to routinely process 50-60 samples/day. Tests conducted to evaluate potential uses of cryopreserved whole blood showed successful FBV transformation (>90%, up to 20 months of storage). In addition, lymphocytes maintained good viability and stable T-cell:B-cell ratios, and T cells maintained the capacity to proliferate in response to solid phase anti-CD3/CD28 plus interleukin 2. Whole blood cryopreservation is a cost-effective approach to large-scale storage of viable cells in epidemiological studies. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Sci Applicat Int Corp Frederick Inc, Clin Serv Program, Frederick, MD 21702 USA. Amer Type Culture Collect, Manassas, VA 20110 USA. RP Hayes, RB (reprint author), NCI, Div Canc Epidemiol & Genet, EPS 8114, Bethesda, MD 20892 USA. NR 10 TC 17 Z9 18 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2002 VL 11 IS 11 BP 1496 EP 1498 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 615WL UT WOS:000179270300032 PM 12433734 ER PT J AU Michaud, DS Hartman, TJ Taylor, PR Pietinen, P Alfthan, G Virtamo, J Albanes, D AF Michaud, DS Hartman, TJ Taylor, PR Pietinen, P Alfthan, G Virtamo, J Albanes, D TI No association between toenail selenium levels and bladder cancer risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SERUM SELENIUM; WOMEN C1 NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. NCI, Canc Res Ctr, Rockville, MD 20852 USA. Penn State Univ, University Pk, PA 16802 USA. Natl Publ Hlth Issue, Dept Epidemiol & Hlth Promot, Helsinki, Finland. RP Michaud, DS (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 320, Rockville, MD 20852 USA. RI Michaud, Dominique/I-5231-2014; Albanes, Demetrius/B-9749-2015 FU NCI NIH HHS [N01CN45035, N01CN45165] NR 5 TC 26 Z9 27 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 NOV PY 2002 VL 11 IS 11 BP 1505 EP 1506 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 615WL UT WOS:000179270300035 PM 12433737 ER PT J AU Sloan, JM Kershaw, MH Touloukian, CE Lapointe, R Robbins, PF Restifo, NP Hwu, P AF Sloan, JM Kershaw, MH Touloukian, CE Lapointe, R Robbins, PF Restifo, NP Hwu, P TI MHC class I and class II presentation of tumor antigen in retrovirally and adenovirally transduced dendritic cells SO CANCER GENE THERAPY LA English DT Article DE adenovirus; retrovirus; gp100; melanoma; antigen presentation ID METASTATIC MELANOMA; T-CELLS; GP100; VIVO; IDENTIFICATION; RESPONSES; INDUCTION; IMMUNITY; PEPTIDES; PROTEINS AB dThe unique antigen-presenting capabilities of dendritic cells (DCs) make them an attractive means with which to initiate an antitumor immune response. Using DCs transduced with tumor antigens for immunotherapy has several theoretical advantages over peptide-pulsed DCs including the possibility that transduced DCs are capable of presenting epitopes on both class I and class II MHC molecules. To test this theory, we inserted the human tumor antigen gp100 into mouse DCs transgenic for HLA-DRbeta1*0401 using either adenoviral vector or a VSV-G pseudotyped retroviral vector. DCs transduced with tumor antigen were able to be recognized by both a murine CD8(+) T-cell clone and a murine CD4(+) T-cell line in a cytokine release assay, thereby demonstrating presentation of both MHC class I and class II gp100 epitopes. This study describes the simultaneous presentation of a tumor-associated antigen to both CD4(+) and CD8(+) T cells and lends support to the use of gene-modified DCs as a means to initiate both CD4(+) and CD8(+) antitumor responses. C1 Natl Canc Inst, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Hwu, P (reprint author), Natl Canc Inst, Ctr Canc Res, NIH, Rm 2B42,Bldg 10, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008; OI Sloan, John/0000-0001-7069-4528; Kershaw, Michael/0000-0002-2697-487X; Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z99 CA999999, Z01 BC010763-01] NR 23 TC 16 Z9 18 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD NOV PY 2002 VL 9 IS 11 BP 946 EP 950 DI 10.1038/sj.cgt.7700509 PG 5 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 610DL UT WOS:000178945400008 PM 12386833 ER PT J AU Tesauro, GM Rowland, JH Lustig, C AF Tesauro, GM Rowland, JH Lustig, C TI Survivorship resources for post-treatment cancer survivors SO CANCER PRACTICE LA English DT Article DE cancer survivor; post-treatment; psychosocial oncology; supportive care service ID QUALITY-OF-LIFE; BREAST-CANCER; CHILDHOOD-CANCER; TERM SURVIVORS; FOLLOW-UP; THERAPY; WOMEN; NEEDS; ADJUSTMENT; SYMPTOMS AB PURPOSE: The purpose of this project was to determine the scope of services and resources available to cancer survivors who have completed active treatment and their families at National Cancer Institute (NCI)-designated comprehensive cancer centers. DESCRIPTION OF STUDY: Patient education program contacts from the 37 NCI-designated comprehensive cancer centers participated in a telephone interview. Program contacts were asked to identify the types of medical and psychosocial services that their respective cancer center offered. RESULTS: Telephone interviews were completed by patient education program contacts from all NCI-designated comprehensive cancer centers for a total response rate of 100%. Services pertaining to lymphedema management were identified in 70% of cancer centers. Other common services identified specifically for post-treatment cancer survivors at cancer centers were professionally led support groups (49% of cancer centers), long-term medical care (38% of cancer centers), school re-entry programs (19% of cancer centers), nutrition counseling (14% of cancer centers), and counseling addressing fertility and sexual concerns (14% of cancer centers). CLINICAL IMPLICATIONS: Results from this project outline the range of services and resources that are provided to post-treatment cancer survivors by NCI-designated comprehensive cancer centers, and can be used to develop standards of care for future cancer control programs. C1 NCI, Off Canc Survivorship, NIH, Bethesda, MD 20892 USA. Univ Maryland, Ctr Aging, College Pk, MD USA. RP Tesauro, GM (reprint author), NCI, Off Canc Survivorship, NIH, 6130 Execut Blvd,RM 4091, Bethesda, MD 20892 USA. NR 35 TC 24 Z9 25 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1065-4704 J9 CANCER PRACT JI Cancer Pract. PD NOV-DEC PY 2002 VL 10 IS 6 BP 277 EP 283 DI 10.1046/j.1523-5394.2002.106007.x PG 7 WC Oncology; Health Care Sciences & Services; Nursing SC Oncology; Health Care Sciences & Services; Nursing GA 608MM UT WOS:000178850100004 PM 12406049 ER PT J AU Slebos, RJC Oh, DS Umbach, DM Taylor, JA AF Slebos, RJC Oh, DS Umbach, DM Taylor, JA TI Mutations in tetranucleotide repeats following DNA damage depend on repeat sequence and carcinogenic agent SO CANCER RESEARCH LA English DT Article ID CANCER CELL-LINES; CULTURED-MAMMALIAN-CELLS; MICROSATELLITE INSTABILITY; LUNG-CANCER; MISMATCH REPAIR; HOMOLOGOUS RECOMBINATION; TUMOR-CELLS; INDUCTION; P53; HYPERMUTABILITY AB Sporadic microsatellite mutations are frequently observed in lung, bladder, and head and neck tumors with intact DNA mismatch repair. AAAG tetranucleotide repeats appear to be especially prone to the accumulation of these mutations. We hypothesized that occurrences of microsatellite mutations in these cancers may be linked to DNA damage caused by exposure to carcinogens in tobacco smoke. To test this hypothesis, we developed a model system based on reactivation of green fluorescent protein (GFP) in which a plasmid vector carries a microsatellite repeat that places the GFP sequence out of frame for protein translation. In this reporter system, DNA slippage mutations can restore the GFP reading frame and become detectable by flow cytometry as GFP-positive cells. Pools of stably transfected RKO cells were treated at four dose levels each of gamma-irradiation, benzo(a)pyrene diol epoxide, N-methyl-N-nitro-N-nitrosoguanidine (MNNG), t-butyl hydrogen peroxide, and UV irradiation and assayed for GFP-positive cells 48 h later. We studied the microsatellite repeats AAAG, ATAG, CAGT, and CA, as well as a control sequence lacking any repetitive elements. A log-linear regression approach was used to discriminate between the effects of repeat unit and dose for each agent. A statistically significant increase in GFP-positive cells was found with increasing dose with all agents, although repeat unit-specific response patterns were only observed with MNNG, t-butyl hydrogen peroxide, and UV irradiation. With MNNG, significant differences in response were observed between dinucleotide and tetranucleotide repeat units. The effects of UV irradiation were consistent with the predicted number of pyrimidine dimers/repeat unit, with higher GFP activation in repeats that had large numbers of adjacent pyrimidines. We found no evidence to indicate that the AAAG repeat responded to any of the DNA-damaging agents with higher levels of GFP activation than other repeat units. These results provide evidence that DNA damage can induce slippage mutations and increase mutation rates in repeated sequences and that there are sequence-specific responses to different types of DNA damage. Our results are compatible with the hypothesis that sporadic microsatellite mutations in human cancer may reflect DNA damage caused by carcinogen exposure. C1 NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. RP Slebos, RJC (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, Maildrop C3-01,POB 12233, Res Triangle Pk, NC 27709 USA. OI taylor, jack/0000-0001-5303-6398 NR 39 TC 29 Z9 30 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 NOV 1 PY 2002 VL 62 IS 21 BP 6052 EP 6060 PG 9 WC Oncology SC Oncology GA 612EW UT WOS:000179062400012 PM 12414628 ER PT J AU Jaboin, J Wild, J Hamidi, H Khanna, C Kim, CJ Robey, R Bates, SE Thiele, CJ AF Jaboin, J Wild, J Hamidi, H Khanna, C Kim, CJ Robey, R Bates, SE Thiele, CJ TI MS-27-275, an inhibitor of histone deacetylase, has marked in vitro and in vivo antitumor activity against pediatric solid tumors SO CANCER RESEARCH LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; HUMAN NEURO-BLASTOMA; RETINOIC ACID; N-MYC; HUMAN NEUROBLASTOMA; CELL-CYCLE; IN-VIVO; TRANSCRIPTION; ACETYLATION; EXPRESSION AB The antitumor efficacy of the synthetic benzamide derivative MS-27-275 (MS-275), an inhibitor of histone deacetylation [T. Suzuki et al., J. Med. Chem., 42: 3001-3003, 1999], was evaluated in a series of pediatric solid tumor cell lines, including neuroblastoma, rhabdomyosarcoma, Ewing's sarcoma (EWS), retinoblastoma, medulloblastoma, undifferentiated sarcoma (US), osteosarcoma, and malignant rhabdoid tumors. Treatment with MS-275 results in an increase in acetylation of histones within 4 h of drug exposure. The cell lines were treated with various concentrations of MS-275 for 3 days and incubated with [H-3]thymidine for 20 h before cell harvest. MS-275 inhibited [H-3]thymidine uptake in a dose-dependent manner in all tumor cell lines examined. The IC50 ranged from 50 nm in the D283 medulloblastoma cell line to 1.3 muM in the US. A common feature of MS-275 treatment of pediatric tumor cell lines was induction of p21mRNA. However, the effects on cell cycle were diverse because in some cases MS-275 induced an increase in G(1) or G(2), whereas in others, there was an induction of apoptosis. In EWS, the EWS/fli chimeric transcription factor created by the t(11;22) suppresses transforming growth factor (TGF) betaRII transcription, however, MS-275 was able to induce an increase in TGF-betaRII mRNA and restore TGF-beta signaling. Using xenograft orthotopic models of US, EWS, and neuroblastoma, we find that the growth of established tumors is inhibited in mice treated with MS-275. C1 NCI, Cell & Mol Biol Sect, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Expt Therapeut Branch, Ctr Canc Res, Bethesda, MD 20892 USA. Seoul Natl Univ Med, Dept Pathol, Seoul 100799, South Korea. RP Thiele, CJ (reprint author), NCI, Cell & Mol Biol Sect, Pediat Oncol Branch, Ctr Canc Res, Bldg 10,Room 13N240,10 Ctr Dr,MSC 1928, Bethesda, MD 20892 USA. RI Seoul National University, Pathology/B-6702-2012 NR 39 TC 166 Z9 173 U1 0 U2 7 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 NOV 1 PY 2002 VL 62 IS 21 BP 6108 EP 6115 PG 8 WC Oncology SC Oncology GA 612EW UT WOS:000179062400019 PM 12414635 ER PT J AU Hyman, E Kauraniemi, P Hautaniemi, S Wolf, M Mousses, S Rozenblum, E Ringner, M Sauter, G Monni, O Elkahloun, A Kallioniemi, OP Kallioniemi, A AF Hyman, E Kauraniemi, P Hautaniemi, S Wolf, M Mousses, S Rozenblum, E Ringner, M Sauter, G Monni, O Elkahloun, A Kallioniemi, OP Kallioniemi, A TI Impact of DNA amplification on gene expression patterns in breast cancer SO CANCER RESEARCH LA English DT Article ID COPY-NUMBER CHANGES; MOLECULAR CLASSIFICATION; CDNA MICROARRAYS; HOMEOBOX GENES; GROWTH-FACTOR; CELL-LINE; HYBRIDIZATION; HOXB7; ANEUPLOIDY; AMPLICON AB Genetic changes underlie tumor progression and may lead to cancer-specific expression of critical genes. Over 1100 publications have described the use of comparative genomic hybridization (CGH) to analyze the pattern of copy number alterations in cancer, but very few of the genes affected are known. Here, we performed high-resolution CGH analysis on cDNA microarrays in breast cancer and directly compared copy number and mRNA expression levels of 13,824 genes to quantitate the impact of genomic changes on gene expression. We identified and mapped the boundaries of 24 independent amplicons, ranging in size from 0.2 to 12 Mb. Throughout the genome, both high- and low-level copy number changes had a substantial impact on gene expression, with 44% of the highly amplified genes showing overexpression and 10.5% of the highly overexpressed genes being amplified. Statistical analysis with random permutation tests identified 270 genes whose expression levels across 14 samples were systematically attributable to gene amplification. These included most previously described amplified genes in breast cancer and many novel targets for genomic alterations, including the HOXB7 gene, the presence of which in a novel amplicon at 17q21.3 was validated in 10.2% of primary breast cancers and associated with poor patient prognosis. In conclusion, CGH on cDNA microarrays revealed hundreds of novel genes whose overexpression is attributable to gene amplification. These genes may provide insights to the clonal evolution and progression of breast cancer and highlight promising therapeutic targets. C1 Univ Tampere, Inst Med Technol, Canc Genet Lab, FIN-33520 Tampere, Finland. NIH, Howard Hughes Med Inst, Bethesda, MD 20892 USA. NIH, Canc Genet Branch, NHGRI, Bethesda, MD 20892 USA. Tampere Univ Hosp, FIN-33520 Tampere, Finland. Tampere Univ Technol, Signal Proc Lab, FIN-33101 Tampere, Finland. Univ Basel, Inst Pathol, CH-4003 Basel, Switzerland. Helsinki Univ Hosp, Biomedicum, Biochip Ctr, FIN-00014 Helsinki, Finland. RP Kallioniemi, A (reprint author), Univ Tampere, Inst Med Technol, Canc Genet Lab, Lenkkeilijankatu 6, FIN-33520 Tampere, Finland. RI Hautaniemi, Sampsa/A-3122-2009; Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012; Ringner, Markus/G-3641-2011; OI Hautaniemi, Sampsa/0000-0002-7749-2694; Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332; Ringner, Markus/0000-0001-5469-8940; Kallioniemi, Anne/0000-0003-3552-8158 NR 32 TC 342 Z9 348 U1 0 U2 9 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 NOV 1 PY 2002 VL 62 IS 21 BP 6240 EP 6245 PG 6 WC Oncology SC Oncology GA 612EW UT WOS:000179062400037 PM 12414653 ER PT J AU Chuang, YYE Chen, YD Chandramouli, GVR Cook, JA Coffin, D Tsai, MH DeGraff, W Yan, HL Zhao, SP Russo, A Liu, ET Mitchell, JB AF Chuang, YYE Chen, YD Chandramouli, GVR Cook, JA Coffin, D Tsai, MH DeGraff, W Yan, HL Zhao, SP Russo, A Liu, ET Mitchell, JB TI Gene expression after treatment with hydrogen peroxide, menadione, or t-butyl hydroperoxide in breast cancer cells SO CANCER RESEARCH LA English DT Article ID LEUKEMIA INHIBITORY FACTOR; METALLOTHIONEIN-I; OXIDATIVE STRESS; REDOX REGULATION; RADIATION; INTERLEUKIN-6; KERATINOCYTES; INACTIVATION; MICROARRAYS; GENERATION AB Global gene expression patterns in breast cancer cells after treatment with oxidants (hydrogen peroxide, menadione, and t-butyl hydroperoxide) were investigated in three replicate experiments. RNA collected after treatment (at 1, 3, 7, and 24 h) rather than after a single time point, enabled an analysis of gene expression patterns. Using a 17,000 microarray, template-based clustering and multidimensional scaling analysis of the gene expression over the entire time course identified 421 genes as being either up- or down-regulated by the three oxidants. In contrast, only 127 genes were identified for any single time point and a 2-fold change criteria. Surprisingly, the patterns of gene induction were highly similar among the three oxidants; however, differences were observed, particularly with respect to p53, IL-6, and heat-shock related genes. Replicate experiments increased the statistical confidence of the study, whereas changes in gene expression patterns over a time course demonstrated significant additional information versus a single time point. Analyzing the three oxidants simultaneously by template cluster analysis identified genes that heretofore have not been associated with oxidative stress. C1 NCI, Radiat Biol Branch, Ctr Canc Res, Bethesda, MD 20827 USA. NIH, Canc Genet Branch, NHGRI, Bethesda, MD 20892 USA. Genome Inst Singapore, Singapore 117528, Singapore. RP Mitchell, JB (reprint author), NCI, Radiat Biol Branch, Ctr Canc Res, Bldg 10,Room B3-B69, Bethesda, MD 20827 USA. RI Liu, Edison/C-4141-2008 NR 40 TC 74 Z9 74 U1 1 U2 9 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 NOV 1 PY 2002 VL 62 IS 21 BP 6246 EP 6254 PG 9 WC Oncology SC Oncology GA 612EW UT WOS:000179062400038 PM 12414654 ER PT J AU Kim, CW Lee, HM Lee, TH Kang, CH Kleinman, HK Gho, YS AF Kim, CW Lee, HM Lee, TH Kang, CH Kleinman, HK Gho, YS TI Extracellular membrane vesicles from tumor cells promote angiogenesis via sphingomyelin SO CANCER RESEARCH LA English DT Article ID BREAST-CARCINOMA CELLS; INTERCELLULAR-ADHESION MOLECULE-1; IN-VITRO; ENDOTHELIAL-CELLS; SURFACE-ANTIGENS; PLASMA-MEMBRANE; GROWTH-FACTOR; MICROPARTICLES; PLATELETS; MIGRATION AB Actively growing tumor cells shed membrane vesicles into the extracellular milieu both in vivo and in vitro. Extracellular membrane vesicles from tumor cells contain most surface antigens and proteases present on these cells. They facilitate the escape of tumors from immune surveillance and promote tumor cell invasion. Here, we demonstrate that tumor membrane vesicles stimulate an additional important activity for tumor growth and metastasis by promoting endothelial cell migration, invasion, and tube formation, and inducing in vivo neovascularization. Our data show that tumor vesicles are one of the multiple effectors involved in tumor-induced angiogenesis. Heat-treated vesicles and lipid extracts from the vesicles also induce endothelial cell migration and in vivo angiogenesis. We identify sphingomyelin as the active component for vesicle-induced endothelial cell migration, tube formation, and neovascularization. Together with previously reported results, our data demonstrate that shed tumor vesicles play multiple roles in tumor growth and metastasis by promoting angiogenesis, tumor invasion, and immune escape. C1 Kyung Hee Univ, Grad Sch E W Med Sci, Dept Oncol, Yongin 449701, South Korea. NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Gho, YS (reprint author), Kyung Hee Univ, Grad Sch E W Med Sci, Dept Oncol, Yongin 449701, South Korea. NR 40 TC 158 Z9 166 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 NOV 1 PY 2002 VL 62 IS 21 BP 6312 EP 6317 PG 6 WC Oncology SC Oncology GA 612EW UT WOS:000179062400046 PM 12414662 ER PT J AU Simmons, DP Andreola, F De Luca, LM AF Simmons, DP Andreola, F De Luca, LM TI Human melanomas of fibroblast and epithelial morphology differ widely in their ability to synthesize retinyl esters SO CARCINOGENESIS LA English DT Article ID ALL-TRANS-RETINOL; NORMAL HUMAN MELANOCYTES; TGF-BETA; HUMAN KERATINOCYTES; BINDING PROTEIN; ACID BIOSYNTHESIS; CELL STRAINS; ORAL CAVITY; RAT-LIVER; METABOLISM AB Reduced retinyl ester synthesis has been associated with several forms of cancer; we therefore proposed studying melanoma development from the perspective of this biochemical pathway. Cultures of human melanoma cells with fibroblastoid morphology showed negligible retinyl ester synthesis; in sharp contrast, those with epithelioid morphology were capable of retinol esterification. Further, isolated proliferating epidermal melanocytes (HFSC/2) esterified retinol, whereas proliferating normal skin fibroblasts (F:CCD-1121.Sk) did not. A primary site cutaneous melanoma and its metastatic match (both of epithelioid morphology) were capable of retinol esterification, while a matched fibroblastoid tumor pair did not synthesize retinyl esters; nevertheless, LRAT (lecithin: retinol acyltransferase) protein was found in microsomal fractions from all four tumors. A mutation screen in the LRAT coding region and adjacent intronic sequences revealed several novel mutations in these melanomas as well as in HFSC/2 and F:CCD-1121.Sk cells: a single nucleotide polymorphism in exon 1(37A-->G), a silent mutation in exon 2a (188 A-->G/186 G-->A), and an insertion in the 5'UTR (9-10insC). CRBP-1 basal expression was present in the HFSC/2, and in both sets of matched tumor pairs; however, steady-state levels in the fibroblastoid melanoma pair were one-third that found in the epithelioid matched tumor pair. Coculture of human primary site epithelioid melanoma with proliferating normal human skin fibroblasts abrogated retinol esterification within 96 h and increased the expression of the active form of TGFbeta-1 by 2.4-fold. A concomitant 3.2-fold downregulation of CRBP-1 expression took place. This is the first study to (1) demonstrate an association between retinyl ester synthesis and cutaneous melanoma morphological phenotypes; (2) suggest the existence of a soluble, diffusible inhibitor of the retinol esterification pathway; (3) report the ability of the isolated, proliferating human epidermal melanocyte to esterify retinol; and (4) provide evidence of DNA variants in the coding region of LRAT. C1 NCI, Ctr Canc Res, NIH, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. RP De Luca, LM (reprint author), NCI, Ctr Canc Res, NIH, Cellular Carcinogenesis & Tumor Promot Lab, Bldg 37,Room 3A-17, Bethesda, MD 20892 USA. NR 41 TC 9 Z9 9 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 NOV PY 2002 VL 23 IS 11 BP 1821 EP 1830 DI 10.1093/carcin/23.11.1821 PG 10 WC Oncology SC Oncology GA 616LV UT WOS:000179306000007 PM 12419830 ER PT J AU Ganesan, S Silver, DP Greenberg, RA Avni, D Drapkin, R Miron, A Mok, SC Randrianarison, V Brodie, S Salstrom, J Rasmussen, TP Klimke, A Marrese, C Marahrens, Y Deng, CX Feunteun, J Livingston, DM AF Ganesan, S Silver, DP Greenberg, RA Avni, D Drapkin, R Miron, A Mok, SC Randrianarison, V Brodie, S Salstrom, J Rasmussen, TP Klimke, A Marrese, C Marahrens, Y Deng, CX Feunteun, J Livingston, DM TI BRCA1 supports XIST RNA concentration on the inactive X chromosome SO CELL LA English DT Article ID MEIOTIC CELLS; BREAST-CANCER; ESTROGEN-RECEPTOR; DNA-REPAIR; TRANSCRIPTION; MUTATION; ASSOCIATION; PROTEINS; COMPLEX; CHROMATIN AB BRCA1, a breast and ovarian tumor suppressor, colocalizes with markers of the inactive X chromosome (Xi) on Xi in female somatic cells and associates with XIST RNA, as detected by chromatin immunoprecipitation. Breast and ovarian carcinoma cells lacking BRCA1 show evidence of defects in Xi chromatin structure. Reconstitution of BRCA1-deficient cells with wt BRCA1 led to the appearance of focal XIST RNA staining without altering XIST abundance. Inhibiting BRCA1 synthesis in a suitable reporter line led to increased expression of an otherwise silenced Xi-located GFP transgene. These observations suggest that loss of BRCA1 in female cells may lead to Xi perturbation and destabilization of its silenced state. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Lab Gynecol Oncol, Boston, MA 02115 USA. Inst Gustave Roussy, Lab Genet Oncol, Lab Vectorol & Transfert Genes, F-94805 Villejuif, France. NIDDKD, Genet Dev & Dis Branch 10 9N105, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Human Genet, Gonda Ctr, Los Angeles, CA 90095 USA. Univ Connecticut, Ctr Regenerat Biol, Storrs, CT 06269 USA. Univ Connecticut, Dept Anim Sci, Storrs, CT 06269 USA. RP Livingston, DM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Drapkin, Ronny/E-9944-2016; deng, chuxia/N-6713-2016 OI Drapkin, Ronny/0000-0002-6912-6977; NR 52 TC 202 Z9 209 U1 2 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD NOV 1 PY 2002 VL 111 IS 3 BP 393 EP 405 DI 10.1016/S0092-8674(02)01052-8 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 611HG UT WOS:000179010100011 PM 12419249 ER PT J AU Jetten, AM Ueda, E AF Jetten, AM Ueda, E TI Retinoid-related orphan receptors (RORs): roles in cell survival, differentiation and disease SO CELL DEATH AND DIFFERENTIATION LA English DT Article ID DNA-BINDING PROPERTIES; ALPHA-DEFICIENT MICE; THYMOCYTE APOPTOSIS; NUCLEAR RECEPTORS; KAPPA-B; STAGGERER; EXPRESSION; BETA; GAMMA; MITOCHONDRION C1 NIEHS, Cell Biol Sect, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. RP Jetten, AM (reprint author), NIEHS, Cell Biol Sect, Div Intramural Res, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. OI Jetten, Anton/0000-0003-0954-4445 NR 44 TC 38 Z9 38 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD NOV PY 2002 VL 9 IS 11 BP 1167 EP 1171 DI 10.1038/sj.cdd.4401085 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 609GM UT WOS:000178895300002 PM 12404115 ER PT J AU Quarles, RH AF Quarles, RH TI Myelin sheaths: glycoproteins involved in their formation, maintenance and degeneration SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE glycoprotein; myelin; myelin-associated glycoprotein; myelin-oligodendrocyte glycoprotein; oligodendrocyte; peripheral myelin protein-22; protein zero; Schwann cell ID PERIPHERAL NERVOUS-SYSTEM; CELL-ADHESION MOLECULES; MULTIPLE-SCLEROSIS LESIONS; EXPERIMENTAL AUTOIMMUNE NEURITIS; EXPERIMENTAL ALLERGIC NEURITIS; INHIBITS AXONAL REGENERATION; ANTERIOR MEDULLARY VELUM; GUILLAIN-BARRE-SYNDROME; ANTI-SGPG ANTIBODIES; FYN TYROSINE KINASE AB Myelin sheaths are formed around axons by extending, biochemically modifying and spiraling plasma membranes of Schwann cells in the peripheral nervous system (PNS) and oligodendrocytes in the central nervous system (CNS). Because glycoproteins are prominent components of plasma membranes, it is not surprising that they have important roles in the formation, maintenance and degeneration of myelin sheaths. The emphasis in this review is on four integral membrane glycoproteins. Two of them, protein zero (PO) and peripheral myelin protein-22 (PMP-22), are components of compact INS myelin. The other two are preferentially localized in membranes of sheaths that are distinct from compact myelin. One is the myelin-associated glycoprotein, which is localized at the inside of sheaths where it functions in glia-axon interactions in both the INS and CNS. The other is the myelin-oligodendrocyte glycoprotein, which is preferentially localized on the outside of CNS myelin sheaths and appears to be an important target antigen in autoimmune demyelinating diseases such as multiple sclerosis. C1 Natl Inst Neurol Disorders & Stroke, Lab Mol & Cellular Neurobiol, Myelin & Brain Dev Sect, NIH, Bethesda, MD 20892 USA. RP Quarles, RH (reprint author), Natl Inst Neurol Disorders & Stroke, Lab Mol & Cellular Neurobiol, Myelin & Brain Dev Sect, NIH, Rm 2A28,Bldg 49,MSC 4440,49 Convent Dr, Bethesda, MD 20892 USA. NR 206 TC 80 Z9 85 U1 0 U2 5 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD NOV PY 2002 VL 59 IS 11 BP 1851 EP 1871 DI 10.1007/PL00012510 PG 21 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 627ZX UT WOS:000179968000007 PM 12530518 ER PT J AU Hanakawa, T Honda, M Sawamoto, N Okada, T Yonekura, Y Fukuyama, H Shibasaki, H AF Hanakawa, T Honda, M Sawamoto, N Okada, T Yonekura, Y Fukuyama, H Shibasaki, H TI The role of rostral Brodmann area 6 in mental-operation tasks: An integrative neuroimaging approach SO CEREBRAL CORTEX LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; SUPPLEMENTARY MOTOR AREA; SPATIAL WORKING-MEMORY; SEQUENTIAL FINGER MOVEMENTS; EVENT-RELATED FMRI; PREMOTOR CORTEX; FRONTAL-LOBE; PREFRONTAL CORTEX; CORTICOSPINAL PROJECTIONS; MACAQUE MONKEY AB Recent evidence indicates that classical 'motor' areas may also have cognitive functions. We performed three neuroimaging experiments to investigate the functional neuroanatomy underlying three types of nonmotor mental-operation tasks: numerical, verbal, and spatial. (i) Positron emission tomography showed that parts of the posterior frontal cortex, which are consistent with the pre-supplementary motor area (pre-SMA) and the rostral part of the dorsolateral premotor cortex (PMdr), were active during all three tasks. We also observed activity in the posterior parietal cortex and cerebellar hemispheres during all three tasks. Electrophysiological monitoring confirmed that there were no skeletomotor, oculomotor or articulatory movements during task performance. (ii) Functional magnetic resonance imaging (fMRI) showed that PMdr activity during the mental-operation tasks was localized in the depths of the superior precentral sulcus, which substantially overlapped the region active during complex finger movements and was located dorsomedial to the presumptive frontal eye fields. (iii) Single-trial fMRI showed a transient increase in activity time-locked to the performance of mental operations in the pre-SMA and PMdr. The results of the present study suggest that the PMdr is important in the rule-based association of symbolic cues and responses in both motor and nonmotor behaviors. C1 Natl Inst Physiol Sci, Lab Cerebral Integrat, Okazaki, Aichi 4448585, Japan. Kyoto Univ, Grad Sch Med, Human Brain Res Ctr, Kyoto, Japan. Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, NIH, Bethesda, MD USA. Japan Sci & Technol Corp, PRESTO, Kawaguchi, Japan. Kyoto Univ, Grad Sch Med, Dept Nucl Med, Kyoto, Japan. Fukui Med Univ, Biomed Imaging Res Ctr, Fukui, Japan. Natl Inst Physiol Sci, Auton Res Project, Okazaki, Aichi 4448585, Japan. RP Honda, M (reprint author), Natl Inst Physiol Sci, Lab Cerebral Integrat, 38 Nishigonaka, Okazaki, Aichi 4448585, Japan. NR 94 TC 115 Z9 119 U1 2 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD NOV PY 2002 VL 12 IS 11 BP 1157 EP 1170 DI 10.1093/cercor/12.11.1157 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 606NQ UT WOS:000178740400005 PM 12379604 ER PT J AU Gopich, IV Szabo, A AF Gopich, IV Szabo, A TI Asymptotic relaxation of reversible bimolecular chemical reactions SO CHEMICAL PHYSICS LA English DT Article ID DIFFUSION-CONTROLLED REACTIONS; ARROW-C; KINETICS; EQUILIBRIUM; BEHAVIOR; BINDING AB The kinetics of the diffusion influenced bimolecular reversible reactions A + B reversible arrow C and A + B reversible arrow C + D is investigated at long times. We use the Poisson representation which treats the underlying many particle problem in a simple and elegant way. In this formalism the master equation can be exactly transformed into a Fokker-Planck or equivalent Langevin equation. Solving these iteratively, we determine the amplitude of the power law (t(-d/2)) decay of the concentrations to equilibrium for arbitrary diffusion constants and concentrations of the reactants. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Gopich, IV (reprint author), NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. RI Szabo, Attila/H-3867-2012 NR 23 TC 22 Z9 22 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0104 J9 CHEM PHYS JI Chem. Phys. PD NOV 1 PY 2002 VL 284 IS 1-2 SI SI BP 91 EP 102 AR PII S0301-0104(02)00541-4 DI 10.1016/S0301-0104(02)00541-4 PG 12 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 613AN UT WOS:000179108100008 ER PT J AU Shvedova, AA Kisin, ER Murray, AR Kommineni, C Castranova, V Mason, RP Kadiiska, MB Gunther, MR AF Shvedova, AA Kisin, ER Murray, AR Kommineni, C Castranova, V Mason, RP Kadiiska, MB Gunther, MR TI Antioxidant balance and free radical generation in vitamin E-deficient mice after dermal exposure to cumene hydroperoxide SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID HUMAN EPIDERMAL-KERATINOCYTES; CULTURED HUMAN KERATINOCYTES; OXIDATIVE STRESS; SOYBEAN LIPOXYGENASE; LIPID-PEROXIDATION; BENZOYL PEROXIDE; TUMOR PROMOTION; SKIN; ADDUCTS; GLUTATHIONE AB Organic peroxides are widely used in the chemical industry as initiators of oxidation for the production of polymers and fiber-reinforced plastics, in the manufacture of polyester resin coatings, and pharmaceuticals. Free radical production is considered to be one of the key factors contributing to skin tumor promotion by organic peroxides. In vitro experiments have demonstrated metal-catalyzed formation of alkoxyl, alkyl, and aryl radicals in keratinocytes incubated with cumene hydroperoxide. The present study investigated in vivo free radical generation in lipid extracts of mouse skin exposed to cumene hydroperoxide. The electron spin resonance (ESR) spin-trapping technique was used to detect the formation of alpha-phenyl-N-tertbutylnitrone (PBN) radical adducts, following intradermal injection of 180 mg/kg PBN. It was found that 30 min after topical exposure, cumene hydroperoxide (12 mmol/kg) induced free radical generation in the skin of female Balb/c mice kept for 10 weeks on vitamin E-deficient diets. In contrast, hardly discernible radical adducts were detected when cumene hydroperoxide was applied to the skin of mice fed a vitamin E-sufficient diet. Importantly, total antioxidant reserve and levels of GSH, ascorbate, and vitamin E decreased 34%, 46.5%. 27%, and 98%, respectively, after mice were kept for 10 weeks on vitamin E-deficient diet. PBN adducts detected by ESR in vitamin E-deficient mice provide direct evidence for in vivo free radical generation in the skin after exposure to cumene hydroperoxide. C1 NIOSH, Pathol & Physiol Res Branch, Hlth Effects Lab Div, Morgantown, WV 26505 USA. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. W Virginia Univ, Dept Biochem & Mol Pharmacol, Morgantown, WV 26505 USA. RP Shvedova, AA (reprint author), NIOSH, Pathol & Physiol Res Branch, Hlth Effects Lab Div, M-S 2015,1095 Willowdale Rd, Morgantown, WV 26505 USA. NR 55 TC 17 Z9 17 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD NOV PY 2002 VL 15 IS 11 BP 1451 EP 1459 DI 10.1021/tx0200313 PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 617TT UT WOS:000179377500013 PM 12437336 ER PT J AU de Serres, FJ AF de Serres, FJ TI Worldwide racial and ethnic distribution of alpha(1)-antitrypsin deficiency - Summary of an analysis of published genetic epidemiologic surveys SO CHEST LA English DT Article DE alpha(1)-antitrypsin deficiency; alpha(1)-protease; alpha(1)-protease inhibitor; genetic epideminology; Pi subtypes; Pi phenotypes; population genetics ID ALPHA-1-ANTITRYPSIN DEFICIENCY; LIVER-DISEASE; CLINICAL-FEATURES; PI Z; PHENOTYPE; RISK; POPULATION; EMPHYSEMA; PATTERNS; INDIANS AB Study objectives: alpha(1)-antitrypsin (AAT) deficiency is a genetic disease that is widely known in Europe as a disease of white individuals, who, along with their descendants in other parts of the world, are at the highest risk for liver and/or lung disease. There is a limited database of individuals affected by this disease worldwide. It has been estimated, for example, that there are 70,000 to 100,00 individuals affected in the United States, with comparable numbers in Europe. Study design: Genetic epidemiologic studies in the peer-reviewed literature have been used in an exploratory study to estimate the number of carriers and the number of those individuals who are homozygous or heterozygous for the two most common defective alleles for AAT deficiency in 58 individual countries. The total country database of 373 control cohorts has been combined to estimate the numbers of carriers and deficiency allele combinations for PiS and PiZ in 11 geographic regions and worldwide. The study was designed to be illustrative rather than comprehensive, and more detailed publication of the enormous database developed in this exploratory study is planned. Conclusions: The database presented indicates that in a total population of 4.4 billion in the countries surveyed worldwide, there are at least 116 million carriers (PiMS and PiMZ) and 3.4 million deficiency allele combinations (PiSS, PiSZ, and PiZZ). Furthermore, this database demonstrates that AAT deficiency is found in various populations of African blacks, Arabs and Jews in the Middle East, whites in Australia/New Zealand, Europe, and North America, central Asians, far east Asians, and southeast Asians. These data demonstrate that AAT deficiency is not just a disease of whites in Europe, but that it affects individuals in all racial subgroups worldwide. in addition, AAT deficiency may be one of the most common serious hereditary disorders in the world. C1 NIEHS, Toxicol Lab, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP de Serres, FJ (reprint author), 632 Rock Creek Rd, Chapel Hill, NC 27514 USA. NR 40 TC 208 Z9 214 U1 0 U2 7 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD NOV PY 2002 VL 122 IS 5 BP 1818 EP 1829 DI 10.1378/chest.122.5.1818 PG 12 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 617TH UT WOS:000179376600049 PM 12426287 ER PT J AU Dennis, TA Cole, PM Zahn-Waxler, C Mizuta, I AF Dennis, TA Cole, PM Zahn-Waxler, C Mizuta, I TI Self in context: Autonomy and relatedness in Japanese and US mother-preschooler dyads SO CHILD DEVELOPMENT LA English DT Article ID UNITED-STATES; AMERICAN-FAMILIES; SOCIAL COMPETENCE; SOCIALIZATION; EMOTION; CULTURE; ANTECEDENTS; DISTRESS; SECURITY; CHILDREN AB Cultural differences and similarities in socialization during two contrasting laboratory tasks were examined in 30 Japanese mothers and their preschoolers, both temporarily residing in the United States, and 30 U.S. mothers and their preschoolers (age: M = 55.8 months, SD = 4.9). Mother and child actions, speech, emotion, and attention were coded from videotaped observations during a free play task and waiting task. Cross-cultural comparisons showed that U.S. mothers had more conversations that emphasized individual experiences, more often acted as playmates and used joint attention, maintained more physical distance, showed more positive emotions, and made more positive responses to child accomplishment. In contrast, Japanese mothers had more conversations that emphasized shared experiences, showed more divided attention, and maintained social role distinctions. Similar, but fewer cultural differences emerged for children. However, maternal and child characteristics also varied by task context. The results suggested an emphasis on autonomy in U.S. dyads and an emphasis on relatedness in Japanese dyads, but the interactions with task context revealed the coexistence of autonomy and relatedness. C1 NYU, Sch Med, Ctr Child Study, New York, NY 10016 USA. Penn State Univ, University Pk, PA 16802 USA. NIMH, Bethesda, MD 20892 USA. Kobe Coll, Kobe, Hyogo, Japan. RP Dennis, TA (reprint author), NYU, Sch Med, Ctr Child Study, 577 1st Ave, New York, NY 10016 USA. EM dennit01@med.nyu.edu NR 76 TC 21 Z9 21 U1 2 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-3920 J9 CHILD DEV JI Child Dev. PD NOV-DEC PY 2002 VL 73 IS 6 BP 1803 EP 1817 DI 10.1111/1467-8624.00507 PG 15 WC Psychology, Educational; Psychology, Developmental SC Psychology GA 621DM UT WOS:000179573300013 PM 12487495 ER PT J AU Reed, GF Lynn, F Meade, BD AF Reed, GF Lynn, F Meade, BD TI Use of coefficient of variation in assessing variability of quantitative assays SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID IMMUNOSORBENT AB We have derived the mathematical relationship between the coefficient of variation associated with repeated measurements from quantitative assays and the expected fraction of pairs of those measurements that differ by at least some given factor, i.e., the expected frequency of disparate results that are due to assay variability rather than true differences. Knowledge of this frequency helps determine what magnitudes of differences can be expected by chance alone when the particular coefficient of variation is in effect. This frequency is an operational index of variability in the sense that it indicates the probability of observing a particular disparity between two measurements under the assumption that they measure the same quantity. Thus the frequency or probability becomes the basis for assessing if an assay is sufficiently precise. This assessment also provides a standard for determining if two assay results for the same subject, separated by an intervention such as vaccination or infection, differ by more than expected from the variation of the assay, thus indicating an intervention effect. Data from an international collaborative study are used to illustrate the application of this proposed interpretation of the coefficient of variation, and they also provide support for the assumptions used in the mathematical derivation. C1 NEI, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD USA. RP Reed, GF (reprint author), NEI, NIH, 31 Ctr Dr,MSC 2510,Bldg 31,room 6A52, Bethesda, MD 20892 USA. NR 5 TC 162 Z9 163 U1 1 U2 25 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD NOV PY 2002 VL 9 IS 6 BP 1235 EP 1239 DI 10.1128/CDLI.9.6.1235-1239.2002 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 615WV UT WOS:000179271100014 PM 12414755 ER PT J AU Kawakami, M Kawakami, K Stepensky, VA Maki, RA Robin, H Muller, W Husain, SR Puri, RK AF Kawakami, M Kawakami, K Stepensky, VA Maki, RA Robin, H Muller, W Husain, SR Puri, RK TI Interleukin 4 receptor on human lung cancer: A molecular target for cytotoxin therapy SO CLINICAL CANCER RESEARCH LA English DT Article ID CIRCULARLY PERMUTED INTERLEUKIN-4; RECOMBINANT HUMAN INTERLEUKIN-4; BREAST-CARCINOMA CELLS; COMMON GAMMA-CHAIN; PSEUDOMONAS EXOTOXIN; ANTITUMOR-ACTIVITY; CHIMERIC PROTEIN; FUSION PROTEIN; IL-4 RECEPTORS; IN-VITRO AB Previous studies have demonstrated that human lung tumor cell lines express interleukin 4 (IL-4) receptors, and IL-4 can mediate modest to moderate antiproliferative activity in vitro and in vivo in animal models of human lung tumors. On the basis of these studies, IL-4 was tested in clinical trials; however, it showed little antitumor activity in lung cancer patients. In the present study, we examined the expression of IL-4 receptors (IL-41ts) in lung tumor samples and normal lung tissues and tested whether an IL-4R targeted agent will have better antitumor activity in vitro and in vivo compared with IL-4. IL-4R expression was tested by immunohistochemistry in 54 lung tumor samples and normal lung tissues in a tissue array, by reverse-transcription PCR and Northern blot analyses in lung tumor cell lines. Cytotoxic activity of IL-4 cytotoxin [IL-4(38-37)-PE38KDEL], composed of a circular permuted IL-4 and a mutated form of Pseudomonas exotoxin (PE38KDEL) was tested by protein synthesis inhibition and clonogenic assays in seven lung tumor cell lines. Antitumor activity of IL-4 cytotoxin was tested in vitro and in immunodeficient animal models of human lung tumors. We observed that IL-4Rs are expressed at higher levels in situ in lung tumor samples compared with normal lung tissues and IL-4 cytotoxin is highly and specifically cytotoxic to lung tumor cell lines in vitro. Intratumoral and i.p. administration of IL-4 cytotoxin to immunodeficient mice with s.c. established human lung H358 non-small cell lung cancer tumors mediated considerable antitumor activity in a dose-dependent manner with the higher dose producing durable complete responses. On the other hand, H460 non-small cell lung cancer tumors expressing low levels of IL-4R did not respond to IL-4 cytotoxin therapy. Because IL-4 cytotoxin mediates its antitumor activity through IL-4R, and a variety of lung tumors expressed high levels of IL-4R, we propose testing the safety of this agent in patients with lung cancer. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol,NIH, Bethesda, MD 20892 USA. Neurosci Biosci Inc, San Diego, CA 92121 USA. Sharp Mem Hosp & Rehabil Ctr, San Diego, CA 90034 USA. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol,NIH, Bldg 29B,Room 2NN10,29 Lincoln Dr MSC 4555, Bethesda, MD 20892 USA. NR 32 TC 30 Z9 31 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2002 VL 8 IS 11 BP 3503 EP 3511 PG 9 WC Oncology SC Oncology GA 615UY UT WOS:000179266400027 PM 12429641 ER PT J AU Hassan, R Lerner, MR Benbrook, D Lightfoot, SA Brackett, DJ Wang, QC Pastan, I AF Hassan, R Lerner, MR Benbrook, D Lightfoot, SA Brackett, DJ Wang, QC Pastan, I TI Antitumor activity of SS(dsFv)PE38 and SS1(dsFv)PE38, recombinant antimesothelin Immunotoxins against human gynecologic cancers grown in organotypic culture in vitro SO CLINICAL CANCER RESEARCH LA English DT Article ID MONOCLONAL-ANTIBODY K1; EPITHELIAL-CELLS; OVARIAN CANCERS; IN-VITRO; MESOTHELIN; CHEMOTHERAPY; RESISTANCE; CARCINOMA; MODEL; PHENOTYPE AB Purpose: Mesothelin, a cell surface glycoprotein over-expressed in ovarian cancer, mesotheliomas, and some squamous cell carcinomas, is an attractive candidate for targeted therapy because it is not shed in significant amounts into the bloodstream and is not present in significant amounts on normal human tissues except for mesothelial cells. The objective of this study was to determine the antitumor activity of SSI(dsFv)PE38, a recombinant antimesothelin immunotoxin, against human gynecologic tumors grown in short-term culture in vitro. Experimental Design: Tumor cells obtained from primary cultures of five ovarian and one cervical tumor were mixed with an equal proportion of NIH-3T3 fibroblasts and plated inside collagen gels in tissue culture plates. After 4-7 days of growth, these organotypic cultures were treated with media alone, SS1(dsFv)PE38, and a control immunotoxin RFB4(dsFv)PE38, which targets the CD22 antigen not present on gynecologic tumors, every other day X 3. The organotypic culture gels were then formalin fixed, paraffin embedded, and evaluated for immunotoxin sensitivity using light microscopic examination of H&E-stained slides and also evaluated for apoptosis using the terminal deoxynucleotidyl transferase-mediated nick end labeling assay. Results: Tumors expressing mesothelin showed a significant dose-dependent sensitivity to SS1(dsFv)PE38 even at concentrations as low as 1 ng/ml, whereas no antitumor activity was seen at 100 ng/ml in tumors that did not express mesothelin. This activity was specifically attributable to mesothelin targeting because RFB4 (dsFv)-PE38 had no activity against mesothelin-expressing tumors. Conclusions: These results demonstrate that ovarian and cervical tumor cells obtained from patients can be grown in short-term culture using an organotypic culture model. Our results also show low concentrations of an immunotoxin targeting mesothelin is cytotoxic to mesothelin-expressing human tumors by inducing apoptosis. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. Univ Oklahoma, Hlth Sci Ctr, Dept Surg, Oklahoma City, OK USA. Univ Oklahoma, Hlth Sci Ctr, Dept Obstet & Gynecol, Oklahoma City, OK 73190 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Oklahoma City, OK 73190 USA. RP Hassan, R (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37,Room 5106,37 Convent Dr, Bethesda, MD 20892 USA. NR 28 TC 48 Z9 49 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 NOV PY 2002 VL 8 IS 11 BP 3520 EP 3526 PG 7 WC Oncology SC Oncology GA 615UY UT WOS:000179266400029 PM 12429643 ER PT J AU Patel, V Lahusen, T Leethanakul, C Igishi, T Kremer, M Quintanilla-Martinez, L Ensley, JF Sausville, EA Gutkind, JS Senderowicz, AM AF Patel, V Lahusen, T Leethanakul, C Igishi, T Kremer, M Quintanilla-Martinez, L Ensley, JF Sausville, EA Gutkind, JS Senderowicz, AM TI Antitumor activity of UCN-01 in carcinomas of the head and neck is associated with altered expression of cyclin D3 and p27(KIP1) SO CLINICAL CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMAS; PROTEIN-KINASE-C; HUMAN CANCER-CELLS; FUNCTIONAL-CHARACTERIZATION; RADIOSENSITIZING AGENT; SELECTIVE INHIBITOR; DEPENDENT KINASES; GROWTH-INHIBITION; DRUG SCREEN; IN-VIVO AB Altered and deregulated cyclin-dependent kinase (cdk) activity is now believed to play a major role in the pathogenesis of head and neck squamous cell carcinomas (HNSCC), thus providing a suitable cellular target for therapeutic intervention. UCN-01 (7-hydroxy-staurosporine), a known protein kinase C and cdk modulator, demonstrates antiproliferative and antitumor properties in many experimental tumor models and may represent a potential candidate to test in HNSCC. In this study, UCN-01 displayed potent antiproliferative properties (IC50 of similar to17-80 nm) in HNSCC cells. Cell cycle analysis revealed that UCN-01 treatment of HNSCC cells for 24 h leads to a G(1) block with a concomitant loss of cells in S and G(2)-M and the emerging sub-G(1) cell population, confirmed to be apoptotic by terminal deoxynucleotidyl transferase-mediated nick end labeling analysis. Additional in vitro studies demonstrated a G(1) arrest that was preceded by depletion in cyclin D3, elevation of p21(WAF1) and p27(KIP1) leading to a loss in activity of G(1) cdks (cdk2, cdk4), and reduction in pRb phosphorylation. Antitumor properties of UCN-01 were also assessed in vivo by treating HN12 xenografts (7.5 mg/kg/i.p./daily) with UCN-01 for 5 consecutive days. Total sustained abolition of tumor growth (P < 0.00001) was obtained with only one cycle of UCN-01 treatment. Terminal deoxynucleotidyl transferase-mediated nick end labeling staining of xenograft samples revealed a higher incidence of apoptosis in treated tissues when compared with control. Additional tissue analysis demonstrated that elevated p27(KIP1) with minimal increase in p21(WAF1) and reduced cyclin D3 levels were readily detected in those animals treated with UCN-01, similar to those observed in HNSCC cells. Thus, UCN-01 exhibits both in vitro and in vivo antitumor properties in HNSCC models, and these effects are associated with a decrease in cyclin D3 and an increase in p27(KIP1) protein levels, thus providing appropriate surrogate markers to follow treatment efficacy in vivo and, therefore, a suitable drug candidate for treating HNSCC patients. C1 Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. NCI, Dev Therapeut Program, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. GSF, Natl Res Ctr Environm & Hlth, Inst Pathol, Neuherberg, Germany. Wayne State Univ, Karmanos Canc Inst, Div Hematol Oncol, Detroit, MI 48201 USA. RP Gutkind, JS (reprint author), NIDR, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Bldg 30,Room 212, Bethesda, MD 20892 USA. RI Gutkind, J. Silvio/A-1053-2009 NR 57 TC 42 Z9 43 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 NOV PY 2002 VL 8 IS 11 BP 3549 EP 3560 PG 12 WC Oncology SC Oncology GA 615UY UT WOS:000179266400032 PM 12429646 ER PT J AU Richard, IH Justus, AW Greig, NH Marshall, F Kurlan, R AF Richard, IH Justus, AW Greig, NH Marshall, F Kurlan, R TI Worsening of motor function and mood in a patient with Parkinson's disease after pharmacologic challenge with oral rivastigmine SO CLINICAL NEUROPHARMACOLOGY LA English DT Review DE Rivastigmine; acetylcholinesterase inhibitors; Parkinson's disease ID ALZHEIMERS-DISEASE; LEWY BODIES; PHYSOSTIGMINE; PSYCHOSIS; DEMENTIA AB Patients with Parkinson's disease (PD) can experience cognitive impairment. There are currently no medications indicated for the treatment of cognitive impairment in PD. Clinicians are faced with the dilemma as to whether or not to treat patients with PD with the acetylcholinesterase inhibitors that are currently approved for use in Alzheimer's disease (AD) and that have shown promise in clinical trials of Dementia with Lewy bodies (DLB). Although these medications may help cognition, there is a theoretical concern that by increasing acetylcholine relative to dopamine, they might worsen motor function. We report the case of a patient with PD and cognitive impairment who developed a marked worsening of motor function, mood, and anxiety in the setting of a pharmacologic challenge study using a 3-mg oral dose of the acetylcholinesterase inhibitor, rivastigmine. We believe that the mechanism of the motor and perhaps psychiatric worsening was increased central cholinergic tone. We conclude that further studies should be done to evaluate the efficacy and tolerability of these agents in this illness but that caution should be exercised when using acetylcholinesterase inhibitors in patients with PD. C1 Univ Rochester, Med Ctr, Dept Neurol, Sch Med & Dent, Rochester, NY 14642 USA. Univ Rochester, Dept Clin & Social Psychol, Rochester, NY 14642 USA. NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Richard, IH (reprint author), Univ Rochester, Med Ctr, Dept Neurol, Sch Med & Dent, Box 673,601 Elmwood Ave, Rochester, NY 14642 USA. FU NCRR NIH HHS [5 M01 RR00044]; NIA NIH HHS [5 P30 AG08665-10]; NINDS NIH HHS [1 K23 NS 02184] NR 13 TC 24 Z9 24 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-5664 J9 CLIN NEUROPHARMACOL JI Clin. Neuropharmacol. PD NOV-DEC PY 2002 VL 25 IS 6 BP 296 EP 299 DI 10.1097/00002826-200211000-00002 PG 4 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 629BP UT WOS:000180030800002 PM 12469000 ER PT J AU Baas, JMP Kenemans, JL Mangun, GR AF Baas, JMP Kenemans, JL Mangun, GR TI Selective attention to spatial frequency: an ERP and source localization analysis SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE evoked potential; spatial frequency; attention; selection; dipole-source analysis ID EVENT-RELATED POTENTIALS; PRIMARY VISUAL-CORTEX; ELECTROPHYSIOLOGICAL ANALYSIS; EVOKED-POTENTIALS; BRAIN POTENTIALS; STRIATE CORTEX; MACAQUE MONKEY; COLOR; LOCATION; SIZE AB Objectives: Physiological correlates of visual selective attention have been observed by recording ERPs to attended versus ignored target stimuli. Over many such studies, spatial attention has been observed to modulate early sensory conponents beginning 70 ms after stimulus onset, while effects of selection based on other stimulus features such as color and spatial frequency occur at longer latencies. Together, these findings argue for a primacy of location in early attentional selection. However, there have been some reports suggesting attention effects on short latency sensory-evoked potentials during selection of spatial frequency. The prime objective of the present study was to assess whether or not spatial frequency-dependent potentials are modulated by attention at a latency as early as 70-100 ms. Methods: Checkerboard patterns were flashed to the subject, one being the target requiring a response. We investigated attentional effects using high-density scalp mapping and inverse dipole modeling. Results: The earliest robust signs of selective attention to spatial frequencies consisted of an occipital election negativity (OSN) and a frontal selection positivity (FSP). The OSN started at a latency of 140 ms, the FSP somewhat earlier Lit 120 ms. These attention effects were readily modeled by sources in cortical areas ventrally and laterally to the more primary areas generating the shorter-latency sensory components. Conclusions: This pattern of results has been found for non-spatial stimulus features in several studies, and is clearly different from the ERP correlates of spatial selection. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 NIMH, Bethesda, MD 20892 USA. Univ Utrecht, Utrecht Inst Pharmaceut Sci, Fac Pharm, Dept Psychopharmacol, NL-3508 TB Utrecht, Netherlands. Univ Calif Davis, Dept Psychol, Davis, CA 95616 USA. Univ Calif Davis, Dept Neurol, Davis, CA 95616 USA. RP Baas, JMP (reprint author), NIMH, 15K North Dr,MSC 2670, Bethesda, MD 20892 USA. EM baasj@intra.nimh.nih.gov OI Baas, Johanna/0000-0001-6267-8712 FU NIMH NIH HHS [MH 02019, MH 55714]; NINDS NIH HHS [NS 41328] NR 54 TC 38 Z9 40 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD NOV PY 2002 VL 113 IS 11 BP 1840 EP 1854 AR PII S1388-2457(02)00269-9 DI 10.1016/S1388-2457(02)00269-9 PG 15 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 615WQ UT WOS:000179270700024 PM 12417240 ER PT J AU Lee, CR Pieper, JA Hinderliter, AL Blaisdell, JA Goldstein, JA AF Lee, CR Pieper, JA Hinderliter, AL Blaisdell, JA Goldstein, JA TI Evaluation of cytochrome P4502C9 metabolic activity with tolbutamide in CYP2C9*1 heterozygotes SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 24-27, 2002 CL ATLANTA, GEORGIA SP Amer Soc Clin Pharmacol Therapeut ID DOSE REQUIREMENT; GENETIC-ANALYSIS; CYP2C9 LOCUS; WARFARIN; PHENYTOIN; POLYMORPHISM; ASSOCIATION; SENSITIVITY; VARIANT; ALLELE AB Objectives: Multiple single-nucleotide polymorphisms in the gene encoding cytochrome P450 (CY-P) 2C9 have been identified, but the functional significance of the various putative defective genotypes in humans merits further study. Methods. Using tolbutamide as a probe of CYP2C9 activity, we evaluated CYP2C9 phenotype in 15 healthy individuals expressing the CYP2C9 *1/*1,*11*2, and *1/*3 genotypes (n = 5 per group). CYP2C9 genotype was determined by polymerase chain reaction-restriction fragment length polymorphism methods. Subjects received 500 mg of tolbutamide, with plasma and urine collected over a 24-hour period. Plasma tolbutamide and urinary tolbutamide, 4'-hydroxytolbutamide, and carboxytolbutamide concentrations were determined by an HPLC method. Results. Tolbutamide area under the plasma concentration-time curve from time zero to infinity [AUC(0-infinity)] significantly increased by 1.5-fold and 1.9-fold, respectively, in subjects expressing the CYP2C9*1/2 and *1/*3 genotypes compared with *1/*1 subjects. Statistically significant reductions in tolbutamide oral clearance (29% and 48%) and formation clearance (38% and 56%) were detected in the *11*2 and *1/*3 individuals, respectively, compared with *1/*1 subjects. The increases in AUC(0-infinity) and decreases in oral clearance observed in the *1/*3 individuals were also significantly greater than those expressing the *11*2 genotype (P < .05). The amount of urinary 4'-hydroxytolbutamide and carboxytolbutamide excreted in the 0- to 12-hour and 6- to 12-hour collection intervals was significantly less in *1/*2 and *1/*3 individuals compared with *1/*1 subjects. With tolbutamide used as a CYP2C9 probe, CYP2C9 genotype was the major determinant of CYP2C9 phenotype (r(2) = 0.77) Conclusions.- CYP2C9 activity was significantly reduced in *1 heterozygotes; compared with *1 homozygotes, and metabolism was more severely impaired in *1/*3 individuals compared with those expressing *11*2. C1 Univ N Carolina, Div Pharmacotherapy, PharmD, Chapel Hill, NC 27599 USA. Univ N Carolina, Div Cardiol, Chapel Hill, NC 27599 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Pieper, JA (reprint author), Univ N Carolina, Div Pharmacotherapy, PharmD, CB 7360,Beard Hall, Chapel Hill, NC 27599 USA. RI Goldstein, Joyce/A-6681-2012; OI Lee, Craig/0000-0003-3595-5301 FU NCRR NIH HHS [RR00046] NR 26 TC 39 Z9 47 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD NOV PY 2002 VL 72 IS 5 BP 562 EP 571 DI 10.1067/mcp.2002.127913 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 619PQ UT WOS:000179485500012 PM 12426520 ER PT J AU Arterberry, ME Bornstein, MH AF Arterberry, ME Bornstein, MH TI Infant perceptual and conceptual categorization: the roles of static and dynamic stimulus attributes SO COGNITION LA English DT Article DE infants; perceptual and conceptual categorization; static and dynamic stimulus attributes ID POINT-LIGHT DISPLAYS; VISUAL-PERCEPTION; GENDER RECOGNITION; BIOLOGICAL MOTION; GAIT PERCEPTION; FORM CATEGORIES; SENSITIVITY; MOVEMENT; DEPTH; ORIENTATION AB Infants' categorization of animals and vehicles based on static vs. dynamic attributes of stimuli was investigated in five experiments (N = 158) using a categorization habituation-of-looking paradigm. In Experiment 1, 6-month-olds categorized static color images of animals and vehicles, and in Experiment 2, 6-month-olds categorized dynamic point-light displays showing only motions of the same animals and vehicles. In Experiments 3, 4, and 5, 6- and 9-month-olds were tested in an habituation-transfer paradigm: half of the infants at each age were habituated to static images and tested with dynamic point-light displays, and the other half were habituated to dynamic point-light displays and tested with static images. Six-month-olds did not transfer. Only 9-month-olds who were habituated to dynamic displays showed evidence of category transfer to static images. Together the findings show that 6-month-olds categorize animals and vehicles based on static and dynamic information, and 9-month-olds can transfer dynamic category information to static images. Transfer, static vs. dynamic information, and age effects in infant categorization are discussed. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Gettysburg Coll, Dept Psychol, Gettysburg, PA 17325 USA. NICHHD, Bethesda, MD 20892 USA. RP Arterberry, ME (reprint author), Gettysburg Coll, Dept Psychol, Gettysburg, PA 17325 USA. NR 64 TC 38 Z9 38 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0010-0277 J9 COGNITION JI Cognition PD NOV PY 2002 VL 86 IS 1 BP 1 EP 24 AR PII S0010-0277(02)00108-7 DI 10.1016/S0010-0277(02)00108-7 PG 24 WC Psychology, Experimental SC Psychology GA 598HL UT WOS:000178270100001 PM 12208649 ER PT J AU Burg, MB AF Burg, MB TI Response of renal inner medullary epithelial cells to osmotic stress SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR AND INTEGRATIVE PHYSIOLOGY LA English DT Article; Proceedings Paper CT 2nd ICCPB Meeting CY AUG 18-24, 2001 CL KASANE, SOUTH AFRICA DE osmotic stress; kidney medulla; hypertonicity; urea; apoptosis; mIMCD3 cells; p53; organic osmolytes ID ORGANIC OSMOLYTES; HYPERTONIC STRESS; MDCK CELLS; P53; APOPTOSIS; INDUCTION; SIGNALS; BCL-2; UREA; BAX AB As part of the urinary concentrating mechanism, renal inner medullary epithelial (IME) cells are normally exposed to variable and often very high interstitial levels of NaCl and urea, yet they survive and function. We have been studying the mechanisms involved, using an established cell line (mIMCD3). Acute increase of NaCl or urea from 300 to > 500 mOsmol/kg causes cell cycle delay and apoptosis. High NaCl, but not high urea, causes DNA double strand breaks. At 500-600 mOsmol/kg inhibition of DNA replication following high NaCl depends on activation of the tumor suppressor protein, p53, and provides time for DNA repair. If p53 expression is suppressed, cells continue to replicate DNA, and many of those cells die. At higher levels of NaCl (>650 mOsmol/kg) the mitochondria rapidly depolarize and most cells die within a few hours despite a high level of p53 protein (which, however, is less phosphorylated than at 500 mOsmol/kg). Since the levels of NaCl and urea that kill mIMCD3 cells are much lower than those that exist in vivo, we investigated the difference, using early passage mouse IME cells under various conditions. Passage 2 IME cells survive higher levels of NaCl and urea than do mIMCD3 cells, but still not levels as high as in vivo. However, when the osmolality is increased linearly over 20 h, as occurs in vivo, rather than as a single step, cell survival increases to levels close to those found in vivo. We conclude that a more gradual increase in osmolality provides time for accumulation of organic osmolytes and activation of heat shock protein, previously known to be important for cell survival. (C) 2002 Elsevier Science Inc. All rights reserved. C1 NHLBI, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. RP Burg, MB (reprint author), NIH, Bldg 10,Rm 6N260, Bethesda, MD 20892 USA. NR 38 TC 28 Z9 30 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1095-6433 J9 COMP BIOCHEM PHYS A JI Comp. Biochem. Physiol. A-Mol. Integr. Physiol. PD NOV PY 2002 VL 133 IS 3 BP 661 EP 666 AR PII S1095-6433(02)00203-9 DI 10.1016/S1095-6433(02)00203-9 PG 6 WC Biochemistry & Molecular Biology; Physiology; Zoology SC Biochemistry & Molecular Biology; Physiology; Zoology GA 628WH UT WOS:000180019200021 PM 12443923 ER PT J AU Piller, LB Davis, BR Cutler, JA Cushman, WC Wright, JT Williamson, JD Leenen, FH Einhorn, PT Randall, OS Golden, JS Haywood, LJ AF Piller, LB Davis, BR Cutler, JA Cushman, WC Wright, JT Williamson, JD Leenen, FH Einhorn, PT Randall, OS Golden, JS Haywood, LJ CA ALLHAT Collaborative Res Grp TI Validation of heart failure events in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants assigned to doxazosin and chlorthalidone SO CURRENT CONTROLLED TRIALS IN CARDIOVASCULAR MEDICINE LA English DT Article DE heart failure; alpha-blocker; diuretic; clinical trial AB Background: The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is a randomized, double-blind, active-controlled trial designed to compare the rate of coronary heart disease events in high-risk hypertensive participants initially randomized to a diuretic (chlorthalidone) versus each of three alternative antihypertensive drugs: alpha-adrenergic blocker (doxazosin), ACE-inhibitor ( lisinopril), and calcium-channel blocker (amlodipine). Combined cardiovascular disease risk was significantly increased in the doxazosin arm compared to the chlorthalidone arm (RR 1.25; 95% CI, 1.17-1.33; P <.001), with a doubling of heart failure ( fatal, hospitalized, or non-hospitalized but treated) ( RR 2.04; 95% CI, 1.79 - 2.32; P <.001). Questions about heart failure diagnostic criteria led to steps to validate these events further. Methods and Results: Baseline characteristics ( age, race, sex, blood pressure) did not differ significantly between treatment groups ( P <.05) for participants with heart failure events. Post-event pharmacologic management was similar in both groups and generally conformed to accepted heart failure therapy. Central review of a small sample of cases showed high adherence to ALLHAT heart failure criteria. Of 105 participants with quantitative ejection fraction measurements provided, (67% by echocardiogram, 31% by catheterization), 29/46 (63%) from the chlorthalidone group and 41/59 (70%) from the doxazosin group were at or below 40%. Two-year heart failure case-fatalities (22% and 19% in the doxazosin and chlorthalidone groups, respectively) were as expected and did not differ significantly ( RR 0.96; 95% CI, 0.67-1.38; P = 0.83). Conclusion: Results of the validation process supported findings of increased heart failure in the ALLHAT doxazosin treatment arm compared to the chlorthalidone treatment arm. C1 Univ Texas, Sch Publ Hlth, Houston, TX 77225 USA. NHLBI, Bethesda, MD 20892 USA. Memphis Vet Affairs Med Ctr, Memphis, TN USA. Case Western Reserve Univ, Sch Med, Cleveland, OH USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Univ Ottawa, Inst Heart, Ottawa, ON, Canada. Howard Univ, Sch Med, Washington, DC 20059 USA. Kaiser Permanente, Mid Atlantic States, Washington, DC USA. Univ So Calif, Keck Sch Med, Los Angeles, CA USA. RP Piller, LB (reprint author), Univ Texas, Sch Publ Hlth, Houston, TX 77225 USA. NR 15 TC 31 Z9 32 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1468-6694 J9 CURR CONTR TRIALS C JI Curr. Control Trials Cardivasc. Med. PD NOV PY 2002 VL 3 AR 10 DI 10.1186/1468-6708-3-10 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 668CZ UT WOS:000182273900002 ER PT J AU Hakim, FT Gress, RE AF Hakim, FT Gress, RE TI Reconstitution of thymic function after stem cell transplantation in humans SO CURRENT OPINION IN HEMATOLOGY LA English DT Article ID BONE-MARROW TRANSPLANTATION; VERSUS-HOST DISEASE; RECEPTOR EXCISION CIRCLES; HIGH-DOSE CHEMOTHERAPY; NAIVE T-CELLS; IMMUNE RECONSTITUTION; HOMEOSTATIC PROLIFERATION; INTENSIVE CHEMOTHERAPY; REPERTOIRE; INTERLEUKIN-7 AB The reconstitution of T-cell populations is a critical component of immune recovery after allogeneic stem cell transplantation. Recent studies have used new techniques to focus on the interplay of thymopoiesis and peripheral expansion that defines T-cell repopulation. Peripheral expansion, driven by host cytokines and antigenic stimulation, dominates early recovery. However, this expansion is often transient and is characterized by limited repertoire diversity. Renewed thymopoiesis has been found to play a critical role in the recovery of repertoire diversity and stable repopulation. The insights gained into the regulation of these processes may provide new therapies to enhance recovery. (C) 2002 Lippincott Williams Wilkins, Inc. C1 NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Hakim, FT (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 58 TC 31 Z9 31 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD NOV PY 2002 VL 9 IS 6 BP 490 EP 496 DI 10.1097/01.MOH.0000031250.01532.54 PG 7 WC Hematology SC Hematology GA 605RD UT WOS:000178690100004 PM 12394170 ER PT J AU Wilfond, B Rothenberg, LS AF Wilfond, B Rothenberg, LS TI Ethical issues in cystic fibrosis newborn screening: from data to public health policy SO CURRENT OPINION IN PULMONARY MEDICINE LA English DT Article ID EARLY DIAGNOSIS; SURVIVAL; GROWTH; BEHAVIOR; REGISTRY; STATE; CF AB Newborn screening for cystic fibrosis (CF) remains controversial largely because its implementation is less a scientific decision than a resolution of different and often conflicting normative values that underlie the policy issues framing the debate. This article summarizes the literature published between May 2001 and April 2002 (and relevant earlier literature) regarding the screening and treatment goals, clinical benefits and harms, and programmatic and ethical issues. Finally, we will present an analysis to argue for one set of ethical considerations that point to very specific policy recommendations that would justify CF newborn screening in certain circumstances and make its implementation more ethically appropriate. C1 NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Med Genet Branch, Natl Ctr Human Genome Res, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Med, Div Med Genet, Los Angeles, CA 90024 USA. RP Wilfond, B (reprint author), NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, 10 Ctr Dr,Bldg 10,Room 1C123, Bethesda, MD 20892 USA. NR 62 TC 15 Z9 15 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-5287 J9 CURR OPIN PULM MED JI Curr. Opin. Pulm. Med. PD NOV PY 2002 VL 8 IS 6 BP 529 EP 534 DI 10.1097/01.MCP.0000030428.69996.06 PG 6 WC Respiratory System SC Respiratory System GA 607BT UT WOS:000178771100008 PM 12394162 ER PT J AU Liu, Y Liu, CQ Yamada, Y Fan, CM AF Liu, Y Liu, CQ Yamada, Y Fan, CM TI growth arrest specific gene 1 acts as a region-specific mediator of the Fgf10/Fgf8 regulatory loop in the limb SO DEVELOPMENT LA English DT Article DE Gas1; Fgf8; Fgf10; limb; growth; apical ectodermal ridge; mouse ID APICAL ECTODERMAL RIDGE; VERTEBRATE LIMB; SONIC-HEDGEHOG; INDIAN HEDGEHOG; MOUSE EMBRYO; CELL-DEATH; INDUCTION; OUTGROWTH; FGF8; INITIATION AB Proximal-to-distal growth of the embryonic limbs requires Fgf10 in the mesenchyme to activate Fgf8 in the apical ectodermal ridge (AER), which in turn promotes mesenchymal outgrowth. We show here that the growth arrest specific gene I (Gas1) is required in the mesenchyme for the normal regulation of Fgf10/Fgf8. Gas1 mutant limbs have defects in the proliferation of the AER and the mesenchyme and develop with small autopods, missing phalanges and anterior digit syndactyly. At the molecular level, Fgf10 expression at the distal tip mesenchyme immediately underneath the AER is preferentially affected in the mutant limb, coinciding with the loss of Fgf8 expression in the AER. To test whether FGF10 deficiency is an underlying cause of the Gas] mutant phenotype, we employed a limb culture system in conjunction with microinjection of recombinant proteins. In this system, FGF10 but not FGF8 protein injected into the mutant distal tip mesenchyme restores Fgf8 expression in the AER. Our data provide evidence that Gas1 acts to maintain high levels of FGF10 at the tip mesenchyme and support the proposal that Fgf10 expression in this region is crucial for maintaining Fgf8 expression in the AER. C1 Carnegie Inst Washington, Dept Embryol, Baltimore, MD 21210 USA. NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Fan, CM (reprint author), Carnegie Inst Washington, Dept Embryol, 115 W Univ Pkwy, Baltimore, MD 21210 USA. RI Liu, Chunqiao/O-3391-2013 OI Liu, Chunqiao/0000-0002-0299-7401 FU NICHD NIH HHS [R01-HD 35596] NR 53 TC 25 Z9 25 U1 0 U2 0 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 NOV PY 2002 VL 129 IS 22 BP 5289 EP 5300 PG 12 WC Developmental Biology SC Developmental Biology GA 623FT UT WOS:000179693200017 PM 12399319 ER PT J AU Gothilf, Y Toyama, R Coon, SL Du, SJ Dawid, IB Klein, DC AF Gothilf, Y Toyama, R Coon, SL Du, SJ Dawid, IB Klein, DC TI Pineal-specific expression of green fluorescent protein under the control of the serotonin-N-acetyltransferase gene regulatory regions in transgenic zebrafish SO DEVELOPMENTAL DYNAMICS LA English DT Article DE pineal gland; zebrafish embryo; serotonin-N-acetyltransferase; transgenic fish; green fluorescent protein; mind-bomb; floating head ID MELATONIN SYNTHESIS; PROTEASOMAL PROTEOLYSIS; CIRCADIAN CLOCK; FLOATING HEAD; BINDING SITE; ACTIVATION; PROMOTER; ORGAN; CELLS; N-ACETYLTRANSFERASE-2 AB Zebrafish serotonin-N-acetyltransferase-2 zfAANAT-2) mRNA is exclusively expressed in the pineal gland (epiphysis) at the embryonic stage. Here, we have initiated an effort to study the mechanisms underlying tissue-specific expression of this gene. DNA constructs were prepared in which green fluorescent protein (GFP) is driven by regulatory regions of the zfAANAT-2 gene. In vivo transient expression analysis in zebrafish embryos indicated that in addition to the 5'-flanking region, a regulatory sequence in the X-flanking region is required for pineal-specific expression. This finding led to an effort to produce transgenic lines expressing GFP under the control of the 5' and 3' regulatory regions of the zfAANAT-2 gene. Embryos transiently expressing GFP were raised to maturity and tested for germ cell transmission of the transgene. Three transgenic lines were produced in which GFP fluorescence in the pineal was detected starting 1 to 2 days after fertilization. One line was crossed with mindbomb and floating head mutants that cause abnormal development of the pineal and an elevation or reduction of zfAANAT-2 mRNA levels, respectively. Homozygous mutant transgenic embryos exhibited similar effects on GFP expression in the pineal gland. These observations indicate that the transgenic lines described here will be useful in studying the development of the pineal gland and the mechanisms that determine pineal-specific gene expression in the zebrafish. Published 2002 Wiley-Liss, lnc. C1 NICHHD, Dev Neurobiol Lab, Sect Neuroendocrinol, NIH, Bethesda, MD 20892 USA. Tel Aviv Univ, George S Wise Fac Sci, Dept Zool, Tel Aviv, Israel. NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. Univ Maryland, Inst Biotechnol, Ctr Marine Biotechnol, Baltimore, MD 21201 USA. RP Klein, DC (reprint author), NICHHD, Dev Neurobiol Lab, Sect Neuroendocrinol, NIH, 49-5A38,49 Convent Dr, Bethesda, MD 20892 USA. NR 40 TC 31 Z9 34 U1 1 U2 6 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 NOV PY 2002 VL 225 IS 3 BP 241 EP 249 DI 10.1002/dvdy.10152 PG 9 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 611GW UT WOS:000179008900003 PM 12412006 ER PT J AU Karges, W Pechhold, K Al Dahouk, S Riegger, I Rief, M Wissmann, A Schirmbeck, R Barth, C Boehm, BO AF Karges, W Pechhold, K Al Dahouk, S Riegger, I Rief, M Wissmann, A Schirmbeck, R Barth, C Boehm, BO TI Induction of autoimmune diabetes through insulin (but not GAD65) DNA vaccination in nonobese diabetic and in RIP-B7.1 mice SO DIABETES LA English DT Article ID GLUTAMIC-ACID DECARBOXYLASE; PANCREATIC BETA-CELLS; REGULATORY T-CELLS; PROTECTS NOD MICE; ORAL INSULIN; PLASMID DNA; PREVENTION; MOUSE; TOLERANCE; ANTIGEN AB Insulin has been used to modify T-cell autoimmunity in experimental models of type 1 diabetes. In a large clinical trial, the effect of insulin to prevent type 1 diabetes is currently investigated. We here show that insulin can adversely trigger autoimmune diabetes in two mouse models of type 1 diabetes, using intramuscular DNA vaccination for antigen administration. In female nonobese diabetic (NOD) mice, diabetes development was enhanced after preproinsulin (ppIns) DNA treatment, and natural diabetes resistance in male NOD mice was diminished by ppIns DNA vaccination. In contrast, GAD65 DNA conferred partial diabetes protection, and empty DNA plasmid was without effect. In RIP-117.1 C57BL/6 mice (expressing the T-cell costimulatory molecule B7.1 in pancreatic beta-cells), autoimmune diabetes occurred in 70% of animals after ppIns vaccination, whereas diabetes did not develop spontaneously in RIP-117.1. mice or after GAD65 or control DNA treatment. Diabetes was characterized by diffuse CD4(+)CD8(+) T-cell infiltration of pancreatic islets and severe insulin deficiency, and ppIns, proinsulin, and insulin DNA were equally effective for disease induction. Our work provides a new model of experimental autoimmune diabetes suitable to study mechanisms and outcomes of insulin-specific T-cell reactivity. In antigen-based prevention of type 1 diabetes, diabetes acceleration should be considered as a potential adverse result. C1 Univ Ulm, Dept Internal Med, Div Endocrinol, D-89081 Ulm, Germany. NIDDK, Navy Transplantat & Autoimmun Branch, Bethesda, MD USA. Univ Ulm, Dept Med Microbiol & Immunol, D-7900 Ulm, Germany. RP Karges, W (reprint author), Univ Ulm, Dept Internal Med, Div Endocrinol, Robert Koch Str, D-89081 Ulm, Germany. RI Boehm, Bernhard/F-8750-2015; OI Al Dahouk, Sascha/0000-0003-3835-0818 NR 33 TC 37 Z9 38 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 2002 VL 51 IS 11 BP 3237 EP 3244 DI 10.2337/diabetes.51.11.3237 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 609PV UT WOS:000178914900012 PM 12401715 ER PT J AU Farook, VS Hanson, RL Wolford, JK Bogardus, C Prochazka, M AF Farook, VS Hanson, RL Wolford, JK Bogardus, C Prochazka, M TI Molecular analysis of KCNJ10 on 1q as a candidate gene for type 2 diabetes in Pima Indians SO DIABETES LA English DT Article ID LINKAGE DISEQUILIBRIUM; MELLITUS; LOCI; SCAN AB The KCNJ10 gene is located within a region on chromosome 1q linked to type 2 diabetes in the Pima Indians and six other populations. We therefore investigated this gene as a potential type 2 diabetes candidate gene in Pima Indians. KCNJ10 consists of two exons, spans similar to33 kb, and we identified eight single-nucleotide polymorphisms (SNPs), including one (SNP2) in the coding region leading to a Glu359Lys substitution. Association studies were carried out in a case-control group composed of 149 affected and 150 unaffected Pimas, and the linkage analysis was performed in a linkage set of 1,338 Pimas. SNP1 in the promoter and SNP2 in the intron, which were in a complete linkage disequilibrium, and SNP5 in the 3' untranslated region showed association with diabetes in the case-control group (P = 0.02 and P = 0.01, respectively). When genotyped in the linkage set, only the KCNJ10-SNP1 variant showed a modest association with type 2 diabetes (P = 0.01). KCNJ10-SNP1 is in a strong linkage disquilibrium with SNP14 of the adjacent KCNJ9 locus, which we previously found to be associated with type 2 diabetes. After adjustment for KCNJ10-SNP1, the original linkage score at this locus was marginally reduced from 3.1 to 2.9. We conclude that these variants in KCNJ10 are unlikely to be the cause of linkage of type 2 diabetes with 1q in Pima Indians. C1 NIDDKD, Clin Diabet & Nutr Sect, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85016 USA. RP Farook, VS (reprint author), NIDDKD, Clin Diabet & Nutr Sect, Phoenix Epidemiol & Clin Res Branch, NIH, 4212 N 16th St, Phoenix, AZ 85016 USA. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 21 TC 13 Z9 14 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 NOV PY 2002 VL 51 IS 11 BP 3342 EP 3346 DI 10.2337/diabetes.51.11.3342 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 609PV UT WOS:000178914900026 PM 12401729 ER PT J AU Saydah, SH Byrd-Holt, D Harris, MI AF Saydah, SH Byrd-Holt, D Harris, MI TI Projected impact of implementing the results of the Diabetes Prevention Program in the US population SO DIABETES CARE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; GLYCOSYLATED HEMOGLOBIN; MELLITUS; DIAGNOSIS; INDIVIDUALS; PREVALENCE AB OBJECTIVE - To determine the feasibility of using either fasting plasma glucose or HbA(1c) to identify individuals in the U.S. population who meet the Diabetes Prevention Program (DPP) criteria for intervention, defined as BMI greater than or equal to 24 kg/m(2), fasting plasma glucose level 96-125 mg/dl, and 2-h glucose level 140-199 mg/dl in an oral glucose tolerance test (OGTT). RESEARCH DESIGN AND METHODS - Analysis of a representative sample of U.S. adults aged 40-74 years with no medical history of diabetes for whom data on height, weight, fasting plasma glucose, HbA(1c), and 2-h plasma glucose during an OGTT were obtained. Sensitivity, specificity, positive predictive value (PPV), and receiver operator characteristic (ROC) curves for fasting glucose and HbA(1c) were determined. RESULTS - Using BMI <24 kg/m(2) as an initial criterion eliminated 27.2% of U.S. adults from further testing. Of the remaining group, 41.1% did not have to be considered for an OGTT because their fasting glucose level was below or above 96-125 mg/dl. Overall, 10.6% of adults aged 40-74 years without medical history of diabetes met the DPP eligibility criteria for intervention. Among individuals with BMI &GE;24 kg/m(2) and fasting glucose level 96-125 mg/dl, applying a fasting plasma glucose cutoff of &GE;105 mg/dl excluded 62.5% of this group and resulted in 56.0% of those with 2-h glucose level 140-199 mg/dl in this group being identified, with a specificity of 72.0% and a PPV of 17.1%. Similar values were obtained for an HbA(1c) cutoff value of &GE;5.5%. CONCLUSIONS - Using data on BMI and setting cutoff values for fasting glucose and HbA(1c) would greatly reduce the number of individuals who would need to undergo an OGTT while achieving adequate sensitivity, specificity; and PPV. C1 Social & Sci Syst, Silver Spring, MD 20903 USA. NIDDKD, Bethesda, MD 20892 USA. RP Saydah, SH (reprint author), 8757 Georgia Ave,12th Floor, Silver Spring, MD 20910 USA. NR 19 TC 32 Z9 32 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2002 VL 25 IS 11 BP 1940 EP 1945 DI 10.2337/diacare.25.11.1940 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 724UG UT WOS:000185504600006 PM 12401736 ER PT J AU Uwaifo, GI Fallon, EM Chin, J Elberg, J Parikh, SJ Yanovski, JA AF Uwaifo, GI Fallon, EM Chin, J Elberg, J Parikh, SJ Yanovski, JA TI Indies of insulin action, disposal, and secretion derived from fasting samples and clamps in normal glucose-tolerant black and white children SO DIABETES CARE LA English DT Article ID HOMEOSTASIS MODEL ASSESSMENT; SENSITIVITY CHECK INDEX; AFRICAN-AMERICAN; PLASMA-GLUCOSE; RESISTANCE; OBESITY; HYPERTENSION; VALIDATION; POPULATION; EPIDEMIC AB OBJECTIVE - To validate fasting indices of insulin sensitivity and secretion in a diverse pediatric population against gold standard estimates from euglycemic and hyperglycemic clamps. RESEARCH DESIGN AND METHODS - A total of 31 children (mean BMI 25.1 +/- 4.9 kg/m(2), mean age 8.7 +/- 1.4 years, 15 girls and 16 boys, 12 black and 19 white) underwent euglycemic and hyperglycemic clamps 2-6 weeks apart to derive insulin sensitivity indices (SI (Eug clamp) and SI (Hyper clamp)). Fasting samples were used to derive the homeostasis model assessment of insulin resistance index (HOMA-IR), HOMA of percent beta-cell function (HOMA-B%), quantitative insulin sensitivity check index (QUICKI), insulinogenic index, antilipolytic insulin sensitivity index (ISI-FFA), and C-peptide-to-insulin ratio. RESULTS - The QUICKI correlated best with SI (Eug clamp) (r = 0.69, P < 0.05) and had greater correlations to SI (Eug clamp) than did either SI (Hyper clamp) (r = 0.45, P < 0.05) or the HOMA-IR (r = -0.51, P < 0.05). Both fasting insulin and the insulinogenic index correlated well with first- an steady-phase insulin secretion (r's from 0.79 to 0.86, P < 0.05) HOMA-B% was not as highly correlated (r = 0.69-0.72, P < 0.05). Fasting C-peptide-to-insulin ratio was not significantly correlated with clamp-derived metabolic clearance rate of insulin. ISI-FFA was, not correlated with the degree of free fatty acid suppression obtained from the clamps. CONCLUSIONS - The QUICKI, fasting insulin, and the insulinogenic index all closely correlate with corresponding clamp-derived indices of insulin sensitivity and secretion in this diverse pediatric cohort. These results, if replicated in similarly diverse populations, suggest that estimates based on fasting samples can be used to rank order insulin secretion and sensitivity in pediatric cohorts. C1 NICHD, Unit Growth & Obes, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Yanovski, JA (reprint author), NICHD, Unit Growth & Obes, Dev Endocrinol Branch, NIH, 10 Ctr Dr,Bldg 10,Rm 10N262,MSC 1862, Bethesda, MD 20892 USA. RI Uwaifo, Gabriel/M-2361-2016; OI Uwaifo, Gabriel/0000-0002-6962-9304; Yanovski, Jack/0000-0001-8542-1637 FU NICHD NIH HHS [HD-00064] NR 44 TC 134 Z9 141 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2002 VL 25 IS 11 BP 2081 EP 2087 DI 10.2337/diacare.25.11.2081 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 724UG UT WOS:000185504600030 PM 12401760 ER PT J AU Yang, X Pratley, RE Tokraks, S Bogardus, C Permana, PA AF Yang, X Pratley, RE Tokraks, S Bogardus, C Permana, PA TI Microarray profiling of skeletal muscle tissues from equally obese, non-diabetic insulin-sensitive and insulin-resistant Pima Indians SO DIABETOLOGIA LA English DT Article DE genes; oligonucleotide array; RT-PCR; insulin resistance; diabetes ID PROTEIN PHOSPHATASE INHIBITOR-2; AUTOSOMAL GENOMIC SCAN; GENE-EXPRESSION; MESSENGER-RNA; RECEPTOR SUBSTRATE-1; GLYCOGEN-SYNTHASE; SECRETORY DYSFUNCTION; MELLITUS PATIENTS; CODING REGION; IGF-I AB Aims/hypothesis. We carried out global. transcript profiling to identify differentially expressed skeletal muscle genes in insulin resistance, a major risk factor for Type II (non-insulin-dependent) diabetes mellitus. This approach also complemented the ongoing, genomic linkage analyses to identify gees linked to insulin resistance and diabetes in Pima Indians. Methods We compared gene expression probes of skeletal muscle tissues from 18 insulin-sensitive versus 17 insulin-resistant equally obese, non-diabetic Pima Indians using oligonucleotide arrays consistmg of about 40,600 transcripts of know genes and expressed sequence tags, and analysed the results with the Wilcoxon rank sum test. We verified the mRNA expression of ten differentially (best-ranked) and ten similarly (worst-ranked) genes using quantitative Peal Tire PCR. Results. There were 185 differentially expressed transcripts by the rank sum test. The deferential expressions of two out of the ten best-raked genes were confirmed and the similar expressions of all ten worst-ranked genes were reproduced. Conclusion/interpretation. Of the 185 differentially expressed transcripts, 20 per cent were true positives and some could generate new hypotheses about the aetiology or pathophysiology of insulin resistance. Furthermore, differentially expressed genes in chromosomal regions with linkage to diabetes anti insulin resistance serve as new diabetes susceptibility genes. C1 NIDDKD, Clin Diabet & Nutr Sect, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85016 USA. Sahlgrenska Univ Hosp, Lundberg Lab Diabet Res, Gothenburg, Sweden. Novartis Pharmaceut Corp, Dept Cardiovasc Metab & Endocrine Clin Res, E Hanover, NJ USA. RP Permana, PA (reprint author), NIDDKD, Clin Diabet & Nutr Sect, Phoenix Epidemiol & Clin Res Branch, NIH, 4212 N 16th St, Phoenix, AZ 85016 USA. NR 62 TC 67 Z9 69 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD NOV PY 2002 VL 45 IS 11 BP 1584 EP 1593 DI 10.1007/s00125-002-0905-7 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 624ZV UT WOS:000179792900015 PM 12436343 ER PT J AU Panter, AT Reeve, BB AF Panter, AT Reeve, BB TI Assessing tobacco beliefs among youth using item response theory models SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE item response theory; smoking beliefs; attitudes; differential item functioning ID HARE PSYCHOPATHY CHECKLIST; SCALE; 21ST-CENTURY; ADOLESCENTS; PARAMETERS; VARIABLES; SMOKING AB Successful intervention research programs to prevent adolescent smoking require well-chosen, psychometrically sound instruments for assessing smoking prevalence and attitudes. Twelve thousand eight hundred and ten adolescents were surveyed about their smoking beliefs as part of the Teenage Attitudes and Practices Survey project, a prospective cohort study of predictors of smoking initiation among US adolescents. Item response theory (IRT) methods are used to frame a discussion of questions that a researcher might ask when selecting an optimal item set. IRT methods are especially useful for choosing items during instrument development, trait scoring, evaluating item functioning across groups, and creating optimal item subsets for use in specialized applications such as computerized adaptive testing. Data analytic steps for IRT modeling are reviewed for evaluating item quality and differential item functioning across subgroups of gender, age, and smoking status. Implications and challenges in the use of these methods for tobacco onset research and for assessing the developmental trajectories of smoking among youth are discussed. (C) 2002 Published by Elsevier Science Ireland Ltd. C1 Univ N Carolina, LL Thurstone Psychometr Lab, Dept Psychol, Chapel Hill, NC 27599 USA. NCI, Bethesda, MD 20892 USA. RP Panter, AT (reprint author), Univ N Carolina, LL Thurstone Psychometr Lab, Dept Psychol, CB 3270,Davie Hall, Chapel Hill, NC 27599 USA. NR 47 TC 13 Z9 13 U1 5 U2 6 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD NOV PY 2002 VL 68 SU 1 BP S21 EP S39 AR PII S0376-8716(02)00213-2 PG 19 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 609LD UT WOS:000178904300004 PM 12324173 ER PT J AU Ferguson, SM Kim, JP AF Ferguson, SM Kim, JP TI Distribution and licensing of drug discovery tools - NIH perspectives SO DRUG DISCOVERY TODAY LA English DT Review AB Now, more than ever, drug discovery conducted at industrial or academic facilities requires rapid access to state-of-the-art research tools. Unreasonable restrictions or delays in the distribution or use of such tools can stifle new discoveries, thus limiting the development of future biomedical products. In grants and its own research programs the National Institutes of Health (NIH) is implementing its new policy to facilitate the exchanges of these tools for research discoveries and product development. C1 NIH, Div Technol Dev & Transfer, Off Technol Transfer, Rockville, MD 20852 USA. RP Ferguson, SM (reprint author), NIH, Div Technol Dev & Transfer, Off Technol Transfer, 6011 Execut Blvd,Suite 325, Rockville, MD 20852 USA. FU Intramural NIH HHS [Z99 OD999999] NR 1 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD NOV 1 PY 2002 VL 7 IS 21 BP 1102 EP 1106 AR PII S1359-6446(02)02499-6 DI 10.1016/S1359-6446(02)02499-6 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 610BM UT WOS:000178940900010 PM 12546842 ER PT J AU Contoreggi, C Ayala, A Grant, S Eckelman, W Webster, E Rice, K AF Contoreggi, C Ayala, A Grant, S Eckelman, W Webster, E Rice, K TI Nonpeptide corticotropin releasing hormone type 1 receptor antagonists as medications, and imaging agents SO DRUGS OF THE FUTURE LA English DT Review ID ANXIOGENIC-LIKE BEHAVIOR; ETHANOL WITHDRAWAL; ANOREXIA-NERVOSA; MAJOR DEPRESSION; IN-VITRO; IDENTIFICATION; PITUITARY; CRH; RESPONSES; STRESS AB Corticotropin-releasing hormone (CRH) is produced in the brain and in the periphery and coordinates the body's response to stress. When CRH is synthesized and released from the hypothalamus, it activates the release of adrenocorticotropic hormone from the pituitary, which stimulates adrenal release of cortisol, the principal adrenal steroid hormone in primates. CRH and CRH-like molecules are produced in the CNS and act as peptide neurotransmitters. The regional actions of CRH in the CNS are varied and only partially understood. In addition to regulation of the hypothalamic-pituitary-adrenal axis, CRH coordinates other hormones as well as autonomic, immune and behavioral responses to stress. Aberrant CRH action is implicated in many diseases including addiction, depression, anxiety and eating disorders. In order to understand the physiological role of CRH and the pharmacological actions of the CRHR1 antagonists, we have developed a radiolabeled CRHR1 ligand as an in vivo imaging agent. C1 NIH, Natl Inst Drug Abuse, Neuroimaging Branch, Baltimore, MD 21224 USA. RP Contoreggi, C (reprint author), NIH, Natl Inst Drug Abuse, Neuroimaging Branch, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 39 TC 5 Z9 5 U1 1 U2 1 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0377-8282 J9 DRUG FUTURE JI Drug Future PD NOV PY 2002 VL 27 IS 11 BP 1093 EP 1100 DI 10.1358/dof.2002.027.11.857018 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 641WB UT WOS:000180769100007 ER PT J AU Pais, GCG Burke, TR AF Pais, GCG Burke, TR TI Novel aryl diketo-containing inhibitors of HIV-1 integrase SO DRUGS OF THE FUTURE LA English DT Review ID VIRUS TYPE-1 INTEGRASE; PREINTEGRATION COMPLEXES; CDNA INTEGRATION; STRAND TRANSFER; TARGET; DESIGN; CELLS; CHEMOTHERAPY; REQUIREMENT; REPLICATION AB HIV-1 integrase is a promising therapeutic target for the development of drugs to treat HIV infection. Aryl diketo-based analogs, disclosed independently by scientists from Merck and Shionogi pharmaceutical companies, are a unique class of compounds that exhibit potent integrase inhibition and display good antiviral effects in HIV-infected cells. The progress of Merck's L-870810 and Shionogi's S-1360 to phase 11 clinical trials has promised the inclusion of integrase inhibitors in "cocktail" combination therapies in the near future. This review presents a critical overview of research related to this new class of integrase inhibitors. C1 NCI, Ctr Canc Res, Med Chem Lab, NIH, Frederick, MD 21702 USA. RP Burke, TR (reprint author), NCI, Ctr Canc Res, Med Chem Lab, NIH, POB B,Bldg 376,Boyles St, Frederick, MD 21702 USA. RI Burke, Terrence/N-2601-2014 NR 53 TC 39 Z9 40 U1 0 U2 0 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0377-8282 J9 DRUG FUTURE JI Drug Future PD NOV PY 2002 VL 27 IS 11 BP 1101 EP 1111 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 641WB UT WOS:000180769100008 ER PT J AU Milne, JLS Shi, D Rosenthal, PB Sunshine, JS Domingo, GJ Wu, XW Brooks, BR Perham, RN Henderson, R Subramaniam, S AF Milne, JLS Shi, D Rosenthal, PB Sunshine, JS Domingo, GJ Wu, XW Brooks, BR Perham, RN Henderson, R Subramaniam, S TI Molecular architecture and mechanism of an icosahedral pyruvate dehydrogenase complex: a multifunctional catalytic machine SO EMBO JOURNAL LA English DT Article DE electron microscopy; molecular machine; pyruvate dehydrogenase; single particle analysis; three-dimensional reconstruction ID SUBUNIT-BINDING DOMAIN; ALPHA-KETOACID DEHYDROGENASE; SYRUP-URINE-DISEASE; MULTIENZYME COMPLEX; BACILLUS-STEAROTHERMOPHILUS; ESCHERICHIA-COLI; DIHYDROLIPOAMIDE ACETYLTRANSFERASE; CRYOELECTRON MICROSCOPY; 3-DIMENSIONAL STRUCTURE; REDUCTIVE ACYLATION AB Electron cryo-microscopy of 'single particles' is a powerful method to determine the three-dimensional (3D) architectures of complex cellular assemblies. The pyruvate dehydrogenase multi-enzyme complex couples the activity of three component enzymes (E1, E2 and E3) in the oxidative decarboxylation of pyruvate to generate acetyl-CoA, linking glycolysis and the tricarboxylic acid cycle. We report here a 3D model for an 11 MDa, icosahedral pyruvate dehydrogenase sub-complex, obtained by combining a 28 Angstrom structure derived from electron cryo-microscopy with previously determined atomic coordinates of the individual E1 and E2 components. A key feature is that the E1 molecules are located on the periphery of the assembly in an orientation that allows each of the 60 mobile lipoyl domains tethered to the inner E2 core to access multiple E1 and E2 active sites from inside the icosahedral complex. This unexpected architecture provides a highly efficient mechanism for active site coupling and catalytic rate enhancement by the motion of the lipoyl domains in the restricted annular region between the inner core and outer shell of the complex. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. MRC, Mol Biol Lab, Cambridge CB2 2QH, England. Univ Cambridge, Dept Biochem, Cambridge Ctr Mol Recognit, Cambridge CB2 1GA, England. RP Milne, JLS (reprint author), NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 41 TC 75 Z9 76 U1 2 U2 19 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD NOV 1 PY 2002 VL 21 IS 21 BP 5587 EP 5598 DI 10.1093/emboj/cdf574 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 611RU UT WOS:000179032200001 PM 12411477 ER PT J AU Leikina, E Ramos, C Markovic, I Zimmerberg, J Chernomordik, LV AF Leikina, E Ramos, C Markovic, I Zimmerberg, J Chernomordik, LV TI Reversible stages of the low-pH-triggered conformational change in influenza virus hemagglutinin SO EMBO JOURNAL LA English DT Article DE influenza hemagglutinin; membrane rearrangements; protein interactions; reversible change; viral fusion ID MEDIATED MEMBRANE-FUSION; RECEPTOR-BINDING; PORE FORMATION; HIV-1 GP41; MECHANISM; ACTIVATION; TRANSMEMBRANE; HEMIFUSION; ECTODOMAIN; PROTEIN AB The refolding of the prototypic fusogenic protein hemagglutinin (HA) at the pH of fusion is considered to be a concerted and irreversible discharge of a loaded spring, with no distinct intermediates between the initial and final conformations. Here, we show that HA refolding involves reversible conformations with a lifetime of minutes. After reneutralization, low pH-activated HA returns from the conformations wherein both the fusion peptide and the kinked loop of the HA2 subunit are exposed, but the HA1 subunits have not yet dissociated, to a structure indistinguishable from the initial one in functional, biochemical and immunological characteristics. The rate of the transition from reversible conformations to irreversible refolding depends on the pH and on the presence of target membrane. Importantly, recovery of the initial conformation is blocked by the interactions between adjacent HA trimers. The existence of the identified reversible stage of refolding can be crucial for allowing multiple copies of HA to synchronize their release of conformational energy, as required for fusion. C1 NICHHD, Lab Cellular & Mol Biophys, Bethesda, MD 20892 USA. RP Chernomordik, LV (reprint author), NICHHD, Lab Cellular & Mol Biophys, Bethesda, MD 20892 USA. NR 49 TC 41 Z9 41 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD NOV 1 PY 2002 VL 21 IS 21 BP 5701 EP 5710 DI 10.1093/emboj/cdf559 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 611RU UT WOS:000179032200012 PM 12411488 ER PT J AU Valasek, L Nielsen, KH Hinnebusch, AG AF Valasek, L Nielsen, KH Hinnebusch, AG TI Direct eIF2-eIF3 contact in the multifactor complex is important for translation initiation in vivo SO EMBO JOURNAL LA English DT Article DE eukaryotic translation initiation factor; multifactor complex; protein synthesis; ternary complex; translational control ID SACCHAROMYCES-CEREVISIAE; RIBOSOME BINDING; YEAST; EIF5; SUBUNITS; PRT1; RNA AB Translation initiation factor 3 (eIF3) of Saccharo myces cerevisiae forms a multifactor complex (MFC) with eIFs 1, 2, 5 and Met-tRNA(i)(Met). We previously constructed a subunit interaction model for the MFC. Here we incorporated affinity tags into the three largest eIF3 subunits (eIF3a/TIF32, eIF3b/PRT1 and eIF3c/NIP1) and deleted predicted binding domains in each tagged protein. By characterizing the mutant subcomplexes, we confirmed all key predictions of our model and uncovered new interactions of NIP1 with PRT1 and of TIF32 with eIF1. In addition to the contact between eIF2 and the N-terminal domain (NTD) of NIP1 bridged by eIF5, the C-terminal domain (CTD) of TIF32 binds eIF2 directly and is required for eIF2-eIF3 association in vivo. Overexpressing a CTD-less form of TIF32 exacerbated the initiation defect of an eIF5 mutation that weakens the NIP1-eIF5-eIF2 connection. Thus, the two independent eIF2-eIF3 contacts have additive effects on translation in vivo. Overexpressing the NIP1-NTD sequestered eIF1-eIF5-eIF2 in a defective subcomplex that derepressed GCN4 translation, providing the first in vivo evidence that association with eIF3 promotes binding of eIF2 and Met-tRNA(i)(Met) to 40S ribosomes. C1 NICHHD, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. RP Hinnebusch, AG (reprint author), NICHHD, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. RI Valasek, Leos/I-5743-2014 NR 15 TC 88 Z9 90 U1 2 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD NOV 1 PY 2002 VL 21 IS 21 BP 5886 EP 5898 DI 10.1093/emboj/cdf563 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 611RU UT WOS:000179032200030 PM 12411506 ER PT J AU Storici, F Henneke, G Ferrari, E Gordenin, DA Hubscher, U Resnick, MA AF Storici, F Henneke, G Ferrari, E Gordenin, DA Hubscher, U Resnick, MA TI The flexible loop of human FEN1 endonuclease is required for flap cleavage during DNA replication and repair SO EMBO JOURNAL LA English DT Article DE FEN1; flap endonuclease; loop domain; repair; replication ID CELL NUCLEAR ANTIGEN; SACCHAROMYCES-CEREVISIAE; FUNCTIONAL-ANALYSIS; MUTATION AVOIDANCE; SUBSTRATE-BINDING; POLYMERASE-DELTA; IN-VIVO; YEAST; SITE; METABOLISM AB The conserved, structure-specific flap endonuclease FEN1 cleaves 5' DNA flaps that arise during replication or repair. To address in vivo mechanisms of flap cleavage, we developed a screen for human FEN1 mutants that are toxic when expressed in yeast. Two targets were revealed: the flexible loop domain and the catalytic site. Toxic mutants caused G(2) arrest and cell death and were unable to repair methyl methanesulfonate lesions. All the mutant proteins retained flap binding. Unlike the catalytic site mutants, which lacked cleavage of any 5' flaps, the loop mutants exhibited partial ability to cut 5' flaps when an adjacent single nucleotide 3' flap was present. We suggest that the flexible loop is important for efficient cleavage through positioning the 5' flap and the catalytic site. C1 Natl Inst Environm Hlth Sci, Genet Mol Lab, NIH, Res Triangle Pk, NC 27709 USA. Univ Zurich, Inst Vet Biochem & Mol Biol, Zurich, Switzerland. RP Resnick, MA (reprint author), Natl Inst Environm Hlth Sci, Genet Mol Lab, NIH, Res Triangle Pk, NC 27709 USA. OI Gordenin, Dmitry/0000-0002-8399-1836 NR 37 TC 35 Z9 36 U1 2 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD NOV 1 PY 2002 VL 21 IS 21 BP 5930 EP 5942 DI 10.1093/emboj/cdf587 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 611RU UT WOS:000179032200034 PM 12411510 ER PT J AU Morens, DM AF Morens, DM TI At the deathbed of consumptive art SO EMERGING INFECTIOUS DISEASES LA English DT Article C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Morens, DM (reprint author), NIAID, NIH, Room 3149,6700 B Rockledge Dr,MSC 7630, Bethesda, MD 20892 USA. NR 50 TC 3 Z9 3 U1 0 U2 2 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD NOV PY 2002 VL 8 IS 11 BP 1353 EP 1358 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 616MN UT WOS:000179307700031 PM 12463180 ER PT J AU Arima, H House, SB Gainer, H Aguilera, G AF Arima, H House, SB Gainer, H Aguilera, G TI Neuronal activity is required for the circadian rhythm of vasopressin gene transcription in the suprachiasmatic nucleus in vitro SO ENDOCRINOLOGY LA English DT Article ID PROTEIN-KINASE-C; MESSENGER-RNA; ARGININE-VASOPRESSIN; PARAVENTRICULAR NUCLEUS; ORGANOTYPIC CULTURES; DIURNAL RHYTHM; MAP KINASE; IN-VITRO; RAT; CLOCK AB Arginine vasopressin (AVP) is synthesized in and secreted by the suprachiasmatic nucleus (SCN) in a circadian pattern. Transcription of the AVP gene in organotypic cultures of rat SCN was studied by using an intronic in situ hybridization. AVP gene transcription in the cultured SCN maintained a daily rhythm with a peak in the daytime. Inhibition of spontaneous activity by the sodium channel blocker, tetrodotoxin (TTX), dramatically decreased AVP heteronuclear RNA levels and suppressed rhythmicity, indicating that ongoing neural activity was required for the AVP gene transcription. In the presence of TTX, the adenylate cyclase stimulator, forskolin, increased AVP transcription in the SCN. In contrast, the protein kinase C activator, phorbol 12-myristate 13-acetate, greatly increased AVP transcription in the absence of TTX, but this effect was blocked by TTX, indicating that the phorbol 12-myristate 13-acetate acted indirectly via synaptic input. Neither protein kinase A nor protein kinase C pathways appear to be involved in the rhythmicity of AVP transcription in the SCN because selective inhibitors of these protein kinases were without effect. In contrast, the MAPK pathway inhibitor, PD98059, profoundly decreased AVP transcription and abolished its daily rhythm. Hence, a functional MAPK signaling pathway appears to be critical for AVP gene expression in the SCN. C1 NICHHD, Sect Endocrine Physiol, NIH, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Arima, H (reprint author), Nagoya Univ, Dept Internal Med 1, 65 Tsurumai Cho, Nagoya, Aichi 4668550, Japan. RI chen, xuanlan/H-4158-2011; Arima, Hiroshi/I-7383-2014 OI Arima, Hiroshi/0000-0003-3746-1997 NR 69 TC 39 Z9 40 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 2002 VL 143 IS 11 BP 4165 EP 4171 DI 10.1210/en.2002-220393 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 608YV UT WOS:000178876700002 PM 12399408 ER PT J AU Yamashita, M Glasgow, E Zhang, BJ Kusano, K Gainer, H AF Yamashita, M Glasgow, E Zhang, BJ Kusano, K Gainer, H TI Identification of cell-specific messenger ribonucleic acids in oxytocinergic and vasopressinergic magnocellular neurons in rat supraoptic nucleus by single-cell differential hybridization SO ENDOCRINOLOGY LA English DT Article ID GROWTH-INHIBITORY FACTOR; SULFATE-ACTIVATING ENZYMES; GENE-EXPRESSION; IMPRINTED GENE; METALLOTHIONEIN-III; PHOSPHOFRUCTOKINASE-C; BRACHYMORPHIC MICE; SYNAPTOTAGMIN-V; HYPOTHALAMONEUROHYPOPHYSEAL SYSTEM; 5'-PHOSPHOSULFATE KINASE AB Magnocellular neurons (MCNs) in the hypothalamo-neurohypophysial system synthesize high levels of the peptides oxytocin (OT) and vasopressin (VP) in separate cells. We used RT-PCR amplification of the RNA from single-cells dissected from supraoptic nuclei of lactating rats to produce cDNAs from identified OT or VP MCNs, which were used to construct OT- and VP-MCN-specific cDNA libraries. These cDNA libraries were then screened using labeled probes from the OT- and VP-cells' amplified cDNAs. Differentially hybridized colonies were isolated and characterized by slot blot hybridization, Southern blot hybridization, DNA sequencing, and in situ hybridization histochemistry. Using this approach, several novel cell-specific mRNAs were identified in the MCNs. One cell-specific clone, phosphofructokinase-C, was isolated from the OT-cell library, and five cell-specific clones were isolated from the VP-cell library. These were identified as paternally expressed gene (Peg)5/neuronatin, metallothionein III, Peg3, synaptotagmin V, and a 3'-phosphoadenosine 5'-phosphosulfate synthase 2-related mRNA. None of these genes would have been-predicted to be differentially expressed in OT and VP MCNs, based on our current knowledge; and hence, this single cell differential gene expression approach has begun to further define the MCN phenotypes by identifying selectively expressed molecules in them. C1 NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Gainer, H (reprint author), NINDS, Neurochem Lab, NIH, Room 4D20,Bldg 36, Bethesda, MD 20892 USA. OI Glasgow, Eric/0000-0001-7729-3954 NR 84 TC 21 Z9 21 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 2002 VL 143 IS 11 BP 4464 EP 4476 DI 10.1210/en.2002-220516 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 608YV UT WOS:000178876700039 PM 12399444 ER PT J AU Pakarinen, P Kimura, S El-Gehani, F Pelliniemi, LJ Huhtaniemi, I AF Pakarinen, P Kimura, S El-Gehani, F Pelliniemi, LJ Huhtaniemi, I TI Pituitary hormones are not required for sexual differentiation of male mice: Phenotype of the T/ebp/Nkx2.1 null mutant mice SO ENDOCRINOLOGY LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; TARGETED DISRUPTION; LUTEINIZING-HORMONE; GONADOTROPIN RECEPTORS; LEYDIG-CELLS; RAT TESTIS; MOUSE; FETAL; ENDOCRINE; STEROIDOGENESIS AB We have studied male sexual differentiation of null mutant mice (-/-) for the thyroid-specific enhancer-binding protein (T/ebp or Nkx2.1) gene, a homeodomain transcription factor that plays a role in organogenesis of the thyroid, lung, ventral forebrain, and pituitary gland. Because the T/ebp/Nkx2.1 (-/-) mice do not develop the pituitary gland, their sexual differentiation, if any, must occur in the absence of action of gonadotropins and other pituitary hormones. The (-/-) mice survive only until birth (embryonic d 19-19.5 of pregnancy), and when their external and internal genitals were inspected at embryonic d 18.5, they were indistinguishable from the (+/-) and (+/+) control mice. The testis weights of (-/-) mice were 20% lower than in (+/+) and (+/-) mice. The testosterone content of the (-/-) testes (13.5 +/- 2.4 pg/gonad, mean +/- SEM, n = 11) was dramatically reduced, compared with (+/-) (165 +/- 22.5 pg, n = 14) and (+/+) (234 +/- 37.3 pg. n = 10) littermates. Light microscopy revealed no difference in seminiferous tubules, interstitial tissue, or relative proportions of the two-cell compartments between the (-/-) and (+/+) testes. However, electron microscopy confirmed that Leydig cells in the testes were much smaller, with smaller mitochondria and proportion of smooth endoplasmic reticulum than found in the controls, which was in support of the low androgen content of the knockout testes. In conclusion, this study on T/ebp/ Nkx2.1 knockout mice, devoid of the pituitary gland, demonstrates that pituitary hormone secretion is not needed for stimulation of sufficient fetal testicular androgen synthesis to induce male sexual differentiation. The endogenous testosterone level in the null mutant testes is 5-10% of the control level, which suggests that there is a considerable safety margin in the amount of testosterone that is needed for the male fetal masculinization. C1 Univ Turku, Dept Physiol, FIN-20520 Turku, Finland. Univ Turku, Electron Microscopy Lab, FIN-20520 Turku, Finland. Univ London Imperial Coll Sci Technol & Med, Fac Med, Inst Reprod & Dev Biol, London W12 0NN, England. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Huhtaniemi, I (reprint author), Univ Turku, Dept Physiol, Kiinamyllynkatu 10, FIN-20520 Turku, Finland. NR 32 TC 29 Z9 30 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 2002 VL 143 IS 11 BP 4477 EP 4482 DI 10.1210/en.2002-220052 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 608YV UT WOS:000178876700040 PM 12399445 ER PT J AU Avakian, MD Dellinger, B Fiedler, H Gullet, B Koshland, C Marklund, S Oberdorster, G Safe, S Sarofim, A Smith, KR Schwartz, D Suk, WA AF Avakian, MD Dellinger, B Fiedler, H Gullet, B Koshland, C Marklund, S Oberdorster, G Safe, S Sarofim, A Smith, KR Schwartz, D Suk, WA TI The origin, fate, and health effects of combustion by-products: A research framework SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE combustion by-products; fine particles; genetic susceptibility; lung pathobiology; metals; polychlorinated dibenzodioxins; polychlorinated dibenzofurans; public health ID FINE PARTICULATE MATTER; NORTH-AMERICAN CHILDREN; INDOOR AIR-POLLUTION; ACUTE LUNG INJURY; ENVIRONMENTAL-HEALTH; DEVELOPING-COUNTRIES; ACID AEROSOLS; ENDOTOXIN; EPITHELIUM; PARTICLES AB Incomplete combustion processes can emit organic pollutants, metals, and fine particles. Combustion by-products represent global human and environmental health challenges that are relevant not only in heavily industrialized nations, but also in developing nations where up to 90% of rural households rely on unprocessed biomass fuels for cooking, warmth, and light. These issues were addressed at the Seventh International Congress on Combustion BY-Products, which convened 4-6 June 2001 in Research Triangle Park, North Carolina. This congress included a diverse group of multidisciplinary researchers and practitioners who discussed recent developments and future goals in the control of combustion by-products and their effects of exposure on human and ecologic health. Participants recommended that interdisciplinary, coordinated research efforts should be focused to capitalize on the important potential synergisms between efforts to reduce the adverse human health effects linked to exposures to combustion by-products and broader efforts to reduce greenhouse gas emissions and save energy through efficiency. In this article we summarize the principal findings and recommendations for research focus and direction. C1 NIEHS, Div Extramural Res & Training, Res Triangle Pk, NC 27709 USA. MDB Inc, Res Triangle Pk, NC USA. Louisiana State Univ, Dept Chem, Baton Rouge, LA 70803 USA. Louisiana State Univ, Inst Biodynam, Baton Rouge, LA 70803 USA. UN, Environm Program Chem, Chatelaine, Switzerland. US EPA, Res Triangle Pk, NC 27711 USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. Umea Univ, Umea, Sweden. Univ Rochester, Dept Environm Med, Rochester, NY USA. Texas A&M Univ, Dept Vet Physiol & Pharmacol, College Stn, TX 77843 USA. Univ Utah, Dept Chem & Fuels Engn, Salt Lake City, UT USA. Duke Univ, Med Ctr, Durham, NC USA. RP Suk, WA (reprint author), NIEHS, Div Extramural Res & Training, POB 12233, Res Triangle Pk, NC 27709 USA. RI Fiedler, Heidelore/P-6115-2015 OI Fiedler, Heidelore/0000-0003-1496-9245 NR 91 TC 27 Z9 27 U1 0 U2 10 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 NOV PY 2002 VL 110 IS 11 BP 1155 EP 1162 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 614NW UT WOS:000179197100038 PM 12417488 ER PT J AU Rowland, AS Baird, DD Long, S Wegienka, G Harlow, SD Alavanja, M Sandler, DP AF Rowland, AS Baird, DD Long, S Wegienka, G Harlow, SD Alavanja, M Sandler, DP TI Influence of medical conditions and lifestyle factors on the menstrual cycle SO EPIDEMIOLOGY LA English DT Article DE menstrual cycle; menstruation; obesity; smoking; thyroid diseases; depression ID CIGARETTE-SMOKING; AGRICULTURAL HEALTH; DIABETES-MELLITUS; WOMEN; RISK; ASSOCIATION; PATTERNS; LENGTH; AGE; EPIDEMIOLOGY AB Background. Few studies have described medical and lifestyle factors associated with various menstrual cycle characteristics. Methods. We analyzed cross-sectional data collected from 3941 premenopausal women from Iowa or North Carolina participating in the Agricultural Health Study between 1994 and 1996. Eligible women were age 21-40, not taking oral contraceptives, and not currently pregnant or breast feeding. We examined four menstrual cycle patterns: short cycles (24 days or less), long cycles (36 days or more), irregular cycles, and intermenstrual bleeding. Results. Long and irregular cycles were less common with advancing age and more common with menarche after age 14, with depression, and with increasing body mass index. The adjusted odds of long cycles increased with increasing body mass index, reaching 5.4 (95% confidence interval [CI] = 2.1-13.7) among women with body mass indexes of 35 or higher compared with the reference category (body mass index of 22-23). Smoking was associated with short cycles. Long cycles, irregular cycles, and intermenstrual bleeding were associated with a history of infertility. Having long cycles was associated with a doubling in the adjusted odds of having a fetal loss among women who had been pregnant within the last 5 years (odds ratio = 2.3; 95% CI = 0.9-5.7). Conclusions. Menstrual patterns are influenced by a number of host and environmental characteristics. Factors that perturb menstruation may increase a woman's risk of other reproductive disorders. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. CODA Westat Inc, Durham, NC USA. Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. NCI, Epidemiol & Biostat Program, Bethesda, MD 20892 USA. RP Rowland, AS (reprint author), Univ New Mexico, Hlth Sci Ctr, Dept Family & Community Med, MPH Program, 2400 Tucker NE, Albuquerque, NM 87131 USA. RI 段, 沛沛/C-9902-2010; Osborne, Nicholas/N-4915-2015; OI Osborne, Nicholas/0000-0002-6700-2284; Baird, Donna/0000-0002-5544-2653; Sandler, Dale/0000-0002-6776-0018 NR 29 TC 94 Z9 99 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2002 VL 13 IS 6 BP 668 EP 674 DI 10.1097/01.EDE.0000024628.42288.8F PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 604TM UT WOS:000178637200011 PM 12410008 ER PT J AU Cooper, GS Savitz, DA Millikan, R Kit, TC AF Cooper, GS Savitz, DA Millikan, R Kit, TC TI Organochlorine exposure and age at natural menopause SO EPIDEMIOLOGY LA English DT Article DE DDE; DDT; PCB; menopause ID BREAST-CANCER; POLYCHLORINATED-BIPHENYLS; BLOOD-LEVELS; WOMEN; MORTALITY; HEALTH; PCB; CAROLINA; DISEASE; SMOKING AB Background. The effect of potential endocrine-modulating organochlorines on menopause has not been extensively examined. Methods. We evaluated the associations of plasma polychlorinated biphenyls (PCBs) and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) with age at natural menopause. We analyzed data from 1407 women in a population-based, case-control study of breast cancer that was carried out in 19931996 in North Carolina. Results. The adjusted hazard ratio estimating the rate of onset of natural menopause was 1.4 (95% confidence interval = 0.9-2.1) for the top decile of DDE compared with values below the median. This association is similar in magnitude to the association between smoking and menopause (hazard ratio 1.4 [1.1-1.9]). No association was seen with PCBs. Conclusions. The suggested effect of DDE on timing of natural menopause encourages further research to corroborate these findings and evaluate potential mechanisms. Prospective studies, in which exposure measurements are taken before menopause, would be particularly useful. C1 NIEHS, Epidemiol Branch, Durham, NC 27709 USA. Univ N Carolina, Sch Med, Dept Epidemiol, Chapel Hill, NC USA. Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. RP Cooper, GS (reprint author), NIEHS, Epidemiol Branch A3 05, POB 12233, Durham, NC 27709 USA. FU NCI NIH HHS [P50-CA58223]; NIEHS NIH HHS [R01-ES07128] NR 36 TC 23 Z9 23 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2002 VL 13 IS 6 BP 729 EP 733 DI 10.1097/01.EDE.0000032362.42083.9E PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 604TM UT WOS:000178637200021 PM 12410018 ER PT J AU Ansher, S Shoemaker, D Christian, M AF Ansher, S Shoemaker, D Christian, M TI The cancer therapy evaluation program initiatives for enhancing industry collaborations SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 14th EORTC/NCI/AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 19-22, 2002 CL FRANKFURT, GERMANY C1 Natl Canc Inst, Canc Therapy Evaluat Program, Rockville, MD USA. NR 0 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 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2002 VL 38 SU 7 MA 204 BP S64 EP S64 PG 1 WC Oncology SC Oncology GA 626VZ UT WOS:000179895700208 ER PT J AU Camphausen, K AF Camphausen, K TI Combination therapy with anti-angiogenic agents and radiotherapy SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 14th EORTC/NCI/AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 19-22, 2002 CL FRANKFURT, GERMANY C1 Natl Canc Inst, Imaging & Mol Therapeut Sect, Bethesda, MD USA. NR 0 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 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2002 VL 38 SU 7 MA 13 BP S10 EP S10 PG 1 WC Oncology SC Oncology GA 626VZ UT WOS:000179895700014 ER PT J AU Chiosis, G Huezo, H Rosen, N Mimnaugh, E Neckers, L Whitesell, L AF Chiosis, G Huezo, H Rosen, N Mimnaugh, E Neckers, L Whitesell, L TI 17AAG low target binding affinity and potent whole cell potency: finding an explanation SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 14th EORTC/NCI/AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 19-22, 2002 CL FRANKFURT, GERMANY C1 Mem Sloan Kettering Canc Ctr, Dept Med & Mol Oncogenesis, New York, NY 10021 USA. Natl Canc Inst, Call & Canc Biol Branch, Rockville, MD USA. Univ Arizona, Steele Mem Childrens Res Ctr, Tucson, AZ 85721 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2002 VL 38 SU 7 MA 203B BP S64 EP S64 PG 1 WC Oncology SC Oncology GA 626VZ UT WOS:000179895700207 ER PT J AU Cho-Chung, Y Nesterova, M Cho, YS Neary, C Klem, RE AF Cho-Chung, Y Nesterova, M Cho, YS Neary, C Klem, RE TI CRE-enhancer DNA decoy as a tumor target-based genetic tool to treat cancer SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 14th EORTC/NCI/AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 19-22, 2002 CL FRANKFURT, GERMANY C1 NCI, NIH, Bethesda, MD 20892 USA. Genta Inc, Berkeley Hts, NJ USA. NR 0 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 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2002 VL 38 SU 7 MA 482 BP S144 EP S144 PG 1 WC Oncology SC Oncology GA 626VZ UT WOS:000179895700484 ER PT J AU Crawford, K Bittman, R Bowen, W AF Crawford, K Bittman, R Bowen, W TI Novel ceramide analogues display selective cytotoxicity for drug-resistant breast tumor cells over normal breast epithelial cells SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 14th EORTC/NCI/AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 19-22, 2002 CL FRANKFURT, GERMANY C1 Howard Univ, Sch Pharm, Washington, DC 20059 USA. Queens Coll, Dept Chem, Flushing, NY USA. NIH, NIDDK, Bethesda, MD 20892 USA. NR 0 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 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2002 VL 38 SU 7 MA 365 BP S108 EP S108 PG 1 WC Oncology SC Oncology GA 626VZ UT WOS:000179895700367 ER PT J AU Dancey, J AF Dancey, J TI Epidermal growth factor inhibitors: issues in clinical development SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 14th EORTC/NCI/AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 19-22, 2002 CL FRANKFURT, GERMANY C1 Natl Canc Inst, NIH, Investigat Drug Branch, Rockville, MD USA. NR 0 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 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2002 VL 38 SU 7 MA 7 BP S4 EP S5 PG 2 WC Oncology SC Oncology GA 626VZ UT WOS:000179895700008 ER PT J AU Easmon, J Peurstinger, G Schmidt, A Hofmann, J Heinisch, G Liao, ZL Pommier, Y AF Easmon, J Peurstinger, G Schmidt, A Hofmann, J Heinisch, G Liao, ZL Pommier, Y TI 2-Benzimidazolylhydrazones derived from alpha-(N)-acyl heteroaromatics: RNA synthesis inhibitors with camptothecin-like activity SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 14th EORTC/NCI/AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 19-22, 2002 CL FRANKFURT, GERMANY C1 Univ Innsbruck, Dept Pharmaceut Chem, A-6020 Innsbruck, Austria. Univ Innsbruck, Inst Med Chem & Biochem, A-6020 Innsbruck, Austria. NCI, NIH, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2002 VL 38 SU 7 MA 422 BP S127 EP S127 PG 1 WC Oncology SC Oncology GA 626VZ UT WOS:000179895700423 ER PT J AU Ferris, DK Yuan, JH Fisher, R Feng, Y Maloid, S Alberts, A AF Ferris, DK Yuan, JH Fisher, R Feng, Y Maloid, S Alberts, A TI Polo-like kinases and mitotic control SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 14th EORTC/NCI/AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 19-22, 2002 CL FRANKFURT, GERMANY C1 NCI, Basic Res Lab, Biol Mech Sect, Frederick, MD 21701 USA. Van Andel Inst, Lab Cell Struct & Signal Integrat, Grand Rapids, MI USA. NR 0 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 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2002 VL 38 SU 7 MA 387 BP S116 EP S116 PG 1 WC Oncology SC Oncology GA 626VZ UT WOS:000179895700388 ER PT J AU Fornace, A Bulavin, D Anderson, C Kallioniemi, A Saito, S Amundson, S Demidov, O Nebreda, A Appella, E AF Fornace, A Bulavin, D Anderson, C Kallioniemi, A Saito, S Amundson, S Demidov, O Nebreda, A Appella, E TI Genomic-stability and growth-control mechanisms involving the p38 MAP kinase signaling pathway - identification of potential targets for cancer therapy SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 14th EORTC/NCI/AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 19-22, 2002 CL FRANKFURT, GERMANY C1 NIH, Ctr Canc Res, Bethesda, MD USA. Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. Univ Tampere, Canc Genet Lab, FIN-33101 Tampere, Finland. European Mol Biol Lab, Heidelberg, Germany. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 0 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 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2002 VL 38 SU 7 MA 390 BP S117 EP S117 PG 1 WC Oncology SC Oncology GA 626VZ UT WOS:000179895700391 ER PT J AU Fry, T Melchionda, G Mackall, CL AF Fry, T Melchionda, G Mackall, CL TI IL-7 as a therapeutic: immunorestorative agent and vaccine adjuvant SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 14th EORTC/NCI/AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 19-22, 2002 CL FRANKFURT, GERMANY C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. NR 0 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 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2002 VL 38 SU 7 MA 36 BP S16 EP S17 PG 2 WC Oncology SC Oncology GA 626VZ UT WOS:000179895700036 ER PT J AU Gonda, T Walker, R Sood, A Hendrix, M Meltzer, P AF Gonda, T Walker, R Sood, A Hendrix, M Meltzer, P TI Gene expression profile of cisplatin resistance in ovarian cancer cell lines SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 14th EORTC/NCI/AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 19-22, 2002 CL FRANKFURT, GERMANY C1 NHGRI, NIH, Bethesda, MD 20892 USA. Howard Hughes Med Inst, NIH HHMI Res Scholars Program, Bethesda, MD 20817 USA. Univ Iowa, Dept Gynecol, Iowa City, IA 52242 USA. NR 0 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 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2002 VL 38 SU 7 MA 529 BP S158 EP S158 PG 1 WC Oncology SC Oncology GA 626VZ UT WOS:000179895700534 ER PT J AU Hanauske-Abel, HM Hanauske, AR Cracchiolo, BM Wolff, E Park, MH Gordon, W Popowicz, AM AF Hanauske-Abel, HM Hanauske, AR Cracchiolo, BM Wolff, E Park, MH Gordon, W Popowicz, AM TI A novel target for antifolates: the dihydrofolate reductase domain of the G1/S transit controlling protein eIF-5A SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 14th EORTC/NCI/AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 19-22, 2002 CL FRANKFURT, GERMANY C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Pediat & Obstet, Newark, NJ 07103 USA. Allgemein Krankenhaus St Georg, Dept Med Oncol, Hamburg, Germany. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Obstet & Gynecol, Newark, NJ 07103 USA. NIH, Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. Rockefeller Univ, Computing Serv, New York, NY 10021 USA. NR 0 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 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2002 VL 38 SU 7 MA 352 BP S105 EP S105 PG 1 WC Oncology SC Oncology GA 626VZ UT WOS:000179895700354 ER PT J AU Michejda, CJ Tarasova, NI Amadei, G Seth, R AF Michejda, CJ Tarasova, NI Amadei, G Seth, R TI Transmembrane inhibitors of ABC transporters SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 14th EORTC/NCI/AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 19-22, 2002 CL FRANKFURT, GERMANY C1 Natl Canc Inst Frederick Mol Aspects Drug Design, SBL, CCR, Frederick, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2002 VL 38 SU 7 MA 399 BP S120 EP S120 PG 1 WC Oncology SC Oncology GA 626VZ UT WOS:000179895700400 ER PT J AU Ng, SSW Kruger, EA Luzzio, FA Eger, K Guetschow, M Hauschildt, S Hecker, T Teubert, U Weiss, M Figg, WD AF Ng, SSW Kruger, EA Luzzio, FA Eger, K Guetschow, M Hauschildt, S Hecker, T Teubert, U Weiss, M Figg, WD TI In vitro antiangiogenic activity of thalidomide analogues SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 14th EORTC/NCI/AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 19-22, 2002 CL FRANKFURT, GERMANY C1 Univ Kentucky, Dept Chem, Louisville, KY USA. Natl Canc Inst, Mol Pharmacol Sect, Dept Canc Therapeut, Louisville, KY USA. Univ Leipzig, Inst Pharm, Dept Pharmazeut Chem, Leipzig, Germany. RI Figg Sr, William/M-2411-2016 NR 0 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 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2002 VL 38 SU 7 MA 263 BP S82 EP S82 PG 1 WC Oncology SC Oncology GA 626VZ UT WOS:000179895700265 ER PT J AU Reinhold, WC Kouros-Mehr, H Maunakea, A Kohn, KW Lababidi, S Pantazis, P Liu, E Kirsch, I Pommier, Y Weinstein, JN AF Reinhold, WC Kouros-Mehr, H Maunakea, A Kohn, KW Lababidi, S Pantazis, P Liu, E Kirsch, I Pommier, Y Weinstein, JN TI Apoptotic response and the mechanism of resistance to camptothecin: a study of gene expression and functional effects SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 14th EORTC/NCI/AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 19-22, 2002 CL FRANKFURT, GERMANY C1 NCI, NIH, Ctr Adv Technol, Bethesda, MD 20892 USA. Brown Univ, Providence, RI 02912 USA. NCI, NIH, CCR, Genet Branch, Bethesda, MD 20892 USA. RI Liu, Edison/C-4141-2008 NR 0 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 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2002 VL 38 SU 7 MA 553 BP S165 EP S165 PG 1 WC Oncology SC Oncology GA 626VZ UT WOS:000179895700558 ER PT J AU Shoemaker, D Setser, A AF Shoemaker, D Setser, A TI The Adverse Event Expedited Reporting System (AdEERS) of the cancer therapy evaluation program SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 14th EORTC/NCI/AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 19-22, 2002 CL FRANKFURT, GERMANY C1 NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. NR 0 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 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2002 VL 38 SU 7 MA 205 BP S64 EP S64 PG 1 WC Oncology SC Oncology GA 626VZ UT WOS:000179895700209 ER PT J AU Smith, A Tomaszewski, J AF Smith, A Tomaszewski, J TI Preclinical and clinical toxicity correlations for cancer drugs developed by the NCI SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 14th EORTC/NCI/AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 19-22, 2002 CL FRANKFURT, GERMANY C1 GenVec Inc, Gaithersburg, MD USA. Natl Canc Inst, Toxicol & Pharmacol Branch, DTP, DCTD, Rockville, MD USA. NR 0 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 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2002 VL 38 SU 7 MA 19 BP S12 EP S12 PG 1 WC Oncology SC Oncology GA 626VZ UT WOS:000179895700020 ER PT J AU Smith, V Sausville, EA Camalier, RF Fiebig, HH Burger, AM AF Smith, V Sausville, EA Camalier, RF Fiebig, HH Burger, AM TI 17-DMAG (NSC 707545), a water-soluble geldanamycin analog, has superior in vitro and in vivo antitumor activity compared to the hsp90 inhibitor 17-AAG SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 14th EORTC/NCI/AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 19-22, 2002 CL FRANKFURT, GERMANY C1 Univ Freiburg, Tumor Biol Ctr, D-7800 Freiburg, Germany. NCI, Dev Therapeut Program, DCTD, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2002 VL 38 SU 7 MA 189 BP S60 EP S60 PG 1 WC Oncology SC Oncology GA 626VZ UT WOS:000179895700191 ER PT J AU Srikant, CB Thangaraju, M AF Srikant, CB Thangaraju, M TI Cyclic AMP inhibits caspase-8-mediated, pH-dependent, apoptosis by attenuating cellular acidification SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 14th EORTC/NCI/AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 19-22, 2002 CL FRANKFURT, GERMANY C1 McGill Univ, Ctr Hlth, Montreal, PQ, Canada. NCI, Regulat Cell Growth Lab, Frederick, MD 21701 USA. NR 0 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 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2002 VL 38 SU 7 MA 567 BP S169 EP S169 PG 1 WC Oncology SC Oncology GA 626VZ UT WOS:000179895700572 ER PT J AU Staudt, LM AF Staudt, LM TI Molecular diagnosis of cancer by gene expression profiling SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 14th EORTC/NCI/AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 19-22, 2002 CL FRANKFURT, GERMANY C1 NCI, NIH, Canc Res Ctr, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2002 VL 38 SU 7 MA 3 BP S3 EP S4 PG 2 WC Oncology SC Oncology GA 626VZ UT WOS:000179895700004 ER PT J AU Tenen, DG Radomska, HS Halmos, B Scudiero, D Sausville, E Shoemaker, R AF Tenen, DG Radomska, HS Halmos, B Scudiero, D Sausville, E Shoemaker, R TI Targeting C/EBP alpha in leukemia and lung cancer SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 14th EORTC/NCI/AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 19-22, 2002 CL FRANKFURT, GERMANY C1 Harvard Univ, Sch Med, Harvard Inst Med, Boston, MA USA. Natl Canc Inst, SAIC Frederick, Screening Technol Branch, Dev Therapeut Program, Frederick, MD USA. NR 0 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 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2002 VL 38 SU 7 MA 219 BP S70 EP S70 PG 1 WC Oncology SC Oncology GA 626VZ UT WOS:000179895700222 ER PT J AU Townsley, C Major, P Siu, LL Dancey, J Vincent, M Pond, G MacLean, M Moore, MJ Oza, AM AF Townsley, C Major, P Siu, LL Dancey, J Vincent, M Pond, G MacLean, M Moore, MJ Oza, AM TI Phase II study of OSI-774 in patients with metastatic colorectal cancer SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 14th EORTC/NCI/AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 19-22, 2002 CL FRANKFURT, GERMANY C1 Princess Margaret Hosp, Dept Med Oncol, Toronto, ON M4X 1K9, Canada. Hamilton Reg Canc Ctr, Dept Med Oncol, Hamilton, ON L8V 1C3, Canada. Natl Canc Inst, Div Canc Treatment Diagnosis Ctr, Rockville, MD USA. London Reg Canc Ctr, Dept Med Oncol, London, England. NR 0 TC 2 Z9 2 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2002 VL 38 SU 7 MA 179 BP S57 EP S57 PG 1 WC Oncology SC Oncology GA 626VZ UT WOS:000179895700181 ER PT J AU Vinson, C Moll, J Asha, A Neun, B Potter, T Reinhart, R Selby, M Stevenson, T Scuderio, D Sausville, SR AF Vinson, C Moll, J Asha, A Neun, B Potter, T Reinhart, R Selby, M Stevenson, T Scuderio, D Sausville, SR TI A high-throughput fluorescent anisotropy screen to identify small molecules that inhibit AP-1 binding to DNA SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 14th EORTC/NCI/AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 19-22, 2002 CL FRANKFURT, GERMANY C1 NCI, Lab Metab, Bethesda, MD 20892 USA. NCI, SAIC Frederick, Screening Technol Branch, Dev Therapeut Program, Frederick, MD 21701 USA. NR 0 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 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2002 VL 38 SU 7 MA 442 BP S133 EP S133 PG 1 WC Oncology SC Oncology GA 626VZ UT WOS:000179895700443 ER PT J AU Weinstein, JN Reinhold, WC Bussey, K Nishizuka, S Kane, D Gray, J Petricoin, E Liotta, L Kirsch, I Buetow, K AF Weinstein, JN Reinhold, WC Bussey, K Nishizuka, S Kane, D Gray, J Petricoin, E Liotta, L Kirsch, I Buetow, K TI An integrated approach to the pharmacogenomics and pharmacoproteomics of cancer SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 14th EORTC/NCI/AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 19-22, 2002 CL FRANKFURT, GERMANY ID MOLECULAR PHARMACOLOGY; EXPRESSION DATABASE; CELL-LINES; INFORMATION; PATTERNS C1 US Natl Canc Inst, Bethesda, MD USA. SRA Int, Fairfax, VA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. US FDA, Bethesda, MD 20014 USA. NR 11 TC 0 Z9 0 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2002 VL 38 SU 7 MA 310 BP S94 EP S95 PG 2 WC Oncology SC Oncology GA 626VZ UT WOS:000179895700312 ER PT J AU Wickerham, DL AF Wickerham, DL TI Tamoxifen versus raloxifene in the prevention of breast cancer SO EUROPEAN JOURNAL OF CANCER LA English DT Article; Proceedings Paper CT 3rd Biennial International Meeting of the Flemish-Gynaecological-Oncology-Group CY DEC, 2001 CL BRUSSELS, BELGIUM SP Flemish Gynaecol Oncol Grp ID WOMEN; TRIAL C1 Four Allegheny Ctr, NSABP, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15212 USA. RP Wickerham, DL (reprint author), Four Allegheny Ctr, NSABP, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15212 USA. FU NCI NIH HHS [U10-CA37377] NR 4 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2002 VL 38 SU 6 BP S20 EP S21 AR PII S0959-8049(02)00271-X PG 2 WC Oncology SC Oncology GA 626VN UT WOS:000179894700005 PM 12409060 ER PT J AU Wolf, M Mousses, S Kauraniemi, P Hyman, E Hautaniemi, S Huusko, P Ringner, M Elkahloun, A Kallioniemi, A Kallioniemi, O AF Wolf, M Mousses, S Kauraniemi, P Hyman, E Hautaniemi, S Huusko, P Ringner, M Elkahloun, A Kallioniemi, A Kallioniemi, O TI A strategy for identification of gene targets by integrating genome and transcriptome data in cancer SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 14th EORTC/NCI/AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 19-22, 2002 CL FRANKFURT, GERMANY C1 NIH, NHGRI, Canc Genet Branch, Tampere, Finland. Univ Tampere, Inst Med Technol, Canc Genet Lab, FIN-33101 Tampere, Finland. Tampere Univ Technol, Inst Signal Proc, FIN-33101 Tampere, Finland. RI Kallioniemi, Olli/H-4738-2012; Kallioniemi, Olli/H-5111-2011 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 0 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 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2002 VL 38 SU 7 MA 332 BP S100 EP S100 PG 1 WC Oncology SC Oncology GA 626VZ UT WOS:000179895700334 ER PT J AU Ying, YM Shen, DW Liang, XJ Gottesman, MM AF Ying, YM Shen, DW Liang, XJ Gottesman, MM TI Co-dominance of cisplatin resistance in somatic cell hybrids SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 14th EORTC/NCI/AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 19-22, 2002 CL FRANKFURT, GERMANY C1 NCI, NIH, Cell Biol Lab, Bethesda, MD 20892 USA. NR 0 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 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2002 VL 38 SU 7 MA 523 BP S156 EP S157 PG 2 WC Oncology SC Oncology GA 626VZ UT WOS:000179895700528 ER PT J AU Zaharevitz, DW Luke, BT Gussio, R McGrath, CF AF Zaharevitz, DW Luke, BT Gussio, R McGrath, CF TI A molecular overlap tool for investigating potential binding mode similarity in sets of compounds SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 14th EORTC/NCI/AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 19-22, 2002 CL FRANKFURT, GERMANY C1 NCI, Dev Therapeut Program, Bethesda, MD 20892 USA. NR 0 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 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2002 VL 38 SU 7 MA 449 BP S135 EP S135 PG 1 WC Oncology SC Oncology GA 626VZ UT WOS:000179895700450 ER PT J AU Dobson-Stone, C Danek, A Rampoldi, L Hardie, RJ Chalmers, RM Wood, NW Bohlega, S Dotti, MT Federico, A Shizuka, M Tanaka, M Watanabe, M Ikeda, Y Brin, M Goldfarb, LG Karp, BI Mohiddin, S Fananapazir, L Storch, A Fryer, AE Maddison, P Sibon, I Trevisol-Bittencourt, PC Singer, C Caballero, IR Aasly, JO Schmierer, K Dengler, R Hiersemenzel, LP Zeviani, M Meiner, V Lossos, A Johnson, S Mercado, FC Sorrentino, G Dupre, N Rouleau, GA Volkmann, J Arpa, J Lees, A Geraud, G Chouinard, S Nemeth, A Monaco, AP AF Dobson-Stone, C Danek, A Rampoldi, L Hardie, RJ Chalmers, RM Wood, NW Bohlega, S Dotti, MT Federico, A Shizuka, M Tanaka, M Watanabe, M Ikeda, Y Brin, M Goldfarb, LG Karp, BI Mohiddin, S Fananapazir, L Storch, A Fryer, AE Maddison, P Sibon, I Trevisol-Bittencourt, PC Singer, C Caballero, IR Aasly, JO Schmierer, K Dengler, R Hiersemenzel, LP Zeviani, M Meiner, V Lossos, A Johnson, S Mercado, FC Sorrentino, G Dupre, N Rouleau, GA Volkmann, J Arpa, J Lees, A Geraud, G Chouinard, S Nemeth, A Monaco, AP TI Mutational spectrum of the CHAC gene in patients with chorea-acanthocytosis SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE choreoacanthocytosis; neuroacanthocytosis; mutational spectrum; CHAC; chorein ID PROTEIN; NEUROACANTHOCYTOSIS; LOCALIZATION; KEX2P AB Chorea-acanthocytosis (ChAc) is an autosomal recessive neurological disorder whose characteristic features include hyperkinetic movements and abnormal red blood cell morphology. Mutations in the CHAC gene on 9q21 were recently found to cause chorea-acanthocytosis. CHAC encodes a large, novel protein with a yeast homologue implicated in protein sorting. In this study, all 73 exons plus flanking intronic sequence in CHAC were screened for mutations by denaturing high-performance liquid chromatography in 43 probands with ChAc. We identified 57 different mutations, 54 of which have not previously been reported, in 39 probands. The novel mutations comprise 15 nonsense, 22 insertion/ deletion, 15 splice-site and two missense mutations and are distributed throughout the CHAC gene. Three mutations were found in multiple families within this or our previous study. The preponderance of mutations that are predicted to cause absence of gene product is consistent with the recessive inheritance of this disease. The high proportion of splice-site mutations found is probably a reflection of the large number of exons that comprise the CHAC gene. The CHAC protein product, chorein, appears to have a certain tolerance to amino-acid substitutions since only two out of nine substitutions described here appear to be pathogenic. C1 Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. Univ Munich, Neurol Klin, Munich, Germany. Human Mol Genet Unit, DIBIT, Milan, Italy. St Georges & Atkinson Morleys Hosp, London, England. Inst Neurol, Dept Mol Pathogenesis, London, England. King Faisal Specialist Hosp & Res Ctr, Dept Neurosci, Riyadh, Saudi Arabia. Res Ctr, Riyadh, Saudi Arabia. Univ Siena, Inst Neurol Sci, Neurometabol Unit, I-53100 Siena, Italy. Gunma Univ, Sch Med, Dept Neurol, Maebashi, Gumma, Japan. Allergan Pharmaceut Inc, Irvine, CA USA. Mt Sinai Sch Med, New York, NY USA. Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. Natl Heart Lung & Blood Inst, Cardiovasc Branch, Inherited Cardiac Dis Sect, Bethesda, MD USA. Univ Ulm, Dept Neurol, Ulm, Germany. Royal Liverpool Childrens Hosp, Dept Clin Genet, Liverpool, Merseyside, England. Pinderfields Hosp, Dept Neurol, Wakefield, England. Hop Pellegrin, Fed Clin Neurosci, Bordeaux, France. Miami Univ, Sch Med, Dept Neurol, Miami, FL USA. Complexo Hosp Univ, Hosp Conxo, Secc Neurol, Santiago De Compostela, Spain. Univ Hosp, Dept Neurol, Trondheim, Norway. Humboldt Univ, Charite, Klin & Poliklin Neurol, Berlin, Germany. Sch Med, Dept Neurol, Hannover, Germany. Psychiat Klin Oberwil, Oberwil, Switzerland. Ist Nazl Neurol C Besta, Milan, Italy. Hadassah Univ Hosp, Dept Human Genet, Jerusalem, Israel. Hadassah Univ Hosp, Dept Neurol, Jerusalem, Israel. Akershus Univ, Nordbyhagen, Norway. Univ Buenos Aires, Fac Med, RA-1053 Buenos Aires, DF, Argentina. Univ Naples, Fac Sci Movement, I-80138 Naples, Italy. McGill Univ, Ctr Res Neurosci, Montreal, PQ H3A 2T5, Canada. McGill Univ, Hlth Ctr, Res Inst, Montreal, PQ, Canada. Univ Kiel, Neurol Klin, D-2300 Kiel, Germany. Hosp Univ La Paz, Serv Neurol, Madrid, Spain. Royal Free & UCL Sch Med, Reta Lila Weston Inst Neurol Studies, Windeyer Med Inst, London, England. CHU Rangueil, Dept Neurol, Toulouse, France. CHUM Hotel Dieu, Unite Troubles Mouvement Andre Barbeau, Montreal, PQ, Canada. Churchill Hosp, Dept Clin Genet, Oxford, England. RP Monaco, AP (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. RI Schmierer, Klaus/C-1712-2008; Monaco, Anthony/A-4495-2010; Lees, Andrew/A-6605-2009; Danek, Adrian/G-7339-2011; Hardie, Richard/L-6950-2013; Zeviani, Massimo/K-2891-2014; Wood, Nicholas/C-2505-2009; OI Monaco, Anthony/0000-0001-7480-3197; Danek, Adrian/0000-0001-8857-5383; Hardie, Richard/0000-0002-4882-8822; Wood, Nicholas/0000-0002-9500-3348; Rampoldi, Luca/0000-0002-0544-7042 NR 21 TC 63 Z9 65 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD NOV PY 2002 VL 10 IS 11 BP 773 EP + DI 10.1038/sj/ejhg.5200866 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 626EY UT WOS:000179860400018 PM 12404112 ER PT J AU Mendel, I Shevach, EM AF Mendel, I Shevach, EM TI The IL-10-producing competence of Th2 cells generated in vitro is IL-4 dependent SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE T regulatory 1 cell; cytokine; autoimmunity; experimental allergic encephalomyelitis ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; ENCEPHALITOGENIC T-CELLS; INTERFERON-GAMMA; FINE SPECIFICITY; RECEPTOR; MICE; INTERLEUKIN-10; INDUCE AB Previous studies have suggested that activation of CD4(+) T cells in the presence of IL-10 results in the generation of a population of T cells, T regulatory 1 (Tr1) cells, that primarily produce IL-10 and TGF-beta, but not IL-4. The relationship between TO cells and conventional Th2 cells remains unclear. We were not successful in our attempts to generate significant numbers of antigen-specific T cells that secreted IL-10, but not IL-4, by culture in the presence of IL-10. The small numbers of cells that produced IL-10 only were completely dependent on the presence of IL-4 for their generation. In a polyclonal model, the development of IL-10 only producers was completely dependent on the presence of signal transducer and activator of transcription 6. Studies with myelin basic protein-specific T cells derived from an IL-4-deficient mouse confirmed the absolute requirement for IL-4 for the generation of IL-10 producers under all culture conditions. These IL-10-producing Th2 cells failed to inhibit EAE in an adoptive transfer model and were pathogenic when transferred to immunodeficient mice. Collectively, our results raise doubts about the existence of a unique population of CD4(+) regulatory T cells that can be generated by activation in the presence of IL-10. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Shevach, EM (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N315, Bethesda, MD 20892 USA. NR 18 TC 22 Z9 24 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD NOV PY 2002 VL 32 IS 11 BP 3216 EP 3224 DI 10.1002/1521-4141(200211)32:11<3216::AID-IMMU3216>3.0.CO;2-H PG 9 WC Immunology SC Immunology GA 615YZ UT WOS:000179276100022 PM 12555667 ER PT J AU Chung, S Sonntag, KC Andersson, T Bjorklund, LM Park, JJ Kim, DW Kang, UJ Isacson, O Kim, KS AF Chung, S Sonntag, KC Andersson, T Bjorklund, LM Park, JJ Kim, DW Kang, UJ Isacson, O Kim, KS TI Genetic engineering of mouse embryonic stem cells by Nurr1 enhances differentiation and maturation into dopaminergic neurons SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE differentiation; dopaminergic neuron; ES cell; Nurr1; Parkinson's disease; transcription factor ID IN-VITRO; TRANSPORTER GENE; TRANSCRIPTION FACTORS; SEROTONERGIC NEURONS; TYROSINE-HYDROXYLASE; CULTURED-CELLS; BRAIN; EXPRESSION; MIDBRAIN; MICE AB Nurr1 is a transcription factor critical for the development of midbrain dopaminergic (DA) neurons. This study modified mouse embryonic stem (ES) cells to constitutively express Nurr1 under the elongation factor-1alpha promoter. The Nurr1-expression in ES cells lead to up-regulation of all DA neuronal markers tested, resulting in about a 4- to 5-fold increase in the proportion of DA neurons. In contrast, other neuronal and glial markers were not significantly changed by Nurr1 expression. It was also observed that there was an additional 4-fold increase in the number of DA neurons in Nurr1-expressing clones following treatment with Shh, FGF8 and ascorbic acid. Several lines of evidence suggest that these neurons may represent midbrain DA neuronal phenotypes; firstly, they coexpress midbrain DA markers such as aromatic L-amino acid decarboxylase, calretinin, and dopamine transporter, in addition to tyrosine hydroxylase and secondly, they do not coexpress other neurotransmitters such as GABA or serotonin. Finally, consistent with an increased number of DA neurons, the Nurr1 transduction enhanced the ability of these neurons to produce and release DA in response to membrane depolarization. This study demonstrates an efficient genetic manipulation of ES cells that facilitates differentiation to midbrain DA neurons, and it will serve as a framework of genetic engineering of ES cells by key transcription factor to regulate their cell fate. C1 Harvard Univ, Sch Med, McLean Hosp, Udall Parkinsons Dis Res Ctr Excellence, Belmont, MA 02478 USA. Harvard Univ, Sch Med, McLean Hosp, Neuroregenerat Labs, Belmont, MA 02478 USA. Harvard Univ, Sch Med, McLean Hosp, Mol Neurobiol Labs, Belmont, MA 02478 USA. Univ Chicago, Dept Neurol, Chicago, IL 60637 USA. RP Isacson, O (reprint author), Harvard Univ, Sch Med, McLean Hosp, Udall Parkinsons Dis Res Ctr Excellence, Belmont, MA 02478 USA. FU NIMH NIH HHS [MH48866, R01 MH048866, R29 MH048866]; NINDS NIH HHS [NS32080, P50 NS039793, P50 NS039793-03S1, P50NS39793, R01 NS032080] NR 52 TC 175 Z9 195 U1 1 U2 7 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD NOV PY 2002 VL 16 IS 10 BP 1829 EP 1838 DI 10.1046/j.1460-9568.2002.02255.x PG 10 WC Neurosciences SC Neurosciences & Neurology GA 620MU UT WOS:000179537800001 PM 12453046 ER PT J AU Cousins, SW Espinosa-Heidmann, DG Alexandriou, A Sall, J Dubovy, S Csaky, K AF Cousins, SW Espinosa-Heidmann, DG Alexandriou, A Sall, J Dubovy, S Csaky, K TI The role of aging, high fat diet and blue light exposure in an experimental mouse model for basal laminar deposit formation SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE macular degeneration; basal laminar deposits; aging; hyperlipidemia; light; mouse model ID AGE-RELATED MACULOPATHY; RETINAL-PIGMENT EPITHELIUM; MACULAR DEGENERATION; BRUCHS MEMBRANE; LIPID-PEROXIDATION; VITAMIN-E; ALPHA-TOCOPHEROL; RISK-FACTORS; ATHEROSCLEROSIS; DRUSEN AB We sought to investigate the role of aging as a susceptibility factor for the capacity of dietary fat intake to increase the development of subretinal deposits. Mice of various ages (2, 9 and 16 months) were fed a normal diet or a diet high in saturated and unsaturated fats for a total four and a half months. Some eyes were also exposed to non-phototoxic levels of blue-green light. The outer retina and choroid were examined by light and transmission electron microscopy, and the characteristics, frequency and severity of subRPE deposits was determined. Aged mice fed normal diets developed only very mild subretinal deposits. However, many eyes of mice aged 9 months or older at the time of initiation of diet developed frequent basal laminar deposits of moderate severity, and only 16 month old mice developed more severe deposits after exposure to blue-green light. Some eyes in this older group also developed endothelial invasion into Bruch's membrane. None of the eyes developed classic drusen or linear deposits. These observations demonstrate that age increases the capacity of dietary fat, especially in the presence of environmental light, to induce subRPE deposits. (C) 2002 Published by Elsevier Science Ltd. C1 Univ Miami, Sch Med, Dept Ophthalmol, Bascom Palmer Eye Inst, Miami, FL 33138 USA. Univ Miami, Sch Med, Vasc Biol Inst, Miami, FL 33138 USA. NEI, NIH, Bethesda, MD 20892 USA. RP Cousins, SW (reprint author), Univ Miami, Sch Med, Dept Ophthalmol, Bascom Palmer Eye Inst, POB 016880, Miami, FL 33138 USA. NR 56 TC 59 Z9 61 U1 0 U2 5 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD NOV PY 2002 VL 75 IS 5 BP 543 EP 553 DI 10.1006/exer.2002.2047 PG 11 WC Ophthalmology SC Ophthalmology GA 617UA UT WOS:000179378200006 PM 12457866 ER PT J AU Cheng, QF Robison, WG Zigler, JS AF Cheng, QF Robison, WG Zigler, JS TI Geranylgeranyl pyrophosphate counteracts the cataractogenic effect of lovastatin on cultured rat lenses SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE rat lens; organ culture; cataract; statins; prenylation; farnesyl pyrophosphate; geranylgeranyl pyrophosphate; lovastatin; apoptosis ID COA REDUCTASE INHIBITORS; COENZYME-A REDUCTASE; GTP-BINDING PROTEINS; MESANGIAL CELLS; INDUCE APOPTOSIS; ISOPRENYLATION; CHOLESTEROL; GTPASES; PROLIFERATION; PRENYLATION AB Statins are commonly prescribed cholesterol-lowering agents which inhibit the rate-limiting enzyme of the cholesterol biosynthetic pathway. In addition to inhibiting cholesterol synthesis, statins also inhibit the synthesis of other sterol and non-sterol compounds produced by the pathway including the isoprenoids, farnesyl (FP) and geranylgeranyl pyrophosphate (GGP). Certain proteins, most notably small GTP-binding proteins of the Ras superfamily, must be post-translationally modified by addition of a farnesyl or geranylgeranyl moiety in order to be properly targeted to membranes and to be active. Statins have been shown to affect cellular processes such as proliferation, signaling and apoptosis and it is likely that these effects are due, at least in part, to decreased isoprenoid synthesis. Certain statins have been shown to produce cataracts in experimental animals. We have previously demonstrated that lenses exposed to lovastatin during organ culture may develop cataracts as well, and we proposed that this resulted from decreased prenylation of small GTP-binding proteins. To test our hypothesis, rat lenses were exposed to lovastatin in organ culture with concomitant supplementation of the medium with GGP and/or FP. The results clearly demonstrated that GGP strongly inhibited lovastatin-induced lens opacification in this system while FP had little effect. GGP also markedly reduced the histological changes and the increased epithelial cell apoptosis induced in the cultured lenses by lovastatin. The data indicate that inhibition of protein prenylation, perhaps of Rho GTPases, is an important factor in the lovastatin-induced cataract In vitro. (C) 2002 Published by Elsevier Science Ltd. C1 NEI, Lab Mech & Ocular Dis, NIH, Bethesda, MD 20892 USA. RP Zigler, JS (reprint author), NEI, Lab Mech & Ocular Dis, NIH, 6 Ctr Dr,MSC 2735, Bethesda, MD 20892 USA. NR 27 TC 7 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD NOV PY 2002 VL 75 IS 5 BP 603 EP 609 DI 10.1006/exer.2002.2053 PG 7 WC Ophthalmology SC Ophthalmology GA 617UA UT WOS:000179378200012 PM 12457872 ER PT J AU Grinevich, V Harbuz, M Ma, XM Jessop, D Tilders, FJH Lightman, SL Aguilera, G AF Grinevich, V Harbuz, M Ma, XM Jessop, D Tilders, FJH Lightman, SL Aguilera, G TI Hypothalamic pituitary adrenal axis and immune responses to endotoxin in rats with chronic adjuvant-induced arthritis SO EXPERIMENTAL NEUROLOGY LA English DT Article DE hypothalamic-pituitary-adrenal axis; corticotropin-releasing hormone; arginine-vasopressin; interleukin-1 beta; interleukin-6; lipopolysaccharide; adjuvant-induced arthritis ID CORTICOTROPIN-RELEASING HORMONE; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; POTENT IMMUNOLOGICAL ADJUVANT; CHRONIC INFLAMMATORY STRESS; MESSENGER-RNA EXPRESSION; BACTERIAL LIPOPOLYSACCHARIDE; ARGININE-VASOPRESSIN; DEFICIENT MICE; MURINE MODEL; HPA AXIS AB We investigated the effect of immune challenge with LPS in both control rats and rats with adjuvant-induced arthritis (AA). Fourteen day-AA rats showed the expected activation of the hypothalamicpituitary adrenal axis associated with increases in vasopressin mRNA and paradoxical decreases in corticotropin-releasing hormone (CRH) mRNA in parvocellular neurons of the hypothalamic paraventricular nucleus (PVN). However, following LPS there was an increase in both CRH and vasopressin mRNA in the PVN. Neither control rats nor rats with AA had measurable plasma levels of IL-6, but plasma levels of IL-1beta were 2.7-fold higher in AA animals. Following LPS injection both IL-1beta and IL-6 increased more markedly in AA than in control rats. Neither controls nor AA rats expressed IL-1beta or IL-6 mRNA in the brain. However, following LPS these were induced in the subfornical organ, choroid plexus, and median eminence of both groups of animals. The areas expressing IL-1b mRNA were larger in the AA animals and exhibited a punctate pattern throughout the brain parenchyma and PVN. These data reveal an increased peripheral and central immunological response to LPS during the chronic inflammatory process of AA, providing a mechanism through which inflammatory disease can influence the response to a novel immunological challenge. (C) 2002 Elsevier Science (USA). C1 NICHD, DEB, Sect Endocrine Physiol, NIH, Bethesda, MD 20892 USA. Univ Bristol, Res Ctr Neuroendocrinol, Bristol BS2 8HW, Avon, England. Free Univ Amsterdam, Dept Pharmacol, NL-1081 BT Amsterdam, Netherlands. RP Aguilera, G (reprint author), NICHD, DEB, Sect Endocrine Physiol, NIH, Bldg 10,Room 10N262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. EM greti_aguilera@nih.gov NR 51 TC 14 Z9 17 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE 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 NOV PY 2002 VL 178 IS 1 BP 112 EP 123 DI 10.1006/exnr.2002.8022 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 623BC UT WOS:000179682400011 PM 12460613 ER PT J AU Sato, K Kadiiska, MB Ghio, AJ Corbett, J Fann, YC Holland, SM Thurman, RG Mason, RP AF Sato, K Kadiiska, MB Ghio, AJ Corbett, J Fann, YC Holland, SM Thurman, RG Mason, RP TI In vivo lipid-derived free radical formation by NADPH oxidase in acute lung injury induced by lipopolysaccharide: a model for ARDS SO FASEB JOURNAL LA English DT Article DE spin trapping; knockout mice; GdCl3 ID GADOLINIUM CHLORIDE; XANTHINE-OXIDASE; SOYBEAN LIPOXYGENASE; ISCHEMIA-REPERFUSION; KUPFFER CELLS; SEPTIC SHOCK; RAT-LIVER; ENDOTOXIN; PEROXIDATION; LEUKOCYTES AB Intratracheal instillation of lipopolysaccharide (LPS) activates alveolar macrophages and infiltration of neutrophils, causing lung injury/acute respiratory distress syndrome. Free radicals are a special focus as the final causative molecules in the pathogenesis of lung injury caused by LPS. Although in vitro investigation has demonstrated radical generation after exposure of cells to LPS, in vivo evidence is lacking. Using electron spin resonance (ESR) and the spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN), we investigated in vivo free radical production by rats treated with intratracheal instillation of LPS. ESR spectroscopy of lipid extract from lungs exposed to LPS for 6 h gave a spectrum consistent with that of a POBN/carbon-centered radical adduct (a(N) =14.94+/-0.07 G and a(beta)(H)=2.42+/-0.06 G) tentatively assigned as a product of lipid peroxidation. To further investigate the mechanism of LPS-initiated free radical generation, rats were pretreated with the phagocytic toxicant GdCl3, which significantly decreased the production of radical adducts with a corresponding decrease in neutrophil infiltration. NADPH oxidase knockout mice completely blocked phagocyte-mediated, ESR-detectable radical production in this model of acute lung injury. Rats treated intratracheally with LPS generate lipid-derived free radicals via activation of NADPH oxidase. C1 NIEHS, Free Rad Metab Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Dept Pharmacol, Hepatobiol & Toxicol Lab, Chapel Hill, NC USA. Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC USA. RP Sato, K (reprint author), NIEHS, Free Rad Metab Sect, Lab Pharmacol & Chem, NIH, POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM sato@niehs.nih.gov NR 45 TC 99 Z9 103 U1 1 U2 3 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 NOV PY 2002 VL 16 IS 13 BP 1713 EP 1720 DI 10.1096/fj.02-0331com PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 632HU UT WOS:000180218500003 PM 12409313 ER PT J AU Soules, MR Parrott, E Rebar, R Santoro, N Sherman, S Utian, W Woods, NF AF Soules, MR Parrott, E Rebar, R Santoro, N Sherman, S Utian, W Woods, NF TI Executive summary? All about validating scales and stages - Reply SO FERTILITY AND STERILITY LA English DT Letter C1 Univ Washington, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Seattle, WA 98195 USA. NICHHD, Reprod Med Gynecol Program, Populat Res Ctr, NIH, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Div Reprod Endocrinol & Infertil, Bronx, NY 10467 USA. NIA, NIH, Bethesda, MD 20892 USA. N Amer Menopause Soc, Cleveland, OH USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Washington, Sch Nursing, Seattle, WA 98195 USA. RP Soules, MR (reprint author), Univ Washington, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Seattle, WA 98195 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD NOV PY 2002 VL 78 IS 5 BP 1139 EP 1140 AR PII S0015-0282(02)04221-8 DI 10.1016/S0015-0282(02)04221-8 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 611PP UT WOS:000179027200040 ER PT J AU Askling, J Linet, M Gridley, G Halstensen, TS Ekstrom, K Ekbom, A AF Askling, J Linet, M Gridley, G Halstensen, TS Ekstrom, K Ekbom, A TI Cancer incidence in a population-based cohort of individuals hospitalized with Celiac disease or dermatitis herpetiformis SO GASTROENTEROLOGY LA English DT Article ID GLUTEN-FREE DIET; T-CELL LYMPHOMA; MALIGNANCY; RISK; MORTALITY; SPRUE; PREVALENCE; CIRRHOSIS; SURVIVAL; MUCOSA AB Background & Aims: Studies of cancer risk in celiac disease (CD) or dermatitis herpetiformis (DH) indicate increased risks for malignant lymphoma and occasionally other neoplasms, but are characterized by small numbers, lack of systematic cancer assessment, and subjects identified from referral institutions. Methods: By using Swedish population-based inpatient and cancer registry data, we followed-up 12,000 subjects with CD or DH, and evaluated cancer incidence by using standardized incidence ratios (SIR). Results: Adults (but not children and adolescents) with CD had an elevated overall risk for cancer (SIR = 1.3) that declined with time and eventually reached unity. Elevated risks were found for malignant lymphomas, small-intestinal, oropharyngeal, esophageal, large intestinal, hepatobiliary, and pancreatic carcinomas. The excess occurrence of malignant lymphomas was confined to adults, decreased with time of follow-up evaluation, and decreased over successive calendar periods. Decreased risks were found for breast cancer. Subjects with DH had a slightly increased overall cancer risk (SIR = 1.2) owing to excesses of malignant lymphoma and leukemia, but no increases of gastrointestinal carcinomas. Conclusions: Albeit increased, the relative risks for lymphomas and gastrointestinal cancers in this study are lower (and declining) than in most previous reports. The overall cancer risk is only moderately increased, and nonelevated during childhood and adolescence. C1 Karolinska Inst Hosp, Dept Med, Clin Epidemiol Unit, SE-17176 Stockholm, Sweden. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Oslo, Inst Oral Biol, Oslo, Norway. Karolinska Inst, Dept Med Epidemiol, Stockholm, Sweden. RP Askling, J (reprint author), Karolinska Inst Hosp, Dept Med, Clin Epidemiol Unit, SE-17176 Stockholm, Sweden. NR 43 TC 243 Z9 248 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2002 VL 123 IS 5 BP 1428 EP 1435 DI 10.1053/gast.2002.36585 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 609UN UT WOS:000178923100006 PM 12404215 ER PT J AU Marth, T Kleen, N Stallmach, A Ring, S Aziz, S Schmidt, C Strober, W Zeitz, M Schneider, T AF Marth, T Kleen, N Stallmach, A Ring, S Aziz, S Schmidt, C Strober, W Zeitz, M Schneider, T TI Dysregulated peripheral and mucosal Th1/Th2 response in Whipple's disease SO GASTROENTEROLOGY LA English DT Article ID TROPHERYMA-WHIPPELII; INTERFERON-GAMMA; INTERLEUKIN-12; BACTERIUM; BACILLUS; INFECTION; DEFECTS; CELLS AB Background & Aims: An impaired monocyte function and impaired interferon (IFN)-gamma production has been suggested as a possible pathogenetic factor in Whipple's disease (WD) and as a cause for the delayed elimination of Tropheryma whipplei in some patients. Methods: We studied, in a series of 20 WD patients with various degrees of disease activity, cellular immune functions. Results: We found an increased in vitro production of interleukin (IL)-4 by peripheral mononuclear blood cells as determined by enzyme-linked immunosorbent assay, but reduced secretion of IFN-gamma and IL-2 as compared with age- and sex-matched controls. In addition, we observed a significantly reduced monocyte IL-12 production in response to various stimuli in WD patients whereas other cytokines were comparable with controls; these immunologic alterations were not significantly different in patients with various disease activities. At the mucosal level, we found decreased CD4 T-cell percentage and a significantly impaired IFN-gamma secretion. Conclusions: Our data define a defective cellular immune response in a large series of WD patients and point to an important pathogenetic role of impaired Th1 responses. The decreased monocyte IL-12 levels may result in reduced peripheral and mucosal IFN-gamma production and lead to an increased susceptibility to T. whipplei infection in certain hosts. C1 Deutsch Klin Diagnost, Div Gastroenterol, D-65191 Wiesbaden, Germany. Deutsch Klin Diagnost, European Study Ctr Whipples Dis, D-65191 Wiesbaden, Germany. Univ Saarland, D-6650 Homburg, Germany. NIAID, Mucosal Immun Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. Free Univ Berlin, Benjamin Franklin Hosp, Dept Internal Med 1, D-1000 Berlin, Germany. RP Marth, T (reprint author), Deutsch Klin Diagnost, Div Gastroenterol, D-65191 Wiesbaden, Germany. NR 38 TC 59 Z9 61 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 NOV PY 2002 VL 123 IS 5 BP 1468 EP 1477 DI 10.1053/gast.2002.36583 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 609UN UT WOS:000178923100011 PM 12404221 ER PT J AU Seegers, D Zwiers, A Strober, W Pena, AS Bouma, G AF Seegers, D Zwiers, A Strober, W Pena, AS Bouma, G TI A Taql polymorphism in the 3 ' UTR of the IL-12 p40 gene correlates with increased IL-12 secretion SO GENES AND IMMUNITY LA English DT Article DE IL-12; gene polymorphism; in vitro secretion; Crohn's disease ID DENDRITIC CELLS; CROHNS-DISEASE; MULTIPLE-SCLEROSIS; INTERLEUKIN-12; SUSCEPTIBILITY; CYTOKINE; EXPRESSION; MOLECULES AB Interleukin-12 (IL-12) is a key cytokine for the induction of Th1 immune responses. We evaluated whether a Taql polymorphism in the 3'UTR of the IL-12 p40 gene affects secretion of IL-12 in vitro, and whether this polymorphism is associated with susceptibility to Crohn's disease (CD). IL-12 p40 and p70 secretion by monocytes in relation to genotype was determined in 63 healthy donors. Genotype and allele frequencies of the Taql polymorphism in 150 CD patients were compared with 145 ethnically matched healthy controls (HC). No significant association was found between genotype and IL-12 p40 secretion after stimulation of monocytes with SAC+IFNgamma. In contrast, increasing IL-12 p70 secretion was found across the categories of non-carriers, heterozygotes and homozygotes for the variant allele (median values +/- SEM: 147 +/- 27, 282 +/- 51 and 482 +/- 34 pg1 ml, respectively; P< 0.005). The allele and genotype frequencies of this polymorphism in patients with CD did not differ statistically significantly from HC. The presence of a Taql polymorphism in the IL12 p40 3'UTR correlates with increased in vitro IL-12 p70, but not p40 secretion. While this polymorphism does not appear to be correlated with susceptibility to CD in the limited population of patients tested here, it could influence the occurrence of the disease in certain subsets of patients. C1 NIAID, Mucosal Immun Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. Vrije Univ Amsterdam, Med Ctr, Immunogenet Lab, Amsterdam, Netherlands. RP Bouma, G (reprint author), NIAID, Mucosal Immun Sect, Clin Invest Lab, NIH, 10 Ctr Dr 11N242, Bethesda, MD 20892 USA. RI bouma, gerd/E-2520-2013 NR 24 TC 116 Z9 120 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD NOV PY 2002 VL 3 IS 7 BP 419 EP 423 DI 10.1038/sj.gene.6363919 PG 5 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 613LQ UT WOS:000179134100006 PM 12424624 ER PT J AU Baffoe-Bonnie, AB Kiemeney, LALM Beaty, TH Bailey-Wilson, JE Schnell, AH Sigvaldason, H Olafsdottir, G Tryggvadottir, L Tulinius, H AF Baffoe-Bonnie, AB Kiemeney, LALM Beaty, TH Bailey-Wilson, JE Schnell, AH Sigvaldason, H Olafsdottir, G Tryggvadottir, L Tulinius, H TI Segregation analysis of 389 Icelandic pedigrees with breast and prostate cancer SO GENETIC EPIDEMIOLOGY LA English DT Article DE breast-prostate cancer phenotype; familial aggregation; codominant model; sibship covariate ID AUTOSOMAL-DOMINANT INHERITANCE; SINGLE BRCA2 MUTATION; SUSCEPTIBILITY LOCUS; OVARIAN-CANCER; FAMILY HISTORY; RISK; POPULATION; GENES; RELATIVES; LINKAGE AB Breast cancer and prostate cancer are the most commonly occurring cancers in females and males, respectively. The objective of this project was to test the hypothesis that breast cancer in females and prostate cancer in males represent homologous cancers that may be controlled by one or more common unidentified genes that may explain some of the observed familial aggregation. We modeled the transmission of a breast-prostate cancer phenotype in 389 pedigrees ascertained through a breast cancer proband drawn from the Icelandic Cancer Registry. Assuming that age at diagnosis of this combined phenotype followed a logistic distribution, segregation analyses were performed to evaluate residual parental effects, a sibship covariate, and a dichotomous cohort effect. The most parsimonious model was a Mendelian codominant model, which could partly explain the familial aggregation of both cancers. Inheritance of a putative high-risk allele (A) predicted gender-specific mean ages of onset for females as 53.8 years, 59.7 years, and 65.6 years for the putative AA, AB, and BB genotypes, respectively. Similarly, the predicted means were 73.7 years, 75.6 years, and 78.3 years, respectively, among males. Under this codominant model, the lifetime risk of a woman being affected was 19% by age 80 years. This implies that when prostate cancer among male relatives of breast cancer probands (unselected for family history or early-onset disease) is considered a pleiotrophic effect of the same gene that increases the risk for breast cancer, women are predicted to have a less than 1 in 5 risk of developing breast cancer when they carry the putative high-risk allele. However, this is a higher risk than in the general Icelandic population. Our results suggest that BRCA2 mutations alone are inadequate to explain all of the excess clustering of prostate cancer cases in families of breast cancer probands, and that additional genes conferring excess risk to both breast and prostate cancer may exist in this population. (C) 2002 Wiley-Liss, Inc. C1 Johns Hopkins Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD USA. Univ Nijmegen, Dept Epidemiol, Nijmegen, Netherlands. Univ Nijmegen, Dept Urol, Nijmegen, Netherlands. Rammelkamp Ctr Educ & Res, SAGE Project, Cleveland, OH USA. Iceland Canc Soc, Canc Registry, Reykjavik, Iceland. RP Beaty, TH (reprint author), Johns Hopkins Sch Hyg & Publ Hlth, Dept Epidemiol, Room 6507,615 N Wolfe St, Baltimore, MD 21205 USA. RI Kiemeney, Lambertus/D-3357-2009; OI Kiemeney, Lambertus/0000-0002-2368-1326; Bailey-Wilson, Joan/0000-0002-9153-2920; Tryggvadottir, Laufey/0000-0001-8067-9030 FU NCI NIH HHS [5R25CA57708, 5T32CA09314, CA-06927] NR 73 TC 9 Z9 9 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2002 VL 23 IS 4 BP 349 EP 363 DI 10.1002/gepi.10188 PG 15 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 618RY UT WOS:000179432100003 PM 12432503 ER PT J AU Bebenek, A Carver, GT Dressman, HK Kadyrov, FA Haseman, JK Petrov, V Konigsberg, WH Karam, JD Drake, JW AF Bebenek, A Carver, GT Dressman, HK Kadyrov, FA Haseman, JK Petrov, V Konigsberg, WH Karam, JD Drake, JW TI Dissecting the fidelity of bacteriophage RB69 DNA polymerase: Site-specific modulation of fidelity by polymerase accessory proteins SO GENETICS LA English DT Article ID CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; REPLICATION FIDELITY; BASE-SUBSTITUTION; NUCLEOTIDE INCORPORATION; TRANSIENT MISALIGNMENT; SPONTANEOUS MUTATION; III HOLOENZYME; ERROR-PRONE; FRAMESHIFT AB Bacteriophage RB69 encodes a replicative B-family DNA polymerase (RB69 gp43) with an associated proofreading 3' exonuclease. Crystal structures have been determined for this enzyme with and without DNA substrates. We previously described the mutation rates and kinds of mutations produced in vivo by the wild-type (Pol(+) Exo(+)) enzyme, an exonuclease-deficient mutator variant (Pol(+) Exo(-)), mutator variants with substitutions at Tyr(567) in the polymerase active site (Pol(M) Exo(+)), and the double mutator Pol(M) Exo(-) Comparing the mutational spectra of the Pol(+) Exo(-) and Pol(+) Exo(+) enzymes revealed the patterns and efficiencies of proofreading, while Tyr(567). was identified as an important determinant of base-selection fidelity. Here, we sought to determine how well the fidelities of the same enzymes are reflected in vitro. Compared to their behavior in vivo, the three mutator polymerases exhibited modestly higher mutation rates in vitro and their mutational predilections were also somewhat different. Although the RB69 gp43 accessory proteins exerted little or no effect on total mutation rates in vitro, they strongly affected mutation rates at many specific sites, increasing some rates and decreasing others. C1 NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Biometry Branch, NIH, Res Triangle Pk, NC 27709 USA. Polish Acad Sci, Inst Biochem & Biophys, PL-02106 Warsaw, Poland. Tulane Univ, Hlth Sci Ctr, Dept Biochem, New Orleans, LA 70112 USA. Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06510 USA. RP Drake, JW (reprint author), NIEHS, Mol Genet Lab, NIH, Room E-344,POB 12233, Res Triangle Pk, NC 27709 USA. NR 62 TC 31 Z9 31 U1 0 U2 3 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD NOV PY 2002 VL 162 IS 3 BP 1003 EP 1018 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 624BL UT WOS:000179739900002 PM 12454051 ER PT J AU Rattray, AJ Shafer, BK McGill, CB Strathern, JN AF Rattray, AJ Shafer, BK McGill, CB Strathern, JN TI The roles of REV3 and RAD57 in double-strand-break-repair-induced mutagenesis of Saccharomyces cerevisiae SO GENETICS LA English DT Article ID DNA-POLYMERASE-ZETA; REPLICATION PROTEIN-A; NUCLEOTIDE EXCISION-REPAIR; SOMATIC HYPERMUTATION; ESCHERICHIA-COLI; MISMATCH REPAIR; IMMUNOGLOBULIN GENES; ADAPTIVE MUTATION; MULTIPLE PATHWAYS; YEAST AB The DNA synthesis associated with recombinational repair of chromosomal double-strand breaks (DSBs) has a lower fidelity than normal replicative DNA synthesis. Here, we use an inverted-repeat substrate to monitor the fidelity of repair of a site-specific DSB. DSB induction made by the HO endonuclease stimulates recombination >5000-fold and is associated with a >1000-fold increase in mutagenesis of an adjacent gene. We demonstrate that most break-repair-induced mutations (BRIMs) are point mutations and have a higher proportion of frameshifts than do spontaneous mutations of the same substrate. Although the REV3 translesion DNA polymerase is not required for recombination, it introduces similar to75% of the BRIMs and similar to90% of the base substitution mutations. Recombinational repair of the DSB is strongly dependent upon genes of the RAD52 epistasis group; however, the residual recombinants present in rad57 mutants are associated with a 5- to 20-fold increase in BRIMs. The spectrum of mutations in rad57 mutants is similar to that seen in the wild-type strain and is similarly affected by REV3. We also find that REV3 is required for the repair of MMS-induccd lesions when recombinational repair is compromised. Our data suggest that Rad55p/Rad57p help limit the generation of substrates that require pol zeta during recombination. C1 NCI, Frederick Canc Res & Dev Ctr, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. RP Strathern, JN (reprint author), NCI, Frederick Canc Res & Dev Ctr, Gene Regulat & Chromosome Biol Lab, Bldg 539,Rm 151,POB B, Frederick, MD 21702 USA. RI Rattray, Alison/A-4847-2008 NR 71 TC 76 Z9 77 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD NOV PY 2002 VL 162 IS 3 BP 1063 EP 1077 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 624BL UT WOS:000179739900007 PM 12454056 ER PT J AU Biesecker, LG AF Biesecker, LG TI Coupling genomics and human genetics to delineate basic mechanisms of development SO GENETICS IN MEDICINE LA English DT Article; Proceedings Paper CT 3rd Joint Asan-Harvard Medical International Symposium on Genomics and Proteomics - Impact on Medicine and Health CY JUL 03-04, 2001 CL SEOUL, SOUTH KOREA SP Univ Ulsan Coll Med, Asan Med Ctr, Harvard Med Sch, Harvard Med Int DE human development; syndrome families; Pallister-Hall syndrome; McKusick-Kaufman syndrome; Old Order Amish of Lancaster County; Pennsylvania ID MCKUSICK-KAUFMAN-SYNDROME; BARDET-BIEDL-SYNDROME; PALLISTER-HALL SYNDROME; MUTATIONS; GLI3 AB This article, based on a presentation given by the author at the third Asan-Harvard Medical International Symposium on "Genomics and Proteomics: Impact on Medicine and Health" in Seoul, Korea, July 3-4, 2001, discusses an iterative translational research approach to delineate the basic mechanism of human development. The study of humans to increase the understanding of mammalian development has critical advantages that make its limitations acceptable for certain types of studies. For instance, by looking at families affected by birth defects, researchers can gain insight into the basic mechanisms of development and how genes program organisms to assume their permanent, or adult, morphological shapes. A number of malformation syndromes have some overlapping manifestations, despite being phenotypically and, in some cases, genetically distinct. What can researchers learn from this? The author's research group clinically and genetically analyzed families affected with the Pallister-Hall syndrome. The researchers then went on to look at the McKusick-Kaufman syndrome, a disorder that is more common among the Old Order Amish of Lancaster County, Pennsylvania, in an attempt to understand more about genes, genetic pathways, and syndrome families. C1 NHGRI, Bethesda, MD 20892 USA. RP Biesecker, LG (reprint author), NHGRI, Bldg 49,Room 4A80, Bethesda, MD 20892 USA. NR 22 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD NOV-DEC PY 2002 VL 4 IS 6 SU S BP 39S EP 42S DI 10.1097/01.GIM.0000040328.04474.05 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 644FQ UT WOS:000180907600008 PM 12544486 ER PT J AU Fee, E Brown, TM AF Fee, E Brown, TM TI The unfulfilled promise of public health: Deja vu all over again SO HEALTH AFFAIRS LA English DT Article AB Many complain about public health's weak infrastructure and poor capacity to respond to threats of bioterrorism. Such complaints are but the anxiety-heightened expression of a periodic rediscovery of the deficiencies and unfulfilled promise of U.S. public health. An overview of more than two centuries suggests that where we are now with public health has been shaped by our earlier, limited, and crisis-focused responses to changing disease threats. We have failed to sustain progress in any coherent manner. If we do not wish to repeat past mistakes, we should learn lessons from the past to guide us in the future. C1 NIH, Hist Med Div, Natl Lib Med, Bethesda, MD 20892 USA. Univ Rochester, Coll Arts & Sci, Dept Hist, New York, NY USA. Univ Rochester, Sch Med & Dent, New York, NY USA. RP Fee, E (reprint author), NIH, Hist Med Div, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. NR 36 TC 23 Z9 23 U1 0 U2 1 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD NOV-DEC PY 2002 VL 21 IS 6 BP 31 EP 43 DI 10.1377/hlthaff.21.6.31 PG 13 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 617BB UT WOS:000179338700009 PM 12442838 ER PT J AU Austin, SM Rau, EH Holcomb, WF Zoon, RA AF Austin, SM Rau, EH Holcomb, WF Zoon, RA TI Reduction in radioactive material use and waste generation at the National Institute's of Health SO HEALTH PHYSICS LA English DT Article DE operational topic; waste disposal; waste management; regulations AB The National Institutes of Health (NIH) has implemented an enhanced and comprehensive program to reduce the rise of radioactive materials and to minimize the generation of radioactive and mixed wastes. The primary drivers for this program were increasing waste management costs, difficulties in disposing of certain types of radioactive wastes, particularly mixed wastes, and the increasing burden of managing radioactive materials in accordance with new regulatory requirements. These minimization efforts, coupled with the development of new on-site waste treatment options and the use of commercially available waste processing facilities, have resulted in significant reductions in the use of radioactive materials in bench research and the resultant amounts of radioactive and mixed waste generated and disposed off-site. A survey of users of radioactive materials was conducted to examine the reasons for this reduction and to predict future ordering trends. The primary factors contributing to reductions in ordering appear to be rapidly increasing use or non-radioactive research techniques, and increasingly burdensome safety and security regulations governing the use of radioactive material, which tend to discourage their use. The downward trends in use and disposal of radioactive materials at the NIH appear to be continuing. C1 CSI Radiat Safety Acad, Gaithersburg, MD 20877 USA. NIH, Radiat Safety Branch, Div Safety, Bethesda, MD 20892 USA. NIH, Environm Protect Branch, Div Safety, Bethesda, MD 20892 USA. RP Austin, SM (reprint author), CSI Radiat Safety Acad, 481 N Frederick Ave, Gaithersburg, MD 20877 USA. EM saustin@radtrain.com NR 16 TC 2 Z9 2 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD NOV PY 2002 VL 83 IS 11 SU S BP S85 EP S95 DI 10.1097/00004032-200211005-00009 PG 11 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 631DR UT WOS:000180152800007 PM 12458925 ER PT J AU Ming, L Thorgeirsson, SS Gail, MH Lu, PX Harris, CC Wang, NJ Shao, YF Wu, ZY Liu, GT Wang, XH Sun, ZT AF Ming, L Thorgeirsson, SS Gail, MH Lu, PX Harris, CC Wang, NJ Shao, YF Wu, ZY Liu, GT Wang, XH Sun, ZT TI Dominant role of hepatitis B virus and cofactor role of aflatoxin in hepatocarcinogenesis in Qidong, China SO HEPATOLOGY LA English DT Article ID HUMAN HEPATOCELLULAR CARCINOMAS; SURFACE-ANTIGEN; P53 GENE; NONHUMAN-PRIMATES; X GENE; MUTATION; RISK; DNA; INTEGRATION; EXPOSURE AB We assessed the separate and combined effects of hepatitis B virus (HBV), hepatitis C virus (HCV), and aflatoxin in causing hepatocellular carcinoma (HCC) in Qidong, China. A consecutive series of 181 pathologic-diagnosed HCC cases were studied for hepatitis B surface antigen (HBsAg), anti-HBc, HBV X gene sequence, anti-HCV, the 249ser-p53 mutation, and chronic hepatitis pathology. Each of the 181 incident HCC cases had markers for HBV infection and hepatitis pathology; only 6 of 119 cases were coinfected with HCV. The 249ser-p53 mutation was found in 54% (97/181) of HCC cases and in all 7 cases with tissue for analysis from the hepatitis cohort but in none of 42 matched cases from Beijing. The estimated cumulative dose of aflatoxin B I in these 7 cases ranged from 0.13 to 0.49 mg/kg. Follow-up data through 13.25 years on a cohort of 145 men with chronic HBV hepatitis showed that the relative risk from aflatoxin exposure was 3.5 (1.5-8.1). A similar relative risk was found using 249ser-p53 mutation as a marker for aflatoxin exposure. In conclusion, HBV hepatitis is ubiquitous in Qidong HCC cases, whereas HCV contributes little to its risk. The 249ser-p53 mutation appears to result from coexposure to aflatoxin and HBV infection. Even modest levels of aflatoxin exposure tripled the risk of HCC in HBV-infected men. C1 Chinese Acad Med Sci, Natl Lab Mol Oncol, Inst Canc, Beijing 100021, Peoples R China. NCI, NIH, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Qidong Liver Canc Inst, Qidong, Peoples R China. RP Sun, ZT (reprint author), Chinese Acad Med Sci, Natl Lab Mol Oncol, Inst Canc, Beijing 100021, Peoples R China. NR 35 TC 122 Z9 134 U1 1 U2 6 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 NOV PY 2002 VL 36 IS 5 BP 1214 EP 1220 DI 10.1053/jhep.2002.36366 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 610EY UT WOS:000178948800022 PM 12395332 ER PT J AU Soza, A Everhart, JE Ghany, MG Doo, E Heller, T Promrat, K Park, Y Liang, TJ Hoofnagle, JH AF Soza, A Everhart, JE Ghany, MG Doo, E Heller, T Promrat, K Park, Y Liang, TJ Hoofnagle, JH TI Neutropenia during combination therapy of interferon alfa and ribavirin for chronic hepatitis C SO HEPATOLOGY LA English DT Article ID INITIAL TREATMENT; RANDOMIZED TRIAL; PLUS RIBAVIRIN; CIRRHOSIS AB Interferon therapy of hepatitis C causes a decrease in neutrophil counts, and neutropenia is a common reason for dose adjustment or early discontinuation. However, it is unclear whether neutropenia caused by interferon is associated with an increased rate of infection. In this study, we assessed factors associated and clinical consequences of neutropenia before and during interferon therapy of chronic hepatitis C. A total of 119 patients with chronic hepatitis C treated with the combination of interferon alfa and ribavirin were analyzed. In these studies, neutropenia was not used as an exclusion or dose modification criterion. In multivariate analysis, only black race was associated with baseline neutropenia. During treatment, neutrophil counts decreased by an average of 34%. Among 3 blacks with baseline neutropenia without cirrhosis or splenomegaly, there was little or no decrease in neutrophil. counts (despite typical decreases in platelet and lymphocyte counts). Documented or suspected bacterial infections developed in 22 patients (18%), but in no patient with neutropenia. United States population estimates suggest that 76,000 blacks with hepatitis C have neutrophil counts below 1,500 cells/muL and might be denied therapy if this exclusion criterion was generally applied. In conclusion, neutropenia is frequent during treatment of hepatitis C with interferon and ribavirin, but it is not usually associated with infection. Constitutional neutropenia, which is common among blacks, should not exclude patients from therapy with interferon as these patients usually have minimal further decreases in neutrophil counts on therapy and are not excessively prone to bacterial infections. C1 NIDDKD, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. RP Soza, A (reprint author), NIDDKD, Liver Dis Sect, NIH, Bldg 10,Room 9B16,10 Ctr Dr, Bethesda, MD 20892 USA. RI Soza, Alejandro/C-2907-2009 NR 21 TC 128 Z9 137 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 2002 VL 36 IS 5 BP 1273 EP 1279 DI 10.1053/jhep.2002.36502 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 610EY UT WOS:000178948800030 PM 12395340 ER PT J AU Di Bisceglie, AM Hoofnagle, JH AF Di Bisceglie, AM Hoofnagle, JH TI Optimal therapy of hepatitis C SO HEPATOLOGY LA English DT Article ID INITIAL TREATMENT; PEGYLATED INTERFERON-ALPHA-2B; PEGINTERFERON ALPHA-2A; PLUS RIBAVIRIN; EFFICACY; SAFETY; TRIAL AB The highest response rates to antiviral therapy for the treatment of chronic hepatitis C have been achieved using the combination of peginterferon and ribavirin. Recently completed controlled trials have reported rates of sustained virological response (SVR) between 50% and 60% in patients treated with higher doses of peginterferon and ribavirin, which was 5% to 10% higher with standard doses of interferon alfa and ribavirin. The major determinant of outcome of therapy is hepatitis C virus (HCV) genotype. With the combination of peginterferon and ribavirin, patients with genotype 1 achieve response rates of 40% to 45%, compared with rates approaching 80% with genotypes 2 or 3. Importantly, patients with HCV genotype 1 achieve higher rates of response with 48 weeks than with 24 weeks of therapy, whereas patients with genotypes 2 and 3 are adequately treated with a 24-week course. Furthermore, patients with genotypes 2 and 3 require only 800 mg of ribavirin daily to achieve optimal response rates, whereas 1,000 to 1,200 mg daily is needed for patients with genotype 1. Future studies should focus on optimizing the dose of peginterferon and ribavirin by patient characteristics, particularly on resolving the issue of weight-based dosing. For patients with good prognostic factors, a lower dose and shorter course of peginterferon may be adequate for full effect. Importantly, research is needed to show how treatment regimens can best be applied to other patient groups with hepatitis C, such as patients with acute hepatitis, human immunodeficiency virus coinfection, renal disease, solid-organ transplant, neuropyschiatric disease, autoimmunity, and alcohol or substance abuse. C1 St Louis Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, St Louis, MO 63110 USA. St Louis Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA. NIDDKD, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Di Bisceglie, AM (reprint author), St Louis Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, 3635 Vista Ave, St Louis, MO 63110 USA. FU NIAID NIH HHS [U19-AI-48220]; NIDDK NIH HHS [N01-DK-09232, R01-DK-56435, U01-DK-60345] NR 10 TC 198 Z9 208 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 NOV PY 2002 VL 36 IS 5 SU 1 BP S121 EP S127 DI 10.1053/jhep.2002.36228 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 611VT UT WOS:000179039000015 PM 12407585 ER PT J AU Hoofnagle, JH AF Hoofnagle, JH TI Course and outcome of hepatitis C SO HEPATOLOGY LA English DT Article ID INTERFERON-ALPHA-2B PLUS RIBAVIRIN; SINGLE-SOURCE OUTBREAK; NON-B-HEPATITIS; TERM FOLLOW-UP; VIRUS-INFECTION; LONG-TERM; NON-A; LIVER-DISEASE; HCV-RNA; EXTRAHEPATIC MANIFESTATIONS AB The hepatitis C virus (HCV) is a small enveloped RNA virus belonging to the family flaviviridae and genus hepacivirus. The HCV RNA genome is 9,600 nucleotides in length and encodes a single polyprotein that is post-translationally cleaved into 10 polypeptides including t3 structural (C, E1, and E2) and multiple nonstructural proteins ([NS] NS2 to NS5). The NS proteins include enzymes necessary for protein processing (proteases) and viral replication (RNA polymerase). The virus replicates at a high rate in the liver and has marked sequence heterogeneity. There are 6 genotypes and more than 90 subtypes of HCV, the most common in the United States being 1a and 1b (approximately 75%), 2a and 2b (approximately 15%), and 3 (approximately 7%). Acute hepatitis C is marked by appearance of HCV RNA in serum within 1 to 2 weeks of exposure followed by serum alanine aminotransferase (ALT) elevations, and then symptoms and jaundice. Antibody to HCV (anti-HCV) tends to arise late. In acute resolving hepatitis, HCV RNA is cleared and serum ALT levels fall to normal. However, 55% to 85% of patients do not dear virus, but develop chronic hepatitis C. Chronic hepatitis C is often asymptomatic, but is usually associated with persistent or fluctuating elevations in ALT levels. The chronic sequelae of hepatitis C include progressive hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. Extra-hepatic manifestations include sicca syndrome, cryoglobulinemia, glomerulonephritis, and porphyria cutanea tarda. Knowledge of the course and outcome of hepatitis C is important in developing approaches to management and therapy. C1 NIDDKD, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Hoofnagle, JH (reprint author), NIDDKD, Div Digest Dis & Nutr, NIH, Bldg 31,Room 9A27,31 Ctr Dr, Bethesda, MD 20892 USA. RI Yang, Chen/G-1379-2010 NR 80 TC 600 Z9 635 U1 6 U2 31 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 NOV PY 2002 VL 36 IS 5 SU 1 BP S21 EP S29 DI 10.1053/jhep.2002.36227 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 611VT UT WOS:000179039000003 PM 12407573 ER PT J AU Seeff, LB AF Seeff, LB TI Natural history of chronic hepatitis C SO HEPATOLOGY LA English DT Article ID TERM FOLLOW-UP; HUMAN-IMMUNODEFICIENCY-VIRUS; TRANSFUSION-ASSOCIATED HEPATITIS; LIVER FIBROSIS PROGRESSION; QUALITY-OF-LIFE; NON-B-HEPATITIS; ALCOHOL-CONSUMPTION; NON-A; HEPATOCELLULAR-CARCINOMA; POSTTRANSFUSION HEPATITIS AB Much controversy surrounds the issue of the natural history of hepatitis C virus (HCV) infection. Many authorities view the disease as inexorably progressive with a high probability of advancing over time to cirrhosis and occasionally hepatocellular carcinoma (HCC) and, therefore, likely to be responsible for causing death. Others regard chronic hepatitis C as having a variable outcome, the majority of infected persons not dying from the disease, but more likely from the comorbid conditions that so often accompany infection by this agent, or from more common medical conditions. Disagreements probably derive from the manner of conduct of the study and the populations studied. Efforts to determine natural history are handicapped by the primary characteristics of the disease, namely that its onset rarely is recognized and its course is prolonged exceedingly. Thus, different outcomes have come from retrospective rather than from prospective studies, but both have concluded that at least 20% of chronically infected adults develop cirrhosis within 20 years. More recent studies that used a retrospective/prospective approach, focusing largely on young infected individuals, have produced different results. Among these young people, particularly young women, spontaneous resolution of the viral infection is more common than previously thought and cirrhosis has been identified in 5% or fewer of them. The major failing for all groups studied, young and old, is that natural history studies have rarely exceeded the first 2 decades, so that outcome beyond this time is not known, other than through modeling. Several host-related and extraneous factors probably affect the natural history. C1 NIDDKD, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Seeff, LB (reprint author), NIDDKD, Div Digest Dis & Nutr, NIH, 31A Ctr Dr,Room 9A27, Bethesda, MD 20892 USA. NR 96 TC 755 Z9 788 U1 5 U2 25 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 NOV PY 2002 VL 36 IS 5 SU 1 BP S35 EP S46 DI 10.1053/jhep.2002.36806 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 611VT UT WOS:000179039000005 PM 12407575 ER PT J AU Seeff, LB Hoofnagle, JH AF Seeff, LB Hoofnagle, JH TI National Institutes of Health Consensus Development Conference: Management of hepatitis C: 2002 SO HEPATOLOGY LA English DT Editorial Material ID VIRUS-INFECTION; UNITED-STATES C1 NIDDKD, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Seeff, LB (reprint author), NIDDKD, Div Digest Dis & Nutr, NIH, Rm 9A27,Bldg 31,31 Ctr Dr, Bethesda, MD 20892 USA. NR 5 TC 160 Z9 169 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 2002 VL 36 IS 5 SU 1 BP S1 EP S2 DI 10.1053/jhep.2002.36992 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 611VT UT WOS:000179039000001 PM 12407571 ER PT J AU Bader, T Zoumakis, E Friedberg, M Chrousos, GP Hochberg, Z AF Bader, T Zoumakis, E Friedberg, M Chrousos, GP Hochberg, Z TI Human adipose tissue under in vitro inhibition of II beta-hydroxysteroid dehydrogenase type 1: Differentiation and metabolism changes SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE II beta-HSD-1; carbenoxolone; cortisone ID STROMAL CELLS; 11-BETA-HYDROXYSTEROID DEHYDROGENASE; ADIPOCYTE DIFFERENTIATION; EXPRESSION; CARBENOXOLONE; OBESITY AB In humans, oxoreducing 11beta-HSD-1 activity appears to be related to body fat distribution in male-type central obesity, but not in female-type peripheral obesity. We postulated that inhibition of 11beta-HSD-1 might have clinical therapeutic significance in oxoreducing mostly visceral fat and its metabolic activity. Our current study investigated the consequence at the cellular level of such inhibition. As an inhibitor of 11beta-HSD-1 activity, we used the licorice derivative carbenoxolone. Carbenoxolone has an inhibitory effect on the activity of both oxidizing 11beta-HSD-2, which converts cortisol to cortisone, and oxoreducing 11beta-HSD-1 [1]; yet, preadipocytes and adipocytes only express the latter. Preadipocytes were retrieved from omental and subcutaneous fat from healthy non-obese individuals and differentiated in vitro to mature adipocytes. Activity of 11beta-HSD-1 was assayed by measuring conversion of added 500 nM cortisone to cortisol. Expression of 11beta-HSD-1 mRNA was determined by real-time PCR, while lipolytic effects were determined by measuring glycerol and triglyceride concentration in the culture medium. Carbenoxolone decreased 11beta-HSD-1 activity in a dose-dependent manner with an IC-50 of 5X10(-6) M, but did not affect the expression of 11beta-HSD-1 mRNA. Cortisone stimulated subcutaneous, but not omental preadipocytes proliferation, an effect that was not abolished by carbenoxolone. Dexamethasone had a stimulatory effect on the maturation of both omental and subcutaneous preadipocytes. Carbenoxolone per se, either with or without cortisone, had a negative effect on preadipocyte maturation. Inhibiting 11beta-HSD-1 activity by carbenoxolone had no impact on leptin secretion. Thus, carbenoxolone has no effect on preadipocyte proliferation, but a dramatic inhibitory effect on preadipocyte differentiation into mature adipocytes. The mechanism is only partly related to its inhibitory effect on 11beta-HSD-1 activity. The present observations lend support to the presence of an intracrine loop of a hormone that is both produced from a precursor and active within the preadipocyte and adipocyte. C1 NICHHD, Pediat & Reprod Endocrinol Branch, Bethesda, MD USA. RP Hochberg, Z (reprint author), Meyer Childrens Hosp, POB 9602, IL-31096 Haifa, Israel. NR 14 TC 15 Z9 15 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD NOV-DEC PY 2002 VL 34 IS 11-12 BP 752 EP 757 DI 10.1055/s-2002-38255 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 662CP UT WOS:000181928800027 PM 12660894 ER PT J AU Urabe, M Ding, CT Kotin, RM AF Urabe, M Ding, CT Kotin, RM TI Insect cells as a factory to produce adeno-associated virus type 2 vectors SO HUMAN GENE THERAPY LA English DT Article ID ADENO-ASSOCIATED VIRUS; FACTOR-IX; GENE-EXPRESSION; PERSISTENT; PARTICLES; PROTEINS; MUTANTS; CAPSIDS; VIRIONS AB Recombinant adeno-associated viruses (rAAV) are produced transiently in mammalian cells usually by co-transfecting two or three plasmids containing AAV genes, adenovirus helper genes, and a vector genome. Expansion and transfection of adherent cells limit the scale of rAAV production. Efficient transfection is performed with cells on solid support media such as tissue culture plates. A large animal study or a human clinical trial may require 10(15) particles of vector, depending on dose. To generate this quantity of rAAV by transfection, more than 10(11) HEK293 cells may be needed, which would require about 5000 x 175 cm(2) flasks. The ability to scale up rAAV production by these methods severely restricts the commercialization and use of AAV vectors. A recombinant baculovirus derived from the Autographa californica nuclear polyhedrosis virus is widely employed for large-scale production of heterologous proteins in cultured insect cells and may provide an attractive alternative. Toward this goal, we have explored the production of rAAV in invertebrate cells. Sf9 cells may be coinfected in suspension cultures with three recombinant baculoviruses (a Rep-baculovirus, a VP-baculovirus, and an AAV ITR vector genome baculovirus) and, 3 days later, rAAV is recovered. The particles produced are indistinguishable from 293 cell-produced rAAV, as determined on the basis of physical properties and biologic activities. Particles produced by either method were composed of similar proteins and nucleic acid. The yield of genome-containing particles produced per Sf9 cell approached 5 3 104, thus, 1000 ml of cultured Sf9 cells produced the equivalent of between 500 to 1000 x 175 cm(2) flasks of 293 cells. This robust system provides a simple, cost-effective method for AAV vector production. C1 NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. RP Kotin, RM (reprint author), NHLBI, Lab Biochem Genet, NIH, Bldg 10,Room 7N264,10 Ctr Dr,MSC 1654, Bethesda, MD 20892 USA. EM kotinr@nhlbi.nih.gov RI kotin, robert/B-8954-2008 NR 27 TC 234 Z9 252 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV PY 2002 VL 13 IS 16 BP 1935 EP 1943 DI 10.1089/10430340260355347 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 766CL UT WOS:000188327800002 PM 12427305 ER PT J AU Kershaw, MH Wang, G Westwood, JA Pachynski, RK Tiffany, HL Marincola, FM Wang, E Young, HA Murphy, PM Hwu, P AF Kershaw, MH Wang, G Westwood, JA Pachynski, RK Tiffany, HL Marincola, FM Wang, E Young, HA Murphy, PM Hwu, P TI Redirecting migration of T cells to chemokine secreted from tumors by genetic modification with CXCR2 SO HUMAN GENE THERAPY LA English DT Article ID RECEIVING ADOPTIVE IMMUNOTHERAPY; HEPATOCELLULAR-CARCINOMA; INFILTRATING LYMPHOCYTES; OVARIAN-CANCER; MELANOMA-CELLS; CC CHEMOKINES; GROWTH-FACTOR; NUDE-MICE; EXPRESSION; RECEPTOR AB T-cell-based immunotherapies provide a promising means of cancer treatment although durable antitumor responses are infrequent. A potential reason for these shortcomings may lie in the observed lack of trafficking of specific T cells to tumor. Our increasing knowledge of the process of trafficking involving adhesion molecules and chemokines affords us the opportunity to intervene and correct deficiencies in this process. Chemokines can be expressed by a range of tumors and may serve as suitable targets for directing specific T cells toward tumor. We initially sought to identify which chemokines were produced by a range of human tumor cell lines, and which chemokines and chemokine receptors were expressed by cultured T cells. We identified two chemokines: Growth-Regulated Oncogene-alpha (Gro-alpha; CXCL1) and Regulated on Activation Normal T Cell-Expressed and Secreted ( RANTES; CCL5), to be secreted by several human tumor cell lines. Expression was also detected in fine-needle aspirates of melanoma from patients. In addition, we determined the expression of several chemokine receptors on cultured human T cells including CCR1, CCR2, CCR4, CCR5, CXCR3, and CXCR4. Cultured, activated human T cells expressed the chemokines lymphotactin (XCL1), RANTES, macrophage inflammatory protein-1alpha (MIP-1alpha; CCL3) and MIP-1beta (CCL4), but no appreciable Gro-alpha. In a strategy to direct T cells toward chemokines expressed by tumors we chose Gro-alpha as the target chemokine because it was produced by tumor and not by T cells themselves. However, T cells did not express the receptor for Gro-alpha, CXCR2, and therefore, T cells were transduced with a retroviral vector encoding CXCR2. Calcium ion mobilization, an important first step in chemokine receptor signaling, was subsequently demonstrated in transduced T cells in response to Gro-alpha. In addition, Gro-alpha was chemotactic for T cells expressing CXCR2 in vitro toward both recombinant protein and tumor-derived chemokine. Interestingly we demonstrate, for the first time, that Gro-alpha was able to induce interferon-gamma (IFN-gamma) secretion from transduced T cells, thereby extending our knowledge of other potential functions of CXCR2. This study demonstrates the feasibility of redirecting the migration properties of T cells toward chemokines secreted by tumors. C1 NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. NCI, Expt Immunol Lab, Frederick, MD 20892 USA. RP Hwu, P (reprint author), NCI, Ctr Canc Res, NIH, Bldg 10,Room 2B42, Bethesda, MD 20892 USA. EM Patrick_Hwu@nih.gov RI Young, Howard/A-6350-2008 OI Young, Howard/0000-0002-3118-5111 NR 47 TC 110 Z9 113 U1 0 U2 5 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 NOV PY 2002 VL 13 IS 16 BP 1971 EP 1980 DI 10.1089/10430340260355374 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 766CL UT WOS:000188327800005 PM 12427307 ER PT J AU Hu, J Takatoku, M Sellers, SE Agricola, BA Metzger, ME Donahue, RE Dunbar, CE AF Hu, J Takatoku, M Sellers, SE Agricola, BA Metzger, ME Donahue, RE Dunbar, CE TI Analysis of origin and optimization of expansion and transduction of circulating peripheral blood endothelial progenitor cells in the rhesus macaque model SO HUMAN GENE THERAPY LA English DT Article ID HEMATOPOIETIC STEM-CELLS; BONE-MARROW; NONHUMAN-PRIMATES; NEOVASCULARIZATION; ANGIOGENESIS; MOBILIZATION; VIVO; TRANSPLANTATION; ANGIOPOIETIN-1; VASCULOGENESIS AB Adult marrow-derived cells have been shown to contribute to various nonhematologic tissues and, conversely, primitive cells isolated from nonhematopoietic tissues have been shown to reconstitute hematopoiesis. Circulating endothelial progenitor cells (EPCs) have been reported to be at least partially donor derived after allogeneic bone marrow transplantation, and shown to contribute to neovascularization in murine ischemia models. However, it is unknown whether these EPCs are actually clonally derived from the same population of stem and progenitor cells that reconstitute hematopoiesis, or from another cell population found in the marrow or mobilized blood that is transferred during transplantation. To approach this question, we characterized circulating EPCs and also endothelial cells from large vessels harvested at autopsy from rhesus macaques previously transplanted with retrovirally transduced autologous CD34-enriched peripheral blood stem cells (PBSCs). Endothelial cells were grown in culture for 21 - 28 days and were characterized as CD31(+)CD14(-) via flow cytometry, as acLDL(+)UEA-1(+) via immunohistochemistry, and as Flk-1(+) by reverse transcriptase-polymerase chain reaction (RT-PCR). Animals had stable vector marking in hematopoietic lineages of 2 - 15%. Neither cultured circulating EPCs collected in steady state (n = 3), nor endothelial cells grown from large vessels (n = 2), had detectable retroviral marking. EPCs were CD34(+) and could be mobilized into the circulation with granulocyte colony-stimulating factor. Under ex vivo culture conditions, in which CD34(+) cells were optimized to transduce hematopoietic progenitor and stem cells, there was a marked depletion of EPCs. Transduction of EPCs was much more efficient under conditions supporting endothelial cell growth. Further elucidation of the origin and in vivo behavior of EPCs may be possible, using optimized transduction conditions and a vascular injury model. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Dunbar, CE (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Room 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. EM dunbarc@nhlbi.nih.gov NR 37 TC 15 Z9 20 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV PY 2002 VL 13 IS 17 BP 2041 EP 2050 DI 10.1089/10430340260395893 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 766CM UT WOS:000188327900004 PM 12489999 ER PT J AU Scheuring, UJ Sabzevari, H Theofilopoulos, AN AF Scheuring, UJ Sabzevari, H Theofilopoulos, AN TI Proliferative arrest and cell cycle regulation in CD8(+)CD28(-) versus CD8(+)CD28(+) T cells SO HUMAN IMMUNOLOGY LA English DT Article DE proliferative arrest; cell cycle; CD8(+)CD28(-) T cells; CD8(+)CD28(+) T cells; TCR zeta-chain ID REPLICATIVE SENESCENCE; DIFFERENTIAL EXPRESSION; P16(INK4A) EXPRESSION; INHIBITORY RECEPTORS; RHEUMATOID-ARTHRITIS; HEALTHY-INDIVIDUALS; HUMAN FIBROBLASTS; IN-VIVO; LYMPHOCYTES; ACTIVATION AB CD8(+)CD28(-) T cells have been characterized by oligoclonal expansions, impaired proliferative responses, but preserved cytotoxicity and reduced telomeres. To examine this subset further and define the underlying mechanisms of proliferation arrest, we investigated several features of this cell type compared with CD8(+)CD28(+) controls. We analyzed expression of various activation markers, thymidine incorporation upon activation, T-cell receptor (TCR) zeta-chain phosphorylation, cell cycle characteristics, and cell cycle related gene expression. Flow cytometry revealed higher expression of CD11b, CD29, CD57, and CD94, and lower expression of CD25 in CD8(+)CD28(-) compared with CD8(+)CD28(+) T cells. Sorted CD8(+)CD16(-)CD28(-) cells exhibited decreased phosphorylation of the TCR zeta-chain in three of four probands. Proliferation of these T cells was impaired, even when activated with mitogens that bypass TCR signaling. Cell cycle profiles demonstrated a lower percentage of cycling cells and significantly higher levels of cyclin dependent kinase inhibitor p161(INK4a) in the CD28(-) subset compared with the CD28(+) control. These observations suggest that expanded CD8(+)CD28(-) T cells in normal elderly individuals have reduced proliferation concomitant with increased p161(INK4a) expression. Defects in TCR signaling were associated with altered TCR zeta-chain phosphorylation. (C) American Society for Histocompatibility and Immunogenetics, 2002. Published by Elsevier Science Inc. C1 JW Goethe Univ Hosp, Dept Hematol & Oncol Infect Dis & Rheumatol, D-60590 Frankfurt, Germany. Scripps Res Inst, Dept Immunol, La Jolla, CA USA. NCI, Lab Tumor Immunol & Biol, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Scheuring, UJ (reprint author), JW Goethe Univ Hosp, Dept Hematol & Oncol Infect Dis & Rheumatol, Theodor Stern Kai 7, D-60590 Frankfurt, Germany. FU NIA NIH HHS [AG15061] NR 53 TC 32 Z9 33 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD NOV PY 2002 VL 63 IS 11 BP 1000 EP 1009 AR PII S0198-8859(02)00683-3 DI 10.1016/S0198-8859(02)00683-3 PG 10 WC Immunology SC Immunology GA 609VA UT WOS:000178924200004 PM 12392852 ER PT J AU Peters, LM Anderson, DW Griffith, AJ Grundfast, KM San Agustin, TB Madeo, AC Friedman, TB Morell, RJ AF Peters, LM Anderson, DW Griffith, AJ Grundfast, KM San Agustin, TB Madeo, AC Friedman, TB Morell, RJ TI Mutation of a transcription factor, TFCP2L3, causes progressive autosomal dominant hearing loss, DFNA28 SO HUMAN MOLECULAR GENETICS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; WAARDENBURG SYNDROME; HUMAN HOMOLOG; NONSYNDROMIC DEAFNESS; MISSENSE MUTATION; READING FRAMES; FACTOR CP2; GENE WFS1; INNER-EAR; IMPAIRMENT AB We ascertained a large American family with an autosomal dominant form of progressive non-syndromic sensorineural hearing loss. After excluding linkage to known deafness loci, we performed a genome-wide scan and found linkage to marker GAAT1A4 on chromosome 8q22 (LOD = 5.12 at theta = 0), and this locus was designated DFNA28. Sequencing of six candidate genes in the 1.4cM linked region identified a frameshift mutation (1609-1610insC) resulting in a premature translation stop codon in exon 14 of the gene TFCP2L3 (transcription factor cellular promoter 2-like 3). TFCP2L3 is a member of a family of transcription factor genes whose archetype is TFCP2, a mammalian homolog of the Drosophila gene grainyhead. Northern blot analyses and in situ hybridization studies show that mouse Tfcp2l3 is expressed in many epithelial tissues, including cells lining the cochlear duct, at embryonic day 18.5 and postnatal day 5. C1 Natl Inst Deafness & Other Commun Disorders, Sect Human Genet, Genet Mol Lab, NIH, Rockville, MD 20850 USA. Natl Inst Deafness & Other Commun Disorders, Sect Gene Struct & Funct, Genet Mol Lab, NIH, Rockville, MD 20850 USA. Natl Inst Deafness & Other Commun Disorders, Sect Hearing, Genet Mol Lab, NIH, Rockville, MD 20850 USA. RP Morell, RJ (reprint author), 5 Res Court ,Room 2A19, Rockville, MD 20850 USA. RI Madeo, Anne/K-2880-2012; OI Morell, Robert/0000-0003-1537-7356 FU NIDCD NIH HHS [1-Z01 DC 00060-01, 1 ZO1 DC000039-05] NR 63 TC 50 Z9 56 U1 0 U2 4 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 NOV 1 PY 2002 VL 11 IS 23 BP 2877 EP 2885 DI 10.1093/hmg/11.23.2877 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 614ZN UT WOS:000179221500008 PM 12393799 ER PT J AU Jaffe, ES Banks, PM Nathwani, B Said, J Swerdlow, SH AF Jaffe, ES Banks, PM Nathwani, B Said, J Swerdlow, SH TI Recommendations for the reporting of lymphoid neoplasms: A report from the Association of Directors of Anatomic and Surgical Pathology. The ad hoc committee on reporting of lymphoid neoplasms SO HUMAN PATHOLOGY LA English DT Article C1 NCI, Hematol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Jaffe, ES (reprint author), NCI, Hematol Sect, Pathol Lab, NIH, Bldg 10,Room 2N202,10 Ctr Dr,MSC-1500, Bethesda, MD 20892 USA. NR 6 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 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD NOV PY 2002 VL 33 IS 11 BP 1064 EP 1068 DI 10.1053/hupa.2002.129205 PG 5 WC Pathology SC Pathology GA 618RZ UT WOS:000179432200002 PM 12454809 ER PT J AU Lloyd-Jones, DM Evans, JC Larson, MG Levy, D AF Lloyd-Jones, DM Evans, JC Larson, MG Levy, D TI Treatment and control of hypertension in the community - A prospective analysis SO HYPERTENSION LA English DT Article DE blood pressure; hypertension, detection and control antihypertensive therapy; epidemiology; population ID ISOLATED SYSTOLIC HYPERTENSION; NUTRITION EXAMINATION SURVEY; DIASTOLIC BLOOD-PRESSURE; CORONARY HEART-DISEASE; NATIONAL-HEALTH; MORTALITY; MORBIDITY; LEVEL; AGE AB Cross-sectional national data indicate poor levels of treatment and control of hypertension. We identified factors that prospectively predict initiation of antihypertensive therapy and attainment of blood pressure control in the community. We included all Framingham Heart Study subjects examined between 1987 and 1999 whoa had untreated or uncontrolled hypertension (systolic greater than or equal to140 or diastolic greater than or equal to90 mm Hg) at a baseline examination and presented for follow-up examination 4 years later. Clinical covariates were examined for their association with initiation or control at follow-up. Among 1103 hypertensive participants who were untreated at baseline, 350 (31.7%) subjects were receiving therapy at follow-up, including 25.7% of subjects with stage 1 and 51.2% of those with stage greater than or equal to2 hypertension at baseline. Multivariate predictors of initiation of therapy included higher systolic and diastolic pressure, prevalent and interim cardiovascular disease, and left ventricular hypertrophy. Other cardiovascular risk factors did not predict initiation of treatment. Among 2475 hypertensive participants who were uncontrolled (treated or untreated) at baseline, 988 (39.9%) were controlled at follow-up. Prevalent cardiovascular disease and interim initiation of therapy predicted control; older age and higher baseline systolic levels predicted lack of control. These data provide estimates of longitudinal rates of treatment and control of hypertension in the community. It appears that global risk was not taken into consideration when making decisions for initiation of therapy. Greater emphasis is needed on achieving blood pressure control in all patients but particularly among older subjects and those with systolic hypertension. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, Boston, MA USA. Boston Univ, Sch Med, Div Epidemiol & Prevent Med, Boston, MA 02118 USA. NHLBI, Bethesda, MD 20892 USA. RP Lloyd-Jones, DM (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. RI Lloyd-Jones, Donald/C-5899-2009; OI Larson, Martin/0000-0002-9631-1254 FU NHLBI NIH HHS [N01-HC-25195, K23 HL04253] NR 24 TC 63 Z9 70 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD NOV PY 2002 VL 40 IS 5 BP 640 EP 646 DI 10.1161/01.HYP.0000035855.44620.DA PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 612QU UT WOS:000179087600009 PM 12411456 ER PT J AU Dubois, S Mariner, J Waldmann, TA Tagaya, Y AF Dubois, S Mariner, J Waldmann, TA Tagaya, Y TI IL-15R alpha recycles and presents IL-15 in trans to neighboring cells SO IMMUNITY LA English DT Article ID RECEPTOR-ALPHA-CHAIN; NATURAL-KILLER; GAMMA-CHAIN; BETA-CHAIN; T-CELLS; INTERLEUKIN-15; ENDOCYTOSIS; EXPRESSION; BINDING; MICE AB We report intriguing aspects of the contribution of IL-15Ralpha to IL-15 functions. Consistent with high-affinity interactions between IL-15 and IL-1513, these two molecules form stable complexes on the cell surface of activated monocytes. The formation of IL-15/IL-15Ralpha complexes on cell surfaces induces a transendosomal recycling of IL-15 leading to the persistence of surface-bound IL-15 due to the constant reappearance of IL-15 on plasma membranes. This complex contributes to the long survival of T cells expressing IL-15Ra after IL-15 withdrawal. Finally, these complexes on activated monocytes present IL-15 in trans to target cells such as CD8+ T cells that express only IL-2/15Rbeta and gammac upon cell-cell interaction. C1 NCI, Metab Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Tagaya, Y (reprint author), NCI, Metab Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NR 34 TC 512 Z9 521 U1 3 U2 14 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV PY 2002 VL 17 IS 5 BP 537 EP 547 DI 10.1016/S1074-7613(02)00429-6 PG 11 WC Immunology SC Immunology GA 616ZX UT WOS:000179335100001 PM 12433361 ER PT J AU Khaled, AR Li, WQ Huang, JQ Fry, TJ Khaled, AS Mackall, CL Muegge, K Young, HA Durum, SK AF Khaled, AR Li, WQ Huang, JQ Fry, TJ Khaled, AS Mackall, CL Muegge, K Young, HA Durum, SK TI Bax deficiency partially corrects interleukin-7 receptor alpha deficiency SO IMMUNITY LA English DT Article ID BCL-2 FAMILY MEMBERS; T-CELL DEVELOPMENT; FORKHEAD TRANSCRIPTION FACTOR; GAMMA GENE REARRANGEMENT; THYMOCYTE DEVELOPMENT; INTRACELLULAR PH; IL-7 RECEPTOR; IN-VIVO; MICE; SURVIVAL AB The requirement for cytokines in hematopoiesis is partly attributable to the protection of cells from apoptosis. Since IL-7 is required for normal T cell development, we evaluated the role of Bax in vivo by generating mice deficient in both Bax and the IL-7 receptor a chain (IL-7R). Starting at birth, we observed complete recovery of all stages of (3 thymocyte development up to 4 weeks of age. However, by 12 weeks of age, thymic cellularity had reverted to that of mice deficient in IL-7R alone. The BH3 only proteins, Bad and Bim, were also part of the death pathway repressed by IL-7. Thus, in young mice, Bax emerges as an essential protein in the death pathway induced by IL-7 deficiency. C1 NCI, Mol Immunoregulat Lab, Canc Res Ctr, Frederick, MD 21702 USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Univ Miami, Dept Pathol, Miami, FL 33136 USA. SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. NCI, Expt Immunol Lab, Canc Res Ctr, Frederick, MD 21702 USA. RP Durum, SK (reprint author), NCI, Mol Immunoregulat Lab, Canc Res Ctr, Frederick, MD 21702 USA. NR 48 TC 70 Z9 70 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV PY 2002 VL 17 IS 5 BP 561 EP 573 DI 10.1016/S1074-7613(02)00450-8 PG 13 WC Immunology SC Immunology GA 616ZX UT WOS:000179335100003 PM 12433363 ER PT J AU Heller, F Fuss, IJ Nieuwenhuis, EE Blumberg, RS Strober, W AF Heller, F Fuss, IJ Nieuwenhuis, EE Blumberg, RS Strober, W TI Oxazolone colitis, a Th2 colitis model resembling ulcerative colitis, is mediated by IL-13-producing NK-T cells SO IMMUNITY LA English DT Article ID CROHNS-DISEASE; TOLERANCE INDUCTION; MURINE MODEL; IFN-GAMMA; B-CELLS; INTERLEUKIN-4; EXPRESSION; MICE; RECEPTOR; CD1D AB Oxazolone colitis (OC) is an experimental colitis that has a histologic resemblance to human ulcerative colitis. Here we show that IL-13 production is a significant pathologic factor in OC since its neutralization by IL-13Ralpha2-Fc administration prevents colitis. We further show that OC is mediated by NK-T cells since it can be induced neither in mice depleted of NK-T cells nor in mice that cannot present antigen to NK-T cells and mice lacking an NK-T cell-associated TCR. Finally, we show that NK-T cells are the source of the IL-13, since they produce IL-13 upon stimulation by a-galactosylceramide, an NK-T cell-specific antigen. These data thus describe a cellular mechanism underlying an experimental colitis that may explain the pathogenesis of ulcerative colitis. C1 NIAID, Mucosal Immun Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Div Gastroenterol, Brigham & Womens Hosp, Boston, MA 02115 USA. Royal Netherland Acad Arts & Sci, Ter Meulen Fund, Amsterdam, Netherlands. RP Strober, W (reprint author), NIAID, Mucosal Immun Sect, Clin Invest Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. FU NIDDK NIH HHS [DK51362, DK44319] NR 49 TC 350 Z9 379 U1 1 U2 12 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV PY 2002 VL 17 IS 5 BP 629 EP 638 DI 10.1016/S1074-7613(02)00453-3 PG 10 WC Immunology SC Immunology GA 616ZX UT WOS:000179335100009 PM 12433369 ER PT J AU Delon, J Stoll, S Germain, RN AF Delon, J Stoll, S Germain, RN TI Imaging of T-cell interactions with antigen presenting cells in culture and in intact lymphoid tissue SO IMMUNOLOGICAL REVIEWS LA English DT Review ID ADAPTIVE IMMUNE-RESPONSE; DENDRITIC CELLS; IN-VIVO; IMMUNOLOGICAL SYNAPSE; SIGNAL-TRANSDUCTION; INTRACELLULAR CALCIUM; ACTIN CYTOSKELETON; CUTTING EDGE; RECEPTOR; ACTIVATION AB The development of an effective immune response requires cell-cell contact between T cells and antigen-bearing cells of several types (dendritic cells, B cells, infected tissue cells). Recent advances in light microscopy have led to intense investigation of the molecular events that accompany these cell interactions, especially the redistribution of membrane proteins into discrete organized subdomains within the zone of cell-cell contact termed the 'immunological synapse'. Here we discuss two aspects of our own studies in this area. First, we highlight results from our in vitro analysis of the role of the cytoskeletal ezrin, radixin, moesin adapter proteins in the exclusion of CD43 from the well-defined T cell receptor (TCR) and integrin-rich zones of the synapse. Based on the molecular mechanism uncovered in this work, we propose a new model for how TCR-signaled changes in cytoskeletal organization indirectly influence both protein distributions and the efficiency of signaling between T cell and presenting cell. We then discuss the development of a new method for dynamic visualization of T cell dendritic cell interactions in intact lymphoid tissue. The remarkable longevity of monogamous lymphocyte-presenting cell interactions is discussed, differences between our observations and those of others are laid out in detail, and prospects for future application of this technical approach to analysis of early immune responses in lymphoid organs and of effector lymphocyte function in tissues are presented. C1 NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Germain, RN (reprint author), NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, 10 Ctr Dr MSC-1892, Bethesda, MD 20892 USA. NR 87 TC 49 Z9 50 U1 1 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD NOV PY 2002 VL 189 BP 51 EP 63 DI 10.1034/j.1600-065X.2002.18906.x PG 13 WC Immunology SC Immunology GA 618GJ UT WOS:000179410100006 PM 12445265 ER PT J AU Warner, HR AF Warner, HR TI Recent progress in understanding the relationships among aging, replicative senescence, cell turnover and cancer SO IN VIVO LA English DT Review DE aging; cancer; replicative senescence; mutations; cell turnover ID LIFE-SPAN; HUMAN TELOMERES; IN-VIVO; P53; FIBROBLASTS; EXTENSION; DIVISION; BIOLOGY; GROWTH; TISSUE AB The link between aging and cancer is more than just the increasing accumulation of mutations with time. Recent research provides evidence that senescent cells are not merely passive bystanders, but may promote cancer through degradation of the tissue microenvironment. Another critical factor in the relationship between aging and cancer is p53 function; its activity level is apparently finely tuned to suppress cancer while regulating both apoptosis and the replacement of damaged cells through stem cell proliferation. The deacetylase activity of the sir2 gene product plays a role in longevity regulation in invertebrates, and also regulates p53 function in mammals, implying yet another link between aging and cancer in mammals. C1 NIA, Biol Aging Program, Bethesda, MD 20892 USA. RP Warner, HR (reprint author), NIA, Biol Aging Program, Bethesda, MD 20892 USA. NR 30 TC 5 Z9 5 U1 0 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0258-851X J9 IN VIVO JI In Vivo PD NOV-DEC PY 2002 VL 16 IS 6 BP 393 EP 396 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 626HT UT WOS:000179866300002 PM 12494881 ER PT J AU Nagorsen, D Marincola, FM AF Nagorsen, D Marincola, FM TI How to analyze ex vivo T-cell responses in cancer patients SO IN VIVO LA English DT Article DE specific T-cells; tetramer; IFN gamma-ELISPOT; flow cytometry; ex vivo ID GAMMA-ELISPOT ASSAY; MELANOMA PATIENTS; IFN-GAMMA; GENE-EXPRESSION; PERIPHERAL-BLOOD; IN-VITRO; ANTIGEN; LYMPHOCYTES; PEPTIDE; QUANTIFICATION AB Tumor-associated antigens are present in several malignancies and represent promising targets for immunotherapeutic approaches. Antigen-specific CD8+ T-cells are an important component of immunosurveillance in malignant diseases as they recognize, target, and kill tumor cells. The induction of T-cells reactive against epitopes of tumor-associated antigens is the major immunological aim of several cancer vaccination trials. In recent years, significant progress has been made in developing methods to detect and characterize these antigen-specific T-cells. Here, we review and compare the most important techniques for specific T-cell analyses including cytokine-based functional assays, HLA class I/epitope tetrameric complexes, and PCR-based methods. We emphasize single cell methods and underline the importance of ex vivo methods without prior culturing. C1 NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), NIH, Dept Transfus Med, Ctr Clin, Bldg 10,Room 1C711,10 Ctr Dr, Bethesda, MD 20892 USA. NR 45 TC 4 Z9 4 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0258-851X J9 IN VIVO JI In Vivo PD NOV-DEC PY 2002 VL 16 IS 6 BP 519 EP 525 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 626HT UT WOS:000179866300017 PM 12494896 ER PT J AU Nagorsen, D Marincola, FM Kaiser, HE AF Nagorsen, D Marincola, FM Kaiser, HE TI Bacteria-related spontaneous and therapeutic remission of human malignancies SO IN VIVO LA English DT Review DE tumor; remission; bacteria; immunology ID ACUTE MYELOID-LEUKEMIA; RENAL-CELL CARCINOMA; TUMOR-INFILTRATING LYMPHOCYTES; ACUTE MYELOGENOUS LEUKEMIA; HUMAN DENDRITIC CELLS; MHC CLASS-I; SPONTANEOUS REGRESSION; HEPATOCELLULAR-CARCINOMA; T-CELLS; CARCINOEMBRYONIC ANTIGEN AB The development of specific immunotherapeutic approaches to cancer treatment is making progress. However, a crucial clinical break-through in cancer vaccination is still missing. Spontaneous clinical remissions of malignancies are a rare phenomenon. The mechanisms are not clear but there are remissions described in correlation with bacterial infections. The use of bacteria or bacterial components might be a promising path for non-specific immunotherapy of tumors and might be a helpful adjuvant for specific immunotherapy. Here, we briefly review spontaneous remissions of various malignancies in humans, the impact of bacterial infection on tumor regression and the utilization of bacterial components in clinical trials. C1 NIH, Ctr Clin, Dept Transfus Med, Immunogenet Sect, Bethesda, MD 20892 USA. RP Nagorsen, D (reprint author), NIH, Ctr Clin, Dept Transfus Med, Immunogenet Sect, Bldg 10,Room 1C711,10 Ctr Dr, Bethesda, MD 20892 USA. NR 107 TC 5 Z9 5 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0258-851X J9 IN VIVO JI In Vivo PD NOV-DEC PY 2002 VL 16 IS 6 BP 551 EP 556 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 626HT UT WOS:000179866300021 PM 12494900 ER PT J AU Nasir, A Copeland, J Gillespie, J Chughtai, OR Andrawis, R Kaiser, HE Manyak, MJ AF Nasir, A Copeland, J Gillespie, J Chughtai, OR Andrawis, R Kaiser, HE Manyak, MJ TI Preneoplastic lesions of the prostate-clinical, pathological and molecular biological aspects SO IN VIVO LA English DT Review DE prostate; preneoplasia; preneoplastic; prostatic intraepithelial neoplasia; PIN; atypical adenomatous hyperplasia; AAH; glandular atypia; atypical small acinar proliferation; ASAP; clinical; pathology; molecular biology; review ID ATYPICAL ADENOMATOUS HYPERPLASIA; SMALL ACINAR PROLIFERATION; NEEDLE-BIOPSY SPECIMENS; INTRAEPITHELIAL NEOPLASIA; PREMALIGNANT LESION; HISTOLOGIC FEATURES; RADICAL PROSTATECTOMY; ANDROGEN DEPRIVATION; INVASIVE-CARCINOMA; PRECURSOR LESIONS AB Needle biopsy is the mainstay of definitive diagnosis of prostate cancer (PCA). While prostate-specific antigen (PSA) screening has facilitated early diagnosis of PCA, it has also resulted in an increase in the proportion of prostate biopsies showing various preneoplastic lesions (PNLs). At times such lesions are the sole finding in the limited amount of tissue available for assessment in an individual biopsy. Hence accurate identification of these lesions is important to avoid errors in the diagnosis of prostatic malignancy and in patient management. Furthermore, some interesting observations have been made regarding the molecular biological aspects of various PNLs during the last decade. In parallel with anatomic and physiological differences in various human races, racial differences have also been observed regarding the incidence of prostatic intra-epithelial neoplasia. This review focuses on prostatic intraepithelial neoplasia (PIN), atypical adenomatous hyperplasia (AAH) and atypical prostatic glands or atypical small acinar proliferation (ASAP) as putative preneoplastic lesions of the prostate. These lesions are reviewed with reference to their overall incidence, histopathological findings, histological differential diagnosis, clinical significance and molecular biological aspects. C1 Univ S Florida, Sch Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Pathol, Tampa, FL 33612 USA. Int Soc Study Comparat Oncol Inc, Silver Spring, MD 20901 USA. Univ Rochester, Med Ctr, Dept Pathol & Lab Med, Rochester, NY 14642 USA. NCI, Sci Applicat Int Corp, Bethesda, MD 20892 USA. Univ Texas, Sch Med, Dept Pathol & Lab Med, Houston, TX 77030 USA. George Washington Univ, Med Ctr, Dept Urol, Washington, DC 20037 USA. Int Inst Anticanc Res, Athens, Greece. RP Nasir, A (reprint author), Univ S Florida, Sch Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Pathol, 12902 Magnolia Dr, Tampa, FL 33612 USA. NR 76 TC 3 Z9 3 U1 1 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0258-851X J9 IN VIVO JI In Vivo PD NOV-DEC PY 2002 VL 16 IS 6 BP 557 EP 566 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 626HT UT WOS:000179866300022 PM 12494901 ER PT J AU Montenegro, SML Abath, FGC Domingues, ALC Melo, WG Morais, CNL Coutinho, EM Mahanty, S Wynn, TA AF Montenegro, SML Abath, FGC Domingues, ALC Melo, WG Morais, CNL Coutinho, EM Mahanty, S Wynn, TA TI Enhanced interleukin-12 and CD40 ligand activities but reduced Staphylococcus aureus Cowan 1-induced responses suggest a generalized and progressively impaired type 1 cytokine pattern for human schistosomiasis SO INFECTION AND IMMUNITY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; BLOOD MONONUCLEAR-CELLS; IFN-GAMMA; MURINE SCHISTOSOMIASIS; GRANULOMA-FORMATION; INFECTED PATIENTS; INTERFERON-GAMMA; CYTOTOXIC ACTIVITY; IMMUNE-RESPONSE; REGULATORY ROLE AB Whole-blood-cell cultures from schistosomiasis patients were stimulated with a variety of T-cell-dependent and T-cell-independent stimuli to determine whether the defect in type 1 cytokine expression observed following helminth infection is associated with alterations in interleukin-12 (IL-12) or CD40 ligand (CD40L) responsiveness. Cultures from uninfected individuals produced abundant gamma interferon in response to Staphylococcus aureus Cowan 1 (SAC), while patients with intestinal and hepatosplenic disease displayed intermediate and weak responses, respectively. Importantly, the decrease in type 1 cytokine expression was not attributed to defects in IL-12- or CD40L-induced activity. Indeed, schistosomiasis patients displayed heightened responses and even produced more biologically active IL-12 when stimulated with SAC and CD40L than did uninfected controls. Finally, additional studies suggested only a partial role for IL-10, since intestinal patients were the only group that overproduced this downregulatory cytokine. Together, these studies demonstrate that the type 1 deficiency in chronic hepatosplenic schistosomiasis is not related to specific defects in IL-12, IL-10, or CD40L activity, although changes in the functional status of antigen-presenting cells appear to be involved. C1 NIAID, Parasit Dis Lab, NIH, MSC 8003, Bethesda, MD 20892 USA. Fiocruz MS, Ctr Pesquisas Aggeu Magalhaes, Dept Imunol, Recife, PE, Brazil. Univ Fed Pernambuco, Recife, PE, Brazil. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Wynn, TA (reprint author), NIAID, Parasit Dis Lab, NIH, MSC 8003, Room 6154,50 South Dr, Bethesda, MD 20892 USA. RI Wynn, Thomas/C-2797-2011; OI Mahanty, Siddhartha/0000-0003-1068-0524 NR 46 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 2002 VL 70 IS 11 BP 5903 EP 5912 DI 10.1128/IAI.70.11.5903-5912.2002 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 605JQ UT WOS:000178675100001 PM 12379664 ER PT J AU Jiao, XN Hirano, T Hou, YC Gu, XX AF Jiao, XN Hirano, T Hou, YC Gu, XX TI Specific immune responses and enhancement of murine pulmonary clearance of Moraxella catarrhalis by intranasal immunization with a detoxified lipooligosaccharide conjugate vaccine SO INFECTION AND IMMUNITY LA English DT Article ID OUTER-MEMBRANE PROTEIN; BRANHAMELLA-CATARRHALIS; HAEMOPHILUS-INFLUENZAE; LYMPHOID-TISSUE; LIPOPOLYSACCHARIDE ANTIGENS; RESPIRATORY-TRACT; MUCOSAL DELIVERY; ANIMAL-MODEL; B-SUBUNIT; ANTIBODY AB Moraxella catarrhalis is an important human mucosal pathogen. This study investigated the effect of intranasal immunization with a detoxified-lipooligosaccharide-cross-reactive mutant of diphtheria toxin (dLOS-CRM) vaccine candidate on pulmonary clearance following an aerosol challenge of mice with M. catarrhalis. Intranasal immunization with dLOS-CRM plus cholera toxin induced a significantly dose-dependent increase of immunoglobulin A (IgA) and IgG in the nasal wash, lung lavage fluid, saliva, and fecal extract. In addition, serum IgG, IgM, and IgA against LOS of M. catarrhalis were detected. LOS-specific antibody-forming cells were found in the nasal passages, spleens, nasally associated lymphoid tissues, cervical lymph nodes, lungs, and Peyer's patches using an enzyme-linked immunospot assay. The dLOS-CRM vaccine induced a significant bacterial clearance (70 to 90%) of both homologous and heterologous strains in the lungs compared to that observed in the controls (P < 0.01). Intriguingly, intranasal immunization with dLOS-CRM showed a higher level of bacterial clearance compared with subcutaneous injections with dLOS-CRM. These data indicate that dLOS-CRM induces specific mucosal and systemic immunity through intranasal immunization and also provides effective bacterial clearance. On the basis of these results, we believe that dLOS-CRM should undergo continued testing to determine whether it would induce protective immune response in humans. C1 Natl Inst Deafness & Other Commun Disorders, NIH, Rockville, MD 20850 USA. RP Gu, XX (reprint author), 5 Res Court, Rockville, MD 20850 USA. NR 45 TC 27 Z9 29 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 2002 VL 70 IS 11 BP 5982 EP 5989 DI 10.1128/IAI.70.11.5982-5989.2002 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 605JQ UT WOS:000178675100010 PM 12379673 ER PT J AU Wipasa, J Xu, HJ Makobongo, M Gatton, M Stowers, A Good, MF AF Wipasa, J Xu, HJ Makobongo, M Gatton, M Stowers, A Good, MF TI Nature and specificity of the required protective immune response that develops postchallenge in mice vaccinated with the 19-kilodalton fragment of Plasmodium yoelii merozoite surface protein 1 SO INFECTION AND IMMUNITY LA English DT Article ID CARBOXYL-TERMINAL FRAGMENT; CD4(+) T-CELLS; MALARIA INFECTION; RODENT MALARIA; IMMUNIZATION; MSP1(19) AB Immunity induced by the 19-kDa fragment of Plasmodium yoelii merozoite surface protein 1 (MSP1(19)) is dependent on high titers of specific antibodies present at the time of challenge and a continuing active immune response postinfection. However, the specificity of the active immune response postinfection has not been defined. In particular, it is not known whether anti-MSP1(19) antibodies that arise following infection alone are sufficient for protection. We developed systems to investigate whether an MSP1(19)-specific antibody response alone both prechallenge and postchallenge is sufficient for protection. We were able to exclude antibodies with other specificities, as well as any contribution of MSP1(19)-specific CD4(+) T cells acting independent of antibody, and we concluded that an immune response focused solely on MSP1(19)-specific antibodies is sufficient for protection. The data imply that the ability of natural infection to boost an MSPI,g-specific antibody response should greatly improve vaccine efficacy. C1 Queensland Inst Med Res, Cooperat Res Ctr Vaccine Technol, Herston, Qld 4029, Australia. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Good, MF (reprint author), Queensland Inst Med Res, Cooperat Res Ctr Vaccine Technol, PO Royal Brisbane Hosp, Herston, Qld 4029, Australia. OI Gatton, Michelle/0000-0003-1188-609X NR 14 TC 14 Z9 15 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 2002 VL 70 IS 11 BP 6013 EP 6020 DI 10.1128/IAI.70.11.6013-6020.2002 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 605JQ UT WOS:000178675100014 PM 12379677 ER PT J AU Somerville, GA Chaussee, MS Morgan, CI Fitzgerald, JR Dorward, DW Reitzer, LJ Musser, JM AF Somerville, GA Chaussee, MS Morgan, CI Fitzgerald, JR Dorward, DW Reitzer, LJ Musser, JM TI Staphylococcus aureus aconitase inactivation unexpectedly inhibits post-exponential-phase growth and enhances stationary-phase survival SO INFECTION AND IMMUNITY LA English DT Article ID BACILLUS-SUBTILIS ACONITASE; RNA-BINDING PROTEIN; STREPTOCOCCUS-PYOGENES; ESCHERICHIA-COLI; VIRULENCE GENES; EXPRESSION; IDENTIFICATION; INFECTION; DIFFERENTIATION; ACTIVATION AB Staphylococcus aureus preferentially catabolizes glucose, generating pyruvate, which is subsequently oxidized to acetate under aerobic growth conditions. Catabolite repression of the tricarboxylic acid (TCA) cycle results in the accumulation of acetate. TCA cycle derepression coincides with exit from the exponential growth phase, the onset of acetate catabolism, and the maximal expression of secreted virulence factors. These data suggest that carbon and energy for post-exponential-phase growth and virulence factor production are derived from the catabolism of acetate mediated by the TCA cycle. To test this hypothesis, the aconitase gene was genetically inactivated in a human isolate of S. aureus, and the effects on physiology, morphology, virulence factor production, virulence for mice, and stationary-phase survival were examined. TCA cycle inactivation prevented the post-exponential growth phase catabolism of acetate, resulting in premature entry into the stationary phase. This phenotype was accompanied by a significant reduction in the production of several virulence factors and alteration in host-pathogen interaction. Unexpectedly, aconitase inactivation enhanced stationary-phase survival relative to the wild-type strain. Aconitase is an iron-sulfur cluster-containing enzyme that is highly susceptible to oxidative inactivation. We speculate that reversible loss of the iron-sulfur cluster in wild-type organisms is a survival strategy used to circumvent oxidative stress induced during host-pathogen interactions. Taken together, these data demonstrate the importance of the TCA cycle in the life cycle of this medically important pathogen. C1 NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. NIAID, Rocky Mt Microscopy Branch, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. Univ Texas, Dept Mol & Cellular Biol, Richardson, TX 75083 USA. RP NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM jmusser@niaid.nih.gov RI Somerville, Greg/B-1326-2013; Reitzer, Larry/A-2510-2016 OI Somerville, Greg/0000-0002-0991-8737; NR 43 TC 101 Z9 105 U1 0 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 2002 VL 70 IS 11 BP 6373 EP 6382 DI 10.1128/IAI.70.11.6373-6382.2002 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 605JQ UT WOS:000178675100054 PM 12379717 ER PT J AU Xue, HH Fink, DW Zhang, XL Qin, J Turck, CW Leonard, WJ AF Xue, HH Fink, DW Zhang, XL Qin, J Turck, CW Leonard, WJ TI Serine phosphorylation of Stat5 proteins in lymphocytes stimulated with IL-2 SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE cytokine; mass spectrometry; retroviral transduction; signal transduction; T lymphocyte ID MAMMARY-GLAND; ACTIVATION; TYROSINE; TRANSACTIVATION; INTERLEUKIN-2; TRANSCRIPTION; EXPRESSION; REQUIRES; PATHWAY; FAMILY AB Tyrosine phosphorylation regulates cytokine-induced dimerization of STAT proteins. Serine phosphorylation has also been found to occur in a number of STAT proteins, including Stat1, Sat3, Stat4, Stat5a, Stat5b and Stat6, and was shown to be important for maximal transcriptional activation mediated by Stat1, Stat3 and Stat4, but not for Stat5a or Stat5b. As these latter proteins were studied in transiently transfected COS-7 cells stimulated with prolactin, we sought to further investigate the significance of their serine phosphorylation in a more physiologically based system in response to IL-2. Both Stat5a and Stat5b were rapidly phosphorylated on serine in response to IL-2 and the phosphorylation site in Stat5a was mapped to Ser780, which is not conserved in Stat5b. In vitro studies with reporter constructs, and experiments in which wild-type and mutant Stat5a retroviruses were used to transduce Stat5a-deficient splenocytes revealed that the serine mutant constructs were not diminished in their ability to mediate IL-2 signaling and if anything exhibited augmented proliferative capability. Thus, in contrast to the apparent importance of serine phosphorylation for transcriptional activation by Stat1, Stat3 and Stat4 in response to IFN, IL-6 and IL-12 respectively, serine phosphorylation of Stat5a does not enhance Stat5a-mediated signaling in response to IL-2. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. US FDA, CBER, Lab Stem Cell Biol Neurotroph Factors, Rockville, MD 20825 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. EM wjl@helix.nih.gov NR 30 TC 14 Z9 15 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD NOV PY 2002 VL 14 IS 11 BP 1263 EP 1271 DI 10.1093/intimm/dxf101 PG 9 WC Immunology SC Immunology GA 611TP UT WOS:000179034100004 PM 12407017 ER PT J AU Jelicks, LA Chandra, M Shirani, J Shtutin, V Tang, BY Christ, GJ Factor, SM Wittner, M Huang, H Weiss, LM Mukherjee, S Bouzahzah, B Petkova, SB Teixeira, MM Douglas, SA Loredo, ML D'Orleans-Juste, P Tanowitz, HB AF Jelicks, LA Chandra, M Shirani, J Shtutin, V Tang, BY Christ, GJ Factor, SM Wittner, M Huang, H Weiss, LM Mukherjee, S Bouzahzah, B Petkova, SB Teixeira, MM Douglas, SA Loredo, ML D'Orleans-Juste, P Tanowitz, HB TI Cardioprotective effects of phosphoramidon on myocardial structure and function in murine Chagas' disease SO INTERNATIONAL JOURNAL FOR PARASITOLOGY LA English DT Article DE Chagas' disease; Trypanosoma cruzi; phosphoramidon endothelin-converting enzyme; endothelin; neutral endopeptidases; cardiac magnetic resonance imaging; echocardiography; mice ID ENDOTHELIN-CONVERTING ENZYME; TRYPANOSOMA-CRUZI INFECTION; CHRONIC HEART-FAILURE; BIG ENDOTHELIN-1; CARDIAC-FUNCTION; BLOOD-FLOW; MICE; EXPRESSION; INHIBITOR; RELEASE AB Chagas' disease is an important cause of cardiomyopathy. Endothelin-1, a vasoactive peptide has been implicated in the pathogenesis of chagasic cardiomyopathy. C57BL/6 X 129sv and CD1 mice were thus, infected with trypomastigotes of Trypanosoma cruzi (Brazil strain) and these infected mice were compared with infected mice treated with phosphoramidon. This compound inhibits endothelin-converting enzyme and neutral endopeptidases and does not affect the growth of the parasite in culture. Phosphoramidon was given in a dose of 10 mg/kg for the initial 15 days post-infection None of the C57B1/6 X 129sv mice died as a result of infection. However, there was marked myocardial inflammation and fibrosis in infected, untreated mice. The hearts of the infected, phosphoramidon-treated mice showed significantly less pathology. Cardiac magnetic resonance imaging of infected mice revealed right ventricular dilation that was less severe in those treated with phosphoramidon. Phosphoramidon-treated CD1 mice survived the acute infection. Transthoracic echocardiography demonstrated left ventricular dilation and reduced percent fractional shortening and relative wall thickness. These alterations were also attenuated as a result of phosphoramidon treatment. These data suggest that endothelin-1 contributes to the pathogenesis of chagasic cardiomyopathy and interventions that inhibit the synthesis of endothelin-1 and/or neutral endopeptidase might have a protective effect on myocardial structure and function in murine Chagas' disease. (C) 2002 Australian Society for Parasitology Inc. Published by Elsevier Science Ltd. All rights reserved. C1 Albert Einstein Coll Med, Dept Pathol, Div Trop Med & Parasitol, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Physiol & Biophys, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Med, Div Cardiol, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Urol, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Med, Div Infect Dis, Bronx, NY 10461 USA. Inst Ciencias Biol, Dept Biochem & Immunol, BR-31270901 Belo Horizonte, MG, Brazil. Glaxo SmithKline, Dept Cardiovasc Pharmacol, King Of Prussia, PA 19406 USA. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. Univ Sherbrooke, Fac Med, Dept Pharmacol, Sherbrooke, PQ J1H 5N4, Canada. RP Tanowitz, HB (reprint author), Albert Einstein Coll Med, Dept Pathol, Div Trop Med & Parasitol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. RI Teixeira, Mauro/A-4587-2008 OI Teixeira, Mauro/0000-0002-6944-3008 FU NIAID NIH HHS [AI-12770, AI-41752] NR 49 TC 29 Z9 29 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0020-7519 J9 INT J PARASITOL JI Int. J. Parasit. PD NOV PY 2002 VL 32 IS 12 BP 1497 EP 1506 AR PII S0020-7519(02)00136-4 DI 10.1016/S0020-7519(02)00136-4 PG 10 WC Parasitology SC Parasitology GA 615CH UT WOS:000179227900007 PM 12392915 ER PT J AU Tchounwou, PB Wilson, BA Abdelghani, AA Ishaque, AB Patlolla, AK AF Tchounwou, P. B. Wilson, B. A. Abdelghani, A. A. Ishaque, A. B. Patlolla, A. K. TI Differential Cytotoxicity and Gene Expression in Human Liver Carcinoma (HepG(2)) Cells Exposed to Arsenic Trioxide, and Monosodium Acid Methanearsonate (MSMA) SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Article DE Arsenic; chemical species; differential toxicity; gene expression; HepG(2) cells ID NF-KAPPA-B; INDUCIBLE TRANSCRIPTION; DRINKING-WATER; DNA-DAMAGE; PROTEIN; ACTIVATION; PROMOTER; AGENTS; FOS; METALLOTHIONEIN AB Research in our laboratory has demonstrated that a trivalent form of arsenic such as arsenic trioxide (AT) has the ability to cause significant cytotoxicity, and induction of a significant number of stress genes in human liver carcinoma cells (HepG(2)). However, the literature also indicates that the toxicity of arsenic depends on its chemical form. To test this hypothesis, we further evaluated the cellular and molecular responses of HepG(2) cells following exposure to monosodium acid methanearsonate (MSMA), a pentavalent and organic form of arsenic. Cytotoxicity was evaluated using the MTT-assay for cell viability, while the gene profile assay was performed to measure the degree of gene induction in 13 different recombinant cell lines generated from a parental HepG(2) cell line. Cytotoxicity experiments yielded LC50 values of 11.9 +/- 2.6 mu g/mL for AT, and 257.3 +/- 51.4 mu g/mL for MSMA; indicating that AT was about 20 times more toxic than MSMA. Exposure of HepG(2) cells to MSMA also resulted in a significant reduction (p < 0.05) in the number of stress genes induced, compared to AT. Upon MSMA exposure, only 2 (HMTIIA and HSP70) out of the 13 constructs evaluated yielded inductions to statistically significant levels (p < 0.05), compared to 11 (GSTYa, XRE, HMTIIA, c-fos, NF-kBRE, HSP70, p53RE, GADD153, GADD45, and GRP78) for AT. These results greatly support the hypothesis that the toxicity of arsenic compounds highly depends on their chemical forms; with the inorganic forms being more potent than the organic ones. C1 [Tchounwou, P. B.; Wilson, B. A.; Ishaque, A. B.; Patlolla, A. K.] Jackson State Univ, Mol Toxicol Res Lab, NIH, Ctr Environm Hlth,Sch Sci & Technol, Jackson, MS 39217 USA. [Abdelghani, A. A.] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Environm Hlth Sci, New Orleans, LA 70112 USA. RP Tchounwou, PB (reprint author), Jackson State Univ, Mol Toxicol Res Lab, NIH, Ctr Environm Hlth,Sch Sci & Technol, 1400 Lynch St,POB 18540, Jackson, MS 39217 USA. EM paul.b.tchounwou@jsums.edu FU National Institutes of Health through the RCMI-Center for Environmental Health at Jackson State University [1G12RR13459] FX This research was financially supported by a grant from the National Institutes of Health (Grant No. 1G12RR13459), through the RCMI-Center for Environmental Health at Jackson State University. We thank Dr. Abdul Mohamed, Dean of the School of Science and Technology at Jackson State University, and Dr. Prescott Deininger, Zimmerman Chair, and Associate Director of Tulane University Cancer Center, for their technical advice on this project. NR 53 TC 19 Z9 20 U1 0 U2 1 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1422-0067 J9 INT J MOL SCI JI Int. J. Mol. Sci. PD NOV-DEC PY 2002 VL 3 IS 11 BP 1117 EP 1132 DI 10.3390/i3111117 PG 16 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA V33ID UT WOS:000209011600002 ER PT J AU D'Antonio, A Losito, S Pignata, S Grassi, M Perrone, F De Luca, A Tambaro, R Bianco, C Gullick, WJ Johnson, GR Iaffaioli, VR Salomon, DS Normanno, N AF D'Antonio, A Losito, S Pignata, S Grassi, M Perrone, F De Luca, A Tambaro, R Bianco, C Gullick, WJ Johnson, GR Iaffaioli, VR Salomon, DS Normanno, N TI Transforming growth factor alpha, amphiregulin and cripto-1 are frequently expressed in advanced human ovarian carcinomas SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE cripto-1; amphiregulin; TGF alpha; ovarian cancer; prognosis ID FACTOR-RELATED PROTEINS; EGF SUPERGENE FAMILY; BREAST-CANCER CELLS; FACTOR RECEPTOR; ANTISENSE OLIGONUCLEOTIDES; IMMUNOHISTOCHEMICAL DETECTION; HUMAN MALIGNANCIES; EPITHELIAL-CELLS; MESSENGER-RNA; COLON AB The expression of transforming growth factor alpha (TGFalpha), amphiregulin (AR) and cripto-1 (CR-1) was assessed by immunohistochemistry in 83 specimens (59 primary ovarian tumors and 24 extra-ovarian carcinomas) that were obtained from 68 ovarian carcinoma patients. Within the 59 primary tumors, 54 (92%) expressed immunoreactive TGFalpha, 45 (76%) expressed AR, and 28 (47%) expressed CR-1. The expression of AR and CR-1 mRNAs in the ovarian carcinomas was also demonstrated by RT-PCR analysis. Seventeen extra-ovarian specimens (71%) were found to express CR-1, whereas AR and TGFalpha were expressed respectively in 21 (87%) and 22 (92%) extra-ovarian tissues. In 15 cases for whom both ovarian and extra-ovarian tissues were available, a statistically significant higher expression of CR-1 was found in extra-ovarian specimens. A statistically significant correlation was found between AR expression in the ovarian carcinomas and both low grade and low proliferative activity. Finally, expression of TGFalpha was predictive of longer progression-free survival. These data strongly suggest that the EGF-related peptides might be involved in the pathogenesis and outcome of human ovarian cancer. C1 ITN Fdn Pascale, Serv Oncol Spimentale D, I-80131 Naples, Italy. ITN Fdn Pascale, Serv Anat Patol, I-80131 Naples, Italy. ITN Fdn Pascale, Div Oncol Med B, I-80131 Naples, Italy. ITN Fdn Pascale, Ufficio Sperimentaz Clin Controllate, I-80131 Naples, Italy. AORN Cardarelli, Naples, Italy. NCI, Tumor Growth Factor Sect, Basic Res Lab, NIH, Bethesda, MD 20892 USA. Univ Kent, Dept Biosci, Canterbury CT2 7NJ, Kent, England. US FDA, DTP, Bethesda, MD 20892 USA. RP Normanno, N (reprint author), ITN Fdn Pascale, Serv Oncol Spimentale D, I-80131 Naples, Italy. RI De Luca, Antonella/J-8737-2016; OI De Luca, Antonella/0000-0001-5762-447X; Normanno, Nicola/0000-0002-7158-2605 NR 32 TC 53 Z9 54 U1 1 U2 3 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD NOV PY 2002 VL 21 IS 5 BP 941 EP 948 PG 8 WC Oncology SC Oncology GA 603RX UT WOS:000178574600003 PM 12370739 ER PT J AU Poggi, MM Kroog, GS Russo, A Muir, C Cook, J Smith, J Mitchell, JB Herscher, LL AF Poggi, MM Kroog, GS Russo, A Muir, C Cook, J Smith, J Mitchell, JB Herscher, LL TI Phase I study of weekly gemcitabine as a radiation sensitizer for unresectable pancreatic cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE gemcitabine; radiation; pancreas; sensitizer ID TRIAL; ADENOCARCINOMA; THERAPY AB Purpose: To determine the maximal tolerated dose and dose-limiting toxicities (DLTs) of weekly gemcitabine with concurrent radiotherapy (RT) in patients with unresectable adenocarcinoma of the pancreas. Methods and Materials: Patients who had locally advanced or recurrent unresectable pancreatic cancer were eligible. Gemcitabine was administered as a 30-min infusion once weekly for a total of five cycles during the course of RT. The starting dose of gemcitabine was 350 mg/m(2)/wk. Doses were escalated by increments of 25% in successive cohorts of 3-6 patients. RT was delivered at 180 cGy/d to a total dose of 5400-5580 cGy to the gross tumor volume. Results: Nineteen patients were entered in this study through three dose levels (350-550 mg/m(2)/wk). The maximal tolerated dose was determined to be 440 mg/m(2)/wk. The DLTs were neutropenia, thrombocytopenia, and failure to receive all five cycles of gemcitabine. Other non-DLTs included 16 Grade III toxicities, which consisted of thrombosis, infection, nausea, vomiting, hypotension, constipation, diarrhea, and fatigue. One patient at each gemcitabine dose level experienced Grade IV vomiting, and the patient at the 550 mg/m(2) dose developed Grade IV anorexia. Conclusion: The maximal tolerated dose of gemcitabine when administered as a 30-min infusion once weekly during RT for unresectable pancreatic cancer was found to be 440 mg/m2/wk. The DLTs were neutropenia, thrombocytopenia, and failure to receive all five cycles of chemotherapy. Concurrent gemcitabine and RT is reasonably well tolerated and deserves additional evaluation against the current standard of care. 0 2002 Elsevier Science Inc. C1 NCI, Radiat Oncol Branch, Radiat Oncol Sci Program, Div Canc Treatment,NIH, Bethesda, MD 20892 USA. RP Poggi, MM (reprint author), NCI, Radiat Oncol Branch, Radiat Oncol Sci Program, Div Canc Treatment,NIH, 9000 Rockville Pike,Bldg 10,Rm B3B69, Bethesda, MD 20892 USA. NR 20 TC 31 Z9 37 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2002 VL 54 IS 3 BP 670 EP 676 AR PII S0360-3016(02)02980-2 DI 10.1016/S0360-3016(02)02980-2 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 606CG UT WOS:000178715200009 PM 12377317 ER PT J AU Maminishkis, A Jalickee, S Blaug, SA Rymer, J Yerxa, BR Peterson, WM Miller, SS AF Maminishkis, A Jalickee, S Blaug, SA Rymer, J Yerxa, BR Peterson, WM Miller, SS TI The P2Y(2) receptor agonist INS37217 stimulates RPE fluid transport in vitro and retinal reattachment in rat SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID PIGMENT-EPITHELIUM; ION-TRANSPORT; INTRACELLULAR CALCIUM; EXTRACELLULAR ATP; SUBRETINAL SPACE; CL CONDUCTANCE; CELLS; ABSORPTION; MOBILIZATION; MECHANISMS AB PURPOSE. To investigate the effects of INS37217, a synthetic P2Y(2) receptor agonist, on intracellular calcium signaling, electrophysiology, and fluid transport in vitro and on experimentally induced retinal detachment in rat eyes in vivo. METHODS. Freshly isolated monolayers of bovine and human fetal RPE were mounted in Ussing chambers for measurements of cytosolic calcium levels ([Ca2+](i)), membrane voltages and resistances, and transepithelial fluid transport. Retinal detachments were experimentally produced in Long-Evans rats by injecting modified phosphate-buffered saline into the subretinal space (SRS). Experimental or vehicle solutions were injected into the vitreous, and the size of blebs in the SRS was scored under masked conditions. RESULTS. Addition of INS37217 to Ringer's solution bathing the apical membrane transiently increased [Ca2+](i), altered membrane voltages and resistances and generally produced responses that were similar in magnitude to those of uridine triphosphate (UTP). In fluid transport experiments performed with the capacitance probe technique, INS37217 significantly increased fluid absorption across freshly isolated bovine and fetal human RPE monolayers. All in vitro results were blocked by apical 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), which has been shown to block P2Y(2) receptors in the RPE. Intravitreal administration of INS37217, but not UTP, in the rat model of retinal detachment enhanced the removal of SRS fluid and facilitated retinal reattachment when compared with vehicle control. CONCLUSIONS. These findings indicate that INS37217 stimulates the RPE fluid "pump" function in vitro by activating P2Y(2) receptors at the apical membrane. In vivo INS37217 enhances the rates of subretinal fluid reabsorption in experimentally induced retinal detachments in rats and may be therapeutically useful for treating a variety of retinal diseases that result in fluid accumulation in the subretinal space. C1 Univ Calif Berkeley, Sch Optometry, Berkeley, CA 94720 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. Inspire Pharmaceut, Durham, NC USA. RP Miller, SS (reprint author), NEI, NIH, Bldg 31,Rm 6A03,31 Ctr Dr MSC 2510, Bethesda, MD 20892 USA. FU NEI NIH HHS [EY02205, EY03176] NR 49 TC 69 Z9 73 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 2002 VL 43 IS 11 BP 3555 EP 3566 PG 12 WC Ophthalmology SC Ophthalmology GA 609AB UT WOS:000178879500026 PM 12407168 ER PT J AU Freedman, MH Alter, BP AF Freedman, MH Alter, BP TI Malignant myeloid transformation in congenital forms of neutropenia SO ISRAEL MEDICAL ASSOCIATION JOURNAL LA English DT Article DE congenital neutropenia; granulocyte colony-stimulating factor; acute myeloid leukemia; myelodysplasia ID STIMULATING-FACTOR-RECEPTOR; SHWACHMAN-DIAMOND-SYNDROME; ACUTE MYELOGENOUS LEUKEMIA; G-CSF; MUTATIONS; GENE; AGRANULOCYTOSIS; PATIENT; ACTIVATION; APOPTOSIS AB Background: Granulocyte colony-stimulating factor has had a major impact on the management of severe chronic neutropenia - a collective term referring to congenital, idiopathic, or cyclic neutropenia. Almost all patients. respond to G-CSF with increased neutrophils,; reduced infections, and improved survival. Some responders with congenital neutropenia (termed Kostmann's syndrome herein) and Shwachman-Diamond syndrome have developed myelodysplastic syndrome and acute myeloid leukemia, which raises the question of the role of G-CSF in pathogenesis. The issue is complicated because both disorders have a propensity for MDS or AML as part of their natural history. Objective and Methods: To address this, the Severe Chronic Neutropenia International Registry used its large database of chronic neutropenia patients treated with G-CSF to determine the incidence of malignant myeloid transformation in the two disorders, and its relationship to treatment and to other patient characteristics. Results: As of January 2001, of the 383 patients with congenital forms of neutropenia in the Registry, 48 had MDS or AML (crude rate, about 12.5%). No statistically significant relationships were found between age at onset of MDS or AML and patient gender, G-CSF dose, or duration of G-CSF therapy. What was observed, however, was the multistep acquisition of aberrant cellular genetic changes in marrow cells from Kostmann's syndrome patients who transformed, including activating vas oncogene mutations, clonal cytogenetic abnormalities, and G-CSF receptor mutations. The latter in murine models produces a hyperproliferative response to G-CSF, confers resistance to apoptosis, and enhances cell survival. Conclusions: Since Kostmann's syndrome and Shwachman-Diamond syndrome are inherited forms of bone marrow failure, G-CSF I may accelerate the propensity for MDS/AML in the genetically altered stem and progenitor cells, especially in those with G-CSF receptor and vas mutations (82% and 50% of Kostmann's syndrome patients who transform, respectively). Alternatively, and equally plausible, G-CSF may simply be an innocent bystander that corrects neutropenia, 1 prolongs patient survival; and allows time for the malignant predisposition to declare itself. Only careful long-term follow-up of the cohort of patients receiving G-CSF will provide the answer. C1 Hosp Sick Children, Div Hematol Oncol, Toronto, ON M5G 1X8, Canada. Hosp Sick Children, Inst Res, Toronto, ON M5G 1X8, Canada. Natl Canc Inst, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Freedman, MH (reprint author), Hosp Sick Children, Div Hematol Oncol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. NR 25 TC 11 Z9 12 U1 1 U2 1 PU ISRAEL MEDICAL ASSOC JOURNAL PI RAMAT GAN PA 2 TWIN TOWERS, 11TH FL, 35 JABOTINSKY ST, PO BOX 3604, RAMAT GAN 52136, ISRAEL SN 1565-1088 J9 ISRAEL MED ASSOC J JI Isr. Med. Assoc. J. PD NOV PY 2002 VL 4 IS 11 BP 1011 EP 1014 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 673HM UT WOS:000182574800011 PM 12489493 ER PT J AU Veech, RL Kashiwaya, Y Gates, DN King, MT Clarke, K AF Veech, RL Kashiwaya, Y Gates, DN King, MT Clarke, K TI The energetics of ion distribution: The origin of the resting electric potential of cells SO IUBMB LIFE LA English DT Review DE Delta G ' of ATP hydrolysis; Gibbs-Donnan equilibrium; ion gradients; membrane potential ID RAT-LIVER; HEART; MG2+; PHOSPHATE; MAGNESIUM; TISSUES; GLUCOSE; ENERGY; STATE; ATP AB The relation between the energies of ion movement and ATP hydrolysis is unknown in tissues with widely varying electric potentials. Consequently, we measured the concentration of the nine major inorganic ions in the extra- and intracellular phases in heart, liver, and red cells with resting electrical potentials, E-N, of -86, -28, and -6 mV, respectively, under six different physiological conditions. We calculated the Nernst electric potential and the energy of ion movement between the phases. We found that the energy of ATP hydrolysis was essentially constant, between -54 and -58 kJ/mol, in all tissues and conditions. In contrast, as EN decreased, the energies of the Na+ and K+ gradients decreased, with slopes approximating their valence. The difference between the energies of Na+ and K+ gradients remained constant at 17 kJ/mol, which is approximately one third of the energy of ATP hydrolysis, demonstrating near-equilibrium of the Na+/K+ ATPase in all tissues under all conditions. All cations, except K+, were pumped out of cells and all anions, except Cl- in liver and red cell, were pumped into cells. We conclude that the energy of ATP was expressed in Na+/K+ ATPase and its linked inorganic ion transporters to create a Gibbs-Donnan near-equilibrium system, an inherent part of which was the electric potential. C1 NIAAA, LMBB, Rockville, MD 20852 USA. Univ Oxford, Dept Biochem, Oxford OX1 3QU, England. RP Veech, RL (reprint author), NIAAA, LMBB, 12501 Washington Ave, Rockville, MD 20852 USA. FU British Heart Foundation [PS/02/002/14893] NR 36 TC 23 Z9 24 U1 0 U2 8 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1521-6543 J9 IUBMB LIFE JI IUBMB Life PD NOV PY 2002 VL 54 IS 5 BP 241 EP 252 DI 10.1080/15216540290114540 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 634GQ UT WOS:000180332000002 PM 12587974 ER EF