FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Hoque, ATMS Smith, RH Kotin, RM Golding, B AF Hoque, ATMS Smith, RH Kotin, RM Golding, B TI High levels of foreign gene expression in hemophiliac mice after intravenous injection of a non-viral vector SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 OBRR, CBER, Food & Drug Adm, Lab Plasma Derivat,Div Hematol, Bethesda, MD USA. NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. NR 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 533 BP S208 EP S208 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300532 ER PT J AU Huszthy, PC Svendsen, A Thorsen, F Enger, PO Tysnes, BB Afione, S Kotin, R Halbert, C Miller, AD Wilson, J Lonning, PE Bjerkvig, R Hoover, F AF Huszthy, PC Svendsen, A Thorsen, F Enger, PO Tysnes, BB Afione, S Kotin, R Halbert, C Miller, AD Wilson, J Lonning, PE Bjerkvig, R Hoover, F TI Transduction of human glioblastoma xenografts in vivo by adeno-associated vector serotypes SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 Haukeland Hosp, Dept Oncol, N-5021 Bergen, Norway. NHLBI, Lab Biochem Genet, NIH, Bethesda, MD USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. Univ Penn, Philadelphia, PA 19104 USA. RI Huszthy, Peter Csaba/H-1414-2016 OI Huszthy, Peter Csaba/0000-0003-0184-8989 NR 0 TC 0 Z9 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 473 BP S185 EP S185 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300472 ER PT J AU Jagadeesh, GJ Wallace, RN Muul, LM Holt, IE Schurman, SH Wolfsberg, TG Candotti, F AF Jagadeesh, GJ Wallace, RN Muul, LM Holt, IE Schurman, SH Wolfsberg, TG Candotti, F TI Retroviral vector insertion sites in patients subjected to T-cell directed gene transfer SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 Natl Human Genome Res Inst, NIH, Bethesda, MD USA. NIH, HHMI Res Scholar Program, Bethesda, MD USA. NR 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 3 BP S1 EP S2 PN 2 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300004 ER PT J AU Kimchi-Sarfaty, C Garfield, S Vieira, WD Alexander, NS Oppenheim, A Gottesman, MM AF Kimchi-Sarfaty, C Garfield, S Vieira, WD Alexander, NS Oppenheim, A Gottesman, MM TI Efficient gene transfer using an SV40 in vitro packaging system SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Hadassah Univ Hosp, Hadassah Med Sch, IL-91010 Jerusalem, Israel. NR 0 TC 1 Z9 1 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 1220 BP S472 EP S472 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740301219 ER PT J AU Kok, MR Voutetakis, A Yamano, S Wang, JH Katano, H Bossis, I Afione, S Schmidt, M Chiorini, JA Tak, PP Baum, BJ AF Kok, MR Voutetakis, A Yamano, S Wang, JH Katano, H Bossis, I Afione, S Schmidt, M Chiorini, JA Tak, PP Baum, BJ TI Immune responses following salivary gland administration of recombinant adenoassociated virus serotype 2 vectors SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 NIH, Gene Therapy & Therapeut Branch, Bethesda, MD USA. Univ Amsterdam, AMC, Div Clin Immunol & Rheumatol, Amsterdam, Netherlands. NR 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 477 BP S187 EP S187 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300476 ER PT J AU Kuramoto, K Laukkanen, MO Sellers, SE Hematti, P Adler, RL Metzger, M Krouse, A Donahue, R von Kalle, C Dunbar, CE AF Kuramoto, K Laukkanen, MO Sellers, SE Hematti, P Adler, RL Metzger, M Krouse, A Donahue, R von Kalle, C Dunbar, CE TI Low-dose busulfan markedly impacts on in vivo hematopoietic stem cell dynamics: A genetic tracking analysis SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 NHLBI, Mol Hematopoiesis Sect, NIH, Bethesda, MD USA. Childrens Hosp Res Fdn, Cincinnati, OH 45229 USA. NR 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 396 BP S156 EP S156 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300396 ER PT J AU Leal-Pinto, E Teixeira, A Henderson, SC Hawkins, ME Klotman, PE Hanss, B AF Leal-Pinto, E Teixeira, A Henderson, SC Hawkins, ME Klotman, PE Hanss, B TI New insight into cellular uptake of nucleic acids: A role for the nucleic acid-conducting channel SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 Mt Sinai Sch Med, New York, NY USA. NCI, Pediat Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 24 BP S10 EP S10 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300025 ER PT J AU Liem, RI Frazar, TF Seidel, NE Garrett, LJ Gallagher, PG Bodine, DM AF Liem, RI Frazar, TF Seidel, NE Garrett, LJ Gallagher, PG Bodine, DM TI Development of a retroviral vector containing the erythroid band 3 promoter flanked by the chicken beta-globin 5 ' HS4 insulator SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Dept Pediat, New Haven, CT USA. NR 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 852 BP S329 EP S329 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300851 ER PT J AU Lodde, BM Delporte, C Goldsmith, CM Tak, PP Baum, BJ AF Lodde, BM Delporte, C Goldsmith, CM Tak, PP Baum, BJ TI Construction of recombinant viral vectors encoding vasoactive intestinal peptide for local applications in a mouse model of Sjogren's syndrome SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 NIDCR, Gene Therapy & Therapeut Branch, DHHS, NIH, Bethesda, MD USA. Acad Med Ctr, Amsterdam, Netherlands. Free Univ Brussels, Dept Biochem & Nutr, Fac Med, Brussels, Belgium. NR 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 1050 BP S404 EP S405 PN 2 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740301049 ER PT J AU Lucas, ML Seidel, N Porada, C Anderson, S Malech, H Quigley, J Abkowitz, J Zanjani, E Bodine, D AF Lucas, ML Seidel, N Porada, C Anderson, S Malech, H Quigley, J Abkowitz, J Zanjani, E Bodine, D TI Pseudotyping retroviral vectors with RD114 or FeLV-C envelopes improves transduction of human HSC SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 Univ Nevada, Reno, NV 89557 USA. NIAID, NIH, Bethesda, MD USA. Washington Univ, St Louis, WA USA. NR 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 393 BP S155 EP S155 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300393 ER PT J AU Moayeri, M Myrup, AC Wagner, SJ Morgan, RA Hawley, TS Hawley, RG Ramezani, A AF Moayeri, M Myrup, AC Wagner, SJ Morgan, RA Hawley, TS Hawley, RG Ramezani, A TI Toward cell therapy for hemophilia A: Recombinant factor VIII production from blood endothelial cells SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 George Washington Univ, Ctr Med, Program Genet, Washington, DC USA. George Washington Univ, Ctr Med, Dept Anat & Cell Biol, Washington, DC USA. Amer Red Cross, Holland Lab, Hematopoiesis Dept, Rockville, MD USA. Amer Red Cross, Holland Lab, Blood & Cell Therapy Dev, Rockville, MD USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NR 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 1019 BP S393 EP S393 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740301018 ER PT J AU Morrison, BJ Sakai, Y Janik, JE Morris, JC AF Morrison, BJ Sakai, Y Janik, JE Morris, JC TI Adenoviral transduction efficiency and phenotype of human monocyte-derived dendritic cells generated in media supplemented with fetal calf serum or human plasma SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 NCI, Ctr Canc Res, Metab Branch, Bethesda, MD 20892 USA. NR 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 718 BP S277 EP S277 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300717 ER PT J AU Pfutzner, W Jensen, T Nachtigall, I Vogel, J AF Pfutzner, W Jensen, T Nachtigall, I Vogel, J TI A preclinical animal model to achieve persistent transgene expression by in-vivo transduction of keratinocytes SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 Univ Munich, Dept Dermatol, D-8000 Munich, Germany. Aarhus Univ, Dept Human Genet, Aarhus, Denmark. NIH, Dermatol Branch, Bethesda, MD USA. NR 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 372 BP S146 EP S146 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300372 ER PT J AU Sachdeva, G Cho, JE Arya, SK AF Sachdeva, G Cho, JE Arya, SK TI External regulation of lentiviral vectors by targeting transcriptional activation loop SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. NR 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 1155 BP S445 EP S445 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740301154 ER PT J AU Sakai, Y Morrison, BJ Burke, JD Park, JM Forni, G Berzofsky, JA Morris, JC AF Sakai, Y Morrison, BJ Burke, JD Park, JM Forni, G Berzofsky, JA Morris, JC TI Vaccination with bone marrow-derived dendritic cells modified by recombinant adenoviral vectors expressing the HER-2/neu oncogene inhibits development of tumors in a transgenic mouse model of breast cancer SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 NCI, Metab Branch, Canc Res Ctr, Bethesda, MD 20892 USA. Univ Turin, Dept Clin & Biol Sci, Turin, Italy. NR 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 47 BP S18 EP S19 PN 2 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300048 ER PT J AU Sellers, SE Tisdale, SF Hematti, P Kuramoto, K Adler, R Laukkanen, M Calmels, B Takatoku, M Hu, J Wu, T Shi, P Agricola, BA Metzger, ME West, E Bonifacino, A An, DS Chen, ISY Donahue, RE Dunbar, CE AF Sellers, SE Tisdale, SF Hematti, P Kuramoto, K Adler, R Laukkanen, M Calmels, B Takatoku, M Hu, J Wu, T Shi, P Agricola, BA Metzger, ME West, E Bonifacino, A An, DS Chen, ISY Donahue, RE Dunbar, CE TI Long-term follow-up of rhesus macaques receiving CD34+cells transduced with retroviral or lentiviral vectors SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NIDDKD, Mol Hematol Branch, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Sch Med, Aids Inst, Los Angeles, CA USA. RI calmels, boris/R-2538-2016 NR 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 395 BP S156 EP S156 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300395 ER PT J AU Smith, BF Morris, GE Kornegay, JN Bartlett, RJ AF Smith, BF Morris, GE Kornegay, JN Bartlett, RJ TI Rapid identification of novel canine models of Duchenne muscular dystrophy SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 Auburn Univ, Scott Ritchey Res Ctr, Auburn, AL 36849 USA. Univ Wales, NEWI, Wrexham, Wales. Univ Missouri, Coll Vet Med, Columbia, MO USA. NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 256 BP S101 EP S101 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300257 ER PT J AU Sumner, SG Davies, LA Varathalingam, A Chiorini, JA Gill, DR Hyde, SC AF Sumner, SG Davies, LA Varathalingam, A Chiorini, JA Gill, DR Hyde, SC TI Investigation of rAAV5 as a vector for gene transfer to mouse lung SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 Univ Oxford, NDCLS, Gene Med Res Grp, Oxford, England. NIDCR, Gene Therapeut Branch, NIH, Bethesda, MD USA. NR 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 484 BP S189 EP S190 PN 2 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300483 ER PT J AU Templeton, NS Roberts, DD AF Templeton, NS Roberts, DD TI Use of expression profiling to create chimeric promoter-enhancer cassettes for robust nonviral gene therapeutics SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 1133 BP S438 EP S438 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740301132 ER PT J AU Terunuma, A Jackson, KL Kapoor, V Telford, WG Vogel, JC AF Terunuma, A Jackson, KL Kapoor, V Telford, WG Vogel, JC TI Side population (SP) cells are present in human epidermis and phenotypically distinct from conventional epidermal stem cell candidates SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NR 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 1037 BP S400 EP S400 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740301036 ER PT J AU Tuan, RS AF Tuan, RS TI Skeletal tissue engineering applications of multipotential mesenchymal stem cells derived from adult human tissues SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 NIAMS, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD USA. NR 0 TC 2 Z9 2 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 270 BP S106 EP S106 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300271 ER PT J AU Verbeek, B Smirnow, I Bauer, M Schuppan, D Feldman, AL Gregor, M Lauer, UM Graepler, F AF Verbeek, B Smirnow, I Bauer, M Schuppan, D Feldman, AL Gregor, M Lauer, UM Graepler, F TI Antiangiogenic gene therapy for the treatment of hepatocellular carcinoma via adenoviral-expressed endostatin SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 Univ Clin Tubingen, Dept Internal Med 1, Tubingen, Germany. Univ Clin Erlangen Nuernberg, Dept Internal Med 1, Erlangen, Germany. NCI, Lab Surg Branch, Bethesda, MD 20892 USA. RI Feldman, Andrew/D-5028-2012 NR 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 1110 BP S428 EP S428 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740301109 ER PT J AU Voutetakis, A Kok, MR Bossis, I Zhang, WT Zheng, CY Marracino, N Goldsmith, CM Chiorini, JA Loh, YP Nieman, LK Baum, BJ Wang, JH AF Voutetakis, A Kok, MR Bossis, I Zhang, WT Zheng, CY Marracino, N Goldsmith, CM Chiorini, JA Loh, YP Nieman, LK Baum, BJ Wang, JH TI Long term functional erythropoietin production from salivary glands after rAAV-Mediated gene transfer SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 NICHD, DHHS, SCN, Lab Dev Neurobiol,NIH, Bethesda, MD USA. NICHD, DHHS, Reprod Endocrinol Branch, NIH, Bethesda, MD USA. Univ Amsterdam, AMC, Div Clin Immunol & Rheumatol, Amsterdam, Netherlands. NIDCR, DHHS, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD USA. NR 0 TC 2 Z9 2 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 474 BP S185 EP S186 PN 2 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300473 ER PT J AU Wang, JH Cawley, NX Voutetakis, A Rodriguez-David, YM Goldsmith, CM Nieman, LK Loh, YP Baum, BJ AF Wang, JH Cawley, NX Voutetakis, A Rodriguez-David, YM Goldsmith, CM Nieman, LK Loh, YP Baum, BJ TI Re-engineering the secretion of transgene-encoded neuroendocrine proteins from rat salivary glands SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 NIDCR, Gene Therapy & Therapeut Branch, NIH, DHHS, Bethesda, MD USA. NICHD, Dev Neurobiol Lab, NIH, DHHS, Bethesda, MD USA. NICHD, Pediat Reprod Endocrinol Branch, NIH, DHHS, Bethesda, MD USA. NR 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 373 BP S146 EP S146 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300373 ER PT J AU Wellner, RB Cotrim, AP Vitolo, JM Marmary, Y Xavier, S Mitchell, JB Baum, BJ AF Wellner, RB Cotrim, AP Vitolo, JM Marmary, Y Xavier, S Mitchell, JB Baum, BJ TI Effect of the overexpression of human manganese superoxide dismutase (hMnSOD) on the irradiation resistance of a rat submandibular epithelial cell line SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 NIDCR, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD USA. Hebrew Univ Jerusalem, Dept Oral Med, Jerusalem, Israel. NCI, Radiat Biol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 1087 BP S419 EP S419 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740301086 ER PT J AU Wu, XL Burgess, S AF Wu, XL Burgess, S TI Transcription start site regions are favored targets for MLV integration in human genome SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 Natl Human Genome Res Inst, Genome Technol Branch, Bethesda, MD USA. NR 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 1 BP S1 EP S1 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300002 ER PT J AU Yamanaka, R Tanaka, R Xanthopoulos, K AF Yamanaka, R Tanaka, R Xanthopoulos, K TI Induction of therapeutic antitumor antiangiogenesis by intratumoral injection of genetically engineered endostatin-producing Semliki Forest virus SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 Niigata Univ, Brain Res Inst, Niigata, Japan. NHGRI, NIH, Bethesda, MD USA. NR 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 316 BP S125 EP S125 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300317 ER PT J AU Zhang, LQ Pepples, ME Collins, PL Pickles, RJ AF Zhang, LQ Pepples, ME Collins, PL Pickles, RJ TI RSV and PIV3 target human ciliated airway epithelial cells: Efficienct gene transfer vectors for cystic fibrosis lung disease? SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 Univ N Carolina, CF Pulm Res & Treatment Ctr, Chapel Hill, NC USA. Rush Presbyterian St Lukes Med Ctr, Dept Immunol & Microbiol, Chicago, IL 60612 USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 91 BP S36 EP S37 PN 2 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300092 ER PT J AU Zheng, CY Baum, BJ AF Zheng, CY Baum, BJ TI Evaluation of viral and mammalian promoters for use in gene delivery to salivary glands SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 NIDCR, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD USA. NR 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 1144 BP S441 EP S441 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740301143 ER PT J AU Hirotsune, S Yoshida, N Chen, A Garrett, L Sugiyama, F Takahashi, S Yagami, K Wynshaw-Boris, A Yoshiki, A AF Hirotsune, S Yoshida, N Chen, A Garrett, L Sugiyama, F Takahashi, S Yagami, K Wynshaw-Boris, A Yoshiki, A TI An expressed pseudogene regulates the messenger-RNA stability of its homologous coding gene SO NATURE LA English DT Article AB A pseudogene is a gene copy that does not produce a functional, full-length protein(1). The human genome is estimated to contain up to 20,000 pseudogenes(2,3). Although much effort has been devoted to understanding the function of pseudogenes, their biological roles remain largely unknown. Here we report the role of an expressed pseudogene-regulation of messenger-RNA stability-in a transgene-insertion mouse mutant exhibiting polycystic kidneys and bone deformity. The transgene was integrated into the vicinity of the expressing pseudogene of Makorin1, called Makorin1-p1. This insertion reduced transcription of Makorin1-p1, resulting in destabilization of Makorin1 mRNA in trans by way of a cis-acting RNA decay element within the 5' region of Makorin1 that is homologous between Makorin1 and Makorin1-p1. Either Makorin1 or Makorin1-p1 transgenes could rescue these phenotypes. Our findings demonstrate a specific regulatory role of an expressed pseudogene, and point to the functional significance of non-coding RNAs. C1 Saitama Med Sch, Res Ctr Genom Med, Div Neurosci, Hidaka, Saitama 3501241, Japan. Japan Sci & Technol Corp, PRESTO, Kawaguchi, Saitama, Japan. NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. Univ Tsukuba, Inst Basic Med Sci, Tsukuba, Ibaraki 3058575, Japan. Univ Tsukuba, Lab Anim Resource Ctr, Tsukuba, Ibaraki 3058575, Japan. Univ Calif San Diego, Sch Med, Ctr Canc, Dept Pediat, La Jolla, CA 92093 USA. Univ Calif San Diego, Sch Med, Ctr Canc, Dept Med, La Jolla, CA 92093 USA. RIKEN Tsukuba Inst, Bioresource Ctr, Dept Biol Syst, Expt Anim Div, Tsukuba, Ibaraki 3050074, Japan. RP Hirotsune, S (reprint author), Saitama Med Sch, Res Ctr Genom Med, Div Neurosci, Yamane 1397-1, Hidaka, Saitama 3501241, Japan. RI Yoshiki, Atsushi/A-6036-2016 OI Yoshiki, Atsushi/0000-0002-9450-5151 NR 8 TC 290 Z9 315 U1 1 U2 25 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 1 PY 2003 VL 423 IS 6935 BP 91 EP 96 DI 10.1038/nature01535 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 673CG UT WOS:000182561600045 PM 12721631 ER PT J AU Cho-Chung, YS Becker, KG AF Cho-Chung, YS Becker, KG TI A genome-wide view of antisense SO NATURE BIOTECHNOLOGY LA English DT Letter ID DNA MICROARRAY; OLIGONUCLEOTIDES C1 NCI, Cellular Biochem Sect, Basic Res Lab, Bethesda, MD 20892 USA. NIA, DNA Array Unit, Baltimore, MD 21224 USA. RP Cho-Chung, YS (reprint author), NCI, Cellular Biochem Sect, Basic Res Lab, Bethesda, MD 20892 USA. NR 6 TC 8 Z9 8 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAY PY 2003 VL 21 IS 5 BP 492 EP 492 DI 10.1038/nbt0503-492a PG 1 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 674WN UT WOS:000182660300013 PM 12721568 ER PT J AU Yamamoto, Y Tsutsumi, Y Yoshioka, Y Nishibata, T Kobayashi, K Okamoto, T Mukai, Y Shimizu, T Nakagawa, S Nagata, S Mayumi, T AF Yamamoto, Y Tsutsumi, Y Yoshioka, Y Nishibata, T Kobayashi, K Okamoto, T Mukai, Y Shimizu, T Nakagawa, S Nagata, S Mayumi, T TI Site-specific PEGylation of a lysine-deficient TNF-alpha with full bioactivity SO NATURE BIOTECHNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; RENAL-CELL CARCINOMA; CHRONIC HEPATITIS-C; POLYETHYLENE-GLYCOL; ANTITUMOR-ACTIVITY; MOLECULAR DESIGN; INTERFERON ALPHA-2A; MUTATIONAL ANALYSIS; SOLID TUMORS; PHASE-II AB Addition of polyethylene glycol to protein (PEGylation) to improve stability and other characteristics is mostly nonspecific and may occur at all lysine residues, some of which may be within or near an active site. Resultant PEGylated proteins are heterogeneous and can show markedly lower bioactivity. We attempted to develop a strategy for site-specific mono-PEGylation using tumor necrosis factor-alpha (TNF-alpha). We prepared phage libraries expressing TNF-alpha mutants in which all the lysine residues were replaced with other amino acids. A fully bioactive lysine-deficient mutant TNF-alpha (mTNF-alpha-Lys(-)) was isolated by panning against TNF-alpha-neutralizing antibody despite reports that some lysine residues were essential for its bioactivity. mTNF-alpha-Lys(-) was site-specifically mono-PEGylated at its N terminus. This mono-PEGylated mTNF-a-Lys(-), with superior molecular uniformity, showed higher bioactivity in vitro and greater antitumor therapeutic potency than randomly mono-PEGylated wild-type TNF-alpha. These results suggest the usefulness of the phage display system for creating functional mutant proteins and of our site-specific PEGylation approach. C1 Osaka Univ, Grad Sch Pharmaceut Sci, Dept Biopharmaceut, Suita, Osaka 5650871, Japan. NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Tsutsumi, Y (reprint author), Osaka Univ, Grad Sch Pharmaceut Sci, Dept Biopharmaceut, 1-6 Yamadaoka, Suita, Osaka 5650871, Japan. NR 33 TC 175 Z9 180 U1 0 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAY PY 2003 VL 21 IS 5 BP 546 EP 552 DI 10.1038/nbt812 PG 7 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 674WN UT WOS:000182660300032 PM 12665803 ER PT J AU Clyne, RK Katis, VL Jessop, L Benjamin, KR Herskowitz, I Lichten, M Nasmyth, K AF Clyne, RK Katis, VL Jessop, L Benjamin, KR Herskowitz, I Lichten, M Nasmyth, K TI Polo-like kinase Cdc5 promotes chiasmata formation and cosegregation of sister centromeres at meiosis I SO NATURE CELL BIOLOGY LA English DT Article ID DOUBLE-STRAND BREAKS; MEIOTIC RECOMBINATION; SACCHAROMYCES-CEREVISIAE; YEAST; PROTEIN; COHESIN; ANAPHASE; DNA; CHROMOSOMES; SPORULATION AB During meiosis, two rounds of chromosome segregation occur after a single round of DNA replication, producing haploid progeny from diploid progenitors. Three innovations in chromosome behaviour during meiosis I accomplish this unique division. First, crossovers between maternal and paternal sister chromatids (detected cytologically as chiasmata) bind replicated maternal and paternal chromosomes together. Second, sister kinetochores attach to microtubules from the same pole (mono-polar orientation), causing maternal and paternal centromere pairs (and not sister chromatids) to be separated. Third, sister chromatid cohesion near centromeres is preserved at anaphase I when cohesion along chromosome arms is destroyed. The finding that destruction of mitotic cohesion is regulated by Polo-like kinases(1,2) prompted us to investigate the meiotic role of the yeast Polo-like kinase Cdc5. We show here that cells lacking Cdc5 synapse homologues and initiate recombination normally, but fail to efficiently resolve recombination intermediates as crossovers. They also fail to properly localize the Lrs4 (ref. 3) and Mam1 (ref. 4) monopolin proteins, resulting in bipolar orientation of sister kinetochores. Cdc5 is thus required both for the formation of chiasmata and for cosegregation of sister centromeres at meiosis I. C1 Res Inst Mol Pathol, A-1030 Vienna, Austria. NCI, Biochem Lab, Canc Res Ctr, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA. RP Nasmyth, K (reprint author), Res Inst Mol Pathol, Dr Bohr Gasse 7, A-1030 Vienna, Austria. RI Lichten, Michael/C-5795-2013; OI Lichten, Michael/0000-0001-9707-2956; Nasmyth, Kim/0000-0001-7030-4403 NR 24 TC 129 Z9 134 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD MAY PY 2003 VL 5 IS 5 BP 480 EP 485 DI 10.1038/ncb977 PG 6 WC Cell Biology SC Cell Biology GA 675JR UT WOS:000182691400024 PM 12717442 ER PT J AU Hunter, K Welch, DR Liu, ET AF Hunter, K Welch, DR Liu, ET TI Genetic background is an important determinant of metastatic potential SO NATURE GENETICS LA English DT Letter ID BREAST-CANCER; MOUSE MODELS; PROGRESSION; EXPRESSION C1 NCI, Lab Populat Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. Genome Inst Singapore, Singapore 117528, Singapore. RP Hunter, K (reprint author), NCI, Lab Populat Genet, Ctr Canc Res, NIH, Bldg 41,Room D702,41 Lib Dr, Bethesda, MD 20892 USA. RI Liu, Edison/C-4141-2008; Welch, Danny/B-7310-2009 OI Welch, Danny/0000-0002-1951-4947 NR 9 TC 66 Z9 70 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAY PY 2003 VL 34 IS 1 BP 23 EP 24 DI 10.1038/ng0503-23b PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 674ZK UT WOS:000182667900008 PM 12721549 ER PT J AU Pollock, PM Cohen-Solal, K Sood, R Namkoong, J Martino, JJ Koganti, A Zhu, H Robbins, C Makalowska, I Shin, SS Marin, Y Roberts, KG Yudt, LM Chen, A Cheng, J Incao, A Pinkett, HW Graham, CL Dunn, K Crespo-Carbone, SM Mackason, KR Ryan, KB Sinsimer, D Goydos, J Reuhl, KR Eckhaus, M Meltzer, PS Pavan, WJ Trent, JM Chen, S AF Pollock, PM Cohen-Solal, K Sood, R Namkoong, J Martino, JJ Koganti, A Zhu, H Robbins, C Makalowska, I Shin, SS Marin, Y Roberts, KG Yudt, LM Chen, A Cheng, J Incao, A Pinkett, HW Graham, CL Dunn, K Crespo-Carbone, SM Mackason, KR Ryan, KB Sinsimer, D Goydos, J Reuhl, KR Eckhaus, M Meltzer, PS Pavan, WJ Trent, JM Chen, S TI Melanoma mouse model implicates metabotropic glutamate signaling in melanocytic neoplasia SO NATURE GENETICS LA English DT Article ID PROTEIN-COUPLED RECEPTORS; MGLUR1 MUTANT MICE; TRANSGENIC MICE; CELL-GROWTH; DEFICIT AB To gain insight into melanoma pathogenesis, we characterized an insertional mouse mutant, TG3, that is predisposed to develop multiple melanomas(1,2). Physical mapping identified multiple tandem insertions of the transgene into intron 3 of Grm1 (encoding metabotropic glutamate receptor 1) with concomitant deletion of 70 kb of intronic sequence. To assess whether this insertional mutagenesis event results in alteration of transcriptional regulation, we analyzed Grm1 and two flanking genes for aberrant expression in melanomas from TG3 mice. We observed aberrant expression of only Grm1. Although we did not detect its expression in normal mouse melanocytes, Grm1 was ectopically expressed in the melanomas from TG3 mice. To confirm the involvement of Grm1 in melanocytic neoplasia, we created an additional transgenic line with Grm1 expression driven by the dopachrome tautomerase promoter. Similar to the original TG3, the Tg(Grm1)EPv line was susceptible to melanoma. In contrast to human melanoma, these transgenic mice had a generalized hyperproliferation of melanocytes with limited transformation to fully malignant metastasis. We detected expression of GRM1 in a number of human melanoma biopsies and cell lines but not in benign nevi and melanocytes. This study provides compelling evidence for the importance of metabotropic glutamate signaling in melanocytic neoplasia. C1 Rutgers State Univ, Ernest Mario Sch Pharm, Dept Biol Chem, Susan Lehman Cullman Lab Canc Res, Piscataway, NJ 08854 USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Genom Technol Branch, NIH, Bethesda, MD 20892 USA. Rutgers State Univ, Ernest Mario Sch Pharm, Dept Pharmacol & Toxicol, Piscataway, NJ 08854 USA. NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Surg, Piscataway, NJ 08854 USA. Canc Inst New Jersey, New Brunswick, NJ 08903 USA. NIH, Vet Resources Program, Off Res Serv, Bethesda, MD 20892 USA. RP Chen, S (reprint author), Rutgers State Univ, Ernest Mario Sch Pharm, Dept Biol Chem, Susan Lehman Cullman Lab Canc Res, Piscataway, NJ 08854 USA. RI Pinkett, Heather/M-9235-2014 NR 20 TC 148 Z9 156 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAY PY 2003 VL 34 IS 1 BP 108 EP 112 DI 10.1038/ng1148 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 674ZK UT WOS:000182667900026 PM 12704387 ER PT J AU Tibbetts, MD Zheng, LX Lenardo, MJ AF Tibbetts, MD Zheng, LX Lenardo, MJ TI The death effector domain protein family: regulators of cellular homeostasis SO NATURE IMMUNOLOGY LA English DT Review ID NF-KAPPA-B; AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; SIGNALING COMPLEX; KINASE-C; CASPASE-8 ACTIVATION; APOPTOSIS REGULATOR; RECEPTOR SIGNALS; FADD; FAS; FLIP AB The death effector domain (DED) occurs in proteins that regulate programmed cell death. Both pro- and anti-apoptotic proteins containing DEDs have been identified. For Fas and possibly other death receptors, homotypic DIED interactions connect the Fas-associated death domain (FADD) protein to caspase-8 and caspase-10 to mediate formation of the death-inducing signal complex. This complex can be inhibited by other DED-containing proteins. Accumulating evidence now suggests that DED-containing proteins have additional roles in controlling pathways of cellular activation and proliferation. Thus, the DED defines a family of proteins that may be pivotal to cellular homeostasis by establishing a 'cell renewal set point' that coregulates proliferation and apoptosis in parallel. C1 NIAID, Immunol Lab, Bethesda, MD 20892 USA. RP Lenardo, MJ (reprint author), NIAID, Immunol Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 74 TC 152 Z9 155 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAY PY 2003 VL 4 IS 5 BP 404 EP 409 DI 10.1038/ni0503-404 PG 6 WC Immunology SC Immunology GA 674YN UT WOS:000182665400003 PM 12719729 ER PT J AU Alberti, J Valenzuela, JG Carruthers, VB Hieny, S Andersen, J Charest, H Sousa, CRE Fairlamb, A Ribeiro, JM Sher, A AF Alberti, J Valenzuela, JG Carruthers, VB Hieny, S Andersen, J Charest, H Sousa, CRE Fairlamb, A Ribeiro, JM Sher, A TI Molecular mimicry of a CCR5 binding-domain in the microbial activation of dendritic cells SO NATURE IMMUNOLOGY LA English DT Article ID TOXOPLASMA-GONDII; CHEMOKINE RECEPTOR; BIOCHEMICAL-CHARACTERIZATION; CYCLOPHILIN; INTERLEUKIN-12; IMMUNOPHILINS; RESISTANCE; IMMUNITY; MALARIA; ANTIGEN AB Toxoplasma gondii releases factors that potently stimulate production of interleukin-12 (IL-12) from dendritic cells (DCs). Purification of this activity showed that cyclophilin-18 (C-18) was its principal component, and antibodies generated against recombinant C-18 inhibited tachyzoite extract-induced synthesis of IL-12. Recombinant C-18 showed high affinity for and triggered cell signaling through CCR5, a chemokine receptor important in parasite-induced IL-12 production by DCs. These findings suggest that the unusual potency of T gondii in inducing IL-12 from DCs results from its synthesis of a unique chemokine mimic that signals through CCR5. The ability to generate this strong protective response may benefit parasite transmission by preventing the protozoan from overwhelming its intermediate hosts. C1 NIAID, Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Med Entomol Sect, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. Johns Hopkins Bloomberg Sch Publ Hlth, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. Canc Res UK, London Res Inst, London WC2A 3PX, England. Univ Dundee, Dept Biochem, Dundee DD1 5EH, Scotland. RP Alberti, J (reprint author), NIAID, Immunol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RI Fairlamb, Alan/A-5272-2009; OI Fairlamb, Alan/0000-0001-5134-0329; Carruthers, Vern/0000-0001-6859-8895; Reis e Sousa, Caetano/0000-0001-7392-2119; Ribeiro, Jose/0000-0002-9107-0818 NR 20 TC 8 Z9 8 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAY PY 2003 VL 4 IS 5 BP 485 EP 490 DI 10.1038/ni915 PG 6 WC Immunology SC Immunology GA 674YN UT WOS:000182665400017 ER PT J AU Gladwin, MT Lancaster, JR Freeman, BA Schechter, AN AF Gladwin, MT Lancaster, JR Freeman, BA Schechter, AN TI Nitric oxide's reactions with hemoglobin: a view through the SNO-storm SO NATURE MEDICINE LA English DT Editorial Material ID HYPOXIC PULMONARY VASOCONSTRICTION; S-NITROSOTHIOL FORMATION; CELL-FREE HEMOGLOBIN; REGIONAL BLOOD-FLOW; RELAXING FACTOR; HUMAN PLASMA; L-ARGININE; BIOCHEMICAL-CHARACTERIZATION; CORONARY CIRCULATION; BIOLOGICAL-ACTIVITY C1 NIDDKD, Dept Crit Care Med, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NIDDKD, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Alabama, Dept Anesthesiol, Birmingham, AL USA. Univ Alabama, UAB Ctr Free Rad Biol, Birmingham, AL USA. RP Gladwin, MT (reprint author), NIDDKD, Dept Crit Care Med, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. RI Freeman, Bruce/H-9342-2012; OI Schechter, Alan N/0000-0002-5235-9408 NR 66 TC 176 Z9 181 U1 0 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 2003 VL 9 IS 5 BP 496 EP 500 DI 10.1038/nm0503-496 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 673ZD UT WOS:000182610600016 PM 12724752 ER PT J AU Francis, DD Szegda, K Campbell, G Martin, WD Insel, TR AF Francis, DD Szegda, K Campbell, G Martin, WD Insel, TR TI Epigenetic sources of behavioral differences in mice SO NATURE NEUROSCIENCE LA English DT Article ID PREPULSE INHIBITION; MATERNAL-BEHAVIOR; MOUSE; RESPONSES; GENETICS; STRAIN; STRESS; CARE C1 NIMH, Bethesda, MD 20892 USA. Emory Univ, Ctr Behav Neurosci, Yerkes Res Ctr, Atlanta, GA 30329 USA. Emory Univ, Transgen Mouse Core, Sch Med, Atlanta, GA 30329 USA. Emory Univ, Dept Psychiat & Behav Sci, Sch Med, Atlanta, GA 30329 USA. RP Insel, TR (reprint author), NIMH, 6001 Execut Blvd,Room 8235,MSC 9669, Bethesda, MD 20892 USA. NR 13 TC 228 Z9 233 U1 4 U2 33 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD MAY PY 2003 VL 6 IS 5 BP 445 EP 446 DI 10.1038/nn1038 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 672ZD UT WOS:000182553200007 PM 12665797 ER PT J AU Spiegel, S Milstien, S AF Spiegel, S Milstien, S TI Sphingosine-1-phosphate: An enigmatic signalling lipid SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID PROTEIN-COUPLED RECEPTOR; GROWTH-FACTOR RECEPTOR; INDUCED CELL MOTILITY; SPHINGOSINE 1-PHOSPHATE; SACCHAROMYCES-CEREVISIAE; DE-NOVO; SPHINGOLIPID BIOSYNTHESIS; ENDOPLASMIC-RETICULUM; FUNCTIONAL EXPRESSION; DEPENDENT ACTIVATION AB The evolutionarily conserved actions of the sphingolipid metabolite, sphingosine-1-phosphate (S1P), in yeast, plants and mammals have shown that it has important functions. In higher eukaryotes, S1P is the ligand for a family of five G-protein-coupled receptors. These S1P receptors are differentially expressed, coupled to various G proteins, and regulate angiogenesis, vascular maturation, cardiac development and immunity, and are important for directed cell movement. C1 Virginia Commonwealth Univ, Dept Biochem, Richmond, VA 23298 USA. NIMH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. RP Spiegel, S (reprint author), Virginia Commonwealth Univ, Dept Biochem, Med Coll Virginia Campus, Richmond, VA 23298 USA. NR 91 TC 1231 Z9 1261 U1 6 U2 66 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD MAY PY 2003 VL 4 IS 5 BP 397 EP 407 DI 10.1038/nrm1103 PG 11 WC Cell Biology SC Cell Biology GA 675HB UT WOS:000182687000020 PM 12728273 ER PT J AU Bonifacino, JS Lippincott-Schwartz, J AF Bonifacino, JS Lippincott-Schwartz, J TI Opinion - Coat proteins: shaping membrane transport SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID ENDOPLASMIC-RETICULUM; LIVING CELLS; GOLGI STACK; CLATHRIN ADAPTERS; SORTING SIGNALS; PLASMA-MEMBRANE; AP-1 COMPLEX; VESICLE; COPII; PURIFICATION C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Bonifacino, JS (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bldg 18T,Room 101, Bethesda, MD 20892 USA. OI Bonifacino, Juan S./0000-0002-5673-6370 NR 52 TC 241 Z9 245 U1 2 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD MAY PY 2003 VL 4 IS 5 BP 409 EP 414 DI 10.1038/nrm1099 PG 6 WC Cell Biology SC Cell Biology GA 675HB UT WOS:000182687000021 PM 12728274 ER PT J AU Kim, MH Cierpicki, T Derewenda, U Krowarsch, D Feng, YY Devedjiev, Y Dauter, Z Walsh, CA Otlewski, J Bushweller, JH Derewenda, ZS AF Kim, MH Cierpicki, T Derewenda, U Krowarsch, D Feng, YY Devedjiev, Y Dauter, Z Walsh, CA Otlewski, J Bushweller, JH Derewenda, ZS TI The DCX-domain tandems of doublecortin and doublecortin-like kinase SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID MICROTUBULE-ASSOCIATED PROTEIN; MOLTEN GLOBULE; STRUCTURAL BASIS; PC MOTIF; NMR; MUTATIONS; HOMOLOGY; APOMYOGLOBIN; REPLACEMENT; RECOGNITION AB The doublecortin-like domains (DCX), which typically occur in tandem, are novel microtubule-binding modules. DCX tandems are found in doublecortin, a 360-residue protein expressed in migrating neurons; the doublecortin-like kinase (DCLK); the product of the RP1 gene that is responsible for a form of inherited blindness; and several other proteins. Mutations in the gene encoding doublecortin cause lissencephaly in males and the 'double-cortex syndrome' in females. We here report a solution structure of the N-terminal DCX domain of human doublecortin and a 1.5 Angstrom resolution crystal structure of the equivalent domain from human DCLK. Both show a stable, ubiquitin-like tertiary fold with distinct structural similarities to GTPase-binding domains. We also show that the C-terminal DCX domains of both proteins are only partially folded. In functional assays, the N-terminal DCX domain of doublecortin binds only to assembled microtubules, whereas the C-terminal domain binds to both microtubules and unpolymerized tubulin. C1 Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA. Univ Wroclaw, Inst Biochem & Mol Biol, PL-50137 Wroclaw, Poland. Beth Israel Deaconess Med Ctr, Dept Neurol, Div Neurogenet, Boston, MA 02115 USA. Brookhaven Natl Lab, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, NCI, Upton, NY 11973 USA. RP Bushweller, JH (reprint author), Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA. RI Otlewski, Jacek/B-6340-2008 NR 55 TC 80 Z9 85 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD MAY PY 2003 VL 10 IS 5 BP 324 EP 333 DI 10.1038/nsb918 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 672RY UT WOS:000182536300007 PM 12692530 ER PT J AU Heymann, JB Cheng, NQ Newcomb, WW Trus, BL Brown, JC Steven, AC AF Heymann, JB Cheng, NQ Newcomb, WW Trus, BL Brown, JC Steven, AC TI Dynamics of herpes simplex virus capsid maturation visualized by time-lapse cryo-electron microscopy SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID CONFORMATIONAL-CHANGES; CRYOELECTRON MICROSCOPY; STRUCTURAL TRANSITIONS; BACTERIAL-VIRUS; RNA VIRUS; PROTEIN; CRYOMICROSCOPY; PROCAPSIDS; TYPE-1; MUTANT AB The capsid of the herpes simplex virus initially assembles as a procapsid that matures through a massive conformational change of its 182 MDa surface shell. This transition, which stabilizes the fragile procapsid, is facilitated by the viral protease that releases the interaction between the shell and the underlying scaffold; however, protease-deficient procapsids mature slowly in vitro. To study procapsid maturation as a time-resolved process, we monitored this reaction by cryo-electron microscopy (cryo-EM). The resulting images were sorted into 17 distinct classes, and three-dimensional density maps were calculated for each. When arranged in a chronological series, these maps yielded molecular movies of procapsid maturation. A single major switching event takes place at stages 8-9, preceded by relatively subtle adjustments in the pattern of interactions and followed by similarly small 'aftershocks'. The primary mechanism underlying maturation is relative rotations of domains of VP5, the major capsid protein. C1 NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Virginia Hlth Syst, Dept Microbiol, Charlottesville, VA 22908 USA. NIH, Imaging Sci Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Steven, AC (reprint author), NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. RI Heymann, Bernard/F-6825-2011; OI Heymann, Bernard/0000-0002-8872-5326 NR 43 TC 107 Z9 110 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD MAY PY 2003 VL 10 IS 5 BP 334 EP 341 DI 10.1038/nsb922 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 672RY UT WOS:000182536300008 PM 12704429 ER PT J AU Saad, ZS Ropella, KM DeYoe, EA Bandettini, PA AF Saad, ZS Ropella, KM DeYoe, EA Bandettini, PA TI The spatial extent of the BOLD response SO NEUROIMAGE LA English DT Article DE activation volume; functional magnetic resonance imaging; visual cortex; MRI methods/techniques ID PRIMARY VISUAL-CORTEX; CEREBRAL BLOOD-FLOW; RAT FOREPAW STIMULATION; TEST-RETEST RELIABILITY; HUMAN EXTRASTRIATE CORTEX; POINT-SPREAD FUNCTION; HUMAN STRIATE CORTEX; HUMAN BRAIN; SOMATOSENSORY CORTEX; OXIDATIVE-METABOLISM AB Functional magnetic resonance imaging is routinely used to localize brain function, with multiple brain scans averaged together to reveal activation volumes. In this study, we examine the seldom-studied effect of multiple scan averaging on the extent of activation volume. Using restricted visual field stimulation, we obtained a large number of scan repetitions and analyzed changes in activation volume with progressively increased averaging and across single scans. Activation volume increased monotonically with averaging and failed to asymptote when as many as 22 scans were averaged together. Expansions in the spatial extent of activation were not random; rather, they were centered about activation loci that appear with little or no averaging. Using empirical and simulated data, changes with averaging in activation volumes and cross correlation coefficient distributions revealed the presence of considerably more activated voxels than commonly surmised. Many voxels have low SNR and remain undetected without extensive averaging. The primary source of such voxels was not downstream venous drainage since there was no significant and consistent delay difference between voxels activated at different averaging levels. Voxels with low SNR may reflect a diffuse subthreshold activity centered about spiking neurons, dephasing gradients from distal veins, or simply a blood flow response extending beyond the locus of neuronal firing. Across single scans, as much as twofold changes in activation volume were observed. These changes were not correlated with the order of scan acquisition, subject task performance, or signal and noise properties of activated voxels. Instead, they may reflect subtle changes between overlapping noise and signal frequency components. (C) 2003 Elsevier Science (USA). All rights reserved. C1 NIMH, Stat & Sci Comp Core, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. Marquette Univ, Dept Biomed Engn, Milwaukee, WI 53233 USA. Med Coll Wisconsin, Dept Cell Biol Neurobiol & Anat, Milwaukee, WI 53226 USA. RP Saad, ZS (reprint author), NIMH, Stat & Sci Comp Core, Lab Brain & Cognit, NIH, 10 Ctr Dr,room 1D80, Bethesda, MD 20892 USA. FU NEI NIH HHS [EY10244]; NIMH NIH HHS [MH51358] NR 86 TC 54 Z9 54 U1 3 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY PY 2003 VL 19 IS 1 BP 132 EP 144 DI 10.1016/S1053-8119(03)00016-8 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 684ZP UT WOS:000183236600011 PM 12781733 ER PT J AU Turner, RS Grafton, ST McIntosh, AR DeLong, MR Hoffman, JM AF Turner, RS Grafton, ST McIntosh, AR DeLong, MR Hoffman, JM TI The functional anatomy of parkinsonian bradykinesia SO NEUROIMAGE LA English DT Review ID MOTOR CORTICAL INHIBITION; VENTRAL PREMOTOR CORTEX; BASAL GANGLIA; GLOBUS-PALLIDUS; LATERAL PREMOTOR; INTRAVENOUS (H2O)-O-15; PARIETAL OVERACTIVITY; SUBTHALAMIC NUCLEUS; COMPUTED-TOMOGRAPHY; BIMANUAL MOVEMENTS AB To investigate the difficulty that patients with Parkinson's disease (PD) have in performing fast movements, we used (H2O)-O-15 PET to study regional cerebral blood flow (rCBF) associated with performance of a simple predictive visuomanual tracking task at three different velocities. Tracking movements in PD patients (versus tracking with the eyes alone) were associated with a general underactivation of the areas normally activated by the task (sensorimotor cortex contralateral to the moving arm, bilateral dorsal premotor cortices, and ipsilateral cerebellum). Presupplementary motor cortex (pre-SMA) ipsilateral to the moving arm had greater than normal movement-related activations. Increasing movement velocity led to increased rCBF in multiple premotor and parietal cortical areas and basal ganglia in the patients as opposed to the few cerebral locations that are normally velocity-related. The functional correlates of PD bradykinesia. are: (1) impaired recruitment of cortical and subcortical systems that normally regulate kinematic parameters of movement such as velocity; and (2) increased recruitment of multiple premotor areas including both regions specialized for visuomotor control (ventral premotor and parietal cortices) and some that are not (pre-SMA). The overactivation of cortical regions observed in patients may be functional correlates of compensatory mechanisms and/or impaired suppression as a facet of the primary pathophysiology of PD. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. NCI, Bethesda, MD 20892 USA. Univ Toronto, Baycrest Ctr Geriatr Care, Rotman Res Inst, Toronto, ON, Canada. Dartmouth Coll, Ctr Cognit Neurosci, Hanover, NH 03755 USA. Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. RP Turner, RS (reprint author), Univ Calif San Francisco, Dept Neurol Surg, Box 0520, San Francisco, CA 94143 USA. RI McIntosh, Anthony/G-4955-2011; OI McIntosh, Anthony/0000-0002-1784-5662 FU NINDS NIH HHS [NS33704, NS37470] NR 101 TC 71 Z9 71 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY PY 2003 VL 19 IS 1 BP 163 EP 179 DI 10.1016/S1053-8119(03)00059-4 PG 17 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 684ZP UT WOS:000183236600014 PM 12781736 ER PT J AU Kellman, P van Gelderen, P de Zwart, JA Duyn, JH AF Kellman, P van Gelderen, P de Zwart, JA Duyn, JH TI Method for functional MRI mapping of nonlinear response SO NEUROIMAGE LA English DT Article ID RECEPTIVE-FIELD; BOLD RESPONSE; BALLOON MODEL; VISUAL-FIELD; BLOOD-FLOW; DYNAMICS; FMRI; NEURONS; KERNELS; BRAIN AB Nonlinear systems analysis combining blood oxygen level dependent (BOLD), functional magnetic resonance imaging (fMRI) and m-sequence stimulation paradigms are proposed as a new method for exploring neuronal responses and interactions. Previous studies of electrical activity in the human visual cortex have observed significant nonlinearities of task-induced activity with temporal dynamics on a timescale of 10-20 Ins. Despite the confounding effect of the seconds-long hemodynamic response, it is demonstrated that BOLD fMRI can be used to probe neuronal interactions on a time scale of tens of ms. Visual activation experiments were performed with various stimuli, and amplitude maps of first and second order kernel coefficients were generated using correlation analysis. Second order nonlinearities in BOLD fMRI were observed and attributed to temporal contrast caused by transitions in the stimulus sequence. In addition, the kernel maps showed significant differences between second order nonlinearities of foveal and peripheral vision. By including a reference experiment with a slightly modified stimulus presentation, a distinction could be made between (fast) neuronal nonlinearities and hemodynamic effects on the time scale of the seconds. The results indicate that BOLD fMRI can probe fast neuronal nonlinearities. C1 NHLBI, Lab Cardiac Energet, NIH, Bethesda, MD 20892 USA. NINDS, Adv MRI, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. RP Kellman, P (reprint author), NHLBI, Lab Cardiac Energet, NIH, 10B1D416,10 Ctr Dr, Bethesda, MD 20892 USA. RI Duyn, Jozef/F-2483-2010 NR 29 TC 21 Z9 23 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY PY 2003 VL 19 IS 1 BP 190 EP 199 DI 10.1016/S1053-8119(03)00056-9 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 684ZP UT WOS:000183236600016 PM 12781738 ER PT J AU Shirley, KL Hon, YY Penzak, SR Lam, YWF Spratlin, V Jann, MW AF Shirley, KL Hon, YY Penzak, SR Lam, YWF Spratlin, V Jann, MW TI Correlation of cytochrome P450 (CYP) 1A2 activity using caffeine phenotyping and olanzapine disposition in healthy volunteers SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE olanzapine; CYP1A2; pharmacokinetics; caffeine ID PLASMA-CONCENTRATIONS; IN-VIVO; METABOLITE RATIOS; CLINICAL-RESPONSE; CLOZAPINE; POLYMORPHISM; SALIVA; SCHIZOPHRENIA; ASSOCIATION; FLUVOXAMINE AB Olanzapine has previously been shown to have predominant metabolism by cytochrome (CYP) P450 1A2. Caffeine has been shown to provide an accurate phenotypic probe for measuring CYP1A2 activity. The purpose of this study is to determine if a significant correlation exists between olanzapine disposition and caffeine metabolic ratios. Subjects were phenotyped for CYP1A2 activity with caffeine probe methodology. After 200-mg caffeine administration, blood (4 h), saliva (6 and 10 h), and urine (8 h total) were collected for high-performance liquid chromatography (HPLC) analysis of caffeine and its metabolites. CYP1A2 activity was measured as plasma (PMR4h), saliva (SMR6h and SMR10h), and three urinary metabolic (UMR1(8h), UMR2(8h), and UMR3(8h)) ratios. Each of the 14 healthy nonsmokers (13 male) received a single 10 mg olanzapine dose after which blood was collected for HPLC determination of olanzapine concentrations at predose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96, and 120 h postdose. Olanzapine pharmacokinetic parameter's in this study were similar to those previously published. All caffeine metabolic ratios (PMR4h, SMR6h, SMR10h, UMR1(8h), and UMR2(8h)) significantly correlated with each other (p<0.001) except for UMR3(8h), which did not correlate. A significant correlation (p<0.05) was also found between olanzapine clearance and PMR4h (r=0.701), SMR6h (r=0.644), SMR10h (r=0.701), UMR1(8h) (r=0.745), and UMR2(8h) (r=0.710). A negative correlation was observed between olanzapine clearance and UMR3(8h) (r=-0.029, p=NS). A significant correlation was found between olanzapine clearance and various caffeine metabolic ratios. Interpatient variability in CYP1A2 activity may explain the wide interpatient variability in olanzapine disposition. Compounds that modulate CYP1A2 activity may be expected to alter olanzapine pharmacokinetics accordingly. C1 Mercer Univ, So Sch Pharm, Dept Clin & Adm Sci, Atlanta, GA 30341 USA. Albany Coll Pharm, Albany, NY USA. NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. RP Jann, MW (reprint author), Mercer Univ, So Sch Pharm, Dept Clin & Adm Sci, 3001 Mercer Univ, Atlanta, GA 30341 USA. NR 23 TC 31 Z9 32 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAY PY 2003 VL 28 IS 5 BP 961 EP 966 DI 10.1038/sj.npp.1300123 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 673QM UT WOS:000182591700017 PM 12644842 ER PT J AU Erickson, K Drevets, W Schulkin, J AF Erickson, K Drevets, W Schulkin, J TI Glucocorticoid regulation of diverse cognitive functions in normal and pathological emotional states SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Review DE glucocorticoids; emotion; cognition; amygdala; medial prefrontal; orbitofrontal; depression ID CORTICOTROPIN-RELEASING FACTOR; RECEPTOR MESSENGER-RNA; CHRONIC MILD STRESS; LEVEL CORTISOL TREATMENT; CHRONIC-FATIGUE-SYNDROME; CEREBRAL BLOOD-FLOW; RAT DENTATE GYRUS; MAJOR DEPRESSION; DECLARATIVE MEMORY; MINERALOCORTICOID RECEPTOR AB The glucocorticoid hormone cortisol is essential for many forms of regulatory physiology and for cognitive appraisal. Cortisol, while associated with fear and stress response, is also the hormone of energy metabolism and it coordinates behavioral adaptation to the environmental and internal conditions through the regulation of many neurotransmitters and neural circuits. Cortisol has diverse effects on many neuropeptide and neurotransmitter systems thus affecting functional brain systems. As a result, cortisol affects numerous cognitive domains including attention, perception, memory, and emotional processing. When certain pathological emotional states are present, cortisol may have a role in differential activation of brain regions, particularly suppression of hippocampal activation, enhancement of amygdala activity, and dendritic reshaping in these regions as well as in the ventral prefrontal cortex. The coordinated actions of glucocorticoid regulation on various brain systems such as those implicated in emotional processing can lead to perceptual and cognitive adaptations and distortions of events that may be relevant for understanding mood disorders. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 NIMH, DHHS, Mol Imaging Branch,Mood & Anxiety Disorders Progr, Sect Neuroimaging,NIH, Bethesda, MD 20814 USA. Georgetown Univ, Sch Med, Dept Physiol & Biophys, Washington, DC 20007 USA. NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Erickson, K (reprint author), NIMH, DHHS, Mol Imaging Branch,Mood & Anxiety Disorders Progr, Sect Neuroimaging,NIH, 5413 W Cedar Lane,Suite 106-C Room 15,MSC 2606, Bethesda, MD 20814 USA. NR 187 TC 196 Z9 200 U1 16 U2 42 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0149-7634 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PD MAY PY 2003 VL 27 IS 3 BP 233 EP 246 DI 10.1016/S0149-7634(03)00033-2 PG 14 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 687JV UT WOS:000183373900004 PM 12788335 ER PT J AU Staudt, LM AF Staudt, LM TI Molecular diagnosis of the hematologic cancers SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID CHRONIC LYMPHOCYTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; B-CELL LYMPHOMA; GENOMIC ABERRATIONS; CD38 EXPRESSION; MUTATION STATUS; GENE; FLT3; PREDICTION C1 NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Staudt, LM (reprint author), NCI, Metab Branch, Ctr Canc Res, NIH, Bldg 10,Rm 4N114,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 40 TC 123 Z9 132 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 MAY 1 PY 2003 VL 348 IS 18 BP 1777 EP 1785 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 672VK UT WOS:000182543500007 PM 12724484 ER PT J AU Reynolds, SJ Bartlett, JG Quinn, TC Beyrer, C Bollinger, RC AF Reynolds, SJ Bartlett, JG Quinn, TC Beyrer, C Bollinger, RC TI Antiretroviral therapy where resources are limited SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID DRUG-RESISTANCE; POOR SETTINGS; COTE-DIVOIRE; HIV; ADULTS; TUBERCULOSIS; INFECTION; SURVIVAL; ABIDJAN; AFRICA C1 Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. NIAID, NIH, Bethesda, MD 20892 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Reynolds, SJ (reprint author), Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. NR 25 TC 21 Z9 22 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 MAY 1 PY 2003 VL 348 IS 18 BP 1806 EP 1809 DI 10.1056/NEJMsb035366 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 672VK UT WOS:000182543500012 PM 12724489 ER PT J AU Xiang, CC Chen, M Ma, L Phan, QN Inman, JM Kozhich, OA Brownstein, MJ AF Xiang, CC Chen, M Ma, L Phan, QN Inman, JM Kozhich, OA Brownstein, MJ TI A new strategy to amplify degraded RNA from small tissue samples for microarray studies - art. no. 53 SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENE-EXPRESSION PATTERNS; CDNA MICROARRAY; AMPLIFICATION; SYSTEM; CANCER AB RNA amplification methods have been used to facilitate making probes from small tissue samples for microarray studies. Our original amplification technique relied on driving the first reverse transcription with oligo(dT) with a T7 RNA polymerase promoter (T7dT) on the 5' end, and subsequent transcriptions with random 9mers with a T3 RNA polymerase promoter (T3N9). Thus, initially, poly(A)(+) RNA is amplified. This creates a potential problem: amplifications based on oligo(dT) priming could be sensitive to RNA degradation; broken mRNA strands should give rise to shorter cDNAs than those seen when intact templates are used. This would be especially troublesome when targets other than those corresponding to the 3' ends of transcripts are printed on an array. To solve this problem, we elected to prime cDNA synthesis with T3N9 at the beginning of each amplification cycle. Following two rounds of amplification, the resulting probes were comparable to those obtained with our original protocol or the Arcturus RiboAmp kit. We show below that as many as four rounds of amplification can be performed reliably. In addition, as predicted, the method works well with degraded templates. C1 NIMH, Genet Lab, NIH, Bethesda, MD 20892 USA. NCI, SAIC Frederick, Frederick, MD 21502 USA. RP Xiang, CC (reprint author), NIMH, Genet Lab, NIH, 36 Convent Dr, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01CO12400, N01-CO-12400] NR 16 TC 61 Z9 67 U1 1 U2 2 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 MAY 1 PY 2003 VL 31 IS 9 AR e53 DI 10.1093/nar/gng053 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 674FX UT WOS:000182627700007 PM 12711698 ER PT J AU Ulrich, CM AF Ulrich, CM TI Research mentors - An understated value? SO NURSING RESEARCH LA English DT Editorial Material C1 NIH, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bethesda, MD 20892 USA. NR 3 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-6562 J9 NURS RES JI Nurs. Res. PD MAY-JUN PY 2003 VL 52 IS 3 BP 139 EP 139 DI 10.1097/00006199-200305000-00001 PG 1 WC Nursing SC Nursing GA 681RP UT WOS:000183049400001 PM 12792253 ER PT J AU Mahady, GB AF Mahady, GB TI Is black cohosh estrogenic? SO NUTRITION REVIEWS LA English DT Review DE black cohosh; botanical; estrogenic; menopause ID CIMICIFUGA-RACEMOSA; MENOPAUSAL SYMPTOMS; BREAST-CANCER; CARCINOGENESIS; EXTRACTS; THERAPY; HERBS; WOMEN AB Many women seek safe and effective alternative therapies for the treatment of menopausal symptoms. Black cohosh, a botanical product, is one such treatment. Its mechanism of action may involve estrogenic effects, but new data dispute the estrogenic theory and indicate that extracts of black cohosh do not bind to the estrogen receptor, up-regulate estrogen-dependent genes, or stimulate the growth of estrogen-dependent tumors in animal models. C1 Univ Illinois, UIC, NIH,Ctr Bot Dietary Supplements Res, Program Collaborat Res Pharmaceut Sci, Chicago, IL 60612 USA. Univ Illinois, Coll Pharm, Dept Pharm Practice, Chicago, IL 60612 USA. RP Mahady, GB (reprint author), Univ Illinois, UIC, NIH,Ctr Bot Dietary Supplements Res, Program Collaborat Res Pharmaceut Sci, Chicago, IL 60612 USA. FU NCCIH NIH HHS [P50 AT000155-049001, P50 AT00155] NR 24 TC 23 Z9 26 U1 0 U2 4 PU INT LIFE SCIENCES INST NORTH AMERICA PI WASHINGTON PA ONE THOMAS CIRCLE, N W, 9TH FLOOR, WASHINGTON, DC 20005 USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD MAY PY 2003 VL 61 IS 5 BP 183 EP 186 DI 10.1301/nr.2003.may.183-186 PN 1 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 738NX UT WOS:000186295700005 PM 12822708 ER PT J AU Feng, NP Adler-Wailes, D Elberg, J Chin, JY Fallon, E Carr, A Frazer, T Yanovski, JA AF Feng, NP Adler-Wailes, D Elberg, J Chin, JY Fallon, E Carr, A Frazer, T Yanovski, JA TI Sequence variants of the POMC gene and their associations with body composition in children SO OBESITY RESEARCH LA English DT Article DE proopiomelanocortin; polymorphism; children; race; MSH ID LIPOTROPIN PRECURSOR GENE; PITUITARY-ADRENAL AXIS; EARLY-ONSET OBESITY; PROOPIOMELANOCORTIN GENE; WHITE GIRLS; MUTATIONS; WOMEN AB We investigated POMC sequence variants in 242 overweight and nonoverweight African-American and white children and examined the associations between body composition and POMC polymorphisms. Three novel polymorphisms and two previously identified sequence variants were found: A7301G, A7429G, and C8246T were all in untranslated regions. A 9-bp (AGC AGC GGC) duplication/insertion was found between positions 7677 and 7678, and one normal-weight African-American girl had a 45-bp triple duplication/insertion at this location. Compared with whites, African-American children were significantly more likely to have polymorphisms A7301G, A7429G, and the 9-bp insertion. However, there were no significant associations between any of the polymorphisms and body composition. Five African-American subjects who were homozygous for A7429G had a trend (p = 0.08) for a greater BMI-SD score (5.3 +/- 5.3 kg/m(2)) compared with wild-type children (BMI-SD score, 2.4 +/- 3.2 kg/m(2)) or heterozygotes (BMI-SD score, 2.7 +/- 3.7 kg/m(2)). However, there were no differences in BMI-SD score for A7429G when African American subjects were studied separately and both gender and height were taken into account. The contribution of the POMC gene variants we studied to pediatric-onset obesity seems to be limited. C1 NICHHD, Unit Growth & Obes, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Ponce Sch Med, Ponce, PR USA. RP Feng, NP (reprint author), NICHHD, Unit Growth & Obes, Dev Endocrinol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 10N262,MSC 1862, Bethesda, MD 20892 USA. FU NICHD NIH HHS [HD-000641] NR 20 TC 8 Z9 8 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD MAY PY 2003 VL 11 IS 5 BP 619 EP 624 DI 10.1038/oby.2003.89 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 679MK UT WOS:000182926100005 PM 12740451 ER PT J AU Andrews, WW Sibai, BM Thom, EA Dudley, D Ernest, JM McNellis, D Leveno, KJ Wapner, R Moawad, A O'Sullivan, MJ Caritis, SN Iams, JD Langer, O Miodovnik, M Dombrowski, M AF Andrews, WW Sibai, BM Thom, EA Dudley, D Ernest, JM McNellis, D Leveno, KJ Wapner, R Moawad, A O'Sullivan, MJ Caritis, SN Iams, JD Langer, O Miodovnik, M Dombrowski, M CA Natl Inst Child Hlth Human Dev Mat TI Randomized clinical trial of metronidazole plus erythromycin to prevent spontaneous preterm delivery in fetal fibronectin-positive women SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID BACTERIAL VAGINOSIS; PREGNANT-WOMEN; BIRTH; INFECTION; PREDICTION; VAGINALIS AB OBJECTIVE: To estimate whether antibiotic treatment of asymptomatic women with a positive cervical or vaginal fetal fibronectin test in the second trimester would reduce the risk of spontaneous preterm delivery. METHODS: Women were screened between 21 weeks 0 days and 25 weeks 6 days of gestation with cervical or vaginal swabs for fetal fibronectin. Women with a positive test (50 ng/mL or more) were randomized to receive metronidazole (250 mg orally three times per day) and erythromycin (250 mg orally four times per day) or identical placebo pills for 10 days. The primary outcome was spontaneous delivery before 37 weeks' gestation after preterm labor or premature membrane rupture. RESULTS: A total of 16,317 women were screened for fetal fibronectin, and 6.6% had a positive test; 715 fetal fibronectin test-positive women consented to randomization. Outcome data were available for 703 women: 347 in the antibiotic group and 356 in the placebo group. The antibiotic and placebo groups were not significantly different for maternal age (P =.051), ethnicity (P =.849), marital status (P =.127), education (P =.244), and bacterial vaginosis (P =.236). No difference was observed in spontaneous preterm birth before 37 weeks' (odds ratio [OR] 1.17, 95% confidence interval [CI] 0.80, 1.70), less than 35 weeks' (OR 0.92, 95% CI 0.54, 1.56), or less than 32 weeks' (OR 1.94, 95% CI 0.83, 4:52) gestation in antibiotic- compared with placebo-treated women. Among women with a prior spontaneous preterm delivery, the rate of repeat spontaneous preterm delivery at less than 37 weeks' gestation was significantly higher in the active drug compared with the placebo group (46.7% versus 23.9%, P =.039). CONCLUSION: Treatment with metronidazole plus erythromycin of asymptomatic women with a positive cervical or vaginal fetal fibronectin test in the late second trimester does not decrease the incidence of spontaneous preterm delivery: (Obstet Gynecol 2003;101:847-55. (C) 2003 by The American College of Obstetricians and Gynecologists). C1 Univ Alabama, Ctr Res Womens Hlth, Dept Obstet & Gynecol, Birmingham, AL 35249 USA. Univ Tennessee, Dept Obstet & Gynecol, Memphis, TN 38103 USA. George Washington Univ, Ctr Biostat, Rockville, MD USA. Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA. Wake Forest Univ, Sch Med, Dept Obstet & Gynecol, Winston Salem, NC 27109 USA. NICHHD, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Obstet & Gynecol, Dallas, TX 75230 USA. Thomas Jefferson Univ, Dept Obstet & Gynecol, Philadelphia, PA 19107 USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. Univ Miami, Dept Obstet & Gynecol, Miami, FL 33152 USA. Univ Pittsburgh, Magee Womens Hosp, Pittsburgh, PA 15213 USA. Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. Univ Texas, Dept Obstet & Gynecol, San Antonio, TX 78285 USA. Univ Cincinnati, Dept Obstet & Gynecol, Cincinnati, OH USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. RP Andrews, WW (reprint author), Univ Alabama, Ctr Res Womens Hlth, Dept Obstet & Gynecol, 619 19th St S,OHB 458, Birmingham, AL 35249 USA. OI caritis, steve/0000-0002-2169-0712 FU NICHD NIH HHS [U10-HD27917, U10-HD21410, U10-HD21414, U10-HD27860, U10-HD27861, U10-HD27869, U10-HD27905, U10-HD27915, U10-HD34116, U10-HD34122, U10-HD34136, U10-HD34208, U10-HD34210, U10-HD36801] NR 20 TC 72 Z9 78 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 2003 VL 101 IS 5 BP 847 EP 855 DI 10.1016/S0029-7844(03)00172-8 PN 1 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 672QD UT WOS:000182531500005 PM 12738139 ER PT J AU Poggi, SH Spong, CY Allen, RH AF Poggi, SH Spong, CY Allen, RH TI Prioritizing posterior arm delivery during severe shoulder dystocia SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID MANEUVERS AB BACKGROUND: Delivery of the posterior arm, or the Barnum maneuver, is at times used late in shoulder dystocia management algorithms, and is not often a first- or second-line management protocol. CASE: A multiparous, diabetic patient, who was morbidly obese and had a residual obstetric brachial plexus injury, experienced a precipitous second stage of labor and severe shoulder dystocia. Attempts at the McRoberts maneuver with traction failed to deliver the fetus. In lieu of alternative maneuvers or continued attempts at traction, the posterior arm was delivered and the fetal trunk followed easily. CONCLUSION: A geometric analysis reveals that using posterior arm delivery reduces the obstruction by more than a factor of two, relative to the McRoberts maneuver. We recommend earlier use of this maneuver during shoulder dystocia management. C1 Georgetown Univ Hosp, Dept Obstet & Gynecol, Washington, DC 20007 USA. NICHHD, Pregnancy & Perinatol Branch, Ctr Res Mothers & Children, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. RP Poggi, SH (reprint author), Georgetown Univ Hosp, Dept Obstet & Gynecol, 3800 Reservoir Rd NW,3PHC, Washington, DC 20007 USA. RI Allen, Robert/A-3731-2010 NR 11 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 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 2003 VL 101 IS 5 SU S BP 1068 EP 1072 DI 10.1016/S0029-7844(02)02332-3 PN 2 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 673CT UT WOS:000182562600009 PM 12738105 ER PT J AU Li, ML Ren, SX Tilli, MT Flaws, JA Lubet, R Grubbs, CJ Furth, PA AF Li, ML Ren, SX Tilli, MT Flaws, JA Lubet, R Grubbs, CJ Furth, PA TI Chemoprevention of mammary carcinogenesis in a transgenic mouse model by alpha-difluoromethylornithine (DFMO) in the diet is associated with decreased cyclin D1 activity SO ONCOGENE LA English DT Article DE DFMO; cell proliferation; apoptosis; cyclin D1; transgenic mouse model; mammary cancer progression ID CANCER CELL-LINES; TUMOR PROGRESSION; ORNITHINE DECARBOXYLASE; GROWTH-INHIBITION; MICE; APOPTOSIS; PROLIFERATION; EXPRESSION; INDUCTION; PROTEIN AB Mechanisms underlying the chemopreventive effect of difluoromethylornithine (DFMO) on the development of mammary cancer were investigated utilizing the whey acidic protein promoter-T antigen transgenic mouse model of breast cancer progression. Mice were exposed to four different doses of DFMO in the diet (3.5, 4.9, 7.0 and 10 g/kg diet). Tumor latency was increased in a dose-dependent manner. DFMO at the highest dose significantly delayed tumor onset (131 days as compared to 109 days in control unexposed mice, P=0.018). Analyses of preneoplastic mammary tissue collected 1 month after DFMO treatment demonstrated that DFMO (10 g/kg diet) significantly increased the ratio of apoptotic to proliferative indices (P = 0.013) and significantly reduced the percentage of cells demonstrating nuclear localized cyclin D1 (P = 0.013). Nuclear localizations of p27, p21 and Stat5a were not affected. Inhibitory effects of DFMO on cell growth and survival were lost as the cells progressed to cancer. In conclusion, the chemopreventive effects of DFMO on mammary cancer progression were mediated by changes in both apoptosis and cell proliferation in preneoplastic cells. Alterations in cyclin D1 activity in preneoplastic cells could represent an early biomarker of chemopreventive action and are consistent with a mechanistic role for cyclin D1 in progression of mammary cancer. C1 Georgetown Univ, Lombardi Canc Ctr, Dept Oncol, Washington, DC 20057 USA. Univ Maryland, Program Human Genet, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. NCI, Div Canc Prevent, Rockville, MD 20892 USA. Univ Alabama, Birmingham, AL 35294 USA. RP Furth, PA (reprint author), Georgetown Univ, Lombardi Canc Ctr, Dept Oncol, Res Bldg,E518,3970 Reservoir Rd NW, Washington, DC 20057 USA. FU NCI NIH HHS [N01-CN-85076-46]; NICHD NIH HHS [HD 38955] NR 34 TC 7 Z9 7 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 MAY 1 PY 2003 VL 22 IS 17 BP 2568 EP 2572 DI 10.1038/sj.onc.1206314 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 673FF UT WOS:000182569000004 PM 12730671 ER PT J AU Teramoto, H Malek, RL Behbahani, B Castellone, MD Lee, NH Gutkind, JS AF Teramoto, H Malek, RL Behbahani, B Castellone, MD Lee, NH Gutkind, JS TI Identification of H-Ras, RhoA, Rac1 and Cdc42 responsive genes SO ONCOGENE LA English DT Article DE foci formation; small GTPases; microarray ID GTP-BINDING PROTEINS; SIGNAL-TRANSDUCTION; CELLS; GTPASES; EXPRESSION; CANCER; TRANSFORMATION; TRANSCRIPTION; ACTIVATION; RECEPTOR AB The superfamily of small GTP-binding proteins has expanded dramatically in recent years. The Ras family has long been associated with signaling pathways contributing to normal and aberrant cell growth, while Rho-related protein function is to integrate extracellular signals with specific targets regulating cell morphology, cell aggregation, tissue polarity, cell motility and cytokinesis. Recent findings suggest that certain Rho proteins, including RhoA, Rac1 and Cdc42, can also play a role in signal transduction to the nucleus and cell growth control. However, the nature of the genes regulated by Ras and Rho GTPases, as well as their contribution to their numerous biological effects is still largely unknown. To approach these questions, we investigated the global gene expression pattern induced by activated forms of H-Ras, RhoA, Rac1 and Cdc42 using cDNA microarrays comprising 19 117 unique elements. Using this approach, we identified 1184 genes that were up- or downregulated by at least twofold. Hierarchical cluster analysis revealed the existence of patterns of gene regulation both unique and common to H-Ras V12, RhoA QL, Rac1 QL and Cdc42 QL activation. For example, H-Ras V12 upregulated osteopontin and Akt 1, and H-Ras and RhoA stimulated cyclin G1, cyclin-dependent kinase 8, cyclin A2 and HMGI-C, while Rac1 QL and Cdc42 QL upregulated extracellular matrix and cell adhesion proteins such as alpha-actinin 4, procollagen type I and V and neuropilin. Furthermore, H-Ras V12 downregulated by >eightfold 52 genes compared to only three genes by RhoA QL, Rac1 QL and Cdc42 QL. These results provide key information to begin unraveling the complexity of the molecular mechanisms underlying the transforming potential of Ras and Rho proteins, as well as the numerous morphological and cell cycle effects induced by these small GTPases. C1 NIDR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. Inst Genom Res, Dept Funct Genom, Rockville, MD 20850 USA. George Washington Univ, Med Ctr, Dept Pharmacol, Washington, DC 20037 USA. RP Gutkind, JS (reprint author), NIDCR, Oral & Pharyngeal Canc Branch, NIH, 9000 Rockville Pike,Bldg 30,Room 212, Bethesda, MD 20892 USA. RI Gutkind, J. Silvio/A-1053-2009; OI CASTELLONE, MARIADOMENICA/0000-0003-0507-8037 NR 27 TC 39 Z9 40 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 1 PY 2003 VL 22 IS 17 BP 2689 EP 2697 DI 10.1038/sj.onc.1206364 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 673FF UT WOS:000182569000017 PM 12730683 ER PT J AU Wong, TY Klein, R Nieto, FJ Klein, BEK Sharrett, AR Meuer, SM Hubbard, LYD Tielsch, JM AF Wong, TY Klein, R Nieto, FJ Klein, BEK Sharrett, AR Meuer, SM Hubbard, LYD Tielsch, JM TI Retinal microvascular abnormalities and 10-year cardiovascular mortality - A population-based case-control study SO OPHTHALMOLOGY LA English DT Article ID BEAVER DAM EYE; DEATH CERTIFICATE DIAGNOSIS; TOTAL SERUM-CHOLESTEROL; CORONARY HEART-DISEASE; ATHEROSCLEROSIS RISK; BLOOD-PRESSURE; AGE; RETINOPATHY; HYPERTENSION; COMMUNITIES AB Purpose: Retinal microvascular abnormalities reflect persistent arteriolar damage from hypertension and independently predict stroke. We examined their associations with long-term cardiovascular mortality. Design: Population-based, nested, case-control study. Population: Cases were Beaver Dam Eye Study participants (age range, 43-84 years) who died of coronary heart disease or stroke between the baseline examination in 1988 to 1990 and 1999 (n = 413). Nearly 3 controls per case were selected from the baseline cohort, frequency-matched on 5-year age intervals and gender (n = 1198). Methods: Retinal photographs of cases and controls at baseline were evaluated for retinopathy, focal arteriolar narrowing, and arteriovenous nicking by graders masked to case-control status using standardized protocols. To obtain an estimate of generalized arteriolar narrowing, photographs were digitized and diameters of individual retinal vessels were measured and summarized by a computer program. Main Outcome Measure: Ten-year cardiovascular mortality. Results: After controlling for systolic blood pressure, diabetes, glycosylated hemoglobin levels, and other risk factors, retinopathy was associated with increased cardiovascular mortality, with odds ratios of 1.8 (95% confidence interval [CI], 1.2, 2.7). For other retinal abnormalities, associations with cardiovascular mortality were present only in younger people, with odds ratios of 2.7 (95% CI, 1.0, 7.4) for focal arteriolar narrowing, 1.8 (95% CI, 0.8, 4.5) for arteriovenous nicking, and 1.9 (95% CI, 1.2, 2.9) for generalized arteriolar narrowing in persons 43 to 74 years of age but odds ratios of 1.1, 0.4, and 1.0 for the corresponding retinal abnormalities in persons 75 years and older. Conclusions: Retinopathy is independently associated with cardiovascular mortality. Associations for other retinal abnormalities were only observed in middle-aged persons. These data support recent studies that suggest retinal microvascular abnormalities provide independent information regarding cardiovascular risk. C1 Natl Univ Singapore, Dept Ophthalmol, Singapore 119260, Singapore. Singapore Natl Eye Ctr, Singapore, Singapore. Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. Univ Wisconsin, Dept Ophthalmol, Madison, WI USA. Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI USA. NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Int Hlth, Baltimore, MD USA. RP Wong, TY (reprint author), Natl Univ Singapore, Dept Ophthalmol, 10 Kent Ridge Crescent, Singapore 119260, Singapore. OI Tielsch, James/0000-0002-1151-060X; Klein, Ronald/0000-0002-4428-6237 FU NEI NIH HHS [EY06594]; NHLBI NIH HHS [HL66018] NR 56 TC 179 Z9 184 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAY PY 2003 VL 110 IS 5 BP 933 EP 940 DI 10.1016/S0161-6420(03)00084-8 PG 8 WC Ophthalmology SC Ophthalmology GA 676LY UT WOS:000182754600024 PM 12750093 ER PT J AU Janket, SJ Baird, AE Chuang, SK Jones, JA AF Janket, SJ Baird, AE Chuang, SK Jones, JA TI Meta-analysis of periodontal disease and risk of coronary heart disease and stroke SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article; Proceedings Paper CT 79th General Session of the International-Association-for-Dental-Research CY JUN 27-30, 2001 CL CHIBA, JAPAN SP Int Assoc Dental Res ID C-REACTIVE PROTEIN; CARDIOVASCULAR-DISEASE; DENTAL INFECTIONS; HEALTH; METAANALYSIS; INFLAMMATION; FIBRINOGEN; LINK AB Objective. The purpose of this study was to analyze published studies and abstracts in order to provide a quantitative summary of periodontal disease as a risk factor for cardiovascular disease and to explore the possible causes for conflicting results in the literature. Study design. We searched all published literature on the Medline literature search engine since 1980. An additional search was performed with bibliographic citations from each article. Nine cohort studies (8 prospective and I retrospective), in which relative risks (Us), Cls, and P values were reported or could be calculated were included. Four researchers independently extracted RRs, Cls, and P values from each study and evaluated the degree of confounding adjustment. The combined result was calculated with weighted average, and sources of disparity were tested with regression analyses. Results. The summary RR was 1.19 (95% Cl, 1.08 1.32), indicating a higher risk of future cardiovascular events in individuals with periodontal disease compared with those without. In an analysis stratified to individuals of less than or equal to65 years of age, the RR was 1.44 (95% Cl, 1.20 to 1.73). When the outcome was restricted to stroke only, the RR was 2.85 (95% Cl, 1.78 to 4.56). In the metaregression analysis, the effects of residual confounding caused an overestimate of the results by 12.9% and, with a proxy for periodontal disease, caused an underestimate of 29.7%. Conclusion. Periodontal disease appears to be associated with a 19% increase in risk of future cardiovascular disease. This increase in RR is more prominent (44%) in persons aged less than or equal to65 years. Although the increment of risk between subjects with or without periodontal disease in the general population is modest, at around 20% because nearly 40% of population has periodontal disease, this modest increase may have a profound public health impact. C1 VA Med Ctr, Dent Serv, Bedford, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Natl Inst Neurol Disorders & Stroke, Stroke Neurosci Unit, NIH, Bethesda, MD USA. RP Janket, SJ (reprint author), Harvard Univ, Sch Med, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. OI Janket, Sok-Ja/0000-0003-0078-3992; Jones, Judith/0000-0002-0126-0790 NR 36 TC 209 Z9 222 U1 1 U2 9 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD MAY PY 2003 VL 95 IS 5 BP 559 EP 569 DI 10.1067/moe.2003.107 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 677TQ UT WOS:000182824000013 PM 12738947 ER PT J AU Kreps, GL Arora, NK Nelson, DE AF Kreps, GL Arora, NK Nelson, DE TI Consumer/provider communication research: directions for development SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE consumer/provider communication; doctor/patient communication; interpersonal communication ID PATIENT COMMUNICATION; HEALTH OUTCOMES AB Communication between health care providers and consumers is a critical part of effective health care delivery. Yet, the strategic use of interpersonal communication in health care delivery is most complex, multifaceted, and often problematic, necessitating careful study of the communication process in health care to increase understanding and help improve health communication practices. The National Cancer Institute (NCI) sponsored an expert symposium on consumer/provider communication research to examine progress and identify gaps in the research literature on doctor/patient communication. This paper and this special issue of Patient Education and Counseling reviews several of the key perspectives and suggestions presented at the symposium for directing future research and applications concerning consumer/provider communication. Published by Elsevier Science Ireland Ltd. C1 NCI, Hlth Commun & Informat Res Branch, Bethesda, MD 20892 USA. NCI, Outcomes Res Branch, Bethesda, MD USA. Ctr Dis Control & Prevent, Hlth Commun Branch, Off Smoking & Hlth, Atlanta, GA USA. RP Kreps, GL (reprint author), NCI, Hlth Commun & Informat Res Branch, 6130 Execut Blvd,EPN 4084,MSC 7365, Bethesda, MD 20892 USA. NR 12 TC 13 Z9 14 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD MAY PY 2003 VL 50 IS 1 BP 3 EP 4 DI 10.1016/S0738-3991(03)00070-3 PG 2 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 726ZB UT WOS:000185630500001 PM 12767575 ER PT J AU Karron, RA Belshe, RB Wright, PF Thumar, B Burns, B Newman, F Cannon, JC Thompson, J Tsai, T Paschalis, M Wu, SL Mitcho, Y Hackell, J Murphy, BR Tatem, JM AF Karron, RA Belshe, RB Wright, PF Thumar, B Burns, B Newman, F Cannon, JC Thompson, J Tsai, T Paschalis, M Wu, SL Mitcho, Y Hackell, J Murphy, BR Tatem, JM TI A live human parainfluenza type 3 virus vaccine is attenuated and immunogenic in young infants SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE parainfluenza; live attenuated vaccine; pediatric ID WEANLING HAMSTERS; HEALTHY INFANTS; CHILDREN; EPIDEMIOLOGY; MUTATIONS; BOVINE; MUTANT; CHIMPANZEES; REPLICATION; INFECTION AB Background. Parainfluenza type 3 virus (PIV-3) infections cause lower respiratory tract illness in children throughout the world. A licensed PIV-3 vaccine is not yet available. Methods. A live attenuated cold-adapted (ca) and temperature-sensitive (ts) PIV-3 vaccine, designated cp-45, was evaluated sequentially in open label studies in 20 adults and in placebo-controlled, double blind studies in 24 PIV-3-seropositive children, 52 PIV-3-seronegative infants and children and 49 infants 1 to 2 months old. A single dose of this intranasal vaccine was evaluated in adults [106 plaque-forming units (pfu)] and seropositive children, and 104 and 105 pfu were evaluated in seronegative children. In the infant study, two 104 pfu doses of vaccine were administered at 1- or 3-month intervals. Safety, infectivity, immunogenicity and phenotypic stability of the vaccine were evaluated in all cohorts. Results. The cp-45 vaccine was well-tolerated in all age groups and infected 94% of vaccinated seronegative children and 94% of vaccinated infants. Although immunization with the first dose of cp-45 diminished the replication of a second dose in all infants, those immunized after 3 months shed vaccine virus more frequently than those immunized after 1 month (62% vs. 24%, respectively). Antibody responses to PIV-3 were readily detected in seronegative children with a variety of assays; however, the IgA response to the viral hemagglutinin-neuraminidase was the best measure of immunogenicity in young infants. Of 109 vaccine virus specimens recovered from nasal washes, 98 were is and 11 were temperature-sensitive intermediate (tsi) viruses, with pinpoint plaques visible at 40degreesC. tsi viruses appeared transiently at the time of peak viral replication, represented a very small proportion of the total virus shed and were not associated with changes in clinical status. ca revertants were not detected. Conclusions. The cp-45 vaccine is appropriately attenuated and immunogenic in infants as young as 1 month of age. Further development of this vaccine is warranted. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Immunizat Res, Dept Int Hlth, Baltimore, MD 21205 USA. St Louis Univ, Dept Med, St Louis, MO 63103 USA. Vanderbilt Univ, Sch Med, Vanderbilt Vaccine Ctr, Dept Pediat, Nashville, TN 37212 USA. NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. Wyeth Res, Viral Vaccines, Pearl River, NY USA. RP Karron, RA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Immunizat Res, Dept Int Hlth, Hampton House 117,624 N Broadway, Baltimore, MD 21205 USA. FU NIAID NIH HHS [N01 AO 62712] NR 33 TC 59 Z9 62 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD MAY PY 2003 VL 22 IS 5 BP 394 EP 405 DI 10.1097/00006454-200305000-00002 PG 12 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 680NM UT WOS:000182984300002 PM 12792378 ER PT J AU Comi, AM Hunt, P Vawter, MP Pardo, CA Becker, KG Pevsner, J AF Comi, AM Hunt, P Vawter, MP Pardo, CA Becker, KG Pevsner, J TI Increased fibronectin expression in Sturge-Weber syndrome fibroblasts and brain tissue SO PEDIATRIC RESEARCH LA English DT Article ID SMOOTH-MUSCLE CELL; PORT-WINE STAINS; BLOOD-VESSELS; EXTRACELLULAR-MATRIX; GROWTH-FACTOR; CONNECTIVE-TISSUE; ANGIOGENESIS; INNERVATION; DISEASE; VASCULOGENESIS AB Sturge-Weber syndrome (SWS) is a neurocutaneous disorder that presents with a facial port-wine stain and a leptomeningeal angioma. Fibronectin expression regulates angiogenesis and vasculogenesis and participates in brain tissue responses to ischemia and seizures. We therefore hypothesized that abnormal gene expression of fibronectin and other extracellular matrix genes would be found in SWS brain tissue and SWS port-wine skin fibroblasts. Fibronectin gene and protein expression from port-wine-derived fibroblasts were compared with that from normal skin-derived fibroblasts of four individuals with SWS using microarrays, reverse transcriptase-PCR, Western analysis, and immunocytochemistry. Fibronectin gene and/or protein expression from eight SWS surgical brain samples was compared with that in two surgical epilepsy brain samples and six postmortem brain samples using microarrays, reverse transcriptase-PCR, and Western analysis. The gene expression of fibronectin was significantly increased (p < 0.05) in the SWS port-wine-derived fibroblasts compared with that of fibroblasts from SWS normal skin. A trend for increased protein levels of fibronectin in port-wine fibroblasts was found by Western analysis. No difference in the pattern of fibronectin staining was detected. The gene expression of fibronectin was significantly increased (p < 0.05), and a trend for increased fibronectin protein expression was found in the SWS surgical brain samples compared with the postmortem controls. These results suggest a potential role for fibronectin in the pathogenesis of SWS and in the brain's response to chronic ischemic injury in SWS. The reproducible differences in fibronectin gene expression between the SWS port-wine-derived fibroblasts and the SWS normal skin-derived fibroblasts are consistent with the presence of a hypothesized somatic mutation underlying SWS. C1 Johns Hopkins Univ, Dept Neurol, Div Pediat Neurol, Sch Med, Baltimore, MD 21287 USA. Johns Hopkins Univ, Dept Genet, Sch Med, Baltimore, MD 21287 USA. Johns Hopkins Univ, Dept Pathol, Sch Med, Baltimore, MD 21287 USA. Johns Hopkins Univ, Dept Neurosci, Sch Med, Baltimore, MD 21287 USA. Kennedy Kreiger Inst, Dept Neurol, Baltimore, MD 21205 USA. NIA, DNA Array Unit, NIH, Baltimore, MD 21224 USA. Univ Calif Irvine, Dept Psychiat, Irvine, CA 92697 USA. RP Comi, AM (reprint author), Johns Hopkins Univ, Dept Neurol, Div Pediat Neurol, Sch Med, 123 Jefferson Bldg,600 N Wolfe St, Baltimore, MD 21287 USA. RI Hunt, Piper/G-1555-2012; OI Hunt, Piper/0000-0003-0538-7606; Becker, Kevin/0000-0002-6794-6656 FU NICHD NIH HHS [HD24061]; NINDS NIH HHS [K12NS01696] NR 36 TC 21 Z9 25 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD MAY PY 2003 VL 53 IS 5 BP 762 EP 769 DI 10.1203/01.PDR.0000058921.54071.19 PG 8 WC Pediatrics SC Pediatrics GA 668ZY UT WOS:000182328500009 PM 12621118 ER PT J AU Krebs, NF Baker, RD Greer, FR Heyman, MB Jaksic, T Lifshitz, F AF Krebs, NF Baker, RD Greer, FR Heyman, MB Jaksic, T Lifshitz, F CA Comm Nutr TI Reimbursement for foods for special dietary use SO PEDIATRICS LA English DT Article AB Foods for special dietary use are recommended by physicians for chronic diseases or conditions of childhood, including inherited metabolic diseases. Although many states have created legislation requiring reimbursement for foods for special dietary use, legislation is now needed to mandate consistent coverage and reimbursement for foods for special dietary use and related support services with accepted medical benefit for children with designated medical conditions. C1 Amer Acad Pediat, Comm Nutr, Elk Grove Village, IL 60007 USA. US FDA, Rockville, MD 20857 USA. USDA, Washington, DC 20250 USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. NIDDKD, Bethesda, MD 20892 USA. RP Krebs, NF (reprint author), Amer Acad Pediat, Comm Nutr, Elk Grove Village, IL 60007 USA. NR 6 TC 2 Z9 2 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD MAY 1 PY 2003 VL 111 IS 5 BP 1117 EP 1119 PG 3 WC Pediatrics SC Pediatrics GA 673KC UT WOS:000182579300049 ER PT J AU Hauck, FR Herman, SM Donovan, M Iyasu, S Moore, CM Donoghue, E Kirschner, RH Willinger, M AF Hauck, FR Herman, SM Donovan, M Iyasu, S Moore, CM Donoghue, E Kirschner, RH Willinger, M TI Sleep environment and the risk of sudden infant death syndrome in an urban population: The Chicago infant mortality study SO PEDIATRICS LA English DT Article DE sudden infant death; infant care; blacks; sleep; risk factors ID BREAST-FEEDING DURATION; AFRICAN-AMERICANS; UNITED-STATES; PACIFIER USE; CLINICAL RESEARCH; OTITIS-MEDIA; NEW-ZEALAND; COT DEATH; POSITION; SIDS AB Objective. To examine risk factors for sudden infant death syndrome ( SIDS) with the goal of reducing SIDS mortality among blacks, which continues to affect this group at twice the rate of whites. Methods. We analyzed data from a population-based case-control study of 260 SIDS deaths that occurred in Chicago between 1993 and 1996 and an equal number of matched living controls to determine the association between SIDS and factors in the sleep environment and other variables related to infant care. Results. The racial/ethnic composition of the study groups was 75.0% black; 13.1% Hispanic white; and 11.9% non-Hispanic white. Several factors related to the sleep environment during last sleep were associated with higher risk of SIDS: placement in the prone position (unadjusted odds ratio [ OR]: 2.4; 95% confidence interval [CI]: 1.7-3.4), soft surface ( OR: 5.1; 95% CI: 3.1-8.3), pillow use ( OR: 2.5; 95% CI: 1.5-4.2), face and/or head covered with bedding ( OR: 2.5; 95% CI: 1.3-4.6), bed sharing overall ( OR: 2.7; 95% CI: 1.8-4.2), bed sharing with parent( s) alone ( OR: 1.9; 95% CI: 1.2-3.1), and bed sharing in other combinations ( OR: 5.4; 95% CI: 2.8-10.2). Pacifier use was associated with decreased risk ( unadjusted OR: 0.3; 95% CI: 0.2-0.5), as was breastfeeding either ever ( OR: 0.2; 95% CI: 0.1-0.3) or currently ( OR: 0.2; 95% CI: 0.1-0.4). In a multivariate model, several factors remained significant: prone sleep position, soft surface, pillow use, bed sharing other than with parent( s) alone, and not using a pacifier. Conclusions. To lower further the SIDS rate among black and other racial/ethnic groups, prone sleeping, the use of soft bedding and pillows, and some types of bed sharing should be reduced. C1 Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Off Med Examiner Cook Cty, Chicago, IL USA. NICHHD, Bethesda, MD 20892 USA. RP Hauck, FR (reprint author), Univ Virginia Hlth Syst, Dept Family Med, Box 800729, Charlottesville, VA 22908 USA. FU NICHD NIH HHS [N01-HD-3-3188]; ODCDC CDC HHS [U50/CCU300860-06] NR 94 TC 150 Z9 156 U1 1 U2 12 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAY PY 2003 VL 111 IS 5 SU S BP 1207 EP 1214 PG 8 WC Pediatrics SC Pediatrics GA 673KG UT WOS:000182579700017 PM 12728140 ER PT J AU Shaywitz, SE Shaywitz, BA AF Shaywitz, SE Shaywitz, BA TI Dyslexia (specific reading disability) SO PEDIATRICS IN REVIEW LA English DT Review C1 NICHD, Yale Ctr Study Learning & Attent, New Haven, CT USA. RP Shaywitz, SE (reprint author), NICHD, Yale Ctr Study Learning & Attent, New Haven, CT USA. NR 9 TC 28 Z9 30 U1 5 U2 14 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0191-9601 J9 PEDIATR REV JI Pediatr. Rev. PD MAY PY 2003 VL 24 IS 5 BP 147 EP 153 DI 10.1542/pir.24-5-147 PG 7 WC Pediatrics SC Pediatrics GA 746DB UT WOS:000186730300001 PM 12728187 ER PT J AU Thompson, PM Egbufoama, S Vawter, MP AF Thompson, PM Egbufoama, S Vawter, MP TI SNAP-25 reduction in the hippocampus of patients with schizophrenia SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE bipolar illness; exocytosis; NMDA; NR1; schizophrenia; SNAP-25 ID SYNAPTOSOMAL-ASSOCIATED PROTEIN; METHYL-D-ASPARTATE; CHRONIC HALOPERIDOL TREATMENT; CELL-ADHESION MOLECULE; BIPOLAR DISORDER; MESSENGER-RNAS; RECEPTOR SUBUNITS; GENE-EXPRESSION; DENTATE GYRUS; NMDA RECEPTOR AB In this study, the authors sought to replicate the findings of reduced synaptosomal associated protein 25 kDa (SNAP-25) immunoreactivity in the hippocampus of patients with schizophrenia. The authors also measured N-methyl-D-aspartate (NMDA) receptor 1 (NR1) receptor subunit to determine if glutamatergic synapses were involved with the loss of SNAP-25. We found 49% less SNAP-25 immunointensity in the schizophrenic group (n=7) compared to the control (n=8) or bipolar groups (n=4) (P=.004). There was no change in NMDA NR1 levels in the three groups. The authors confirm the previous report of less SNAP-25 immunoreactivity in the hippocampus using a different cohort of patients with schizophrenia. It also appears that NMDA NR1 was unchanged, indicating that the overall level of NMDA glutamatergic synapses in hippocampus is normal. These data add to evidence suggesting that in schizophrenia the molecular pathology of the hippocampus involves presynaptic components. (C) 2003 Elsevier Science Inc. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, Mood & Anxiety Disorders Div, San Antonio, TX 78229 USA. NIDA, Intramural Res Program, NIH, Baltimore, MD USA. Univ Calif Irvine, Dept Psychiat, Irvine, CA 92717 USA. RP Thompson, PM (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, Mood & Anxiety Disorders Div, 7703 Floyd Curl Dr,Mailcode 7792, San Antonio, TX 78229 USA. NR 58 TC 60 Z9 61 U1 2 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD MAY PY 2003 VL 27 IS 3 BP 411 EP 417 DI 10.1016/S0278-5846(03)00027-7 PG 7 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 671JX UT WOS:000182462600008 PM 12691775 ER PT J AU Nixon, JB Kamitani, H Baek, SJ Eling, TE AF Nixon, JB Kamitani, H Baek, SJ Eling, TE TI Evaluation of eicosanoids and NSAIDs as PPAR gamma ligands in colorectal carcinoma cells SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article DE PPAR gamma; lipoxygenase; 15-LO-1; eicosanoids; cyclooxygenase inhibitors; NSAIDs ID ACTIVATED RECEPTOR-GAMMA; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; HUMAN COLON-CANCER; TERMINAL DIFFERENTIATION; CACO-2 CELLS; EXPRESSION; APOPTOSIS; 15-LIPOXYGENASE-1; CYCLOOXYGENASE; INHIBITION AB The activation of peroxisome proliferator activated receptor gamma (PPARgamma) may play a role in the control of colorectal carcinogenesis. The expression of PPARgamma was examined by Western blotting in human colorectal tumors and matched normal adjacent tissues, as well as in various colorectal carcinoma cell lines. In the tissues, the expression of PPARgamma was elevated in tumors relative to the adjacent normal tissues. Each colorectal carcinoma cell line expressed PPARgamma. The ability of various eicosanoids to bind PPARgamma in colorectal carcinoma cells was investigated using luciferase reporter assays. The well-known PPARgamma ligands, troglitazone and 15-deoxy-Delta(12,14)-prostaglandin J(2) strongly induced PPARgamma binding activity. Products of lipoxygenases displayed moderate binding activity, while other prostaglandins and fatty acids displayed little or no reporter activation. The activation of PPARgamma by 13(S)-HODE, the major metabolite of 15-lipoxygenase-1 from linoleic acid, was concentration dependent reaching maximum at 10 muM (35-fold activation). The endogenous production of 13(S)-HODE by expression of 15-LO-1 did not activate PPARgamma. The ability of various nonsteroidal anti-inflammatory drugs (NSAIDs) to induce PPAR,( activation was also evaluated. The conventional NSAIDs that inhibit both cyclooxygenases (COX-1 and COX-2) also induced PPARgamma binding activity. In general, however, neither COX-1- nor COX-2-specific inhibitors induced the activation of PPARgamma. Taken together, the metabolites of 15-lipoxygenase and the conventional NSAIDs were confirmed as exogenous ligands for PPARgamma in colorectal carcinoma cells. Published by Elsevier Science Ltd. C1 NIEHS, Eicosanoid Biochem Sect, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. Tottori Univ, Inst Neurol Sci, Dept Neurosurg, Yonago, Tottori 6838504, Japan. RP Eling, TE (reprint author), NIEHS, Eicosanoid Biochem Sect, Mol Carcinogenesis Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. OI Baek, Seung/0000-0001-7866-7778 NR 30 TC 20 Z9 20 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD MAY PY 2003 VL 68 IS 5 BP 323 EP 330 DI 10.1016/S0952-3278(03)00023-1 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 676QE UT WOS:000182762800005 PM 12711249 ER PT J AU Dorjsuren, D Badralmaa, Y Mikovits, J Li, AQ Fisher, R Ricciardi, R Shoemaker, R Sei, S AF Dorjsuren, D Badralmaa, Y Mikovits, J Li, AQ Fisher, R Ricciardi, R Shoemaker, R Sei, S TI Expression and purification of recombinant Kaposi's sarcoma-associated herpesvirus DNA polymerase using a Baculovirus vector system SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article ID HELICASE-PRIMASE INHIBITORS; CAVITY-BASED LYMPHOMAS; EPSTEIN-BARR-VIRUS; IDENTIFICATION; REPLICATION; DISEASE; SEQUENCES; INFECTION; SENSITIVITY; BIOLOGY AB The DNA polymerase (POL) of Kaposi's sarcoma-associated herpesvirus (KSHV) is essential for viral DNA replication and, thus, may be considered as a viable target for anti-KSHV therapeutics. To produce large quantities of homogeneous and pure POL required for high-throughput screening (HTS) for inhibitors, we generated a recombinant baculovirus vector encoding a hexahistidine (His6)-tagged POL and infected Spodoptera frugiperda Sf-9 insect cells. High expression of recombinant POL (rPOL) was achieved for up to 72h post-infection. The rPOL was solubilized in lysis buffer containing 0.3% Cymal-5 detergent, purified by metal-chelating and dsDNA-cellulose affinity chromatography, and analyzed by anti-His antibody Western blot and mass spectrometry. The functionality of rPOL was confirmed by its DNA synthesis activity in vitro, which was effectively blocked by the antiherpetic DNA polymerase inhibitors, foscarnet and cidofovir diphosphate, in a dose-dependent manner. The POL expressed and purified from the recombinant baculovirus-infected insect cells may be useful toward the development of FITS of large chemical libraries to identify novel KSHV DNA polymerase inhibitors. (C) 2003 Elsevier Science (USA). All rights reserved. C1 SAIC Frederick, Lab Antiviral Drug Mech, Ft Detrick, MD 21702 USA. SAIC Frederick, Clin Serv Program, Lab Mol Cell Biol, Ft Detrick, MD 21702 USA. SAIC Frederick, Prot Chem Lab, Ft Detrick, MD 21702 USA. Univ Penn, Dept Microbiol, Philadelphia, PA USA. Univ Penn, Dept Biochem & Biophys, Philadelphia, PA USA. NCI Frederick, Screening Technol Branch, Dev Therapeut Program, Ft Detrick, MD 21702 USA. RP Dorjsuren, D (reprint author), SAIC Frederick, Lab Antiviral Drug Mech, POB B, Ft Detrick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 34 TC 4 Z9 5 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 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD MAY PY 2003 VL 29 IS 1 BP 42 EP 50 DI 10.1016/S1046-5928(03)00017-2 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 678JM UT WOS:000182863800006 PM 12729724 ER PT J AU Cornilescu, CC Bouamr, F Carter, C Tjandra, N AF Cornilescu, CC Bouamr, F Carter, C Tjandra, N TI Backbone N-15 relaxation analysis of the N-terminal domain of the HTLV-I capsid protein and comparison with the capsid protein of HIV-1 SO PROTEIN SCIENCE LA English DT Article DE HTLV-1; capsid protein; retrovirus; NMR spectroscopy; relaxation; mutant; CyP-A ID IMMUNODEFICIENCY-VIRUS TYPE-1; NMR-SPECTROSCOPY; CYCLOPHILIN-A; ROTATIONAL DIFFUSION; DYNAMICS; VESICLES; VITRO AB Human T-cell leukemia virus type I (HTLV-I) is an oncogenic retrovirus that exhibits specific tropism for human T-cells. The capsid (CA) proteins of retroviruses share highly conserved secondary and tertiary structures. However, they can form quaternary structures (assembled cores) that are conical (e.g., the lentivirus subgroup, including HIV) or spherical (e.g., the oncovirus subgroup, including HTLV). The intrinsic features that drive these differences are not understood. So far, only structural studies have been used as a basis for comparison. Dynamics may play a role in particle formation. High-resolution nuclear magnetic resonance (NMR) N-15 relaxation data (T-1, T-1rho, and NOE) have been used to characterize the backbone dynamics of the N-terminal domain (NTD) of the oncovirus HTLV-I and to compare with the CA NTD of HIV-I. Large variations in the N-15 heteronuclear NOES and transversal relaxation rates for individual residues are consistent with the bundle RMSD of the previously calculated NMR structures. The beta-hairpin and CyP-A loop exhibit different mobility in HTLV-I and HIV-I. The overall hydrodynamic property of the HTLV-I capsid NTD is quite distinct from the HIV-I. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA. Univ Maryland, Chem Phys Program, College Pk, MD 20742 USA. RP Tjandra, N (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 50,Room 3503, Bethesda, MD 20892 USA. RI Cornilescu, Claudia/H-1959-2012; Cornilescu, Claudia/K-1981-2015 OI Cornilescu, Claudia/0000-0002-2401-7806 FU NIGMS NIH HHS [GM 48294, R01 GM048294] NR 31 TC 3 Z9 3 U1 1 U2 4 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD MAY PY 2003 VL 12 IS 5 BP 973 EP 981 DI 10.1110/ps.0235903 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 671WB UT WOS:000182486800009 PM 12717020 ER PT J AU Wang, GS Keifer, PA Peterkofsky, A AF Wang, GS Keifer, PA Peterkofsky, A TI Solution structure of the N-terminal amphitropic domain of Escherichia coli glucose-specific enzyme IIA in membrane-mimetic micelles SO PROTEIN SCIENCE LA English DT Article DE amphitropism; dihexanoylphosphatidylglycerol; IIA(G1c); lipid binding; NMR; membrane proteins; signal transduction ID SIGNAL-TRANSDUCING PROTEIN; PHOSPHORYL TRANSFER COMPLEX; 2D NMR-SPECTRA; PHOSPHOTRANSFERASE SYSTEM; SALMONELLA-TYPHIMURIUM; SECONDARY STRUCTURE; SPECTROSCOPY; IIIGLC; HPR; TRANSPORTER AB The N-terminal domain of enzyme IIA(Glc) of the Escherichia coli phosphoenolpyruvate:sugar phosphotransferase system confers amphitropism to the protein, allowing IIA(Glc), to shuttle between the cytoplasm and the membrane. To further understand this amphitropic protein, we have elucidated, by NMR spectroscopy, the solution structure of a synthetic peptide corresponding to the N-terminal domain of IIA(Glc). In water, this peptide is predominantly disordered, consistent with previous data obtained in the absence of membranes. In detergent micelles of dihexanoylphosphatidylglycerol (DHPG) or sodium dodecylsulfate (SDS), however, residues Phe 3-Val 10 of the peptide adopt a helical conformation in the ensemble of structures calculated on the basis of NOE-derived distance restraints. The root mean square deviations for superimposing the backbone atoms of the helical region are 0.18 Angstrom in DHPG and 0.22 Angstrom in SDS. The structure, chemical shifts, and spin-spin coupling constants all indicate that, of the four lysines in the N-terminal domain of IIA(Glc), only Lys 5 and Lys 7 in the amphipathic helical region interact with DHPG. In addition, the peptide-detergent interactions were investigated using intermolecular NOESY experiments. The aliphatic chains of anionic detergents DHPG, SDS, and 2,2-dimethyl-2-silapentane-5-sulfonate sodium salt (DSS) all showed intermolecular NOE cross-peaks to the peptide, providing direct evidence for the putative membrane anchor of IIA(Glc) in binding to the membrane-mimicking micelles. C1 Univ Nebraska, Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA. NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Wang, GS (reprint author), Univ Nebraska, Med Ctr, Eppley Canc Inst, Room ECI3018,986805 Nebraska Med Ctr, Omaha, NE 68198 USA. NR 44 TC 40 Z9 40 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD MAY PY 2003 VL 12 IS 5 BP 1087 EP 1096 DI 10.1110/ps.0301503 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 671WB UT WOS:000182486800019 PM 12717030 ER PT J AU Wu, CK Dailey, TA Dailey, HA Wang, BC Rose, JP AF Wu, CK Dailey, TA Dailey, HA Wang, BC Rose, JP TI The crystal structure of augmenter of liver regeneration: A mammalian FAD-dependent sulfhydryl oxidase SO PROTEIN SCIENCE LA English DT Article DE FAD dependent sulfhydryl oxidase; augmenter of liver regeneration; crystal structure; ERV2 ID DISULFIDE BOND FORMATION; EGG-WHITE; PROTEINS; PATHWAY; GENE; EXPRESSION; SITE; RATS AB The crystal structure of recombinant rat augmenter of liver regeneration (ALRp) has been determined to 1.8 Angstrom. The protein is a homodimer, stabilized by extensive noncovalent interactions and a network of hydrogen bonds, and possesses a noncovalently bound FAD in a motif previously found only in the related protein ERV2p. ALRp functions in vitro as a disulfide oxidase using dithiothreitol as reductant. Reduction of the flavin by DTT occurs under aerobic conditions resulting in a spectrum characteristic of a neutral semiquinone. This semiquinone is stable and is only fully reduced by addition of dithionite. Mutation of either of two cysteine residues that are located adjacent to the FAD results in inactivation of the oxidase activity. A comparison of ALRp with ERV2p is made that reveals a number of significant structural differences, which are related to the in vivo functions of these two proteins. Possible physiological roles of ALR are examined and a hypothesis that it may serve multiple roles is proposed. C1 Univ Georgia, Dept Biochem & Mol Biol, Athens, GA 30602 USA. NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Rose, JP (reprint author), Univ Georgia, Dept Biochem & Mol Biol, B204B Life Sci Bldg, Athens, GA 30602 USA. FU NIDDK NIH HHS [R01 DK032303] NR 27 TC 90 Z9 99 U1 0 U2 5 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD MAY PY 2003 VL 12 IS 5 BP 1109 EP 1118 DI 10.1110/ps.0238103 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 671WB UT WOS:000182486800021 PM 12717032 ER PT J AU Haspel, N Tsai, CJ Wolfson, H Nussinov, R AF Haspel, N Tsai, CJ Wolfson, H Nussinov, R TI Hierarchical protein folding pathways: A computational study of protein fragments SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE protein folding; building blocks; protein structure prediction; hierarchical folding; protein fragments; folding complexity ID STRUCTURE-PREDICTION; LIMITED PROTEOLYSIS; STRUCTURE ALIGNMENT; GLOBULAR-PROTEINS; LOCAL-STRUCTURE; CLASSIFICATION; NUCLEATION; MECHANISM; RESIDUES; BINDING AB We have previously presented a building block folding model. The model postulates that protein folding is a hierarchical top-down process. The basic unit from which a fold is constructed, referred to as a hydrophobic folding unit, is the outcome of combinatorial assembly of a set of "building blocks." Results obtained by the computational cutting procedure yield fragments that are in agreement with those obtained experimentally by limited proteolysis. Here we show that as expected, proteins from the same family give very similar building blocks. However, different proteins can also give building blocks that are similar in structure. In such cases the building blocks differ in sequence, stability, contacts with other building blocks, and in their 3D locations in the protein structure. This result, which we have repeatedly observed in many cases, leads us to conclude that while a building block is influenced by its environment, nevertheless, it can be viewed as a stand-alone unit. For small-sized building blocks existing in multiple conformations, interactions with sister building blocks in the protein will increase the population time of the native conformer. With this conclusion in hand, it is possible to develop an algorithm that predicts the building block assignment of a protein sequence whose structure is unknown. Toward this goal, we have created sequentially nonredundant databases of building block sequences. A protein sequence can be aligned against these, in order to be matched to a set of potential building blocks. (C) 2003 Wiley-Liss. C1 NCI, SAIC Inc, Lab Expt & Computat Biol, Intramural Res Support Program, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Fac Exact Sci, Sch Comp Sci, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, SAIC Inc, Lab Expt & Computat Biol, Intramural Res Support Program, Bldg 469,Room 151, Frederick, MD 21702 USA. RI Wolfson, Haim/A-1837-2011; Haspel, Nurit/D-1961-2017 FU NCI NIH HHS [N01-CO-12400] NR 47 TC 19 Z9 19 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-3585 J9 PROTEINS JI Proteins PD MAY 1 PY 2003 VL 51 IS 2 BP 203 EP 215 DI 10.1002/prot.10294 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 663DB UT WOS:000181990000006 PM 12660989 ER PT J AU Benyamini, H Gunasekaran, K Wolfson, H Nussinov, R AF Benyamini, H Gunasekaran, K Wolfson, H Nussinov, R TI Conservation and amyloid formation: A study of the gelsolin-like family SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE sequence and structure conservation; beta-sheet stability; amyloid; gelsolin; cofilin ID SH3 DOMAIN; FIBRIL FORMATION; PROTEIN STABILITY; ACTIN-BINDING; FINNISH TYPE; PI-STACKING; IDENTIFICATION; MUTANT; STABILIZATION; ALIGNMENT AB The mechanism through which globular proteins transform into amyloid fibrils is still not understood. Here we analyze the structure and sequence conservation to assess the differential stability of segments from two structurally related protein families: the amyloidogenic gelsolin-like and its structurally related cofilin-like. The two families belong to the actin depolymerizing proteins, with a central beta-sheet stacked between 2 and 4 alpha-helices. Although sequentially remote, the two families share regions of high and low conservation and stability. Our results show a highly conserved hydrophobic and aromatic cluster, located at a central buried beta-hairpin. The geometry of the aromatic residues with respect to each other is strictly conserved, suggesting involvement in strand registering and beta-sheet stabilization. Consistent with experiment, we find a region of weak conservation and stability at one of the exposed beta-strands (strand B in the gelsolin-like family). This region was recently found to be affected by a point mutation-mediated destabilization of the human gelsolin domain 2, which facilitates the first proteolytic event in the formation of the amyloidogenic fragment. Thus, both experimental and computational conservation analyses suggest that this unstable region may constitute a first step in amyloid formation. Our analysis uses a recently developed multiple-structure comparison algorithm in which molecules are aligned simultaneously. (C) 2003 Wiley-Liss, Inc. C1 NCI, Lab Expt & Computat Biol, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Comp Sci, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Lab Expt & Computat Biol, SAIC Frederick Inc, Basic Res Program, Bldg 469,Room 151, Frederick, MD 21702 USA. RI Wolfson, Haim/A-1837-2011 FU NCI NIH HHS [N01-CO-12400] NR 45 TC 10 Z9 10 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-3585 J9 PROTEINS JI Proteins PD MAY 1 PY 2003 VL 51 IS 2 BP 266 EP 282 DI 10.1002/prot.10359 PG 17 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 663DB UT WOS:000181990000012 PM 12660995 ER PT J AU Teplyakov, A Obmolova, G Khil, PP Howard, AJ Camerini-Otero, RD Gilliland, GL AF Teplyakov, A Obmolova, G Khil, PP Howard, AJ Camerini-Otero, RD Gilliland, GL TI Crystal structure of the Escherichia coli YcdX protein reveals a trinuclear zinc active site SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article ID DNA C1 Univ Maryland, Inst Biotechnol, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA. NIST, Rockville, MD USA. NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD USA. IIT, Ctr Synchrotron Radiat Res & Instrumentat, Biol Chem & Phys Sci Dept, Chicago, IL 60616 USA. RP Gilliland, GL (reprint author), Univ Maryland, Inst Biotechnol, Ctr Adv Res Biotechnol, 9600 Gudelsky Dr, Rockville, MD 20850 USA. OI Khil, Pavel/0000-0002-4903-8777; Teplyakov, Alexey/0000-0003-0296-0016 FU NIGMS NIH HHS [P01-GM567890] NR 19 TC 33 Z9 34 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-3585 J9 PROTEINS JI Proteins PD MAY 1 PY 2003 VL 51 IS 2 BP 315 EP 318 DI 10.1002/prot.10352 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 663DB UT WOS:000181990000017 PM 12661000 ER PT J AU Yang, YK Chen, CC Lee, IH Chou, YH Chiu, NT Jeffries, KJ Tsai, TT Yeh, TL AF Yang, YK Chen, CC Lee, IH Chou, YH Chiu, NT Jeffries, KJ Tsai, TT Yeh, TL TI Association between regional cerebral blood flow and eye-tracking performance and the Wisconsin Card Sorting Test in schizophrenics: a single photon emission computed tomography study SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE regional cerebral blood flow; schizophrenia; Wisconsin Card Sorting Test; eye tracking dysfunction ID GLUCOSE-METABOLISM; PSYCHOTIC-PATIENTS; DEFICIT SYNDROME; DYSFUNCTION; MOVEMENTS; SPECT; MECHANISMS; ACTIVATION; DISORDER; CORTEX AB The objectives of this study were (1) to examine the changes in regional cerebral blood flow (rCBF) during Wisconsin Card Sorting Test (WCST) performance in two different eye-tracking groups; (2) to explore the relationship between eye-tracking movement and rCBF at rest; and (3) to estimate the association between WCST performance and rCBF in patients with schizophrenia. A total of 17 patients with schizophrenia were recruited. SPECT with Tc-99m HMPAO (Tc-99m hexamethylpropyleneamine oxime) was carried out while patients were performing the WCST and resting. Brodmann area 9 of the prefrontal cortex, a part of the dorsal lateral prefrontal cortex (DLPFC), was less activated during performance of the WCST in poor trackers (relative to good trackers). The eye pursuit tracking error measure in schizophrenic patients was negatively associated with decreases in rCBF in the middle temporal area, superior parietal lobule, thalami, and caudate nuclei. The rCBF increased significantly in the superior temporal gyri, inferior parietal lobe, and some frontal regions during WCST performance; however, this was not the case in the DLPFC. Additionally, significant correlations were found between WCST scores and rCBF during WCST performance in the prefrontal lobes, and in thalamic and cerebellar regions. Our findings suggest that the rCBF changes during WCST performance may be distinctive in different eye-tracking groups. Our results confirm the hypothesis that the middle temporal area, superior parietal lobule, thalami, and caudate nuclei-mainly parts of the oculomotor circuit-are involved in eye pursuit tracking. Surprisingly, no significant association was found in the frontal eye field. Although the frontal lobe plays a significant role in WCST performance, our findings demonstrate that WCST performance is widely involved with other regions in patient's with schizophrenia. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved. C1 Natl Cheng Kung Univ, Coll Med, Dept Psychiat, Tainan 70428, Taiwan. Natl Cheng Kung Univ Hosp, Tainan 70428, Taiwan. Pharmacia Taiwan Inc, Taipei 105, Taiwan. St Martine Gen Hosp, Dept Psychiat, Chiai 600, Taiwan. Natl Cheng Kung Univ, Coll Med, Tainan 70428, Taiwan. Univ Hosp, Coll Med, Tainan 70428, Taiwan. Natl Inst Deafness & Other Commun Disorders, Language Sect, Voice Speech & Language Branch, NIH, Bethesda, MD 20892 USA. Natl Cheng Kung Univ Hosp, Coll Med, Dept Neurol, Tainan 70428, Taiwan. RP Yeh, TL (reprint author), Natl Cheng Kung Univ, Coll Med, Dept Psychiat, 138 Sheng Li Rd, Tainan 70428, Taiwan. NR 47 TC 12 Z9 12 U1 1 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD MAY 1 PY 2003 VL 123 IS 1 BP 37 EP 48 DI 10.1016/S0925-4927(03)00021-0 PG 12 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 681LA UT WOS:000183036600003 PM 12738342 ER PT J AU Williams, KL Ko, MCH Rice, KC Woods, JH AF Williams, KL Ko, MCH Rice, KC Woods, JH TI Effect of opioid receptor antagonists on hypothalamic-pituitary-adrenal activity in rhesus monkeys SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE opioid antagonists; naltrexone; adrenocorticotropic hormone; cortisol; ethanol ID SQUIRREL-MONKEYS; DELTA-RECEPTOR; KAPPA-RECEPTOR; ACTH RELEASE; MU-RECEPTOR; NALTREXONE; NALOXONE; ALCOHOL; MORPHINE; HORMONE AB Some opioid antagonists increase the release of adrenocorticotropic hormone (ACTH) and cortisol in humans and, therefore, may indicate that endogenous opioids modulate hypothalamic-pituitary-adrenal axis activity. The type of opioid receptor that may be related to these endocrine effects is unknown. The purpose of this experiment was to evaluate the ability of different opioid antagonists to increase ACTH and cortisol plasma levels in rhesus monkeys. Eight monkeys received intramuscular injections of various antagonists: 0.0032-1.0 mg/kg naltrexone, 0.1-3.2 mg/kg naltrindole (delta-selective), 0.032-0.32 mg/kg clocinnamox (mu-selective), and 1-3.2 mg/kg nor-binaltorphimine (kappa-selective). Naltrexone, 0.1-1.0 mg/kg, increased ACTH levels, whereas naltrindole and clocinnamox failed to increase ACTH levels. Nor-binaltorphimine, 1-3.2 mg/kg, increased ACTH concentrations on the day of injection, but not at a time when other assays continue to demonstrate K-antagonism (24 h). Cortisol concentrations generally followed the same pattern as the ACTH concentrations, but the incremental differences in cortisol release between doses were less clear. Thus, opioid modulation of ACTH and cortisol plasma levels is not clearly associated with a particular opioid receptor. Although the K-antagonist increased ACTH and cortisol release on the day of injection, some evidence suggests that this endocrine effect may be due to mechanisms other than those mediated by the kappa-receptor. Alternatively, the naltrexone-induced increase of ACTH and cortisol plasma levels may be caused by activity at multiple opioid receptors or some uncharacterized receptor. Finally, the increased release of ACTH and cortisol may be a response to naltrexone's aversive properties. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Grand Valley State Univ, Dept Psychol, Allendale, MI 49401 USA. Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA. NIDDK, NIH, Baltimore, MD 21224 USA. RP Williams, KL (reprint author), Grand Valley State Univ, Dept Psychol, 2224 Au Sable Hall,1 Campus Dr, Allendale, MI 49401 USA. RI Ko, Mei-Chuan/C-9468-2009 OI Ko, Mei-Chuan/0000-0003-2436-4506 NR 43 TC 14 Z9 15 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD MAY PY 2003 VL 28 IS 4 BP 513 EP 528 DI 10.1016/S0306-4530(02)00037-7 PG 16 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 678JP UT WOS:000182864000003 PM 12689609 ER PT J AU Jobe, JB AF Jobe, JB TI Cognitive psychology and self-reports: Models and methods SO QUALITY OF LIFE RESEARCH LA English DT Article; Proceedings Paper CT Seminar on Assessing Health-Related Quality of Life CY 2000 CL UNIV HULL, KINGSTON HULL, ENGLAND HO UNIV HULL DE autobiographical memory; cognitive interviews; focus groups; information processing models ID QUESTIONNAIRES; MEMORY; RETRIEVAL; HISTORY AB This article describes the models and methods that cognitive psychologists and survey researchers use to evaluate and experimentally test cognitive issues in questionnaire design and subsequently improve self-report instruments. These models and methods assess the cognitive processes underlying how respondents comprehend and generate answers to self- report questions. Cognitive processing models are briefly described. Non- experimental methods - expert cognitive review, cognitive task analysis, focus groups, and cognitive interviews - are described. Examples are provided of how these methods were effectively used to identify cognitive self- report issues. Experimental methods - cognitive laboratory experiments, field tests, and experiments embedded in field surveys - are described. Examples are provided of: ( a) how laboratory experiments were designed to test the capability and accuracy of respondents in performing the cognitive tasks required to answer self- report questions, ( b) how a field experiment was conducted in which a cognitively designed questionnaire was effectively tested against the original questionnaire, and ( c) how a cognitive experiment embedded in a field survey was conducted to test cognitive predictions. C1 NHLBI, Behav Med Sci Res Grp, Bethesda, MD 20892 USA. RP Jobe, JB (reprint author), NHLBI, Behav Med Sci Res Grp, 6701 Rockledge Dr,MSC 7936, Bethesda, MD 20892 USA. EM jobej@nhlbi.gov NR 37 TC 79 Z9 79 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD MAY PY 2003 VL 12 IS 3 BP 219 EP 227 DI 10.1023/A:1023279029852 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 664PL UT WOS:000182069400002 PM 12769134 ER PT J AU Perussi, JR Paltoo, DN Toppin, VAL Canada, RG AF Perussi, JR Paltoo, DN Toppin, VAL Canada, RG TI Synergism between dipyridamole and cisplatin in human breast cancer cells in vitro SO QUIMICA NOVA LA Portuguese DT Article; Proceedings Paper CT 26th Annual Meeting of the Sociedad-Brasileira-de-Quimica CY MAY 26-29, 2003 CL POCOS DE CALDAS, BRAZIL SP Soc Brasileira Quim DE cisplatin; dipyridamole; synergism ID OVARIAN-CARCINOMA CELLS; CELLULAR ACCUMULATION; RESISTANCE; CYTOTOXICITY; CHEMOTHERAPY; PHARMACOLOGY; COMBINATION; PACLITAXEL; MECHANISMS; TERBIUM AB Cisplatin is very effective in the treatment of metastatic breast cancer. However, the development of cellular resistance is a serious problem in cisplatin chemotherapy. In the present work, the effects of dipyridamole (DPM) on the cellular accumulation and cytotoxicity of cisplatin was studied in cisplatin-sensitive (MDA/S) and cisplatin-resistant (MDA/R) human breast cancer cells. In the presence of 30 muM DPM, the IC50 of cisplatin was reduced by 39% for both cell lines. Combination index analysis revealed that cisplatin and dipyridamole interact synergistically in MDA/R cells. In the MDA/S cells, the cellular accumulation of cisplatin increased by 57 +/- 8% in the presence of 30 muM DPM. In the MDA/R cells, the cellular accumulation of cisplatin remained the same with or without 30 muM DPM. The results suggest that the enhancement of cisplatin cytotoxicity by DPM in MDA/S cells may be related to a DPM-induced increase in cisplatin accumulation, but the enhanced cytotoxicity in MDA/R cells employs a mechanism that does not involve an increase in the cellular accumulation of cisplatin. C1 Univ Sao Paulo, Inst Quim, BR-13560970 Sao Carlos, SP, Brazil. NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. Howard Univ, Coll Med, Dept Physiol & Biophys, Washington, DC 20059 USA. RP Perussi, JR (reprint author), Univ Sao Paulo, Inst Quim, CP 780, BR-13560970 Sao Carlos, SP, Brazil. NR 33 TC 1 Z9 1 U1 0 U2 3 PU SOC BRASILEIRA QUIMICA PI SAO PAULO PA CAIXA POSTAL 26037, 05599-970 SAO PAULO, BRAZIL SN 0100-4042 J9 QUIM NOVA JI Quim. Nova PD MAY-JUN PY 2003 VL 26 IS 3 BP 340 EP 343 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 688CM UT WOS:000183414900009 ER PT J AU Rebois, RV Hebert, TE AF Rebois, RV Hebert, TE TI Protein complexes involved in heptahelical receptor-mediated signal transduction SO RECEPTORS & CHANNELS LA English DT Review DE G proteins; heptahelical receptors; protein-protein interaction; signaling; specificity ID BETA-GAMMA-SUBUNITS; HETEROTRIMERIC G-PROTEINS; ROD OUTER SEGMENTS; GTP-BINDING PROTEINS; CYCLIC-GMP PHOSPHODIESTERASE; GROWTH-FACTOR RECEPTOR; PHOSPHOLIPASE-C ISOZYMES; II AT(1) RECEPTOR; MUSCARINIC ACETYLCHOLINE-RECEPTOR; BOVINE PHOTORECEPTOR-MEMBRANES AB Signal transduction mediated by heterotrimeric G proteins that couple to heptahelical receptors requires the involvement of many different proteins. Although some of the early evidence suggested that signal transduction components were assembled into complexes, much of the data supported an alternative hypothesis positing that the process involved transient interactions driven by random collision events. However, recent data indicate that many of the components involved in signal transduction do indeed form complexes. Here we review the evidence for these complexes and how they contribute to the specificity and efficiency of signaling in cells that must manage numerous signal transduction pathways. C1 Inst Cardiol Montreal, Ctr Rech, Montreal, PQ H1T 1C8, Canada. Univ Montreal, Dept Anesthesiol, Montreal, PQ H1T 1C8, Canada. NINDS, Membrane Biochem Sect, Mol & Cellular Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Hebert, TE (reprint author), Inst Cardiol Montreal, Ctr Rech, 5000 Rue Belanger Est, Montreal, PQ H1T 1C8, Canada. EM hebertt@icm.umontreal.ca NR 405 TC 62 Z9 63 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1060-6823 J9 RECEPTOR CHANNEL JI Recept. Channels PD MAY-JUN PY 2003 VL 9 IS 3 BP 169 EP 194 DI 10.1080/10606820390203820 PG 26 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 739KT UT WOS:000186344200004 PM 12775338 ER PT J AU Brouwers, FM Lenders, JWM Eisenhofer, G Pacak, K AF Brouwers, FM Lenders, JWM Eisenhofer, G Pacak, K TI Pheochromocytoma as an endocrine emergency SO REVIEWS IN ENDOCRINE & METABOLIC DISORDERS LA English DT Review DE paraganglioma; hypertensive crises; catecholamines ID CATECHOLAMINE-INDUCED CARDIOMYOPATHY; ACUTE-RENAL-FAILURE; HEART-TRANSPLANT CANDIDATE; CALCIUM-CHANNEL BLOCKADE; DILATED CARDIOMYOPATHY; MYOCARDIAL-INFARCTION; PSEUDO-OBSTRUCTION; PULMONARY-EDEMA; HYPERTROPHIC CARDIOMYOPATHY; MALIGNANT PHEOCHROMOCYTOMA C1 NICHHD, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20892 USA. Univ Nijmegen, Med Ctr, Dept Gen Internal Med, Nijmegen, Netherlands. NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. RP Pacak, K (reprint author), NICHHD, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20892 USA. RI Lenders, J.W.M./L-4487-2015 NR 129 TC 37 Z9 38 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1389-9155 J9 REV ENDOCR METAB DIS JI Rev. Endocr. Metab. Disord. PD MAY PY 2003 VL 4 IS 2 BP 121 EP 128 DI 10.1023/A:1022981801344 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 717NB UT WOS:000185095100001 PM 12766539 ER PT J AU Sarlis, NJ Gourgiotis, L AF Sarlis, NJ Gourgiotis, L TI Thyroid emergencies SO REVIEWS IN ENDOCRINE & METABOLIC DISORDERS LA English DT Article DE thyrotoxicosis; hypothyroidism; myxedema; metabolic coma; thyroid storm; levothyroxine; liothyronine ID IMPAIRED WATER-EXCRETION; MYXEDEMA COMA; PRIMARY HYPOTHYROIDISM; FREE TRIIODOTHYRONINE; THYROTOXIC CRISIS; HYPER-THYROIDISM; SECRETION RATE; L-THYROXINE; STORM; HYPERTHYROIDISM C1 NIDDKD, Div Intramural Res, NIH, Bethesda, MD 20892 USA. NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Sarlis, NJ (reprint author), NIDDKD, Div Intramural Res, NIH, Bethesda, MD 20892 USA. NR 67 TC 30 Z9 34 U1 0 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1389-9155 J9 REV ENDOCR METAB DIS JI Rev. Endocr. Metab. Disord. PD MAY PY 2003 VL 4 IS 2 BP 129 EP 136 DI 10.1023/A:1022933918182 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 717NB UT WOS:000185095100002 PM 12766540 ER PT J AU Emerson, SU Purcell, RH AF Emerson, SU Purcell, RH TI Hepatitis E virus SO REVIEWS IN MEDICAL VIROLOGY LA English DT Review ID PREGNANT RHESUS-MONKEYS; CAPSID PROTEIN; UNITED-STATES; ORF3 PROTEIN; EXPERIMENTAL-INFECTION; CYNOMOLGUS MACAQUES; RECOMBINANT VACCINE; SWINE; HEV; ANTIBODIES AB Hepatitis E virus (HEV) is a positive-stranded RNA virus with a 7.2 kb genome that is capped and polyadenylated. The virus is currently unclassified: the organisation of the genome resembles that of the Caliciviridae but sequence analyses suggest it is more closely related to the Togaviridae. Hepatitis E virus is an enterically transmitted virus that causes both epidemics and sporadic cases of acute hepatitis in many countries of Asia and Africa but only rarely causes disease in more industrialised countries. Initially the virus was believed to have a limited geographical distribution. However, serological studies suggest that HEV may be endemic also in the United States and Europe even though it infrequently causes overt disease in these countries. Many different animal species worldwide recently have been shown to have antibodies to HEV suggesting that hepatitis E may be zoonotic. Although two related strains have been experimentally transmitted between species, direct transmission from an animal to a human has not been documented. There are four currently recognised genotypes and two of the four contain viruses isolated from swine as well as from humans. Regardless of country of origin or genotype of the virus, most, if not all, strains belong to a single serotype. A promising recombinant vaccine candidate comprised of a truncated capsid protein is currently under evaluation in Nepal. Published in 2003 by John Wiley Sons, Ltd. C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Emerson, SU (reprint author), Bldg 50-6537,50 S Dr MSC 8009, Bethesda, MD 20892 USA. NR 52 TC 297 Z9 330 U1 4 U2 23 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1052-9276 J9 REV MED VIROL JI Rev. Med. Virol. PD MAY-JUN PY 2003 VL 13 IS 3 BP 145 EP 154 DI 10.1002/rmv.384 PG 10 WC Virology SC Virology GA 679FZ UT WOS:000182911200003 PM 12740830 ER PT J AU Zheng, ZM AF Zheng, ZM TI Split genes and their expression in Kaposi's sarcoma-associated herpesvirus SO REVIEWS IN MEDICAL VIROLOGY LA English DT Review ID EPSTEIN-BARR-VIRUS; OPEN READING FRAME; PRIMARY EFFUSION LYMPHOMA; PROTEIN-COUPLED RECEPTOR; IMMEDIATE-EARLY REGION; MARROW BIOPSY SAMPLES; RIBOSOME ENTRY SITE; SIMPLEX VIRUS; HUMAN CYTOMEGALOVIRUS; MULTIPLE-MYELOMA AB A split or interrupted gene is defined as a gene consisting of introns and exons. Removal (splicing) of the intron(s) from a primary transcript (pre-mRNA) is essential for creating a mRNA. Initial assignment of a potential protein coding region in the KSHV genome was based on the initiation codon context and predicted protein size larger than 100 amino acids, but the gene discontinuity was disregarded. Experimental investigation of the assigned ORFs has demonstrated that there are up to 25 split genes, more than one fourth of the total KSHV genes described in the KSHV genome. This includes the genes involved in all phases (latent, immediate early, early and late) of KSHV infection. The complexity of a split gene expression depends upon the availability of a proximal promoter and polyadenylation (pA) signal. Sharing a single promoter or a single pA signal by two or three genes is not uncommon in the expression of KSHV split genes and the resulting transcripts are usually polycistronic, Among those of KSHV split genes, 15 genes express a bicistronic or tricistronic RNA and 10 genes express a monocistronic RNA. Alternative RNA splicing could happen in a particular pre-mRNA due to intron or exon inclusion or skipping or the presence of an alternative 5' splice site or 3' splice site. This may, respectively, result in at least 8 species of K8 and 14 species of K15 transcripts. This appears to be related to cell differentiation and stages of the virus infection, presumably involving viral cis elements and trans splicing factors. Published in 2003 by John Wiley Sons, Ltd. C1 NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Zheng, ZM (reprint author), NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, 10 Ctr Dr,Rm 10 S255 MSC 1868, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 SC010357-08] NR 103 TC 27 Z9 30 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1052-9276 J9 REV MED VIROL JI Rev. Med. Virol. PD MAY-JUN PY 2003 VL 13 IS 3 BP 173 EP 184 DI 10.1002/rmv.387 PG 12 WC Virology SC Virology GA 679FZ UT WOS:000182911200005 PM 12740832 ER PT J AU Hansen, A Jacobi, A Pruss, A Kaufmann, O Scholze, J Lipsky, PE Dorner, T AF Hansen, A Jacobi, A Pruss, A Kaufmann, O Scholze, J Lipsky, PE Dorner, T TI Comparison of immunoglobulin heavy chain rearrangements between peripheral and glandular B cells in a patient with primary Sjogren's syndrome SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Article ID LABIAL SALIVARY-GLANDS; SOMATIC HYPERMUTATION; LYMPHOID-TISSUE; EXPRESSION; GENES; REPERTOIRE; DISEASE; REGION; CLASSIFICATION; INDIVIDUALS AB Myoepithelial sialadenitis (MESA) of the major salivary glands is a characteristic feature of primary Sjogren's syndrome (pSS). To delineate systemic and organ-specific influences on B cells in a patient with pSS and benign MESA, individual B cells were simultaneously obtained from the peripheral blood and inflamed parotid gland. Immunoglobulin variable heavy chain (V-H ) rearrangements in single sorted CD19(+) B cells were subsequently amplified, sequenced and analysed. Despite the presence of two clonal expansions using V-H 1-08 and V-H 2-70 segments, respectively, the majority of glandular B cells were polyclonal, resembling the V-H gene usage and mutational pattern of the corresponding blood population. However, striking differences were observed in the proportion of cells expressing mutated V-H rearrangements (blood, 28.9% versus parotid, 80.4%; P < 0.0001). Moreover, the glandular productive V-H rearrangements differed significantly from their blood counterparts by a higher mutational frequency (P < 0.0001), shorter CDR3 lengths (P = 0.001) and a less frequent usage of J(H) 6 (P = 0.0292), indicating an accumulation of memory B cells in the inflamed parotid. Thus, both preferential influx/homing of memory B cells and local proliferation may contribute to the pattern of benign MESA in pSS. Notably, one of the glandular clonal rearrangements (using V-H 1-08) was also detected in the patient's peripheral repertoire. C1 Univ Hosp Charite, Dept Med, D-10098 Berlin, Germany. Univ Hosp Charite, Dept Transfusiol, D-10098 Berlin, Germany. Univ Hosp Charite, Dept Pathol, D-10098 Berlin, Germany. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Hansen, A (reprint author), Univ Hosp Charite, Outpatients Dept, Schumannstr 20-21, D-10098 Berlin, Germany. NR 44 TC 20 Z9 21 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD MAY PY 2003 VL 57 IS 5 BP 470 EP 479 DI 10.1046/j.1365-3083.2003.01226.x PG 10 WC Immunology SC Immunology GA 674TN UT WOS:000182652200009 PM 12753504 ER PT J AU Quan, SF Hunt, CE AF Quan, SF Hunt, CE TI In pursuit of knowledge SO SLEEP LA English DT Editorial Material C1 NHLBI, Sleep Disorders Res Advisory Board, Natl Ctr Sleep Disorders Res, Tucson, AZ USA. NHLBI, Natl Ctr Sleep Disorders Res, DHHS, NIH, Bethesda, MD 20892 USA. RP Quan, SF (reprint author), NHLBI, Sleep Disorders Res Advisory Board, Natl Ctr Sleep Disorders Res, Tucson, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI ROCHESTER PA 6301 BANDEL RD, STE 101, ROCHESTER, MN 55901 USA SN 0161-8105 J9 SLEEP JI Sleep PD MAY 1 PY 2003 VL 26 IS 3 BP 250 EP 250 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 670ZC UT WOS:000182439100003 PM 12749540 ER PT J AU Cortez, K Kottilil, S Mermel, LA AF Cortez, K Kottilil, S Mermel, LA TI Intracerebral tuberculoma misdiagnosed as neurosarcoidosis SO SOUTHERN MEDICAL JOURNAL LA English DT Article AB We describe two patients who had tuberculomas that were initially misdiagnosed as neurosarcoidosis, leading to prolonged steroid therapy before initiation of antituberculous medications. Neither patient was infected with the human immunodeficiency virus, and one of the patients had a negative tuberculosis skin test. C1 Rhode Isl Hosp, Div Infect Dis, Providence, RI 02903 USA. Brown Univ, Sch Med, Div Infect Dis, Providence, RI 02912 USA. Natl Inst Allergy Immunol & Infect Dis, Div Clin Mycol, NIH, Bethesda, MD USA. Natl Inst Allergy Immunol & Infect Dis, Immunoregulat Lab, NIH, Bethesda, MD USA. RP Mermel, LA (reprint author), Rhode Isl Hosp, Div Infect Dis, 593 Eddy St, Providence, RI 02903 USA. NR 7 TC 4 Z9 5 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD MAY PY 2003 VL 96 IS 5 BP 494 EP 496 DI 10.1097/01.SMJ.0000048150.02504.99 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 681XP UT WOS:000183061100015 PM 12911190 ER PT J AU Beard, WA Wilson, SH AF Beard, WA Wilson, SH TI Structural insights into the origins of DNA polymerase fidelity SO STRUCTURE LA English DT Review ID ERROR-PRONE; CRYSTAL-STRUCTURE; REVERSE-TRANSCRIPTASE; SULFOLOBUS-SOLFATARICUS; XERODERMA-PIGMENTOSUM; TERNARY COMPLEXES; SOS MUTAGENESIS; BINDING POCKET; LARGE FRAGMENT; GENE ENCODES AB DNA polymerases discriminate from a pool of structurally similar molecules to insert the correct nucleotide to preserve Watson-Crick base pairing rules. The ability to choose between "right and wrong" is highly dependent on the identity of the polymerase. Because naturally occurring polymerases with divergent fidelities insert incorrect nucleotides with comparable efficiencies, fidelity is primarily governed by the ability to insert the correct nucleotide. DNA polymerases generally bind the correct nucleotide with similar affinities, but low-fidelity polymerases insert correct nucleotides more slowly than higher fidelity enzymes. A comparison of crystallographic ternary substrate complexes of DNA polymerases from five families exhibiting a range of nucleotide insertion rates reveals possible structural features that lead to rapid, efficient, and faithful DNA synthesis. C1 NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM wilson5@niehs.nih.gov NR 52 TC 102 Z9 102 U1 0 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0969-2126 J9 STRUCTURE JI Structure PD MAY PY 2003 VL 11 IS 5 BP 489 EP 496 DI 10.1016/S0969-2126(03)00051-0 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 677ZC UT WOS:000182838900005 PM 12737815 ER PT J AU Pozsgay, V Coxon, B Glaudemans, CPJ Schneerson, R Robbins, JB AF Pozsgay, V Coxon, B Glaudemans, CPJ Schneerson, R Robbins, JB TI Towards an oligosaccharide-based glycoconjugate vaccine against Shigella dysenteriae type 1 SO SYNLETT LA English DT Article DE polysaccharide; oligosaccharides; monosaccharides; antibodies ID O-SPECIFIC POLYSACCHARIDE; INFLUENZAE TYPE-B; PROTEIN CONJUGATE VACCINES; NUCLEAR-MAGNETIC-RESONANCE; OCTASACCHARIDE FRAGMENT; CARBOHYDRATE-CHEMISTRY; TETRA-SACCHARIDE; ANTIBODIES; IMMUNOGENICITY; ANTIGEN AB This review summarizes the authors' studies in the past decade aimed at developing a synthetic oligosaccharide-based glycoconjugate vaccine to prevent a serious human disease caused by the Gram negative bacterium Shigella dysenteriae type 1. Starting from simple monosaccharides, oligosaccharides as large as a 24 monosaccharide-containing linear polymer, were assembled. Under suitable conditions, oligosaccharides containing 4 to 16 hexopyranose residues were covalently attached to an immunogenic protein. The serum response to the synthetic glycoconjugates depends, both on the size of the oligosaccharides, and on the molar ratio of the oligosaccharides to the carrier protein. Also reviewed are studies of the fine specificities of the interaction between oligosaccharides and anti-polysaccharide monoclonal antibodies as well as conformational studies of the synthetic oligosaccharides. C1 NICHHD, NIH, Bethesda, MD 20892 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Pozsgay, V (reprint author), NICHHD, NIH, 6 Ctr Dr,MSC 2720, Bethesda, MD 20892 USA. NR 73 TC 9 Z9 9 U1 2 U2 8 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0936-5214 J9 SYNLETT JI Synlett PD MAY PY 2003 IS 6 BP 743 EP 767 DI 10.1055/s-2003-38724 PG 25 WC Chemistry, Organic SC Chemistry GA 676WY UT WOS:000182776600001 ER PT J AU Rotman-Pikielny, P Brucker-Davis, F Turner, ML Sarlis, NJ Skarulis, MC AF Rotman-Pikielny, P Brucker-Davis, F Turner, ML Sarlis, NJ Skarulis, MC TI Lack of effect of long-term octreotide therapy in severe thyroid-associated dermopathy SO THYROID LA English DT Article; Proceedings Paper CT 11th International Congress of Endocrinology CY OCT 29-NOV 02, 2000 CL SYDNEY, AUSTRALIA ID GROWTH-FACTOR-I; PRETIBIAL MYXEDEMA; GRAVES-DISEASE; FIBROBLASTS; OPHTHALMOPATHY; PATHOGENESIS; SCINTIGRAPHY; CELLS; EXOPHTHALMOS; THYROTROPIN AB Severe thyroid associated dermopathy (TAD), a rare complication of Graves' disease, currently lacks effective treatment. Mediators of growth and inflammation, including insulin-like growth factor-1 (IGF-1) and somatostatin (SST) have been implicated in its pathogenesis. Octreotide, a potent SST analogue, has been used in TAD with anecdotal success. Therefore, we evaluated the efficacy of long-term octreotide therapy in moderate to severe TAD. Three obese women with TAD were studied. Baseline treatment included levothyroxine, methimazole, fluocinonide ointment under occlusive dressing, and physiotherapy for lymphedema. After establishing baseline clinical status, octreotide was started (300 pug subcutaneously daily) for 10 to 28 months. Studies obtained at baseline and every 3 months included: leg circumference, skin examination, clinical photography, self-reported clinical status, body mass index (BMI), serum thyrotropin (TSH) and free thyroxine, titers of antithyroidal and anti-TSH receptor antibodies. Minimal changes in the edema, erythema, skin texture and size of nodules were observed. The minor changes seen followed significant decreases in the patients' BMI, and hence, cannot be specifically attributed to octreotide administration. No clinically significant benefit from long-term octreotide therapy was demonstrated in three patients with moderate to severe TAD. Weight loss and measures such as compression bandaging and topical corticosteroid application still remain the most cost effective treatment modalities for TAD. C1 NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Nice, Ctr Hosp, Dept Med, Nice, France. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Div Intramural Res, NIH, Bethesda, MD USA. RP Skarulis, MC (reprint author), NIDDK, Clin Endocrinol Branch, NIH, Bldg 10,Room 8S235B,10 Ctr Dr,MSC 1771, Bethesda, MD 20892 USA. NR 25 TC 5 Z9 6 U1 1 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD MAY PY 2003 VL 13 IS 5 BP 465 EP 470 DI 10.1089/105072503322021124 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 693KX UT WOS:000183717700007 PM 12855013 ER PT J AU Yim, SH Ward, JM Dragan, Y Yamada, A Scacheri, PC Kimura, S Gonzalez, FJ AF Yim, SH Ward, JM Dragan, Y Yamada, A Scacheri, PC Kimura, S Gonzalez, FJ TI Microarray analysis using amplified mRNA from laser capture microdissection of microscopic hepatocellular precancerous lesions and frozen hepatocellular carcinomas reveals unique and consistent gene expression profiles SO TOXICOLOGIC PATHOLOGY LA English DT Article DE cDNA microarray; indirect labeling; amplified mRNA; laser capture microdissection ID MOLECULAR ANALYSIS; TISSUE; LIVER AB The indirect labeling cDNA microarray technique was used to evaluate gene expression profiles of pure cell populations from frozen sections of carcinomas and adenomas harvested from precancerous hepatocellular lesions by using laser capture microdissection (LCM). The levels of differentially expressed genes were investigated using a cDNA microarray with 9,984 features with only 2 ug of two-round amplified aRNA, equivalent to 35 cells from LCM-adenomas and frozen samples of carcinomas from simian virus 40 (SV40) large T antigen transgenic rats. A total of 855 genes were identified as being 3-fold or more differentially expressed in carcinomas or adenomas as compared to normal tissue controls. Among these 855 genes, 71 genes were differentially expressed in both carcinomas and adenomas. Commonly up-regulated genes in both carcinoma and adenomas were 28 while 41 of the 71 genes were commonly down-regulated. Two genes, Igh1 (immunoglobulin heavy chain 1(Serum IgG2a), Image clone ID: 875880) and EST clone (AI893585, Image clone ID: 596604) were more than 7-fold up-regulated in carcinomas and 6-fold down-regulated in adenomas. In Cy5 and Cy3 reciprocal experiments for screening out false positive signals, the amplified carcinomas showed higher Pearson Correlation Coefficient values (-0.94 and -0.92) than the LCM-amplified adenoma samples (-0.79 and -0.84). LCM-amplified samples provided higher signal intensities over backgrounds and a greater average of Cy5:Cy3 ratios. Expression levels of mRNAs from selected genes, determined by using traditional dot blot analysis, revealed that 36 of 40 tested expression profiles were consistent with the microarray data. Thus, amplified aRNA harvested from homogeneous cell types using LCM can be applied to study gene expression profiles by use of microarray analysis. C1 NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Vet & Tumor Pathol Sect, Ctr Canc Res, Frederick, MD 21701 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bldg 37,Room 2A19,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 16 TC 20 Z9 21 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD MAY-JUN PY 2003 VL 31 IS 3 BP 295 EP 303 DI 10.1080/01926230390204333 PG 9 WC Pathology; Toxicology SC Pathology; Toxicology GA 712GA UT WOS:000184788400007 PM 12746117 ER PT J AU Johnson, FM AF Johnson, FM TI Are rodent carcinogenicity bioassays relevant? Banging the drum softly SO TOXICOLOGIC PATHOLOGY LA English DT Letter ID FOOD-ADDITIVES AMENDMENT; FLAVORING INGREDIENTS; GRAS SUBSTANCES; RECENT PROGRESS C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Johnson, FM (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 42 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD MAY-JUN PY 2003 VL 31 IS 3 BP 350 EP 352 DI 10.1080/01926230390204261 PG 3 WC Pathology; Toxicology SC Pathology; Toxicology GA 712GA UT WOS:000184788400015 ER PT J AU Kamil, AA Khalil, EAG Musa, AM Modabber, F Mukhtar, MM Ibrahim, ME Zijlstra, EE Sacks, D Smith, PG Zicker, F El-Hassan, AM AF Kamil, AA Khalil, EAG Musa, AM Modabber, F Mukhtar, MM Ibrahim, ME Zijlstra, EE Sacks, D Smith, PG Zicker, F El-Hassan, AM TI Alum-precipitated autoclaved leishmania major plus bacille calmette-guerrin, a candidate vaccine for visceral leishmaniasis: safety, skin-delayed type hypersensitivity response and dose finding in healthy volunteers SO TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE LA English DT Article DE visceral leishmaniasis; Leishmania major; alum; bacille Calmette-Guerrin; vaccine; Sudan ID KALA-AZAR; CUTANEOUS LEISHMANIASIS; BCG; DONOVANI; SUDAN; IMMUNOGENICITY; ADJUVANTS; REACTIVITY; PROSPECTS; INFECTION AB In a previous efficacy study, autoclaved Leishmania major (ALM) + bacille Calmette-Guerrin (BCG) vaccine was shown to be safe, but not superior to BCG alone, in protecting against visceral leishmaniasis. From June 1999 to June 2000, we studied the safety and immunogenicity of different doses of alum-precipitated ALM + BCG vaccine mixture administered intradermally to evaluate whether the addition of alum improved the immunogenicity of ALM. Twenty-four healthy adult volunteers were recruited and sequentially allocated to receive either 10 mug, 100 mug, 200 mug, or 400 mug of leishmanial protein in the alum-precipitated ALM + BCG vaccine mixture. Side effects were minimal for all doses and confined to the site of injection. All volunteers in the 10 mug, 100 mug, and 400 mug groups had a leishmanin skin test (LST) reaction of greater than or equal to 5 mm by day 42 and this response was maintained when tested after 90 d. Only 1 volunteer out of 5 in the 200 mug group had a LST reaction of greater than or equal to 5 mm by day 42 and the reasons for the different LST responses in this group are unclear. This is the first time that an alum adjuvant with ALM has been in used in humans and the vaccine mixture was safe and induced a strong delayed type hypersensitivity (DTH) reaction in the study volunteers. On the basis of this study we suggest that 100 mug of leishmanial protein in the vaccine mixture is a suitable dose for future efficacy studies, as it induced the strongest DTH reaction following vaccination. C1 Univ Khartoum, Inst Endem Dis, Leishmaniasis Res Grp, Khartoum, Sudan. Infect Dis Res Inst, Seattle, WA USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. London Sch Hyg & Trop Med, London WC1, England. WHO, TDR, CH-1211 Geneva, Switzerland. RP Khalil, EAG (reprint author), Univ Khartoum, Inst Endem Dis, Leishmaniasis Res Grp, POB 45235, Khartoum, Sudan. EM eltahirk@iend.org RI Zicker, Fabio/I-4138-2012; Zicker, Fabio/B-4209-2009 OI Zicker, Fabio/0000-0002-9751-7430 NR 28 TC 37 Z9 39 U1 0 U2 0 PU ROYAL SOC TROPICAL MEDICINE PI LONDON PA MANSON HOUSE 26 PORTLAND PLACE, LONDON W1N 1EY, ENGLAND SN 0035-9203 J9 T ROY SOC TROP MED H JI Trans. Roy. Soc. Trop. Med. Hyg. PD MAY-JUN PY 2003 VL 97 IS 3 BP 365 EP 368 DI 10.1016/S0035-9203(03)90171-4 PG 4 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 834AM UT WOS:000222383800024 PM 15228261 ER PT J AU Stroncek, D Shawker, T Follmann, D Leitman, S AF Stroncek, D Shawker, T Follmann, D Leitman, S TI G-CSF-induced spleen size changes in peripheral blood progenitor cell donors SO TRANSFUSION LA English DT Article ID COLONY-STIMULATING FACTOR; HEALTHY DONORS; STEM-CELLS; MOBILIZATION; TRANSPLANTATION; COLLECTION; MICE AB BACKGROUND: PBPC donors given G-CSF experience splenic enlargement and, rarely, spontaneous rupture of the spleen. This study evaluated the incidence and time course of splenic enlargement in PBPC concentrate donors and assessed factors affecting size changes. STUDY DESIGN AND METHODS: Twenty healthy adults were given G-CSF (10 mug/kg/day) for 5 days and a PBPC concentrate was collected by apheresis. Ultrasound was used to assess craniocaudal spleen length before giving G-CSF, on the day of apheresis and 3 or 4 days after apheresis. The effects of donor age, gender, race, and changes in blood chemistries, blood counts, and CD34+ cell counts on spleen length change were assessed. RESULTS: Spleen length increased in 19 of 20 donors. Mean length changed from 10.9 +/- 2.0 cm before G-CSF to 12.3 +/- 2.1 cm on the day of apheresis (p < 0.001). The mean increase in length was 1.5 +/- 0.9 cm or 13.8 +/- 9.1 percent. Spleen length increased 20 percent or more in six subjects. The spleen length fell to 11.3 +/- 1.8 cm (p < 0.001) 3 or 4 days after apheresis, but it remained greater than baseline levels (p = 0.03). Spleen length change was not affected by donor gender, race, or age. There was no relationship between changes in spleen length and 1) baseline and apheresis-day blood counts and chemistries, or 2) changes in blood counts and chemistries. CONCLUSIONS: Spleen size increases in almost all PBPC donors. Enlargement is transient but may be marked in some donors and may place them at risk for splenic rupture. C1 NHLBI, Dept Transfus Med, NIH, Bethesda, MD 20892 USA. NHLBI, Dept Diagnost Radiol, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NHLBI, Biostat Res Stn, Bethesda, MD 20892 USA. RP Stroncek, D (reprint author), NHLBI, Dept Transfus Med, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 19 TC 62 Z9 65 U1 0 U2 1 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAY PY 2003 VL 43 IS 5 BP 609 EP 613 DI 10.1046/j.1537-2995.2003.00384.x PG 5 WC Hematology SC Hematology GA 670PV UT WOS:000182418300012 PM 12702182 ER PT J AU Rigden, DJ Jedrzejas, MJ Galperin, MY AF Rigden, DJ Jedrzejas, MJ Galperin, MY TI Amidase domains from bacterial and phage autolysins define a family of gamma-D,L-glutamate-specific amidohydrolases SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID GLUTATHIONYLSPERMIDINE SYNTHETASE/AMIDASE; LISTERIA-MONOCYTOGENES; ESCHERICHIA-COLI; BINDING-PROTEIN; GENE; DATABASE; IDENTIFICATION; STREPTOCOCCUS; PREDICTION; SEQUENCE AB Several phage-encoded peptidoglycan hydrolases have been found to share a conserved amidase domain with a variety of bacterial autolysins (N-acetylmuramoyl-L-alanine amidases), bacterial and eukaryotic glutathionylspermidine amidases, gamma-D-glutamyl-L-diamino acid endopeptidase and NLP/P60 family proteins. All these proteins contain conserved cysteine and histidine residues and hydrolyze gamma-glutamyl-containing substrates. These cysteine residues have been shown to be essential for activity of several of these amidases and their thiol groups apparently function as the nucleophiles in the catalytic mechanisms of all enzymes containing this domain. The CHAP (cysteine, histidine-dependent amidohydrolases/peptidases) superfamily includes a variety of previously uncharacterized proteins, including the tail assembly protein K of phage lambda. Some members of this superfamily are important surface antigens in pathogenic bacteria and might represent drug and/or vaccine targets. C1 Natl Ctr Genet Res & Biotechnol, Cenargen, Embrapa, BR-70770900 Brasilia, DF, Brazil. Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Rigden, DJ (reprint author), Natl Ctr Genet Res & Biotechnol, Cenargen, Embrapa, BR-70770900 Brasilia, DF, Brazil. RI Galperin, Michael/B-5859-2013; OI Galperin, Michael/0000-0002-2265-5572; Rigden, Daniel/0000-0002-7565-8937 FU NIAID NIH HHS [AI44079] NR 32 TC 104 Z9 106 U1 2 U2 4 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD MAY PY 2003 VL 28 IS 5 BP 230 EP 234 DI 10.1016/S0968-0004(03)00062-8 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 689AE UT WOS:000183468800004 PM 12765833 ER PT J AU Franco, R Canals, M Marcellino, D Ferre, S Agnati, L Mallol, J Casado, V Ciruela, F Fuxe, K Lluis, C Canela, EI AF Franco, R Canals, M Marcellino, D Ferre, S Agnati, L Mallol, J Casado, V Ciruela, F Fuxe, K Lluis, C Canela, EI TI Regulation of heptaspanning-membrane-receptor function by dimerization and clustering SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Editorial Material ID A(1) ADENOSINE RECEPTORS; BRAIN CORTICAL MEMBRANES; A(2A) RECEPTORS; HIGH-AFFINITY; DOPAMINE D-1; DEAMINASE; PROTEIN; BINDING; CELLS; DESENSITIZATION AB G-protein-coupled receptors form homomers and heteromers; agonist-induced conformational changes within interacting receptors of the oligomer modify their pharmacology, signalling and/or trafficking. When these receptors are activated, the oligomers rearrange and cluster and a novel mechanism of receptor-operation regulation by oligomer intercommunication is possible. This intercommunication would be assisted by components of the plasma membrane and by scaffolding proteins. Receptor cross-sensitization, cross-desensitization and novel, integrated receptor responses can then develop between oligomeric receptor complexes of the cluster without direct contact between them. This concept gives a new perspective to the understanding of neurotransmission and neuronal plasticity. C1 Univ Barcelona, Dept Biochem Mol Biol, E-08028 Barcelona, Spain. NIDA, Preclin Pharmacol Sect, US Dept HHS, NIH,IRP, Baltimore, MD 21224 USA. Univ Modena, Dept Biomed Sci, Physiol Sect, I-41100 Modena, Italy. Dept Rehabil, Ludes, Paradiso, Switzerland. Karolinska Inst, Div Cell & Mol Neurochem, Dept Neurosci, S-17177 Stockholm, Sweden. RP Franco, R (reprint author), Univ Barcelona, Dept Biochem Mol Biol, Marti Franques 1, E-08028 Barcelona, Spain. RI Ferre, Sergi/K-6115-2014; Ciruela, Francisco/A-5096-2013; Franco, Rafael/C-3694-2015; Casado, Vicent/K-1660-2014; Canela, Enric I./M-8726-2013; OI Ferre, Sergi/0000-0002-1747-1779; Fuxe, Kjell/0000-0001-8491-4288; Canals, Meritxell/0000-0002-7942-5006; Ciruela, Francisco/0000-0003-0832-3739; Franco, Rafael/0000-0003-2549-4919; Canela, Enric I./0000-0003-4992-7440; Casado, Vicent/0000-0002-1764-3825; Marcellino, Daniel/0000-0002-4618-7267 NR 40 TC 70 Z9 70 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD MAY PY 2003 VL 28 IS 5 BP 238 EP 243 DI 10.1016/S0968-0004(03)00065-3 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 689AE UT WOS:000183468800006 PM 12765835 ER PT J AU Patino, WD Mian, OY Shizukuda, Y Hwang, PM AF Patino, WD Mian, OY Shizukuda, Y Hwang, PM TI Current and future applications of SAGE to cardiovascular medicine SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Review ID GENE-EXPRESSION PROFILES; ENDOTHELIAL PROGENITOR CELLS; SERIAL ANALYSIS; HUMAN MONOCYTES; BREAST-CANCER; IDENTIFICATION; TRANSCRIPTOME; HEART; TUMOR; CARDIOMYOPATHY AB The recently sequenced mammalian genomes represent unprecedented resources for advancing our understanding of human diseases. Characterizing gene expression is an important step in translating genomic sequences into clinically useful information. Currently, gene expression studies are revolutionizing the approaches taken to address both basic science and clinical questions. Two major methods have emerged for the global examination of the transcriptome: microarrays and Serial Analysis of Gene Expression (SAGE). The SAGE technique comprehensively maps gene transcription by using the genomic database, yet it remains relatively underutilized for studying cardiovascular biology. This review describes current cardiovascular studies using the SAGE technique and outlines some potential strategies for employing this powerful tool to further our understanding of the cardiovascular system in health and in disease. C1 NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. RP Hwang, PM (reprint author), NHLBI, Cardiovasc Branch, NIH, Bldg 10,Room 7B15,10 Ctr Dr, Bethesda, MD 20892 USA. OI Mian, Omar/0000-0002-8133-8120 NR 46 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD MAY PY 2003 VL 13 IS 4 BP 163 EP 168 AR PII S1050-1738(03)00055-0 DI 10.1016/S1050-1738(03)00055-0 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 677GR UT WOS:000182799000007 PM 12732451 ER PT J AU Mocellin, S Rossi, CR Pilatil, P Nitti, D Marincola, FM AF Mocellin, S Rossi, CR Pilatil, P Nitti, D Marincola, FM TI Quantitative real-time PCR: a powerful ally in cancer research SO TRENDS IN MOLECULAR MEDICINE LA English DT Review ID POLYMERASE-CHAIN-REACTION; MINIMAL RESIDUAL DISEASE; ACUTE LYMPHOBLASTIC-LEUKEMIA; GENE-EXPRESSION ANALYSIS; CHRONIC MYELOID-LEUKEMIA; RT-PCR; COLORECTAL-CANCER; MELANOMA PATIENTS; MESSENGER-RNA; PERIPHERAL-BLOOD AB In this era of the Human Genome Project, quantitation of gene expression in tumor or host cells is of paramount importance for investigating the gene patterns responsible for cancer development, progression and response or resistance to treatment. Quantitative real-time PCR (qrt-PCR) technology has recently reached a level of sensitivity, accuracy and practical ease that supports its use as a routine bioinstrumentation for gene level measurement. Several applications have already been implemented in the field of cancer research, and others are being validated, showing that this molecular biology tool can provide both researchers and clinicians with precious information concerning the behavior of tumors. Knowledge of the biochemical principles underlying this biotechnology can be of great value to interpret correctly qrt-PCR data. C1 Univ Padua, Dept Oncol & Surg Sci, Surg Branch, I-35128 Padua, Italy. NIH, Immunogenet Lab, Dept Transfus Med, Ctr Clin, Bethesda, MD 20814 USA. RP Mocellin, S (reprint author), Univ Padua, Dept Oncol & Surg Sci, Surg Branch, Via Giustiniani 2, I-35128 Padua, Italy. EM mocellins@hotmail.com RI Rossi, Carlo Riccardo/A-7685-2010 OI Rossi, Carlo Riccardo/0000-0001-7875-5655 NR 63 TC 104 Z9 112 U1 2 U2 23 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PD MAY PY 2003 VL 9 IS 5 BP 189 EP 195 DI 10.1016/S1471-4914(03)00047-9 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 689WL UT WOS:000183515900003 PM 12763523 ER PT J AU Mattson, MP Kroemer, G AF Mattson, MP Kroemer, G TI Mitochondria in cell death: novel targets for neuroprotection and cardioprotection SO TRENDS IN MOLECULAR MEDICINE LA English DT Review ID DEPENDENT POTASSIUM CHANNELS; PERMEABILITY TRANSITION PORE; AMYLOID BETA-PEPTIDE; K-ATP CHANNEL; CYCLOSPORINE-A; NEURODEGENERATIVE DISORDERS; SUPEROXIDE-DISMUTASE; SYNAPTIC PLASTICITY; HIPPOCAMPAL-NEURONS; REPERFUSION INJURY AB Post-mitotic neurons and heart muscle cells undergo apoptotic cell death in a variety of acute and chronic degenerative diseases. The intrinsic pathway of apoptosis involves the permeabilization of mitochondrial membranes, which leads to the release of protease and nuclease activators, and to bioenergetic failure. Mitochondrial permeabilization is induced by a variety of pathologically relevant second messengers, including reactive oxygen species, calcium, stress kinases and pro-apoptotic members of the Bcl-2 family. Several pharmacological agents act on mitochondria to prevent the permeabilization of their membranes, thereby inhibiting apoptosis. Such agents include inhibitors of the permeability transition pore complex (in particular ligands of cyclophilin D), openers of mitochondrial ATP-sensitive or Ca2+ -activated K+ channels, and proteins from the Bcl-2 family engineered to cross the plasma membrane. In addition, manipulations that modulate the expression or activity of mitochondrial uncoupling proteins can prevent the death of post-mitotic cells. Such agents hold promise for use in clinical neuroprotection and cardioprotection. C1 NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. Inst Gustave Roussy, CNRS, UMR 1599, F-94805 Villejuif, France. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012; Kroemer, Guido/B-4263-2013 NR 74 TC 192 Z9 228 U1 0 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PD MAY PY 2003 VL 9 IS 5 BP 196 EP 205 DI 10.1016/S1471-4914(03)00046-7 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 689WL UT WOS:000183515900004 PM 12763524 ER PT J AU Dirnagl, U Simon, RP Hallenbeck, JM AF Dirnagl, U Simon, RP Hallenbeck, JM TI Ischemic tolerance and endogenous neuroprotection SO TRENDS IN NEUROSCIENCES LA English DT Review ID FOCAL CEREBRAL-ISCHEMIA; NEURONAL DAMAGE; TNF-ALPHA; RAT-BRAIN; MEDIATED NEUROPROTECTION; SUPEROXIDE-DISMUTASE; PROTEIN-SYNTHESIS; ANOXIA TOLERANCE; ARTERY OCCLUSION; GENE-EXPRESSION AB Practically any stimulus capable of causing injury to a tissue or organ can, when applied close to (but below) the threshold of damage, activate endogenous protective mechanisms - thus potentially lessening the impact of subsequent, more severe stimuli. A sub-threshold ischemic insult applied to the brain, for example, activates certain cellular pathways that can help to reduce damage caused by subsequent ischemic episodes - a phenomenon known as 'ischemic preconditioning' (IP) or 'ischemic tolerance' (IT). Although investigated for some time in model organisms, IP/IT has recently been shown in human brain. This opens a window into endogenous neuroprotection and, potentially, a window of opportunity to utilize these mechanisms in the clinic to treat patients with stroke and other CNS disorders. C1 Humboldt Univ, Charite Hosp, D-10098 Berlin, Germany. RS Dow Neurobiol Labs, Portland, OR 97232 USA. NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. RP Dirnagl, U (reprint author), Humboldt Univ, Charite Hosp, D-10098 Berlin, Germany. OI Dirnagl, Ulrich/0000-0003-0755-6119 NR 76 TC 490 Z9 514 U1 2 U2 39 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD MAY PY 2003 VL 26 IS 5 BP 248 EP 254 DI 10.1016/S0166-2236(03)00071-7 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 682XC UT WOS:000183116800008 PM 12744841 ER PT J AU Shah, BH Catt, KJ AF Shah, BH Catt, KJ TI A central role of EGF receptor transactivation in angiotensin II - induced cardiac hypertrophy SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID GROWTH-FACTOR RECEPTOR; PROTEIN-KINASE-C; LEFT-VENTRICULAR HYPERTROPHY; SMOOTH-MUSCLE CELLS; FACTOR-KAPPA-B; CARDIOMYOCYTE HYPERTROPHY; SIGNAL-TRANSDUCTION; TYROSINE KINASE; MYOCARDIAL HYPERTROPHY; TYPE-1 RECEPTOR AB In addition to their physiological roles in the cardiovascular system (CVS), G-protein-coupled receptor (GPCR) agonists; such as noradrenaline, endothelin-1 and angiotensin II (Ang II) are known to be involved in the development of cardiac hypertrophy. Recent studies using targeted overexpression of the angiotensin AT, receptor in cardiomyocytes suggest that Ang II can directly promote the growth of cardiomyocytes via transactivation of the epidermal growth factor (EGF) receptor and subsequent activation of mitogen-activated protein kinases (MAPKs). This process is mediated by the production of heparin-binding EGF (HB-EGF) by metalloproteases. Blockade of the generation of HB-EGF by metalloprotease inhibitors, or abrogation of EGF receptor kinase activity by selective pharmacological inhibitors or antisense oligonucleotides, protects against Ang II-mediated cardiac hypertrophy. These approaches offer a potential therapeutic strategy to prevent cardiac remodeling and hypertrophy, and possibly prevent progression to heart failure. C1 NICHHD, NIH, Endocrinol & Reprod Res Branch, Bethesda, MD 20892 USA. RP Shah, BH (reprint author), NICHHD, NIH, Endocrinol & Reprod Res Branch, Bethesda, MD 20892 USA. NR 60 TC 84 Z9 87 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD MAY PY 2003 VL 24 IS 5 BP 239 EP 244 DI 10.1016/S0165-6147(03)00079-8 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 689AJ UT WOS:000183469200011 PM 12767723 ER PT J AU Simons, SS AF Simons, SS TI The importance of being varied in steroid receptor transactivation SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID GLUCOCORTICOID MODULATORY ELEMENT; NUCLEAR HORMONE RECEPTORS; HUMAN ESTROGEN-RECEPTOR; LIGAND-BINDING DOMAIN; ANDROGEN RECEPTOR; GENE-EXPRESSION; INDUCTION PROPERTIES; TRANSCRIPTION FACTOR; COREPRESSOR BINDING; COACTIVATOR GRIP1 AB A major response of steroid receptors to steroid hormones is the induction of gene transcription. Two relevant, albeit less studied, properties of these receptors are the EC50 values of the receptor-agonist complexes and the partial agonist activity of the receptor-antagonist complexes. Contrary to earlier expectations, neither the EC50 value nor the partial agonist activity is constant for a given receptor-steroid complex. This variation is, however, beneficial to cells and organisms because it provides a mechanism both for differential control of gene expression by a single concentration of circulating hormone and for limiting side-effects during endocrine therapies. In this article, the factors and proposed mechanisms for the modulation of the EC50 value and partial agonist activity of receptor-steroid complexes are discussed. C1 NIDDK, NIH, Steroid Hormones Section, Bethesda, MD 20892 USA. RP Simons, SS (reprint author), NIDDK, NIH, Steroid Hormones Section, Bldg 8,Room B2A-07, Bethesda, MD 20892 USA. NR 65 TC 36 Z9 36 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD MAY PY 2003 VL 24 IS 5 BP 253 EP 259 DI 10.1016/S0165-6147(03)00101-9 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 689AJ UT WOS:000183469200013 ER PT J AU Zhan, C Correa-de-Araujo, R Wickizer, S Miller, MR Bierman, A AF Zhan, C Correa-de-Araujo, R Wickizer, S Miller, MR Bierman, A TI Inappropriate drug prescribing in outpatient care for the elderly: The case of potentially harmful drug-drug and drug-disease combinations SO VALUE IN HEALTH LA English DT Meeting Abstract C1 AHRQ, Rockville, MD USA. NCI, Frederick, MD 21701 USA. Johns Hopkins Childrens Ctr, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 3 U2 4 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2003 VL 6 IS 3 BP 196 EP 197 DI 10.1016/S1098-3015(10)63847-8 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 688DX UT WOS:000183419000049 ER PT J AU Snyder, C Lipscomb, J Gotay, CC AF Snyder, C Lipscomb, J Gotay, CC TI Developing a measurement strategy for patient-reported outcomes: Findings from the NCI's cancer outcomes measurement working group SO VALUE IN HEALTH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Univ Hawaii, Honolulu, HI 96822 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2003 VL 6 IS 3 BP 236 EP 236 DI 10.1016/S1098-3015(10)63942-3 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 688DX UT WOS:000183419000144 ER PT J AU Hague, BF Zhao, TM Kindt, TJ AF Hague, BF Zhao, TM Kindt, TJ TI Binding of HTLV-1 virions to T cells occurs by a temperature and calcium-dependent process and is blocked by certain type 2 adenosine receptor antagonists SO VIRUS RESEARCH LA English DT Article DE HTLV-1; adenosine receptor antagonists; retrovirus receptor ID LEUKEMIA-VIRUS TYPE-1; SYNCYTIUM FORMATION; INVITRO INFECTION; CELLULAR RECEPTOR; HUMAN MACROPHAGES; PLASMA-MEMBRANE; GLYCOPROTEIN; ANTIBODIES; ENTRY; INHIBITION AB A flow cytometric assay that measures binding of human T-lymphotropic virus type 1 (HTLV-1) virions to target cells was used to investigate the binding process and to screen for compounds affecting viral binding. Results showed that adenosine receptor type 2 antagonists effectively inhibit viral binding at concentrations below 10 muM; no inhibition was seen when antagonist was used to pretreat cells or was added post binding, suggesting direct interference with virus attachment. Efficient HTLV-1 binding required divalent calcium ions and temperatures greater than 20 degreesC. Disruption of lipid rafts by cholesterol depletion compromised viral binding but cleavage of glycosyl-phosphatidylinositol linkages had no effect. A monoclonal antibody (mAb) that recognizes HTLV-1 envelope positions 190-209 impaired binding of virus while other anti-envelope antibodies had no effect. These findings place major constraints on the nature of the HTLV-1 cell binding process and identify a class of inhibitors that may have potential for treatment of infection. (C) 2003 Elsevier Science B.V. All rights reserved. C1 NIAID, Mol & Cellular Immunogenet Sect, NIH, Bethesda, MD 20892 USA. RP Hague, BF (reprint author), NIAID, Mol & Cellular Immunogenet Sect, NIH, Bldg 50,Rm 5515,50 South Dr, Bethesda, MD 20892 USA. NR 39 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD MAY PY 2003 VL 93 IS 1 BP 31 EP 39 DI 10.1016/S0168-1702(03)00048-0 PG 9 WC Virology SC Virology GA 678LH UT WOS:000182868300004 PM 12727340 ER PT J AU Dabdoub, A Jinks, RN Wang, YJ Battelle, BA Payne, R AF Dabdoub, A Jinks, RN Wang, YJ Battelle, BA Payne, R TI Desensitization of the photoresponse in Limulus ventral photoreceptors by protein kinase C precedes rhabdomere disorganization and endocytosis SO VISUAL NEUROSCIENCE LA English DT Article DE PKC; quantum bumps; inhibition; microvilli ID PDZ-DOMAIN PROTEIN; PHOTOTRANSDUCTIVE MEMBRANE TURNOVER; LATERAL EYE; DROSOPHILA PHOTORECEPTORS; INTRACELLULAR CALCIUM; SIGNALING COMPLEXES; VISUAL EXCITATION; LIGHT ADAPTATION; PHORBOL ESTER; CELLS AB Limulus photoreceptors utilize the phosphoinositide pathway to generate light-induced single photon events (quantum bumps) that sum to form the depolarizing receptor potential. The protein kinase C (PKC) activator, (-)-indolactam V (ILV) rapidly desensitizes the light response in Limulus ventral nerve photoreceptors. Within 10 min of extracellular application, 100 nM (-)-ILV caused a decrease in the mean amplitude of quantum bumps to 38% of control values. PKC activation by (-)-ILV also causes photosensitive membrane disorganization and endocytosis. To investigate whether this precedes desensitization of the electrical response, we fixed cells after 10-min incubation with 25 muM (-)-ILV, a concentration sufficient to cause a 1000-fold desensitization of the receptor potential. The photosensitive microvilli of these photoreceptors remained narrow, densely packed, and well organized. Increasing the incubation time to 60 min did, however, induce disorganization and swelling of the microvilli and endocytosis of the photosensitive membrane, as previously reported. Measurement of membrane capacitance did not indicate a significant reduction in membrane area accompanying desensitization by (-)-ILV. PKC-induced reduction in light sensitivity therefore precedes the detection of ultrastructural changes in the rhabdomeral membrane and is not due to a net loss of membrane. C1 Univ Maryland, Dept Biol, College Pk, MD 20742 USA. NIDCD, NIH, Rockville, MD USA. Franklin & Marshall Coll, Dept Biol, Lancaster, PA 17604 USA. Univ Florida, Whitney Lab, St Augustine, FL 32086 USA. RP Payne, R (reprint author), Univ Maryland, Dept Biol, College Pk, MD 20742 USA. RI Wang, Youjun/H-4016-2013 OI Wang, Youjun/0000-0003-0961-1716 FU NEI NIH HHS [EY-07743, EY-13196, R15 EY013196] NR 41 TC 3 Z9 3 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0952-5238 J9 VISUAL NEUROSCI JI Visual Neurosci. PD MAY-JUN PY 2003 VL 20 IS 3 BP 241 EP 248 DI 10.1017/S0952523803203035 PG 8 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 726NU UT WOS:000185606400003 PM 14570246 ER PT J AU Lieberman, R AF Lieberman, R TI Evolving strategies for prostate cancer chemoprevention trials SO WORLD JOURNAL OF UROLOGY LA English DT Article DE chemoprevention; prostate cancer; intraepithelial neoplasia; agents; cohorts; surrogate endpoints ID PROLIFERATIVE INFLAMMATORY ATROPHY; INTRAEPITHELIAL NEOPLASIA; BETA-CAROTENE; PREVENTION; CARCINOMA; SUPPLEMENTATION; PROTEIN; DESIGN AB Prostate cancer chemoprevention (CP) can be defined as the use of natural and synthetic agents that inhibit, reverse or regress precancer and delay progression to invasive cancer. During the past two decades several CP strategies have evolved. The first generation of CP trials tested the efficacy of antioxidants and vitamins including B-carotene, vitamin A, retinol, 13 cis retinoic acid, vitamins E, C and selenium. Although these trials were disappointing, provocative hypotheses were generated for selenium and vitamin E that set the stage for future prostate trials. In the 1990s, the NCI launched a second generation of large CP trials aimed at breast and prostate cancer. One of these trials is the PCPT, testing the efficacy of a 5 alpha-reductase inhibitor-finasteride to prevent prostate cancer in 18,000 men. Although PCPT is still in progress, the NCI recently launched a second large primary prostate CP trial called SELECT, testing the efficacy of selenium and vitamin E in 32,400 men. The Prostate Cancer Progress Report to the Director of NCI in 1998 challenged the research community to design more efficient CP trials for prostate cancer. In response, the NCI has evolved a third generation of CP trials. This involves pharmacologically driven translational science research including agents and their targets, biomarker endpoints, suitable clinical models for testing agents and efficient trial designs employing high risk cohorts and surrogate endpoints. In summary, a dual strategy for CP is being developed which includes public health measures and a medical intervention approach. C1 NCI, Div Canc Prevent, Rockville, MD 20852 USA. RP Lieberman, R (reprint author), 9404 Garden Court, Potomac, MD 20854 USA. NR 32 TC 13 Z9 13 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0724-4983 J9 WORLD J UROL JI World J. Urol. PD MAY PY 2003 VL 21 IS 1 BP 3 EP 8 DI 10.1007/s00345-003-0317-4 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 694BB UT WOS:000183751900002 PM 12682772 ER PT J AU Klein, EA Lippman, SM Thompson, IM Goodman, PJ Albanes, D Taylor, PR Coltman, C AF Klein, EA Lippman, SM Thompson, IM Goodman, PJ Albanes, D Taylor, PR Coltman, C TI The Selenium and Vitamin E Cancer Prevention Trial SO WORLD JOURNAL OF UROLOGY LA English DT Article DE prostate cancer; chemoprevention; selenium; vitamin E ID NUTRITION INTERVENTION TRIALS; DISEASE-SPECIFIC MORTALITY; KINASE-C ACTIVITY; PROSTATE-CANCER; BETA-CAROTENE; ALPHA-TOCOPHEROL; COLORECTAL-CANCER; LUNG-CANCER; COLON-CANCER; FOLLOW-UP AB Background: Evidence suggests that both selenium and vitamin E reduce the risk of prostate cancer. The Selenium and Vitamin E Cancer Prevention Trial (SELECT) is a randomized, prospective, double-blind study designed to determine whether selenium and vitamin E alone and in combination can reduce the risk of prostate cancer among healthy men. Materials and methods: The preclinical and epidemiological evidence supporting a role for selenium and vitamin E as chemopreventive agents in prostate cancer are reviewed, and details of the trial design are presented. Results: Preclinical, epidemiological, and phase III data from randomized, placebo-controlled clinical trials suggest that both selenium and vitamin E have potential efficacy in prostate cancer prevention. SELECT is a 2x2 factorial study with an accrual goal of 32,400 men with nonsuspicious DRE and serum PSA of 4 ng/ml or lower. Conclusions: SELECT is the second large-scale study of chemoprevention for prostate cancer. Enrollment began in 2001 with final results anticipated in 2013. C1 Cleveland Clin Fdn, Inst Urol, Sect Urol Oncol, Cleveland, OH 44195 USA. Univ Texas, MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77030 USA. Univ Texas, Hlth Sci Ctr, Div Urol, San Antonio, TX USA. Fred Hutchinson Canc Res Ctr, SW Oncol Grp, Ctr Stat, Seattle, WA 98104 USA. NCI, Div Clin Sci, Canc Prevent Studies Branch, Washington, DC USA. SW Oncol Grp, San Antonio, TX USA. RP Cleveland Clin Fdn, Inst Urol, Sect Urol Oncol, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM kleine@ccf.org RI Albanes, Demetrius/B-9749-2015 NR 57 TC 94 Z9 100 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-4983 EI 1433-8726 J9 WORLD J UROL JI World J. Urol. PD MAY PY 2003 VL 21 IS 1 BP 21 EP 27 DI 10.1007/s00345-002-0314-z PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 694BB UT WOS:000183751900005 PM 12756490 ER PT J AU Tadaki, DK Williams, A Lee, KP Kirk, AD Harlan, DM AF Tadaki, DK Williams, A Lee, KP Kirk, AD Harlan, DM TI Porcine CD80: cloning, characterization, and evidence for its role in direct human T-cell activation SO XENOTRANSPLANTATION LA English DT Article DE B7; CD80; MLR; porcine ID HEART ALLOGRAFT ACCEPTANCE; ANTIGEN-PRESENTING CELLS; ENDOTHELIAL-CELLS; PASSENGER LEUKOCYTES; VASCULARIZED XENOGRAFTS; COSTIMULATORY MOLECULES; RECOGNITION PATHWAY; DENDRITIC CELLS; TNF-ALPHA; EXPRESSION AB Previous studies has shown that human anti-pig reactivity in mixed lymphocyte cultures require the indirect presentation of antigens by human antigen presenting cells (APC). Xenoreactivity was inhibited by blockade of human costimulatory molecules. We investigated the role of porcine costimulatory molecules in their ability to activate human T cells directly. Porcine CD80 was cloned from lipopolysaccharide (LPS)-activated porcine lymphocytes. Sequence analysis showed a high degree of conservation in residues involved in CD28/CTLA4. COS cells transfected with porcine CD80 was able to activate human T cells in a cyclosporine independent manner, demonstrating that porcine CD80 can costimulate human T cells. Tumor necrosis factor-alpha (TNF-alpha) activated porcine splenocytes have been shown to up-regulate B7s. In order to test the effect of costimulation blockade in a xeno system, activated splenocytes were cultured with purified CD4+ T cells. The results demonstrated that these cells were capable of activating human T cells and this activation can be blocked by using an antihuman CD80 antibody that demonstrated cross-reactivity to porcine CD80. Non-cross reactive antibodies had no effect, again suggesting direct activation of the human T cells. These data suggest that a reagent that can block both the direct and indirect activation is necessary for a discordant xenotransplant. C1 USN, NIDDK, Navy Transplantat & Autoimmun Branch, Med Res Ctr, Bethesda, MD 20889 USA. Gene Log Inc, Gaithersburg, MD USA. Univ Miami, Sch Med, Miami, FL USA. RP Tadaki, DK (reprint author), USN, NIDDK, Navy Transplantat & Autoimmun Branch, Med Res Ctr, 8901 Wisconsin Ave,Bldg 42 Room 2416, Bethesda, MD 20889 USA. RI Kirk, Allan/B-6905-2012 NR 39 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD MAY PY 2003 VL 10 IS 3 BP 252 EP 258 DI 10.1034/j.1399-3089.2003.02004.x PG 7 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 667YK UT WOS:000182262300007 PM 12694545 ER PT J AU Botkin, JR Smith, KR Croyle, RT Baty, BJ Wylie, JE Dutson, D Chan, A Hamann, HA Lerman, C McDonald, J Venne, V Ward, JH Lyon, E AF Botkin, JR Smith, KR Croyle, RT Baty, BJ Wylie, JE Dutson, D Chan, A Hamann, HA Lerman, C McDonald, J Venne, V Ward, JH Lyon, E TI Genetic testing for a BRCA1 mutation: Prophylactic surgery and screening behavior in women 2 years post testing SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE BRCA1; genetic testing; mammography; prophylactic surgery; breast cancer; ovarian cancer ID OVARIAN-CANCER FAMILIES; BREAST-CANCER; HEREDITARY BREAST; EVENT SCALE; MASTECTOMY; SUSCEPTIBILITY; OOPHORECTOMY; CARRIERS; IMPACT; RISKS AB Mutations in the BRCA1 gene are associated with an increased risk of breast and ovarian cancer in carrier women. An understanding of behavioral responses to BRCA1 mutation testing by mutation carriers and non-carriers is important to guide the clinical application of this new technology. This study examined the utilization of genetic testing for a BRCA1 mutation in high-risk individuals and the response of tested women with respect to interventions for early cancer detection and prevention. This study assessed the utilization of genetic testing for both men and women in a large kindred and the behavioral responses by women with respect to use of health care interventions during the 2 years following testing. Participants were offered BRCA1 mutation testing. Surveillance behaviors related to breast and ovarian cancer were assessed by computer-assisted telephone interviews at baseline (prior to genetic counseling and testing), 1-2 weeks, 4-6 months, 1 and 2 years after the provision of test results. Mutation carriers, non-carriers, and individuals of unknown mutation status were compared to determine the impact of test results. Utilization of genetic testing for both men and women are reported and, for women, mammography, breast self-exam, clinical breast exam, mastectomy, oophorectomy, transvaginal ultrasound, and CA125 screening were assessed. Of those fully informed of the opportunity for testing, 55% of the women and 52% of the men pursued genetic testing. With respect to mammography for women 40 years and older, 82% of mutation carriers obtained a mammogram in each year following testing compared to 72% of non-carrier women the first year and 67% the second year. This mammography utilization represents a significant increase over baseline for both mutation carriers and non-carriers. Younger carrier women also significantly increased their mammography utilization from baseline. Overall, 29% of the carrier women did not obtain a single mammogram by 2 years post-testing. At 2 years, 83% of the carrier women and 74% of the non-carriers reported adherence to recommendations for breast self-exam and over 80% of carrier women had obtained a clinical breast examination each year following testing. None of the carrier women had obtained a prophylactic mastectomy by 2 years after testing, although 11% were considering this procedure. Of carrier women 25 years of age and older who had at least one intact ovary at the time of testing, 46% of carriers had obtained an oophorectomy 2 years after testing, including 78% of women 40 years of age and older. The majority of carrier women (73%) had discussed their genetic test results with a medical doctor or health care provider. Our results indicate utilization of genetic testing by a majority of high-risk individuals who received information about testing. Both carriers and non-carriers increased their utilization of mammography and breast self-exam following testing. Oophorectomy was obtained by a large proportion of carrier women in contrast to mastectomy which was not utilized within the first 2 years following testing. (C) 2003 Wiley-Liss, Inc. C1 Univ Utah, Dept Pediat, Salt Lake City, UT USA. Univ Utah, Dept Family & Consumer Studies, Salt Lake City, UT 84112 USA. NCI, Div Canc Control & Populat Sci, Rockville, MD USA. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. US Bur Census, Div Stat Res, Washington, DC USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA. Univ Utah, Dept Oncol Sci, Salt Lake City, UT USA. Univ Utah, Dept Pathol, Salt Lake City, UT USA. RP Botkin, JR (reprint author), Primary Childrens Med Ctr, Dept Pediat, 100 N Med Dr, Salt Lake City, UT 84113 USA. FU NCI NIH HHS [CA63681]; NCRR NIH HHS [M01-RR00064]; NHGRI NIH HHS [HG00199] NR 37 TC 132 Z9 134 U1 0 U2 8 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 A JI Am. J. Med. Genet. A PD APR 30 PY 2003 VL 118A IS 3 BP 201 EP 209 DI 10.1002/ajmg.a.10102 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 670HM UT WOS:000182401500001 PM 12673648 ER PT J AU Lee, SK Kim, SM Lee, YJ Yamada, KM Yamada, Y Chi, JG AF Lee, SK Kim, SM Lee, YJ Yamada, KM Yamada, Y Chi, JG TI The structure of the rat ameloblastin gene and its expression in amelogenesis SO MOLECULES AND CELLS LA English DT Article DE alternative splicing; rat ameloblastin gene; specific expression; subtypes ID DYNAMIC LIGHT-SCATTERING; RECOMBINANT AMELOGENIN; PROTEIN INTERACTIONS; AUTOSOMAL-DOMINANT; ENAMELIN TUFTELIN; IMMUNOLOCALIZATION; LOCALIZATION; DEGRADATION; IMPERFECTA; SEQUENCE AB Ameloblastin (also designated amelin and sheathlin) is an enamel matrix protein expressed within the ameloblast lineage. In this study we analyzed the structure of the rat ameloblastin gene and characterized its subtypes. The promoter sequence contains several E-box-like elements, and consensus sequences for AP1 and SP1. The gene is about 6 kb in length and contains 12 exons. Exon 1 was mapped by primer extension and encodes 90 bp of 5' untranslated leader sequence, followed by the coding sequences of exon 2 (309 bp), alternatively spliced exon 3a (45 bp), exon A (198 bp), exon 4 (36 bp), exon 5 (60 bp), exon 6 (45 bp), exon 7 (150 bp), and exon 8 (448 bp) containing coding sequence (426 bp) and 3' untranslated sequence (22 bp), followed by exon 9 (39 bp); exon 10 (143 bp); exon 11 (342 bp); and exon 12. Exon 3a, encoding YEYSL-PVHPPPLPSQ, has a potential SH3 binding domain. Analysis of ameloblastin subclones showed that exon 3a and 11 were potential alternative splicing sites, producing 4 types of ameloblastin mRNA, from which ameloblastin I and II could be translated. Using in situ hybridization, immunohistochemistry, Western blot and RT-PCR methods we found that ameloblastin II, containing exon 3a, was more strongly expressed at the late maturation stage of ameloblasts than at the secretory stage, while a common probe for both ameloblastin subtypes showed wide expression throughout the presecretory, secretory and postsecretory stages. From the above results we propose that ameloblastin II plays an important role in the mineralization of ameloblasts during the maturation stages. C1 Seoul Natl Univ, Dept Pathol, Seoul 110744, South Korea. Kangnung Natl Univ, Coll Dent, Dept Oral Pathol, Kangnung 210702, South Korea. Kangnung Natl Univ, Coll Dent, Dept Oral & Maxillofacial Surg, Kangnung 210702, South Korea. NIDCD, NIH, Bethesda, MD 20892 USA. RP Chi, JG (reprint author), Seoul Natl Univ, Dept Pathol, Seoul 110744, South Korea. RI Chi, Je Geun/G-4989-2011; OI Chi, Je-Geun/0000-0002-9950-2072; Yamada, Kenneth/0000-0003-1512-6805 NR 38 TC 20 Z9 20 U1 0 U2 0 PU SPRINGER-VERLAG SINGAPORE PTE LTD PI SINGAPORE PA #04-01 CENCON I, 1 TANNERY RD, SINGAPORE 347719, SINGAPORE SN 1016-8478 J9 MOL CELLS JI Mol. Cells PD APR 30 PY 2003 VL 15 IS 2 BP 216 EP 225 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 673PF UT WOS:000182588800012 PM 12803485 ER PT J AU Bash, R Wang, H Yodh, J Hager, G Lindsay, SM Lohr, D AF Bash, R Wang, H Yodh, J Hager, G Lindsay, SM Lohr, D TI Nucleosomal arrays can be salt-reconstituted on a single-copy MMTV promoter DNA template: Their properties differ in several ways from those of comparable 5S concatameric arrays SO BIOCHEMISTRY LA English DT Article ID ATOMIC-FORCE MICROSCOPY; CORE PARTICLE; GLUCOCORTICOID RECEPTOR; STRUCTURAL FEATURES; NONRANDOM BEHAVIOR; MOLECULAR-BIOLOGY; CHROMATIN ARRAYS; HISTONE OCTAMER; IN-VITRO; SEQUENCES AB Subsaturated nucleosomal arrays were reconstituted on a single-copy MMTV promoter DNA fragment by salt dialysis procedures and studied by atomic force microscopy. Up to an occupation level of approximately eight nucleosomes on this 1900 by template, salt reconstitution produces nucleosomal arrays which look very similar to comparably loaded 5S rDNA nucleosomal arrays; i.e., nucleosomes are dispersed on the DNA template. Thus, at these occupation levels, the single-copy MMTV template forms arrays suitable for biophysical analyses. A quantitative comparison of the population features of subsaturated MMTV and 5S arrays detects differences between the two: a requirement for higher histone levels to achieve a given level of nucleosome occupation on MMTV templates, indicating that nucleosome loading is thermodynamically less favorable on this template; a preference for pairwise nucleosome occupation of the MMTV (but not the 5S) template at midrange occupation levels; and an enhanced salt stability for nucleosomes on MMTV versus 5S arrays, particularly in the midrange of array occupation. When average occupation levels exceed approximately eight nucleosomes per template, MMTV arrays show a significant level of mainly intramolecular compaction; 5S arrays do not. Taken together, these results show clearly that the nature of the underlying DNA template can affect the physical properties of nucleosomal arrays. DNA sequence-directed differences in the physical properties of chromatin may have important consequences for functional processes such as gene regulation. C1 Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA. Midwestern Univ, Arizona Coll Osteopath Med, Div Basic Sci, Glendale, AZ 85308 USA. Arizona State Univ, Dept Phys & Astron, Tempe, AZ 85287 USA. NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Lohr, D (reprint author), Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA. FU NCI NIH HHS [CA-85990] NR 60 TC 16 Z9 17 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 29 PY 2003 VL 42 IS 16 BP 4681 EP 4690 DI 10.1021/bi026887o PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 671JB UT WOS:000182460700009 PM 12705831 ER PT J AU Noskov, VN Kouprina, N Leem, SH Ouspenski, I Barrett, JC Larionov, V AF Noskov, VN Kouprina, N Leem, SH Ouspenski, I Barrett, JC Larionov, V TI A general cloning system to selectively isolate any eukaryotic or prokaryotic genomic region in yeast SO BMC GENOMICS LA English DT Article ID TRANSFORMATION-ASSOCIATED RECOMBINATION; SACCHAROMYCES-CEREVISIAE; ARTIFICIAL CHROMOSOMES; ESCHERICHIA-COLI; DNA; SEQUENCE; TAR AB Background: Transformation-associated recombination ( TAR) cloning in yeast is a unique method for selective isolation of large chromosomal fragments or entire genes from complex genomes. The technique involves homologous recombination, during yeast spheroplast transformation, between genomic DNA and a TAR vector that has short (similar to60 bp) 5' and 3' gene targeting sequences (hooks). Result: TAR cloning requires that the cloned DNA fragment carry at least one autonomously replicating sequence (ARS) that can function as the origin of replication in yeast, which prevents wide application of the method. In this paper, we describe a novel TAR cloning system that allows isolation of genomic regions lacking yeast ARS-like sequences. ARS is inserted into the TAR vector along with URA3 as a counter-selectable marker. The hooks are placed between the TATA box and the transcription initiation site of URA3. Insertion of any sequence between hooks results in inactivation of URA3 expression. That inactivation confers resistance to 5-fluoroorotic acid, allowing selection of TAR cloning events against background vector recircularization events. Conclusion: The new system greatly expands the area of application of TAR cloning by allowing isolation of any chromosomal region from eukaryotic and prokaryotic genomes regardless of the presence of autonomously replicating sequences. C1 NCI, Lab Biosyst & Canc, NIH, Bethesda, MD 20892 USA. RP Larionov, V (reprint author), NCI, Lab Biosyst & Canc, NIH, Bethesda, MD 20892 USA. NR 35 TC 18 Z9 19 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD APR 29 PY 2003 VL 4 AR 16 DI 10.1186/1471-2164-4-16 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 685FJ UT WOS:000183249900002 PM 12720573 ER PT J AU McConville, P Fishbein, KW Lakatta, EG Spencer, RGS AF McConville, P Fishbein, KW Lakatta, EG Spencer, RGS TI Differences in the bioenergetic response of the isolated perfused rat heart to selective beta(1)- and beta(2)-adrenergic receptor stimulation SO CIRCULATION LA English DT Article DE receptors, adrenergic, beta; metabolism; oxygen; imaging ID NOREPINEPHRINE INFUSION; MAGNETIC-RESONANCE; ENERGY-METABOLISM; P-31-NMR; PHOSPHORYLATION; ADENOSINE; INCREASE; CELLS; TURNOVER; CAMP AB Background-In the heart, striking functional differences exist after stimulation of the beta(1)- and beta(2)-adrenergic receptor (AR) subtypes. These may be linked to differences in metabolic response during beta(1)- and beta(2)-AR stimulation. Methods and Results-The relation between work and metabolism was examined during selective beta(1)- and beta(2)-AR stimulation (beta(1) and beta(2) groups, respectively) in the isolated perfused rat heart. Measurements were made of rate-pressure product (RPP=LV developed pressure x heart rate), phosphorus-containing metabolites, and pH by P-31 nuclear magnetic resonance spectroscopy and of O-2 consumption by fiber-optic oximetry. Experiments were performed under high constant flow (HCF) and under flow-limiting conditions (constant pressure, CP). Despite substantially greater RPP increases relative to baseline during beta(1)-AR (HCF, 475%; CP, 150%) than beta(2)-AR (HCF, 90%; CP, 72%) stimulation, the relative decrease in the intracellular energy charge relative to baseline was similar for the beta(1) (HCF, 49%; CP, 64%) and beta(2) (HCF, 59%; CP, 55%) groups. For each group, an increase in oxygen consumption (MV. O-2) occurred commensurate with workload during HCF (beta(1), 141%; beta(2), 30%). During CP, however, the MV. O-2 increase was similar (beta(1), 39%; beta(2), 34%), despite the large RPP difference between the groups. During both protocols, there was greater acidosis during beta(1)-AR than during beta(2)-AR stimulation. Thus, at a given workload, intracellular energy charge decreased, and MV. O-2 (CP) increased to a greater extent during beta(2) than beta(1)-AR stimulation. Conclusions-The bioenergetic differences are consistent with access to an additional substrate pool during beta(1)-AR stimulation. This may occur via increased glycogenolysis during beta(1)-AR stimulation, facilitating increased energy production by oxidative phosphorylation, and under flow-limiting conditions, anaerobic glycolysis. C1 NIA, NMR Unit, Clin Invest Lab,Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NIA, NMR Unit, Lab Cardiovasc Sci,Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Spencer, RGS (reprint author), NIA, NMR Unit, Clin Invest Lab,Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 21 TC 8 Z9 8 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 APR 29 PY 2003 VL 107 IS 16 BP 2146 EP 2152 DI 10.1161/01.CIR.0000062686.72615.9B PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 672MU UT WOS:000182525300028 PM 12707247 ER PT J AU Pavlov, YI Mian, IM Kunkel, TA AF Pavlov, YI Mian, IM Kunkel, TA TI Evidence for preferential mismatch repair of lagging strand DNA replication errors in yeast SO CURRENT BIOLOGY LA English DT Article ID CELL NUCLEAR ANTIGEN; SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; MUTAGENESIS; MECHANISM; IDENTIFICATION; 8-OXO-GUANINE; 8-OXOGUANINE; MSH2-MSH6; INTERACT AB Duplex DNA is replicated in the 5'-3'direction by coordinated copying of leading and lagging strand templates with somewhat different proteins and mechanics, providing the potential for differences in the fidelity of replication of the two strands. We previously showed that in Saccharomyces cerevisiae, active replication origins establish a strand bias in the rate of base substitutions resulting from replication of unrepaired 8-oxo-guanine (GO) in DNA [1]. Lower mutagenesis was associated with replicating lagging strand templates. Here, we test the hypothesis that this bias is due to more efficient repair of lagging stand mismatches by measuring mutation rates in ogg1 strains with a reporter allele in two orientations at loci on opposite sides of a replication origin on chromosome Ill. We compare a MMR-proficient strain to strains deleted for the MMR genes MSH2, MSH6, MLH1, or EXOI. Loss of MMR reduces the strand bias by preferentially increasing mutagenesis for lagging strand replication. We conclude that GO-A mismatches generated during lagging strand replication are more efficiently repaired. This is consistent with the hypothesis that 5' ends of Okazaki fragments and PCNA, present at high density during lagging strand replication, are used as strand discrimination signals for mismatch repair in vivo. C1 NIEHS, Mol Genet Lab, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. Duke Univ, Durham, NC 27708 USA. RP Kunkel, TA (reprint author), NIEHS, Mol Genet Lab, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. NR 30 TC 93 Z9 96 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD APR 29 PY 2003 VL 13 IS 9 BP 744 EP 748 DI 10.1016/S0960-9822(03)00284-7 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 674ME UT WOS:000182639900021 PM 12725731 ER PT J AU Zanuy, D Aleman, C AF Zanuy, D Aleman, C TI Molecular dynamics simulations of surfactant-poly(alpha,L-glutamate) complexes in chloroform solution: Influence of the chemical constitution of the surfactant in the molecular organization SO LANGMUIR LA English DT Article ID SOLID-STATE; POLYPEPTIDES; ALPHA; ACID; POLYELECTROLYTES; PROTEINS; MOTION AB Results of molecular dynamics simulations of different stoichiometric complexes constituted by poly(alpha,L-glutamate) and oppositely charged amphiphilic surfactants (n-hexylammonium, n-dodecylammonium, n-hexyltrimethylammonium and n-dodecyltrimethylammonium) are presented. Simulations were performed in dilute chloroform solution using explicit solvent molecules. It is shown that the conformation of the polypeptide chain is strongly influenced by the constitution of the surfactant polar headgroup. Thus, the polypeptide adopts a canonical alpha-helix conformation in complexes containing n-alkyltrimethylammonium surfactants, while a nonregular but also elongated conformation was found in complexes formed by alkylammonium surfactants. The latter structure is due to the interaction of alkylammonium cations with the amide group of the polypeptide chain. On the other hand, we show the intrinsic tendency of the molecular cations to form multiple interactions with the polypeptide chain, independently of their constitution. C1 NCI, Lab Expt & Computat Biol, Frederick, MD 21702 USA. Univ Politecn Catalunya, ETSEIB, Dept Engn Quim, E-08028 Barcelona, Spain. RP Zanuy, D (reprint author), NCI, Lab Expt & Computat Biol, Bldg 469,Room 151, Frederick, MD 21702 USA. RI Zanuy, David/G-3930-2014 OI Zanuy, David/0000-0001-7704-2178 NR 24 TC 13 Z9 14 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0743-7463 J9 LANGMUIR JI Langmuir PD APR 29 PY 2003 VL 19 IS 9 BP 3987 EP 3995 DI 10.1021/la026549o PG 9 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA 671LW UT WOS:000182467100060 ER PT J AU Bonner, WM AF Bonner, WM TI Low-dose radiation: Thresholds, bystander effects, and adaptive responses SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID DOUBLE-STRAND BREAKS; C3H 10T(1)/(2) CELLS; IONIZING-RADIATION; ALPHA-PARTICLES; HISTONE H2AX; NEOPLASTIC TRANSFORMATION; DNA-DAMAGE; INDUCE; MICE; GAMMA-H2AX C1 NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Bonner, WM (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bldg 37,Room 5050A,MSC 4255,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 35 TC 88 Z9 103 U1 3 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 29 PY 2003 VL 100 IS 9 BP 4973 EP 4975 DI 10.1073/pnas.1031538100 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 673ZY UT WOS:000182612600002 PM 12704228 ER PT J AU Root, MJ Hamer, DH AF Root, MJ Hamer, DH TI Targeting therapeutics to an exposed and conserved binding element of the HIV-1 fusion protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ENVELOPE GLYCOPROTEIN; MEMBRANE-FUSION; POTENT INHIBITORS; ATOMIC-STRUCTURE; COILED-COIL; TYPE-1 GP41; ENTRY; IMMUNOTOXIN; REPLICATION AB There is an urgent need for new drugs that can kill HIV type 1 (HIV-1)-infected cells. HIV-1 glycoprotein Env, which promotesviral membrane fusion through receptor-mediated conformational changes, is an attractive target for such agents because it is expressed on the surface of both virions and infected cells. Unfortunately, conserved binding elements on this protein frequently are buried under a canopy of flexible, glycosylated peptide loops or exposed only transiently during the fusion process. Here, we investigate the exposure of the C-terminal region of the Env ectodomain outside the context of membrane fusion. This binding element is the target of the 5-Helix protein, a designed entry inhibitor that disrupts conformational changes in Env subunit gp41, essential for the fusion process. We show that 5-Helix is capable of interacting with HIV-1 Env in a receptor-independent fashion and that a chimeric 5-Helix / Pseudomonas exotoxin protein recognizes cells expressing Env from a broad spectrum of HIV-1 strains including primary isolates from clades B, D, E, G, and H. This recombinant toxin selectively kills HIV-1-infected cells and blocks spreading infection while still maintaining potent inhibitory activity against membrane fusion. Our results demonstrate that the C-terminal region of the gp41 ectodomain is an accessible target on HIV-1-infected cells for the development of antiviral therapeutics and neutralizing antibodies. C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Ctr Human Virol, Philadelphia, PA 19107 USA. RP Hamer, DH (reprint author), NCI, Biochem Lab, NIH, Bldg 37,Room 6002,9000 Rockville Pike, Bethesda, MD 20892 USA. FU NIGMS NIH HHS [GM66682, R01 GM066682] NR 35 TC 35 Z9 36 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 29 PY 2003 VL 100 IS 9 BP 5016 EP 5021 DI 10.1073/pnas.0936926100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 673ZY UT WOS:000182612600012 PM 12702763 ER PT J AU Curtis, J Kim, G Wehr, NB Levine, RL AF Curtis, J Kim, G Wehr, NB Levine, RL TI Group B streptococcal phospholipid causes pulmonary hypertension SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BETA-2-GLYCOPROTEIN-I; PIGLETS; SHEEP; CARDIOLIPIN; INHIBITION; RESPONSES; BINDING; LIPIDS AB Group B Streptococcus is the most common cause of bacterial infection in the newborn. Infection in many cases causes persistent pulmonary hypertension, which impairs gas exchange in the lung. We purified the bacterial components causing pulmonary hypertension and identified them as cardiolipin and phosphatidylglycerol. Synthetic cardiolipin or phosphatidylglycerol also induced pulmonary hypertension in lambs. The recognition that bacterial phospholipids may cause pulmonary hypertension in newborns with Group B streptococcal infection opens new avenues for therapeutic intervention. C1 NHLBI, Biochem Lab, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Natl Naval Med Ctr, Bethesda, MD 20814 USA. RP Levine, RL (reprint author), NHLBI, Biochem Lab, Bldg 10, Bethesda, MD 20892 USA. RI Levine, Rodney/D-9885-2011 NR 29 TC 8 Z9 8 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 29 PY 2003 VL 100 IS 9 BP 5087 EP 5090 DI 10.1073/pnas.0931493100 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 673ZY UT WOS:000182612600024 PM 12702761 ER PT J AU Wang, J Tekle, E Oubrahim, H Mieyal, JJ Stadtman, ER Chock, PB AF Wang, J Tekle, E Oubrahim, H Mieyal, JJ Stadtman, ER Chock, PB TI Stable and controllable RNA interference: Investigating the physiological function of glutathionylated actin SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GENOMIC ANALYSIS; MAMMALIAN-CELLS; MESSENGER-RNA; PATHWAY; THIOLTRANSFERASE; GLUTATHIOLATION; GLUTAREDOXIN; DROSOPHILA; CLEAVAGE; SIRNAS AB RNA interference is an effective method to silence specific gene expression. Its application to mammalian cells, however, has been hampered by various shortcomings. Recently, it was reported that introduction of 22-bp double-stranded RNAs (dsRNAs) would specifically suppress expression of endogenous and heterogeneous genes in various mammalian cell lines. However, using this method, we failed to knock out proteins of interest effectively. Here we report the development of a stable and controllable method for generating dsRNA intracellularly. Tetracycline-responsive transactivator-containing cells were transfected with a vector capable of tetracycline-induced bidirectionally overexpressing sense and antisense RNA to form dsRNA in vivo. With this method, glutaredoxin, monitored by Western blot, was knocked out by overexpressing 290-base sense and antisense RNA in NIH 3T3 cells controlled by tetracycline or doxycycline. By using these glutaredoxin knocked-out cells, we have demonstrated that actin deglutathionylation plays a key role in growth factor-mediated actin polymerization, translocalization, and reorganization near the cell periphery. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA. RP Chock, PB (reprint author), NHLBI, Biochem Lab, NIH, Bldg 3, Bethesda, MD 20892 USA. NR 31 TC 111 Z9 115 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 29 PY 2003 VL 100 IS 9 BP 5103 EP 5106 DI 10.1073/pnas.0931345100 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 673ZY UT WOS:000182612600027 PM 12697895 ER PT J AU Chevion, S Moran, DS Heled, Y Shani, Y Regev, G Abbou, B Berenshtein, E Stadtman, ER Epstein, Y AF Chevion, S Moran, DS Heled, Y Shani, Y Regev, G Abbou, B Berenshtein, E Stadtman, ER Epstein, Y TI Plasma antioxidant status and cell injury after severe physical exercise SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RAT SKELETAL-MUSCLE; INDUCED OXIDATIVE STRESS; HUMAN-BLOOD-PLASMA; LIPID-PEROXIDATION; FREE-RADICALS; VITAMIN-E; CYCLIC VOLTAMMETRY; ENDURANCE EXERCISE; PROTEIN OXIDATION; MARATHON RUN AB Strenuous exercise leads to an increase in metabolic rate, increased production of reactive oxygen species, and compromised antioxidant defense systems. To study the effects of oxidative stress during strenuous exercise, a homogeneous group of 31 male subjects participated in a 6-month, 5 days/week training schedule involving two extreme marches of 50 km and 80 km at sea level, separated by 2 weeks of regular training. Each participant carried 35 kg of extra weight. Blood samples were drawn imediately before and after each march. Twenty-nine subjects completed the 50-km march, and only 16 completed the 80-km march. Plasma levels of reduced ascorbic acid, total ascorbate, and dehydroascorbate did not undergo significant changes during either march. However, the 50- and 80-km marches led to 25% and 37% increases, respectively, in plasma levels of uric acid; due presumably to increases in the metabolic rate and consequent pyrimidine nucleotide metabolism. Both marches led to approximate to10-fold increase leakage of creatine phosphokinase into the plasma. Likewise, plasma levels of aspartate transaminase, a characteristic marker of liver injury, increased approximate to4-fold. Plasma levels of bilirubin, creatine, urea, and glucose also increased. Plasma protein carbonyl content, a marker of protein oxidative damage, decreased significantly during each march. These results are discussed with respect to the consideration that elevation of the respiration rate during exercise leads to production of more reactive oxygen species than the antioxidant systems can scavenge. Plausible explanations for leakage of molecules into the plasma are discussed. C1 Chaim Sheba Med Ctr, Heller Inst Med Res, IL-52621 Tel Hashomer, Israel. Hebrew Univ Jerusalem, Hadassah Med Sch, IL-91120 Jerusalem, Israel. Hebrew Univ Jerusalem, Hadassah Sch Dent Med, IL-91120 Jerusalem, Israel. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Chevion, S (reprint author), Chaim Sheba Med Ctr, Heller Inst Med Res, IL-52621 Tel Hashomer, Israel. NR 62 TC 123 Z9 130 U1 3 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 29 PY 2003 VL 100 IS 9 BP 5119 EP 5123 DI 10.1073/pnas.0831097100 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 673ZY UT WOS:000182612600030 PM 12702774 ER PT J AU Kostrouchova, M Kostrouch, Z Saudek, V Piatigorsky, J Rall, JE AF Kostrouchova, M Kostrouch, Z Saudek, V Piatigorsky, J Rall, JE TI BIR-1, a Caenorhabditis elegans homologue of Survivin, regulates transcription and development SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID STRIATED-MUSCLE DEVELOPMENT; HISTONE H3 PHOSPHORYLATION; THYROID-HORMONE RECEPTOR; MITOTIC PHOSPHORYLATION; PROTEIN; KINASE; GENE; ACETYLATION; ACTIVATION; CHROMATIN AB bir-1, a Caenorhabditis elegans inhibitor-of-apoptosis gene homologous to Survivin is organized in an operon with the transcription cofactor C elegans SKIP (skp-1). Because genes arranged in operons are frequently linked functionally, we have asked whether BIR-1 also functions in transcription. bir-1 inhibition resulted in multiple developmental defects that overlapped with C elegans SKIP loss-of-function phenotypes: retention of eggs, dumpy, movement defects, and lethality. bir-1 RNA-mediated interference decreased expression of several gfp transgenes and the endogenous genes dpy-7 and hlh-1. Immunoblot analysis revealed decreased phosphoacetylated histones in bir-1 RNA-mediated interference-treated worms. In a heterologous transfection system, BIR-1 augments thyroid hormone-regulated transcription and has an additive effect with SKIP. These results show that BIR-1 functions in the regulation of transcription and development. C1 Charles Univ, Fac Med 1, Inst Inherited Metab Disorders, Lab Mol Biol & Genet, CZ-12801 Prague 2, Czech Republic. Charles Univ, Fac Med 1, Inst Inherited Metab Disorders, Lab Mol Pathol, CZ-12801 Prague, Czech Republic. NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Rall, JE (reprint author), Charles Univ, Fac Med 1, Inst Inherited Metab Disorders, Lab Mol Biol & Genet, Ke Karlovu 2, CZ-12801 Prague 2, Czech Republic. NR 43 TC 8 Z9 14 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 29 PY 2003 VL 100 IS 9 BP 5240 EP 5245 DI 10.1073/pnas.0730770100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 673ZY UT WOS:000182612600051 PM 12682297 ER PT J AU Kim, HC Zhou, JG Wilson, HR Mogilnitskiy, G Court, DL Gottesman, ME AF Kim, HC Zhou, JG Wilson, HR Mogilnitskiy, G Court, DL Gottesman, ME TI Phage HK022 nun protein represses translation of phage lambda N (transcription termination/translation repression) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ESCHERICHIA-COLI; BACTERIOPHAGE-LAMBDA; TERMINATION FACTOR; ELONGATION-FACTOR; RNA-POLYMERASE; MESSENGER-RNA; BINDING; GENE; ANTITERMINATION; MUTATIONS AB The N-terminal arginine-rich motif of phage HK022 Nun protein binds to NUT sequences in phage A nascent transcripts and induces transcription termination. Interactions between the Nun C terminus and RNA polymerase as well as the DNA template are required for termination. We have isolated Nun C-terminal point and deletion mutants that are unable to block transcription. The mutants bind NUT RNA and inhibit translation of the lambda N gene. Thus HK022 excludes A both by terminating transcription on the phage chromosome and by preventing translation of the essential A N gene. Like N autoregulation, translation repression by Nun requires host RNaseIII deficiency (rnc) or a mutation in the RNaseIII processing site (rIII) located between NUTL and the beginning of the N coding sequence. Our data support the idea that Nun bound at NUTL causes steric interference with ribosome attachment to the nearby IN coding sequence. Two models, Nun acting alone or in complex with host proteins, are discussed. C1 Columbia Univ, Coll Phys & Surg, Dept Biochem & Mol Biophys, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Canc Res Inst, New York, NY 10032 USA. NCI, Mol Control & Genet Sect, NIH, Frederick, MD 21702 USA. Inst Biotechnol, Beijing 100850, Peoples R China. RP Gottesman, ME (reprint author), Columbia Univ, Coll Phys & Surg, Dept Biochem & Mol Biophys, New York, NY 10032 USA. FU NIGMS NIH HHS [GM37219, R01 GM037219, R56 GM037219] NR 29 TC 8 Z9 9 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 29 PY 2003 VL 100 IS 9 BP 5308 EP 5312 DI 10.1073/pnas.0430995100 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 673ZY UT WOS:000182612600063 PM 12684530 ER PT J AU Fang, NY Greiner, TC Weisenburger, DD Chan, WC Vose, JM Smith, LM Armitage, JO Mayer, RA Pike, BL Collins, FS Hacia, JG AF Fang, NY Greiner, TC Weisenburger, DD Chan, WC Vose, JM Smith, LM Armitage, JO Mayer, RA Pike, BL Collins, FS Hacia, JG TI Oligonucleotide microarrays demonstrate the highest frequency of ATM mutations in the mantle cell subtype of lymphoma SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; ATAXIA-TELANGIECTASIA GENE; MISSENSE MUTATIONS; PROLYMPHOCYTIC LEUKEMIA; SEQUENCE-ANALYSIS; PATHOGENIC ROLE; BREAST-CANCER; 11Q DELETIONS; T-PLL; INACTIVATION AB Mutations have been described in the ataxia telangiectasia mutated (ATM) gene in small numbers of cases of lymphoid neoplasia. However, surveys of the ATM mutation status in lymphoma have been limited due to the large size (62 exons) and complex mutational spectrum of this gene. We have used microarray-based assays with 250,000 oligonucleotides to screen lymphomas from 120 patients for all possible ATM coding and splice junction mutations. The subtypes included were diffuse large B cell, mantle cell, immunoblastic large B cell, follicular, posttransplant lymphoproliferative disorder, and peripheral T cell lymphoma. We found the highest percentage of ATM mutations within the mantle cell (MCL) subtype (43%, 12 of 28 cases), followed by a lower level (10% of cases) in the other subtypes. A frame-shift ATM mutation was found in one peripheral T cell lymphoma patient. In six MCL cases examined, four ATM variants were due to somatic mutation in the tumor cells whereas two others seemed to be germ-line in origin. There was no difference in p53 mutation status in the ATM mutant and wild-type groups of MCL. There was no statistically significant difference in the median overall survival of patients with wild-type vs. mutated ATM in MCL. Additional mutational and functional analyses are needed to determine whether ATM mutations contribute to the development and progression of MCL or are just the consequence of genomic instability in MCL. C1 Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. Univ Nebraska, Med Ctr, Dept Prevent & Societal Med, Omaha, NE 68198 USA. Univ Nebraska, Med Ctr, Dept Internal Med, Omaha, NE 68198 USA. NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. Univ So Calif, Inst Med Genet, Los Angeles, CA 90089 USA. RP Fang, NY (reprint author), Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, 600 S 42nd St, Omaha, NE 68198 USA. FU NCI NIH HHS [CA 36727, P30 CA036727, U01 CA084967, U01-CA84967] NR 51 TC 64 Z9 69 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 29 PY 2003 VL 100 IS 9 BP 5372 EP 5377 DI 10.1073/pnas.0831102100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 673ZY UT WOS:000182612600074 PM 12697903 ER PT J AU Samuni, AM Chuang, EY Krishna, MC Stein, W DeGraff, W Russo, A Mitchell, JB AF Samuni, AM Chuang, EY Krishna, MC Stein, W DeGraff, W Russo, A Mitchell, JB TI Semiquinone radical intermediate in catecholic estrogen-mediated cytotoxicity and mutagenesis: Chemoprevention strategies with antioxidants SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BREAST-CANCER CELLS; DNA-DAMAGE; MECHANISMS; INDUCTION; CARCINOGENESIS; TRANSFORMATION; INITIATION; SUPEROXIDE; METABOLISM; KIDNEY AB Modulation of the cytotoxicity and mutagenicity of 4-hydroxyestradiol (4-OHE2), an oxidative metabolite of estrogen, by antioxidants was assessed in human MCF7 cells and TK-6 lymphoblast cells. The cytotoxicity of the catecholic estrogens was potentiated by depletion of intracellular glutathione and was independent of oxygen concentration. Agents such as the nitroxide Tempol can facilitate the oxidation of the semiquinone to the Q and enhanced 4-OHE2 cytoxicity. Conversely, reducing agents such as ascorbate, cysteine, and 1,4-dihydroxytetramethylpiperidine (THP) protected against cytotoxicity and decreased mutation induction, presumably by reducing the semiquinone to the hydroquinone. Our results support the proposition that oxidation of the semiquinone to the corresponding Q is crucial in eliciting the deleterious effects of catecholic estrogens. Furthermore, because the deleterious effects of 4-OHE2 were abrogated by dietary and synthetic antioxidants, our results would support the chemopreventive use of diets rich in reducing substances (vitamins and added synthetic antioxidants) as a means of decreasing the risks associated with estrogen exposure and developing of breast cancer. C1 NCI, Ctr Canc Res, Radiol Biol Branch, Bethesda, MD 20892 USA. RP Mitchell, JB (reprint author), NCI, Ctr Canc Res, Radiol Biol Branch, Bldg 10,Room B3-B69,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 37 TC 46 Z9 49 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 29 PY 2003 VL 100 IS 9 BP 5390 EP 5395 DI 10.1073/pnas.0930078100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 673ZY UT WOS:000182612600077 PM 12702779 ER PT J AU Paolocci, N Katori, T Champion, HC St John, ME Miranda, KM Fukuto, JM Wink, DA Kass, DA AF Paolocci, N Katori, T Champion, HC St John, ME Miranda, KM Fukuto, JM Wink, DA Kass, DA TI Positive inotropic and lusitropic effects of HNO/NO- in failing hearts: Independence from beta-adrenergic signaling SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE nitroxyl; contractility; heart failure; nitric oxide; CGRP ID GENE-RELATED PEPTIDE; MYOCARDIAL OXYGEN-CONSUMPTION; NITRIC-OXIDE; IN-VIVO; CONTRACTILE RESPONSE; CARDIAC-PERFORMANCE; ANGIOTENSIN-II; NITROXYL ANION; UP-REGULATION; FAILURE AB Nitroxyl anion (HNO/NO-), the one-electron reduced form of nitric oxide (NO), induces positive cardiac inotropy and selective venodilation in the normal in vivo circulation. Here we tested whether HNO/NO- augments systolic and diastolic function of failing hearts, and whether contrary to NO/nitrates such modulation enhances rather than blunts beta-adrenergic stimulation and is accompanied by increased plasma calcitonin gene-related peptide (CGRP). HNO/NO- generated by Angelis' salt (AS) was infused (10 mug/kg per min, im.) to conscious dogs with cardiac failure induced by chronic tachycardia pacing. AS nearly doubled contractility, enhanced relaxation, and lowered cardiac preload and afterload (all P < 0.001) without altering plasma cGMP. This contrasted to modest systolic depression induced by an NO donor diethylamine(DEA)/NO or nitroglycerin (NTG). Cardiotropic changes from AS were similar in failing hearts as in controls despite depressed beta-adrenergic and calcium signaling in the former. Inotropic effects of AS were additive to dobutamine, whereas DEA/NO blunted beta-stimulation and NTG was neutral. Administration of propranolol to nonfailing hearts fully blocked isoproterenol stimulation but had minimal effect on AS inotropy and enhanced lusitropy. Arterial plasma CGRP rose 3-fold with AS but was unaltered by DEA/NO or NTG, supporting a proposed role of this peptide to HNO/NO- cardiotropic action. Thus, HNO/NO- has positive inotropic and lusitropic action, which unlike NO/nitrates is independent and additive to beta-adrenergic stimulation and stimulates CGRIP release. This suggests potential of HNO/NO- donors for the treatment of heart failure. C1 Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21287 USA. NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Mol Pharmacol, Los Angeles, CA 90095 USA. RP Kass, DA (reprint author), Johns Hopkins Univ Hosp, Halsted 500,600 N Wolfe St, Baltimore, MD 21287 USA. RI Miranda, Katrina/B-7823-2009; OI Paolocci, Nazareno/0000-0001-7011-997X FU NHLBI NIH HHS [HL-47511, P50-HL52307, R01 HL047511] NR 43 TC 191 Z9 196 U1 4 U2 16 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 29 PY 2003 VL 100 IS 9 BP 5537 EP 5542 DI 10.1073/pnas.0937302100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 673ZY UT WOS:000182612600102 PM 12704230 ER PT J AU Sausville, EA AF Sausville, EA TI Imatinib for chronic myelogenous leukaemia: a 9 or 24 carat gold standard? SO LANCET LA English DT Editorial Material ID ABL TYROSINE KINASE; CHRONIC MYELOID-LEUKEMIA; PHILADELPHIA-CHROMOSOME; INHIBITOR; APOPTOSIS; MESYLATE; PATIENT; STI571; CELLS C1 NCI, Dev Therapeut Program, Rockville, MD 20852 USA. RP Sausville, EA (reprint author), NCI, Dev Therapeut Program, Rockville, MD 20852 USA. NR 15 TC 6 Z9 8 U1 0 U2 3 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD APR 26 PY 2003 VL 361 IS 9367 BP 1400 EP 1401 DI 10.1016/S0140-6736(03)13145-5 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 672HZ UT WOS:000182516300002 PM 12727387 ER PT J AU Masubachi, Y Bourdi, M Reilly, TP Graf, MLM George, JW Pohl, LR AF Masubachi, Y Bourdi, M Reilly, TP Graf, MLM George, JW Pohl, LR TI Role of interleukin-6 in hepatic heat shock protein expression and protection against acetaminophen-induced liver disease SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE acetaminophen; protein-adducts; hepatotoxicity; interleukin-6; interleukin-11; oncostatin M; leukemia inhibitory factor; acute-phase response; heme-oxygenase; heat shock proteins ID NECROSIS-FACTOR-ALPHA; INDUCED HEPATOTOXICITY; DOWN-REGULATION; KNOCKOUT MICE; MURINE MODEL; INJURY; REGENERATION; INDUCTION; FAILURE; CELLS AB Recent experimental data suggest that the idiosyncratic nature of drug-induced liver disease (DILD) may be due in part to a deficiency of one or more hepatoprotective factors. In this study we have investigated whether interleukin (IL)-6 may also be one of these factors. Following the induction of liver injury with acetaminophen (APAP), a time-dependent increase in liver mRNA expression of IL-6 and its family members IL-11, leukemia inhibitory factor, and oncostatin M was observed in wild type (WT) mice, suggesting a possible hepatoprotective role played by this cytokine family. Indeed, mice lacking IL-6 (IL-6(-/-)) were more susceptible than were WT mice to APAP-induced liver injury. The increased susceptibility of the IL-6(-/-) mice was associated with a deficiency in the expression of hepatic heat shock protein (HSP)25, 32, and 40 as well as inducible HSP70 following APAP treatment. These results suggest that IL-6 and possibly other family members may protect the liver from injury, at least in part, by up-regulating the hepatic expression of several cytoprotective HSPs. (C) 2003 Elsevier Science (USA). All rights reserved. C1 NHLBI, Lab Mol Immunol, Mol & Cellular Toxicol Sect, DHHS NIH, Bethesda, MD 20892 USA. RP Bourdi, M (reprint author), NHLBI, Lab Mol Immunol, Mol & Cellular Toxicol Sect, DHHS NIH, Bldg 10,Rm 8N110, Bethesda, MD 20892 USA. NR 47 TC 92 Z9 99 U1 0 U2 6 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 APR 25 PY 2003 VL 304 IS 1 BP 207 EP 212 DI 10.1016/S0006-291X(03)00572-2 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 673PN UT WOS:000182589500034 PM 12705907 ER PT J AU Castle, PE Solomon, D Hildesheim, A Herrero, R Bratti, MC Sherman, ME Rodriguez, AC Alfaro, M Hutchinson, ML Dunn, ST Kuypers, J Schiffman, M AF Castle, PE Solomon, D Hildesheim, A Herrero, R Bratti, MC Sherman, ME Rodriguez, AC Alfaro, M Hutchinson, ML Dunn, ST Kuypers, J Schiffman, M TI Stability of archived liquid-based cervical cytologic specimens SO CANCER CYTOPATHOLOGY LA English DT Article DE liquid-based cytology; HPV; DNA; stability; archival ID PAPANICOLAOU TESTS; COSTA-RICA; CELLS; TIME; DNA AB BACKGROUND. Exfoliated cervical cell specimens collected in PreservCyt(R), a methanol-based medium used in ThinPrep(R) liquid-based cytology, have been archived in epidermologic studies. However, long-term DNA stability and cytologic stability of these biospecimens have not been evaluated. METHODS. Cervical specimens were collected into PreservCyt from participants in a natural history study of human papillomavirus (HPV) infection and cervical carcinoma in Guanacaste, Costa Rica (1993-2000), and stored at ambient temperatures. Thirty specimens classified as low-grade squamous intraepithelial lesions by liquid-based cytology were randomly chosen from each collection year (except for 1994) and selectively assessed for molecular and cytologic stability. Specimens were tested in 2001 for 1) HPV DNA by the Hybrid Capture 2 test, 2) P-globin DNA by polymerase chain reaction amplification of multiple length fragments (268, 610, and 1327 bp), and 3) nuclear preservation by visual inspection of newly made liquid-based cytology slides. All testing was done masked to year of collection. Associations of stability and storage time were evaluated using standard contingency tables and chi-square tests for trend. RESULTS. Human papillomavirus DNA, as detected by the Hybrid Capture 2 test, was unaffected by storage time. Stability of P-globin DNA (P-Trend < 0.0001) and nuclear preservation (PTrend < 0.0001) declined with increasing storage time. Approximately 15% of specimens could not be amplified for any P-globin DNA fragment after 5 years of storage (collected in 1996). In addition, cytology slides made from 41% specimens were rated as marginal (32%) or unsatisfactory (9%) after 8 years of storage (collected in 1993). CONCLUSIONS. Cervical specimens archived in PreservCyt underwent partial DNA and cytologic degradation after several years of storage. Methodologic studies to optimize long-term storage of cervical cells for epidemiologic studies of cervical carcinoma are needed. Cancer (Gancer Cytopathol) 2003;99:89-96. Published 2003 by the American Cancer Society*. C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. NCI, Div Canc Prevent, Rockville, MD USA. Proyecto Epidemiol Guanacaste, San Jose, Costa Rica. Womens & Infants Hosp, Providence, RI USA. Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA. Qiagen Genomics Inc, Bothell, WA USA. RP Castle, PE (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 7074,EPS MSC 7234, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01CP21081, N01CP31061] NR 14 TC 29 Z9 31 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD APR 25 PY 2003 VL 99 IS 2 BP 89 EP 96 DI 10.1002/cncr.11058 PG 8 WC Oncology; Pathology SC Oncology; Pathology GA 672FA UT WOS:000182509500004 PM 12704688 ER PT J AU Chou, MW Yan, J Nichols, J Xia, QS Beland, FA Chan, PC Fu, PP AF Chou, MW Yan, J Nichols, J Xia, QS Beland, FA Chan, PC Fu, PP TI Correlation of DNA adduct formation and riddelliine-induced liver tumorigenesis in F344 rats and B6C3F(1) mice SO CANCER LETTERS LA English DT Article DE riddelliine; pyrrolizidine alkaloid; DNA adducts; hemangiosarcomas ID PYRROLIZIDINE ALKALOIDS; HEPATOCYTES; HONEY; CELLS AB Riddelliine is a naturally occurring pyrrolizidine alkaloid that induces liver hemangiosarcomas in male and female F344 rats and male B6C3F(1) mice. We previously reported that eight dehydroretronecine (DHR)-derived DNA adducts were formed in liver DNA of rats treated with riddelliine. In order to examine the relationship between DNA adduct levels and the incidence of hemangiosarcomas, we have measured DHR-derived DNA adduct levels in purified rat and mouse liver endothelial cells, the cells of origin for the hemangiosarcomas. F344 rats and B6C3F(1) mice were treated by gavage 5 days per week for 2 weeks with riddelliine at 1.0 mg/kg for rats and 3.0 mg/kg for mice. One, 3, 7, and 28 days after the last dose, liver parenchymal and endothelial cell fractions were isolated, and the quantities of DHR-derived DNA adducts were determined by (32)Ppostlabeling/HPLC. The DHR-derived DNA adduct levels in the endothelial cells were significantly greater than in the parenchymal cells. The DNA adduct levels in rat endothelial cells were greater than in the mouse endothelial cells. These results indicate that the levels of riddelliine-induced DNA adducts in specific populations of liver cells correlate with the preferential induction of liver hemangiosarcomas by riddelliine. Published by Elsevier Science Ireland Ltd. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Natl Inst Environm Hlth, Res Triangle Pk, NC 27709 USA. RP Chou, MW (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NR 15 TC 35 Z9 36 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD APR 25 PY 2003 VL 193 IS 2 BP 119 EP 125 DI 10.1016/S0304-3835(03)00045-4 PG 7 WC Oncology SC Oncology GA 680CJ UT WOS:000182958500001 PM 12706867 ER PT J AU Starke, DW Chock, PB Mieyal, JJ AF Starke, DW Chock, PB Mieyal, JJ TI Glutathione-thiyl radical scavenging and transferase properties of human glutaredoxin (thioltransferase) - Potential role in redox signal transduction SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN S-THIOLATION; HYDROGEN-PEROXIDE; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; OXIDATIVE STRESS; ANTIOXIDANT FUNCTION; RESPIRATORY BURST; DISULFIDE; REDUCTION; CELLS; COMPLEXES AB Glutaredoxin (GRx, thioltransferase) is implicated in cellular redox regulation, and it is known for specific and efficient catalysis of reduction of protein-S-S-glutathione-mixed disulfides (protein-SSG) because of its remarkably low thiol pK(a) (approximate to3.5) and its ability to stabilize a catalytic S-glutathionyl intermediate (GRx-SSG). These unique properties suggested that GRx might also react with glutathione-thiyl radicals (GS(.)) and stabilize a disulfide anion radical intermediate (GRx-SSG(.)), thereby facilitating the conversion of GS(.) to GSSG or transfer of GS(.) to form protein-SSG. We found that GRx catalyzes GSSG formation in the presence of GS-thiyl radical generating systems (Fe2+/ADP/H2O2 + GSH or horseradish peroxidase/H2O2 + GSH). Catalysis is dependent on 02 and results in concomitant superoxide formation, and it is distinguished from glutathione peroxidase-like activity. With the horseradish peroxidase system and [S-35]GSH, GRx enhanced the rate of GS-radiolabel incorporation into GAPDH. GRx also enhanced the rate of S-glutathionylation of glyceraldehyde-3-phosphate dehydrogenase with GSSG or S-nitrosoglutathione, but these glutathionyl donors were much less efficient. Both actin and protein-tyrosine phosphatase-1B were superior substrates for GRx-facilitated S-glutathionylation with GS-radical. These studies characterize GRx as a versatile catalyst, facilitating GS-radical scavenging and S-glutathionylation of redox signal mediators, consistent with a critical role in cellular regulation. C1 Case Western Reserve Univ, Sch Med, Dept Pharmacol, Cleveland, OH 44106 USA. NHLBI, Biochem Sect, NIH, Bethesda, MD 20892 USA. RP Mieyal, JJ (reprint author), Case Western Reserve Univ, Sch Med, Dept Pharmacol, Cleveland, OH 44106 USA. FU NIA NIH HHS [AG15885] NR 41 TC 115 Z9 117 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 APR 25 PY 2003 VL 278 IS 17 BP 14607 EP 14613 DI 10.1074/jbc.M210434200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 672HX UT WOS:000182516100006 PM 12556467 ER PT J AU Kang, DK Jeong, J Drake, SK Wehr, NB Rouault, TA Levine, RL AF Kang, DK Jeong, J Drake, SK Wehr, NB Rouault, TA Levine, RL TI Iron regulatory protein 2 as iron sensor - Iron-dependent oxidative modification of cysteine SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROLYL HYDROXYLATION; CATALYZED OXIDATION; AMINOMALONIC ACID; ESCHERICHIA-COLI; ISOPENICILLIN-N; BINDING PROTEIN; HIF-ALPHA; DEGRADATION; MECHANISM; DESTRUCTION AB Iron regulatory protein 2 coordinates cellular regulation of iron metabolism by binding to iron responsive elements in mRNA. The protein is synthesized constitutively but is rapidly degraded when iron stores are replete. This iron-dependent degradation requires the presence of a 73-residue degradation domain, but its functions have not yet been established. We now show that the domain can act as an iron sensor, mediating its own covalent modification. The domain forms an iron-binding site with three cysteine residues located in the middle of the domain. It then reacts with molecular oxygen to generate a reactive oxidizing species at the iron-binding site. One cysteine residue is oxidized to dehydrocysteine and other products. This covalent modification may thus mark the protein molecule for degradation by the proteasome system. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Levine, RL (reprint author), NHLBI, Biochem Lab, NIH, Bldg 50,Rm 2351, Bethesda, MD 20892 USA. RI Levine, Rodney/D-9885-2011 NR 26 TC 41 Z9 42 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 APR 25 PY 2003 VL 278 IS 17 BP 14857 EP 14864 DI 10.1074/jbc.M300616200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 672HX UT WOS:000182516100037 PM 12591920 ER PT J AU Baron, GS Caughey, B AF Baron, GS Caughey, B TI Effect of glycosylphosphatidylinositol anchor-dependent and -independent prion protein association with model raft membranes on conversion to the protease-resistant isoform SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID N-TERMINAL TRUNCATION; CELL-FREE FORMATION; SCRAPIE ISOFORM; BINDING-SITES; CULTURED-CELLS; COPPER-BINDING; NEUROBLASTOMA-CELLS; MASS-SPECTROMETRY; SULFATED GLYCANS; IN-VITRO AB Prion protein (PrP) is usually bound to membranes by a glycosylphosphatidylinositol (GPI) anchor that associates with detergent-resistant membranes, or rafts. To examine the effect of membrane association on the interaction between the normal protease-sensitive PrP isoform (PrP-sen) and the protease-resistant isoform (PrP-res), a model system was employed using PrP-sen reconstituted into sphingolipid-cholesterol-rich raftlike liposomes (SCRLs). Both full-length (GPI(+)) and GPI anchor-deficient (GPI(-)) PrP-sen produced in fibroblasts stably associated with SCRLs. The latter, alternative mode of membrane association was not detectably altered by glycosylation and was markedly reduced by deletion of residues 34-94. The SCRL-associated PrP molecules were not removed by treatments with either high salt or carbonate buffer. However, only GPI(+) PrP-sen resisted extraction with cold Triton X-100. PrP-sen association with SCRLs was pH-independent. PrP-sen was also one of a small subset of phosphatidylinositol-specific phospholipase C (PI-PLC)-released proteins from fibroblast cells found to bind SCRLs. A cell-free conversion assay was used to measure the interaction of SCRL-bound PrP-sen with exogenous PrP-res as contained in microsomes. SCRL-bound GPI(+) PrP-sen was not converted to PrP-res until PI-PLC was added to the reaction or the combined membrane fractions were treated with the membrane-fusing agent polyethylene glycol (PEG). In contrast, SCRL-bound GPI(-) PrP-sen was converted to PrP-res without PI-PLC or PEG treatment. Thus, of the two forms of raft membrane association by PrP-sen, only the GPI anchor-directed form resists conversion induced by exogenous PrP-res. C1 NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Caughey, B (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. NR 57 TC 76 Z9 77 U1 1 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 APR 25 PY 2003 VL 278 IS 17 BP 14883 EP 14892 DI 10.1074/jbc.M210840200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 672HX UT WOS:000182516100040 PM 12594216 ER PT J AU Kramata, P Zajc, B Sayer, JM Jerina, DM Wei, CSJ AF Kramata, P Zajc, B Sayer, JM Jerina, DM Wei, CSJ TI A single site-specific trans-opened 7,8,9,10-tetrahydrobenzo[alpha]pyrene 7,8-diol 9,10-epoxide N-2-deoxyguanosine adduct induces mutations at multiple sites in DNA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; DIASTEREOMERIC BENZOPYRENE 7,8-DIOL-9,10-EPOXIDES; GUANINE PHOSPHORIBOSYLTRANSFERASE GENE; (+)-ANTI-BENZOPYRENE DIOL EPOXIDE; DOSE-DEPENDENT DIFFERENCES; OPTICAL ENANTIOMERS; SEQUENCE CONTEXT; STRUCTURAL CHARACTERIZATION; DEOXYGUANOSINE ADDUCTS; ENERGY MINIMIZATION AB Site-specific mutagenicity of trans-opened adducts at the exocyclic N-2-imino group of guanine by the (+)-(7R,8S,9S,10R)- and (-)-(7S,8R,9R,10S)-enantiomers of a benzo[a]pyrene 7,8-diol 9,10-epoxide (7-hydroxyl and epoxide oxygen are trans, BPDE-2) has been determined in Chinese hamster V79 cells and their repair-deficient counterpart, V-H1 cells. Four vectors containing single 10S-BPDE-dG or 10R-BPDE-dG adducts positioned at Go or G(-1) in the analyzed 5'-ACTG(0)G(-1)GA sequence of the non-transcribed strand were separately transfected into the cells. Mutations at each of the seven nucleotides were analyzed by a novel primer extension assay using a mixture of one dNTP complementary to the mutated nucleotide and three other ddNTPs and were optimized to quantify levels of a mutation as low as 1%. Only G --> T mutations were detected at the adducted sites; the 10S adduct derived from the highly carcinogenic (+)-diol epoxide was 40-50 and 75-140% more mutagenic than the 10R adduct in V79 and V-H1 cells, respectively. Importantly, the 10S adducts, but not the 10R adducts, induced separate non-targeted mutations at sites 5' to the G(-1) and G(0) lesions (G(0) --> T and C --> T, respectively) in both cell lines. Neither the T 5' to G(0) nor sites 3' to the lesions showed mutations. Non-targeted mutations may enhance overall mutagenicity of the 10S-BPDE-dG lesion and contribute to the much higher carcinogenicity and mutagenicity of (+)-BPDE-2 compared with its (-)enantiomer. Our study reports a definitive demonstration of mutations distal to a site-specific polycyclic aromatic hydrocarbon adduct. C1 Rutgers State Univ, Coll Pharm, Dept Biol Chem, Susan Lehman Cullman Lab Canc Res, Piscataway, NJ 08854 USA. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Kramata, P (reprint author), Rutgers State Univ, Coll Pharm, Dept Biol Chem, Susan Lehman Cullman Lab Canc Res, 164 Frelinghuysen Rd, Piscataway, NJ 08854 USA. NR 51 TC 10 Z9 10 U1 1 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 APR 25 PY 2003 VL 278 IS 17 BP 14940 EP 14948 DI 10.1074/jbc.M211557200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 672HX UT WOS:000182516100048 PM 12595542 ER PT J AU Miller, M Shuman, JD Sebastian, T Dauter, Z Johnson, PF AF Miller, M Shuman, JD Sebastian, T Dauter, Z Johnson, PF TI Structural basis for DNA recognition by the basic region leucine zipper transcription factor CCAAT/enhancer-binding protein alpha SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; C/EBP-ALPHA; CRYSTAL-STRUCTURE; COMPLEX; IDENTIFICATION; DOMAIN; GCN4; GENE; GRANULOPOIESIS; ADIPOGENESIS AB CCAAT/enhancer-binding proteins (C/EBPs) are basic region leucine zipper (bZIP) transcription factors that regulate cell differentiation, growth, survival, and inflammation. To understand the molecular basis of DNA recognition by the C/EBP family we determined the x-ray structure of a C/EBPalpha bZIP polypeptide bound to its cognate DNA site (A(-5)T(-4)T(-3)G(-2)C(-1)G(1)A(3)T(5)) and characterized several basic region mutants. Binding specificity is provided by interactions of basic region residues Arg(289), Asn(292), Ala(295), Val(296), Ser(299), and Arg(300) with DNA bases. A striking feature of the C/EBPalpha protein-DNA interface that distinguishes it from known 89 bZIP-DNA complexes is the central role of Are, which is hydrogen-bonded to base A(3), phosphate, Asn(292) (invariant in bZlPs), and Asn(293). The conformation of Arg(289) is also restricted by Tyr(285). In accordance with the structural model, mutation of Arg(289) or a pair of its interacting partners (Tyr(285) and Asn(293)) abolished C/EBPalpha binding activity. Val(296) (Ala in most other bZlPs) contributes to C/EBPalpha specificity by discriminating against purines at position -3 and imposing steric restraints on the invariant Arg(300). Mutating Val(296) to Ala strongly enhanced C/EBPalpha binding to cAMP response element (CRE) sites while retaining affinity for C/EBP sites. Thus, Arg(289) is essential for formation of the complementary protein-DNA interface, whereas Val(296) functions primarily to restrict interactions with related sequences such as CRE sites rather than specifying binding to C/EBP sites. Our studies also help to explain the phenotypes of mice carrying targeted mutations in the C/EBPalpha bZIP region. C1 NCI, Macromol Crystallog Lab, Prot Struct Sect, Frederick, MD 21702 USA. NCI, Regulat Cell Growth Lab, Frederick, MD 21702 USA. Natl Canc Inst, Macromol Crystallog Lab, Synchrotron Radiat Res Sect, Upton, NY 11973 USA. Brookhaven Natl Lab, Upton, NY 11973 USA. RP Miller, M (reprint author), NCI, Macromol Crystallog Lab, Prot Struct Sect, Frederick, MD 21702 USA. RI Johnson, Peter/A-1940-2012; Miller, Maria/I-1636-2013; OI Johnson, Peter/0000-0002-4145-4725; Miller, Maria/0000-0003-0252-5348; Shuman, Jon/0000-0001-8412-9087 NR 40 TC 81 Z9 84 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 APR 25 PY 2003 VL 278 IS 17 BP 15178 EP 15184 DI 10.1074/jbc.M300417200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 672HX UT WOS:000182516100077 PM 12578822 ER PT J AU Shi, CS Kehrl, JH AF Shi, CS Kehrl, JH TI Tumor necrosis factor (TNF)-induced germinal center kinase-related (GCKR) and stress-activated protein-kinase (SAPK) activation depends upon the E2/E3 complex Ubc13-Uev1A/TNF receptor-associated factor 2 (TRAF2) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID N-TERMINAL KINASE; TNF RECEPTOR-1; KAPPA-B; APOPTOSIS; PATHWAY; ASK1; JNK; THIOREDOXIN; INDUCTION; INHIBITOR AB Tumor necrosis factor (TNF)-induced activation of apoptosis signal-regulating kinase 1 (ASK1.) and germinal center kinases (GCKs) and the subsequent activation of stress-activated protein kinases (SAPKs and c-Jun NH2-terminal kinases) requires TNF receptor-associated factor 2 (TRAF2). Although the TRAF2 TRAF domain binds ASK1, GCK, and the highly related kinase GCKR, the RING finger domain is needed for their activation. Here, we report that TNF activates GCKR and the SAPK pathway in a manner that depends upon TRAF2 and Ubc13, a member along with Uev1A of a dimeric ubiquitin-conjugating enzyme complex. Interference with LTbc13 function or expression inhibits both TNF- and TRAF2-mediated GCKR and SAPK activation, but has a minimal effect on ASK1. activation. TNF signaling leads to TRAF2 polyubiquitination and oligomerization and to the oligomerization, ubiquitination, and activation of GCKR, all of which are sensitive to the disruption of Ubc13 function. These results indicate that the assembly of a TRAF2 lysine 63-linked polyubiquitin chain by LTbc13/Uev1A is required for TNF-mediated GCKR and SAPK activation, but may not be required for ASK1 activation. C1 NIAID, Cell Immunol Sect B, NIH, Bethesda, MD 20892 USA. RP Kehrl, JH (reprint author), NIAID, Cell Immunol Sect B, NIH, Bldg 10,RmB-08,10 Ctr Dr,MSC 1876, Bethesda, MD 20892 USA. OI Kehrl, John/0000-0002-6526-159X NR 21 TC 125 Z9 131 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 APR 25 PY 2003 VL 278 IS 17 BP 15429 EP 15434 DI 10.1074/jbc.M211796200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 672HX UT WOS:000182516100109 PM 12591926 ER PT J AU Buxton, DB Golomb, E Adelstein, RS AF Buxton, DB Golomb, E Adelstein, RS TI Induction of nonmuscle myosin heavy chain II-C by butyrate in RAW 264.7 mouse macrophages SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTIONAL REGULATION; GENE-EXPRESSION; SP1 BINDING; SODIUM-BUTYRATE; CELLULAR MYOSIN; MESSENGER-RNAS; CELLS; PROTEIN; LIPOPOLYSACCHARIDE; PROMOTER AB RAW 264.7 macrophages express nonmuscle myosin heavy chain II-A as the only significant nonmuscle myosin heavy chain isoform,with expression of nonmuscle myosin heavy chain II-B and II-C low or absent. Treatment of the cells with sodium butyrate, an inhibitor of historic deacetylase, led to the dose-dependent induction of nonniuscle myosin heavy chain II-C. Trichostatin A, another inhibitor of histone deacetylase, also induced nonmuscle myosin heavy chain II-C. Induction of nonmuscle myosin heavy chain II-C in response to these histone deacetylase inhibitors was attenuated by mithramycin, an inhibitor of Spl binding to GC-rich DNA sequences. Bacterial lipopolysaccharide alone had no effect on basal nonmuscle myosin heavy chain II-C expression, but attenuated butyrate-mediated induction of nonmuscle myosin heavy chain II-C. The effects of lipopolysaccharide were mimicked by the nitric oxide donors sodium nitroprusside and spermine NONOate, suggesting a role for nitric oxide in the lipopolysaccharide-mediated down-regulation of nonmuscle myosin heavy chain II-C induction. This was supported by experiments with the inducible nitric-oxide synthase inhibitor 1400W, which partially blocked the lipopolysaccharide-mediated attenuation of nonmuscle myosin heavy chain induction. 8-Bromo-cGMP had no effect on nonmuscle myosin heavy chain induction, consistent with a cGMP-independent mechanism for nitric oxide-mediated inhibition of nonmuscle myosin heavy chain II-C induction. C1 NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Buxton, DB (reprint author), Rockledge Ctr 2, Heart Res Program, 6701 Rockledge Dr,Suite 9044,MSC 7940, Bethesda, MD 20892 USA. OI Buxton, Denis/0000-0003-3077-6435; Adelstein, Robert/0000-0002-8683-2144 NR 42 TC 19 Z9 20 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 APR 25 PY 2003 VL 278 IS 17 BP 15449 EP 15455 DI 10.1074/jbc.M210145200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 672HX UT WOS:000182516100112 PM 12598534 ER PT J AU Anderton, MJ Jukes, R Lamb, JH Manson, MM Gescher, A Steward, WP Williams, ML AF Anderton, MJ Jukes, R Lamb, JH Manson, MM Gescher, A Steward, WP Williams, ML TI Liquid chromatographic assay for the simultaneous determination of indole-3-carbinol and its acid condensation products in plasma SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE indole-3-carbinol; 3,3 '-diindolylmethane ID IN-VIVO; MCF-7 CELLS; RAT-LIVER; INVIVO; 3,3'-DIINDOLYLMETHANE; DISPOSITION; MODULATION; INDUCTION; INVITRO AB A high-performance liquid chromatographic method was developed for the simultaneous determination of indole-3-carbinol (I3C), 3,3' diindolylmethane (DIM), [2-(indol-3-ylmethyl)-indol-3-yl]indol-3-ylmethane (LTr1), and indolo[3,2b]carbazole (ICZ). Compounds were extracted from mouse plasma using tert.-butyl methyl ether, incorporating 4-methoxy-indole as internal standard. Chromatographic separation utilized a Waters Symmetry RP18 in tandem with a Thermoquest BDS C-18 column, an acetonitrile-water gradient and UV (280 nm) in series with fluorescence (ex. 335 nm; em. 415 nm) detection. Calibration curves were linear (r(2>)0.99) between 50 and 15,000 ng/ml for I3C; 150 and 15,000 ng/ml for LTr1; and 0.15 and 37.5 ng/ml for ICZ and the method was reproducible and precise (within-day and between-day coefficients of variation below 9.7 and 13%, respectively). The method described is suitable for comprehensive pharmacokinetic studies with indole-3-carbinol. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NIA, NIH, Gerontol Res Ctr, Bioanalyt & Drug Discovery Unit, Baltimore, MD 21224 USA. Univ Leicester, Leicester Royal Infirm, Dept Oncol, Leicester LE2 7LX, Leics, England. MRC, Toxicol Unit, Leicester, Leics, England. Univ Leicester, Bioctr, Dept Biochem, Leicester LE1 7RH, Leics, England. Univ Leicester, Bioctr, Dept Oncol, Leicester LE1 7RH, Leics, England. RP Williams, ML (reprint author), NIA, NIH, Gerontol Res Ctr, Bioanalyt & Drug Discovery Unit, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 24 TC 34 Z9 35 U1 1 U2 5 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 APR 25 PY 2003 VL 787 IS 2 BP 281 EP 291 DI 10.1016/S1570-0232(02)00923-6 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 664HH UT WOS:000182055300005 PM 12650751 ER PT J AU Woo, HA Chae, HZ Hwang, SC Yang, KS Kang, SW Kim, K Rhee, SG AF Woo, HA Chae, HZ Hwang, SC Yang, KS Kang, SW Kim, K Rhee, SG TI Reversing the inactivation of peroxiredoxins caused by cysteine sulfinic acid formation SO SCIENCE LA English DT Article ID THIOL-SPECIFIC ANTIOXIDANT; THIOREDOXIN PEROXIDASE; 2-CYS PEROXIREDOXIN; HYDROGEN-PEROXIDE; CRYSTAL-STRUCTURE; OXIDATION; PROTEINS; ACTIVATION; REDUCTASE; CATALYSIS AB The active-site cysteine of peroxiredoxins is selectively oxidized to cysteine sulfinic acid during catalysis, which leads to inactivation of peroxidase activity. This oxidation was thought to be irreversible. However, by metabolic labeling of mammalian cells with S-35, we show that the sulfinic form of peroxiredoxin I, produced during the exposure of cells to H2O2, is rapidly reduced to the catalytically active thiol form. The mammalian cells' ability to reduce protein sulfinic acid might serve as a mechanism to repair oxidatively damaged proteins or represent a new type of cyclic modification by which the function of various proteins is regulated. C1 NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. Ewha Womans Univ, Ctr Cell Signaling Res, Seoul 120750, South Korea. Ewha Womans Univ, Div Mol Life Sci, Seoul 120750, South Korea. RP Rhee, SG (reprint author), NHLBI, Lab Cell Signaling, NIH, Bldg 10, Bethesda, MD 20892 USA. OI Hwang, Sung Chul/0000-0003-2401-619X NR 26 TC 379 Z9 393 U1 1 U2 17 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 25 PY 2003 VL 300 IS 5619 BP 653 EP 656 DI 10.1126/science.1080273 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 671FB UT WOS:000182453700046 PM 12714748 ER PT J AU Bour, S Akari, H Miyagi, E Strebel, K AF Bour, S Akari, H Miyagi, E Strebel, K TI Naturally occurring amino acid substitutions in the HIV-2 ROD envelope glycoprotein regulate its ability to augment viral particle release SO VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; PIG-TAILED MACAQUES; VPU PROTEIN; MOLECULAR-CLONING; ION CHANNELS; SIV-MAC; DOMAIN; ENV; FUSION; IDENTIFICATION AB The envelope glycoprotein of HIV-2 ROD10 has the intriguing ability to enhance the rate of viral particle release from infected cells. However, not all HIV-2 envelope glycoproteins are active in this regard. Indeed, we have previously noted that, despite a high degree of identity with that of ROD10, the envelope protein of the ROD14 isolate was unable to enhance virus production. In this study, site-directed mutagenesis was employed to reveal that a single naturally occurring alanine-to-threonine substitution at position 598, located in the extracellular part of the TM subunit, fully accounted for the lack of activity of the ROD14 Env in HeLa and 12D7 cells. A second mutation at position 422, substituting a lysine residue in ROD10 for an arginine in ROD14, was additionally required for efficient virus release from infected H9 cells, suggesting cell-type-specific requirements for this activity. Interestingly, the ROD14 Env protein exhibited a transdominant negative effect on particle release by ROD10 Env, suggesting that the viral release activity of the HIV-2 ROD envelope protein may be regulated by its ability to assemble into functional oligomeric structures. (C) 2003 Elsevier Science (USA). All rights reserved. C1 NIAID, Viral Biochem Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Bour, S (reprint author), NIAID, Viral Biochem Sect, Mol Microbiol Lab, NIH, 4 Ctr Dr,Room 310C,MSC-0460, Bethesda, MD 20892 USA. NR 32 TC 34 Z9 34 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 0042-6822 J9 VIROLOGY JI Virology PD APR 25 PY 2003 VL 309 IS 1 BP 85 EP 98 DI 10.1016/S0042-6822(02)00128-9 PG 14 WC Virology SC Virology GA 675ZK UT WOS:000182727300009 PM 12726729 ER PT J AU Schott, EJ Robledo, JAF Wright, AC Silva, AM Vasta, GR AF Schott, EJ Robledo, JAF Wright, AC Silva, AM Vasta, GR TI Gene organization and homology modeling of two iron superoxide dismutases of the early branching protist Perkinsus marinus SO GENE LA English DT Article DE Apicomplexa; evolution; intron; oxidative stress; promoter ID CRASSOSTREA-VIRGINICA HEMOCYTES; TOXOPLASMA-GONDII; IN-VITRO; EXPRESSION; ELEMENT; CLONING; IDENTIFICATION; PROLIFERATION; APICOMPLEXA; METABOLISM AB The facultative intracellular oyster parasite, Perkinsus marinus, taxonomically related to both dinoflagellates and apicomplexans, possesses at least two distinct genes (PmSOD1 and PmSOD2) predicted to encode iron-containing superoxide dismutases (FeSOD). DNA blots and sequence analysis suggest that both PmSOD1 and PmSOD2 are single copy and are unlinked. PmSOD1 and PmSOD2 are composed of five and six exons, respectively. All introns are delimited by canonical GT/AG boundaries, and have some features more similar to apicomplexan than dinoflagellate introns. Interestingly, exon 1 of PmSOD2 encodes putative transmembrane and spacer domains with no homology to FeSODs, while exon 2 begins with a methionine codon and is homologous to the N-terminus of FeSODs. The position of introns is not highly conserved between PmSOD1 and PmSOD2, although one intron is in a similar location. Comparison of the intron positions of PmSOD1 and PmSOD2 to those of available apicomplexan FeSODs shows that the intron position shared by PmSOD1 and PmSOD2 is also observed in the FeSOD of Toxoplasma gondii. Comparison of the untranscribed regions 5' and 3' of the coding regions for PmSOD1 and PmSOD2 reveals few motifs in common. Instead, each gene possesses a distinct set of putative upstream transcription factor binding sites. Although the proteins encoded by PmSOD1 and PmSOD2 are only 38% identical to each other, homology modeling indicates that they have nearly identical active site structures. The divergent genomic organizations of two FeSOD genes in the same organism illustrates the complexity of the antioxidant system of even simple, early-branching protists such as P. marinus. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Univ Maryland, Ctr Marine Biotechnol, Inst Biotechnol, Baltimore, MD 21202 USA. NCI, Struct Biochem Program, SAIC, Frederick, MD 21701 USA. RP Vasta, GR (reprint author), Univ Maryland, Ctr Marine Biotechnol, Inst Biotechnol, 701 E Pratt St, Baltimore, MD 21202 USA. NR 31 TC 21 Z9 22 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD APR 24 PY 2003 VL 309 IS 1 BP 1 EP 9 DI 10.1016/S0378-1119(03)000469-4 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 679UD UT WOS:000182939600001 PM 12727353 ER PT J AU Sigano, DM Peach, ML Nacro, K Choi, Y Lewin, NE Nicklaus, MC Blumberg, PM Marquez, VE AF Sigano, DM Peach, ML Nacro, K Choi, Y Lewin, NE Nicklaus, MC Blumberg, PM Marquez, VE TI Differential binding modes of diacylglycerol (DAG) and DAG lactones to protein kinase C (PK-C) SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CONFORMATIONALLY CONSTRAINED ANALOGS; 5-DISUBSTITUTED TETRAHYDRO-2-FURANONE TEMPLATE; GREEN FLUORESCENT PROTEIN; LIVING CELLS; AFFINITY; TRANSLOCATION; RECOGNITION; ACTIVATION; ALGORITHM; BACKBONE AB Diacylglycerol lactones (DAG lactones), analogous to highly potent diacylglycerols (DAGs) were synthesized to demonstrate the ability of PK-C to discriminate between two differential binding modes, sn-1 and sn-2. While both sn-1 and sn-2 binding modes are allowable in terms of hydrogen bonding, it has been found that in general, DAGs prefer to bind sn-1, while the corresponding analogous DAG lactones prefer to bind sn-2. However, this binding orientation can be directly influenced by the disposition and nature of the acyl substituent, particularly if it is highly branched. When the "binding driving force" (i.e., the larger branched acyl chain) is in the sn-2 position, a dramatic increase in binding affinity is observed in the DAG lactone as compared to its open chain DAG counterpart. As these analogous DAGs and DAG lactones have almost identical log P values, this difference in binding affinity is a direct result of the entropic advantage of constraining the glycerol backbone. C1 NCI, Med Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. NCI, Ctr Canc Res, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. RP Marquez, VE (reprint author), NCI, Med Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. EM marquezv@mail.nih.gov RI Sigano, Dina/M-6144-2014; Nicklaus, Marc/N-4183-2014; Choi, Yongseok/F-8375-2012 OI Sigano, Dina/0000-0001-7489-9555; Choi, Yongseok/0000-0002-3622-3439 NR 28 TC 19 Z9 19 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD APR 24 PY 2003 VL 46 IS 9 BP 1571 EP 1579 DI 10.1021/jm0204760 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 671WR UT WOS:000182488300002 PM 12699375 ER PT J AU Mu, FR Hamel, E Lee, DJ Pryor, DE Cushman, M AF Mu, FR Hamel, E Lee, DJ Pryor, DE Cushman, M TI Synthesis, anticancer activity, and inhibition of tubulin polymerization by conformationally restricted analogues of lavendustin A SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE KINASE; IN-VITRO; ANTINEOPLASTIC AGENTS; ANTIMITOTIC AGENTS; COLCHICINE; GROWTH; SERIES; CELLS; POTENT; COMBRETASTATIN-A-4 AB Compounds in the lavendustin A series have been shown to inhibit both protein-tyrosine kinases (PTKs) and tubulin polymerization. Since certain lavendustin A derivatives can exist in conformations that resemble both the trans-stilbene structure of the PTK inhibitor piceatannol and the cis-stilbene structure of the tubulin polymerization inhibitor combretastatin A-4, the possibility exists that the ratio of the two types of activities of the lavendustins could be influenced through the synthesis of conformationally restricted analogues. Accordingly, the benzylaniline structure of a series of pharmacologically active lavendustin A fragments was replaced by either their cis- or their trans-stilbene relatives, and effects on both inhibition of tubulin polymerization and cytotoxicity in cancer cell cultures were monitored. Both dihydrostilbene and 1,2-diphenylalkyne congeners were also prepared and evaluated biologically. Surprisingly, conformational restriction of the bridge between the two aromatic rings of the lavendustins had no significant effect on biological activity. On the other hand, conversion of the three phenolic hydroxyl groups of the lavendustin A derivatives to their corresponding methyl ethers consistently abolished their ability to inhibit tubulin polymerization and usually decreased cytotoxicity in cancer cell cultures as well, indicating the importance of at least one of the phenolic hydroxyl groups. Further investigation suggested that the phenolic hydroxyl group in the salicylamide ring was required for activity, while the two phenol moieties in the hydroquinone ring could be methylated with retention of activity. Two of the lavendustin A derivatives displayed IC50 values of 1.4muM for inhibition of tubulin polymerization, which ranks them among the most potent of the known tubulin polymerization inhibitors. C1 Purdue Univ, Sch Pharm & Pharmaceut Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. NCI, Div Canc Treatment & Diagnosis, Screening Technol Branch, Dev Therapeut Program,NIH, Frederick, MD 21702 USA. RP Cushman, M (reprint author), Purdue Univ, Sch Pharm & Pharmaceut Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. EM cushman@pharmacy.purdue.edu NR 37 TC 37 Z9 37 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD APR 24 PY 2003 VL 46 IS 9 BP 1670 EP 1682 DI 10.1021/jm020292 PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 671WR UT WOS:000182488300012 PM 12699385 ER PT J AU Tamamura, H Koh, Y Ueda, S Sasaki, Y Yamasaki, T Aoki, M Maeda, K Watai, Y Arikuni, H Otaka, A Mitsuya, H Fujii, N AF Tamamura, H Koh, Y Ueda, S Sasaki, Y Yamasaki, T Aoki, M Maeda, K Watai, Y Arikuni, H Otaka, A Mitsuya, H Fujii, N TI Reduction of peptide character of HIV protease inhibitors that exhibit nanomolar potency against multidrug resistant HIV-1 strains SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ORALLY BIOAVAILABLE INHIBITOR; STEREOSELECTIVE SYNTHESIS; DIPEPTIDE ISOSTERES; ACTIVE-SITE; DESIGN; DISCOVERY; ANALOGS; ENZYME; ACIDS AB Novel HIV protease inhibitors containing a hydroxyethylamine dipeptide isostere as a transition state-mimic king structure were synthesized by combining substructures of known HIV protease inhibitors. Among them, TYA5 and TYB5 were proven to be not only potent enzyme inhibitors (K-i = 0.12 nM and 0.10 nM, respectively) but also strong anti-HIV agents (IC50 = 9.5 nM and 66 nM, respectively), even against viral strains with multidrug resistance. Furthermore, insertion of an (E)-alkene dipeptide isostere at the P-1-P-2 position of TYB5 led to development of a purely nonpeptidic protease inhibitor, TYB1 (K-i = 0.38 nM, IC50 = 160 nM). C1 Kyoto Univ, Grad Sch Pharmaceut Sci, Sakyo Ku, Kyoto 6068501, Japan. Kumamoto Univ, Sch Med, Dept Internal Med 2, Kumamoto 8608556, Japan. SC biosci Corp, Yokohama Lab, Hodogaya Ku, Yokohama, Kanagawa 2400005, Japan. NCI, Div Clin Sci, Med Branch, Expt Retrovirol Sect,NIH, Bethesda, MD 20892 USA. RP Tamamura, H (reprint author), Kyoto Univ, Grad Sch Pharmaceut Sci, Sakyo Ku, Kyoto 6068501, Japan. EM tamamura@pharm.kyoto-u.ac.jp; nfujii@pharm.kyoto-u.ac.jp NR 21 TC 42 Z9 42 U1 2 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD APR 24 PY 2003 VL 46 IS 9 BP 1764 EP 1768 DI 10.1021/jm020537i PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 671WR UT WOS:000182488300022 PM 12699395 ER PT J AU Collins, FS Green, ED Guttmacher, AE Guyer, MS AF Collins, FS Green, ED Guttmacher, AE Guyer, MS TI A vision for the future of genomics research SO NATURE LA English DT Article ID GENETIC INFORMATION; MOUSE GENOME; SEQUENCE; DNA; MEDICINE; DISEASE; PRIVACY; PROJECT C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Collins, FS (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. NR 44 TC 938 Z9 1003 U1 9 U2 75 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 24 PY 2003 VL 422 IS 6934 BP 835 EP 847 DI 10.1038/nature01626 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 670WR UT WOS:000182432600044 PM 12695777 ER PT J AU Lodovichi, C Belluscio, L Katz, LC AF Lodovichi, C Belluscio, L Katz, LC TI Functional topography of connections linking mirror-symmetric maps in the mouse olfactory bulb SO NEURON LA English DT Article ID INTRABULBAR ASSOCIATIONAL SYSTEM; ODORANT RECEPTOR EXPRESSION; DOMAIN ORGANIZATION; MICE DEFICIENT; VISUAL-CORTEX; AXON GUIDANCE; SENSORY MAPS; CHANNEL; INFORMATION; PROJECTIONS AB In rodents, each main olfactory bulb contains two mirror-symmetric glomerular maps, a feature not found in the initial topographic maps of other sensory systems. Targeting tracer injections to identified glomeruli revealed that isofunctional odor columns - translaminar assemblies connected to a given glomerulus-were specifically and reciprocally interconnected through a mutually inhibitory circuit with exquisite topographic specificity. Thus, instead of containing two mirror-symmetric maps, we propose that the olfactory bulb contains a single integrated map in which isofunctional odor columns are connected through an intrabulbar link, analogous to the specific horizontal connections linking iso-orientation columns in primary visual cortex. C1 Duke Univ, Med Ctr, Howard Hughes Med Inst, Dept Neurobiol, Durham, NC 27710 USA. NINDS, Dev Neural Plast Unit, NIH, Bethesda, MD 20892 USA. RP Katz, LC (reprint author), Duke Univ, Med Ctr, Howard Hughes Med Inst, Dept Neurobiol, Durham, NC 27710 USA. NR 58 TC 62 Z9 65 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD APR 24 PY 2003 VL 38 IS 2 BP 265 EP 276 DI 10.1016/S0896-6273(03)00194-6 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 672AM UT WOS:000182498300015 PM 12718860 ER PT J AU Ben-Yosef, T Ness, SL Madeo, AC Bar-Lev, A Wolfman, JH Ahmed, ZM Desnick, RJ Willner, JP Avraham, KB Ostrer, H Oddoux, C Griffith, AJ Friedman, TB AF Ben-Yosef, T Ness, SL Madeo, AC Bar-Lev, A Wolfman, JH Ahmed, ZM Desnick, RJ Willner, JP Avraham, KB Ostrer, H Oddoux, C Griffith, AJ Friedman, TB TI Brief report - A mutation of PCDH15 among Ashkenazi Jews with the type 1 Usher syndrome SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RECESSIVE DEAFNESS; GENE; POPULATION; FREQUENCY; FAMILIES; PROFILE; DISEASE; CDH23; GJB2 C1 NIDCD, Mol Genet Lab, NIH, Rockville, MD 20850 USA. CUNY Mt Sinai Sch Med, Dept Human Genet, New York, NY 10029 USA. Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. NYU, Sch Med, Human Genet Program, New York, NY USA. RP Friedman, TB (reprint author), NIDCD, Mol Genet Lab, NIH, 5 Res Ct,Rm 2A15, Rockville, MD 20850 USA. RI Madeo, Anne/K-2880-2012 FU NCRR NIH HHS [RR-M01-00071]; NIDCD NIH HHS [1 Z01 DC 00039-06, 1 Z01 DC00060-01] NR 27 TC 59 Z9 61 U1 1 U2 3 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 24 PY 2003 VL 348 IS 17 BP 1664 EP 1670 DI 10.1056/NEJMoa021502 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 670PB UT WOS:000182416300006 PM 12711741 ER PT J AU Zhang, XW Chen, Z Chen, YL Tong, TJ AF Zhang, XW Chen, Z Chen, YL Tong, TJ TI Delivering antisense telomerase RNA by a hybrid adenovirus/adeno-associated virus significantly suppresses the malignant phenotype and enhances cell apoptosis of human breast cancer cells SO ONCOGENE LA English DT Article DE telomerase RNA; antisense; adenovirus; adeno-associated virus; gene therapy; breast cancer ID SITE-SPECIFIC INTEGRATION; ADENOASSOCIATED VIRUS; REVERSE-TRANSCRIPTASE; CATALYTIC SUBUNIT; HUMAN FIBROBLASTS; IMMORTAL CELLS; HIGH-CAPACITY; GENE-TRANSFER; TUMOR-CELLS; DNA AB Activated tetomerase is frequently detected in cancer cells and is able to maintain and stabilize the integrity of telomeres; it also contributes to unlimited divisions in cancer cells. Recently, a new generation of selective anticancer strategies is under development targeting the blockage of telomerase activity either at the protein level or telomerase RNA. Here, we report suppression of the malignant phenotype by the expression of the full-length antisense human telomerase RNA (hTR) delivered by a novel hybrid vector recombining adenovirus and adenoassociated virus (vAd-AAV). The hybrid vector vAd-AAV retained the unique traits from two parental viruses, such as high efficiency of gene transfer in mammalian cells and the ability to integrate into the genomic DNA of host cells. The stable expression of antisense hTR in MCF-7, cells significantly suppressed telomerase activity and progressively shortened telomere length for 30 population doublings (PD30). Expression of antisense hTR leads to a telomere-based growth arrest and the induction of spontaneous apoptosis. Antisense hTR decreased soft agar colony formation and reduced the cell proliferation, leading to exit from the cell cycle at G1 at PD15. The expression of antisense hTR also sensitized MCF-7 cells to apoptosis induced by sodium butyrate or serum starvation. Our study demonstrates that delivering antisense hTR by the hybrid Ad/AAV vector is an effective antineoplastic gene therapeutic strategy, which significantly suppresses the malignant phenotype and enhances apoptosis of human breast cancer cells. C1 Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Beijing 100083, Peoples R China. Natl Inst Deafness & Commun Disorders, Head & Neck Surg Branch, Tumor Biol Sect, NIH, Bethesda, MD 20892 USA. RP Tong, TJ (reprint author), Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Beijing 100083, Peoples R China. NR 70 TC 23 Z9 25 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 APR 24 PY 2003 VL 22 IS 16 BP 2405 EP 2416 DI 10.1038/sj.onc.1206317 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 670AD UT WOS:000182383500003 PM 12717417 ER PT J AU Kim, JH Leem, SH Sunwoo, Y Kouprina, N AF Kim, JH Leem, SH Sunwoo, Y Kouprina, N TI Separation of long-range human TERT gene haplotypes by transformation-associated recombination cloning in yeast SO ONCOGENE LA English DT Article DE hTERT; VNTR; polymorphism; haplotypes; TAR cloning ID TELOMERASE ACTIVITY; COLORECTAL CARCINOGENESIS; ENZYMATIC AMPLIFICATION; SEQUENCE; DNA; MINISATELLITES; POLYMORPHISMS; CHROMOSOMES; EXPRESSION; REGIONS AB The hTERT gene encoding a catalytic subunit of human telomerase contains four blocks of variable number of tandem repeats (VNTRs) - two in intron 2 and two in intron 6. The segregation of hTERT VNTRs was analysed in families, revealing that all of them were transmitted through meiosis following a Mendelian inheritance. The work reports a further characterization of the minisatellites in hTERT. We employed transformation-associated recombination (TAR) cloning to isolate parental hTERT alleles and determined the specific combination of minisatellites at each of the polymorphic sites. A long-range haplotyping of hTERT determined by TAR cloning was verified by classical Mendelian analysis. Since such a strategy can be applied for any chromosomal locus, we conclude that recombinational gene capture could greatly facilitate haplotypes analysis. C1 NCI, Lab Biosyst & Canc, NIH, Bethesda, MD 20892 USA. Dong A Univ, Dept Biol, Pusan 604714, South Korea. RP Kouprina, N (reprint author), NCI, Lab Biosyst & Canc, NIH, Bldg 37,Room 5032, Bethesda, MD 20892 USA. NR 21 TC 10 Z9 12 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 24 PY 2003 VL 22 IS 16 BP 2452 EP 2456 DI 10.1038/sj.onc.1206316 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 670AD UT WOS:000182383500008 PM 12717422 ER PT J AU Appel, LJ Champagne, CM Harsha, DW Cooper, LS Obarzanek, E Elmer, PJ Stevens, VJ Vollmer, WM Lin, PH Svetkey, LP Stedman, SW Young, DR AF Appel, LJ Champagne, CM Harsha, DW Cooper, LS Obarzanek, E Elmer, PJ Stevens, VJ Vollmer, WM Lin, PH Svetkey, LP Stedman, SW Young, DR CA PREMIER Collaborative Res Grp TI Effects of comprehensive lifestyle modification on blood pressure - Control main results of the PREMIER clinical trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RANDOMIZED CONTROLLED TRIAL; WEIGHT-LOSS; HYPERTENSION PREVENTION; DIETARY PATTERNS; SODIUM REDUCTION; LIFE-STYLE; RISK; POPULATION; DISEASE; WOMEN AB Context Weight loss, sodium reduction, increased physical activity, and limited alcohol intake are established recommendations that reduce blood pressure (BP). The Dietary Approaches to Stop Hypertension (DASH) diet also lowers BP. To date, no trial has evaluated the effects of simultaneously implementing these lifestyle recommendations. Objective To determine the effect on BP of 2 multicomponent, behavioral interventions. Design, Setting, and Participants Randomized trial with enrollment at 4 clinical centers (January 2000-June 2001) among 810 adults (mean [SD] age, 50 [8.9] years; 62% women; 34% African American) with above-optimal BP, including stage 1 hypertension (120-159 mm Hg systolic and 80-95 mm Hg diastolic), and who were not taking anti hypertensive medications. Intervention Participants were randomized to one of 3 intervention groups: (1) "established," a behavioral intervention that implemented established recommendations (n=268); (2) "established plus DASH, "which also implemented the DASH diet (n=269); and (3) an "advice only" comparison group (n=273). Main Outcome Measures Blood pressure measurement and hypertension status at 6 months. Results Both behavioral interventions significantly reduced weight, improved fitness, and lowered sodium intake. The established plus DASH intervention also increased fruit, vegetable, and dairy intake. Across the groups, gradients in BP and hypertensive status were evident. After subtracting change in advice only, the mean net reduction in systolic BP was 3.7 mm Hg (P<.001) in the established group and 4.3 mm Hg (P<.001) in the established plus DASH group; the systolic BP difference between the established and established plus DASH groups was 0.6 mm Hg (P=.43). Compared with the baseline hypertension prevalence of 38%, the prevalence at 6 months was 26% in the advice only group, 17% in the established group (P=.01 compared with the advice only group), and 12% in the established plus DASH group (P<.001 compared with the advice only group; P=.12 compared with the established group). The prevalence of optimal BP (<120 mm Hg systolic and <80 mm Hg diastolic) was 19% in the advice only group, 30% in the established group (P=.005 compared with the advice only group), and 35% in the established plus DASH group (P<001 compared with the advice only group; P=.24 compared with the established group). Conclusion individuals with above-optimal BP, including stage 1 hypertension, can make multiple lifestyle changes that lower BP and reduce their cardiovascular disease risk. C1 Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Epidemiol, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Int Hlth Human Nutr, Baltimore, MD 21205 USA. Pennington Biomed Res Ctr, Baton Rouge, LA USA. NHLBI, Bethesda, MD 20892 USA. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. Duke Univ, Med Ctr, Duke Hypertens Ctr, Durham, NC USA. Duke Univ, Med Ctr, Sarah W Stedman Ctr Nutr Studies, Durham, NC USA. Univ Maryland, Dept Kinesiol, College Pk, MD 20742 USA. RP Appel, LJ (reprint author), Johns Hopkins Med Inst, Dept Med, 2024 E Monument St,Suite 2-645, Baltimore, MD 21205 USA. FU NCRR NIH HHS [M01 RR00052]; NHLBI NIH HHS [UO1 HL60571, UO1 HL60573, UO1 HL60574, UO1 HL62828, UO1 HL60570] NR 36 TC 674 Z9 699 U1 2 U2 45 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 23 PY 2003 VL 289 IS 16 BP 2083 EP 2093 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 669WW UT WOS:000182374300024 PM 12709466 ER PT J AU Sunderland, T Linker, G Mirza, N Putnam, KT Friedman, DL Kimmel, LH Bergeson, J Manetti, GJ Zimmermann, M Tang, B Bartko, JJ Cohen, RM AF Sunderland, T Linker, G Mirza, N Putnam, KT Friedman, DL Kimmel, LH Bergeson, J Manetti, GJ Zimmermann, M Tang, B Bartko, JJ Cohen, RM TI Decreased beta-amyloid(1-42) and increased tau levels in cerebrospinal fluid of patients with Alzheimer disease SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID AMYLOID-BETA-PROTEIN; APOLIPOPROTEIN-E GENOTYPE; CSF-TAU; BIOCHEMICAL MARKER; CLINICAL-DIAGNOSIS; FRONTOTEMPORAL DEMENTIA; INVERSE CORRELATION; PHOSPHORYLATED TAU; LARGE-SCALE; MULTICENTER AB Context Alzheimer disease (AD) is characterized by pathological results at autopsy of amyloid plaques and tau-associated neurofibrillary tangles, but the clinical diagnosis of AD is determined on the basis of medical history, cognitive symptoms, and exclusionary criteria. The search for antemortem biomarkers is intense and has focused on cerebrospinal fluid (CSF) beta-amyloid(1-42) and tau proteins. Objectives To compare CSF beta-amyloid and tau levels in a new population of AD patients and controls. To perform a meta-analysis of studies of CSF beta-amyloid and tau levels in AD patients and controls. Design Cross-sectional study of the comparison of baseline CSF beta-amyloid(1-42) and tau levels in AD patients and controls. Meta-analysis involved 17 studies of CSF beta-amyloid and 34 studies of CSF tau. Setting Clinical research unit of the National Institute of Mental Health, Bethesda, Md. Patients The Geriatric Psychiatry Branch evaluated AD patients as inpatients at the National Institutes of Health Clinical Center between May 1985 and January 2001. A total of 203 patients participated in this study (131 with AD and 72 controls). None had other serious illnesses, and 31 of 131 AD cases had AD confirmed at autopsy. Meta-analysis provided an additional 3133 AD patients and 1481 controls. Main Outcome Measures Levels of CSF beta-amyloid(1-42) were measured by a sandwich enzyme-linked immunoabsorbent assay with a polyclonal capture antibody and a monoclonal detection antibody. Levels of CSF tau were measured with a standard commercial immunoassay. Results Levels of CSF beta-amyloid(1-42) were significantly lower in the AD patients vs controls (mean [SD], 183 [121] pg/mL vs 491 [245] pg/mL; P<.001). Levels of CSF tau were significantly higher in AD patients (mean [SD], 587 [365] pg/mL vs 244 [156] pg/mL; P<.001). The cutpoints of 444 pg/mL for CSF beta-amyloid(1-42) and 195 pg/mL for CSF tau gave a sensitivity and specificity of 92% and 89%, respectively, to distinguish AD patients from controls, which is comparable with rates with clinical diagnosis. Meta-analyses of studies comparing CSF beta-amyloid and tau levels in AD participants and controls confirmed an overall difference between levels in these 2 groups. Conclusions Alzheimer disease is associated with a significant decrease in CSF beta-amyloid(1-42) levels along with an increase in CSF tau levels. These findings suggest that the 2 measures are biological markers of AD pathophysiology. While these CSF measures may have a potential clinical utility as biomarkers of disease, the preliminary and retrospective nature of the findings, the absence of assay standardization, and the lack of comparison patient populations must be addressed in future studies testing the usefulness of these CSF measures for predictive, diagnostic, or treatment evaluation purposes. C1 NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. Pfizer Inc, Cent Res, Pharmacogenom & Clin Bochem Measurements Div, Groton, CT 06340 USA. Vertex Pharmaceut, Proteom Grp, Cambridge, MA USA. RP Sunderland, T (reprint author), NIMH, Geriatr Psychiat Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. FU NIMH NIH HHS [ZO1 MH00330-14] NR 78 TC 371 Z9 382 U1 0 U2 22 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 23 PY 2003 VL 289 IS 16 BP 2094 EP 2103 DI 10.1001/jama.289.16.2094 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 669WW UT WOS:000182374300025 PM 12709467 ER PT J AU Bateman, OA Purkiss, AG van Montfort, R Slingsby, C Graham, C Wistow, G AF Bateman, OA Purkiss, AG van Montfort, R Slingsby, C Graham, C Wistow, G TI Crystal structure of eta-crystallin: Adaptation of a class 1 aldehyde dehydrogenase for a new role in the eye lens SO BIOCHEMISTRY LA English DT Article ID RETINOL-BINDING PROTEIN; MACROMOLECULAR STRUCTURES; RETINALDEHYDE DEHYDROGENASE; ULTRAVIOLET FILTER; GENE RECRUITMENT; EXPRESSION; PROGRAM; FOLD; CRYSTALLOGRAPHY; SPECIFICITY AB eta-Crystallin is a retinal dehydrogenase that has acquired a role as a structural protein in the eye lens of elephant shrews, members of an ancient order of mammals. While it retains some activity toward retinal, which is oxidized to retinoic acid, the protein has acquired a number of specific sequence changes that have presumably been selected to enhance the lens role. The crystal structure of eta-crystallin, in common with class I and 2 ALDHs, is a dimer of dimers. It has a better-defined NAD binding site than those of related mammalian ALDH1 enzymes with the cofactor bound in the "hydride transfer" position in all four monomers with small differences about the dimer dyads. Although the active site is well conserved, the substrate-binding site is larger in eta-crystallin, and there are some mutations to the substrate access tunnel that might affect binding or release of substrate and product. It is possible that eta-crystallin has lost flexibility to improve its role in the lens. Enhanced binding of cofactor could enable it to act as a UV/blue light filter in the lens, improving visual acuity. The structure not only gives a view of a "natural mutant" of ALDH1 illustrating the adaptive conflict that can arise in multifunctional proteins, but also provides a well-ordered NAD binding site structure for this class of enzymes with important roles in development and health. C1 Univ London Birkbeck Coll, Sch Crystallog, London WC1E 7HX, England. NEI, Sect Mol Struct & Funct, NIH, Bethesda, MD 20892 USA. NCI DBS EIB, NIH, Bethesda, MD USA. RP Slingsby, C (reprint author), Univ London Birkbeck Coll, Sch Crystallog, Malet St, London WC1E 7HX, England. RI van Montfort, Rob/D-3248-2009 NR 47 TC 17 Z9 19 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 22 PY 2003 VL 42 IS 15 BP 4349 EP 4356 DI 10.1021/bi027367w PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 670QK UT WOS:000182420000004 PM 12693930 ER PT J AU Rajini, B Graham, C Wistow, G Sharma, Y AF Rajini, B Graham, C Wistow, G Sharma, Y TI Stability, homodimerization, and calcium-binding properties of a single, variant beta gamma-crystallin domain of the protein absent in melanoma 1 (AIM1) SO BIOCHEMISTRY LA English DT Article ID SPORE COAT PROTEIN; DYE STAINS-ALL; X-RAY-ANALYSIS; EYE LENS; SPHERULIN 3A; CIRCULAR-DICHROISM; S-CRYSTALLIN; PHYSARUM-POLYCEPHALUM; PRECURSOR STRUCTURE; MALIGNANT-MELANOMA AB AIM 1 (absent in melanoma), a candidate suppressor of malignancy in melanoma, is a nonlens member of the betagamma-crystallin superfamily, which contains six predicted betagamma domains. The first fly-crystallin domain of AIM1 (AIM1-g1) diverges most in sequence from the superfamily consensus. To examine its ability to fold and behave like a normal betagamma domain, we cloned AIM1-g1 and overexpressed it in Escherichia coli as a recombinant protein. The recombinant domain was found to be a stable, soluble protein, similar to lens protein gammaB-crystallin in secondary structure. The tertiary structure of AIM1-g1 is dominated by the contribution of aromatic amino acids and cysteine. AIM1-g1 undergoes concentration-independent, noncovalent homodimerization with no trace of monomer, similar to a one-domain protein spherulin 3a. Since many betagamma domain proteins bind calcium, we have also investigated the calcium-binding properties of AIM1-g1 by various methods. AIM1-g1 binds the calcium-mimic dye Stains-all, the calcium probe terbium (with K-D 170 muM), and Ca-45 when blotted on a membrane. AIM1-g1 binds calcium (K-D 30 muM) with a comparatively higher affinity than bovine lens gamma-crystallin (90muM). However, calcium binding does not induce significant change in the protein conformation in the near- and far-UV CD and in fluorescence. The AIM1-g1 domain is as stable as domains of betagamma-crystallins (betaB2- or gammaS-crystallins) as monitored by guanidinium. chloride unfolding (midpoint of unfolding transition is 1.8 M GdmCl), and the stability of the protein is not altered upon binding calcium as evaluated by equilibrium unfolding. These results show that, despite the sequence variation, AIM1-g1 folds such as a fly domain, binds calcium and undergoes dimerization. C1 Ctr Cellular & Mol Biol, Hyderabad 500007, Andhra Pradesh, India. NEI, Sect Mol Struct & Funct, NIH, Bethesda, MD 20892 USA. RP Sharma, Y (reprint author), Ctr Cellular & Mol Biol, Uppal Rd, Hyderabad 500007, Andhra Pradesh, India. NR 59 TC 24 Z9 24 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 22 PY 2003 VL 42 IS 15 BP 4552 EP 4559 DI 10.1021/bi0273841 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 670QK UT WOS:000182420000026 PM 12693952 ER PT J AU Bauernhofer, T Kuss, I Friebe-Hoffmann, U Baum, AS Dworacki, G Vonderhaar, BK Whiteside, TL AF Bauernhofer, T Kuss, I Friebe-Hoffmann, U Baum, AS Dworacki, G Vonderhaar, BK Whiteside, TL TI Role of prolactin receptor and CD25 in protection of circulating T lymphocytes from apoptosis in patients with breast cancer SO BRITISH JOURNAL OF CANCER LA English DT Article DE apoptosis; prolactin; annexin V; Fas; prolactin receptor ID ZETA-CHAIN EXPRESSION; INDUCED CELL-DEATH; PERIPHERAL-BLOOD; SIGNAL-TRANSDUCTION; GROWTH-HORMONE; OVARIAN-CANCER; IN-VIVO; ACTIVATION; MECHANISM; MELANOMA AB Prolactin (PRL) has been reported to inhibit apoptosis in various cell types and to serve. as a cofactor in the upregulation of CD25 on T cells during activation. We investigated a possible relation between prolactin receptor (PRL-R) or IL-2 receptor alpha (IL-2Ralpha, CD25) expression on circulating T lymphocytes and their apoptosis in patients with breast cancer. Peripheral blood mononuclear cells obtained from 25 patients, 25 normal controls (NC) and three cord blood samples were evaluated for Annexin V binding and expression of CD95, CD25, and PRL-R on CD3(+) T cells by multicolour flow cytometry. Plasma levels of PRL, sCD95L, and sIL-2R were determined in patients and controls and related to T-cell apoptosis. The ability of PRL to protect T cells from apoptosis induced by various agents was also studied. Expression of PRL-R on the surface of T cells was comparable in patients with breast cancer and NC, but PRL plasma levels in patients were significantly lower (P < 0.05). In patients, 18+/-11% (mean +/- s.d.) of CD3(+) cells bound Annexin V, compared to 9 +/- 6% in NC (P < 0.0004). Percentages of CD3(+)Fas(+) and CD3(+)CD25(+) cells were higher in the peripheral circulation of patients than NC (P < 0.0001 and <0.04, respectively). Levels of sFasL were lowest in plasma of the patients with the highest proportions of CD3(+)Fas(+) T cells. Most T cells undergoing apoptosis were CD3(+)CD25(-) in patients, and the proportion of CD3(+)CD25(-) Annexin V+ cells was significantly increased in patients compared to NC (P < 0.006). Ex vivo PRL protected T cells from starvation-induced or anti-CD3Ab-induced but not from Fas/FasL-dependent apoptosis. These results indicate that expression of CD25 but not of PRL-R on the surface of activated T lymphocytes appears to be involved in modulating Fas/Fas- ligand interactions, which are, in part, responsible for apoptosis of T lymphocytes and excessive turnover of immune cells in the circulation of patients with breast cancer. C1 Univ Pittsburgh, Pittsburgh Canc Inst, Hillman Canc Ctr, Pittsburgh, PA 15213 USA. NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. RP Whiteside, TL (reprint author), Univ Pittsburgh, Pittsburgh Canc Inst, Hillman Canc Ctr, Res Pavil,Suite 1-27,5117 Ctr Ave, Pittsburgh, PA 15213 USA. NR 35 TC 8 Z9 9 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD APR 22 PY 2003 VL 88 IS 8 BP 1301 EP 1309 DI 10.1038/sj.bjc.6600860 PG 9 WC Oncology SC Oncology GA 678XD UT WOS:000182891200025 PM 12698200 ER PT J AU Chauhan, SS Liang, XJ Su, AW Pai-Panandiker, A Shen, DW Hanover, JA Gottesman, MM AF Chauhan, SS Liang, XJ Su, AW Pai-Panandiker, A Shen, DW Hanover, JA Gottesman, MM TI Reduced endocytosis and altered lysosome function in cisplatin-resistant cell lines SO BRITISH JOURNAL OF CANCER LA English DT Article DE cisplatin-resistance; EGF binding; fluid-phase/receptor-mediated endocytosis; endosomal/lysosomal acidification; Pseudomonas exotoxin ID EPIDERMAL GROWTH-FACTOR; CROSS-RESISTANCE; BINDING-PROTEINS; CATHEPSIN-L; ACCUMULATION; REPAIR; PH; DEGRADATION; FIBROBLASTS; GLUTATHIONE AB We isolated human KB adenocarcinoma cisplatin-resistant (CP-r) cell lines with multidrug-resistance phenotypes because of reduced accumulation of cisplatin and other cytotoxic compounds such as methotrexate and heavy metals. The uptake of horseradish peroxidase (HRPO) and Texas Red dextran was decreased several-fold in KB-CP-r cells, indicating a general defect in fluid-phase endocytosis. In contrast, although EGF receptors were decreased in amount, the kinetics of EGF uptake, a marker of receptor-mediated endocytosis, was similar in sensitive and resistant cells. However, 40-60% of the I-125-EGF released into the medium after uptake into lysosomes of KB-CP-r cells was TCA precipitable as compared to only 10% released by sensitive cells. These results indicate inefficient degradation of internalised I-125-EGF in the lysosomes of KB-CP-r cells, consistent with slower processing of cathepsin L, a lysosomal cysteine protease. Treatment of KB cells by bafilomycin A(1), a known inhibitor of the vacuolar proton pump, mimicked the phenotype seen in KB-CP-r cells with reduced uptake of HRPO, I-125-EGF, C-14-carboplatin, and release of TCA precipitable I-125-EGF. KB-CP-r cells also had less acidic lysosomes. KB-CP-r cells were crossresistant to Pseudomonas exotoxin, and Pseudomonas exotoxin-resistant KB cells were crossresistant to cisplatin. Since cells with endosomal acidification defects are known to be resistant to Pseudomonas exotoxin and blocking of endosomal acidification mimics the CP-r phenotype, we conclude that defective endosomal acidification may contribute to acquired cisplatin resistance. C1 NCI, Cell Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20842 USA. NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, Canc Res Ctr, NIH, 37 Convent Dr,Room 1A09, Bethesda, MD 20842 USA. NR 45 TC 57 Z9 59 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD APR 22 PY 2003 VL 88 IS 8 BP 1327 EP 1334 DI 10.1038/sj.bjc.6600861 PG 8 WC Oncology SC Oncology GA 678XD UT WOS:000182891200028 PM 12698203 ER PT J AU Kraitchman, DL Sampath, S Castillo, E Derbyshire, JA Boston, RC Bluemke, DA Gerber, BL Prince, JL Osman, NF AF Kraitchman, DL Sampath, S Castillo, E Derbyshire, JA Boston, RC Bluemke, DA Gerber, BL Prince, JL Osman, NF TI Quantitative ischemia detection during cardiac magnetic resonance stress testing by use of FastHARP SO CIRCULATION LA English DT Article DE magnetic resonance imaging; myocardial contraction; coronary disease; systole; ischemia ID MYOCARDIAL-ISCHEMIA; WALL-MOTION; SPATIAL MODULATION; ECHOCARDIOGRAPHY; HEART; MRI; ABNORMALITIES; DYSFUNCTION; PERFUSION; CASCADE AB Background-Because ECG alterations caused by ischemia cannot be reliably detected in the high-field MRI environment, detection of wall motion abnormalities is often used to ensure patient safety during stress testing. However, an experienced observer is needed to detect these abnormalities. In this study, we investigate the use of fast harmonic phase (FastHARP) MRI for the quantitative, operator-independent detection of the onset of ischemia during acute coronary occlusion. Methods and Results-Eight mongrel dogs underwent an acute 2-minute closed-chest coronary artery occlusion while continuous FastHARP images were acquired. Full regional wall strain was determined every other heartbeat in a single short-axis imaging slice. After 5 minutes of reperfusion, a second 2-minute ischemic episode was induced during the acquisition of conventional cine wall-motion images. The time at which ECG alterations were observed during the first ischemic period was recorded. The time from occlusion to the detection of ischemia, based on a consensus of 2 blinded observers, was determined for MRI. No significant ischemia was present in 2 animals. In the remaining animals, the onset of ischemia was detected significantly earlier by FastHARP than by cine MRI (9.5+/-5 versus 33+/-14 seconds, P<0.01). HARP ischemia detection preceded ECG changes, on average, by 54 seconds. Conclusions-The rapid acquisition and detection of induced ischemia with FastHARP MRI shows promise as a nonsubjective method to diagnose significant coronary lesions during MR stress testing. C1 Johns Hopkins Univ, Sch Med, Dept Radiol, MRI, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Elect Engn, Baltimore, MD USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Penn, Sch Vet Med, Kennett Sq, PA 19348 USA. RP Kraitchman, DL (reprint author), Johns Hopkins Univ, Sch Med, Dept Radiol, MRI, 601 N Caroline St,No 4231, Baltimore, MD 21287 USA. RI Prince, Jerry/A-3281-2010; Gerber, Bernhard/H-5838-2011; OI Prince, Jerry/0000-0002-6553-0876; Bluemke, David/0000-0002-8323-8086 FU NHLBI NIH HHS [R01-HL63439, R01-HL45090, K02-HL04193, R01-HL47405] NR 20 TC 61 Z9 61 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 22 PY 2003 VL 107 IS 15 BP 2025 EP 2030 DI 10.1161/01.CIR.0000062684 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 669VK UT WOS:000182371000016 PM 12668517 ER PT J AU Ravina, BM Fagan, SC Hart, RG Hovinga, CA Murphy, DD Dawson, TM Marler, JR AF Ravina, BM Fagan, SC Hart, RG Hovinga, CA Murphy, DD Dawson, TM Marler, JR TI Neuroprotective agents for clinical trials in Parkinson's disease - A systematic assessment SO NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; GM1 GANGLIOSIDE TREATMENT; TRANSGENIC ANIMAL-MODEL; COENZYME Q(10); OXIDATIVE STRESS; MPTP MODEL; CREATINE; THERAPY; MINOCYCLINE; NEUROTOXICITY AB Background: Current therapies for PD ameliorate symptoms in the early phases of disease but become less effective over time, as the underlying disease progresses. Therapies that slow the progression of PD are needed. However, there have been relatively few clinical trials aimed at demonstrating neuroprotection. The authors sought to identify potential neuroprotective agents for testing in clinical trials. Methods: First a broad array of compounds were identified by working with clinicians and researchers in academics and industry. Specific criteria were drafted for drug evaluation, including scientific rationale, blood-brain barrier penetration, safety and tolerability, and evidence of efficacy in animal models or humans. Agents were prioritized based on these criteria. Results: The authors identified 59 potential neuroprotective compounds, proposed by 42 clinicians and scientists from 13 countries. After systematic reviews using the specified criteria they found 12 compounds to be attractive candidates for further clinical trials in PD. Conclusions: Several potential neuroprotective compounds, representing a wide range of mechanisms, are available and merit further investigation in PD. C1 NINDS, Ctr Neurosci, NIH, Rockville, MD 20892 USA. Med Coll Georgia, Dept Pharmacol, Augusta, GA 30912 USA. Cleveland Clin Fdn, Dept Pharm, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Neurol, Cleveland, OH 44195 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Ravina, BM (reprint author), NINDS, Ctr Neurosci, NIH, Rm 2225,6001 Execut Blvd, Rockville, MD 20892 USA. RI Fagan, Susan /D-3281-2009 NR 55 TC 181 Z9 189 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 22 PY 2003 VL 60 IS 8 BP 1234 EP 1240 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 671XD UT WOS:000182489600007 PM 12707423 ER PT J AU Zhai, P Pagan, F Statland, J Butman, JA Floeter, MK AF Zhai, P Pagan, F Statland, J Butman, JA Floeter, MK TI Primary lateral sclerosis - A heterogeneous disorder composed of different subtypes? SO NEUROLOGY LA English DT Article; Proceedings Paper CT 53rd Annual Meeting of the American-Academy-of-Neurology CY MAY 05-12, 2001 CL PHILADELPHIA, PENNSYLVANIA SP Amer Acad Neurol ID MOTOR-NEURON DISEASE; TRANSCRANIAL MAGNETIC STIMULATION; H-1-MAGNETIC RESONANCE SPECTROSCOPY; LUMBOSACRAL MOTONEURONS; ACOUSTIC STARTLE; CORTEX; MODULATION; ABNORMALITIES; INVOLVEMENT; EXCITATION AB Objective: To determine identifiable subgroups of patients with primary lateral sclerosis (PLS) with distinct clinical features as a first step in identifying patients likely to have the same disorder. Methods: Twenty-five patients meeting previously proposed diagnostic criteria for PLS were seen for examination, measurement of gait and finger tapping speed, and physiologic tests to assess motor pathways. Motor cortex excitability and central motor conduction time were assessed with transcranial magnetic stimulation. Brainstem motor pathways were assessed by the acoustic startle reflex. MRS was performed in a subgroup of patients to assess metabolites in the motor cortex. Results: Fifty-six percent of the patients with PLS had a similar pattern of symptom progression, which the authors termed ascending. In these patients spasticity began in the legs and progressed slowly and steadily. Spasticity in the arms developed 3.6 years after the legs, on average, and speech impairment followed 1.5 years later. Motor evoked potentials were absent. MRS showed a mean reduction of N-acetylaspartate/creatinine in the motor cortex. The remaining patients with PLS had heterogeneous patterns of symptom progression and physiology. Conclusions: Patients with PLS with an ascending progression of symptoms form a distinct clinical subgroup that may be amenable to investigations of etiology and treatment. C1 NINDS, EMG Sect, NIH, Bethesda, MD 20892 USA. NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP Floeter, MK (reprint author), NINDS, EMG Sect, NIH, 10 Ctr Dr MSC 1404,Bld 10 Room 5C101, Bethesda, MD 20892 USA. RI Butman, John/A-2694-2008; OI Butman, John/0000-0002-1547-9195 NR 49 TC 34 Z9 35 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 22 PY 2003 VL 60 IS 8 BP 1258 EP 1265 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 671XD UT WOS:000182489600011 PM 12707427 ER PT J AU Goldstein, DS Holmes, C Sharabi, Y Brentzel, S Eisenhofer, G AF Goldstein, DS Holmes, C Sharabi, Y Brentzel, S Eisenhofer, G TI Plasma levels of catechols and metanephrines in neurogenic orthostatic hypotension SO NEUROLOGY LA English DT Article ID CARDIAC SYMPATHETIC DENERVATION; MULTIPLE SYSTEM ATROPHY; PARKINSONS-DISEASE; AUTONOMIC FAILURE; ELECTROCHEMICAL DETECTION; LIQUID-CHROMATOGRAPHY; NOREPINEPHRINE; REMOVAL; MIBG AB Background: Neurogenic orthostatic hypotension (NOH) usually results from deficient release of the sympathetic neurotransmitter norepinephrine (NE) when the patient stands up. In pure autonomic failure (PAF) and PD with NOH, sympathetic denervation can explain this deficiency, whereas in multiple-system atrophy (MSA), deficient baroreflex regulation of sympathetic traffic to intact terminals probably causes the NOH. From the concept of a unitary sympathoadrenomedullary system, one might predict parallel sympathoneural and adrenomedullary abnormalities in NOH. Objective: To test the concept of parallel sympathoneural and adrenomedullary abnormalities in NOH by simultaneous measurements of plasma levels of catechols and metanephrines. Methods: Antecubital venous blood drawn via an indwelling cannula with the subject supine was assayed for catecholamines (NE, epinephrine [EPI]), dihydroxyphenylglycol (DHPG), and metanephrines (normetanephrine [NMN] and metanephrine [MN]) in patients with PAF, PD + NOH, or MSA + NOH. Control subjects had PD lacking NOH or were normal volunteers at least 35 years old. Cardiac sympathetic innervation was assessed by 6-[F-18]fluorodopamine PET scanning. Results: The three NOH groups differed clearly in patterns of plasma catechols and metanephrines. The PAF group had low NE, DHPG, NMN, EPI, and MN levels, the group with MSA + NOH had generally normal levels, and the PD + NOH group low NMN levels and low DHPG levels for given NE levels but normal mean NE, EPI, and MN levels. All patients with PAF or PD + NOH had markedly decreased 6-[F-18]fluorodopamine-derived radioactivity throughout the left ventricular myocardium; all patients with MSA + NOH had normal radioactivity. Conclusions: PAF involves generalized loss of sympathoadrenomedullary cells, MSA + NOH intact sympathoadrenomedullary cells, and PD + NOH intact adrenomedullary cells but organ-selective sympathetic denervation, especially in the heart. C1 NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, NIH, 10 Ctr Dr,Bldg 10,Rm 6N252,MSC-1620, Bethesda, MD 20892 USA. NR 27 TC 58 Z9 59 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 22 PY 2003 VL 60 IS 8 BP 1327 EP 1332 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 671XD UT WOS:000182489600021 PM 12707437 ER PT J AU Pagan, FL Butman, JA Dambrosia, JM Hallett, M AF Pagan, FL Butman, JA Dambrosia, JM Hallett, M TI Evaluation of essential tremor with multi-voxel magnetic resonance spectroscopy SO NEUROLOGY LA English DT Article ID BRAIN AB The pathologic substrate of essential tremor (ET) remains unknown. The authors studied 10 patients with ET and 10 volunteers using a multislice MR spectroscopy imaging sequence. Left and right cerebellar hemisphere NAA/CR and NAA/Cho ratios were significantly smaller in the ET patients than healthy subjects. The authors' data suggest that the decreased NAA/Cr and NAA/Cho ratios within the cerebellum may represent an abnormality in neuronal function. C1 NINDS, Med Neurol Branch, NIH, HMCS, Bethesda, MD 20892 USA. NINDS, Biostat Branch, NIH, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Med Neurol Branch, NIH, HMCS, Bldg 10,Room 5N226,10 Ctr Dr,MSC1428, Bethesda, MD 20892 USA. RI Butman, John/A-2694-2008; OI Butman, John/0000-0002-1547-9195 NR 9 TC 72 Z9 72 U1 0 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 APR 22 PY 2003 VL 60 IS 8 BP 1344 EP 1347 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 671XD UT WOS:000182489600024 PM 12707440 ER PT J AU Scher, AI Lipton, RB Stewart, WF AF Scher, AI Lipton, RB Stewart, WF TI Habitual snoring as a risk factor for chronic daily headache SO NEUROLOGY LA English DT Article ID SLEEP-APNEA AB Frequent headache is associated with a variety of sleep disorders. The authors compared the prevalence of snoring in a group of chronic daily headache (CDH) subjects (n = 206) with a control group of episodic headache subjects (n = 507). Habitual snoring was more common in the CDH subjects than in the control subjects (24 vs 14%; p < 0.05); the difference remained after adjusting for factors related to sleep-disordered breathing (OR = 2.9; p < 0.005). If this association proves causal, sleep-disordered breathing may provide a target for therapeutic interventions for chronic daily headache. C1 NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Dept Neurol, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Epidemiol, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Social Med, Bronx, NY 10467 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. Innovat Med Res, Hunt Valley, MD USA. RP Scher, AI (reprint author), NIA, Lab Epidemiol Demog & Biometry, NIH, Gateway Bldg,Suite 3C-309,7201 Wisconsin Ave,MSC, Bethesda, MD 20892 USA. NR 10 TC 75 Z9 79 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 22 PY 2003 VL 60 IS 8 BP 1366 EP 1368 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 671XD UT WOS:000182489600031 PM 12707447 ER PT J AU Anlauf, M Schafer, MKH Eiden, L Weihe, E AF Anlauf, M Schafer, MKH Eiden, L Weihe, E TI Chemical coding of the human gastrointestinal nervous system: Cholinergic, VIPergic, and catecholaminergic phenotypes SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Review DE dopamine; neurotransmitters; tyrosine hydroxylase; vasoactive intestinal peptide; vesicular acetylcholine transporter; vesicular monoamine transporters ID VESICULAR ACETYLCHOLINE TRANSPORTER; PIG SMALL-INTESTINE; NITRIC-OXIDE SYNTHASE; INTRINSIC ADRENERGIC NEURONES; INFERIOR MESENTERIC GANGLIA; SEROTONIN-BINDING PROTEIN; PRIMARY AFFERENT NEURONS; MUSCLE MOTOR-NEURONS; GUINEA-PIG; MYENTERIC PLEXUS AB The aim of this investigation was to identify the proportional neurochemical codes of enteric neurons and to determine the specific terminal fields of chemically defined nerve fibers in all parts of the human gastrointestinal (GI) tract. For this purpose, antibodies against the vesicular monoamine transporters (VMAT1/2), the vesicular acetylcholine transporter (VAChT), tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), serotonin (5-HT), vasoactive intestinal peptide (VIP), and protein gene product 9.5 (PGP 9.5) were used. For in situ hybridization (35)S-labeled VMAT1, VMAT2, and VAChT riboprobes were used. In all regions of the human GI tract, 50-70% of the neurons were cholinergic, as judged by staining for VAChT. The human gut unlike the rodent gut exhibits a cholinergic innervation, which is characterized by an extensive overlap with VIPergic innervation. Neurons containing VMAT2 constituted 14-20% of all intrinsic neurons in the upper GI tract, and there was an equal number of TH-positive neurons. In contrast, DBH was absent from intrinsic neurons. Cholinergic and monoaminergic phenotypes proved to be completely distinct phenotypes. In conclusion, the chemical coding of human enteric neurons reveals some similarities with that of other mammalian species, but also significant differences. VIP is a cholinergic cotransmitter in the intrinsic innervation of the human gut. The substantial overlap between VMAT2 and TH in enteric neurons indicates that the intrinsic catecholaminergic innervation is a stable component of the human GI tract throughout life. The absence of DBH from intrinsic catecholaminergic neurons indicates that these neurons have a dopaminergic phenotype. (C) 2003 Wiley-Liss, Inc. C1 Univ Marburg, Inst Anat & Cell Biol, Dept Mol Neurosci, D-35037 Marburg, Germany. Univ Kiel, Dept Pathol, D-24105 Kiel, Germany. NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. RP Weihe, E (reprint author), Univ Marburg, Inst Anat & Cell Biol, Dept Mol Neurosci, Robert Koch Str 6, D-35037 Marburg, Germany. EM weihe@mailer.uni-marburg.de OI Eiden, Lee/0000-0001-7524-944X NR 105 TC 108 Z9 111 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD APR 21 PY 2003 VL 459 IS 1 BP 90 EP 111 DI 10.1002/cne.10599 PG 22 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 658WT UT WOS:000181744600007 PM 12629668 ER PT J AU Margulies, DH AF Margulies, DH TI CD28, costimulator or agonist receptor? SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Editorial Material ID T-CELL RECEPTOR; IMMUNOLOGICAL SYNAPSE; CTLA-4; ACTIVATION; COMPLEX; TRANSPLANTATION; IMMUNOTHERAPY; LYMPHOCYTES; SEGREGATION; PATHWAYS C1 NIAID, Mol Biol Sect, Immunol Lab, NIH,DHHS, Bethesda, MD 20892 USA. RP Margulies, DH (reprint author), NIAID, Mol Biol Sect, Immunol Lab, NIH,DHHS, Bldg 10,Room 11N311, Bethesda, MD 20892 USA. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 NR 28 TC 18 Z9 19 U1 1 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 21 PY 2003 VL 197 IS 8 BP 949 EP 953 DI 10.1084/jem.20030303 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 671HV UT WOS:000182460000001 PM 12707298 ER PT J AU Yoshimoto, T Min, BK Sugimoto, T Hayashi, N Ishikawa, Y Sasaki, Y Hata, H Takeda, K Okumura, K Van Kaer, L Paul, WE Nakanishi, K AF Yoshimoto, T Min, BK Sugimoto, T Hayashi, N Ishikawa, Y Sasaki, Y Hata, H Takeda, K Okumura, K Van Kaer, L Paul, WE Nakanishi, K TI Nonredundant roles for CD1d-restricted natural killer T cells and conventional CD4(+) T cells in the induction of immunoglobulin e antibodies in response to interleukin 18 treatment of mice SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE IL-18R; CD4(+) NK1.1(+) T cells; Th2 cytokines; CD40 ligand; allergy ID IFN-GAMMA PRODUCTION; V(ALPHA)14 NKT CELLS; INTERFERON-GAMMA; RECEPTOR EXPRESSION; DENDRITIC CELLS; IL-18 RECEPTOR; IGE PRODUCTION; B-CELLS; ACTIVATION; CYTOKINE AB Interleukin (IL)-18 synergizes with IL-12 to promote T helper cell (Th)1 responses. Somewhat paradoxically, IL-18 administration alone strongly induces immunoglobulin (Ig)E production and allergic inflammation, indicating a role for IL-18 in the generation of Th2 responses. The ability of IL-18 to induce IgE is dependent on CD4(+) T cells, IL-4, and signal transducer and activator of transcription (stat)6. Here, we show that IL-18 fails to induce IgE both in CD1d(-/-) mice that lack natural killer T (NKT) cells and in class II-/- mice that lack conventional CD4(+) T cells. However, class II-/- mice reconstituted with conventional CD4(+) T cells show the capacity to produce IgE in response to IL-18. NKT cells express high levels of IL-18 receptor (R)alpha chain and produce significant amounts of IL-4, IL-9, and IL-13, and induce CD40 ligand expression in response to IL-2 and IL-18 stimulation in vitro. In contrast, conventional CD4(+) T cells express low levels of IL-18Ralpha and poorly respond to IL-2 and IL-18. Nevertheless, conventional CD4(+) T cells are essential for B cell IgE responses after the administration of IL-1.8. These findings indicate that NKT cells might be the major source of IL-4 in response to IL-18 administration and that conventional CD4(+) T cells demonstrate their helper function in the presence of NKT cells. C1 Hyogo Med Univ, Dept Immunol & Med Zool, Nishinomiya, Hyogo 6638501, Japan. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Juntendo Univ, Sch Med, Dept Immunol, Tokyo 1138521, Japan. Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37232 USA. RP Nakanishi, K (reprint author), Hyogo Med Univ, Dept Immunol & Med Zool, 1-1 Mukogawa Cho, Nishinomiya, Hyogo 6638501, Japan. RI Van Kaer, Luc/H-1033-2015 OI Van Kaer, Luc/0000-0001-5275-2309 NR 35 TC 78 Z9 80 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 21 PY 2003 VL 197 IS 8 BP 997 EP 1005 DI 10.1084/jem.20021701 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 671HV UT WOS:000182460000006 PM 12695491 ER PT J AU de Sanjose, S Shah, KV Domingo-Domenech, E Engels, EA de Sevilla, AF Alvaro, T Garcia-Villanueva, M Romagosa, V Gonzalez-Barca, E Viscidi, RP AF de Sanjose, S Shah, KV Domingo-Domenech, E Engels, EA de Sevilla, AF Alvaro, T Garcia-Villanueva, M Romagosa, V Gonzalez-Barca, E Viscidi, RP TI Lack of serological evidence for an association between simian virus 40 and lymphoma SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID SIMIAN-VIRUS-40 AB Recent studies have implicated simian virus 40 (SV40) in non-Hodgkin's lymphomas based on detection of SV40 DNA sequences. We employed a virus-like-particle (VLP)-based enzyme immunoassay for antibodies to SV40 to test sera from 520 lymphoma cases and 587 controls in Spain. The SV40 seroprevalence was 9.5% in controls and 5.9% in cases. Antibody levels of the positive sera were low. There was no association of SV40 seropositivity with any subtype of lymphoma. VLPs of the human BK virus substantially inhibited the SV40 reactivity of human sera. There was no serological evidence of widespread SV40 infection and no association of SV40 seropositivity with human lymphomas in Spain. (C) 2003 Wiley-Liss, Inc. C1 NCI, Viral Epidemiol Branch, Rockville, MD 20852 USA. Inst Catala Oncol, Barcelona, Spain. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21218 USA. Hosp Verge Cinta, Tortosa, Spain. Ramon & Cajal, Madrid, Spain. Ciutat Sanitaria & Univ Bellvitge, Barcelona, Spain. Johns Hopkins Univ, Sch Med, Dept Pediat, Stanley Div Dev Neurovirol, Baltimore, MD 21205 USA. RP de Sanjose, S (reprint author), NCI, Viral Epidemiol Branch, 6120 Execut Plaza S,Room 8005, Rockville, MD 20852 USA. RI de Sanjose Llongueras, Silvia/H-6339-2014; Tomas, Alvaro/L-5531-2015 OI Tomas, Alvaro/0000-0002-7858-2384 FU NIAID NIH HHS [R01-AI42058] NR 6 TC 59 Z9 60 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD APR 20 PY 2003 VL 104 IS 4 BP 522 EP 524 DI 10.1002/ijc.10993 PG 3 WC Oncology SC Oncology GA 655RQ UT WOS:000181566800019 PM 12584752 ER PT J AU Franklin, SS Wong, ND Kannel, WB AF Franklin, SS Wong, ND Kannel, WB TI Age-specific relevance of usual blood pressure to vascular mortality SO LANCET LA English DT Letter C1 Univ Calif Irvine, Prevent Cardiol Program, Irvine, CA 92697 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Franklin, SS (reprint author), Univ Calif Irvine, Prevent Cardiol Program, Irvine, CA 92697 USA. NR 5 TC 2 Z9 2 U1 0 U2 2 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD APR 19 PY 2003 VL 361 IS 9366 BP 1389 EP 1389 DI 10.1016/S0140-6736(03)13059-0 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 669HP UT WOS:000182346100036 PM 12711495 ER PT J AU Ikemoto, S Witkin, BM Morales, M AF Ikemoto, S Witkin, BM Morales, M TI Rewarding injections of the cholinergic agonist carbachol into the ventral tegmental area induce locomotion and c-Fos expression in the retrosplenial area and supramammillary nucleus SO BRAIN RESEARCH LA English DT Article DE reinforcement; nucleus accumbens; limbic system; Papez's emotion circuit; rat ID DOPAMINERGIC-NEURONS; BRAIN-STIMULATION; SUBSTANTIA NIGRA; RAT-BRAIN; ACCUMBENS; RECEPTORS; NICOTINE; CORTEX; SYSTEM; PROJECTIONS AB Previously we found that intra-ventral tegmental injections of the cholinergic agonist carbachol induce reward; such injections induce conditioned place preference and rats learn quickly to self-administer carbachol directly into the ventral tegmental area (VTA). To determine what brain regions are activated by such rewarding injections we studied the expression of the transcription factor c-Fos in local and distant brain regions following ventral tegmental injections of carbachol in rats. We also measured locomotion induced by such injections. Carbachol injections into the VTA induced vigorous locomotion while carbachol injections into the regions I turn dorsal or I mm lateral to the VTA induced delayed attenuated locomotion. Ventral tegmental injections of carbachol induced c-Fos expression throughout the brain. Significant correlations between locomotion c-Fos positive nuclei were found in the retrosplenial area the posterior hypothalamus including the supramammillary nucleus. These results suggest that the retrosplenial area supramammillary nucleus may be parts of the circuitry for the reward triggered by ventral tegmental cholinergic stimulation. Published by Elsevier Science B.V. C1 NIDA, Behav Neurosci Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. NIDA, Cellular Neurophysiol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Ikemoto, S (reprint author), NIDA, Behav Neurosci Sect, Intramural Res Program, NIH, 550 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Ikemoto, Satoshi/0000-0002-0732-7386 NR 33 TC 16 Z9 17 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD APR 18 PY 2003 VL 969 IS 1-2 BP 78 EP 87 DI 10.1016/S0006-8993(03)02280-7 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 677CV UT WOS:000182790100009 PM 12676367 ER PT J AU Boshoff, HIM Reed, MB Barry, CE Mizrahi, V AF Boshoff, HIM Reed, MB Barry, CE Mizrahi, V TI DnaE2 polymerase contributes to in vivo survival and the emergence of drug resistance in Mycobacterium tuberculosis SO CELL LA English DT Article ID IRRADIATED ESCHERICHIA-COLI; POL-II; REPLICATION RESTART; DAMAGE INDUCTION; MUTATION-RATES; ERROR-PRONE; EXPRESSION; SMEGMATIS; REPAIR; GENES AB The presence of multiple copies of the major replicative DNA polymerase (DnaE) in some organisms, including important pathogens and symbionts, has remained an unresolved enigma. We postulated that one copy might participate in error-prone DNA repair synthesis. We found that UV irradiation of Mycobacterium tuberculosis results in increased mutation frequency in the surviving fraction. We identified dnaE2 as a gene that is upregulated in vitro by several DNA damaging agents, as well as during infection of mice. Loss of this protein reduces both survival of the bacillus after UV irradiation and the virulence of the organism in mice. Our data suggest that DnaE2, and not a member of the Y family of error-prone DNA polymerases, is the primary mediator of survival through inducible mutagenesis and can contribute directly to the emergence of drug resistance in vivo. These results may indicate a potential new target for therapeutic intervention. C1 NIAID, TB Res Sect, Host Def Lab, NIH, Rockville, MD 20852 USA. Univ Witwatersrand, Sch Pathol, MRC, NHLS,WITS Mol Mycobacteriol Res Unit, Johannesburg, South Africa. Natl Hlth Lab Serv, Johannesburg, South Africa. RP Barry, CE (reprint author), NIAID, TB Res Sect, Host Def Lab, NIH, Twinbrook 2,12441 Parklawn Dr, Rockville, MD 20852 USA. RI Barry, III, Clifton/H-3839-2012 FU Intramural NIH HHS [Z01 AI000783-11] NR 48 TC 207 Z9 218 U1 2 U2 13 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD APR 18 PY 2003 VL 113 IS 2 BP 183 EP 193 DI 10.1016/S0092-8674(03)00270-8 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 672EP UT WOS:000182508500008 PM 12705867 ER PT J AU Yang, IY Miller, H Wang, ZG Frank, EG Ohmori, H Hanaoka, F Moriya, M AF Yang, IY Miller, H Wang, ZG Frank, EG Ohmori, H Hanaoka, F Moriya, M TI Mammalian translesion DNA synthesis across an acrolein-derived deoxyguanosine adduct - Participation of DNA polymerase eta in error-prone synthesis in human cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID XERODERMA-PIGMENTOSUM VARIANT; ESCHERICHIA-COLI; LOW FIDELITY; Y-FAMILY; 1,N-2-PROPANODEOXYGUANOSINE ADDUCTS; LESION-BYPASS; HUMAN HOMOLOG; HUMAN REV1; POL-KAPPA; UV-LIGHT AB alpha-OH-PdG, an acrolein-derived deoxyguanosine adduct, inhibits DNA synthesis and miscodes significantly in human cells. To probe the cellular mechanism underlying the error-free and error-prone translesion DNA syntheses, in vitro primer extension experiments using purified DNA polymerases and site-specific alpha-OH-PdG were conducted. The results suggest the involvement of pol eta in the cellular error-prone translesion synthesis. Experiments with xeroderma pigmentosum variant cells, which lack pol eta, confirmed this hypothesis. The in vitro results also suggested the involvement of pol iota and/or REV1 in inserting correct dCMP opposite alpha-OH-PdG during error-free synthesis. However, none of translesion-specialized DNA polymerases catalyzed significant extension from a dC terminus when paired opposite alpha-OH-PdG. Thus, our results indicate the following. (i) Multiple DNA polymerases are involved in the bypass of alpha-OH-PdG in human cells. (ii) The accurate and inaccurate syntheses are catalyzed by different polymerases. (iii) A modification of the current eukaryotic bypass model is necessary to account for the accurate bypass synthesis in human cells. C1 SUNY Stony Brook, Dept Pharmacol Sci, Biol Chem Lab, Stony Brook, NY 11794 USA. Univ Kentucky, Grad Ctr Toxicol, Lexington, KY 40536 USA. NICHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. Kyoto Univ, Inst Virus Res, Dept Genet & Mol Biol, Lab Genet Informat Anal, Kyoto 6068507, Japan. Osaka Univ, Grad Sch Frontier Biosci, Suita, Osaka 5650871, Japan. RP Moriya, M (reprint author), SUNY Stony Brook, Dept Pharmacol Sci, Biol Chem Lab, Stony Brook, NY 11794 USA. RI Miller, Holly/I-6942-2015 OI Miller, Holly/0000-0002-9076-5335 FU NCI NIH HHS [CA92528, CA76163, CA47995] NR 60 TC 34 Z9 36 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 APR 18 PY 2003 VL 278 IS 16 BP 13989 EP 13994 DI 10.1074/jbc.M212535200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 670JV UT WOS:000182405000056 PM 12584190 ER PT J AU Wang, HB Faucette, S Sueyoshi, T Moore, R Ferguson, S Negishi, M LeCluyse, EL AF Wang, HB Faucette, S Sueyoshi, T Moore, R Ferguson, S Negishi, M LeCluyse, EL TI A novel distal enhancer module regulated by pregnane x receptor/constitutive androstane receptor is essential for the maximal induction of CYP2B6 gene expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN CYTOCHROME P4502B6; HUMAN HEPATOCYTES; HUMAN LIVER; TRANSCRIPTIONAL REGULATION; NUCLEAR TRANSLOCATION; CATALYTIC ACTIVITY; DRUG-METABOLISM; PRIMARY CULTURE; CAR; ACTIVATION AB CYP2B6 plays an important role in the metabolism of a variety of structurally unrelated xenobiotics, including the anticancer drugs cyclophosphamide and ifosfamide. Previous studies have shown that the nuclear receptors constitutive androstane receptor (CAR) and pregnane X receptor (PXR) are involved in the transcriptional regulation of CYP2B genes through the phenobarbital-responsive enhancer module (PBREM). However, for human CYP2B6 the relatively weak response of the PBREM to PXR and CAR activation in transfection assays fails to describe the potent induction observed in primary human hepatocyte cultures. In this report, a novel nuclear receptor response module located -8.5 kilobases upstream from the CYP2B6 encoding region is described. Several potential PXR/CAR binding motifs were identified within the distal regulatory cluster. In electrophoretic mobility shift assays, one DR4 motif showed the strongest binding to both PXR and CAR. Transient transfection assays in HepG2 cells demonstrated that the novel distal response cluster could be activated by PXR and CAR. In primary human hepatocytes, both PBREM and the distal responsive element were activated individually by endogenous nuclear receptors upon exposure to prototypical inducers. However, in both HepG2 cells and primary human hepatocytes maximal reporter activation was observed in a construct containing both PBREM and the distal responsive element. In mouse tail-vein injection experiments, a construct containing both the distal responsive element and the proximal PBREM exhibited a strong synergistic expression in phenobarbital-treated mice. These results show that a novel xenobiotic-responsive enhancer module in the distal region of the CYP2B6 promoter (CYP2B6-XREM) together with the PBREM mediates optimal drug-induced expression of CYP2B6. C1 Univ N Carolina, Sch Pharm, Div Drug Delivery & Disposit, Chapel Hill, NC 27599 USA. NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP LeCluyse, EL (reprint author), Univ N Carolina, Sch Pharm, Div Drug Delivery & Disposit, Chapel Hill, NC 27599 USA. OI LeCluyse, Edward/0000-0002-2149-8990 FU NIDDK NIH HHS [P30 DK34987]; NIEHS NIH HHS [P30 ES10126] NR 38 TC 145 Z9 152 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 APR 18 PY 2003 VL 278 IS 16 BP 14146 EP 14152 DI 10.1074/jbc.M212482200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 670JV UT WOS:000182405000075 PM 12571232 ER PT J AU Iwatani, Y Rosen, AE Guo, JH Musier-Forsyth, K Levin, JG AF Iwatani, Y Rosen, AE Guo, JH Musier-Forsyth, K Levin, JG TI Efficient initiation of HIV-1 reverse transcription in vitro - Requirement for RNA sequences downstream of the primer binding site abrogated by nucleocapsid protein-dependent primer-template interactions SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACID-CHAPERONE ACTIVITY; ZINC-FINGER STRUCTURES; MURINE LEUKEMIA-VIRUS; STRAND DNA-SYNTHESIS; STRONG-STOP DNA; PSI-C LOOP; SECONDARY STRUCTURE; VIRAL-RNA; ANNEALING ACTIVITIES AB Synthesis of HIV-1 (-) strong-stop DNA is initiated following annealing of the 3' IS nucleotides (nt) of tRNA(3)(Lys) to the primer binding site (PBS) near the 5' terminus of viral RNA. Here, we have investigated whether sequences downstream of the PBS play a role in promoting efficient (-) strong-stop DNA synthesis. Our findings demonstrate a template requirement for at least 24 bases downstream of the PBS when tRNA(3)(Lys) or an 18-nt RNA complementary to the PBS (1118), but not an 18-nt DNA primer, are used. Additional assays using 18-nt DNA-RNA chimeric primers, as well as melting studies and circular dichroism spectra of 18-nt primer: PBS duplexes, suggest that priming efficiency is correlated with duplex conformation and stability. Interestingly, in the presence of nucleocapsid protein (NC), the 24 downstream bases are dispensable for synthesis primed by tRNA(3)(Lys) but not by R18. We present data supporting the conclusion that NC promotes extended interactions between the anticodon stem and variable loop of tRNA(3)(Lys) and a sequence upstream of the A-rich loop in the template. Taken together, this study leads to new insights into the initiation of HIV-1 reverse transcription and the functional role of NC-facilitated tRNA-template interactions in this process. C1 NICHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Dept Chem, Minneapolis, MN 55455 USA. RP Levin, JG (reprint author), NICHD, Mol Genet Lab, NIH, Bldg 6B,Rm 216, Bethesda, MD 20892 USA. EM jlevin@mail.nih.gov FU NIAID NIH HHS [AI65056]; NIGMS NIH HHS [T32-GM08700] NR 79 TC 36 Z9 36 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 APR 18 PY 2003 VL 278 IS 16 BP 14185 EP 14195 DI 10.1074/jbc.M211618200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 670JV UT WOS:000182405000080 PM 12560327 ER PT J AU Fitzsimmons, TJ Zhao, XL Wank, SA AF Fitzsimmons, TJ Zhao, XL Wank, SA TI The extracellular domain of receptor activity-modifying protein 1 is sufficient for calcitonin receptor-like receptor function SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GENE-RELATED PEPTIDE; PARATHYROID-HORMONE; BINDING; ADRENOMEDULLIN; SELECTIVITY; EXPRESSION AB A functional calcitonin gene-related peptide (CGRP) receptor requires dimerization of calcitonin receptor-like receptor (CRLR) with receptor activity-modifying protein 1 (RAMP 1). To determine the function of the three domains (extracellular, ECD; transmembrane, TM; and tail domains) of human RAMP 1, three mutants were constructed: RAMP 1 without the cytoplasmic tail, a chimera consisting of the ECD of PUMP I and the TM and tail of the platelet-derived growth factor receptor, and the ECD of RAMP 1 alone. These RAMP I mutants were examined for their ability to associate with CRLR to effect CGRP-stimulated cAMP accumulation, CGRP binding, CRLR trafficking, and cell surface expression. All RAMP 1 mutants were able to associate with CRLR with full efficacy for CGRP-stimulated cAMP accumulation. However, the RAMP 1/platelet-derived growth factor receptor chimera demonstrated a 10-fold decrease in potency for CGRP signaling and binding, and the RAMP 1-ECD mutant had a 4000-fold decrease in potency. In conclusion, the ECD of RAMP 1 is sufficient for normal CRLR association and efficacy. The presence of a TM domain and the specific sequence of the RAMP 1 TM domain contribute to CGRP affinity and potency. The C-terminal tail of RAMP 1 is unnecessary for CRLR function. C1 NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Wank, SA (reprint author), NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. NR 14 TC 45 Z9 48 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 APR 18 PY 2003 VL 278 IS 16 BP 14313 EP 14320 DI 10.1074/jbc.M211946200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 670JV UT WOS:000182405000095 PM 12574158 ER PT J AU Pedersen, LC Dong, J Taniguchi, F Kitagawa, H Krahn, JM Pedersen, LG Sugahara, K Negishi, M AF Pedersen, LC Dong, J Taniguchi, F Kitagawa, H Krahn, JM Pedersen, LG Sugahara, K Negishi, M TI Crystal structure of an alpha 1,4-N-acetylhexosaminyltransferase (EXTL2), a member of the exostosin gene family involved in heparan sulfate biosynthesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR SUPPRESSORS; DONOR; ALPHA-1,3-GALACTOSYLTRANSFERASE; GLYCOSYLTRANSFERASES; ALIGNMENT; SEQUENCE; COMPLEX AB EXTL2, an alpha1,4-N-acetylhexosaminyltransferase, catalyzes the transfer reaction of N-acetylglucosamine and N-acetylgalactosamine from the respective UDP-sugars to the non-reducing end of [glucuronic acid]beta1-3[galactose]/beta1-O-naphthalenemethanol, an acceptor substrate analog of the natural common linker of various glycosylaminoglycans. We have solved the x-ray crystal structure of the catalytic domain of mouse EXTL2 in the apo-form and with donor substrates UDP-N-acetylglucosamine and UDP-N-acetylgalactosamine. In addition, a structure of the ternary complex with UDP and the acceptor substrate analog [glucuronic acid]beta1-3[galactose]beta1-O-naphthalenemethanol has been determined. These structures reveal three highly conserve residues, Asn-243, Asp-246, and Arg-293, located at the active site. Mutation of these residues greatly decreases the activity. In the ternary complex, an interaction exists between the P-phosphate of the UDP leaving group and the acceptor hydroxyl of the substrate that may play a functional role in catalysis. These structures represent the first structures from the exostosin gene family and provide important insight into the mechanisms of alpha1,4N-acetylhexosaminyl transfer in heparan biosynthesis. C1 Kobe Pharmaceut Univ, Dept Biochem, Higashinada Ku, Kobe, Hyogo 6858858, Japan. NIH, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. NIH, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Sugahara, K (reprint author), Kobe Pharmaceut Univ, Dept Biochem, Higashinada Ku, Kobe, Hyogo 6858858, Japan. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 NR 27 TC 74 Z9 77 U1 0 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 18 PY 2003 VL 278 IS 16 BP 14420 EP 14428 DI 10.1074/jbc.M210532200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 670JV UT WOS:000182405000109 PM 12562774 ER PT J AU Harries, D May, S Ben-Shaul, A AF Harries, D May, S Ben-Shaul, A TI Curvature and charge modulations in lamellar DNA-lipid complexes SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID POISSON-BOLTZMANN THEORY; SPHERICAL COLLOIDAL PARTICLES; CATIONIC LIPOSOMES; PHASE-TRANSITION; HEXAGONAL-PHASE; COLUMNAR PHASE; MEMBRANES; STABILITY; RELEASE; DIOLEOYLPHOSPHATIDYLETHANOLAMINE AB To model the possible formation of coupled spatial corrugations and charge density modulations in lamellar DNA-lipid complexes, we use a free energy functional which includes the electrostatic, lipid mixing, and elastic degrees of freedom in a self-consistent manner. We find that the balance of forces favors membrane corrugations that are expected to be stable with respect to thermal membrane undulations for a certain range of lipid (charged and uncharged) composition. This may lead to locking between DNA strands in adjacent galleries of the complex. Furthermore, the possibility of membrane corrugations renders the lamellar complex more stable with respect to another, hexagonal, DNA-lipid phase. C1 Hebrew Univ Jerusalem, Dept Phys Chem, IL-91904 Jerusalem, Israel. Hebrew Univ Jerusalem, Fritz Haber Res Ctr, IL-91904 Jerusalem, Israel. Univ Jena, Inst Mol Biol, D-07745 Jena, Germany. RP Harries, D (reprint author), NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RI Harries, Daniel/F-7016-2012 OI Harries, Daniel/0000-0002-3057-9485 NR 39 TC 25 Z9 26 U1 0 U2 7 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 APR 17 PY 2003 VL 107 IS 15 BP 3624 EP 3630 DI 10.1021/jp026637h PG 7 WC Chemistry, Physical SC Chemistry GA 666FY UT WOS:000182167500039 ER PT J AU Rogan, WJ Ware, JH AF Rogan, WJ Ware, JH TI Exposure to lead in children - How low is low enough? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID LEVEL C1 NIEHS, Res Triangle Pk, NC 27709 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Rogan, WJ (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 NR 5 TC 53 Z9 57 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 17 PY 2003 VL 348 IS 16 BP 1515 EP 1516 DI 10.1056/NEJMp030025 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 667TT UT WOS:000182248900001 PM 12700370 ER PT J AU Canfield, RL Henderson, CR Cory-Slechta, DA Cox, C Jusko, TA Lanphear, BP AF Canfield, RL Henderson, CR Cory-Slechta, DA Cox, C Jusko, TA Lanphear, BP TI Intellectual impairment in children with blood lead concentrations below 10 mu g per deciliter SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the Behavioral-Toxicology-Society CY APR 20-22, 2002 CL RES TRIANGLE PK, NORTH CAROLINA SP Behav Toxicol Soc ID PORT-PIRIE COHORT; ENVIRONMENTAL LEAD; COGNITIVE FUNCTION; NEUROPSYCHOLOGICAL DEVELOPMENT; PRESCHOOL-CHILDREN; PRIMARY PREVENTION; BONE LEAD; EXPOSURE; INTELLIGENCE; LEVEL AB BACKGROUND: Despite dramatic declines in children's blood lead concentrations and a lowering of the Centers for Disease Control and Prevention's level of concern to 10 microg per deciliter (0.483 micromol per liter), little is known about children's neurobehavioral functioning at lead concentrations below this level. METHODS: We measured blood lead concentrations in 172 children at 6, 12, 18, 24, 36, 48, and 60 months of age and administered the Stanford-Binet Intelligence Scale at the ages of 3 and 5 years. The relation between IQ and blood lead concentration was estimated with the use of linear and nonlinear mixed models, with adjustment for maternal IQ, quality of the home environment, and other potential confounders. RESULTS: The blood lead concentration was inversely and significantly associated with IQ. In the linear model, each increase of 10 microg per deciliter in the lifetime average blood lead concentration was associated with a 4.6-point decrease in IQ (P=0.004), whereas for the subsample of 101 children whose maximal lead concentrations remained below 10 microg per deciliter, the change in IQ associated with a given change in lead concentration was greater. When estimated in a nonlinear model with the full sample, IQ declined by 7.4 points as lifetime average blood lead concentrations increased from 1 to 10 microg per deciliter. CONCLUSIONS: Blood lead concentrations, even those below 10 microg per deciliter, are inversely associated with children's IQ scores at three and five years of age, and associated declines in IQ are greater at these concentrations than at higher concentrations. These findings suggest that more U.S. children may be adversely affected by environmental lead than previously estimated. C1 Cornell Univ, Coll Human Ecol, Div Nutr Sci, Ithaca, NY 14853 USA. Cornell Univ, Coll Human Ecol, Dept Human Dev, Ithaca, NY USA. Univ Rochester, Sch Med, Dept Environm Med, Rochester, NY USA. Univ Rochester, Sch Med, Dept Biostat & Computat Biol, Rochester, NY USA. NICHHD, Div Epidemiol Stat & Prevent, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. Childrens Hosp, Med Ctr, Cincinnati Childrens Environm Hlth Ctr, Cincinnati, OH 45229 USA. RP Canfield, RL (reprint author), Cornell Univ, Coll Human Ecol, Div Nutr Sci, Ithaca, NY 14853 USA. FU NIEHS NIH HHS [ES01247, P30 ES001247, R01 ES008388, R01 ES08388] NR 53 TC 1014 Z9 1074 U1 6 U2 67 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 17 PY 2003 VL 348 IS 16 BP 1517 EP 1526 DI 10.1056/NEJMoa022848 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 667TT UT WOS:000182248900002 PM 12700371 ER PT J AU Stabler, SP Mudd, SH AF Stabler, SP Mudd, SH TI Population screening SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID DEFICIENCY C1 Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. NIMH, Bethesda, MD 20892 USA. RP Stabler, SP (reprint author), Univ Colorado, Hlth Sci Ctr, 4200 E 9th Ave, Denver, CO 80262 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 17 PY 2003 VL 348 IS 16 BP 1604 EP 1605 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 667TT UT WOS:000182248900026 PM 12700387 ER PT J AU Zhang, SL Qian, XL Redman, C Bliskovski, V Ramsay, ES Lowy, DR Mock, BA AF Zhang, SL Qian, XL Redman, C Bliskovski, V Ramsay, ES Lowy, DR Mock, BA TI p16(INK4a) gene promoter variation and differential binding of a repressor, the ras-responsive zinc-finger transcription factor, RREB SO ONCOGENE LA English DT Article DE p16 promoter; RREB; plasmacytoma; NIH 3T3 ID PLASMACYTOMA SUSCEPTIBILITY; CELLULAR SENESCENCE; MICE; PROTEIN; TUMORIGENESIS; EXPRESSION; P19(ARF); CDKN2A; REGION; INTERLEUKIN-6 AB BALB/c mice are susceptible to the development of pristane-induced plasma cell tumors, and have a rare allelic variant in the coding region of the p16(INK4a) (p16) tumor suppressor gene that produces a protein with impaired activity. We have now found that the BALB/c p16 promoter has an allelic variant that may also compromise p16 activity. Following pristane treatment, BALB/c p16 mRNA levels in B cells were lower than that in DBA/2 or C.D2-Petr1, a resistant BALB/c congenic strain that harbors DBA/2 chromatin surrounding the p16 locus. Four sequence variants were found between BALB/c and DBA/2 in the p16 promoter region. In reporter assays, the DBA promoter was at least four times more active in driving luciferase expression than the BALB/c promoter. Most of the difference in activity was localized to a single nucleotide deletion in BALB/c. This deletion created a consensus binding site for RREB, a ras-responsive transcriptional element with zinc-finger binding motifs. Transient transfections with RREB confirmed that the p16 promoter can be downregulated by RREB, in a Ras- or Mek-dependent manner, and that the BALB/c promoter is more sensitive than DBA/2 to regulation by RREB. BALB/c mice have both regulatory and coding region defects that may contribute to the impairment of p16 gene function. C1 NCI, Ctr Canc Res, Genet Lab, NIH, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. RP Mock, BA (reprint author), NCI, Ctr Canc Res, Genet Lab, NIH, 37 COnvent Dr,MSC 4255,Bldg 37,Rm 2B-08, Bethesda, MD 20892 USA. NR 39 TC 57 Z9 58 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 APR 17 PY 2003 VL 22 IS 15 BP 2285 EP 2295 DI 10.1038/sj.onc.1206257 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 667KV UT WOS:000182231500007 PM 12700664 ER PT J AU Uren, A Merchant, MS Sun, CJ Vitolo, MI Sun, Y Tsokos, M Illei, PB Ladanyi, M Passaniti, A Mackall, C Toretsky, JA AF Uren, A Merchant, MS Sun, CJ Vitolo, MI Sun, Y Tsokos, M Illei, PB Ladanyi, M Passaniti, A Mackall, C Toretsky, JA TI Beta-platelet-derived growth factor receptor mediates motility and growth of Ewing's sarcoma cells SO ONCOGENE LA English DT Article DE PDGF; PDGF receptors; Ewing's sarcoma ID FACTOR-I RECEPTOR; SIGNAL-TRANSDUCTION; PDGF-C; TUMORS; LIGAND; TRANSFORMATION; FIBROBLASTS; INHIBITION; EXPRESSION; EWS/FLI-1 AB The Ewing's sarcoma family of tumors (ESFT) contain a translocation, t(11;22), which results in the novel oncogenic fusion protein EWS/FLI1. Platelet-derived growth factors (PDGF) and their receptors (PDGFR) are involved in the induction and proliferation of numerous solid tumors and are the potential candidates for novel targeted antitumor therapy. Since a relation was reported between PDGF-C and EWS/FLI1, we sought to characterize the PDGF signaling pathway in ESFT. Eight out of nine ESFT cell tines were found to express significant levels of beta-PDGFR. Interestingly, none of the tested cell lines expressed alpha-PDGFR, which is the receptor isotype required for PDGF-C binding. By immunohistochemical staining 47 of 52 (90.4%) archival tumor samples from patients with ESFT were positive for beta-PDGFR. ESFT cell lines were treated with PDGF-AA or PDGF-BB ligands to evaluate downstream signaling. Autophosphorylation of beta-PDGFR and tyrosine phosphorylation of PLC-gamma, PI3Kp85 and She were detected only in PDGF-BB-stimulated cells that express beta-PDGFR. Receptor function was further evaluated using chemotaxis assays that showed TC-32 cell migration towards PDGF-BB. A specific PDGFR kinase inhibitor AG1295 blocked beta-PDGFR activation, downstream signaling, growth in cell culture and chemotaxis of TC-32 cells. AG1295 also delayed tumor formation and prolonged survival in an ESFT animal model. We conclude that ESFT express beta-PDGFR and that this is a functional and potentially crucial signaling pathway. Therefore, beta-PDGFRs may provide a novel therapeutic target in ESFT that can be utilized to design better treatment modalities. C1 Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20057 USA. NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Pathol, Baltimore, MD 21201 USA. Univ Maryland, Dept Pediat, Baltimore, MD 21201 USA. Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. RP Uren, A (reprint author), Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Res Bldg,Room W316,3970 Reservoir Rd,NW Box 57146, Washington, DC 20057 USA. FU NCI NIH HHS [R01 CA88004] NR 28 TC 56 Z9 57 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 17 PY 2003 VL 22 IS 15 BP 2334 EP 2342 DI 10.1038/sj.onc.1206330 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 667KV UT WOS:000182231500011 PM 12700668 ER PT J AU Feller, SE Gawrisch, K Woolf, TB AF Feller, SE Gawrisch, K Woolf, TB TI Rhodopsin exhibits a preference for solvation by polyunsaturated docosohexaenoic acid SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; EQUILIBRIUM; CHOLESTEROL C1 Wabash Coll, Dept Chem, Crawfordsville, IN 47933 USA. NIAAA, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA. RP Feller, SE (reprint author), Wabash Coll, Dept Chem, 301 W Wabash, Crawfordsville, IN 47933 USA. NR 11 TC 66 Z9 66 U1 2 U2 5 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 APR 16 PY 2003 VL 125 IS 15 BP 4434 EP 4435 DI 10.1021/ja0345874 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 665TR UT WOS:000182137800017 PM 12683809 ER PT J AU Anderson, BD Smith, MA Reaman, GH Kodish, ED AF Anderson, BD Smith, MA Reaman, GH Kodish, ED TI Re: Views of American oncologists about the purposes of clinical trials SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID INFORMED CONSENT; CANCER C1 NCI CTEP, Clin Invest Branch, Rockville, MD 20852 USA. Childrens Oncol Grp, Bethesda, MD USA. Rainbow Babies & Childrens Hosp, Childrens Oncol Grp, Bioeth Comm, Cleveland, OH USA. RP Anderson, BD (reprint author), NCI CTEP, Clin Invest Branch, 6130 Execut Blvd,EPN 7025, Rockville, MD 20852 USA. NR 4 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 APR 16 PY 2003 VL 95 IS 8 BP 630 EP 631 PG 2 WC Oncology SC Oncology GA 667YM UT WOS:000182262500018 PM 12697860 ER PT J AU Legato, J Knepper, MA Star, RA Mejia, R AF Legato, J Knepper, MA Star, RA Mejia, R TI Database for renal collecting duct regulatory and transporter proteins SO PHYSIOLOGICAL GENOMICS LA English DT Article; Proceedings Paper CT SIAM Annual Meeting CY JUL 10-14, 2000 CL RIO GRANDE, PUERTO RICO SP SIAM DE regulatory protein; transporter protein; microarray ID MOUSE; TRANSCRIPTOME; VASOPRESSIN; DISEASE; GENOME AB The mammalian kidney collecting duct plays an important role in the fine regulation of Na, K, water, and acid-base balance. Functional genomic and proteomic studies of the kidney offer new opportunities in the understanding of renal physiology and pathophysiology, and the collecting duct is an appropriate target tissue because of the relative simplicity of its cells and the ease of isolating or culturing large numbers of collecting duct cells. Study of the collecting duct includes assessment of gene expression and protein regulation and abundance. For example, DNA and protein microarrays can be used to quantitate gene expression and protein regulation and abundance under varying physiological conditions. An Internet-accessible database has been devised for major collecting duct proteins involved in transport and regulation of cellular processes. The individual proteins included in this database are those culled from literature searches and from previously published studies involving cDNA arrays and serial analysis of gene expression ( SAGE). Design of microarray targets for the study of kidney collecting duct tissues is facilitated by the database, which includes links to curated base pair and amino acid sequence data, relevant literature, and related databases. Use of the database is illustrated by a search for water channel proteins, aquaporins, and by a subsequent search for vasopressin receptors. Links are shown to the literature and to sequence data for human, rat, and mouse, as well as to relevant web-based resources. Extension of the database is dynamic and is done through a maintenance interface. This permits creation of new categories, updating of existing entries, and addition of new ones. C1 NIDDKD, Math Res Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. RP Mejia, R (reprint author), NIDDKD, Math Res Branch, NIH, 12 S Dr,Rm 4007,MSC 5621, Bethesda, MD 20892 USA. OI Mejia, Raymond/0000-0001-6237-5893 FU Intramural NIH HHS [Z99 HL999999, Z01 HL001285-21] NR 25 TC 19 Z9 21 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD APR 16 PY 2003 VL 13 IS 2 BP 179 EP 181 DI 10.1152/physiolgenomics.00021.2003 PG 3 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 668FA UT WOS:000182278600011 PM 12646711 ER PT J AU Langford, CA Talar-Williams, C Barron, KS Sneller, MC AF Langford, CA Talar-Williams, C Barron, KS Sneller, MC TI Use of a cyclophosphamide-induction methotrexate-maintenance regimen for the treatment of Wegener's granulomatosis: Extended follow-up and rate of relapse SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID REMISSION AB PURPOSE: To determine the relapse rate and outcome in patients with Wegener's granulomatosis treated with daily cyclophosphamide and glucocorticoids to induce remission followed by methotrexate for remission maintenance. METHODS: We performed an open-label prospective study in 42 patients with active Wegener's granulomatosis. All patients were treated with a standardized regimen. Outcomes were assessed using predetermined definitions based on clinical characteristics and pathologic, laboratory, and radiographic findings. RESULTS: All patients achieved disease remission. The median time to remission was 3 months, and the median time to discontinuation of glucocorticoids was 8 months. During a median of 32 months of follow-up, 1 patient died (of a myocardial infarction not related to vasculitis). Two patients, (5%) had to withdraw from the study because of medication toxicity. Twenty-two patients (52%) relapsed, with glomerulonephritis occurring in 16 patients. Of these 16 patients, 4 had an increase of >0.2 mg/dL in serum creatinine level. All 4 patients returned to their prior level of renal function with treatment. None of the 22 relapses met the criteria for severe disease. CONCLUSION: The use of cyclophosphamide and glucocorticoids for induction and methotrexate for maintaining remission is an effective and well-tolerated therapeutic approach in patients with active Wegener's granulomatosis. Am J Med. 2003;114:463-469. (C) 2003 by Excerpta Medica Inc. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Langford, CA (reprint author), NIAID, Immunoregulat Lab, NIH, 10 Ctr Dr,MSC 1876,Bldg 11B-13, Bethesda, MD 20892 USA. NR 15 TC 111 Z9 117 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD APR 15 PY 2003 VL 114 IS 6 BP 463 EP 469 DI 10.1016/S0002-9343(03)00077-9 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 672YR UT WOS:000182551900005 PM 12727579 ER PT J AU Freed, AN McCulloch, S Meyers, T Suzuki, R AF Freed, AN McCulloch, S Meyers, T Suzuki, R TI Neurokinins modulate hyperventilation-induced bronchoconstriction in canine peripheral airways SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE animal model; exercise-induced asthma; neurokinins ID EXERCISE-INDUCED BRONCHOCONSTRICTION; HYPERPNEA-INDUCED BRONCHOCONSTRICTION; NK2 RECEPTOR ANTAGONISTS; AIR-INDUCED CONSTRICTION; SUBSTANCE-P RELEASE; GUINEA-PIGS; DRY AIR; 5-LIPOXYGENASE INHIBITOR; ISOCAPNIC HYPERPNEA; ASTHMATIC-PATIENTS AB This study was designed to test the hypotheses that (1) neurokinin (NK) receptor activity modulates hyperventilation-induced bronchoconstriction (HIB) in canine peripheral airways and (2) INK receptor activity is stimulated via hyperventilation-induced eicosanoid production and release. A bronchoscope was used in anesthetized dogs to record peripheral airway resistance (Rp); to test airway reactivity to NK A (NKA), substance P, and hypertonic saline; and to examine HIB before and after combined treatment with NK-1 (CP 99,994) and NK-2 (SR 48,968) receptor antagonists. Bronchoalveolar lavage fluid cells, prostaglandin D-2, and cysteinyl leukotrienes from hyperventilated airways pretreated with either vehicle or INK antagonists were also measured. Pretreatment with NK-1 and NK-2 antagonists significantly attenuated HIB and the response to substance P, virtually abolished the response to NKA, and had little effect on the response to HS. Blockade of NK-1 and NK-2 receptors did not affect either the cell profiles or the mediator concentrations recovered in bronchoalveolar lavage fluid after hyperventilation. We conclude that NKs modulate the development of HIB and appear to do so via hyperventilation-induced eicosanoid production and release. C1 Johns Hopkins Univ, Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA. RP Freed, AN (reprint author), NHLBI, 2 Rockledge Ctr,Suite 7186,6701 Rockledge Dr, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [HL51930, HL63186] NR 57 TC 14 Z9 14 U1 0 U2 0 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 APR 15 PY 2003 VL 167 IS 8 BP 1102 EP 1108 DI 10.1164/rccm.200201-055OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 666HP UT WOS:000182171900012 PM 12574071 ER PT J AU Croxton, TL Weinmann, GG Senior, RM Wise, RA Crapo, JD Buist, AS AF Croxton, TL Weinmann, GG Senior, RM Wise, RA Crapo, JD Buist, AS TI Clinical research in chronic obstructive pulmonary disease - Needs and opportunities SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE chronic obstructive pulmonary disease; lung diseases; obstructive; National Institutes of Health ID VOLUME REDUCTION SURGERY; STAGE LUNG-DISEASE; SMOKING CESSATION; UNITED-STATES; EXERCISE PERFORMANCE; ACUTE EXACERBATIONS; SURVIVAL BENEFIT; MORTALITY RISK; HEALTH-STATUS; IN-VIVO AB Chronic obstructive pulmonary disease (COPD) is a common condition, and one difficult to manage. Available treatments, other than smoking cessation, are only minimally effective, and the knowledge basis for clinical decision making is limited. To identify areas in which further clinical research may lead to significant improvements in the care of patients with COPD, the National Heart, Lung, and Blood Institute convened a Working Group, entitled "Clinical Research in COPD: Needs and Opportunities," on March 21-22, 2002. This group of experts identified important questions in the field and made the following recommendations: (1) establish a multicenter Clinical Research Network to perform multiple, short-term clinical trials of treatments in patients with moderate-to-severe COPD; (2) create a system for the standardized collection, processing, and distribution of lung tissue specimens and associated clinical and laboratory data; (3) develop standards for the classification and staging of COPD; (4) characterize the development and progression of COPD using measures and biomarkers that relate to current concepts of pathogenesis; and (5) evaluate indications for longterm oxygen therapy for patients with COPD. C1 NHLBI, DLD, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. Barnes Jewish Hosp, St Louis, MO 63110 USA. Johns Hopkins Univ, Dept Med, Baltimore, MD USA. Natl Jewish Med & Res Ctr, Dept Med, Denver, CO USA. Oregon Hlth & Sci Univ, Dept Med, Portland, OR USA. RP Croxton, TL (reprint author), NHLBI, DLD, Room 10208,6701 Rockledge Dr, Bethesda, MD 20892 USA. OI Wise, Robert/0000-0002-8353-2349 NR 81 TC 74 Z9 77 U1 0 U2 1 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 APR 15 PY 2003 VL 167 IS 8 BP 1142 EP 1149 DI 10.1164/rccm.200207-756WS PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 666HP UT WOS:000182171900019 PM 12684252 ER PT J AU Emanuel, EJ Young-Xu, Y Levinsky, NG Gazelle, G Saynina, O Ash, AS AF Emanuel, EJ Young-Xu, Y Levinsky, NG Gazelle, G Saynina, O Ash, AS TI Chemotherapy use among medicare beneficiaries at the end of life SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CELL LUNG-CANCER; QUALITY-OF-LIFE; RANDOMIZED TRIAL; EXPECTATIONS; MITOMYCIN; CISPLATIN; SURVIVAL AB Background: Although many observers believe that cancer chef motherapy is overused at the end of life, there are no published data on this. Objective: To determine the frequency and duration of chemotherapy use in the last 6 months of life stratified by type of cancer, age, and sex. Design: Retrospective cohort Analysis. Setting: Administrative databases from Massachusetts and California. Patients: All Medicare patients Who died of cancer in Massachusetts and 5% of Medicare cancer decedents in California in 1996. Measurements: Use of intravenous chemotherapy agents, chemotherapy administration, or medical evaluation for chemotherapy from Medicare billing data for each patient in 30-day periods from the date of death backward. Results: in Massachusetts, 33% of cancer decedents older than 65 years of age received chemotherapy in the last 6 months of life, 23% in the last 3 months, and 9% in the last month. In California, the percentages were 26%, 20%, and 9%, respectively. Chemotherapy use greatly declined with age. Chemotherapy use was similar for patients with breast, colon, and ovarian cancer and those with cancer generally considered unresponsive to chemotherapy, such as pancreatic, hepatocellular, or renal-cell cancer or melanoma. Patients with types of cancer that are unresponsive to chemotherapy had shorter duration of chemotherapy use. Conclusion: Among patients who died of cancer, chemotherapy was used frequently in the last 3 months of life. The cancer's responsiveness to chemotherapy does not seem to influence whether dying patients receive chemotherapy at the end of life. C1 NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Natl Bur Econ Res, Palo Alto, CA USA. Harvard Vanguard Associates, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Emanuel, EJ (reprint author), NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. NR 20 TC 137 Z9 140 U1 0 U2 3 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 15 PY 2003 VL 138 IS 8 BP 639 EP 643 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 666JH UT WOS:000182173800006 PM 12693886 ER PT J AU Chen, DT Miller, FG Rosenstein, DL AF Chen, DT Miller, FG Rosenstein, DL TI Clinical research and the physician-patient relationship SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID THERAPEUTIC MISCONCEPTION; TRIALS; ETHICS; CARE AB All practicing physicians should be prepared to respond to requests from patients for advice about participating in clinical trials research. Even physicians who choose not to conduct clinical trials but rather devote their practice to clinical care may have patients who consider volunteering for research. In advising patients about clinical research, physicians enhance the physician-patient relationship and contribute to the overall goals of evidence-based medicine. We discuss several ethical and practical challenges facing physicians who wish to help their patients make decisions about volunteering for clinical trials. in addition, We suggest how preparation for advising patients about clinical research participation can be incorporated into the medical education process. C1 NIMH, Dept Clin Bioeth, NIH, Bethesda, MD 20892 USA. RP Chen, DT (reprint author), NIMH, Dept Clin Bioeth, NIH, 10 Ctr Dr,Room 10-1C118, Bethesda, MD 20892 USA. NR 26 TC 35 Z9 35 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 15 PY 2003 VL 138 IS 8 BP 669 EP 672 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 666JH UT WOS:000182173800010 PM 12693890 ER PT J AU Lane, HC Neaton, JD AF Lane, HC Neaton, JD TI When to start therapy for HIV infection: A swinging pendulum in search of data SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID ACTIVE ANTIRETROVIRAL THERAPY; SOCIETY-USA PANEL; UPDATED RECOMMENDATIONS; CLINICAL-TRIALS; ADULTS C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Minneapolis, MN 55414 USA. RP Lane, HC (reprint author), NIAID, Immunoregulat Lab, NIH, 10 Ctr Dr,MSC 1894, Bethesda, MD 20892 USA. NR 14 TC 28 Z9 28 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 15 PY 2003 VL 138 IS 8 BP 680 EP 681 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 666JH UT WOS:000182173800013 PM 12693893 ER PT J AU Kim, JK Yang, IS Rhee, S Dauter, Z Lee, YS Park, SS Kim, KH AF Kim, JK Yang, IS Rhee, S Dauter, Z Lee, YS Park, SS Kim, KH TI Crystal structures of glutaryl 7-aminocephalosporanic acid acylase: Insight into autoproteolytic activation SO BIOCHEMISTRY LA English DT Article ID N-TERMINAL NUCLEOPHILE; CEPHALOSPORIN ACYLASE; PSEUDOMONAS SP; INTRAMOLECULAR PROTEOLYSIS; ESCHERICHIA-COLI; STRAIN; SUBUNIT; CLONING; ENZYME; DOMAIN AB Glutaryl 7-aminocephalosporanic acid acylase (GCA, EC 3.5.1.11) is a member of N-terminal nucleophile (Ntn) hydrolases. The native enzyme is an (alpha,beta)(2) heterotetramer originated from an enzymatically inactive precursor of a single polypeptide. The activation of precursor GCA consists of primary and secondary autoproteolytic cleavages, generating a terminal residue with both a nucleophile and a base and releasing a nine amino acid spacer peptide. We have determined the crystal structures of the recombinant selenomethionyl native and S170A mutant precursor from Pseudomonas sp. strain GK16. Precursor activation is likely triggered by conformational constraints within the spacer peptide, probably inducing a peptide flip. Autoproteolytic site solvent molecules, which have been trapped in a hydrophobic environment by the spacer peptide, may play a role as a general base for nucleophilic attack. The activation results in building up a catalytic triad composed of Ser170/His192/Glu624. However, the triad is not linked to the usual hydroxyl but the free alpha-amino group of the N-terminal serine residue of the native GCA. Mutagenesis and structural data support the notion that the stabilization of a transient hydroxazolidine ring during autoproteolysis would be critical during the N --> O acyl shift. The autoprotecilytic activation mechanism for GCA is described. C1 Korea Univ, Grad Sch Biotechnol, Seoul 136701, South Korea. Seoul Natl Univ, Coll Agr & Life Sci, Suwon 740644, South Korea. NCI, Synchrotron Radiat Res Stn, Brookhaven Natl Lab, Upton, NY 11973 USA. RP Kim, KH (reprint author), Korea Univ, Grad Sch Biotechnol, Seoul 136701, South Korea. NR 38 TC 34 Z9 36 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 15 PY 2003 VL 42 IS 14 BP 4084 EP 4093 DI 10.1021/bi027181x PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 666KX UT WOS:000182177400011 PM 12680762 ER PT J AU Yan, B Sen, A Chalovich, JM Chen, YD AF Yan, B Sen, A Chalovich, JM Chen, YD TI Theoretical studies on competitive binding of caldesmon and myosin S1 to actin: Prediction of apparent cooperativity in equilibrium and slow-down in kinetics of S1 binding by caldesmon SO BIOCHEMISTRY LA English DT Article ID SMOOTH-MUSCLE CALDESMON; ATPASE ACTIVITY; TROPONIN-TROPOMYOSIN; HEAVY-MEROMYOSIN; SKELETAL-MUSCLE; CHICKEN GIZZARD; THIN-FILAMENTS; F-ACTIN; SUBFRAGMENT-1; STATES AB Several laboratories have reported cooperative binding of SI to actin in the presence of caldesmon. This cooperative binding has been interpreted with a model similar to that proposed for the binding of S1 to regulated actins in which the binding affinity of S1 is controlled by the position of the tropomyosin filaments. In a recent paper [Sen, A., Chen, Y., Yan, B., and Chalovich, J. M. (2001) Biochemistry 40, 5757-64], we showed qualitatively that S1 binding resulted in rapid dissociation of caldesmon from actin or actin-tropomyosin. This suggests that the cooperativity observed in the case of caldesmon is not due to a conformational change in actin-caldesmon but to the displacement of caldesmon. We show in this paper that the pure competitive binding model, in which both S1 and caldesmon are competing for the same binding sites on actin, can simulate quantitatively the effect of caldesmon on both the equilibrium and the kinetics of S1 binding to actin. This model successfully predicts an apparent cooperativity for the binding of S1 to actin-caldesmon without the need to assume multiple actin-caldesmon structures and produces a decreased rate of S1 binding to actin in the presence of caldesmon. This suggests that the inhibitory action of caldesmon on the actin-activated ATPase activity of myosin in solution and on the generation of active force in a contracting muscle may be simply due to the blocking of myosin binding sites on actin by caldesmon. C1 NIDDKD, Math Res Branch, NIH, Bethesda, MD 20892 USA. E Carolina Univ, Sch Med, Dept Biochem, Greenville, NC 27858 USA. RP Chen, YD (reprint author), NIDDKD, Math Res Branch, NIH, Bethesda, MD 20892 USA. OI Chalovich, Joseph/0000-0002-1243-4055 FU NIAMS NIH HHS [AR35216] NR 41 TC 8 Z9 8 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 15 PY 2003 VL 42 IS 14 BP 4208 EP 4216 DI 10.1021/bi0273009 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 666KX UT WOS:000182177400024 PM 12680775 ER PT J AU Soares, ML Centola, M Chae, JJ Saraiva, MJ Kastner, DL AF Soares, ML Centola, M Chae, JJ Saraiva, MJ Kastner, DL TI Human transthyretin intronic open reading frames are not independently expressed in vivo or part of functional transcripts SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE transthyretin; open reading frame; expression; mRNA ID NEUROFIBROMATOSIS TYPE-1 GENE; ACUTE-PHASE RESPONSE; CHOROID-PLEXUS; MESSENGER-RNA; SITE MUTATION; DNA STRANDS; XIST GENE; PREALBUMIN; SEQUENCE; PROTEIN AB The human transthyretin (TTR) gene encodes a protein composed of four identical subunits with an important role in the plasma transport of thyroid hormone T-4 and retinol. TTR spans 7.6 kilobases and consists of four exons. Two independent open reading frames (ORFs) with putative regulatory sequences have been described in the first and third introns, but their function-if any-is unknown. We have screened human cDNA libraries to determine if these sequences are transcribed. Transcripts of both ORFs were found in liver, pancreas and brain. Hybridization of the two sequences with multiple-tissue Northern blots further confirmed these results and revealed transcript sizes of similar to 1.5 and similar to 2.2 kb for ORF 1, and similar to 5.2 and similar to 7.8 kb for ORF 2. Rapid Amplification of cDNA Ends (RACE) was performed to characterize the full-length cDNAs containing each sequence. All products containing the ORFs were continuous in the genomic sequence corresponding to unspliced or partially spliced TTR. No evidence was found for novel transcripts containing productively spliced products of either ORF, or for shorter transcripts using the promoter and polyadenylation signals associated with them. ORF I RACE products identified in liver, pancreas and brain correspond to TTR transcripts in which intron I had not been removed; the transcripts containing ORF 2 may represent TTR hnRNA. Neither ORF is productively expressed as part of a larger transcript, or as an independent polypeptide. Published by Elsevier Science B.V. C1 NIAMSD, Arthrit & Rheumatism Branch, Genet Sect, Bethesda, MD 20892 USA. Inst Biol Mol & Celular, Amyloid Unit, Oporto, Portugal. Inst Ciencias Biomed Abel Salazar, Oporto, Portugal. RP Kastner, DL (reprint author), NIAMSD, Arthrit & Rheumatism Branch, Genet Sect, Bldg 10,Rm 9N216,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Saraiva, Maria Joao/K-3907-2013 OI Saraiva, Maria Joao/0000-0002-3360-6899 NR 34 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD APR 15 PY 2003 VL 1626 IS 1-3 BP 65 EP 74 DI 10.1016/S0167-4781(03)00043-5 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 670PY UT WOS:000182418600009 PM 12697331 ER PT J AU Sackeim, HA Manji, HK Perera, TD Santarelli, L Kornack, D Kempermann, G Eisch, A AF Sackeim, HA Manji, HK Perera, TD Santarelli, L Kornack, D Kempermann, G Eisch, A TI Environmental and pharmacological regulation of hippocampal neurogenesis SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Columbia Univ, NYSPI, New York, NY USA. NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. Univ Rochester, Med Ctr, Ctr Aging & Dev Biol, Rochester, NY 14642 USA. Humboldt Univ, Charite Hosp, Dept Neurol, Berlin, Germany. Max Delbruck Ctr Mol Med, Res Grp, Berlin, Germany. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 8 BP 3S EP 3S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000005 ER PT J AU Weinberger, DR AF Weinberger, DR TI Cortical regulation of striatolimbic dopamine SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 14 BP 5S EP 5S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000011 ER PT J AU Ernst, M Pine, DS Nelson, E Monk, CS McClure, E Eshel, N Leibenluft, E Charney, DS Hoberman, A Montgomery, LA Munson, S AF Ernst, M Pine, DS Nelson, E Monk, CS McClure, E Eshel, N Leibenluft, E Charney, DS Hoberman, A Montgomery, LA Munson, S TI Anxiety and reward circuitry SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RI Monk, Christopher/J-1805-2014 NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 20 BP 7S EP 7S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000017 ER PT J AU Drevets, WC AF Drevets, WC TI The role of medial prefrontal cortex in modulating anxiety SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Sect Neuroimaging Mood & Anxiety Disorders, Bethesda, MD 20892 USA. NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 22 BP 8S EP 8S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000019 ER PT J AU Sokolov, BP Jiang, L Aston, C AF Sokolov, BP Jiang, L Aston, C TI Transcription profiling indicates altered myelination and synaptic function in schizophrenia and a possible role for epigenetic mechanisms SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIDA, Mol Neuropsychiat Sect, NIH, Baltimore, MD 21224 USA. Wyeth Ayerst Res, Neurosci Discovery Res, Princeton, NJ 08543 USA. NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 32 BP 11S EP 12S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000029 ER PT J AU Du, J Gray, N Falke, C Yuan, P Szabo, S Gould, T Manji, HK AF Du, J Gray, N Falke, C Yuan, P Szabo, S Gould, T Manji, HK TI Regulation of synaptic plasticity by mood stabilizers: The role of AMPA glutamate receptor subunit GluR1 synaptic expression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 39 BP 14S EP 14S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000036 ER PT J AU Mishara, AL Goldberg, TE AF Mishara, AL Goldberg, TE TI A meta-analysis of conventional neuroleptic treatment and cognition: Opening a closed book SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. Rutgers State Univ, Dept Clin Psychol, New Brunswick, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 43 BP 16S EP 16S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000040 ER PT J AU Gopal, AA Hariri, AR Callicott, JH Mattay, VS Egan, MF Weinberger, DR AF Gopal, AA Hariri, AR Callicott, JH Mattay, VS Egan, MF Weinberger, DR TI Schizophrenics exhibit decreased amygdala and PFC activity during the linguistic appraisal of emotional stimuli SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RI Hariri, Ahmad/D-5761-2011 NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 61 BP 22S EP 22S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000058 ER PT J AU Dalby, JW Singhal, NS Hyde, TM Kleinman, JE Akil, M AF Dalby, JW Singhal, NS Hyde, TM Kleinman, JE Akil, M TI The expression of GAD65/67 in the mesencephalon of normal controls and patients with schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 80 BP 29S EP 29S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000077 ER PT J AU Erickson, K Sahakian, BJ Bain, EE Clark, L Zarate, CA Manji, HK Charney, DS Drevets, WC AF Erickson, K Sahakian, BJ Bain, EE Clark, L Zarate, CA Manji, HK Charney, DS Drevets, WC TI Performance of unmedicated depressed patients on tasks of affective and decision-making processes SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Univ Cambridge, Cambridge, England. NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 86 BP 31S EP 31S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000083 ER PT J AU Zarate, CA Tohen, M Quiroz, JA Payne, JL Luckenbaugh, DA AF Zarate, CA Tohen, M Quiroz, JA Payne, JL Luckenbaugh, DA TI A double-blind study examining the six-month outcome after antipsychotic discontinuation following acute mania SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Psychiat, Belmont, MA 02178 USA. NR 0 TC 2 Z9 2 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 103 BP 37S EP 37S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000100 ER PT J AU Zarate, CA Payne, J Quiroz, J Farzad, N Manji, HK Charney, DS AF Zarate, CA Payne, J Quiroz, J Farzad, N Manji, HK Charney, DS TI A double-blind study examining the efficacy of clozapine in treatment-resistant mania and mixed states SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorder Program, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 104 BP 37S EP 37S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000101 ER PT J AU Rosen, VM Harwell, A Bergeson, J Putnam, K Sunderland, T AF Rosen, VM Harwell, A Bergeson, J Putnam, K Sunderland, T TI Apolipoprotein E and category fluency: It's all about access SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 118 BP 42S EP 42S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000115 ER PT J AU Szabo, ST Gold, MS Goldberger, BA Blier, P AF Szabo, ST Gold, MS Goldberger, BA Blier, P TI Effects of sustained gamma-hydroxybutyrate(GHB) treatments on spontaneous and evoked firing activity of locus coeruleus neurons SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. Univ Florida, McKnight Brain Inst, Gainesville, FL USA. Univ Florida, William R Maples Ctr Forens Med, Lab Med, Gainesville, FL USA. NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 119 BP 43S EP 43S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000116 ER PT J AU Feder, A Goetz, RR Coplan, JD Mathew, SJ Pine, DS Greenwald, S Dahl, RE Ryan, ND Weissman, MM AF Feder, A Goetz, RR Coplan, JD Mathew, SJ Pine, DS Greenwald, S Dahl, RE Ryan, ND Weissman, MM TI A reanalysis of 24-hour cortisol secretion in prepubertal children with or without major depression in light of adult clinical follow-up data SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CA SP Soc Biol Psychiat C1 Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. SUNY, Hlth Sci Ctr, Brooklyn, NY USA. NIMH, Intramural Res Program, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 137 BP 49S EP 49S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000134 ER PT J AU Furey, NL AF Furey, NL TI Evaluating the spatial and temporal features of selective visual attention: fMRI and MEG compared SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 153 BP 54S EP 54S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000150 ER PT J AU Bertolino, A Caforio, G Blasi, G Latorre, V Antonucci, N De Candia, M Altamura, M Scarabino, T Callicott, JH Weinberger, DR Nardini, M AF Bertolino, A Caforio, G Blasi, G Latorre, V Antonucci, N De Candia, M Altamura, M Scarabino, T Callicott, JH Weinberger, DR Nardini, M TI The effects of treatment with olanzapine on the working memory cortical network in schizophrenia: Preliminary results SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Univ Bari, Dept Psychiat & Neurol, Psychiat Neurosci Grp, Bari, Italy. IRCCSS Casa Sollievo Sofferenza, Dept Neuroradiol, Foggia, Italy. NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 175 BP 62S EP 62S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000172 ER PT J AU Mathe, AA Husum, H Jimenez-Vasquez, P Bolwig, TG Overstreet, DH Li, TK Riley, EP Slawecki, CJ Heilig, CM Ehlers, CL AF Mathe, AA Husum, H Jimenez-Vasquez, P Bolwig, TG Overstreet, DH Li, TK Riley, EP Slawecki, CJ Heilig, CM Ehlers, CL TI Neuropeptide Y is the marker of mood disorders and risk for alcohol dependence? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Karolinska Inst, Inst Physiol & Pharmacol, Dept Pharmacol, Stockholm, Sweden. Rigshosp, Dept Psychiat, DK-2100 Copenhagen, Denmark. Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. Scripps Res Inst, Dept Neuropharmacol, La Jolla, CA USA. NIAAA, Bethesda, MD USA. RI Riley, Edward/E-6369-2013 OI Riley, Edward/0000-0001-8747-891X NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 192 BP 68S EP 68S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000189 ER PT J AU Bremner, JD Vythilingam, M Vermetten, E Charney, DS AF Bremner, JD Vythilingam, M Vermetten, E Charney, DS TI Neural correlates of memory for emotionally valenced (sad) words in patients with mid-life unipolar depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Emory Univ, Sch Med, Atlanta, GA USA. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Atlanta VAMC, Psychiat Serv, Decatur, GA USA. NR 0 TC 4 Z9 4 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 194 BP 69S EP 69S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000191 ER PT J AU Engel, SR Einat, H Yuan, P Hao, Y Gould, TD Zhang, L Manji, HK Chen, G AF Engel, SR Einat, H Yuan, P Hao, Y Gould, TD Zhang, L Manji, HK Chen, G TI A novel antimanic target of mood-stabilizers: The extracellular signal-regulated kinase (ERK) pathway SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, IRB, MAP,Unit Mol Neurotherapeut, LMP,NIH, Bethesda, MD 20892 USA. RI Chen, Guang/A-2570-2017 NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 203 BP 72S EP 72S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000200 ER PT J AU Hao, Y Zhang, L Manji, HK Chen, G AF Hao, Y Zhang, L Manji, HK Chen, G TI Mood-stabilizer valproate enhances cortical neuron growth/regeneration and survival SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, IRB, MAP,Unit Mol Neurotherapeut, LMP,NIH, Bethesda, MD 20892 USA. RI Chen, Guang/A-2570-2017 NR 0 TC 1 Z9 1 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 204 BP 72S EP 72S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000201 ER PT J AU Gould, TD Gray, NA Manji, HK AF Gould, TD Gray, NA Manji, HK TI Effects of a glycogen synthase kinase-3 inhibitor, lithium, in the adenomatous polyposis coli mutant mouse model of tumorigenesis SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 225 BP 80S EP 80S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000222 ER PT J AU Moses-Kolko, EL Thase, ME Price, JC Kupfer, DJ Frank, E Mathis, C Drevets, WC AF Moses-Kolko, EL Thase, ME Price, JC Kupfer, DJ Frank, E Mathis, C Drevets, WC TI Ssri effects on 5HT1A receptor binding potential in depression using PET and [11C]WAY-100635 SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. NIMH, Mood & Anxiety Disorders Res Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 270 BP 96S EP 97S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000267 ER PT J AU Nelson, EE Monk, CS McClure, EB Zarahn, E Leibenluft, E Munson, S Eshel, N Charney, DS Pine, DS Ernst, M AF Nelson, EE Monk, CS McClure, EB Zarahn, E Leibenluft, E Munson, S Eshel, N Charney, DS Pine, DS Ernst, M TI Risky business: Event-related fMRI of decision, anticipation and attainment in a reward task SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Sect Dev & Affect Neurosci, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RI Monk, Christopher/J-1805-2014 NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 271 BP 97S EP 97S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000268 ER PT J AU Drevets, WC AF Drevets, WC TI Abnormalities in the neural circuits subserving decision and reward processing in mood disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Sect Neuroimaging Mood & Anxiety Disorders, Bethesda, MD 20892 USA. NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 286 BP 101S EP 102S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000278 ER PT J AU Leibenluft, E Ernst, M McClure, EB Monk, CS Puri, R Schachar, RJ Charney, DS Pine, DS AF Leibenluft, E Ernst, M McClure, EB Monk, CS Puri, R Schachar, RJ Charney, DS Pine, DS TI Studying motor inhibition and emotion in pediatric bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Mood & Anxiety Program, Bethesda, MD 20892 USA. Pepperdine Univ, Grad Sch Educ & Psychol, Los Angeles, CA USA. Hosp Sick Children, Dept Psychiat Res, Toronto, ON M5G 1X8, Canada. RI Monk, Christopher/J-1805-2014 NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 288 BP 102S EP 102S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000280 ER PT J AU Hariri, AR Kolachana, BS Goldberg, TE Mattay, VS Callicott, JH Egan, MF Weinberger, DR AF Hariri, AR Kolachana, BS Goldberg, TE Mattay, VS Callicott, JH Egan, MF Weinberger, DR TI BDNF val(66)met genetic variation and the response of the human hippocampus SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RI Hariri, Ahmad/D-5761-2011 NR 0 TC 0 Z9 0 U1 0 U2 3 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 319 BP 113S EP 113S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000311 ER PT J AU Finnegan, RW Roca, CA Rubinow, DR AF Finnegan, RW Roca, CA Rubinow, DR TI Administration of the Hamilton Depression Rating Scale, seasonal affective disorder version (SIGH-SAD) using interactive secure web technology SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Behav Endocrinol Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 325 BP 115S EP 115S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000317 ER PT J AU Hariri, AR Gopal, AA Callicott, JH Mattay, VS Egan, MF Weinberger, DR AF Hariri, AR Gopal, AA Callicott, JH Mattay, VS Egan, MF Weinberger, DR TI Schizophrenics exhibit normal amygdala activity during the perceptual processing of emotional stimuli SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RI Hariri, Ahmad/D-5761-2011 NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 331 BP 117S EP 117S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000323 ER PT J AU Cannon-Spoor, EH Zubenko, GS Levy, J Zubenko, WN Mizra, N Putnam, KT Cohen, RM Sunderland, T AF Cannon-Spoor, EH Zubenko, GS Levy, J Zubenko, WN Mizra, N Putnam, KT Cohen, RM Sunderland, T TI Effects of prior major depressive illness on cognition in Alzheimer's disease patients SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 393 BP 138S EP 138S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000385 ER PT J AU Einat, H Yuan, P Dogra, S Manji, HK AF Einat, H Yuan, P Dogra, S Manji, HK TI Does the PKC signaling pathway play a role in the pathophysiology and treatment of bipolar disorder? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. NIMH, Behav Endcrinol Branch, Bethesda, MD 20892 USA. NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 399 BP 140S EP 141S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000391 ER PT J AU Weickert, CS Halim, N Weinberger, DR Lipska, BK AF Weickert, CS Halim, N Weinberger, DR Lipska, BK TI Antipsychotic drugs and BrdU incorporation in the adult rat hippocampus SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, CBDB, IRP, Bethesda, MD 20892 USA. NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 398 BP 140S EP 140S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000390 ER PT J AU Gray, NA Du, J Pei-Xiong, Y Chen, G Manji, HK AF Gray, NA Du, J Pei-Xiong, Y Chen, G Manji, HK TI Synapsin, a regulator of neuronal plasticity, is a common target of mood stabilizers SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. RI Chen, Guang/A-2570-2017 NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 402 BP 142S EP 142S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000394 ER PT J AU Kose, S Lorberbaum, JP Horwitz, AR Dubno, JR Newman, JD Lester, BM Hamner, MB George, MS AF Kose, S Lorberbaum, JP Horwitz, AR Dubno, JR Newman, JD Lester, BM Hamner, MB George, MS TI A method of inducing an infant cry that parents can easily identify as their own infant's cry SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. Med Univ S Carolina, Dept Otolaryngol, Charleston, SC 29425 USA. NICHHD, Comparat Ethol Lab, Poolesville, MD USA. Brown Univ, Infant Dev Ctr, Providence, RI 02912 USA. NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 439 BP 155S EP 156S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000431 ER PT J AU Green, MF Marder, SR Fenton, W Davis, KL AF Green, MF Marder, SR Fenton, W Davis, KL TI Overcoming obstacles in treating cognitive deficits in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Univ Calif Los Angeles, Geffen Sch Med, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Psychiat Serv, Los Angeles, CA USA. NIMH, NIH, Bethesda, MD 20892 USA. Mt Sinai Sch Med, New York, NY USA. NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 449 BP 158S EP 158S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000436 ER PT J AU Olie, JP Sunderland, T Dehaene, S Robert, P Goergieff, N Blin, O Paillere-Martinot, ML AF Olie, JP Sunderland, T Dehaene, S Robert, P Goergieff, N Blin, O Paillere-Martinot, ML TI Linking motivational and intentional processes with brain activity in the major psychiatric disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, NIH, Bethesda, MD 20892 USA. NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 452 BP 159S EP 160S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000439 ER PT J AU Rapoport, J AF Rapoport, J TI Childhood onset schizophrenia: Phenomenology and neurobiology SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 457 BP 161S EP 162S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000444 ER PT J AU Gogtay, N AF Gogtay, N TI Atypical psychosis in children and adolescents SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RI Gogtay, Nitin/A-3035-2008 NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 458 BP 162S EP 162S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000445 ER PT J AU Leibeffluft, E Villaluz, JL Treland, J Sporn, A Gochman, P Rapoport, JL AF Leibeffluft, E Villaluz, JL Treland, J Sporn, A Gochman, P Rapoport, JL TI Psychosis in childhood bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Mood & Anxiety Program, Bethesda, MD 20892 USA. NYU, Sch Med, New York, NY USA. NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 459 BP 162S EP 162S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000446 ER PT J AU Bergen, AW van den Bree, MBM Yeager, M Welch, R Ganjei, JK Haque, K Bacanu, S Berrettini, WH Grice, DE Bulik, CM Klump, K Fichter, M Halmi, K Kaplan, A Strober, M Treasure, J Woodside, DB Kaye, WH AF Bergen, AW van den Bree, MBM Yeager, M Welch, R Ganjei, JK Haque, K Bacanu, S Berrettini, WH Grice, DE Bulik, CM Klump, K Fichter, M Halmi, K Kaplan, A Strober, M Treasure, J Woodside, DB Kaye, WH TI Candidate genes for anorexia nervosa in the 1p33-36 linkage region: Serotonin 1D and delta opioid receptors display significant association to anorexia nervosa SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Biognosis US Inc, Gaithersburg, MD USA. NCI, Core Genotyping Facil, Gaithersburg, MD USA. Univ Wales Coll Med, Div Psychol Med, Cardiff CF4 4XN, S Glam, Wales. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA. Hosp Behav Med, Klin Roseneck, Munich, Germany. Cornell Univ, New York Presbyterian Hosp Westchester, Weill Med Coll, White Plains, NY USA. Toronto Hosp, Dept Psychiat, Toronto, ON M5T 2S8, Canada. Univ Calif Los Angeles, Sch Med, Neuropsychiat Inst & Hosp, Los Angeles, CA USA. Bethlem Royal & Maudsley Hosp, Inst Psychiat, London, England. NR 0 TC 1 Z9 2 U1 0 U2 1 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 467 BP 165S EP 165S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000454 ER PT J AU McMahon, FJ AF McMahon, FJ TI How will genetic discoveries affect clinical diagnosis in psychiatry? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 469 BP 165S EP 166S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000456 ER PT J AU Hariri, AR AF Hariri, AR TI Imaging genomics: Exploring the influence of genes on brain systems underlying emotional behavior SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RI Hariri, Ahmad/D-5761-2011 NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 471 BP 166S EP 166S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000458 ER PT J AU Neumeister, A Drevets, WC Cabral, CC Geraci, M Bain, E Herscovitch, P Wymore, A Goldman, D Charney, DS AF Neumeister, A Drevets, WC Cabral, CC Geraci, M Bain, E Herscovitch, P Wymore, A Goldman, D Charney, DS TI Genetic eterminance of the behavioral and neural responses to tryptophan depletion in remitted depressed patients and controls SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NIH, PET Dept, Ctr Clin, Bethesda, MD USA. NIAAA, NIH, Bethesda, MD USA. NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 470 BP 166S EP 166S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000457 ER PT J AU Brown, AS Begg, MD Gravenstein, S Schaefer, CA Wyatt, RJ Bresnahan, M Babulas, V Susser, ES AF Brown, AS Begg, MD Gravenstein, S Schaefer, CA Wyatt, RJ Bresnahan, M Babulas, V Susser, ES TI Serologic evidence for prenatal influenza in the etiology of schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Columbia Univ, New York State Psychiat Inst, New York, NY USA. Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. Eastern Virginia Med Sch, Norfolk, VA 23501 USA. Kaiser Permanente, Div Res, Oakland, CA USA. NIMH, Bethesda, MD 20892 USA. Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 3 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 474 BP 167S EP 167S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000461 ER PT J AU Polesskaya, OO Haroutunian, V Davis, KL Hernandez, I Sokolov, BP AF Polesskaya, OO Haroutunian, V Davis, KL Hernandez, I Sokolov, BP TI A novel gene from 11q14 produces decreased levels of RNA transcripts in brains of patients with schizophrenia and displays features of nonprotein-coding RNA gene SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIDA, Mol Neurobiol Branch, NIH, Baltimore, MD USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. NIDA, Mol Neuropsychiatry Sect, NIH, Baltimore, MD USA. NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 473 BP 167S EP 167S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000460 ER PT J AU Straub, RE Egan, MF Hashimoto, R Matsumoto, M Weickert, CS Goldberg, TE Callicott, JH Hyde, TM Kleinman, JE Weinberger, DR AF Straub, RE Egan, MF Hashimoto, R Matsumoto, M Weickert, CS Goldberg, TE Callicott, JH Hyde, TM Kleinman, JE Weinberger, DR TI The schizophrenia susceptibility gene dysbindin (dtnbp1, 6p22.3): Analysis of haplotypes, intermediate phenotypes and alternative transcripts SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RI Matsumoto, Mitsuyuki/G-3207-2012; Hashimoto, Ryota/P-8572-2014 OI Matsumoto, Mitsuyuki/0000-0002-1172-2354; Hashimoto, Ryota/0000-0002-5941-4238 NR 0 TC 6 Z9 6 U1 0 U2 1 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 475 BP 167S EP 168S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000462 ER PT J AU Colantuoni, C Hyde, T Creswell, J Kolachana, B Straub, R Kleinman, J Weinberger, D AF Colantuoni, C Hyde, T Creswell, J Kolachana, B Straub, R Kleinman, J Weinberger, D TI Functional genomics in the frontal cortex of normal and schizophrenic individuals SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 533 BP 188S EP 188S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000520 ER PT J AU Drevets, WC Wymore, AC Earle, B Tan, H Marrett, S Talagala, L Koretsky, A Price, J Manji, HK Charney, DS AF Drevets, WC Wymore, AC Earle, B Tan, H Marrett, S Talagala, L Koretsky, A Price, J Manji, HK Charney, DS TI Neuromorphometric MRI assessment of the hippocampal subiculum in mood disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. NINDS, NMR Ctr, Bethesda, MD 20892 USA. Washington Univ, St Louis, MO USA. NR 0 TC 1 Z9 1 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 537 BP 189S EP 189S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000524 ER PT J AU Payne, J Zarate, CA Quiroz, J Charney, D Manji, HK AF Payne, J Zarate, CA Quiroz, J Charney, D Manji, HK TI The use of a dopaminergic agonist with neurotrophic properties to treat bipolar depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. NIMH, Mood & Anxiety Disorder Program, Bethesda, MD 20892 USA. NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 543 BP 192S EP 192S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000530 ER PT J AU Quiroz, J Zarate, CA Payne, J Sporn, J Manji, HK Charney, DS AF Quiroz, J Zarate, CA Payne, J Sporn, J Manji, HK Charney, DS TI Riluzole: An investigation of the antidepressant efficacy of an antiglutamatergic agent with neurotrophic properties SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorder Program, Bethesda, MD 20892 USA. NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 542 BP 192S EP 192S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000529 ER PT J AU Zarate, CA Quiroz, J Sporn, J Payne, J Manji, HK Charney, DS AF Zarate, CA Quiroz, J Sporn, J Payne, J Manji, HK Charney, DS TI Modulators of the glutamatergic system: A new class of antidepressants? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. NIMH, Mood & Anxiety Disorder Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 544 BP 192S EP 192S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000531 ER PT J AU Witek, MW Miller, LS Gouley, KK Castellanos, R Alvir, J Pine, DS AF Witek, MW Miller, LS Gouley, KK Castellanos, R Alvir, J Pine, DS TI Salivary cortisol in low-income preschoolers in three contexts SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 NYU, Sch Med, Ctr Child Study, New York, NY USA. NIMH, Sect Dev Affect Neurosci, Bethesda, MD 20892 USA. NR 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 563 BP 199S EP 200S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000550 ER PT J AU Kupfer, DJ Charney, DS AF Kupfer, DJ Charney, DS TI "Difficult-to-Treat depression" SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID MOOD DISORDERS C1 Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. NIMH, Bethesda, MD 20892 USA. RP Kupfer, DJ (reprint author), Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, 3811 OHara St, Pittsburgh, PA 15213 USA. NR 5 TC 10 Z9 11 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 APR 15 PY 2003 VL 53 IS 8 BP 633 EP 634 DI 10.1016/S0006-3223(03)00188-4 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 669PV UT WOS:000182360400001 PM 12706948 ER PT J AU Manji, HK Quiroz, JA Sporn, J Payne, JL Denicoff, K Gray, NA Zarate, CA Charney, DS AF Manji, HK Quiroz, JA Sporn, J Payne, JL Denicoff, K Gray, NA Zarate, CA Charney, DS TI Enhancing neuronal plasticity and cellular resilience to develop novel, improved therapeutics for difficult-to-treat depression SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Difficult-to-Treat Depression CY APR 21-22, 2002 CL SAN FRANCISCO, CALIFORNIA SP Soc Biol Psychiat DE neuroplasticity; lithium; glutamate; brain-derived neurotrophic factor; bcl-2; mitogen activated protein kinase ID BIPOLAR AFFECTIVE-DISORDER; ANTERIOR CINGULATE CORTEX; CORTICOTROPIN-RELEASING HORMONE; DORSOLATERAL PREFRONTAL CORTEX; RECURRENT MAJOR DEPRESSION; EXCITATORY AMINO-ACIDS; NMDA RECEPTOR COMPLEX; GRAY-MATTER VOLUME; ANTIDEPRESSANT ADMINISTRATION INCREASES; PHOSPHODIESTERASE INHIBITOR ROLIPRAM AB There is growing evidence from neuroimaging and postmortem studies that severe mood disorders, which have traditionally been conceptualized as neurochemical disorders, are associated with impairments of structural plasticity and cellular resilience. It is thus noteworthy that recent preclinical studies have shown that critical molecules in neurotrophic signaling cascades (most notably cyclic adenosine monophosphate [CAMP] response element binding protein, brain-derived neurotrophic factor, bcl-2, and mitogen activated protein [MAP] kinases) are long-term targets for antidepressant agents and antidepressant potentiating modalities. This suggests that effective treatments provide both trophic and neurochemical support, which serves to enhance and maintain normal synaptic connectivity, thereby allowing the chemical signal to reinstate the optimal functioning of critical circuits necessary for normal affective functioning. For many refractory patients; drugs mimicking "traditional" strategies, which directly or indirectly alter monoaminergic levels, may be of limited benefit. Newer "plasticity enhancing" strategies that may have utility in the treatment of refractory depression include N-methyl-D-aspartate antagonists, alpha-amino-3-hydroxy-5-methylisoxazole propionate (AMPA) potentiators, CAMP phosphodiesterase inhibitors, and glucocorticoid receptor antagonists. Small-molecule agents that regulate the activity of growth factors, MAP kinases cascades, and the bcl-2 family of proteins are also promising future avenues. The development of novel, nonaminergic-based therapeutics holds much promise for improved treatment of severe, refractory mood disorders. C1 NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. NIMH, Expt Therapeut & Pathophysiol Branch, Mood & Anxiety Program, Bethesda, MD 20892 USA. RP Manji, HK (reprint author), NIMH, Mol Pathophysiol Lab, Bldg 49,Room B1EE16,49 Convent Dr,MSC 4405, Bethesda, MD 20892 USA. NR 287 TC 335 Z9 358 U1 7 U2 25 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 APR 15 PY 2003 VL 53 IS 8 BP 707 EP 742 DI 10.1016/S0006-3223(03)00117-3 PG 36 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 669PV UT WOS:000182360400010 PM 12706957 ER PT J AU Nath, MD Ruscetti, FW Petrow-Sadowski, C Jones, KS AF Nath, MD Ruscetti, FW Petrow-Sadowski, C Jones, KS TI Regulation of the cell-surface expression of an HTLV-1 binding protein in human T cells during immune activation SO BLOOD LA English DT Article ID VIRUS TYPE-I; TROPICAL SPASTIC PARAPARESIS; LEUKEMIA-VIRUS; MONOCLONAL-ANTIBODIES; RECEPTOR EXPRESSION; SYNCYTIUM FORMATION; CHILD TRANSMISSION; BLOOD-TRANSFUSION; DENDRITIC CELLS; LIPID RAFTS AB Little is known about the requirements for human T-cell leukemia virus type I (HTLV-I) entry, including the identity of the cellular receptor(s). Recently, we have generated an HTLV-I surface glycoprotein (SU) immunoadhesin, HTSU-IgG, which binds specifically to cell-surface protein(s) critical for HTLV-I-mediated entry in cell lines. Here, expression of the HTLV-I SU binding protein on primary cells of the immune system was examined. The immunoadhesin specifically bound to adult T cells, B cells, NK cells, and macrophages. Cell stimulation dramatically increased the amount of binding, with the highest levels of binding on CD4(+) and CD8(+) T cells. Naive (CD45RA(high), CD62L(high)) CD4(+) T cells derived from cord blood cells, in contrast to other primary cells and all cell lines examined, bound no detectable HTLV-I SU. However, following stimulation, the level of HTSU-IgG binding was rapidly induced (fewer than 6 hours), reaching the level of binding seen on adult CD4+ T cells by 72 hours. In contrast to HTLV-I virions, the soluble HTSU-IgG did not effect T-cell activation or proliferation. When incubated with human peripheral blood mononuclear cells in a mixed leukocyte reaction, HTSU-IgG inhibited proliferation at less than 1 ng/ mL. These results indicate that cell-surface expression of the HTLV SU binding protein is up-regulated during in vitro activation and suggest a role for the HTLV-I SU binding proteins in the immunobiology of CD4(+) T cells. (C) 2003 by The American Society of Hematology. C1 Natl Canc Inst Frederick, Basic Res Lab, Ctr Canc Res, Ft Detrick, MD 21702 USA. SAIC Frederick, Basci Res Program, Ft Detrick, MD 21702 USA. RP Ruscetti, FW (reprint author), Natl Canc Inst Frederick, Basic Res Lab, Ctr Canc Res, Bldg 567,Rm 253, Ft Detrick, MD 21702 USA. FU NCI NIH HHS [N01-CO-12400] NR 49 TC 28 Z9 28 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 APR 15 PY 2003 VL 101 IS 8 BP 3085 EP 3092 DI 10.1182/blood-2002-07-2277 PG 8 WC Hematology SC Hematology GA 665CE UT WOS:000182101400034 PM 12506039 ER PT J AU Shin, MG Kajigaya, S Levin, BC Young, NS AF Shin, MG Kajigaya, S Levin, BC Young, NS TI Mitochondrial DNA mutations in patients with myelodysplastic syndromes SO BLOOD LA English DT Article ID MARROW-PANCREAS-SYNDROME; CYTOCHROME-C-OXIDASE; SIDEROBLASTIC ANEMIA; OXIDATIVE DAMAGE; POINT MUTATIONS; GENOME; REPAIR; CELLS; ABNORMALITIES; INSTABILITY AB We undertook to systematically analyze the entire mitochondrial genome by gene amplification and direct sequencing in 10 patients with myelodysplasia; results were compared with concomitantly studied 8 healthy volunteers as well as mtDNA sequences in a standard database. Nucleotide changes that were present in our healthy controls as well as those in published databases were counted as polymorphisms. Overall, there was no increase in the number of mtDNA genes harboring polymorphisms or "new" mutations between our patients and, healthy controls, although there were a few more mtDNA changes resulting in amino acid changes in myelodysplasia (9 in 8 controls versus 16 in 10 patients). Thirty new mutations, all nucleotide substitutions, were found among the 10 patients, distributed throughout the mitochondrial genome; 5 mutations resulted in amino acid changes. None of the mutations in controls produced amino acid changes. We were not able. to confirm previously described mutations in sideroblastic anemia or "hot spots" in the cytochrome c oxidase I and II, genes. Our data do not support a major role for mitochondrial genomic instability in myelodysplasia, and they fail to reproduce previous reports of significant or widespread mitochondrial mutations in this disease. Modest changes in mutation numbers and mitochondrial microsatellites may be evidence of increased mutagenesis in mtDNA, or, more likely, a reflection of limited clonality among hematopoletic stem cells in this bone marrow failure syndrome. (C) 2003 by The American Society of Hematology. C1 Natl Heart Lung & Blood Inst, Hematol Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Standards & Technol, Chem Sci & Technol Lab, Biotechnol Div, Gaithersburg, MD USA. RP Young, NS (reprint author), Natl Heart Lung & Blood Inst, Hematol Branch, NIH, Bldg 10,Rm 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 36 TC 57 Z9 60 U1 1 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 APR 15 PY 2003 VL 101 IS 8 BP 3118 EP 3125 DI 10.1182/blood-2002-06-1825 PG 8 WC Hematology SC Hematology GA 665CE UT WOS:000182101400039 PM 12446454 ER PT J AU Quintanilla-Martinez, L Davies-Hill, T Fend, F Calzada-Wack, J Sorbara, L Campo, E Jaffe, ES Raffeld, M AF Quintanilla-Martinez, L Davies-Hill, T Fend, F Calzada-Wack, J Sorbara, L Campo, E Jaffe, ES Raffeld, M TI Sequestration of p27(Kip1) protein by cyclin D1 in typical and blastic variants of mantle cell lymphoma (MCL): implications for pathogenesis SO BLOOD LA English DT Article ID DEPENDENT KINASE INHIBITOR; CDK INHIBITOR; S-PHASE; AGGRESSIVE VARIANTS; DEGRADATION; EXPRESSION; P27; OVEREXPRESSION; PROGRESSION; CANCER AB p27 is a cyclin-dependent kinase inhibitor that plays a critical role in regulating G(1)/S progression, and whose activity is, in part, regulated through interactions with D-type cyclins. Mantle cell lymphoma (MCL) is characterized by the t(11;14) translocation resulting in deregulated cyclin D1. We previously showed that p27 expression in MCL, as assessed by immunohistochemistry (IHC), does not show the usual inverse relationship to proliferate seen in most other lymphomas that do not overexpress cyclin D1. This suggested that the normal expression or control of p27 activity on cell growth might be altered through potential interactions with cyclin D1. Using Western blot and colmmunoprecipitation studies, we assessed the interrelationship between cyclin D1 and p27 in several cyclin D1(+) cell lines and primary MCL cases. Similar to our previous results by IHC, typical MCLs showed lower expression of p27 when compared to the more highly proliferative blastic cases or cell lines (mean arbitrary units: 58 versus 236 versus 120). Cyclin D1 was expressed at variable levels in both typical and blastic MCLS. p27 protein could be consistently coimmunoprecipitated with cyclin D1 from both cell lines and cases. Using techniques of exhaustive immunoprecipitation, we could demonstrate that most p27 protein was sequestered into complexes containing cyclin D1. We hypothesize that mantle cell lymphomagenesis results not only from direct consequences of inappropriate cyclin D1 expression, but also from the ability of overexpressed cyclin D1 to buffer physiologic changes in p27 levels, thereby rendering p27 ineffective as an inhibitor of cellular growth. (C) 2003 by The American Society of Hematology. C1 NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. Tech Univ, Inst Pathol, Munich, Germany. GSF Natl Res Ctr Environm & Hlth, Inst Pathol, Neuherberg, Germany. Univ Barcelona, Hosp Clin Provincial, Barcelona, Spain. RP Raffeld, M (reprint author), NCI, Hematopathol Sect, Pathol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. OI Calzada, Julia/0000-0003-0816-9305; Campo, elias/0000-0001-9850-9793 NR 47 TC 53 Z9 53 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 APR 15 PY 2003 VL 101 IS 8 BP 3181 EP 3187 DI 10.1182/blood-2002-01-0263 PG 7 WC Hematology SC Hematology GA 665CE UT WOS:000182101400047 PM 12515730 ER PT J AU Fairhurst, RM Fujioka, H Hayton, K Collins, KF Wellems, TE AF Fairhurst, RM Fujioka, H Hayton, K Collins, KF Wellems, TE TI Aberrant development of Plasmodium falciparum in hemoglobin CC red cells: implications for the malaria protective effect of the homozygous state SO BLOOD LA English DT Article ID MECHANISM; POPULATION; RESISTANCE; ANTIGENS; SEVERITY; SURFACE; STRESS; GROWTH; KNOBS; TRAIT AB Although selection of hemoglobin C (HbC) by malaria has been speculated for decades, only recently have epidemiologic studies provided support for HbC protection against malaria in West Africa. A reduced risk of malaria associated with the homozygous CC state has been attributed to the inability of CC cells to support parasite multiplication in vitro. However, there have been conflicting data and conclusions regarding the ability of CC red cells to support parasite replication. Reports that parasites cannot multiply in CC cells in vitro contrast with detection of substantial parasite densities in CC patients with malaria. We have therefore investigated Plasmodium falciparum growth in CC cells in vitro. Our data show that the multiplication rate of several P falciparum lines is measurable in CC cells, but lower than that in AA (HbA-normal) cells. A high proportion of ring forms and trophozoites disintegrates within a subset of CC cells, an observation that accounts for the overall lower replication rate. In addition, knobs present on the surface of infected CC cells are fewer in number and morphologically aberrant when compared with those on AA cells. Events in malaria pathogenesis that involve remodeling of the erythrocyte surface and the display of parasite antigens may be affected by these knob abnormalities. Our data suggest that only a subset of CC cells supports normal parasite replication and that components of malaria protection associated with the CC state may affect the parasite's replication capacity and involve aberrant knob formation on CC cells. (C) 2003 by The American Society of Hematology. C1 NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Inst Pathol, Cleveland, OH 44106 USA. RP Wellems, TE (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Bldg 4,Rm 126,4 Ctr Dr, Bethesda, MD 20892 USA. NR 41 TC 61 Z9 64 U1 4 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 APR 15 PY 2003 VL 101 IS 8 BP 3309 EP 3315 DI 10.1182/blood-2002-10-3105 PG 7 WC Hematology SC Hematology GA 665CE UT WOS:000182101400064 PM 12480691 ER PT J AU Mai, V Colbert, LH Berrigan, D Perkins, SN Pfeiffer, R Lavigne, JA Lanza, E Haines, DC Schatzkin, A Hursting, SD AF Mai, V Colbert, LH Berrigan, D Perkins, SN Pfeiffer, R Lavigne, JA Lanza, E Haines, DC Schatzkin, A Hursting, SD TI Calorie restriction and diet composition modulate spontaneous intestinal tumorigenesis in Apc(Min) mice through different mechanisms SO CANCER RESEARCH LA English DT Article ID COLORECTAL-CANCER; MIN MOUSE; NEOPLASIA; GROWTH; MODEL; FAT; CARCINOGENESIS; SUPPRESSES; MUTATION; POLYPS AB We evaluated the effects of diet on intestinal tumorigenesis in male Apc(Min) mice by comparing AIN-76A diet fed ad libitum (CON); calorie intake restricted by 40% of the CON (CR); diet high in olive oil and supplemented with freeze-dried fruit and vegetable extracts (OFV); and diet high in total fat (HF). Compared with CON, the frequency of intestinal polyps was reduced by 57% by CR (P < 0.001) and by 33% OFV diet (P = 0.04). Both effective interventions reduced total body weight, lean mass, and fat mass and increased daily urinary corticosterone output, but only CR reduced serum insulin-like growth factor I and leptin. We conclude that dietary interventions can partially offset genetic susceptibility to intestinal carcinogenesis. C1 NCI, Off Prevent Oncol, Canc Prevent Fellowship Program, Div Canc Prevent, Bethesda, MD 20892 USA. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Lab Biosyst & Canc, Canc Res Ctr, Bethesda, MD 20892 USA. NCI, Appl Res Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Ctr Canc Res, Canc Prevent Studies Branch, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Pathol Histotechnol Lab, Frederick, MD 21702 USA. RP Hursting, SD (reprint author), NCI, Off Prevent Oncol, Canc Prevent Fellowship Program, Div Canc Prevent, 6130 Execut Blvd, Bethesda, MD 20892 USA. RI Pfeiffer, Ruth /F-4748-2011 FU NCI NIH HHS [N01-CO-12400] NR 20 TC 92 Z9 96 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2003 VL 63 IS 8 BP 1752 EP 1755 PG 4 WC Oncology SC Oncology GA 668TE UT WOS:000182308600006 PM 12702556 ER PT J AU Loganzo, F Discafani, CM Annable, T Beyer, C Musto, S Hari, M Tan, XZ Hardy, C Hernandez, R Baxter, M Singanallore, T Khafizova, G Poruchynsky, MS Fojo, T Nieman, JA Ayral-Kaloustian, S Zask, A Andersen, RJ Greenberger, LM AF Loganzo, F Discafani, CM Annable, T Beyer, C Musto, S Hari, M Tan, XZ Hardy, C Hernandez, R Baxter, M Singanallore, T Khafizova, G Poruchynsky, MS Fojo, T Nieman, JA Ayral-Kaloustian, S Zask, A Andersen, RJ Greenberger, LM TI HTI-286, a synthetic analogue of the tripeptide hemiasterlin, is a potent antimicrotubule agent that circumvents P-glycoprotein-mediated resistance in vitro and in vivo SO CANCER RESEARCH LA English DT Article ID MULTIDRUG-RESISTANCE; CYTOTOXIC PEPTIDES; DOLASTATIN ANALOG; DRUG-RESISTANCE; CARCINOMA-CELLS; BETA-TUBULIN; CANCER; EXPRESSION; MECHANISMS; ADRIAMYCIN AB Hemiasterlin is a natural product derived from marine sponges that, like other structurally diverse peptide-like molecules, binds to the Vincapeptide site in tubulin, disrupts normal microtubule dynamics, and, at stoichiometric amounts, depolymerizes microtubules. Total synthesis of hemiasterlin and its analogues has been accomplished, and optimal pharmacological features of the series have been explored. The biological profile of one analogue, HTI-286, was studied here. HTI-286 inhibited the polymerization of purified tubulin, disrupted microtubule organization in cells, and induced mitotic arrest, as well as apoptosis. HTI-286 was a potent inhibitor of proliferation (mean IC50 = 2.5 +/- 2.1 nm in 18 human tumor cell lines) and had substantially less interaction with multidrug resistance protein (P-glycoprotein) than currently used antimicrotubule agents, including paclitaxel, docetaxel, vinorelbine, or vinblastine. Resistance to HTI-286 was not detected in cells overexpressing the drug transporters MRP1 or MXR. In athymic mice implanted with human tumor xenografts, HTI-286 administered i.v. in saline inhibited the growth of numerous human tumors derived from carcinoma of the skin, breast, prostate, brain, and colon. Marked tumor regression was observed when used on established tumors that were >1 gram in size. Moreover, HTI-286 inhibited the growth of human tumor xenografts (e.g., HCT-15, DLD-1, MX-1W, and KB-8-5) where paclitaxel and vincristine were ineffective because of inherent or acquired resistance associated with P-glycoprotein. Efficacy was also achieved with p.o. administration of HTI-286. These data suggest that HTI-286 has excellent preclinical properties that may translate into superior clinical activity, as well as provide a useful synthetic reagent to probe the drug contact sites of peptide-like molecules that interact with tubulin. C1 Wyeth Res, Oncol Res, Pearl River, NY 10965 USA. Wyeth Res, Chem Sci, Pearl River, NY 10965 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. Univ British Columbia, Dept Chem, Vancouver, BC V6T 1Z1, Canada. RP Loganzo, F (reprint author), Wyeth Res, Oncol Res, 401 N Middletown Rd,200-4709, Pearl River, NY 10965 USA. FU NCI NIH HHS [CA-67786-07] NR 32 TC 95 Z9 102 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 APR 15 PY 2003 VL 63 IS 8 BP 1838 EP 1845 PG 8 WC Oncology SC Oncology GA 668TE UT WOS:000182308600021 PM 12702571 ER PT J AU Kuzmin, I Liu, LM Dammann, R Geil, L Stanbridge, EJ Wilczynski, SP Lerman, MI Pfeifer, GP AF Kuzmin, I Liu, LM Dammann, R Geil, L Stanbridge, EJ Wilczynski, SP Lerman, MI Pfeifer, GP TI Inactivation of RAS association domain family 1A gene in cervical carcinomas and the role of human papillomavirus infection SO CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR GENE; HUMAN-CHROMOSOME 3P21.3; CELL-LINES; EPIGENETIC INACTIVATION; CPG ISLAND; PROMOTER HYPERMETHYLATION; DNA METHYLATION; BREAST CANCERS; MULTIPLE GENES; RASSF1A GENE AB Recently, we have identified a new putative tumor suppressor gene, RASSF1A (Ras association domain family 1A gene), located at human chromosome 3p21.3, the segment that is often lost in many types of human cancers. The RASSF1A promoter was shown to be frequently hypermethylated in various epithelial tumors, including small cell lung, breast, bladder, prostate, gastric, and renal cell carcinomas. In this study, we have analyzed the methylation status of the RASSF1A gene in primary human cervical cancers and in eight cervical cancer cell lines. The RASSF1A promoter is hypermethylated in 4 of 42 (= 10%) of squamous cell carcinomas, in 4 of 19 (= 21%) of adenosquamous carcinomas, and in 8 of 34 I(= 24%) of cervical adenocarcinomas. Although in adenocarcinomas, methylation of RASSF1A and presence of human papillomavirus (HPV) type 16 or 18 sometimes coexisted, not a single case of HPV-16/18-positive squamous cell carcinomas had RASSF1A methylation. Similarly, in all eight analyzed cervical cell lines, RASSF1A inactivation and HPV infection were mutually exclusive (Fisher's exact test; P = 0.0357): two HPV-negative cervical cancer cell lines had a methylated and silenced RASSF1A promoter (C-33A and HT-3), whereas the other six HPV-positive lines expressed RASSF1A mRNA (ME 180, MS751, SiHa, C-4I, HeLa, and CaSki). For cervical tumors and cell lines combined, the Pearson's chi(2) test (chi(2) = 3.99; P less than or equal to 0.05) indicates a borderline-significant reverse correlation between inactivation of RASSF1A and the presence of high-risk HPVs. Our data imply that the presence of HPVs in cervical carcinomas alleviates the requirement for RASSF1A inactivation and suggests that these two events may engage the same tumorigenic pathway. C1 NCI Frederick, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. NCI Frederick, Immunobiol Lab, Frederick, MD 21702 USA. City Hope Natl Med Ctr, Beckman Res Inst, Dept Biol, Duarte, CA 91010 USA. City Hope Natl Med Ctr, Dept Anat Pathol, Dept Biol, Duarte, CA 91010 USA. Univ Halle Wittenberg, Inst Humangenet & Med Biol, D-06097 Halle Saale, Germany. Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92697 USA. RP Kuzmin, I (reprint author), NCI Frederick, SAIC Frederick Inc, Basic Res Program, Bldg 560,Room 12-34, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-12400, CA88873] NR 53 TC 49 Z9 64 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 APR 15 PY 2003 VL 63 IS 8 BP 1888 EP 1893 PG 6 WC Oncology SC Oncology GA 668TE UT WOS:000182308600029 PM 12702579 ER PT J AU Herbert, BS Pearce, VP Hynan, LS LaRue, DM Wright, WE Kopelovich, L Shay, JW AF Herbert, BS Pearce, VP Hynan, LS LaRue, DM Wright, WE Kopelovich, L Shay, JW TI A peroxisome proliferator-activated receptor-gamma agonist and the p53 rescue drug CP-31398 inhibit the spontaneous immortalization of breast epithelial cells SO CANCER RESEARCH LA English DT Article ID HUMAN-DIPLOID FIBROBLASTS; LARGE T-ANTIGEN; TELOMERASE ACTIVITY; LIFE-SPAN; IN-VITRO; CELLULAR SENESCENCE; RETINOIC ACID; MUTANT P53; PPAR-GAMMA; CANCER AB Cell immortalization is a critical and rate-limiting step in cancer progression. Agents that inhibit cell immortalization may have utility for novel molecular chemopreventive strategies. Preimmortal breast epithelial cells derived from a patient with the Li-Fraumeni Syndrome (LFS) can spontaneously immortalize in vitro at a measurable and reproducible frequency. In the present study, these cells were treated in vitro with low (nm) concentrations of potential and otherwise clinically validated chemopreventive agents, including several nonsteroidal anti-inflammatory drugs, rosiglitazone maleate, and the p53 rescue drug CP-31398. Rosiglitazone maleate (P < 0.05) and CP-31398 (P < 0.05) significantly inhibited the frequency of spontaneous immortalization of LFS breast epithelial cells compared with untreated controls. Nonsteroidal anti-inflammatory drugs, including specific cyclooxengenase-2 inhibitors, only moderately inhibited the spontaneous immortalization of preimmortal LFS breast epithelial cells. The significant effects of the p53 rescue drug CP-31398 correlated with the increase in cellular death induced by telomere shortening-induced DNA damage signals, including increases in p53 and p21 protein levels. Because immortalization is one step in cancer progression, these studies show the potential usefulness of a cell-based model system to screen the effects of known and potentially novel chemopreventive agents, using cell immortalization as an end point. C1 Univ Texas, SW Med Ctr, Dept Cell Biol, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Acad Comp Serv, Dallas, TX 75390 USA. NCI, CADRG, DCP, Bethesda, MD 20892 USA. RP Herbert, BS (reprint author), Univ Texas, SW Med Ctr, Dept Cell Biol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. RI Shay, Jerry/F-7878-2011 FU NCI NIH HHS [N01-CN-0501763-63, N01-CN-15015-40] NR 50 TC 15 Z9 15 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2003 VL 63 IS 8 BP 1914 EP 1919 PG 6 WC Oncology SC Oncology GA 668TE UT WOS:000182308600033 PM 12702583 ER PT J AU Camphausen, K Moses, MA Menard, C Sproull, M Beecken, WD Folkman, J O'Reilly, MS AF Camphausen, K Moses, MA Menard, C Sproull, M Beecken, WD Folkman, J O'Reilly, MS TI Radiation abscopal antitumor effect is mediated through p53 SO CANCER RESEARCH LA English DT Article ID ANGIOGENESIS; RADIOTHERAPY; IRRADIATION; REGRESSION; CANCER; TUMOR; MICE; SUPPRESSION; ANGIOSTATIN; EXPRESSION AB The observation that radiation treatment to a local area of the body results in an antitumor effect for tumors distant to the radiation site has been termed the "abscopal effect." To understand the mechanism of this unusual phenomenon, we examined whether the effect was mediated through p53, a protein complex up-regulated in irradiated cells. Non-tumor-bearing legs of C57BL/6 (wild-type p53) and p53 null B6.129S2-TrP53(tm1Tyj) mice were irradiated to determine whether an abscopal effect could be observed against Lewis lung carcinoma (LLC) and T241 (fibrosarcoma) implanted at a distant site. In mice with wild-type p53, both LLC and T241 tumors implanted into the midline dorsum grew at a significantly slower rate when the leg of the animal was exposed to five 10-Gy fractions of radiation compared with sham-irradiated animals, suggesting that the abscopal effect is not tumor specific. When the radiation dose to the leg was reduced (twelve fractions of 2 Gy each), the inhibition of LLC tumor growth was decreased indicating a radiation-dose dependency for the abscopal effect. In contrast, when the legs of p53 null animals or wild-type p53 mice treated with pifithrin-alpha (a p53 blocker) were irradiated (five 10-Gy fractions), tumor growth was not delayed. These data implicate p53 as a key mediator of the radiation-induced abscopal effect and suggest that pathways downstream of p53 are important in eliciting this response. C1 NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Childrens Hosp, Surg Res Lab, Boston, MA 02115 USA. Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Dept Radiat Oncol & Canc Biol, Houston, TX 77030 USA. Univ Frankfurt, Dept Urol, D-6000 Frankfurt, Germany. RP Camphausen, K (reprint author), NCI, Radiat Oncol Branch, NIH, 10 Ctr Dr,Bldg 10,Room B3B69, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA83106, P01 CA45548] NR 21 TC 110 Z9 114 U1 1 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 APR 15 PY 2003 VL 63 IS 8 BP 1990 EP 1993 PG 4 WC Oncology SC Oncology GA 668TE UT WOS:000182308600043 PM 12702593 ER PT J AU Sun, GY AF Sun, GY TI Theoretical C-13 NMR chemical shifts of the stable isomers of fullerene C-90 SO CHEMICAL PHYSICS LA English DT Article ID DENSITY-FUNCTIONAL THEORY; IPR ISOMERS; SPECTRA; C-60; C-84; IDENTIFICATION; CARBON; FORM; C-70 AB Density functional theory has been employed to study fullerene C-90. Structures of all 46 IPR isomers were optimized at the B3LYP/STO-3G level. Geometry optimization for those isomers with relative energies less than 25 kcal/mol were performed using basis sets up to 6-31G. and the C-13 NMR chemical shifts were calculated using the GIAO method. Isomer 45 is the most stable species, while other stable isomers include 28, 30, 32, 35, 40 and 46. Comparison between prediction and experiment shows that the reported NMR spectrum likely arises from isomers 35 and 46 instead of isomer 36 and one C-2 isomer. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Georgetown Univ, Dept Chem, Washington, DC 20057 USA. RP Sun, GY (reprint author), NCI, Med Chem Lab, NIH, 376 Boyles St, Frederick, MD 21702 USA. NR 35 TC 21 Z9 22 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0104 J9 CHEM PHYS JI Chem. Phys. PD APR 15 PY 2003 VL 289 IS 2-3 BP 371 EP 380 DI 10.1016/S0301-0104(03)00079-X PG 10 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 665DH UT WOS:000182104000017 ER PT J AU Wright, ME Suzman, DL Csaky, KG Masur, H Polis, MA Robinson, MR AF Wright, ME Suzman, DL Csaky, KG Masur, H Polis, MA Robinson, MR TI Extensive retinal neovascularization as a late finding in human immunodeficiency virus-infected patients with immune recovery uveitis SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID ACTIVE ANTIRETROVIRAL THERAPY; CYTOMEGALOVIRUS RETINITIS; OPTIC DISC; AIDS; HIV; ERA AB Sixteen human immunodeficiency virus (HIV)-infected patients with inactive cytomegalovirus (CMV) retinitis who had discontinued systemic anti-CMV therapy while receiving highly active antiretroviral therapy (HAART) were prospectively observed. Fifteen patients developed immune recovery uveitis (IRU); 3 of the patients developed extensive retinal neovascularization, 1 of whom required vitrectomy for recurrent vitreous hemorrhages. These late complications indicate a need for continued ophthalmologic follow-up of HIV-infected patients who have a history of CMV retinitis, even for individuals who have not required anti-CMV therapy for >4 years. C1 NIAID, Immunoregulat Lab, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NEI, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Polis, MA (reprint author), NIAID, Immunoregulat Lab, NIH, US Dept Hlth & Human Serv, Bldg 10,Rm 11C103,10 Ctr Dr, Bethesda, MD 20892 USA. OI Polis, Michael/0000-0002-9151-2268 NR 16 TC 11 Z9 13 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 APR 15 PY 2003 VL 36 IS 8 BP 1063 EP 1066 DI 10.1086/374050 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 665MK UT WOS:000182124700019 PM 12684920 ER PT J AU Bennett, JE Powers, J de Pauw, B Dismukes, W Galgiani, J Glauser, M Herbrecht, R Kauffman, C Lee, J Pappas, P Rex, J Verweij, P Viscoli, C Walsh, T AF Bennett, JE Powers, J de Pauw, B Dismukes, W Galgiani, J Glauser, M Herbrecht, R Kauffman, C Lee, J Pappas, P Rex, J Verweij, P Viscoli, C Walsh, T TI Forum report: Issues in the design of trials of drugs for the treatment of invasive aspergillosis SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT John E Bennett Forum on Deep Mycoses Study Design CY JAN 25-27, 2002 CL NEW YORK, NEW YORK ID AMPHOTERICIN-B; MANAGEMENT; CANCER AB A recent trial of drugs for invasive aspergillosis was used as a background for discussing critical features in the design of antifungal trials. The study under discussion allowed stopping either drug without classifying the patient as having treatment failure, so the trial should be understood as a comparison of 2 treatment strategies, not just 2 drugs. Although the study was a noninferiority trial, the outcome permitted a claim of superiority. Use of the category of "probable" in addition to "proven" aspergillosis permitted inclusion of patients for whom the diagnosis was less certain but who were still early enough in the disease progression to respond to therapy. Different opinions still exist about some of the criteria for the diagnosis of "probable" aspergillosis. A blinded data review committee was helpful in evaluating efficacy in this unblinded trial but had limited value in assessing toxicity. An understanding of these features of design of antifungal drug trials is important in applying the results to clinical practice. C1 NIAID, Clin Mycol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. US FDA, Div Special Pathogen & Immunol Drug Prod, Rockville, MD USA. Univ Alabama, Birmingham, AL USA. VA Med Ctr, Tucson, AZ USA. Univ Arizona, Tucson, AZ USA. VA Med Ctr, Ann Arbor, MI USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Texas, Sch Med, Houston, TX USA. Univ Nijmegen St Radboud Hosp, NL-6500 HB Nijmegen, Netherlands. Univ Lausanne Hosp, Lausanne, Switzerland. Hop Hautepierre, Strasbourg, France. Univ Genoa, Natl Inst Canc Res, I-16126 Genoa, Italy. RP Bennett, JE (reprint author), NIAID, Clin Mycol Sect, Clin Invest Lab, NIH, Bldg 10,Room 11C304, Bethesda, MD 20892 USA. RI Herbrecht, Raoul/D-3471-2013; Verweij, P.E./H-8108-2014 NR 6 TC 6 Z9 6 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 APR 15 PY 2003 VL 36 SU 3 BP S113 EP S116 DI 10.1086/367838 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 665MN UT WOS:000182125000003 PM 12679894 ER PT J AU Bennett, JE Powers, J Walsh, T Viscoli, C de Pauw, B Dismukes, W Galgiani, J Glauser, M Herbrecht, R Kauffman, C Lee, J Pappas, P Rex, J Verweij, P AF Bennett, JE Powers, J Walsh, T Viscoli, C de Pauw, B Dismukes, W Galgiani, J Glauser, M Herbrecht, R Kauffman, C Lee, J Pappas, P Rex, J Verweij, P TI Forum report: Issues in clinical trials of empirical antifungal therapy in treating febrile neutropenic patients SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT John E Bennett Forum on Deep Mycoses Study Design CY JAN 25-27, 2002 CL NEW YORK, NEW YORK ID LIPOSOMAL AMPHOTERICIN-B; PERSISTENT FEVER; RANDOMIZED TRIAL; CANCER AB There is inferential evidence that some patients with prolonged neutropenia and fever not responding to antibacterial agents are at sufficient risk of deep mycoses to warrant empirical therapy, although superiority of an antifungal agent over placebo has not been conclusively demonstrated. Amphotericin B deoxycholate, liposomal amphotericin B, and intravenous itraconazole followed by oral itraconazole solution are licensed in the United States for this indication. Fluconazole and voriconazole have given favorable results in clinical trials of patients with low and high risk of deep mold infections, respectively. Design features that can profoundly influence outcome of empirical trials are (1) inclusion of low-risk patients, (2) failure to blind the study, (3) obscuration of antifungal effects by changing antibacterial antibiotics, (4) failure to balance both arms of the study in terms of patients with prior antifungal prophylaxis or with severe comorbidities, (5) the merging of end points evaluating safety with those of efficacy, and (6) choice of different criteria for resolution of fever. C1 NIAID, Clin Mycol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. US FDA, Div Special Pathogen & Immunol Drug Prod, Rockville, MD 20857 USA. Univ Alabama, Birmingham, AL USA. VA Med Ctr, Tucson, AZ USA. Univ Arizona, Tucson, AZ USA. VA Med Ctr, Ann Arbor, MI USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Texas, Sch Med, Houston, TX USA. Univ Nijmegen St Radboud Hosp, NL-6500 HB Nijmegen, Netherlands. Univ Genoa, Natl Inst Canc Res, Genoa, Italy. Univ Lausanne Hosp, Lausanne, Switzerland. Hop Hautepierre, Strasbourg, France. RP Bennett, JE (reprint author), NIAID, Clin Mycol Sect, Clin Invest Lab, NIH, Bldg 10,Room 11C304, Bethesda, MD 20892 USA. RI Herbrecht, Raoul/D-3471-2013; Verweij, P.E./H-8108-2014 NR 11 TC 40 Z9 41 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 APR 15 PY 2003 VL 36 SU 3 BP S117 EP S122 DI 10.1086/367839 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 665MN UT WOS:000182125000004 PM 12679895 ER PT J AU Bennett, JE Kauffman, C Walsh, T de Pauw, B Dismukes, W Galgiani, J Glauser, M Herbrecht, R Lee, J Pappas, P Powers, J Rex, J Verweij, P Viscoli, C AF Bennett, JE Kauffman, C Walsh, T de Pauw, B Dismukes, W Galgiani, J Glauser, M Herbrecht, R Lee, J Pappas, P Powers, J Rex, J Verweij, P Viscoli, C TI Forum report: Issues in the evaluation of diagnostic tests, use of historical controls, and merits of the current multicenter collaborative groups SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT John E Bennett Forum on Deep Mycoses Study Design CY JAN 25-27, 2002 CL NEW YORK, NEW YORK ID ALTERNATIVE TRIAL DESIGNS; INVASIVE ASPERGILLOSIS; CANCER AB This forum report contains conclusions about 3 different issues relevant to conducting clinical trials in deep mycoses. (1) Trials of diagnostic tests for deep mycoses must define the population appropriate for testing and the clinical question being asked. The unanswered question for the serum Aspergillus galactomannan assay is whether knowledge of results can change use of empirical therapy to treat febrile patients at high risk of invasive aspergillosis. (2) Use of historical controls is suboptimal but offers a pragmatic solution for studying rare mycoses; use of contemporaneous controls, matched for critical variables and evaluated by a blinded data review committee using detailed criteria, appears optimal. (3) Established groups of independent investigators, such as the European Organization for Research on Treatment of Cancer's Invasive Fungal Infections Group and National Institute of Allergy and Infectious Diseases's Bacteriology and Mycology Study Group, provide a pool of experienced investigators, defined operating rules, impartiality, and specialized expertise. Considering the enormous investment required for adequately powered efficacy trials of antifungal agents and the importance of these trials to guide clinical practice, use of collaborative groups outweighs the extra administrative time that is sometimes required. C1 NIAID, Clin Mycol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. US FDA, Div Special Pathogen & Immunol Drug Prod, Rockville, MD 20857 USA. VA Med Ctr, Ann Arbor, MI USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Alabama, Birmingham, AL USA. VA Med Ctr, Tucson, AZ USA. Univ Arizona, Tucson, AZ USA. Univ Texas, Sch Med, Houston, TX USA. Univ Nijmegen St Radboud Hosp, NL-6500 HB Nijmegen, Netherlands. Univ Lausanne Hosp, Lausanne, Switzerland. Hop Hautepierre, Strasbourg, France. Univ Genoa, Natl Inst Canc Res, Genoa, Italy. RP Bennett, JE (reprint author), NIAID, Clin Mycol Sect, Clin Invest Lab, NIH, Bldg 10,Room11C304, Bethesda, MD 20892 USA. RI Herbrecht, Raoul/D-3471-2013; Verweij, P.E./H-8108-2014 NR 7 TC 7 Z9 8 U1 0 U2 2 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 APR 15 PY 2003 VL 36 SU 3 BP S123 EP S127 DI 10.1086/367840 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 665MN UT WOS:000182125000005 PM 12679896 ER PT J AU Bennett, JE de Pauw, B Dismukes, W Galgiani, J Glauser, M Herbrecht, R Kauffman, C Lee, J Pappas, P Powers, J Rex, J Verweij, P Viscoli, C Walsh, T AF Bennett, JE de Pauw, B Dismukes, W Galgiani, J Glauser, M Herbrecht, R Kauffman, C Lee, J Pappas, P Powers, J Rex, J Verweij, P Viscoli, C Walsh, T TI Introduction to the forum report on advances in the design of antifungal clinical trials SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material C1 NIAID, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. Univ Nijmegen St Radboud Hosp, NL-6500 HB Nijmegen, Netherlands. Univ Alabama, Birmingham, AL USA. Univ Arizona, Tucson, AZ USA. Univ Lausanne Hosp, Lausanne, Switzerland. Hop Hautepierre, Strasbourg, France. Vet Adm Med Ctr, Ann Arbor, MI 48105 USA. Univ Michigan, Ann Arbor, MI 48109 USA. US FDA, Div Special Pathogen & Immunolog Drug Prod, Rockville, MD 20857 USA. Univ Texas, Sch Med, Houston, TX USA. Univ Genoa, Natl Inst Canc Res, Genoa, Italy. RP Bennett, JE (reprint author), NIH, Clin Mycol Sect, Clin Invest Lab, Bldg 10,Room 11C304, Bethesda, MD 20892 USA. RI Herbrecht, Raoul/D-3471-2013; Verweij, P.E./H-8108-2014 NR 0 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 APR 15 PY 2003 VL 36 SU 3 BP S112 EP S112 DI 10.1086/367837 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 665MN UT WOS:000182125000002 ER PT J AU Kamakaka, RT AF Kamakaka, RT TI Heterochromatin: Proteins in flux lead to stable repression SO CURRENT BIOLOGY LA English DT Editorial Material ID CHROMATIN; GENE AB Heterochromatin is a phenotypically stable entity, but recent studies on the binding of HP1 protein in heterochromatin indicate that the individual components within these domains are not stably bound but in constant flux. These results force us to reexamine previous models of heterochromatin. C1 NICHD, Unit Chromatin & Transcript, NIH, Bethesda, MD 20892 USA. RP Kamakaka, RT (reprint author), NICHD, Unit Chromatin & Transcript, NIH, Bldg 18T,Room 106,18 Lib Dr, Bethesda, MD 20892 USA. NR 20 TC 10 Z9 10 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD APR 15 PY 2003 VL 13 IS 8 BP R317 EP R319 DI 10.1016/S0960-9822(03)00236-7 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 671XG UT WOS:000182490000013 PM 12699644 ER PT J AU Man, DL Wang, WW Sabehi, G Aravind, L Post, AF Massana, R Spudich, EN Spudich, JL Beja, O AF Man, DL Wang, WW Sabehi, G Aravind, L Post, AF Massana, R Spudich, EN Spudich, JL Beja, O TI Diversification and spectral tuning in marine proteorhodopsins SO EMBO JOURNAL LA English DT Article DE diversity; rhodopsin; SAR86; spectral tuning; structure modeling ID VISUAL PIGMENTS; COMMUNITY STRUCTURE; RHODOPSIN; BACTERIORHODOPSIN; LIGHT; SEA; PROCHLOROCOCCUS; PHOTOTROPHY; MECHANISMS; PHYSIOLOGY AB Proteorhodopsins, ubiquitous retinylidene photoactive proton pumps, were recently discovered in the cosmopolitan uncultured SAR86 bacterial group in oceanic surface waters. Two related proteorhodopsin families were found that absorb light with different absorption maxima, 525 nm (green) and 490 nm (blue), and their distribution was shown to be stratified with depth. Using structural modeling comparisons and mutagenesis, we report here on a single amino acid residue at position 105 that functions as a spectral tuning switch and accounts for most of the spectral difference between the two pigment families. Furthermore, looking at natural environments, we found novel proteorhodopsin gene clusters spanning the range of 540-505 nm and containing changes in the same identified key switch residue leading to changes in their absorption maxima. The results suggest a simultaneous diversification of green proteorhodopsin and the new key switch variant pigments. Our observations demonstrate that this single-residue switch mechanism is the major determinant of proteorhodopsin wavelength regulation in natural marine environments. C1 Technion Israel Inst Technol, Dept Biol, IL-32000 Haifa, Israel. Hebrew Univ Jerusalem, Dept Microbiol & Mol Ecol, Interuniv Inst Marine Sci, H Steinitz Marine Biol Lab, Jerusalem, Israel. Univ Texas, Sch Med, Ctr Membrane Biol, Houston, TX 77030 USA. Univ Texas, Sch Med, Dept Biochem & Mol Biol, Houston, TX 77030 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. CSIC, Inst Ciencias Mar, Dept Biol Marine & Oceanog, E-08003 Barcelona, Spain. RP Spudich, JL (reprint author), Technion Israel Inst Technol, Dept Biol, IL-32000 Haifa, Israel. OI Massana, Ramon/0000-0001-9172-5418 FU NIGMS NIH HHS [R01 GM27750] NR 35 TC 151 Z9 159 U1 1 U2 23 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD APR 15 PY 2003 VL 22 IS 8 BP 1725 EP 1731 DI 10.1093/emboj/cdg183 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 666CW UT WOS:000182159900001 PM 12682005 ER PT J AU Wink, DA Mitchell, JB AF Wink, DA Mitchell, JB TI Nitric oxide and cancer: An introduction SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Editorial Material ID WOODCHUCK HEPATITIS-VIRUS; N-NITROSODIETHANOLAMINE; NITRATE BIOSYNTHESIS; MARMOTA-MONAX; TARGET-CELLS; STOMACH; RATS; GENOTOXICITY; MACROPHAGES; SUPEROXIDE C1 NCI, Radiat Biol Branch, Canc Res Ctr, Tumor Biol Sect, Bethesda, MD 20892 USA. RP Wink, DA (reprint author), NCI, Radiat Biol Branch, Ctr Canc Res, Tumor Biol Sect, Bldg 10,B3-B69, Bethesda, MD 20892 USA. EM wink@box-w.nih.gov NR 42 TC 65 Z9 70 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD APR 15 PY 2003 VL 34 IS 8 BP 951 EP 954 DI 10.1016/S0891-5849(02)01362-X PG 4 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 667KL UT WOS:000182230700001 PM 12684080 ER PT J AU Hofseth, LJ Hussain, SP Wogan, GN Harris, CC AF Hofseth, LJ Hussain, SP Wogan, GN Harris, CC TI Nitric oxide in cancer and chemoprevention SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; TUMOR-SUPPRESSOR GENE; INFLAMMATORY-BOWEL-DISEASE; SYNTHASE-II GENE; ARGININE METHYL-ESTER; HUMAN BREAST-CANCER; NF-KAPPA-B; HELICOBACTER-PYLORI GASTRITIS; TRINITROBENZENE SULFONIC-ACID; CYTOKINE-INDUCED EXPRESSION AB Nitric oxide (NO) is a key molecule involved in many physiological functions. However, evidence is accumulating that sustained high levels of NO over extended periods of time contribute to carcinogenesis. This article reviews recent data and outlines a dual role of NO in animal carcinogenesis. Following an inhibition of NO production, some studies find a protection, while others find an exacerbation of tumorigenesis. These studies reflect the importance of (i) choosing the appropriate compound for NO inhibition; and (ii) genetic background, target tissue, levels of NO, and surrounding free radicals in the overall affects of NO on the tumor growth. These findings highlight the importance of further study of the use of NO inhibitors to inhibit human carcinogenesis. Published by Elsevier Inc. C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. MIT, Dept Chem, Cambridge, MA 02139 USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, NIH, Bldg 37 Rm 2C05,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. EM Curtis_Harris@nih.gov NR 219 TC 150 Z9 159 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD APR 15 PY 2003 VL 34 IS 8 BP 955 EP 968 DI 10.1016/S0891-5849(02)01363-1 PG 14 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 667KL UT WOS:000182230700002 PM 12684081 ER PT J AU Qian, SY Yue, GH Tomer, KB Mason, RP AF Qian, SY Yue, GH Tomer, KB Mason, RP TI Identification of all classes of spin-trapped carbon-centered radicals in soybean lipoxygenase-dependent lipid peroxidations of omega-6 polyunsaturated fatty acids via LC/ESR, LC/MS, and tandem MS SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE lipid-derived radicals; on-line LC/ESR; on-line LC/MS; tandem mass spectrometry; lipoxygenase-dependent lipid peroxidation; free radicals ID MURINE LEUKEMIA-CELLS; FAST-ATOM-BOMBARDMENT; IN-VIVO EVIDENCE; MASS-SPECTROMETRY; PHOTOFRIN PHOTOSENSITIZATION; LIQUID-CHROMATOGRAPHY; LINOLEIC-ACID; RESONANCE; DISEASE; ADDUCTS AB Using the combined techniques of on-line high performance liquid chromatography/electron spin resonance (LC/ESR) and mass spectrometry (MS), we previously identified spin-trapped adducts of all expected carbon-centered lipid-derived radicals (L-.(d)) formed in linoleic acid peroxidation. In the present study, spin trapped lipid-derived carbon-centered radicals formed from the reactions of two omega-6 polyunsaturated fatty acids (PUFAs: linoleic and arachidonic acids) with soybean lipoxygenase in the presence of alpha-[4-pyridyl 1-oxide]-N-tert-butyl nitrone (POBN) were identified using a combination of LC/ESR and LC/MS. All expected lipid-derived carbon-centered radicals in lipoxygenase-dependent peroxidations of linoleic acid and arachidonic acid were detected and identified by the combination of LC/ESR and LC/MS with confirmation by tandem mass spectrometry (MS/MS). The five classes of L-.(d) formed from both omega-6 PUFAs including lipid alkyl radicals (L-.), epoxyallyic radicals (OL.), dihydroxyallyic radicals (L-.(OH)(2)), and a variety of R-. and (RCOOH)-R-. from beta-scission of lipid alkoxyl radicals, gave distinct retention times: POBN/L-.(OH)(2) similar to4-6 min, POBN/R-. and POBN/(RCOOH)-R-. similar to8-22 min, POBN/L-. and PBON/OL. similar to25-36 min. The major beta-scission products in peroxidations of omega-6 PUFAs were the pentyl radicals. The ratio of P-scission products, however, varied significantly depending on pH, [PUFA], as well as [O-2]. (C) 2003 Elsevier Inc. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Qian, SY (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RI Tomer, Kenneth/E-8018-2013 NR 27 TC 45 Z9 48 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD APR 15 PY 2003 VL 34 IS 8 BP 1017 EP 1028 DI 10.1016/S0891-5849(03)00031-5 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 667KL UT WOS:000182230700007 PM 12684086 ER PT J AU Chignell, CF Sik, RH AF Chignell, CF Sik, RH TI A photochemical study of cells loaded with 2 ',7 '-dichlorofluorescin: Implications for the detection of reactive oxygen species generated during UVA irradiation SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE UVA; HaCaT keratinocytes; reactive oxygen species; free radicals ID HUMAN SKIN FIBROBLASTS; ULTRAVIOLET-A RADIATION; SINGLET OXYGEN; INTERSTITIAL COLLAGENASE; 2',7'-DICHLOROFLUORESCIN; KERATINOCYTES; GLUTATHIONE; EXPRESSION; INDUCTION; EFFECTOR AB There have been several attempts to implicate reactive oxygen species in UVA-induced damage by loading cells with 2',7'-dichlorofluorescin (DCFH) and following the appearance of 2',7'-dichlorofluorescein (DCF), its highly fluorescent oxidation product. However, both DCF and DCFH have significant absorption in the 300-400 nut range so it is possible that photochemical reactions will occur in cells containing these dyes when they are irradiated with UVA. HaCaT keratinocytes loaded with DCFH were irradiated with 0, 1, 2, or 4 J/cm(2) UVA and DCF fluorescence was measured. A dose-dependent increase in DCF fluorescence was observed, with the cells exposed to 4 J/cm(2) UVA exhibiting an almost 10-fold increase over dark controls. However, there was no difference in cell viability, as measured by the NITS assay or LDH release, between the dark and the 4 J/cm(2) UVA-exposed groups. Furthermore, a large increase in DCF fluorescence was observed when a cell-free system containing DCF, DCFH, and horseradish peroxidase was UVA irradiated. As a control, keratinocytes loaded with DCFH were incubated in the dark with either exogenously added H2O2 or 5-hydroxy-1,4-naphthoquinone (juglone), which redox cycles to generate superoxide (and H2O2.). In both cases, the cells showed a concentration-dependent increase in DCF fluorescence and a concomitant decrease in viability. Our findings suggest that DCFH can not be used to detect the UVA-induced generation of reactive oxygen species in cells when the dye is present during exposure. Published by Elsevier Inc. C1 NIEHS, Lab Pharmacol & Chem, Photochem & Photobiol Workgrp, NIH, Res Triangle Pk, NC 27709 USA. RP Chignell, CF (reprint author), NIEHS, Lab Pharmacol & Chem, Photochem & Photobiol Workgrp, NIH, MD F0-05,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 27 TC 39 Z9 41 U1 0 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD APR 15 PY 2003 VL 34 IS 8 BP 1029 EP 1034 DI 10.1016/S0891-5849(03)00022-4 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 667KL UT WOS:000182230700008 PM 12684087 ER PT J AU Mbulaiteye, SM Biggar, RJ Goedert, JJ Engels, EA AF Mbulaiteye, SM Biggar, RJ Goedert, JJ Engels, EA TI Immune deficiency and risk for malignancy among persons with AIDS SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE CD4 counts; Kaposi sarcoma; non-Hodgkin lymphoma; cancer; AIDS; epidemiology ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; EPSTEIN-BARR-VIRUS; SARCOMA-ASSOCIATED HERPESVIRUS; ACTIVE ANTIRETROVIRAL THERAPY; NON-HODGKINS-LYMPHOMAS; KAPOSIS-SARCOMA; DISEASE PROGRESSION; CIGARETTE-SMOKING; DNA-SEQUENCES; INFECTION AB Background: People with AIDS have an elevated risk for cancer. We studied the relationship between cancer risk and AIDS-related immunosuppression as measured by CD4 count at AIDS onset. Methods: We linked records from AIDS and cancer registries in 11 US regions (1990-1996). We studied 82,217 (86.6%) adults who had a CD4 count measured at AIDS onset and survived into the follow-up period. We calculated standardized incidence ratios (SIRs) for AIDS-defining (Kaposi sarcoma [KS], non-Hodgkin lymphoma [NHL] and cervical cancer) as well as non-AIDS-defining cancers in the 2 years after AIDS onset. For each cancer, the change in SIRS across CD4 counts (0-49 cells/mm(3), 50-99 cells/mm(3), 100-199 cells/mm(3), and greater than or equal to200 cells/mm(3)) was modeled using Poisson regression. Results: The SIRS for KS, NHL, and cervical cancer were 258, 78, and 8.8, respectively. For each fall of 100 CD4 cells/mm(3), RRs were 1.36 (95% CI: 1.29-1.43) for KS and 1.48 (95% CI: 1.37-1.59) for NHL. Among NHL subtypes, the association with lower CD4 counts was strongest for immunoblastic lymphoma (RR = 1.64, 95% CI: 1.37-1.96, per decline of 100 CD4 cells/mm(3)) and central nervous system lymphoma (RR = 2.29, 95% CI: 1.95-2.69). The SIR for cervical cancer did not vary with CD4 count (p = .74). For non-AIDS-defining cancers (overall SIR = 2.1), neither the combined risk nor the risk of specific types was associated with declining CD4 counts. Conclusions: KS and NHL risk increased with level of immunosuppression at AIDS onset. Risks for other cancers, including cervical cancer, were unrelated to CD4 counts. Elevated risks for non-AIDS cancers may be a result of lifestyle factors. C1 Natl Canc Inst, Div Ctr Epidemiol & Genet, Bethesda, MD USA. RP Mbulaiteye, SM (reprint author), 6120 Execut Blvd,EPS Room 8007,MSC 7248, Rockville, MD 20852 USA. NR 35 TC 136 Z9 140 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD APR 15 PY 2003 VL 32 IS 5 BP 527 EP 533 DI 10.1097/00126334-200304150-00010 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 667CH UT WOS:000182212900010 PM 12679705 ER PT J AU Seghatoleslami, MR Roman-Blas, JA Rainville, AM Modarresi, R Danielson, KG Tuan, RS AF Seghatoleslami, MR Roman-Blas, JA Rainville, AM Modarresi, R Danielson, KG Tuan, RS TI Progression of chondrogenesis in C3H10T1/2 cells is associated with prolonged and tight regulation of ERK1/2 SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE AP-1; SRF; ERK1/2; PD 98059; BMP-2; C3H1OT1/2 mesenchymal cells; chondrogenesis; micromass cultures ID SERUM RESPONSE FACTOR; TERNARY COMPLEX FACTORS; C-FOS PROTOONCOGENE; IN-VITRO; TRANSCRIPTIONAL ACTIVATION; CARTILAGE DIFFERENTIATION; GLUCOCORTICOID RECEPTOR; LIMB CHONDROGENESIS; MICROMASS CULTURES; MESENCHYMAL CELLS AB Close contact of mesenchymal cells in vivo and also in super dense micromass cultures in vitro results in cellular condensation and alteration of existing cellular signaling required for initiation and progression of chondrogenesis. To investigate chondrogenesis related changes in the activity of ubiquitous cell signaling mediated by mitogen-activated protein kinases (MAP kinase), we have compared the effect of cell seeding of pluripotent C3H10T1/2 mesenchymal cells as monolayers (non-chondrogenic culture) or high density micromass cultures (chondrogenic) on the regulation and phosphorylation state of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and also on regulation of ERK1/2 nuclear targets, namely, activation protein-1 (AP-1) and serum response factor (SRF). Increasing cell density resulted in reduced DNA binding as well as activity of AP-1. SRF activity, on the other hand, was up-regulated in confluent monolayer cultures but like AP-1 was inhibited in micromass cultures. Low levels of PD 98059 (5 muM), a specific inhibitor of ERK1/2, resulted in delayed induction of AP-1 and SRF activity whereas higher concentrations of this inhibitor (10-50 muM) conferred an opposite effect. Increasing concentrations of the PD 98059 inhibitor in long term monolayer or micromass cultures (2.5 day) resulted in differential regulation of c-Fos and c-jun protein levels as well as total expression and phosphorylation levels of ERK1/2. PD 98059 treatment of C3H10T1/2 micromass cultures also resulted in up-regulation of type IIB collagen and Sox9 gene expression. While high expression of aggrecan and type IIB collagen genes were dependent on BMP-2 signaling, ERK inhibition of BMP-2 treated micromass cultures resulted in reduced activity of both genes. Our findings show that the activity of ERK1/2 in chondrogenic cultures of C3H10T1/2 cells is tightly controlled and can cross interact with other signaling activities mediated by BMP-2 to positively regulate chondrogensis. Published 2003 Wiley-Liss, Inc.(up arrow). C1 Thomas Jefferson Univ, Dept Med, Div Rheumatol, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Dept Orthopaed Surg, Philadelphia, PA 19107 USA. NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. RP Thomas Jefferson Univ, Dept Med, Div Rheumatol, Room 506,233 S 10th St, Philadelphia, PA 19107 USA. EM reza.seghatoleslami@mexil.tju.edu OI Roman-Blas, Jorge A./0000-0003-1142-1946 FU NIDCR NIH HHS [DE12864] NR 50 TC 27 Z9 28 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0730-2312 EI 1097-4644 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR 15 PY 2003 VL 88 IS 6 BP 1129 EP 1144 DI 10.1002/jcb.10458 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 663HA UT WOS:000181999100007 PM 12647296 ER PT J AU Berezhkovskii, AM Zitserman, VY Shvartsman, SY AF Berezhkovskii, AM Zitserman, VY Shvartsman, SY TI Diffusivity in periodic arrays of spherical cavities SO JOURNAL OF CHEMICAL PHYSICS LA English DT Letter ID POROUS MATERIALS; SYSTEMS; COLLOIDS C1 NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. Russian Acad Sci, Inst High Temp, Thermophys Ctr, Moscow 127412, Russia. Princeton Univ, Dept Chem Engn, Princeton, NJ 08544 USA. Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA. Karpov Inst Phys Chem, Moscow 103064, Russia. RP Shvartsman, SY (reprint author), Princeton Univ, Dept Chem Engn, Princeton, NJ 08544 USA. NR 17 TC 38 Z9 38 U1 0 U2 1 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD APR 15 PY 2003 VL 118 IS 15 BP 7146 EP 7147 DI 10.1063/1.1561615 PG 2 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 662KE UT WOS:000181945200047 ER PT J AU Citron, ML Berry, DA Cirrincione, C Hudis, C Winer, EP Gradishar, WJ Davidson, NE Martino, S Livingston, R Ingle, JN Perez, EA Carpenter, J Hurd, D Holland, JF Smith, BL Sartor, CI Leung, EH Abrams, J Schilsky, RL Muss, HB Norton, L AF Citron, ML Berry, DA Cirrincione, C Hudis, C Winer, EP Gradishar, WJ Davidson, NE Martino, S Livingston, R Ingle, JN Perez, EA Carpenter, J Hurd, D Holland, JF Smith, BL Sartor, CI Leung, EH Abrams, J Schilsky, RL Muss, HB Norton, L TI Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: First report of intergroup trial C9741/cancer and leukemia group B trial 9741 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CYCLOPHOSPHAMIDE; DOXORUBICIN; GROWTH AB Purpose: Using a 2 X 2 factorial design, we studied the adjuvant chemotherapy of women with axillary node-positive breast cancer to compare sequential doxorubicin (A), paclitaxel (T), and cyclophosphamide (C) with concurrent doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T) for disease-free (DFS) and overall survival (OS); to determine whether the dose density of the agents improves DFS and OS; and to compare toxicities. Patients and Methods: A total of 2,005 female patients were randomly assigned to receive one of the following regimens: (I) sequential A x 4 (doses) --> T x 4 --> C x 4 with doses every 3 weeks, (11) sequential A x 4 T x 4 --> C x 4 every 2 weeks with filgrastim, (111) concurrent AC x 4 T x 4 every 3 weeks, or (IV) concurrent AC x 4 --> T x 4 every 2 weeks with filgrastim. Results: A protocol-specified analysis was performed at a median follow-up of 36 months: 315 patients had experienced relapse or died, compared with 515 expected treatment failures. Dose-dense treatment improved the primary end point, DFS (risk ratio [RR] = 0.74; P = .010), and OS (RR = 0.69; P = .013). Four-year DFS was 82% for the dose-dense regimens and 75% for the others. There was no difference in either DFS or OS between the concurrent and sequential schedules. There was no interaction between density and sequence. Severe neutropenia was less frequent in patients who received the dose-dense regimens. Conclusion: Dose density improves clinical outcomes significantly, despite the lower than expected number of events at this time. Sequential chemotherapy is as effective as concurrent chemotherapy. (C) 2003 by American Society of Clinical Oncology. C1 ProHlth Care Associates, LLP, Lake Success, NY 11042 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Wake Forest Univ, Ctr Comprehens Canc, Winston Salem, NC 27109 USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Northwestern Univ, Chicago, IL 60611 USA. Cent Off, Canc & Leukemia Grp B, Chicago, IL 60611 USA. Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Natl Canc Inst, Bethesda, MD USA. John Wayne Canc Inst, Santa Monica, CA USA. Univ Washington, Seattle, WA 98195 USA. Mayo Clin, Rochester, MN USA. Mayo Clin, Jacksonville, FL 32224 USA. Univ Alabama, Birmingham, AL USA. Univ Vermont, Burlington, VT USA. RP Citron, ML (reprint author), ProHlth Care Associates, LLP, 2800 Marcus Ave, Lake Success, NY 11042 USA. NR 21 TC 831 Z9 871 U1 2 U2 13 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 15 PY 2003 VL 21 IS 8 BP 1431 EP 1439 DI 10.1200/JCO.2003.09.081 PG 9 WC Oncology SC Oncology GA 668NN UT WOS:000182300200003 PM 12668651 ER PT J AU Smith, JW Walker, EB Fox, BA Haley, D Wisner, KP Doran, T Fisher, B Justice, L Wood, W Vetto, J Maecker, H Dols, A Meijer, S Hu, HM Romero, P Alvord, WG Urba, WJ AF Smith, JW Walker, EB Fox, BA Haley, D Wisner, KP Doran, T Fisher, B Justice, L Wood, W Vetto, J Maecker, H Dols, A Meijer, S Hu, HM Romero, P Alvord, WG Urba, WJ TI Adjuvant immunization of HLA-A2-positive melanoma patients with a modified gp100 peptide induces peptide-specific CD8(+) T-cell responses SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID I TETRAMERIC COMPLEXES; METASTATIC MELANOMA; ANTIGEN GP100; TUMOR-REGRESSION; IMMUNE-RESPONSE; VACCINE; LYMPHOCYTES; FREQUENCY; THERAPY; IMMUNOTHERAPY AB Purpose: To measure the CD8(+) T-cell response to a melanoma peptide vaccine and to compare an every-2-weeks with an every-3-weeks vaccination schedule. Patients and Methods: Thirty HLA-A2-positive patients with resected stage I to III melanoma were randomly assigned to receive vaccinations every 2 weeks (13 vaccines) or every 3 weeks (nine vaccines) for 6 months. The synthetic, modified gp100 peptide, g209-2M, and a control peptide, HPV16 E7, were mixed in incomplete Freund's adjuvant and injected subcutaneously. Peripheral blood mononuclear cells obtained before and after vaccination by leukapheresis were analyzed using a fluorescence-based HLA/peptide-tetramer binding assay and cytokine flow cytometry. Results: Vaccination induced an increase in peptide-specific T cells in 28 of 29 patients. The median frequency of CDB+ T cells specific for the g209-2M peptide increased markedly from 0.02% before to 0.34% after vaccination (P < .0001). Eight patients (28%) exhibited peptide-specific CD8(+) T-cell frequencies greater than 1%, including two patients with frequencies of 4.96% and 8.86%, respectively. Interferon alfa-2b-treated patients also had significant increases in tetramer-binding cells (P < .0001). No difference was observed between the every-2-weeks and the every-3-weeks vaccination schedules (P = .59). Conclusion: Flow cytometric analysis of HLA/peptide-tetramer binding cells was a reliable means of quantifying the CD8(+) T-cell response to peptide immunization. This assay may be suitable for use in future trials to optimize different vaccination strategies. Concurrent interferon treatment did not inhibit the development of a peptide-specific immune response and vaccination every 2 weeks, and every 3 weeks produced similar results. J Clin Oncol 21:1562-1573. (C) 2003 by American Society of Clinical Oncology. C1 Providence Portland Med Ctr, Robert W Franz Canc Res Ctr, Earle A Chiles Res Inst, Portland, OR 97213 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Ludwig Inst Canc Res, Div Oncol Immunol, Lausanne, Switzerland. NCI, Frederick Canc Res & Dev Ctr, Data Management Serv, Frederick, MD USA. Becton Dickinson Biosci, San Jose, CA USA. RP Smith, JW (reprint author), Providence Portland Med Ctr, Robert W Franz Canc Res Ctr, Earle A Chiles Res Inst, 4805 NE Glisan St,5F40, Portland, OR 97213 USA. FU PHS HHS [1R21-CS82614-01] NR 28 TC 83 Z9 89 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 15 PY 2003 VL 21 IS 8 BP 1562 EP 1573 DI 10.1200/JCO.2003.09.020 PG 12 WC Oncology SC Oncology GA 668NN UT WOS:000182300200022 PM 12697882 ER PT J AU Goorin, AM Schwartzentruber, DJ Devidas, M Gebhardt, MC Ayala, AG Harris, MB Helman, LJ Grier, HE Link, MP AF Goorin, AM Schwartzentruber, DJ Devidas, M Gebhardt, MC Ayala, AG Harris, MB Helman, LJ Grier, HE Link, MP TI Presurgical chemotherapy compared with immediate surgery and adjuvant chemotherapy for nonmetastatic osteosarcoma: Pediatric oncology group study POG-8651 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HIGH-DOSE METHOTREXATE; PRIMARY OSTEOGENIC-SARCOMA; NEOADJUVANT CHEMOTHERAPY; DELAYED SURGERY; INTERGROUP RHABDOMYOSARCOMA; PREOPERATIVE CHEMOTHERAPY; OPERABLE OSTEOSARCOMA; PROGNOSTIC FACTORS; RADIATION-THERAPY; CANCER AB Purpose: Successful therapeutic interventions to prevent disease progression in patients with nonmetastatic osteosarcoma have included surgery with adjuvant chemotherapy. Presurgical chemotherapy has been advocated for these patients because of putative improvement in event-free survival (EFS). The advantages of presurgical chemotherapy include early administration of systemic chemotherapy, shrinkage of primary tumor, and pathologic identification of risk groups. The theoretic disadvantage is that it exposes a large tumor burden to marginally effective chemotherapy. The contribution of chemotherapy and surgery timing has not been tested rigorously. Patients and Methods: Between 1986 and 1993, we conducted a prospective trial in patients with nonmetastatic osteosarcoma who were assigned randomly to immediate surgery or presurgical chemotherapy. Except for the timing of surgery (week 0 or 10), patients received 44 weeks of identical combination chemotherapy that included high-dose methotrexate with leucovorin rescue, doxorubicin, cisplatin, bleomycin, cyclophosphamide, and dactinomycin. Results: One hundred six patients were enrolled onto this study. Six were excluded from analysis. Of the remaining 100 patients, 45 were randomly assigned to immediate chemotherapy, and 55 were randomly assigned to immediate surgery. Sixty-seven patients remain disease-free. At 5 years, the projected EFS +/- SE is 65% +/- 6% (69% +/- 8% for immediate surgery and 61% +/- 8% for presurgical chemotherapy; P = .8). The treatment arms had similar incidence of limb salvage (55% for immediate surgery and 50% for presurgical chemotherapy). Conclusion: Chemotherapy was effective in both treatment groups. There was no advantage in EFS for patients given presurgical chemotherapy. J Clin Oncol 21:1574-1580. (C) 2003 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. Childrens Hosp, Div Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NCI, Surg Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Univ Florida, Dept Stat, Gainesville, FL 32611 USA. Pediat Oncol Grp, Stat Off, Gainesville, FL USA. Univ Texas, Dept Surg Pathol, Houston, TX USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Tomorrows Childrens Inst, Hackensack, NJ USA. Univ Med Ctr, Newark, NJ USA. Univ Med & Dent New Jersey, Newark, NJ 07103 USA. Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. RP Goorin, AM (reprint author), Dana Farber Canc Inst, Dept Pediat, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA-15525, CA-03161, CA-05587, CA-11233, CA-15898, CA-20549, CA-25408, CA-28383, CA-28439, CA-28476, CA-29139, CA-29293, CA-30969, CA-32053, CA-33587, CA-33603, CA-33625, CA-41573, CA-69177, CA-69478] NR 34 TC 156 Z9 171 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 15 PY 2003 VL 21 IS 8 BP 1574 EP 1580 DI 10.1200/JCO.2003.08.165 PG 7 WC Oncology SC Oncology GA 668NN UT WOS:000182300200023 PM 12697883 ER PT J AU Zhang, MF Vacchio, MS Vistica, BP Lesage, S Egwuagu, CE Yu, CR Gelderman, MP Kennedy, MC Wawrousek, EF Gery, I AF Zhang, MF Vacchio, MS Vistica, BP Lesage, S Egwuagu, CE Yu, CR Gelderman, MP Kennedy, MC Wawrousek, EF Gery, I TI T cell tolerance to a neo-self antigen expressed by thymic epithelial cells: The soluble form is more effective than the membrane-bound form SO JOURNAL OF IMMUNOLOGY LA English DT Article ID REACTIVE LYMPHOCYTES-B; NEGATIVE SELECTION; GENE-EXPRESSION; STROMAL CELLS; INTERCELLULAR TRANSFER; TRANSGENIC MICE; LYMPHOID ORGANS; APOPTOSIS; INACTIVATION; ELIMINATION AB We have previously shown that transgenic (Tg) mice expressing either soluble or membrane-bound hen egg lysozyme (sHEL or mHEL, respectively) under control of the alphaA-crystallin promoter develop tolerance due to thymic expression of minuscule amounts of HEL. To further address the mechanisms by which this tolerance develops, we mated these two lines of Tg mice with the 3A9 line of HEL-specific TCR Tg mice, to produce double-Tg mice. Both lines of double-Tg mice showed deletion of HEL-specific T cells, demonstrated by reduction in numbers of these cells in the thymus and periphery, as well as by reduced proliferative response to HEL in vitro. In addition, the actual deletional process in thymi of the double-Tg mice was visualized in situ by the TUNEL assay and measured by binding of Annexin V. Notably, the apoptosis localized mainly in the thymic medulla, in line with the finding that the populations showing deletion and increased Annexin V binding consisted mainly of single- and double-positive thymocytes. Interestingly, the thymic deletional effect of sHEL was superior to that of mHEL in contrast to the opposite differential tolerogenic effects of these HEL forms on B cells specific to this Ag. Analysis of bone marrow chimeras indicates that both forms of HEL are produced by irradiation-resistant thymic stromal cells and the data suggest that sHEL is more effective in deleting 3A9 T cells due mainly to its higher accessibility to cross-presentation by dendritic APC. C1 NIH, NEI, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. Australian Natl Univ, John Curtin Sch Med Res, Med Genome Ctr, Canberra, ACT 2601, Australia. RP Gery, I (reprint author), NIH, NEI, Bldg 10,Room 10N112, Bethesda, MD 20892 USA. RI Wawrousek, Eric/A-4547-2008 NR 37 TC 37 Z9 37 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2003 VL 170 IS 8 BP 3954 EP 3962 PG 9 WC Immunology SC Immunology GA 666HG UT WOS:000182171100003 PM 12682222 ER PT J AU Kawamura, T Gatanaga, H Borris, DL Connors, M Mitsuya, H Blauvelt, A AF Kawamura, T Gatanaga, H Borris, DL Connors, M Mitsuya, H Blauvelt, A TI Decreased stimulation of CD4(+) T cell proliferation and IL-2 production by highly enriched populations of HIV-infected dendritic cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ENVELOPE GLYCOPROTEIN GP120; RECOMBINANT SOLUBLE CD4; LANGERHANS CELLS; IN-VITRO; ANTIRETROVIRAL THERAPY; VIRAL REPLICATION; BLOOD MONOCYTES; DC-SIGN; PHASE-I AB APC infection and dysfunction may contribute to the immunopathogenesis of HIV disease. In this study, we examined immunologic function of highly enriched populations of HIV-infected monocyte-derived dendritic cells (DC). Compared with uninfected DC, HIV-infected DC markedly down-regulated surface expression of CD4. HIV p24(+) DC were then enriched by negative selection of CD4(+)HIV p24(-) DC and assessed for cytokine secretion and immunologic function. Although enriched populations of HIV-infected DC secreted increased IL-12p70 and decreased IL-10, these cells were poor stimulators of allogeneic CD4(+) T cell proliferation and IL-2 production. Interestingly, HIV-infected DC secreted HIV gp120 and the addition of soluble (s) CD4 (a known ligand for HIV gp120) to DC-CD4(+) T cell cocultures restored T cell proliferation in a dose-dependent manner. By contrast, addition of antiretroviral drugs did not affect CD4(+) T cell proliferation. Furthermore, recombinant HIV gp120 inhibited proliferation in uninfected cocultures of allogeneic DC and CD4(+) T cells, an effect that was also reversed by addition of sCD4. In summary, we show that HIV gp120 produced by DC infected by HIV in vitro impairs normal CD4(+) T cell function and that sCD4 completely reverses HIV gp120-mediated immunosuppression. We hypothesize that HIV-infected DC may contribute to impaired CD4(+) T cell-mediated immune responses in vivo and that agents that block this particular immunosuppression may be potential immune adjuvants in HIV-infected individuals. C1 NCI, Ctr Canc Res, Dermatol Branch, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Expt Retrovirol Branch, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. RP Blauvelt, A (reprint author), NCI, Ctr Canc Res, Dermatol Branch, Bldg 10 Room 12N238,10 Ctr Dr MSC 1908, Bethesda, MD 20892 USA. NR 51 TC 56 Z9 57 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2003 VL 170 IS 8 BP 4260 EP 4266 PG 7 WC Immunology SC Immunology GA 666HG UT WOS:000182171100041 PM 12682260 ER PT J AU Malkevitch, N Patterson, LJ Aldrich, K Richardson, E Alvord, WG Robert-Guroff, M AF Malkevitch, N Patterson, LJ Aldrich, K Richardson, E Alvord, WG Robert-Guroff, M TI A replication competent adenovirus 5 host range mutant-simian immunodeficiency virus (SIV) recombinant priming/subunit protein boosting vaccine regimen induces broad, persistent SIV-speeific cellular immunity to dominant and subdominant epitopes in Mamu-A*01 Rhesus macaques SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CLASS-I MOLECULE; HIV-1/SIV CHIMERIC VIRUS; CYTOTOXIC T-LYMPHOCYTES; NEUTRALIZING ANTIBODIES; CD8(+) LYMPHOCYTES; ENVELOPE GLYCOPROTEIN; MUCOSAL CHALLENGE; DNA VACCINATION; HIGH-FREQUENCY; LYMPH-NODES AB CTL are important in controlling HIV and SIV infection. To quantify cellular immune responses induced by immunization, CD8(+) T cells specific for the subdominant Env p15m and p54m epitopes and/or the dominant Gag p11C epitope were evaluated by tetramer staining in nine macaques immunized with an adenovirus (Ad) 5 host range mutant (Ad5hr)-SIVenv/rev recombinant and in four of nine which also received an Ad5hr-SlVgag recombinant. Two Ad5hr-SIV recombinant priming immunizations were followed by two boosts with gp120 protein or an envelope polypeptide representing the CD4 binding domain. Two mock-immunized macaques served as controls. IFN-gamma-secreting cells were also assessed by ELISPOT assay using p11C, p15m, and p54m peptide stimuli and overlapping pooled Gag and Env peptides. As shown by tetramer staining, Ad-recombinant priming elicited a high frequency of persistent CD8(+) T cells able to recognize p11C, p15m, and p54m epitopes. The presence of memory cells 38 wk postinitial immunization was confirmed by expansion of tetramer-positive CD8(+) T cells following in vitro stimulation. The SIV-specific CD8(+) T cells elicited were functional and secreted IFN-gamma in response to SIV peptide stimuli. Although the level and frequency of response of peripheral blood CD8(+) T cells to the subdominant Env epitopes were not as great as those to the dominant p11C epitope, elevated responses were observed when lymph node CD8(+) T cells were evaluated. Our data confirm the potency and persistence of functional cellular immune responses elicited by replication competent Ad-recombinant priming. The cellular immunity elicited is broad and extends to subdominant epitopes. C1 NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. NCI, Data Management Serv, Frederick, MD 21702 USA. RP Robert-Guroff, M (reprint author), NCI, Basic Res Lab, NIH, 41 Lib Dr,Bldg 41 Room D804, Bethesda, MD 20892 USA. NR 52 TC 36 Z9 36 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2003 VL 170 IS 8 BP 4281 EP 4289 PG 9 WC Immunology SC Immunology GA 666HG UT WOS:000182171100044 PM 12682263 ER PT J AU Cohen, CJ Sarig, O Yamano, Y Tomaru, U Jacobson, S Reiter, Y AF Cohen, CJ Sarig, O Yamano, Y Tomaru, U Jacobson, S Reiter, Y TI Direct phenotypic analysis of human MHC class I antigen presentation: Visualization, quanititation, and in situ detection of human viral epitopes using peptide-specific, MHC-restricted human recombinant antibodies SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL LEUKEMIA; VIRUS TYPE-I; RECEPTOR-LIKE SPECIFICITY; TUMOR-ASSOCIATED ANTIGENS; TAX GENE; MONOCLONAL-ANTIBODY; COMPLEX; LYMPHOCYTES; PROTEIN; QUANTITATION AB The advent in recent years of the application of tetrameric arrays of class I peptide-MHC complexes now enables us to detect and study rare populations of Ag-specific CD8(+) T cells. However, aviailable methods cannot visualize or determine the number and distribution of these TCR ligands on individual cells nor detect APCs in tissues. In this study, we describe for the first time studies of human class I peptide-MHC ligand presentation. These studies were facilitated by applying novel tools in the form of peptide-specific, HLA-A2-restricted human recombinant Abs directed toward a viral epitope derived from human T cell lymphotropic virus type I. Using a large human Ab phage display library, we isolated a large panel of recombinant Fab Abs that are specific for a particular peptide-MHC class I complex in a peptide-dependent, MHC-restricted manner. We used these Abs to visualize the specific complex on APCs and virus-infected cells by flow cytometry, to quantify the number of, and visualize in situ, a particular complex on the surface of APCs bearing complexes formed by naturally occurring active intracellular processing of the cognate viral Ag. These findings demonstrate our ability to transform the unique fine specificity, but low intrinsic affinity of TCRs into high affinity soluble Ab molecules endowed with a TCR-like specificity toward human viral epitopes. These molecules may prove to be crucial useful tools for studying MHC class I Ag presentation in health and disease as well as for therapeutic purposes in cancer, infectious diseases, and autoimmune disorders. C1 Technion Israel Inst Technol, Fac Biol, IL-32000 Haifa, Israel. NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Reiter, Y (reprint author), Technion Israel Inst Technol, Fac Biol, Room 333, IL-32000 Haifa, Israel. NR 48 TC 47 Z9 48 U1 1 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2003 VL 170 IS 8 BP 4349 EP 4361 PG 13 WC Immunology SC Immunology GA 666HG UT WOS:000182171100053 PM 12682272 ER PT J AU Hou, YC Gu, XX AF Hou, YC Gu, XX TI Development of peptide mimotopes of lipooligosaccharide from nontypeable Haemophilus influenzae as vaccine candidates SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MULTIPLE ANTIGEN PEPTIDES; NONTYPABLE HEMOPHILUS-INFLUENZAE; PHAGE-DISPLAY; OTITIS-MEDIA; CAPSULAR POLYSACCHARIDE; CRYPTOCOCCUS-NEOFORMANS; ANTICARBOHYDRATE ANTIBODIES; NEISSERIA-MENINGITIDIS; DETOXIFIED LIPOOLIGOSACCHARIDE; CIRCUMSPOROZOITE PROTEIN AB Nontypeable Haemophilus influenzae (NTHi) is a common cause of otitis media in children and lower respiratory tract diseases in adults. So far there is no effective vaccine against NTHi. A major surface-exposed component of NTHi, lipooligosaccharide (LOS), is a virulence factor as well as a potential protective Ag. LOS is too toxic to be administered in humans. However, detoxified LOS is a T cell-independent small molecule and is poorly immunogenic in vivo, so we converted LOS into a nontoxic T cell-dependent Ag through the use of peptides that mimic the LOS by screening a phage-display peptide library with a rabbit Ab specific for NTHi LOS. Fifty-six phage clones were found to share LOS mimicry molecules. Among them, 22 clones were subjected to DNA sequencing, and four consensus sequences were identified as NMMRFTSQPPNN, NMMNYIMDPRTH, NMMKYISP PIFL, and NMMRFTELSTPS. Three of the four synthetic peptides showed strong binding reactivity to the rabbit anti-LOS Ab, and also a mouse bactericidal monoclonal anti-LOS Ab in vitro, and elicited specific serum anti-LOS Abs in rabbits (27- to 81-fold) after conjugation with keyhole limpet hemocyanin. Passive immunization with the rabbit antiscra resulted in a significantly enhanced pulmonary bacterial clearance in a mouse model. The enhanced bacterial clearance was eliminated if the rabbit serum was preabsorbed with NTHi LOS. These data indicate that the peptide mimotopes of LOS that we have identified might be potential components of peptide vaccines against NTHi. C1 NIDCD, NIH, Rockville, MD 20850 USA. RP Gu, XX (reprint author), NIDCD, NIH, 5 Res Court,2A31, Rockville, MD 20850 USA. NR 56 TC 32 Z9 38 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2003 VL 170 IS 8 BP 4373 EP 4379 PG 7 WC Immunology SC Immunology GA 666HG UT WOS:000182171100055 PM 12682274 ER PT J AU Bacon, RM Biggerstaff, BJ Schriefer, ME Gilmore, RD Philipp, MT Steere, AC Wormser, GP Marques, AR Johnson, BJB AF Bacon, RM Biggerstaff, BJ Schriefer, ME Gilmore, RD Philipp, MT Steere, AC Wormser, GP Marques, AR Johnson, BJB TI Serodiagnosis of Lyme disease by kinetic enzyme-linked immunosorbent assay using recombinant VlsE1 or peptide antigens of Borrelia burgdorferi compared with 2-tiered testing using whole-cell lysates SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 100th Annual Meeting of the American-Society-for-Microbiology CY MAY 21-25, 2000 CL LOS ANGELES, CALIFORNIA SP Amer Soc Microbiol ID IMMUNODOMINANT CONSERVED REGION; SURFACE PROTEIN-C; CONFIDENCE-INTERVALS; ANTIBODY-RESPONSE; IMMUNOBLOT; DIAGNOSIS; INFECTION; NEUROBORRELIOSIS; PROPORTIONS; LIPOPROTEIN AB In a study of US patients with Lyme disease, immunoglobulin (Ig) G and IgM antibody responses to recombinant Borrelia burgdorferi antigen VlsE1 (rVlsE1), IgG responses to a synthetic peptide homologous to a conserved internal sequence of VlsE (C6), and IgM responses to a synthetic peptide comprising the C-terminal 10 amino acid residues of a B. burgdorferi outer-surface protein C (pepC10) were evaluated by kinetic enzyme-linked immunoassay. At 99% specificity, the overall sensitivities for detecting IgG antibody to rVlsE1 or C6 in samples from patients with diverse manifestations of Lyme disease were equivalent to that of 2-tiered testing. When data were considered in parallel, 2 combinations (IgG responses to either rVlsE1 or C6 in parallel with IgM responses to pepC10) maintained high specificity (98%) and were significantly more sensitive than 2-tiered analysis in detecting antibodies to B. burgdorferi in patients with acute erythema migrans. In later stages of Lyme disease, the sensitivities of the in parallel tests and 2-tiered testing were high and statistically equivalent. C1 Ctr Dis Control & Prevent, Div Vector Borne Infect Dis, Natl Ctr Infect Dis, Ft Collins, CO 80522 USA. Tulane Univ, Hlth Sci Ctr, Tulane Natl Primate Res Ctr, Covington, LA USA. Tufts Univ, Sch Med, New England Med Ctr, Boston, MA 02111 USA. New York Med Coll, Dept Med, Div Infect Dis, Valhalla, NY 10595 USA. NIAID, Clin Invest Lab, Bethesda, MD 20892 USA. RP Johnson, BJB (reprint author), Ctr Dis Control & Prevent, Div Vector Borne Infect Dis, Natl Ctr Infect Dis, POB 2087, Ft Collins, CO 80522 USA. NR 50 TC 153 Z9 155 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 APR 15 PY 2003 VL 187 IS 8 BP 1187 EP 1199 DI 10.1086/374395 PG 13 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 662WL UT WOS:000181972000003 PM 12695997 ER PT J AU Murphy, BR Morens, DM Simonsen, L Chanock, RM La Montagne, JR Kapikian, AZ AF Murphy, BR Morens, DM Simonsen, L Chanock, RM La Montagne, JR Kapikian, AZ TI Reappraisal of the association of intussusception with the licensed live rotavirus vaccine challenges initial conclusions SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID DEVELOPING-COUNTRIES; YOUNG-CHILDREN; INFANTS; DIARRHEA; FUTURE; PREVENTION; INFECTION; BENEFITS C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Murphy, BR (reprint author), NIAID, NIH, Bldg 50,Rm 6517,50 South Dr,MSC 8007, Bethesda, MD 20892 USA. OI Simonsen, Lone/0000-0003-1535-8526 NR 37 TC 78 Z9 85 U1 0 U2 2 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 APR 15 PY 2003 VL 187 IS 8 BP 1301 EP 1308 DI 10.1086/367895 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 662WL UT WOS:000181972000016 PM 12696010 ER PT J AU Ma, L Huang, YZ Pitcher, GM Valtschanoff, JG Ma, YH Feng, LY Lu, B Xiong, WC Salter, MW Weinberg, RJ Mei, L AF Ma, L Huang, YZ Pitcher, GM Valtschanoff, JG Ma, YH Feng, LY Lu, B Xiong, WC Salter, MW Weinberg, RJ Mei, L TI Ligand-dependent recruitment of the ErbB4 signaling complex into neuronal lipid rafts SO JOURNAL OF NEUROSCIENCE LA English DT Article DE lipid rafts; ErbB4; NRG; PSD-95; postsynaptic density; long-term potentiation; synaptic plasticity ID RECEPTOR GENE-EXPRESSION; SOMATIC SENSORY CORTEX; LONG-TERM POTENTIATION; NERVOUS-SYSTEM; POSTSYNAPTIC DENSITY; NEUREGULIN RECEPTOR; NEUROMUSCULAR-JUNCTION; TRANSMEMBRANE DOMAIN; HIPPOCAMPAL-NEURONS; CONTAINING PROTEINS AB Neuregulin (NRG) regulates synapse formation and synaptic plasticity, but little is known about the regulation of NRG signaling at synapses. Here we show that the NRG receptor ErbB4 was localized in anatomically defined postsynaptic densities in the brain. In cultured cortical neurons, ErbB4 was recruited to the neuronal lipid raft fraction after stimulation by NRG. Along with ErbB4, adaptor proteins Grb2 and Shc were translocated to lipid rafts by NRG stimulation. In transfected human embryonic kidney 293 cells, the partitioning of ErbB4 into a detergent-insoluble fraction that includes lipid rafts was increased by PSD-95 ( postsynaptic density-95), through interaction of the ErbB4 C terminus with the PDZ [PSD-95/Discs large/zona occludens-1] domains of PSD-95. Disruption of lipid rafts inhibited NRG-induced activation of Erk and prevented NRG-induced blockade of induction of long-term potentiation at hippocampal CA1 synapses. Thus, our results indicate that NRG stimulation causes translocation of ErbB4 into lipid rafts and that lipid rafts are necessary for signaling by ErbB4. C1 Univ Alabama, Sch Med, Dept Neurobiol, Civitan Int Res Ctr 516, Birmingham, AL 35294 USA. Univ Alabama, Sch Med, Dept Pathol, Civitan Int Res Ctr 516, Birmingham, AL 35294 USA. Univ Alabama, Sch Med, Dept Phys Med & Rehabil, Civitan Int Res Ctr 516, Birmingham, AL 35294 USA. Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Neurosci, Shanghai 200031, Peoples R China. Hosp Sick Children, Programme Brain & Behav, Toronto, ON M5G 1X8, Canada. Hosp Sick Children, Programme Cell Biol, Toronto, ON M5G 1X8, Canada. Univ Toronto, Dept Physiol, Toronto, ON M5G 1X8, Canada. Univ N Carolina, Dept Cell & Dev Biol, Chapel Hill, NC 27599 USA. Univ N Carolina, Ctr Neurosci, Chapel Hill, NC 27599 USA. NICHHD, Unit Synapse Dev & Plast, NIH, Bethesda, MD 20892 USA. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. RP Mei, L (reprint author), Univ Alabama, Sch Med, Dept Neurobiol, Civitan Int Res Ctr 516, 1719 6th Ave S, Birmingham, AL 35294 USA. RI Lu, Bai/A-4018-2012; Mei, Lin/G-8755-2012 FU NINDS NIH HHS [NS40480, NS39444] NR 76 TC 99 Z9 100 U1 0 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 15 PY 2003 VL 23 IS 8 BP 3164 EP 3175 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 671QH UT WOS:000182475200011 PM 12716924 ER PT J AU Resnick, SM Pham, DL Kraut, MA Zonderman, AB Davatzikos, C AF Resnick, SM Pham, DL Kraut, MA Zonderman, AB Davatzikos, C TI Longitudinal magnetic resonance imaging studies of older adults: A shrinking brain SO JOURNAL OF NEUROSCIENCE LA English DT Article DE magnetic resonance imaging; aging; brain volumes; longitudinal studies; gray matter loss; white matter loss ID WHITE-MATTER CHANGES; ALZHEIMERS-DISEASE; IN-VIVO; TEMPORAL-LOBE; AGING BRAIN; AGE; ATROPHY; IMAGES; MORPHOMETRY; TOMOGRAPHY AB Age-related loss of brain tissue has been inferred from cross-sectional neuroimaging studies, but direct measurements of gray and white matter changes from longitudinal studies are lacking. We quantified longitudinal magnetic resonance imaging (MRI) scans of 92 non-demented older adults (age 59-85 years at baseline) in the Baltimore Longitudinal Study of Aging to determine the rates and regional distribution of gray and white matter tissue loss in older adults. Using images from baseline, 2 year, and 4 year follow-up, we found significant age changes in gray (p<0.001) and white (p<0.001) volumes even in a subgroup of 24 very healthy elderly. Annual rates of tissue loss were 5.4 +/- 0.3, 2.4 +/- 0.4, and 3.1 +/- 0.4 cm(3) per year for total brain, gray, and white volumes, respectively, and ventricles increased by 1.4 +/- 0.1 cm(3) per year (3.7, 1.3, 2.4, and 1.2 cm(3), respectively, in very healthy). Frontal and parietal, compared with temporal and occipital, lobar regions showed greater decline. Gray matter loss was most pronounced for orbital and inferior frontal, cingulate, insular, inferior parietal, and to a lesser extent mesial temporal regions, whereas white matter changes were widespread. In this first study of gray and white matter volume changes, we demonstrate significant longitudinal tissue loss for both gray and white matter even in very healthy older adults. These data provide essential information on the rate and regional pattern of age-associated changes against which pathology can be evaluated and suggest slower rates of brain atrophy in individuals who remain medically and cognitively healthy. C1 NIA, Lab Personal & Cognit, Baltimore, MD 21224 USA. Johns Hopkins Univ, Dept Radiol, Baltimore, MD 21287 USA. RP Resnick, SM (reprint author), NIA, Lab Personal & Cognit, Box 03,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Zonderman, Alan B/0000-0002-6523-4778 NR 40 TC 607 Z9 612 U1 3 U2 36 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 15 PY 2003 VL 23 IS 8 BP 3295 EP 3301 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 671QH UT WOS:000182475200023 PM 12716936 ER PT J AU Myers, LJ Lowery, M O'Malley, M Vaughan, CL Heneghan, C Gibson, ASC Harley, YXR Sreenivasan, R AF Myers, LJ Lowery, M O'Malley, M Vaughan, CL Heneghan, C Gibson, ASC Harley, YXR Sreenivasan, R TI Rectification and non-linear pre-processing of EMG signals for cortico-muscular analysis SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE rectification; EMG; coherence; motor unit firing rate; surrogate data; model ID ISOMETRIC CONTRACTION; TIME-SERIES; MUSCLE; COHERENCE; SURROGATE; HUMANS; CONDUCTION; FREQUENCY; CORTEX AB Rectification of the electromyographic (EMG) signal is a commonly used pre-processing procedure that allows detection of significant coherence between EMG and measured cortical signals. However, despite its accepted and wide-spread use, no detailed analysis has been presented to offer insight into the precise function of rectification. We begin this paper with arguments based on single motor unit action potential (AP) trains to demonstrate that rectification effectively enhances the firing rate information of the signal. Enhancement is achieved by shifting the peak of the A-P spectrum toward the lower firing rate frequencies, whilst maintaining the firing rate spectra. A similar result is obtained using the analytic envelope of the signal extracted using the Hilbert transform. This argument is extended to simulated EMG signals generated using a published EMG model. Detection of firing rate frequencies is obtained using phase randomised surrogate data, where the original EMG power spectrum exceeds the averaged rectified surrogate spectra at integer multiples of firing rate frequencies. Model simulations demonstrate that this technique accurately determines grouped firing rate frequencies. Extraction of grouped firing rate frequencies prior to coherency analyses may further aid interpretation of significant cortico-muscular coherence findings. 2003 Elsevier Science B.V. All rights reserved. C1 Univ Coll Dublin, Dept Elect & Elect Engn, Dublin 4, Ireland. NW Univ, Sensory Motor Performance Program, Rehabil Inst Chicago, Chicago, IL USA. Univ Cape Town, Dept Human Biol, Cape Town, South Africa. NINDS, NIH, Bethesda, MD USA. RP Myers, LJ (reprint author), Univ Coll Dublin, Dept Elect & Elect Engn, Dublin 4, Ireland. RI Lowery, Madeleine/K-6153-2012 OI Lowery, Madeleine/0000-0001-6743-360X NR 26 TC 138 Z9 139 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD APR 15 PY 2003 VL 124 IS 2 BP 157 EP 165 DI 10.1016/S0165-0270(03)00004-9 PG 9 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 678XZ UT WOS:000182893100005 PM 12706845 ER PT J AU Jeffries, KJ Fritz, JB Braun, AR AF Jeffries, KJ Fritz, JB Braun, AR TI Words in melody: an H-2 O-15 PET study of brain activation during singing and speaking SO NEUROREPORT LA English DT Article DE brain; music; lateralization; right hemisphere; singing ID HUMAN AUDITORY-CORTEX; TEMPORAL-LOBE; MOTOR CORTEX; CEREBRAL-ACTIVITY; SPEECH PRODUCTION; MUSIC CORRELATE; PERCEPTION; LANGUAGE; MEMORY; MONKEY AB We used (H2O)-O-15 PET to characterize the interaction of words and melody by comparing brain activity measured while subjects spoke or sang the words to a familiar song. Relative increases in activity during speaking vs singing were observed in the left hemisphere, in classical perisylvian language areas including the posterior superior temporal gyrus, supramarginal gyrus, and frontal operculum, as well as in Rolandic cortices and putamen. Relative increases in activity during singing were observed in the right hemisphere: these were maximal in the right anterior superior temporal gyrus and contiguous portions of the insula; relative increases associated with singing were also detected in the right anterior middle temporal gyrus and superior temporal sulcus, medial and dorsolateral prefrontal cortices, mesial temporal cortices and cerebellum, as well as in Rolandic cortices and nucleus accumbens. These results indicate that the production of words in song is associated with activation of regions within right hemisphere areas that are not mirror-image homologues of left hemisphere perisylvian language areas, and suggest that multiple neural networks may be involved in different aspects of singing. Right hemisphere mechanisms may support the fluency-evoking effects of singing in neurological disorders such as stuttering or aphasia. C1 NIDCD, Language Sect, NIH, Bethesda, MD 20892 USA. RP Braun, AR (reprint author), NIDCD, Language Sect, NIH, Bldg 10,Room 5N118A, Bethesda, MD 20892 USA. EM braund@nidcd.nih.gov NR 46 TC 89 Z9 91 U1 3 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD APR 15 PY 2003 VL 14 IS 5 BP 749 EP 754 DI 10.1097/00001756-200304150-00018 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 678HB UT WOS:000182860100018 PM 12692476 ER PT J AU Hall, MC Shcherbakova, PV Fortune, JM Borchers, CH Dial, JM Tomer, KB Kunkel, TA AF Hall, MC Shcherbakova, PV Fortune, JM Borchers, CH Dial, JM Tomer, KB Kunkel, TA TI DNA binding by yeast Mlh1 and Pms1: implications for DNA mismatch repair SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ESCHERICHIA-COLI; MUTL HOMOLOGS; CROSSING-OVER; ATP BINDING; PROTEINS; GENE; IDENTIFICATION; HETERODIMER; HYDROLYSIS; MUTATIONS AB The yeast Mlh1-Pms1 heterodimer required for mismatch repair (MMR) binds to DNA. Here we map DNA binding to N-terminal fragments of Mlh1 and Pms1. We demonstrate that Mlh1 and Pms1 N-terminal domains (NTDs) independently bind to double-stranded and single-stranded DNA, in the absence of dimerization and with different affinities. Full-length Mlh1p alone, which can homodimerize, also binds to DNA. Substituting conserved positively charged amino acids in Mlh1 produces mutator phenotypes in a haploid yeast strain characteristic of reduced MMR. These substitutions strongly reduce DNA binding by the Mlh1 NTD and, to a lesser extent, they also reduce DNA binding by full-length Mlh1 and the Mlh1-Pms1 heterodimer. Replacement of a homologous Pms1 residue has a much smaller effect on mutation rate and does not reduce DNA binding. The results demonstrate that NTDs of yeast Mlh1 and Pms1 contain independent DNA binding sites and they suggest that the C-terminal region of Mlh1p may also contribute to DNA binding. The differential mutator effects and binding properties observed here further suggest that Mlh1 and Pms1 differ in their interactions with DNA. Finally, the results are consistent with the hypothesis that DNA binding by Mlh1 is important for MMR. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Kunkel, TA (reprint author), NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RI Tomer, Kenneth/E-8018-2013 NR 42 TC 31 Z9 33 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD APR 15 PY 2003 VL 31 IS 8 BP 2025 EP 2034 DI 10.1093/nar/gkg324 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 666DK UT WOS:000182161400007 PM 12682353 ER PT J AU Huang, Y McGillicuddy, E Weindel, M Dong, S Maraia, RJ AF Huang, Y McGillicuddy, E Weindel, M Dong, S Maraia, RJ TI The fission yeast TFIIB-related factor limits RNA polymerase III to a TATA-dependent pathway of TBP recruitment SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TRANSCRIPTION FACTOR IIB; INITIATION-FACTOR TFIIIB; BINDING PROTEIN; SCHIZOSACCHAROMYCES-POMBE; IN-VITRO; SACCHAROMYCES-CEREVISIAE; FLANKING SEQUENCES; GENE-EXPRESSION; MESSENGER-RNA; 2 STEPS AB The RNA polymerase (pol) III-transcribed (e.g. tRNA and 5S rRNA) genes of traditionally studied organisms rely on gene-internal promoters that precisely position the initiation factor, TFIIIB, on the upstream promoter-less DNA. This is accomplished by the ability of the TFIIIB subunit, TFIIB-related factor (Brf1), to make stable protein-protein interactions with TATA-binding protein (TBP) and place it on the promoter-less upstream DNA. Unlike traditional model organisms, Schizosaccharomyces pombe tRNA and 5S rRNA genes contain upstream TATA promoters that are required to program functional pol III initiation complexes. In this study we demonstrate that S.pombe (Sp)Brf does not form stable interactions with TBP in the absence of DNA using approaches that do reveal stable association of TBP and S.cerevisiae (Sc)Brf1. Gel mobility analyses demonstrate that a TBP-TATA DNA complex can recruit SpBrf to a Pol III promoter. Consistent with this, overproduction of SpBrf in S.pombe increases the expression of a TATA-dependent, but not a TATA-less, suppressor tRNA gene. Since previous whole genome analysis also revealed TATA elements upstream of tRNA genes in Arabidopsis, this pathway may be more widespread than appreciated previously. C1 NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Maraia, RJ (reprint author), NICHHD, Lab Mol Growth Regulat, NIH, Bld 6,Rm 416, Bethesda, MD 20892 USA. NR 57 TC 8 Z9 9 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD APR 15 PY 2003 VL 31 IS 8 BP 2108 EP 2116 DI 10.1093/nar/gkg301 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 666DK UT WOS:000182161400015 PM 12682361 ER PT J AU Zhang, ZP Teng, CT AF Zhang, ZP Teng, CT TI Phosphorylation of Kruppel-like factor 5 (KLF5/IKLF) at the CBP interaction region enhances its transactivation function SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CREB-BINDING-PROTEIN; TRANSCRIPTIONAL ACTIVATION DOMAIN; MOUSE LACTOFERRIN GENE; RNA-POLYMERASE-II; FACTOR EKLF; HISTONE ACETYLTRANSFERASES; IN-VIVO; HEMATOPOIETIC TRANSCRIPTION; STIMULATES TRANSCRIPTION; CHROMATIN DISRUPTION AB The Kruppel-like factor 5 (KLF5/IKLF) belongs to the Kruppel family of genes which bind GC-rich DNA elements and activate or repress their target genes in a promoter context and/or cellular environment-dependent manner. In the present study, we used the Gal4 fusion assay system to characterize the mechanism of transactivation by KLF5. We demonstrated that the transactivation function of KLF5 was enhanced by CREB-binding protein (CBP) and blocked by wild-type but not mutant E1A. Over expression of CBP reversed the inhibition effect of E1A. With various lengths of KLF5 fusion protein, the transactivation functions were localized to 156 amino acid residues at the N-terminal region and 133 amino acid residues adjacent to the Zn finger motif. We mapped the CBP and KLF5 interaction domain to the N-terminal region of CBP (amino acids 1-232) and the N-terminal region of KLF5 (amino acids 1-238) where one of the activation functions resides. The histone acetyltransferase (HAT) activity of CBP does not play a role in the transactivation function of KLF5 nor does it acetylate KLF5 in vitro. However, phosphorylation is important in KLF5 transactivation activity. Inhibition of protein kinase activity by H7 or calphostin C blocked both full-length and N-terminal fragment (amino acids 1-238) KLF5 activities. Mutation at a potential protein kinase C phosphorylation site within the CBP interaction domain of KLF5 reduces its transactivation function. Furthermore, using the GST pull-down approach, we showed that phosphorylation of KLF5 enhances its interaction with CBP. The results of the present study provide a mechanism for KLF5 transactivation function. C1 NIEHS, Gene Regulat Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Teng, CT (reprint author), NIEHS, Gene Regulat Sect, Reprod & Dev Toxicol Lab, NIH, POB 12233,MD E2-01, Res Triangle Pk, NC 27709 USA. NR 67 TC 51 Z9 53 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD APR 15 PY 2003 VL 31 IS 8 BP 2196 EP 2208 DI 10.1093/nar/gkg310 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 666DK UT WOS:000182161400024 PM 12682370 ER PT J AU Suer, S Misra, S Saidi, LF Hurley, JH AF Suer, S Misra, S Saidi, LF Hurley, JH TI Structure of the GAT domain of human GGA1: A syntaxin amino-terminal domain fold in an endosomal trafficking adaptor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID EAR HOMOLOGY DOMAIN; GAMMA-ADAPTIN; VHS DOMAINS; 3-DIMENSIONAL STRUCTURE; MEMBRANE-FUSION; BINDING-SITE; TRANS-GOLGI; PROTEIN; COMPLEX; FAMILY AB The Golgi-associated, gamma-adaptin homologous, ADP-ribosylation factor (ARF)-interacting proteins (GGAs) are adaptors that sort receptors from the trans-Golgi network into the endosomal/lysosomal pathway. The GGAs and TOM1 (GAT) domains of the GGAs are responsible for their ARF-dependent localization. The 2.4-Angstrom crystal structure of the GAT domain of human GGA1 reveals a three-helix bundle, with a long N-terminal helical extension that is not conserved in GAT domains that do not bind ARF. The ARF binding site is located in the N-terminal extension and is separate from the core three-helix bundle. An unanticipated structural similarity to the N-terminal domain of syntaxin 1 a was discovered, comprising the entire three-helix bundle. A conserved binding site on helices 2 and 3 of the GAT domain three-helix bundle is predicted to interact with coiled-coil-containing proteins. We propose that the GAT domain is descended from the same ancestor as the syntaxin la N-terminal domain, and that both protein families share a common function in binding coiled-coil domain proteins. C1 NIDDKD, Mol Biol Lab, US Dept HHS, NIH, Bethesda, MD 20892 USA. RP Hurley, JH (reprint author), NIDDKD, Mol Biol Lab, US Dept HHS, NIH, Bethesda, MD 20892 USA. OI Misra, Saurav/0000-0002-1385-8554 NR 52 TC 36 Z9 37 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 15 PY 2003 VL 100 IS 8 BP 4451 EP 4456 DI 10.1073/pnas.0831133100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 668RC UT WOS:000182306100023 PM 12668765 ER PT J AU Danilkovitch-Miagkova, A Duh, FM Kuzmin, I Angeloni, D Liu, SL Miller, AD Lerman, MI AF Danilkovitch-Miagkova, A Duh, FM Kuzmin, I Angeloni, D Liu, SL Miller, AD Lerman, MI TI Hyaluronidase 2 negatively regulates RON receptor tyrosine kinase and mediates transformation of epithelial cells by jaagsiekte sheep retrovirus SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MACROPHAGE-STIMULATING PROTEIN; LUNG-CANCER; TRUNCATED FORM; VIRUS; GENE; REGION; STK; IDENTIFICATION; ENCODES; GROWTH AB The candidate tumor-suppressor gene hyaluroniclase 2 (HYAL2) encodes a glycosylphosphatidylinositol-anchored cell-surface protein that serves as an entry receptor for jaagsiekte sheep retrovirus, a virus that causes contagious lung cancer in sheep that is morphologically similar to human bronchioloalveolar carcinoma. The viral envelope (Env) protein alone can transform cultured cells, and we hypothesized that Env could bind and sequester the HYAL2 receptor and thus liberate a potential oncogenic factor bound and negatively controlled by HYAL2. Here we show that the HYAL2 receptor protein is associated with the RON receptor tyrosine kinase (also called MST1R or Stk in the mouse), rendering it functionally silent. In human cells expressing a jaagsiekte sheep retrovirus Env transgene, the Env protein physically associates with HYAL2. RON liberated from the association with HYAL2 becomes functionally active and consequently activates the Akt and mitogen-activated protein kinase pathways leading to oncogenic transformation of immortalized human bronchial epithelial cells. We find activated RON in a subset of human bronchioloalveolar carcinoma tumors, suggesting RON involvement in this type of human lung cancer. C1 NCI, Immunobiol Lab, Ctr Canc Res, Frederick, MD 21702 USA. NCI, Basic Res Program, Sci Applicat Int Corp SAIC Frederick Inc, Frederick, MD 21702 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. RP Danilkovitch-Miagkova, A (reprint author), PPD Dev, Dept Immunochem, 2244 Dabney Rd, Richmond, VA 23230 USA. RI Liu, Shan-Lu/L-5923-2016; OI Liu, Shan-Lu/0000-0003-1620-3817; Miller, Dusty/0000-0002-3736-3660 FU NCI NIH HHS [N01-CO-12400, N01CO12400, N01-CO-56000]; NHLBI NIH HHS [HL54881, P50 HL054881]; NIDDK NIH HHS [P30 DK047754, DK47754] NR 32 TC 69 Z9 78 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 15 PY 2003 VL 100 IS 8 BP 4580 EP 4585 DI 10.1073/pnas.0837136100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 668RC UT WOS:000182306100045 PM 12676986 ER PT J AU Liang, TB Spence, J Liu, LX Strother, WN Chang, HW Ellison, JA Lumeng, L Li, TK Foroud, T Carr, LG AF Liang, TB Spence, J Liu, LX Strother, WN Chang, HW Ellison, JA Lumeng, L Li, TK Foroud, T Carr, LG TI alpha-Synuclein maps to a quantitative trait locus for alcohol preference and is differentially expressed in alcohol-preferring and -nonpreferring rats SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MESSENGER-RNA STABILITY; CENTRAL-NERVOUS-SYSTEM; PARKINSONS-DISEASE; 3'-UNTRANSLATED REGION; NUCLEUS-ACCUMBENS; LEWY BODIES; DOPAMINE; PROTEIN; GENES; DEPENDENCE AB Total gene expression analysis (TOGA) was used to identify genes that are differentially expressed in brain regions between the alcohol-naive, inbred alcohol-preferring (iP), and -nonpreferring (NIP) rats. alpha-Synuclein, expressed at >2-fold higher levels in the hippocampus of the iP than the iNP rat, was prioritized for further study. In situ hybridization was used to determine specific brain regions and cells expressing alpha-synuclein in the iP and iNP rats. Similar to alpha-synuclein mRNA levels, protein levels in the hippocampus were higher in iP rats than iNP rats. Higher protein levels were also observed in the caudate putamen of iP rats compared with iNP rats. Sequence analysis identified two single nucleotide polymorphisms in the 3' UTR of the cDNA. The polymorphism was used to map the gene, by using recombination-based methods, to chromosome 4, within a quantitative trait locus for alcohol consumption that was identified in the iP and iNP rats. A nucleotide exchange in the iNP 3' UTR reduced expression of the luciferase reporter gene in SK-N-SH neuroblastoma cells. These results suggest that differential expression of the alpha-synuclein gene may contribute to alcohol preference in the iP rats. C1 Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Pharmacol, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. NIAAA, NIH, Bethesda, MD 20892 USA. Digital Gene Technol Inc, La Jolla, CA 92037 USA. RP Carr, LG (reprint author), Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA. FU NIAAA NIH HHS [AA10707, AA00285, AA07611, P50 AA007611, P60 AA007611, R01 AA010707] NR 44 TC 91 Z9 96 U1 3 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 15 PY 2003 VL 100 IS 8 BP 4690 EP 4695 DI 10.1073/pnas.0737182100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 668RC UT WOS:000182306100064 PM 12665621 ER PT J AU Jongeneel, CV Iseli, C Stevenson, BJ Riggins, GJ Lal, A Mackay, A Harris, RA O'Hare, MJ Neville, AM Simpson, AJG Strausberg, RL AF Jongeneel, CV Iseli, C Stevenson, BJ Riggins, GJ Lal, A Mackay, A Harris, RA O'Hare, MJ Neville, AM Simpson, AJG Strausberg, RL TI Comprehensive sampling of gene expression in human cell lines with massively parallel signature sequencing SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID 3 ABUNDANCE CLASSES; MESSENGER-RNA; HUMAN TRANSCRIPTOME; HETEROGENEITY; TAGS; ANATOMY; GENOME AB Whereas information is rapidly accumulating about the structure and position of genes encoded in the human genome, less is known about the complexity and relative abundance of their expression in individual human cells and tissues. Here, we describe the characteristics of the transcriptomes of two cultured cell lines, HB4a (normal breast epithelium) and HCT-116 (colon adenocarcinoma), using massively parallel signature sequencing (MPSS). We generated in excess of 107 short signature sequences per cell line, thus providing a comprehensive snapshot of gene expression, within the technical limitations of the method. The number of genes expressed at one copy per cell or more in either of the lines was estimated to be between 10,000 and 15,000. The vast majority of the transcripts found in these cells can be mapped to known genes and their polyadenylation variants. Among the genes that could be identified from their signature sequences, approximate to8,500 were expressed by both cell lines, whereas 6,000 showed cellular specificity. Taking into account sequence tags that map uniquely to the genome but not to known transcripts, overall the data are consistent with an upper limit of 17,000 for the total number of genes expressed at more than one copy per cell in one or both of the two cell lines examined. C1 Ludwig Inst Canc Res, Off Informat Technol, CH-1066 Epalinges, Switzerland. Swiss Inst Bioinformat, CH-1066 Epalinges, Switzerland. Ludwig Inst Canc Res, New York, NY 10012 USA. NCI, Off Canc Genom, Bethesda, MD 20892 USA. London UCL Branch, Ludwig Inst Canc Res, London W1W 7BS, England. Duke Univ, Sch Med, Dept Pathol, Durham, NC 27710 USA. RP Jongeneel, CV (reprint author), Ludwig Inst Canc Res, Off Informat Technol, 155 Chemin Boveresses, CH-1066 Epalinges, Switzerland. RI Jongeneel, Cornelis/B-2135-2012; OI Iseli, Christian/0000-0002-2296-2863 NR 18 TC 83 Z9 85 U1 1 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 15 PY 2003 VL 100 IS 8 BP 4702 EP 4705 DI 10.1073/pnas.0831040100 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 668RC UT WOS:000182306100066 PM 12671075 ER PT J AU Radu, RA Mata, NL Nusinowitz, S Liu, XR Sieving, PA Travis, GH AF Radu, RA Mata, NL Nusinowitz, S Liu, XR Sieving, PA Travis, GH TI Treatment with isotretinoin inhibits lipofuscin accumulation in a mouse model of recessive Stargardt's macular degeneration SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RETINAL-PIGMENT EPITHELIUM; OCULAR AGE PIGMENT; RIM PROTEIN; FUNDUS FLAVIMACULATUS; 13-CIS-RETINOIC ACID; NIGHT BLINDNESS; BINDING PROTEIN; NEURAL RETINA; A-WAVE; ABCR AB Recessive Stargardt's macular degeneration is an inherited blinding disease of children caused by mutations in the ABCR gene. The primary pathologic defect in Stargardt's disease is accumulation of toxic lipofuscin pigments such as N-retinylidene-N-retinylethanolamine (A2E) in cells of the retinal pigment epithelium. This accumulation appears to be responsible for the photoreceptor death and severe visual loss in Stargardt's patients. Here, we tested a therapeutic strategy to inhibit lipofuscin accumulation in a mouse model of recessive Stargardt's disease. Isotretinoin (Accutane) has been shown to slow the synthesis of 11-cis-retinaldehyde and regeneration of rhodopsin by inhibiting 11-cis-retinol dehydrogenase in the visual cycle. Light activation of rhodopsin results in its release of all-trans-retinaldehyde, which constitutes the first reactant in A2E biosynthesis. Accordingly, we tested the effects of isotretinoin on lipofuscin accumulation in abcr(-/-) knockout mice. Isotretinoin blocked the formation of A2E biochemically and the accumulation of lipofuscin pigments by electron microscopy. We observed no significant visual loss in treated abcr(-/-) mice by electroretinography. Isotretinoin also blocked the slower, age-dependent accumulation of lipofuscin in wild-type mice. These results corroborate the proposed mechanism of A2E biogenesis. Further, they suggest that treatment with isotretinoin may inhibit lipofuscin accumulation and thus delay the onset of visual loss in Stargardt's patients. Finally, the results suggest that isotretinoin may be an effective treatment for other forms of retinal or macular degeneration associated with lipofuscin accumulation. C1 Univ Calif Los Angeles, Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA. Univ Texas, SW Med Ctr, Ctr Basic Neurosci, Dallas, TX 75235 USA. NEI, NIH, Bethesda, MD 20892 USA. RP Travis, GH (reprint author), Univ Calif Los Angeles, Sch Med, Jules Stein Eye Inst, 100 Stein Plaza, Los Angeles, CA 90095 USA. NR 40 TC 130 Z9 133 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 15 PY 2003 VL 100 IS 8 BP 4742 EP 4747 DI 10.1073/pnas.0737855100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 668RC UT WOS:000182306100073 PM 12671074 ER PT J AU Itoh, Y Esaki, T Shimoji, K Cook, M Law, MJ Kaufman, E Sokoloff, L AF Itoh, Y Esaki, T Shimoji, K Cook, M Law, MJ Kaufman, E Sokoloff, L TI Dichloroacetate effects on glucose and lactate oxidation by neurons and astroglia in vitro and on glucose utilization by brain in vivo SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PYRUVATE-DEHYDROGENASE; AEROBIC GLYCOLYSIS; ENERGY-METABOLISM; PRIMARY CULTURES; ASTROCYTES; ACTIVATION; RAT; MECHANISM; CORTEX; ACIDS AB Neuronal cultures in vitro readily oxidized both D-[C-14]glucose and L-[C-14] lactate to (CO2)-C-14, whereas astroglial cultures oxidized both substrates sparingly and metabolized glucose predominantly to lactate and released it into the medium. [C-14]Glucose oxidation to (CO2)-C-14 varied inversely with unlabeled lactate concentration in the medium, particularly in neurons, and increased progressively with decreasing lactate concentration. Adding unlabeled glucose to the medium inhibited [C-14]lactate oxidation to (CO2)-C-14 only in astroglia but not in neurons, indicating a kinetic preference in neurons for oxidation of extracellular lactate over intracellular pyruvate/ lactate produced by glycolysis. Protein kinase-catalyzed phosphorylation inactivates pyruvate dehydrogenase (PDH), which regulates pyruvate entry into the tricarboxylic acid cycle. Dichloroacetate inhibits this kinase, thus enhancing PDH activity. In vitro dichloroacetate stimulated glucose and lactate oxidation to CO2 and reduced lactate release mainly in astroglia, indicating that limitations in glucose and lactate oxidation by astroglia may be due to a greater balance of PDH toward the inactive form. To assess the significance of astroglial export of lactate to neurons in vivo, we attempted to diminish this traffic in rats by administering dichloroacetate (50 mg/kg) intravenously to stimulate astroglial lactate oxidation and then examined the effects on baseline and functionally activated local cerebral glucose utilization (ICMRglc,). Dichloroacetate raised baseline ICMRglc throughout the brain and decreased the percent increases in ICMRglc evoked by functional activation. These studies provide evidence in support of the compartmentalization of glucose metabolism between astroglia and neurons but indicate that the compartmentalization may be neither complete nor entirely obligatory. C1 NIMH, Cerebral Metab Lab, NIH, Bethesda, MD 20892 USA. NIH, Positron Emiss Tomog Dept, Ctr Clin, Bethesda, MD 20892 USA. RP Sokoloff, L (reprint author), NIMH, Cerebral Metab Lab, NIH, Bldg 36, Bethesda, MD 20892 USA. NR 28 TC 133 Z9 138 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 15 PY 2003 VL 100 IS 8 BP 4879 EP 4884 DI 10.1073/pnas.0831078100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 668RC UT WOS:000182306100096 PM 12668764 ER PT J AU Fitch, RW Xiao, YX Kellar, KJ Daly, JW AF Fitch, RW Xiao, YX Kellar, KJ Daly, JW TI Membrane potential fluorescence: A rapid and highly sensitive assay for nicotinic receptor channel function SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BLASTOMA CELL-LINE; ACETYLCHOLINE-RECEPTORS; CHOLINERGIC RECEPTORS; NEUROBLASTOMA-CELLS; CLONAL LINE; BINDING; CA2+; ELECTROPHYSIOLOGY; DESENSITIZATION; INDICATORS AB Seven cell lines expressing native and transfected nicotinic receptor subtypes were evaluated functionally by using fluorescent assays based on membrane potential and calcium dynamics with "no-wash" dye systems. Both assays provided the same rank orders of potency for (+/-)-epibatidine, 2S-(-)-nicotine, 7R,9S-(-)cytisine, and 1,1-dimethyl-4-phenylpiperazinium in a cell line expressing rat alpha3beta4 receptors. Nicotinic antagonists mecamylamine and dihydro-beta-erythroidine inhibited responses in both assays. Both agonist and antagonist activity were assessed within the same experiment. Agonists seemed more potent in the membrane potential assay than in the calcium assay, whereas the converse was true for antagonists. The membrane potential assay afforded robust responses in K-177 cells expressing human alpha4beta2 receptors, in IMR-32 and SH-SY5Y cells expressing human ganglionic receptors, and in TE-671 cells expressing human neuromuscular receptors. These lines gave weak to modest calcium responses. Moreover, membrane potential responses were obtained in cell lines expressing rat alpha4beta2 and alpha4beta4 receptors, which were devoid of calcium responses. Thus, membrane potential serves as a sensitive measure of nicotinic activity, and the resulting depolarization may be as important as calcium in cell signaling. C1 NIDDKD, Bioorgan Chem Lab, Sect Pharmacodynam, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Sch Med, Dept Pharmacol, Washington, DC 20057 USA. RP Daly, JW (reprint author), NIDDKD, Bioorgan Chem Lab, Sect Pharmacodynam, NIH, Bethesda, MD 20892 USA. NR 41 TC 79 Z9 80 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 APR 15 PY 2003 VL 100 IS 8 BP 4909 EP 4914 DI 10.1073/pnas.0630641100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 668RC UT WOS:000182306100101 PM 12657731 ER PT J AU Zudaire, E Cuttitta, F Martinez, A AF Zudaire, E Cuttitta, F Martinez, A TI Regulation of pancreatic physiology by adrenomedullin and its binding protein SO REGULATORY PEPTIDES LA English DT Review DE complement factor H; CRLR; glucose homeostasis; diabetes; insulinoma ID GENE-RELATED-PEPTIDE; ACTIVITY-MODIFYING PROTEINS; RECEPTOR-LIKE RECEPTOR; TERMINAL 20 PEPTIDE; DEPENDENT DIABETES-MELLITUS; COMPLEMENT FACTOR-H; TUMOR-CELL LINES; PLASMA ADRENOMEDULLIN; INSULIN-SECRETION; IMMUNOREACTIVE ADRENOMEDULLIN AB Adrenomedullin (AM) is a 52 amino acid, multifunctional hormone. It is expressed in many tissues of the human body including the pancreas, where it is mainly localized to the periphery of the islets of Langerhans and specifically to the pancreatic polypeptide-expressing cells. The AM receptor, a complex formed by calcitonin receptor-like receptor,(CRLR) and receptor activity-modifying proteins (RAMPs), and the recently discovered AM-binding protein, complement factor H (fH), are expressed in the insulin-producing P-cells. The colocalization of these key elements of the AM system in the endocrine portion of the pancreas implicates AM in the control of both normal and altered pancreatic physiologies. AM inhibits insulin secretion both in vitro (isolated rat islets) and in vivo (oral glucose tolerance test in rats) in a dose-dependent manner. The addition of fH to isolated rat islets produces a further reduction of insulin secretion in the presence of AM. Furthermore, AM is elevated in plasma from patients with pancreatic dysfunctions such as type 1 or type 2 diabetes and insulinoma. Using a diabetic model in rats, we have shown that AM increases circulating glucose levels whereas a blocking monoclonal antibody against AM has the opposite effect and improves postprandial recovery. Such experimental evidence implicates AM as a fundamental factor in maintaining insulin homeostasis and normoglycemia, and suggests the implication of AM as a possible causal agent in diabetes. Further investigation focused on the development of blocking agents for AM could result in new treatments for pancreatic AM-related disorders. Published by Elsevier Science B.V. C1 NCI, Dept Cell & Canc Biol, NIH, Bethesda, MD 20892 USA. RP Martinez, A (reprint author), NCI, Dept Cell & Canc Biol, NIH, 9000 Rockville Pike,Bldg 10,Room 13N262, Bethesda, MD 20892 USA. RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 108 TC 21 Z9 25 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD APR 15 PY 2003 VL 112 IS 1-3 BP 121 EP 130 DI 10.1016/S0167-0115(03)00030-2 PG 10 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 669LP UT WOS:000182353000016 PM 12667633 ER PT J AU Zudaire, E Martinez, A Cuttitta, F AF Zudaire, E Martinez, A Cuttitta, F TI Adrenomedullin and cancer SO REGULATORY PEPTIDES LA English DT Review ID GENE-RELATED-PEPTIDE; PROTEIN-COUPLED RECEPTOR; INDUCIBLE FACTOR-I; ANGIOGENIC FACTOR ADRENOMEDULLIN; ADRENOCORTICAL CARCINOMA-CELLS; POSSIBLE PROMOTION MECHANISM; ACTIVITY-MODIFYING PROTEINS; CEREBRAL-ARTERY OCCLUSION; HUMAN NEUROBLASTOMA-CELLS; AORTIC ENDOTHELIAL-CELLS AB Adrenomedullin (AM) is a pluripotent hormone with structural similarities to calcitonin gene-related peptide (CGRP), which is expressed by many tissues in the body and shows a remarkable range of effects mediated by paracrine/autocrine and possibly endocrine mechanisms. AM has been implicated as a mediator of several pathologies such as cardiovascular and renal disorders, sepsis, inflammation, diabetes and cancer, among others. AM is expressed in a variety of tumors where it aggravates several of the molecular and physiological features of malignant cells. AM has been shown to be a mitogenic factor stimulating growth in several cancer types and to encourage a more aggressive tumor phenotype. In addition, AM is an apoptosis survival factor for cancer cells and an indirect suppressor of the immune response through its binding protein, complement factor H, and regulation in expression of cytokines. AM plays an important role in environments subjected to low oxygen tensions, which is a typical feature in the proximity of solid tumors. Under these conditions, AM is upregulated through a hypoxia-inducible factor 1 (HIF-1)-dependent pathway and acts as a potent angiogenic factor promoting neovascularization. The collective findings brought together over the last years place AM as a major regulator of carcinogenesis-tumor progression and identifies its autocrine loop as a putative target for developing new strategies against human cancers. Published by Elsevier Science B.V. C1 NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA. RP Zudaire, E (reprint author), NCI, Cell & Canc Biol Branch, NIH, Bldg 10,Room 13N262, Bethesda, MD 20892 USA. RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 114 TC 104 Z9 116 U1 4 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD APR 15 PY 2003 VL 112 IS 1-3 BP 175 EP 183 DI 10.1016/S0167-0115(03)00037-5 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 669LP UT WOS:000182353000023 PM 12667640 ER PT J AU Yang, Q Tofler, GH Cupples, LA Larson, MG Feng, DL Lindpaintner, K Levy, D D'Agostino, RB O'Donnell, CJ AF Yang, Q Tofler, GH Cupples, LA Larson, MG Feng, DL Lindpaintner, K Levy, D D'Agostino, RB O'Donnell, CJ TI A genome-wide search for genes affecting-circulating fibrinogen levels in the Framingham Heart Study SO THROMBOSIS RESEARCH LA English DT Article DE genome-wide scan; genetic linkage; fibrinogen; HindIII beta-148; cardiovascular disease; variance component analysis; Framingham Heart Study ID TRAIT LINKAGE ANALYSIS; PLASMA-FIBRINOGEN; BETA-FIBRINOGEN; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; RISK-FACTORS; POLYMORPHISMS; ASSOCIATION; LOCI; ATHEROSCLEROSIS AB Introduction: Circulating levels of fibrinogen are associated with atherosclerosis and predict future coronary heart disease and stroke. Levels of fibrinogen are correlated among family members, suggesting a heritable component. Variants of the beta-fibrinogen gene subunit on 4q28 are associated with fibrinogen levels but explain only a small proportion of the total genetic variability. It remains unknown what role, if any, is played by other genetic variants in the inter-individual variability in levels of fibrinogen in the general population. Materials and methods: We conducted a 10-cM spaced genome-wide scan using 402 original cohort subjects and 1193 offspring subjects from 330 extended families of the Framingham Heart Study. Heritability and linkage analyses were carried out using variance component methods. Regression analyses were performed to adjust for traditional risk factors and HindIII beta-148 genotypes. Results and Discussions: The total heritability was estimated as 0.24. The highest and second highest LOD scores of linkage were found on chromosomes 2 (LOD= 1.5 at 243 cM) and 10 (LOD = 2.4 at 87 cM) using only offspring subjects in the analysis, and on chromosomes 2 (LOD = 2.1 at 242 cM) and 10(LOD = 1.4 at 86 cM), 17 (LOD = 1.4 at 96 cM) and 20 (LOD = 1.4 at 80 cM) using both original cohort and offspring. These results suggest that there may be influential genetic regions on these chromosomes. While no linkage with genome-wide significance was detected, further research to confirm our findings is warranted. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Royal N Shore Hosp, Sydney, NSW, Australia. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Max Delbruck Ctr Mol Med, Berlin, Germany. F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Yang, Q (reprint author), Boston Univ, Sch Publ Hlth, Dept Biostat, 715 Albany St,T-4E, Boston, MA 02118 USA. RI Yang, Qiong/G-5438-2014; OI Yang, Qiong/0000-0002-3658-1375; Cupples, L. Adrienne/0000-0003-0273-7965; Larson, Martin/0000-0002-9631-1254 NR 29 TC 21 Z9 22 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PD APR 15 PY 2003 VL 110 IS 1 BP 57 EP 64 DI 10.1016/S0049-3848(03)00288-3 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 708WV UT WOS:000184593900010 PM 12877910 ER PT J AU Raju, R Malloy, A Shah, T Smith, R Oaks, M Hosenpud, JD AF Raju, R Malloy, A Shah, T Smith, R Oaks, M Hosenpud, JD TI Alloimmune induction of endothelial cell-derived interferon-gamma-inducible chemokines SO TRANSPLANTATION LA English DT Article ID ALLOGRAFT-REJECTION; FRACTALKINE AB Background. The interaction between host lymphocytes and endothelial cells on the transplanted organ is believed to play an important role in acute and chronic graft rejection. Trafficking and recruitment of lymphocytes to the site of inflammation is known to be controlled by several cytokines and chemokines. It is unclear whether endothelial cells themselves can be a source of inflammatory chemoattractant molecules on alloinunune induction. Methods. Using a semiquantitative polymerase chain reaction method, the authors analyzed the expression of chemokine mRNA coding for interferon (IFN)-gamma-induced protein 10 (IP-10) and monokine induced by IFN-gamma (Mig) in a pool of human aortic endothelial cells. Both of these chemokines are known to be induced by IFN-gamma. Endothelial cell-derived chemokine mRNA was assayed at rest, after IFN-gamma activation, and after co-culture with allogeneic peripheral blood mononuclear cells (PBMC) from normal blood donors with and without a monoclonal antibody to IFN-gamma. Finally, protein release into the media was assayed using an enzyme-linked immunosorbent assay to IP-10. Results. Mig and IP-10 were expressed in human endothelial cells both after IFN-gamma treatment and after PBMC co-culture. Furthermore, the expression of both of these endothelial cell-derived chemokines was dependent on IFN-gamma because PBMC-induced expression was blocked with anti-IFN-gamma. IP-10 levels in the endothelial cell supernatant increased from a baseline of 13.4 +/- 10.8 pg/mL to 299.5 +/- 13.4 pg/mL (P<0.0001) with exposure to PBMC and was likewise inhibited by anti-IFN-gamma A-b (33.8 +/- 17.8 pg/mL). Conclusions. Vascular endothelial cells are capable of producing inflammatory chemokines when activated and potentially serve to amplify the allogeneic response. C1 St Lukes Hosp, Chron Reject Lab, Milwaukee, WI USA. RP Raju, R (reprint author), NIH, Bldg 10,Room 4N252,10 Ctr Dr, Bethesda, MD 20892 USA. RI Raju, Raghavan/E-9219-2011 FU NHLBI NIH HHS [HL 56747] NR 12 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 2003 VL 75 IS 7 BP 1072 EP 1074 DI 10.1097/01.TP.0000058349.08707.E6 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 669EG UT WOS:000182338500034 PM 12698106 ER PT J AU Agrawal, A Lingappa, JR Jabbar, A Agrawal, S Leppla, SH Quinn, C Pulendran, B AF Agrawal, A Lingappa, JR Jabbar, A Agrawal, S Leppla, SH Quinn, C Pulendran, B TI Anthrax toxin, lethal factor impairs dendritic cells and adaptive immunity SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Emory Univ, Vaccine Ctr, Atlanta, GA 30329 USA. Ctr Dis Control, Div Bacterial & Mycot Dis, Atlanta, GA 30333 USA. Emory Univ, Atlanta, GA 30322 USA. NIH, NIDCR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C15 EP C16 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000074 ER PT J AU Ahmadzadeh, M Patke, D Bingaman, AW Farber, DL AF Ahmadzadeh, M Patke, D Bingaman, AW Farber, DL TI Generation and maintenance of CD4 T cell memory in the absence of cognate antigen SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIH, NCI, Bethesda, MD 20892 USA. Univ Maryland, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C245 EP C245 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001140 ER PT J AU Anderson, SK Saleh, AM AF Anderson, SK Saleh, AM TI Stochastic switches control Ly49 gene expression SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. NCI, Expt Immunol Lab, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C99 EP C100 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000461 ER PT J AU Baskar, S Kwak, LW AF Baskar, S Kwak, LW TI T cell responses against human B cell tumor-associated antigens SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NCI Frederick, Expt Transplantat & Immunol Branch, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C327 EP C327 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001529 ER PT J AU Blumenkron, F Slota, R Lipsky, PE Grammer, AC AF Blumenkron, F Slota, R Lipsky, PE Grammer, AC TI Bidirectional modulatory influences of CD154/CD40-ligand expressed on the surface of activated lymphocytes during T cell-B cell collaboration SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIAMS, Cell Biol Grp B, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C214 EP C215 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000994 ER PT J AU Borrego, F Sanni, TB Coligan, JE AF Borrego, F Sanni, TB Coligan, JE TI Lateral mobility of CD94/NKG2A receptors on the cell surface SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIH, NIAID, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C317 EP C317 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001481 ER PT J AU Boyaka, PN Tafaro, A Fischer, R Leppla, SH Jackson, RJ Fujihashi, K McGhee, JR AF Boyaka, PN Tafaro, A Fischer, R Leppla, SH Jackson, RJ Fujihashi, K McGhee, JR TI Neutralizing antibodies and T helper cell responses following nasal immunization with anthrax protective antigen SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Univ Alabama, Birmingham, AL 35294 USA. NIH, NIAID, Microbial Pathogenesis Sect, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C320 EP C320 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001495 ER PT J AU Brescia, AC Thurber, DB Hurt, EM Phillips, TM Young, HA Staudt, LM Lipsky, PE Grammer, AC AF Brescia, AC Thurber, DB Hurt, EM Phillips, TM Young, HA Staudt, LM Lipsky, PE Grammer, AC TI Analysis of the relationship between the degree of CD40 receptor occupancy on human B cells and patterns of gene expression SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIAMS, Cell Biol Grp B, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NIH, Ultramicro Analyt Immunochem Resource, OD, Bethesda, MD 20892 USA. NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C262 EP C262 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001221 ER PT J AU Candon, S McHugh, R Foucras, G Mage, M Natarajan, K Schevach, EE Margulies, DH AF Candon, S McHugh, R Foucras, G Mage, M Natarajan, K Schevach, EE Margulies, DH TI A Th2 transgenic model of autoimmune gastritis SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RI Margulies, David/H-7089-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C274 EP C274 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001277 ER PT J AU Caspi, RR Avichezer, D Chan, CC Mattapallil, MJ Raber, JM Wiggert, B Liou, GI AF Caspi, RR Avichezer, D Chan, CC Mattapallil, MJ Raber, JM Wiggert, B Liou, GI TI A major role for central selection mechanisms in setting the threshold of autoimmune responsiveness to an immunologicallly privileged retinal antigen SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Med Coll Georgia, Immunol Lab, NEI, NIH, Atlanta, GA USA. NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NEI, VRB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C175 EP C175 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000811 ER PT J AU Chi, AWS Kole, HK Bolland, S AF Chi, AWS Kole, HK Bolland, S TI Hyper responsiveness of mature T cells in SHIP deficient mice SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIAID, Autoimmun & Funct Genomics Sect, LIG, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C223 EP C223 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001035 ER PT J AU Cho, JA Yeo, DJ Jung, DS Son, HY Ko, JK Lee, MJ Cho, SH Kim, CW AF Cho, JA Yeo, DJ Jung, DS Son, HY Ko, JK Lee, MJ Cho, SH Kim, CW TI Tumor-derived exosomes as a vehicle of target immunogens SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Tumor Immun Med Res Ctr, Dept Pathol, Seoul 110799, South Korea. Canc Res Inst, Seoul 110799, South Korea. NIH, Dept Pathol, Washington, DC USA. iNtRON Biotechnol, Dept Pathol, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C123 EP C123 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000569 ER PT J AU Coligan, JE Maasho, K Borrego, F Lieto, LD AF Coligan, JE Maasho, K Borrego, F Lieto, LD TI Human CD94 gene expression : Dual promoters differing in IL-2 responsiveness, alternative transcripts and post transcriptional regulation SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIAID, LAD, RCBS, DIR,NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C97 EP C98 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000452 ER PT J AU Criado, G Wange, RW Madrenas, J AF Criado, G Wange, RW Madrenas, J TI Superantigen stimulation reveals the contribution of Lck to negative regulation of T cell activation SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 John P Robarts Res Inst, London, ON N6A 5K8, Canada. NIA, Cellular & Mol Immunol Lab, NIH, Baltimore, MD 21224 USA. Univ Western Ontario, London, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C224 EP C224 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001039 ER PT J AU de Coelho, V Rangel, L Radmacher, M Cheadle, C Becker, K Morin, P Westin, E Nagel, J Taub, DD AF de Coelho, V Rangel, L Radmacher, M Cheadle, C Becker, K Morin, P Westin, E Nagel, J Taub, DD TI Gene expression profile and architectural changes within the aging thymus: Possible role for differentiating preadipocytes during the involution process SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. Kenyon Coll, Gambier, OH 43022 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C7 EP C7 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000032 ER PT J AU Dwivedi, S Chang, J Raben, N Collins, B Nagaraju, K Plotz, P AF Dwivedi, S Chang, J Raben, N Collins, B Nagaraju, K Plotz, P TI Liver and skeletal muscle cells are differentially susceptible to MHC class I over-expression SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIAMS, Arthrit & Rheumat Branch, NIH, Ctr Clin, Bethesda, MD 20892 USA. Johns Hopkins Sch Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C38 EP C38 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000179 ER PT J AU Faeder, JR Hlavacek, WS Blinov, ML Redondo, A Wofsy, C Reischl, I Metzger, H Goldstein, B AF Faeder, JR Hlavacek, WS Blinov, ML Redondo, A Wofsy, C Reischl, I Metzger, H Goldstein, B TI Mathematical modeling of early events in Fc epsilon RI-mediated signaling SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Los Alamos Natl Lab, Los Alamos, NM 87545 USA. Los Alamos Natl Lab, Theoret Chem & Mol Phys Grp, Los Alamos, NM USA. NIH, Arthritis & Rheumatism Branch, NIAMS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C15 EP C15 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000073 ER PT J AU Fann, M Catalfamo, M Li, MY Henkart, P Weng, NP AF Fann, M Catalfamo, M Li, MY Henkart, P Weng, NP TI General and differential gene expression profiles of human naive, effector, and memory CD8+T cells SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIA, NIH, Baltimore, MD 21224 USA. EIB, NCI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C243 EP C243 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001132 ER PT J AU Feng, CG Collazo-Custodio, C Cheever, A Taylor, G Sher, A AF Feng, CG Collazo-Custodio, C Cheever, A Taylor, G Sher, A TI Mice deficient in LRG47, an IFN-g-induced GTP-binding protein, display increased susceptibility to mycobacterial infection associated with profound lymphopenia SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Duke Univ, Ctr Study Aging & Human Dev, Durham, NC USA. Duke Univ, Dept Immunol, Durham, NC USA. Duke Univ, Dept Med, Durham, NC USA. NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C154 EP C154 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000712 ER PT J AU Fischer, RT Sohn, HW Longo, N Illei, G Pierce, S Lipsky, PE Grammer, A AF Fischer, RT Sohn, HW Longo, N Illei, G Pierce, S Lipsky, PE Grammer, A TI Circulating anergic B cells in the periphery of active SLE patients: functional and phenotypic characterization SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 BCBG, NIAMS, NIH, Bethesda, MD 20892 USA. NIAID, Bethesda, MD 20892 USA. NIAMSD, NIAMS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C187 EP C187 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000867 ER PT J AU Foster, MH Brady, GF Lobenhofer, EK Clark, AG AF Foster, MH Brady, GF Lobenhofer, EK Clark, AG TI Unique gene expression patterns in MRL and B6 tolerant B cells revealed by microarray SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Duke Univ, Durham, NC 27705 USA. Durham VAMC, Durham, NC 27705 USA. NIEHS, Natl Ctr Toxicogenom, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C180 EP C180 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000833 ER PT J AU Gagnon, SJ Biddison, WE Turner, RV Cohen, CJ AF Gagnon, SJ Biddison, WE Turner, RV Cohen, CJ TI Tax peptide/HLA-A2-specific fabs and T cell receptors regcognize similar structural features on HLA-A2 SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NINDS, Neuroimmunol Branch, Mol Immunol Sect, NIH, Bethesda, MD 20892 USA. Technion Israel Inst Technol, Fac Biol, Haifa, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C122 EP C122 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000562 ER PT J AU Gonzalez-Espinosa, C Odom, S Olivera, A Hobson, JP Martinez, MEC Oliveira-dos-Santos, A Barra, L Spiegel, S Penninger, J Rivera, J AF Gonzalez-Espinosa, C Odom, S Olivera, A Hobson, JP Martinez, MEC Oliveira-dos-Santos, A Barra, L Spiegel, S Penninger, J Rivera, J TI Weak stimulation of the high affinity IgE receptor on mast cells causes preferential signaling and induction of selected lymphokines. SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 CINVESTAV Zona Sur, Mexico City 14330, DF, Mexico. NIAMS, Bethesda, MD USA. VCU, Richmond, VA USA. IMB, Vienna, Austria. RI Penninger, Josef/I-6860-2013 OI Penninger, Josef/0000-0002-8194-3777 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C11 EP C11 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000051 ER PT J AU Grammer, AC Slota, R Fischer, R Gur, H Girschick, H Illei, G Lipsky, P AF Grammer, AC Slota, R Fischer, R Gur, H Girschick, H Illei, G Lipsky, P TI Evidence of abnormal GC reactions in active SLE: assessment by in vivo blockade of CD154-CD40 interactions SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIAMS, Cell Biol Grp B, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C179 EP C179 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000830 ER PT J AU Grosenbach, DW Schlom, J Gritz, L Yafal, AG Hodge, J AF Grosenbach, DW Schlom, J Gritz, L Yafal, AG Hodge, J TI A recombinant vector expressing transgenes for four T-cell costimulatory molecules (OX40L, B7-1, ICAM-1, LFA-3) induces sustained CD4+and CD8+T-cell activation, protection from apoptosis and enhanced cytokine production SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NCI, CCR, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20879 USA. Ther Biol Corp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C330 EP C330 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001542 ER PT J AU Hoque, ATMS Smith, RH Kotin, RM Golding, B AF Hoque, ATMS Smith, RH Kotin, RM Golding, B TI Mechanism of tolerance against factor VIII in hemophiliac mice after intravenous injection of a non-viral vector SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 US FDA, Ctr Biol Evaluat & Res, OBRR DH, Bethesda, MD 20892 USA. NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C218 EP C218 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001009 ER PT J AU Huang, YP Seminario, MC Precht, P Wange, R AF Huang, YP Seminario, MC Precht, P Wange, R TI Effect of PTEN expression in a PTEN-null T cell line on the protein expression pattern SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C223 EP C224 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001037 ER PT J AU Inobe, M Schwartz, RH AF Inobe, M Schwartz, RH TI The role of CD28, CTLA4 and Fas molecules in adaptive tolerance SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIAID, LCMI, NIH, Bethesda, MD 20892 USA. RI INOBE, Manabu/D-8393-2015 NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C211 EP C212 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000980 ER PT J AU Iribarren, P Cui, YH Le, YY Ying, GG Zhang, X Gong, WH Wang, JM AF Iribarren, P Cui, YH Le, YY Ying, GG Zhang, X Gong, WH Wang, JM TI Interleukin 4 inhibits the expression of G-protein coupled receptor FPR2/FPRL1 in microglial cells activated by pro-inflammatory stimulants. SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NCI, Mol Immunoregulat Lab, Frederick, MD 21702 USA. Lauzhou Mil Med Univ, Biochem Sect, Lauzhou, Peoples R China. NCI, Expt Immunol Lab, Frederick, MD 21701 USA. SAIC Frederick, Basic Res Program, Frederick, MD USA. RI Zhang, Xia/B-8152-2008 OI Zhang, Xia/0000-0002-9040-1486 NR 0 TC 0 Z9 0 U1 1 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C263 EP C264 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001228 ER PT J AU Jankovic, D Kullberg, MC Hieny, S Sher, A AF Jankovic, D Kullberg, MC Hieny, S Sher, A TI Th1/Th2 effector choice in parasitic infection correlates with the activation state of DC rather than their production of IL-12/IL-4 SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C197 EP C197 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000911 ER PT J AU Jaruga, B Sun, R Hong, F Radaeva, S Gan, S AF Jaruga, B Sun, R Hong, F Radaeva, S Gan, S TI Critical role of interleukin-4/STAT6 in T cell-mediated hepatitis SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIAAA, Sect Liver Biol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C117 EP C117 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000541 ER PT J AU Johnson, TR Collins, PL Teng, MN Graham, BS AF Johnson, TR Collins, PL Teng, MN Graham, BS TI Immune responses to respiratory syncytial virus (RSV) G glycoprotein are not necessary for formalin-inactivated RSV (FI-RSV) vaccine-enhanced disease SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIAID, VRC, Viral Pathogenesis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RI Teng, Michael/I-5006-2012 OI Teng, Michael/0000-0002-0722-3659 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C24 EP C24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000112 ER PT J AU Johnson, TR Varga, SM Braciale, TJ Graham, BS AF Johnson, TR Varga, SM Braciale, TJ Graham, BS TI Respiratory syncytial virus (RSV) G-induced vaccine enhanced disease, but not FI-RSV-induced disease, is mediated by V beta 14+ T cells SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIAID, Viral Pathogenesis Lab, VRC, NIH, Bethesda, MD 20892 USA. Univ Virginia, Beirne Carter Ctr Immunol Res, Charlottesville, VA USA. Univ Virginia, Charlottesville, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C18 EP C18 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000087 ER PT J AU Karandikar, NJ Crawford, M Yan, X Ortega, S Price, D Douek, DC Koup, R Racke, MK AF Karandikar, NJ Crawford, M Yan, X Ortega, S Price, D Douek, DC Koup, R Racke, MK TI Prevalence of neuroantigen-specific CD8+T cell responses in multiple sclerosis SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 UT, SW Med Ctr, Dallas, TX 75390 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RI Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C33 EP C33 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000154 ER PT J AU Khaled, AR Li, WQ Durum, SK AF Khaled, AR Li, WQ Durum, SK TI Death in the absence of cytokine signaling: Lessons learned from BAX/IL-7 receptor double deficient mice SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Univ Cent Florida, Biomol Sci Ctr, Orlando, FL 32826 USA. NCI, Lab Mol Immunoregulat, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C247 EP C247 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001149 ER PT J AU Kovarova, M Odom, S Furumoto, Y Gonzalez-Espinosa, C Gomez, G Harder, KW Rivera, J AF Kovarova, M Odom, S Furumoto, Y Gonzalez-Espinosa, C Gomez, G Harder, KW Rivera, J TI Lyn kinase is required for Csk-binding protein (Cbp) phosphorylation and negative regulation of Fyn kinase in mast cells SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIH, NIAMS, Bethesda, MD 20892 USA. CINVESTAV Zona Sur, Mexico City, DF, Mexico. Ludwig Inst Canc Res, Melbourne, Vic 3050, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C12 EP C12 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000058 ER PT J AU Kroczek, RA Grimbacher, B Hutloff, A Schlesier, M Glocker, E Warnatz, K Drager, R Eibel, H Fischer, B Schaffer, AA Mages, HW Peter, HH AF Kroczek, RA Grimbacher, B Hutloff, A Schlesier, M Glocker, E Warnatz, K Drager, R Eibel, H Fischer, B Schaffer, AA Mages, HW Peter, HH TI Homozygous loss of ICOS causes adult-onset common variable immunodeficiency SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Robert Koch Inst, D-13353 Berlin, Germany. Univ Freiburg, Clin Res Unit Rheumatol, Freiburg, Germany. NIH, Clin Res Unit Rheumatol, Bethesda, MD 20892 USA. RI Schaffer, Alejandro/F-2902-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C217 EP C217 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001005 ER PT J AU Laiosa, MD Laky, K Matechak, E Fowlkes, BJ AF Laiosa, MD Laky, K Matechak, E Fowlkes, BJ TI Syk and Zap70 kinases have distinct and overlapping functions during early T-cell development SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C218 EP C218 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001011 ER PT J AU Lankford, CSR Nguyen, BV Yamane, H Rodriguez, RVC Paul, WE Frucht, DM AF Lankford, CSR Nguyen, BV Yamane, H Rodriguez, RVC Paul, WE Frucht, DM TI An important role for IFN-gamma R signaling in TH1 priming but not in IFN-gamma production by TH1 effector cells or antigen presenting cells SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 US FDA, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C202 EP C202 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000934 ER PT J AU Li, WQ Jiang, Q Khaled, A Durum, S AF Li, WQ Jiang, Q Khaled, A Durum, S TI Interleukin (IL)-7 activates PI3 kinase pathway and inactivates Bad both of which are associated with T cell survival SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NCI, Mol Immunoregulat Lab, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C294 EP C294 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001374 ER PT J AU Liu, XL Adams, A Wildt, K Aronow, BJ Feigenbaum, L Bosselut, R AF Liu, XL Adams, A Wildt, K Aronow, BJ Feigenbaum, L Bosselut, R TI Dissecting survival and differentiation during thymocyte selection by restricting Zap70 expression and TCR signaling to CD4+8+thymocytes SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NCI, LICB, NIH, Bethesda, MD 20892 USA. NCI, EIB, NIH, Bethesda, MD 20892 USA. Cincinnati Childrens Hosp Res Fdn, Div Dev Biol, Cincinnati, OH USA. Cincinnati Childrens Hosp Res Fdn, Div Pediat Informat, Cincinnati, OH USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick, MD 21701 USA. RI Aronow, Bruce/F-8438-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C3 EP C3 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000016 ER PT J AU Lougaris, V Jennings, N Fischer, R Plebani, A Lipsky, P Grammer, AC AF Lougaris, V Jennings, N Fischer, R Plebani, A Lipsky, P Grammer, AC TI Engagement of CD154 expressed by human tonsillar B cells induces proximal signaling events and differentiation to Ig-secreting plasma cells SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIAMS, Cell Biol Grp B, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. Univ Brescia, Brescia, Italy. RI Plebani, Alessandro/C-8593-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C263 EP C263 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001224 ER PT J AU Mazzoni, A Leifer, CA Mullen, GED Kennedy, MN Segal, DM AF Mazzoni, A Leifer, CA Mullen, GED Kennedy, MN Segal, DM TI Histamine modulates the polarizing activities of human dendritic cells SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIH, Expt Immunol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C257 EP C257 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001199 ER PT J AU Melenhorst, JJ Follmann, DA Barrett, AJ AF Melenhorst, JJ Follmann, DA Barrett, AJ TI TCRV beta alllele frequencies in mature human T cells are largely determined during beta-selection SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NHLBI, Allogene Stem Cell Transplantat Sect, NIH, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C1 EP C1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000005 ER PT J AU Mentink-Kane, MM Chiaramonte, MG Jacobson, BA Cheever, AW Whitters, MJ Goad, MEP Wong, A Donaldson, DD Collins, M Grusby, MJ Wynn, TA AF Mentink-Kane, MM Chiaramonte, MG Jacobson, BA Cheever, AW Whitters, MJ Goad, MEP Wong, A Donaldson, DD Collins, M Grusby, MJ Wynn, TA TI The IL-13 receptor alpha 2 is induced by and acts as a functional decoy receptor for the Th2 response SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIAID, NIH, Bethesda, MD 20892 USA. Wyeth Ayerst Res, Inst Genet, Cambridge, MA USA. Biomed Res Inst, Rockville, MD 20852 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RI Wynn, Thomas/C-2797-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C254 EP C254 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001182 ER PT J AU Mix, H Lohse, AW Rehermann, B AF Mix, H Lohse, AW Rehermann, B TI CD4+T cells target epitopes within soluble liver antigen (SLA/LP), a major B cell antigen in autoimmune hepatitis SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIDDK, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. Univ Mainz, Dept Med 1, D-6500 Mainz, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C185 EP C185 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000857 ER PT J AU Mongini, PKA Jackson, AE Fattah, RJ Inman, JK AF Mongini, PKA Jackson, AE Fattah, RJ Inman, JK TI Complement-binding CD21/CD19 complex enhances human B cell protection from fas apoptosis SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NYU, Hosp Joint Dis, Ctr Med, New York, NY 10003 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C185 EP C185 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000856 ER PT J AU Monsurro, V Wang, E Jacobson, S Marincola, F AF Monsurro, V Wang, E Jacobson, S Marincola, F TI Genetic profiling of antigen-specific circulating CD8+cells in humans SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. NINDS, Viral Immunol Sect, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C127 EP C127 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000588 ER PT J AU Morel, L Croker, BP Morse, H AF Morel, L Croker, BP Morse, H TI B cell developmental defects correlate with lupus pathogenesis in the NZM model SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Univ Florida, Gainesville, FL 32610 USA. NIAID, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C182 EP C183 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000845 ER PT J AU Nagase, H Lira, R Paul, WE Sacks, DL Noben-Trauth, N AF Nagase, H Lira, R Paul, WE Sacks, DL Noben-Trauth, N TI The relative contribution of IL-4 receptor signaling and IL-10 in Leishmania major susceptibility SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 George Washington Univ, Dept Immunol, Med Ctr, Washington, DC 20037 USA. NIAID, NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C195 EP C195 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000904 ER PT J AU Natarajan, K Dimasi, N Dam, J Guan, RJ Mariuzza, RA Margulies, DH AF Natarajan, K Dimasi, N Dam, J Guan, RJ Mariuzza, RA Margulies, DH TI Recognition of MHC-I molecules by ly49 NK cell receptors: Structure of the Lv49C/H-2Kb complex SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Univ Maryland, Ctr Adv Res Biotechnol, Rockville, MD USA. RI Margulies, David/H-7089-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C51 EP C51 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000235 ER PT J AU Palaniappan, R Singh, S Singh, UP Briles, DE Hollingshead, SK Paton, JC Taub, DD Edwin, WA Lillard, JW AF Palaniappan, R Singh, S Singh, UP Briles, DE Hollingshead, SK Paton, JC Taub, DD Edwin, WA Lillard, JW TI Role of RANTES in pneumococcal immunopathogenesis SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Morehouse Sch Med, Atlanta, GA 30310 USA. Univ Alabama, Birmingham, AL USA. Womens & Childrens Hosp, Adelaide, SA, Australia. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. RI Paton, James/A-9920-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C85 EP C85 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000391 ER PT J AU Pardigon, N Darche, S Guy-Grand, D Bennink, J Yewdell, J AF Pardigon, N Darche, S Guy-Grand, D Bennink, J Yewdell, J TI Interaction of IELs and TL antigen in the small intestine of normal, knockout and virus-infected mice SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIAID, LVD, CBS VIS, NIH, Bethesda, MD 20814 USA. Inst Pasteur, Paris, France. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C86 EP C86 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000398 ER PT J AU Peng, Z Beaven, MA AF Peng, Z Beaven, MA TI Essential role for phospholipase D in the activation of protein kinase C and degranulation in mast cells SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C12 EP C12 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000057 ER PT J AU Perez-Diez, A Matzinger, P Lab, G AF Perez-Diez, A Matzinger, P Lab, G TI CD4 cells can be more efficient at tumor rejection than CD8 cells SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C74 EP C75 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000343 ER PT J AU Pesce, JT Anthony, RM Chaussabel, D Urban, JF Gause, WC AF Pesce, JT Anthony, RM Chaussabel, D Urban, JF Gause, WC TI Comparative analysis of Th2 immune response initiation using high density oligonucleotide microarray analysis SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIAID, NIH, Bethesda, MD 20892 USA. USDA, Beltsville, MD 20705 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C228 EP C229 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001062 ER PT J AU Princiotta, MF Finzi, D Qian, SB Gibbs, J Bennink, JR Yewdell, JW AF Princiotta, MF Finzi, D Qian, SB Gibbs, J Bennink, JR Yewdell, JW TI Quantitating viral protein synthesis, degradation and endogenous antigen processing SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIAID, LVD, NIH, Bethesda, MD 20892 USA. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C119 EP C119 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000550 ER PT J AU Pullmann, R Stancato, C Khairallah, R Agarwal, R Nagy, G Phillips, PE Perl, A AF Pullmann, R Stancato, C Khairallah, R Agarwal, R Nagy, G Phillips, PE Perl, A TI Immunopathogenicity of the HRES-1 endogenous retrovirus in SLE SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 SUNY, Syracuse, NY 13210 USA. NEI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C35 EP C35 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000164 ER PT J AU Radaeva, S Jaruga, B Gao, B AF Radaeva, S Jaruga, B Gao, B TI Interferon-gamma (IFN-gamma) inhibits IFN-gamma-activated signals in hepatic cells through the induction of STAT1: implication in resistance to IFN-alpha therapy SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIAAA, Sect Liver Biol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C66 EP C66 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000306 ER PT J AU Rodriguez-Galan, MC Young, HA AF Rodriguez-Galan, MC Young, HA TI Thymocytes can express a different cytokines and chemokines receptors profile after in vitro stimulation with interleukin-18 (IL18) in combination with IL-2 or IL-12 SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NCI Frederick, Lab Expt Immunol, NIH, Ft Detrick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C140 EP C140 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000647 ER PT J AU Rutigliano, JA Chen, M Graham, BS AF Rutigliano, JA Chen, M Graham, BS TI Viral clearance and illness in respiratory syncytial virus (RSV) infection are mediated by different cytotoxic T lymphocyte (CTL) effector functions SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C17 EP C17 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000080 ER PT J AU Saikh, KU Kissner, TL Sultana, A Dyas, B Tropea, JE Waugh, DS Ulrich, RG AF Saikh, KU Kissner, TL Sultana, A Dyas, B Tropea, JE Waugh, DS Ulrich, RG TI Primary human T-cell responses to virulence determinants of the Yersinia pestis type III secretion system and identification of new vaccine targets SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 USA, Med Res Inst Infect Dis, Frederick, MD 21702 USA. NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C30 EP C30 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000139 ER PT J AU Saitoh, S Odom, S Gomez, G Young, HA Rivera, J Samelson, LE AF Saitoh, S Odom, S Gomez, G Young, HA Rivera, J Samelson, LE TI The role of LAT tyrosine residues in mast cell function SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Osaka Univ, Sch Med, Suita, Osaka 565, Japan. NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol Lab, Fed Govt, NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C11 EP C11 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000054 ER PT J AU Scanga, CA Feng, CG Collazo-Custodio, CM Cheever, AW Sher, A AF Scanga, CA Feng, CG Collazo-Custodio, CM Cheever, AW Sher, A TI Mice deficient in MyD88 display profound defects in acute resistance and type 1 cytokine responses to Mycobacterium avium infection SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Biomed Res Inst, Genet Inst, Rockville, MD 20852 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C288 EP C288 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001346 ER PT J AU Seong, SY Matzinger, P AF Seong, SY Matzinger, P TI Hydrophobic molecules from necrotic cells activate dendritic cells by way of Toll-like receptor 2 and 4 SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIAID, Ghost Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C56 EP C56 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000262 ER PT J AU Shen, JJ Ragheb, JA AF Shen, JJ Ragheb, JA TI Complex regulation of biphasic CD40L expression in PBMC SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NEI, LI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C211 EP C211 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000978 ER PT J AU Shorts, LH Blazar, BR Murphy, W Back, T Wiltrout, R AF Shorts, LH Blazar, BR Murphy, W Back, T Wiltrout, R TI CD40 signaling in renal cell carcinoma leads to increased cytokine expression and decreased tumor size SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NCI, Intramural Res Support Program, Frederick, MD 21702 USA. Univ Minnesota, Dept Pediat, Minneapolis, MN USA. Univ Nevada, Dept Microbiol, Sch Med, Reno, NV 89557 USA. SAIC, Expt Immunol Lab, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C237 EP C237 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001102 ER PT J AU Silver, PB Agarwal, R Su, SB Chan, CC Caspi, R AF Silver, PB Agarwal, R Su, SB Chan, CC Caspi, R TI Peripheral expression of a sequestered autoantigen by DNA vaccination protects from autoimmune disease SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C175 EP C175 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000810 ER PT J AU Singh, UP Singh, S Taub, DD Lillard, JW AF Singh, UP Singh, S Taub, DD Lillard, JW TI Clinical correlates of CXCR3 ligand expression in Crohn's disease SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Morehouse Sch Med, Atlanta, GA 30310 USA. NIA, Gerentol Res Ctr, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C322 EP C322 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001505 ER PT J AU Singh, UP Singh, S Taub, DD Lillard, JW AF Singh, UP Singh, S Taub, DD Lillard, JW TI Inhibition of IP-10 abrogates colitis in murine Crohn's disease SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Morehouse Sch Med, Atlanta, GA 30310 USA. NIA, Gerentol Res Ctr, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C321 EP C321 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001500 ER PT J AU Skapenko, A Lipsky, PE Kalden, JR Schulze-Koops, H AF Skapenko, A Lipsky, PE Kalden, JR Schulze-Koops, H TI Regulation of human Th1 inflammation in vivo SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Univ Erlangen Nurnberg, Nikolaus Fiebiger Ctr Mol Med, D-91054 Erlangen, Germany. NIH, Natl Arthritis & Musculosceletel & Skin Dis, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C131 EP C131 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000603 ER PT J AU Skwor, T Cassidy, C LiWang, P Allen, SS Yoshimura, T McMurray, DN AF Skwor, T Cassidy, C LiWang, P Allen, SS Yoshimura, T McMurray, DN TI Recombinant guinea pig RANTES (gpCCL5) differentially upregulates IL-12p40 and TNF alpha mRNA levels in guinea pig phagocytes infected with virulent and attenuated Mycobacterium tuberculosis SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Texas A&M Univ, Syst Hlth Sci Ctr, College Stn, TX 77843 USA. NCI Frederick, Lab Mol Immunoregulat, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C134 EP C134 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000619 ER PT J AU Smith, CL Melsacther, AN Fischer, RT Phillips, TM Lipsky, PE Grammer, AC AF Smith, CL Melsacther, AN Fischer, RT Phillips, TM Lipsky, PE Grammer, AC TI CD40 engagement on human B cells induces MAPK activation, translocation of AP-1 components and gene expression SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIAMS, BCBG, NIH, Bethesda, MD 20892 USA. NIH, ORS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C262 EP C262 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001222 ER PT J AU Stebbins, C Watzl, C Billadeau, D Leibson, P Burshtyn, D Long, E AF Stebbins, C Watzl, C Billadeau, D Leibson, P Burshtyn, D Long, E TI Vav1 is the key substrate of the tyrosine phosphatase SHP-1 targeted during KIR mediated inhibition in NK cells SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIAID, NIH, Rockville, MD 20852 USA. Mayo Clin & Mayo Fdn, Dept Immunol, Rochester, MN USA. Univ Alberta, Dept Med Microbiol & Immunol, Edmonton, AB, Canada. RI Watzl, Carsten/B-4911-2013 OI Watzl, Carsten/0000-0001-5195-0995 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C316 EP C316 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001479 ER PT J AU Stork, ACJ van Laar, JM Longo, N Olson, D Satorius, C Lipsky, PE AF Stork, ACJ van Laar, JM Longo, N Olson, D Satorius, C Lipsky, PE TI B cell immunoglobulin repertoire in severe rheumatoid arthritis SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIAMSD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C188 EP C188 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000871 ER PT J AU Su, SB Silver, PB Wang, P Chan, CC Caspi, RR AF Su, SB Silver, PB Wang, P Chan, CC Caspi, RR TI Dissociating the enhancing and inhibitory effects of pertussis toxin on autoimmune disease SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C272 EP C272 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001268 ER PT J AU Teng, O van Laar, J Mohammadi, R Grivel, JC Margolis, L Lipsky, P Grammer, A AF Teng, O van Laar, J Mohammadi, R Grivel, JC Margolis, L Lipsky, P Grammer, A TI Blocking endogenous CD154-CD40 interactions in human tonsillar histocultures inhibits differentiation of memory B cells to Ig-secreting plasma cells SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIAMS, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. NICHD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C214 EP C214 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000993 ER PT J AU Tkaczyk, C Luskova, P Horejsi, V Metcalfe, DD Gilfillan, AM Draber, P AF Tkaczyk, C Luskova, P Horejsi, V Metcalfe, DD Gilfillan, AM Draber, P TI Both p56(lny)-dependent and p56(lyn) independent pathways regulate the phosphorylation of Non T cell activation linker (NTAL) in Fc epsilon RI activated mouse bone marrow derived mast cells (BMMCs) SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIAID, Lab Allerg dis, NIH, Bethesda, MD 20892 USA. Acad Sci Czech Republ, Inst Mol Genet, Prague, Czech Republic. RI Horejsi, Vaclav/G-3113-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C12 EP C12 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000059 ER PT J AU Uehara, S Love, PE AF Uehara, S Love, PE TI Characterization of CCR9 transgenic mice: Early and/or enhanced CCR9 expression impairs T cell development SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NICHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C106 EP C106 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000490 ER PT J AU van Laar, JM Mohammadi, R Teng, O Snapper, CM Grivel, JC Margolis, L Lipsky, PE Grammer, AC AF van Laar, JM Mohammadi, R Teng, O Snapper, CM Grivel, JC Margolis, L Lipsky, PE Grammer, AC TI C-polysaccharide conjugated pneumococcal surface antigen protein A induces an antigen-specific humoral response in human tonsillar histocultures SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIAMS, BCBG, NIH, Bethesda, MD 20892 USA. USUHS, Bethesda, MD USA. NICHD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C87 EP C87 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000403 ER PT J AU Yan, X Ortega, S Mehta, R Douek, DC Koup, R Racke, MK Karandikar, NJ AF Yan, X Ortega, S Mehta, R Douek, DC Koup, R Racke, MK Karandikar, NJ TI Oligoclonal CD8+ T-cell responses to glatiramer acetate (GA; Copaxone (R)) in patients with multiple sclerosis SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Univ Texas, SW Med Ctr, Dallas, TX 75390 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C275 EP C275 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001283 ER PT J AU Yang, D Chen, Y Hoover, DM Staley, PG Tucker, KD Lubkowiski, J Oppenheim, JJ AF Yang, D Chen, Y Hoover, DM Staley, PG Tucker, KD Lubkowiski, J Oppenheim, JJ TI Many chemokines including CCL20/MIP-3 alpha, display in vitro antimicrobial activity SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NCI, SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. NCI, Mol Immunoregulat Lab, Frederick, MD 21702 USA. NCI, SAIC Frederick, Macromol Crystallog Lab, Frederick, MD 21702 USA. NCI, SAIC Frederick, Opportunist Infect Lab, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C116 EP C116 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000537 ER PT J AU Yoshimura, T Matsuyama, W Kamohara, H Faure, M Galligan, C AF Yoshimura, T Matsuyama, W Kamohara, H Faure, M Galligan, C TI Interaction of discoidin receptor 1 isoform b (DDR1b) with collagen activates p38 mitogen-activated protein (MAP) kinase and promotes differentiation of macrophages SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NCI, Ft Detrick, MD 21702 USA. SUGEN Inc, Lab Mol Immunoregulat, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C315 EP C315 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001472 ER PT J AU Zhang, X Lipsky, PE He, LS Melsaether, A Grammer, AC AF Zhang, X Lipsky, PE He, LS Melsaether, A Grammer, AC TI CD40 induced NF-kappaB activation in human B lymphocytes is mediated by diverse signaling pathways involving syk, p70-s6k, NIK, MEKK1 and RAF1 SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 NIH, Cell Biol Grp B, Bethesda, MD 20892 USA. NIAMS, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. NIAMS, Cell Biol Grp B, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C262 EP C262 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001220 ER PT J AU Belachew, S Chittajallu, R Aguirre, AA Yuan, XQ Kirby, M Anderson, S Gallo, V AF Belachew, S Chittajallu, R Aguirre, AA Yuan, XQ Kirby, M Anderson, S Gallo, V TI Postnatal NG2 proteoglycan-expressing progenitor cells are intrinsically multipotent and generate functional neurons SO JOURNAL OF CELL BIOLOGY LA English DT Article DE stem cell; oligodendrocyte progenitor; differentiation; adult neurogenesis; glia ID CENTRAL-NERVOUS-SYSTEM; NEURAL STEM-CELLS; OLIGODENDROCYTE PRECURSOR CELLS; GREEN FLUORESCENT PROTEIN; RADIAL GLIAL-CELLS; ADULT-RAT; DENTATE GYRUS; OPTIC-NERVE; HIPPOCAMPUS; MOUSE AB Neurogenesis is known to persist in the adult mammalian central nervous system (CNS). The identity of the cells that generate new neurons in the postnatal CNS has become a crucial but elusive issue. Using a transgenic mouse, we show that NG2 proteoglycan-positive progenitor cells that express the 2',3'-cyclic nucleoticle 3'-phosphodiesterase gene display a multipotent phenotype in vitro and generate electrically excitable neurons, as well as astrocytes and oligodendrocytes. The fast kinetics and the high rate of multipotent fate of these NG2(+) progenitors in vitro reflect an intrinsic property rather than reprogramming. We demonstrate in the hippocampus in vivo that a sizeable fraction of postnatal NG2(+) progenitor cells are proliferative precursors whose progeny appears to differentiate into GABAergic neurons capable of propagating action potentials and displaying functional synaptic inputs. These data show that at least a subpopulation of postnatal NG2-expressing cells are CNS multipotent precursors that may underlie adult hippocampal neurogenesis. C1 Childrens Natl Med Ctr, Childrens Res Inst, Ctr Neurosci Res, Washington, DC 20010 USA. Natl Inst Child Hlth & Human Dev, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Flow Cytometry Core Unit, Gene Transfer Lab, Hematopoiesis Sect,NIH, Bethesda, MD 20892 USA. RP Gallo, V (reprint author), Childrens Natl Med Ctr, Childrens Res Inst, Ctr Neurosci Res, Rm 5345,111 Michigan Ave NW, Washington, DC 20010 USA. FU NICHD NIH HHS [P30 HD040677, P30HD40677] NR 46 TC 359 Z9 369 U1 0 U2 9 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD APR 14 PY 2003 VL 161 IS 1 BP 169 EP 186 DI 10.1083/jcb.200210110 PG 18 WC Cell Biology SC Cell Biology GA 669GP UT WOS:000182343800016 PM 12682089 ER PT J AU Maitra, R Grigoryev, DN Bera, TK Pastan, IH Lee, B AF Maitra, R Grigoryev, DN Bera, TK Pastan, IH Lee, B TI Cloning, molecular characterization, and expression analysis of Copine 8 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE copine; cloning; functional genomics; expression analysis; isoforms; prostate ID PROSTATE-CANCER; NUCLEAR-PROTEIN; N-COPINE; CELLS; GENES AB Copines are ubiquitously expressed, phospholipid-binding proteins that have been conserved through evolution. In this paper, we report the cloning and molecular characterization of a new member of the Copine family, Copine 8. This gene has been isolated and characterized using a combination of bioinformatic and experimental approaches. Using an algorithm to cluster ESTs (expressed sequence tags) that are available through the public "GoldenPath" database, Copine 8 was initially identified as a gene predominantly expressed in prostate and testis. Cloning and molecular analysis revealed that this gene is expressed in low-levels in most tissues examined. Two different isoforms of this gene have been isolated. Strongest expression of Copine 8 mRNA is seen in the prostate, heart, and brain. Taken together, this data suggest that Copine 8 may have an important role to play in prostate regulation and development. (C) 2003 Elsevier Science (USA). All rights reserved. C1 NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Lee, B (reprint author), NCI, Mol Biol Lab, Canc Res Ctr, NIH, 37 Convent Dr Room 5120 MSC 4262, Bethesda, MD 20892 USA. RI Grigoryev, Dmitry/C-9422-2015 OI Grigoryev, Dmitry/0000-0002-1849-1763 NR 16 TC 16 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 11 PY 2003 VL 303 IS 3 BP 842 EP 847 DI 10.1016/S0006-291X(03)00445-5 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 669QD UT WOS:000182361200016 PM 12670487 ER PT J AU Rigden, DJ Jedrzejas, MJ Galperin, MY AF Rigden, DJ Jedrzejas, MJ Galperin, MY TI An extracellular calcium-binding domain in bacteria with a distant relationship to EF-hands SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE genome analysis; calcium-binding site; protein domain; cell envelope; S-layer; nuclease; calmodulin; evolution ID PROTEIN SECONDARY STRUCTURE; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; COPPER CHAPERONES; DATABASE SEARCH; SURFACE-LAYER; PREDICTION; CALMODULIN; EVOLUTION; RECOGNITION AB Extracellular Ca2+-dependent nuclease YokF from Bacillus subtilis and several other surface-exposed proteins from diverse bacteria are encoded in the genomes in two paralogous forms that differ by a similar to45 amino acid fragment, which comprises a novel conserved domain. Sequence analysis of this domain revealed a conserved DxDxDGxxCE motif, which is strikingly similar to the Ca2+-binding loop of the calmodulin-like EF-hand domains, suggesting an evolutionary relationship between them. Functions of many of the other proteins in which the novel domain, named Excalibur (extracellular calcium-binding region), is found, as well as a structural model of its conserved motif are consistent with the notion that the Excalibur domain binds calcium. This domain is but one more example of the diversity of structural contexts surrounding the EF-hand-like calcium-binding loop in bacteria. This loop is thus more widespread than hitherto recognized and the evolution of EF-hand-like domains is probably more complex than previously appreciated. (C) 2003 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. EMBRAPA, Cenargen, Natl Ctr Genet Resources & Biotechnol, BR-70770900 Brasilia, DF, Brazil. Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RI Galperin, Michael/B-5859-2013; OI Galperin, Michael/0000-0002-2265-5572; Rigden, Daniel/0000-0002-7565-8937 FU NIAID NIH HHS [AI44079] NR 46 TC 27 Z9 27 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 APR 11 PY 2003 VL 221 IS 1 BP 103 EP 110 DI 10.1016/S0378-1097(03)00160-5 PG 8 WC Microbiology SC Microbiology GA 669QE UT WOS:000182361300015 PM 12694917 ER PT J AU Morris, CR Petersen, JL Vargas, SE Turnquist, HR McIlhaney, MM Sanderson, SD Bruder, JT Yu, YYL Burgert, HG Solheim, JC AF Morris, CR Petersen, JL Vargas, SE Turnquist, HR McIlhaney, MM Sanderson, SD Bruder, JT Yu, YYL Burgert, HG Solheim, JC TI The amyloid precursor-like protein 2 and the adenoviral E3/19K protein both bind to a conformational site on H-2K(d) and regulate H-2K(d) expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MHC CLASS-I; CELL-SURFACE EXPRESSION; HEAVY-CHAIN; ENDOPLASMIC-RETICULUM; K-D; MOLECULES; ANTIGEN; TAP; COMPLEX; TAPASIN AB A protein of unknown physiological function, called amyloid precursor-like protein 2 (APLP2), forms an association with the murine class I molecule K-d that is up-regulated by the presence of the adenoviral protein E3/19K. We have extended these findings to show that APLP2 and E3/19K associate preferentially with folded Kd and not with the open form. APLP2 was detectable at the cell surface, but its surface expression was not upregulated by the concurrent expression of K-d. Experimental down-regulation of APLP2 expression caused a consistent increase in the surface expression of K-d, indicating that APLP2 normally reduces K-d surface expression. These data suggest a role for APLP2 in controlling the maturation of major histocompatibility complex class I molecules. C1 Univ Nebraska, Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. Univ Nebraska, Med Ctr, Dept Biochem & Mol Biol, Omaha, NE 68198 USA. Univ Nebraska, Med Ctr, Sch Allied Hlth Profess, Omaha, NE 68198 USA. NCI, NIH, Bethesda, MD 20892 USA. Univ Warwick, Dept Biol Sci, Coventry CV4 7AL, W Midlands, England. RP Solheim, JC (reprint author), Univ Nebraska, Med Ctr, Eppley Inst Res Canc & Allied Dis, 986805 Nebraska Med Ctr, Omaha, NE 68198 USA. RI Turnquist, Heth/L-2319-2016 OI Turnquist, Heth/0000-0002-4173-4014 FU NCI NIH HHS [T32 CA09476]; NIGMS NIH HHS [GM57428] NR 47 TC 14 Z9 14 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 APR 11 PY 2003 VL 278 IS 15 BP 12618 EP 12623 DI 10.1074/jbc.M208203200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 666RD UT WOS:000182189500006 PM 12506118 ER PT J AU Li, J Gorospe, M Barnes, J Liu, Y AF Li, J Gorospe, M Barnes, J Liu, Y TI Tumor promoter arsenite stimulates histone H3 phosphoacetylation of proto-oncogenes c-fos and c-jun chromatin in human diploid fibroblasts SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL-REGULATED KINASE; MAP KINASE; DRINKING-WATER; CELL-PROLIFERATION; TERMINAL DOMAIN; AP-1 ACTIVITY; PHOSPHORYLATION; TRANSCRIPTION; ACTIVATION; INDUCTION AB Although epidemiological studies have long established that inorganic arsenic is a potent human carcinogen, the underlying mechanisms are still poorly understood. Recent studies suggest that inorganic arsenic may act as a tumor promoter by perturbing key signaling transduction pathways. We have shown previously that arsenite can potently activate the mitogen-activated protein kinase cascades and induce the expression of proliferation-associated genes, including protooncogenes c-jun and c-fos. In order to elucidate further the molecular mechanisms underlying its tumor-promoting properties, we investigated the signaling events involved in arsenite-mediated induction of c-fos and c-jun. We found that induction of both c-fos and c-jun by arsenite can be substantially inhibited by the MEK-selective inhibitor U0126, suggesting that the ERK pathway is critically involved in their up-regulation. Interestingly, arsenite dramatically induced the phosphorylation and acetylation of histone H3 preceding the induction of mRNAs encoding c-fos and c-jun. Finally, chromatin immunoprecipitation assays revealed that arsenite treatment markedly induced the phosphorylation/acetylation of histone H3 associated with the c-fos and c-jun genes through an ERK-dependent pathway. Our results strongly suggest that arsenic-triggered alterations in chromatin structure perturb specific gene transcription, including that of proto-oncogenes c-jun and c-fos, and may thereby contribute to the carcinogenic process. C1 NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Liu, Y (reprint author), Ohio State Univ, Columbus Childrens Hosp, Ctr Dev Pharmacol & Toxicol, Columbus Childrens Res Inst,Dept Pediat, 700 Childrens Dr, Columbus, OH 43205 USA. RI Liu, Yusen/E-3527-2011 NR 48 TC 49 Z9 51 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 APR 11 PY 2003 VL 278 IS 15 BP 13183 EP 13191 DI 10.1074/jbc.M300269200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 666RD UT WOS:000182189500076 PM 12547826 ER PT J AU Stein, EG Ghirlando, R Hubbard, SR AF Stein, EG Ghirlando, R Hubbard, SR TI Structural basis for dimerization of the Grb10 Src homology 2 domain - Implications for ligand specificity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AFFINITY PHOSPHOTYROSYL PEPTIDE; RECEPTOR TYROSINE KINASE; GROWTH-FACTOR RECEPTOR; FACTOR-I RECEPTORS; INSULIN-RECEPTOR; SH2 DOMAIN; CRYSTAL-STRUCTURE; CATALYTIC ACTIVITY; ADAPTER GRB14; PROTEIN AB Grb7, Grb10, and Grb14 are members of a distinct family of adapter proteins that interact with various receptor tyrosine kinases upon receptor activation. Proteins in this family contain several modular signaling domains including a pleckstrin homology (PH) domain, a BPS (between PH and SH2) domain, and a C-terminal Src homology 2 (SH2) domain. Although SH2 domains are typically monomeric, we show that the Grb10 SH2 domain and also full-length Grb10gamma are dimeric in solution under physiologic conditions. The crystal structure of the Grb10 SH2 domain at 1.65-Angstrom resolution reveals a non-covalent dimer whose interface comprises residues within and flanking the C-terminal a helix, which are conserved in the Grb7/Grb10/Grb14 family but not in other SH2 domains. Val-522 in the BG loop (BG3) and Asp-500 in the EF loop (EF1) are positioned to interfere with the binding of the P+3 residue of a phosphopeptide ligand. These structural features of the Grb10 SH2 domain will favor binding of dimeric, turn-containing phosphotyrosine sequences, such as the phosphorylated activation loops in the two Beta subunits of the insulin and insulin-like growth factor-1 receptors. Moreover, the structure suggests the mechanism by which the Grb7 SH2 domain binds selectively to pTyr-1139 (pYVNQ) in Her2, which along with Grb7 is co-amplified in human breast cancers. C1 NYU, Sch Med, Skirball Inst Biomol Med, New York, NY 10016 USA. NYU, Sch Med, Dept Pharmacol, New York, NY 10016 USA. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hubbard, SR (reprint author), NYU, Sch Med, Skirball Inst Biomol Med, 540 1st Ave, New York, NY 10016 USA. RI Ghirlando, Rodolfo/A-8880-2009; OI Hubbard, Stevan/0000-0002-2707-9383 FU NIDDK NIH HHS [DK52916] NR 46 TC 40 Z9 44 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 APR 11 PY 2003 VL 278 IS 15 BP 13257 EP 13264 DI 10.1074/jbc.M212026200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 666RD UT WOS:000182189500084 PM 12551896 ER PT J AU Chauhan, A Turchan, J Pocernich, C Bruce-Keller, A Roth, S Butterfield, DA Major, EO Nath, A AF Chauhan, A Turchan, J Pocernich, C Bruce-Keller, A Roth, S Butterfield, DA Major, EO Nath, A TI Intracellular human immunodeficiency virus tat expression in astrocytes promotes astrocyte survival but induces potent neurotoxicity at distant sites via axonal transport SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEPARAN-SULFATE PROTEOGLYCANS; REGULATORY PROTEIN TAT; OXIDATIVE STRESS; HIV-1; CELLS; ACTIVATION; TRANSACTIVATION; MECHANISMS; DAMAGE; BRAIN AB The human immunodeficiency virus (HM-Tat protein has been implicated in the neuropathogenesis of HrV infection. However, its role in modulating astroglial-neuronal relationships is poorly understood. Astrocyte infection with HIV has been associated with rapid progression of dementia. We thus initially transfected astrocytes with HIV proviral. DNA and confirmed Tat production in. these cells. Subsequently, using stably Tat-producing asytocyte cell lines, we observed that Tat promoted astrocyte survival by causing a prominent antioxidant effect and resistance to cell injury in these cells. Tat was released extracellularly where it could be taken up by other cells. Tat remained functionally active following uptake and caused long terminal repeat (LTR) transactivation in lymphocytic and astrocytic cell lines. Tat released from astrocytes caused mitochondrial dysfunction, trimming of neurites, and cell death in neurons. Tat neurotoxicity was attenuated by antiTat antibodies, kynurenate or heparan sulfate. The neurotoxic effects of Tat were caused at concentrations lower than that needed to cause LTR transactivation. When Tat-expressing cells were injected into the rat dentate gyrus, Tat was taken up by granule cells and transported along neuronal pathways to the CA3 region where it caused glial cell activation and neurotoxicity. The arginine-rich domain of Tat was essential for both the LTR transactivation and the neurotoxic properties of Tat. Thus HIV-Tat is a potent neurotoxin that may act at distant sites while at the same time it assures its production by preventing cell death in astrocytes where it is produced. C1 Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA. Univ Kentucky, Dept Chem Anat, Lexington, KY 40536 USA. Univ Kentucky, Dept Neurobiol, Lexington, KY 40536 USA. Univ Kentucky, Dept Microbiol & Immunol, Lexington, KY 40536 USA. NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. RP Nath, A (reprint author), Johns Hopkins Univ Hosp, Dept Neurol, 600 N Wolfe St,Pathol 509, Baltimore, MD 21287 USA. NR 43 TC 114 Z9 120 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 APR 11 PY 2003 VL 278 IS 15 BP 13512 EP 13519 DI 10.1074/jbc.M209381200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 666RD UT WOS:000182189500115 PM 12551932 ER PT J AU Nishigaki, K Thompson, D Yugawa, T Rulli, K Hanson, C Cmarik, J Gutkind, JS Teramoto, H Ruscetti, S AF Nishigaki, K Thompson, D Yugawa, T Rulli, K Hanson, C Cmarik, J Gutkind, JS Teramoto, H Ruscetti, S TI Identification and characterization of a novel Ste20/germinal center kinase-related kinase, polyploidy-associated protein kinase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GERMINAL CENTER KINASE; N-TERMINAL KINASE; ANCHORAGE-INDEPENDENT GROWTH; HUMAN STE20-LIKE KINASE; C-JUN; STE20-RELATED KINASE; SIGNAL-TRANSDUCTION; CELLULAR STRESSES; MOLECULAR-CLONING; PATHWAY AB A novel protein kinase, polyploidy-associated protein kinase (PAPK), was isolated using a subtraction cDNA library approach from a mouse erythroleukemia cell line that had been induced to polyploidy after serum withdrawal. PAPK shares homology with members of the Ste20/germinal center kinase family of protein kinases and is ubiquitously expressed as two spliced forms, PAPK-A and PAPK-B, that encode for proteins of 418 and 189 amino acids, respectively. The expression of endogenous PAPK-A protein increased after growth factor withdrawal in murine hematopoietic and fibroblast cells. When tested in an in vitro kinase assay, PAPK-A was activated in response to the stress-inducing agent hydrogen peroxide and slightly by fetal calf serum. Biochemical characterization of the PAPK-A-initiated pathway revealed that this novel kinase does not affect MAP kinase activity but can stimulate both c-Jun N-terminal kinase 1 (JNK1) and ERK6/p38gamma. The kinase activity of PAPK appears to be required for the activation of ERK6/p38gamma but not JNK1. When an inducible construct of PAPK-A was expressed in stably transfected NIH3T3 cells, the cells exhibited distinct cytoskeletal changes and became resistant to apoptotic cell death induced by serum withdrawal, effects of PAPK that require its kinase activity. These data suggest that PAPK is a new member of the Ste20/germinal center kinase family that modulates cytoskeletal organization and cell survival. C1 NCI Frederick, Basic Res Lab, NIH, Ft Detrick, MD 21702 USA. NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Nishigaki, K (reprint author), NCI Frederick, Basic Res Lab, NIH, Bldg 469,Rm 205, Ft Detrick, MD 21702 USA. RI Gutkind, J. Silvio/A-1053-2009 NR 73 TC 13 Z9 18 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 APR 11 PY 2003 VL 278 IS 15 BP 13520 EP 13530 DI 10.1074/jbc.M208601200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 666RD UT WOS:000182189500116 PM 12574163 ER PT J AU Ma, XF Tu, PF Chen, YJ Zhang, TY Wei, Y Ito, Y AF Ma, XF Tu, PF Chen, YJ Zhang, TY Wei, Y Ito, Y TI Preparative isolation and purification of two isoflavones from Astragalus membranaceus Bge. var. mongholicus (Bge.) Hsiao by high-speed counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE Astragalus membranaceus; counter-current chromatography; plant materials; preparative chromatography; isoflavones; calyposin glycoside; formononetin glycoside; glycosides ID SEPARATION; FLAVONOIDS AB Two isoflavones, calycosin-7-O-beta-D-glycoside and formononetin-7-O-beta-D-glycoside, were separated from n-butanol extract of the root of Astragalus membranaceus Bge. var. mongholicus (Bge.) Hsiao by high-speed counter-current chromatography in two steps using two different solvent systems composed of ethyl acetate-ethanol-n-butanol-water (30:10:6:50, v/v) and ethyl acetate-ethanol-water (5:1:5, v/v). From 200 mg of crude extract, calycosin-7-O-beta-D-glycoside (12 mg) and formononetin-7-O-beta-D-glycoside (10 mg) were isolated at over 95% purity by HPLC analyses, and their structures were identified by MS, H-1 NMR and C-13 NMR. (C) 2003 Elsevier Science B.V. All rights reserved. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Peking Univ, Modern Res Ctr Tradit Chinese Med, Beijing 100083, Peoples R China. Shenyang Pharmaceut Univ, Shenyang 110016, Peoples R China. Beijing Inst New Technol Applicat, Beijing 100035, Peoples R China. RP Ito, Y (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 50,Rm 3334,50 South Dr,MSC 8014, Bethesda, MD 20892 USA. NR 16 TC 44 Z9 52 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD APR 11 PY 2003 VL 992 IS 1-2 BP 193 EP 197 DI 10.1016/S0021-9673(03)00315-74 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 665XY UT WOS:000182147600019 PM 12735475 ER PT J AU Collins, FS Morgan, M Patrinos, A AF Collins, FS Morgan, M Patrinos, A TI The human genome project: Lessons from large-scale biology SO SCIENCE LA English DT Article AB The Human Genome Project has been the first major foray of the biological and medical research communities into "big science." In this Viewpoint, we present some of our experiences in organizing and managing such a complicated, publicly funded, international effort. We believe that many of the lessons we learned will be applicable to future large-scale projects in biology. C1 NHGRI, NIH, Bethesda, MD 20892 USA. Wellcome Trust Res Labs, London NW1 2BE, England. US DOE, Washington, DC 20585 USA. RP Collins, FS (reprint author), NHGRI, NIH, Bldg 31,Room 4B09,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 14 TC 354 Z9 383 U1 6 U2 74 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 11 PY 2003 VL 300 IS 5617 BP 286 EP 290 DI 10.1126/science.1084564 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 665RQ UT WOS:000182135400043 PM 12690187 ER PT J AU Strausberg, RL Schreiber, SL AF Strausberg, RL Schreiber, SL TI From knowing to controlling: A path from Genomics to drugs using small molecule probes SO SCIENCE LA English DT Article ID STOCK SOLUTION APPROACH; CHEMICAL GENETICS; ONE-BEAD AB The National Cancer Institute Initiative in Chemical Genetics is designed to encourage the development of small molecular probes. The probes are useful for activating or inactivating protein functions, thereby providing resources that help discern the functions of gene products in normal and disease cells, as well as in tissues. This initiative includes "ChemBank," a suite of informatics tools and databases aimed at promoting the development and use of chemical genetics by scientists worldwide. The information generated with such tools should provide a critical link from genomic discovery to drug development. C1 NCI, Canc Genom Off, Bethesda, MD 20892 USA. Harvard Univ, Dept Chem & Biol Chem, Howard Hughes Med Inst, Cambridge, MA 02115 USA. RP Strausberg, RL (reprint author), NCI, Canc Genom Off, 31 Ctr Dr, Bethesda, MD 20892 USA. NR 9 TC 205 Z9 208 U1 0 U2 14 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 11 PY 2003 VL 300 IS 5617 BP 294 EP 295 DI 10.1126/science.1083395 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 665RQ UT WOS:000182135400045 PM 12690189 ER PT J AU Joy, DA Feng, XR Mu, JB Furuya, T Chotivanich, K Krettli, AU Ho, M Wang, A White, NJ Suh, E Beerli, P Su, XZ AF Joy, DA Feng, XR Mu, JB Furuya, T Chotivanich, K Krettli, AU Ho, M Wang, A White, NJ Suh, E Beerli, P Su, XZ TI Early origin and recent expansion of Plasmodium falciparum SO SCIENCE LA English DT Article ID MITOCHONDRIAL GENOME; POPULATION-GROWTH; STATISTICAL TESTS; GENE TREES; MALARIA; DNA; EVOLUTION; COALESCENT; NEUTRALITY; INFERENCE AB The emergence of virulent Plasmodium falciparum in Africa within the past 6000 years as a result of a cascade of changes in human behavior and mosquito transmission has recently been hypothesized. Here, we provide genetic evidence for a sudden increase in the African malaria parasite population about 10,000 years ago, followed by migration to other regions on the basis of variation in 100 worldwide mitochondrial DNA sequences. However, both the world and some regional populations appear to be older (50,000 to 100,000 years old), suggesting an earlier wave of migration out of Africa, perhaps during the Pleistocene migration of human beings. C1 NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. Mahidol Univ, Wellcome Trust Mahidol Univ Oxford Trop Med Res P, Bangkok 10400, Thailand. Fiocruz MS, Ctr Pesquisas Rene Rachou, Malaria Lab, BR-30190002 Belo Horizonte, MG, Brazil. Univ Calgary, Dept Microbiol & Infect Dis, Calgary, AB T2N 1N4, Canada. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. Florida State Univ, Dirac Sci Lib, Sch Computat Sci & Informat Technol, Tallahassee, FL 32306 USA. RP Joy, DA (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RI White, Nicholas/I-4629-2012; feng, xiaorong/G-4811-2010; Beerli, Peter/A-3638-2009; Furuya, Tetsuya/J-5916-2013; Furuya, Tetsuya/H-2412-2013; OI feng, xiaorong/0000-0001-8410-3020; Beerli, Peter/0000-0003-0947-5451; Furuya, Tetsuya/0000-0003-3979-7072; Su, Xinzhuan/0000-0003-3246-3248 NR 27 TC 226 Z9 237 U1 2 U2 30 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 11 PY 2003 VL 300 IS 5617 BP 318 EP 321 DI 10.1126/science.1081449 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 665RQ UT WOS:000182135400054 PM 12690197 ER PT J AU Jaboin, J Hong, A Kim, CJ Thiele, CJ AF Jaboin, J Hong, A Kim, CJ Thiele, CJ TI Cisplatin-induced cytotoxicity is blocked by brain-derived neurotrophic factor activation of TrkB signal transduction path in neuroblastoma SO CANCER LETTERS LA English DT Article DE neuroblastoma; cisplatin; TrkB; brain-derived neurotrophic factor; phosphatidylinositol 3 '-kinase ID CEREBELLAR GRANULE NEURONS; GLUTAMATE-INDUCED NEUROTOXICITY; INDUCED APOPTOSIS; CNS NEURONS; CELL-DEATH; IN-VIVO; BDNF; EXPRESSION; SURVIVAL; PROTECTS AB We evaluated the ability of brain-derived neurotrophic factor (BDNF) to decrease the chemosensitivity of neuroblastoma cells to cisplatin. Two cell lines, one derived from SH-SY5Y (SY5Y-TB8) and the other from SK-N-AS (AS-TB8), transfected with a TrkB plasmid were generated, and used to assess the effects of activation of the TrkB signal transduction path on cisplatin (Cis) induced apoptosis. BDNF treatment of each of the TrkB expressing cells blocked cisplatin-induced cell death. BDNF's ability to rescue the cells from cisplatin-induced cell death was inhibited by treatment with the Trk tyrosine kinase inhibitor, K252a, and the phosphatidylinositol 3'-kinase (PI)-3-kinase inhibitor, LY294002. This indicates that the activation of the TrkB path through PI-3-kinase is required for BDNF's survival-promoting effects. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved. C1 NCI, Canc Res Ctr, Pediat Oncol Branch, Cell & Mol Biol Sect, Bethesda, MD 20892 USA. Seoul Natl Univ, Coll Med, Dept Pathol, Seoul 151742, South Korea. RP Thiele, CJ (reprint author), NCI, Canc Res Ctr, Pediat Oncol Branch, Cell & Mol Biol Sect, 10 Ctr Dr,MSC-1928, Bethesda, MD 20892 USA. RI Seoul National University, Pathology/B-6702-2012; OI Calderwood, Audrey/0000-0001-7486-8310 NR 25 TC 20 Z9 22 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD APR 10 PY 2003 VL 193 IS 1 BP 109 EP 114 DI 10.1016/S0304-3835(02)00723-1 PG 6 WC Oncology SC Oncology GA 672FE UT WOS:000182509900014 PM 12691830 ER PT J AU Nau, MM Lipkowitz, S AF Nau, MM Lipkowitz, S TI Comparative genomic organization of the cbl genes SO GENE LA English DT Article DE cbl family; gene evolution ID C-CBL; DOWN-REGULATION; V-CBL; TYROSINE KINASES; IN-VIVO; PROTOONCOGENE; PROTEIN; FAMILY; ONCOGENE; ACTIVATION AB The genomic organization of cbl genes from a variety of mammalian and non-mammalian species was determined by a combination of cloning and database searches. Humans and mice have three cbl genes (c-cbl,(1) cblb, and cblc) which show remarkable conservation of the intron/exon structure over the region of the genes which encode the highly conserved N-terminal region of the proteins including the RING finger. Searches of genomic, cDNA, and EST databases revealed that one or more cbl genes exist in chordates, insects, and worms. Comparison of the complexity and genomic organization of the cbl gene family and the predicted Cbl proteins from various species suggests that the three mammalian cbl genes arose by two duplications of an ancestral gene. The genomic organization of the cbl genes from various species provides insight into the evolution of the cbl gene family. (C) 2003 Elsevier Science B.V. All rights reserved. C1 NCI, Genet Branch, Ctr Canc Res, Natl Naval Med Ctr, Bethesda, MD 20889 USA. Uniformed Serv Univ Hlth Sci, Cell & Mol Biol Program, Bethesda, MD 20889 USA. RP Lipkowitz, S (reprint author), NCI, Genet Branch, Ctr Canc Res, Natl Naval Med Ctr, Bldg 8,Room 5101, Bethesda, MD 20889 USA. NR 33 TC 32 Z9 33 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD APR 10 PY 2003 VL 308 BP 103 EP 113 DI 10.1016/S0378-1119(03)00471-2 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 679UC UT WOS:000182939500011 PM 12711395 ER PT J AU Somasundaram, R Swoboda, R Caputo, L Lee, A Jackson, N Marincola, FM Guerry, D Herlyn, D AF Somasundaram, R Swoboda, R Caputo, L Lee, A Jackson, N Marincola, FM Guerry, D Herlyn, D TI A CD4(+), HLA-DR7-restricted T-helper lymphocyte clone recognizes an antigen shared by human malignant melanoma and glioma SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE CD4(+); T-helper cell; melanoma; glioma; shared antigen ID MHC CLASS-I; RESTRICTED TUMOR-ANTIGENS; OPTIMAL INDUCTION; INFILTRATING LYMPHOCYTES; ANTITUMOR IMMUNITY; SYNTHETIC PEPTIDES; PERIPHERAL-BLOOD; MURINE LEUKEMIA; CELLS; EFFECTOR AB CD4(+) Th cells that are restricted by MHC class II molecules play an important role in the induction of antitumor immune responses. We have established a stable CD4(+) Th cell clone (Th35-1A) from the PBMCs of a patient with primary cutaneous melanoma. The Th cell clone is noncytolytic and proliferates specifically in the presence of irradiated autologous melanoma cells or autologous EBV-transformed B cells pulsed with melanoma tumor cell lysates. Th35-1A produces IFN-gamma (a Th1-type cytokine) after autologous tumor cell stimulation, and its proliferative reactivity is HLA class II-restricted. Th cells showed helper activity for PWM responses of PBMCs. Using a panel of HLA class II-matched and unmatched EBV-B cells as APCs and allogeneic melanoma tumor cell lysate as stimulant, DR7 was delineated as the HLA class II restriction element used by the Th cell clone. In agreement with these results, transfection of an allogeneic melanoma cell line with HLA-DR7 isolated from autologous EBV-B cells rendered the cell line stimulatory for Th35-1A cells. Specificity studies using autologous EBV-B cells (EBV-B35) pulsed with a panel of allogeneic tumor cell lysates of various tissue origins indicated that the Th cell clone recognizes an antigen shared by melanoma and glioma cells. The availability of the Th cell clone may lead to the development of new therapies against melanoma, using adoptive Th cell transfer and/or active immunization with a shared Th cell antigen. (C) 2003 Wiley-Liss, Inc. C1 Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. NIH, Bethesda, MD 20892 USA. Hosp Univ Penn, Dept Med, Div Hematol Oncol, Philadelphia, PA 19104 USA. Univ Penn, Ctr Canc, Melanoma Program, Philadelphia, PA 19104 USA. RP Herlyn, D (reprint author), Wistar Inst Anat & Biol, 3601 Spruce St, Philadelphia, PA 19104 USA. FU NCI NIH HHS [CA10815, CA25874, CA88198] NR 51 TC 10 Z9 10 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD APR 10 PY 2003 VL 104 IS 3 BP 362 EP 368 DI 10.1002/ijc.10964 PG 7 WC Oncology SC Oncology GA 649UP UT WOS:000181226600017 PM 12569560 ER PT J AU Greiner, E Prisinzano, T Johnson, EM Dersch, CM Marcus, J Partilla, JS Rothman, RB Jacobson, AE Rice, KC AF Greiner, E Prisinzano, T Johnson, EM Dersch, CM Marcus, J Partilla, JS Rothman, RB Jacobson, AE Rice, KC TI Structure-activity relationship studies of highly selective inhibitors of the dopamine transporter: N-benzylpiperidine analogues of 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PIPERIDINE ANALOGS; COCAINE-ABUSE; GBR-12909; AFFINITY; BINDING; 4-<2-(DIPHENYLMETHOXY)ETHYL>-1-BENZYLPIPERIDINE; IDENTIFICATION; SUBSTITUTIONS; SEROTONIN; MONKEYS AB A series of 4-[2-[bis(4-fluorophenyl)methoxylethyl-1-benzylpiperidines were examined for their ability to bind to the dopamine transporter (DAT), the serotonin transporter (SERT), and the norepinephrine transporter (NET). Binding results indicated that the presence of an electron-withdrawing group in the C-4-position of the N-benzyl group is beneficial for binding to the DAT. Several analogues have been identified with high affinity for the DAT, up to 500-fold selectivity over the SERT and about 170-fold selectivity over the NET in binding and uptake inhibition assays. C1 NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NIDA, Addict Res Ctr, Clin Psychopharmacol Sect, DHHS, Baltimore, MD 21224 USA. RP Rice, KC (reprint author), NIDDKD, Med Chem Lab, NIH, 8 Ctr Dr,MSC 0815,Bldg 8,Room B1-23, Bethesda, MD 20892 USA. EM kr21f@nih.gov RI Prisinzano, Thomas/B-7877-2010 NR 22 TC 18 Z9 18 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD APR 10 PY 2003 VL 46 IS 8 BP 1465 EP 1469 DI 10.1021/jm020419v PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 663YZ UT WOS:000182036100021 PM 12672246 ER PT J AU Kim, BJ Ghil, SH Kim, MJ Park, SY Kim, DS Kim, SH Chin, H Birnbaumer, L Jiang, M Hong, SY Suh-Kim, H Lee, YD AF Kim, BJ Ghil, SH Kim, MJ Park, SY Kim, DS Kim, SH Chin, H Birnbaumer, L Jiang, M Hong, SY Suh-Kim, H Lee, YD TI Modulation of the N-type calcium channel gene expression by the alpha subunit of Go SO MOLECULAR BRAIN RESEARCH LA English DT Article DE N-type calcium channel; Go; cAMP; F11; neuron; differentiation ID NEURONAL CA2+ CHANNELS; BETA-GAMMA-SUBUNITS; CELL-LINE; DEVELOPMENTAL-CHANGES; NEURITE OUTGROWTH; BINDING PROTEINS; PC12 CELLS; RECEPTORS; MIGRATION; F-11 AB Go, a heterotrimeric G-protein, is enriched in brain and neuronal growth cones. Although several reports suggest that Go may be involved in modulation of neuronal differentiation, the precise role of Go is not clear. To investigate the function of Go in neuronal differentiation, we determined the effect of Goalpha, the a subunit of Go, on the expression of Ca(v)2.2, the pore-forming unit of N-type calcium channels, at the transcription level. Treatment with cyclic AMP (cAMP), which triggers neurite outgrowth in neuroblastoma F11 cells, increased the mRNA level and the promoter activity of the Ca(v)2.2 gene. Overexpression of Goa inhibited neurite extension in F11 cells and simultaneously repressed the stimulatory effect of cAMP on the Ca(v)2.2 gene expression to the basal level. Targeted mutation of the Goa gene also increased the level of Ca(v)2.2 in the brain. These results suggest that Go may regulate neuronal differentiation through modulation of gene expression of target genes such as N-type calcium channels. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Ajou Univ, Sch Med, Dept Anat, Paldal Gu, Suwon 442749, South Korea. Ajou Univ, Dept Pediat, Suwon 441749, South Korea. Ajou Univ, Brain Dis Res Ctr, Suwon 441749, South Korea. Kyungpook Natl Univ, Dept Anat, Taegu 702701, South Korea. NIMH, Genet Res Branch, DNBBS, NIH, Bethesda, MD USA. Univ Calif Los Angeles, Dept Anesthesiol, Los Angeles, CA 90024 USA. NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. Sungkyunkwan Univ, Dept Gen Engn, Suwon 440746, South Korea. RP Lee, YD (reprint author), Ajou Univ, Sch Med, Dept Anat, Paldal Gu, San 5 Wonchon Dong, Suwon 442749, South Korea. EM yd11217@madang.ajou.ac.kr NR 39 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD APR 10 PY 2003 VL 112 IS 1-2 BP 95 EP 102 DI 10.1016/S0169-328X(03)00053-6 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 668YQ UT WOS:000182325300011 ER PT J AU Keusch, GT Medlin, CA AF Keusch, GT Medlin, CA TI Tapping the power of small institutions - Now is the time to create a virtual, global network for health research. SO NATURE LA English DT Editorial Material ID SCIENCE; EUROPE C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Univ Calif San Francisco, Inst Global Hlth, San Francisco, CA 94105 USA. RP Keusch, GT (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. NR 9 TC 13 Z9 13 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 10 PY 2003 VL 422 IS 6932 BP 561 EP 562 DI 10.1038/422561a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 665GN UT WOS:000182111400017 PM 12686973 ER PT J AU Maduke, M Mindell, JA AF Maduke, M Mindell, JA TI The poststructural festivities begin SO NEURON LA English DT Editorial Material ID CHLORIDE CHANNELS AB CIC chloride channels orchestrate the movement of chloride necessary for proper neuronal, muscular, cardiovascular, and epithelial function. In this issue of Neuron, Jentsch, Pusch, and colleagues use the structure of a bacterial CIC homolog to guide a mutagenic analysis of inhibitor binding to CIC-0, CIC-1, and CIC-2. C1 Stanford Univ, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA. NINDS, Membrane Transport Biophys Unit, NIH, Bethesda, MD 20892 USA. RP Maduke, M (reprint author), Stanford Univ, Dept Mol & Cellular Physiol, B155 Beckman Ctr,279 Campus Dr, Stanford, CA 94305 USA. OI Mindell, Joseph/0000-0002-6952-8247 NR 12 TC 1 Z9 1 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD APR 10 PY 2003 VL 38 IS 1 BP 1 EP 3 DI 10.1016/S0896-6273(03)00204-6 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 666XT UT WOS:000182202300001 PM 12691656 ER PT J AU Soler-Llavina, GJ Holmgren, M Swartz, KJ AF Soler-Llavina, GJ Holmgren, M Swartz, KJ TI Defining the conductance of the closed state in a voltage-gated K+ channel SO NEURON LA English DT Article ID SHAKER POTASSIUM CHANNELS; SCORPION TOXIN RECEPTOR; CHARYBDOTOXIN BLOCK; ACTIVATION GATE; GATING CHARGE; ION CHANNELS; PEPTIDE INHIBITOR; PORE; INACTIVATION; SELECTIVITY AB The opening and closing of the ion conduction pathway in ion channels underlies the generation and propagation of electrical signals in biological systems. Although electrophysiological approaches to measuring the flow of ions in the open state have contributed profoundly to our understanding of ion permeation and gating, it remains unclear how much the ion-throughput rate decreases upon closure of the ion conduction pore. To address this fundamental question, we expressed the Shaker Kv channel at high levels and then measured macroscopic K+ currents at negative membrane voltages and counted the number of channels by quantifying the translocation of gating charge. Our results show that the conductance of the closed state is between 0 and 0.16 fS, or at least 100,000 times lower than for the open state of the channel, indicating that the flow of ions is very tightly regulated in this class of K+ channels. C1 NINDS, Mol Physiol & Biophys Unit, NIH, Bethesda, MD 20892 USA. NINDS, Mol Neurophysiol Unit, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Swartz, KJ (reprint author), NINDS, Mol Physiol & Biophys Unit, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [ZIA NS002945-13] NR 55 TC 20 Z9 21 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD APR 10 PY 2003 VL 38 IS 1 BP 61 EP 67 DI 10.1016/S0896-6273(03)00157-0 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 666XT UT WOS:000182202300009 PM 12691664 ER PT J AU Ridker, PM Goldhaber, SZ Danielson, E Rosenberg, Y Eby, CS Deitcher, SR Cushman, M Moll, S Kessler, CM Elliott, CG Paulson, R Wong, T Bauer, KA Schwartz, BA Miletich, JP Bounameaux, H Glynn, RJ Ridker, PM Glynn, RJ Danielson, EM Bates, D Christen, W DeFonce, P Griffin, W Jackson, F Murray, A Taylor, K Johnson, K McKenna, K Pierre, J Holman, B Dessources, F Quinn, P Laurinaitis, T MacFadyen, J Eby, C Miletich, JP Porche-Sorbet, R Goldhaber, SZ Morrison, RB MacDougall, RC Morrison, RM Lamas, G Bailey, K Gersh, B Pellegrino, E Rick, M Vaughan, D Rosenberg, Y Goldhaber, SZ Morrison, RB MacDougall, RC Morrison, RM Deitcher, SR Olin, J Sulzer, S Cushman, M Cohen, R Moll, S Jones, S Kessler, CM Lee, A Elliott, CG Kitterman, N Jafri, S Wulbrecht, N Bauer, K Mahony, M Paulson, R Vold, D Wong, T Erickson-Nesmith, S Bounameaux, H de Lucia, S Chagnon, I Schwartz, B Thackery, R Gates, N Nguyen, P Paris, S LeCours, B Oliver, M Hodapp, K Grad, G Bank, B Rindels, J Leano, C Haire, W O'Grady, D Schneider, J Key, N Christie, B Blostein, M Strulovitch, C Usedom, J Oskins, D Eby, C Lee, V Heuerman, S Kerins, D Roberts, B White, R Castro, E Riddle, E Ingram, M Becker, RC Emery, C Wong, L Dent, S Comp, P Havarda, D Galichia, JP Terry, L Waldren, S Hambleton, J Pineo, G Hull, R Sheldon, J Tsapatsaris, N Woodhead, G Mann, M Welsh, C Schoch, T Goldsmith, J Anthony, T Walters, J Caprini, J Maher, ML Medica, K Rabbitt, S Finocchio, J Keaton, K Lee, H McLean, S Barban, K Mohler, E Medenilla, E Wolfe, M deLemos, A Rubenfire, M McDevitt, S Housholder, S Siegel, JE Bradley, B Brophy, M Reilly, C Brown, E Valeria, A Rodriguez, L Kumar, A Pekron, J Wagner, J Richart, J Jones, J Weber, V Fellin, C Sim, J Graham, M Sutton, D Tezcan, H Herbst, S Waldrum, M Meadows, T Carlson, W Welch-Costantino, M Gosset, J Nonnweiler, J Kumar, A Green, K Tapson, V Krichman, A Yeo, E Boross-Harmer, S AF Ridker, PM Goldhaber, SZ Danielson, E Rosenberg, Y Eby, CS Deitcher, SR Cushman, M Moll, S Kessler, CM Elliott, CG Paulson, R Wong, T Bauer, KA Schwartz, BA Miletich, JP Bounameaux, H Glynn, RJ Ridker, PM Glynn, RJ Danielson, EM Bates, D Christen, W DeFonce, P Griffin, W Jackson, F Murray, A Taylor, K Johnson, K McKenna, K Pierre, J Holman, B Dessources, F Quinn, P Laurinaitis, T MacFadyen, J Eby, C Miletich, JP Porche-Sorbet, R Goldhaber, SZ Morrison, RB MacDougall, RC Morrison, RM Lamas, G Bailey, K Gersh, B Pellegrino, E Rick, M Vaughan, D Rosenberg, Y Goldhaber, SZ Morrison, RB MacDougall, RC Morrison, RM Deitcher, SR Olin, J Sulzer, S Cushman, M Cohen, R Moll, S Jones, S Kessler, CM Lee, A Elliott, CG Kitterman, N Jafri, S Wulbrecht, N Bauer, K Mahony, M Paulson, R Vold, D Wong, T Erickson-Nesmith, S Bounameaux, H de Lucia, S Chagnon, I Schwartz, B Thackery, R Gates, N Nguyen, P Paris, S LeCours, B Oliver, M Hodapp, K Grad, G Bank, B Rindels, J Leano, C Haire, W O'Grady, D Schneider, J Key, N Christie, B Blostein, M Strulovitch, C Usedom, J Oskins, D Eby, C Lee, V Heuerman, S Kerins, D Roberts, B White, R Castro, E Riddle, E Ingram, M Becker, RC Emery, C Wong, L Dent, S Comp, P Havarda, D Galichia, JP Terry, L Waldren, S Hambleton, J Pineo, G Hull, R Sheldon, J Tsapatsaris, N Woodhead, G Mann, M Welsh, C Schoch, T Goldsmith, J Anthony, T Walters, J Caprini, J Maher, ML Medica, K Rabbitt, S Finocchio, J Keaton, K Lee, H McLean, S Barban, K Mohler, E Medenilla, E Wolfe, M deLemos, A Rubenfire, M McDevitt, S Housholder, S Siegel, JE Bradley, B Brophy, M Reilly, C Brown, E Valeria, A Rodriguez, L Kumar, A Pekron, J Wagner, J Richart, J Jones, J Weber, V Fellin, C Sim, J Graham, M Sutton, D Tezcan, H Herbst, S Waldrum, M Meadows, T Carlson, W Welch-Costantino, M Gosset, J Nonnweiler, J Kumar, A Green, K Tapson, V Krichman, A Yeo, E Boross-Harmer, S CA PREVENT Investigators TI Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID FACTOR-V-LEIDEN; ORAL ANTICOAGULANT-THERAPY; COAGULATION-FACTOR-V; ACTIVATED PROTEIN-C; PROTHROMBIN GENE; DOSE WARFARIN; FIRST EPISODE; RISK FACTOR; THROMBOSIS; MUTATION AB BACKGROUND: Standard therapy to prevent recurrent venous thromboembolism includes 3 to 12 months of treatment with full-dose warfarin with a target international normalized ratio (INR) between 2.0 and 3.0. However, for long-term management, no therapeutic agent has shown an acceptable benefit-to-risk ratio. METHODS: Patients with idiopathic venous thromboembolism who had received full-dose anticoagulation therapy for a median of 6.5 months were randomly assigned to placebo or low-intensity warfarin (target INR, 1.5 to 2.0). Participants were followed for recurrent venous thromboembolism, major hemorrhage, and death. RESULTS: The trial was terminated early after 508 patients had undergone randomization and had been followed for up to 4.3 years (mean, 2.1). Of 253 patients assigned to placebo, 37 had recurrent venous thromboembolism (7.2 per 100 person-years), as compared with 14 of 255 patients assigned to low-intensity warfarin (2.6 per 100 person-years), a risk reduction of 64 percent (hazard ratio, 0.36 [95 percent confidence interval, 0.19 to 0.67]; P<0.001). Risk reductions were similar for all subgroups, including those with and those without inherited thrombophilia. Major hemorrhage occurred in two patients assigned to placebo and five assigned to low-intensity warfarin (P=0.25). Eight patients in the placebo group and four in the group assigned to low-intensity warfarin died (P=0.26). Low-intensity warfarin was thus associated with a 48 percent reduction in the composite end point of recurrent venous thromboembolism, major hemorrhage, or death. According to per-protocol and as-treated analyses, the reduction in the risk of recurrent venous thromboembolism was between 76 and 81 percent. CONCLUSIONS: Long-term, low-intensity warfarin therapy is a highly effective method of preventing recurrent venous thromboembolism. C1 Brigham & Womens Hosp, Ctr Cardiovasc Dis Prevent, Boston, MA 02215 USA. Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA. Brigham & Womens Hosp, Div Cardiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. NIH, Bethesda, MD 20892 USA. Washington Univ, St Louis, MO USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ Vermont, Burlington, VT USA. Univ N Carolina, Chapel Hill, NC USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. LDS Hosp, Salt Lake City, UT USA. Altru Res Clin, Grand Forks, ND USA. St Boniface Gen Hosp, Winnipeg, MB R2H 2A6, Canada. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Modwest Pulm Consultants, Kansas City, MO USA. Univ Hosp Geneva, Geneva, Switzerland. RP Ridker, PM (reprint author), Brigham & Womens Hosp, Ctr Cardiovasc Dis Prevent, 900 Commonwealth Ave E, Boston, MA 02215 USA. EM pridker@partners.org NR 30 TC 514 Z9 528 U1 1 U2 13 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 10 PY 2003 VL 348 IS 15 BP 1425 EP 1434 DI 10.1056/NEJMoa035029 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 665CU UT WOS:000182102700002 PM 12601075 ER PT J AU Schechter, AN Gladwin, MT AF Schechter, AN Gladwin, MT TI Hemoglobin and the paracrine and endocrine functions of nitric oxide SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID BIOAVAILABILITY C1 NIDDK, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Schechter, AN (reprint author), NIDDK, Biol Chem Lab, NIH, Bldg 10,Rm 9N-307, Bethesda, MD 20892 USA. OI Schechter, Alan N/0000-0002-5235-9408 NR 6 TC 138 Z9 145 U1 3 U2 5 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 10 PY 2003 VL 348 IS 15 BP 1483 EP 1485 DI 10.1056/NEJMcibr023045 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 665CU UT WOS:000182102700011 PM 12686706 ER PT J AU Grady, C Emanuel, EJ Horng, S AF Grady, C Emanuel, EJ Horng, S TI Consent forms for oncology trials - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID CLINICAL-TRIALS; QUALITY; CANCER C1 NIH, Bethesda, MD 20892 USA. RP Grady, C (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 10 PY 2003 VL 348 IS 15 BP 1497 EP 1497 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 665CU UT WOS:000182102700026 ER PT J AU Husain, M Weisberg, A Moss, B AF Husain, M Weisberg, A Moss, B TI Topology of epitope-tagged F13L protein, a major membrane component of extracellular vaccinia virions SO VIROLOGY LA English DT Article ID POST-GOLGI VESICLES; ENVELOPE PROTEIN; INTRACELLULAR MOVEMENT; PHOSPHOLIPASE-D; VIRUS; MICROTUBULES; ANTIGEN; MOTIF; P37; DISSEMINATION AB The protein encoded by the vaccinia virus F13L open reading frame is required for the wrapping of intracellular mature virions by cisternae derived from trans-Golgi or endosomal membranes and is an abundant, palmitylated component of the outer membrane of extracellular virions. To study the topology of the F13L protein, we constructed recombinant vaccinia viruses and plasmids that express the F13L protein with an N- or C-terminal HA epitope tag. The recombinant viruses formed normal-size plaques and the tagged proteins were incorporated into the two outer membranes of intracellular enveloped virions (IEV), indicating that the epitope-tagged proteins were functional. By selective permeabilization of the plasma membrane of infected or transfected cells, we demonstrated that the N- and C-termini of the F13L proteins in the outer IEV membrane, as well as cellular membranes, were oriented toward the cytoplasm. After fusion of the outer viral membrane with the plasma membrane, externalized virions retain the inner of the two IEV membranes. The N- and C-termini of the F13L protein were exposed on the inner surface of this extracellular viral membrane, consistent with the accepted model of biogenesis of the IEV membrane by a wrapping process. Using a coupled in vitro transcription and translation system modified by the addition of microsomes, we determined that the F13L protein associated posttranslationally with membranes. The N- and C-termini were susceptible to protease digestion and the protein could be extracted with sodium carbonate, consistent with a peripheral mode of association. (C) 2003 Elsevier Science (USA). All rights reserved. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 31 TC 17 Z9 18 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD APR 10 PY 2003 VL 308 IS 2 BP 233 EP 242 DI 10.1016/S0042-6822(03)00063-1 PG 10 WC Virology SC Virology GA 671LZ UT WOS:000182467400004 PM 12706074 ER PT J AU Yanovski, JA Yanovski, SZ AF Yanovski, JA Yanovski, SZ TI Treatment of pediatric and adolescent obesity SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID BODY-MASS INDEX; CHILDREN; PREVALENCE; OVERWEIGHT; TRENDS; HYPERTENSION; GROWTH; TRIAL C1 NICHHD, Unit Growth & Obes, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Div Digest Dis & Nutr, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Yanovski, JA (reprint author), NICHHD, Unit Growth & Obes, Dev Endocrinol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 10N262,MSC 1862, Bethesda, MD 20892 USA. OI Yanovski, Jack/0000-0001-8542-1637 FU NICHD NIH HHS [ZO1 HD-00641] NR 27 TC 42 Z9 42 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 9 PY 2003 VL 289 IS 14 BP 1851 EP 1853 DI 10.1001/jama.289.14.1851 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 664ZJ UT WOS:000182094900032 PM 12684365 ER PT J AU DeRose, EF Darden, T Harvey, S Gabel, S Perrino, FW Schaaper, RM London, RE AF DeRose, EF Darden, T Harvey, S Gabel, S Perrino, FW Schaaper, RM London, RE TI Elucidation of the epsilon-theta subunit interface of Escherichia coli DNA polymerase III by NMR spectroscopy SO BIOCHEMISTRY LA English DT Article ID CHEMICAL-SHIFT; BACKBONE ASSIGNMENT; STRUCTURAL BASIS; PROTEINS; DOMAIN; SENSITIVITY; EXONUCLEASE; HOLOENZYME; HOMOLOGY; PROGRAM AB The DNA polymerase III holoenzyme (HE) is the primary replicative polymerase of Escherichia coli. The epsilon (epsilon) subunit of HE provides the 3'-->5' exonucleolytic proofreading activity for this complex. epsilon consists of two domains: an N-terminal domain containing the proofreading exonuclease activity (residues 1-186) and a C-terminal domain required for binding to the polymerase (alpha) subunit (residues 187-243). In addition to alpha-, epsilon also binds the small (8 kDa) theta (theta) subunit. The function of theta is unknown, although it has been hypothesized to enhance the 3'-->5' exonucleolytic proofreading activity of epsilon. Using NMR analysis and molecular modeling, we have previously reported a structural model of epsilon186, the N-terminal catalytic domain of epsilon [DeRose et al. (2002) Biochemistry 41, 94]. Here, we have performed 3D triple resonance NMR experiments to assign the backbone and C-beta resonances of [U-H-2,C-13,N-15] methyl protonated epsilon186 in complex with unlabeled theta. A structural comparison of the epsilon186-theta complex with free epsilon186 revealed no major changes in secondary structure, implying that the overall structure is not significantly perturbed in the complex. Amide chemical shift comparisons between bound and unbound epsilon186 revealed a potential binding surface on epsilon for interaction with theta involving structural elements near the epsilon catalytic site. The most significant shifts observed for the epsilon186 amide resonances are localized to helix alpha1 and beta-strands 2 and 3 and to the region near the beginning of alpha-helix 7. Additionally, a small stretch of residues (K158-L161), which previously had not been assigned in uncomplexed epsilon186, is predicted to adopt beta-strand secondary structure in the epsilon186-theta complex and may be significant for interaction with theta. The amide shift pattern was confirmed by the shifts of aliphatic methyl protons, for which the larger shifts generally were concentrated in the same regions of the protein. These chemical shift mapping results also suggest an explanation for how the unstable dnaQ49 mutator phenotype of E may be stabilized by binding theta. C1 NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. Wake Forest Univ, Med Ctr, Dept Biochem, Winston Salem, NC 27157 USA. RP London, RE (reprint author), NIEHS, Struct Biol Lab, Box 12233, Res Triangle Pk, NC 27709 USA. FU NCI NIH HHS [CA75350] NR 33 TC 25 Z9 25 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 8 PY 2003 VL 42 IS 13 BP 3635 EP 3644 DI 10.1021/bi0205451 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 663FV UT WOS:000181996300001 PM 12667053 ER PT J AU Gunasekaran, K Ma, BY Ramakrishnan, B Qasba, PK Nussinov, R AF Gunasekaran, K Ma, BY Ramakrishnan, B Qasba, PK Nussinov, R TI Interdependence of backbone flexibility, residue conservation, and enzyme function: A case study on 1,4-galactosyltransferase-I SO BIOCHEMISTRY LA English DT Article ID LIMITED PROTEOLYSIS; CRYSTAL-STRUCTURE; CONFORMATIONAL CHANGE; MOLECULAR-DYNAMICS; ALPHA-LACTALBUMIN; ESCHERICHIA-COLI; PROTEIN FUNCTION; ENERGY FUNCTION; DOMAINS; LOOP AB beta1,4-Galactosyltransferase-I (beta4Gal-T1) catalyzes the transfer of a galactose from UDP-galactose to N-acetylglucosamine. A recent crystal structure determination of the substrate-bound enzyme reveals a large conformational change, which creates binding sites for the oligosaccharide and alpha-lactalbumin, when compared to the ligand-free structure. The conformational changes take place in a 21-residue-long loop (I345-H365) and in a smaller loop containing a tryptophan residue (W314) flanked by glycines (Y311-G316; Trp loop). A series of molecular dynamics simulations carried out with an implicit solvent model and with explicit water successfully identify flexibility in the two loops and in another interacting loop. These observations are confirmed by limited proteolysis experiments that reveal an intrinsic flexibility of the long loop. The multiple simulation runs starting with the substrate-free structure show that the long loop moves toward its conformation in the ligand-bound structure; however, it gets stabilized in an intermediate position. The Trp loop moves in the opposite direction to that of the long loop, making contacts with residues in the long loop. Remarkably, when the Trp loop is restrained in its starting conformation, no large conformational change takes place in the long loop, indicating residue communication of flexibility. Sequence and structural analysis of the beta4Gal-T1 family with 37 known sequences reveals that in contrast to the unconserved. long loop, which undergoes a much larger conformational change, the Trp loop including the glycines is highly conserved. These observations lead us to propose a new functional mechanism that may be conserved by evolution to perform a variety of functions. C1 NCI, Lab Expt & Computat Biol, Struct Glycobiol Sect, Frederick, MD 21702 USA. NCI, Lab Expt & Computat Biol, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Qasba, PK (reprint author), NCI, Lab Expt & Computat Biol, Struct Glycobiol Sect, Bldg 469,Room 151-221, Frederick, MD 21702 USA. RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU NCI NIH HHS [N01-CO-12400] NR 41 TC 22 Z9 24 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 8 PY 2003 VL 42 IS 13 BP 3674 EP 3687 DI 10.1021/bi034046r PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 663FV UT WOS:000181996300005 PM 12667057 ER PT J AU Berezhkovskii, AM Barzykin, AV AF Berezhkovskii, AM Barzykin, AV TI Escape and reentry of a Brownian particle through a hole in a cavity SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID KINETICS C1 NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. AIST, Tsukuba, Ibaraki 3058565, Japan. LY Karpov Phys Chem Res Inst, Moscow 103064, Russia. RP Berezhkovskii, AM (reprint author), NIH, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. NR 7 TC 3 Z9 3 U1 0 U2 1 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD APR 8 PY 2003 VL 118 IS 14 BP 6700 EP 6701 DI 10.1063/1.1560931 PG 2 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 660LP UT WOS:000181834900065 ER PT J AU Bretsky, P Guralnik, JM Launer, L Albert, M Seeman, TE AF Bretsky, P Guralnik, JM Launer, L Albert, M Seeman, TE TI The role of APOE-epsilon 4 in longitudinal cognitive decline - MacArthur studies of successful aging SO NEUROLOGY LA English DT Article ID APOLIPOPROTEIN-E EPSILON-4; SPORADIC ALZHEIMERS-DISEASE; APOE GENOTYPE; COMMUNITY RESIDENTS; FOLLOW-UP; ALLELE; DEMENTIA; POPULATION; PERFORMANCE; RISK AB Background: While a genetic risk factor for late-onset AD, the effects of the is an element of4 allele of the APOE gene on cognitive functioning more generally remain unclear. Objective: To assess the role of the is an element of4 allele of the APOE gene in longitudinal cognitive decline. Methods: Multiple measures of cognitive function were assessed longitudinally in the MacArthur Successful Aging Study, a population-based cohort free of frank impairment at baseline. Subjects were 965 Caucasian and African American men and women from Durham NC, East Boston, MA, and New Haven, CT, aged 70 to 79 years, recruited in 1988 through 1989, who completed two follow-up evaluations, one at 3 years and another at 7 years. Results: At the first follow-up, modest but significant declines in naming and spatial ability were associated with the APOE-is an element of4 genotype. By the second follow-up, more pronounced and significant associations were noted between the APOE-is an element of4 genotype and cognitive decline from six of the eight cognitive outcomes. After 7 years, APOE-is an element of4 allele carriers were twice as likely to have declined on a global cognitive score (odds ratio = 2.0; 95% CI: 1.1, 3.6) as noncarriers. Conclusions: APOE-is an element of4 is associated with cognitive decline among a high-functioning elderly cohort, with effects most pronounced after 7 years of follow-up. Hence, the is an element of4 allele either may function as a risk factor for cognitive impairment in normal aging across a broad spectrum of domains or may exert detectable effects early in a long prodromal AD trajectory. C1 Univ So Calif, Norris Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. Univ Calif Los Angeles, Div Geriatr, Dept Med, Los Angeles, CA USA. NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat Gerontol, Boston, MA USA. RP Bretsky, P (reprint author), Univ So Calif, Norris Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. FU NIA NIH HHS [AG-17265, AG-17056] NR 47 TC 150 Z9 155 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 8 PY 2003 VL 60 IS 7 BP 1077 EP 1081 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 675EP UT WOS:000182680300005 PM 12682309 ER PT J AU Brenner, S Malech, HL AF Brenner, S Malech, HL TI Current developments in the design of onco-retrovirus and lentivirus vector systems for hematopoietic cell gene therapy SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Review DE onco-retrovirus; gene therapy; lentivirus ID HUMAN-IMMUNODEFICIENCY-VIRUS; APE LEUKEMIA-VIRUS; AMINO-ACID TRANSPORTER; HUMAN CD34(+) CELLS; IN-VIVO SELECTION; NOD/SCID-REPOPULATING CELLS; NONDIVIDING HUMAN-CELLS; BLOOD PROGENITOR CELLS; BONE-MARROW CELLS; HUMAN BETA-GLOBIN AB Over the past dozen years, the majority of clinical gene therapy trials for inherited genetic diseases and cancer therapy have been performed using murine onco-retrovirus as the gene delivery vector. The earliest systems used were relatively inefficient in both the rates of transduction and expression of the transgene. Formidable obstacles inherent in the cell biology and/or the immunology of the target cell systems limited the efficacy of gene therapy for many target diseases. Development of novel retrovirus gene transfer systems that are in progress have begun to overcome these obstacles. Evidence of this progress is the recent successful functional correction of the immune T and B lymphocyte deficiency in patients with X-linked severe combined immunodeficiency (X-SCID) and adenosine deaminase (ADA)-deficient SCID following onco-retrovirus vector ex vivo transduction of autologous marrow stem cells [Science 296 (2002) 2410; Science 288 (2000) 669; N. Engl. J. Med. 346 (2002) 1185]. These achievements of prolonged clinical benefit from gene therapy were tempered by the finding of insertional mutageneses in two of the treated X-SCID patients. C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Brenner, S (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RI Brenner, Sebastian/D-7456-2013; OI Malech, Harry/0000-0001-5874-5775 NR 192 TC 40 Z9 40 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD APR 7 PY 2003 VL 1640 IS 1 BP 1 EP 24 DI 10.1016/S0167-4889(03)00024-7 PG 24 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 665UP UT WOS:000182139900001 PM 12676350 ER PT J AU Lewis, D Zhang, Y Prisinzano, T Dersch, CM Rothman, RB Jacobson, AE Rice, KC AF Lewis, D Zhang, Y Prisinzano, T Dersch, CM Rothman, RB Jacobson, AE Rice, KC TI Further exploration of 1-{2-[bis-(4-fluorophenyl)methoxy]ethyl}piperazine (GBR 12909): Role of N-aromatic, N-heteroaromatic, and 3-oxygenated N-phenylpropyl substituents on affinity for the dopamine and serotonin transporter SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID ABUSE THERAPEUTIC AGENTS; 1-<2-ETHYL>-4-(3-PHENYLPROPYL)PIPERAZINES GBR-12935; REUPTAKE INHIBITORS; ANALOGS; PIPERAZINE; 1-<2-(DIPHENYLMETHOXY)ETHYL>-4-(3-PHENYLPROPYL)PIPERAZINES; POTENT; USERS; DERIVATIVES; DECANOATE AB A series of N-aromatic, N-heteroaromatic, and oxygenated N-phenylpropyl derivatives of 1-(2-benzhydryloxyethyl)piperazine and 1-{2-[bis-(4-fluorophenyl)methoxy]ethyl}piperazine, analogues of GBR 12909 (1a) and 12935 (1b), was synthesized and examined for their dopamine (DAT) and serotonin (SERT) transporter binding properties. One of these compounds, racemic 3-[4-(2-benzhydryloxyethyl)piperazin-1-yl]-1-(3-fluorophenyl)-propan-l-ol (33), had DAT affinity as good as, or better than, GBR 12909 and 12935, and was more selective for DAT over SERT than the GBR compounds. Both trans- (43) and cis- (47) (+/-)-2-(4-{2-[bis-(4-fluorophenyl)-methoxy]ethyl}piperazin-1-ylmethyl)-6-methoxy-1,2,3,4-tetrahydronaphthalen-l-ol had relatively good SERT selectivity and, as well, showed high affinity for SERT. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 NIDDK, Med Chem Lab, NIH, Rockville, MD 20857 USA. NIDA, Addict Res Ctr, Psychopharmacol Sect, Baltimore, MD 21224 USA. RP Rice, KC (reprint author), NIDDK, Med Chem Lab, NIH, Rockville, MD 20857 USA. RI Prisinzano, Thomas/B-7877-2010 NR 26 TC 9 Z9 9 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD APR 7 PY 2003 VL 13 IS 7 BP 1385 EP 1389 DI 10.1016/S0960-894X(03)00108-2 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 662WG UT WOS:000181971600037 PM 12657288 ER PT J AU Gu, ZQ Li, M AF Gu, ZQ Li, M TI A concise synthesis of (2S,4R)- and (2S,4S)-4-methylglutamic acid SO TETRAHEDRON LETTERS LA English DT Article DE 4-methylglutamic acid; synthesis; enantiomerically pure ID DIASTEREOSELECTIVE SYNTHESIS; BIOLOGICAL EVALUATION; GLUTAMATE RECEPTORS; KAINATE RECEPTORS; HIGH-AFFINITY; ANALOGS; SYM-2081; PROBES; LIGAND AB A concise, multi-gram scale method for producing the bioactive and enantiomerically pure epimers, (2S,4R)- and (2S,4S)-glutamic acids, in a single synthetic scheme is described. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Sunmack Sci Inc, Gaithersburg, MD 20898 USA. NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Li, M (reprint author), Sunmack Sci Inc, POB 7002, Gaithersburg, MD 20898 USA. NR 14 TC 6 Z9 6 U1 0 U2 1 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 APR 7 PY 2003 VL 44 IS 15 BP 3203 EP 3205 DI 10.1016/S0040-4039(03)00429-5 PG 3 WC Chemistry, Organic SC Chemistry GA 662ZC UT WOS:000181978800043 ER PT J AU Janini, GM Conrads, TP Veenstra, TD Issaq, HJ AF Janini, GM Conrads, TP Veenstra, TD Issaq, HJ TI Development of a two-dimensional protein-peptide separation protocol for comprehensive proteome measurements SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE proteomes; proteins; peptides ID MASS-SPECTROMETRY; IDENTIFICATION TECHNOLOGY; LIQUID-CHROMATOGRAPHY; ELECTROPHORESIS; PREFRACTIONATION; MIXTURES; GELS AB We have developed an effective two-dimensional fractionation protocol of complex proteome mixtures that extends the ability to conduct more comprehensive proteome measurements. A sample containing intact proteins extracted from Saccharomyces cerevisiae was fractionated by liquid phase isoelectric focusing, followed by tryptic digestion and solid-phase extraction (SPE) clean-up and reversed-phase liquid chromatography-electrospray ionization tandem mass spectrometry (LC-MS-MS) of the resultant peptides. The clean-up step is designed to desalt the fractions and rid them of urea and ampholytes prior to analysis by LC-MS-MS. Fifty milligrams of protein were separated into 20 fractions by liquid-phase isoelectric focusing, spanning a pH range of 3-10. The effectiveness of the removal of ampholytes was monitored by capillary zone electrophoresis and LC-MS-MS. The ability to analyze all of the 20 fractions without any noticeable decrease in the separation efficiency demonstrates the overall effectiveness of the SPE clean-up step. The results show that the separation strategy is effective for high throughput characterization of proteins from complex proteomic mixtures. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NCI, Analyt Chem Lab, Separat Technol Grp, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Issaq, HJ (reprint author), NCI, Analyt Chem Lab, Separat Technol Grp, SAIC Frederick Inc, POB B, Frederick, MD 21702 USA. EM issaqh@mail.ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 27 TC 23 Z9 26 U1 1 U2 3 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 APR 5 PY 2003 VL 787 IS 1 BP 43 EP 51 DI 10.1016/S1570-0232(02)00616-5 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 659XW UT WOS:000181804900005 PM 12659732 ER PT J AU Michalek, J Collins, RH Hill, BJ Brenchley, JM Douek, DC AF Michalek, J Collins, RH Hill, BJ Brenchley, JM Douek, DC TI Identification and monitoring of graft-versus-host specific T-cell clone in stem cell transplantation SO LANCET LA English DT Article ID DISEASE AB Allogeneic haemopoietic stem cell transplantation can be complicated by acute graft-versus-host disease (GVHD). If the alloreactive T-cell clones responsible for this disorder could be identified before stem cell transplantation, they could be quantitatively monitored afterwards to allow initiation of immunosuppression before GVHD becomes apparent. We identified an alloreactive CD4(+) T-cell clone from a donor before stem cell transplantation, and then monitored its frequency in the recipient's peripheral blood after transplantation by use of clonotypic quantitative real-time PCR. Greatly increased concentrations of this clone (nearly 100% of circulating CD4(+) T cells) preceded and closely correlated with the onset of clinical GVHD, suggesting that a sole alloreactive T-cell clone was responsible for initiation of this disease in vivo. This simple identification and monitoring of potentially GVHD-causing clones can be undertaken before stem cell transplantation with no previous knowledge of the alloantigen responsible, and could allow earlier diagnosis and intervention in GVHD. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Ctr Canc Immunobiol, Dallas, TX 75235 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Bone Marrow Transplant Unit, Dallas, TX USA. RP Douek, DC (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA. NR 5 TC 54 Z9 58 U1 0 U2 4 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD APR 5 PY 2003 VL 361 IS 9364 BP 1183 EP 1185 DI 10.1016/S0140-6736(03)12917-0 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 664ZF UT WOS:000182094600013 PM 12686042 ER PT J AU Negishi, M Dong, J Darden, TA Pedersen, LG Pedersen, LC AF Negishi, M Dong, J Darden, TA Pedersen, LG Pedersen, LC TI Glucosaminylglycan biosynthesis: what we can learn from the X-ray crystal structures of glycosyltransferases GlcAT1 and EXTL2 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Editorial Material ID HEPARAN-SULFATE; BLOOD-GROUP; DONOR; BETA-1,3-GLUCURONOSYLTRANSFERASE-I; ALPHA-1,3-GALACTOSYLTRANSFERASE; SPECIFICITY; MECHANISM; BINDING; COMPLEX AB The X-ray crystal structures of two glycosyltransferases (GTs)-beta1,3-glucuronyltransferase I (GlcAT1) and alpha1,4-N-acetyl-hexosaminyltransferase (EXTL2)-have now been determined in the presence of both donor and acceptor substrates. These enzymes are involved in glucosaminylglycan (GAG) synthesis where they catalyze inverting and retaining transfer reactions, respectively. As members of a large family of enzymes that transfer sugar groups from donor nucleotide-sugars to acceptor substrates, GlcAT1 and EXTL2 retain conserved GT folds. Comparative analysis of these structures reveals signature features for selecting specific donor sugars. Adaptive binding of the disaccharide moiety of the acceptor sugars enables the enzymes to catalyze either an inverting S(N)2-type displacement reaction or a retaining S(N)i-like transfer reaction. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Pharmacogenet Sect, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC USA. Struct Biol Lab, Res Triangle Pk, NC USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Negishi, M (reprint author), Pharmacogenet Sect, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC USA. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 NR 24 TC 44 Z9 45 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 4 PY 2003 VL 303 IS 2 BP 393 EP 398 DI 10.1016/S0006-291X(03)00356-5 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 666LB UT WOS:000182177800001 PM 12659829 ER PT J AU Ayad, NG Rankin, S Murakami, M Jebanathirajah, J Gygi, S Kirschner, MW AF Ayad, NG Rankin, S Murakami, M Jebanathirajah, J Gygi, S Kirschner, MW TI Tome-1, a trigger of mitotic entry, is degraded during G1 via the APC SO CELL LA English DT Article ID SISTER-CHROMATID SEPARATION; ANAPHASE-PROMOTING COMPLEX; CELL-CYCLE; SUBSTRATE RECOGNITION; MITOSIS; KINASE; CDH1; DEGRADATION; PROTEOLYSIS; INHIBITOR AB Entry into mitosis requires the activation of cdk1/ cyclin B, while mitotic exit is achieved when the same kinase activity decreases, as cyclin B is degraded. Cyclin B proteolysis is mediated by the anaphase promoting complex, or APC, an E3 ligase that is active at anaphase in mitosis through G1. We have identified a G1 substrate of the APC that we have termed Tome-1, for trigger of mitotic entry. Tome-1 is a cytosolic protein required for proper activation of cdk1/cyclin B and mitotic entry. Tome-1 associates with Skp-1 and is required for degradation of the cdk1 inhibitory tyrosine kinase wee1; Tome-1 therefore appears to be acting as part of an SCF-type E3 for wee1. Degradation of Tome-1 during G1 allows for wee 1 accumulation during interphase, thereby providing a critical link between the APC and SCF pathways in regulation of cclk1/cyclin B activity and thus mitotic entry and exit. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Taplin Biol Mass Spectrometry Facil, Boston, MA 02115 USA. NCI, Frederick, MD 21702 USA. RP Kirschner, MW (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 200 Longwood Ave, Boston, MA 02115 USA. OI Rankin, Susannah/0000-0002-4056-6610 FU NHGRI NIH HHS [HG00041] NR 32 TC 101 Z9 105 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD APR 4 PY 2003 VL 113 IS 1 BP 101 EP 113 DI 10.1016/S0092-8674(03)00232-0 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 668GX UT WOS:000182282900010 PM 12679038 ER PT J AU Yang, DM Song, LS Zhu, WZ Chakir, K Wang, W Wu, CH Wang, YB Xiao, RP Chen, SRW Cheng, H AF Yang, DM Song, LS Zhu, WZ Chakir, K Wang, W Wu, CH Wang, YB Xiao, RP Chen, SRW Cheng, H TI Calmodulin regulation of excitation-contraction coupling in cardiac myocytes SO CIRCULATION RESEARCH LA English DT Article DE calmodulin; Ca2+/calmodulin-dependent protein kinase II; L-type Ca2+ channels; phospholamban ID CA2+/CALMODULIN-DEPENDENT PROTEIN-KINASE; CA2+ RELEASE; RYANODINE RECEPTOR; CALCIUM CHANNELS; MUSCLE; PHOSPHOLAMBAN; INACTIVATION; BINDING; PHOSPHORYLATION; APOCALMODULIN AB Calmodulin (CaM) as a ubiquitous Ca2+ sensor interacts with multiple key molecules involved in excitation-contraction (EC) coupling. In the present study, we report that adenoviral expression of a mutant CaM lacking all of its four Ca2+-binding sites, CaM(1-4), at a level 6.5- fold over endogenous CaM markedly increases the amplitude and abbreviates the decay time of Ca2+ transients and contraction in cultured rat ventricular myocytes. To determine the underlying mechanisms, we examined the properties of L-type Ca2+ channels, Ca2+/CaM-dependent protein kinase II (CaMKII), and phospholamban (PLB) in the sarcoplasmic reticulum (SR). We found that CaM(1-4) expression markedly augmented L-type Ca2+ current amplitude and slowed its inactivation. Surprisingly, overexpression of CaM(1-4) increased CaMKII activity and phosphorylation of PLB-Thr-17. Moreover, CaM(1-4) elevated diastolic Ca2+ and caffeine-labile Ca2+ content of the SR. Inhibition of CaMKII by KN-93 or a myristoylated autocamtide-2 related inhibitory peptide prevented the aforementioned PLB phosphorylation and reversed the positive inotropic and relaxant effects, indicating that CaMKII is essential to CaM(1-4) actions. These results demonstrate that CaM modulates Ca2+ influx, SR Ca2+ release, and Ca2+ recycling during cardiac EC coupling. A novel finding of this study is that expression of a Ca2+-insensitive CaM mutant can lead to activation of CaMKII in cardiac myocytes. C1 NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. Peking Univ, Coll Life Sci, Natl Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China. Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. Univ Calgary, Cardiovasc Res Grp, Dept Physiol & Biophys, Calgary, AB, Canada. Univ Calgary, Cardiovasc Res Grp, Dept Biochem & Mol Biol, Calgary, AB, Canada. RP Cheng, H (reprint author), NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. RI Song, Long-Sheng/D-5899-2012; OI Wang, Yibin/0000-0003-0852-0767 NR 36 TC 17 Z9 20 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD APR 4 PY 2003 VL 92 IS 6 BP 659 EP 667 DI 10.1161/01.RES.0000064566.91495.0C PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 663PE UT WOS:000182013300015 PM 12609973 ER PT J AU Yasar, S Bergman, J Munzar, P Redhi, G Tober, C Knebel, N Zschiesche, M Paronis, C AF Yasar, S Bergman, J Munzar, P Redhi, G Tober, C Knebel, N Zschiesche, M Paronis, C TI Evaluation of the novel antiepileptic drug, AWD 131-138, for benzodiazepine-like discriminative stimulus and reinforcing effects in squirrel monkeys SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE anticonvulsant; benzodiazepine; AWD 131-138; midazolam; diazepam; drug discrimination; self-administration; monkey ID CONFERENCE EILAT-V; PROGRESS REPORT; SELF-INJECTION; FIXED-RATIO; MIDAZOLAM; RECEPTOR; AWD-131-138; SCHEDULES; BEHAVIOR; ANIMALS AB AWD 131-138 {1-(4-chlorophenyl)-4-morpholino-imidazolin-2-one}, a new low-affinity partial benzodiazepine receptor agonist with potent anticonvulsant and anxiolytic properties in rodent models, was studied in squirrel monkeys trained to discriminate intramuscular (i.m.) injections of midazolam (0.3 mg/kg) from injections of vehicle. Diazepam produced midazolam-like responding at cumulative doses of 1.0 and 3.0 mg/kg i.m. and decreased rates of responding at 3.0 mg/kg (plasma levels of about 400 ng/ml). In contrast, AWD 131-138 did not produce midazolam-like responding or alter response rates at cumulative doses up to 18.0 mg/kg i.m. (plasma levels over 2100 ng/ml). Other monkeys were trained to intravenously (i.v.) self-administer cocaine (56.0 mug/kg/injection). When AWD 131-138 (10-100 mug/kg/injection) was studied by substitution, responding declined to vehicle substitution levels within three sessions. At the dose of 100 mug/kg i.v. AWD 131138, sufficient drug was self-administered during the first session (about 3.5 mg/kg) to produce plasma levels above 1000 ng/ml, yet responding over the next two sessions dropped to vehicle levels. The failure of AWD 131-138 to produce benzodiazepine-like discriminative effects and the absence of drug self-administration behavior when substituted for cocaine suggest that its abuse liability is low. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Baltimore, MD USA. Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD USA. Harvard Med Sch, Dept Psychiat, Boston, MA USA. Arzneimittelwerk Dresden GmbH, Dept Pharmacol, Radebeul, Germany. ASTA Med AG, Dept Pharmacokinet & Bioanalyt, Frankfurt, Germany. Univ Greifswald, Inst Pharmacol, Greifswald, Germany. AWD Pharma GmbH & Co KG, Marketing Serv, Dresden, Germany. RP Yasar, S (reprint author), Johns Hopkins Bayview Med Ctr, 5505 Hopkins Bayview Circle, Baltimore, MD 21224 USA. FU PHS HHS [10566, 03774, 11453] NR 34 TC 9 Z9 9 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD APR 4 PY 2003 VL 465 IS 3 BP 257 EP 265 DI 10.1016/S0014-2999(03)01533-4 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 663TX UT WOS:000182023000007 PM 12681437 ER PT J AU Dehaye, JP Nagy, A Premkumar, A Turner, RJ AF Dehaye, JP Nagy, A Premkumar, A Turner, RJ TI Identification of a functionally important conformation-sensitive region of the secretory Na+-K+-2Cl(-) cotransporter (NKCC1) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID K-CL COTRANSPORTER; CHLORIDE COTRANSPORT; BUMETANIDE BINDING; ION-TRANSPORT; CHANNEL; PHOSPHORYLATION; ACCESSIBILITY; TOPOLOGY; DOMAINS AB The secretory Na+-K+-2Cl(-) cotransporter (NKCC1) is a member of a small gene family of electroneutral salt transporters that play essential roles in salt and water homeostasis in many mammalian tissues. We have identified a highly conserved residue (Ala-483) in the sixth membrane-spanning segment of rat NKCC1 that when mutated to cysteine renders the transporter sensitive to inhibition by the sulfhydryl reagents 2-aminoethyl methanethiosulfonate (MTSEA) and 2-(trimethylammonium)ethyl methanethiosulfonate (MTSET). The mutation of Ala-483 to cysteine (A483C) results in little or no change in the affinities of NKCC1 for substrate ions but produces a 6-fold increase in sensitivity to the inhibitor bumetanide, suggesting a specific modification of the bumetanide binding site. When residues surrounding Ala-483 were mutated to cysteine, only 1484C was sensitive to inhibition by MTSEA and MTSET. Surprisingly 1484C showed increased transport activity in the presence of low concentrations of mercury (1-10 mum), whereas A483C showed inhibition. The inhibition of A483C by MTSEA was unaffected by the presence or absence of sodium and potassium but required the presence of extracellular chloride. Taken together, our results indicate that Ala-483 lies at or near an important functional site of NKCC1 and that the exposure of this site to the extracellular medium is dependent on the conformation of the transporter. Specifically, our results indicate that the cysteine introduced at residue 483 is only available for interaction with MTSEA when chloride is bound to NKCC1 at the extracellular surface. C1 NIDCR, Gene Therapy & Therapeut Branch, Membrane Biol Sect, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. Free Univ Brussels, Inst Pharm, Lab Biochim & Biol Cellulaire, B-1050 Brussels, Belgium. RP Turner, RJ (reprint author), NIDCR, Gene Therapy & Therapeut Branch, Membrane Biol Sect, Dept Hlth & Human Serv,NIH, Bldg 10,Rm 1A01,10 Ctr Dr,MSC 1190, Bethesda, MD 20892 USA. NR 19 TC 11 Z9 11 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 APR 4 PY 2003 VL 278 IS 14 BP 11811 EP 11817 DI 10.1074/jbc.M213148200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 663QF UT WOS:000182015700013 PM 12556450 ER PT J AU Muller, JR Siebenlist, U AF Muller, JR Siebenlist, U TI Lymphotoxin beta receptor induces sequential activation of distinct NF-kappa B factors via separate signaling pathways SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ALYMPHOPLASIA ALY MICE; DEFICIENT MICE; SPLENIC MICROARCHITECTURE; TRANSCRIPTIONAL ACTIVITY; INCONTINENTIA PIGMENTI; LYMPHOID-TISSUES; CELL ACTIVATION; KINASE-ALPHA; IKK-ALPHA; ORGANOGENESIS AB Lymphotoxin beta receptor (LTbetaR)-induced activation of NF-kappaB in mouse embryo fibroblasts was mediated by the classical pathway and by an alternative or second pathway. The classical pathway involved the IkappaB kinase (IKK)beta- and IKKgamma-dependent degradation of IkappaBalpha and resulted in the rapid but transient activation of primarily RelA-containing NF-kappaB dimers. The alternative or second pathway proceeded via NF-kappaB-inducing kinase (NIK)-, IKKalpha-, and protein synthesis-dependent processing of the inhibitory NF-kappaB2 p100 precursor protein to the p52 form and resulted in a delayed but sustained activation of primarily RelB-containing NF-kappaB dimers. This second pathway was independent of the classical IKK complex, which is governed by its central IKKgamma regulatory subunit. The sequential engagement of two distinct pathways, coupled with the negative feedback inhibition of RelA complexes by NF-kappaB-induced resynthesis of IkappaBalpha, resulted in a pronounced temporal change in the nature of the NF-kappaB activity during the course of stimulation. Initially dominant ReIA complexes were replaced with time by RelB complexes. Therefore, the alternative activation path mediated by processing of p100 was necessary for sustained NF-kappaB activity in mouse embryo fibroblasts in response to LTbetaR stimulation. Based on the phenotype of mice deficient in various components of the LTbetaR-induced activation of p100 processing, we conclude that this pathway is critically involved in the function of stromal cells during the generation of secondary lymphoid organ microarchitectures. C1 NIAID, NIH, Immunoregulat Lab, Bethesda, MD 20892 USA. RP Siebenlist, U (reprint author), NIAID, NIH, Immunoregulat Lab, Bldg 10,Rm 11B16, Bethesda, MD 20892 USA. NR 34 TC 122 Z9 127 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 APR 4 PY 2003 VL 278 IS 14 BP 12006 EP 12012 DI 10.1074/jbc.M210768200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 663QF UT WOS:000182015700039 PM 12556537 ER PT J AU Chahdi, A Choi, WS Kim, YM Beaven, MA AF Chahdi, A Choi, WS Kim, YM Beaven, MA TI Mastoparan selectively activates phospholipase D2 in cell membranes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; ADP-RIBOSYLATION FACTOR; GTP-BINDING PROTEINS; MUSCARINIC ACETYLCHOLINE-RECEPTOR; RAT-BRAIN; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; RBL-2H3 CELLS; MAST-CELLS; SIGNAL-TRANSDUCTION; PEPTIDE AB Both known isoforms of phospholipase (PL) D, PLD1 and PLD2, require phosphatidylinositol 4,5-bisphosphate for activity. However, PLD2 is fully active in the presence of this phospholipid, whereas PLD1 activation is dependent on additional factors such as ADP-ribosylation factor-1 (ARF-1) and protein kinase Calpha. We find that mastoparan, an activator of G(i) and mast cells, stimulates an intrinsic PLD activity, most likely PLD2, in fractions enriched in plasma membranes from rat basophilic leukemia 2H3 mast cells. Overexpression of PLD2, but not of PLD1, results in a large increase in the mastoparan-inducible PLD activity in membrane fractions, particularly those enriched in plasma membranes. As in previous studies, expressed PLD2 is localized primarily in the plasma membrane and PLD1 in granule membranes. Studies with pertussis toxin and other agents indicate that mastoparan stimulates PLD2 independently of G(i), ARF-1, protein kinase C, and calcium. Kinetic studies indicate that mastoparan interacts synergistically with phosphatidylinositol 4,5-bisphosphate and that oleate, itself a weak stimulant of PLD2 at low concentrations, is a competitive inhibitor of mastoparan stimulation of PLD2. Therefore, mastoparan may be useful for investigating the regulation of PLD2, particularly in view of the well studied molecular interactions of mastoparan with certain other strategic signaling proteins. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. Med Coll Wisconsin, Dept Med Nephrol, Milwaukee, WI 53226 USA. Konkuk Univ, Coll Med, Dept Immunol, Chungcheongbuk Do 380701, South Korea. RP Beaven, MA (reprint author), NHLBI, Lab Mol Immunol, NIH, Rm 8N109,Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 52 TC 28 Z9 29 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 APR 4 PY 2003 VL 278 IS 14 BP 12039 EP 12045 DI 10.1074/jbc.M212084200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 663QF UT WOS:000182015700043 PM 12556526 ER PT J AU da Costa, CA Mattson, MP Ancolio, K Checler, F AF da Costa, CA Mattson, MP Ancolio, K Checler, F TI The C-terminal fragment of presenilin 2 triggers p53-mediated staurosporine-induced apoptosis, a function independent of the presenilinase-derived N-terminal counterpart SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; ALPHA-SYNUCLEIN; ENDOPLASMIC-RETICULUM; PARKINSONS-DISEASE; NEURONAL CELLS; APP-ALPHA; WILD-TYPE; CLEAVAGE; BETA AB Mutations on presenilins are responsible for most of familial forms of Alzheimer's disease. These holoproteins undergo rapid maturation by presenilinase mainly in the endoplasmic reticulum, leading to the production of N- and C-terminal fragments. We show first that overexpression of the presenilinase-derived maturation product of presenilin 2 (CTF-PS2) increases Abeta recovery, the production of which is almost abolished by a caspase 3 inhibitor and increased by staurosporine. This and the observation that the apoptotic inducer staurosporine enhances CTF-PS2 degradation clearly link CTF-PS2 to apoptotic cascade effectors. This prompted us to analyze the putative ability of CTF-PS2 to modulate cell death. CTF-PS2 overexpression decreases cell viability and augments both caspase 3 activity and immunoreactivity. This is accompanied by lowered bcl2-like immunoreactivity and increased poly(ADP-ribose) polymerase cleavage and cytochrome c translocation into the cytosol. Interestingly, CTF-PS2-induced caspase 3 activation is prevented by pifithrin-alpha, a selective blocker of p53 transcriptional activity. On line with the latter data, CTF-PS2 drastically increases p53 immunoreactivity and transcriptional activity. Of most interest is our observation that CTF-PS2 expression also triggers increased caspase 3 activity and immunoreactivity in fibroblasts in which presenilins had been deleted. Therefore, CTF-PS2 could modulate cell death out of the NTF/CTF heterodimeric complex thought to correspond to the biologically functional entity. This is the first direct demonstration that CTF-PS2 could exhibit some of its functions in the absence of the presenilin 2 N-terminal fragment (NTF-PS2) counterpart derived from the presenilinase cleavage. C1 CNRS, Inst Pharmacol Mol & Cellulaire, UMR6097, F-06560 Valbonne, France. NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Checler, F (reprint author), CNRS, Inst Pharmacol Mol & Cellulaire, UMR6097, 660 Route des Lucioles,Sophia Antipolis, F-06560 Valbonne, France. EM checler@ipmc.cnrs.fr RI Mattson, Mark/F-6038-2012; alves da Costa, cristine/G-8075-2011; Checler, Frederic/C-1241-2009 OI alves da Costa, cristine/0000-0002-7777-005X; Checler, Frederic/0000-0003-2098-1750 NR 38 TC 46 Z9 47 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 APR 4 PY 2003 VL 278 IS 14 BP 12064 EP 12069 DI 10.1074/jbc.M212379200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 663QF UT WOS:000182015700046 PM 12556443 ER PT J AU Mueller, SO Hall, JM Swope, DL Pedersen, LC Korach, KS AF Mueller, SO Hall, JM Swope, DL Pedersen, LC Korach, KS TI Molecular determinants of the stereoselectivity of agonist activity of estrogen receptors (ER) alpha and beta SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LIGAND-BINDING DOMAIN; DIETHYLSTILBESTROL METABOLITES; CONFORMATIONAL-CHANGES; TISSUE DISTRIBUTION; CELL-LINES; WILD-TYPE; TRANSACTIVATION; ANTIESTROGENS; ANALOGS; IDENTIFICATION AB The two known estrogen receptors, ERalpha and ERbeta, are hormone-inducible transcription factors that have distinct roles in regulating cell proliferation and differentiation. Previously, our laboratory demonstrated that ERalpha exhibits stereoselective ligand binding and transactivation for several structural derivatives and metabolites of the synthetic estrogen diethylstilbestrol. We have previously described the properties of indenestrol A (IA) enantiomers on ERalpha. In the study presented here, the estrogenic properties of the S and R enantiomers of IA, IA-S and IA-R, respectively, were expanded to exam. ine the activity in different cell and promoter contexts using ERalpha and ERbeta. Using human cell lines stably expressing either ERalpha or ERbeta, we found that IA-S was a more potent activator of transcription than IA-R through ERalpha in human endometrial Ishikawa and breast MDA-MB 231 (MDA) cells. Interestingly, IA-R was more potent on ERbeta when compared with ERalpha in MDA, but not in Ishikawa cells, and IA-R exhibited equally low binding affinities to ERalpha and ERbeta in vitro in contrast to its cell line-dependent preferential activation of ERG. Alignment of the protein structures of the ligand-binding domains of ERalpha and ERbeta revealed one mismatched residue, Leu-384 in ERalpha and Met-283 in ERbeta, which may be responsible for making contact with the methyl substituent at the chiral carbon of IA-S and IA-R. Mutagenesis and exchange of this one residue showed that the binding of IA-R and IA-S was not affected by this mutation in ERalpha and ERbeta. However, in transactivation studies, IA-R showed higher potency in activating L384M-mutated ERalpha and wild-type ERbeta compared with wild-type ERalpha and M283L-mutated ERbeta in all cell and promoter contexts examined. Furthermore, IA-R-bound ERalpha L384M and wild-type ERbeta displayed enhanced interactions with the nuclear receptor interaction domains of the coactivators SRC-1 and GRIP1. These data demonstrate that a single residue in the ligand-binding domain determines the stereoselectivity of ERalpha and ERbeta for indenestrol ligands and that IA-R shows cell type selectivity through ERbeta. C1 NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Korach, KS (reprint author), Merck KGaA, Inst Toxicol, POB 64271, Darmstadt, Germany. OI Korach, Kenneth/0000-0002-7765-418X NR 36 TC 29 Z9 30 U1 1 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 APR 4 PY 2003 VL 278 IS 14 BP 12255 EP 12262 DI 10.1074/jbc.M203578200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 663QF UT WOS:000182015700070 PM 12547836 ER PT J AU Harrod, R Nacsa, J Van Lint, C Hansen, J Karpova, T McNally, J Franchini, G AF Harrod, R Nacsa, J Van Lint, C Hansen, J Karpova, T McNally, J Franchini, G TI Human immunodeficiency virus type-1 Tat/Co-activator acetyltransferase interactions inhibit p53(Lys-320) acetylation and p53-responsive transcription SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADENOVIRAL ONCOPROTEIN E1A; CREB-BINDING-PROTEIN; HIV-1 TAT; HISTONE-ACETYLTRANSFERASE; DNA-DAMAGE; PCAF BROMODOMAIN; KAPOSIS-SARCOMA; P53 RESPONSE; UV-RADIATION; IN-VIVO AB Patients with AIDS are at increased risk for developing various neoplasms, including Hodgkin's and non. Hodgkin's lymphomas, Kaposi's sarcomas, and anal-rectal carcinomas, suggestive that human immunodeficiency virus type-1 infection might promote establishment of AIDS-related cancers. Tat, the viral transactivator, can be endocytosed by uninfected cells and has been shown to inhibit p53 functions, providing a candidate mechanism through which the human immunodeficiency virus type-1 might contribute to malignant transformation. Because Tat has been shown to interact with histone acetyltransferase domains of p300/cAMP-responsive element-binding protein (CREB)-binding protein and p300/CREB-binding protein-associated factor, we have investigated whether Tat might alter p53 acetylation and tumor suppressor-responsive transcription. Here, we demonstrate that both Tat and p53 co-localize with p300/ CREB-binding protein-associated factor and p300 in nuclei of IMR-32 human neuroblastoma cells and in PC-12 pheochromocytoma cells. Further, p53 trans-activation of the 14-3-3sigma promoter was markedly repressed by Tathistone acetyltransferase interactions, and p53 acetylation by p300/CREB-binding protein-associated factor on residue Lys(320) was diminished as a result of Tat-histone acetyltransferase binding in vivo and in vitro. Tat also inhibited p53 acetylation by p300 in a dosage-dependent manner in vitro. Finally, HIV-1-infected Molt-4 cells displayed reduced p53 acetylation on lysines 320 and 373 in response to UV irradiation. Our results allude to a mechanism whereby the human immunodeficiency virus type-1 trans-activator might impair tumor suppressor functions in immune/neuronal-derived cells, thus favoring the establishment of neoplasia during AIDS. C1 So Methodist Univ, Dept Biol Sci, Mol Virol Lab, Dallas, TX 75275 USA. NCI, Basic Res Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Free Univ Brussels, Inst Med Biol, Serv Chim Biol, Virol Lab, B-6041 Gosselies, Belgium. NCI, Lab Receptor Biol & Gene Express, Imaging Facil, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Harrod, R (reprint author), So Methodist Univ, Dept Biol Sci, Mol Virol Lab, 334-DLS,6501 Airline Dr, Dallas, TX 75275 USA. NR 57 TC 27 Z9 27 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 APR 4 PY 2003 VL 278 IS 14 BP 12310 EP 12318 DI 10.1074/jbc.M211167200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 663QF UT WOS:000182015700077 PM 12501250 ER PT J AU Maruvada, P Baumann, CT Hager, GL Yen, PM AF Maruvada, P Baumann, CT Hager, GL Yen, PM TI Dynamic shuttling and intranuclear mobility of nuclear hormone receptors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FLUORESCENT PROTEIN CHIMERA; ESTROGEN-RECEPTOR; GLUCOCORTICOID RECEPTOR; PROGESTERONE-RECEPTOR; LIVING CELLS; LOCALIZATION SIGNAL; 26S PROTEASOME; EXPORT SIGNAL; ALPHA; COACTIVATOR AB We expressed green fluorescent protein (GFP) chimeras of estrogen, retinoic acid, and thyroid hormone receptors (ERs, RARs, and TRs, respectively) in HeLa cells to examine nucleocytoplasmic shuttling and intranuclear mobility of nuclear hormone receptors (NRs) by confocal microscopy. These receptors were predominantly in the nucleus and, interestingly, underwent intranuclear reorganization after ligand treatment. Nucleocytoplasmic shuttling was demonstrated by heterokaryon experiments and energy-dependent blockade of nuclear import and leptomycin-dependent blockade of nuclear export. Ligand addition decreased shuttling by GFP-ER, whereas heterodimerization with retinoid X receptor helped maintain TR and RAR within the nucleus. Intranuclear mobility of the GFP-NRs was studied by fluorescence recovery after photo-bleaching +/- cognate ligands. Both GFP-TR and GFP-RAR moved rapidly in the nucleus, and ligand binding did not significantly affect their mobility. In contrast, estrogen binding decreased the mobility of GFP-ER and also increased the fraction of GFP-ER that was unable to diffuse. These effects were even more pronounced with tamoxifen. Co-transfection of the co-activator, SRC-1, further slowed the mobility of liganded GFP-ER. Our findings suggest estradiol and tamoxifen exert differential effects on the intranuclear mobility of GFP-ER. They also show that ligand-binding and protein-protein interactions can affect the intracellular mobility of some NRs and thereby may contribute to their biological activity. C1 NIDDK, Mol Regulat & Neuroendocrinol Sect, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Yen, PM (reprint author), NIDDK, Mol Regulat & Neuroendocrinol Sect, Clin Endocrinol Branch, NIH, Bldg 10,Rm 8D12, Bethesda, MD 20892 USA. NR 31 TC 122 Z9 125 U1 2 U2 11 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 4 PY 2003 VL 278 IS 14 BP 12425 EP 12432 DI 10.1074/jbc.M202752200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 663QF UT WOS:000182015700092 PM 12506123 ER PT J AU Chreneik, JE Burgin, AB Pommier, Y Stewart, L Redinbo, MR AF Chreneik, JE Burgin, AB Pommier, Y Stewart, L Redinbo, MR TI Structural impact of the leukemia drug 1-beta-D-arabinofuranosyleytosine (Ara-C) on the covalent human topoisomerase I-DNA complex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CATALYTIC MECHANISM; CLEAVAGE COMPLEXES; CRYSTAL-STRUCTURES; ACTIVE-SITE; CAMPTOTHECIN; INDUCTION; ENZYME; ARABINOSYLCYTOSINE; MOLSCRIPT AB 1-beta-D-Arabinofuranosylcytosine (Ara-C) is a potent antineoplastic drug used in the treatment of acute leukemia. Previous biochemical studies indicated the incorporation of Ara-C into DNA reduced the catalytic activity of human topoisomerase I by decreasing the rate of single DNA strand religation by the enzyme by 2-3-fold. We present the 3.1 Angstrom crystal structure of human topoisomerase I in covalent complex with an oligonucleotide containing Ara-C at the + 1 position of the non-scissile DNA strand. The structure reveals that a hydrogen bond formed between the 2'-hydroxyl of Ara-C and the O4' of the adjacent -1 base 5' to the damage site stabilizes a C3'-endo pucker in the Ara-C arabinose ring. The structural distortions at the site of damage are translated across the DNA double helix to the active site of human topoisomerase I. The free sulfhydryl at the 5'-end of the nicked DNA strand in this trapped covalent complex is shifted out of alignment with the 3'-phosphotyrosine linkage at the catalytic tyrosine 723 residue, producing a geometry not optimal for religation. The subtle structural changes caused by the presence of Ara-C in the DNA duplex may contribute to the cytotoxicity of this leukemia drug by prolonging the lifetime of the covalent human topoisomerase I-DNA complex. C1 Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. DeCODE Genet Inc, Biostruct Grp, Bainbridge Isl, WA 98110 USA. NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. RP Redinbo, MR (reprint author), Univ N Carolina, Dept Chem, Campus Box 3290, Chapel Hill, NC 27599 USA. NR 41 TC 34 Z9 36 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 APR 4 PY 2003 VL 278 IS 14 BP 12461 EP 12466 DI 10.1074/jbc.M212930200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 663QF UT WOS:000182015700096 PM 12533542 ER PT J AU Rojkova, AM Woodard, GE Huang, TC Combs, CA Zhang, JH Simonds, WF AF Rojkova, AM Woodard, GE Huang, TC Combs, CA Zhang, JH Simonds, WF TI G gamma subunit-selective G protein beta(5) mutant defines regulators of G protein signaling protein binding requirement for nuclear localization SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RGS PROTEINS; SUBCELLULAR-LOCALIZATION; CRYSTAL-STRUCTURE; DOMAIN; BRAIN; EXPRESSION; INTERACTS; G-BETA(5); TISSUES; TRANSLOCATION AB The signal transducing function of Gbeta(5) in brain is unknown. When studied in vitro Gbeta(5) is the only heterotrimeric Gbeta subunit known to interact with both Ggamma subunits and regulators of G protein signaling (RGS) proteins. When tested with Ggamma, Gbeta(5) interacts with other classical components of heterotrimeric G protein signaling pathways such as Galpha and phospholipase C-beta. We recently demonstrated nuclear expression of Gbeta(5) in neurons and brain (Zhang, J. H., Barr, V. A., Mo, Y., Rojkova, A M., Liu, S., and Simonds, W. F. (2001) J. Biol. Chem. 276, 10284-10289). To gain further insight into the mechanism of Gbeta(5) nuclear localization, we generated a Gbeta(5) mutant deficient in its ability to interact with RGS7 while retaining its ability to bind Ggamma, and we compared its properties to the wild-type Gbeta(5). In HEK-293 cells co-transfection of RGS7 but not Ggamma(2) supported expression in the nuclear fraction of transfected wild-type Gbeta(5). In contrast the Ggamma-preferring Gbeta(5), mutant was not expressed in the HEK-293 cell nuclear fraction with either co-transfectant. The Ggamma-selective Gbeta(5) mutant was also excluded from the cell nucleus of transfected PC12 cells analyzed by laser confocal microscopy. These results define a requirement for RGS protein binding for Gbeta(5) nuclear expression. C1 NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Confocal Microscopy Core Facil, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Simonds, WF (reprint author), NIDDK, Metab Dis Branch, NIH, Bldg 10,Rm 8C-101,10 Ctr Dr,MSC 1752, Bethesda, MD 20892 USA. RI Woodard, Geoffrey/A-8608-2009; Rozhkova, Alexandra/E-5607-2014 OI Rozhkova, Alexandra/0000-0003-4901-4705 NR 48 TC 26 Z9 27 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 APR 4 PY 2003 VL 278 IS 14 BP 12507 EP 12512 DI 10.1074/jbc.M207302200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 663QF UT WOS:000182015700102 PM 12551930 ER PT J AU Speare, JO Rush, TS Bloom, ME Caughey, B AF Speare, JO Rush, TS Bloom, ME Caughey, B TI The role of helix 1 aspartates and salt bridges in the stability and conversion of prion protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SCRAPIE-ASSOCIATED FORM; CELL-FREE CONVERSION; RESISTANT STATE; SECONDARY STRUCTURE; PRP 27-30; ISOFORM; PURIFICATION; SIMULATIONS; SPECIFICITY; AGGREGATION AB A key event in the pathogenesis of transmissible spongiform encephalopathies is the conversion of PrP-sen to PrP-res. Morrissey and Shakhnovich (Morrissey, M. P., and Shakhnovich, E. I. (1999) Proc. Natl. Acad. Sci. U. S. A. 96, 11293-11298) proposed that the conversion mechanism involves critical interactions at helix 1 (residues 144-153) and that the helix is stabilized on PrP-sen by intra-helix salt bridges between two aspartic acid-arginine ion pairs at positions 144 and 148 and at 147 and 151, respectively. Mutants of the hamster prion protein were constructed by replacing the aspartic acids with either asparagines or alanines to destabilize the proposed helix 1 salt bridges. Thermal and chemical denaturation experiments using circular dichroism spectroscopy indicated the overall structures of the mutants are not substantially destabilized but appear to unfold differently. Cell-free conversion reactions per. formed using ionic denaturants, detergents, and salts (conditions unfavorable to salt bridge formation) showed no significant differences between conversion efficiencies of mutant and wild type proteins. Using conditions more favorable to salt bridge formation, the mutant proteins converted with up to 4-fold higher efficiency than the wild type protein. Thus, although spectroscopic data indicate the salt bridges do not substantially stabilize PrP-sen, the cell-free conversion data suggest that Asp-144 and Asp-147 and their respective salt bridges stabilize PrP-sen from converting to PrP-res. C1 NIAID, Rocky Mt Lab, Lab Persistent Viral Dis, NIH, Hamilton, MT 59840 USA. Univ Montana, Dept Chem, Missoula, MT 59812 USA. RP Caughey, B (reprint author), NIAID, Rocky Mt Lab, Lab Persistent Viral Dis, NIH, Hamilton, MT 59840 USA. NR 46 TC 61 Z9 64 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 APR 4 PY 2003 VL 278 IS 14 BP 12522 EP 12529 DI 10.1074/jbc.M211599200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 663QF UT WOS:000182015700104 PM 12551897 ER PT J AU Deng, WP Nam, G Fan, JF Kirk, KL AF Deng, WP Nam, G Fan, JF Kirk, KL TI Syntheses of beta,beta-difluorotryptamines SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID IMIDAZOLE AB Tryptamines disubstituted at the beta-position with fluorine have been synthesized as part of our research program to study the effects of fluorine substitution on the biological activities of neuroactive amines. Treatment of N-Boc-3-azidoacetyl indoles, prepared from readily available 2-chloracetylindoles, with dimethoxyethylamino sulfurtrifluoride produced the corresponding 3-(2-azido-1,1-difluoroethyl)indoles. Reduction of the azide to amine with hydrogen over Pd-C and careful removal of the N-Boc protecting group produced beta,beta-difluorotryptamines. C1 NIDDKD, Bioorgan Chem Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Kirk, KL (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM kennethk@bdg8.niddk.nih.gov NR 11 TC 12 Z9 12 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD APR 4 PY 2003 VL 68 IS 7 BP 2798 EP 2802 DI 10.1021/jo020731c PG 5 WC Chemistry, Organic SC Chemistry GA 662NM UT WOS:000181953700034 PM 12662054 ER PT J AU Lippincott-Schwartz, J Patterson, GH AF Lippincott-Schwartz, J Patterson, GH TI Development and use of fluorescent protein markers in living cells SO SCIENCE LA English DT Review ID IN-VIVO; CORRELATION SPECTROSCOPY; PHOTOBLEACHING RECOVERY; ENDOPLASMIC-RETICULUM; MEMBRANE-TRANSPORT; PLASMA-MEMBRANE; LIVE CELLS; DYNAMICS; GFP; MICROSCOPY AB The ability to visualize, track, and quantify molecules and events in living cells with high spatial and temporal resolution is essential for understanding biological systems. Only recently has it become feasible to carry out these tasks due to the advent of fluorescent protein technology. Here, we trace the development of highly visible and minimally perturbing fluorescent proteins that, together with updated fluorescent imaging techniques, are providing unprecedented insights into the movement of proteins and their interactions with cellular components in living cells. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Lippincott-Schwartz, J (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. EM jlippin@helix.nih.gov NR 59 TC 559 Z9 591 U1 10 U2 140 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 4 PY 2003 VL 300 IS 5616 BP 87 EP 91 DI 10.1126/science.1082520 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 663CP UT WOS:000181988900036 PM 12677058 ER PT J AU Swedlow, JR Goldberg, I Brauner, E Sorger, PK AF Swedlow, JR Goldberg, I Brauner, E Sorger, PK TI Informatics and quantitative analysis in biological Imaging SO SCIENCE LA English DT Article ID MICROSCOPY AB Biological imaging is now a quantitative technique for probing cellular structure and dynamics and is increasingly used for cell-based screens. However, the bioinformatics tools required for hypothesis-driven analysis of digital images are still immature. We are developing the Open Microscopy Environment (OME) as an informatics solution for the storage and analysis of optical microscope image data. OME aims to automate image analysis, modeling, and mining of large sets of images and specifies a flexible data model, a relational database, and an XML-encoded. le standard that is usable by potentially any software tool. With this design, OME provides a first step toward biological image informatics. C1 Univ Dundee, Wellcome Trust Bioctr, Div Gene Regulat & Express, Dundee DD1 5EH, Scotland. NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. Harvard Univ, Sch Med, Inst Chem & Cell Biol, Boston, MA 02115 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Swedlow, JR (reprint author), Univ Dundee, Wellcome Trust Bioctr, Div Gene Regulat & Express, Dundee DD1 5EH, Scotland. EM j.swedlow@dundee.ac.uk RI Goldberg, Ilya/H-5307-2011 OI Goldberg, Ilya/0000-0001-8514-6110 FU Wellcome Trust [067433] NR 10 TC 143 Z9 149 U1 0 U2 23 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 4 PY 2003 VL 300 IS 5616 BP 100 EP 102 DI 10.1126/science.1082602 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 663CP UT WOS:000181988900039 PM 12677061 ER PT J AU Brewer, HB AF Brewer, HB TI The American Journal of Cardiology - Introduction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material ID DENSITY-LIPOPROTEIN CHOLESTEROL; CORONARY HEART-DISEASE; RISK C1 NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20814 USA. RP Brewer, HB (reprint author), NHLBI, Mol Dis Branch, NIH, Bldg 10 Magnuson CC,Room 7N115,10 Ctr Dr, Bethesda, MD 20814 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 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 APR 3 PY 2003 VL 91 IS 7A SU S BP 1E EP 2E DI 10.1016/S0002-9149(02)03381-7 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 664TT UT WOS:000182077800001 ER PT J AU Brewer, HB Santamarina-Fojo, S AF Brewer, HB Santamarina-Fojo, S TI New insights into the role of the adenosine triphosphate-binding cassette transporters in high-density lipoprotein metabolism and reverse cholesterol transport SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT Symposium on High-Density Lipoprotein Cholesterol esterol CY OCT 11-12, 2001 CL NEW YORK, NEW YORK ID SCAVENGER RECEPTOR BI; TANGIER-DISEASE; ABCA1 TRANSPORTER; WHITE GENE; SITOSTEROLEMIA; MUTATIONS; MICE; XANTHOMATOSIS; DEFICIENCY; ATHEROSCLEROSIS AB Four adenosine triphosphate-binding cassette (ABC) transporters-A:BCA1, ABCG1, ABCG5 and ABCG8-have been identified and shown to modulate cholesterol and lipoprotein metabolism. Recent analyses of ABCA1 indicate that upregulation of ABCA1 in the liver and macrophages of transgenic mice is, associated with increased plasma high-density lipoprotein (HDL) cholesterol levels, increased net flux of cholesterol to the liver, and reduced diet-induced atherosclerosis. In ABCA1 transgenic mice, the enhanced expression of hepatic ABCA1 transporters is associated with increased plasma HDL cholesterol levels, suggesting that the liver plays an important role in the levels of plasma HDL cholesterol. Overexpression of ABCG1 in the liver of mice using recombinant ABCG1 vectors results in decreased plasma HDL levels and indicates that ABCG1 can modulate plasma lipoprotein levels in vivo. The potential importance of ABCG1 in reverse cholesterol transport has not been definitively established. Studies in patients with sitosterolemia have identified 2 major new transporters, ABCG5 and ABCG8, that play a pivotal role in the regulation of intestinal cholesterol, plant, and shellfish absorption. Modulation of the expression of ABCG5 and ABCG8 represents an important new mechanism in the regulation of cholesterol absorption in the intestine. The ABC transporters currently represent excellent targets for the development of new drugs for the treatment of patients with increased risk of premature cardiovascular disease. (C) 2003 by Excerpta Medica, Inc. C1 NHLBI, NIH, Mol Dis Branch, Bethesda, MD 20892 USA. RP Brewer, HB (reprint author), NHLBI, NIH, Mol Dis Branch, Bldg 10 Magnuson CC,Room 7N115,10 Ctr Dr,MSC-1666, Bethesda, MD 20892 USA. NR 39 TC 53 Z9 54 U1 0 U2 4 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 APR 3 PY 2003 VL 91 IS 7A SU S BP 3E EP 11E DI 10.1016/S0002-9149(02)03382-9 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 664TT UT WOS:000182077800002 PM 12679197 ER PT J AU Nemukhin, AV Grigorenko, BL Topol, IA Burt, SK AF Nemukhin, AV Grigorenko, BL Topol, IA Burt, SK TI Quantum chemical simulations of the proton transfer in water wires attached to molecular walls SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID INFLUENZA-A VIRUS; FRAGMENT POTENTIAL METHOD; OVOMUCOID 3RD DOMAIN; VALENCE-BOND MODEL; M2 CHANNEL; ENERGY MINIMIZATION; ION-CHANNEL; MECHANICAL METHOD; H+ CONDUCTION; DYNAMICS AB Quantum chemical methods are applied to study the stages of the proton transfer in water wires attached to molecular walls containing the side chains of His and Asp residues. Several molecular models of variable complexity are considered by using different techniques. and in every case, the most important reactions of cleavage and formation of chemical bonds in proton wires are treated at the ab initio level. The largest molecular model, which mimics structural elements of the M2 ion channel, is investigated with the help of a quantum mechanical-molecular mechanical (QM/MM) method with flexible effective fragments, Smaller models are considered at nonempirical levels in order to purify conclusions of the QM/MM approach. The results of calculations show that the only transition state structure found on the proton-transfer route refers to the stage of proton detachment from the N, atom of the imidazole ring to the neighboring water molecule. The corresponding energy barriers are estimated. C1 Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119899, Russia. Natl Canc Inst Frederick, SAIC Frederick, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. RP Nemukhin, AV (reprint author), Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119899, Russia. RI Nemukhin, Alexander/P-9662-2015 NR 54 TC 15 Z9 17 U1 1 U2 3 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 APR 3 PY 2003 VL 107 IS 13 BP 2958 EP 2965 DI 10.1021/jp027283x PG 8 WC Chemistry, Physical SC Chemistry GA 662AC UT WOS:000181922300015 ER PT J AU Yin, YX Liu, YX Jin, YJ Hall, EJ Barrett, JC AF Yin, YX Liu, YX Jin, YJ Hall, EJ Barrett, JC TI PAC1 phosphatase is a transcription target of p53 in signalling apoptosis and growth suppression SO NATURE LA English DT Article ID OXIDATIVE STRESS; DNA-BINDING; ACTIVATION; DEFICIENCY; DOMAIN; P21 AB p53 has a role in many cellular processes through the transcriptional regulation of target genes(1,2). PAC1 ( phosphatase of activated cells 1; also known as dual specificity phosphatase 2, DUSP2) is a dual threonine/tyrosine phosphatase that specifically dephosphorylates and inactivates mitogen-activated protein (MAP) kinases(3,4). Here we show that during apoptosis, p53 activates transcription of PAC1 by binding to a palindromic site in the PAC1 promoter. PAC1 transcription is induced in response to serum deprivation and oxidative stress, which results in p53-dependent apoptosis, but not in response to gamma-irradiation, which causes cell cycle arrest(5,6). Reduction of PAC1 transcription using small interfering RNA inhibits p53-mediated apoptosis, whereas overexpression of PAC1 increases susceptibility to apoptosis and suppresses tumour formation. Moreover, activation of p53 significantly inhibits MAP kinase activity. We conclude that, under specific stress conditions, p53 regulates transcription of PAC1 through a new p53-binding site, and that PAC1 is necessary and sufficient for p53-mediated apoptosis. Identification of a palindromic motif as a p53-binding site may reveal a novel mechanism whereby p53 regulates its target genes. C1 Columbia Univ, Coll Phys & Surg, Dept Radiat Oncol, New York, NY 10032 USA. NCI, Lab Biosyst & Canc, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Yin, YX (reprint author), Columbia Univ, Coll Phys & Surg, Dept Radiat Oncol, 630 W 168th St, New York, NY 10032 USA. EM yy151@columbia.edu NR 21 TC 95 Z9 99 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 3 PY 2003 VL 422 IS 6931 BP 527 EP 531 DI 10.1038/nature01519 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 662TW UT WOS:000181965400039 PM 12673251 ER PT J AU Nussbaum, RL Ellis, CE AF Nussbaum, RL Ellis, CE TI Genomic medicine: Alzheimer's disease and Parkinson's disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID RECESSIVE JUVENILE PARKINSONISM; POSITRON EMISSION TOMOGRAPHY; AMYLOID PRECURSOR PROTEIN; ALPHA-SYNUCLEIN; LEWY BODIES; APOLIPOPROTEIN-E; F-18 DOPA; PRESENILIN-1 MUTATIONS; CLINICAL-DIAGNOSIS; TRANSGENIC MICE C1 NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Nussbaum, RL (reprint author), NHGRI, Genet Dis Res Branch, NIH, 49 Convent Dr,Rm 4A72, Bethesda, MD 20892 USA. EM rlnuss@nhgri.nih.gov NR 85 TC 476 Z9 500 U1 0 U2 35 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 3 PY 2003 VL 348 IS 14 BP 1356 EP 1364 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 662LW UT WOS:000181949100008 PM 12672864 ER PT J AU Miller, FG Rosenstein, DL AF Miller, FG Rosenstein, DL TI The therapeutic orientation to clinical trials SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID PROFESSIONAL INTEGRITY; CONSENT; ETHICS C1 NIH, Dept Clin Bioeth, Ctr Clin, Bethesda, MD 20892 USA. NIH, Psychiat Consultat Liaison Serv, Bethesda, MD 20892 USA. RP Miller, FG (reprint author), NIH, Dept Clin Bioeth, Ctr Clin, Bldg 10,Rm 1C118, Bethesda, MD 20892 USA. EM fmiller@nih.gov NR 24 TC 148 Z9 149 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 3 PY 2003 VL 348 IS 14 BP 1383 EP 1386 DI 10.1056/NEJMsb030228 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 662LW UT WOS:000181949100012 PM 12672867 ER PT J AU Phornphutkul, C Introne, WJ Gahl, WA AF Phornphutkul, C Introne, WJ Gahl, WA TI Alkaptonuria SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Brown Univ, Providence, RI 02903 USA. NHGRI, Bethesda, MD 20892 USA. RP Phornphutkul, C (reprint author), Brown Univ, Providence, RI 02903 USA. EM bgahl@helix.nih.gov NR 3 TC 1 Z9 1 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 3 PY 2003 VL 348 IS 14 BP 1408 EP 1408 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 662LW UT WOS:000181949100031 ER PT J AU Kominsky, SL Argani, P Korz, D Evron, E Raman, V Garrett, E Rein, A Sauter, G Kallioniemi, OP Sukumar, S AF Kominsky, SL Argani, P Korz, D Evron, E Raman, V Garrett, E Rein, A Sauter, G Kallioniemi, OP Sukumar, S TI Loss of the tight junction protein claudin-7 correlates with histological grade in both ductal carcinoma in situ and invasive ductal carcinoma of the breast SO ONCOGENE LA English DT Article DE breast cancer; tight junction; claudin-7; methylation ID GENE-EXPRESSION; CANCER; CELLS; HYPERMETHYLATION; METHYLATION; OCCLUDIN; CADHERIN; STRANDS; TUMORS; ZO-1 AB Claudius are transmembrane proteins that seal tight junctions, and are critical for maintaining cell-to-cell adhesion in epithelial cell sheets. However, their role in cancer progression remains largely unexplored. Here, we report that Claudin-7 (CLDN-7) expression is lower in invasive ductal carcinomas (IDC) of the breast than in normal breast epithelium, as determined by both RT-PCR (9/10) and Western analysis (6/8). Immunohistochemical (IHC) analysis of ductal carcinoma in situ (IDS) and IDC showed that the loss of CLDN-7 expression correlated with histological grade in both MIS (P<0.001, n=38) and IDC (P=0.014, n=31), occurring predominantly in high-grade (Nuclear and Elston grade 3) lesions. Tissue array analysis of 355 IDC cases further confirmed the inverse correlation between CLDN-7 expression and histological grade (P = 0.03). This pattern of expression is consistent with the biological function of CLDN-7, as greater discohesion is typically observed in high-grade lesions. In line with this observation, by IHC analysis, CLDN-7 expression was lost in the vast majority (13/17) of cases of lobular carcinoma in situ, which is defined by cellular discohesion. In fact, inducing disassociation of MCF-7 and T47D cells in culture by treating with HGF/scatter factor resulted in a loss of CLDN-7 expression within 24h. Silencing of CLDN-7 expression correlated with promoter hypermethylation as determined by methylation-specific PCR (MSP) and nucleotide sequencing in breast cancer cell lines (3/3), but not in IDCs (0/5). In summary, these studies provide insight into the potential role of CLDN-7 in the progression and ability of breast cancer cells to disseminate. C1 Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Breast Canc Program, Baltimore, MD 21231 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21231 USA. Johns Hopkins Univ, Sch Med, Dept Oncol Biostat, Baltimore, MD 21231 USA. Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21231 USA. NCI, HIV Drug Resistance Program, Frederick, MD 21072 USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Basel, Inst Pathol, CH-4003 Basel, Switzerland. RP Sukumar, S (reprint author), Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Breast Canc Program, BBCRB Room 410,1650 Orleans St, Baltimore, MD 21231 USA. RI Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 FU NCI NIH HHS [P50 CA88843] NR 25 TC 295 Z9 309 U1 1 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 3 PY 2003 VL 22 IS 13 BP 2021 EP 2033 DI 10.1038/sj.onc.1206199 PG 13 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 662UR UT WOS:000181967700012 PM 12673207 ER PT J AU Junop, MS Yang, W Funchain, P Clendenin, W Miller, JH AF Junop, MS Yang, W Funchain, P Clendenin, W Miller, JH TI In vitro and in vivo studies of MutS, MutL and MutH mutants: correlation of mismatch repair and DNA recombination SO DNA REPAIR LA English DT Article DE MutS; MutL and MutH; DNA mismatch repair and homeologous recombination ID SACCHAROMYCES-CEREVISIAE MSH2; NEGATIVE MUTATOR MUTATIONS; ESCHERICHIA-COLI; RESTRICTION ENDONUCLEASES; SALMONELLA-TYPHIMURIUM; CRYSTAL-STRUCTURE; ATPASE ACTIVITY; STRAND TRANSFER; SLIDING CLAMP; BINDING MOTIF AB We have used the recently determined crystal structures of Escherichia coli (E. coli) MutS, MutL and MutH to guide construction of 47 amino-acid substitutions in these proteins and analyzed their behavior in mismatch repair and recombination in vitro and in vivo. We find that the active site of the MutH endonuclease is composed of regions from two separate structural domains and that the C-terminal 5 residues of MutH influence both DNA binding and cleavage. We also find that the non-specific DNA-binding activity of MutL is required for mismatch repair and probably functions after strand cleavage by MutH. Alteration of residues in either the mismatch recognition domain, the ATPase active site, or the domain interfaces linking the two activities can diminish the differential binding of MutS to homoduplex versus heteroduplex and results in the loss of mismatch-specific MutH activation. Finally, every mutation that abolishes mismatch repair is deficient in blocking homeologous recombination, suggesting that mismatch repair and prevention of homeologous recombination use the same MutS-MutL complexes for signaling in E. coli. Published by Elsevier Science B.V. C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Inst Mol Biol, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90024 USA. RP Yang, W (reprint author), NIDDK, Mol Biol Lab, NIH, 9000 Rockville Pike,Bldg 5,Room B1-03, Bethesda, MD 20892 USA. RI Yang, Wei/D-4926-2011; Junop, Murray/E-4160-2015 OI Yang, Wei/0000-0002-3591-2195; Junop, Murray/0000-0001-6676-5717 FU NIEHS NIH HHS [ES0110875] NR 45 TC 78 Z9 78 U1 0 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD APR 2 PY 2003 VL 2 IS 4 BP 387 EP 405 DI 10.1016/S1568-7864(02)00245-8 PG 19 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 657CZ UT WOS:000181649000003 PM 12606120 ER PT J AU Steinberg, MH Barton, F Castro, S Pegelow, CH Ballas, SK Kutlar, A Orringer, E Bellevue, R Olivieri, N Varma, M Ramirez, G Adler, B Smith, W Carlos, T Ataga, K DeCastro, L Bigelow, C Saunthararajah, Y Teller, M Vichinsky, E Claster, S Shurin, S Bridges, K Waclawiw, M Bonds, D Terrin, M AF Steinberg, MH Barton, F Castro, S Pegelow, CH Ballas, SK Kutlar, A Orringer, E Bellevue, R Olivieri, N Varma, M Ramirez, G Adler, B Smith, W Carlos, T Ataga, K DeCastro, L Bigelow, C Saunthararajah, Y Teller, M Vichinsky, E Claster, S Shurin, S Bridges, K Waclawiw, M Bonds, D Terrin, M TI Effect of hydroxyurea on mortality. and morbidity in adult sickle cell anemia - Risks and benefits up to 9 years of treatment SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACUTE CHEST SYNDROME; POLYCYTHEMIA-VERA; ESSENTIAL THROMBOCYTHEMIA; ACUTE-LEUKEMIA; DISEASE; THERAPY; RATES; AGE AB Context Hydroxyurea increases levels of fetal hemoglobin (HbF) and decreases morbidity from vaso-occlusive complications in patients with sickle cell anemia (SCA). High HbF levels reduce morbidity and mortality. Objective To determine whether hydroxyurea attenuates mortality in patients with SCA. Design Long-term observational follow-up study of mortality in patients with SCA who originally participated in the randomized, double-blind, placebo-controlled Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH), conducted in 1992-1995, to determine if hydroxyurea reduces vaso-occlusive events. In the MSH Patients' Followup, conducted in 1996-2001, patients could continue, stop, or start hydroxyurea. Data were collected during the trial and in the follow-up period. Setting Inpatients and outpatients in 21 sickle cell referral centers in the United States and Canada. Patients Two-hundred ninety-nine adult patients with frequent painful episodes enrolled in the follow-up. Follow-up data through May 2001 were complete for 233 patients. Intervention In the MSH, patients were randomly assigned to receive hydroxyurea (n = 152) or placebo (n = 147). Main Outcome Measures Mortality, HbF levels, painful episodes, acute chest syndrome, and blood cell counts. The randomized trial was not designed to detect specified differences in mortality. Results Seventy-five of the original 299 patients died, 28% from pulmonary disease. Patients with reticulocyte counts less than 250000/mm(3) and hemoglobin levels lower than 9 g/dL had increased mortality (P=.002). Cumulative mortality at 9 years was 28% when HbF levels were lower than 0.5 g/dL after the trial was completed compared with 15% when HbF levels were 0.5 g/dL or higher (P=.03). Individuals who had acute chest syndrome during the trial had 32% mortality compared with 18% of individuals without acute chest syndrome (P=.02). Patients with 3 or more painful episodes per year during the trial had 27% mortality compared with 17% of patients with less frequent episodes (P=.06). Taking hydroxyurea was associated with a 40% reduction in mortality (P=.04) in this observational follow-up with self-selected treatment. There were 3 cases of cancer, 1 fatal. Conclusions Adult patients taking hydroxyurea for frequent painful sickle cell episodes appear to have reduced mortality after 9 of years follow-up. Survival was related to HbF levels and frequency of vaso-occlusive events. Whether indications for hydroxyurea treatment should be expanded is unknown. C1 Boston Univ, Sch Med, Ctr Excellence Sickle Cell Dis, Boston Med Ctr, Boston, MA 02118 USA. Univ Mississippi, Sch Med, Jackson, MS 39216 USA. Maryland Med Res Inst, Baltimore, MD USA. Howard Univ, Sch Med, Ctr Sickle Cell Dis, Washington, DC 20059 USA. Univ Miami, Sch Med, Miami, FL USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Med Coll Georgia, Augusta, GA 30912 USA. Univ N Carolina, Chapel Hill, NC USA. New York Methodist Hosp, Brooklyn, NY USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Emory Univ, Sickle Cell Ctr, Atlanta, GA 30322 USA. Univ Med & Dent New Jersey, Newark, NJ 07103 USA. Roosevelt Med Ctr, New York, NY USA. Univ Alabama, Birmingham, AL USA. Virginia Commonwealth Univ, Richmond, VA USA. Univ Pittsburgh, Pittsburgh, PA USA. Duke Univ, Sch Med, Durham, NC USA. Univ Illinois, Chicago, IL USA. Michael Reese Med Ctr, Chicago, IL USA. Childrens Hosp & Res Ctr Oakland, Oakland, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NHLBI, Bethesda, MD 20892 USA. RP Steinberg, MH (reprint author), Boston Univ, Sch Med, Ctr Excellence Sickle Cell Dis, Boston Med Ctr, 88 E Newton St, Boston, MA 02118 USA. EM msteinberg@medicine.bu.edu FU NHLBI NIH HHS [N01-HB-67129] NR 33 TC 425 Z9 443 U1 6 U2 23 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 2 PY 2003 VL 289 IS 13 BP 1645 EP 1651 DI 10.1001/jama.289.13.1645 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 662JX UT WOS:000181944500027 PM 12672732 ER PT J AU Mozaffarian, D Kumanyika, SK Lemaitre, RN Olson, JL Burke, GL Siscovick, DS AF Mozaffarian, D Kumanyika, SK Lemaitre, RN Olson, JL Burke, GL Siscovick, DS TI Cereal, fruit, and vegetable fiber intake and the risk of cardiovascular disease in elderly individuals SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Heart-Associations-Epidemiology-Council CY APR 24, 2002 CL HONOLULU, HAWAII SP Amer Heart Assoc Epidemiol Council ID CORONARY HEART-DISEASE; FOOD FREQUENCY QUESTIONNAIRE; DIETARY FIBER; HEALTH; MEN; MORTALITY; WOMEN; CANCER; REDUCE; DEATH AB Context People older than 65 years are the fastest-growing segment of the population and account for the majority of cardiovascular disease (CVD) morbidity, mortality, and health care expenditures. Additionally, the influence of dietary habits on risk may be less pronounced in elderly persons, when atherosclerosis is more advanced. However, few data address the influence of diet on CVD risk in this population. Objective To determine whether fiber consumption from fruit, vegetable, and cereal sources (including whole grains and bran) is associated with incident CVD in elderly persons. Design Prospective cohort study conducted from 1989 to June 2000. Setting and Participants Population-based, multicenter study among 3588 men and women aged 65 years or older and free of known CVD at baseline in 1989-1990. Usual dietary fiber consumption was assessed at baseline (mean participant age, 72 years) using a 99-item food frequency questionnaire. Main Outcome Measure Incident CVD (combined stroke, ischemic heart disease death, and nonfatal myocardial infarction). Results During 8.6 years mean follow-up, there were 811 incident CVD events. After adjustment for age, sex, education, diabetes, ever smoking, pack-years of smoking, daily physical activity, exercise intensity, alcohol intake, and fruit and vegetable fiber consumption, cereal fiber consumption was inversely associated with incident CVD (P for trend=.02), with 21% lower risk (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.62-0.99) in the highest quintile of intake, compared with the lowest quintile. In similar analyses, neither fruit fiber intake (P for trend=.98) nor vegetable fiber intake (P for trend=.95) were associated with incident CVD. When CVD events were separately evaluated, higher cereal fiber intake was associated with lower risk of total stroke and ischemic stroke and a trend toward lower risk of ischemic heart disease death. In a post hoc analysis, dark breads such as wheat, rye, or pumpernickel were associated with a lower risk of incident CVD (HR, 0.76; 95% CI, 0.64-0.90) rather than cereal fiber from other sources. Conclusions Cereal fiber consumption late in life is associated with lower risk of incident CVD, supporting recommendations for elderly individuals to increase consumption of dietary cereal fiber. C1 Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA. Univ Washington, Div Cardiol, Seattle, WA 98101 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. RP Mozaffarian, D (reprint author), Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, 1730 Minor Ave,Suite 1360, Seattle, WA 98101 USA. EM darymd@hotmail.com RI Mozaffarian, Dariush/B-2276-2008 FU NHLBI NIH HHS [N01-HC-85079, N01-HC-85086, N01-HC-15103, N01-HC-35129] NR 39 TC 155 Z9 172 U1 0 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 2 PY 2003 VL 289 IS 13 BP 1659 EP 1666 DI 10.1001/jama.289.13.1659 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 662JX UT WOS:000181944500029 PM 12672734 ER PT J AU Taraphder, S Hummer, G AF Taraphder, S Hummer, G TI Protein side-chain motion and hydration in proton-transfer pathways. Results for cytochrome P450cam SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID PHOTOSYNTHETIC REACTION-CENTER; HEME-COPPER OXIDASES; ACTIVE-SITE; C-OXIDASE; OXYGEN ACTIVATION; CRYSTAL-STRUCTURES; ELECTRON-TRANSFER; AMINO-ACID; MOLECULAR-DYNAMICS; DISORDERED WATER AB Proton-transfer reactions form an integral part of bioenergetics and enzymatic catalysis. The identification of proton-conducting pathways inside a protein is a key to understanding the mechanisms of biomolecular proton transfer. Proton pathways are modeled here as hydrogen bonded networks of proton-conducting groups, including proton-exchanging groups of amino acid side chains and bound water molecules. We focus on the identification of potential proton-conducting pathways inside a protein of known structure. However, consideration of the static structure alone is often not sufficient to detect suitable proton-transfer paths, leading, for example, from the protein surface to the active site buried inside the protein. We include dynamic fluctuations of amino acid side chains and water molecules into our analysis. To illustrate the method, proton transfer into the active site of cytochrome P450cam is studied. The cooperative rotation of amino acids and motion of water molecules are found to connect the protein surface to the molecular oxygen. Our observations emphasize the intrinsic dynamical nature of proton pathways where critical connections in the network may be transiently provided by mobile groups. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Indian Inst Technol, Dept Chem, Kharagpur 721302, W Bengal, India. RP Hummer, G (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X NR 78 TC 53 Z9 53 U1 1 U2 9 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 APR 2 PY 2003 VL 125 IS 13 BP 3931 EP 3940 DI 10.1021/ja016860c PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA 660YM UT WOS:000181863200051 PM 12656628 ER PT J AU Baker, SG AF Baker, SG TI The central role of receiver operating characteristic (ROC) curves in evaluating tests for the early detection of cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID PROTEOMIC PATTERNS; OVARIAN-CANCER; EARLY INTERVENTION; SERUM; IDENTIFICATION; MAMMOGRAPHY C1 NCI, Biometry Res Grp, Bethesda, MD 20892 USA. RP Baker, SG (reprint author), NCI, Biometry Res Grp, EPN 3131,6130 Execut Blvd,MSC 7354, Bethesda, MD 20892 USA. NR 24 TC 97 Z9 98 U1 0 U2 3 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 APR 2 PY 2003 VL 95 IS 7 BP 511 EP 515 PG 5 WC Oncology SC Oncology GA 660ZQ UT WOS:000181866400009 PM 12671018 ER PT J AU Freedman, AN Graubard, BI Rao, SR McCaskill-Stevens, W Ballard-Barbash, R Gail, MH AF Freedman, AN Graubard, BI Rao, SR McCaskill-Stevens, W Ballard-Barbash, R Gail, MH TI Estimates of the number of US women who could benefit from tamoxifen for breast cancer chemoprevention SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SURGICAL-ADJUVANT-BREAST; PREVENTION; TRIAL; VALIDATION; RISK AB Background: The Breast Cancer Prevention Trial demonstrated that tamoxifen treatment produced a 49% reduction in the risk of invasive breast cancer among women at elevated risk for the disease. The U.S. Food and Drug Administration (FDA) subsequently approved tamoxifen for women aged 35 years or older with a 5-year breast cancer risk of 1.67% or higher for breast cancer chemoprevention. However, tamoxifen use has been associated with adverse outcomes, and not all eligible women have a positive benefit/risk ratio. Methods: We used weighted data from the year 2000 National Health Interview Survey Cancer Control Module to estimate the total number of U.S. women, aged 35-79 years, who were eligible for tamoxifen chemoprevention based on the FDA eligibility criteria. We also estimated the numbers of white and black women who would benefit from tamoxifen chemoprevention on the basis of a positive benefit/risk index developed by Gail et al. Results: Of the 65826074 women aged 35-79 years without reported breast cancer in the United States in 2000, 10232816 women (15.5%, 95% confidence interval [CI] = 14.7% to 16.3%) would be eligible for tamoxifen chemoprevention. The percentage of U.S. women who would be eligible varied dramatically by race, with 18.7% (95% CI = 17.8% to 19.7%) of white women, 5.7% (95% CI = 4.3% to 7.5%) of black women, and 2.9% (95% CI = 2.1% to 3.9%) of Hispanic women being eligible. Of the 50 104 829 white U.S. women aged 3579 years, 2431911 (4.9%, 95% CI = 4.3% to 5.4%) would have a positive benefit/risk index for tamoxifen chemoprevention. Of the 7481779 black U.S. women aged 35-79 years, only 42768 (0.6%, 95% CI = 0.2% to 1.3%) would have a positive benefit/risk index. Among white women, 28492 (95% CI = 24693 to 32292) breast cancers would be prevented or deferred if those women who have a positive net benefit index took tamoxifen over the next 5 years. Conclusion: A substantial percentage of U.S. women would be eligible for tamoxifen chemoprevention according to FDA criteria, but a much smaller percentage would have an estimated net benefit. Nevertheless, this latter percentage corresponds to more than two million women. [J Natl Cancer Inst 2003;95:526-32] C1 NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Freedman, AN (reprint author), NCI, Div Canc Control & Populat Sci, EPN 4005 MSC 7344,6130 Execut Blvd, Bethesda, MD 20892 USA. NR 18 TC 136 Z9 139 U1 0 U2 7 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 APR 2 PY 2003 VL 95 IS 7 BP 526 EP 532 PG 7 WC Oncology SC Oncology GA 660ZQ UT WOS:000181866400011 PM 12671020 ER PT J AU Engels, EA Katki, HA Nielsen, NM Winther, JF Hjalgrim, H Gjerris, F Rosenberg, PS Frisch, M AF Engels, EA Katki, HA Nielsen, NM Winther, JF Hjalgrim, H Gjerris, F Rosenberg, PS Frisch, M TI Cancer incidence in Denmark following exposure to poliovirus vaccine contaminated with simian virus 40 SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HUMAN BRAIN-TUMORS; DNA-SEQUENCES; PLEURAL MESOTHELIOMA; SV40-LIKE SEQUENCES; SV40 DNA; JC VIRUS; BK VIRUS; SIMIAN-VIRUS-40; POLYOMAVIRUSES; ASSOCIATION AB Background: Early poliovirus vaccines were accidentally contaminated with simian virus 40 (SV40). In Denmark, poliovirus vaccine was administered to most children from 1955 through 1961. SV40 DNA sequences have been detected in several human malignancies, including mesothelioma, ependymoma, choroid plexus tumors, and non-Hodgkin's lymphoma. To clarify whether SV40 infection increases risk of these cancers or of cancers arising in children, we examined cancer incidence in three Danish birth cohorts. Methods: Population-based cancer incidence data from 1943 through 1997 were obtained from the Danish Cancer Registry. The relationship between exposure to SV40-contaminated vaccine and cancer incidence was evaluated by examining incidence in birth cohorts that differed in exposure to SV40-contaminated vaccine. In addition, cancer incidence was examined in children who were 0-4 years of age before, during, and after the period of vaccine contamination. Incidence was compared using Poisson regression, adjusting for age differences. All statistical tests were two-sided. Results: After 69.5 million person-years of follow-up, individuals exposed to SV40-contaminated poliovirus vaccine as infants (i.e., born 1955-1961) or children (i.e., born 1946-1952) had lower overall cancer risk (age-adjusted relative risk [RR] = 0.86, 95% confidence interval [CI] = 0.81 to 0.91 and RR = 0.79, 95% CI = 0.75 to 0.84, respectively; P<.001 for both) than unexposed individuals (i.e., born 1964-1970, after the vaccine was cleared of SV40 contamination). Specifically, SV40 exposure was not associated with increased incidence of mesothelioma, ependymoma, choroid plexus tumor, or non-Hodgkin's lymphoma. After 19.5 million person-years of follow-up, incidence of all cancers combined, of intracranial tumors, and of leukemia among children aged 0-4 years was also not associated with SV40 exposure. Ependymoma incidence was higher during the exposed period than during the unexposed period (RR = 2.59, 95% CI = 1.36 to 4.92; P = .004 versus the period before contamination); however, incidence peaked in 1969, after the vaccine was cleared of SV40. Conclusion: Exposure to SV40-contaminated poliovirus vaccine in Denmark was not associated with increased cancer incidence. [J Nad Cancer Inst 2003;95:532-9] C1 NCI, Div Canc Epidemiol & Genet, Viral Epidemiol Branch, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Statens Serum Inst, Danish Epidemiol Sci Ctr, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark. Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. Univ Copenhagen, Rigshosp, HS, Neurosci Ctr,Clin Neurosurg, DK-2100 Copenhagen, Denmark. RP Engels, EA (reprint author), NCI, Div Canc Epidemiol & Genet, Viral Epidemiol Branch, Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 8010, Bethesda, MD 20892 USA. RI Katki, Hormuzd/B-4003-2015; Frisch, Morten/E-9206-2016 OI Frisch, Morten/0000-0002-3864-8860 NR 44 TC 40 Z9 42 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 APR 2 PY 2003 VL 95 IS 7 BP 532 EP 539 PG 8 WC Oncology SC Oncology GA 660ZQ UT WOS:000181866400012 PM 12671021 ER PT J AU Zou, LL Miles, AP Wang, J Stowers, AW AF Zou, LL Miles, AP Wang, J Stowers, AW TI Expression of malaria transmission-blocking vaccine antigen Pfs25 in Pichia pastoris for use in human clinical trials SO VACCINE LA English DT Article DE transmission-blocking vaccine; malaria vaccine; TBV25H ID PLASMODIUM-FALCIPARUM; RECOMBINANT PFS25; ANTIBODIES; CANDIDATE; YEAST; PVS25; VIVAX; IMMUNOGENICITY; PURIFICATION; INDUCTION AB In previously published studies, Saccharomyces cerevisiae recombinant protein expression systems have been employed to express the malaria parasite antigen Pfs25, a candidate transmission-blocking vaccine antigen against Plasmodium falciparum malaria. However, despite having been in two Phase I trials, the recombinant Pfs25 so produced (previously called TBV25H) exists as a mixture of two monomeric protein conformational forms, Pfs25H-A and Pfs25H-B. In this study, we optimized the expression and purification of the two Pfs25H conformers in S. cerevisiae, and characterized their biochemical and antigenic properties, immunogenicities, and transmission-blocking activities. Pfs25H-A is apparently homogeneous, and has the correct conformation as measured by monoclonal antibody recognition. It is, however, expressed at a low yield of only 0.19 mg/l. By contrast, Pfs25H-B is produced as a heterogeneous population of molecules that do not seem to have the correct conformation. Nonetheless, both forms appear equally effective in their ability to produce transmission-blocking antibodies in mice. To address the low yield seen with S. cerevisiae, we also expressed Pfs25 in Pichia pastoris. P pastoris is apparently superior to S. cerevisiae in producing higher yield, immunologically more potent, biologically more active Pfs25H-A. Published by Elsevier Science Ltd. C1 NIAID, Malaria Vaccine Dev Unit, NIH, Rockville, MD 20852 USA. RP Stowers, AW (reprint author), CSL Ltd, 45 Poplar Rd, Parkville, Vic 3052, Australia. NR 19 TC 45 Z9 49 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD APR 2 PY 2003 VL 21 IS 15 BP 1650 EP 1657 AR PII S0264-410X(02)00701-6 DI 10.1016/S0264-410X(02)00701-6 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 663LX UT WOS:000182008000011 PM 12639486 ER PT J AU Baker, T Dauter, Z AF Baker, T Dauter, Z TI DNA and beyond SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Editorial Material C1 Univ Auckland, Sch Biol Sci, Auckland 1, New Zealand. NCI, Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. RP Baker, T (reprint author), Univ Auckland, Sch Biol Sci, Private Bag 92-019, Auckland 1, New Zealand. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD APR PY 2003 VL 59 BP 619 EP 619 DI 10.1107/S0907444903005900 PN 4 PG 1 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 660CE UT WOS:000181815600001 ER PT J AU Yang, T AF Yang, T TI Regulation of cyclooxygenase-2 in renal medulla SO ACTA PHYSIOLOGICA SCANDINAVICA LA English DT Article DE cyclooxygenase-2; hyperosmolality; lipopolysaccharide; mitogen-activated protein kinases; renal medulla ID NF-KAPPA-B; NITRIC-OXIDE SYNTHASE; MESANGIAL CELLS; MESSENGER-RNA; PROSTAGLANDIN PRODUCTION; DIFFERENTIAL REGULATION; COLLECTING DUCT; SODIUM-INTAKE; EXPRESSION; SALT AB Aims: Renal medulla is a major site for production and action of prostaglandins (PGs). The renal medullary functions as well as structural integrity are in part dependent on PGs under certain physiological or pathophysiological conditions. The two COX isoforms, COX-1 (constitutive form) and COX-2 (inducible form) are both abundantly expressed in renal inner medulla at basal state, raising a question of which COX isoform may mediate the known functions of PGs in the region. As in many other cell types, COX-1 expression in renal medulla is unlikely subject to robust regulation. In contrast, COX-2 expression in renal medulla is markedly stimulated by chronic salt loading, dehydration and endotoxaemia in vivo. At cellular levels, the signalling pathways responsible for the COX-2 stimulation in renal medullary cells seem to involve both the mitogen-activated protein kinases and NF-kappaB. It is likely that in response to various insults that are detrimental to renal medulla, the induction of PG synthesis may become more dependent on COX-2 than COX-1, and this phenomenon may be relevant to the cytoprotective response against the insults. C1 Vet Affairs Med Ctr, Res Serv 151 E, Salt Lake City, UT 84148 USA. NIDDK, NIH, Bethesda, MD USA. Univ Utah, Sch Med, Div Nephrol, Salt Lake City, UT USA. RP Yang, T (reprint author), Vet Affairs Med Ctr, Res Serv 151 E, 500 Foothill Dr, Salt Lake City, UT 84148 USA. NR 41 TC 19 Z9 19 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0001-6772 J9 ACTA PHYSIOL SCAND JI Acta Physiol. Scand. PD APR PY 2003 VL 177 IS 4 BP 417 EP 421 DI 10.1046/j.1365-201X.2003.01102.x PG 5 WC Physiology SC Physiology GA 658RB UT WOS:000181733300002 PM 12648158 ER PT J AU Kampman, K Majewska, MD Tourian, K Dackis, C Cornish, J Poole, S O'Brien, C AF Kampman, K Majewska, MD Tourian, K Dackis, C Cornish, J Poole, S O'Brien, C TI A pilot trial of piracetam and ginkgo biloba for the treatment of cocaine dependence SO ADDICTIVE BEHAVIORS LA English DT Article DE cocaine; piracetam; ginkgo biloba; clinical trial ID NEUROPSYCHOLOGICAL DEFICITS; CEREBRAL PERFUSION; MEMORY IMPAIRMENT; DOUBLE-BLIND; EXTRACT; ABUSERS; DEMENTIA; ABNORMALITIES; OUTPATIENTS; VOLUNTEERS AB Background: Chronic cocaine use is associated with cognitive deficits that may reduce the effectiveness of psychosocial treatment and promote relapse in newly abstinent cocaine-dependent patients. Nootropic agents, such as piracetam. and ginkgo biloba, may improve cognitive function and reduce the incidence of relapse in these patients. Methods: This was a 10-week, double-blind, placebo-controlled pilot trial involving 44 cocaine-dependent subjects. Subjects received either piracetam (4.8 g/day), ginkgo biloba (120 mg/day), or placebo. Subjects were required to attain abstinence from cocaine during a 2-week baseline phase demonstrated by providing at least one benzoylecgonine (BE)-negative urine toxicology screen. Outcome measures included treatment retention, urine toxicology screens, Clinical Global Impression (CGI) scores, and results from the Addiction Severity Index (ASI). Results: Ginkgo biloba was not superior to placebo in any outcome measure. Piracetam was associated with more cocaine use and lower CGI scores compared to placebo. Conclusions: Neither piracetam nor ginkgo biloba appears to be a promising medication for the treatment of cocaine dependence. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Univ Penn, Treatment Res Ctr, Dept Psychiat, Sch Med, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Natl Inst Drug Abuse, Bethesda, MD USA. Belmont Ctr, Philadelphia, PA USA. RP Kampman, K (reprint author), Univ Penn, Treatment Res Ctr, Dept Psychiat, Sch Med, 2900 Chestnut St, Philadelphia, PA 19104 USA. EM kampman_k@mail.trc.upenn.edu FU NIDA NIH HHS [K20 DA00238, YO1 DA30012] NR 42 TC 12 Z9 12 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD APR PY 2003 VL 28 IS 3 BP 437 EP 448 DI 10.1016/S0306-4603(02)00226-5 PG 12 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 658DK UT WOS:000181706200003 PM 12628617 ER PT J AU Getchell, TV Peng, XJ Stromberg, AJ Chen, KC Green, CP Subhedar, NK Shah, DS Mattson, MP Getchell, ML AF Getchell, TV Peng, XJ Stromberg, AJ Chen, KC Green, CP Subhedar, NK Shah, DS Mattson, MP Getchell, ML TI Age-related trends in gene expression in the chemosensory-nasal mucosae of senescence-accelerated mice SO AGEING RESEARCH REVIEWS LA English DT Review DE aging; senescence-accelerated mouse; DNA microarrays; gene profiling; olfactory receptor; vomeronasal receptor ID OLFACTORY RECEPTOR NEURONS; LEUKEMIA INHIBITORY FACTOR; MESSENGER-RNA EXPRESSION; DNA MICROARRAY ANALYSIS; FACTOR-BINDING-PROTEIN; MOUSE SAM; TARGET ABLATION; ADULT-MOUSE; 11-BETA-HYDROXYSTEROID DEHYDROGENASE; NEURODEGENERATIVE DISORDERS AB We have utilized high-density GeneChip oligonucleotide arrays to investigate the use of the senescence-accelerated mouse (SAM) as a biogerontological resource to identify patterns of gene expression in the chemosensory-nasal mucosa. Gene profiling in chronologically young and old mice of the senescence-resistant (SAMR) and senescence-prone (SAMP) strains revealed 133 known genes that were modulated by a three-fold or greater change either in one strain or the other or in both strains during aging. We also identified known genes in our study which based on their encoded proteins were identified as aging-related genes in the aging neocortex and cerebellum of mice as reported by Lee et al. (2000) [Nat. Genet. 25 (2000) 294]. Changes in gene profiles for chemosensory-related genes including olfactory and vomeronasal receptors, sensory transduction-associated proteins, and odor and pheromone transport molecules in the young SAMR and SAMP were compared with age-matched C57BL/6J mice. An analysis of known gene expression profiles suggests that changes in the expression of immune factor genes and genes associated with cell cycle progression and cell death were particularly prominent in the old SAM strains. A preliminary cellular validation study supported the dysregulation of cell cycle-related genes in the old SAM strains. The results of our initial study indicated that the use of the SAM models of aging could provide substantive information leading to a more fundamental understanding of the aging process in the chemosensory-nasal mucosa at the genomic, molecular, and cellular levels. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Kentucky, Sanders Brown Ctr Aging 309, Dept Physiol, Lexington, KY 40536 USA. Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. Univ Kentucky, Dept Stat, Lexington, KY 40536 USA. Univ Kentucky, Dept Mol & Biomed Pharmacol, Lexington, KY 40536 USA. Univ Kentucky, Dept Anat & Neurobiol, Lexington, KY 40536 USA. NIA, Dept Lab Neurosci, Baltimore, MD 21224 USA. RP Univ Kentucky, Sanders Brown Ctr Aging 309, Dept Physiol, 800 S Limestone St, Lexington, KY 40536 USA. EM tgetche@uky.edu RI Mattson, Mark/F-6038-2012 FU NCRR NIH HHS [1P20RR16481-01]; NIA NIH HHS [AG-016824-22] NR 143 TC 19 Z9 20 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1568-1637 EI 1872-9649 J9 AGEING RES REV JI Ageing Res. Rev. PD APR PY 2003 VL 2 IS 2 BP 211 EP 243 AR PII S1568-1637(02)00066-1 DI 10.1016/S1568-1637(02)00066-1 PG 33 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 691HG UT WOS:000183599600006 PM 12605961 ER PT J AU Taaffe, DR Lang, TF Harris, TB AF Taaffe, DR Lang, TF Harris, TB TI Poor correlation of mid-femoral measurements by CT and hip measurements by DXA in the elderly SO AGING CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE bone mineral density; computerized tomography (CT); dual X-ray absorptiometry (DXA); elderly; hip fracture; mid-femur ID BONE-MINERAL DENSITY; X-RAY ABSORPTIOMETRY; QUANTITATIVE COMPUTED-TOMOGRAPHY; OSTEOPOROTIC FRACTURES; PHOTON-ABSORPTIOMETRY; SHORT-TERM; WOMEN; SITES; MEN; INTERRELATIONSHIPS AB Background and aims: Hip fracture is a devastating event in terms of outcome in the elderly, and the best predictor of hip fracture risk is hip bone density, usually measured by dual X-ray absorptiometry (DXA). However, bone density can also be ascertained from computerized tomography (CT) scans, and mid-thigh scans are frequently employed to assess the muscle and fat composition of the lower limb. Therefore, we examined if it was possible to predict hip bone density using mid-femoral bone density. Methods: Subjects were 803 ambulatory white and black women and men, aged 70-79 years, participating in the Health, Aging and Body Composition (Health ABC) Study. Bone mineral content (BMC, g) and volumetric bone mineral density (vBMD, mg/cm(3)) of the mid-femur were obtained by CT, whereas BMC and areal bone mineral density (aBMD, g/cm(2)) of the hip (femoral neck and trochanter) were derived from DXA. Results: In regression analyses stratified by race and sex, the coefficient of determination was low with mid-femoral BMC, explaining 6-27% of the variance in hip BMC, with a standard error of estimate (SEE) ranging from 16 to 22% of the mean. For mid-femur vBMD, the variance explained in hip aBMD was 2-17% with a SEE ranging from 15 to 18%. Adjusting aBMD to approximate volumetric density did not improve the relationships. In addition, the utility of fracture prediction was examined. Forty-eight subjects had one or more fractures (various sites) during a mean follow-up of 4.07 years. In logistic regression analysis, there was no association between mid-femoral vBMD and fracture (all fractures), whereas a 1 SD increase in hip BMD was associated with reduced odds for fracture of similar to60%. Conclusions: These results do not support the use of CT-derived mid-femoral vBMD or BMC to predict DXA-measured hip bone mineral status, irrespective of race or sex in older adults. Further, in contrast to femoral neck and trochanter BMD, mid-femur vBMD was not able to predict fracture (all fractures). (C) 2003, Editrice Kurtis. C1 Univ Queensland, Sch Human Movement Studies, Fac Hlth Sci, St Lucia, Qld 4072, Australia. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. RP Taaffe, DR (reprint author), Univ Queensland, Sch Human Movement Studies, Fac Hlth Sci, Connell Bldg, St Lucia, Qld 4072, Australia. RI Lang, Thomas/B-2685-2012 OI Lang, Thomas/0000-0002-3720-8038 FU NIA NIH HHS [N01-AG-6-2102, N01-AG-6-2103, N01-AG-6-2106] NR 30 TC 1 Z9 1 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 1594-0667 J9 AGING CLIN EXP RES JI Aging Clin. Exp. Res. PD APR PY 2003 VL 15 IS 2 BP 131 EP 135 PG 5 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 700VD UT WOS:000184131100006 PM 12889844 ER PT J AU Morgan, TR Brenner, D Everhart, J French, SW Fried, MW Gretch, DR Koziel, MJ McClain, CJ Peters, MG Weinman, SA Lucas, DL AF Morgan, TR Brenner, D Everhart, J French, SW Fried, MW Gretch, DR Koziel, MJ McClain, CJ Peters, MG Weinman, SA Lucas, DL TI Hepatitis C and alcohol: Fundamental and translational research directions SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article ID SYMPTOMATIC LIVER-CIRRHOSIS; OXIDATIVE STRESS; VIRUS-INFECTION; RISK-FACTORS; FIBROSIS PROGRESSION; DISEASE; CONSUMPTION; PROTEIN; INJURY AB Infection with hepatitis C and the alcohol abuse that frequently accompanies it, impose major worldwide healthcare burdens. The scientific knowledge base that would inform and direct the development of more effective treatment and intervention strategies for these linked pandemics is inadequate. Therefore, the National Institute on Alcohol Abuse and Alcoholism (NIAAA) organized a workshop in which a multi-disciplinary group of experts was asked to review the state-of-the-science specific to alcohol in the context of hepatitis C infection. The panel was charged with identifying newly emerging areas likely to lead to advances in fundamental research and to identify those with the greatest, potential for accelerating the development of more effective treatment options. The workshop panel made recommendations for research in four major categories: clinical studies of alcohol and HCV; virology and immunology; liver fibrosis and mechanisms of liver injury; and the development of model systems. This article summarizes the panel's deliberations and their recommendations for future research on alcohol and hepatitis C. C1 NIAAA, NIH, Bethesda, MD 20892 USA. Vet Adm Med Ctr, Dept Med, Long Beach, CA 90822 USA. Univ N Carolina, Dept Med, Chapel Hill, NC USA. NIDDK, NIH, Bethesda, MD USA. Univ Calif Los Angeles, Los Angeles Cty Harbor Med Ctr, Dept Pathol, Torrance, CA 90509 USA. Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. Deaconess Beth Israel Hosp, Harvard Inst Med, Boston, MA USA. Univ Louisville, Div Gastroenterol, Louisville, KY 40292 USA. Univ Calif San Francisco, Div Gastroenterol, San Francisco, CA USA. Univ Texas, Med Branch, Dept Physiol & Biophys, Galveston, TX 77550 USA. RP Lucas, DL (reprint author), NIAAA, NIH, 6000 Execut Blvd,Rm 402,MSC 7003, Bethesda, MD 20892 USA. RI Weinman, Steven/E-7012-2011 NR 18 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD APR PY 2003 VL 27 IS 4 BP 726 EP 731 DI 10.1097/01.ALC.0000062741.58464.19 PG 6 WC Substance Abuse SC Substance Abuse GA 669CT UT WOS:000182334900019 PM 12711937 ER PT J AU Black, S AF Black, S TI The hidden history of the genetic code SO AMERICAN BIOLOGY TEACHER LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. RP Black, S (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 1 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 APR PY 2003 VL 65 IS 4 BP 245 EP 245 PG 1 WC Biology; Education, Scientific Disciplines SC Life Sciences & Biomedicine - Other Topics; Education & Educational Research GA 677YK UT WOS:000182836900001 ER PT J AU Marroquin, OC Holubkov, R Edmundowicz, D Rickens, C Pohost, G Buchthal, S Pepine, CJ Sopko, G Sembrat, RC Meltzer, CC Reis, SE AF Marroquin, OC Holubkov, R Edmundowicz, D Rickens, C Pohost, G Buchthal, S Pepine, CJ Sopko, G Sembrat, RC Meltzer, CC Reis, SE TI Heterogeneity of microvascular dysfunction in women with chest pain not attributable to coronary artery disease: Implications for clinical practice SO AMERICAN HEART JOURNAL LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; MYOCARDIAL BLOOD-FLOW; L-ARGININE SUPPLEMENTATION; SYNDROME EVALUATION WISE; ANGINA-PECTORIS; SYNDROME-X; RESERVE; ISCHEMIA; QUANTIFICATION; VASODILATION AB Background Women with chest pain in the absence of obstructive coronary artery disease (CAD) frequently have coronary microvascular dysfunction and inducible myocardial ischemia. Microvascular dysfunction is commonly diagnosed by demonstrating abnormal flow reserve in a single coronary artery during angiography. Therefore, diagnostic accuracy is dependent on homogeneity of microvascular dysfunction in the myocardium. Methods In the Women's Ischemia Syndrome Evaluation (WISE) 34 women with chest pain and no significant CAD and 9 female control subjects underwent N-13-NH3 positron emission tomography to measure adenosine-induced changes in myocardial perfusion (ie, coronary flow reserve [CFR]). Flow reserve was correlated among the left anterior descending (LAD), circumflex (LCx), and right (RCA) coronary artery distributions. Results The mean CFR in the LAD, LCx, and RCA was 2.85 +/- 1.35, 2.58 +/- 0.94, and 3.24 +/- 1.42, respectively. Concordance in the classification of microvascular function as normal (CFR greater than or equal to2.5) versus abnormal was present in the LAD and RCA, LAD and LCx, and, RCA and LCx distributions in only 71.8%, 66.7%, and 61.6% of patients, respectively. There was a modest degree of correlation of CFR between the LAD and RCA (r = 0.79, P < .001), LAD and LCx (r =. 0.61, P < .001), and LCx and RCA (r = 0.57, P < .001). Comparison of CFR in the 3 coronary arteries simultaneously in all patients demonstrated that the LCx had values that were significantly lower than the RCA and LAD distributions. Conclusion Substantial discordance of classification of microvascular function among coronary artery distributions in women with chest pain and no CAD suggests that microvascular dysfunction is distributed heterogeneously in the myocardium. Assessment of CFR in a single coronary artery during cardiac catheterization may not provide an accurate assessment of the coronary microcirculation in women with chest pain not attributable to CAD. C1 Univ Pittsburgh, Cardiovasc Inst, Pittsburgh, PA 15260 USA. Univ Utah, Sch Med, Dept Family & Prevent Med, Salt Lake City, UT USA. Univ Alabama, Dept Med, Div Cardiol, Birmingham, AL 35294 USA. Univ Florida, Dept Med, Div Cardiol, Gainesville, FL 32611 USA. NHLBI, Div Heart & Vasc Dis, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15260 USA. RP Reis, SE (reprint author), WISE Coordinating Ctr, 127 Parran Hall,130 DeSoto St, Pittsburgh, PA 15261 USA. RI Reis, Steven/J-3957-2014; Marroquin, Oscar/F-2214-2015 OI Marroquin, Oscar/0000-0002-0909-0319 FU NHLBI NIH HHS [N01-HV-68163, N01-HV-68162, N01-HV-68161, N01-HV-68164] NR 26 TC 25 Z9 26 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 APR PY 2003 VL 145 IS 4 BP 628 EP 635 DI 10.1067/mhj.2003.95 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 666TH UT WOS:000182192200013 PM 12679758 ER PT J AU Rivenes, SM Colan, SD Easley, KA Kaplan, S Jenkins, KJ Khan, MN Lai, WW Lipshultz, SE Moodie, DS Starc, TJ Sopko, G Zhang, WH Bricker, JT AF Rivenes, SM Colan, SD Easley, KA Kaplan, S Jenkins, KJ Khan, MN Lai, WW Lipshultz, SE Moodie, DS Starc, TJ Sopko, G Zhang, WH Bricker, JT CA Pediatric Pulmonary Cardiovascular TI Usefulness of the pediatric electrocardiogram in detecting left ventricular hypertrophy: Results from the prospective pediatric pulmonary and cardiovascular complications of vertically transmitted HIV infection (P2C2 HIV) multicenter study SO AMERICAN HEART JOURNAL LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CHILDREN AB Background A shortcoming of the pediatric electrocardiogram (ECG) appears to be its inability to accurately detect left ventricular hypertrophy (LVH). This study prospectively assesses the usefulness of the pediatric ECG as a screening,modality for LVH. methods Concomitant echocardiograms and ECGs from a large cohort of children who were I exposed to the human immunodeficiency virus (HIV; uninfected) and children who were infected with HIV were compared. By use of the values of Davignon et al, qualitative determination of LVH and quantitative criteria for LVH (RV6, SV1, RV6 + SV1, QV(6), and Q(III) >98% for age, R/SV1 <98% for age, and [-]TV6) were compared to body surface area adjusted for left ventricular (LV) mass z score. Results were then. stratified according to weight and weight-for-height z scores. New age-adjusted predicted values were then constructed from children of a mixed race who were HIV-uninfected, less than or equal to6 Years old, and similarly assessed. Results The sensitivity rate was <20% for detecting increased LV mass, irrespective of HIV status; the specificity rate. was 88% to 92%. The sensitivity rate of the individual criteria ranged from 0 to 35%; the specificity rate was 76% to 99%. Test sensitivities remained low when stratified by weight and weight-for-height z scores. Areas under the receiver operator characteristic curves were between 0.59 and 0.70, also suggesting poor accuracy of the ECG criteria. By use of new age-adjusted predicted values, the sensitivity rate decreased to <17%, and the specificity rate increased to 94% to 100%. Conclusion The ECG is a poor screening tool for identifying LVH in children. Sensitivity is not improved with revision of current criteria. C1 Texas Childrens Hosp, Baylor Coll Med, Div Pediat Cardiol, Dept Pediat, Houston, TX 77030 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat,Dept Cardiol, Boston, MA 02115 USA. Cleveland Clin, Dept Biostat & Epidemiol, Cleveland, OH 44106 USA. Cleveland Clin, Div Pediat, Cleveland, OH 44106 USA. Univ Calif Los Angeles, Med Ctr, Dept Pediat, Div Pediat Cardiol, Los Angeles, CA 90024 USA. Sch Med, Los Angeles, CA USA. Mt Sinai Sch Med, Div Pediat Cardiol, Dept Pediat, New York, NY USA. Columbia Univ, Sch Med,Presbyterian Hosp, Div Pediat Cardiol, Dept Pediat, New York, NY USA. NHLBI, Bethesda, MD 20892 USA. RP Rivenes, SM (reprint author), Texas Childrens Hosp, Baylor Coll Med, Div Pediat Cardiol, Dept Pediat, MC 19345-C,6621 Fannin St, Houston, TX 77030 USA. RI Easley, Kirk/K-6910-2015 OI Easley, Kirk/0000-0003-4419-2617 FU NCRR NIH HHS [M01 RR000645, RR-00645, RR-00865, RR-00043, M01 RR000865, M01 RR000043, K01 RR000188, M01 RR000071, M01 RR000188, M01 RR000533, RR-00071, RR-00188, RR-00533]; NHLBI NIH HHS [N01-HR-96040, N01-HR-96041, N01-HR-96038, N01-HR-96042, N01 HR096037, N01 HR096043, N01-HR-96039] NR 14 TC 17 Z9 17 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 APR PY 2003 VL 145 IS 4 BP 716 EP 723 DI 10.1067/mhj.2003.15 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 666TH UT WOS:000182192200026 PM 12679770 ER PT J AU Hirsch, GA Blumenthal, RS AF Hirsch, GA Blumenthal, RS TI Usefulness of non-high-density lipoprotein cholesterol determinations in the diagnosis and treatment of dyslipidemia SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material ID CORONARY-ARTERY DISEASE; ISCHEMIC-HEART-DISEASE; APOLIPOPROTEIN-A-I; CARDIOVASCULAR-DISEASE; ATHEROSCLEROSIS; PREDICTOR; EVENTS; SIZE; RISK; PROGRESSION C1 Johns Hopkins Ciccarone Prevent Cardiol Ctr, Baltimore, MD USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Blumenthal, RS (reprint author), Johns Hopkins Ciccarone Ctr Prevent Heart Dis, Div Cardiol, Carnegie 538,600 N Wolfe St, Baltimore, MD 21287 USA. NR 30 TC 6 Z9 7 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 APR 1 PY 2003 VL 91 IS 7 BP 827 EP 830 DI 10.1016/S0002-9149(03)00018-3 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 663EY UT WOS:000181994300009 PM 12667569 ER PT J AU Miltyk, W Craciunescu, CN Fischer, L Jeffcoat, RA Koch, MA Lopaczynski, W Mahoney, C Jeffcoat, RA Crowell, J Paglieri, J Zeisel, SH AF Miltyk, W Craciunescu, CN Fischer, L Jeffcoat, RA Koch, MA Lopaczynski, W Mahoney, C Jeffcoat, RA Crowell, J Paglieri, J Zeisel, SH TI Lack of significant genotoxicity of purified soy isoflavones (genistein, daidzein, and glycitein) in 20 patients with prostate cancer SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE genistein; daidzein; glycitein; soy isoflavones; lymphocytes; genotoxicity; prostate cancer ID TOPOISOMERASE-II INHIBITORS; BLOCK MICRONUCLEUS ASSAY; BREAST-CANCER; DNA-DAMAGE; HUMAN-LYMPHOCYTES; PHYTO-ESTROGENS; INFANT LEUKEMIA; IN-VITRO; MLL GENE; MAMMARY-CANCER AB Background: Genistein may be useful in the prevention or treatment of prostate cancer; however, it causes genetic damage in cultured human cells. Objective: The objective was to assess the potential genotoxicity of a purified soy unconjugated isoflavone mixture in men with prostate cancer. Design: Twenty patients with prostate cancer were treated with 300 mg genistein/d for 28 d and then with 600 mg/d for another 56 d. In peripheral lymphocytes, DNA strand breaks were assessed as nuclear tail moment, chromosomal damage was assessed as micronucleus frequency (MF), and translocations of the MLL gene (11q23) were assessed by using fluorescence in situ hybridization. Values are also reported for 6 healthy men. The studies were performed under Investigational New Drug application no. 54 137 at a tertiary referral academic medical center. Results: No changes in group average or individual nuclear tail moment and MF were observed. We observed a single elevated MF value in one subject that exceeded a clinical threshold set before we initiated the study. A significant decrease in average COMET tail moment was observed on day 28 relative to day 0. We detected no genistein-induced rearrangements of the MLL gene in the 3 subjects we studied with this technique. MF increased significantly in lymphocytes exposed in vitro to unconjugated genistein at concentrations greater than or equal to 100 mumol/L. Total genistein never exceeded a peak concentration of 27.1 mumol/L, and unconjugated genistein never exceeded a peak concentration of 0.32 mumol/L. Conclusion: Although isoflavones are capable of inducing genetic damage in vitro, a similar effect was not observed in subjects treated with a purified soy unconjugated isoflavone mixture. C1 Univ N Carolina, Sch Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Chapel Hill, NC 27599 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. NCI, Div Canc Prevent, Chemoprevent Agent Dev Res Grp, Rockville, MD USA. RP Zeisel, SH (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Nutr, CB 7400 McGavran Greenberg Bldg, Chapel Hill, NC 27599 USA. EM steven_zeisel@unc.edu FU NCI NIH HHS [CN75035]; NCRR NIH HHS [RR00046]; NIDDK NIH HHS [DK56350] NR 51 TC 75 Z9 77 U1 0 U2 3 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 2003 VL 77 IS 4 BP 875 EP 882 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 658YA UT WOS:000181747600020 PM 12663286 ER PT J AU Doody, MM Sigurdson, AS Kampa, D Chimes, K Alexander, BH Ron, E Tarone, RE Linet, MS AF Doody, MM Sigurdson, AS Kampa, D Chimes, K Alexander, BH Ron, E Tarone, RE Linet, MS TI Randomized trial of financial incentives and delivery methods for improving response to a mailed questionnaire SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cohort studies; data collection; epidemiologic methods; motivation; nonresponse; postal service; questionnaires; randomized controlled trials ID FOLLOW-UP; MONETARY INCENTIVES; COST-EFFECTIVENESS; HEALTH SURVEY; PHYSICIANS RESPONSES; NONRESPONSE BIAS; RATES; POPULATION; STRATEGIES; MORTALITY AB In a follow-up study, only 64% of 126,628 US radiologic technologists completed a questionnaire during 19941997 after two mailings. The authors conducted a randomized trial of financial incentives and delivery methods to identify the least costly approach for increasing overall participation. They randomly selected nine samples of 300 nonresponders each to receive combinations of no, $1.00, $2.00, and $5.00 cash or check incentives delivered by first-class mail or Federal Express. Federal Express delivery did not achieve greater participation than first-class mail (23.2% vs. 23.7%). In analyses pooled across delivery methods, the response was significantly greater for the $2.00 bill (28.9%, 95% confidence interval (CI): 25.2, 32.7; p<0.0001), $5.00 check (27.5%, 95% CI: 22.5, 33.0; p=0.0001), $1.00 bill (24.6%, 95% CI: 21.2, 28.3; p=0.0007), and $2.00 check (21.8%, 95% CI: 18.5, 25.3; p=0.02) compared with no incentive (16.6%, 95% CI: 13.7, 19.9). The response increased significantly with increasing incentive amounts from $0.00 to $2.00 cash (p trend<0.0001). The $2.00 bill achieved a 30% greater response than did a $2.00 check (p=0.005). For incentives sent by first-class mail, the $5.00 check yielded 30% greater participation than did the $2.00 check (p=0.07). A $1.00 bill, chosen instead of the $2.00 bill because of substantially lower overall cost and sent by first-class mail to the remaining 42,717 nonresponders, increased response from 64% to 72%. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Minnesota, Div Environm & Occupat Hlth, Minneapolis, MN USA. Westat Corp, Rockville, MD USA. RP Doody, MM (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Execut Plaza S,Room 7088, Bethesda, MD 20892 USA. NR 47 TC 33 Z9 32 U1 0 U2 2 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 APR 1 PY 2003 VL 157 IS 7 BP 643 EP 651 DI 10.1093/aje/kwg033 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 665QF UT WOS:000182131600009 PM 12672684 ER PT J AU Berrington de Gonzalez, A Ekbom, A Glass, AG Galanti, MR Grimelius, L Allison, MJ Inskip, PD AF Berrington de Gonzalez, A Ekbom, A Glass, AG Galanti, MR Grimelius, L Allison, MJ Inskip, PD TI Comparison of documented and recalled histories of exposure to diagnostic X-rays in case-control studies of thyroid cancer SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE interviews; medical records; radiography; recall; thyroid neoplasms ID TUBERCULOSIS PATIENTS; RADIATION; MASSACHUSETTS; RADIOGRAPHY; MORTALITY; LEUKEMIA; COHORT; SWEDEN AB Most information concerning possible cancer risks attributable to lifetime exposure to diagnostic x-rays comes from studies in which x-ray history was ascertained by interview or questionnaire, but little is known about the accuracy of such information. The authors assessed agreement between medical x-ray histories obtained through interview and by review of medical records from thyroid cancer case-control studies conducted in Sweden (1985-1992; 123 cases and 123 controls) and from members of a prepaid health plan in the United States (1986-1991; 50 cases and 50 controls). In both studies, substantial disagreement was found between the numbers of x-ray examinations reported in the interview and in the medical records. There was an indication of relatively poorer reporting among controls, particularly for certain types of x-ray examinations and for large numbers of such examinations. Estimates of the risk associated with exposure to diagnostic x-rays were similar, regardless of whether interview or medical record data were used, even though ordinal dose classifications based on the two sources differed considerably. In populations with a high frequency of exposure, spurious associations with numbers of x-ray examinations or estimated thyroid dose might arise because of differences in recall. However, in the present data, reporting errors by cases and controls seemed to be largely nondifferential. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Oxford, Canc Res UK Epidemiol Unit, Oxford, England. Karolinska Inst, Dept Med Epidemiol, Stockholm, Sweden. Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Kaiser Permanente Med Care Program, Portland, OR USA. Ctr Tobacco Prevent, Stockholm, Sweden. RP Inskip, PD (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Execut Plaza S,Room 7052, Bethesda, MD 20892 USA. NR 18 TC 11 Z9 11 U1 1 U2 3 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 APR 1 PY 2003 VL 157 IS 7 BP 652 EP 663 DI 10.1093/aje/kwg026 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 665QF UT WOS:000182131600010 PM 12672685 ER PT J AU Lin, JP Cupples, A Wilson, PWF Heard-Costa, N O'Donnell, CJ AF Lin, JP Cupples, A Wilson, PWF Heard-Costa, N O'Donnell, CJ TI Evidence for a gene influencing serum bilirubin on chromosome 2q telomere: A genomewide scan in the Framingham Study SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID CORONARY-ARTERY DISEASE; HEART-DISEASE; GILBERTS-SYNDROME; LINKAGE ANALYSIS; RISK; ASSOCIATION; TRAIT; UDP-GLUCURONOSYLTRANSFERASE-1; LIPOPROTEIN; PEDIGREES AB There is an inverse relationship between serum bilirubin concentrations and risk of coronary artery disease. The strength of the association is similar to that of smoking, systolic blood pressure, and HDL cholesterol. We carried out a genomewide scan in a Framingham Heart Study. Our study sample consisted of 330 families with 1,394 sibling pairs, 681 cousin pairs, and 89 avuncular pairs. Using variance-component methods, the heritability was estimated to be 49% +/- 6%, and the genome scan demonstrated significant evidence of linkage of serum bilirubin to chromosome 2q, with a LOD score of 3.8 at location 243 cM. The peak multipoint LOD score is located 1 cM away from the uridine diphosphate glycosyltransferase 1 (UGT1A1) gene. UGT1A1 catalyzes the conjugation of bilirubin with glucuronic acid and thus enhances bilirubin elimination; therefore, it is an important candidate gene for serum bilirubin. Gilbert syndrome, a hyperbilirubinemic syndrome, has a population frequency of 2%-19% and is mainly due to a TA insertion at the promoter region of UGT1A1. Only one other region in the genome produced a multipoint LOD score >1 (LOD = 1.3). Our findings suggest that UGT1A1 may be a major gene controlling serum bilirubin levels in the population. C1 NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Lin, JP (reprint author), NHLBI, Div Epidemiol & Clin Applicat, NIH, 6701 Rockledge Dr,Suite 8217, Bethesda, MD 20892 USA. NR 27 TC 34 Z9 40 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 APR PY 2003 VL 72 IS 4 BP 1029 EP 1034 DI 10.1086/373964 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 662WT UT WOS:000181972600024 PM 12618960 ER PT J AU Abbott, KC Reynolds, JC Trespalacios, FC Cruess, D Agodoa, LY AF Abbott, KC Reynolds, JC Trespalacios, FC Cruess, D Agodoa, LY TI Survival by time of day of hemodialysis: Analysis of United States Renal Data System Dialysis Morbidity and Mortality Waves III/IV SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE morning shift hemodialysis (HD); evening shift hemodialysis (HD); time of day; hemodialysis (HD); US Renal Data System (USRDS); survival ID MAINTENANCE HEMODIALYSIS; DISEASE PATIENTS; VASCULAR ACCESS; BLOOD-PRESSURE; INCREASED RISK; ASSOCIATION; PATIENTS/; PRODUCT; COHORT; DEATH AB Background. Whether morning shift hemodialysis is associated with improved survival in comparison to patients receiving afternoon shift hemodialysis has not been shown for a representative sample of US chronic hemodialysis patients. Methods: We conducted a historical cohort study of a national database (US Renal Data System Dialysis Morbidity and Mortality Waves III/IV) of 6,939 patients who started hemodialysis therapy from January 1, 1990, through December 31,1993. Patients were followed up through April 9,2000, and censored at the time of change to a different modality, including transplantation. We estimated the adjusted hazard ratio for all-cause mortality based on the time of day of hemodialysis (0500 to 1200 for morning shift, 1200 to 1800 for afternoon shift, 1800 to midnight for evening shift). Cox regression analysis was used to adjust for other factors associated with survival. Results: For patients aged 60 years and older, the unadjusted 4-year survival rate for patients on morning shift hemodialysis was 28.8% versus 24.1% for patients on afternoon shift hemodialysis and 38.7% for patients on evening shift hemodialysis (P < 0.01 by log-rank test for both versus afternoon shift hemodialysis). Both morning shift (adjusted hazard ratio, 0.90; 95% confidence interval [CI], 0.83 to 0.98; P = 0.02) and evening shift hemodialysis (adjusted hazard ratio, 0.62; 95% CI, 0.48 to 0.80; P less than or equal to 0.001) were independently associated with a lower risk for mortality compared with afternoon shift hemodialysis. No such differences were seen for patients younger than 60 years. Both morning shift and evening shift hemodialysis were independently associated with improved survival compared with afternoon shift hemodialysis in elderly chronic hemodialysis patients. No such association was found for younger patients. This is a US government work. There are no restrictions on its use. C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, NIDDK, NIH, Bethesda, MD USA. USA Nephrol Serv, Madigan Army Med Ctr, Ft Lewis, WA 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 33 TC 19 Z9 19 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2003 VL 41 IS 4 BP 796 EP 806 DI 10.1016/S0272-6386(03)00027-1 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 675EG UT WOS:000182679600011 PM 12666066 ER PT J AU Morris, R Knepper, MA Chou, CL AF Morris, R Knepper, MA Chou, CL TI "Corticalization" of the inner medulla of aquaporin-1 null mice: studies in gene expression and immunocytochemistry SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT Annual Clinical Meeting of the National-Kidney-Foundation CY APR 02-06, 2003 CL DALLAS, TEXAS SP Natl Kidney Fdn C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2003 VL 41 IS 4 MA 60 BP A26 EP A26 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 675EG UT WOS:000182679600089 ER PT J AU Iwayama-Shigeno, Y Yamada, K Toyota, T Shimizu, H Hattori, E Yoshitsugu, K Fujisawa, T Yoshida, Y Kobayashi, T Toru, M Kurumaji, A Detera-Wadleigh, S Yoshikawa, T AF Iwayama-Shigeno, Y Yamada, K Toyota, T Shimizu, H Hattori, E Yoshitsugu, K Fujisawa, T Yoshida, Y Kobayashi, T Toru, M Kurumaji, A Detera-Wadleigh, S Yoshikawa, T TI Distribution of Haplotypes derived from three common variants of the NR4A2 gene in Japanese patients with schizophrenia SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE dopamine; NGFI-B family; retinoid; polymorphism; heterogeneity ID RETINOIC ACID; CHOLINERGIC DIFFERENTIATION; NURR1-DEFICIENT MICE; SYMPATHETIC NEURONS; MUTATION ANALYSIS; NURR1; EXPRESSION; AGENESIS; DISEASE AB Dysregulation in dopaminergic neurotransmission might play a role in the pathogenesis of schizophrenia, and therefore genetic components of the dopamine (DA) pathway may confer risk. The NR4A2 (Nurr1) gene is essential for the development and maintenance of mesencephalic DA-synthesizing neurons. Moreover, Nurr1 forms a heterodimer with the retinoid X receptor and disturbances in the retinoid-signaling cascade may be involved in susceptibility to schizophrenia. To investigate the potential genetic contribution of NR4A2, we performed a case-control association study using three common variants in the gene [-2922(C)2-3, IVS6 + 17similar to+18insG, EX8 + 657 (CA)9-10] that were in strong linkage disequilibrium with each other. We did not detect a significant allelic or genotypic association. Haplotypes derived from all three polymorphisms generated similar results. These data do not support the notion that the NR4A2 gene plays a major role in risk for schizophrenia among Japanese individuals. (C) 2003 Wiley-Liss, Inc. C1 RIKEN, Brain Sci Inst, Lab Mol Psychiat, Wako, Saitama 3510198, Japan. Tokyo Med & Dent Univ, Dept Neuropsychiat, Tokyo, Japan. Hokushin Gen Hosp, Dept Neuropsychiat, Nagano, Japan. NIMH, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Yoshikawa, T (reprint author), RIKEN, Brain Sci Inst, Lab Mol Psychiat, 2-1 Hirosawa, Wako, Saitama 3510198, Japan. NR 20 TC 11 Z9 11 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 B JI Am. J. Med. Genet. B PD APR 1 PY 2003 VL 118B IS 1 BP 20 EP 24 DI 10.1002/ajmg.b.10053 PG 5 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 670HQ UT WOS:000182401800004 PM 12627459 ER PT J AU Schulze, TG Cichon, S Nothen, MM Propping, P Maier, W Rietschel, M AF Schulze, TG Cichon, S Nothen, MM Propping, P Maier, W Rietschel, M TI Is there a phenotypic difference between probands in case-control versus family-based association studies? SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Letter C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Univ Bonn, Dept Psychiat, D-53105 Bonn, Germany. Univ Bonn, Inst Human Genet, D-53111 Bonn, Germany. Univ Instelling Antwerp, Dept Med Genet, B-2610 Antwerp, Belgium. Cent Inst Mental Hlth, D-68072 Mannheim, Germany. RP Schulze, TG (reprint author), NIMH, Mood & Anxiety Disorders Program, Bldg 36 Rm 4C12,36 Convent Dr, Bethesda, MD 20892 USA. RI Schulze, Thomas/H-2157-2013; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014; OI Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X; Nothen, Markus/0000-0002-8770-2464 NR 3 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD APR 1 PY 2003 VL 118B IS 1 BP 25 EP 26 DI 10.1002/ajmg.b.10060 PG 2 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 670HQ UT WOS:000182401800005 PM 12627460 ER PT J AU Levy, LM Henkin, RI AF Levy, LM Henkin, RI TI Why should neuroradiologists study patients with smell loss? SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Editorial Material ID FUNCTIONAL MRI FMRI; BRAIN ACTIVATION; OLFACTION; HYPOSMIA; TASTE; ODORS; IDENTIFICATION; LOCALIZATION; IMAGINATION C1 George Washington Univ, Med Ctr, Dept Radiol, Washington, DC 20037 USA. NINDS, NIH, Bethesda, MD 20892 USA. Taste & Smell Clin, Washington, DC USA. RP Levy, LM (reprint author), George Washington Univ, Med Ctr, Dept Radiol, Washington, DC 20037 USA. NR 27 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD APR PY 2003 VL 24 IS 4 BP 556 EP 558 PG 3 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 670RP UT WOS:000182422900004 PM 12695180 ER PT J AU Jenkins, J Collins, F AF Jenkins, J Collins, F TI Are you genetically literate? April 2003 is Human Genome Month SO AMERICAN JOURNAL OF NURSING LA English DT Editorial Material C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Jenkins, J (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD APR PY 2003 VL 103 IS 4 BP 13 EP 13 PG 1 WC Nursing SC Nursing GA 665AU UT WOS:000182098100001 PM 12677116 ER PT J AU Bingha, RJ AF Bingha, RJ TI Reflections - Taking the air SO AMERICAN JOURNAL OF NURSING LA English DT Article C1 Natl Inst Nursing Res, Bethesda, MD USA. RP Bingha, RJ (reprint author), Natl Inst Nursing Res, 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 0002-936X J9 AM J NURS JI Am. J. Nurs. PD APR PY 2003 VL 103 IS 4 BP 31 EP 31 PG 1 WC Nursing SC Nursing GA 665AU UT WOS:000182098100022 PM 12677119 ER PT J AU Blaug, S Rymer, J Jalickee, S Miller, SS AF Blaug, S Rymer, J Jalickee, S Miller, SS TI P2 purinoceptors regulate calcium-activated chloride and fluid transport in 31EG4 mammary epithelia SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE P2Y purinoceptor; P2U purinoceptor; adenosine trisphosphate; uridine trisphosphate; microelectrodes; mammary physiology; electrophysiology; cystic fibrosis; fluid movement; leaky and tight epithelia ID RETINAL-PIGMENT EPITHELIUM; PROTEIN-KINASE-C; EXTRACELLULAR ATP; CYSTIC-FIBROSIS; ION-TRANSPORT; INTRACELLULAR CALCIUM; BREAST-CANCER; P2-PURINERGIC RECEPTORS; SIGNAL-TRANSDUCTION; AIRWAY EPITHELIUM AB It has been reported that secretory mammary epithelial cells (MEC) release ATP, UTP, and UDP upon mechanical stimulation. Here we examined the physiological changes caused by ATP/UTP in nontransformed, clonal mouse mammary epithelia (31EG4 cells). In control conditions, transepithelial potential (apical side negative) and resistance were -4.4 +/- 1.3 mV (mean +/- SD, n = 12) and 517.7 +/- 39.4 Omega.cm(2), respectively. The apical membrane potential was -43.9 +/- 1.7 mV, and the ratio of apical to basolateral membrane resistance (R-A/R-B) was 3.5 +/- 0.2. Addition of ATP or UTP to the apical or basolateral membranes caused large voltage and resistance changes with an EC50 of similar to24 muM (apical) and similar to30 muM (basal). Apical ATP/UTP (100 muM) depolarized apical membrane potential by 17.6 +/- 0.8 mV (n = 7) and decreased R-A/R-B by a factor of approximate to3. The addition of adenosine to either side (100 muM) had no effect on any of these parameters. The ATP/UTP responses were partially inhibited by DIDS and suramin and mediated by a transient increase in free intracellular Ca2+ concentration (427 +/- 206 nM; 15-25 muMATP, apical; n = 6). This Ca2+ increase was blocked by cyclopiazonic acid, by BAPTA, or by xestospongin C. 31EG4 MEC monolayers also secreted or absorbed fluid in the resting state, and ATP or UTP increased fluid secretion by 5.6 +/- 3 mul.cm(-2).h(-1) (n = 10). Pharmacology experiments indicate that 31EG4 epithelia contain P2Y(2) purinoceptors on the apical and basolateral membranes, which upon activation stimulate apical Ca2+ dependent Cl channels and cause fluid secretion across the monolayer. This suggests that extracellular nucleotides could play a fundamental role in mammary gland paracrine signaling and the regulation of milk composition in vivo. C1 Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. Univ Calif Berkeley, Sch Optometry, Berkeley, CA 94720 USA. RP Miller, SS (reprint author), NEI, NIH, Bldg 31,6A20,31 Ctr Dr, Bethesda, MD 20892 USA. NR 58 TC 20 Z9 21 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD APR PY 2003 VL 284 IS 4 BP C897 EP C909 DI 10.1152/ajpcell.00238.2002 PG 13 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 652JR UT WOS:000181376500010 PM 12456394 ER PT J AU Guo, HT Wei, JP Inoue, Y Gonzalez, FJ Kuo, PC AF Guo, HT Wei, JP Inoue, Y Gonzalez, FJ Kuo, PC TI Serine/threonine phosphorylation regulates HNF-4 alpha-dependent redox-mediated iNOS expression in hepatocytes SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE kinase; phosphorylation; nitric oxide; Cre-lox; transcription; inducible nitric oxide synthase; hepatocyte nuclear factor-4 alpha ID NUCLEAR FACTOR 4-ALPHA; OXIDE SYNTHASE GENE; ACYL-COA THIOESTERS; NITRIC-OXIDE; DNA-BINDING; RAT HEPATOCYTES; TRANSCRIPTIONAL ACTIVATION; PROTEIN DIMERIZATION; OXIDATIVE STRESS; INJURY AB Nitric oxide (NO), endogenously synthesized by inducible NO synthase (iNOS), serves antioxidant and antiapoptotic functions in settings characterized by oxidative stress and proinflammatory cytokines such as sepsis and shock. However, the redox-sensitive mechanisms regulating hepatocyte expression of iNOS are largely unknown. In interleukin-1beta (IL-1beta)-stimulated hepatocytes exposed to superoxide, we demonstrate that hepatocyte nuclear factor-4alpha (HNF-4alpha) acts as an activator of redox-associated hepatocyte iNOS expression at the level of protein, mRNA, and promoter activation. In the absence of HNF-4alpha, this redox-mediated enhancement is ablated. HNF-4alpha functional activity is associated with a unique serine/threonine kinase-mediated phosphorylation pattern. This suggests that a redox-sensitive kinase pathway targets HNF-4alpha to augment hepatocyte iNOS expression. Previous studies have not addressed a redox-dependent kinase signaling pathway that targets HNF-4alpha and enhances hepatocyte iNOS gene transcription. A unique pattern of phosphorylation determines HNF-4alpha activity as a trans-activator of IL-1beta-mediated hepatocyte iNOS expression in the presence of oxidative stress. C1 Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. NCI, NIH, Bethesda, MD 20817 USA. RP Kuo, PC (reprint author), Duke Univ, Med Ctr, Dept Surg, 110 Bell Bldg,Box 3522, Durham, NC 27710 USA. FU NIAID NIH HHS [AI-44629]; NIGMS NIH HHS [GM-65113] NR 43 TC 22 Z9 22 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD APR PY 2003 VL 284 IS 4 BP C1090 EP C1099 DI 10.1152/ajpcell.00394.2002 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 652JR UT WOS:000181376500030 PM 12466152 ER PT J AU Chen, H Sullivan, G Yue, LQ Katz, A Quon, MJ AF Chen, H Sullivan, G Yue, LQ Katz, A Quon, MJ TI QUICKI is a useful index of insulin sensitivity in subjects with hypertension SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE insulin resistance; diabetes; glucose clamp ID HOMEOSTASIS MODEL ASSESSMENT; GLUCOSE-TOLERANCE TEST; MINIMAL-MODEL; CHECK INDEX; PREMATURE ADRENARCHE; 2-COMPARTMENT MODEL; DIABETES-MELLITUS; ACCURATE INDEX; RESISTANCE; DISEASE AB Insulin resistance may link disorders of metabolic homeostasis such as diabetes and obesity with disorders of hemodynamic homeostasis such as hypertension. Thus it is of interest to validate simple methods for quantifying insulin sensitivity in hypertensive patients. The quantitative insulin-sensitivity check index (QUICKI) is a novel mathematical transformation of fasting blood glucose and insulin levels. In obese and diabetic subjects, QUICKI has a significantly better linear correlation with glucose clamp determinations of insulin sensitivity than minimal-model estimates. To determine whether QUICKI is also useful in hypertensive subjects, we performed glucose clamps and frequently sampled intravenous glucose tolerance tests (FSIVGTT) on 27 hypertensive subjects taken off antihypertensive medication. Indexes of insulin sensitivity derived from glucose clamp studies (SIClamp) were compared with QUICKI, minimal-model analysis of FSIVGTTs (SIMM), and homeostasis model assessment (HOMA). The correlation between QUICKI and SIClamp (r = 0.84) was significantly better than that between SIMM and SIClamp (r = 0.65; P < 0.028). The correlation between QUICKI and SIClamp was comparable to that between 1/HOMA and SIClamp (r = 0.82). When studies were repeated in 14 subjects who had resumed antihypertensive medications, the percent changes in SIClamp for each of these patients were significantly correlated with percent changes in QUICKI (r = 0.61) and HOMA (r = -0.54) but not SIMM (r = -0.18). We conclude that QUICKI is a simple, robust index of insulin sensitivity that is useful for evaluating and following the insulin resistance of hypertensive subjects in both research studies and clinical practice. C1 NIH, Diabet Unit, Clin Invest Lab, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. US FDA, Ctr Devices & Radiol Hlth, Div Biostat, Rockville, MD 20850 USA. RP Quon, MJ (reprint author), NIH, Diabet Unit, Clin Invest Lab, Natl Ctr Complementary & Alternat Med, Bldg 10,Rm 8C-218,10 Ctr Dr,MSC 1755, Bethesda, MD 20892 USA. RI Quon, Michael/B-1970-2008 NR 44 TC 63 Z9 64 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD APR PY 2003 VL 284 IS 4 BP E804 EP E812 DI 10.1152/ajpendo.00330.2002 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 653GD UT WOS:000181426100019 PM 12678026 ER PT J AU Shivakumar, K Dostal, DE Boheler, K Baker, KM Lakatta, EG AF Shivakumar, K Dostal, DE Boheler, K Baker, KM Lakatta, EG TI Differential response of cardiac fibroblasts from young adult and senescent rats to ANG II SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE renin-angiotensin system; transforming growth factor-beta; angiotensin type 1 receptor; collagen; cardiac fibrosis ID ANGIOTENSIN-CONVERTING ENZYME; LEFT-VENTRICULAR HYPERTROPHY; MESSENGER-RNA; GENE-EXPRESSION; MYOCARDIAL-INFARCTION; RECEPTOR SUBTYPES; HEART-FAILURE; PRESSURE-OVERLOAD; IN-VITRO; RENIN AB The intracardiac ANG II-forming pathway is activated in the senescent myocardium, raising the possibility of enhanced ANG II effects on cardiac fibroblasts. This study established an in vitro model of cultured cardiac fibroblasts from aged rats to examine if the response of these cells to ANG II is modified in the aged heart. Levels of mRNA encoding renin, angiotensinogen, and the AT(1) receptor subtype in cardiac fibroblasts from young adult and senescent rats were quantified by RT-PCR, net collagen production by a hydroxyproline-based assay, and transforming growth factor (TGF)-beta levels using a commercial kit. In cardiac fibroblasts from young adult rats, ANG II significantly enhanced AT(1) mRNA levels, net collagen production, and TGF-beta production. In fibroblasts from the aged myocardium, ANG II downregulated AT(1) mRNA expression, had a less pronounced effect on net collagen production, and had no effect on TGF-beta production. Such age-related modification of the response of cardiac fibroblasts to ANG II may counteract the effects of augmented intracardiac ANG II production in the senescent heart, limiting fibrogenesis. C1 NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Texas A&M Univ, Syst Hlth Sci Ctr, Cardiovasc Res Inst, Div Mol Cardiol, Temple, TX 76504 USA. RP Shivakumar, K (reprint author), Sree Chitra Tirunal Inst Med Sci & Technol, Div Cellular & Mol Cardiol, Trivandrum 695011, Kerala, India. EM shivak@sctimst.ker.nic.in FU NHLBI NIH HHS [HL-44883] NR 43 TC 30 Z9 32 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 EI 1522-1539 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD APR PY 2003 VL 284 IS 4 BP H1454 EP H1459 DI 10.1152/ajpheart.00766.2002 PG 6 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 653GB UT WOS:000181425900048 PM 12595286 ER PT J AU Kitsiou, PV Tzinia, AK Stetler-Stevenson, WG Michael, AF Fan, WW Zhou, B Tsilibary, EC AF Kitsiou, PV Tzinia, AK Stetler-Stevenson, WG Michael, AF Fan, WW Zhou, B Tsilibary, EC TI Glucose-induced changes in integrins and matrix-related functions in cultured human glomerular epithelial cells SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE matrixins; tissue inhibitors of metalloproteinases; signaling; diabetes ID COLLAGENASE GENE-EXPRESSION; HUMAN MESANGIAL CELLS; GROWTH-FACTOR-BETA; SIGNAL-TRANSDUCTION; ALPHA-3-BETA-1 INTEGRIN; IV COLLAGEN; COORDINATED EXPRESSION; EXTRACELLULAR-MATRIX; BASEMENT-MEMBRANE; INVASION AB In cultured human glomerular epithelial cells (HGEC), 25 mM glucose resulted in decreased expression of alpha(3)-, alpha(2)-, and beta(1)-integrins and increased expression of alpha(5)- and alpha(v)beta(3)-integrins. This change was accompanied by decreased binding of HGEC to type IV collagen. In the presence of normal (5 mM) glucose concentration, cell binding to type IV collagen was primarily mediated by alpha(2)beta(1)- and alpha(5)beta(1)-integrins, as indicated by experiments in which cell adhesion to type IV collagen was competed by specific anti-integrin monoclonal antibodies. In the presence of high (25 mM) glucose, the upregulated alpha(5)- and alpha(v)beta(3)-integrins were mainly involved in cell binding to type IV collagen. Furthermore, high glucose decreased expression of matrix metalloproteinase-2 (MMP-2), a collagenase regulated in part by alpha(3)beta(1)-integrin, as suggested by the use of ligand-mimicking antibodies against these integrins, which resulted in release of increased amounts of MMP-2 in the culture medium. Finally, tissue inhibitor of metalloproteinase-2, the specific inhibitor of MMP-2, was upregulated in high glucose and could contribute to matrix accumulation. These changes could help explain basement membrane thickening in diabetes. C1 Natl Ctr Sci Res Demokritos, Inst Biol, Athens, Greece. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Sch Med, Dept Pediat, Minneapolis, MN 55455 USA. RP Kitsiou, PV (reprint author), Natl Ctr Sci Res Demokritos, Inst Biol, 15310 Agia Paraskevi, Athens, Greece. EM pkit@mail.demokritos.gr RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 FU NIAID NIH HHS [AI-0708] NR 47 TC 48 Z9 55 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD APR PY 2003 VL 284 IS 4 BP F671 EP F679 DI 10.1152/ajprenal.00266.2002 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 652JW UT WOS:000181376900007 PM 12620921 ER PT J AU Schweda, F Wagner, C Kramer, BK Schnermann, J Kurtz, A AF Schweda, F Wagner, C Kramer, BK Schnermann, J Kurtz, A TI Preserved macula densa-dependent renin secretion in A(1) adenosine receptor knockout mice SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE loop diuretics; low salt; high salt ID TUBULOGLOMERULAR FEEDBACK; JUXTAGLOMERULAR APPARATUS; MOLECULAR-BIOLOGY; DEFICIENT MICE; RAT-KIDNEY; CYCLOOXYGENASE-2; RELEASE; INHIBITION; GENE; SALT AB Recent studies demonstrated that the influence of the macula densa on glomerular filtration is abolished in adenosine A(1) receptor (A(1)AR) knockout mice. Inasmuch as the macula densa not only regulates glomerular filtration but also controls the activity of the renin system, the present study aimed to determine the role of the A(1)AR in macula densa control of renin synthesis and secretion. Although a high-salt diet over 1 wk suppressed renin mRNA expression and renal renin content to similar degrees in A(1)AR(+/+), A(1)AR(+/-), and A(1)AR(-/-) mice, stimulation of Ren-1 mRNA expression and renal renin content by salt restriction was markedly enhanced in A(1)AR(-/-) compared with wild-type mice. Pharmacological blockade of macula densa salt transport with loop diuretics stimulated renin expression in vivo (treatment with furosemide at 1.2 mg/day for 6 days) and renin secretion in isolated perfused mouse kidneys (treatment with 100 muM bumetanide) in all three genotypes to the same extent. Taken together, our data are consistent with the concept of a tonic inhibitory role of the A(1)AR in the renin system, whereas they indicate that the A(1)AR is not indispensable in macula densa control of the renin system. C1 Univ Regensburg, Inst Physiol, D-93040 Regensburg, Germany. Univ Regensburg, Klin & Poliklin Innere Med, D-93040 Regensburg, Germany. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Schweda, F (reprint author), Univ Regensburg, Inst Physiol, D-93040 Regensburg, Germany. EM frank.schweda@klinik.uni-regensburg.de NR 37 TC 54 Z9 54 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD APR PY 2003 VL 284 IS 4 BP F770 EP F777 DI 10.1152/ajprenal.00280.2002 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 652JW UT WOS:000181376900018 PM 12475747 ER PT J AU Sweet, DH Chan, LMS Walden, R Yang, XP Miller, DS Pritchard, JB AF Sweet, DH Chan, LMS Walden, R Yang, XP Miller, DS Pritchard, JB TI Organic anion transporter 3 (Slc22a8) is a dicarboxylate exchanger indirectly coupled to the Na(+) gradient SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE kidney; proximal tubule; transport; Oat1; estrone sulfate ID BASOLATERAL MEMBRANE-VESICLES; PARA-AMINOHIPPURIC ACID; PROTEIN-KINASE-C; RAT-KIDNEY; MOLECULAR-CLONING; INDOXYL SULFATE; GLOMERULAR SCLEROSIS; EXPRESSION CLONING; LIVER; IDENTIFICATION AB Basolateral uptake of organic anions in renal proximal tubule cells is indirectly coupled to the Na(+) gradient through Na(+) dicarboxylate cotransport and organic anion/dicarboxylate exchange. One member of the organic anion transporter (OAT) family, Oat1, is expressed in the proximal tubule and is an organic anion/dicarboxylate exchanger. However, a second organic anion carrier, Oat3, is also highly expressed in the renal proximal tubule, but its mechanism is unclear. Thus we have assessed Oat3 function in Xenopus laevis oocytes and rat renal cortical slices. Probenecid-sensitive uptake of p-aminohippurate (PAH, an Oat1 and Oat3 substrate) and estrone sulfate (ES, an Oat3 substrate) in rat Oat3-expressing oocytes was significantly trans-stimulated by preloading the oocytes with the dicarboxylate glutarate (GA). GA stimulation of ES transport by oocytes coexpressing rabbit Na(+) dicarboxylate cotransporter 1 and rat Oat3 was significantly inhibited when the preloading medium contained Li(+) or methylsuccinate (MS) or when Na(+) was absent. All these treatments inhibit the Na(+)-dicarboxylate cotransporter, but not rat Oat3. Li(+), MS, and Na(+) removal had no effect when applied during the ES uptake step, rather than during the GA preloading step. Concentrative ES uptake in rat renal cortical slices was also demonstrated to be probenecid and Na(+) sensitive. Accumulation of ES was stimulated by GA, and this stimulation was completely blocked by probenecid, Li(+), MS, taurocholate, and removal of N+. Thus Oat3 functions as an organic anion/dicarboxylate exchanger that couples organic anion uptake indirectly to the Na(+) gradient. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Med Univ S Carolina, Dept Pharmaceut Sci, Charleston, SC 29425 USA. RP Pritchard, JB (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM pritcha3@niehs.nih.gov RI Sweet, Douglas/H-7914-2013 OI Sweet, Douglas/0000-0002-8911-9184 NR 55 TC 161 Z9 163 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD APR PY 2003 VL 284 IS 4 BP F763 EP F769 DI 10.1152/ajprenal.00405/2002 PG 7 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 652JW UT WOS:000181376900017 PM 12488248 ER PT J AU Anderson, LM Shinn, C Fullilove, MT Scrimshaw, SC Fielding, JE Normand, J Carande-Kulis, VG AF Anderson, LM Shinn, C Fullilove, MT Scrimshaw, SC Fielding, JE Normand, J Carande-Kulis, VG CA Task Force Community Preventive Se TI The effectiveness of early childhood development programs - A systematic review SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Review ID COMMUNITY PREVENTIVE SERVICES; ATTENDING HEAD-START; FOLLOW-UP; EARLY INTERVENTION; PRESCHOOL PROGRAMS; NO PRESCHOOL; CHILDREN; HEALTH; PERSPECTIVE; ACHIEVEMENT AB Early childhood development is influenced by characteristics of the child, the family, and the broader social environment. Physical health, cognition, language, and social and emotional development underpin school readiness. Publicly funded, center-based, comprehensive early childhood development programs are a community resource that promotes the well-being of young children. Programs such as Head Start are designed to close the gap in readiness to learn between poor children and their more economically advantaged peers. Systematic reviews of the scientific literature demonstrate effectiveness of these programs in preventing developmental delay, as assessed by reductions in retention in grade and placement in special education. C1 Ctr Dis Control & Prevent, Community Guide Branch, Div Prevent Res & Analyt Methods, Epidemiol Program Off, Atlanta, GA 30341 USA. Task Force Community Prevent Serv, New York, NY USA. Columbia Univ, New York, NY USA. Univ Illinois, Sch Publ Hlth, Chicago, IL USA. Task Force Community Prevent Serv, Chicago, IL USA. Los Angeles Dept Hlth Serv, Task Force Community Prevent Serv, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. NIDA, NIH, Bethesda, MD 20892 USA. RP Anderson, LM (reprint author), Ctr Dis Control & Prevent, Community Guide Branch, Div Prevent Res & Analyt Methods, Epidemiol Program Off, 4770 Buford Highway,MS-K73, Atlanta, GA 30341 USA. NR 61 TC 169 Z9 176 U1 5 U2 54 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD APR PY 2003 VL 24 IS 3 SU S BP 32 EP 46 DI 10.1016/S0749-3797(02)00655-4 PG 15 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 668NM UT WOS:000182300100010 PM 12668197 ER PT J AU Anderson, LM St Charles, J Fullilove, MT Scrimshaw, SC Fielding, JE Normand, J AF Anderson, LM St Charles, J Fullilove, MT Scrimshaw, SC Fielding, JE Normand, J CA Task Force Community Preventive Se TI Providing affordable family housing and reducing residential segregation by income - A systematic review SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Review ID COMMUNITY PREVENTIVE SERVICES; CORONARY HEART-DISEASE; MULTILEVEL ANALYSIS; NEIGHBORHOOD; HEALTH; CHILDREN; SUBURBS; GUIDE AB The inadequate supply of affordable housing for low-income families and the increasing spatial segregation of some households by income, race, ethnicity, or social class into unsafe neighborhoods are among the most prevalent community health concerns related to family housing. When affordable housing is not available to low-income households, family resources needed for food, medical or dental care, and other necessities are diverted to housing costs. Two housing programs intended to provide affordable housing and, concurrently, reduce the residential segregation of low-income families into unsafe neighborhoods of concentrated poverty, are reviewed: the creation of mixed-income housing developments and the Department of Housing and Urban Development (HUD) Section 8 Rental Voucher Program. The effectiveness of mixed-income housing developments could not be ascertained by this systematic review because of a lack of comparative research. Scientific evidence was sufficient to conclude that rental voucher programs improve household safety as measured by reduced exposure to crimes against person and property and decreased neighborhood social disorder. Effectiveness of rental voucher programs on youth health risk behaviors, mental health status, and physical health status could not be determined because too few studies of adequate design and execution reported these outcomes. C1 Ctr Dis Control & Prevent, Community Guide Branch, Div Prevent Res & Analyt Methods, Epidemiol Program Off, Atlanta, GA 30341 USA. Task Force Community Prevnet Serv, New York, NY USA. Columbia Univ, New York, NY USA. Task Force Community Prevent Serv, Chicago, IL USA. Univ Chicago, Sch Publ Hlth, Chicago, IL 60637 USA. Los Angeles Dept Hlth Serv, Task Force Community Prevent Serv, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. NIDA, NIH, Bethesda, MD 20892 USA. RP Anderson, LM (reprint author), Ctr Dis Control & Prevent, Community Guide Branch, Div Prevent Res & Analyt Methods, Epidemiol Program Off, 4770 Buford Highway,MS-K73, Atlanta, GA 30341 USA. NR 74 TC 51 Z9 51 U1 2 U2 41 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD APR PY 2003 VL 24 IS 3 SU S BP 47 EP 67 DI 10.1016/S0749-3797(02)00656-6 PG 21 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 668NM UT WOS:000182300100011 PM 12668198 ER PT J AU Anderson, LM Scrimshaw, SC Fullilove, MT Fielding, JE Normand, J AF Anderson, LM Scrimshaw, SC Fullilove, MT Fielding, JE Normand, J CA Task Force Community Preventive Se TI Culturally competent healthcare systems - A systematic review SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Review ID AFRICAN-AMERICAN ADOLESCENTS; AIDS RISK KNOWLEDGE; LANGUAGE BARRIERS; UNITED-STATES; CARE; RACE; PERCEPTIONS; ETHNICITY; EMERGENCY; EDUCATION AB Culturally competent healthcare systems-those that provide culturally and linguistically appropriate services-have the potential to reduce racial and ethnic health disparities. When clients do not understand what their healthcare providers are telling them, and providers either do not speak the client's language or are insensitive to cultural differences, the quality of health care can be compromised. We reviewed five interventions to improve cultural competence in healthcare systems-programs to recruit and retain staff members who reflect the cultural diversity of the community served, use of interpreter services or bilingual providers for clients with limited English proficiency, cultural competency training for healthcare providers, use of linguistically and culturally appropriate health education materials, and culturally specific healthcare settings. We could not determine the effectiveness of any of these interventions, because there were either too few comparative studies, or studies did not examine the outcome measures evaluated in this review: client satisfaction with care, improvements in health status, and inappropriate racial or ethnic differences in use of health services or in received and recommended treatment. C1 Ctr Dis Control & Prevent, Community Guide Branch, Div Prevent Res & Analyt Methods, Epidemiol Program Off, Atlanta, GA 30341 USA. Task Force Community Prevent Serv, Chicago, IL USA. Univ Illinois, Sch Publ Hlth, Chicago, IL USA. Task Force Community Prevent Serv, New York, NY USA. Columbia Univ, New York, NY USA. Los Angeles Dept Hlth Serv, Task Force Community Prevent Serv, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. NIDA, NIH, Bethesda, MD 20892 USA. RP Anderson, LM (reprint author), Ctr Dis Control & Prevent, Community Guide Branch, Div Prevent Res & Analyt Methods, Epidemiol Program Off, 4770 Buford Highway,MS-K73, Atlanta, GA 30341 USA. NR 42 TC 232 Z9 237 U1 9 U2 55 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD APR PY 2003 VL 24 IS 3 SU S BP 68 EP 79 DI 10.1016/S0749-3797(02)00657-8 PG 12 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 668NM UT WOS:000182300100012 PM 12668199 ER PT J AU Nirenberg, M AF Nirenberg, M TI The genetic revolution: The importance of files and worms SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material C1 NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. RP Nirenberg, M (reprint author), NHLBI, Lab Biochem Genet, NIH, Bldg 10,Room 7N315,31 Ctr Dr,MSC 4036, Bethesda, MD 20892 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 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 APR PY 2003 VL 160 IS 4 BP 615 EP 615 DI 10.1176/appi.ajp.160.4.615 PG 1 WC Psychiatry SC Psychiatry GA 664ZZ UT WOS:000182096300003 PM 12668344 ER PT J AU Insel, TR Collins, FS AF Insel, TR Collins, FS TI Psychiatry in the genomics era SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID GENETIC-VARIATION; 6P22.3 GENE; SCHIZOPHRENIA; SUSCEPTIBILITY; NEUREGULIN-1; ASSOCIATION; DYSBINDIN; GENOTYPE; SEQUENCE C1 NIMH, Bethesda, MD 20892 USA. NHGRI, Bethesda, MD 20892 USA. RP NIMH, 6001 Execut Blvd, Bethesda, MD 20892 USA. EM insel@mail.nih.gov NR 26 TC 43 Z9 44 U1 1 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 2003 VL 160 IS 4 BP 616 EP 620 DI 10.1176/appi.ajp.160.4.616 PG 5 WC Psychiatry SC Psychiatry GA 664ZZ UT WOS:000182096300004 PM 12668345 ER PT J AU Moldin, SO AF Moldin, SO TI NIMH Human Genetics Initiative: 2003 update SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material C1 NIMH, Genet Res Branch, Div Neurosci & Basic Behav Sci, Bethesda, MD 20892 USA. RP Moldin, SO (reprint author), NIMH, Genet Res Branch, Div Neurosci & Basic Behav Sci, 6001 Execut Blvd,Room 7189,MSC 9643, Bethesda, MD 20892 USA. NR 1 TC 15 Z9 15 U1 0 U2 0 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 APR PY 2003 VL 160 IS 4 BP 621 EP 622 DI 10.1176/appi.ajp.160.4.621 PG 2 WC Psychiatry SC Psychiatry GA 664ZZ UT WOS:000182096300005 PM 12668346 ER PT J AU Merikangas, KR Risch, N AF Merikangas, KR Risch, N TI Will the genomics revolution revolutionize psychiatry.? SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Review ID GENE-ENVIRONMENT INTERACTIONS; COMPLEX HUMAN-DISEASES; SAMPLE-SIZE CALCULATIONS; POPULATION-BASED SAMPLE; AFFECTIVE-DISORDERS; EPIDEMIOLOGIC RESEARCH; ALZHEIMER-DISEASE; BIPOLAR-DISORDER; SUSCEPTIBILITY LOCUS; EMERGING IMPORTANCE C1 NIMH, Sect Dev Genet Epidemiol, Mood & Disorders Program, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Kaiser Permanente, Div Res, Oakland, CA USA. Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. RP Merikangas, KR (reprint author), NIMH, Sect Dev Genet Epidemiol, Mood & Disorders Program, NIH,Dept Hlth & Human Serv, 15K North Dr,MSC 2670, Bethesda, MD 20892 USA. NR 131 TC 76 Z9 77 U1 1 U2 6 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 2003 VL 160 IS 4 BP 625 EP 635 DI 10.1176/appi.ajp.160.4.625 PG 11 WC Psychiatry SC Psychiatry GA 664ZZ UT WOS:000182096300007 PM 12668348 ER PT J AU Gottesman, II Gould, TD AF Gottesman, II Gould, TD TI The endophenotype concept in psychiatry: Etymology and strategic intentions SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Review ID DORSOLATERAL PREFRONTAL CORTEX; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; SCHIZOTYPAL PERSONALITY-DISORDER; POSITRON-EMISSION-TOMOGRAPHY; WORKING-MEMORY PERFORMANCE; EYE-MOVEMENT DYSFUNCTION; RECEPTOR SUBUNIT GENE; FRONTAL-LOBE FUNCTION; LONG-QT SYNDROME; SCHIZOPHRENIC-PATIENTS AB Endophenotypes, measurable components unseen by the unaided eye along the pathway between disease and distal genotype, have emerged as an important concept in the study of complex neuropsychiatric diseases. An endophenotype may be neurophysiological, biochemical, endocrinological, neuroanatomical, cognitive, or neuropsychological (including configured self-report data) in nature. Endophenotypes represent simpler clues to genetic underpinnings than the disease syndrome itself, promoting the view that psychiatric diagnoses can be decomposed or deconstructed, which can result in more straightforward-and successful-genetic analysis. However, to be most useful, endophenotypes for psychiatric disorders must meet certain criteria, including association with a candidate gene or gene region, heritability that is inferred from relative risk for the disorder in relatives, and disease association parameters. in addition to furthering genetic analysis, endophenotypes can clarify classification and diagnosis and foster the development of animal models. The authors discuss the etymology and strategy behind the use of endophenotypes in neuropsychiatric research and, more generally, in research on other diseases with complex genetics. C1 Univ Minnesota, Sch Med, Dept Psychiat, Minneapolis, MN 55454 USA. NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Gottesman, II (reprint author), Univ Minnesota, Sch Med, Dept Psychiat, 2450 Riverside Ave, Minneapolis, MN 55454 USA. EM Gotte003@UMN.edu RI G, I/D-8042-2011; Gottesman, Irving/B-9303-2011; OI Gottesman, Irving/0000-0001-7584-621X NR 141 TC 2912 Z9 2982 U1 13 U2 146 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 2003 VL 160 IS 4 BP 636 EP 645 DI 10.1176/appi.ajp.160.4.636 PG 10 WC Psychiatry SC Psychiatry GA 664ZZ UT WOS:000182096300008 PM 12668349 ER PT J AU Callicott, JH Egan, MF Mattay, VS Bertolino, A Bone, AD Verchinksi, B Weinberger, DR AF Callicott, JH Egan, MF Mattay, VS Bertolino, A Bone, AD Verchinksi, B Weinberger, DR TI Abnormal fMRI response of the dorsolateral prefrontal cortex in cognitively intact siblings of patients with schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID WORKING-MEMORY DEFICITS; CEREBRAL BLOOD-FLOW; FRONTAL-LOBE FUNCTION; LINKAGE DISEQUILIBRIUM; TWINS DISCORDANT; VERBAL FLUENCY; NAIVE PATIENTS; GENETIC RISK; HUMAN BRAIN; ACTIVATION AB Objective: The identification of neurobiological intermediate phenotypes may hasten the search for susceptibility genes in complex psychiatric disorders such as schizophrenia. Earlier family studies have suggested that deficits in executive cognition and working memory may be related to genetic susceptibility for schizophrenia, but the biological basis for this behavioral phenotype has not been identified. Method: The authors used functional magnetic resonance imaging (fMRI) during performance of the N-back working memory task to assess working memory-related cortical physiology in nonschizophrenic, cognitively intact siblings of patients with schizophrenia. They compared 23 unaffected siblings of schizophrenic patients to 18 matched comparison subjects. As a planned replication, they studied another 25 unaffected siblings and 15 comparison subjects. Results: In both cohorts, there were no group differences in working memory performance. Nevertheless, both groups of siblings showed an exaggerated physiological response in the right dorsolateral prefrontal cortex that was qualitatively similar to results of earlier fMRI studies of patients with schizophrenia. Conclusions: These fMRI data provide direct evidence of a primary physiological abnormality in dorsolateral prefrontal cortex function in individuals at greater genetic risk for schizophrenia, even in the absence of a manifest cognitive abnormality. This exaggerated fMRI response implicates inefficient processing of memory information at the level of intrinsic prefrontal circuitry, similar to earlier findings in patients with schizophrenia. These data predict that inheritance of alleles that contribute to inefficient prefrontal information processing will increase risk for schizophrenia. C1 NIMH, Clin Brain Disorders Branch, IRP, NIH, Bethesda, MD 20892 USA. RP Callicott, JH (reprint author), NIMH, Clin Brain Disorders Branch, IRP, NIH, Bldg 10,Ctr Dr,Rm 4D-20 MSC1389, Bethesda, MD 20892 USA. RI Callicott, Joseph/C-9102-2009; Bertolino, Alessandro/O-6352-2016 OI Callicott, Joseph/0000-0003-1298-3334; Bertolino, Alessandro/0000-0002-1251-1380 NR 67 TC 296 Z9 302 U1 1 U2 18 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 APR PY 2003 VL 160 IS 4 BP 709 EP 719 DI 10.1176/appi.ajp.160.4.709 PG 11 WC Psychiatry SC Psychiatry GA 664ZZ UT WOS:000182096300019 PM 12668360 ER PT J AU Matthay, MA Zimmerman, GA Esmon, C Bhattacharya, J Coller, B Doerschuk, CM Floros, J Gimbrone, MA Hoffman, E Hubmayr, RD Leppert, M Matalon, S Munford, R Parsons, P Slutsky, AS Tracey, KJ Ward, P Gail, DB Harabin, AL AF Matthay, MA Zimmerman, GA Esmon, C Bhattacharya, J Coller, B Doerschuk, CM Floros, J Gimbrone, MA Hoffman, E Hubmayr, RD Leppert, M Matalon, S Munford, R Parsons, P Slutsky, AS Tracey, KJ Ward, P Gail, DB Harabin, AL TI Future research directions in acute lung injury - Summary of a National Heart, Lung, and Blood Institute working group SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE pulmonary inflammation; critical care; genomics; pulmonary; edema; acute respiratory distress syndrome ID RESPIRATORY-DISTRESS SYNDROME; SEPTIC SHOCK; MECHANICAL VENTILATION; SEVERE SEPSIS; SYSTEMIC INFLAMMATION; HEMORRHAGIC-SHOCK; GENE-EXPRESSION; CROHNS-DISEASE; ORGAN FAILURE; SUSCEPTIBILITY AB Acute lung injury (ALI) and its more severe form, the acute respiratory distress syndrome (ARDS), are syndromes of acute respiratory failure that result from acute pulmonary edema and inflammation. The development of ALI/ARDS is associated with several clinical disorders including direct pulmonary injury from pneumonia and aspiration as well as indirect pulmonary injury from trauma, sepsis, and other disorders such as acute pancreatitis and drug overdose. Although mortality from AWARDS has decreased in the last decade, it remains high. Despite two major advances in treatment, low V-T ventilation for ALI/ARDS and activated protein C for severe sepsis (the leading cause of ALI/ARDS), additional research is needed to develop specific treatments and improve understanding of the pathogenesis of these syndromes. The NHLBI convened a working group to develop specific recommendations for future ALI/ARDS research. Improved understanding of disease heterogeneity through use of evolving biologic, genomic, and genetic approaches should provide major new insights into pathogenesis of ALI. Cellular and molecular methods combined with animal and clinical studies should lead to further progress in the detection and treatment of this complex disease. C1 NHLBI, Div Lung Dis, Bethesda, MD 20892 USA. Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. Univ Utah, Program Human Mol Biol & Genet, Salt Lake City, UT USA. Univ Utah, Dept Human Genet, Salt Lake City, UT USA. Oklahoma Med Res Fdn, Cardiovasc & Biol Res Program, Howard Hughes Med Inst, Oklahoma City, OK USA. Mayo Clin & Mayo Fdn, Crit Care Serv, Rochester, MI USA. N Shore LIJ Res Inst, Lab Biomed Sci, Manhasset, NY USA. Columbia Univ Coll Phys & Surg, Dept Med & Physiol, New York, NY USA. Rockefeller Univ, Dept Blood & Vasc Biol, New York, NY USA. Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA. Penn State Univ, Coll Med, Dept Cellular & Mol Physiol & Pediat, Hershey, PA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Excellence Vasc Biol, Boston, MA USA. Childrens Natl Med Ctr, Res Ctr Genet Med, Washington, DC 20010 USA. Univ Alabama, Dept Anesthesiol, Birmingham, AL USA. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX USA. Univ Vermont, Dept Pulm & Crit Care Med, Burlington, VT USA. Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. Univ Toronto, St Michaels Hosp, Interdepartmental Div Crit Care Med, Toronto, ON M5B 1W8, Canada. Univ Toronto, St Michaels Hosp, Dept Med, Toronto, ON M5B 1W8, Canada. RP Harabin, AL (reprint author), NHLBI, Div Lung Dis, Bldg 10, Bethesda, MD 20892 USA. RI Slutsky, Arthur/A-6013-2008; OI Slutsky, Arthur/0000-0002-6063-3876; Tracey, Kevin J/0000-0003-1884-6314 NR 77 TC 326 Z9 361 U1 1 U2 14 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 APR 1 PY 2003 VL 167 IS 7 BP 1027 EP 1035 DI 10.1164/rccm.200208-966WS PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 661YF UT WOS:000181917100015 PM 12663342 ER PT J AU Taddesse-Heath, L Pittaluga, S Sorbara, L Bussey, M Raffeld, M Jaffe, ES AF Taddesse-Heath, L Pittaluga, S Sorbara, L Bussey, M Raffeld, M Jaffe, ES TI Marginal zone B-cell lymphoma in children and young adults SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 90th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR, 2000 CL ATLANTA, GEORGIA SP US Canadian Acad Pathol DE pediatric lymphoma; marginal zone B-cell lymphoma; extranodal MALT lymphoma; B-cell lymphoma; autoimmune disease ID PEDIATRIC-PATIENTS; GERMINAL-CENTERS; PROGRESSIVE TRANSFORMATION; MALIGNANT-LYMPHOMA; HODGKINS-DISEASE; FOLLICULAR LYMPHOMA; TISSUE; MALT; REARRANGEMENT; LYMPHOCYTES AB We describe the clinicopathologic findings of 48 cases of marginal zone B-cell lymphoma (MZL) in children and young adults, a disease that has been recognized previously only rarely in this age group. Patients ranged in age from 2 to 29 years, with pediatric patients (less than or equal to18 years) comprising 52% of the cases. As in adults, both primary nodal (N) and extranodal (E) MZL were observed. However, primary NMZL comprised the majority of the cases (67%) and demonstrated distinctive clinical and histologic features. NMZL occurred most commonly in young males (median 16 years, male/female ratio 5.4:1), with no underlying disease, presenting as localized adenopathy (90% stage 1), with excellent prognosis and low rate of recurrence. In contrast, EMZL were much less common, and patients were older (median 24.5 years), with only a slight male predominance (male/female ratio 1.2:1). Most patients had localized disease (73% stage 1) with excellent prognosis and infrequent recurrences. In addition, an association with autoimmune disease was observed in 19% of the EMZL. Both primary NMZL and EMZL in young patients shared similar morphologic and immunophenotypic findings to those described in adults and were monoclonal B-cell proliferations with monoclonality demonstrated in 94% of the cases. A common morphologic feature in NMZL was disruption of residual follicles resembling progressive transformation of germinal centers (PTGC), observed in 66% of the cases. Although the precise relationship of primary NMZL and the PTGC-like changes is unclear, it is possible that NMZL arises in a background of PTGC, as florid PTGC often occurs in young males. We conclude that EMZL in children and young adults are similar to EMZL of mucosa-associated lymphoma tissue occurring in older patients. However, pediatric NMZL appear to have distinctive clinical and histologic features. C1 NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Jaffe, ES (reprint author), NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res,NIH, Bldg 10,Room 2N202,10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. NR 31 TC 68 Z9 69 U1 0 U2 2 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 APR PY 2003 VL 27 IS 4 BP 522 EP 531 DI 10.1097/00000478-200304000-00014 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA 661DP UT WOS:000181876200014 PM 12657939 ER PT J AU Franceschini, N Cheng, O Zhang, XJ Ruiz, P Mannon, RB AF Franceschini, N Cheng, O Zhang, XJ Ruiz, P Mannon, RB TI Inhibition of prolyl-4-hydroxylase ameliorates chronic rejection of mouse kidney allografts SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article ID GROWTH-FACTOR; T-CELL; TRANSFORMING GROWTH-FACTOR-BETA-1; RENAL-FUNCTION; IN-VIVO; FIBROSIS; NEPHROPATHY; EXPRESSION; DISEASE; RAT AB Interstitial fibrosis, glomerulosclerosis and arteriosclerosis are the major components of chronic allograft nephropathy (CAN), the leading cause of late graft failure after transplantation. To investigate the mechanism of collagen deposition in CAN, we studied the effects of prolyl-hydroxylase inhibitor (PHI), an enzyme essential for collagen formation, using a mouse model of kidney transplantation. Kidneys from H-2(b) mice were transplanted into MHC-incompatible H-2(d) recipients (allografts) and at 3 weeks post-transplant, received either PHI or vehicle treatment daily for 3 weeks. At 6 weeks; post-transplant, GFR was significantly improved in the allografts; receiving PHI (3.3 +/- 0.5 mL/min/kg) compared with those receiving vehicle (1.8 +/- 0.5mL/min/kg, p<0.05), while renal function was relatively unimpaired in the nonrejecting isografts (6.45 +/- 0.53 mL/min/kg). Allografts had histologic changes of CAN but the severity was significantly reduced with PHI treatment compared with vehicle, with reductions in interstitial inflammation and fibrosis. Furthermore, TGFi and connective tissue growth factor mRNA expression was enhanced in both allograft groups compared with the isografts. In conclusion, PHI-treated allografts had improved renal function and reduced the severity of renal injury as a result of CAN. Inhibition of matrix synthesis may be a useful adjunct in ameliorating the development of CAN in humans. C1 NIDDK, Transplantat & Autoimmun Branch, NIH, Bethesda, MD USA. Duke VA Med Ctr, Dept Med, Div Nephrol, Durham, NC USA. Durham VA Med Ctr, Dept Med, Div Nephrol, Durham, NC USA. Univ Miami, Dept Pathol, Miami, FL 33152 USA. RP Mannon, RB (reprint author), NIDDK, Transplantat & Autoimmun Branch, NIH, Bethesda, MD USA. FU NIAID NIH HHS [1K08 AI 01389-01] NR 47 TC 10 Z9 10 U1 0 U2 0 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 APR PY 2003 VL 3 IS 4 BP 396 EP 402 DI 10.1034/j.1600-6143.2003.00081.x PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA 674WK UT WOS:000182660000006 PM 12694061 ER PT J AU Abbott, KC Schenkman, N Swanson, SJ Agodoa, LY AF Abbott, KC Schenkman, N Swanson, SJ Agodoa, LY TI Hospitalized nephrolithiasis after renal transplantation in the United States SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE complications; extracorporeal shock wave lithotripsy (ESWL); female; National Center for Health Statistics; nephrolithiasis; percutaneous nephrolithotripsy; stones; ureteroscopy; United States Renal Data System (USRDS) ID UROLOGICAL COMPLICATIONS; KIDNEY; UROLITHIASIS; FAILURE; RISK AB The national incidence of and risk factors for hospitalized nephrolithiasis (NEP) in renal transplant (RT) recipients has not been reported. We conducted a historical cohort study of 42096 RT recipients in the United States Renal Data System between 1 July 1994 and 30 June 1998. The 1-year incidence of NEP (ICD-9 codes 592.x) after RT in 1997 was compared to the rate of NEP in the general population using the National Hospital Discharge Survey. Associations with time to hospitalizations for a primary diagnosis of nephrolithiasis were assessed by Cox Regression. NEP was uncommon after RT (104 cases per 100000 person years in 1997). However, females, but not males, had a statistically significant increased risk of NEP compared to the general population (rate ratio for females, 2.84, 95% confidence interval, 2.35-3.58). Kidney stones were more common than ureteral stones, and percutaneous procedures were more common than ureteroscopy or extracorporeal shock wave lithotripsy (ESWL). The only risk factor identified for NEP was renal failure due to stone disease (only one case). NEP was uncommon after RT, but was still more common than in the general population. We identified differences in the presentation and management of NEP after RT in comparison to the general 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, Serv Urol, Washington, DC 20307 USA. Walter Reed Army Med Ctr, Organ Transplant 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 21 TC 27 Z9 30 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 APR PY 2003 VL 3 IS 4 BP 465 EP 470 DI 10.1034/j.1600-6143.2003.00080.x PG 6 WC Surgery; Transplantation SC Surgery; Transplantation GA 674WK UT WOS:000182660000015 PM 12694070 ER PT J AU Abbott, KC Reynolds, JC Taylor, AJ Agodoa, LY AF Abbott, KC Reynolds, JC Taylor, AJ Agodoa, LY TI Hospitalized atrial fibrillation after renal transplantation in the United States SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE atrial fibrillation; complications; graft loss; hospitalization; hypertension; obesity; rejection; United States Renal Data System (USRDS) ID CONGESTIVE-HEART-FAILURE; CYCLOSPORINE MICROEMULSION; DIALYSIS PATIENTS; RISK-FACTORS; TACROLIMUS; HYPERTROPHY; PREVALENCE AB Renal transplant recipients have a high incidence of hypertension, a known risk factor for atrial fibrillation (AF), as well as factors that could increase their risk of AF. However, the incidence of, risk factors for, and mortality associated with AF after renal transplantation have not been reported. We present a historical cohort study of 39628 renal transplant recipients in the United States Renal Data System between 1 July 1994 and 30 June 1998. Data source: USRDS files through May 2000. Associations with hospitalizations for a primary diagnosis of AF (ICD-9 codes 427.31) after renal transplant were assessed by Cox Regression analysis. Tacrolimus was not approved for use by the FDA during the time-frame of the study. The incidence of AF after renal transplantation was 5.8 episodes/1000 person-years. In Cox Regression analysis, recipients who were older age, experienced graft loss, rejection, had higher body mass index, renal failure due to hypertension, and cyclosporine use (vs. tacrolimus use) were associated with increased risk of hospitalized AF. Atrial fibrillation was not uncommon after renal transplantation, and was associated with increased risk of mortality, primarily from cardiovascular disease. The strongest risk factors for AF after renal transplantation were older age, allograft rejection, graft loss and obesity. C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. Walter Reed Army Med Ctr, Serv Cardiol, Washington, DC USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 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 30 TC 13 Z9 14 U1 0 U2 0 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 APR PY 2003 VL 3 IS 4 BP 471 EP 476 DI 10.1034/j.1600-6143.2003.00071.x PG 6 WC Surgery; Transplantation SC Surgery; Transplantation GA 674WK UT WOS:000182660000016 PM 12694071 ER PT J AU De Benedictis, J Chow-Shaffer, E Costero, A Clark, GG Edman, JD Scott, TW AF De Benedictis, J Chow-Shaffer, E Costero, A Clark, GG Edman, JD Scott, TW TI Identification of the people from whom engorged Aedes aegypti took blood meals in Florida, Puerto Rico, using polymerase chain reaction-based DNA profiling SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID POPULATION-DYNAMICS; PLUS SUGAR; CULICIDAE; DIPTERA; DENGUE; TRANSMISSION; THAILAND; MOSQUITOS; FECUNDITY; SURVIVAL AB We used polymerase chain reaction-based DNA profiling to construct allelic profiles for residents and visitors of 22 houses in Florida, Puerto Rico, and human DNA from blood meals in Aedes aegypti that were collected in those homes. Complete profiles were obtained for less than or equal to 2 days after blood ingestion. Eighteen percent of the meals came from two different people. There was no evidence of meals from greater than or equal to 2 people. Eighty percent of the meal sources were identified, > 70% were taken from residents of the collection house, and > 90% were from residents of the study community. Across the community, feeding was non-random with a bias towards young adults and males. Three people accounted for 56% of the meals. Our results confirm that multiple feeding on different people is an important component in the role of Ae. aegypti in dengue virus transmission and help explain the spatial distribution of dengue cases in a previous epidemic in Florida, Puerto Rico. C1 Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. Univ Maryland, Dept Entomol, College Pk, MD 20742 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Dengue Branch, San Juan, PR 00920 USA. RP Scott, TW (reprint author), Univ Calif Davis, Dept Entomol, 1 Shields Ave, Davis, CA 95616 USA. EM twscott@ucdavis.edu FU NIAID NIH HHS [AI-22119] NR 40 TC 37 Z9 37 U1 1 U2 6 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 EI 1476-1645 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD APR PY 2003 VL 68 IS 4 BP 437 EP 446 PG 10 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 670RX UT WOS:000182423600015 PM 12875293 ER PT J AU Tarr, PE Miele, PS Peregoy, KS Smith, MA Neva, FA Lucey, DR AF Tarr, PE Miele, PS Peregoy, KS Smith, MA Neva, FA Lucey, DR TI Case report: Rectal adminstration of ivermectin to a patient with Strongyloides hyperinfection syndrome SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID OVERWHELMING STRONGYLOIDIASIS; KIDNEY-TRANSPLANT; STERCORALIS; THIABENDAZOLE; TRANSMISSION; CYCLOSPORINE; ALBENDAZOLE; INFECTIONS; RECIPIENTS; TRIAL AB Strongyloides hyperinfection syndrome may be complicated by paralytic ileus that interferes with the absorption of oral anti-helminthics. We report on the administration of ivermectin as a rectal enema preparation to a renal transplant recipient with Strongyloides hyperinfection syndrome and progressive ileus. Attempts at treatment using nasogastric albendazole and ivermectin were unsuccessful despite clamping the nasogastric tube after drug administration. Ivermectin tablets were ground to a powder, resuspended in a commercially available suspending agent, and administered per rectum. The suspending agent was chosen for its near-physiologic osmolality to allow longer retention, in contrast to many enema preparations that have a laxative effect. The patient improved markedly within 72 hours of initiation of the therapy per rectum and recovered fully. Ivermectin administered as an enema may be beneficial in patients with severe strongyloidiasis who are unable to absorb or tolerate oral therapy. C1 Washington Hosp Ctr, Dept Med, Infect Dis Sect, Washington, DC 20010 USA. Washington Hosp Ctr, Dept Pharm, Washington, DC 20010 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Tarr, PE (reprint author), CHU Vaudois, Div Infect Dis, CH-1011 Lausanne, Switzerland. NR 24 TC 42 Z9 43 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD APR PY 2003 VL 68 IS 4 BP 453 EP 455 PG 3 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 670RX UT WOS:000182423600017 PM 12875295 ER PT J AU Patenaude, AF Guttmacher, AE Collins, FS AF Patenaude, AF Guttmacher, AE Collins, FS TI Psychologists' contributions to the genetic revolution SO AMERICAN PSYCHOLOGIST LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NHGRI, Bethesda, MD 20892 USA. RP Patenaude, AF (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 3 TC 1 Z9 1 U1 0 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0003-066X J9 AM PSYCHOL JI Am. Psychol. PD APR PY 2003 VL 58 IS 4 BP 319 EP 320 DI 10.1037/0003-066X.58.4.319b PG 2 WC Psychology, Multidisciplinary SC Psychology GA 694QV UT WOS:000183786200013 PM 12866400 ER PT J AU Issaq, HJ Conrads, TP Prieto, DA Tirumalai, R Veenstra, TD AF Issaq, HJ Conrads, TP Prieto, DA Tirumalai, R Veenstra, TD TI SELDI-TOF MS for diagnostic proteomics. SO ANALYTICAL CHEMISTRY LA English DT Article ID MASS-SPECTROMETRY; CANCER PROGRESSION; PROSTATE-CANCER; PROTEIN BIOCHIP; BREAST-CANCER; SERUM; IDENTIFICATION; CAPTURE; BENIGN C1 NCI, SAIC Frederick, Analyt Chem Lab, Frederick, MD 21702 USA. RP Issaq, HJ (reprint author), NCI, SAIC Frederick, Analyt Chem Lab, POB B, Frederick, MD 21702 USA. NR 25 TC 98 Z9 108 U1 1 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 APR 1 PY 2003 VL 75 IS 7 BP 148A EP 155A DI 10.1021/ac031249c PG 8 WC Chemistry, Analytical SC Chemistry GA 663EQ UT WOS:000181993600004 PM 12705580 ER PT J AU Janini, GM Conrads, TP Wilkens, KL Issaq, HJ Veenstra, TD AF Janini, GM Conrads, TP Wilkens, KL Issaq, HJ Veenstra, TD TI A sheathless nanoflow electrospray interface for on-line capillary electrophoresis mass spectrometry SO ANALYTICAL CHEMISTRY LA English DT Article ID ZONE-ELECTROPHORESIS; PROTEIN IDENTIFICATION; PEPTIDES; MS; PERFORMANCE; BLOOD; LEVEL; JOINT AB A novel, rugged capillary electrophoresis-electrospray ionization (CE-ESI) interface where the separation column, an electrical porous junction, and the spray tip are integrated on a single piece of a fused-silica capillary is described. ESI is accomplished by applying an electrical potential through an easily prepared porous junction across a 3-4-mm length of fused silica. A stable electrospray is produced at nanoflow rates generated in the capillary by electrophoretic and electroosmotic forces. The interface is particularly well suited for the detection of low-femtomole levels of proteins and peptides. The ruggedness of this interface was evident by the continuous operation of the same column for over a 2-week period with no detectable deterioration in separation or electrospray performance. The new interface was used for the LC-ESI-MS separation and analysis of peptides and proteins. Injection of 25 fmol of [Glu(1)]-fibrinopeptide B using the new device produced a CE-ESI-MS electropherogram with a signal-to-noise ratio of over 100 for this peptide. C1 NCI, Analyt Chem Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Janini, GM (reprint author), NCI, Analyt Chem Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-12400] NR 30 TC 72 Z9 74 U1 4 U2 24 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD APR 1 PY 2003 VL 75 IS 7 BP 1615 EP 1619 DI 10.1021/ac020661+ PG 5 WC Chemistry, Analytical SC Chemistry GA 663EQ UT WOS:000181993600017 PM 12705593 ER PT J AU Braun, A AF Braun, A TI New findings on cortical anatomy and implications for investigating the evolution of language SO ANATOMICAL RECORD PART A-DISCOVERIES IN MOLECULAR CELLULAR AND EVOLUTIONARY BIOLOGY LA English DT Editorial Material ID PARS OPERCULARIS; PLANUM TEMPORALE; BROCAS-AREA; GREAT APES; MRI; ASYMMETRIES; REGION; SPEECH; BRAIN; CYTOARCHITECTURE C1 NICOCD, Language Sect Voice Speech & Language Branch, NIH, Bethesda, MD 20892 USA. RP Braun, A (reprint author), NICOCD, Language Sect Voice Speech & Language Branch, NIH, Bldg 10,Room 5N118A, Bethesda, MD 20892 USA. NR 19 TC 2 Z9 2 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 0003-276X J9 ANAT REC PART A JI Anat. Rec. Part A PD APR PY 2003 VL 271A IS 2 BP 273 EP 275 DI 10.1002/ar.a.10051 PG 3 WC Anatomy & Morphology SC Anatomy & Morphology GA 670RJ UT WOS:000182422400001 PM 12629669 ER PT J AU McBratney, BM Margaryan, E Ma, WB Urban, Z Lozanoff, S AF McBratney, BM Margaryan, E Ma, WB Urban, Z Lozanoff, S TI Frontonasal dysplasia in 3H1 Br/Br mice SO ANATOMICAL RECORD PART A-DISCOVERIES IN MOLECULAR CELLULAR AND EVOLUTIONARY BIOLOGY LA English DT Article DE median facial cleft; presphenoid; Br; mutation ID ANTERIOR CRANIAL BASE; RETINOIC-ACID; MIDFACIAL RETRUSION; IONIZING-RADIATION; NERVOUS-SYSTEM; BRACHYRRHINE MICE; SONIC HEDGEHOG; GENETIC RISKS; NEURAL CREST; MOUSE AB The adult Brachyrrhine (3141 Br/+) mouse displays severe midfacial retrognathia, with a "pugnose" external appearance, but information concerning craniofacial morphology of the homozygote (3141 Br/Br) mutant is lacking. This study characterized craniofacial phenotype and genotypic features of the homozygous condition. Segregation analysis was performed by phenotypic scoring of offspring from 3141 Br/+ reciprocal matings. Whole-mount staining was undertaken to determine the presence or absence of cranial base structures in newborn and adult mice, while features of cranial base chondrification were examined using light microscopy and type II collagen immunohistochemistry. Karyotype analysis was performed to determine whether gross chromosomal aberrations were present. Finally, microsatellite mapping analysis was undertaken to provide further resolution of the Br locus. Results showed that Br was inherited as an autosomal semidominant feature. 3141 Br/Br mice consistently lacked a presphenoid (with its lateral projections, including a preoptic root, postoptic root, and lesser wing). Karyotyping did not reveal major gross aberrations; however, microsatellite analysis localized Br to distal mouse chromosome 17 in the vicinity of D17Mit155. These results indicated that 3141 Br/Br mice show characteristic features of frontonasal dysplasia, including median facial clefting and bifid cranium, as well sphenoidal malformations. Furthermore, this mutant should serve as a useful model for examining mechanisms of frontonasal dysplasia. (C) 2003 Wiley-Liss, Inc. C1 Univ Hawaii, John A Burns Sch Med, Dept Anat & Reprod Biol, Honolulu, HI 96822 USA. Harvard Univ, Dept Anthropol, Cambridge, MA 02138 USA. Univ Hawaii, John A Burns Sch Med, Grad Program Cell & Mol Biol, Honolulu, HI 96822 USA. NCI, Immunol Lab, Frederick, MD 21701 USA. Univ Hawaii, John A Burns Sch Med, Pacific Biotechnol Res Ctr, Dept Anat & Reprod Biol, Honolulu, HI 96822 USA. RP Lozanoff, S (reprint author), Univ Hawaii, John A Burns Sch Med, Dept Anat & Reprod Biol, Honolulu, HI 96822 USA. RI Urban, Zsolt/B-1977-2008; Urban, Zsolt/A-2018-2013 OI Urban, Zsolt/0000-0003-3890-1843 NR 54 TC 18 Z9 18 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0003-276X J9 ANAT REC PART A JI Anat. Rec. Part A PD APR PY 2003 VL 271A IS 2 BP 291 EP 302 DI 10.1002/ar.a.10034 PG 12 WC Anatomy & Morphology SC Anatomy & Morphology GA 670RJ UT WOS:000182422400004 PM 12629672 ER PT J AU Klein, HG AF Klein, HG TI Getting older is not necessarily getting better SO ANESTHESIOLOGY LA English DT Editorial Material ID COLORECTAL-CANCER; BLOOD-TRANSFUSION; SURGERY; INFECTION; STORAGE; FUTURE; CELLS C1 Warren G Magnuson Clin Ctr, Dept Transfus Med, NIH, Bethesda, MD 20892 USA. RP Klein, HG (reprint author), Warren G Magnuson Clin Ctr, Dept Transfus Med, NIH, Bethesda, MD 20892 USA. NR 12 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD APR PY 2003 VL 98 IS 4 BP 807 EP 808 DI 10.1097/00000542-200304000-00003 PG 2 WC Anesthesiology SC Anesthesiology GA 660ZG UT WOS:000181865500002 PM 12657838 ER PT J AU Faris, OP Evans, FJ Ennis, DB Helm, PA Taylor, JL Chesnick, AS Guttman, MA Ozturk, C McVeigh, ER AF Faris, OP Evans, FJ Ennis, DB Helm, PA Taylor, JL Chesnick, AS Guttman, MA Ozturk, C McVeigh, ER TI Novel technique for cardiac electromechanical mapping with magnetic resonance imaging tagging and an epicardial electrode sock SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE electrical activation; mechanical activation; asynchrony; heart; MRI; tagging; mapping ID TAGGED MR-IMAGES; LEFT-VENTRICULAR FUNCTION; CANINE LEFT-VENTRICLE; HEART-FAILURE; MECHANICAL ACTIVATION; DILATED CARDIOMYOPATHY; CONDUCTION DELAY; PACED HEART; CHEST DOGS; SEQUENCE AB Near-simultaneous measurements of electrical and mechanical activation over the entire ventricular surface are now possible using magnetic resonance imaging tagging and a multielectrode epicardial sock. This new electromechanical mapping technique is demonstrated in the ventricularly paced canine heart. A 128-electrode epicardial sock and pacing electrodes were placed on the hearts of four anesthetized dogs. In the magnetic resonance scanner, tagged cine images (8-15 ms/frame) and sock electrode recordings (1000 Hz) were acquired under right-ventricular pacing and temporally referenced to the pacing stimulus. Electrical recordings were obtained during intermittent breaks in image acquisition, so that both data sets represented the same physiologic state. Since the electrodes were not visible in the images, electrode recordings and cine images were spatially registered with Gd-DTPA markers attached to the sock. Circumferential strain was calculated at locations corresponding to electrodes. For each electrode location, electrical and mechanical activation times were calculated and relationships between the two activation patterns were demonstrated. This method holds promise for improving understanding of the relationships between the patterns of electrical activation and contraction in the heart. (C) 2003 Biomedical Engineering Society. C1 NHLBI, Natl Inst Hlth, Cardiac Energet Lab, Bethesda, MD USA. RP NHLBI, Natl Inst Hlth, Cardiac Energet Lab, 10 Ctr Dr,Room B1D412, Bethesda, MD USA. EM fariso@nih.gov RI Ozturk, Cengizhan/A-6177-2016 OI Ozturk, Cengizhan/0000-0002-6966-0774 FU Intramural NIH HHS [Z01 HL004609-08] NR 43 TC 51 Z9 52 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0090-6964 EI 1573-9686 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD APR PY 2003 VL 31 IS 4 BP 430 EP 440 DI 10.1114/1.1560618 PG 11 WC Engineering, Biomedical SC Engineering GA 686RV UT WOS:000183335500007 PM 12723684 ER PT J AU Sarntinoranont, M Banerjee, RK Lonser, RR Morrison, PF AF Sarntinoranont, M Banerjee, RK Lonser, RR Morrison, PF TI A computational model of direct interstitial infusion of macromolecules into the spinal cord SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE microinfusion; convection; diffusion; albumin; porous; FEM; mathematical model; hydraulic conductivity; permeability ID CONVECTION-ENHANCED DELIVERY; SUBARACHNOID PERFUSION; BULK FLOW; DIFFUSION; BRAIN; TISSUE; PRESSURE; HYDROCEPHALUS; TRANSPORT; MONKEYS AB Convection-enhanced interstitial infusion can deliver macromolecular drugs to large tissue volumes of the central nervous system. To characterize infusion into the spinal cord, an image-based three-dimensional finite element model of the rat spinal cord was developed. The model incorporated convection and diffusion through white and gray matter, including anisotropic transport due to alignment of white matter tracts. Spatial and temporal distribution of the marker substance albumin within the interstitial space was determined. Consistent with previous experiments, predicted distribution was highly anisotropic. Infusing into the dorsal column, albumin was primarily confined to white matter with limited penetration into adjacent gray matter. Distribution was determined primarily by the ratio of fiber-parallel to fiber-perpendicular hydraulic conductivity tensor components (k(wm-z)/k(wm-x)), the ratio of transverse white and gray matter hydraulic conductivity (k(wm-x)/k(gm)), and tissue porosity. Fits to previous experimental measures of axial and transverse spread, distribution volume, and protein recovery yielded an optimum k(wm-z)/k(wm-x) of approximately 20 at 0.1 mul/min. k(wm-x)/k(gm) of 100 was sufficient to match experimental transverse distribution data. Best fits to data at 0.1 mul/min were achieved by porosities characteristic of moderate edema (e.g., 0.26). Distribution also varied with catheter placement with more medial placement resulting in greater distribution volumes. (C) 2003 Biomedical Engineering Society. C1 ORS, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD USA. Univ Cincinnati, Dept Engn Mech, Cincinnati, OH USA. RP Sarntinoranont, M (reprint author), ORS, Div Bioengn & Phys Sci, Bldg 13,Room 3N17,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Kipke, Daryl/A-2167-2009 NR 37 TC 32 Z9 34 U1 0 U2 5 PU BIOMEDICAL ENGINEERING SOC AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD APR PY 2003 VL 31 IS 4 BP 448 EP 461 DI 10.1114/1.1558032 PG 14 WC Engineering, Biomedical SC Engineering GA 686RV UT WOS:000183335500009 PM 12723686 ER EF