FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Lee, S Chen, JJ Zhou, GL Touma, E Shi, R Sun, M Kocherginsky, M Karrison, TG Kim, YC Ge, XJ Jayathilaka, N Emmanuel, N Bouffard, G Dietrich, N Young, A Green, E Liu, PP Li, XM Wang, SM Rowley, JD AF Lee, S Chen, JJ Zhou, GL Touma, E Shi, R Sun, M Kocherginsky, M Karrison, TG Kim, YC Ge, XJ Jayathilaka, N Emmanuel, N Bouffard, G Dietrich, N Young, A Green, E Liu, PP Li, XM Wang, SM Rowley, JD TI Gene expression profiles in acute myeloid leukemias (AML): A novel approach using SAGE and custom microarray SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Univ Chicago, Chicago, IL 60637 USA. Northwestern Univ, ENH Res Inst, Evanston, IL USA. NHGRI, NIH, Bethesda, MD 20892 USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 197 BP 60A EP 61A PN 1 PG 2 WC Hematology SC Hematology GA 871JM UT WOS:000225127500200 ER PT J AU Robbiani, DF Colon, K Szabo, P Affer, M Nickerson, H Qi, CF Morse, HC Chesi, M Bergsagel, PL AF Robbiani, DF Colon, K Szabo, P Affer, M Nickerson, H Qi, CF Morse, HC Chesi, M Bergsagel, PL TI Engineered oncogene activation by somatic hypermutation results in a faithful mouse model of MGUS/multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Cornell Univ, Weill Med Coll, Dept Med, New York, NY USA. Mayo Clin, Ctr Canc, Scottsdale, AZ USA. NIAID, NIH, Immunopathol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 211 BP 64A EP 64A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500214 ER PT J AU Machado, RF Martyr, SE Anthi, A Kato, GJ Hunter, LA Coles, WA Nichols, JS Castro, OL Gladwin, MT AF Machado, RF Martyr, SE Anthi, A Kato, GJ Hunter, LA Coles, WA Nichols, JS Castro, OL Gladwin, MT TI Pulmonary hypertension in sickle cell disease: Cardiopulmonary evaluation and response to chronic phosphodiesterase 5 inhibitor therapy. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, Cardiovasc Branch, Vasc Therapeut Sect, Bethesda, MD 20892 USA. NIDDKD, Biol Chem Lab, Bethesda, MD 20892 USA. Howard Univ, Coll Med, Ctr Sickle Cell Dis, Washington, DC USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 2 Z9 2 U1 2 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 235 BP 71A EP 71A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500238 ER PT J AU Morris, CR Kato, G Poljakovic, M Blackwelder, WC Hazen, S Vichinsky, EP Morris, SM Gladwin, MT AF Morris, CR Kato, G Poljakovic, M Blackwelder, WC Hazen, S Vichinsky, EP Morris, SM Gladwin, MT TI The arginine-to-ornithine ratio: Biomarker of arginase activity and predictor of mortality in sickle cell disease. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Childrens Hosp & Res Ctr, Oakland, CA USA. NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Cleveland Clin, Cleveland, OH 44106 USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 2 Z9 2 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 237 BP 71A EP 72A PN 1 PG 2 WC Hematology SC Hematology GA 871JM UT WOS:000225127500240 ER PT J AU Dejam, A Gladwin, MT Christian, HCJ Hsu, L Grear, JJ Tarekegn, S Shruti, S Kelm, M Schechter, AN AF Dejam, A Gladwin, MT Christian, HCJ Hsu, L Grear, JJ Tarekegn, S Shruti, S Kelm, M Schechter, AN TI Characterization of the distribution of nitrite in human blood. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NIDDKD, NIH, Biol Chem Lab, Bethesda, MD 20892 USA. Ctr Clin, Bethesda, MD USA. NHLBI, Cardiovasc Branch, Bethesda, MD 20892 USA. LSU, Hlth Sci Ctr, Shreveport, LA USA. Univ Dusseldorf, Dept Med, Div Cardiol Pulm Dis Angiol, D-4000 Dusseldorf, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 238 BP 72A EP 72A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500241 ER PT J AU Kato, GJ Hunter, C Hunter, L Dejam, A Machado, R Mack, K Villagra, J Nichols, J Coles, W Sachdev, V Cannon, R Gladwin, MT AF Kato, GJ Hunter, C Hunter, L Dejam, A Machado, R Mack, K Villagra, J Nichols, J Coles, W Sachdev, V Cannon, R Gladwin, MT TI Atorvastatin therapy restores nitric oxide-dependent vascular responsiveness in patients with sickle cell disease. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, Cardiovasc Branch, Vasc Therapeut Sect, Bethesda, MD 20892 USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 239 BP 72A EP 72A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500242 ER PT J AU Chakrabarti, S Takahashi, Y Srinivasan, R Espinoza, I Igarashi, T Suffredini, D Marquesen, M Shalabi, RA Bolan, CD Leitman, SF Barrett, AJ Young, NS Childs, R AF Chakrabarti, S Takahashi, Y Srinivasan, R Espinoza, I Igarashi, T Suffredini, D Marquesen, M Shalabi, RA Bolan, CD Leitman, SF Barrett, AJ Young, NS Childs, R TI Durable engraftment and long-term survival following fludarabine-based nonmyeloablative hematopoietic cell transplantation (HCT) in patients with ATG-refractory severe aplastic anemia (SAA) and other nonmalignant hematological disorders. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 BP 75A EP 75A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500254 ER PT J AU Sloand, EM Mainwaring, L Wong, E Tang, Y Horne, MK Young, NS AF Sloand, EM Mainwaring, L Wong, E Tang, Y Horne, MK Young, NS TI A role for plasma urokinase plasminogen activator receptor (uPAR) in thrombosis in paroxysmal nocturnal hemoglobinuria (PNH) SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Div Intramural Res, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 281 BP 84A EP 84A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500283 ER PT J AU Konno, A Jagadeesh, GJ Moratto, D Bosticardo, M Holt, I Muul, LM Schurman, SH Wolfsberg, T Candotti, F AF Konno, A Jagadeesh, GJ Moratto, D Bosticardo, M Holt, I Muul, LM Schurman, SH Wolfsberg, T Candotti, F TI Analysis of retroviral vector insertion sites after T-Cell directed gene therapy SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 289 BP 86A EP 86A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500291 ER PT J AU Calmels, B Ferguson, C Adler, R Sellers, S Laukkanen, M Hematti, P Donahue, R Dunbar, C AF Calmels, B Ferguson, C Adler, R Sellers, S Laukkanen, M Hematti, P Donahue, R Dunbar, C TI Recurrent retroviral vector integration at the MDS1-EVI1 locus in rhesus long-term repopulating hematopoietic stem cells SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, NIH, Hematol Branch, Mol Hematopoiesis Sect, Bethesda, MD 20892 USA. RI calmels, boris/R-2538-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 292 BP 87A EP 87A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500294 ER PT J AU Aue, G Carroll, N Horne, M AF Aue, G Carroll, N Horne, M TI DIC with ulcerative colitis: The combined effects of prothrombin G20210A, APC resistance, and endotoxemia double right arrow. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, Bethesda, MD 20892 USA. NCI, Surg Branch, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 4034 BP 94B EP 94B PN 2 PG 1 WC Hematology SC Hematology GA 871JO UT WOS:000225127700363 ER PT J AU Nichols, KE Hom, J Ganguly, A Ma, CS Tangye, SG Cannons, JL Schwartzberg, PL Koretzky, GA Stein, PL AF Nichols, KE Hom, J Ganguly, A Ma, CS Tangye, SG Cannons, JL Schwartzberg, PL Koretzky, GA Stein, PL TI Regulation of NKT cell development by SAP, the adaptor mutated in X-linked lymphoproliferative disease. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA USA. Centanary Inst Canc Med & Cell Biol, Newtown, PA USA. NHGRI, Bethesda, MD 20892 USA. Northwestern Univ, Sch Med, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 317 BP 94A EP 94A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500319 ER PT J AU Byrd, JC Lin, TS Dalton, JT Wu, D Fischer, B Moran, ME Blum, KA Shank, RS Lucas, DM Lucas, MS Suarez, JR Colevas, AD Grever, MR AF Byrd, JC Lin, TS Dalton, JT Wu, D Fischer, B Moran, ME Blum, KA Shank, RS Lucas, DM Lucas, MS Suarez, JR Colevas, AD Grever, MR TI Flavopiridol administered as a pharmacologically-derived schedule demonstrates marked clinical activity in refractory, genetically high risk, chronic lymphocytic leukemia (CLL) SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Ohio State Univ, Div Hematol Oncol, Columbus, OH 43210 USA. Ohio State Univ, Coll Pharm, Columbus, OH 43210 USA. Aventis Inc, Bridgewater, MA USA. NCI, Bethesda, MD 20892 USA. RI Blum, Kristie/E-2768-2011 NR 0 TC 12 Z9 12 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 341 BP 101A EP 101A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500343 ER PT J AU Lin, YW Slape, C Zhang, ZH Aplan, PD AF Lin, YW Slape, C Zhang, ZH Aplan, PD TI NUP98-HOXD13 transgenic mice develop myelodysplastic syndrome, acute myeloid leukemia, and pre-T lymphoblastic leukemia SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RI Slape, Christopher/H-8586-2016; Aplan, Peter/K-9064-2016 OI Slape, Christopher/0000-0002-8407-3092; NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 345 BP 102A EP 102A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500347 ER PT J AU Lin, YW Deveney, R Aplan, PD AF Lin, YW Deveney, R Aplan, PD TI Overexpression of BHLHB1 (OLIG 2) causes precursor T-Cell lymphoblastic lymphoma/leukemia (pre-T LBL) in the presence of LMO1 overexpression SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RI Aplan, Peter/K-9064-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 343 BP 102A EP 102A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500345 ER PT J AU Nemeth, MJ Anderson, SM Garrett-Beal, LJ Bodine, DM AF Nemeth, MJ Anderson, SM Garrett-Beal, LJ Bodine, DM TI Hmgb3 deficiency inhibits down-regulation of c-kit in hematopoietic stem cells SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHGRI, Hematopoiesis Sect, Bethesda, MD USA. NHGRI, Transgen Mouse Core, Bethlehem, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 372 BP 110A EP 110A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500375 ER PT J AU Oneal, PA Schwartz, JD Gantt, N Bhanu, N Lee, YT Gherman, R Schechter, AN Luban, NLC Miller, J AF Oneal, PA Schwartz, JD Gantt, N Bhanu, N Lee, YT Gherman, R Schechter, AN Luban, NLC Miller, J TI Two cellular mechanisms for gamma-globin gene and protein silencing in humans SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NIDDK, LCB, NIH, Bethesda, MD USA. NHLBI, HB, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Lab Med & Pathol, Washington, DC 20010 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 374 BP 110A EP 110A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500377 ER PT J AU Pilon, AM Wong, C Garrett-Beal, LJ Weiss, M Gallagher, PG Bodine, DM AF Pilon, AM Wong, C Garrett-Beal, LJ Weiss, M Gallagher, PG Bodine, DM TI Chromatin remodeling of the mouse AHSP gene requires EKLF SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHGRI, GMBB, Bethesda, MD 20892 USA. Yale Univ, New Haven, CT USA. CHOP, Philadelphia, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 375 BP 110A EP 111A PN 1 PG 2 WC Hematology SC Hematology GA 871JM UT WOS:000225127500378 ER PT J AU Boyer, J Jacoub, J Dave, H Savani, B Schechter, G AF Boyer, J Jacoub, J Dave, H Savani, B Schechter, G TI Autoimmune hemolytic anemia after non-myeloablative stem cell transplantation: Association with Rh alloreactivity induced by platelet transfusions. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Vet Affairs Med Ctr, Washington, DC 20422 USA. George Washington Univ, Washington, DC 20052 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 4100 BP 111B EP 111B PN 2 PG 1 WC Hematology SC Hematology GA 871JO UT WOS:000225127700429 ER PT J AU Ortiz, M Liu, P Tessarollo, L Rachel, RA Nakamura, T Stull, SW Jenkins, NA Copeland, NG Keller, JR AF Ortiz, M Liu, P Tessarollo, L Rachel, RA Nakamura, T Stull, SW Jenkins, NA Copeland, NG Keller, JR TI Deletion of Bc111a gene reveals roles in lymphoid, mycloid, and leukemic cell development. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NCI, Basic Res Program, SAIC Frederick Inc, Fredericksburg, VA USA. NCI, Mouse Canc Genet Program, Frederick, MD USA. Japanese Fdn Canc Res, Tokyo, Japan. Wellcome Trust Sanger Inst, Cambridge, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 385 BP 113A EP 114A PN 1 PG 2 WC Hematology SC Hematology GA 871JM UT WOS:000225127500388 ER PT J AU Cairo, MS Wagner, E Cohen, G Fraser, J Jensen, LA Carter, S van de Ven, C Kernan, NA Kurtzberg, J AF Cairo, MS Wagner, E Cohen, G Fraser, J Jensen, LA Carter, S van de Ven, C Kernan, NA Kurtzberg, J TI Cord blood (CB) bank log CD34(+) and CD34(+) subsets (CD38(-)CD61(+)CD90(+)) are significantly correlated to log total CFU, CFU-GEMM, CFU-GM and BFU-E: A report from the COBLT program SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Georgetown Univ, Washington, DC USA. Emmes Corp, Rockville, MD USA. Univ Calif Los Angeles, Los Angeles, CA USA. Natl Heart Lung Blood Inst, Bethesda, MD USA. Mem Sloan Kettering Canc Ctr, New York, NY USA. Duke Univ, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 406 BP 119A EP 119A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500409 ER PT J AU Chinen, J Puck, JM Davis, J Linton, GF Whiting-Theobald, NL Woltz, PC Buckley, RH Malech, HL AF Chinen, J Puck, JM Davis, J Linton, GF Whiting-Theobald, NL Woltz, PC Buckley, RH Malech, HL TI Ex vivo gene therapy of a preadolescent with x-linked severe combined immunodeficiency SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 DHHS, NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD USA. DHHS, NIAID, Lab Host Def, NIH, Bethesda, MD USA. Duke Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 410 BP 120A EP 120A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500413 ER PT J AU Takahashi, Y Chakrabarti, S Sriniivasan, R Lundqvist, A Read, EJ Khuu, H Leitman, S Bolan, C Barrett, AJ Calandra, G Childs, R AF Takahashi, Y Chakrabarti, S Sriniivasan, R Lundqvist, A Read, EJ Khuu, H Leitman, S Bolan, C Barrett, AJ Calandra, G Childs, R TI A detailed phenotypic analysis using six color flow cytometry of lymphocyte subsets mobilized with AMD3100 compared to G-CSF SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD USA. DTM, NIH, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 408 BP 120A EP 120A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500411 ER PT J AU Zettl, A Bea, S Wright, G Salaverria, I Jehn, P Ott, G Chan, WC Jaffe, E Weisenburger, D Greiner, T Armitage, J Gascoyne, R Connors, J Grogan, T Miller, T Fisher, R Delabie, J Kvaloy, S Mueller-Hermelink, HK Burek, C Moreno, V Montserrat, E Wilson, W Staudt, L Rosenwald, A Campo, E AF Zettl, A Bea, S Wright, G Salaverria, I Jehn, P Ott, G Chan, WC Jaffe, E Weisenburger, D Greiner, T Armitage, J Gascoyne, R Connors, J Grogan, T Miller, T Fisher, R Delabie, J Kvaloy, S Mueller-Hermelink, HK Burek, C Moreno, V Montserrat, E Wilson, W Staudt, L Rosenwald, A Campo, E CA Leukemia Lymphoma Mol Profiling P TI Chromosomal imbalances in germinal center B-cell-like and activated B-cell-like diffuse large B-cell lymphoma influence gene expression signatures and improve gene expression-based survival prediction (the first two authors contributed equally to this work) SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Univ Wurzburg, Dept Pathol, D-8700 Wurzburg, Germany. Univ Barcelona, Hosp Clin, Barcelona, Spain. Natl Canc Inst, Bethesda, MD USA. Univ Nebraska, Ctr Med, Omaha, NE 68583 USA. Hematopathol Sect, NCI, Bethesda, MD USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Univ Arizona, Ctr Canc, SW Oncol Grp, Tuscan, AZ USA. Norwegian Radium Hosp, Oslo, Norway. NR 0 TC 0 Z9 0 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 NOV 16 PY 2004 VL 104 IS 11 MA 415 BP 122A EP 122A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500418 ER PT J AU Solomon, SR Tran, T Carter, CS Hensel, N Wisch, L Mielke, S Read, E Ghetie, V Schindler, J Vitetta, E Barrett, J AF Solomon, SR Tran, T Carter, CS Hensel, N Wisch, L Mielke, S Read, E Ghetie, V Schindler, J Vitetta, E Barrett, J TI Selective depletion of alloreacting CD25+cells from stem cell allografts can reduce acute graft-versus-host disease following matched related donor transplantation. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, NIH, Bethesda, MD 20892 USA. Natl Lib Med, NIH, Bethesda, MD 20209 USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. UTSWMC, Ctr Canc Immunobiol, Dallas, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 426 BP 125A EP 125A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500429 ER PT J AU Chen, L Jean-Noel, S Hall, K Shi, Y Rodgers, GP AF Chen, L Jean-Noel, S Hall, K Shi, Y Rodgers, GP TI In vitro hematopoietic lineage interconversion from human bone marrow stem and progenitor cells SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD USA. NIDDK, Lab Biol Modeling, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 4160 BP 126B EP 127B PN 2 PG 2 WC Hematology SC Hematology GA 871JO UT WOS:000225127700489 ER PT J AU Sloand, EM Ramkissoon, S Mainwaring, L Barrett, J Young, NS AF Sloand, EM Ramkissoon, S Mainwaring, L Barrett, J Young, NS TI Granulocyte colony stimulating factor preferentially causes proliferation of pre-existing monosomy 7 cells in aplastic anemia and myelodysplastic syndrome because of abnormal truncated GCSF-receptors on these cells. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Div Intramural Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 458 BP 134A EP 134A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500461 ER PT J AU Gore, SD Baylin, SB Dauses, T Grever, MR Jiemjit, A Manning, J Miller, CB Murgo, AJ Zwiebel, JA Herman, JG AF Gore, SD Baylin, SB Dauses, T Grever, MR Jiemjit, A Manning, J Miller, CB Murgo, AJ Zwiebel, JA Herman, JG TI Changes in promoter methylation and gene expression in patients with MDS and MDS-AML treated with 5-azacitidine and sodium phenylbutyrate SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Johns Hopkins Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Ohio State Univ, James Canc Ctr, Columbus, OH 43210 USA. Natl Canc Inst, Div Canc Treatment, Rockville, MD USA. NR 0 TC 6 Z9 7 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 469 BP 137A EP 137A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500472 ER PT J AU Sloand, EM Rezvani, K Barrett, J Mainwaring, L Kurlander, R Gostick, E Ramkissoon, S Tang, Y Douek, D Price, D Young, NS AF Sloand, EM Rezvani, K Barrett, J Mainwaring, L Kurlander, R Gostick, E Ramkissoon, S Tang, Y Douek, D Price, D Young, NS TI Myelodysplasia with trisomy 8 is associated with a cytotoxic CD8 T cell immune response to Wilms tumor-1 protein (WT1). SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, Div Intramural Res, Hematol Branch, Bethesda, MD 20892 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. Univ Oxford, Nuffield Dept Med, Oxford OX1 2JD, England. RI Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 NR 0 TC 1 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 474 BP 138A EP 139A PN 1 PG 2 WC Hematology SC Hematology GA 871JM UT WOS:000225127500477 ER PT J AU Goh, SH Lee, YT Bhanu, N Gherman, R Cam, MC Miller, JL AF Goh, SH Lee, YT Bhanu, N Gherman, R Cam, MC Miller, JL TI Characterization of a newly discovered human alpha-globin gene. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NIDDK, Biol Chem Lab, NIH, Bethesda, MD USA. NIDDK, Microarray Core Facil, NIH, Bethesda, MD USA. Bethesda Naval Hosp, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 502 BP 146A EP 146A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500505 ER PT J AU Kuo, YH Heilman, S Chen, A Liu, PP Gernstein, R Kogan, S Castilla, LH AF Kuo, YH Heilman, S Chen, A Liu, PP Gernstein, R Kogan, S Castilla, LH TI Cbfb-MYHII induces expansion of a Lin-Kit+Sca1-abnormal progenitor compartment that predisposes acute myeloid leukemia in mice. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 543 BP 158A EP 158A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500546 ER PT J AU Du, Y Jenkins, NA Copeland, NG Dave, UP AF Du, Y Jenkins, NA Copeland, NG Dave, UP TI Genetic identification of hematopoietic stem cell immortalization genes. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Natl Canc Inst, Mouse Canc Genet Program, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 4324 BP 166B EP 166B PN 2 PG 1 WC Hematology SC Hematology GA 871JO UT WOS:000225127700654 ER PT J AU Liem, RI Cline, AP Garrett-Beal, LJ Owen, AN Gallagher, PG Bodine, DM AF Liem, RI Cline, AP Garrett-Beal, LJ Owen, AN Gallagher, PG Bodine, DM TI Defining the active chromatin domain of the erythroid ankyrin promoter. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHGRI, GMBB, Bethesda, MD 20892 USA. Yale Univ, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 575 BP 166A EP 166A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500578 ER PT J AU Haining, WN Neuberg, D Keczkemethy, H Evans, J Rivoli, S Guenaga, J Douek, D Sallan, S Guinan, E Nadler, L AF Haining, WN Neuberg, D Keczkemethy, H Evans, J Rivoli, S Guenaga, J Douek, D Sallan, S Guinan, E Nadler, L TI Protective, antigen-specific immunity in children treated for ALL is due to selective preservation of T-cell memory SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NIAID, NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 600 BP 173A EP 173A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500603 ER PT J AU O'Connor, O Wright, J Moskowitz, C MacGregor-Cortelli, B Straus, D Evans, A Winter, J Koc, O Horvath, N Blumel, S Vose, J Schenkein, D Zelenetz, A AF O'Connor, O Wright, J Moskowitz, C MacGregor-Cortelli, B Straus, D Evans, A Winter, J Koc, O Horvath, N Blumel, S Vose, J Schenkein, D Zelenetz, A TI A Multicenter experience with single agent bortezomib in non-Hodgkin's lymphoma reveals marked differences in sub-type sensitivity to proteasome inhibition SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. NCI, Bethesda, MD 20892 USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Case Western Reserve Univ, Univ Hosp Cleveland, Dept Med, Cleveland, OH 44106 USA. Univ Nebraska, Dept Med, Omaha, NE 68182 USA. Millennium Pharmaceut, Cambridge, MA USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 607 BP 175A EP 175A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500610 ER PT J AU Wiestner, A Chiorazzi, M Lai, R Rosenwald, A Muller-Hermelink, HK Ott, G Chan, WC Greiner, TC Weisenburger, DD Vose, J Armitage, JO Gascoyne, RD Connors, JM Campo, E Montserrat, E Bosch, F Smeland, EB Kvaloy, S Holte, H Delabie, J Fisher, RI Grogan, TM Miller, TP Wilson, WH Jaffe, ES Staudt, LM AF Wiestner, A Chiorazzi, M Lai, R Rosenwald, A Muller-Hermelink, HK Ott, G Chan, WC Greiner, TC Weisenburger, DD Vose, J Armitage, JO Gascoyne, RD Connors, JM Campo, E Montserrat, E Bosch, F Smeland, EB Kvaloy, S Holte, H Delabie, J Fisher, RI Grogan, TM Miller, TP Wilson, WH Jaffe, ES Staudt, LM TI High cyclin D1 expression is associated with increased proliferation rate and decreased survival in mantle cell lymphoma (MCL) and is caused by genomic deletions and mutations that enhance stability of cyclin D1 mRNA. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NCI, CCR, Bethesda, MD 20892 USA. Univ Alberta, Edmonton, AB, Canada. Univ Wurzburg, Wurzburg, Germany. Univ Nebraska, Med Ctr, Omaha, NE 68182 USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Univ Barcelona, Barcelona, Spain. Norwegian Radium Hosp, Oslo, Norway. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 697 BP 200A EP 200A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500700 ER PT J AU Dave, SS Wright, G Tan, B Rosenwald, A Chan, WC Greiner, TC Weisenburger, DD Lynch, JC Vose, JM Armitage, JO Fisher, RI Braziel, RM Rimsza, LM Grogan, TM Miller, TP LeBlanc, M Smeland, EB Kvaloy, S Holte, H Delabie, J Muller-Hermelink, HK Ott, G Gascoyne, RD Connors, JM Campo, E Montserrat, E Wilson, WH Jaffe, ES Lister, TA Davies, AJ Norton, AJ Simon, R Yang, L Powell, J Palma, J Warrington, J Zhao, H Chiorazzi, M Staudt, LM AF Dave, SS Wright, G Tan, B Rosenwald, A Chan, WC Greiner, TC Weisenburger, DD Lynch, JC Vose, JM Armitage, JO Fisher, RI Braziel, RM Rimsza, LM Grogan, TM Miller, TP LeBlanc, M Smeland, EB Kvaloy, S Holte, H Delabie, J Muller-Hermelink, HK Ott, G Gascoyne, RD Connors, JM Campo, E Montserrat, E Wilson, WH Jaffe, ES Lister, TA Davies, AJ Norton, AJ Simon, R Yang, L Powell, J Palma, J Warrington, J Zhao, H Chiorazzi, M Staudt, LM TI LymphDx: A custom microarray for molecular diagnosis and prognosis in non-Hodgkin lymphoma. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NCI, NIH, Bethesda, MD 20892 USA. Univ Nebraska, Lincoln, NE 68583 USA. Univ Wurzburg, D-97070 Wurzburg, Germany. Univ Barcelona, E-08007 Barcelona, Spain. St Bartholomews Hosp, London, England. NR 0 TC 1 Z9 1 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 NOV 16 PY 2004 VL 104 IS 11 MA 701 BP 201A EP 201A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500704 ER PT J AU Dierov, J Padilla-Nash, H Ried, T Carroll, M AF Dierov, J Padilla-Nash, H Ried, T Carroll, M TI BCR/ABL expression increases the formation of chromosomal translocations after DNA damage. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Univ Penn, Philadelphia, PA 19104 USA. NCI, Dept Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 713 BP 204A EP 205A PN 1 PG 2 WC Hematology SC Hematology GA 871JM UT WOS:000225127500716 ER PT J AU Sobeck, A Stone, S deGraaf, B Costanzo, V deWinter, J Wang, WD Joenje, H Gautier, J Hoatlin, ME AF Sobeck, A Stone, S deGraaf, B Costanzo, V deWinter, J Wang, WD Joenje, H Gautier, J Hoatlin, ME TI Coordinated chromatin-association of Fanconi anemia network proteins requires replication-coupled DNA damage recognition. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Oregon Hlth Sci Univ, Div Mol Med, Portland, OR 97201 USA. Free Univ Amsterdam, Med Ctr, Dept Clin Genet & Human Genet, Amsterdam, Netherlands. NIA, NIH, Bethesda, MD 20892 USA. Columbia Univ, Dept Genet & Dev, New York, NY USA. RI Gautier, jean/A-2774-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 723 BP 207A EP 207A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500726 ER PT J AU Chu, YW Yakar, S LeRoith, D Gress, R AF Chu, YW Yakar, S LeRoith, D Gress, R TI Insulin-like growth factor I is a positive regulator of thymic function. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NIH, Expt Immunol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. NIDDK, Diabet Branch, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 732 BP 210A EP 210A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500735 ER PT J AU Neelapu, SS Gause, BL Harvey, L Frye, AR Horton, J Robb, RJ Popescu, MC Kwak, LW AF Neelapu, SS Gause, BL Harvey, L Frye, AR Horton, J Robb, RJ Popescu, MC Kwak, LW TI Human autologous tumor-specific T-cell responses induced by liposome encapsulated lymphoma membrane proteins. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 UT, MD Anderson Canc Ctr, Houston, TX USA. NCI, Expt & Transplantat Immunol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, SAIC, Frederick, MD 21701 USA. Biomira USA Inc, Cranbury, NJ USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 749 BP 214A EP 214A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500751 ER PT J AU Yee, KWL Garcia-Manero, G Thomas, D Ani, FRK Verstovsek, S Andreeff, M Dancey, JE Giles, FJ AF Yee, KWL Garcia-Manero, G Thomas, D Ani, FRK Verstovsek, S Andreeff, M Dancey, JE Giles, FJ TI A phase II study of temsirolimus (CCI-779) in patients with advanced leukemias. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, Canc Therapy Evaluat Program, Rockville, MD USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 4523 BP 214B EP 214B PN 2 PG 1 WC Hematology SC Hematology GA 871JO UT WOS:000225127700853 ER PT J AU Carrasco, R Tonon, G Brennan, C Protopopov, A Sinha, R Feng, B Leo, C Zhang, YY Zhang, J Zhan, FH Protopopova, M Mitsiades, C Munshi, N Chin, L Bergsagel, P Kuehl, M Shaughnessy, J Anderson, K DePinho, R AF Carrasco, R Tonon, G Brennan, C Protopopov, A Sinha, R Feng, B Leo, C Zhang, YY Zhang, J Zhan, FH Protopopova, M Mitsiades, C Munshi, N Chin, L Bergsagel, P Kuehl, M Shaughnessy, J Anderson, K DePinho, R TI Comprehensive genome-wide profile of regional gains and losses in multiple myeloma using array-CGH: The 1q21 amplification and potential role of the BCL-9 gene in multiple myeloma pathogenesis SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. NCI, Genet Dept, Bethesda, MD USA. Univ Arkansas, Lambert Lab Myeloma Genet, Little Rock, AR USA. Cornell Univ, Dept Med, New York, NY USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 785 BP 225A EP 225A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500787 ER PT J AU Takahashi, Y Chakrabarti, S Srinivasan, R Igarashi, T Lundqvist, A Espinoza, I Suffredini, D McCoy, JP Barrett, AJ Young, NS Childs, R AF Takahashi, Y Chakrabarti, S Srinivasan, R Igarashi, T Lundqvist, A Espinoza, I Suffredini, D McCoy, JP Barrett, AJ Young, NS Childs, R TI The graft-vs-host hematopoietic effect generated after nonmyeloablative allogeneic stem cell transplantation (NST) cures patients with severe PNH SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD USA. NIA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 811 BP 231A EP 232A PN 1 PG 2 WC Hematology SC Hematology GA 871JM UT WOS:000225127500813 ER PT J AU Bishop, MR Neelapu, S Fowler, DH Krumlauf, M Gress, R Kwak, LW AF Bishop, MR Neelapu, S Fowler, DH Krumlauf, M Gress, R Kwak, LW TI Preliminary results of sibling donor immunization with patient-derived Id-KLH vaccine prior to reduced-intensity allogeneic stem cell transplantation for multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD USA. MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 814 BP 232A EP 232A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500816 ER PT J AU Bunting, KD Couldrey, C Moriggl, R Cui, YZ Wright, H Wang, DM Ryan, JJ Ihle, JN Hennighausen, L AF Bunting, KD Couldrey, C Moriggl, R Cui, YZ Wright, H Wang, DM Ryan, JJ Ihle, JN Hennighausen, L TI Endogenous N-terminal truncated STAT5 expressed from alternative start codons promotes SCF signaling in murine primary mast cell cultures. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 CWRU, Med, Cleveland, OH USA. Computercraft, Tech, Bethesda, MD USA. IMP, Biochem, Vienna, Austria. NIDDK, NIH, Bethesda, MD USA. VCU, Richmond, VA USA. Blood Res Inst, Milwaukee, WI USA. St Jude Childrens Res Hosp, Memphis, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 815 BP 233A EP 233A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500817 ER PT J AU Lahlil, R Martin, R Aplan, PD Begley, CG Damen, JE Krystal, G Hoang, T AF Lahlil, R Martin, R Aplan, PD Begley, CG Damen, JE Krystal, G Hoang, T TI The SCL transcription factor supports erythroid cell survival and differentiation downstream of the erythropoietin receptor. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Univ Montreal, Inst Immunol & Canc, Montreal, PQ, Canada. NCI, Gaithersburg, MD USA. British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC, Canada. RI Aplan, Peter/K-9064-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 818 BP 233A EP 234A PN 1 PG 2 WC Hematology SC Hematology GA 871JM UT WOS:000225127500820 ER PT J AU Decker, T Wagner, M Oelsner, M Kreitman, RJ Pastan, I Peschel, C Licht, T AF Decker, T Wagner, M Oelsner, M Kreitman, RJ Pastan, I Peschel, C Licht, T TI BL22, a recombinant anti-CD22 immunotoxin, induces cell cycle arrest and apoptosis in B-cell lymphoma. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Munich, Dept Hematol Oncol, Klinikum Rechts Isar, Munich, Germany. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 4613 BP 237B EP 237B PN 2 PG 1 WC Hematology SC Hematology GA 871JO UT WOS:000225127700943 ER PT J AU Dell'Agnola, C Wojciechowski, W Marshall, S Lopez, NE Li, HF Bowen, WD Espinoza-Delgado, IJ AF Dell'Agnola, C Wojciechowski, W Marshall, S Lopez, NE Li, HF Bowen, WD Espinoza-Delgado, IJ TI Sigma 2-agonist CB-64D induces apoptosis in non Hodgkin's lymphoma cells: Association with decreased Akt expression. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NIA, Hematol Oncol Sect, NIH, Baltimore, MD 21224 USA. NIDDK, Unit Receptor Biochem & Pharmacol, Med Chem Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 4619 BP 238B EP 238B PN 2 PG 1 WC Hematology SC Hematology GA 871JO UT WOS:000225127700949 ER PT J AU Lancet, JE Gotlib, J Gojo, I Feldman, EJ Morris, L Thibault, A Liesveld, JL Greer, J Dugan, K Raponi, M Wright, JJ Greenberg, PL Karp, JE AF Lancet, JE Gotlib, J Gojo, I Feldman, EJ Morris, L Thibault, A Liesveld, JL Greer, J Dugan, K Raponi, M Wright, JJ Greenberg, PL Karp, JE TI Tipifarnib (ZARNESTRA (TM)) in previously untreated poor-risk AML of the elderly: Updated results of a multicenter phase 2 trial. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY USA. Stanford Univ, Dept Hematol, Stanford, CA USA. Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD USA. Cornell Univ, New York, NY USA. Blood & Marrow Transplant Grp, Atlanta, GA USA. Johnson & Jonson PRD, Raritan, NJ USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Veridex LLC, San Diego, CA USA. NCI, Bethesda, MD USA. NR 0 TC 16 Z9 16 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 874 BP 249A EP 249A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500876 ER PT J AU Ozpolat, B Tirado-Gomez, M Colburn, NH Berestein, GL AF Ozpolat, B Tirado-Gomez, M Colburn, NH Berestein, GL TI All-trans-retinoic acid (ATRA) and arsenic trioxide-induced expression and regulation of programmed cell death 4 (PDCD4) in acute promyelocytic leukemia. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Natl Canc Inst Frederick, Gene Regulat Sect, Ctr Canc Res, Frederick, MD USA. RI Ozpolat, Berkant/Q-6981-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 886 BP 253A EP 253A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500888 ER PT J AU Oscier, DG Gardiner, AC Mould, SJ Glide, S Davis, ZA Corcoran, M Wiestner, A Staudt, LM Thomas, P Orchard, JA AF Oscier, DG Gardiner, AC Mould, SJ Glide, S Davis, ZA Corcoran, M Wiestner, A Staudt, LM Thomas, P Orchard, JA TI The natural history of mutated, stage AO chronic lymphocytic leukemia. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Royal Bournemouth Hosp, Bournemouth, Dorset, England. NCI, Metab Branch, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 954 BP 273A EP 273A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127500956 ER PT J AU Yavuz, SA Hartmann, DP Baidas, S Lipsky, PE Ozdemirli, M AF Yavuz, SA Hartmann, DP Baidas, S Lipsky, PE Ozdemirli, M TI Demonstration of biclonal chronic lymphocytic leukemia with mutated and unmutated clones and concurrent but clonally unrelated myeloma in the same patient by single cell immunoglobulin heavy and light chain gene analysis. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NIAMS, Autoimmun Branch, NIH, Bethesda, MD USA. Georgetown Univ Hosp, Washington, DC 20007 USA. Istanbul Univ Med, Istanbul, Turkey. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 4772 BP 276B EP 276B PN 2 PG 1 WC Hematology SC Hematology GA 871JO UT WOS:000225127701098 ER PT J AU Lehrnbecher, T Bernig, T Hanisch, M Koehl, U Reinhardt, D Creutzig, U Chanock, SJ Klingebiel, T Schwabe, D AF Lehrnbecher, T Bernig, T Hanisch, M Koehl, U Reinhardt, D Creutzig, U Chanock, SJ Klingebiel, T Schwabe, D TI Common polymorphisms of the interleukin-6 and chitotriosidase genes are associated with the risk for infection with gram-negative bacteria in children undergoing therapy for acute myeloid leukemia SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Univ Frankfurt, D-6000 Frankfurt, Germany. NCI, NIH, Bethesda, MD 20892 USA. Univ Munster, D-4400 Munster, Germany. RI Reinhardt, Dirk/D-3939-2011 OI Reinhardt, Dirk/0000-0003-4313-9056 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 1061 BP 302A EP 302A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127501063 ER PT J AU Ise, T Nagata, S Maeda, H Kreitman, R Stetler-Stevenson, M Pastan, I AF Ise, T Nagata, S Maeda, H Kreitman, R Stetler-Stevenson, M Pastan, I TI IRTA2 protein on lymphoma cell lines and hairy cell leukemia cells detected by novel monoclonal antibodies SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RI Nagata, Satoshi/B-5781-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 1101 BP 313A EP 313A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127501103 ER PT J AU Kim, KT Baird, K Davis, S Levis, M Piloto, O Li, L Chen, PL Meltzer, P Small, D AF Kim, KT Baird, K Davis, S Levis, M Piloto, O Li, L Chen, PL Meltzer, P Small, D TI Constitutive FLT3 activation results in specific changes in gene expression in myeloid leukemic cells SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 1115 BP 316A EP 316A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127501117 ER PT J AU Lundqvist, A Srinivasan, R Suffredini, D Takahashi, Y Wynberg, J Igarashi, T Reese, A Shlomchik, W Childs, R AF Lundqvist, A Srinivasan, R Suffredini, D Takahashi, Y Wynberg, J Igarashi, T Reese, A Shlomchik, W Childs, R TI Potent graft-versus-renal cell carcinoma (RCC) effects in a murine minor histocompatibility antigen (mHa)-mismatched allogeneic transplant model. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, NIH, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Sect Med Oncol, New Haven, CT 06520 USA. Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT 06520 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 4982 BP 327B EP 327B PN 2 PG 1 WC Hematology SC Hematology GA 871JO UT WOS:000225127701308 ER PT J AU Takahashi, Y Mena, O Srinivasan, R Igarashi, T Lundqvist, A Suffredini, D McCoy, JP Hanada, K Linehan, M Childs, R AF Takahashi, Y Mena, O Srinivasan, R Igarashi, T Lundqvist, A Suffredini, D McCoy, JP Hanada, K Linehan, M Childs, R TI CD8+T-cells specifically cytotoxic to renal cell carcinoma (RCC) cells can be isolated from patients with regressing metastatic kidney cancer after allogeneic nonmyeloablative hematopoietic cell transplantation (NMHCT). SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, NIH, Bethesda, MD USA. NCI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 4984 BP 327B EP 328B PN 2 PG 2 WC Hematology SC Hematology GA 871JO UT WOS:000225127701310 ER PT J AU Elshal, M Takahashi, Y Chakrabarti, S Srinivasan, R Suffredini, D Igarashi, T Solomon, S Lundqvist, A Barrett, AJ McCoy, JP Childs, R AF Elshal, M Takahashi, Y Chakrabarti, S Srinivasan, R Suffredini, D Igarashi, T Solomon, S Lundqvist, A Barrett, AJ McCoy, JP Childs, R TI Complex alterations in serum cytokines and increased IL-4 levels characterize patients developing chronic thrombocytopenia after allogeneic hematopoietic cell transplantation. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, Bethesda, MD 20892 USA. RI Elshal, Mohamed/H-7953-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 4985 BP 328B EP 328B PN 2 PG 1 WC Hematology SC Hematology GA 871JO UT WOS:000225127701311 ER PT J AU Abkowitz, JL LaRochelle, A Dunbar, CE Chen, J AF Abkowitz, JL LaRochelle, A Dunbar, CE Chen, J TI Mobilization as a preparative regimen for hematopoietic stem cell (HSC) transplantation. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Univ Washington, Seattle, WA 98195 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 1187 BP 336A EP 336A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127501189 ER PT J AU Seggewiss, R Lore, K Guenaga, JF Pittaluga, S Metzger, ME Krouse, A Donahue, RE Ambrozak, D Douek, DC Dunbar, CE AF Seggewiss, R Lore, K Guenaga, JF Pittaluga, S Metzger, ME Krouse, A Donahue, RE Ambrozak, D Douek, DC Dunbar, CE TI In vitro culture during retroviral transduction improves thymic repopulation and output after TBI and autologous PBPC transplantation in rhesus macaques. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, US Dept HHS, NIH, Bethesda, MD 20892 USA. NHLBI, Vaccine Res Ctr, US Dept HHS, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, HIH, US Dept HHS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 1196 BP 338A EP 339A PN 1 PG 2 WC Hematology SC Hematology GA 871JM UT WOS:000225127501198 ER PT J AU Sterner, L Miyazaki, T Swift, L Dean, A Little, J AF Sterner, L Miyazaki, T Swift, L Dean, A Little, J TI Endogenous elevations of short chain fatty acids up-regulate embryonic globin gene expression during primitive erythropoiesis. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Ctr Immunol, Dallas, TX USA. Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 1210 BP 342A EP 343A PN 1 PG 2 WC Hematology SC Hematology GA 871JM UT WOS:000225127501212 ER PT J AU Dean, RM Donley, KM Gea-Banacloche, J Steinberg, SM Odom, J Krumlauf, M Castro, K Chinn, T Fowler, DH Gress, RE Bishop, MR AF Dean, RM Donley, KM Gea-Banacloche, J Steinberg, SM Odom, J Krumlauf, M Castro, K Chinn, T Fowler, DH Gress, RE Bishop, MR TI Engraftment syndrome after reduced-intensity allogeneic hematopoietic stem cell transplantation: Impact of graft-versus-host disease prophylaxis and T cell dose. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, Bethesda, MD USA. NCI, Canc Res Ctr, Biostat & Data Management Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 5052 BP 345B EP 346B PN 2 PG 2 WC Hematology SC Hematology GA 871JO UT WOS:000225127701378 ER PT J AU Srinivasan, R Geller, N Chakrabarti, S Espinoza-Delgado, I Donohue, T Leitman, S Bolan, CD Read, EJ Barrett, JA Childs, RW AF Srinivasan, R Geller, N Chakrabarti, S Espinoza-Delgado, I Donohue, T Leitman, S Bolan, CD Read, EJ Barrett, JA Childs, RW TI Evaluation of three different cyclosporine-based graft versus host disease (GVHD) prophylaxis regimens following nonmyeloablative hematopoietic stem cell transplantation (NST). SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, HB, Bethesda, MD 20892 USA. NCI, UOB, Bethesda, MD 20892 USA. NIH, NIA, Bethesda, MD 20892 USA. NIH, DTM, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 1236 BP 349A EP 349A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127501238 ER PT J AU Boyiadzis, M Carson, JM Memon, SA Dean, R Castro, K Odom, J Bishop, MR Gress, RE Hakim, FT AF Boyiadzis, M Carson, JM Memon, SA Dean, R Castro, K Odom, J Bishop, MR Gress, RE Hakim, FT TI Increased expression of activating receptors on NK cells in the post-transplant period. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Natl Canc Inst, Expt Transplantat & Immunol Branch, Bethesda, MD USA. RI Memon, Sarfraz/E-1198-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 1249 BP 353A EP 353A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127501251 ER PT J AU Donley, KM Gea-Banacloche, JC Dean, RM Steinberg, SM Childs, RW Odom, J Castro, K Chinn, T Fowler, DH Bishop, MR AF Donley, KM Gea-Banacloche, JC Dean, RM Steinberg, SM Childs, RW Odom, J Castro, K Chinn, T Fowler, DH Bishop, MR TI Comparison of empiric versus prophylactic administration of ceftazidime during neutropenia associated with reduced-intensity allogeneic stem cell transplantation (RIST). SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 5100 BP 358B EP 359B PN 2 PG 2 WC Hematology SC Hematology GA 871JO UT WOS:000225127701426 ER PT J AU Bernig, T Breunis, W Brouwer, N Roos, D Kuijpers, TW Chanock, SJ AF Bernig, T Breunis, W Brouwer, N Roos, D Kuijpers, TW Chanock, SJ TI Functional consequences of genetic variation across the entire MBL2 locus: Possible identification of 3 ' SNPs that could modify circulating levels of MBL. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NCI, Sect Genomiv Variat, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Univ Amsterdam, Emma Childrens Hosp, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. Sanquin Res, Amsterdam, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 1330 BP 374A EP 375A PN 1 PG 2 WC Hematology SC Hematology GA 871JM UT WOS:000225127501333 ER PT J AU Cordonnier, C Walsh, TJ Bresnik, M AF Cordonnier, C Walsh, TJ Bresnik, M TI Liposomal amphotericin B (L-AMB) is superior to amphotericin B deoxycholate (AmB-d) in preventing breakthrough fungal infections in patients with prolonged neutropenia and fever: Results of a sub-group analysis of an empirical antifungal therapy trial. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Hop Henri Mondor, Serv Hematol Clin, F-94010 Creteil, France. NCI, Pediat Branch, Infect Dis Sect, Bethesda, MD 20892 USA. Gilead Sci Inc, Clin Dev Adm, Foster City, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 1336 BP 376A EP 376A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127501339 ER PT J AU Seggewiss, R Lore, K Greiner, E Magnusson, MK Price, DA Douek, DC Dunbar, CE Wiestner, A AF Seggewiss, R Lore, K Greiner, E Magnusson, MK Price, DA Douek, DC Dunbar, CE Wiestner, A TI Proliferation of CD8(+) T-cells specific for CMV and EBV in response to TCR mediated recognition of cognate antigen is inhibited by imatinib in a dose-dependent manner. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, US Dept HHS, NIH, Bethesda, MD 20892 USA. NIAID, Vaccine Res Ctr, US Dept HHS, NIH, Bethesda, MD 20892 USA. NIDDK, Med Chem Lab, US Dept HHS, NIH, Bethesda, MD 20892 USA. Landspitali Univ Hosp, Dept Hematol, Reykjavik, Iceland. Landspitali Univ Hosp, Dept Genet & Mol Med, Reykjavik, Iceland. NCI, Metab Branch, US Dept HHS, 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 AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 1342 BP 377A EP 377A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127501345 ER PT J AU Fujiwara, H Melenhorst, JJ El Ouriaghli, F Kajigaya, S Grube, M Sconocchia, G Rezvani, K Price, DA Hensel, NF Douek, DC Barrett, AJ AF Fujiwara, H Melenhorst, JJ El Ouriaghli, F Kajigaya, S Grube, M Sconocchia, G Rezvani, K Price, DA Hensel, NF Douek, DC Barrett, AJ TI In vitro induction of myeloid leukemia specific CD4 and CD8 T-cells by CD40 ligand activated B cells gene-modified to express primary granule proteins. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NIAID, Vaccine Res Ctr, 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 AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 1351 BP 380A EP 380A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127501354 ER PT J AU Dunleavy, K Janik, J Gea-Banacloche, J Shovlin, M White, T Goldschmidt, N Grant, N Koc, O Pittaluga, S Jaffe, E Staudt, L Wilson, WH AF Dunleavy, K Janik, J Gea-Banacloche, J Shovlin, M White, T Goldschmidt, N Grant, N Koc, O Pittaluga, S Jaffe, E Staudt, L Wilson, WH TI Phase I/II study of bortezomib alone and bortezomib with dose-adjusted EPOCH chemotherapy in relapsed or refractory aggressive B-cell lymphoma. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA. Univ Hosp Cleveland, Ireland Canc Ctr, Cleveland, OH 44106 USA. NR 0 TC 9 Z9 10 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 1385 BP 389A EP 389A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127501388 ER PT J AU Sloand, EM Saunthrararajah, Y Battiwalla, M Nakamura, R Boss, C Aliyu, ZY Young, NS Barrett, J AF Sloand, EM Saunthrararajah, Y Battiwalla, M Nakamura, R Boss, C Aliyu, ZY Young, NS Barrett, J TI Immunosuppression for myelodysplastic syndrome: Association between a score based on presenting features and long-term survival. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 1431 BP 401A EP 401A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127501434 ER PT J AU Kurzrock, R Verstovsek, S Wright, JJ Pilat, SR Cortes, JE Estey, EH Giles, FJ Beran, M Kantarjian, HM AF Kurzrock, R Verstovsek, S Wright, JJ Pilat, SR Cortes, JE Estey, EH Giles, FJ Beran, M Kantarjian, HM TI Phase I study using alternate week administration of the farnesyl transferase inhibitor R115777 (Zarnestra (TM)) in patients with myelodysplastic syndrome. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, CTEP, Invest Drug Branch, Bethesda, MD 20892 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 1436 BP 402A EP 402A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127501439 ER PT J AU Dale, DC Bolyard, AA Schwinzer, B Pracht, G Bonilla, MA Boxer, L Freedmad, M Donadieu, J Kannourakis, G Alter, BP Cham, B Winkelstein, J Kinsey, SE Fier, C Zeidler, C Welte, K AF Dale, DC Bolyard, AA Schwinzer, B Pracht, G Bonilla, MA Boxer, L Freedmad, M Donadieu, J Kannourakis, G Alter, BP Cham, B Winkelstein, J Kinsey, SE Fier, C Zeidler, C Welte, K TI The Severe Chronic Neutropenia International Registry - 10 years of follow-up. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Univ Washington, Seattle, WA 98195 USA. KinderKlin, Med Hsch, Hannover, Germany. St Josephs Hosp, Paterson, NJ USA. Univ Michigan, Womens Hosp, Ann Arbor, MI 48109 USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Hosp Trousseau, Serv Hematol & Oncol Pediat, Paris, France. Ctr Canc Res, Ballarat Oncol & Haematol Serv, Ballarat, Vic, Australia. NCI, Rockville, MD USA. CancerCare Manitoba, Winnipeg, MB, Canada. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. St James Univ Hosp, Leeds LS9 7TF, W Yorkshire, England. Amgen Inc, Boulder, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 1458 BP 408A EP 408A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127501461 ER PT J AU Hayakawa, T Angata, T Margulies, EH Mikkelsen, T Green, ED Varki, A AF Hayakawa, T Angata, T Margulies, EH Mikkelsen, T Green, ED Varki, A TI Gene conversion of sialic acid binding domains in CD33-Related siglecs by adjacent pseudogenes: A novel mechanism to change sialic acid binding specificity. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. Natl Inst Adv Ind Sci & Technol, Tsukuba, Ibaraki, Japan. NHGRI, NIH, Intramural Sequencing Ctr, Bethesda, MD 20892 USA. Broad Inst, Cambridge, MA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2004 VL 104 IS 11 MA 1471 BP 411A EP 411A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127501474 ER PT J AU Gallagher, PG Nilson, DG Lin, J Bodine, DM AF Gallagher, PG Nilson, DG Lin, J Bodine, DM TI Sequences downstream of the erythroid promoter promote high-level expression of the human alpha-spectrin gene by providing boundary activity and positive regulatory elements SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Yale Univ, New Haven, CT USA. NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 1572 BP 438A EP 438A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127501574 ER PT J AU Takemoto, CM Shahlaee, AH Ye, Y Zeller, KI Zablocki, D Huynh, J Huang, SM DeKoter, RP Jegga, AG Aronow, BJ Dang, CV McDevitt, MA AF Takemoto, CM Shahlaee, AH Ye, Y Zeller, KI Zablocki, D Huynh, J Huang, SM DeKoter, RP Jegga, AG Aronow, BJ Dang, CV McDevitt, MA TI Transcriptional regulation of a distinct GATA-1 isoform during selection of the mast and erythroid lineages. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Johns Hopkins Univ, Baltimore, MD USA. Univ Florida, Gainesville, FL USA. NIH, Mol Biol Lab, Bethesda, MD 20892 USA. Univ Cincinnati, Cincinnati, OH USA. RI DeKoter, Rodney/A-9415-2009; Aronow, Bruce/F-8438-2012 OI DeKoter, Rodney/0000-0002-9201-1983; NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 1600 BP 445A EP 446A PN 1 PG 2 WC Hematology SC Hematology GA 871JM UT WOS:000225127501602 ER PT J AU Gallagher, PG Pilon, AM Arcasoy, MO Bodine, DM AF Gallagher, PG Pilon, AM Arcasoy, MO Bodine, DM TI Multiple defects in erythroid gene expression in erythroid krupple-like factor (EKLF) target genes in EKLF-deficient mice. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Yale Univ, New Haven, CT USA. NHGRI, NIH, GMBB, Bethesda, MD 20892 USA. Duke Univ, Durham, NC USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 1602 BP 446A EP 446A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127501604 ER PT J AU Suh, HC Gooya, J Renn, K Friedman, A Johnson, P Keller, J AF Suh, HC Gooya, J Renn, K Friedman, A Johnson, P Keller, J TI CCAAT enhancer binding protein-alpha (C/EBP alpha) determines myeloid versus erythroid cell fate in multipotential progenitors. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NCI, BRP, SAIC Frederick Inc, Frederick, MD 21701 USA. Johns Hopkins Univ, Div Pediat Oncol, Baltimore, MD USA. NCI, LPDS, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 1603 BP 446A EP 446A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127501605 ER PT J AU Ershler, WB Shan, S McKelvey, J Artz, AS Denduluri, N Tecson, J Taub, DD Brant, L Ferrucci, L Longo, DL AF Ershler, WB Shan, S McKelvey, J Artz, AS Denduluri, N Tecson, J Taub, DD Brant, L Ferrucci, L Longo, DL TI Serum erythropoietin and aging: A longitudinal analysis. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Inst Adv Studies Aging, Washington, DC USA. NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 1628 BP 452A EP 452A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127501630 ER PT J AU Cesari, M Pahor, M Lauretani, F Penninx, BWHJ Bartali, B Russo, R Cherubini, A Woodman, RC Bandinelli, S Guralnik, JM Ferrucci, L AF Cesari, M Pahor, M Lauretani, F Penninx, BWHJ Bartali, B Russo, R Cherubini, A Woodman, RC Bandinelli, S Guralnik, JM Ferrucci, L TI Hemoglobin levels and bone density in older persons: Results from the Inchianti study. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Wake Forest Univ, Sch Med, Sticht Ctr Aging, Winston Salem, NC 27109 USA. INRCA, Dept Geriatr, Lab Clin Epidemiol, Florence, Italy. Vrije Univ Amsterdam, Dept Psychiat, Amsterdam, Netherlands. Univ Perugia, Dept Gerontol & Geriatr, I-06100 Perugia, Italy. Ortho Biotech Clin Affairs LLC, Bridgewater, NJ USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. NIA, Longitudinal Studies Sect, Clin Branch Res, Baltimore, MD 21224 USA. RI Cesari, Matteo/A-4649-2008 OI Cesari, Matteo/0000-0002-0348-3664 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 1630 BP 453A EP 453A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127501632 ER PT J AU Ferrucci, L Guralnik, JM Woodman, RC Bandinelli, S Lauretani, F Corsi, A Chaves, PHM Ershler, WB Longo, DL AF Ferrucci, L Guralnik, JM Woodman, RC Bandinelli, S Lauretani, F Corsi, A Chaves, PHM Ershler, WB Longo, DL TI Circulating erythropoietin (EPO) and pro-inflammatory markers in elderly (>/=65) persons with and without anemia. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Ortho Biotech Clin Affairs LLC, Bridgewater, NJ USA. NIA, Intramural Res Program, Baltimore, MD 21224 USA. NIA, Lab Epidemiol Demog & Biometry, Baltimore, MD 21224 USA. INRCA, Lab Clin Epidemiol, Florence, Italy. Johns Hopkins Univ, Ctr Aging & Hlth, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 1629 BP 453A EP 453A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127501631 ER PT J AU Bishop, MR Dean, RM Wilson, WH Odom, J Steinberg, S Krumlauf, M Sportes, CK Pavletic, SZ Castro, K Chinn, T Gress, R Fowler, DH AF Bishop, MR Dean, RM Wilson, WH Odom, J Steinberg, S Krumlauf, M Sportes, CK Pavletic, SZ Castro, K Chinn, T Gress, R Fowler, DH TI Immunotherapy and chemotherapy can result in long-term survival for patients with recurrent or progressive non-Hodgkin's lymphoma after reduced-intensity allogeneic stem cell transplantation. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 1643 BP 457A EP 457A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127501645 ER PT J AU Kato, GJ Martyr, S Machado, R Sachdev, V Ernst, I Hunter, L Coles, W Nichols, J Hunter, CJ Gladwin, MT AF Kato, GJ Martyr, S Machado, R Sachdev, V Ernst, I Hunter, L Coles, W Nichols, J Hunter, CJ Gladwin, MT TI Acute on chronic pulmonary hypertension in patients with sickle cell disease. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NIH, Vasc Therapeut Sect, Cardiovasc Branch, Bethesda, MD USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 1669 BP 464A EP 464A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127501671 ER PT J AU Wu, CJ Gladwin, MT Krishnamurti, L Biernacki, M Rogers, SA Wang, XD Antin, JH Ritz, J AF Wu, CJ Gladwin, MT Krishnamurti, L Biernacki, M Rogers, SA Wang, XD Antin, JH Ritz, J TI Mixed chimerism following nonmyeloablative stem cell transplantation for sickle cell disease prevents intravascular hemolysis and restores endothelial function. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Childrens Hosp Pittsburgh, Div Hematol Oncol, Pittsburgh, PA 15213 USA. Childrens Hosp Pittsburgh, BMT, Pittsburgh, PA 15213 USA. NHLBI, Vasc Therapeut Sect, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 1679 BP 467A EP 467A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127501681 ER PT J AU Klarmann, K Gough, D Asefa, B Clarke, C Renn, K Johnstone, R Keller, J AF Klarmann, K Gough, D Asefa, B Clarke, C Renn, K Johnstone, R Keller, J TI Growth suppressors IFI-204 and IFI-205 inhibit primitive hematopoietic cell proliferation in vitro and in vivo SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NCI, Mol Immunoregulat Lab, Frederick, MD 21701 USA. SAIC Frederick, BRP, Frederick, MD USA. Peter MacCallum Canc Inst, Gene Regulat Lab, Melbourne, Vic 3000, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 1691 BP 470A EP 470A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127501693 ER PT J AU English, MA Lei, L Giannetti, M Lyons, SE Liu, PP AF English, MA Lei, L Giannetti, M Lyons, SE Liu, PP TI A genetic screen for zebrafish mutants affecting early hematopoiesis SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHGRI, NIH, Bethesda, MD 20892 USA. Univ Michigan, Dept Internal Med, Div Hematol Oncol, Ann Arbor, MI 48109 USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 1702 BP 473A EP 473A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127501704 ER PT J AU Dean, RM Fowler, DH Hakim, FT Odom, J Castro, K Chinn, T Wilson, WH Gress, RE Bishop, MR AF Dean, RM Fowler, DH Hakim, FT Odom, J Castro, K Chinn, T Wilson, WH Gress, RE Bishop, MR TI Immunoablative chemotherapy before reduced-intensity allogeneic stem cell transplantation: A strategy to provide disease control and to enhance early graft-versus-lymphoma effects. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NCI, Expt Transplant & Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 1829 BP 506A EP 507A PN 1 PG 2 WC Hematology SC Hematology GA 871JM UT WOS:000225127501830 ER PT J AU Savani, B Montero, A Gochiuo, B Nlonda, N Childs, R Solomon, S Barrett, J AF Savani, B Montero, A Gochiuo, B Nlonda, N Childs, R Solomon, S Barrett, J TI Prediction and prevention of transplant related mortality from pulmonary causes following total body irradiation and allogeneic stem cell transplantation. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, Stem Cell Allotransplantat, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 1836 BP 508A EP 509A PN 1 PG 2 WC Hematology SC Hematology GA 871JM UT WOS:000225127501837 ER PT J AU Bernig, T Burdette, L Lehrnbecher, T Graubner, UB den Boer, ML Pieters, R Janka-Schaub, GE Chanock, SJ AF Bernig, T Burdette, L Lehrnbecher, T Graubner, UB den Boer, ML Pieters, R Janka-Schaub, GE Chanock, SJ TI Germ-line genetic variations in TP53 and risk for pediatric acute lymphoblastic leukemia. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NCI, Sect Genom Variat, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Core Genotyping Facil, NIH, Bethesda, MD 20892 USA. Childrens Univ Hosp 3, Frankfurt, Germany. Univ Munich, Dr Von Haunerschen Kinderspital, D-80337 Munich, Germany. Sophia Childrens Univ Hosp, Rotterdam, Netherlands. Childrens Univ Hosp, Hamburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 1890 BP 523A EP 524A PN 1 PG 2 WC Hematology SC Hematology GA 871JM UT WOS:000225127501891 ER PT J AU Varga, T Aplan, PD AF Varga, T Aplan, PD TI Chromosomal rearrangements induced by DNA double-strand breaks. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. RI Aplan, Peter/K-9064-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 1965 BP 542A EP 542A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127501966 ER PT J AU Gurevich, RM Aplan, PD Humphries, RK AF Gurevich, RM Aplan, PD Humphries, RK TI Generation of a pre-leukemic, transplantable cell line from the AML-Associated NUP98-TOP1 fusion gene as a new model to test potential collaborating genes. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NCI, CCR, Genet Branch, NIH, Bethesda, MD 20892 USA. BC Canc Agcy, Terry Fox LAb, Vancouver, BC, Canada. RI Aplan, Peter/K-9064-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 1969 BP 543A EP 544A PN 1 PG 2 WC Hematology SC Hematology GA 871JM UT WOS:000225127501970 ER PT J AU Kolaris, CP Liu, ML Foote, K Aplan, PD Ahuja, HG Osheroff, N Felix, CA AF Kolaris, CP Liu, ML Foote, K Aplan, PD Ahuja, HG Osheroff, N Felix, CA TI NUP98 translocation breakpoints in treatment-related MDS are drug-stimulated DNA topoisomerase II cleavage sites. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. Natl Canc Inst, Gaithersburg, MD USA. Univ Wisconsin, Ctr Canc, Wausau, WI USA. RI Aplan, Peter/K-9064-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 1970 BP 544A EP 544A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127501971 ER PT J AU Pearce, CL Mack, WJ Levine, AM Gravink, J Cohen, MH Machtinger, EL Anastos, K Silverberg, MJ Young, MA Minkoff, H Watts, DH AF Pearce, CL Mack, WJ Levine, AM Gravink, J Cohen, MH Machtinger, EL Anastos, K Silverberg, MJ Young, MA Minkoff, H Watts, DH TI Thrombocytopenia is a strong predictor of all-cause and AIDS-specific mortality in women with HIV: The women's interagency HIV study. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 USC, Keck Sch Med, Med Div Hematol, Los Angeles, CA USA. Cook Cty Hosp, Chicago, IL 60612 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Johns Hopkins Univ, Baltimore, MD USA. Georgetown Univ, Ctr Med, Washington, DC USA. Suny Downstate Med Ctr, Maimonides Med Ctr, Brooklyn, NY 11203 USA. NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 2068 BP 569A EP 570A PN 1 PG 2 WC Hematology SC Hematology GA 871JM UT WOS:000225127502069 ER PT J AU Chandra, J Tracy, J Gorre, M Talpaz, M Griffin, J Verstovsek, S Beran, M Sawyers, C Sausville, E Kaufmann, S AF Chandra, J Tracy, J Gorre, M Talpaz, M Griffin, J Verstovsek, S Beran, M Sawyers, C Sausville, E Kaufmann, S TI Effects of adaphostin, a novel tyrphostin inhibitor, in diverse models of imatinib mesylate resistance. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 MD Anderson Canc Ctr, Dept Pediat Res, Houston, TX USA. MD Anderson Canc Ctr, Dept Leukemia, Houston, TX USA. Univ Calif Los Angeles, Div Hematol Oncol, Los Angeles, CA USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NCI, Dev Therapeut Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. Mayo Clin, Div Oncol Res & Hematol, Rochester, MN USA. RI Sawyers, Charles/G-5327-2016 NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 2097 BP 577A EP 577A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127502098 ER PT J AU Pule, MA Rousseau, A Kang, E Ueda, T von Kalle, C Nienhuis, AW Heslop, H Vanin, E Tisdale, JF AF Pule, MA Rousseau, A Kang, E Ueda, T von Kalle, C Nienhuis, AW Heslop, H Vanin, E Tisdale, JF TI Multiple integration events into several putative oncogenes was required to cause leukemogenesis in two primate recipients of RCR contaminated stem-cells. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. NIDDK, NIH, Mol & Clin Hematol Branch, Bethesda, MD USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 2102 BP 578A EP 578A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127502103 ER PT J AU Bozorgmehr, F Bus, EC Laufs, S Nagy, KZ Sellers, S Zeller, WJ Dunbar, CE Fruehauf, S AF Bozorgmehr, F Bus, EC Laufs, S Nagy, KZ Sellers, S Zeller, WJ Dunbar, CE Fruehauf, S TI New aspects on the safety of multidrug-resistance 1 gene transfers: No indication for clonal dominance after long-term follow-up in a primate transplantation model. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 German Canc Res Ctr, Res Program Innovat Canc Diag & Therapy, D-6900 Heidelberg, Germany. Univ Heidelberg, Dept Internal Med 5, Heidelberg, Germany. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 2108 BP 580A EP 580A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127502109 ER PT J AU Laufs, S Giordano, F Lauterborn, D Nagy, KZ Fellemberg, K Hotz-Wagenblatt, A Guenechea, G Fehse, B Bueren, JB Zander, A Dunbar, CE Zeller, WJ Fruehauf, S AF Laufs, S Giordano, F Lauterborn, D Nagy, KZ Fellemberg, K Hotz-Wagenblatt, A Guenechea, G Fehse, B Bueren, JB Zander, A Dunbar, CE Zeller, WJ Fruehauf, S TI Collaborative RISC-score database: Creation of an international database for retroviral integration analysis. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 German Canc Res Ctr, HUSAR Bioinformat Lab, D-6900 Heidelberg, Germany. German Canc Res Ctr, Dept Funct Genome Anal, D-6900 Heidelberg, Germany. CIEMAT, Marcelino Botin Fdn, Hematopoiet Gene Therapy Program, E-28040 Madrid, Spain. Univ Hamburg Hosp, D-2000 Hamburg, Germany. NHGRI, NIH, Genome Technol Branch, Bethesda, MD 20892 USA. Univ Heidelberg, Dept Internal Med 5, Heidelberg, Germany. RI Fehse, Boris/A-8721-2012; Guenechea, Guillermo/L-6119-2014; Bueren, Juan/L-6112-2014 OI Guenechea, Guillermo/0000-0001-7679-0895; Bueren, Juan/0000-0002-3228-7013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 2110 BP 580A EP 580A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127502111 ER PT J AU Gu, YC Bauer, TR Tuschong, LM Sokolic, RA Donahue, RE Hickstein, DD AF Gu, YC Bauer, TR Tuschong, LM Sokolic, RA Donahue, RE Hickstein, DD TI Correction of the phenotype in canine leukocyte adhesion deficiency following non-myeloablative, matched littermate transplant. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. RI Sokolic, Robert/I-6072-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 2143 BP 589A EP 590A PN 1 PG 2 WC Hematology SC Hematology GA 871JM UT WOS:000225127502144 ER PT J AU Aerbajinai, WL Natarajan, BV Gantt, N Oneal, P Goh, SH Lee, YT Miller, JL AF Aerbajinai, WL Natarajan, BV Gantt, N Oneal, P Goh, SH Lee, YT Miller, JL TI Adenosine signaling regulates adult erythropoiesis. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NIDDKD, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 2171 BP 597A EP 597A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127502172 ER PT J AU Karlsson, G Liu, YC Goumans, MJ Larsson, J Lee, JS Thorgeirsson, SS Ringner, M Karlsson, S AF Karlsson, G Liu, YC Goumans, MJ Larsson, J Lee, JS Thorgeirsson, SS Ringner, M Karlsson, S TI Global gene expression analysis demonstrates that transforming growth factor beta 1 (TGF-beta 1) signals exclusively through receptor complexes involving TGF-beta receptor I and identifies numerous targets of TGF-beta signaling SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Univ Lund Hosp, S-22185 Lund, Sweden. Lund Univ, Div Complex Syst, Lund, Sweden. Netherlands Canc Inst, Div Cellular Biochem, NL-1066 CX Amsterdam, Netherlands. NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 2178 BP 598A EP 598A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127502179 ER PT J AU Aliyu, ZY Bordner, MA Henderson, DK Sloand, EM Young, NS Childs, R Bennett, J Barrett, J AF Aliyu, ZY Bordner, MA Henderson, DK Sloand, EM Young, NS Childs, R Bennett, J Barrett, J TI Low morbidity but prolonged viral shedding characterize parainfluenza virus 3 infections in allogeneic peripheral stem cell transplant recipients. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Off Director, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 2234 BP 614A EP 614A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127502235 ER PT J AU Lee, A Davies, A Clear, A Calaminici, M Matthews, J Norton, A Wright, G Staudt, LM Fitzgibbon, J Lister, TA Goff, L AF Lee, A Davies, A Clear, A Calaminici, M Matthews, J Norton, A Wright, G Staudt, LM Fitzgibbon, J Lister, TA Goff, L TI Tissue microarray is a useful tool in the evaluation of genes implicated in transformation of follicular lymphoma. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 St Bartholomews Hosp, Dept Histopathol, London, England. St Bartholomews Hosp, Canc Res UK, London, England. NCI, Lymphoid Malignacies Sect, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 2267 BP 624A EP 624A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127502268 ER PT J AU Solomon, SR Childs, R Montero, A Sloand, E Wisch, L Wehrlen, L Barrett, J AF Solomon, SR Childs, R Montero, A Sloand, E Wisch, L Wehrlen, L Barrett, J TI Improved outcomes for peripheral blood stem cell transplantation in advanced myelodysplastic syndrome . SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 2304 BP 633A EP 634A PN 1 PG 2 WC Hematology SC Hematology GA 871JM UT WOS:000225127502305 ER PT J AU Badros, AZ Goloubeva, O Ratterree, B Natt, S Rapoport, A Bolanos-Meade, J Zhang, B Zeldis, J Frankel, S Meisenberg, B Zwiebel, J Flaws, J Tomic, D Fenton, R AF Badros, AZ Goloubeva, O Ratterree, B Natt, S Rapoport, A Bolanos-Meade, J Zhang, B Zeldis, J Frankel, S Meisenberg, B Zwiebel, J Flaws, J Tomic, D Fenton, R TI Phase II trial of oblimersen sodium (G3139), dexamethasone (Dex) and thalidomide (Thai) in relapsed multiple myeloma patients (Pts) SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. NCI, CTEP, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 2400 BP 659A EP 660A PN 1 PG 2 WC Hematology SC Hematology GA 871JM UT WOS:000225127502400 ER PT J AU Kumar, S Raje, N Hideshima, T Ishitsuka, K Roccaro, A Shiraishi, N Hamasaki, M Yasui, H Munshi, NC Figg, WD Anderson, KC AF Kumar, S Raje, N Hideshima, T Ishitsuka, K Roccaro, A Shiraishi, N Hamasaki, M Yasui, H Munshi, NC Figg, WD Anderson, KC TI Anti-myeloma activity of two novel N-substituted and tetraflourinated thalidomide analogues SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. NCI, Mol Pharmacol Sect, Canc Therapeut Branch, NIH, Bethesda, MD 20892 USA. RI Kumar, Shaji/A-9853-2008; Figg Sr, William/M-2411-2016 OI Kumar, Shaji/0000-0001-5392-9284; NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 2406 BP 661A EP 661A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127502406 ER PT J AU Lemery, SJ Robyn, JA McCoy, JP Kubofcik, J Kim, YJ Nutman, TB Dunbar, CE Klion, AD AF Lemery, SJ Robyn, JA McCoy, JP Kubofcik, J Kim, YJ Nutman, TB Dunbar, CE Klion, AD TI Lineage analysis of the FIPL1-PDGFR alpha fusion gene in myeloproliferative hypereosinophilic syndrome SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 2441 BP 670A EP 671A PN 1 PG 2 WC Hematology SC Hematology GA 871JM UT WOS:000225127502441 ER PT J AU Lin, TS Fischer, B Moran, ME Lucas, DM Shank, RS Kraut, EH Farag, SS Lucas, MS Colevas, AD Grever, MR Byrd, JC AF Lin, TS Fischer, B Moran, ME Lucas, DM Shank, RS Kraut, EH Farag, SS Lucas, MS Colevas, AD Grever, MR Byrd, JC TI Phase I dose escalation study of flavopiridol in combination with fludarabine and rituximab: Activity in indolent B-cell lymphoproliferative disorders and mantle cell lymphoma. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Ohio State Univ, Coll Med, Columbus, OH 43210 USA. Natl Canc Inst, Canc Therapy Evaluat Program, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 2492 BP 683A EP 684A PN 1 PG 2 WC Hematology SC Hematology GA 871JM UT WOS:000225127502492 ER PT J AU Palena, C McIntosh, L Schlom, J Foon, K Panicali, D Tsang, KY AF Palena, C McIntosh, L Schlom, J Foon, K Panicali, D Tsang, KY TI Modification of B-CLL cells via infection with a replication-defective MVA virus encoding three costimulatory molecules: A potential approach to tumor cell immunotherapy of B-CLL. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Ctr Canc Res, Tumor Immunol & Biol Lab, NCI, NIH, Bethesda, MD USA. Univ Pittsburgh, Inst Canc, Div Hematol Oncol, UPMC, Pittsburgh, PA USA. Therion Biol, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 2516 BP 690A EP 690A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127502516 ER PT J AU Rezvani, K Brenchley, J Price, D Kilical, Y Grube, M Gostick, E Tang, Y Sconocchia, G Fujiwara, H Sloand, E Douek, DC Barrett, J AF Rezvani, K Brenchley, J Price, D Kilical, Y Grube, M Gostick, E Tang, Y Sconocchia, G Fujiwara, H Sloand, E Douek, DC Barrett, J TI T cell responses directed against HLA A*0201-restricted epitopes derived from WT1 are readily identifiable in patients with AML and CML, but not in patients with ALL. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. Nuffield Dept Med, Oxford, England. RI Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 2526 BP 692A EP 693A PN 1 PG 2 WC Hematology SC Hematology GA 871JM UT WOS:000225127502526 ER PT J AU Rezvani, K Tawab, A Kilical, Y Sconocchia, G Li, JM Hensel, N Kurlander, R Barrett, J AF Rezvani, K Tawab, A Kilical, Y Sconocchia, G Li, JM Hensel, N Kurlander, R Barrett, J TI PRAME-specific CD8+ T cells are spontaneously present in a large proportion of healthy donors and leukemic HLA-A0201 patients. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Lab Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 2535 BP 695A EP 695A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127502535 ER PT J AU Tawab, A Takahashi, Y Richard, C Roger, KJ AF Tawab, A Takahashi, Y Richard, C Roger, KJ TI Cultured human B cell APCs expanded using IL-4 and CD40 ligand preferentially promote a type 2 T cell response to alloimmune stimulation SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Natl Inst Hlth, Dept Lab Med, Ctr Clin, Bethesda, MD USA. NHLBI, Natl Inst Hlth, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 2668 BP 729A EP 729A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127502668 ER PT J AU Adler, RL Hematti, P Calmels, B Ferguson, CJ Keyvanfar, K Wu, C Follmann, D Dunbar, CE AF Adler, RL Hematti, P Calmels, B Ferguson, CJ Keyvanfar, K Wu, C Follmann, D Dunbar, CE TI Analysis of clonal contributions to T lymphoid and myeloid lineages during early hematopoiesis following autologous transplantation in the rhesus macaque SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, NIH, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. RI calmels, boris/R-2538-2016 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 2672 BP 730A EP 730A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127502672 ER PT J AU Larochelle, A Krouse, A Orlic, D Donahue, RE Dunbar, CE Hematti, P AF Larochelle, A Krouse, A Orlic, D Donahue, RE Dunbar, CE Hematti, P TI AMD3100-mobilized CD34+ cells are phenotypically different and better targets for retroviral transduction than G-CSF-mobilized CD34+ cells in rhesus macaques SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, NIH, Bethesda, MD 20892 USA. NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 2686 BP 733A EP 733A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127502686 ER PT J AU Bolan, CD Yau, YY Kim, CS Celi, FS Leitman, SF AF Bolan, CD Yau, YY Kim, CS Celi, FS Leitman, SF TI Prevalence and clinical impact of abnormal thyroid function tests (TFTs) in hereditary hemochromatosis (HH). SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. Walter Reed Army Inst Res, Headquarters Co, Silver Spring, MD USA. NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 2724 BP 744A EP 744A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127502725 ER PT J AU Issaragrisil, S Kaufman, DW Anderson, TE Chansung, K Leaverton, P Shapiro, S Young, NS AF Issaragrisil, S Kaufman, DW Anderson, TE Chansung, K Leaverton, P Shapiro, S Young, NS TI Final results of the Thai-NHLBI epidemiological study of aplastic anemia. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Mahidol Univ, Sirriraj Hosp, Dept Med, Bangkok 10700, Thailand. Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. Khon Kaen Univ, Dept Med, Khon Kaen, Thailand. Univ S Florida, Sch Publ Hlth, Tampa, FL USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 2814 BP 770A EP 770A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127502815 ER PT J AU Kalmadi, SR Wu, R Plasilova, M Sloand, E Galili, N Raza, A Maciejewski, JP AF Kalmadi, SR Wu, R Plasilova, M Sloand, E Galili, N Raza, A Maciejewski, JP TI A pilot application of SELDI serum proteomics in bone marrow failure syndromes. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA. NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA. Rush Univ, Ctr Med, Myeloid Dis & MDS Ctr, Chicago, IL 60612 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 2822 BP 772A EP 772A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127502823 ER PT J AU Ly, H Calado, RT Allard, PA Baerlocher, GM Lansdorp, PM Young, NS Parslow, TG AF Ly, H Calado, RT Allard, PA Baerlocher, GM Lansdorp, PM Young, NS Parslow, TG TI Functional characterization of telomerase RNA variants found in patients with hematological disorders. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Emory Univ, Atlanta, GA 30322 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Univ British Columbia, Terry Fox Lab, Vancouver, BC V5Z 1M9, Canada. RI Calado, Rodrigo/G-2619-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 2832 BP 774A EP 774A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127502833 ER PT J AU Chakrabarti, S Takahashi, Y Read, EJ Khuu, H Goodwin, R Leitman, S Bolan, CD Srinivasan, R Barrett, AJ Calandra, G Childs, R AF Chakrabarti, S Takahashi, Y Read, EJ Khuu, H Goodwin, R Leitman, S Bolan, CD Srinivasan, R Barrett, AJ Calandra, G Childs, R TI Comparison of Apheresis cell content collected from the same donors mobilized with granulocyte colony stimulating factor (G-CSF) vs. a single injection of AMD3100. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 2853 BP 780A EP 780A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127502854 ER PT J AU Provenzano, M Mocellin, S Marincola, FM Stroncek, DF AF Provenzano, M Mocellin, S Marincola, FM Stroncek, DF TI The use of algorithms with a novel score standardization method for the selection of candidate immunogenic HLA-specific peptides led to the identification of new immunogenic HLA-A*0201 cytomegalovirus epitopes. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NIH, Mol Immunol Sect, Dept Transfus Med, Bethesda, MD 20892 USA. NIH, Immunogenet Sect, Dept Transfus Med, Bethesda, MD 20892 USA. Univ Padua, Surg Branch, Dept Oncol & Surg Sci, Padua, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 2862 BP 782A EP 783A PN 1 PG 2 WC Hematology SC Hematology GA 871JM UT WOS:000225127502863 ER PT J AU Ghei, M Stroncek, DF Provenzano, M AF Ghei, M Stroncek, DF Provenzano, M TI Analysis of memory T lymphocytes activity following stimulation with HLA-A24, A1 and Cw4 restricted 9-and 10-mer cytomegalovirus pp65 overlapping peptides. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NIH, Mol Immunol Sect, DTM, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 2876 BP 786A EP 786A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127502877 ER PT J AU Arcasoy, MO Hanlon, P Fu, P Steenbergen, C Murphy, E AF Arcasoy, MO Hanlon, P Fu, P Steenbergen, C Murphy, E TI Mechanisms of erythropoietin-mediated cardioprotection during ischemia-reperfusion injury: Role of protein kinase C signaling. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Duke Univ, Ctr Med, Durham, NC USA. Natl Inst Environm Hlth Sci, Lab Signal Transduct, Res Triangle Pk, NC USA. Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 2907 BP 794A EP 795A PN 1 PG 2 WC Hematology SC Hematology GA 871JM UT WOS:000225127502908 ER PT J AU Sconocchia, G Lau, M Provenzano, M Rezvani, K Fujiwara, H Ferrone, S Barrett, J AF Sconocchia, G Lau, M Provenzano, M Rezvani, K Fujiwara, H Ferrone, S Barrett, J TI The antileukemic effect of NK and NK-T cells against chronic myelogenous leukemia is dominated by interactions between activating molecules and their ligands which overcome inhibitory KIR-MHC class I interaction. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. Roswell Pk Canc Inst, Dept Immunol, Buffalo, NY 14263 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 2948 BP 806A EP 806A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127502949 ER PT J AU Rezvani, K Price, DA Brenchley, J Kilical, Y Gostick, E Sewell, AK Sconocchia, G Kurlander, R Douek, DC Barrett, J AF Rezvani, K Price, DA Brenchley, J Kilical, Y Gostick, E Sewell, AK Sconocchia, G Kurlander, R Douek, DC Barrett, J TI Transfer of specific T cell clones with graft-versus-leukemia (GVL) activity from donor to recipient in stem cell transplantation: Identification, quantification and characterization. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. Nuffield Dept Med, Oxford, England. NIH, Dept Lab Med, Warren Grant Magnuson Clin Ctr, 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 AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 2958 BP 808A EP 808A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127502959 ER PT J AU Sokolic, RA Gu, YC Burkholder, T Tuschong, LM Hai, M Bauer, TR Hickstein, DD AF Sokolic, RA Gu, YC Burkholder, T Tuschong, LM Hai, M Bauer, TR Hickstein, DD TI Non-myeloablative conditioning with busulfan prior to allogeneic hematopoietic stem cell transplant results in mixed chimerism and reversal of the phenotype in canine leukocyte adhesion deficiency with minimal regimen related toxicity and without graft-vs.-host disease. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NIH, Vet Med Branch, Bethesda, MD 20892 USA. RI Sokolic, Robert/I-6072-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 3064 BP 837A EP 837A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127503065 ER PT J AU Dunleavy, K Little, R Gea-Banacloche, J Grant, N Steinberg, S Yarchoan, R Pittaluga, S Jaffe, E Janik, J Wilson, WH AF Dunleavy, K Little, R Gea-Banacloche, J Grant, N Steinberg, S Yarchoan, R Pittaluga, S Jaffe, E Janik, J Wilson, WH TI Abbreviated treatment with short-course dose-adjusted EPOCH and rituximab (DA-EPOCH-R) is highly effective in AIDS-related lymphoma (ARL). SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 3111 BP 850A EP 850A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127503113 ER PT J AU Hai, MH Bauer, TR Gu, YC Tuschong, LM Sokolic, RA Hickstein, DD AF Hai, MH Bauer, TR Gu, YC Tuschong, LM Sokolic, RA Hickstein, DD TI Retroviral-mediated gene transfer of CD18 into hematopoietic stem cells in dogs with canine leukocyte adhesion deficiency reverses the severe deficiency phenotype SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. RI Sokolic, Robert/I-6072-2012 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 3169 BP 866A EP 866A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127503171 ER PT J AU Barton, JC Acton, RT Dawkins, FW Adams, PC Lovato, L Leiendecker-Foster, C McLaren, CE Reboussin, DM Speechley, MR Gordeuk, VR McLaren, GD Sholinsky, P Harris, EL AF Barton, JC Acton, RT Dawkins, FW Adams, PC Lovato, L Leiendecker-Foster, C McLaren, CE Reboussin, DM Speechley, MR Gordeuk, VR McLaren, GD Sholinsky, P Harris, EL TI Initial screening transferrin saturations, serum ferritin concentrations, and HFE genotypes in whites and blacks in the hemochromatosis and iron overload screening (HEIRS) study SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Univ Alabama, Birmingham, AL USA. Howard Univ, Washington, DC 20059 USA. London Hlth Sci Ctr, London, ON, Canada. Wake Forest Univ, Winston Salem, NC 27109 USA. Univ Minnesota, Laab Med & Pathol, Minneapolis, MN 55455 USA. Univ Calif Irvine, Irvine, CA USA. VA Long Beach Healthcare Syst, Long Beach, CA USA. NHLBI, Bethesda, MD 20892 USA. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 3202 BP 874A EP 874A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127503204 ER PT J AU Acton, RT Snively, BM Barton, JC Adams, PC Eckfeldt, JH Harris, EL Dawkins, FW McLaren, CE Gordeuk, VR McLaren, GD Reboussin, DM Sholinsky, P Speechley, MR Holup, J Leienclecker-Foster, C AF Acton, RT Snively, BM Barton, JC Adams, PC Eckfeldt, JH Harris, EL Dawkins, FW McLaren, CE Gordeuk, VR McLaren, GD Reboussin, DM Sholinsky, P Speechley, MR Holup, J Leienclecker-Foster, C TI Geographic and racial/ethnic differences in HFE mutation frequencies and iron phenotypes in the hemochromatosis and iron overload screening (HEIRS) study SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Univ Alabama, Birmingham, AL USA. Wake Forest Univ, Winston Salem, NC 27109 USA. London Hlth Sci Ctr, London, ON, Canada. Univ Minnesota, Minneapolis, MN 55455 USA. Kaiser Permanente, Ctr Hlth Res, Portland, OR USA. Howard Univ, Washington, DC 20059 USA. Univ Calif Irvine, Irvine, CA USA. VA Long Beach Healthcare Syst, Long Beach, CA USA. NHLBI, Bethesda, MD 20892 USA. Kaiser Permanente, Ctr Hlth Res, Honolulu, HI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 3211 BP 877A EP 877A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127503213 ER PT J AU Ogasawara, Y Nakayama, K Tarnowka, M McCoy, JP Molldrem, JJ Levin, BC Kajigaya, S Young, NS AF Ogasawara, Y Nakayama, K Tarnowka, M McCoy, JP Molldrem, JJ Levin, BC Kajigaya, S Young, NS TI Mitochondrial DNA (mtDNA) sequence heterogeneity among and within single human CD34 cells, T cells, B cells and granulocytes SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA. MD Anderson Canc Ctr, Sect Transplant Immunol, Houston, TX 77030 USA. NIST, Div Biotechnol, Chem Sci & Technol Lab, Gaithersburg, MD 20899 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 3217 BP 879A EP 879A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127503219 ER PT J AU Ueda, T Brenner, S Malech, H Langemeijer, S Kirby, M Phang, O Krouse, A Donahue, RE Kang, EM Tisdale, JF AF Ueda, T Brenner, S Malech, H Langemeijer, S Kirby, M Phang, O Krouse, A Donahue, RE Kang, EM Tisdale, JF TI Cloning and functional analysis of the rhesus macaque ABCG2 gene: Forced expression confers an SP phenotype among hematopoietic stem cell progeny in vivo SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD USA. Univ Clin Carl Gustav Carus, Dept Pediat, Dresden, Germany. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RI Brenner, Sebastian/D-7456-2013 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 3219 BP 879A EP 879A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127503221 ER PT J AU Zhao, L Cannons, JL Castilla, LH Schwartzberg, PL Liu, PP AF Zhao, L Cannons, JL Castilla, LH Schwartzberg, PL Liu, PP TI The role of CBF beta in T cell development SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 3234 BP 883A EP 883A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127503236 ER PT J AU El Kassar, N Lucas, PJ Flomerfelt, F Merchant, M Bare, CV Mahmud, S Mackall, CL Bhandoola, A Gress, RE AF El Kassar, N Lucas, PJ Flomerfelt, F Merchant, M Bare, CV Mahmud, S Mackall, CL Bhandoola, A Gress, RE TI Interleukin-7 over-expression regulates T cell versus B cell lineage development in the thymus SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. Estab Francais Sang PL, Fac Med, Angers, France. NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 3238 BP 884A EP 884A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127503240 ER PT J AU Kochenderfer, J Chien, C Gress, R AF Kochenderfer, J Chien, C Gress, R TI Synergism between CpG ODN and IL-2 leads to massive CD8(+) T cell responses against a self-antigen and epitope-specific anti-tumor immunity SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 3239 BP 884A EP 884A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127503241 ER PT J AU Melenhorst, JJ Follmann, D Fujiwara, H Barrett, AJ AF Melenhorst, JJ Follmann, D Fujiwara, H Barrett, AJ TI The spectrum of human T cell receptor (TCR)-V beta frequencies are established prior to thymic selection SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, NIH, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. Kagoshima Univ, Post Grad Sch, Kagoshima 890, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 3240 BP 884A EP 885A PN 1 PG 2 WC Hematology SC Hematology GA 871JM UT WOS:000225127503242 ER PT J AU Pavletic, S Zhou, GM Sobocinski, K Doney, K DiPersio, J Feremans, W Foroni, L Prentice, HG LeMaistre, C Bandini, G Ferrant, A Jacobsen, N Khouri, I Gale, RP Giralt, S Montserrat, E Chan, J Bredeson, C AF Pavletic, S Zhou, GM Sobocinski, K Doney, K DiPersio, J Feremans, W Foroni, L Prentice, HG LeMaistre, C Bandini, G Ferrant, A Jacobsen, N Khouri, I Gale, RP Giralt, S Montserrat, E Chan, J Bredeson, C TI Identical-twin transplants for B-cell chronic lymphocytic leukemia (B-CLL). SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NCI, ETIB, Bethesda, MD 20892 USA. Univ Nebraska, Ctr Med, Omaha, NE 68198 USA. Med Coll Wisconsin, CIBMTR, Milwaukee, WI 53226 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Washington Univ, Sch Med, St Louis, MO USA. Erasme Univ Hosp, B-1070 Brussels, Belgium. Royal Free Hosp, London NW3 2QG, England. London Clin, London, England. Texas Transplant Inst, San Antonio, TX USA. St Orsola Hosp, Bologna, Italy. Clin Univ St Luc, B-1200 Brussels, Belgium. Univ Copenhagen, Rigshosp, DK-2100 Copenhagen, Denmark. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Ctr Adv Studies Leuk, Los Angeles, CA USA. Hosp Clin Barcelona, E-08036 Barcelona, Spain. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 3330 BP 909A EP 910A PN 1 PG 2 WC Hematology SC Hematology GA 871JM UT WOS:000225127503332 ER PT J AU Savani, B Kurlander, R Read, E Leitman, S Nlonda, N Young, N Childs, R Solomon, S Barrett, J AF Savani, B Kurlander, R Read, E Leitman, S Nlonda, N Young, N Childs, R Solomon, S Barrett, J TI The post-transplant day 30 lymphocyte count strongly correlates with transplanted Cd34 dose and is predictive for minimal residual disease and mortality in patients with Cml undergoing allogeneic stem cell transplants from matched siblings. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 3335 BP 911A EP 912A PN 1 PG 2 WC Hematology SC Hematology GA 871JM UT WOS:000225127503337 ER PT J AU Neelapu, SS Munshi, NC Jagannath, S Watson, TM Pennington, R Barlogie, B Kwak, LW AF Neelapu, SS Munshi, NC Jagannath, S Watson, TM Pennington, R Barlogie, B Kwak, LW TI Tumor antigen immunization of sibling stem cell transplant donors in multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. St Vincents Catholic Med Ctr, New York, NY USA. NCI, Expt & Transplantat Immunol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC, Frederick, MD USA. Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 3340 BP 913A EP 913A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127503342 ER PT J AU Shami, PJ Kaur, G Thillainathan, J Jia, L Saavedra, JE Keefer, LK AF Shami, PJ Kaur, G Thillainathan, J Jia, L Saavedra, JE Keefer, LK TI JS-K, a novel nitric oxide (NO) generator, shows potent anti-angiogenic activity. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Univ Utah, Salt Lake City, UT USA. NCI, NIH, Frederick, MD 21701 USA. NCI, NIH, Rockville, MD USA. SAIC, Frederick, MD USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 3414 BP 931A EP 931A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127503416 ER PT J AU Shami, PJ Udupi V Yu, M Malaviya, S Saavedra, JE Keefer, LK AF Shami, PJ Udupi, V Yu, M Malaviya, S Saavedra, JE Keefer, LK TI JS-K, a novel nitric oxide (NO) generator, induces cytochrome c release and caspase activation in HL-60 myeloid leukemia cells. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Univ Utah, Salt Lake City, UT USA. SAIC, Frederick, MD USA. NCI, NIH, Frederick, MD USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 3415 BP 931A EP 931A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127503417 ER PT J AU Kundu, M Compton, S Garrett, L Stacy, T Starost, M Eckhaus, M Speck, NA Liu, PP AF Kundu, M Compton, S Garrett, L Stacy, T Starost, M Eckhaus, M Speck, NA Liu, PP TI RUNX1 deficiency predisposes mice to T-cell lymphoblastic lymphoma. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NHGRI, GMBB, NIH, Bethesda, MD 20892 USA. NHGRI, GDRB, NIH, Bethesda, MD 20892 USA. Dartmouth Coll Sch Med, Dept Biochem, Hanover, NH USA. NIH, Natl Ctr Res Resources, Vet Resources Program, Bethesda, MD 20892 USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 3490 BP 951A EP 951A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127503492 ER PT J AU Dave, UP Akagi, K Dupuy, A Suzuki, T Jenkins, NA Copeland, NG AF Dave, UP Akagi, K Dupuy, A Suzuki, T Jenkins, NA Copeland, NG TI Proviral tagging combined with human microarray data reveals genes and pathways that cooperate in disease induction. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NCI, Mouse Canc Genet Program, Frederick, MD 21701 USA. Kyoto Univ, Grad Sch Med, HMRO, Canc Genet Unit, Kyoto, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 3492 BP 952A EP 952A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127503493 ER PT J AU Simak, J Gelderman, MP Yu, H Wright, V Alberts-Grill, N Stranix, JT Baird, AE AF Simak, J Gelderman, MP Yu, H Wright, V Alberts-Grill, N Stranix, JT Baird, AE TI Elevated circulating endothelial microparticles in acute stroke patients: A correlation with brain lesion volume and outcome. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 US FDA, Ctr Biol Evaluat & Res, Lab Celllular Hematol, Rockville, MD 20857 USA. NINDS, Struct Neurosci Unit, NIH, Bethesda, MD 20892 USA. RI Simak, Jan/C-1153-2011 NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 3504 BP 954A EP 954A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127503505 ER PT J AU Potti, A Hoke, H Ward, S Peddada, S Wu, JG Ortel, TL Nyska, A AF Potti, A Hoke, H Ward, S Peddada, S Wu, JG Ortel, TL Nyska, A TI A novel chemically induced Fischer F344 rat model for thrombotic sequelae of hemolytic anemias. SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 Duke Univ, Med Ctr, Div Hematol, Durham, NC 27706 USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC USA. NIEHS, Dept Biostat, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 3519 BP 958A EP 958A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127503520 ER PT J AU Hsu, LL Gladwin, M Cui, XZ Li, Y Schechter, AN Noguchi, CT Schimel, D Diwan, B Manci, EA Eichacker, PQ AF Hsu, LL Gladwin, M Cui, XZ Li, Y Schechter, AN Noguchi, CT Schimel, D Diwan, B Manci, EA Eichacker, PQ TI Mouse pneumonia model of sickle cell acute chest syndrome SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 St Christophers Hosp Children, Philadelphia, PA 19133 USA. NIH, Bethesda, MD 20892 USA. NCI, Sci Applicat Int Corp, Frederick, MD 21701 USA. Univ S Alabama, Sickel Cell Pathol Unit, Mobile, AL 36688 USA. RI Hsu, Lewis/A-3360-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 3582 BP 974A EP 974A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127503583 ER PT J AU Minneci, PC Deans, KJ Zhi, H Cushenberry, K Grant, P Banks, SM Natanson, C Gladwin, MT Solomon, SB AF Minneci, PC Deans, KJ Zhi, H Cushenberry, K Grant, P Banks, SM Natanson, C Gladwin, MT Solomon, SB TI Hemolysis-endothelial dysfunction syndrome: A novel paradigm of disease mechanism SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. NHLBI, Cardiovasc Branch, Vasc Therapeut Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 3581 BP 974A EP 974A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127503582 ER PT J AU Bhanu, NV Oneal, P Gantt, N Goh, SH Aerbajinai, W Miller, JL AF Bhanu, NV Oneal, P Gantt, N Goh, SH Aerbajinai, W Miller, JL TI Inhibition of fetal hemoglobin reactivation in adult human erythroblasts SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NIDDK, Biol Chem Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 3589 BP 976A EP 976A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127503590 ER PT J AU Rogers, HM Yu, XB Noguchi, CT AF Rogers, HM Yu, XB Noguchi, CT TI Hydroxyurea cytotoxicity and fetal hemoglobin induction SO BLOOD LA English DT Meeting Abstract CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol C1 NIDDK, NIH, Biol Chem Lab, Bethesda, MD USA. Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2004 VL 104 IS 11 MA 3607 BP 981A EP 981A PN 1 PG 1 WC Hematology SC Hematology GA 871JM UT WOS:000225127503608 ER PT J AU Tamura, T Yamamoto, S Takahata, M Sakaguchi, H Tanaka, H Stadtman, TC Inagaki, K AF Tamura, T Yamamoto, S Takahata, M Sakaguchi, H Tanaka, H Stadtman, TC Inagaki, K TI Selenophosphate synthetase genes from lung adenocarcinoma cells: Sps1 for recycling L-selenocysteine and Sps2 for selenite assimilation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ESCHERICHIA-COLI; SELENOPROTEIN SYNTHESIS; SELD HOMOLOG; IDENTIFICATION; MECHANISM; PRODUCT; MONOSELENOPHOSPHATE; BIOSYNTHESIS; PURIFICATION; SEQUENCE AB A labile selenium donor compound monoselenophosphate is synthesized from selenide and ATP by selenophosphate synthetase (SPS). In the present study, Sps1 and Sps2 were cloned from a cDNA library prepared from human lung adenocarcinoma cells (NCI-H441). The human lung Sps1 has been cloned as an ORF of 1,179 bp, identical in sequence to that of the recently revised human liver Sps1. The in-frame TGA codon of the lung Sps2 was genetically altered to TGT (Cys) to obtain the Sps2Cys gene. Expression of the recombinant plasmids containing Spsi or Sps2Cys was highly toxic to Escherichia coli host cells grown aerobically. Accordingly, the human lung Sps homologs were characterized by an in vivo complementation assay using a selD mutant strain. An added selenium source and a low salt concentration (0.1-0.25% NaCl) in the medium were required for reproducible and sensitive in vivo complementation. Sps2Cys effectively complemented the selD mutant, and the resulting formate dehydrogenase H activity was as high as that of WT E. coli MC4100. In contrast, only a weak complementation of the selD mutant by the Sps1 gene was observed when cells were grown in selenite media. Better complementation with added L-selenocysteine suggested involvement of a selenocysteine lyase for mobilization of selenium. Based on this apparent substrate specificity of the Sps1 and Sps2 gene products we suggest that the Sps1-encoded enzyme depends on a selenium salvage system that recycles L-selenocysteine, whereas the Sps2 enzyme can function with a selenite assimilation system. C1 Okayama Univ, Grad Sch Nat Sci & Technol, Dept Biofunct Chem, Okayama 7008530, Japan. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Tamura, T (reprint author), Okayama Univ, Grad Sch Nat Sci & Technol, Dept Biofunct Chem, Okayama 7008530, Japan. EM tktamura@cc.okayama-u.ac.jp NR 26 TC 51 Z9 53 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 NOV 16 PY 2004 VL 101 IS 46 BP 16162 EP 16167 DI 10.1073/pnas.0406313101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 872RO UT WOS:000225226200016 PM 15534230 ER PT J AU Ivanov, AI Rovescalli, AC Pozzi, P Yoo, S Mozer, B Li, HP Yu, SH Higashida, H Guo, V Spencer, M Nirenberg, M AF Ivanov, AI Rovescalli, AC Pozzi, P Yoo, S Mozer, B Li, HP Yu, SH Higashida, H Guo, V Spencer, M Nirenberg, M TI Genes required for Drosophila nervous system development identified by RNA interference SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE embryonic nervous system; neural mutants; neural development ID BINDING PROTEIN; CELL-DIVISION; C-ELEGANS; KINASE; MELANOGASTER; RECEPTOR; PATHWAY; GENOME; SCREEN; SIGNAL AB RNA interference was used to screen 3,314 Drosophila double-stranded RNAs, corresponding to approximate to25% of Drosophila genes, for genes that affect the development of the embryonic nervous system. RNA-interference-mediated gene silencing in Drosophila embryos resulted in loss-of-function mutant phenotypes for 43 genes, which is 1.3% of the genes that were screened. We found 18 genes that were not known previously to affect the development of the nervous system. The functions of some of the genes are unknown. Other genes encode protein kinases, transcription factors, and signaling proteins, as well as proteins with other functions. C1 NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. Kanazawa Univ, Grad Sch Med, Dept Biophys Genet, Kanazawa, Ishikawa 9208640, Japan. RP Nirenberg, M (reprint author), NHLBI, Lab Biochem Genet, NIH, Bldg 10, Bethesda, MD 20892 USA. EM mnirenberg@nih.gov OI higashida, haruhiro/0000-0002-1779-0606 NR 50 TC 40 Z9 43 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 16 PY 2004 VL 101 IS 46 BP 16216 EP 16221 DI 10.1073/pnas.0407188101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 872RO UT WOS:000225226200025 PM 15534205 ER PT J AU Tsai, CJ Leitzmann, MF Hu, FB Willett, WC Giovannucci, EL AF Tsai, CJ Leitzmann, MF Hu, FB Willett, WC Giovannucci, EL TI A prospective cohort study of nut consumption and the risk of gallstone disease in men SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE gallstones; men; nuts; prospective studies ID CORONARY-HEART-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; SATURATED FATTY-ACIDS; SERUM-LIPID PROFILE; GALLBLADDER-DISEASE; COFFEE CONSUMPTION; DIETARY-FAT; WOMEN; HAMSTERS; WALNUTS AB Gallstone disease is a major source of morbidity in Western countries. Nuts are rich in several compounds that may be protective against gallstones. The objective of the study was to examine the relation between nut consumption and gallstone disease in the Health Professionals Follow-up Study. The consumption of nuts was assessed starting in. 1986 as part of a 131-item semiquantitative food frequency questionnaire. The main outcome measure was newly diagnosed symptomatic gallstones. During 457,305 person-years of follow-up, 1,833 participants reported gallstone disease. After adjustment for age and other known or suspected risk factors, men consuming 5 or more units of nuts per week (frequent consumption) had a significantly lower risk of gallstone disease (relative risk = 0.70, 95% confidence interval: 0.60, 0.86; p(trend) < 0.001) than did men who never ate or who ate less than 1 unit per month (rare consumption) (1 unit = 1 ounce (0.028 kg) of nuts). Further adjustment for fat consumption (saturated fat, trans-fat, polyunsaturated fat, and monounsaturated fat) did not materially alter the relation. In analyses examining consumption of peanuts and other nuts separately, both were significantly associated with, a lower risk of gallstone disease in the age-adjusted and multivariate models. Our findings suggest that frequent nut consumption is associated with a reduced risk of gallstone disease in men. C1 Univ Kentucky, Med Ctr, Div Digest Dis & Nutr, Lexington, KY 40536 USA. Harvard Univ, Sch Med, Dept Med, Channing Lab, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Tsai, CJ (reprint author), Univ Kentucky, Med Ctr, Div Digest Dis & Nutr, 800 Rose St,MN649, Lexington, KY 40536 USA. EM hpcjt@channing.harvard.edu FU NCI NIH HHS [CA55075]; NIDDK NIH HHS [DK46200] NR 45 TC 19 Z9 19 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 15 PY 2004 VL 160 IS 10 BP 961 EP 968 DI 10.1093/aje/kwh302 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 871KW UT WOS:000225133600004 PM 15522852 ER PT J AU Eaker, ED Sullivan, LM Kelly-Hayes, M D'Agostino, RB Benjamin, EJ AF Eaker, ED Sullivan, LM Kelly-Hayes, M D'Agostino, RB Benjamin, EJ TI Re: "Does job strain increase the risk for coronary heart disease or death in men and women? The Framingham Offspring Study" - Reply SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter C1 Eaker Epidemiol Enterprises LLC, Chili, WI 54420 USA. Boston Univ, Sch Publ Hlth, Dept Math & Stat, Boston, MA 02118 USA. NHLBI, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Cardiol, Boston, MA 02118 USA. RP Eaker, ED (reprint author), Eaker Epidemiol Enterprises LLC, Chili, WI 54420 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 15 PY 2004 VL 160 IS 10 BP 1032 EP 1032 DI 10.1093/aje/kwh321 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 871KW UT WOS:000225133600014 ER PT J AU Prathikanti, S Schulze, TG Chen, YS Harr, B Akula, N Hennessy, K Potluri, S Lyons, J Nguyen, T McMahon, FJ AF Prathikanti, S Schulze, TG Chen, YS Harr, B Akula, N Hennessy, K Potluri, S Lyons, J Nguyen, T McMahon, FJ TI Neither single-marker nor haplotype analyses support an association between genetic variation near NOTCH4 and bipolar disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE bipolar disorder; NOTCH4; chromosome 6p21.3; association studies ID LINKAGE DISEQUILIBRIUM; FOLLOW-UP; MANIC DEPRESSION; SCHIZOPHRENIA; SUSCEPTIBILITY; HLA; TRANSMISSION; ILLNESS; REGION; LOCI AB Markers near the NOTCH4 locus on chromosome 6p21.3 have been reported to be associated with schizophrenia in some studies. Since schizophrenia and bipolar affective disorder (BPAD) may share genetic determinants, we tested markers in and near NOTCH4 in a sample of 153 parent-offspring triads ascertained through a sibling pair with BPAD for evidence of association. This sample would have 80% power to detect an association at or above a genotype relative risk of 2.4 at the 10(-7) level of significance. In addition to the two markers previously showing the most significant association with schizophrenia, three additional nearby markers were studied. The five markers were genotyped using validated methods. Both single-marker and 3-marker haplotype data was analyzed using family-based association methods. No genome-wide significant association was detected between any of the five SNP-markers and BPAD in this sample. One marker showed nominal evidence of association (P=0.049), but this evidence was not supported by haplotype analyses including nearby flanking markers or by case-control analysis using 93 Caucasian controls. These results do not support an association between genetic variation near NOTCH4 and BPAD in this sample. (C) 2004 Wiley-Liss, Inc. C1 Univ Chicago, Dept Psychiat, Knapp Med Ctr, Chicago, IL 60615 USA. Univ Chicago, Dept Ecol & Evolut, Chicago, IL 60637 USA. Univ Illinois, Chicago, IL USA. NIMH, Mood & Anxiety Program, NIH, US Dept HHS, Washington, DC USA. Cent Inst Mental Hlth, Div Genet Epidemiol Psychiat, D-6800 Mannheim, Germany. RP Prathikanti, S (reprint author), Univ Chicago, Dept Psychiat, Knapp Med Ctr, Chicago, IL 60615 USA. EM sprathik@yoda.bsd.uchicago.edu RI McMahon, Francis/A-7290-2009; Schulze, Thomas/H-2157-2013; OI McMahon, Francis/0000-0002-9469-305X NR 25 TC 2 Z9 2 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-7299 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD NOV 15 PY 2004 VL 131B IS 1 BP 10 EP 15 DI 10.1002/ajmg.b.20123 PG 6 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 866RP UT WOS:000224790900003 PM 15384085 ER PT J AU Brown, AM Gordon, D Lee, H Caudy, M Hardy, J Haroutunian, V Blass, JP AF Brown, AM Gordon, D Lee, H Caudy, M Hardy, J Haroutunian, V Blass, JP TI Association of the dihydrolipoamide dehydrogenase gene with Alzheimer's disease in an Ashkenazi Jewish population SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; HARDY-WEINBERG PROPORTIONS; APOLIPOPROTEIN-E; MITOCHONDRIAL DISEASES; FREQUENCY ESTIMATION; COMPLEX ACTIVITY; ALPHA-SUBUNIT; TYPE-4 ALLELE; ONSET; MUTATIONS AB Abundant biochemical evidence links deficient activity of mitochondrial a-ketoglutarate dehydrogenase with neuropathologically confirmed Alzheimer's disease (AD). Reduced a-ketoglutarate dehydrogenase activity has also been associated with anti-mortem measures of clinical disability. One of the genes encoding this complex, namely, DLD, lies within a chromosome 7 region that is in linkage disequilibrium. with AD. We therefore examined the hypothesis that variation in DLD is associated with AD risk. Denaturing HPLC was used to search for sequence variations in the coding and flanking regions of all exons of DLD, but no abundant variants that alter protein sequence were found. However, four common SNPs were identified and genotyped in a case-control series of 297 Caucasians from New York City, including 229 residents of a Jewish nursing home. Logistic regression analysis was performed for the four-locus DLD genotype, sex, and ApoE4 status to determine the association of these independent variables with AD. Significant associations with AD were observed for ApoE4 (P<10(-6)) and sex combined with DLD genotype (P=0.013). The association with the DLD genotypes appears only in the male population in both the Caucasian series (P=0.0009, n=83) and the Ashkenazi Jewish subseries (P=0.017, n=49). The DLD genotype appears to operate independently of APOE in conferring AD risk. (C) 2004 Wiley-Liss, Inc. C1 Dementia Res Serv, Burke Med Res Inst, White Plains, NY 10605 USA. Cornell Univ, Weill Med Coll, Dept Biochem, New York, NY USA. Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, New York, NY USA. Cornell Univ, Weill Med Coll, Dept Med, New York, NY USA. Rockefeller Univ, Lab Stat Genet, New York, NY 10021 USA. NINDS, Neurogenet Lab, Bethesda, MD 20892 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. RP Brown, AM (reprint author), Dementia Res Serv, Burke Med Res Inst, 785 Mamaroneck Ave, White Plains, NY 10605 USA. EM ambrown@med.cornell.edu RI Hardy, John/C-2451-2009 FU NHGRI NIH HHS [K01-HG00055]; NIA NIH HHS [P01-AG02219, P01-AG14930]; NIMH NIH HHS [MH44292] NR 48 TC 11 Z9 11 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-7299 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD NOV 15 PY 2004 VL 131B IS 1 BP 60 EP 66 DI 10.1002/ajmg.b.30008 PG 7 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 866RP UT WOS:000224790900011 PM 15389771 ER PT J AU Zuck, P Murray, EM Stec, E Grobler, JA Simon, AJ Strulovici, B Inglese, J Flores, OA Ferrer, M AF Zuck, P Murray, EM Stec, E Grobler, JA Simon, AJ Strulovici, B Inglese, J Flores, OA Ferrer, M TI A cell-based beta-lactamase reporter gene assay for the identification of inhibitors of hepatitis C virus replication SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE ~ ID RNA REPLICATION; QUANTITATION AB This report describes the development, optimization, and implementation of a cell-based assay for high-throughput screening (HTS) to identify inhibitors to hepatitis C virus (HCV) replication. The assay is based on a HCV subgenomic RNA replicon that expresses beta-lactamase as a reporter for viral replication in enhanced Huh-7 cells. The drug targets in this assay are viral and cellular enzymes required for HCV replication, which are monitored by fluorescence resonance energy transfer using cell-permeable CCF4-AM as a beta-lactamase substrate. Digital image processing was used to visualize cells that harbor viral RNA and to optimize key assay development parameters such as transfection and culturing conditions to obtain a cell line which produced a robust assay window. Formatting the assay for compound screening was problematic due to small signal-to-background ratio and reduced potency to known HCV inhibitors. These technical difficulties were solved by using clavulanic acid, an irreversible inhibitor of beta-lactamase, to eliminate residual beta-lactamase activity after HCV replication was terminated, thus resulting in an improved assay window. HTS was carried out in 384-well microplate format, and the signal-to-background ratio and Z factor for the assay plates during the screen were approximately 13-fold and 0.5, respectively. (C) 2004 Elsevier Inc. All rights reserved. C1 Merck & Co Inc, Dept Automated Biotechnol, N Wales, PA 19454 USA. Merck & Co Inc, Dept Biol Chem, W Point, PA 19468 USA. NIH, Chem Genom Ctr, Bethesda, MD 20892 USA. RP Zuck, P (reprint author), Merck & Co Inc, Dept Automated Biotechnol, 502 Louise Lane, N Wales, PA 19454 USA. EM paul_zuck@merck.com NR 21 TC 41 Z9 43 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD NOV 15 PY 2004 VL 334 IS 2 BP 344 EP 355 DI 10.1016/j.ab.2004.07.031 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 866ZK UT WOS:000224811700017 PM 15494142 ER PT J AU Ruotolo, BT Gillig, KJ Woods, AS Egan, TF Ugarov, MV Schultz, JA Russell, DH AF Ruotolo, BT Gillig, KJ Woods, AS Egan, TF Ugarov, MV Schultz, JA Russell, DH TI Analysis of phosphorylated peptides by ion mobility-mass spectrometry SO ANALYTICAL CHEMISTRY LA English DT Article ID GAS-PHASE; UNSOLVATED PEPTIDES; TRYPTIC PEPTIDES; METAL-ION; PROTEIN; MALDI; IDENTIFICATION; DISSOCIATION AB An ion mobility-mass spectrometry technique for rapid screening of phosphopeptides in protein digests is described. A data set of 43 sequences (ranging in mass from 400 to 3000 m/z) of model and tryptic peptides, including serine, threonine, and tyrosine phosphorylation, was investigated, and the data support our previously reported observation (Ruotolo, B. T.; Verbeck, G. F., IV; Thomson, L. M.; Woods, A. S.; Gillig, K. J.; Russell, D. H. J. Proteome Res. 2002, 1, 303.) that the drift time-m/z relationship for singly charged phosphorylated peptide ions is different from that for nonphosphorylated peptides. The data further illustrate that a combined data-dependent IM-MS/MS approach for phosphopeptide screening would have enhanced throughput over conventional MS/MS-based methodologies. C1 Texas A&M Univ, Dept Chem, Lab Biol Mass Spectrometry, College Stn, TX 77843 USA. NIDA, Intramural Program, NIH, Baltimore, MD 21224 USA. Ionwerks Inc, Houston, TX 77005 USA. RP Russell, DH (reprint author), Texas A&M Univ, Dept Chem, Lab Biol Mass Spectrometry, College Stn, TX 77843 USA. EM russell@mail.chem.tamu.edu RI Ruotolo, Brandon/F-2669-2013; Russell, David/C-3618-2015 OI Ruotolo, Brandon/0000-0002-6084-2328; Russell, David/0000-0003-0830-3914 FU NCRR NIH HHS [1 R01 RR019587-01] NR 37 TC 47 Z9 49 U1 0 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD NOV 15 PY 2004 VL 76 IS 22 BP 6727 EP 6733 DI 10.1021/ac0498009 PG 7 WC Chemistry, Analytical SC Chemistry GA 870RU UT WOS:000225076400027 PM 15538797 ER PT J AU Ugarov, MV Egan, T Khabashesku, DV Schultz, JA Peng, HQ Khabashesku, VN Furutani, H Prather, KS Wang, HWJ Jackson, SN Woods, AS AF Ugarov, MV Egan, T Khabashesku, DV Schultz, JA Peng, HQ Khabashesku, VN Furutani, H Prather, KS Wang, HWJ Jackson, SN Woods, AS TI MALDI matrices for biomolecular analysis based on functionalized carbon nanomaterials SO ANALYTICAL CHEMISTRY LA English DT Article ID ASSISTED-LASER-DESORPTION/IONIZATION; FLIGHT MASS-SPECTROMETRY; DESORPTION-IONIZATION; FULLERENE DERIVATIVES; AEROSOL-PARTICLES; TOF MS; NANOTUBES; PROTEINS; PEPTIDES; ACID AB When used in small molar ratios of matrix to analyte, derivatized fullerenes and single wall nanotubes are shown to be efficient matrices for matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. The mixing of an acidic functionalized fullerene with a solution of bioanalyte, depositing a dried droplet, and irradiating with a pulsed nitrogen laser yields protonated or cationized molecular ions. Derivatized fullerenes could offer several advantages over conventional MALDI matrices: a high analyte ionization efficiency, a small molar ratios (less than 1) of matrix/analyte, and a broader optical absorption spectrum, which should obviate specific wavelength lasers for MALDI acquisitions. The major disadvantage to the use of fullerenes is the isobaric interference between matrix and analyte ions; however, it is overcome by using MALDI-ion mobility time-of-flight (IM-oTOF) mass spectrometry to preseparate carbon cluster ions from bioanalyte ions prior to TOF mass analysis. However, an alternative to the dried droplet preparation of fullerene MALDI samples is the aerosolization of matrix-analyte solutions (or slurries) followed by impacting the aerosol onto a stainless surface. We also demonstrate that the fullerene matrices can be used to acquire spectra from rat brain tissue. C1 Ionwerks Inc, Houston, TX 77005 USA. Rice Univ, Dept Chem, Houston, TX 77005 USA. Rice Univ, Ctr Nanoscale Sci & Technol, Houston, TX 77005 USA. Univ Calif San Diego, Dept Chem & Biochem, San Diego, CA 92093 USA. NIDA, IRP, NIH, Baltimore, MD 21224 USA. RP Woods, AS (reprint author), Ionwerks Inc, 2472 Bolsover,Suite 255, Houston, TX 77005 USA. EM awoods@intra.nida.nih.gov RI Prather, Kimberly/A-3892-2008 OI Prather, Kimberly/0000-0003-3048-9890 NR 25 TC 75 Z9 78 U1 2 U2 33 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD NOV 15 PY 2004 VL 76 IS 22 BP 6734 EP 6742 DI 10.1021/ac049192x PG 9 WC Chemistry, Analytical SC Chemistry GA 870RU UT WOS:000225076400028 PM 15538798 ER PT J AU Gao, ZG Mamedova, LK Chen, PR Jacobson, KA AF Gao, ZG Mamedova, LK Chen, PR Jacobson, KA TI 2-Substituted adenosine derivatives: affinity and efficacy at four subtypes of human adenosine receptors SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE adenosine receptors; purines; nucleosides; GPCR; efficacy; structure-activity relationships ID A(3) RECEPTOR; SELECTIVE AGONISTS; STRUCTURAL DETERMINANTS; CORONARY-ARTERY; POTENT; LIGANDS; BINDING; ANTAGONISTS; NUCLEOSIDES; ANALOGS AB The affinity and efficacy at four subtypes (A(1), A(2A), A(2B) and A(3)) of human adenosine receptors (ARs) of a wide range of 2-substituted adenosine derivatives were evaluated using radioligand binding assays and a cyclic AMP functional assay in intact CHO cells stably expressing these receptors. Similar to previous studies of the N-6-position, several 2-substituents were found to be critical structural determinants for the A(3)AR activation. The following adenosine 2-ethers were moderately potent partial agonists (K-i, nM): benzyl (117), 3-chlorobenzyl (72), 2-(3-chlorophenyl)ethyl (41), and 2-(2-naphthyl)ethyl (130). The following adenosine 2-ethers were A(3)AR antagonists: 2,2-diphenylethyl, 2-(2-norbornan)ethyl, R- and S-2-phenylbutyl, and 2-(2-chlorophenyl)ethyl. 2-(S-2-Phenylbutyloxy)adenosine as an A(3)AR antagonist right-shifted the concentration-response curve for the inhibition by NECA of cyclic AMP accumulation with a K-B value of 212 nM, which is similar to its binding affinity (K-i = 175 nM). These 2-substituted adenosine derivatives were generally less potent at the A(1)AR in comparison to the A(3)AR, but fully efficacious, with binding K-i values over 100 nM. The 2-phenylethyl moiety resulted in higher A(3)AR affinity (K-i in nM) when linked to the 2-position of adenosine through an ether group (54), than when linked through an amine (310) or thioether (1960). 2-[2-(1-Naphthyl)ethyloxyladenosine (K-i = 3.8 nM) was found to be the most potent and selective (>50-fold) A(2A) agonist in this series. Mixed A(2A)/A(3)AR agonists have been identified. Interestingly, although most of these compounds were extremely weak at the A(2B)AR, 2-[2-(2-naphthyl)ethyloxyladenosine (EC50 = 1.4 muM) and 2-[2-(2-thienyl)-ethyloxy]adenosine (EC50 = 1.8 (M) were found to be relatively potent A(2B) agonists, although less potent than NECA (EC50 = 140 nM). (C) 2004 Elsevier Inc. All rights reserved. C1 NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Jacobson, KA (reprint author), NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20] NR 37 TC 40 Z9 42 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD NOV 15 PY 2004 VL 68 IS 10 BP 1985 EP 1993 DI 10.1016/j.bcp.2004.06.011 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 865PF UT WOS:000224714300009 PM 15476669 ER PT J AU Cattaneo, M Lecchi, A Ohno, M Joshi, LV Besada, P Tchilibon, S Lombardi, R Bischofberger, N Harden, TK Jacobson, KA AF Cattaneo, M Lecchi, A Ohno, M Joshi, LV Besada, P Tchilibon, S Lombardi, R Bischofberger, N Harden, TK Jacobson, KA TI Antiaggregatory activity in human platelets of potent antagonists of the P2Y(1) receptor SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE P2Y(1) nucleotide receptor; G protein-coupled receptor; acyclic nucleotides; purines; platelet aggregation; carbocyclic nucleotides ID ADP RECEPTORS; P2Y(1)-DEFICIENT MICE; ANTITHROMBOTIC DRUGS; P2 RECEPTORS; ANALOGS; IDENTIFICATION; AGGREGATION; THROMBOSIS; INHIBITION; EXPRESSION AB Activation of the P2Y(1) nucleotide receptor in platelets by ADP causes changes in shape and aggregation, mediated by activation of phospholipase C (PLC). Recently, MRS2500 (2-iodo-N-6-methyl-(N)-methanocarba-2'-deoxyadenosine-3',5'-bisphosphate) was introduced as a highly potent and selective antagonist for this receptor. We have studied the actions of MRS2500 in human platelets and compared these effects with the effects of two acyclic nucleotide analogues, a bisphosphate MRS2298 and a bisphosphonate derivative MRS2496, which act as P2Y(1) receptor antagonists, although less potently than MRS2500. Improved synthetic methods for MRS2500 and MRS2496 were devised. The bisphosphonate is predicted to be more stable in general in biological systems than phosphate antagonists due to the non-hydrolyzable C-P bond. MRS2500 inhibited the ADP-induced aggregation of human platelets with an IC50 value of 0.95 nM. MRS2298 and MRS2496 also both inhibited the ADP-induced aggregation of human platelets with IC50 values of 62.8 nM and 1.5 muM, respectively. A similar order of potency was observed for the three antagonists in binding to the recombinant human P2Y(1) receptor and in inhibition of ADP-induced shape change and ADP-induced rise in intracellular Ca2+. No substantial antagonism of the pathway linked to the inhibition of cyclic AMP was observed for the nucleotide derivatives, indicating no interaction of these three P2Y(1) receptor antagonists with the proaggregatory P2Y(12) receptor, which is also activated by ADP. Thus, all three of the bisphosphate derivatives are highly selective antagonists of the platelet P2Y(1) receptor, and MRS2500 is the most potent such antagonist yet reported. (C) 2004 Elsevier Inc. All rights reserved. C1 NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Milan, Osped Maggiore, IRCCS, Dept Internal Med,Hemophilia & Thrombosis Ctr, I-20122 Milan, Italy. Gilead Sci Inc, Foster City, CA 94404 USA. Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009; Besada Pereira, Pedro/E-6051-2012; OI Jacobson, Kenneth/0000-0001-8104-1493; Besada Pereira, Pedro/0000-0002-9985-9063; Cattaneo, Marco/0000-0002-7343-4534 FU Intramural NIH HHS [Z01 DK031116-20] NR 30 TC 60 Z9 61 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD NOV 15 PY 2004 VL 68 IS 10 BP 1995 EP 2002 DI 10.1016/j.bcp.2004.06.026 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 865PF UT WOS:000224714300010 PM 15476670 ER PT J AU Chearwae, W Anuchapreeda, S Nandigama, K Ambudkar, SV Limtrakul, P AF Chearwae, W Anuchapreeda, S Nandigama, K Ambudkar, SV Limtrakul, P TI Biochemical mechanism of modulation of human P-glycoprotein (ABCB1) by curcumin I, II, and III purified from Turmeric powder SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE ABC transporter; ATP hydrolysis; chemosensitizers; curcumin; multidrug resistance; P-glycoprotein ID MULTIDRUG-RESISTANCE; DIETARY CURCUMIN; ATP HYDROLYSIS; CATALYTIC CYCLE; CELLS; TRANSPORTERS; INHIBITION; RAT; EXPRESSION; TOXICITY AB P-glycoprotein (Pgp, ABCB1) is an ATP-dependent drug efflux pump linked to development of multidrug resistance (MDR) in cancer cells. Previously [Biochem Pharmacol 2002;64:573-82], we reported that a curcumin mixture could modulate both function and expression of Pgp. This study focuses on the effect of three major curcuminoids - curcumin I, II and III purified from a curcumin mixture - on modulation of Pgp function in a multidrug resistant human cervical carcinoma cell line (KB-V1). The similar IC50 values for cytotoxicity of curcuminoids of KB-V1, and KB-3-1 (parental drug sensitive cell line) suggest that these curcuminoids may not be substrates for Pgp. Treating the cells with non-toxic doses of curcuminoids increased their sensitivity to vinblastine only in the Pgp expressing drug resistant cell line, KB-V1, and curcumin I retained the drug in KB-V1 cells more effectively than curcumin II and III, respectively. Effects of each curcuminoid on rhodamine123, calcein-AM, and bodipy-FL-vinblastine accumulation confirmed these findings. Curcumin I, II and III increased the accumulation of fluorescent substrates in a dose-dependent manner, and at 15 muM, curcumin I was the most effective. The inhibitory effect in a concentration-dependent manner of curcuminoids on verapamil-stimulated ATPase activity and photoaffinity labeling of Pgp with the [I-125]-iodoarylazidoprazosin offered additional support; curcumin I was the most potent modulator. Taken together, these results indicate that curcumin I is the most effective MDR modulator among curcuminoids, and may be used in combination with conventional chemotherapeutic drugs to reverse MDR in cancer cells. (C) 2004 Elsevier Inc. All rights reserved. C1 NCI, Cell Biol Lab, Canc Res Ctr, DHHS,NIH, Bethesda, MD 20892 USA. Chiang Mai Univ, Fac Med, Dept Biochem, Chiang Mai 50200, Thailand. Chiang Mai Univ, Fac Associated Med Sci, Dept Clin Microscopy, Chiang Mai 50200, Thailand. RP Ambudkar, SV (reprint author), NCI, Cell Biol Lab, Canc Res Ctr, DHHS,NIH, Bethesda, MD 20892 USA. EM ambudkar@helix.nih.gov; plimtrak@mail.med.cmu.ac.th RI Ambudkar, Suresh/B-5964-2008 NR 33 TC 144 Z9 149 U1 1 U2 18 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD NOV 15 PY 2004 VL 68 IS 10 BP 2043 EP 2052 DI 10.1016/j.bcp.2004.07.009 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 865PF UT WOS:000224714300015 PM 15476675 ER PT J AU Hoffmann, C Soltysiak, K West, PL Jacobson, KA AF Hoffmann, C Soltysiak, K West, PL Jacobson, KA TI Shift in purine/pyrimidine base recognition upon exchanging extracellular domains in P2Y(1/6) chimeric receptors SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE P2Y(1); nucleotide receptor; G protein-coupled receptor; pyrimidines; mutagenesis; phospholipase C ID PROTEIN-COUPLED RECEPTORS; SITE-DIRECTED MUTAGENESIS; PHOSPHOLIPASE-C; P2 RECEPTORS; PLATELET-AGGREGATION; LIGAND RECOGNITION; BINDING-SITE; ACTIVATION; AGONIST; P2Y(6) AB P2Y receptors are G protein-coupled receptors stimulated by extracellular nucleotides. Both the P2Y(1) and the P2Y(6) receptors are preferentially activated by nucleoside 5'-diphosphates, but favor different base moieties. In the case of the P2Y(1) receptor the preferred base is adenine, while the P2Y(6) receptor is activated by uracil nucleotides. To identify potential amino acid domains that interact with the base moiety, we used a chimeric receptor approach, employing the human P2Y(1) receptor as core structure to investigate the role in receptor activation of extracellular loops (ELs) and transmembrane domains (TMs) of the rat P2Y(6) receptor. The chimeric receptors were expressed in COS-7 cells and measured for stimulation of phospholipase C (PLC) induced by the potent P2Y(1) receptor agonist 2-MeSADP or the potent P2Y(6) receptor agonist UDR Replacement of the N-terminus or EL2 resulted in low (similar to50 muM) potency of the agonist 2-MeSADP, thus confirming the importance of EL2 in ligand recognition. Upon replacement of several regions, the potency of the P2Y(1) agonist 2-MeSADP was either 1-2 muM (N-terminus and EL1, or EL1 and EL3) or 72 muM (N-terminus and EL3). Concurrent replacement of three regions (N-terminus, EL1, and EL3) completely precluded activation by 2-MeSADP. Our study identified domains of the P2Y(6) receptor that contribute to receptor activation by UDP and hence seem to be involved in uracil recognition. Upon replacement with extracellular domains of the P2Y(6) receptor sequence we observed a trend toward gain of receptor-induced PLC activation by UDP, for example, in the chimera containing replacements of both the N-terminus and EL1. Exchange of three receptor domains led to a construct with an EC50 value for UDP of 19 muM and a maximal mositol phosphate accumulation similar to the native P2Y(6) receptor. Within receptor constructs of combined domain exchanges the additional substitution of Tyr(110) by the corresponding Asn from the P2Y(6) receptor showed a significant increase for activation by UDP, but only when combined with the N-terminal domain and TM1. The residue Tyr(110) was identified to play an important role in the recognition of the nucleobase in the P2Y(1) and P2Y(6) receptors. Published by Elsevier Inc. C1 NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z99 DK999999, Z01 DK031116-20] NR 41 TC 6 Z9 6 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD NOV 15 PY 2004 VL 68 IS 10 BP 2075 EP 2086 DI 10.1016/j.bcp.2004.07.014 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 865PF UT WOS:000224714300018 PM 15476678 ER PT J AU O'Brien, CP Charney, DS Lewis, L Cornish, JW Post, RM Woody, GE Zubieta, JK Anthony, JC Blaine, JD Bowden, CL Calabrese, JR Carroll, K Kosten, T Rounsaville, B Childress, AR Oslin, DW Pettinati, HM Davis, MA DeMartino, R Drake, RE Fleming, MF Fricks, L Glassman, AH Levin, FR Nunes, EV Johnson, RL Jordan, C Kessler, RC Laden, SK Regier, DA Renner, JA Ries, RK Sklar-Blake, T Weisner, C AF O'Brien, CP Charney, DS Lewis, L Cornish, JW Post, RM Woody, GE Zubieta, JK Anthony, JC Blaine, JD Bowden, CL Calabrese, JR Carroll, K Kosten, T Rounsaville, B Childress, AR Oslin, DW Pettinati, HM Davis, MA DeMartino, R Drake, RE Fleming, MF Fricks, L Glassman, AH Levin, FR Nunes, EV Johnson, RL Jordan, C Kessler, RC Laden, SK Regier, DA Renner, JA Ries, RK Sklar-Blake, T Weisner, C TI Priority actions to improve the care of persons with co-occurring substance abuse and other mental disorders: A call to action SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID PLACEBO-CONTROLLED-TRIAL; COGNITIVE-BEHAVIORAL THERAPY; MAJOR DEPRESSIVE DISORDER; BUPRENORPHINE-MAINTAINED PATIENTS; METHADONE-MAINTENANCE PATIENTS; NATIONAL COMORBIDITY SURVEY; BIPOLAR SPECTRUM DISORDERS; OPIATE-DEPENDENT PATIENTS; CONTROLLED CLINICAL-TRIAL; DOUBLE-BLIND C1 Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Mt Sinai Sch Med, New York, NY USA. Depress & Bipolar Support Alliance, Chicago, IL USA. Univ Penn, Sch Med, VAMC, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA 19104 USA. NIMH, Bethesda, MD 20892 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Michigan State Univ, E Lansing, MI 48824 USA. Biopharmaceut Res Consultants Inc, Ann Arbor, MI USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. Depress & Bipolar Support Alliance Pink & Blues, Philadelphia, PA USA. Subst Abuse & Mental Hlth Serv Adm, Washington, DC USA. Dartmouth Coll Sch Med, Hanover, NH USA. Univ Wisconsin, Sch Med, Madison, WI 53706 USA. Georgia Div Mental Hlth, Atlanta, GA USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. Univ Med & Dent New Jersey, Newark, NJ 07103 USA. Natl Alliance Mentally Ill, Nashville, TN USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. MSE Commun, Cheshire, CT USA. Amer Psychiat Inst Res & Educ, Arlington, VA USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP O'Brien, CP (reprint author), Univ Penn, Sch Med, Dept Psychiat, 3900 Chestnut St, Philadelphia, PA 19104 USA. EM obrien@mail.trc.upenn.edu RI Carroll, Kathleen/A-7526-2009; OI Carroll, Kathleen/0000-0003-3263-3374 FU NIDA NIH HHS [K05 DA000457, K05 DA015799] NR 122 TC 77 Z9 77 U1 8 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 15 PY 2004 VL 56 IS 10 BP 703 EP 713 DI 10.1016/j.biopsych.2004.10.002 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 874KM UT WOS:000225349300001 PM 15556110 ER PT J AU Volkow, ND AF Volkow, ND TI The reality of comorbidity: Depression and drug abuse SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID SUBSTANCE USE DISORDERS; MAJOR DEPRESSION; CIGARETTE-SMOKING; DEPENDENCE; DOPAMINE; NICOTINE; STRESS; BRAIN; METHYLPHENIDATE; PERIADOLESCENCE C1 NIDA, Bethesda, MD 20892 USA. RP Volkow, ND (reprint author), NIDA, 6001 Execut Blvd,Suite 5274, Bethesda, MD 20892 USA. NR 36 TC 80 Z9 82 U1 2 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 15 PY 2004 VL 56 IS 10 BP 714 EP 717 DI 10.1016/j.biopsych.2004.07.007 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 874KM UT WOS:000225349300002 PM 15556111 ER PT J AU Li, TK Hewitt, BG Grant, BF AF Li, TK Hewitt, BG Grant, BF TI Alcohol use disorders and mood disorders: A National Institute on Alcohol Abuse and Alcoholism perspective SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID COMORBIDITY-SURVEY; LIFETIME; RISK C1 NIAAA, US Dept HHS, NIH, Bethesda, MD 20892 USA. RP Li, TK (reprint author), NIAAA, US Dept HHS, NIH, 5635 Fishers Lane,Room 2000, Bethesda, MD 20892 USA. NR 9 TC 71 Z9 71 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 15 PY 2004 VL 56 IS 10 BP 718 EP 720 DI 10.1016/j.biopsych.2004.03.006 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 874KM UT WOS:000225349300003 PM 15556112 ER PT J AU Gonzales, J Insel, TR AF Gonzales, J Insel, TR TI The conundrum of co-occurring mental and substance use disorders: Opportunities for research SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material C1 NIMH, Bethesda, MD 20892 USA. RP Gonzales, J (reprint author), NIMH, 6001 Execut Blvd,Room 8235, Bethesda, MD 20892 USA. EM tinsel@mail.nih.gov NR 8 TC 9 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 15 PY 2004 VL 56 IS 10 BP 723 EP 725 DI 10.1016/j.biopsych.2004.09.007 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 874KM UT WOS:000225349300005 PM 15556114 ER PT J AU Krajewski, K Marchand, C Long, YQ Pommier, Y Roller, PP AF Krajewski, K Marchand, C Long, YQ Pommier, Y Roller, PP TI Synthesis and HIV-1 integrase inhibitory activity of dimeric and tetrameric analogs of indolicidin SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE indolicidin; integrase inhibitors; multimeric peptides ID PEPTIDE; PROTEIN; CELLS AB We found that indolicidin, a natural antimicrobial peptide, has HIV-1 integrase inhibitory activity. Subsequently, we also discovered analogs of indolicidin with substantially higher inhibitory potency. The dimers and tetramers of the most active sequence (ILPWKWPWWPWPP) were prepared by connection of the monomers' C-terminal ends, using lysine as a linker. The inhibitory potency of the dimeric peptide is higher than the monomeric peptide. The tetrameric peptide, prepared by connection of two dimers at C-ends using again lysine as the linker, is the most potent integrase inhibitor with IC50 value of 0.6 muM for both 3'-end processing and strand transfer. (C) 2004 Elsevier Ltd. All rights reserved. C1 NCI, CCR, Med Chem Lab, NIH, Ft Detrick, MD 21702 USA. NCI, Mol Pharmacol Lab, CCR, NIH, Bethesda, MD 20892 USA. Chinese Acad Sci, SIMM, SIBS, State Key Lab Drug Res, Shanghai 201203, Peoples R China. RP Roller, PP (reprint author), NCI, CCR, Med Chem Lab, NIH, Ft Detrick, MD 21702 USA. EM proll@helix.nih.gov RI Marchand, Christophe/D-8559-2016 NR 11 TC 28 Z9 31 U1 0 U2 4 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 NOV 15 PY 2004 VL 14 IS 22 BP 5595 EP 5598 DI 10.1016/j.bmcl.2004.08.061 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 865PP UT WOS:000224715300028 PM 15482931 ER PT J AU Gwynn, B Martina, JA Bonifacino, JS Sviderskaya, EV Lamoreux, ML Bennett, DC Moriyama, K Huizing, M Helip-Wooley, A Gahl, WA Webb, LS Lambert, AJ Peters, LL AF Gwynn, B Martina, JA Bonifacino, JS Sviderskaya, EV Lamoreux, ML Bennett, DC Moriyama, K Huizing, M Helip-Wooley, A Gahl, WA Webb, LS Lambert, AJ Peters, LL TI Reduced pigmentation (rp), a mouse model of Hermansky-Pudlak syndrome, encodes a novel component of the BLOG-1 complex SO BLOOD LA English DT Article ID STORAGE POOL DEFICIENCY; PLATELET-DENSE GRANULES; AP-3 ADAPTER COMPLEX; PALE EAR EP; PROTEIN COMPLEX; VESICLE FORMATION; BETA-3A SUBUNIT; LIGHT-EAR; GENE; BIOGENESIS AB Hermansky-Pudlak syndrome (HPS), a disorder of organelle biogenesis, affects lysosomes, melanosomes, and platelet dense bodies. Seven genes cause HPS in humans (HPS1-HPS7) and at least 15 nonallelic mutations cause HPS in mice. Where their function is known, the HPS proteins participate in protein trafficking and vesicle docking/fusion events during organelle biogenesis. HPS-associated genes participate in at least 4 distinct protein complexes: the adaptor complex AP-3; biogenesis of lysosome-related or ganelles complex 1 (BLOC-1), consisting of 4 HPS proteins (pallidin, muted, cappuccino, HPS7/sandy); BLOC-2, consisting of HPS6/ruby-eye, HPS5/ruby-eye-2, and HPS3/cocoa; and BLOC-3, consisting of HPS1/pale ear and HPS4/light ear. Here, we report the cloning of the mouse HPS mutation reduced pigmentation (rp). We show that the wild-type rp gene encodes a novel, widely expressed 195-amino acid protein that shares 87% amino acid identity with its human orthologue and localizes to punctate cytoplasmic structures. Further, we show that phosphorylated RP is part of the BLOC-1 complex. In mutant rp/rp mice, a premature stop codon truncates the protein after 79 amino acids. Defects in all the 5 known components of BLOC-1, including PIP, cause severe HPS in mice, suggesting that the subunits are nonredundant and that BLOC-1 plays a key role in organelle biogenesis. (C) 2004 by The American Society of Hematology. C1 Jackson Lab, Bar Harbor, ME 04609 USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Univ London St Georges Hosp, Sch Med, Dept Basic Med Sci, London SW17 0RE, England. Texas A&M Univ, Coll Vet Med, College Stn, TX USA. NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Peters, LL (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. EM luanne@jax.org RI Bennett, Dorothy/C-2418-2008; Sviderskaya, Elena/D-2419-2009 OI Bennett, Dorothy/0000-0002-3639-7527; FU NCI NIH HHS [CA34196]; NCRR NIH HHS [RR01183]; NHLBI NIH HHS [HL55321, R01 HL055321] NR 55 TC 32 Z9 34 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2004 VL 104 IS 10 BP 3181 EP 3189 DI 10.1182/blood-2004-04-1538 PG 9 WC Hematology SC Hematology GA 870YF UT WOS:000225094100035 PM 15265785 ER PT J AU Zhang, X Rodriguez-Galan, MC Subleski, JJ Ortaldo, JR Hodge, DL Wang, JM Shimozato, O Reynolds, DA Young, HA AF Zhang, X Rodriguez-Galan, MC Subleski, JJ Ortaldo, JR Hodge, DL Wang, JM Shimozato, O Reynolds, DA Young, HA TI Peroxisome proliferator-activated receptor-gamma and its ligands attenuate biologic functions of human natural killer cells SO BLOOD LA English DT Article ID PROTEASOME-DEPENDENT DEGRADATION; MACROPHAGE-GENE-EXPRESSION; ASIALO GM1 ANTIBODY; PPAR-GAMMA; T-BET; INTERFERON-GAMMA; 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2); PROSTAGLANDIN J(2); DIFFERENTIAL REGULATION; NOD MICE AB Interferon-gamma (IFN-gamma) production and cytolytic activity are 2 major biologic functions of natural killer (NK) cells that are important for innate immunity. We demonstrate here that these functions are compromised in human NK cells treated with peroxisome proliferator-activated-gamma (PPAR-gamma) ligands via both PPAR-gamma-dependent and -independent pathways due to variation in PPAR-gamma expression. In PPAR-gamma-null NK cells, 15-deoxy-Delta(12,14) prostaglandin J(2) (15d-PGJ(2)), a natural PPAR-gamma ligand, reduces IFN-gamma production that can be reversed by MG132 and/or chloroquine, and it inhibits cytolytic activity of NK cells through reduction of both conjugate formation and CD69 expression. In PPARgamma-positive NK cells, PPAR-gamma activation by 15d-PGJ2 and ciglitazone (a synthetic ligand) leads to reduction in both mRNA and protein levels of IFN-gamma. Overexpression of PPAR-gamma in PPAR-gamma-null NK cells reduces IFN-gamma gene expression. However, PPAR-gamma expression and activation has no effect on NK cell cytolytic activity. In addition, 15d-PGJ(2) but not ciglitazone reduces expression of CD69 in human NK cells, whereas CD44 expression is not affected. These results reveal novel pathways regulating NK cell biologic functions and provide a basis for the design of therapeutic agents that can regulate the function of NK cells within the innate immune response. (C) 2004 by The American Society of Hematology. C1 NCI, Expt Immunol Lab, Canc Res Ctr, NIH, Frederick, MD 21702 USA. NCI, Mol Immunoregulat Lab, Canc Res Ctr, NIH, Frederick, MD 21702 USA. RP Young, HA (reprint author), NCI, Expt Immunol Lab, Canc Res Ctr, NIH, Bldg 560,Rm 31-23, Frederick, MD 21702 USA. EM youngh@mail.ncifcrf.gov RI Young, Howard/A-6350-2008; Zhang, Xia/B-8152-2008 OI Young, Howard/0000-0002-3118-5111; Zhang, Xia/0000-0002-9040-1486 NR 67 TC 29 Z9 31 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2004 VL 104 IS 10 BP 3276 EP 3284 DI 10.1182/blood-2004-02-0664 PG 9 WC Hematology SC Hematology GA 870YF UT WOS:000225094100048 PM 15265789 ER PT J AU Janik, JE Morris, JC Pittaluga, S McDonald, K Raffeld, M Jaffe, ES Grant, N Gutierrez, M Waldmann, TA Wilson, WH AF Janik, JE Morris, JC Pittaluga, S McDonald, K Raffeld, M Jaffe, ES Grant, N Gutierrez, M Waldmann, TA Wilson, WH TI Elevated serum-soluble interleukin-2 receptor levels in patients with anaplastic large cell lymphoma SO BLOOD LA English DT Article ID TUMOR-MARKER; CD30; LEUKEMIA; HODGKIN; DISEASE; CLASSIFICATION; RECEPTOR; SUBTYPE AB Levels of serum soluble interleukin 2 receptor (sIL-2R) provide a reliable marker of disease activity in patients with hairy cell leukemia and adult T-cell leukemia/lymphoma. The malignant cells in patients with anaplastic large cell lymphoma (ALCL) express CD30 and are usually positive for expression of CD25. We measured serum sIL-2R and soluble CD30 (sCD30) levels in patients with ALCL treated with EPOCH (etoposide, prednisone, Oncovin, Cytoxan, hydroxydaunorubicin) infusional chemotherapy. Serum sCD30 levels were elevated and decreased in response to therapy as previously reported. Serum sIL-2R levels were elevated in 7 of 9 patients with ALCL and decreased in response to treatment. Baseline serum sIL-2R levels varied but correlated well with serum sCD30 levels (r = 0.97). Patients positive for the anaplastic lymphoma kinase (ALK) gene showed elevated sIL-2R levels, whereas those negative for ALK had normal serum sIL-2R levels and their tumors lacked CD25 expression. Serum sIL-2R levels were elevated in both patients with recurrent disease. (C) 2004 by The American Society of Hematology. C1 NCI, Ctr Canc Res, Metab Branch, NIH, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Hematopathol Sect, Lab Pathol,NIH, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Janik, JE (reprint author), NCI, Ctr Canc Res, Metab Branch, NIH, Bldg 10,Rm 4N115,10 Ctr Dr, Bethesda, MD 20892 USA. EM janikj@mail.nih.gov NR 27 TC 33 Z9 33 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2004 VL 104 IS 10 BP 3355 EP 3357 DI 10.1182/blood-2003-11-3922 PG 3 WC Hematology SC Hematology GA 870YF UT WOS:000225094100059 PM 15205267 ER PT J AU Embury, SH Matsui, NM Ramanujam, S Mayadas, TN Noguchi, C Diwan, HA Mohandas, N Cheung, ATW AF Embury, SH Matsui, NM Ramanujam, S Mayadas, TN Noguchi, C Diwan, HA Mohandas, N Cheung, ATW TI The contribution of endothelial cell P-selectin to the microvascular flow of mouse sickle erythrocytes in vivo SO BLOOD LA English DT Article ID GRANULE MEMBRANE-PROTEIN; NECROSIS-FACTOR-ALPHA; MOLECULAR-WEIGHT HEPARINS; VON-WILLEBRAND-FACTOR; BLOOD-FLOW; MONOCLONAL-ANTIBODIES; INTRAVITAL MICROSCOPY; VASCULAR ENDOTHELIUM; TRANSGENIC MICE; TNF-ALPHA AB Microvascular occlusion in sickle cell disease can be initiated by adhesion of sickle red blood cells (RBCs) to the endothelium. Our objective in this study was to verify the relevance in vivo of our discovery that sickle RBCs adhere abnormally to endothelial P-selectin in vitro. We used computer-assisted intravital microscopy to characterize RBC flow velocity (V-RBC) in mice. We found faster V-RBC of sickle RBCs in P-selectin knock-out and control mice than in sickle cell mice, which have increased endothelial cell P-selectin expression. Agonist peptide for murine protease-activated receptor-1 (PAR-1), which selectively activates mouse endothelial cells but not platelets, was used to assess the effects of endothelial cell P-selectin on microvascular flow. Suffusion of venules with this agonist stopped flow promptly in normal and sickle mice but not in P-selectin knock-out mice or in control mice pretreated with anti-P-selectin monoclonal antibody or unfraction-ated heparin (UFH). Agonist-induced slowing of flow was reversed rapidly by suffusion with UFH, provided flow had not already stopped. We conclude that endothelial cell P-selectin contributes to the microcirculatory abnormalities in sickle cell disease and that blocking P-selectin may be useful for preventing painful vasooccluslon in sickle cell disease. (C) 2004 by The American Society of Hematology. C1 San Francisco Gen Hosp, No Calif Comprehens Sickle Cell Ctr, San Francisco, CA 94110 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. Univ Calif Davis, Med Ctr, Dept Med Pathol, Sacramento, CA 95817 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. NIDDKD, Biol Chem Lab, NIH, Bethesda, MD USA. NCI, Sci Applicat Int Corp, Basic Res Program, Frederick, MD 21701 USA. New York Blood Ctr, New York, NY 10021 USA. RP Embury, SH (reprint author), San Francisco Gen Hosp, No Calif Comprehens Sickle Cell Ctr, Bldg 100,Rm 263,1001 Potrero Ave, San Francisco, CA 94110 USA. EM sembury@itsa.ucsf.edu FU NCI NIH HHS [N01-CO-12400]; NHLBI NIH HHS [R01 HL064396, HL64396, HL67432, HL31579, HL20985] NR 78 TC 52 Z9 54 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2004 VL 104 IS 10 BP 3378 EP 3385 DI 10.1182/blood-2004-02-0713 PG 8 WC Hematology SC Hematology GA 870YF UT WOS:000225094100064 PM 15271798 ER PT J AU Arbab, AS Yocum, GT Kalish, H Jordan, EK Anderson, SA Khakoo, AY Read, EJ Frank, JA AF Arbab, AS Yocum, GT Kalish, H Jordan, EK Anderson, SA Khakoo, AY Read, EJ Frank, JA TI Feride-protamine sulfate labeling does not alter differentiation of mesenchymal stem cells SO BLOOD LA English DT Letter C1 NIH, Lab Diagnost Radiol Res, Expt Neuroimaging Sect, Bethesda, MD 20892 USA. RP Arbab, AS (reprint author), NIH, Lab Diagnost Radiol Res, Expt Neuroimaging Sect, Bldg 10,Rm B1N256, Bethesda, MD 20892 USA. EM saali@cc.nih.gov NR 6 TC 11 Z9 13 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2004 VL 104 IS 10 BP 3412 EP 3413 PG 2 WC Hematology SC Hematology GA 870YF UT WOS:000225094100071 ER PT J AU O'Farrell, TJ Ghosh, P Dobashi, N Sasaki, CY Longo, DL AF O'Farrell, TJ Ghosh, P Dobashi, N Sasaki, CY Longo, DL TI Comparison of the effect of mutant and wild-type p53 on global gene expression SO CANCER RESEARCH LA English DT Article ID GAIN-OF-FUNCTION; HISTONE DEACETYLASE INHIBITOR; GROWTH-FACTOR; TUMOR-SUPPRESSOR; FUNCTION MUTATIONS; TRANSCRIPTIONAL ACTIVATION; FUNCTION PHENOTYPE; BINDING PROTEIN; CELL-CYCLE; PROMOTER AB The mechanisms for "gain-of-function" phenotypes produced by mutant p53s such as enhanced proliferation, resistance to transforming growth factor-beta-mediated growth suppression, and increased tumorigenesis are not known. One theory is that these phenotypes are caused by novel transcriptional regulatory events acquired by mutant p53s. Another explanation is that these effects are a result of an imbalance of functions caused by the retention of some of the wild-type transcriptional regulatory events in the context of a loss of other counterbalancing activities. An analysis of the ability of DNA-binding domain mutants A138P and R175H, and wild-type, p53 to regulate the expression levels of 6.9 x 10(3) genes revealed that the mutants retained only <5% of the regulatory activities of the wild-type protein. A138P p53 exhibited mostly retained wild-type regulatory activities and few acquired novel events. However, R175H p53 possessed an approximately equal number of wild-type regulatory events and novel activities. This is the first report that, after examination of the regulation of a large unfocused set of genes, provides data indicating that remaining wild-type transcriptional regulatory functions existing in the absence of counterbalancing activities as well as acquired novel events both contribute to the gain-of-function phenotypes produced by mutant p53s. However, mutant p53s are likely to be distinct in terms of the extent to which each mechanism contributes to their gain-of-function phenotypes. C1 NIA, Gerontol Res Ctr, Lab Immunol, NIH, Baltimore, MD 21224 USA. RP Longo, DL (reprint author), NIA, Gerontol Res Ctr, Lab Immunol, NIH, 5600 Nathan Shock Dr,Box 21, Baltimore, MD 21224 USA. EM LongoD@nih.gov NR 58 TC 34 Z9 34 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2004 VL 64 IS 22 BP 8199 EP 8207 DI 10.1158/0008-5472.CAN-03-3639 PG 9 WC Oncology SC Oncology GA 872CA UT WOS:000225182300012 PM 15548685 ER PT J AU Bhoumik, A Gangi, L Ronai, Z AF Bhoumik, A Gangi, L Ronai, Z TI Inhibition of melanoma growth and metastasis by ATF2-derived peptides SO CANCER RESEARCH LA English DT Article ID NF-KAPPA-B; TRANSCRIPTION FACTOR; C-JUN; MALIGNANT-MELANOMA; INDUCED APOPTOSIS; MAMMALIAN-CELLS; DOWN-REGULATION; CYCLIN-E; EXPRESSION; ACTIVATION AB The resistance of melanoma to apoptosis, as well as its growth am metastasis capabilities, can be overcome by expression of a peptide derived from amino acid (aa) 51 to 100 of ATF2. Here we show that expression of ATF2((51-100)) in human melanoma cells reduced their growl in nude mice, which was additionally inhibited upon treatment with protein kinase inhibitors UCN-01 or SB203580. Injection of a fusion protein consisting of HIV-TAT and as 51 to 100 of ATF2 into SW melanomas efficiently inhibits their growth and their metastasis up to complete regression. Additionally, expression of a 10aa peptide that cor responds to as 51 to 60 of ATF2 sensitizes melanoma cells to spontaneous apoptosis, which coincides with activation of caspase 9 and poly(ADP-ribose) polymerase cleavage, and inhibit their growth in vivo. The 10aa peptide increases the association of c-Jun NH2-terminal kinase with c-Jun but not with ATF2, resulting in concomitant increase in TRE-mediated transcription. Our study points to mechanisms underlying the activities of the ATF2 peptide while highlighting its possible use in drug design. C1 Ruttenberg Canc Ctr, Mt Sinai Sch Med, Dept Oncol Sci, New York, NY 10029 USA. NCI, Lab Mol Technol, Frederick, MD USA. RP Ronai, Z (reprint author), Ruttenberg Canc Ctr, Mt Sinai Sch Med, Dept Oncol Sci, New York, NY 10029 USA. EM zeev.ronai@mssm.edu OI RONAI, ZEEV/0000-0002-3859-0400 FU NCI NIH HHS [CA99961] NR 35 TC 36 Z9 38 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2004 VL 64 IS 22 BP 8222 EP 8230 DI 10.1158/0008-5472.CAN-04-0714 PG 9 WC Oncology SC Oncology GA 872CA UT WOS:000225182300015 PM 15548688 ER PT J AU Merchant, MS Yang, XZ Melchionda, F Romero, M Klein, R Thiele, CJ Tsokos, M Kontny, HU Mackall, CL AF Merchant, MS Yang, XZ Melchionda, F Romero, M Klein, R Thiele, CJ Tsokos, M Kontny, HU Mackall, CL TI Interferon gamma enhances the effectiveness of tumor necrosis factor-related apoptosis-inducing ligand receptor agonists in a xenograft model of Ewing's sarcoma SO CANCER RESEARCH LA English DT Article ID TRAIL-INDUCED APOPTOSIS; IN-VIVO; CHEMOTHERAPEUTIC-AGENTS; TUMORICIDAL ACTIVITY; ANTITUMOR-ACTIVITY; NATURAL-KILLER; MELANOMA-CELLS; T-CELLS; EXPRESSION; CASPASE-8 AB Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces selective apoptosis in a variety of tumors, including most cell lines derived from Ewing's sarcoma family of tumors, an aggressive sarcoma that afflicts children and young adults. To determine the in vivo efficacy of TRAIL receptor agonists in Ewing's sarcoma family of tumors, mice with orthotopic xenografts were treated with anti-TRAIL-R2 monoclonal antibody or TRAIL/Apo2L in a model that can identify effects on both primary tumors and metastases. Administration of either agonist slowed tumor growth in 60% of animals and induced durable remissions in 11 to 19% but did not alter the incidence of metastatic disease. Response rates were not improved by concurrent doxorubicin treatment. Cells recovered from both TRAIL receptor agonist-treated and nontreated tumors were found to be resistant to TRAIL-induced death in vitro unless pretreated with interferon (IFN) gamma. This resistance coincided with a selective down-regulation of TRAIL receptor expression on tumor cells. In vivo treatment with IFNgamma increased tumor expression of TRAIL receptors and caspase 8, but did not increase the antitumor effect of TRAIL receptor agonists on primary tumors. However, IFNgamma treatment alone or in combination with a TRAIL receptor agonist significantly decreased the incidence of metastatic disease and the combination of TRAIL receptor agonist therapy with IFNgamma-mediated impressive effects on both primary tumors and metastatic disease. These data demonstrate that in vivo growth favors TRAIL resistance but that TRAIL receptor agonists are active in Ewing's sarcoma family of tumors and that the combination of TRAIL receptor agonists with IFNgamma is a potent regimen in this disease capable of controlling both primary and metastatic tumors. C1 NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Univ Bologna, S Orsola M Malpighi Hosp, Dept Pediat Hematol Oncol, I-40126 Bologna, Italy. Univ Freiburg, Childrens Hosp, Freiburg, Germany. RP Merchant, MS (reprint author), NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. EM merchanm@mail.nih.gov NR 38 TC 50 Z9 55 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2004 VL 64 IS 22 BP 8349 EP 8356 DI 10.1158/0008-5472.CAN-04-1705 PG 8 WC Oncology SC Oncology GA 872CA UT WOS:000225182300031 PM 15548704 ER PT J AU Li, X Hui, AM Sun, L Hasegawa, K Torzilli, G Minagawa, M Takayama, T Makuuchi, M AF Li, X Hui, AM Sun, L Hasegawa, K Torzilli, G Minagawa, M Takayama, T Makuuchi, M TI p16(INK4A) hypermethylation is associated with hepatitis virus infection, age, and gender in hepatocellular carcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID CPG ISLAND METHYLATION; ABERRANT METHYLATION; DNA METHYLATION; PROMOTER METHYLATION; GASTRIC-CARCINOMA; COLORECTAL-CANCER; MESSENGER-RNA; LUNG-CANCER; GENE; INACTIVATION AB Purpose: The tumor suppressor gene p16(INK4A) is mainly inactivated by an epigenetic change involving promoter hypermethylation in hepatocarcinogenesis. The possible clinical impact of p16(INK4A) methylation and the potential risk factors for this epigenetic alteration have not been thoroughly investigated. Experimental Design: We studied the methylation status and mRNA and protein expression of p16(INK4A) in 50 hepatocellular carcinomas and corresponding nonneoplastic liver lesions using methylation-specific PCR, reverse transcription-PCR, and immunohistochemical techniques. Results: p16(INK4A) hypermethylation was observed in 58% (29 of 50) of the hepatocellular carcinomas and 16% (6 of 38) of the corresponding chronic hepatitis and cirrhosis tissue samples. p16(INK4A) methylation was significantly associated with mRNA and protein expression (P < 0.001 and P = 0.003, respectively). All of the p16(INK4A)-methylated tumors were positive for hepatitis B virus or hepatitis C virus markers, but none of the virus-negative tumors exhibited p16(INK4A) methylation (P = 0.006). The frequency of p16(INK4A) hypermethylation tended to be higher in hepatitis C virus-related tumors (23 of 32, 72%) than in hepatitis B virus-related tumors (6 of 13, 46%; P = 0.1). Aberrant methylation of p16(INK4A) was also related significantly to increasing age, female gender, and normal levels of serum PIVKA-II (P = 0.02, 0.04, and 0.04, respectively). No statistically significant difference in survival was observed between patients with p16(INK4A) hypermethylation and those without. Conclusions: Our observations suggest that p16(INK4A) hypermethylation may contribute to hepatocarcinogenesis from an early stage and that multiple risk factors, such as viral infections, age, and gender, may be associated with p16(INK4A) hypermethylation in hepatocarcinogenesis. C1 Univ Tokyo, Grad Sch Med, Dept Surg, Hepatobilary Pancreat Surg Div, Tokyo, Japan. RP Hui, AM (reprint author), NCI, Neurooncol Branch, NIH, Bldg 35,Room 2B207,35 Lincoln Dr, Rockville, MD 20852 USA. EM huia@mail.nih.gov RI 幕内, 雅敏/A-2140-2012 NR 35 TC 68 Z9 70 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2004 VL 10 IS 22 BP 7484 EP 7489 DI 10.1158/1078-0432.CCR-04-1715 PG 6 WC Oncology SC Oncology GA 874LH UT WOS:000225351400006 PM 15569978 ER PT J AU Stearns, V Coop, A Singh, B Gallagher, A Yamauchi, H Lieberman, R Pennanen, M Trock, B Hayes, DF Ellis, MJ AF Stearns, V Coop, A Singh, B Gallagher, A Yamauchi, H Lieberman, R Pennanen, M Trock, B Hayes, DF Ellis, MJ TI A pilot surrogate end point biomarker trial of perillyl alcohol in breast neoplasia SO CLINICAL CANCER RESEARCH LA English DT Article ID D-LIMONENE; CANCER CHEMOPREVENTION; MAMMARY-TUMORS; CLINICAL-TRIAL; BIOPSY SPECIMENS; INHIBITION; PREVENTION; REGRESSION; TAMOXIFEN; APOPTOSIS AB Purpose: Efficient strategies to screen promising agents in early phase development are essential for rapid progress in breast cancer chemoprevention. We report our experience with the natural compound perillyl alcohol (POH) administered in a short-term surrogate end point biomarker (SEB) protocol, using the "window" between diagnostic and definitive surgery. Experimental Design: Eligible patients included those with a diagnosis of atypical ductal hyperplasia, ductal carcinoma in situ, lobular carcinoma in situ, or invasive carcinoma (< 3 cm in size) that required further surgery. Thirty-seven of 267 women screened were enrolled in the study (14%). Five women received single-dose POH (1.5 g/m(2)) 2 days before surgery, 16 received escalating doses of POH (1.2 g/m(2) to 4.8 g/m(2)/day) for 2 days before surgery, and 16 served as untreated controls. Exploratory SEB analysis [estrogen receptor, progesterone receptor, proliferation, apoptosis, M6P/insulin-like growth factor (IGF)-2R, IGF1, IGF2 and transforming growth factor beta] was conducted before and after POH. Results: Only a small portion of the population screened entered the study. Reasons for nonparticipation included protocol ineligibility, conflict of timing of surgery, miscellaneous logistical reasons, or patient's choice. POH administration was well tolerated and did not interfere with surgical management. The power to observe changes in candidate SEB was diminished by a 44% incidence of cases in which the index lesion was not present in the definitive surgical specimen. Conclusions: Preoperative POH exposure was safe and suitable for a more definitive phase II SEB study. Further investigations must overcome logistical obstacles to accrual, and they must focus on approaches to maximize tissue collection and to incorporate genomic analysis of target lesions. C1 Georgetown Univ, Breast Canc Program, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. Georgetown Univ, Dept Oncol, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. Georgetown Univ, Dept Pathol, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. Georgetown Univ, Dept Surg, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. Georgetown Univ, Dept Canc Prevent & Control, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. NCI, Chemoprevent Branch, Bethesda, MD 20892 USA. RP Hayes, DF (reprint author), Univ Michigan, Med Ctr, 6312 CCGC,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM hayesdf@umich.edu FU NCI NIH HHS [N01-CN-65003] NR 36 TC 11 Z9 12 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2004 VL 10 IS 22 BP 7583 EP 7591 DI 10.1158/1078-0432.CCR-04-0295 PG 9 WC Oncology SC Oncology GA 874LH UT WOS:000225351400017 PM 15569989 ER PT J AU Kobayashi, H Reijnders, K English, S Yordanov, AT Milenic, DE Sowers, AL Citrin, D Krishna, MC Waldmann, TA Mitchell, JB Brechbiel, MW AF Kobayashi, H Reijnders, K English, S Yordanov, AT Milenic, DE Sowers, AL Citrin, D Krishna, MC Waldmann, TA Mitchell, JB Brechbiel, MW TI Application of a macromolecular contrast agent for detection of alterations of tumor vessel permeability induced by radiation SO CLINICAL CANCER RESEARCH LA English DT Article ID POLYAMIDOAMINE DENDRIMER CORE; ENDOTHELIAL GROWTH-FACTOR; SINGLE-CHAIN FV; MONOCLONAL-ANTIBODY; IN-VIVO; SOLID TUMORS; MICROVASCULAR PERMEABILITY; PHARMACOKINETIC PROPERTIES; VASCULAR-PERMEABILITY; MR-ANGIOGRAPHY AB Permeability of tumor vasculature can be a major barrier to successful drug delivery, particularly for high molecular weight agents such as monoclonal antibodies and their diagnostic or therapeutic conjugates. In this study, changes in permeability of SCCVII tumor vessels after radiation treatment were evaluated by dynamic magnetic resonance imaging as a function of time after irradiation using a generation-8 polyamidoamine dendrimer (G8-Gd-D)-based magnetic resonance imaging contrast agent shown previously to be confined to tumor blood vessels. Tumor irradiation consisted of either single doses (2-15 Gy) or various daily fractionated doses (5 days). A single radiation dose of 15 Gy resulted in significant transient image enhancement of the tumor tissue with a maximum occurring between 7 and 24 hours after radiation treatment. No observable enhancement was recorded for fractionated radiation doses. Use of dynamic magnetic resonance imaging coupled with G8-Gd-D provides an exquisite methodology capable of defining the timing of enhanced permeability of macromolecules in tumors after irradiation. Such information might be applied to optimize the efficacy of subsequent or concurrent therapies including radiolabeled antibodies or other anticancer agents in combination with external beam therapies. C1 NCI, Mol Imaging Program, NIH, Canc Res Ctr,Metab Branch, Bethesda, MD 20892 USA. NCI, Radiat Biol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, NIH, Canc Res Ctr,Metab Branch, Bldg 10,Room B3B69,10 Ctr Dr, Bethesda, MD 20892 USA. EM Kobayashi@mail.nih.gov NR 62 TC 47 Z9 49 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2004 VL 10 IS 22 BP 7712 EP 7720 DI 10.1158/1078-0432.CCR-04-1175 PG 9 WC Oncology SC Oncology GA 874LH UT WOS:000225351400033 PM 15570005 ER PT J AU van Burik, JAH Ratanatharathorn, V Stepan, DE Miller, CB Lipton, JH Vesole, DH Bunin, N Wall, DA Hiemenz, JW Satoi, Y Lee, JM Walsh, TJ AF van Burik, JAH Ratanatharathorn, V Stepan, DE Miller, CB Lipton, JH Vesole, DH Bunin, N Wall, DA Hiemenz, JW Satoi, Y Lee, JM Walsh, TJ CA Natl Inst Allergy Infect Dis TI Micafungin versus fluconazole for prophylaxis against invasive fungal infections during neutropenia in patients undergoing hematopoietic stem cell transplantation SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID MARROW TRANSPLANTATION; CANDIDA-ALBICANS; CONTROLLED TRIAL; DOUBLE-BLIND; FK463; LIPOPEPTIDE; PHARMACOKINETICS; RECIPIENTS; EFFICACY; SYNTHASE AB We hypothesized that chemoprophylaxis with the echinocandin micafungin would be an effective agent for antifungal prophylaxis during neutropenia in patients undergoing hematopoietic stem cell transplantation (HSCT). We therefore conducted a randomized, double-blind, multi-institutional, comparative phase III trial, involving 882 adult and pediatric patients, of 50 mg of micafungin (1 mg/kg for patients weighing < 50 kg) and 400 mg of fluconazole (8 mg/kg for patients weighing < 50 kg) administered once per day. Success was defined as the absence of suspected, proven, or probable invasive fungal infection (IFI) through the end of therapy and as the absence of proven or probable IFI through the end of the 4-week period after treatment. The overall efficacy of micafungin was superior to that of fluconazole as antifungal prophylaxis during the neutropenic phase after HSCT (80.0% in the micafungin arm vs. 73.5% in the fluconazole arm [difference, 6.5%]; 95% confidence interval, 0.9% - 12%; P = .03). This randomized trial demonstrates the efficacy of an echinocandin for antifungal prophylaxis in neutropenic patients. C1 NCI, Bethesda, MD 20892 USA. Univ Minnesota, Minneapolis, MN USA. Univ Michigan, Ann Arbor, MI 48109 USA. Oregon Hlth & Sci Univ, Portland, OR USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Cardinal Glennon Childrens Hosp, St Louis, MO USA. Med Coll Georgia, Augusta, GA 30912 USA. Fujisawa Healthcare, Dearborn, IL USA. Univ Alabama Birmingham, Birmingham, AL USA. RP Walsh, TJ (reprint author), NCI, Bldg 10,Rm 13N-240,10 Ctr Dr, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov RI Young, Jo-Anne/G-2617-2013 OI Young, Jo-Anne/0000-0003-4182-341X FU NIAID NIH HHS [N01-AI-65296] NR 21 TC 380 Z9 397 U1 0 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV 15 PY 2004 VL 39 IS 10 BP 1407 EP 1416 DI 10.1086/422312 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 904JH UT WOS:000227492000001 PM 15546073 ER PT J AU Rao, M AF Rao, M TI Conserved and divergent paths that regulate self-renewal in mouse and human embryonic stem cells SO DEVELOPMENTAL BIOLOGY LA English DT Review DE human embryonic stem cells; self-renewal; conserved and divergent paths ID LEUKEMIA INHIBITORY FACTOR; PLURIPOTENCY SUSTAINING FACTOR; PUTATIVE DOWNSTREAM GENES; CYCLIN D1 EXPRESSION; TARGETED DISRUPTION; X-CHROMOSOME; MAMMALIAN DEVELOPMENT; FACULTATIVE HETEROCHROMATIN; DEVELOPMENTAL EXPRESSION; UNDIFFERENTIATED STATE AB The past few years have seen remarkable progress in our understanding of embryonic stem cell (ES cell) biology. The necessity of examining human ES cells in culture, coupled with the wealth of genomic data and the multiplicity of cell lines available, has enabled researchers to identify critical conserved pathways regulating self-renewal and identify markers that tightly correlate with the ES cell state. Comparison across species has suggested additional pathways likely to be important in long-term self-renewal of ES cells including heterochronic genes, microRNAs, genes involved in telomeric regulation, and polycomb repressors. In this review, we have discussed information on molecules known to be important in ES cell self-renewal or blastocyst development and highlighted known differences between mouse and human ES cells. We suggest that several additional pathways required for self-renewal remain to be discovered and these likely include genes involved in antisense regulation, microRNAs, as well as additional global repressive pathways and novel genes. We suggest that cross species comparisons using large-scale genomic analysis tools are likely to reveal conserved and divergent paths required for ES cell self-renewal and will allow us to derive ES lines from species and strains where this has been difficult. Published by Elsevier Inc. C1 NIA, Neurosci Lab, Gerontol Res Ctr, Natl Inst Hlth,Stem Cell Sect, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Rao, M (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr, Natl Inst Hlth,Stem Cell Sect, 5600 Nathan Shock Dr,Room 4E02, Baltimore, MD 21224 USA. EM raomah@grc.nia.nih.gov NR 146 TC 120 Z9 137 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD NOV 15 PY 2004 VL 275 IS 2 BP 269 EP 286 DI 10.1016/j.ydbio.2004.08.013 PG 18 WC Developmental Biology SC Developmental Biology GA 868ZS UT WOS:000224952500001 PM 15501218 ER PT J AU Brown, P Rau, EH Lemieux, P Johnson, BK Bacote, AE Gajdusek, DC AF Brown, P Rau, EH Lemieux, P Johnson, BK Bacote, AE Gajdusek, DC TI Infectivity studies of both ash and air emissions from simulated incineration of scrapie-contaminated tissues SO ENVIRONMENTAL SCIENCE & TECHNOLOGY LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; BOVINE SPONGIFORM ENCEPHALOPATHY; PRION PROTEIN ACCUMULATION; RISK-ASSESSMENT; THEORETICAL IMPLICATIONS; BRAIN-TISSUE; AGENTS; BSE; INACTIVATION; SURVIVAL AB We investigated the effectiveness of 15 min exposures to 600 and 1000 degreesC in continuous flow normal and starved-air incineration-like conditionsto inactivate samples of pooled brain macerates from hamsters infected with the 263K strain of hamster-adapted scrapie with an infectivity titer in excess of 109 mean lethal doses (LD50) per g. Bioassays of the ash, outflow tubing residues, and vented emissions from heating 1 g of tissue samples yielded a total of two transmissions among 21 inoculated animals from the ash of a single specimen burned in normal air at 600 degreesC. No other ash, residue, or emission from samples heated at either 600 or 1000 degreesC, under either normal or starved-air conditions, transmitted disease. We conclude that at temperatures approaching 1000 degreesC under the air conditions and combustion times used in these experiments, contaminated tissues can be completely inactivated, with no release of infectivity into the environment from emissions. The extent to which this result can be realized in actual incinerators and other combustion devices will depend on equipment design and operating conditions during the heating process. C1 NINDS, Lab Cent Nervous Syst Studies, Bethesda, MD 20892 USA. US Dept Hlth & Human Serv, Div Environm Protect, Off Res Facil Dev & Operat, NIH, Bethesda, MD 20892 USA. US EPA, Natl Homeland Secur Res Ctr, Off Res & Dev, Res Triangle Pk, NC 27711 USA. CNRS, Inst Alfred Fessard, F-91198 Gif Sur Yvette, France. RP Brown, P (reprint author), NINDS, Lab Cent Nervous Syst Studies, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM paulwbrown@comcast.net FU PHS HHS [RW75938614] NR 35 TC 24 Z9 25 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0013-936X J9 ENVIRON SCI TECHNOL JI Environ. Sci. Technol. PD NOV 15 PY 2004 VL 38 IS 22 BP 6155 EP 6160 DI 10.1021/es040301z PG 6 WC Engineering, Environmental; Environmental Sciences SC Engineering; Environmental Sciences & Ecology GA 873IC UT WOS:000225272100046 PM 15575075 ER PT J AU Bialkowski, K Kasprzak, KS AF Bialkowski, K Kasprzak, KS TI Cellular 8-oxo-7,8-dihydro-2 '-deoxyguanosine 5 '-triphosphate pyrophosphohydrolase activity of human and mouse MTH1 proteins does not depend on the proliferation rate SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE MTH1; 8-oxo-2 ' deoxyguanosine 5 '-triphosphate; 8-oxo-7,8-dihydro-2 '-deoxyguanosine 5 '-triphosphatase; pyrophosphohydrolase; antimutagenic enzyme; MutT homolog; oxidative DNA damage; DNA repair; Cancer marker; free radicals ID HUMAN MUTT HOMOLOG; HMTH1 MESSENGER-RNA; 8-OXO-DGTPASE ACTIVITY; OXIDATIVE STRESS; 8-OXODEOXYGUANOSINE TRIPHOSPHATE; TRANSVERSION MUTATION; PARTIAL-HEPATECTOMY; LIVER-REGENERATION; ESCHERICHIA-COLI; DNA-POLYMERASES AB Mammalian MTH1 proteins, homologs of Escherichia coli MutT, are enzymes decomposing 8-oxo-7,8-dihydro-2'- deoxyguanosine 5'-triphosphate (8-oxo-dGTP) to 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-monophosphate and inorganic pyrophosphate. They play an antimutagenic role by preventing the incorporation of promutagenic 8-oxo-dGTP into DNA. MTH1 gene expression is higher in some physiological types of mammalian cells and in numerous cancer cells, but the mechanism of that upregulation still remains unclear. It has been hypothesized that MTH1 expression might be associated with a proliferation rate of the cells. Therefore, we tested this hypothesis by comparing the functional levels of MTH1 gene expression measured as the 8-oxo-dGTPase activity of its protein products in normal mouse livers and hepatectomized regenerating livers. Although the proliferation rate of the hepatocytes in the regenerating livers was much higher than that in control livers, as confirmed by immunohistochemical assay of proliferating cell nuclear antigen, the 8-oxo-dGTPase activity was not different. In a second approach, we used 57 lines of human cancer cells in which 8-oxo-dGTPase activity was measured and confronted with cell population doubling time. No significant correlations between 8-oxo-dGTPase activity and proliferation rate were observed within groups of six leukemia, eight melanoma, nine lung, seven colon, six central nervous system, six ovarian, eight renal, and seven breast cancer cell lines. Thus, we conclude that the MTH1 expression manifested as the 8-oxo-dGTPase activity of its protein products in mammalian cells is not associated with proliferation rate. Our results will help in further testing of the hypothesis that MTH1 overexpression may be a specific marker of carcinogenesis and/or oxidative stress. (C) 2004 Elsevier Inc. All rights reserved. C1 Ludwik Rydygier Med Univ, Dept Clin Biochem, PL-85092 Bydgoszcz, Poland. NCI, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA. RP Bialkowski, K (reprint author), Ludwik Rydygier Med Univ, Dept Clin Biochem, Karlowicza 24, PL-85092 Bydgoszcz, Poland. EM karolb@amb.bydgoszcz.pl RI Bialkowski, Karol/E-2328-2014 NR 49 TC 6 Z9 7 U1 0 U2 5 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 NOV 15 PY 2004 VL 37 IS 10 BP 1534 EP 1541 DI 10.1016/j.freeradbiomed.2004.07.018 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 866SA UT WOS:000224792100003 PM 15477005 ER PT J AU Chen, YR Chen, CL Liu, XP Li, HT Zweier, JL Mason, RP AF Chen, YR Chen, CL Liu, XP Li, HT Zweier, JL Mason, RP TI Involvement of protein radical, protein aggregation, and effects on NO metabolism in the hypochlorite-mediated oxidation of mitochondrial cytochrome c SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE cytochrome c; hypochlorite; protein radical; protein aggregates; nitric oxide metabolism; free radicals ID NITRIC-OXIDE; METHIONINE OXIDATION; LIPID-PEROXIDATION; HYDROGEN-PEROXIDE; TYROSINE NITRATION; BIOLOGICAL-SYSTEMS; HUMAN-NEUTROPHILS; ELECTRON-TRANSFER; XANTHINE-OXIDASE; HUMAN MYOGLOBIN AB Cytochrome c (cyt c)-derived protein radicals, radical adduct aggregates, and protein tyrosine nitration have been implicated in the pro-apoptotic event connecting inflammation to the development of diseases. During inflammation, one of the reactive oxygen species metabolized via neutrophil activation is hypochlorite (HOC1); destruction of the mitochondrial electron transport chain by hypochlorite is considered to be a damaging factor. Previous study has shown that HOC1 induces the site-specific oxidation of cyt c at met-80. In this work, we have assessed the hypothesis that exposure of cyt c to physiologically relevant concentrations of HOC1 leads to protein-derived radical and consequent protein aggregation, which subsequently affects cyt c's regulation of nitric oxide metabolism. Reaction intermediates, chemical pathways available for protein aggregation, and protein nitration were examined. A weak ESR signal for immobilized nitroxide derived from the protein was detected when a high concentration of cyt c was reacted with hypochlorite in the presence of the nitroso spin trap 2-methyl-2-nitrosopropane. When a low concentration of cyt c was exposed to the physiologically relevant levels of HOC1 in the presence of 5,5-dimethyl-pyrroline N-oxide (DMPO), we detected DMPO nitrone adducts derived from both protein and protein aggregate radicals as assessed by Western blot using an antibody raised against the DMPO nitrone adduct. The cyt c-derived protein radicals formed by HOC1 were located on lysine and tyrosine residues, with lysine predominating. Cyt c-derived protein aggregates induced by HOC1 involved primarily lysine residues and hydrophobic interaction. In addition, HOC1-oxidized cyt c (HOC1-cyt c) exhibited a higher affinity for NO and enhancement of nonenzymatic NO synthesis from nitrite reduction. Furthermore, HOC1-mediated cyt c oxidation also resulted in a significant elevation of cyt c nitration derived from either NO trapping of the cyt c-derived tyrosyl radical or cyt c-catalyzed one-electron oxidation of nitrite. (C) 2004 Elsevier Inc. All rights reserved. C1 Ohio State Univ, Coll Med, Div Cardiovasc Med, Dept Internal Med,Davis Heart & Lung Res Inst, Columbus, OH 43210 USA. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Chen, YR (reprint author), Ohio State Univ, Coll Med, Div Cardiovasc Med, Dept Internal Med,Davis Heart & Lung Res Inst, 473 W 12th Ave, Columbus, OH 43210 USA. EM chen-12@medctr.osu.edu RI Liu, Xiaoping/A-4516-2008 FU NHLBI NIH HHS [R01S-HL38324, HL65608, HL63744]; NIEHS NIH HHS [K22 ES011031, K22-ES11031] NR 52 TC 37 Z9 39 U1 1 U2 6 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 NOV 15 PY 2004 VL 37 IS 10 BP 1591 EP 1603 DI 10.1016/j.freeradbiomed.2004.07.013 PG 13 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 866SA UT WOS:000224792100008 PM 15477010 ER PT J AU Samuni, AM DeGraff, W Cook, JA Krishna, MC Russo, A Mitchell, JB AF Samuni, AM DeGraff, W Cook, JA Krishna, MC Russo, A Mitchell, JB TI The effects of antioxidants on radiation-induced apoptosis pathways in TK6 cells SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE nitroxides; L-NAC; caspase; PARP; ionizing radiation; apoptosis; free radicals ID ACTIVATED PROTEIN-KINASE; SIGNAL-TRANSDUCTION PATHWAYS; INDUCED DNA-DAMAGE; N-ACETYLCYSTEINE; OXIDATIVE STRESS; IN-VITRO; CLONOGENIC SURVIVAL; HYDROGEN-PEROXIDE; MAMMALIAN-CELLS; CANCER CELLS AB This study was designed to determine if radiation-mediated activation of the apoptotic pathways would be influenced by antioxidants and if a correlation would be found between radioprotection and changes in transduction pathways. Human lymphoblastoid TK6 cells, known to undergo apoptosis as a result of radiation, were irradiated (6 Gy) with and without antioxidants, and then whole-cell lysates were collected. Parallel studies were conducted to assess the survival (clonogenic assay) and apoptotic index. The impacts of two nitroxide antioxidants, tempol and CAT-1, differing in cell permeability, as well as the sulfhydryl antioxidant N-acetyl-L-cysteine (L-NAC), were estimated. Changes in apoptotic pathway proteins and p53 were assessed by Western blotting. Fraction of apoptotic cells was determined by flow cytometry. Tempol (10 mM), which readily enters cells, partially radioprotected TK6 cells against clonogenic killing, but had no effect on radiation-induced apoptotic parameters such as cleaved caspase 3 or cleaved PARP. Tempol alone did not induce cytotoxicity, yet did increase cleaved PARP levels. The radiation-induced increase in p53 protein was partly inhibited by tempol, but was unaffected by CAT-1 and L-NAC. Both CAT-1 (10 mM), which does not enter cells, and L-NAC (10 mM) had no radioprotective effect on cell survival. Although L-NAC did not protect against radiation-induced cytotoxicity, it completely inhibited radiation-induced increase in cleaved caspase 3 and cleaved PART. Collectively, the results question the validity of using selected apoptosis pathway members as sole indicators of cytotoxicity. Published by Elsevier Inc. C1 NCI, Canc Res Ctr, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. RP Mitchell, JB (reprint author), NCI, Canc Res Ctr, Radiat Biol Branch, NIH, Bldg 10,Room B3-B69, Bethesda, MD 20892 USA. EM jbm@helix.nih.gov NR 61 TC 28 Z9 28 U1 0 U2 3 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 NOV 15 PY 2004 VL 37 IS 10 BP 1648 EP 1655 DI 10.1016/j.freeradbiomed.2004.08.006 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 866SA UT WOS:000224792100014 PM 15477016 ER PT J AU Pavlicek, A Noskov, VN Kouprina, N Barrett, JC Jurka, J Larionov, V AF Pavlicek, A Noskov, VN Kouprina, N Barrett, JC Jurka, J Larionov, V TI Evolution of the tumor suppressor BRCA1 locus in primates: implications for cancer predisposition SO HUMAN MOLECULAR GENETICS LA English DT Article ID BREAST-CANCER; OVARIAN-CANCER; REPETITIVE ELEMENTS; POSITIVE SELECTION; MISSENSE MUTATIONS; SEQUENCE ALIGNMENT; GENOMIC DELETIONS; INFORMATION CORE; DNA-SEQUENCES; KB DELETION AB Germ-line mutations in the BRCA1 gene predispose affected individuals to breast and ovarian cancer syndromes. In an attempt to systematically analyze a broader spectrum of genetic changes ranging from frequent exon deletions and duplications to amino acid replacements and protein truncations, we isolated and characterized full size BRCA1 homologues from a representative group of non-human primates. Our analysis represents the first comprehensive sequence comparison of primate BRCA1 loci and corresponding proteins. The comparison revealed an unusually high proportion of indels in non-coding DNA. The major force driving evolutionary changes in non-coding BRCA1 sequences was Alu-mediated rearrangements, including Alu transpositions and Alu-associated deletions, indicating that structural instability of this locus may be intrinsic in anthropoids. Analysis of the non-synonymous/synonymous ratio in coding portions of the gene revealed the presence of both conserved and rapidly evolving regions in the BRCA1 protein. Previously, a rapidly evolving region with evidence of positive evolutionary selection in human and chimpanzee had been identified only in exon 11. Here, we show that most of the internal BRCA1 sequence is variable between primates and evolved under positive selection. In contrast, the terminal regions of BRCA1, which encode the RING finger and BRCT domains, experienced negative selection, which left them almost identical between the compared primates. Distribution of the reported missense mutations, but not frameshift and nonsense mutations, is positively correlated with BRCA1 protein conservation. Finally, on the basis of protein sequence conservation, we identified missense changes that are likely to compromise BRCA1 function. C1 NCI, Lab Biosyst & Canc, Bethesda, MD 20892 USA. Genet Informat Res Inst, Mountain View, CA USA. RP Larionov, V (reprint author), NCI, Lab Biosyst & Canc, Bethesda, MD 20892 USA. EM larionov@mail.nih.gov FU NLM NIH HHS [2 P41 LM 06252-04A1] NR 69 TC 50 Z9 55 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV 15 PY 2004 VL 13 IS 22 BP 2737 EP 2751 DI 10.1093/hmg/ddh301 PG 15 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 873BG UT WOS:000225253100002 PM 15385441 ER PT J AU Petereit, DG Rogers, D Govern, F Coleman, N Osburn, CH Howard, SP Kaur, J Burhansstipanov, L Fowler, JF Chappell, R Mehta, MP AF Petereit, DG Rogers, D Govern, F Coleman, N Osburn, CH Howard, SP Kaur, J Burhansstipanov, L Fowler, JF Chappell, R Mehta, MP TI Increasing access to clinical cancer trials and emerging technologies for minority populations: The Native American project SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID DOSE-RATE BRACHYTHERAPY; PROSTATE-CANCER; RADIATION C1 John T Vucurevich Canc Care Inst, Rapid City, SD USA. Univ Wisconsin, Ctr Comprehens Canc, Dept Human Oncol, Madison, WI 53706 USA. John T Vucurevich Canc Care Inst, Bethesda, MD USA. NCI, Radiat Res Program, NIH, Bethesda, MD USA. NCI, Radiat Res Program, NIH, Frederick, MD USA. SAIC Frederick, Sci Applicat Int Corp, Frederick, MD USA. Univ Wisconsin, Ctr Comprehens Canc, Dept Human Oncol, Madison, WI 53706 USA. Mayo Clin Comprehens Canc Ctr, Rochester, MN USA. Nat Amer Canc Res Corp, Pine, CO USA. Univ Wisconsin, Ctr Comprehens Canc, Dept Human Oncol, Madison, WI USA. RP Petereit, DG (reprint author), John T Vucurevich Canc Care Inst, Rapid City, SD USA. OI mehta, minesh/0000-0002-4812-5713 FU AHRQ HHS [P01 HS010854]; NCI NIH HHS [1U56CA99010-01, N01-CO-12400] NR 18 TC 18 Z9 18 U1 0 U2 1 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 NOV 15 PY 2004 VL 22 IS 22 BP 4452 EP 4455 DI 10.1200/JCO.2004.01.119 PG 4 WC Oncology SC Oncology GA 871ZP UT WOS:000225175600005 PM 15542797 ER PT J AU Picker, LJ Hagen, SI Lum, R Reed-Inderbitzin, EF Daly, LM Sylwester, AW Walker, JM Siess, DC Piatak, M Wang, CX Allison, DB Maino, VC Lifson, JD Kodama, T Axthelm, MK AF Picker, LJ Hagen, SI Lum, R Reed-Inderbitzin, EF Daly, LM Sylwester, AW Walker, JM Siess, DC Piatak, M Wang, CX Allison, DB Maino, VC Lifson, JD Kodama, T Axthelm, MK TI Insufficient production and tissue delivery of CD4(+) memory T cells in rapidly progressive simian immunodeficiency virus infection SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE AIDS; CD4(+) T lymphocytes; lymphocyte depletion; immunologic memory; rhesus macaque ID RHESUS MACAQUES; DISEASE PROGRESSION; VIRAL REPLICATION; GASTROINTESTINAL-TRACT; HIV-1 INFECTION; CHEMOKINE RECEPTORS; ANTIBODY-RESPONSES; LYMPHOID-TISSUE; SIV INFECTION; DEPLETION AB The mechanisms linking human immunodeficiency virus replication to the progressive immunodeficiency of acquired immune deficiency syndrome are controversial, particularly the relative contribution of CD4(+) T cell destruction. Here, we used the simian immunodeficiency virus (SIV) model to investigate the relationship between systemic CD+ T cell dynamics and rapid disease progression. Of 18 rhesus macaques (RMs) infected with CCR5-tropic SIVmac239 (n = 14) or CXCR4-tropic SIVmac155T3 (n = 4), 4 of the former group manifested end-stage SIV disease by 200 d after infection. In SIVmac155T3 infections, naive CD4(+) T cells were dramatically depleted, but this population was spared by SIVmac239, even in rapid progressors. In contrast, all SIVmac239-infected RMs demonstrated substantial systemic depletion of CD4(+) memory T cells by day 28 after infection. Surprisingly, the extent of CD4(+) memory T cell depletion was not, by itself, a strong predictor of rapid progression. However, in all RMs destined for stable infection, this depletion was countered by a striking increase in production of short-lived CD4(+) memory T cells, many of which rapidly migrated to tissue. In all rapid progressors (P < 0.0001), production of these cells initiated but failed by day 42 of infection, and tissue delivery of new CD4(+) memory T cells ceased. Thus, although profound depletion of tissue CD4(+) memory T cells appeared to be a prerequisite for early pathogenesis, it was the inability to respond to this depletion with sustained production of tissue-homing CD4(+) memory T cells that best distinguished rapid progressors, suggesting that mechanisms of the CD4(+) memory T cell generation play a crucial role in maintaining immune homeostasis in stable SIV infection. C1 Oregon Hlth Sci Univ, Vaccine & Gene Therapy Inst, Dept Pathol, Beaverton, OR 97006 USA. Oregon Hlth Sci Univ, Dept Mol Microbiol & Immunol, Beaverton, OR 97006 USA. Oregon Hlth Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA. Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA. Becton Dickinson Biosci, San Jose, CA 95131 USA. NCI, Sci Applicat Int Corp Frederick Inc, AIDS Vaccine Program, Ft Detrick, MD 21702 USA. Univ Pittsburgh, Dept Mol Genet & Biochem, Pittsburgh, PA 15260 USA. RP Picker, LJ (reprint author), Oregon Hlth Sci Univ, Vaccine & Gene Therapy Inst, Dept Pathol, W Campus,505 NW 185th Ave, Beaverton, OR 97006 USA. EM pickerl@ohsu.edu OI Allison, David/0000-0003-3566-9399 FU NCI NIH HHS [N01-CO-124000]; NCRR NIH HHS [U24 RR018107, P51 RR000163, P51-RR00163, U24-RR018107, U42 RR016025, U42-RR016025]; NIAID NIH HHS [R01 AI054292, R01-AI054292] NR 60 TC 231 Z9 243 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 15 PY 2004 VL 200 IS 10 BP 1299 EP 1314 DI 10.1084/jem.20041049 PG 16 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 875EY UT WOS:000225404300008 PM 15545355 ER PT J AU Smyth, MJ Swann, J Kelly, JM Cretney, E Yokoyama, WM Diefenbach, A Sayers, TJ Hayakawa, Y AF Smyth, MJ Swann, J Kelly, JM Cretney, E Yokoyama, WM Diefenbach, A Sayers, TJ Hayakawa, Y TI NKG2D recognition and perforin effector function mediate effective cytokine immunotherapy of cancer SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE tumor; NK cell; Fas ligand; IL-2; IL-18 ID NATURAL-KILLER-CELLS; I-RELATED CHAIN; DELTA-T-CELLS; NK CELLS; INTERFERON-GAMMA; CUTTING EDGE; IFN-GAMMA; UL16-BINDING PROTEINS; GLYCOPROTEIN UL16; TUMOR-METASTASIS AB Single and combination cytokines offer promise in some patients with advanced cancer. Many spontaneous and experimental cancers naturally express ligands for the lectin-like type-2 transmembrane stimulatory NKG2D immunoreceptor; however, the role this tumor recognition pathway plays in immunotherapy has not been explored to date. Here, we show that natural expression of NKG2D ligands on tumors provides an effective target for some cytokine-stimulated NK cells to recognize and suppress tumor metastases. In particular, interleukin (IL)-2 or IL-12 suppressed tumor metastases largely via NKG2D ligand recognition and perforin-mediated cytotoxicity. By contrast, IL-18 required tumor sensitivity to Fas ligand (FasL) and surprisingly did not depend on the NKG2D-NKG2D ligand pathway. A combination of IL-2 and IL-18 stimulated both perform and FasL effector mechanisms with very potent effects. Cytokines that stimulated perforin-mediated cytotoxicity appeared relatively more effective against tumor metastases expressing NKG2D ligands. These findings indicate that a rational choice of cytokines can be made given the known sensitivity of tumor cells to perform, FasL, and tumor necrosis factor-related apoptosis-inducing ligand and the NKG2D ligand status of tumor metastases. C1 Peter MacCallum Canc Ctr, Canc Immunol Program, Trescowthick Labs, Melbourne, Vic 8006, Australia. Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA. NYU, Ctr Med, Skirball Inst Biomol Med, New York, NY 10016 USA. Natl Canc Inst, SAIC Frederick Inc, Basic Res Program, Ft Detrick, MD 21702 USA. RP Smyth, MJ (reprint author), Peter MacCallum Canc Ctr, Canc Immunol Program, Trescowthick Labs, Locked Bag 1,A Beckett St, Melbourne, Vic 8006, Australia. EM mark.smyth@petermac.org RI Sayers, Thomas/G-4859-2015; Smyth, Mark/H-8709-2014 OI Smyth, Mark/0000-0001-7098-7240 FU PHS HHS [N01-C0-12400] NR 57 TC 101 Z9 111 U1 0 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 NOV 15 PY 2004 VL 200 IS 10 BP 1325 EP 1335 DI 10.1084/jem.20041522 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 875EY UT WOS:000225404300010 PM 15545356 ER PT J AU Ma, G Greenwell-Wild, T Lei, KJ Jin, WW Swisher, J Hardegen, N Wild, CT Wahl, SM AF Ma, G Greenwell-Wild, T Lei, KJ Jin, WW Swisher, J Hardegen, N Wild, CT Wahl, SM TI Secretory leukocyte protease inhibitor binds to annexin II, a cofactor for macrophage HIV-1 infection SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE retrovirus; monocytes; AIDS; fusion; phosphatidylserine ID IMMUNODEFICIENCY-VIRUS TYPE-1; PHOSPHATIDYLSERINE EXPRESSION; MONOCYTIC CELLS; KAPPA-B; RECEPTORS; APOPTOSIS; ELASTASE; PHAGOCYTOSIS; REPLICATION; LYMPHOCYTES AB The distribution of secretory leukocyte protease inhibitor (SLPI) at entry portals indicates its involvement in defending the host from pathogens, consistent with the ability of SLPI to inhibit human immunodeficiency virus (HIV)-1 infection by an unknown mechanism. We now demonstrate that SLPI binds to the membrane of human macrophages through the phospholipid-binding protein, annexin II. Based on the recent identification of human cell membrane phosphatidylserine (PS) in the outer coat of HIV-1, we define a novel role for annexin II, a PS-binding moiety, as a cellular cofactor supporting macrophage HIV-1 infection. Moreover, this HIV-1 PS interaction with annexin II can be disrupted by SLPI or other annexin II-specific inhibitors. The PS-annexin II connection may represent a new target to prevent HIV-1 infection. C1 NIDCR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. Panacos Pharmaceut Inc, Gaithersburg, MD 20877 USA. RP Wahl, SM (reprint author), NIDCR, Oral Infect & Immun Branch, NIH, 30 Convent Dr,MSC 4352,Bldg 30,Room 320, Bethesda, MD 20892 USA. EM smwahl@dir.nidcr.nih.gov NR 46 TC 139 Z9 148 U1 0 U2 8 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 15 PY 2004 VL 200 IS 10 BP 1337 EP 1346 DI 10.1084/jem.20041115 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 875EY UT WOS:000225404300011 PM 15545357 ER PT J AU Chen, B Blair, DG Plisov, S Vasiliev, G Perantoni, AO Chen, Q Athanasiou, M Wu, JY Oppenheim, JJ Yang, D AF Chen, B Blair, DG Plisov, S Vasiliev, G Perantoni, AO Chen, Q Athanasiou, M Wu, JY Oppenheim, JJ Yang, D TI Cutting edge: Bone morphogenetic protein antagonists Drm/Gremlin and Dan interact with slits and act as negative regulators of monocyte chemotaxis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GREMLIN; FAMILY; GROWTH; CELLS; LIMB; OUTGROWTH; REPELLENT; RECEPTOR; GENE AB Drm/Gremlin and Dan, two homologous secreted antagonist of bone morphogenic proteins have been shown to regulate early development, tumorigenesis, and renal pathophysiology. In this study, we report that Drm and Dan physically and functionally interact with Slit1 and Slit2 proteins. Drm binding to Slits depends on its glycosylation and is not interfered with by bone morphogenic proteins. Importantly, Drm and Dan function as inhibitors for monocyte migration induced by stromal cell-derived factor 1alpha (SDF-1alpha) or fMLP. The inhibition of SDF-1alpha-induced monocyte chemotaxis by Dan is not due to blocking the binding of SDF-1alpha to its receptor. Thus, the results identify that Drm and Dan can interact with Slit proteins and act as inhibitors of monocyte chemotaxis, demonstrating a previously unidentified biological role for these proteins. C1 NCI, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. NCI, Basic Res Lab, Ctr Canc Res, Frederick, MD 21702 USA. NCI, Comparat Carcinogenesis Lab, Canc Res Ctr, Frederick, MD 21702 USA. NCI, Mol Immunoregulat Lab, Ctr Canc Res, Frederick, MD 21702 USA. Vanderbilt Univ, Med Ctr, Nashville, TN 37232 USA. RP Yang, D (reprint author), NCI, SAIC Frederick Inc, Basic Res Program, Bldg 560,Room 31-19,1050 Boyles St, Frederick, MD 21702 USA. EM dyang@ncifcrf.gov FU NCI NIH HHS [N01 CO 12400] NR 17 TC 41 Z9 46 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2004 VL 173 IS 10 BP 5914 EP 5917 PG 4 WC Immunology SC Immunology GA 869QL UT WOS:000224999000003 PM 15528323 ER PT J AU Yang, D Chen, Q Rosenberg, HF Rybak, SM Newton, DL Wang, ZY Fu, Q Tchernev, VT Wang, MJ Schweitzer, B Kingsmore, SF Patel, DD Oppenheim, JJ Howard, OMZ AF Yang, D Chen, Q Rosenberg, HF Rybak, SM Newton, DL Wang, ZY Fu, Q Tchernev, VT Wang, MJ Schweitzer, B Kingsmore, SF Patel, DD Oppenheim, JJ Howard, OMZ TI Human ribonuclease A superfamily members, eosinophil-derived neurotoxin and pancreatic ribonuclease, induce dendritic cell maturation and activation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ROLLING-CIRCLE AMPLIFICATION; TRANSFER-RNA SYNTHETASE; ANTIMICROBIAL PEPTIDES; DIFFERENTIAL REGULATION; ADAPTIVE IMMUNITY; GENE-EXPRESSION; HOST-DEFENSE; MAST-CELLS; IN-VITRO; RECEPTOR AB A number of mammalian antimicrobial proteins produced by neutrophils and cells of epithelial origin have chemotactic and activating effects on host cells, including cells of the immune system. Eosinophil granules contain an antimicrobial protein known as eosinophil-derived neurotoxin (EDN), which belongs to the RNase A superfamily. EDN has antiviral and chemotactic activities in vitro. In this study, we show that EDN, and to a lesser extent human pancreatic RNase (hPR), another RNase A superfamily member, activates human dendritic cells (DCs), leading to the production of a variety of inflammatory cytokines, chemokines, growth factors, and soluble receptors. Human angiogenin, a RNase evolutionarily more distant to EDN and hPR, did not display such activating effects. Additionally, EDN and hPR also induced phenotypic and functional maturation DCs. These RNases were as efficacious as TNF-alpha, but induced a different set of cytokine mediators. Furthermore, EDN production by human macrophages could be induced by proinflammatory stimuli. The results reveal the DC-activating activity of EDN and hPR and suggest that they are likely participants of inflammatory and immune responses. A number of endogenous mediators in addition to EDN have been reported to have both chemotactic and activating effects on APCs, and can thus amplify innate and Ag-specific immune responses to danger signals. We therefore propose these mediators be considered as endogenous multifunctional immune alarmins. C1 NCI, Canc Res Ctr, Mol Immunoregulat Lab, Frederick, MD 21702 USA. NCI, Basic Res Program, Frederick, MD 21702 USA. NCI, Div Canc Treatment, Frederick, MD 21702 USA. Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA. Univ N Carolina, Thurston Arthrit Res Ctr, Chapel Hill, NC 27599 USA. NCI, Diag Dev Therapeut Program Support Program, Sci Applicat Int Corp, Frederick, MD 21702 USA. NCI, Diag Dev Therapeut Program Support Program, SAIC Frederick, Frederick, MD 21702 USA. NCI, Diag Dev Therapeut Program Support Program, SAIC Frederick, Frederick, MD 21702 USA. NIAID, Eosinophil Pathophysiol Sect, Lab Host Def, NIH, Bethesda, MD 20892 USA. RP Howard, OMZ (reprint author), NCI, Canc Res Ctr, Mol Immunoregulat Lab, POB B, Frederick, MD 21702 USA. EM howardz@mail.ncifcrf.gov RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 FU NCI NIH HHS [N01CO12400, N01 CO 12400]; NIAID NIH HHS [U01 AI066569, U01 AI066569-01]; NICHD NIH HHS [U19 HD077693] NR 54 TC 76 Z9 80 U1 1 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2004 VL 173 IS 10 BP 6134 EP 6142 PG 9 WC Immunology SC Immunology GA 869QL UT WOS:000224999000030 PM 15528350 ER PT J AU Estes, JD Thacker, TC Hampton, DL Kell, SA Keele, BF Palenske, EA Druey, KM Burton, GF AF Estes, JD Thacker, TC Hampton, DL Kell, SA Keele, BF Palenske, EA Druey, KM Burton, GF TI Follicular dendritic cell regulation of CXCR4-Mediated germinal center CD4 T cell migration SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LYMPHOID-TISSUE CHEMOKINE; HIGH ENDOTHELIAL VENULES; B-CELLS; IMMUNOLOGICAL MEMORY; IMMUNE-COMPLEXES; IN-VITRO; LYMPHOCYTES; RECEPTOR; ANTIGEN; FOLLICLES AB Follicular dendritic cells (FDCs) up-regulate the chemokine receptor CXCR4 on CD4 T cells, and a major subpopulation of germinal center (GC) T cells (CD4(+)CD57(+)), which are adjacent to FDCs in vivo, expresses high levels of CXCR4. We therefore reasoned that GC T cells would actively migrate to stromal cell-derived factor-1 (CXCL12), the CXCR4 ligand, and tested this using Transwell migration assays with GC T cells and other CD4 T cells (CD57(-)) that expressed much lower levels of CXCR4. Unexpectedly, GC T cells were virtually nonresponsive to CXCL12, whereas CD57(-)CD4 T cells migrated efficiently despite reduced CXCR4 expression. In contrast, GC T cells efficiently migrated to B cell chemoattractant-l/CXCL13 and FDC supernatant, which contained CXCL13 produced by FDCs. Importantly, GC T cell nonresponsiveness to CXCL12 correlated with high ex vivo expression of regulator of G protein signaling (RGS), RGS13 and RGS16, mRNA and expression of protein in vivo. Furthermore, FDCs up-regulated both RGS13 and RGS16 mRNA expression in non-GC T cells, resulting in their impaired migration to CXCL12. Finally, GC T cells down-regulated RGS13 and RGS.16 expression in the absence of FDCs and regained migratory competence to CXCL12. Although GC T cells express high levels of CXCR4, signaling through this receptor appears to be specifically inhibited by FDC-mediated expression of RGS13 and RGS16. Thus, FDCs appear to directly affect GC T cell migration within lymphoid follicles. C1 Brigham Young Univ, Dept Chem & Biochem, Provo, UT 84602 USA. Brigham Young Univ, Dept Microbiol & Mol Biol, Provo, UT 84602 USA. NIAID, Mol Signal Transduct Sect, Lab Allerg Dis, NIH, Rockville, MD 20852 USA. RP Burton, GF (reprint author), Brigham Young Univ, Dept Chem & Biochem, Room C-211A BNSN, Provo, UT 84602 USA. EM gburton@chem.byu.edu OI Thacker, Tyler/0000-0001-6779-7649 FU NIAID NIH HHS [AI 39963] NR 66 TC 47 Z9 49 U1 0 U2 9 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2004 VL 173 IS 10 BP 6169 EP 6178 PG 10 WC Immunology SC Immunology GA 869QL UT WOS:000224999000034 PM 15528354 ER PT J AU Gonsky, R Deem, RL Bream, J Young, HA Targan, SR AF Gonsky, R Deem, RL Bream, J Young, HA Targan, SR TI Enhancer role of STAT5 in CD2 activation of IFN-gamma gene expression SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELLS; MEDIATED PROLIFERATION; SIGNAL-TRANSDUCTION; GROWTH-FACTOR; DNA-BINDING; RECEPTOR; PROTEINS; STIMULATION; INTERLEUKIN-2; INHIBITION AB IFN-gamma is an important immunoregulatory protein with tightly controlled expression in activated T and NK cells. Three potential STAT binding regions have been recognized within the IFN-gamma promoter: 1) an IL-12-mediated STAT4 binding site at -236 bp; 2) a newly identified IL-2-induced STAT5 binding element at -3.6 kb; and 3) CD2-mediated STAT1 and STAT4 binding to an intronic element in mucosal T cells. However, functional activation of these sites remains unclear. In this study we demonstrate CD2-mediated activation of the newly characterized -3.6-kb IFN-gamma STAT5 binding region. CD2 signaling of human PBMC results in activation of the -3.6-kb IFN-gamma promoter, whereas mutation of the -3.6-kb STAT5 site attenuates promoter activity. Functional activation is accompanied by STAT5A but little STAT513 nucleoprotein binding to the IFN-gamma STAT5 site, as determined by competition and supershift assays. STAT5 activation via CD2 occurs independent of IL-2. Western and FACS analysis shows increased phospho-STAT5 following CD2 signaling. AG490, a tyrosine kinase inhibitor affecting Jak proteins, inhibits CD2-mediated IFN-gamma mRNA expression, secretion, and nucleoprotein binding to the IFN-gamma STAT5 site in a dose-dependent fashion. This report is the first to describe CD2-mediated activation of STAT5 and supports STAT5 involvement in regulation of IFN-gamma expression. C1 Cedars Sinai Med Ctr, Inflammatory Bowel Dis Res Ctr, Los Angeles, CA 90048 USA. NIAMSD, Lymphocyte Cell Biol Sect, Mol Immunol & Inflammat Branch, Intramural Res Program,NIH, Bethesda, MD 20892 USA. NCI, Cellular & Mol Immunol Sect, Expt Immunol Lab, Frederick, MD 21702 USA. RP Targan, SR (reprint author), Cedars Sinai Med Ctr, Inflammatory Bowel Dis Res Ctr, 8700 Beverly Blvd,D4063, Los Angeles, CA 90048 USA. EM targans@cshs.org FU NIDDK NIH HHS [DK 46773, DK 43211] NR 48 TC 14 Z9 15 U1 2 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 NOV 15 PY 2004 VL 173 IS 10 BP 6241 EP 6247 PG 7 WC Immunology SC Immunology GA 869QL UT WOS:000224999000042 PM 15528362 ER PT J AU Purev, E Cai, DW Miller, E Swoboda, R Klein-Szanto, A Marincola, FM Mick, R Otvos, L Wunner, W Birebent, B Somasundaram, R Wikstrand, CJ Bigner, D DeMichele, A Acs, G Berlin, JA Herlyn, D AF Purev, E Cai, DW Miller, E Swoboda, R Klein-Szanto, A Marincola, FM Mick, R Otvos, L Wunner, W Birebent, B Somasundaram, R Wikstrand, CJ Bigner, D DeMichele, A Acs, G Berlin, JA Herlyn, D TI Immune responses of breast cancer patients to mutated epidermal growth factor receptor (EGF-RvIII, Delta EGF-R, and de2-7 EGF-R) SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CONFERS ENHANCED TUMORIGENICITY; CYTOTOXIC T-LYMPHOCYTES; HUMAN TUMOR-ANTIGENS; HUMAN GLIOBLASTOMA; VACCINE DEVELOPMENT; LUNG CARCINOMAS; OVARIAN-CANCER; COLON-CANCER; CELL; EGFRVIII AB Mutated epidermal growth factor receptor (EGF-RvIII, DeltaEGF-R, and de2-7 EGF-R) is the result of an 801-bp deletion within the extracellular domain of wild-type EGF-R and is expressed by breast carcinomas, but not by normal breast tissues. EGF-RvIII is expressed both on the surface and in the cytoplasm of tumor cells. Thus, EGF-RvIII is a potential tumor-specific target for both Abs and T cells. However, it is not known whether breast cancer patients can raise immune responses to EGF-RvIII expressed by their tumors. The demonstration of EGF-RvIII-specific immune responses in patients would suggest that immunization of patients with EGF-RvIII vaccines is feasible, because these vaccines may boost a pre-existing immune response. We have evaluated humoral and cellular immune responses to EGF-RvIII in 16 breast cancer patients and three healthy donors. Seven of 16 patients developed EGF-RvIII-specific Abs that bound to isolated EGF-RvIII protein or the protein expressed by EGF-RvIII-transfected mouse fibroblasts. The Abs that bound to EGF-RvIII did not bind to wild-type EGF-R, and anti-EGF-RvIII Abs were not found in the sera of healthy donors. Three patients had EGF-RvIII peptide-specific lymphoproliferative responses, and two of these patients also had humoral immune responses. Humoral and cellular immune responses correlated with EGF-RvIII expression by patients' tumors in most cases. These studies demonstrate that breast cancer patients specifically recognize EGF-RvIII with an overall immune response rate of 50%, suggesting that patients may benefit from vaccination against EGF-RvIII, boosting preexisting immune responses. C1 Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. Virtua Mem Hosp, Mt Holly, NJ 08060 USA. Albert Einstein Med Ctr, Philadelphia, PA 19141 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Duke Univ, Durham, NC 27710 USA. RP Herlyn, D (reprint author), 3601 Spruce St, Philadelphia, PA 19104 USA. EM dherlyn@wistar.upenn.edu RI Klein-Szanto, Andres/E-6218-2010 FU NCI NIH HHS [CA 90748, CA 10815] NR 45 TC 19 Z9 20 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2004 VL 173 IS 10 BP 6472 EP 6480 PG 9 WC Immunology SC Immunology GA 869QL UT WOS:000224999000069 PM 15528389 ER PT J AU MacLennan, C Fieschi, C Lammas, DA Picard, C Dorman, SE Sanal, O MacLennan, JM Holland, SM Ottenhoff, THM Casanova, JL Kumararatne, DS AF MacLennan, C Fieschi, C Lammas, DA Picard, C Dorman, SE Sanal, O MacLennan, JM Holland, SM Ottenhoff, THM Casanova, JL Kumararatne, DS TI Interleukin (IL)-12 and IL-23 are key cytokines for immunity against salmonella in humans SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Symposium on Macrophage Activation and Deactivation - Links Between Innate and Adaptive Immunity CY JAN 22-27, 2001 CL Keystone, CO ID INFECTIOUS-DISEASES; HOST-DEFENSE; RESISTANCE; MICE; MYCOBACTERIA; GAMMA AB Patients with inherited deficiency of the interleukin (IL)-12/IL-23-interferon (IFN)-gamma axis show increased susceptibility to invasive disease caused by the intramacrophage pathogens salmonellae and mycobacteria. We analyzed data on 154 patients with such deficiency. Significantly more patients with IL-12/IL-23-component deficiency had a history of salmonella disease than did those with IFN-gamma-component deficiency. Salmonella disease was typically severe, extraintestinal, and caused by nontyphoidal serovars. These findings strongly suggest that IL-12/IL-23 is a key cytokine for immunity against salmonella in humans and that IL-12/IL-23 mediates this protective effect partly through IFN-gamma-independent pathways. Investigation of the IL-12/IL-23-IFN-gamma axis should be considered in patients with invasive salmonella disease. C1 Coll Med, Malawi Liverpool Wellcome Trust Clin Res Programm, Blantyre 3, Malawi. Univ Birmingham, MRC, Ctr Immune Regulat, Div Immun & Infect, Birmingham, W Midlands, England. Addenbrookes Hosp, Dept Biochem & Clin Immunol, Cambridge, England. Univ Oxford, Dept Zool, Oxford OX1 3PS, England. Johns Hopkins Univ, Sch Med, Ctr TB Res, Baltimore, MD USA. NIAID, Immunopathogenesis Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. Hacettepe Univ, Childrens Hosp, Div Immunol, Ankara, Turkey. Univ Paris Rene Descartes, INSERM,U550, Necker Med Sch, Lab Human Genet Infect Dis, Paris, France. Hop Necker Enfants Malad, Pediat Immunol & Hematol Unit, Paris, France. Leids Univ Med Ctr, Dept Immunohematol & Blood Transfus, Leiden, Netherlands. RP MacLennan, C (reprint author), Coll Med, Malawi Liverpool Wellcome Trust Clin Res Programm, POB 30096, Blantyre 3, Malawi. EM cmaclennan@mlw.medcol.mw RI MacLennan, Calman/L-9343-2014 OI MacLennan, Calman/0000-0001-9694-0846 NR 13 TC 114 Z9 117 U1 1 U2 7 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2004 VL 190 IS 10 BP 1755 EP 1757 DI 10.1086/425021 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 865KG UT WOS:000224700800005 PM 15499529 ER PT J AU Burns-Cusato, M Scordalakes, EM Rissman, EF AF Burns-Cusato, M Scordalakes, EM Rissman, EF TI Of mice and missing data: what we know (and need to learn) about male sexual behavior SO PHYSIOLOGY & BEHAVIOR LA English DT Review DE androgen receptor; estrogen receptor; inbred strain; knockout; mice; medial preoptic area; masculinization ID ESTROGEN-RECEPTOR-ALPHA; IN-HOUSE MICE; MALE-TYPICAL BEHAVIORS; MEDIAL PREOPTIC AREA; INTRACRANIAL ANDROGENIC ACTIVATION; NITRIC-OXIDE SYNTHASE; CASTRATED MALE-MICE; MOUSE MUS-MUSCULUS; SWISS-WEBSTER MICE; 2 INBRED STRAINS AB With recent advances in molecular genetics, the popularity of mice as subjects for behavioral neuroscience is increasing at an exponential rate. Unfortunately, the existing body of knowledge on sexual behavior in male mice is not large and many basic gaps exist. The assumption that what is true of rats is also true of mice is a dangerous one that can misdirect and, in the worst case, impede progress. We summarize the current knowledge about the sexual behavior of male mice, with an emphasis on hormonal bases of these behaviors. Behavioral differences between strains, developmental actions of steroids, activational actions of steroids given peripherally and in the brain, and data generated in various receptor knockout and related mice are discussed. In addition, suggestions are made for the standardization of experimental protocols used in investigations of the sexual physiology and behavior of male mice in order to facilitate between-experiment and between-laboratory comparisons and to expedite the growth of knowledge in this area. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Virginia, Sch Med, Dept Biochem & Mol Genet, Charlottesville, VA 22909 USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Burns-Cusato, M (reprint author), Univ Virginia, Sch Med, Dept Biochem & Mol Genet, 1300 Jefferson Pk Ave,POB 800733, Charlottesville, VA 22909 USA. EM mc3fw@virginia.edu FU NICHD NIH HHS [HD072323]; NIMH NIH HHS [K02 MH01349, R01 MH57759] NR 108 TC 31 Z9 31 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD NOV 15 PY 2004 VL 83 IS 2 BP 217 EP 232 DI 10.1016/j.physbeh.2004.08.015 PG 16 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 867WQ UT WOS:000224873900005 PM 15488541 ER PT J AU Gunasekaran, K Ma, BY Nussinov, R AF Gunasekaran, K Ma, BY Nussinov, R TI Is allostery an intrinsic property of all dynamic proteins? SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Review DE allostery; conformational ensembles; allosteric transition; drug discovery; population redistribution; energy landscape; function ID COLI ASPARTATE TRANSCARBAMOYLASE; HIV-1 REVERSE-TRANSCRIPTASE; P53 CORE DOMAIN; CONFORMATIONAL-CHANGES; CRYSTAL-STRUCTURE; HYDROGEN-EXCHANGE; ENZYME FUNCTION; BINDING-SITES; GLYCOGEN-PHOSPHORYLASE; ACETYLCHOLINE-RECEPTOR AB Allostery involves coupling of conformational changes between two widely separated binding sites. The common view holds that allosteric proteins are symmetric oligomers, with each subunit existing in "at least" two conformational states with a different affinity for ligands. Recent observations such as the allosteric behavior of myoglobin, a classical example of a nonallosteric protein, call into question the existing allosteric dogma. Here we argue that all (nonfibrous) proteins are potentially allosteric. Allostery is a consequence of re-distributions of protein conformational ensembles. In a nonallosteric protein, the binding site shape may not show a concerted second-site change and enzyme kinetics may not reflect an allosteric transition. Nevertheless, appropriate ligands, point mutations, or external conditions may facilitate a population shift, leading a presumably nonallosteric protein to behave allosterically. In principle, practically any potential drug binding to the protein surface can alter the conformational. redistribution. The question is its effectiveness in the redistribution of the ensemble, affecting the protein binding sites and its function. Here, we review experimental observations validating this view of protein allostery. (C) 2004 Wiley-Liss, Inc. C1 SAIC Frederick Inc, Basic Res Program, Lab Expt & Computat Biol, NCI, Ft Detrick, MD 21702 USA. Tel Aviv Univ, Sackler Sch Med, Dept Human Genet, Sackler Inst Mol Med, Tel Aviv, Israel. RP Nussinov, R (reprint author), SAIC Frederick Inc, Basic Res Program, Lab Expt & Computat Biol, NCI, Bldg 469,Rm 151, Ft Detrick, MD 21702 USA. EM ruthn@ncifcrf.gov RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU NCI NIH HHS [N01-CO-12400] NR 97 TC 466 Z9 468 U1 12 U2 82 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-3585 J9 PROTEINS JI Proteins PD NOV 15 PY 2004 VL 57 IS 3 BP 433 EP 443 DI 10.1002/prot.20232 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 863RC UT WOS:000224578400001 PM 15382234 ER PT J AU Panchenko, AR Madej, T AF Panchenko, AR Madej, T TI Analysis of protein homology by assessing the (dis)similarity in protein loop regions SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article DE protein evolution; structural alignment; Hausdorff metric; loops ID SEQUENCE ALIGNMENT; DIVERGENT EVOLUTION; DATABASE; IDENTIFICATION; RECOGNITION; DOMAIN; FOLDS; CLASSIFICATION; SIMILARITIES; PREDICTION AB Two proteins are considered to have a similar fold if sufficiently many of their secondary structure elements are positioned similarly in space and are connected in the same order. Such a common structural scaffold may arise due to either divergent or convergent evolution. The intervening unaligned regions ("loops") between the superimposable helices and strands can exhibit a wide range of similarity and may offer clues to the structural evolution of folds. One might argue that more closely related proteins differ less in their nonconserved loop regions than distantly related proteins and, at the same time, the degree of variability in the loop regions in structurally similar but unrelated proteins is higher than in homologs. Here we introduce a new measure for structural (dis)similarity in loop regions that is based on the concept of the Hausdorff metric. This measure is used to gauge protein relatedness and is tested on a benchmark of homologous and analogous protein structures. It has been shown that the new measure can distinguish homologous from analogous proteins with the same or higher accuracy than the conventional measures that are based on comparing proteins in structurally aligned regions. We argue that this result can be attributed to the higher sensitivity of the Hausdorff (dis)similarity measure in detecting particularly evident dissimilarities in structures and draw some conclusions about evolutionary relatedness of proteins in the most populated protein folds. (C) 2004 Wiley-Liss, Inc. C1 NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Panchenko, AR (reprint author), NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Bldg 38A, Bethesda, MD 20894 USA. EM panch@ncbi.nlm.nih.gov FU NLM NIH HHS [Z01 LM000057-12] NR 43 TC 18 Z9 19 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-3585 J9 PROTEINS JI Proteins PD NOV 15 PY 2004 VL 57 IS 3 BP 539 EP 547 DI 10.1002/prot.20237 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 863RC UT WOS:000224578400010 PM 15382231 ER PT J AU Schisterman, EF Faraggi, D Reiser, B AF Schisterman, EF Faraggi, D Reiser, B TI Adjusting the generalized ROC curve for covariates SO STATISTICS IN MEDICINE LA English DT Article DE diagnostic markers; Box-Cox transformations; best linear combination; sensitivity; specificity ID OPERATING CHARACTERISTIC CURVES; TRANSFORMATION MODELS; DIAGNOSTIC MARKERS; TESTS; COMBINATIONS; BIOMARKERS; DISEASE; AREA AB Receiver operating characteristic (ROC) curves and in particular the area under the curve (AUC), are widely used to examine the effectiveness of diagnostic markers. Diagnostic markers and their corresponding ROC curves can be strongly influenced by covariate variables. When several diagnostic markers are available, they can be combined by a best linear combination such that the area under the ROC curve of the combination is maximized among all possible linear combinations. In this paper we discuss covariate effects on this linear combination assuming that the multiple markers, possibly transformed, follow a multivariate normal distribution. The ROC curve of this linear combination when markers are adjusted for covariates is estimated and approximate confidence intervals for the corresponding AUC are derived. An example of two biomarkers of coronary heart disease for which covariate information on age and gender is available is used to illustrate this methodology. Copyright (C) 2004 John Wiley Sons, Ltd. C1 Univ Haifa, Fac Social Sci, Dept Stat, IL-31905 Haifa, Israel. NICHD, Div Epidemiol Stat & Prevent, NIH, Bethesda, MD 20892 USA. RP Faraggi, D (reprint author), Univ Haifa, Fac Social Sci, Dept Stat, IL-31905 Haifa, Israel. EM faraggi@stat.haifa.ac.il RI Reiser, Benjamin/G-6591-2012; OI Reiser, Benjamin/0000-0002-9797-9029; Schisterman, Enrique/0000-0003-3757-641X NR 27 TC 33 Z9 33 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 15 PY 2004 VL 23 IS 21 BP 3319 EP 3331 DI 10.1002/sim.1908 PG 13 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 867UO UT WOS:000224868200006 PM 15490426 ER PT J AU Kang, SU Burke, TR AF Kang, SU Burke, TR TI A one-step synthesis of N-alpha-Fmoc-4-O-[O ',O ''-di-tert-butyl-2-(2-fluoromalonyl)]-L-tyrosine from commercially available starting material SO TETRAHEDRON LETTERS LA English DT Article DE OMT; FOMT; phosphotyrosyl mimetic; amino acid analogue; electrophilic flourination ID PROTEIN-TYROSINE-PHOSPHATASE; SIGNAL-TRANSDUCTION INHIBITORS; POTENT INHIBITION; PHOSPHOTYROSYL MIMETICS; GRB2-SH2 DOMAIN; PEPTIDES; 1B; L-O-(2-MALONYL)TYROSINE; ANALOGS; BINDING AB A one-step high yield synthesis from commercially available starting material is reported for the novel phosphotyrosyl mimetic, N-alpha-Fmoc-4-O-[O',O"-di-tert-butyl-2-(2-fluoromalonyl)]-L-tyrosine. The conditions employed for this transformation may also be applicable for the direct electrophilic fluorination of other N-alpha-Fmoc-protected amino acids. Published by Elsevier Ltd. C1 NCI, Med Chem Lab, Canc Res Ctr, NIH, Frederick, MD 21702 USA. RP Burke, TR (reprint author), NCI, Med Chem Lab, Canc Res Ctr, NIH, Frederick, MD 21702 USA. EM tburke@helix.nih.gov RI Burke, Terrence/N-2601-2014 NR 20 TC 0 Z9 0 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD NOV 15 PY 2004 VL 45 IS 47 BP 8611 EP 8613 DI 10.1016/j.tetlet.2004.09.163 PG 3 WC Chemistry, Organic SC Chemistry GA 867TP UT WOS:000224865600003 ER PT J AU Hooth, MJ Herbert, RA Haseman, JK Orzech, DP Johnson, JD Bucher, JR AF Hooth, MJ Herbert, RA Haseman, JK Orzech, DP Johnson, JD Bucher, JR TI Toxicology and carcinogenesis studies of dipropylene glycol in rats and mice SO TOXICOLOGY LA English DT Article DE dipropylene glycol; drinking water; toxicity; rats; mice; nephropathy; inflammation; olfactory epithelial degeneration ID ZERO DOSE CONTROL; DIETHYLENE GLYCOL; ETHYLENE-GLYCOL; DEVELOPMENTAL TOXICITY; FOOD RESTRICTION; METABOLISM; TESTS AB Dipropylene glycol (DPG) is a component of many commercial products such as antifreeze, air fresheners, cosmetic products, solvents, and plastics. Male and female F344/N rats and B6C3F(l) mice were exposed to DPG in the drinking water for 2 weeks, 3 months, or 2 years. In the 2-week and 3-month studies, rats and mice were exposed to 0, 5000, 10,000, 20,000, 40,000, or 80,000 ppm DPG. There was no mortality in the 2-week studies. In the 3-month rat study, all animals survived to the end of the study. Liver weights of rats exposed to 10,000 ppm or greater and kidney weights of rats exposed to 40,000 and 80,000 ppm were greater than those of the controls. The incidences of liver and kidney lesions were significantly increased in males exposed to 20,000 ppm or greater and females exposed to 80,000 ppm. Focal olfactory epithelial degeneration was present in all rats exposed to 80,000 ppm. In males, the incidences of testicular atrophy, epididymal hypospermia, and preputial gland atrophy were significantly increased in the 80,000 ppm group. In the 3-month mouse study, three males and one female exposed to 80,000 ppm died. Liver weights were increased, as was the incidence of centrilobular hypertrophy in males exposed to 40,000 ppm and males and females exposed to 80,000 ppm. In the 2-year studies, exposure groups were 0, 2500 (rats only), 10,000, 20,000 (mice only) or 40,000 ppm DPG. Survival of male rats exposed to 40,000 ppm and mean body weights of males and females exposed to 40,000 ppm were significantly less than controls. In male rats, exposure to DPG resulted in increased incidences and severities of nephropathy and secondary lesions in the parathyroid and forestomach. Increased incidences of focal histiocytic and focal granulomatous inflammation of the liver were also observed. In male and female rats, there were increased incidences of bile duct hyperplasia and changes in the olfactory epithelium of the nose. In mice, survival of males and females was similar to controls. Mean body weights and water consumption of males exposed to 40,000 ppm were less than that of the controls. Treatment-related nonneoplastic lesions did not occur in mice. Treatment-related neoplastic lesions did not occur in rats or mice. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Battelle Labs, Columbus, OH 43201 USA. RP Hooth, MJ (reprint author), NIEHS, Mail Drop EC-35,79 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM hooth@niehs.nih.gov NR 35 TC 5 Z9 5 U1 1 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD NOV 15 PY 2004 VL 204 IS 2-3 BP 123 EP 140 DI 10.1016/j.tox.2004.06.019 PG 18 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 863ZB UT WOS:000224601100004 PM 15388239 ER PT J AU Anam, K Akpinar, E Craighead, N Black, AT Hale, DA AF Anam, K Akpinar, E Craighead, N Black, AT Hale, DA TI Targeted T-cell depletion or CD154 blockade generates mixed hemopoietic chimerism and donor-specific tolerance in mice treated with sirolimus and donor bone marrow SO TRANSPLANTATION LA English DT Article DE chimerism; immunosuppression; tolerance; transplantation; sirolimus ID ANTILYMPHOCYTE SERUM; ALLOGRAFT TOLERANCE; CLONAL DELETION; INDUCTION; ENGRAFTMENT; TRANSPLANTATION; MECHANISMS; REJECTION; GLOBULIN; SURVIVAL AB Background. The administration of donor specific bone marrow (DSBM) to mice conditioned with antilymphocyte serum (ALS) and sirolimus can result in stable multilineage mixed chimerism and long-term graft survival. This study seeks to determine if either the targeted depletion of CD4 and/or CD8 pos T cells or costimulation blockade can substitute for ALS and preserve the efficacy of this regimen. Methods. C57BL/6 recipients of BALB/c skin allografts were treated with DSBM (150 X 10(6) cells), sirolimus (24 mg/kg intraperitonealy), and either ALS or various monoclonal antibodies (alphaCD4, alphaCD8, alphaCD154 alone or in combination). Recipient peripheral blood mononuclear cell (PBMC) depletion, donor chimerism, and deletion of donor reactive T cells were assessed using flow cytometry. The specificity of immunologic nonreactivity and the presence of immunoregulatory activity were assessed through a mixed lymphocyte reaction assay. Results. The administration of ALS, sirolimus, and DSBM resulted in sustained recipient PBMC depletion, transient chimerism, and prolonged graft survival. The substitution of an equivalent degree and duration of targeted depletion of either CD4 or CD8 pos T cells alone for ALS failed to produce chimerism or prolonged graft survival. In contrast, depletion of both CD4 and CD8 pos T cells resulted in durable multilineage chimerism, indefinite allograft acceptance (>350 days), and donor-specific tolerance to secondary skin grafts. Substitution of alphaCD 154 monoclonal antibody for ALS also resulted in a state of mixed chimerism and donor specific tolerance. This tolerant state appears to be maintained at least partially through clonal deletion and suppression. Conclusion. Either combined CD4 and CD8 T-cell depletion or alphaCD154 blockade can effectively substitute for ALS in producing chimerism and tolerance in this model. C1 NIDDKD, Transplantat Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Hale, DA (reprint author), Room 5-5-750,Bldg 10,Ctr Dr, Bethesda, MD 20892 USA. EM douglash@intra.niddk-nih.gov RI AKPINAR, Edip/C-3402-2014 OI AKPINAR, Edip/0000-0003-1445-8680 NR 33 TC 13 Z9 14 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV 15 PY 2004 VL 78 IS 9 BP 1290 EP 1298 DI 10.1097/01.TP.0000138097.08050.D7 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 872FI UT WOS:000225192700008 PM 15548965 ER PT J AU Horne, AD Clifford, J Goldenthal, KL Kleppinger, C Lachenbruch, PA AF Horne, AD Clifford, J Goldenthal, KL Kleppinger, C Lachenbruch, PA TI Preventive vaccines against bioterrorism: evaluation of efficacy and safety SO VACCINE LA English DT Article DE immunogenicity; non-inferiority; Animal Rule ID COMBINATION VACCINES/; TERRORISM; SMALLPOX; ANTHRAX AB This paper discusses the US Food and Drug Administration's approach to evaluation of vaccines in general, and vaccines against diseases of bioterrorism in particular. We summarize the scientific bases for development and approval of vaccines and then discuss specific issues regarding vaccines against disease organisms that could potentially be used as weapons of bioterrorism. Published by Elsevier Ltd. C1 US FDA, Div Biostat, Off Biostat & Epidemiol, CBER, Rockville, MD 20852 USA. US FDA, Div Vaccines & Related Prod Applicat, Off Vaccine Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NIDA, Ctr Clin Trials Network, NIH, Bethesda, MD 20892 USA. RP Horne, AD (reprint author), US FDA, Div Biostat, Off Biostat & Epidemiol, CBER, HFM-217,1401 Rockville Pike, Rockville, MD 20852 USA. EM horne@cber.fda.gov NR 20 TC 4 Z9 5 U1 0 U2 1 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 NOV 15 PY 2004 VL 23 IS 1 BP 84 EP 90 DI 10.1016/j.vaccine.2004.04.037 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 872IM UT WOS:000225200900012 PM 15519711 ER PT J AU Jia, ST Yamada, T Grewal, SIS AF Jia, ST Yamada, T Grewal, SIS TI Heterochromatin regulates cell type-specific long-range chromatin interactions essential for directed recombination SO CELL LA English DT Article ID MATING-TYPE INTERCONVERSION; BETA-GLOBIN LOCUS; FISSION YEAST; SCHIZOSACCHAROMYCES-POMBE; MEIOTIC RECOMBINATION; LYSINE-9 METHYLATION; V(D)J RECOMBINATION; EPIGENETIC CONTROL; DNA-REPLICATION; CHROMOSOME-III AB Mating-type switching in Schizosaccharomyces pombe involves replacing genetic information at the expressed mat1 locus with sequences copied from one of two silent donor loci, mat2-P or mat3-M, located within a 20-kb heterochromatic domain. Donor selection is dictated by cell type: mat2 is the preferred donor in M cells, and mat3 is the preferred donor in P cells. Here we show that a recombination-promoting complex (RPC) containing Swi2 and Swi5 proteins exhibits cell type-specific localization pattern at the silent mating-type region and this differential localization modulates donor preference during mating-type switching. In P cells, RPC localization is restricted to a recombination enhancer located adjacent to mat3, but in M cells, RPC spreads in cis across the entire silent mating-type interval in a heterochromatin-dependent manner. Our analyses implicate heterochromatin in long-range regulatory interactions and suggest that heterochromatin imposes at the mating-type region structural organization that is important for the donor-choice mechanism. C1 NCI, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Grewal, SIS (reprint author), NCI, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM grewals@mail.nih.gov NR 48 TC 56 Z9 60 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD NOV 12 PY 2004 VL 119 IS 4 BP 469 EP 480 DI 10.1016/j.cell.2004.10.020 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 872CI UT WOS:000225183200006 PM 15537537 ER PT J AU Lam, AKM Ko, BCB Tam, S Morris, R Yang, JY Chung, SK Chung, SSM AF Lam, AKM Ko, BCB Tam, S Morris, R Yang, JY Chung, SK Chung, SSM TI Osmotic response element-binding protein (OREBP) is an essential regulator of the urine concentrating mechanism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NEPHROGENIC DIABETES-INSIPIDUS; MEDULLARY COLLECTING DUCT; A UREA TRANSPORTER; RAT-KIDNEY; VASOPRESSIN ANTAGONIST; TRANSCRIPTION FACTOR; WATER PERMEABILITY; GENE-EXPRESSION; IN-VIVO; AQUAPORIN-2 AB OREBP (osmotic response element-binding protein), also called TonEBP or NFAT5, is thought to induce the expression of genes that increase the accumulation of organic osmolytes to protect cells against a hypertonic environment. To investigate the consequences of lacking OREBP activity, transgenic (Tg) mice that overexpress OREBPdn (dominant negative form of OREBP) specifically in the epithelial cells of the renal collecting tubules were generated. These mice showed impairment in their urine concentrating mechanism, most likely due to reduced expression of the aquaporin AQP2 and the urea transporter UT-A1 and UT-A2 mRNAs. When deprived of water or after the administration of a vasopressin analogue, urine osmolality of the Tg mice was significantly increased but not to the same extent as that of the wild type mice. The expression of AQP2 and UT-A1, but not UT-A2 mRNAs, was increased to the same level as that of the wild type mice in the water deprivation state, indicating that the vasopressin regulatory mechanism was not affected by OREBPdn. These data indicate that in addition to vasopressin, OREBP is another essential regulator of the urine concentrating mechanism. Furthermore, the OREBPdn Tg mice developed progressive hydronephrosis soon after weaning, confirming the osmoprotective function of OREBP implicated by the in vitro experiments. C1 Univ Hong Kong, Inst Mol Technol Drug Discovery & Synth, Hong Kong, Hong Kong, Peoples R China. Univ Hong Kong, Inst Mol Biol, Hong Kong, Hong Kong, Peoples R China. Univ Hong Kong, Dept Chem, Hong Kong, Hong Kong, Peoples R China. Univ Hong Kong, Div Clin Biochem, Hong Kong, Hong Kong, Peoples R China. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Ko, BCB (reprint author), Univ Hong Kong, Inst Mol Technol Drug Discovery & Synth, Hong Kong, Hong Kong, Peoples R China. EM cbko@hkucc.hku.hk; smchung@hkucc.hku.hk OI Ko, Ben Chi Bun/0000-0003-2027-5899 NR 38 TC 59 Z9 61 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 12 PY 2004 VL 279 IS 46 BP 48048 EP 48054 DI 10.1074/jbc.M407224200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 869BJ UT WOS:000224957000076 PM 15347663 ER PT J AU Woo, JR Kim, SJ Jeong, WJ Cho, YH Lee, SC Chung, YJ Rhee, SG Ryu, SE AF Woo, JR Kim, SJ Jeong, WJ Cho, YH Lee, SC Chung, YJ Rhee, SG Ryu, SE TI Structural basis of cellular redox regulation by human TRP14 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID THIOREDOXIN-RELATED PROTEIN; DNA-BINDING ACTIVITY; CRYSTAL-STRUCTURES; DISULFIDE; IDENTIFICATION; SUPERFAMILY; ASSOCIATION; APOPTOSIS; MECHANISM; REDUCTASE AB Thioredoxin-related protein 14 (TRP14) is involved in regulating tumor necrosis factor-alpha-induced signaling pathways in a different manner from human thioredoxin 1 (Trx1). Here, we report the crystal structure of human TRP14 determined at 1.8-Angstrom resolutions. The structure reveals a typical thioredoxin fold with characteristic structural features that account for the substrate specificity of the protein. The surface of TRP14 in the vicinity of the active site includes an extended loop and an additional alpha-helix, and the distribution of charged residues in the surface is different from Trx1. The distinctive dipeptide between the redox-active cysteines contributes to stabilizing the thiolate anion of the active site cysteine 43, increasing reactivity of the cysteine toward substrates. These structural differences in the active site suggest that TRP14 has evolved to regulate cellular redox signaling by recognizing a distinctive group of substrates that would complement the group of proteins regulated by Trx1. C1 Korea Res Inst Biosci & Biotechnol, Ctr Cellular Switch Prot Struct, Taejon 305806, South Korea. Korea Res Inst Biosci & Biotechnol, Systemic Proteom Res Ctr, Taejon 305806, South Korea. Chungbuk Natl Univ, Dept Biochem, Chonju 360763, South Korea. NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. Ewha Womans Univ, Div Mol Life Sci, Seoul 120750, South Korea. RP Ryu, SE (reprint author), Korea Res Inst Biosci & Biotechnol, Ctr Cellular Switch Prot Struct, 52 Euh Eun Dong, Taejon 305806, South Korea. EM ryuse@kribb.re.kr NR 35 TC 13 Z9 15 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 12 PY 2004 VL 279 IS 46 BP 48120 EP 48125 DI 10.1074/jbc.M407079200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 869BJ UT WOS:000224957000085 PM 15355959 ER PT J AU Gerber, D Pritsker, M Gunther-Ausborn, S Johnson, B Blumenthal, R Shai, Y AF Gerber, D Pritsker, M Gunther-Ausborn, S Johnson, B Blumenthal, R Shai, Y TI Inhibition of HIV-1 envelope glycoprotein-mediated cell fusion by a DL-amino acid-containing fusion peptide - Possible recognition of the fusion complex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; FLUORESCENCE ENERGY-TRANSFER; MEMBRANE-FUSION; INFLUENZA HEMAGGLUTININ; PHOSPHOLIPID-MEMBRANES; INFRARED-SPECTROSCOPY; TRANSMEMBRANE PROTEIN; CHEMOKINE RECEPTORS; TERMINAL PEPTIDE; DEPENDENT FUSION AB The N-terminal fusion peptide ( FP) of human immunodeficiency virus-1 (HIV-1) is a potent inhibitor of cell-cell fusion, possibly because of its ability to recognize the corresponding segments inside the fusion complex within the membrane. Here we show that a fusion peptide in which the highly conserved Ile(4), Phe(8), Phe(11), and Ala(14) were replaced by their D-enantiomers (IFFA) is a potent inhibitor of cell-cell fusion. Fourier transform infrared spectroscopy confirmed that despite these drastic modifications, the peptide preserved most of its structure within the membrane. Fluorescence energy transfer studies demonstrated that the diastereomeric peptide interacted with the wild type FP, suggesting this segment as the target site for inhibition of membrane fusion. This is further supported by the similar localization of the wild type and IFFA FPs to microdomains in T cells and the preferred partitioning into ordered regions within sphingomyelin/phosphatidyl-choline/cholesterol giant vesicles. These studies provide insight into the mechanism of molecular recognition within the membrane milieu and may serve in designing novel HIV entry inhibitors. C1 Weizmann Inst Sci, IL-76100 Rehovot, Israel. NCI, Sect Membrane Struct & Funct, Lab Expt & Computat Biol, Ctr Canc Res,NIH, Frederick, MD 21701 USA. RP Shai, Y (reprint author), Weizmann Inst Sci, IL-76100 Rehovot, Israel. EM Yechiel.Shai@weizmann.ac.il NR 63 TC 25 Z9 25 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 12 PY 2004 VL 279 IS 46 BP 48224 EP 48230 DI 10.1074/jbc.M403436200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 869BJ UT WOS:000224957000097 PM 15339935 ER PT J AU Vidal, AE Kannouche, P Podust, VN Yang, W Lehmann, AR Woodgate, R AF Vidal, AE Kannouche, P Podust, VN Yang, W Lehmann, AR Woodgate, R TI Proliferating cell nuclear antigen-dependent coordination of the biological functions of human DNA polymerase iota SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID XERODERMA-PIGMENTOSUM; REPLICATION MACHINERY; TRANSLESION SYNTHESIS; CRYSTAL-STRUCTURE; PCNA-BINDING; ERROR-PRONE; Y-FAMILY; ETA; DELTA; MECHANISM AB Y-family DNA polymerases are believed to facilitate the replicative bypass of damaged DNA in a process commonly referred to as translesion synthesis. With the exception of DNA polymerase eta (poleta), which is defective in humans with the Xeroderma pigmentosum variant (XP-V) phenotype, little is known about the cellular function(s) of the remaining human Y-family DNA polymerases. We report here that an interaction between human DNA polymerase iota (poliota) and the proliferating cell nuclear antigen (PCNA) stimulates the processivity of poliota in a template-dependent manner in vitro. Mutations in one of the putative PCNA-binding motifs (PIP box) of poliota or the interdomain connector loop of PCNA diminish the binding between poliota and PCNA and concomitantly reduce PCNA-dependent stimulation of poliota activity. Furthermore, although retaining its capacity to interact with poleta in vivo, the poliota-PIP box mutant fails to accumulate in replication foci. Thus, PCNA, acting as both a scaffold and a modulator of the different activities involved in replication, appears to recruit and coordinate replicative and translesion DNA synthesis polymerases to ensure genome integrity. C1 NICHD, Lab Genome Integr, NIH, Bethesda, MD 20892 USA. Univ Sussex, Genome Damage & Stabil Ctr, Brighton BN1 9RQ, E Sussex, England. Vanderbilt Univ, Dept Biol Sci, Nashville, TN 37232 USA. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Woodgate, R (reprint author), NICHD, Lab Genome Integr, NIH, Bethesda, MD 20892 USA. EM woodgate@nih.gov RI Yang, Wei/D-4926-2011 OI Yang, Wei/0000-0002-3591-2195 NR 44 TC 57 Z9 60 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 12 PY 2004 VL 279 IS 46 BP 48360 EP 48368 DI 10.1074/jbc.M406511200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 869BJ UT WOS:000224957000111 PM 15342632 ER PT J AU Wang, WG Yang, XL Kawai, T de Silanes, IL Mazan-Mamczarz, K Chen, PL Chook, YM Quensel, C Kohler, M Gorospe, M AF Wang, WG Yang, XL Kawai, T de Silanes, IL Mazan-Mamczarz, K Chen, PL Chook, YM Quensel, C Kohler, M Gorospe, M TI AMP-activated protein kinase-regulated phosphorylation and acetylation of importin alpha 1 - Involvement in the nuclear import of RNA-binding protein HuR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AU-RICH ELEMENTS; MESSENGER-RNA; LOCALIZATION SIGNAL; GENE-EXPRESSION; NUCLEOCYTOPLASMIC TRANSPORT; STRUCTURAL BASIS; MAMMALIAN-CELLS; PHOSPHATASE 2A; UP-REGULATION; ELAV PROTEIN AB Nuclear import of HuR, a shuttling RNA-binding protein, is associated with reduced stability of its target mRNAs. Increased function of the AMP-activated protein kinase (AMPK), an enzyme involved in responding to metabolic stress, was recently shown to reduce the cytoplasmic levels of HuR. Here, we provide evidence that importin alpha1, an adaptor protein involved in nuclear import, contributes to the nuclear import of HuR through two AMPK-modulated mechanisms. First, AMPK triggered the acetylation of importin alpha1 on Lys(22), a process dependent on the acetylase activity of p300. Second, AMPK phosphorylated importin alpha1 on Ser(105). Accordingly, expression of importin alpha1 proteins bearing K22R or S105A mutations failed to mediate the nuclear import of HuR in intact cells. Our results point to importin alpha1 as a critical downstream target of AMPK and key mediator of AMPK-triggered HuR nuclear import. C1 NIA, LCMB, IRP, NIH, Baltimore, MD 21224 USA. Johns Hopkins Med Inst, Sydney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75390 USA. Max Delbruck Ctr Mol Med, HELIOS Clin Franz Volhard Clin, D-13125 Berlin, Germany. RP Wang, WG (reprint author), NIA, LCMB, IRP, NIH, Box 12,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM wewang@uchc.edu; myriam-gorospe@nih.gov RI Lopez de Silanes, Isabel/K-4962-2015 OI Lopez de Silanes, Isabel/0000-0001-6762-9792 NR 77 TC 82 Z9 84 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 12 PY 2004 VL 279 IS 46 BP 48376 EP 48388 DI 10.1074/jbc.M409014200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 869BJ UT WOS:000224957000113 PM 15342649 ER PT J AU Forrer, P Chang, CS Ott, D Wlodawer, A Pluckthun, A AF Forrer, P Chang, CS Ott, D Wlodawer, A Pluckthun, A TI Kinetic stability and crystal structure of the viral capsid protein SHP SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE bacteriophage; kinetic stability; protein oligomerization; protein structure; virus stability ID ALPHA-LYTIC PROTEASE; BACTERIOPHAGE-LAMBDA; X-RAY; UNFOLDED CONFORMATIONS; PROGRAM; HYSTERESIS; MOLSCRIPT; LONGEVITY; INHIBITOR; BARRIERS AB SHP, the capsid-stabilizing protein of lambdoid phage 21, is highly resistant against denaturant-induced unfolding. We demonstrate that this high functional stability of SHP is due to a high kinetic stability with a half-life for unfolding of 25 days at zero denaturant, while the thermodynamic stability is not unusually high. Unfolding experiments demonstrated that the trimeric state (also observed in crystals and present on the phage capsid) of SHP is kinetically stable in solution, while the monomer intermediate unfolds very rapidly. We also determined the crystal structure of trimeric SHP at 1.5 Angstrom resolution, which was compared to that of its functional homolog gpD. This explains how a tight network of H-bonds rigidifies crucial interpenetrating residues, leading to the observed extremely slow trimer dissociation or denaturation. Taken as a whole, our results provide molecular-level insights into natural strategies to achieve kinetic stability by taking advantage of protein oligomerization. Kinetic stability may be especially needed in phage capsids to allow survival in harsh environments. (C) 2004 Elsevier Ltd. All rights reserved. C1 Univ Zurich, Inst Biochem, CH-8057 Zurich, Switzerland. NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. RP Pluckthun, A (reprint author), Univ Zurich, Inst Biochem, Winterthurerstr 190, CH-8057 Zurich, Switzerland. EM plueckthun@bioc.unizh.ch RI Pluckthun, Andreas/C-2746-2009 OI Pluckthun, Andreas/0000-0003-4191-5306 NR 47 TC 24 Z9 25 U1 0 U2 2 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD NOV 12 PY 2004 VL 344 IS 1 BP 179 EP 193 DI 10.1016/j.jmb.2004.09.030 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 868PY UT WOS:000224926700013 PM 15504410 ER PT J AU Doan, L Yagi, H Jerina, DM Whalen, DL AF Doan, L Yagi, H Jerina, DM Whalen, DL TI Synthesis and hydrolysis of a cis-chlorohydrin derived from a benzo[a]pyrene 7,8-diol 9,10-epoxide SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID DIOL EPOXIDE; PRODUCT DISTRIBUTIONS; ADDUCT FORMATION; CHLORIDE-ION; BAY-REGION; BENZOPYRENE; HYDROCARBONS; INTERMEDIATE; HALOHYDRINS; CONVERSION AB (+/-)-7beta8alpha-Dihydroxy-9beta,10beta-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (DE-1) undergoes reaction with anhydrous HCl in dioxane to yield predominantly (similar to94%) a single chlorohydrin. This chlorohydrin was assigned structure 9, in which the chloro goup at C-10 is located cis to the C-9 hydroxyl group, on the basis of its H-1 NMR spectrum. This result is in contrast to the reaction of a diastereomeric benzo[a]pyrene 7,8-diol 9,10-epoxide (DE-2) with HCl, which yields only transchlorohydrin 8. The hydrolysis of cis-chlorohydrin 9 in 10:90 dioxane-water solutions yields the same ratio of tetrols (similar to89% cis/11% trans) as that formed by acid-catalyzed hydrolysis of DE-1. This result again contrasts with the hydrolysis of trans-chlorohydrin 8, which undergoes hydrolysis to give tetrols in a ratio different from that from acid-catalyzed hydrolysis of DE-2. A marked common ion rate depression in the hydrolysis of cis-chlorohydrin 9 is observed, which shows that hydrolysis proceeds via an intermediate carbocation that has a sufficient lifetime to be trapped by external chloride ion. The observation that DE-1 reacts with HCl to give mainly the cis-chlorohydrin is rationalized by quantum chemical calculations that suggest that the cis-chlorohydrin is more stable than the epimeric trans-chlorohydrin. C1 Univ Maryland Baltimore Cty, Dept Chem & Biochem, Baltimore, MD 21250 USA. NIDDK, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Whalen, DL (reprint author), Univ Maryland Baltimore Cty, Dept Chem & Biochem, Baltimore, MD 21250 USA. EM whalen@umbc.edu NR 17 TC 4 Z9 4 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD NOV 12 PY 2004 VL 69 IS 23 BP 8012 EP 8017 DI 10.1021/jo040234r PG 6 WC Chemistry, Organic SC Chemistry GA 869ZQ UT WOS:000225024200033 PM 15527284 ER PT J AU Austin, CP Brady, LS Insel, TR Collins, FS AF Austin, CP Brady, LS Insel, TR Collins, FS TI NIH Molecular Libraries Initiative SO SCIENCE LA English DT Editorial Material ID DRUG DISCOVERY; HUMAN GENOME; INNOVATION; BIOLOGY C1 NHGRI, NIH, Bethesda, MD 20892 USA. NIMH, NIH, Bethesda, MD 20892 USA. RP Austin, CP (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. EM austinc@mail.nih.gov NR 13 TC 241 Z9 246 U1 2 U2 12 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 NOV 12 PY 2004 VL 306 IS 5699 BP 1138 EP 1139 DI 10.1126/science.1105511 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 872FM UT WOS:000225193100031 PM 15542455 ER PT J AU Luthi, A Wikstrom, MA Palmer, MJ Matthews, P Benke, TA Isaac, JTR Collingridge, GL AF Luthi, A Wikstrom, MA Palmer, MJ Matthews, P Benke, TA Isaac, JTR Collingridge, GL TI Bi-directional modulation of AMPA receptor unitary conductance by synaptic activity SO BMC NEUROSCIENCE LA English DT Article ID LONG-TERM POTENTIATION; EXCITATORY AMINO-ACIDS; GLUTAMATE RECEPTORS; HIPPOCAMPAL-NEURONS; PRESYNAPTIC COMPONENT; SILENT SYNAPSES; PROTEIN-KINASE; CA1 SYNAPSES; AREA CA1; DEPRESSION AB Background: Knowledge of how synapses alter their efficiency of communication is central to the understanding of learning and memory. The most extensively studied forms of synaptic plasticity are long-term potentiation (LTP) and its counterpart long-term depression (LTD) of AMPA receptor-mediated synaptic transmission. In the CA1 region of the hippocampus, it has been shown that LTP often involves a rapid increase in the unitary conductance of AMPA receptor channels. However, LTP can also occur in the absence of any alteration in AMPA receptor unitary conductance. In the present study we have used whole-cell dendritic recording, failures analysis and non-stationary fluctuation analysis to investigate the mechanism of depotentiation of LTP. Results: We find that when LTP involves an increase in unitary conductance, subsequent depotentiation invariably involves the return of unitary conductance to pre-LTP values. In contrast, when LTP does not involve a change in unitary conductance then depotentiation also occurs in the absence of any change in unitary conductance, indicating a reduction in the number of activated receptors as the most likely mechanism. Conclusions: These data show that unitary conductance can be bi-directionally modified by synaptic activity. Furthermore, there are at least two distinct mechanisms to restore synaptic strength from a potentiated state, which depend upon the mechanism of the previous potentiation. C1 Univ Bristol, Dept Anat, MRC, Ctr Synapt Plast, Bristol BS8 1TD, Avon, England. Friedrich Miescher Inst, CH-4058 Basel, Switzerland. Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden. Univ Keele, Sch Life Sci, MacKay Inst, Keele ST5 5BG, Staffs, England. Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. NIH, Bethesda, MD 20892 USA. RP Collingridge, GL (reprint author), Univ Bristol, Dept Anat, MRC, Ctr Synapt Plast, Bristol BS8 1TD, Avon, England. EM Andreas.Luthi@fmi.ch; martin.wikstrom@neuro.ki.se; m.j.palmer@cns.keele.ac.uk; Paul.Matthews@Bris.ac.uk; Tim.Benke@UCHSC.edu; isaacj@ninds.nih.gov; g.l.collingridge@bris.ac.uk RI Collingridge, Graham/C-4605-2015 OI Collingridge, Graham/0000-0002-9572-5359 FU Medical Research Council [G9532377] NR 51 TC 40 Z9 41 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2202 J9 BMC NEUROSCI JI BMC Neurosci. PD NOV 11 PY 2004 VL 5 AR 44 DI 10.1186/1471-2202-5-44 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 877UV UT WOS:000225600300001 PM 15538948 ER PT J AU Perera, L Darden, TA Duke, RE Venkateswarlu, D Pedersen, LG AF Perera, L Darden, TA Duke, RE Venkateswarlu, D Pedersen, LG TI Early unfolding response of a stable protein domain to environmental changes SO JOURNAL OF PHYSICAL CHEMISTRY A LA English DT Article ID MOLECULAR-DYNAMICS SIMULATION; BLOOD-COAGULATION FACTOR; PARTICLE MESH EWALD; CARBOXYGLUTAMIC ACID PROTEINS; FACTOR-IX; MEMBRANE-BINDING; PROTHROMBIN FRAGMENT-1; CRYSTAL-STRUCTURE; EXPLICIT WATER; GLA DOMAIN AB The X-ray crystal structure of gamma-carboxyglutamic acid (Gla) domains is well-established. These domains are stable to long all-atom simulations in explicit solvent. Here we extend a prior simulation on the Gla domain of factor VIIa, an essential vitamin K-dependent protein involved in the initiation of blood coagulation, to similar to20 ns in order to establish a reference point. We also subject this domain to a set of rational environmental changes using molecular dynamics techniques that accommodate long-range electrostatics accurately: (a) we move the seven bound calcium ions to > 17.5 Angstrom from any Gla residue and then simulate for 25 ns, and (b) in a separate calculation, we change all of the calcium ions to sodium ions and simulate for 20 ns. For both perturbed systems, the N-terminus chelation complex is initially greatly weakened, leading to increased motion of the omega loop (residues 1-11). In technique a, most calcium ions return to the preperturbation coordinating units within the time scale of the simulation. We track and display the sequence of calcium ion rebinding. The response of this complex, nonstandard system to the perturbations as estimated by accurate all-atom dynamics gives new details on the degree of sampling in early refolding events. C1 Univ N Carolina, High Performance Comp Grp, Informat Technol Serv, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. NIEHS, Lab Quantitat & Computat Biol, Res Triangle Pk, NC 27709 USA. RP Perera, L (reprint author), Univ N Carolina, High Performance Comp Grp, Informat Technol Serv, CB 3455, Chapel Hill, NC 27599 USA. EM Lalith_Perera@unc.edu; Lee_Pedersen@unc.edu RI perera, Lalith/B-6879-2012; Pedersen, Lee/E-3405-2013; Venkateswarlu, Divi/K-1815-2014 OI perera, Lalith/0000-0003-0823-1631; Pedersen, Lee/0000-0003-1262-9861; Venkateswarlu, Divi/0000-0003-2481-7480 NR 49 TC 0 Z9 0 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5639 J9 J PHYS CHEM A JI J. Phys. Chem. A PD NOV 11 PY 2004 VL 108 IS 45 BP 9834 EP 9840 DI 10.1021/jp0483851 PG 7 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 869ON UT WOS:000224994000026 ER PT J AU Braunwald, E Pfeffer, MA Domanski, M Fowler, S Rice, M Rosenberg, Y Dunlap, M Flaker, G Geller, N Gersh, B Goldberg, A Hsia, J Limacher, M Maggioni, A Mills, P Rouleau, J Warnica, J Wasserman, A Domanski, M Rosenberg, Y Geller, N Mills, P Fowler, S Cleary, P Close, N Davey, T Green, J Hsia, J Jablonski, K Mason, D Pakalapati, S Rice, M Verter, J Wasserman, A Weir, J Yalamanchili, V Maggioni, A Fabbri, G Gorini, M Lorimer, A Lucci, D Sarti, L Hsia, J Clemenza, F Cuddy, T Goldberg, A Huynh, T Maggioni, A Starling, M Title, L Zabalgoitia, M Fye, C Gagne, W Steffes, M Bucksa, J Rynders, G Frye, R Cooper, E Davis, C Grimes, C Nanda, N Pellegrino, E Stokes, L Dunlap, M Ortiz, J Fleegle, R Armstrong, A Jafri, S Goldberg, A Frank, D Piotrowski, K Kotlewski, A Mahrer, P Browning, R Sharma, A Nediratta, S Ely, G Allen, V Goodfield, P Tredinnick, K Hundley, R Mabry, V Sparrow, T Cunningham, P Owens, S Nelson, D Lewis, S Kelley, D Starling, M Majors, C Flaker, G Belew, K Rodeheffer, R Anderson, P Dodin, E Vold, D Wertheimer, J McKinney, V Ouyang, P Wingo, J Erenrich, N Grumbach, C Serfas, D Oskins, D Denny, D VanVactor, B Chaitman, B Aubuchon, S Brachfeld, C McKinster, B Logemann, T Joyce, D Smith, E Pacheco, R Limacher, M Bryant, B Wolinsky, D Westlake-Hicks, L Lopez, M Schenks, R Graham, S Jackson, J Durr, S De Raad, R Solomon, S Mercier, R Lader, E Meyer, M Wickemeyer, W Young, N Omar, B Clark, L Reddy, P Norwood, T Perry, J Romero, T Eastburn, T Hicks, K Jain, A Limon, L Vetrovec, G Damico, K Liang, CS Perkins, E Katz, R Arevalo, J Thadani, U Thresher, M Weiss, R Brennan, B Ackell, P Noble, M Kahl, F Soots, S Marzo, K Hodnett, P Seaworth, J Farris, S Jiang, L Duquette, M Ziperman, D Greene-Nashold, J Timmis, G Clark, C Colfer, H Ronquist, M Wagner, S Olliges, M Mohiuddin, S Rasmussen, L Sheikh, K Hengerer-Yates, T Palmeri, S Casazza, L Leimbach, W Ritter, D Zabalgoitia, M Paredes, A Golden, J McCaskill, B Duvernoy, W Cunningham, D Goldman, S Ohm, J McBride, J Foster, B Rosenson, R Dahle, K Schmidt, P Ness, C Patton, J Davison, C Riba, A Draus, C Herzog, E Tormey, D Keller, A Obeid, M Hendrix, G Schulz, M Larry, J Homan, J Kutscher, A Calhoon, W Medici, S Amidi, M Bell, M Khadra, S Bax, J Wool, K Parker, J Smith, M Feick, P Schulman, P Folger, J Shanes, J Guard, K Solomon, S English, M Ellis, J Kelly, D Menapace, F Kleman, M Fitzpatrick, P Sass, A Gillespie, J Cohen, L Kowey, P Heaney, S Kussmaul, W Mark, L Bugni, W Sweeney, S Kereiakes, D Ibanez, K Slater, W Guerra, B Brown, E Valeria, A Fifer, M Benard, P Feicht, C Crist, K Capone, R Omorogbe, T Desai, V Pierre-Louis, J Jutzy, K Bishop, V Dadkhah, S Fisch, A Costantino, T Basilious, M Smitherman, T Rosenfelder, D Canaday, D Baxter, J DeWood, M Chapman, D Olson, W Lamas, G Hussein, S Stein, R Varvatsas, J Smith, E Davison, C Kazmierski, J O'Mara, K Smith, J Cromer, C DiCola, J Dolan, S Martin, W Manns, H Kipperman, R Zhang, Y Grossman, D Morrison, B Chiaramida, A Gaven, R DeQuattro, V Song, Z Bergin, P Masengil, J Ely, D Reynolds, F Dennish, G Horton, N Bates, E Luciano, A Moloo, J Kaminski, M Geltman, E Flanagan, J Hayden, CT Felicetta, J Beckner, L Kaushik, V Mueco, A Lee, R Metcalf, A Fowles, R Summers, K Heerema, M Jacobson, M Diggs, P Roeske, M Rosenstein, R Dawley, D Dorst, D Warnica, J Smith, B Walker, L Scarcelli, D Tam, J Cuddy, T Courcelles, P Miller, N Gosselin, G Ducharme, A Marquis, J Lamy, M Title, L Johnstone, D Francis, M Cossett, J Dion, D St-Hilaire, R Morissette, A Poulin, F Arnold, M Krupa, M Boulianne, M Campeau, J Ouimet, F Roberge, B Huynh, T Finkenbine, S St Jacques, B Boudreault, C Borts, D Bonafede, N Burtcher, J Edwards, C Baigrie, R Gee, F Judge, J Reilly, K Bernstein, V MacDonald, K Mooney, S Rouleau, J Vienneau, R Mayer, JP Mitges, S Nawaz, S Dhaliwal, R Talbot, P Talbot, M Sussex, B Newman, S Baird, M Fraser, M Guimond, C Leboeuf, J Moe, G Day, D Rajakumar, G Kroeger, B Khouri, M Zello, N Lee, H Barban, K Kostuk, W Powell, AM Smilovitch, M Toyota, V Phaneuf, D Duclos, R Goulet, G Primeau, L Machel, T Morash, J Gossard, D Boutin, L Vizel, S Fox, B Stanton, E Lawrence, M Sullivan, H Paterson, R Hoag, G Ilott, K Dufton, J Sweeney, R Garcia-Palmieri, M Banchs, H Gonzalez, M Perez, M Colon, P Vazquez, N Schweiger, C Frisinghelli, A Galati, A Palma, P Di Pasquale, P Clemenza, F Filorizzo, G Petacchi, R Cogo, R Ferrari, M Battaglia, A Mancino, F D'Alessandro, B Truncellito, L Maina, M Romanzi, S Chieffo, C Cardillo, A De Lorenzi, E Bergarno, A Boccalatte, A Gaeta, G Neri, G Masaro, G Perticone, F Maio, R De Biase, M Carrone, M Scrutinio, D La Gioia, R Leonzio, L Tullio, D Santarone, M Tagliagambe, L Zonzin, P Capanna, M Di Giovanni, N Fiore, I Gavazzi, A Mazzoleni, D Pinelli, G Ribani, M Mangiameli, S Rubino, V Viecca, M Sala, R Porcu, M Salis, S Amici, R Patteri, G Bortolini, F Turelli, A Maresta, A Dalla Valle, G Braschi, G Abrignani, M Terrosu, P Castellaccio, M Boccanelli, A Morosetti, P Tartarini, G Levantesi, D Grieco, A Cazzaniga, A Poggio, G Giani, S Ferrari, G Belluschi, R Del Citerna, F Balli, E Maiolino, P Pedon, L Mininni, N Monda, V AF Braunwald, E Pfeffer, MA Domanski, M Fowler, S Rice, M Rosenberg, Y Dunlap, M Flaker, G Geller, N Gersh, B Goldberg, A Hsia, J Limacher, M Maggioni, A Mills, P Rouleau, J Warnica, J Wasserman, A Domanski, M Rosenberg, Y Geller, N Mills, P Fowler, S Cleary, P Close, N Davey, T Green, J Hsia, J Jablonski, K Mason, D Pakalapati, S Rice, M Verter, J Wasserman, A Weir, J Yalamanchili, V Maggioni, A Fabbri, G Gorini, M Lorimer, A Lucci, D Sarti, L Hsia, J Clemenza, F Cuddy, T Goldberg, A Huynh, T Maggioni, A Starling, M Title, L Zabalgoitia, M Fye, C Gagne, W Steffes, M Bucksa, J Rynders, G Frye, R Cooper, E Davis, C Grimes, C Nanda, N Pellegrino, E Stokes, L Dunlap, M Ortiz, J Fleegle, R Armstrong, A Jafri, S Goldberg, A Frank, D Piotrowski, K Kotlewski, A Mahrer, P Browning, R Sharma, A Nediratta, S Ely, G Allen, V Goodfield, P Tredinnick, K Hundley, R Mabry, V Sparrow, T Cunningham, P Owens, S Nelson, D Lewis, S Kelley, D Starling, M Majors, C Flaker, G Belew, K Rodeheffer, R Anderson, P Dodin, E Vold, D Wertheimer, J McKinney, V Ouyang, P Wingo, J Erenrich, N Grumbach, C Serfas, D Oskins, D Denny, D VanVactor, B Chaitman, B Aubuchon, S Brachfeld, C McKinster, B Logemann, T Joyce, D Smith, E Pacheco, R Limacher, M Bryant, B Wolinsky, D Westlake-Hicks, L Lopez, M Schenks, R Graham, S Jackson, J Durr, S De Raad, R Solomon, S Mercier, R Lader, E Meyer, M Wickemeyer, W Young, N Omar, B Clark, L Reddy, P Norwood, T Perry, J Romero, T Eastburn, T Hicks, K Jain, A Limon, L Vetrovec, G Damico, K Liang, CS Perkins, E Katz, R Arevalo, J Thadani, U Thresher, M Weiss, R Brennan, B Ackell, P Noble, M Kahl, F Soots, S Marzo, K Hodnett, P Seaworth, J Farris, S Jiang, L Duquette, M Ziperman, D Greene-Nashold, J Timmis, G Clark, C Colfer, H Ronquist, M Wagner, S Olliges, M Mohiuddin, S Rasmussen, L Sheikh, K Hengerer-Yates, T Palmeri, S Casazza, L Leimbach, W Ritter, D Zabalgoitia, M Paredes, A Golden, J McCaskill, B Duvernoy, W Cunningham, D Goldman, S Ohm, J McBride, J Foster, B Rosenson, R Dahle, K Schmidt, P Ness, C Patton, J Davison, C Riba, A Draus, C Herzog, E Tormey, D Keller, A Obeid, M Hendrix, G Schulz, M Larry, J Homan, J Kutscher, A Calhoon, W Medici, S Amidi, M Bell, M Khadra, S Bax, J Wool, K Parker, J Smith, M Feick, P Schulman, P Folger, J Shanes, J Guard, K Solomon, S English, M Ellis, J Kelly, D Menapace, F Kleman, M Fitzpatrick, P Sass, A Gillespie, J Cohen, L Kowey, P Heaney, S Kussmaul, W Mark, L Bugni, W Sweeney, S Kereiakes, D Ibanez, K Slater, W Guerra, B Brown, E Valeria, A Fifer, M Benard, P Feicht, C Crist, K Capone, R Omorogbe, T Desai, V Pierre-Louis, J Jutzy, K Bishop, V Dadkhah, S Fisch, A Costantino, T Basilious, M Smitherman, T Rosenfelder, D Canaday, D Baxter, J DeWood, M Chapman, D Olson, W Lamas, G Hussein, S Stein, R Varvatsas, J Smith, E Davison, C Kazmierski, J O'Mara, K Smith, J Cromer, C DiCola, J Dolan, S Martin, W Manns, H Kipperman, R Zhang, Y Grossman, D Morrison, B Chiaramida, A Gaven, R DeQuattro, V Song, Z Bergin, P Masengil, J Ely, D Reynolds, F Dennish, G Horton, N Bates, E Luciano, A Moloo, J Kaminski, M Geltman, E Flanagan, J Hayden, CT Felicetta, J Beckner, L Kaushik, V Mueco, A Lee, R Metcalf, A Fowles, R Summers, K Heerema, M Jacobson, M Diggs, P Roeske, M Rosenstein, R Dawley, D Dorst, D Warnica, J Smith, B Walker, L Scarcelli, D Tam, J Cuddy, T Courcelles, P Miller, N Gosselin, G Ducharme, A Marquis, J Lamy, M Title, L Johnstone, D Francis, M Cossett, J Dion, D St-Hilaire, R Morissette, A Poulin, F Arnold, M Krupa, M Boulianne, M Campeau, J Ouimet, F Roberge, B Huynh, T Finkenbine, S St Jacques, B Boudreault, C Borts, D Bonafede, N Burtcher, J Edwards, C Baigrie, R Gee, F Judge, J Reilly, K Bernstein, V MacDonald, K Mooney, S Rouleau, J Vienneau, R Mayer, JP Mitges, S Nawaz, S Dhaliwal, R Talbot, P Talbot, M Sussex, B Newman, S Baird, M Fraser, M Guimond, C Leboeuf, J Moe, G Day, D Rajakumar, G Kroeger, B Khouri, M Zello, N Lee, H Barban, K Kostuk, W Powell, AM Smilovitch, M Toyota, V Phaneuf, D Duclos, R Goulet, G Primeau, L Machel, T Morash, J Gossard, D Boutin, L Vizel, S Fox, B Stanton, E Lawrence, M Sullivan, H Paterson, R Hoag, G Ilott, K Dufton, J Sweeney, R Garcia-Palmieri, M Banchs, H Gonzalez, M Perez, M Colon, P Vazquez, N Schweiger, C Frisinghelli, A Galati, A Palma, P Di Pasquale, P Clemenza, F Filorizzo, G Petacchi, R Cogo, R Ferrari, M Battaglia, A Mancino, F D'Alessandro, B Truncellito, L Maina, M Romanzi, S Chieffo, C Cardillo, A De Lorenzi, E Bergarno, A Boccalatte, A Gaeta, G Neri, G Masaro, G Perticone, F Maio, R De Biase, M Carrone, M Scrutinio, D La Gioia, R Leonzio, L Tullio, D Santarone, M Tagliagambe, L Zonzin, P Capanna, M Di Giovanni, N Fiore, I Gavazzi, A Mazzoleni, D Pinelli, G Ribani, M Mangiameli, S Rubino, V Viecca, M Sala, R Porcu, M Salis, S Amici, R Patteri, G Bortolini, F Turelli, A Maresta, A Dalla Valle, G Braschi, G Abrignani, M Terrosu, P Castellaccio, M Boccanelli, A Morosetti, P Tartarini, G Levantesi, D Grieco, A Cazzaniga, A Poggio, G Giani, S Ferrari, G Belluschi, R Del Citerna, F Balli, E Maiolino, P Pedon, L Mininni, N Monda, V CA PEACE Trial Investigators TI Angiotensin-converting-enzyme inhibition in stable coronary artery disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID LEFT-VENTRICULAR DYSFUNCTION; CONGESTIVE-HEART-FAILURE; MYOCARDIAL-INFARCTION; EJECTION FRACTIONS; CARDIOVASCULAR EVENTS; ENLARGEMENT TRIAL; AMERICAN-COLLEGE; CLINICAL-TRIALS; TASK-FORCE; ENALAPRIL AB Background: Angiotensin-converting-enzyme (ACE) inhibitors are effective in reducing the risk of heart failure, myocardial infarction, and death from cardiovascular causes in patients with left ventricular systolic dysfunction or heart failure. ACE inhibitors have also been shown to reduce atherosclerotic complications in patients who have vascular disease without heart failure. Methods: In the Prevention of Events with Angiotensin Converting Enzyme Inhibition (PEACE) Trial, we tested the hypothesis that patients with stable coronary artery disease and normal or slightly reduced left ventricular function derive therapeutic benefit from the addition of ACE inhibitors to modern conventional therapy. The trial was a double-blind, placebo-controlled study in which 8290 patients were randomly assigned to receive either trandolapril at a target dose of 4 mg per day (4158 patients) or matching placebo (4132 patients). Results: The mean (+/-SD) age of the patients was 64+/-8 years, the mean blood pressure 133+/-17/78+/-10 mm Hg, and the mean left ventricular ejection fraction 58+/-9 percent. The patients received intensive treatment, with 72 percent having previously undergone coronary revascularization and 70 percent receiving lipid-lowering drugs. The incidence of the primary end point -- death from cardiovascular causes, myocardial infarction, or coronary revascularization -- was 21.9 percent in the trandolapril group, as compared with 22.5 percent in the placebo group (hazard ratio in the trandolapril group, 0.96; 95 percent confidence interval, 0.88 to 1.06; P=0.43) over a median follow-up period of 4.8 years. Conclusions: In patients with stable coronary heart disease and preserved left ventricular function who are receiving ``current standard'' therapy and in whom the rate of cardiovascular events is lower than in previous trials of ACE inhibitors in patients with vascular disease, there is no evidence that the addition of an ACE inhibitor provides further benefit in terms of death from cardiovascular causes, myocardial infarction, or coronary revascularization. C1 Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NHLBI, Bethesda, MD 20892 USA. George Washington Univ, Rockville, MD USA. Mayo Clin Fdn, Rochester, MN USA. George Washington Univ, Washington, DC USA. Univ Montreal, Montreal, PQ, Canada. RP Braunwald, E (reprint author), Brigham & Womens Hosp, TIMI Study Grp, 350 Longwood Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [N01 HC065149-12, N01 HC065149] NR 30 TC 641 Z9 677 U1 2 U2 19 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 11 PY 2004 VL 351 IS 20 BP 2058 EP 2068 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 869TM UT WOS:000225007200007 PM 15531767 ER PT J AU Mannon, PJ Fuss, IJ Mayer, L Elson, CO Sandborn, WJ Present, D Dolin, B Goodman, N Groden, C Hornung, RL Quezado, M Neurath, MF Salfeld, J Veldman, GM Schwertschlag, U Strober, W AF Mannon, PJ Fuss, IJ Mayer, L Elson, CO Sandborn, WJ Present, D Dolin, B Goodman, N Groden, C Hornung, RL Quezado, M Neurath, MF Salfeld, J Veldman, GM Schwertschlag, U Strober, W CA Anti-IL-12 Crohn's Dis Study Grp TI Anti-interleukin-12 antibody for active Crohn's disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PROPRIA MONONUCLEAR-CELLS; EXPERIMENTAL COLITIS; INTERFERON-GAMMA; IFN-GAMMA; T-CELLS; INTERLEUKIN-12; MICE; EXPRESSION; IL-12; RESPONSES AB Background: Crohn's disease is associated with excess cytokine activity mediated by type 1 helper T (Th1) cells. Interleukin-12 is a key cytokine that initiates Th1-mediated inflammatory responses. Methods: This double-blind trial evaluated the safety and efficacy of a human monoclonal antibody against interleukin-12 (anti-interleukin-12) in 79 patients with active Crohn's disease. Patients were randomly assigned to receive seven weekly subcutaneous injections of 1 mg or 3 mg of anti-interleukin-12 per kilogram of body weight or placebo, with either a four-week interval between the first and second injection (Cohort 1) or no interruption between the two injections (Cohort 2). Safety was the primary end point, and the rates of clinical response (defined by a reduction in the score for the Crohn's Disease Activity Index [CDAI] of at least 100 points) and remission (defined by a CDAI score of 150 or less) were secondary end points. Results: Seven weeks of uninterrupted treatment with 3 mg of anti-interleukin-12 per kilogram resulted in higher response rates than did placebo administration (75 percent vs. 25 percent, P=0.03). At 18 weeks of follow-up, the difference in response rates was no longer significant (69 percent vs. 25 percent, P=0.08). Differences in remission rates between the group given 3 mg of anti-interleukin-12 per kilogram and the placebo group in Cohort 2 were not significant at either the end of treatment or the end of follow-up (38 percent and 0 percent, respectively, at both times; P=0.07). There were no significant differences in response rates among the groups in Cohort 1. The rates of adverse events among patients receiving anti-interleukin-12 were similar to those among patients given placebo, except for a higher rate of local reactions at injection sites in the former group. Decreases in the secretion of interleukin-12, interferon-(gamma), and tumor necrosis factor (alpha) by mononuclear cells of the colonic lamina propria accompanied clinical improvement in patients receiving anti-interleukin-12. Conclusions: Treatment with a monoclonal antibody against interleukin-12 may induce clinical responses and remissions in patients with active Crohn's disease. This treatment is associated with decreases in Th1-mediated inflammatory cytokines at the site of disease. C1 NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. NCI, Surg Pathol Sect, NIH, Bethesda, MD 20892 USA. CUNY Mt Sinai Sch Med, Immunobiol Ctr, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Div Gastroenterol, New York, NY 10029 USA. Univ Alabama, Sch Med, Div Gastroenterol, Birmingham, AL USA. Mayo Clin, Rochester, MN USA. Hlth Advance Inst, Peoria, IL USA. Wyeth, Cambridge, MA USA. Sci Applicat Int Corp, Clin Serv Program, Frederick, MD USA. Univ Mainz, Med Klin 1, D-6500 Mainz, Germany. Abbott Biores Ctr, Worcester, MA USA. RP Mannon, PJ (reprint author), NIAID, Mucosal Immun Sect, Host Def Lab, NIH, 10 Ctr Dr,Rm 11-N238, Bethesda, MD 20892 USA. EM pmannon@niaid.nih.gov FU NCI NIH HHS [N01-CO-12400] NR 20 TC 544 Z9 571 U1 0 U2 10 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 11 PY 2004 VL 351 IS 20 BP 2069 EP 2079 DI 10.1056/NEJMoa033402 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 869TM UT WOS:000225007200008 PM 15537905 ER PT J AU Kleta, R O'Brien, K AF Kleta, R O'Brien, K TI Aldosterone revisited SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Kleta, R (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM kletar@mail.nih.gov NR 3 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 11 PY 2004 VL 351 IS 20 BP 2131 EP 2131 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 869TM UT WOS:000225007200029 PM 15543661 ER PT J AU Pereira, LHM Sigurdson, AJ Doody, MM Pineda, MA Alexander, BH Greene, MH Struewing, JP AF Pereira, LHM Sigurdson, AJ Doody, MM Pineda, MA Alexander, BH Greene, MH Struewing, JP TI CHEK2 : 1100delC and female breast cancer in the United States SO INTERNATIONAL JOURNAL OF CANCER LA English DT Letter ID LI-FRAUMENI-SYNDROME; MUTATIONS; CHEK2-ASTERISK-1100DELC; FAMILIES; BRCA1; RISK; POPULATION C1 NCI, Lab Populat Genet, Bethesda, MD 20892 USA. NCI, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. Univ Minnesota, Div Environm & Occupat Hlth, Minneapolis, MN 55455 USA. NCI, Clin Genet Branch, Bethesda, MD 20892 USA. RP Struewing, JP (reprint author), NCI, Lab Populat Genet, 41 Lib Dr,Room D702, Bethesda, MD 20892 USA. EM js140a@nih.gov RI Struewing, Jeffery/C-3221-2008; Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 NR 15 TC 10 Z9 10 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 10 PY 2004 VL 112 IS 3 BP 541 EP 543 DI 10.1002/ijc.20439 PG 3 WC Oncology SC Oncology GA 862NA UT WOS:000224496400026 ER PT J AU Yaffe, K Kanaya, A Lindquist, K Simonsick, EM Harris, T Shorr, RI Tylavsky, FA Newman, AB AF Yaffe, K Kanaya, A Lindquist, K Simonsick, EM Harris, T Shorr, RI Tylavsky, FA Newman, AB TI The metabolic syndrome, inflammation, and risk of cognitive decline SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID C-REACTIVE PROTEIN; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; CARDIOVASCULAR EVENTS; ELDERLY-MEN; OLDER WOMEN; DEMENTIA; DISEASE; ADULTS; CHOLESTEROL AB Context Several studies have reported an association between the metabolic syndrome and cardiovascular disease. Despite an increasing awareness that cardiovascular risk factors increase risk of cognitive decline and dementia, there are few data on the metabolic syndrome and cognition. Objective To determine if the metabolic syndrome is a risk factor for cognitive decline and if this association is modified by inflammation. Design and Setting A 5-year prospective observational study conducted from 1997 to 2002 at community clinics at 2 sites. Participants A total of 2632 black and white elders (mean age, 74 years). Main Outcome Measures Association of the metabolic syndrome (measured using National Cholesterol Education Program guidelines) and high inflammation (defined as above median serum level of interleukin 6 and C-reactive protein) with change in cognition (Modified Mini-Mental State Examination [3MS]) at 3 and 5 years. Cognitive impairment was defined as at least a 5-point decline. Results Compared with those without the metabolic syndrome (n=1616), elders with the metabolic syndrome (n=1016) were more likely to have cognitive impairment (26% vs 21%, multivariate adjusted relative risk [RR], 1.20; 95% confidence interval [CI], 1.02-1.41). There was a statistically significant interaction with inflammation and the metabolic syndrome (P=.03) on cognitive impairment. After stratifying for inflammation, those with the metabolic syndrome and high inflammation (n=348) had an increased likelihood of cognitive impairment compared with those without the metabolic syndrome (multivariate adjusted RR, 1.66; 95% CI, 1.19-2.32). Those with the metabolic syndrome and low inflammation (n=668) did not exhibit an increased likelihood of impairment (multivariate adjusted RR, 1.08; 95% CI, 0.89-1.30). Stratified multivariate random-effects models demonstrated that participants with the metabolic syndrome and high inflammation had greater 4-year decline on 3MS (P=.04) compared with those without the metabolic syndrome, whereas those with the metabolic syndrome and low inflammation did not (P=.44). Conclusion These findings support the hypothesis that the metabolic syndrome contributes to cognitive impairment in elders, but primarily in those with high level of inflammation. C1 Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Geriatr, San Francisco, CA 94143 USA. NIA, Clin Res Branch, Baltimore, MD USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD USA. Univ Tennessee, Dept Prevent Med, Memphis, TN USA. Univ Pittsburgh, Sch Med, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, Dept Psychiat, Box 181,4150 Clement St, San Francisco, CA 94121 USA. EM kyaffe@itsa.ucsf.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NIA NIH HHS [N01-AG-2106, N01-AG-6-2101, R01 AG021918-01, N01-AG-2103] NR 34 TC 482 Z9 497 U1 0 U2 35 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 10 PY 2004 VL 292 IS 18 BP 2237 EP 2242 DI 10.1001/jama.292.18.2237 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 870PK UT WOS:000225070000024 PM 15536110 ER PT J AU Pezawas, L Verchinski, BA Mattay, VS Callicott, JH Kolachana, BS Straub, RE Egan, MF Meyer-Lindenberg, A Weinberger, DR AF Pezawas, L Verchinski, BA Mattay, VS Callicott, JH Kolachana, BS Straub, RE Egan, MF Meyer-Lindenberg, A Weinberger, DR TI The brain-derived neurotrophic factor val66met polymorphism and variation in human cortical morphology SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Alzheimer; Down syndrome; gene; Huntington; memory; morphometry; neurotrophic; schizophrenia; BDNF; voxel-based; VBM; imaging genomics ID ACTIVITY-DEPENDENT SECRETION; HUMAN-MEMORY; BDNF; CORTEX; SCHIZOPHRENIA; PLASTICITY AB A variation in the BDNF gene ( val66met) affects the function of BDNF in neurons, predicts variation in human memory, and is associated several neurological and psychiatric disorders. Here, we show that, in magnetic resonance imaging scans of a large sample of normal this polymorphism affects the anatomy of the hippocampus and prefrontal cortex, identifying a genetic mechanism of in brain morphology related to learning and memory. C1 NIMH, Genes Cognit & Psychosis Program, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Weinberger, DR (reprint author), NIMH, Genes Cognit & Psychosis Program, Intramural Res Program, NIH, Room 4S-235,10 Ctr Dr, Bethesda, MD 20892 USA. EM weinberd@intra.nimh.nih.gov RI Callicott, Joseph/C-9102-2009; OI Callicott, Joseph/0000-0003-1298-3334; Pezawas, Lukas/0000-0002-1329-6352; Meyer-Lindenberg, Andreas/0000-0001-5619-1123 NR 26 TC 550 Z9 562 U1 4 U2 24 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 10 PY 2004 VL 24 IS 45 BP 10099 EP 10102 DI 10.1523/JNEUROSCI.2680-04.2004 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 869ZA UT WOS:000225022600009 PM 15537879 ER PT J AU Seeger, T Fedorova, I Zheng, F Miyakawa, T Koustova, E Gomeza, J Basile, AS Alzheimer, C Wess, J AF Seeger, T Fedorova, I Zheng, F Miyakawa, T Koustova, E Gomeza, J Basile, AS Alzheimer, C Wess, J TI M-2 muscarinic acetylcholine receptor knock-out mice show deficits in behavioral flexibility, working memory, and hippocampal plasticity SO JOURNAL OF NEUROSCIENCE LA English DT Article DE acetylcholine; hippocampus; knock-out mice; learning and memory; long-term potentiation; muscarinic receptors; synaptic plasticity ID LONG-TERM POTENTIATION; PREFRONTAL CORTEX; RAT HIPPOCAMPUS; CHOLINERGIC INNERVATION; SYNAPTIC PLASTICITY; ALZHEIMERS-DISEASE; MUTANT MICE; M2; SCOPOLAMINE; BRAIN AB Muscarinic acetylcholine receptors are known to play key roles in facilitating cognitive processes. However, the specific roles of the individual muscarinic receptor subtypes (M-1-M-5) in learning and memory are not well understood at present. In the present study, we used wild-type ( M2(+/+)) and M-2 receptor-deficient ( M2(-/-)) mice to examine the potential role of M-2 receptors in learning and memory and hippocampal synaptic plasticity. M2(-/-) mice showed significant deficits in behavioral flexibility and working memory in the Barnes circular maze and the T-maze delayed alternation tests, respectively. The behavioral deficits of M2(-/-) mice were associated with profound changes in neuronal plasticity studied at the Schaffer-CA1 synapse of hippocampal slices. Strikingly, short-term potentiation ( STP) was abolished, and long-term potentiation ( LTP) was drastically reduced after high-frequency stimulation of M2(-/-) hippocampi. Treatment of M2(-/-) hippocampal slices with the GABA(A) receptor antagonist, bicuculline, restored STP and significantly increased LTP. Whole-cell recordings from CA1 pyramidal cells demonstrated a much stronger disinhibition of GABAergic than glutamatergic transmission in M2(-/-) hippocampi, which was particularly prominent during stimulus trains. Increased strength of GABAergic inhibition is thus a likely mechanism underlying the impaired synaptic plasticity observed with M2(-/-) hippocampi. Moreover, the persistent enhancement of excitatory synaptic transmission in CA1 pyramidal cells induced by the transient application of a low concentration of a muscarinic agonist ( referred to as LTPm) was totally abolished in M2(-/-) mice. Because impaired muscarinic cholinergic neurotransmission is associated with Alzheimer's disease and normal aging processes, these findings should be of considerable therapeutic relevance. C1 NIDDKD, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Munich, Dept Physiol, D-80336 Munich, Germany. NIDDKD, Neurosci Grp, NIH, Bethesda, MD 20892 USA. Univ Kiel, Dept Physiol, D-24098 Kiel, Germany. Kyoto Univ, Fac Med, Lab Genet Engn & Funct Genom, Kyoto 6068501, Japan. RP Alzheimer, C (reprint author), NIDDKD, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bldg 8A,Room B1A-05,8 Ctr Dr, Bethesda, MD 20892 USA. EM c.alzheimer@physiologie.uni-kiel.de; jwess@helix.nih.gov RI Miyakawa, Tsuyoshi/A-7741-2008 OI Miyakawa, Tsuyoshi/0000-0003-0137-8200 NR 56 TC 117 Z9 121 U1 2 U2 11 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 10 PY 2004 VL 24 IS 45 BP 10117 EP 10127 DI 10.1523/JNEUROSCI.3581-04.2004 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 869ZA UT WOS:000225022600012 PM 15537882 ER PT J AU Goti, D Katzen, SM Mez, J Kurtis, N Kiluk, J Ben-Haiem, L Jenkins, NA Copeland, NG Kakizuka, A Sharp, AH Ross, CA Mouton, PR Colomer, V AF Goti, D Katzen, SM Mez, J Kurtis, N Kiluk, J Ben-Haiem, L Jenkins, NA Copeland, NG Kakizuka, A Sharp, AH Ross, CA Mouton, PR Colomer, V TI A mutant ataxin-3 putative-cleavage fragment in brains of Machado-Joseph disease patients and transgenic mice is cytotoxic above a critical concentration SO JOURNAL OF NEUROSCIENCE LA English DT Article DE neurotoxicity; Machado-Joseph; spinocerebellar ataxia type 3; ataxin-3; mouse model; cleavage fragment ID EXPANDED POLYGLUTAMINE PROTEIN; BULBAR MUSCULAR-ATROPHY; HUNTINGTONS-DISEASE; SPINOCEREBELLAR ATAXIA; INTRANUCLEAR INCLUSIONS; GENE-PRODUCT; DEPENDENT PROTEOLYSIS; NUCLEAR INCLUSIONS; TERMINAL FRAGMENTS; CEREBELLAR-ATAXIA AB Machado-Joseph disease ( MJD) is an inherited neurodegenerative disorder caused by ataxin-3 with a polyglutamine expansion. It is proposed that a toxic cleavage fragment of mutant ataxin-3 alternatively spliced isoform mjd1a triggers neurodegeneration, although this fragment has not yet been detected in the brains of MJD patients or in animal models. We have now generated transgenic mice expressing human mutant ( Q71) or normal ( Q20) ataxin-3 mjd1a under the control of the mouse prion promoter. Q71 transgenic mice expressing mutant ataxin-3 mjd1a above a critical level developed a phenotype similar to MJD including progressive postural instability, gait and limb ataxia, weight loss, premature death, neuronal intranuclear inclusions, and decreased tyrosine hydroxylase-positive neurons in the substantia nigra ( determined by unbiased stereology). Q20 transgenic mice had normal behavior and pathology. Brains from sick Q71 transgenic mice contained an abundant mutant ataxin-3 mjd1a putative-cleavage fragment ( Fragment), which was scarce in normal Q71 transgenic mice. Reactivity of the Fragment with a panel of antibodies and comigration with truncations of mutant ataxin-3 revealed that it contained residues C terminal to amino acid 221 to include the polyglutamine expansion. A similar portion of mutant ataxin-3 mjd1a expressed in transfected neuroblastoma cells was toxic above a critical concentration. The Fragment was more abundant in two affected brain regions of MJD patients. Thus, we have developed a murine model for mutant ataxin-3 mjd1a toxicity and identified a putative cleavage fragment of the disease protein in the brains of these transgenic mice and MJD patients that is cytotoxic above a critical concentration. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21287 USA. Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France. Natl Canc Inst, Mouse Canc Genet Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Kyoto Univ, Lab Funct Biol, Kyoto 6068501, Japan. Case Western Reserve Univ, Sch Med, Dept Gen Med Sci, Cleveland, OH 44106 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Div Neurobiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Stereol Res Ctr Inc, Chester, MD 21619 USA. RP Colomer, V (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat, 600 N Wolfe St,Meyer Res Bldg,Room4-158, Baltimore, MD 21287 USA. EM vcolomer@jhu.edu OI Mez, Jesse/0000-0003-1438-5442 FU NINDS NIH HHS [NS16375, NS38144, NS42731] NR 62 TC 108 Z9 111 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 10 PY 2004 VL 24 IS 45 BP 10266 EP 10279 DI 10.1523/JNEUROSCI.2734-04.2004 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 869ZA UT WOS:000225022600029 PM 15537899 ER PT J AU Prikhod'ko, EA Prikhod'ko, GG Siegel, RM Thompson, P Major, ME Cohen, JI AF Prikhod'ko, EA Prikhod'ko, GG Siegel, RM Thompson, P Major, ME Cohen, JI TI The NS3 protein of hepatitis C virus induces caspase-8-mediated apoptosis independent of its protease or helicase activities SO VIROLOGY LA English DT Article DE hepatitis C virus; apoptosis; caspase-8; flavivirus ID ALPHA-MEDIATED APOPTOSIS; NECROSIS-FACTOR RECEPTOR; TNF-INDUCED APOPTOSIS; CORE PROTEIN; VIRAL-HEPATITIS; CELL-DEATH; IN-VITRO; SUBCELLULAR-LOCALIZATION; SERINE PROTEINASE; LANGAT FLAVIVIRUS AB Apoptosis has been implicated in the pathogenesis of hepatitis C virus (HCV)-related disease. Here, we show that expression of HCV NS3, or the NS2/NS3 precursor protein, in mammalian cells results in induction of apoptosis and activation of caspases. HCV NS3-induced apoptosis was blocked by a caspase-8, but not a caspase-9-specific inhibitor. HCV NS3 coimmunoprecipitated with caspase-8, but not with other caspases or with FADD. Coexpression of HCV NS3 and caspase-8 resulted in aggregation of the caspase in punctate structures that colocalized with HCV NS3. Cell lines stably expressing low levels HCV NS3 showed increased sensitivity to Fas-induced cell death. Point mutations of NS3 showed that the pro-apoptotic function of the protein is distinct from its protease and helicase activities. These findings suggest that HCV NS3 promotes caspase-8 induced apoptosis at a pathway site distal to FADD, and that flavivirus NS3 may represent a new class of pro-apoptotic proteins. Published by Elsevier Inc. C1 NIAID, Med Virol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. Amer Red Cross, Holland Lab, Plasma Derivatives Dept, Rockville, MD 20855 USA. NIAID, Mol Dev Immune Syst Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Lab Hepatitis Res, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Cohen, JI (reprint author), NIAID, Med Virol Sect, Lab Clin Infect Dis, NIH, Bldg 10,Room 11N228m10 Ctr Dr, Bethesda, MD 20892 USA. EM jcohen@niaid.nih.gov RI Siegel, Richard/C-7592-2009 OI Siegel, Richard/0000-0001-5953-9893 NR 74 TC 53 Z9 57 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 0042-6822 J9 VIROLOGY JI Virology PD NOV 10 PY 2004 VL 329 IS 1 BP 53 EP 67 DI 10.1016/j.virol.2004.08.012 PG 15 WC Virology SC Virology GA 865PQ UT WOS:000224715400006 PM 15476874 ER PT J AU Sandstrom, C Berteau, O Gemma, E Oscarson, S Kenne, L Gronenborn, AM AF Sandstrom, C Berteau, O Gemma, E Oscarson, S Kenne, L Gronenborn, AM TI Atomic mapping of the interactions between the antiviral agent cyanovirin-N and oligomannosides by saturation-transfer difference NMR SO BIOCHEMISTRY LA English DT Article ID HIV-INACTIVATING PROTEIN; HIGH-MANNOSE OLIGOSACCHARIDES; STRUCTURAL BASIS; LIGAND-BINDING; GP120; VIRUS; AFFINITY; SPECTROSCOPY; RECEPTOR; SITE AB The minimum oligosaccharide structure required for binding to the potent HIV-inactivating protein cyanovirin-N (CV-N) was determined by saturation-transfer difference (STD) NMR spectroscopy. Despite the low molecular mass of the protein (11 kDa), STD-NMR spectroscopy allowed the precise atomic mapping of the interactions between CV-N and various di- and trimannosides, substructures of Man-9, the predominant oligosaccharide on the HIV viral surface glycoprotein gp120. Contacts with mannosides containing the terminal Manalpha(1-->2)Manalpha unit of Man-9 were observed, while (1-->3)- and (1-6)-linked di- and trimannosides showed no interactions, demonstrating that the terminal Maalpha(1-->2)Manalpha structure plays a key role in the interaction. Precise epitope mapping revealed that, for Manalpha(1-->2)ManalphaOMe, Manalpha(1-->2)Manalpha(1-->3)ManalphaOMe, and Manalpha(1-->2)Manalpha(1-->6)ManalphaOMe, the protein is in close contact with H2, H3, and H4 of the nonreducing terminal mannose unit. In contrast, the STD-NMR spectrum of the CV-N/trisaccharide Manalpha(1-->2)Manalpha(1-->2)ManalphaOMe complex was markedly different, with resonances on all sugar units displaying equal enhancements, suggesting that CV-N is able to discriminate between the three structurally related trisaccharides. C1 Swedish Univ Agr Sci, Dept Chem, SE-75007 Uppsala, Sweden. Stockholm Univ, Arrhenius Lab, Dept Organ Chem, SE-10691 Stockholm, Sweden. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Sandstrom, C (reprint author), Swedish Univ Agr Sci, Dept Chem, POB 7015, SE-75007 Uppsala, Sweden. EM corine.sandstrom@kemi.slu.se OI Oscarson, Stefan/0000-0002-8273-4918; Gronenborn, Angela M/0000-0001-9072-3525 NR 24 TC 32 Z9 33 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 9 PY 2004 VL 43 IS 44 BP 13926 EP 13931 DI 10.1021/bi048676k PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 868UV UT WOS:000224939400005 PM 15518540 ER PT J AU Poruchynsky, MS Kim, JH Nogales, E Annable, T Loganzo, F Greenberger, LM Sackett, DL Fojo, T AF Poruchynsky, MS Kim, JH Nogales, E Annable, T Loganzo, F Greenberger, LM Sackett, DL Fojo, T TI Tumor cells resistant to a microtubule-depolymerizing hemiasterlin analogue, HTI-286, have mutations in alpha- or beta-tubulin and increased microtubule stability SO BIOCHEMISTRY LA English DT Article ID CYTOTOXIC PEPTIDES; TRIPEPTIDE HEMIASTERLIN; SYNTHETIC ANALOG; MITOTIC ARREST; EPOTHILONE-B; CANCER-CELLS; TAXOL; MECHANISMS; RESOLUTION; VINBLASTINE AB Hemiasterlins are sponge-derived tripeptides that inhibit cell growth by depolymerizing existing microtubules and inhibiting microtubule assembly. Since hemiasterlins are poor substrates for P-glycoprotein, they are attractive candidates for cancer therapy and have been undergoing clinical trials. The basis of resistance to a synthetic analogue of hemiasterlin, HTI-286 (HTI), was examined in cell populations derived from ovarian carcinoma (A2780/1A9) cells selected in HTI-286. 1A9-HTI-resistant cells (1A9-HTIR series) were 57-89-fold resistant to HTI. Cross-resistance (3-186-fold) was observed to other tubulin depolymerizing drugs, with collateral sensitivity (2-14-fold) to tubulin polymerizing agents. Evaluation of the percentage of polymerized and soluble tubulin in 1A9 parental and 1A9-HTIR Cells corroborated the HTI cytotoxicity data. At 22 degreesC or 37 degreesC, in the absence of any drug, the percentage of polymerized microtubules for each of the 1A9-HTIR populations was greater than that in the 1A9 parental cells, consistent with more stable microtubules. Furthermore, microtubules in the 1A9-HTIR populations were also more resistant to depolymerization at 4 degreesC and had more acetylated and detyrosinated (Glu-tubulin) alpha-tubulin, all characteristic of more stable microtubules. The 1A9-HTIR cell populations exhibited either a single nucleotide change in the M40 beta-tubulin isotype, S172A, or in two cell populations where no beta-tubulin mutation was detected, mutations in the Kalpha-1 alpha-tubulin isotype, S165P and R221H in one resistant cell population and 1384V in another. Unlike reports of mutations resulting in reduced drug affinity, the experimental data and location of mutations are consistent with resistance to HTI-286 mediated by microtubule-stabilizing mutations in beta- or alpha-tubulin. C1 NCI, Ctr Canc Res, Canc Therapeut Branch, Bethesda, MD 20892 USA. Univ Calif Berkeley, Howard Hughes Med Inst, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. Wyeth Ayerst Res, Oncol Res, Pearl River, NY 10965 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Poruchynsky, MS (reprint author), NCI, Ctr Canc Res, Canc Therapeut Branch, Bethesda, MD 20892 USA. EM mporuch@helix.nih.gov NR 54 TC 41 Z9 45 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 9 PY 2004 VL 43 IS 44 BP 13944 EP 13954 DI 10.1021/bi049300 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 868UV UT WOS:000224939400008 PM 15518543 ER PT J AU Freeman, JM Nelson, KB AF Freeman, JM Nelson, KB TI Expert medical testimony - Responsibilities of medical societies SO NEUROLOGY LA English DT Article AB Expert witnesses for plaintiff and defense should be able to provide evidence-based literature to support their testimony in depositions and in the courtroom. Specialty societies, such as the American Academy of Neurology, should be willing to review complaints about unsubstantiated testimony and, at times, publicly discipline offending experts. C1 Johns Hopkins Med Inst, Dept Neurol, Baltimore, MD 21205 USA. NINDS, Div Neuroepidemiol, NIH, Bethesda, MD 20892 USA. RP Freeman, JM (reprint author), Johns Hopkins Univ Hosp, Meyer 2-147,600 N Wolf St, Baltimore, MD 21287 USA. EM Jfreeman@jhmi.edu NR 2 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV 9 PY 2004 VL 63 IS 9 BP 1557 EP 1558 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 869MJ UT WOS:000224987700005 PM 15534235 ER PT J AU Seshadri, S Wolf, PA Beiser, A Elias, MF Au, R Kase, CS D'Agostino, RB DeCarli, C AF Seshadri, S Wolf, PA Beiser, A Elias, MF Au, R Kase, CS D'Agostino, RB DeCarli, C TI Stroke risk profile, brain volume, and cognitive function - The Framingham Offspring Study SO NEUROLOGY LA English DT Article ID SPONTANEOUSLY HYPERTENSIVE RATS; MIDLIFE BLOOD-PRESSURE; MIDDLE-AGED ADULTS; WHITE-MATTER; CARDIOVASCULAR HEALTH; VASCULAR DEMENTIA; CEREBRAL ATROPHY; TEST-PERFORMANCE; OLDER-ADULTS; NHLBI TWIN AB Background: Mid-life stroke risk factors have been related to late-life cognitive impairment. This association may result not only from clinical strokes but also from subclinical brain injury, such as a global atrophy demonstrable on quantitative brain MRI. Methods: The authors evaluated the community-based cohort of Framingham Offspring Study participants. A total of 1,841 subjects (mean age, 62 years; 857 men, 984 women) who underwent quantitative MRI and cognitive testing between 1999 and 2001 and were free of clinical stroke and dementia constituted our study sample. The authors used age- and sex-adjusted linear regression models to relate previous (1991 to 1995) and recent ( 1998 to 2001) Framingham Stroke Risk Profile (FSRP) scores to the total cerebral brain volume ratio (TCBVr) on follow-up MRI, and further to relate the TCBVr with education-adjusted scores on neuropsychological tests administered at the time of imaging. Results: There was an inverse association between FSRP scores and TCBVr. The TCBVr also showed a significant positive association with performance on tests of attention (Trails A), executive function (Trails B), and visuospatial function ( visual reproduction, Hooper visual organization), but not with performance on tests of verbal memory or naming. Conclusions: The Framingham Stroke Risk Profile may identify subjects with smaller brains and poorer cognitive function among stroke- and dementia-free subjects, reinforcing the importance of managing stroke risk factors. C1 Boston Univ, Sch Med, Dept Neurol, Neurol Epidemiol & Genet Div, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. Boston Univ, Dept Math & Stat, Boston, MA 02118 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Univ Calif Davis, Dept Neurol, Sacramento, CA 95817 USA. Univ Calif Davis, Ctr Neurosci, Sacramento, CA 95817 USA. RP Wolf, PA (reprint author), Boston Univ, Sch Med, Dept Neurol, Neurol Epidemiol & Genet Div, 715 Albany St,B-608, Boston, MA 02118 USA. EM pawolf@bu.edu RI DeCarli, Charles/B-5541-2009 FU NHLBI NIH HHS [N01-HC-38038]; NIA NIH HHS [5R01-AG08122, 5R01-AG16495-05, P30 AG13846]; NINDS NIH HHS [5R01-NS17950-23] NR 57 TC 132 Z9 134 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV 9 PY 2004 VL 63 IS 9 BP 1591 EP 1599 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 869MJ UT WOS:000224987700011 PM 15534241 ER PT J AU Miller, TM da Silva, MRD Miller, HA Kwiecinski, H Mendell, JR Tawil, R McManis, P Griggs, RC Angelini, C Servidei, S Petajan, J Dalakas, MC Ranum, LPW Fu, YH Ptacek, LJ AF Miller, TM da Silva, MRD Miller, HA Kwiecinski, H Mendell, JR Tawil, R McManis, P Griggs, RC Angelini, C Servidei, S Petajan, J Dalakas, MC Ranum, LPW Fu, YH Ptacek, LJ TI Correlating phenotype and genotype in the periodic paralyses SO NEUROLOGY LA English DT Article; Proceedings Paper CT 56th Annual Meeting of the American-Academy-of-Neurology CY APR 24-MAY 01, 2004 CL San Francisco, CA SP Amer Acad Neurol ID SODIUM-CHANNEL MUTATIONS; MYOTONIC-DYSTROPHY TYPE-2; PARAMYOTONIA-CONGENITA; SLOW INACTIVATION; SKELETAL-MUSCLE; ANDERSEN-SYNDROME; GENE-MUTATIONS; FAMILIES; WEAKNESS; MYOPATHY AB Background: Periodic paralyses and paramyotonia congenita are rare disorders causing disabling weakness and myotonia. Mutations in sodium, calcium, and potassium channels have been recognized as causing disease. Objective: To analyze the clinical phenotype of patients with and without discernible genotype and to identify other mutations in ion channel genes associated with disease. Methods: The authors have reviewed clinical data in patients with a diagnosis of hypokalemic periodic paralysis (56 kindreds, 71 patients), hyperkalemic periodic paralysis ( 47 kindreds, 99 patients), and paramyotonia congenita ( 24 kindreds, 56 patients). For those patients without one of the classically known mutations, the authors analyzed the entire coding region of the SCN4A, KCNE3, and KCNJ2 genes and portions of the coding region of the CACNA1S gene in order to identify new mutations. Results: Mutations were identified in approximately two thirds of kindreds with periodic paralysis or paramyotonia congenita. The authors found differences between the disorders and between those with and without identified mutations in terms of age at onset, frequency of attacks, duration of attacks, fixed proximal weakness, precipitants of attacks, myotonia, electrophysiologic studies, serum potassium levels, muscle biopsy, response to potassium administration, and response to treatment with acetazolamide. Conclusions: Hypokalemic periodic paralysis, hyperkalemic periodic paralysis, and paramyotonia congenita may be distinguished based on clinical data. This series of 226 patients ( 127 kindreds) confirms some clinical features of this disorder with notable exceptions: In this series, patients without mutations had a less typical clinical presentation including an older age at onset, no changes in diet as a precipitant, and absence of vacuolar myopathy on muscle biopsy. C1 Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Med Acad Warsaw, Dept Neurol, PL-02032 Warsaw, Poland. Ohio State Univ, Sch Med, Dept Neurol, Columbus, OH 43210 USA. Univ Rochester, Dept Neurol, Rochester, NY 14627 USA. Univ Sydney, Dept Neurol, Sydney, NSW 2006, Australia. Univ Padua, Dept Neurol, I-35100 Padua, Italy. Univ Sacred Heart, Inst Neurol, I-00168 Rome, Italy. Univ Utah, Dept Neurol, Med Ctr SR210, Salt Lake City, UT 84112 USA. NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Dept Genet, Minneapolis, MN USA. Univ Minnesota, Inst Human Genet, Minneapolis, MN 55455 USA. RP Ptacek, LJ (reprint author), Univ Calif San Francisco, Dept Neurol, Box 2922,19B Mission Bay,Room 548,1550 4th St, San Francisco, CA 94143 USA. EM ptacek@itsa.ucsf.edu RI Dias da Silva, Magnus/B-9132-2012; OI Dias da Silva, Magnus/0000-0002-8516-966X; Angelini, Corrado/0000-0002-9554-8794 FU NINDS NIH HHS [NS38616]; Telethon [GTF02009] NR 38 TC 79 Z9 91 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV 9 PY 2004 VL 63 IS 9 BP 1647 EP 1655 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 869MJ UT WOS:000224987700020 PM 15534250 ER PT J AU Dumbacher, JP Wako, A Derrickson, SR Samuelson, A Spande, TF Daly, JW AF Dumbacher, JP Wako, A Derrickson, SR Samuelson, A Spande, TF Daly, JW TI Melyrid beetles (Choresine): A putative source for the batrachotoxin alkaloids found in poison-dart frogs and toxic passerine birds SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Pitohui; Ifrita; Phyllobates; APC; mass spectrometry; dietary arthropods ID HOMOBATRACHOTOXIN; DENDROBATIDAE; DEFENSE; ANTS; SKIN AB Batrachotoxins are neurotoxic steroidal alkaloids first isolated from a Colombian poison-dart frog and later found in certain passerine birds of New Guinea. Neither vertebrate group is thought to produce the toxins de novo, but instead they likely sequester them from dietary sources. Here we describe the presence of high levels of batrachotoxins in a little-studied group of beetles, genus Choresine (family Melyridae). These small beetles and their high toxin concentrations suggest that they might provide a toxin source for the New Guinea birds. Stomach content analyses of Pitohui birds revealed Choresine beetles in the diet, as well as numerous other small beetles and arthropods. The family Melyridae is cosmopolitan, and relatives in Colombian rain forests of South America could be the source of the batrachotoxins found in the highly toxic Phyllobates frogs of that region. C1 Smithsonian Conservat Res Ctr, Front Royal, VA 22630 USA. Calif Acad Sci, Dept Birds & Mammals, San Francisco, CA 94103 USA. Bernice P Bishop Museum, Honolulu, HI 96813 USA. NIDDK, Bioorgan Chem Lab, Natl Inst Hlth, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Dumbacher, JP (reprint author), Smithsonian Conservat Res Ctr, Front Royal, VA 22630 USA. EM jdumbacher@calacademy.org NR 19 TC 75 Z9 80 U1 7 U2 41 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 9 PY 2004 VL 101 IS 45 BP 15857 EP 15860 DI 10.1073/pnas.0407197101 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 872GX UT WOS:000225196800008 PM 15520388 ER PT J AU Myung, K Smith, S Kolodner, RD AF Myung, K Smith, S Kolodner, RD TI Mitotic checkpoint function in the formation of gross chromosomal rearrangements in Saccharomyces cerevisiae SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE genome instability; mutation; spindle; DNA damage ID STRAND BREAK REPAIR; DNA MISMATCH REPAIR; BUDDING YEAST; SPINDLE CHECKPOINT; S-PHASE; GENOMIC INSTABILITY; TELOMERE ELONGATION; DAMAGE RESPONSE; SYNDROME GENE; HUMAN CANCERS AB The accumulation of gross chromosomal rearrangements (GCRs) is characteristic of cancer cells. Multiple pathways that prevent GCRs, including S-phase cell cycle checkpoints, homologous recombination, telomere maintenance, suppression of de novo telomere addition, chromatin assembly, and mismatch repair, have been identified in Saccharomyces cerevisiae. However, pathways that promote the formation of GCRs are not as well understood. Of these, the de novo telomere addition pathway and nonhomologous end-joining are the best characterized. Here, we demonstrate that defects in the mitotic checkpoint and the mitotic exit network can suppress GCRs in strains containing defects that increase the GCR rate. These data suggest that functional mitotic checkpoints can play a role in the formation of genome rearrangements. C1 NHGRI, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, La Jolla, CA 92093 USA. RP Kolodner, RD (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. EM rkolodner@ucsd.edu FU NIGMS NIH HHS [GM 26017, R01 GM026017, R37 GM026017] NR 83 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 NOV 9 PY 2004 VL 101 IS 45 BP 15980 EP 15985 DI 10.1073/pnas.0407010101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 872GX UT WOS:000225196800031 PM 15514023 ER PT J AU Wendler, D AF Wendler, D TI Can we ensure that all research subjects give valid consent? SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID INFORMED-CONSENT; CLINICAL RESEARCH; OLDER PATIENTS; COMPREHENSION; PERCEPTIONS; PSYCHOSIS; CAPACITY; DISEASE; QUALITY AB To ensure that research subjects provide valid consent, most commentators direct clinical investigators to formally assess potential subjects who are at increased risk for lacking the capacity to consent. Current data reveal, however, that subjects with no known cognitive impairments often fail to give valid consent. These data imply that the prevailing focus on individuals' capacity to consent is too narrow. To protect subjects, as well as the integrity of clinical research, the actual consent of all subjects should be formally assessed. Recent development of several preliminary consent assessment tools suggests that, in addition to being ethically preferable, with additional research this approach may be practically feasible. Future research should focus on developing a postdecision questionnaire that can be adapted to individual studies and used to assess the voluntariness and understanding of all research subjects. C1 NIH, Dept Clin Bioethics, Bethesda, MD 20892 USA. RP Wendler, D (reprint author), NIH, Dept Clin Bioethics, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM dwendler@nih.gov NR 25 TC 31 Z9 31 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 8 PY 2004 VL 164 IS 20 BP 2201 EP 2204 DI 10.1001/archinte.164.20.2201 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 869EG UT WOS:000224965600003 PM 15534155 ER PT J AU Berezhkovskii, A Szabo, A AF Berezhkovskii, A Szabo, A TI Ensemble of transition states for two-state protein folding from the eigenvectors of rate matrices SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID KINETICS; DIFFUSION; REGIME; MODELS C1 NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. LY Karpov Phys Chem Res Inst, Moscow 103064, Russia. RP Berezhkovskii, A (reprint author), NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. EM berezh@helix.nih.gov RI Szabo, Attila/H-3867-2012 NR 15 TC 23 Z9 23 U1 0 U2 4 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 NOV 8 PY 2004 VL 121 IS 18 BP 9186 EP 9187 DI 10.1063/1.1802674 PG 2 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 866UM UT WOS:000224798900061 PM 15527389 ER PT J AU Schmittner, J Schroeder, JR Epstein, DH Preston, KL AF Schmittner, J Schroeder, JR Epstein, DH Preston, KL TI QT interval increased after single dose of lofexidine SO BRITISH MEDICAL JOURNAL LA English DT Article C1 NIDA, NIH, Intramural Res Program, Baltimore, MD 21224 USA. RP Schmittner, J (reprint author), NIDA, NIH, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM jschmitt@intra.nida.nih.gov RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 NR 4 TC 6 Z9 6 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD NOV 6 PY 2004 VL 329 IS 7474 BP 1075 EP 1075 DI 10.1136/bmj.329.7474.1075 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 870PN UT WOS:000225070300021 PM 15528619 ER PT J AU Mathur, R Lim, WK Chan, CC Chee, SP AF Mathur, R Lim, WK Chan, CC Chee, SP TI Reactive iris lymphoid proliferation presenting as the AIDS-defining event in an HIV patient with systemic SO AIDS LA English DT Letter ID IMMUNODEFICIENCY C1 Singapore Natl Eye Ctr, Singapore, Singapore. Singapore Eye Res Inst, Singapore, Singapore. Natl Univ Singapore, Singapore 117548, Singapore. NEI, NIH, Bethesda, MD 20892 USA. RP Mathur, R (reprint author), Singapore Natl Eye Ctr, Singapore, Singapore. NR 4 TC 0 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD NOV 5 PY 2004 VL 18 IS 16 BP 2215 EP 2216 DI 10.1097/00002030-200411050-00020 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 869DX UT WOS:000224964700020 PM 15577661 ER PT J AU Akahane, T Akahane, M Shah, A Thorgeirsson, UP AF Akahane, T Akahane, M Shah, A Thorgeirsson, UP TI TIMP-1 stimulates proliferation of human aortic smooth muscle cells and Ras effector pathways SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE aortic smooth muscle cells; proliferation; TIMP-1; GM6001; Ras; ERK; PI3K ID TISSUE INHIBITOR; MATRIX METALLOPROTEINASES; IN-VITRO; EXTRACELLULAR-MATRIX; ANEURYSM FORMATION; GROWTH-FACTOR; CANCER-CELLS; MIGRATION; INJURY; CYCLE AB Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a multifunctional protein, which is found in most tissues and body fluids. Here, we demonstrated that recombinant TIMP-1 but not the synthetic matrix metalloproteinase inhibitor, GM6001, stimulated proliferation of human aortic smooth muscle cells (AoSMC) in a dose-dependent manner. The mitogenic effect was associated with activation of Ras, increased phosphorylation of ERK, and stimulation of cyclin D1 expression. The phosphatidylinositol 3-kinase (PI3K) signaling pathway was also involved since the PI3K inhibitor, LY294002, abolished the TIMP-1-mediated growth stimulation. These data suggest that TIMP-1 activates Ras, which then turns on the ERK and PI3K signaling pathways to promote cell cycle progression of the AoSMC. (C) 2004 Elsevier Inc. All rights reserved. C1 Ctr Canc Res, Cellular Carcinogenesis & Tumor Promot Lab, NCI, NIH, Bethesda, MD 20892 USA. RP Akahane, T (reprint author), Ctr Canc Res, Cellular Carcinogenesis & Tumor Promot Lab, NCI, NIH, Bethesda, MD 20892 USA. EM akahane@m5.kcn.ne.jp NR 48 TC 32 Z9 36 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 5 PY 2004 VL 324 IS 1 BP 440 EP 445 DI 10.1016/j.bbrc.2004.09.063 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 863WX UT WOS:000224595300066 PM 15465038 ER PT J AU Cowan, MJ Yao, XL Pawliczak, R Huang, XL Logun, C Madara, P Alsaaty, S Wu, T Shelhamer, JH AF Cowan, MJ Yao, XL Pawliczak, R Huang, XL Logun, C Madara, P Alsaaty, S Wu, T Shelhamer, JH TI The role of TFIID, the initiator element and a novel 5 ' TFIID binding site in the transcriptional control of the TATA-less human cytosolic phospholipase A(2)-alpha promoter SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Review DE TFIID; initiator element; cytosolic phospholipase A(2)-alpha ID ARACHIDONIC-ACID RELEASE; ACTIVATED PROTEIN-KINASE; RNA-POLYMERASE-II; RELAXATION MAGNETIC-RESONANCE; STIMULATED HUMAN PLATELETS; LIPID 2ND MESSENGERS; RAT MESANGIAL CELLS; EPITHELIAL-CELLS; A(2) GENE; MAMMALIAN-CELLS AB Human cytosolic phospholipase A(2)-alpha (cPLA(2)-alpha) is a critical enzyme in the liberation of arachidonic acid (AA) from cellular membranes and the subsequent formation of prostaglandins (PGs), leukotrienes (LTs), hydroxyeicosatetraenoic acids (HETEs) and platelet activating factor in many different cell types. Much is known of the effect of posttranslational phosphorylation and calcium binding events on the enzymatic activity of cPLA2-alpha, but to date little is known about its specific transcriptional control. Through the use of reporter gene constructs and eletrophoretic mobility shift assays (EMSAs), this study determined the minimal promoter required for basal transcriptional activity of the human cPLA2-alpha promoter to include base pairs -40 through the transcription start site (TSS). In addition, it confirms the importance of an initiator (Inr) element at the TSS by deletion reporter gene analysis, and further identifies bases -3 (C) and -2 (T) as critical bases in the Inr function by mutation reporter gene analysis. Finally, this study describes a novel AAGGAG motif at -30 to -35 which is bound by TATA-box binding protein (TBP) and is critical for basal transcriptional activity. Published by Elsevier B.V. C1 Univ Maryland, Div Pulm & Crit Care Med, Baltimore, MD 21201 USA. NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. Med Univ Lodz, Dept Allergy & Clin Immunol, PL-92213 Lodz, Poland. RP Cowan, MJ (reprint author), Univ Maryland, Div Pulm & Crit Care Med, 10 N Greene St,Room 3D-127, Baltimore, MD 21201 USA. EM mark.cowan@verizon.net RI Pawliczak, Rafal/S-9649-2016 NR 101 TC 12 Z9 14 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 NOV 5 PY 2004 VL 1680 IS 3 BP 145 EP 157 DI 10.1016/j.bbaexp.2004.09.006 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 868UK UT WOS:000224938300002 PM 15507318 ER PT J AU Ishii, S Yoshioka, H Mannen, K Kulkarni, AB Fan, JQ AF Ishii, S Yoshioka, H Mannen, K Kulkarni, AB Fan, JQ TI Transgenic mouse expressing human mutant alpha-galactosidase A in an endogenous enzyme deficient background: a biochemical animal model for studying active-site specific chaperone therapy for Fabry disease SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Article DE transgenic; alpha-galactosidase A; Fabry disease; active-site specific chaperone; 1-deoxygalactonojirimycin ID REPLACEMENT THERAPY; ATYPICAL VARIANT; MICE; GENE; LYMPHOBLASTS; HYPERTROPHY; SAFETY; TRIAL; CELLS; FORM AB Fabry disease is an inborn error of glycosphingolipid metabolism caused by the deficiency of lysosomal alpha-galactosidase A (alpha-Gal A). We have established transgenic mice that exclusively express human mutant alpha-Gal A (R301Q) in an alpha-Gal A knock-out background (TgM/KO mice). This serves as a biochemical model to study and evaluate active-site specific chaperone (ASSC) therapy for Fabry disease, which is specific for those missense mutations that cause misfolding of alpha-Gal A. The alpha-Gal A activities in the heart, kidney, spleen, and liver of homozygous TgM/KO mice were 52.6, 9.9, 29.6 and 44.4 unit/mg protein, respectively, corresponding to 16.4-, 0.8-, 0.6- and 1.4-fold of the endogenous enzyme activities in the same tissues of non-transgenic mice with a similar genetic background. Oral administration of 1-deoxygalactonojirimycin (DGJ), a competitive inhibitor of alpha-Gal A and an effective ASSC for Fabry disease, at 0.05 mM in the drinking water of the mice for 2 weeks resulted in 13.8-, 3.3-, 3.9-, and 2.6-fold increases in enzyme activities in the heart, kidney, spleen and liver, respectively. No accumulation of globotriaosylceramide, a natural substrate of alpha-Gal A, could be detected in the heart of TgM/KO mice after DGJ treatment, indicating that degradation of the glycolipid in the heart was not inhibited by DGJ at that dosage. The alpha-Gal A activity in homozygous or heterozygous fibroblasts established from TgM/KO mice (TMK cells) was approximately 39 and 20 unit/mg protein, respectively. These TgM/KO mice and TMK cells are useful tools for studying the mechanism of ASSC therapy, and for screening ASSCs for Fabry disease. (C) 2004 Elsevier B.V. All rights reserved. C1 Mt Sinai Sch Med, Dept Human Genet, New York, NY 10029 USA. Usuki Bio Res Ctr, Usuki, Oita, Japan. Oita Med Sch, Oita, Japan. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. RP Fan, JQ (reprint author), Mt Sinai Sch Med, Dept Human Genet, 5th Ave 100th St, New York, NY 10029 USA. EM jian-qiang.fan@mssm.edu NR 25 TC 49 Z9 54 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD NOV 5 PY 2004 VL 1690 IS 3 BP 250 EP 257 DI 10.1016/j.bbadis.2004.07.001 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 870LG UT WOS:000225058000008 PM 15511632 ER PT J AU Price, DM Chik, CL Terriff, D Weller, J Humphries, A Carter, DA Klein, DC Ho, AK AF Price, DM Chik, CL Terriff, D Weller, J Humphries, A Carter, DA Klein, DC Ho, AK TI Mitogen-activated protein kinase phosphatase-1 (MKP-1): > 100-fold nocturnal and norepinephrine-induced changes in the rat pineal gland SO FEBS LETTERS LA English DT Article DE MAP kinase phosphatase-1; pineal; mitogen-activated protein kinase; arylalkylamine-N-acetyltransferase; circadian; adrenergic; photoneuroendocrinology ID SEROTONIN N-ACETYLTRANSFERASE; ADRENERGIC REGULATION; MELATONIN SYNTHESIS; GENE; INHIBITION; EXPRESSION; PHOSPHORYLATION; ACCUMULATION; STIMULATION; NUCLEUS AB The norepinephrine-driven increase in mitogen-activated protein kinase (MAPK) activity is part of the mechanism that regulates arylalkylamine N-acetyltransferase (AA-NAT) activity in the rat pineal gland. We now report a marked nocturnal increase in the expression of a MAPK phosphatase, MAP kinase phosphatase-1 (MKP-1), that was blocked by maintaining animals in constant light or treatment with propranolol. MKP-1 expression was regulated by norepinephrine acting through both alpha- and beta-adrenergic receptors. These results establish a nocturnal increase in pineal MKP-1 expression that is under the control of a photoneural system. Because substrates of MKP-1 can influence AA-NAT activity, our findings suggest the involvement of MKP-1 in the regulation of the nocturnal AA-NAT signal. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 Univ Alberta, Fac Med & Dent, Dept Med, Edmonton, AB T6G 2H7, Canada. Univ Alberta, Fac Med & Dent, Dept Physiol, Edmonton, AB T6G 2H7, Canada. NICHHD, Sect Neuroendocrinol, NIH, Bethesda, MD 20892 USA. Cardiff Univ, Sch Biosci, Cardiff, S Glam, Wales. RP Chik, CL (reprint author), Univ Alberta, Fac Med & Dent, Dept Med, Edmonton, AB T6G 2H7, Canada. EM echik@ualberta.ca RI Carter, David/A-4479-2010 OI Carter, David/0000-0002-8419-3975 NR 36 TC 26 Z9 27 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 5 PY 2004 VL 577 IS 1-2 BP 220 EP 226 DI 10.1016/j.febslet.2004.09.083 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 871JW UT WOS:000225128600038 PM 15527789 ER PT J AU Harry, JB Kobrinsky, E Abernethy, DR Soldatov, NM AF Harry, JB Kobrinsky, E Abernethy, DR Soldatov, NM TI New short splice variants of the human cardiac Ca-v beta(2) subunit - Redefining the major functional motifs implemented in modulation of the Ca(v)1.2 channel SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT CA2+ CHANNELS; CALCIUM-CHANNEL; BETA-SUBUNIT; SKELETAL-MUSCLE; HUMAN HEART; EXPRESSION; DOMAIN; CELLS; BRAIN; HETEROGENEITY AB Two new short splice variants of the Ca2+ channel beta(2) subunit were cloned from human heart poly(A)(+) mRNA. The 410-amino acid beta(2f) subunit is encoded by exons 1A, 2A, 3, 4, 12, 13, and 14 of the human Ca(v)beta(2) gene and lacks the protein kinase A phosphorylation site, the beta-interaction domain (De Waard, M., Pragnell, M., and Campbell, K. P. (1994) Neuron 13, 495-503), 40% of the beta-SH3 domain, and 73% of the guanylate kinase domain of the putative membrane-associated guanylate kinases module (McGee, A. W., Nunziato, D. A., Maltez, J. M., Prehoda, K. E., Pitt, G. S., and Bredt, D. S. (2004) Neuron 42, 89-99), and helix alpha3 of the alpha(1)-subunit binding pocket (Van Petegem F., Clark, K. A., Chatelain, F. C., and Minor, D. L., Jr. (2004) Nature 429, 671-675). The beta(2g) transcript has two potential initiation codons. With the second ATG codon, it generates the 164-amino acid beta(2Deltag) subunit encoded essentially by the distal part of exon 14, and thus beta(2Deltag) completely lacks any of the above motifs. Immunoprecipitation analysis confirmed stable association of beta(2f) and beta(2Deltag) with the alpha(1C) subunit. The plasma membrane localization of beta(2f) and beta(2Deltag) was substantially increased by co-expression of the alpha(1C,77) and alpha(2)delta subunits. In COS1 cells, beta(2f) and beta(2Deltag) increased plasma membrane targeting of the pore-forming alpha(1C) subunit and differentially facilitated (beta(2f) > beta(2Deltag)) the voltage gating of otherwise silent Ca(v)1.2 channels. We conclude that it is unlikely that the beta-interaction domain, membrane-associated guanylate kinases module, and the alpha(1)-subunit binding pocket helix alpha3 are essential for the interaction of the alpha(1C) and beta(2) subunits and suggest that in addition to the alpha(1)-subunit binding pocket helices alpha5 and alpha8, a yet unresolved C-terminal beta(2) region plays a crucial role. C1 NIA, NIH, Baltimore, MD 21224 USA. RP Soldatov, NM (reprint author), NIA, NIH, Baltimore, MD 21224 USA. EM soldatovN@grc.nia.nih.gov NR 27 TC 26 Z9 27 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 5 PY 2004 VL 279 IS 45 BP 46367 EP 46372 DI 10.1074/jbc.M409523200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 867HE UT WOS:000224832400005 PM 15339916 ER PT J AU Catalano, A Rodilossi, S Rippo, MR Caprari, P Procopio, A AF Catalano, A Rodilossi, S Rippo, MR Caprari, P Procopio, A TI Induction of stem cell factor/c-Kit/Slug signal transduction in multidrug-resistant malignant mesothelioma cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GASTROINTESTINAL STROMAL TUMORS; PROTOONCOGENE C-KIT; GROWTH-FACTOR; P-GLYCOPROTEIN; EXPRESSION; CANCER; GENE; ACTIVATION; THERAPY; LINE AB Malignant mesothelioma (MM) is strongly resistant to conventional chemotherapy by unclear mechanisms. We and others have previously reported that cytokine- and growth factor-mediated signal transduction is involved in the growth and progression of MM. Here, we identified a pathway that involves stem cell factor (SCF)/c-Kit/Slug in mediating multidrug resistance of MM cells. When we compared gene expression profiles between five MM cells and their multidrug-resistant (MM DX) sublines, we found that MM DX cells expressed both SCF and c-Kit and had higher mRNA levels of Slug. Knockdown of c-Kit or Slug expression with their respective small interfering RNA sensitized MM DX cells to the induction of apoptosis by different chemotherapeutic agents, including doxorubicin, paclitaxel, and vincristine. Transfection of c-Kit in parental MM cells in the presence of SCF up-regulated Slug and increased resistance to the chemotherapeutic agents. Moreover, MM cells expressing Slug showed a similar increased resistance to the chemotherapeutic agents. These results indicate that induction of Slug by autocrine production of SCF and c-Kit activation plays a key role in conferring a broad spectrum chemoresistance on MM cells and reveal a novel signal transduction pathway for pharmacological or genetic intervention of MM patients. C1 Polytech Univ Marche, Dept Mol Pathol & Innovat Therapies, I-60131 Ancona, Italy. Italian Natl Res Ctr Aging, Lab Cytol, I-60124 Ancona, Italy. NCI, Neural Dev Grp, Mouse Canc Genet Program, NIH, Frederick, MD 21701 USA. RP Catalano, A (reprint author), Polytech Univ Marche, Dept Mol Pathol & Innovat Therapies, Via Ranieri, I-60131 Ancona, Italy. EM catgfp@yahoo.it NR 45 TC 71 Z9 75 U1 2 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 5 PY 2004 VL 279 IS 45 BP 46706 EP 46714 DI 10.1074/jbc.M406696200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 867HE UT WOS:000224832400048 PM 15337769 ER PT J AU Ribeiro-Neto, F Leon, A Urbani-Brocard, J Lou, LG Nyska, A Altschuler, DL AF Ribeiro-Neto, F Leon, A Urbani-Brocard, J Lou, LG Nyska, A Altschuler, DL TI cAMP-dependent oncogenic action of Rap1b in the thyroid gland SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSGENIC MICE; CYCLIC-AMP; BINDING PROTEINS; CELL-ADHESION; GROWTH; RAS; ACTIVATION; GTPASE; GENE; INHIBITION AB cAMP signaling leads to activation and phosphorylation of Rap1b. Using cellular models where cAMP stimulates cell proliferation, we have demonstrated that cAMP-mediated activation, as well as phosphorylation of Rap1b, is critical for cAMP stimulation of DNA synthesis. To determine whether Rap1b stimulates mitogenesis in vivo, we have constructed a transgenic mouse where a constitutively active G12V-Rap1b, flanked by Cre recombinase LoxP sites, is followed by the dominant negative S17N mutant. Employing this novel mouse model, we have switched, in a tissue-specific ( thyroid) and temporally controlled manner, the expression of Rap1b from a stimulatory to an inhibitory form. These experiments provide conclusive evidence that Rap1b is oncogenic in the thyroid in ways linked to transduction of the cAMP mitogenic signal. C1 Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15261 USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Altschuler, DL (reprint author), Univ Pittsburgh, Sch Med, Dept Pharmacol, 200 Lothrop St, Pittsburgh, PA 15261 USA. EM altschul@server.pharm.pitt.edu FU NIDDK NIH HHS [DK063069] NR 55 TC 20 Z9 21 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 5 PY 2004 VL 279 IS 45 BP 46868 EP 46875 DI 10.1074/jbc.M406858200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 867HE UT WOS:000224832400068 PM 15331589 ER PT J AU Liang, W Fishman, PH AF Liang, W Fishman, PH TI Resistance of the human beta(1)-adrenergic receptor to agonist-induced ubiquitination - A mechanism for impaired receptor degradation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; CLATHRIN-MEDIATED ENDOCYTOSIS; BETA-ADRENERGIC-RECEPTORS; BETA(2)-ADRENERGIC RECEPTOR; DOWN-REGULATION; PROMOTED UBIQUITINATION; MEMBRANE TRAFFICKING; OPIOID RECEPTORS; ARRESTIN; INTERNALIZATION AB Down-regulation is a classic response of most G protein-coupled receptors to prolonged agonist stimulation. We recently showed that when expressed in baby hamster kidney cells, the human beta(1)-but not the beta(2)-adrenergic receptor (AR) is totally resistant to agonist-mediated down-regulation, whereas both have similar rates of basal degradation (Liang, W., Austin, S., Hoang, Q., and Fishman, P. H. (2003) J. Biol. Chem. 278, 39773-39781). To identify the underlying mechanism(s) for this resistance, we investigated the role of proteasomes, lysosomes, and ubiquitination in the degradation of beta(1)AR expressed in baby hamster kidney and human embryonic kidney 293 cells. Both lysosomal and proteasomal inhibitors reduced beta(1)AR degradation in agonist-stimulated cells but were less effective on basal degradation. To determine whether beta(1)AR trafficked to lysosomes we used confocal fluorescence microscopy. We observed some colocalization of beta(1)AR and lysosomal markers in agonist-treated cells but much less than that of beta(2)AR even in cells co-transfected with arrestin-2, which increases beta(1)AR internalization. Ubiquitination of beta(2)AR readily occurred in agonist-stimulated cells, whereas ubiquitination of beta(1)AR was not detectable even under conditions optimal for that of beta(2)AR. Moreover, in cells expressing betaAR chimeras in which the C termini have been switched, the chimeric beta(1)AR with beta(2)AR C-tail underwent ubiquitination and down-regulation, but the chimeric beta(2)AR with beta(1)AR C-tail did not. Our results demonstrate for the first time that beta(1)AR and beta(2)AR differ in the ability to be ubiquitinated. Because ubiquitin serves as a signal for sorting membrane receptors to lysosomes, the lack of agonist-mediated ubiquitination of beta(1)AR may prevent its extensive trafficking to lysosomes and, thus, account for its resistance to down-regulation. C1 NINDS, Membrane Biochem Sect, Mol & Cellular Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Fishman, PH (reprint author), NINDS, Membrane Biochem Sect, Mol & Cellular Neurobiol Lab, NIH, Bldg 49,Rm 2A28,49 Convent Dr,MSC4440, Bethesda, MD 20892 USA. EM fishmanp@ninds.nih.gov NR 41 TC 22 Z9 22 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 5 PY 2004 VL 279 IS 45 BP 46882 EP 46889 DI 10.1074/jbc.M406501200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 867HE UT WOS:000224832400070 PM 15331590 ER PT J AU Hobson, JP Netzel-Arnett, S Szabo, R Rehault, SM Church, FC Strickland, DK Lawrence, DA Antalis, TM Bugge, TH AF Hobson, JP Netzel-Arnett, S Szabo, R Rehault, SM Church, FC Strickland, DK Lawrence, DA Antalis, TM Bugge, TH TI Mouse DESC1 is located within a cluster of seven DESC1-like genes and encodes a type II transmembrane serine protease that forms serpin inhibitory complexes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AUTOSOMAL RECESSIVE DEAFNESS; PLASMINOGEN-ACTIVATOR INHIBITOR-1; SURFACE PROTEOLYTIC-ENZYMES; TUMOR-CELLS EXPRESS; C INHIBITOR; PROSTATE-CANCER; MICE DEFICIENT; HUMAN-LIVER; HEPSIN; CLONING AB We report the identification and functional analysis of a type II transmembrane serine protease encoded by the mouse differentially expressed in squamous cell carcinoma ( DESC) 1 gene, and the definition of a cluster of seven homologous DESC1-like genes within a 0.5-Mb region of mouse chromosome 5E1. This locus is syntenic to a region of human chromosome 4q13.3 containing the human orthologues of four of the mouse DESC1-like genes. Bioinformatic analysis indicated that all seven DESC1-like genes encode functional proteases. Direct cDNA cloning showed that mouse DESC1 encodes a multidomain serine protease with an N-terminal signal anchor, a SEA ( sea urchin sperm protein, enterokinase, and agrin) domain, and a C-terminal serine protease domain. The mouse DESC1 mRNA was present in epidermal, oral, and male reproductive tissues and directed the translation of a membrane-associated 60-kDa N-glycosylated protein with type II topology. Mouse DESC1 was synthesized in insect cells as a zymogen that could be activated by exposure to trypsin. The purified activated DESC1 hydrolyzed synthetic peptide substrates, showing a preference for Arg in the P-1 position. DESC1 proteolytic activity was abolished by generic inhibitors of serine proteases but not by other classes of protease inhibitors. Most interestingly, DESC1 formed stable inhibitory complexes with both plasminogen activator inhibitor-1 and protein C inhibitor that are expressed in the same tissues with DESC1, suggesting that type II transmembrane serine proteases may be novel targets for serpin inhibition. Together, these data show that mouse DESC1 encodes a functional cell surface serine protease that may have important functions in the epidermis, oral, and reproductive epithelium. C1 NIDCR, Proteases & Tissue Remodeling Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Physiol, Rockville, MD 20855 USA. Univ Maryland, Sch Med, Dept Surg, Rockville, MD 20855 USA. Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. RP Bugge, TH (reprint author), NIDCR, Proteases & Tissue Remodeling Unit, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Rm 211, Bethesda, MD 20892 USA. EM thomas.bugge@nih.gov FU NCI NIH HHS [CA098369]; NHLBI NIH HHS [HL50784, HL007698, HL50710, HL54710, HL32656, HL55374, HL-06350, HL55747] NR 62 TC 33 Z9 40 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 5 PY 2004 VL 279 IS 45 BP 46981 EP 46994 DI 10.1074/jbc.M403299200 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 867HE UT WOS:000224832400082 PM 15328353 ER PT J AU Feng, HQ Vu, ND Bai, YW AF Feng, HQ Vu, ND Bai, YW TI Detection and structure determination of an equilibrium unfolding intermediate of Rd-apocytochrome b(562): Native fold with non-native hydrophobic interactions SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE hydrophobic repacking; protein structure; folding intermediates; folding pathway ID STATE HYDROGEN-EXCHANGE; 3-HELIX BUNDLE PROTEIN; TRANSITION-STATE; RIBONUCLEASE-A; PHAGE-DISPLAY; CYTOCHROME-C; NMR EVIDENCE; PATHWAYS; COOPERATIVITY; KINETICS AB The absence of detectable kinetic and equilibrium folding intermediates by optical probes is commonly taken to indicate that protein folding is a two-state process. However, for some small proteins with apparent two-state behavior, unfolding intermediates have been identified in native-state hydrogen exchange or kinetic unfolding experiments monitored by nuclear magnetic resonance. Rd-apocytochrome b(562), a four-helix bundle, is one such protein. Here, we found another unfolding intermediate for Rd-apocytochrome b(562). It is based on a cooperative transition of N-15 chemical shifts of amide protons as a function of urea concentrations before the global unfolding. We have solved the high-resolution structure of the protein at 2.8 M urea, which is after this cooperative transition but before the global unfolding. All four helices remained intact, but a number of hydrophobic core residues repacked. This intermediate provides a possible structural interpretation for the kinetic unfolding intermediates observed using nuclear magnetic resonance methods for several proteins and has important implications for theoretical studies of protein folding. Published by Elsevier Ltd. C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Bai, YW (reprint author), NCI, Biochem Lab, NIH, Bldg 37,Room 6114E, Bethesda, MD 20892 USA. EM yawen@helix.nih.gov NR 58 TC 25 Z9 25 U1 1 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD NOV 5 PY 2004 VL 343 IS 5 BP 1477 EP 1485 DI 10.1016/j.jmb.2004.08.099 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 867JL UT WOS:000224838800023 PM 15491625 ER PT J AU West, AG Huang, SM Gaszner, M Litt, MD Felsenfeld, G AF West, AG Huang, SM Gaszner, M Litt, MD Felsenfeld, G TI Recruitment of histione modifications by USF proteins at a vertebrate barrier element SO MOLECULAR CELL LA English DT Article ID BETA-GLOBIN LOCUS; TRANSCRIPTION FACTOR USF; HISTONE H3; COACTIVATORS P300; ENHANCER BLOCKING; PROMOTER DNA; INSULATOR; METHYLATION; CHROMATIN; ACETYLATION AB The chicken beta-globin 5'HS4 insulator element acts as a barrier to the encroachment of chromosomal silencing. Endogenous 5'HS4 sequences are highly enriched with histone acetylation and H3K4 methylation regardless of neighboring gene expression. We report here that 5'HS4 elements recruit these histone modifications when protecting a reporter transgene from chromosomal silencing. Deletion studies identified a single protein binding site within 5'HS4, footprint IV, that is necessary for the recruitment of histone modifications and for barrier activity. We have determined that USF proteins bind to footprint IV. USF1 is present in complexes with histone modifying enzymes in cell extracts, and these enzymes specifically interact with the endogenous 5'HS4 element. Knockdown of USF1 expression leads to a loss of histone modification recruitment and subsequent encroachment of H3K9 methylation. We propose that barrier activity requires the constitutive recruitment of H3K4 methylation and histone acetylation at multiple residues to counteract the propagation of condensed chromatin structures. C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Felsenfeld, G (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM gary.felsenfeld@nih.gov OI West, Adam/0000-0003-3502-7804 NR 35 TC 163 Z9 173 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD NOV 5 PY 2004 VL 16 IS 3 BP 453 EP 463 DI 10.1016/j.molcel.2004.10.005 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 869SN UT WOS:000225004500012 PM 15525517 ER PT J AU Daly, MJ Gaidamakova, EK Matrosova, VY Vasilenko, A Zhai, M Venkateswaran, A Hess, M Omelchenko, MV Kostandarithes, HM Makarova, KS Wackett, LP Fredrickson, JK Ghosal, D AF Daly, MJ Gaidamakova, EK Matrosova, VY Vasilenko, A Zhai, M Venkateswaran, A Hess, M Omelchenko, MV Kostandarithes, HM Makarova, KS Wackett, LP Fredrickson, JK Ghosal, D TI Accumulation of Mn(II) in, Deinococcus radiodurans facilitates gamma-radiation resistance SO SCIENCE LA English DT Article ID IONIZING-RADIATION; MICROCOCCUS-RADIODURANS; SUPEROXIDE-DISMUTASE; TARGETED MUTAGENESIS; HYDROGEN-PEROXIDE; GENOME SEQUENCE; BACTERIUM; IRON; DNA; RADIORESISTANCE AB Deinococcus radiodurans is extremely resistant to ionizing radiation. How this bacterium can grow under chronic gamma radiation [50 grays (Gy) per hour] or recover from acute doses greater than 10 kGy is unknown. We show that D. radiodurans accumulates very high intracellular manganese and low iron levels compared with radiation-sensitive bacteria and that resistance exhibits a concentration-dependent response to manganous chloride [Mn(II)]. Among the most radiation-resistant bacterial groups reported, Deinococcus, Enterococcus, Lactobacillus, and cyanobacteria accumulate Mn(II). in contrast, Shewanella oneidensis and Pseudomonas putida have high iron but low intracellular manganese concentrations and are very sensitive. We propose that Mn(II) accumulation facilitates recovery from radiation injury. C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIH, Bethesda, MD 20894 USA. Pacific NW Natl Lab, Richland, WA 99352 USA. Univ Minnesota, St Paul, MN 55108 USA. RP Daly, MJ (reprint author), Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. EM mdaly@usuhs.mil RI Hess, Matthias/B-1783-2012 NR 27 TC 296 Z9 314 U1 8 U2 51 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 NOV 5 PY 2004 VL 306 IS 5698 BP 1025 EP 1028 DI 10.1126/science.1103185 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 869RG UT WOS:000225001100041 PM 15459345 ER PT J AU Tzchori, I Degani, G Elisha, R Eliyahu, R Hurvitz, A Vaya, J Moav, B AF Tzchori, I Degani, G Elisha, R Eliyahu, R Hurvitz, A Vaya, J Moav, B TI The influence of phytoestrogens and oestradiol-17 beta on growth and sex determination in the European eel (Anguilla anguilla) SO AQUACULTURE RESEARCH LA English DT Article DE European eel; sex differentiation; sex determination; oestradiol-17 beta; phytooestrogens; licorice; genistein ID BODY-COMPOSITION; JAPANESE EEL; FISH DIETS; DIFFERENTIATION; STEROIDS; GONAD; 17-ALPHA-METHYLTESTOSTERONE; CHROMOSOMES; RATIOS; FEMINIZATION AB Under aquaculture conditions, European eels (Anguilla anguilla) produce a high percentage of males (80-95%) that normally stop growing at 100-200 g. Females continue to grow to 500-750 g and obtain higher market value. Therefore, increasing the percentage of females in a population would be beneficial to the culture of eels. The present study was carried out in order to examine the effect of oestradiol and phytooestrogens on sex differentiation and growth rate of eels. Juvenile European eels with undifferentiated gonads were fed pellets containing oestradiol-17beta (E2) or phytooestrogens for 100-150 days. Feeding E2 resulted in 50-61% increase in body weight compared with the control. Oestradiol-17beta and phytooestrogens both elevated significantly the percentage of females in the population. Feeding E2 at 20 mg kg(-1) feed resulted in 70% females, while lower concentration of E2 (2 mg kg(-1)) resulted in only 30% after 100 days (Experiment 1). The same dose given for 150 days (Experiment 2) resulted in 88% females, indicating that both, the concentration and duration of E2 treatments had a significant effect on sex differentiation. Fish fed genistein at 2 mg kg(-1) for 100 days, resulted in 55% of females, but at a higher dose of 20 mg kg(-1) there were only 15% females. These results demonstrate that phytooestrogens can be used as alternatives to gonadal steroids for sex manipulation in eels, but the optimal concentrations and duration are still to be determined. C1 Tel Aviv Univ, Dept Zool, IL-69978 Tel Aviv, Israel. Galilee Technol Ctr, MIGAL, Kiryat Shmona, Israel. Acad Tel Hai Coll, Sch Sci & Technol, Haifa, Israel. RP Tzchori, I (reprint author), NICHD, LMGD, NIH, 6 Ctr Dr Bldg 6B, Bethesda, MD 20892 USA. EM tzchorii@mail.nih.gov NR 42 TC 14 Z9 16 U1 2 U2 9 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1355-557X J9 AQUAC RES JI Aquac. Res. PD NOV 4 PY 2004 VL 35 IS 13 BP 1213 EP 1219 DI 10.1111/j.1365-2109.2004.01129.x PG 7 WC Fisheries SC Fisheries GA 861UL UT WOS:000224444000005 ER PT J AU Nagarajan, M Morrell, A Fort, BC Meckley, MR Antony, S Kohlhagen, G Pommier, Y Cushman, M AF Nagarajan, M Morrell, A Fort, BC Meckley, MR Antony, S Kohlhagen, G Pommier, Y Cushman, M TI Synthesis and anticancer activity of simplified indenoisoquinoline topoisomerase I inhibitors lacking substituents on the aromatic rings SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID BIOLOGICAL EVALUATION; MOLECULAR REQUIREMENTS; CLEAVAGE COMPLEXES; BACTERIAL SYSTEM; CYTOSTATIC DRUGS; CAMPTOTHECIN; CELLS; TRANSPORT; TOPOTECAN; INDUCTION AB The indenoisoquinolines are a class of cytotoxic topoisomerase I inhibitors that offer certain advantages over the camptothecins, including the greater stabilities of the compounds themselves, as well as the greater stabilities of their drug-enzyme-DNA cleavage complexes. To investigate the possible biological roles of the di(methoxy) and methylenedioxy substituents present on the aromatic rings of the previously synthesized indenoisoquinoline topoisomerase I inhibitors, a series of compounds lacking these substituents was synthesized and tested for both cytotoxicity in cancer cell cultures and for enzyme inhibitory activity. The results indicate that the aromatic substituents make a small, but consistently observable contribution to the biological activity. Molecular models derived for the binding of the unsubstituted indenoisoquinolines in ternary complex with DNA and topoisomerase I indicate that the substituents on the lactam nitrogen project out of the major groove, and the carbonyl group is directed out of the minor groove, where it is involved in a hydrogen bonding interaction with the side chain guanidine group of Arg364. The DNA cleavage patterns observed in the presence of topoisomerase I and various indenoisoquinolines were similar, although significant differences were detected. There were also variations in the DNA cleavage pattern seen with camptothecin vs the indenoisoquinolines, which indicates that these two classes of topoisomerase I inhibitors are likely to target the cancer cell genome differently, resulting in different spectra of anticancer activity. The most cytotoxic of the presently synthesized indenoisoquinolines has a 4-amino-n-butyl group on the lactam nitrogen. C1 Purdue Univ, Sch Pharm & Pharmacal Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. NCI, Canc Res Ctr, Mol Pharmacol Lab, Bethesda, MD 20892 USA. RP Cushman, M (reprint author), Purdue Univ, Sch Pharm & Pharmacal Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. EM cushman@pharmacy.purdue.edu FU NCI NIH HHS [N01-CO-56000, T32 CA09634-12, U01 CA89566] NR 41 TC 88 Z9 89 U1 0 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 NOV 4 PY 2004 VL 47 IS 23 BP 5651 EP 5661 DI 10.1021/jm040025z PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 867KN UT WOS:000224841600011 PM 15509164 ER PT J AU Truong, JG Newman, AH Hanson, GR Fleckenstein, AE AF Truong, JG Newman, AH Hanson, GR Fleckenstein, AE TI Dopamine D2 receptor activation increases vesicular dopamine uptake and redistributes vesicular monoamine transporter-2 protein SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE quinpirole; vesicle; NGB2904; eticlopride; clozapine; traffick ID AGONIST PRAMIPEXOLE; METHAMPHETAMINE; STRIATUM; ANTAGONISTS; AMPHETAMINE; SUBTYPES; RATS; PSYCHOSTIMULANTS; TRAFFICKING; METABOLISM AB Recent studies demonstrate that multiple dopamine receptor subtypes contribute to the regulation of vesicular monoamine transporter-2 (VMAT-2) activity. The present studies extend these findings by demonstrating that administration of the nonselective dopamine D2 receptor family agonist, quinpirole, rapidly increased vesicular dopamine uptake in purified rat striatal vesicles. This effect occurred in both postnatal day 40 and 90 rats, and was associated with redistribution of the vesicular monoamine transporter-2 (VMAT-2) within nerve terminals. Neither a full nor a partial dopamine D1 receptor family agonist (SKF81297 nor SKF38393, respectively) affected vesicular dopamine uptake per se, nor the effect of quinpirole. Neither the dopamine D3 nor the D4 receptor antagonists, NGB2904 and clozapine, respectively, altered the quinpirole-mediated increase in uptake. However, the nonselective dopamine D2 receptor family antagonist, eticlopride, prevented the quinpirole-induced increase. Taken together, these data demonstrate that dopamine D2 receptor subtype activation increases vesicular dopamine uptake. Implications of this phenomenon with regard to the treatment of Parkinson's disease will be discussed. (C) 2004 Elsevier B.V. All rights reserved. C1 Univ Utah, Salt Lake City, UT 84112 USA. Natl Inst Drug Abuse, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Fleckenstein, AE (reprint author), Univ Utah, Salt Lake City, UT 84112 USA. EM fleckenstein@hsc.utah.edu FU NIDA NIH HHS [DA00869, DA11367, DA11389, DA04222, DA015976] NR 30 TC 24 Z9 26 U1 0 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 NOV 3 PY 2004 VL 504 IS 1-2 BP 27 EP 32 DI 10.1016/j.ejphar.2004.09.049 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 871KC UT WOS:000225129300004 PM 15507217 ER PT J AU Schatzkin, A Kipnis, V AF Schatzkin, A Kipnis, V TI Could exposure assessment problems give us wrong answers to nutrition and cancer questions? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID COLORECTAL-CANCER; MEASUREMENT ERROR; DIETARY FIBER; BREAST-CANCER; BIOMARKER; WOMEN; RISK; FOOD C1 NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. NCI, Div Canc Prevent, Biometry Res Grp, Bethesda, MD 20892 USA. RP Schatzkin, A (reprint author), NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Ste 320,Rm 3040, Rockville, MD 20852 USA. EM schatzka@mail.nih.gov NR 18 TC 83 Z9 84 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 NOV 3 PY 2004 VL 96 IS 21 BP 1564 EP 1565 DI 10.1093/jnci/djh329 PG 2 WC Oncology SC Oncology GA 868IV UT WOS:000224908200001 PM 15523078 ER PT J AU Mathijssen, RHJ de Jong, FA van Schaik, RHN Lepper, ER Friberg, LE Rietveld, T de Bruijn, P Graveland, WJ Figg, WD Verweij, J Sparreboom, A AF Mathijssen, RHJ de Jong, FA van Schaik, RHN Lepper, ER Friberg, LE Rietveld, T de Bruijn, P Graveland, WJ Figg, WD Verweij, J Sparreboom, A TI Prediction of irinotecan pharmacokinetics by use of cytochrome p450 3A4 phenotyping probes SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 31-JUN 03, 2003 CL CHICAGO, IL SP Amer Soc Clin Oncol ID ERYTHROMYCIN BREATH TEST; PERFORMANCE LIQUID-CHROMATOGRAPHY; COLORECTAL-CANCER; CLINICAL PHARMACOKINETICS; DOCETAXEL CLEARANCE; ANTICANCER AGENTS; HUMAN PLASMA; PHASE-II; IN-VIVO; METABOLISM AB Background: Irinotecan is a topoisomerase I inhibitor that has been approved for use as a first- and second-line treatment for colorectal cancer. The response to irinotecan is variable, possibly because of interindividual variation in the expression of the enzymes that metabolize irinotecan, including cytochrome P450 3A4 (CYP3A4) and uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1). We prospectively explored the relationships between CYP3A phenotype, as assessed by erythromycin metabolism and midazolam clearance, and the metabolism of irinotecan and its active metabolite SN-38. Methods: Of the 30 white cancer patients, 27 received at least two treatments with irinotecan administered as one 90-minute infusion (dose, 600 mg) with 3 weeks between treatments, and three received only one treatment. Before the first and second treatments, patients underwent an erythromycin breath test and a midazolam clearance test as phenotyping probes for CYP3A4. Erythromycin metabolism was assessed as the area under the curve for the flux of radioactivity in exhaled CO2 within 40 minutes after administration of [N-methyl-C-14]erythromycin. Midazolam and irinotecan were measured by high-performance liquid chromatography. Genomic DNA was isolated from blood and screened for genetic variants in CYP3A4 and UGT1A1. All statistical tests were two-sided. Results: CYP3A4 activity varied sevenfold (range = 0.223%-1.53% of dose) among patients, whereas midazolam clearance varied fourfold (range = 262-1012 mL/min), although intraindividual variation was small. Erythromycin metabolism was not statistically significantly associated with irinotecan clearance (P = .090), whereas midazolam clearance was highly correlated with irinotecan clearance (r = .745, P < .001). In addition, the presence of a UGT1A1 variant with a (TA)7 repeat in the promoter (UGTIAI*28) was associated with increased exposure to SN-38 (435 ng (.) h/mL, 95% confidence interval [CI] = 339 to 531 ng (.) h/mL in patients who are homozygous for wild-type UGT1A1; 631 ng (.) h/mL, 95% CI = 499 to 762 ng (.) h/mL in heterozygous patients; and 1343 ng (.) h/mL, 95% CI = 0 to 4181 ng (.) h/mL in patients who are homozygous for UGTIAI*28) (P = .006). Conclusion: CYP3A4 phenotype, as assessed by midazolam clearance, is statistically significantly associated with irinotecan pharmacokinetics. Evaluation of midazolam clearance combined with UGT1A1*28 genotyping may assist with optimization of irinotecan chemotherapy. C1 NCI, Clin Pharmacol Res Core, Bethesda, MD 20892 USA. Erasmus Univ, Med Ctr, Dept Med Oncol, Rotterdam, Netherlands. Erasmus Univ, Med Ctr, Dept Clin Chem, Rotterdam, Netherlands. Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands. Erasmus Univ, Med Ctr, Dept Biostat, Rotterdam, Netherlands. Univ Uppsala, Dept Pharmaceut Biosci, S-75105 Uppsala, Sweden. RP Sparreboom, A (reprint author), NCI, Clin Pharmacol Res Core, 9000 Rockville Pike,Bldg 10,Rm 5A01, Bethesda, MD 20892 USA. EM sparreba@mail.nih.gov RI Sparreboom, Alex/B-3247-2008; de Jong, Floris/F-5486-2011; Figg Sr, William/M-2411-2016 NR 56 TC 81 Z9 84 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 3 PY 2004 VL 96 IS 21 BP 1585 EP 1592 DI 10.1093/jnci/djh298 PG 8 WC Oncology SC Oncology GA 868IV UT WOS:000224908200009 PM 15523087 ER PT J AU Minneci, PC Deans, KJ Banks, SM Eichacker, PQ Natanson, C AF Minneci, PC Deans, KJ Banks, SM Eichacker, PQ Natanson, C TI Corticosteroids for septic shock SO ANNALS OF INTERNAL MEDICINE LA English DT Letter ID HYDROCORTISONE C1 NIH, Bethesda, MD 20892 USA. RP Minneci, PC (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 8 TC 12 Z9 13 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 NOV 2 PY 2004 VL 141 IS 9 BP 742 EP 743 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 867JT UT WOS:000224839600026 PM 15520444 ER PT J AU Cao, HP AF Cao, HP TI Expression, purification, and biochemical characterization of the antiinflammatory tristetraprolin: A zinc-dependent mRNA binding protein affected by posttranslational modifications SO BIOCHEMISTRY LA English DT Article; Proceedings Paper CT Joint World Congress of the 2nd Human Proteomics Organization/19th International-Union-of-Biochemistry-and-Molecular-Biology CY OCT 08-11, 2003 CL Montreal, CANADA SP Int Union Biochem & Mol Biol ID AU-RICH ELEMENT; NECROSIS-FACTOR-ALPHA; FINGER TRANSCRIPTION FACTOR; SECONDARY STRUCTURE; MAIZE ENDOSPERM; KINASE P38; DOMAIN; GENE; PHOSPHORYLATION; DEADENYLATION AB Tristetraprolin (TTP) is a hyperphosphorylated protein that destabilizes mRNA by binding to an AU-rich element (ARE). Mice deficient in TTP develop a severe inflammatory syndrome. The biochemical properties of TTP have not been adequately characterized, due to the difficulties in protein purification and lack of a high-titer antiserum. Full-length human TTP was expressed in human HEK293 cells and purified to at least 70% homogeneity. The purified protein was free of endogenous ARE binding activity, and was used for investigating its size, zinc dependency, and binding kinetics for tumor necrosis factor of mRNA ARE. A high-titer rabbit antiserum was raised against the MBP-hTTP fusion protein expressed in Escherichia coli. Cellular localization studies of the transfected cells indicated that approximately 80% of the expressed TTP was in the cytosol, with 20% in the nuclei. TTP from both locations bound to the ARE and formed similar complexes. The purified TTP was shown to be intact by N-terminal His-tag purification, C-terminal peptide sequencing, and mass spectrometry analysis. Results from size exclusion chromatography are consistent with the predominant form of active TTP being a tetramer. TTP's ARE binding activity was increased by 10 muM Zn2+. The half-maximal binding of TTP from HEK293 cells was approximately 30 nM in assays containing 10 nM ARE. This value was about twice that of TTP from E. coli. TTP from HEK293 cells was highly phosphorylated, and its electrophoretic mobility was increased by alkaline phosphatase treatment and somewhat by T271A mutation, but not by PNGase F or S186A mutation. The gel mobility of TTP from E. coli was decreased by in vitro phosphorylation with p42/ERK2 and p38 mitogen-activated protein kinases. These results suggest that TTP's zinc-dependent ARE binding affinity is reduced by half by posttranslational modifications, mainly by phosphorylation but not by glycosylation, in mammalian cells. The results support a model in which each subunit of the TTP tetramer binds to one of the five overlapping UUAUUUAUU sequences of the ARE, resulting in a stable TTP-ARE complex. C1 Natl Inst Environm Hlth Sci, Lab Neurobiol, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Lab Signal Transduct, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. RP Natl Inst Environm Hlth Sci, Lab Neurobiol, Dept Hlth & Human Serv, NIH, Mail Drop F3-04,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM cao2@niehs.nih.gov FU NIEHS NIH HHS [Z01 ES090080-08]; PHS HHS [TAXP003505] NR 59 TC 40 Z9 44 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 NOV 2 PY 2004 VL 43 IS 43 BP 13724 EP 13738 DI 10.1021/bi049014y PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 866TG UT WOS:000224795500012 PM 15504035 ER PT J AU Li, Y Nowotny, P Holmans, P Smemo, S Kauwe, JSK Hinrichs, AL Tacey, K Doil, L van Luchene, R Garcia, V Rowland, C Schrodi, S Leong, D Gogic, G Chan, J Cravchik, A Ross, D Lau, K Kwok, S Chang, SY Catanese, J Sninsky, J White, TJ Hardy, J Powell, J Lovestone, S Morris, JC Thal, L Owen, M Williams, J Goate, A Grupe, A AF Li, Y Nowotny, P Holmans, P Smemo, S Kauwe, JSK Hinrichs, AL Tacey, K Doil, L van Luchene, R Garcia, V Rowland, C Schrodi, S Leong, D Gogic, G Chan, J Cravchik, A Ross, D Lau, K Kwok, S Chang, SY Catanese, J Sninsky, J White, TJ Hardy, J Powell, J Lovestone, S Morris, JC Thal, L Owen, M Williams, J Goate, A Grupe, A TI Association of late-onset Alzheimer's disease with genetic variation in multiple members of the GAPD gene family SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; SUSCEPTIBILITY LOCUS; POPULATION-STRUCTURE; INDUCED APOPTOSIS; GENOME SCREEN; CHROMOSOME 12; GENOTYPE DATA; RAT-BRAIN; IDENTIFICATION; PROTEIN AB Although several genes have been implicated in the development of the early-onset autosomal dominant form of Alzheimer's disease (AD), the genetics of late-onset AD (LOAD) is complex. Loci on several chromosomes have been linked to the disease, but so far only the apolipoprotein E gene has been consistently shown to be a risk factor. We have performed a large-scale single-nucleotide polymorphism (SNP)-based association study, across the region of linkage on chromosome 12, in multiple case-control series totaling 1,089 LOAD patients and 1,196 control subjects and report association with SNPs in the glyceraldehyde-3-phosphate dehydrogenase (GAPD) gene. Subsequent analysis of GAPD paralogs on other chromosomes demonstrated association with two other paralogs. A significant association between LOAD and a compound genotype of the three GAPD genes was observed in all three sample sets. Individually, these SNPs make differential contributions to disease risk in each of the case-control series, suggesting that variants in functionally similar genes may account for series-to-series heterogeneity of disease risk. Our observations raise the possibility that GAPD genes are AD risk factors, a hypothesis that is consistent with the role of GAPD in neuronal apoptosis. C1 Celera Diagnost, Alameda, CA 94502 USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. Cardiff Univ, Wales Coll Med, Biostat & Bioinformat Unit, Cardiff CF14 4XN, S Glam, Wales. Cardiff Univ, Wales Coll Med, Dept Psychol Med, Cardiff CF14 4XN, S Glam, Wales. NIA, Bethesda, MD 20892 USA. Kings Coll London, Inst Psychiat, Dept Neurosci, London SE5 8AF, England. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. RP Grupe, A (reprint author), Celera Diagnost, Alameda, CA 94502 USA. EM andrew.grupe@celeradiagnostics.com RI Lovestone, Simon/E-8725-2010; turton, miranda/F-4682-2011; Powell, John/G-4412-2011; Kauwe, John/B-2034-2009; Morris, John/A-1686-2012; Hardy, John/C-2451-2009; Holmans, Peter/F-4518-2015; OI Powell, John/0000-0001-6124-439X; Kauwe, John/0000-0001-8641-2468; Holmans, Peter/0000-0003-0870-9412; Schrodi, Steven/0000-0003-2304-8528 FU NIA NIH HHS [P01 AG 03991, P01 AG003991, P50 AG 05131, P50 AG 05681, P50 AG005131, P50 AG005681, R01 AG 16208, R01 AG016208, U24 AG021886] NR 43 TC 109 Z9 110 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 2 PY 2004 VL 101 IS 44 BP 15688 EP 15693 DI 10.1073/pnas.0403535101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 868OG UT WOS:000224922300027 PM 15507493 ER PT J AU Li, KCP AF Li, KCP TI A primer on molecular biology for imagers: IX. How to become a "Molecular imager" SO ACADEMIC RADIOLOGY LA English DT Article ID PERSONALIZED MEDICINE; DNA MICROARRAYS; HEALTH-CARE; PROTEOMICS; MICRODISSECTION; VALIDATION; TUMORS; GUIDE; MODEL C1 NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. RP Li, KCP (reprint author), NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bldg 10 1C626,10 Ctr Dr MSC 1182, Bethesda, MD 20892 USA. EM Kingli@nih.gov NR 26 TC 2 Z9 2 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD NOV PY 2004 VL 11 IS 11 BP 1274 EP 1277 DI 10.1016/j.acra.2004.08.004 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 874FZ UT WOS:000225337600010 PM 15561574 ER PT J AU Dai, J Park, G Perry, JL Il'Ichev, YV Bow, DAJ Pritchard, JB Faucet, V Pfohl-Leszkowicz, A Manderville, RA Simon, JD AF Dai, J Park, G Perry, JL Il'Ichev, YV Bow, DAJ Pritchard, JB Faucet, V Pfohl-Leszkowicz, A Manderville, RA Simon, JD TI Molecular aspects of the transport and toxicity of ochratoxin A SO ACCOUNTS OF CHEMICAL RESEARCH LA English DT Review ID HUMAN SERUM-ALBUMIN; C8-DEOXYGUANOSINE NUCLEOSIDE ADDUCT; PROXIMAL TUBULE; PROTEIN-BINDING; C8 REACTIVITY; DNA ADDUCTION; IN-VIVO; RAT; DAMAGE; CELLS AB Ochratoxins are a class of naturally occurring compounds produced by several fungi. The most toxic is ochratoxin A (OTA), and occurrence of some human nephropathies and tumors correlate with enhanced OTA exposure. In this Account, the following areas are examined: molecular details of the binding of OTA to human serum albumin (HSA), the influences of binding to HSA on the transport of OTA across epithelial cell membranes by organic anion transport proteins, the oxidative activation of OTA, and the formation of OTA adducts with biological molecules. These studies are beginning to provide a detailed chemical model for the transport, accumulation, and genotoxic and carcinogenic effects of OTA. C1 Wake Forest Univ, Dept Chem, Winston Salem, NC 27106 USA. Duke Univ, Dept Chem, Durham, NC 27708 USA. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Ecole Natl Super Agron Toulouse, UMR CNRS 5503, Lab Genie Chim, Dept Toxicol & Food Safety, F-31326 Castanet Tolosan, France. RP Manderville, RA (reprint author), Wake Forest Univ, Dept Chem, Winston Salem, NC 27106 USA. EM rmanderv@uoguelph.ca; jsimon@duke.edu FU NCI NIH HHS [R01-CA080787] NR 50 TC 28 Z9 28 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0001-4842 J9 ACCOUNTS CHEM RES JI Accounts Chem. Res. PD NOV PY 2004 VL 37 IS 11 BP 874 EP 881 DI 10.1021/ar0302134 PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA 888GE UT WOS:000226361400006 PM 15612677 ER PT J AU Zwart, PH Banumathi, S Dauter, M Dauter, Z AF Zwart, PH Banumathi, S Dauter, M Dauter, Z TI Radiation-damage-induced phasing with anomalous scattering: substructure solution and phasing SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID X-RAYS; PROTEIN; REFINEMENT; IODINATION; ABSORPTION; WAVELENGTH; TYROSINE; CRYSTALS; SHELXD AB Substructure-solution and phasing procedures using a combination of anomalous scattering and radiation-damage-induced isomorphous differences have been investigated. The tyrosine residues in thaumatin were iodinated with N-iodosuccinimide in the crystalline form as well as prior to crystallization. Several data sets were collected from both forms and used for substructure solution and phasing using various protocols, employing anomalous, isomorphous or both these signals. It was shown that combination of the anomalous and isomorphous signals in the form of the RIPAS (radiation-damage-induced phasing with anomalous scattering) strategy is beneficial for both locating the substructure and subsequent phasing. C1 Brookhaven Natl Lab, Natl Canc Inst, MCL, Synchrotron Radiat Res Sect, Upton, NY 11973 USA. Brookhaven Natl Lab, Basic Res Program, SAIC Frederick Inc, Upton, NY 11973 USA. RP Dauter, Z (reprint author), Brookhaven Natl Lab, Natl Canc Inst, MCL, Synchrotron Radiat Res Sect, Upton, NY 11973 USA. EM dauter@bnl.gov FU NCI NIH HHS [N01-CO-12400] NR 30 TC 35 Z9 36 U1 0 U2 4 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 NOV PY 2004 VL 60 BP 1958 EP 1963 DI 10.1107/S0907444904021730 PN 11 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 863WW UT WOS:000224595200005 PM 15502302 ER PT J AU Schubot, FD Waugh, DS AF Schubot, FD Waugh, DS TI A pivotal role for reductive methylation in the de novo crystallization of a ternary complex composed of Yersinia pestis virulence factors YopN, SycN and YscB SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID LYSINE RESIDUES; PROTEIN CRYSTALLIZATION; ANGSTROM RESOLUTION; MUTATIONS; CHAPERONE; RHOGDI AB Structural studies of a ternary complex composed of the Yersina pestis virulence factors YopN, SycN and YscB were initially hampered by poor solubility of the individual proteins. Co-expression of all three proteins in Escherichia coli yielded a well behaved complex, but this sample proved to be recalcitrant to crystallization. As crystallization efforts remained fruitless, even after the proteolysis-guided engineering of a truncated YopN polypeptide, reductive methylation of lysine residues was employed to alter the surface properties of the complex. The methylated complex yielded crystals that diffracted X-rays to a maximal resolution of 1.8 Angstrom. The potential utility of reductive methylation as a remedial strategy for high-throughput structural biology was further underscored by the successful modi cation of a selenomethionine-substituted sample. C1 NCI, Prot Engn Sect, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Waugh, DS (reprint author), NCI, Prot Engn Sect, Macromol Crystallog Lab, Ctr Canc Res, POB B, Frederick, MD 21702 USA. EM waughd@ncifcrf.gov NR 17 TC 29 Z9 29 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD NOV PY 2004 VL 60 BP 1981 EP 1986 DI 10.1107/S0907444904023005 PN 11 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 863WW UT WOS:000224595200008 PM 15502305 ER PT J AU Saxena, AK Singh, K Long, CA Garboczi, DN AF Saxena, AK Singh, K Long, CA Garboczi, DN TI Preparation, crystallization and preliminary X-ray analysis of a complex between the Plasmodium vivax sexual stage 25 kDa protein Pvs25 and a malaria transmission-blocking antibody Fab fragment SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID VACCINE CANDIDATE AB The Plasmodium vivax sexual stage 25 kDa protein Pvs25, located on the surface of the ookinete form of the parasite, is a vaccine candidate designed to elicit immunity that blocks the transmission of malaria by mosquitoes. The 2A8 murine monoclonal antibody directed against recombinant Pvs25 prevents the formation of P. vivax oocysts in mosquitoes fed in the laboratory. The complex between recombinant Pvs25 and the Fab fragment of 2A8 forms crystals that diffract X-rays to 3.5 Angstrom. Two native data sets, A and B, have been collected from crystals of the Pvs25-Fab complex. Both crystals belong to space group P2(1), with unit-cell parameters of a=86.3, b=61.7, c=142.7 Angstrom, P=101.7degrees for data set A and a=86.8, b=61.0, c=149.3 Angstrom, beta=104.3degrees for data set B, and contain two complex molecules per asymmetric unit. Efforts are under way to reveal the structure of the Pvs25-Fab complex by molecular replacement. The three-dimensional structure of the Pvs25-Fab complex will provide an understanding of the interaction between Pvs25 and the 2A8 antibody that inhibits ookinete development in the mosquito and should aid in the development of transmission-blocking vaccines against P. vivax malaria. C1 NIAID, Struct Biol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD 20852 USA. RP Garboczi, DN (reprint author), NIAID, Struct Biol Sect, Immunogenet Lab, NIH, Twinbrook 2,12441 Parklawn Dr, Rockville, MD 20852 USA. EM dgarboczi@niaid.nih.gov NR 14 TC 3 Z9 4 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 NOV PY 2004 VL 60 BP 2054 EP 2057 DI 10.1107/S0907444904021584 PN 11 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 863WW UT WOS:000224595200028 PM 15502325 ER PT J AU Singh, DD Saikrishnan, K Kumar, P Dauter, Z Sekar, K Surolia, A Vijayan, M AF Singh, DD Saikrishnan, K Kumar, P Dauter, Z Sekar, K Surolia, A Vijayan, M TI Purification, crystallization and preliminary X-ray structure analysis of the banana lectin from Musa paradisiaca SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID BETA-PRISM FOLD; CRYSTAL-STRUCTURE; CARBOHYDRATE SPECIFICITIES; PLANT-LECTINS; RECOGNITION; MANNOSE; JACALIN; AGGLUTININ; ARTOCARPIN; REVEALS AB The banana lectin from Musa paradisiaca, MW 29.4 kDa, has been isolated, purified and crystallized. The trigonal crystals contain one dimeric molecule in the asymmetric unit. The structure has been solved using molecular replacement to a resolution of 3 Angstrom. The structure of the subunit is similar to that of jacalin-like lectins. C1 Indian Inst Sci, Mol Biophys Unit, Bangalore 560012, Karnataka, India. NCI, Synchrotron Radiat Res Sect, MCL, Brookhaven Natl Lab, Upton, NY 11973 USA. Indian Inst Sci, Bioinformat Ctr, Bangalore 560012, Karnataka, India. Indian Inst Sci, Supercomp Educ & Res Ctr, Bangalore 560012, Karnataka, India. RP Vijayan, M (reprint author), Indian Inst Sci, Mol Biophys Unit, Bangalore 560012, Karnataka, India. EM my@mbu.iisc.ernet.in RI SUROLIA, AVADESHA/C-5442-2009 NR 22 TC 10 Z9 10 U1 1 U2 3 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 NOV PY 2004 VL 60 BP 2104 EP 2106 DI 10.1107/S0907444904024114 PN 11 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 863WW UT WOS:000224595200044 PM 15502341 ER PT J AU Lowman, C AF Lowman, C TI Developing effective evidence-based interventions for adolescents with alcohol use disorders - Introduction SO ADDICTION LA English DT Editorial Material C1 NIAAA, Div Treatment & Recovery Res, Bethesda, MD 20892 USA. RP Lowman, C (reprint author), NIAAA, Div Treatment & Recovery Res, 5635 Fishers Lane,Room 2051, Bethesda, MD 20892 USA. EM clowman@willco.niaaa.nih.gov NR 15 TC 1 Z9 1 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD NOV PY 2004 VL 99 SU 2 BP 1 EP 4 DI 10.1111/j.1360-0443.2004.00850.x PG 4 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 871UD UT WOS:000225158300001 PM 15488101 ER PT J AU Sigmon, SC Wong, CJ Chausmer, AL Liebson, IA Bigelow, GE AF Sigmon, SC Wong, CJ Chausmer, AL Liebson, IA Bigelow, GE TI Evaluation of an injection depot formulation of buprenorphine: placebo comparison SO ADDICTION LA English DT Article DE buprenorphine; depot; detoxification; opioid; sustained-release; withdrawal ID OPIOID-DEPENDENT HUMANS; CONTROLLED TRIAL; CLINICAL-TRIAL; MAINTENANCE TREATMENT; HEROIN-ADDICTS; ABUSE; WITHDRAWAL; DETOXIFICATION; METHADONE; NALOXONE AB Aims Buprenorphine is a mu-opioid partial agonist that is marketed in a sublingual formulation as a treatment for opioid dependence. A microcapsule depot sustained-release formulation has been developed which may offer effective treatment of opioid dependence while also minimizing risks of illicit diversion or patient non-compliance. The present study examined the efficacy of depot buprenorphine in suppressing the opioid withdrawal syndrome and in attenuating the effects of exogenous opioid challenge. Design A placebo-controlled, double-blind, randomized trial. Setting A closed residential research facility. Participants A total of 15 opioid-dependent participants were enrolled into the 6-week study. Intervention Fifteen participants were randomized to receive a single subcutaneous depot injection containing buprenorphine (58 mg) or placebo. Two participants, both of whom received placebo, terminated participation after depot administration. Thirteen participants (six buprenorphine, seven placebo) completed the 6-week study and were assessed throughout the study for signs and symptoms of opioid withdrawal and for response to weekly subcutaneous challenges with 3 mg hydromorphone. Measurement Subjective, physiological and observer-rated indices of opioid withdrawal and opioid agonist effects. Findings Depot buprenorphine provided more effective relief from opioid withdrawal than placebo, as evidenced by significantly fewer buprenorphine participants requiring supplemental medications for withdrawal suppression after depot administration compared to participants receiving placebo. In the weekly hydromorphone challenge sessions, depot buprenorphine significantly reduced opioid response on measures of subjective effects and pupillary diameter. Conclusions Results from this double-blind, placebo-controlled study indicate that depot buprenorphine is effective in providing both withdrawal suppression and opioid blockade. Future studies examining additional doses and repeated dosing regimens with depot buprenorphine are warranted. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. Natl Inst Drug Abuse, Div Neurosci & Behav Res, Bethesda, MD USA. RP Bigelow, GE (reprint author), 5510 Nathan Shock Dr, Baltimore, MD 21224 USA. EM bigelow@jhmi.edu FU NIDA NIH HHS [N01DA-7-8074, P50-DA05273, K05-DA00050, T32-DA07209] NR 41 TC 19 Z9 23 U1 2 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD NOV PY 2004 VL 99 IS 11 BP 1439 EP 1449 DI 10.1111/j.1360-0443.2004.00834.x PG 11 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 871BF UT WOS:000225103600016 PM 15500597 ER PT J AU Pang, PT Lu, B AF Pang, PT Lu, B TI Regulation of late-phase UP and long-term memory in normal and aging hippocampus: role of secreted proteins tPA and BDNF SO AGEING RESEARCH REVIEWS LA English DT Review DE brain-derived neurotrophic factor; long-term memory; synaptic plasticity ID TISSUE-PLASMINOGEN ACTIVATOR; ELEMENT-BINDING PROTEIN; DEPENDENT NEURONAL PLASTICITY; HIGH-FREQUENCY STIMULATION; AMPA RECEPTOR TRAFFICKING; MESSENGER-RNA EXPRESSION; NERVE GROWTH-FACTOR; NEUROTROPHIC FACTOR; SYNAPTIC PLASTICITY; DENTATE GYRUS AB Long-lasting forms of memory are generally believed to be mediated by protein synthesis-dependent, late-phase long-term potentiation (L-LTP). L-LTP exhibits at least two distinctive characteristics compared with early phase UP (E-LTP): synaptic growth and requirement of gene transcription and new protein synthesis. In this review, we discuss the cellular and molecular mechanisms underlying the structural and functional changes of hippocampal synapses during L-LTP, in the context of long-term memory. We describe experiments that reveal the critical role of cAMP/protein kinase A and MAP kinase pathways, and the downstream transcription factor CREB. Because transcription-dependent long-term changes are input specific, we also discuss the role of "local protein synthesis" and "synaptic tagging" mechanisms that may confer synapse specificity. We then focus on brain-derived neurotrophic factor (BDNF) and tissue plasmigonen activator (tPA), two secreted proteins that have been repeatedly implicated in L-LTP Biochemical and molecular biology experiments indicate that the expression and secretion of both factors are enhanced by strong tetanic stimulation that induces L-LTP as well as by training in hippocampal-dependent memory tasks. Inhibition of either tPA or BDNF by gene knockout and specific inhibitors results in a significant impairments in L-LTP and long-term memory. Further work will be required to address the relationship between BDNF and tPA in various forms of synaptic plasticity, and the mechanisms by which BDNF/tPA achieves synapse-specific modulation. Finally, we discuss how the aging process affects L-LTP and long-term memory. Published by Elsevier Ireland Ltd. C1 NICHD, Sect Neural Dev & Plast, NIH, Bethesda, MD 20892 USA. RP Lu, B (reprint author), NICHD, Sect Neural Dev & Plast, NIH, Bldg 49,Rm 6A80,49 Convent Dr,MSC4480, Bethesda, MD 20892 USA. EM bailu@mail.nih.gov NR 174 TC 175 Z9 184 U1 1 U2 10 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1568-1637 J9 AGEING RES REV JI Ageing Res. Rev. PD NOV PY 2004 VL 3 IS 4 BP 407 EP 430 DI 10.1016/j.arr.2004.07.002 PG 24 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 890JV UT WOS:000226508400004 ER PT J AU Mattson, MP Maudsley, S Martin, B AF Mattson, MP Maudsley, S Martin, B TI A neural signaling triumvirate that influences ageing and age-related disease: insulin/IGF-1, BDNF and serotonin SO AGEING RESEARCH REVIEWS LA English DT Review DE autonomic nervous system; CREB; hippocampus; hypothalamus; PI3 kinase; stress response ID GROWTH-FACTOR-I; MESSENGER-RNA EXPRESSION; ACTIVATED PROTEIN-KINASE; HUNTINGTIN MUTANT MICE; LONG-TERM-MEMORY; NEUROTROPHIC-FACTOR; DIETARY RESTRICTION; LIFE-SPAN; GLUCOSE-METABOLISM; COGNITIVE FUNCTION AB The ageing process and its associated diseases all involve perturbed energy metabolism, oxidative damage. and an impaired ability of the organism and its cells to cope with adversity. We propose that some specific signaling pathways in the brain may be important determinants of health during ageing. Among such specific signaling modalities are those activated in neurons by insulin-like growth factors (IGFs), brain-derived neurotrophic factor (BDNF) and serotonin. This triumvirate may be particularly important because of their cooperative influence on energy metabolism, food intake, stress responses and cardiovascular function. The health benefits to the periphery and central nervous system of dietary restriction and exercise may be mediated by this triumvirate of signals in the brain. At the molecular level, BDNF, serotonin and IGFs can all stimulate the production of proteins involved in cellular stress adaptation, growth and repair, neurogenesis, learning and memory and cell survival. The importance of this triumvirate is emphasized when it is seen that their general roles in energy metabolism, stress adaptation and disease resistance are conserved among diverse organisms consistent with important roles in the ageing process. Published by Elsevier Ireland Ltd. C1 Natl Inst Aging Intramural Res Program, Lab Neurosci, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD USA. RP Mattson, MP (reprint author), Natl Inst Aging Intramural Res Program, Lab Neurosci, Baltimore, MD USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 NR 113 TC 147 Z9 150 U1 0 U2 14 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1568-1637 J9 AGEING RES REV JI Ageing Res. Rev. PD NOV PY 2004 VL 3 IS 4 BP 445 EP 464 DI 10.1016/j.arr.2004.08.001 PG 20 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 890JV UT WOS:000226508400006 PM 15541711 ER PT J AU Brazel, CY Rao, MS AF Brazel, CY Rao, MS TI Aging and neuronal replacement SO AGEING RESEARCH REVIEWS LA English DT Review DE aging; neurogenesis; neural stem cells ID FIBROBLAST-GROWTH-FACTOR; NEURAL STEM-CELLS; ADULT-RAT HIPPOCAMPUS; FETAL NIGRAL TRANSPLANTATION; ROSTRAL MIGRATORY STREAM; CENTRAL-NERVOUS-SYSTEM; MAMMALIAN SPINAL-CORD; DENTATE GYRUS; SUBVENTRICULAR ZONE; PARKINSONS-DISEASE AB Neural stem cells contribute to neurogenesis in both the embryonic and adult brain. However, while adult neural stem cells produce new neurons that populate the olfactory bulb and the granule cell layer of the hippocampus, they do not normally participate in reparative neurogenesis following injury or disease affecting regions distant from the subventricular zone or the dentate gyrus. Here we review differences between neural stem cells found in the embryo and the adult, and describe factors that enhance neuronal output from these cells in vivo. Additionally, we review evidence that neural stem cells can be transplanted into injured regions of the adult brain to enhance compensatory neurogenesis from endogenous precursors. Pre-differentiation of neural stem cells into immature neurons prior to transplantation can also aid in functional recovery following injury or disease. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 NIA, Lab Neurosci, Baltimore, MD 21224 USA. RP Brazel, CY (reprint author), NIA, Lab Neurosci, 333 Cassell Dr,Triad 406A, Baltimore, MD 21224 USA. EM brazelch@grc.nia.nih.gov NR 123 TC 41 Z9 42 U1 0 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1568-1637 J9 AGEING RES REV JI Ageing Res. Rev. PD NOV PY 2004 VL 3 IS 4 BP 465 EP 483 DI 10.1016/j.arr.2004.04.003 PG 19 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 890JV UT WOS:000226508400007 PM 15541712 ER PT J AU Bernstein, HB Kinter, AL Jackson, R Fauci, AS AF Bernstein, HB Kinter, AL Jackson, R Fauci, AS TI Neonatal natural killer cells produce chemokines and suppress HIV replication in vitro SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; DEPENDENT CELLULAR CYTOTOXICITY; HERPES-SIMPLEX; TARGET-CELLS; CORD BLOOD; UNINFECTED INFANTS; INFECTED MOTHERS; CYTO-TOXICITY; T-CELLS; ANTIBODY AB The innate immune system may be critical in the prevention of perinatal HIV infection. Since neonates have limited immunological experience, they may rely more on the ability of the innate immune system to defend against infection than their adult counterparts. To assess the potential of human neonatal natural killer (nNK) cells to suppress HIV infection in a noncytolytic manner, we evaluated their ability to secrete chemokines and inhibit HIV replication in vitro. nNK cells were cocultured with autologous, HIV-infected CD4(+) T cells and their suppressive activity against HIV was compared to nCD8(+) T cells and adult NK cells. We found that nNK cells could suppress HIV replication in autologous CD4(+) T cells infected with a CCR5-utilizing virus, but were unable to suppress replication by a CXCR4-utilizing virus. nNK cell-mediated suppression of HIV replication was comparable to that of nCD8(+) T cells and greater than that of NK cells from adults. Suppression was mediated by soluble factors, and was abrogated by the addition of an excess of anti-CC-chemokine Ab directed at CCR5 ligand chemokines. In contrast, inhibition of HIV replication by autologous nCD8(+) T cells was not fully abrogated with anti-CC-chemokine Abs indicating, as previously reported in HIV-infected adults, that other factors in addition to chemokines play a role in CD8(+) T cell-mediated suppression of HIV replication. Our results show that nNK cells can inhibit HIV replication via a chemokine-mediated mechanism, and support a potential role for the innate immune system in preventing perinatal transmission of HIV in a noncytolytic manner. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20814 USA. RP Bernstein, HB (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, 10833 Le Conte Ave,CHS 22-150, Los Angeles, CA 90095 USA. EM hbernstein@mednet.ucla.edu FU NICHD NIH HHS [5K12HD01400, 5K12HD00849] NR 34 TC 27 Z9 27 U1 0 U2 0 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 2004 VL 20 IS 11 BP 1189 EP 1195 DI 10.1089/0889222042544983 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 877ND UT WOS:000225576400007 PM 15588341 ER PT J AU Lelievre, JD Petit, F Perrin, L Mammano, F Arnoult, D Ameisen, JC Corbeil, J Gervaix, A Estaquier, J AF Lelievre, JD Petit, F Perrin, L Mammano, F Arnoult, D Ameisen, JC Corbeil, J Gervaix, A Estaquier, J TI The density of coreceptors at the surface of CD4(+) T cells contributes to the extent of human immunodeficiency virus type 1 viral replication-mediated T cell death SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID SYNCYTIUM-INDUCING PHENOTYPE; HIV-1 DISEASE PROGRESSION; CHEMOKINE RECEPTOR CXCR4; HUMAN LYMPHOID-TISSUE; HTLV-III/LAV ENVELOPE; PRIMARY CD4+T CELLS; CCR5 DENSITY; IN-VITRO; UNINFECTED INDIVIDUALS; ANTIRETROVIRAL THERAPY AB Chemokine receptors serve as coreceptors for HIV-1 entry into CD4(+) T cells. Several reports have mentioned that density of CCR5 expression modulates in vitro viral replication and in vivo the course of the disease. Our goal was to investigate the impact of coreceptor density at the surface of a CD4(+) cell line on HIV-1 entry, replication, spreading, and programmed cell death. We engineered a CEM cell line that expresses constitutively CD4 and CXCR4 and CCR5 after transfection. This model allows us to compare the effect of the X4 and R5 strains to induce T cell death in the same T cell host. We show here that the extent of T cell death correlates with the rate of virus replication. X4 induces faster T cell death than R5 that depends at least in part on the higher density of CXCR4 compared to CCR5. Furthermore, sorting CEM populations expressing low, intermediate, and high densities of CCR5 molecules but constant amount of CD4, we found that the capacity to induce T cell death depends at least in part on the level of CCR5 when low amount of virus was used to infect the CEM cells. Moreover, viral transcription, assessed by cell-associated HIV-1 RNA/DNA ratio, was increased in CCR5high as compared to CCR5low cells, while inhibition of replication by zidovudine was more effective in CCR5low cells. Our data indicate that the density of chemokine receptors expressed on CD4(+) T cells may be a critical parameters for the cytopathic effect of HIV strains and may have major impact on CD4 T cell depletion during HAART. C1 Inst Pasteur, Unite Physiopathol Infect Lentivirales, F-75724 Paris 15, France. Univ Geneva, Virol Lab, Geneva, Switzerland. Hop Bichat Claude Bernard, APHP, INSERM, U552, F-75877 Paris, France. NINDS, Biochem Sect, NIH, Bethesda, MD 20892 USA. Univ Paris 07, INSERM, EMIU 9922, Hop Bichat Claude Bernard, Paris, France. Univ Calif San Diego, Dept Pathol & Med, La Jolla, CA 92093 USA. Univ Geneva, Dept Pediat, Geneva 14, Switzerland. RP Estaquier, J (reprint author), Inst Pasteur, Unite Physiopathol Infect Lentivirales, 28 Rue Dr Roux, F-75724 Paris 15, France. EM jestaqui@pasteur.fr FU NIAID NIH HHS [AI43237, AI27670, AI29164, AI36214, AI38858, AI43638] NR 81 TC 12 Z9 13 U1 0 U2 3 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 2004 VL 20 IS 11 BP 1230 EP 1243 DI 10.1089/0889222042545045 PG 14 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 877ND UT WOS:000225576400011 PM 15588345 ER PT J AU Liang, TB Habegger, K Spence, JP Foroud, T Ellison, JA Lumeng, L Li, TK Carr, LG AF Liang, TB Habegger, K Spence, JP Foroud, T Ellison, JA Lumeng, L Li, TK Carr, LG TI Glutathione S-transferase 8-8 expression is lower in alcohol-preferring than in alcohol-nonpreferring rats SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE rat GST 8-8; alcoholism; mRNA expression; polymorphism; rat ID QUANTITATIVE TRAIT LOCUS; MESSENGER-RNA STABILITY; SMOOTH-MUSCLE-CELLS; ETHANOL-CONSUMPTION; 3'-UNTRANSLATED REGION; PREFERENCE DRINKING; LIPID-PEROXIDATION; ALPHA-SYNUCLEIN; IDENTIFICATION; DETOXICATION AB Objective: A primary focus of alcohol research is to provide novel targets for alcohol treatment by identifying genes that predispose individuals to drink alcohol. Animal models of alcoholism developed by selective breeding are invaluable tools to elucidate both the genetic nature and the underlying biological mechanisms that contribute to alcohol dependence. These selected lines (high alcohol preferring and low alcohol preferring) display phenotypic and genetic differences that can be studied to further our understanding of alcohol preference and related genetic traits. By combining molecular techniques, genetic and physiological factors that underlie the cause of alcoholism can be identified. Methods: Total gene expression analysis was used to identify genes that are differentially expressed in specific brain regions between alcohol-naive, inbred alcohol-preferring (iP) and -nonpreferring (iNP) rats. Quantitative reverse transcriptase-polymerase chain reaction, in situ hybridization, Western blot, and sequence analysis were used to further characterize rat glutathione S-transferase 8-8 (rGST 8-8). Results: Lower expression of rGST 8-8 mRNA was observed in discrete brain regions of iP compared with iNP animals, and these expression differences were confirmed. To determine additional expression patterns of rGST 8-8, we used in situ hybridization. Rat GST 8-8 was highly expressed in hippocampus, the choroid plexus of the dorsal third ventricle and the lateral ventricle, and ependymal cells along the dorsal third ventricle and the third ventricle. Western blot analysis showed that rGST 8-8 protein levels were lower in the hippocampus and the amygdala of iP compared with iNP. A silent single-nucleotide polymorphism in the coding region and three single-nucleotide polymorphisms in the 3'-UTR were identified in the rGST 8-8 cDNA. Conclusion: There is regional variation of rGST 8-8 expression in the brain, at both the mRNA and protein level, and the iP strain has lower innate rGST 8-8 levels than the iNP strain in discrete brain regions. 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. Digital Gene Technol Inc, La Jolla, CA USA. NIAAA, NIH, Bethesda, MD USA. RP Carr, LG (reprint author), Indiana Univ, Sch Med, Dept Med, Med Res & Lib Bldg,Room 407,975 W Walnut St, Indianapolis, IN 46202 USA. EM lcarr@iupui.edu FU NIAAA NIH HHS [P60 AA007611, AA10707, AA07611, AA00285, P50 AA007611, R01 AA010707] NR 47 TC 12 Z9 12 U1 1 U2 4 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 NOV PY 2004 VL 28 IS 11 BP 1622 EP 1628 DI 10.1097/01.ALC.0000145686.79141.57 PG 7 WC Substance Abuse SC Substance Abuse GA 872IW UT WOS:000225201900004 PM 15547447 ER PT J AU Walsh, KE Miller, MR Vinci, RJ Bauchner, H AF Walsh, KE Miller, MR Vinci, RJ Bauchner, H TI Pediatric resident education about Medicaid errors SO AMBULATORY PEDIATRICS LA English DT Article DE education; medical errors; patient safety; pediatric resident ID EMERGENCY-MEDICINE; EVENTS AB Background.-National organizations have called for patient safety curricula to help reduce the incidence of errors. Little is known about what trainees are taught about medical errors. Objective.-1) To determine the amount and type of training that pediatric residents have about medical errors and 2) to assess pediatric chief resident knowledge about medical errors. Methods.-We surveyed chief residents from a national sample of 51 pediatric training programs by selecting every fourth program from the American Council on Graduate Medical Education list of accredited programs. The 21-item telephone survey was developed with patient safety specialists and piloted on several chief residents. It asked about patient-safety training sessions and awareness and knowledge about medical errors. Results.-The 51 chief residents helped teach 2176 residents, approximately one third of all pediatric residents. One third of programs had no lectures about medical errors and 23% did not have morbidity and mortality rounds. Sixty-one percent of respondents stated that outpatient medical errors were rarely discussed. Informal teaching was most often reported as the primary method for educating residents about medical errors. Although 58% of respondents did not know that a systemic change should be made in response to a medical error, 83% felt that residents are adequately trained to deal with a medical error. Discussion.-Pediatric resident education about medical errors varies widely. Attention by pediatric residency training programs to this important issue seems limited. C1 Boston Univ, Med Ctr, Sch Med, Dept Pediat, Boston, MA 02118 USA. Natl Inst Hlth, Agcy Healthcare Res & Qual, Bethesda, MD USA. Johns Hopkins Univ, Dept Pediat, Baltimore, MD 21218 USA. RP Walsh, KE (reprint author), Boston Univ, Med Ctr, Sch Med, Dept Pediat, Matern Bldg,Room 4104,91 E Concord St, Boston, MA 02118 USA. EM Kathleen.walsh@bmc.org NR 17 TC 11 Z9 11 U1 0 U2 1 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1530-1567 J9 AMBUL PEDIATR JI Ambul. Pediatr. PD NOV-DEC PY 2004 VL 4 IS 6 BP 514 EP 517 DI 10.1367/A04-009R1.1 PG 4 WC Pediatrics SC Pediatrics GA 873JI UT WOS:000225275400010 PM 15548104 ER PT J AU Collins, F AF Collins, F TI Genomics and the family physician: Realizing the potential SO AMERICAN FAMILY PHYSICIAN LA English DT Editorial Material ID LUNG-CANCER; THERAPY; GEFITINIB; MUTATIONS C1 NHGRI, NIH, Washington, DC USA. RP Collins, F (reprint author), NHGRI, NIH, 31 Ctr Dr,Bldg 31 4B09, Bethesda, MD 20892 USA. NR 8 TC 5 Z9 5 U1 0 U2 0 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD NOV 1 PY 2004 VL 70 IS 9 BP 1637 EP + PG 2 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 869XB UT WOS:000225016800001 PM 15554479 ER PT J AU Peters, U Chatterjee, N McGlynn, KA Schoen, RE Church, TR Bresalier, RS Gaudet, MM Flood, A Schatzkin, A Hayes, RB AF Peters, U Chatterjee, N McGlynn, KA Schoen, RE Church, TR Bresalier, RS Gaudet, MM Flood, A Schatzkin, A Hayes, RB TI Calcium intake and colorectal adenoma in a US colorectal cancer early detection program(1-3) SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE colorectal adenoma; calcium; supplements; nutritional epidemiology ID VITAMIN-D-RECEPTOR; GROWTH-FACTOR-I; COLON-CANCER; DAIRY-PRODUCTS; UNITED-STATES; SCREENING TRIAL; DIETARY CALCIUM; RECTAL-CANCER; WOMENS HEALTH; OLDER WOMEN AB Background: Calcium can reduce the risk of colorectal tumors by binding secondary bile and fatty acids, which leads to antiproliferative effects in the bowel, or by acting directly on the colonic epithelium, which affects differentiation and apoptosis. Objective: We investigated calcium intake and risk of colon adenoma to evaluate the association of calcium intake with early stages of colorectal tumor development. Design: We compared the supplemental and dietary calcium intakes of 3696 participants with histologically verified adenoma of the distal colon (ie, descending colon, sigmoid colon, or rectum) with the calcium intakes of 34 817 sigmoidoscopy-negative control participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Calcium intake was assessed at study entry with a 137-item food-frequency questionnaire and additional questions on the amount and duration of calcium supplement use. Results: After adjustment for known risk factors, adenoma risk was lower by 12% for participants in the highest quintile of total calcium intake (>1767 mg/d) than for participants in the lowest quintile (<731 mg/d) (odds ratio: 0.88; 95% CI: 0.76, 1.02; P for trend = 0.04). The protective association between total calcium and colorectal adenoma was largely due to calcium supplement use, with a 27% decrease in adenoma risk for participants taking >1200 mg/d than for nonusers of supplements (odds ratio: 0.73; 95% CI: 0.56, 0.91; P for trend = 0.005). The protective associations of total and supplemental calcium were strongest for colon adenoma (descending and sigmoid colon). Conclusion: High calcium intake, particularly from supplements, is associated with a reduced risk of distal colorectal adenoma. C1 NCI, Div Canc Epidemiol & Genet, Natl Inst Hlth, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. RP Peters, U (reprint author), Fred Hutchinson Canc Res Ctr, Canc Prevent Res Program, POB 19024,M4-B402, Seattle, WA 98109 USA. EM upeters@fhcrc.org OI Church, Timothy R./0000-0003-3292-5035 NR 67 TC 31 Z9 33 U1 0 U2 1 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD NOV PY 2004 VL 80 IS 5 BP 1358 EP 1365 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 870EE UT WOS:000225036000035 PM 15531687 ER PT J AU Lee, JS Weyant, RJ Corby, P Kritchevsky, SB Harris, T Rooks, R Rubin, SM Newman, AB AF Lee, JS Weyant, RJ Corby, P Kritchevsky, SB Harris, T Rooks, R Rubin, SM Newman, AB TI Edentulism and malnutrition in elderly patients - Reply to JC Desport SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Letter C1 Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Dent Med, Pittsburgh, PA 15261 USA. Wake Forest Univ, J Paul Sticht Ctr Aging, Winston Salem, NC 27109 USA. Natl Inst Aging, Bethesda, MD USA. Kent State Univ, Dept Sociol, Kent, OH 44242 USA. Univ Calif San Francisco, Prevent Sci Grp, San Francisco, CA 94143 USA. Univ Pittsburgh, Dept Epidemiol & Med, Pittsburgh, PA 15261 USA. RP Lee, JS (reprint author), Univ Pittsburgh, Dept Epidemiol, 130 N Bellefield Ave,5th Floor, Pittsburgh, PA 15261 USA. EM leej@edc.pitt.edu NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD NOV PY 2004 VL 80 IS 5 BP 1453 EP 1454 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 870EE UT WOS:000225036000060 ER PT J AU Michaud, DS Wright, ME Cantor, KP Taylor, PR Virtamo, J Albanes, D AF Michaud, DS Wright, ME Cantor, KP Taylor, PR Virtamo, J Albanes, D TI Arsenic concentrations in prediagnostic toenails and the risk of bladder cancer in a cohort study of male smokers SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE arsenic; bladder neoplasms; cohort studies; nails; smoking ID DRINKING-WATER; WELL WATER; MALIGNANT NEOPLASMS; INTERNAL CANCERS; ENDEMIC AREA; LUNG-CANCER; MORTALITY; TAIWAN; RESIDENTS; ARGENTINA AB At high concentrations, inorganic arsenic can cause bladder cancer in humans. However, it is unclear whether low exposure to inorganic arsenic in drinking water (<100 mug/liter) is related to bladder cancer risk. No study has been known to use biomarkers to assess the relation between individual arsenic exposure and bladder cancer risk. Toenail samples provide an integrated measure of internal arsenic exposure and reflect long-term exposure. The authors examined the relation between toenail arsenic levels and bladder cancer risk among participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a cohort of Finnish male smokers aged 50-69 years. Data for 280 incident bladder cancer cases, identified between baseline (1985-1988) and April 1999, were available for analysis. One control was matched to each case on the basis of age, toenail collection date, intervention group, and smoking duration. Arsenic levels in toenail samples were determined by using neutron activation analysis. Logistic regression analyses were performed to estimate odds ratios. Arsenic toenail concentrations in this Finnish study were similar to those reported in US studies (range: 0.02-17.5 mug/g). The authors observed no association between inorganic arsenic concentration and bladder cancer risk (odds ratio = 1.13, 95% confidence interval: 0.70, 1.81 for the highest vs. lowest quartile). These findings suggest that low-level arsenic exposure is unlikely to explain a substantial excess risk of bladder cancer. C1 Harvard Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA 02115 USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. NCI, Ctr Canc Res, Rockville, MD USA. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. RP Michaud, DS (reprint author), Harvard Univ, Dept Epidemiol, Sch Publ Hlth, 677 Huntington Ave,Kresge 920, Boston, MA 02115 USA. EM dmichaud@hsph.harvard.edu RI Michaud, Dominique/I-5231-2014; Albanes, Demetrius/B-9749-2015 FU NCI NIH HHS [N01CN45035, N01CN45165] NR 30 TC 38 Z9 38 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 1 PY 2004 VL 160 IS 9 BP 853 EP 859 DI 10.1093/aje/kwh295 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 865LC UT WOS:000224703600003 PM 15496537 ER PT J AU Hou, L Ji, BT Blair, A Dai, Q Gao, YT Chow, WH AF Hou, L Ji, BT Blair, A Dai, Q Gao, YT Chow, WH TI Commuting physical activity and risk of colon cancer in Shanghai, China SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE body mass index; case-control studies; China; colonic neoplasms; motor activity; risk ID COLORECTAL-CANCER; DIETARY FACTORS; INSULIN; MEN; WOMEN AB Colon cancer incidence rates have been rapidly increasing in Shanghai, China, for reasons still unclear. Low physical activity is a known risk factor for colon cancer. The authors examined the effects of physical activity, particularly commuting physical activity, and its joint effects with body mass index on colon cancer risk in a population-based, case-control study. The study included 931 incident colon cancer patients and 1,552 randomly selected controls in Shanghai between 1990 and 1993. Colon cancer risk was significantly reduced among subjects with high commuting physical activity (odds ratio (OR) = 0.52, 95% confidence interval (CI): 0.27, 0.87 for men; OR = 0.56, 95% CI: 0.21, 0.91 for women), particularly among those who had high commuting physical activity for at least 35 years (OR = 0.34, 95% CI: 0.09, 0.76 for men; OR = 0.31, 95% CI: 0.07, 0.72 for women). Commuting physical activity significantly modified the risk conferred by high body mass index, with the highest risk observed among those at the highest quintile of body mass index and the lowest activity level (OR = 6.43, 95% CI: 1.82, 8.54 for men; OR = 7.42, 95% CI: 2.84, 10.01 for women). Our results suggest that regular and frequent physical activity over a long period of time protects from colon cancer and significantly modifies the body mass index-associated risk. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. RP Hou, L (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8123, Bethesda, MD 20892 USA. EM lifangh2@mail.nih.gov NR 19 TC 42 Z9 43 U1 1 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 1 PY 2004 VL 160 IS 9 BP 860 EP 867 DI 10.1093/aje/kwh301 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 865LC UT WOS:000224703600004 PM 15496538 ER PT J AU Alavanja, MCR Dosemeci, M Samanic, C Lubin, J Lynch, CF Knott, C Barker, J Hoppin, JA Sandler, DP Coble, J Thomas, K Blair, A AF Alavanja, MCR Dosemeci, M Samanic, C Lubin, J Lynch, CF Knott, C Barker, J Hoppin, JA Sandler, DP Coble, J Thomas, K Blair, A TI Pesticides and lung cancer risk in the agricultural health study cohort SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE lung neoplasms; pesticides ID PHENOXY HERBICIDES; NONSMOKING WOMEN; UNITED-STATES; MORTALITY; WORKERS; APPLICATORS; EXPOSURE; DIOXINS; IOWA; ACID AB The authors examined the relation between 50 widely used agricultural pesticides and lung cancer incidence in the Agricultural Health Study, a prospective cohort study of 57,284 pesticide applicators and 32,333 spouses of farmer applicators with no prior history of lung cancer. Self-administered questionnaires were completed at enrollment (1993-1997). Cancer incidence was determined through population-based cancer registries from enrollment through December 31, 2001. A lung cancer standardized incidence ratio of 0.44 (95% confidence interval: 0.39, 0.49) was observed overall, due in large part to a low cigarette smoking prevalence. Two widely used herbicides, metolachlor and pendimethalin (for low-exposed groups to four higher exposure categories: odds ratio (OR) = 1.0, 1.6, 1.2, 5.0; p(trend) = 0.0002; and OR = 1.0, 1.6, 2.1, 4.4; p(trend) = 0.003, respectively), and two widely used insecticides, chlorpyrifos and diazinon (OR = 1.0, 1.1, 1.7, 1.9; p(trend) = 0.03; and OR = 1.0, 1.6, 2.7, 3.7; p(trend) = 0.04, respectively), showed some evidence of exposure response for lung cancer. These excesses could not be explained by previously identified lung cancer risk factors. The usage levels in this cohort are considerably higher than those typically experienced by the general population. An excess risk among spouses directly exposed to pesticides could not be evaluated at this time. C1 Univ Iowa, Dept Epidemiol, Coll Publ Hlth, Iowa City, IA USA. Battelle Ctr Publ Hlth Res & Evaluat, Durham, NC USA. IMS Inc, Silver Spring, MD USA. NIEHS, Res Triangle Pk, NC 27709 USA. US EPA, Res Triangle Pk, NC 27711 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Alavanja, MCR (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 8000, Bethesda, MD 20892 USA. EM alavanjm@mail.nih.gov OI Sandler, Dale/0000-0002-6776-0018 NR 31 TC 77 Z9 86 U1 0 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 1 PY 2004 VL 160 IS 9 BP 876 EP 885 DI 10.1093/aje/kwh290 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 865LC UT WOS:000224703600006 PM 15496540 ER PT J AU Harik-Khan, RI Muller, DC Wise, RA AF Harik-Khan, RI Muller, DC Wise, RA TI Racial difference in lung function in African-American and White children: Effect of anthropometric, socioeconomic, nutritional, and environmental factors SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE anthropometry; antioxidants; continental population groups; reference values; respiratory function tests; socioeconomic factors ID TOBACCO-SMOKE EXPOSURE; PULMONARY-FUNCTION; NATIONAL-HEALTH; WEIGHT-GAIN; VITAMIN-C; POPULATION; DISEASE; VALUES; ADULTS; GIRLS AB African-American children have lower lung volumes than White children. However, the contributions of anthropometric, socioeconomic, nutritional, and environmental factors to this difference are unknown. From participants in the Third National Health and Nutrition Examination Survey (1988-1994), the authors selected 1,462 healthy nonsmoking children (623 White and 839 African-American) aged 8-17 years. The African-American children were taller and heavier but had lower lung function. African Americans were poorer and had lower levels of the antioxidant vitamins A and C and alpha-carotene. The authors performed regression analyses using data on anthropometric, socioeconomic, and nutritional factors and smoke exposure. Adjustment for sitting height explained 42-53% of the racial difference. Socioeconomic factors and antioxidant vitamin levels accounted for an additional 7-10%. Overall, the authors could account for only 50-63% of the racial difference. Exposure to tobacco in the home was weakly associated with forced expiratory volume in 1 second in girls, accounting for 1% of the difference. In children aged 8-12 years (n = 752), birth weight explained 3-5% of the racial difference, whereas in-utero exposure to maternal smoking had no significant effect. The authors conclude that in healthy children, the major explanatory variable for the racial difference in lung function is body habitus; socioeconomic, nutritional, and environmental confounders play a smaller role. C1 Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21224 USA. NIA, Clin Res Branch, Baltimore, MD 21224 USA. RP Wise, RA (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, 5501 Hopkins Bayview Circle, Baltimore, MD 21224 USA. EM rwise@jhmi.edu OI Wise, Robert/0000-0002-8353-2349 NR 23 TC 46 Z9 46 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 NOV 1 PY 2004 VL 160 IS 9 BP 893 EP 900 DI 10.1093/aje/kwh297 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 865LC UT WOS:000224703600008 PM 15496542 ER PT J AU Thombs, DL Baldwin, J Beck, KH Colwell, B Olds, RS Simons-Morton, B Murdock, PO Sciacca, JP Werch, CE AF Thombs, DL Baldwin, J Beck, KH Colwell, B Olds, RS Simons-Morton, B Murdock, PO Sciacca, JP Werch, CE TI AAHB initiative to establish doctoral research competencies: A first step SO AMERICAN JOURNAL OF HEALTH BEHAVIOR LA English DT Editorial Material C1 Kent State Univ, ACHVE Dept, Kent, OH 44242 USA. No Arizona Univ, Flagstaff, AZ 86011 USA. Univ Maryland, College Pk, MD 20742 USA. Texas A&M Univ, Hlth Sci Ctr, College Stn, TX 77843 USA. NICHD, Bethesda, MD 20892 USA. Middle Tennessee State Univ, Murfreesboro, TN 37130 USA. No Arizona Univ, Flagstaff, AZ 86011 USA. Univ N Florida, Jacksonville, FL 32224 USA. RP Thombs, DL (reprint author), Kent State Univ, ACHVE Dept, 316 White Hall, Kent, OH 44242 USA. EM dthombs@kent.edu NR 12 TC 4 Z9 4 U1 0 U2 1 PU PNG PUBLICATIONS PI STAR CITY PA PO BOX 4593, STAR CITY, WV 26504-4593 USA SN 1087-3244 J9 AM J HEALTH BEHAV JI Am. J. Health Behav. PD NOV-DEC PY 2004 VL 28 IS 6 BP 483 EP 486 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 891BB UT WOS:000226555200001 PM 15569582 ER PT J AU Velazquez, I Alter, BP AF Velazquez, I Alter, BP TI Androgens and liver tumors: Fanconi's anemia and non-Fanconi's conditions SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE androgens; anabolic steroids; liver tumors; hepatocellular carcinomas; hepatomas; adenomas ID ANABOLIC-STEROID-THERAPY; MULTIPLE HEPATIC ADENOMAS; INDUCED HEPATOCELLULAR ADENOMA; LONG-TERM METHYLTESTOSTERONE; BONE-MARROW-TRANSPLANTATION; HEREDITARY ANGIO-EDEMA; APLASTIC-ANEMIA; PELIOSIS HEPATIS; DANAZOL THERAPY; CELL ADENOMA AB The association between anabolic androgenic steroids and liver tumors was first noted in patients with Fanconi's anemia (FA). The hypotheses which led to this review were as follows: (1) androgen-treated individuals who do not have FA are also at risk of liver tumors; (2) parenteral as well as oral androgens may be responsible for liver tumors; (3) FA patients develop liver tumors after smaller and briefer androgen exposure than non-FA individuals; (4) the risk of hepatic neoplasms may depend on the specific androgen. Medline and Web of Science were searched for all cases of liver tumors associated with androgens. Information from individual cases was entered into a spreadsheet and descriptive statistical analyses were performed. Thirty-six FA cases and 97 non-FA cases with both nonhematologic disorders and acquired aplastic anemia (non-FA AA) were identified. The most common androgens were oxymetholone, methyltestosterone, and danazol. Hepatocellular carcinomas (HCC) were more often associated with oxymetholone and methyltestosterone, while adenomas were associated with danazol. Tumors were reported in six patients who received only parenteral and not oral androgens. FA patients were younger than non-FA patients when androgen use was initiated, and the FA patients developed tumors at younger ages. Non-AA patients were treated with androgens for longer periods of time, compared with FA and non-FA AA patients. All patients on anabolic androgenic steroids are at risk of liver tumors, regardless of underlying diagnosis. The magnitude of the risk cannot be determined from currently available ata, because the number of patients receiving androgens is unknown. Published 2004 Wiley-Liss, Inc.(dagger) C1 NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, US Dept HHS, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Pediat, Div Pediat Hematol Oncol, Washington, DC 20010 USA. RP Alter, BP (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS Room 7020, Rockville, MD 20852 USA. EM alterb@mail.nih.gov NR 87 TC 91 Z9 97 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD NOV PY 2004 VL 77 IS 3 BP 257 EP 267 DI 10.1002/ajh.20183 PG 11 WC Hematology SC Hematology GA 866MO UT WOS:000224777800008 PM 15495253 ER PT J AU Chen, JS Lipska, BK Halim, N Ma, QD Matsumoto, M Melhem, S Kolachana, BS Hyde, TM Herman, MM Apud, J Egan, MF Kleinman, JE Weinberger, DR AF Chen, JS Lipska, BK Halim, N Ma, QD Matsumoto, M Melhem, S Kolachana, BS Hyde, TM Herman, MM Apud, J Egan, MF Kleinman, JE Weinberger, DR TI Functional analysis of genetic variation in catechol-o-methyltransferase (COMT): Effects on mRNA, protein, and enzyme activity in postmortem human brain SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DORSOLATERAL PREFRONTAL CORTEX; DOPAMINE TRANSPORTER; BIOCHEMICAL GENETICS; THERMAL-STABILITY; BIPOLAR DISORDER; SCHIZOPHRENIA; EXPRESSION; GENOTYPE; MICE; IMMUNOREACTIVITY AB Catechol-O-methyltransferase (COMT) is a key enzyme in the elimination of dopamine in the prefrontal cortex of the human brain. Genetic variation in the COMT gene (MIM 116790) has been associated with altered prefrontal cortex function and higher risk for schizophrenia, but the specific alleles and their functional implications have been controversial. We analyzed the effects of several single-nucleotide polymorphisms (SNPs) within COMT on mRNA expression levels (using reverse-transcriptase polymerase chain reaction analysis), protein levels (using Western blot analysis), and enzyme activity (using catechol methylation) in a large sample (n = 108) of postmortem human prefrontal cortex tissue, which predominantly expresses the -membrane-bound isoform. A common coding SNP, Val158Met (rs4680), significantly affected protein abundance and enzyme activity but not mRNA expression levels, suggesting that differences in protein integrity account for the difference in enzyme activity between alleles. A SNP in intron 1 (rs737865) and a SNP in the 3' flanking region (rs165599) - both of which have been reported to contribute to allelic expression differences and to be associated with schizophrenia as part of a haplotype with Val - had no effect on mRNA expression levels, protein immunoreactivity, or enzyme activity. In lymphocytes from 47 subjects, we confirmed a similar effect on enzyme activity in samples with the Val/Met genotype but no effect in samples with the intron 1 or 3 a SNPs. Separate analyses revealed that the subject's sex, as well as the presence of a SNP in the P2 promoter region (rs2097603), had small effects on COMT enzyme activity. Using site-directed mutagenesis of mouse COMT cDNA, followed by in vitro translation, we found that the conversion of Leu at the homologous position into Met or Val progressively and significantly diminished enzyme activity. Thus, although we cannot exclude a more complex genetic basis for functional effects of COMT, Val is a predominant factor that determines higher COMT activity in the prefrontal cortex, which presumably leads to lower synaptic dopamine levels and relatively deleterious prefrontal function. C1 NIMH, NIH, Genes Cognit & Psychosis Program, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RP Weinberger, DR (reprint author), NIMH, NIH, Genes Cognit & Psychosis Program, Clin Brain Disorders Branch, Room 42-235,10 Center Dr, Bethesda, MD 20892 USA. EM daniel.weinberger@mail.nih.gov RI Matsumoto, Mitsuyuki/G-3207-2012; Lipska, Barbara/E-4569-2017 OI Matsumoto, Mitsuyuki/0000-0002-1172-2354; NR 45 TC 874 Z9 897 U1 11 U2 73 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2004 VL 75 IS 5 BP 807 EP 821 DI 10.1086/425589 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 859YE UT WOS:000224303500006 PM 15457404 ER PT J AU Hodgkinson, CA Goldman, D Jaeger, J Persaud, S Kane, JM Lipsky, RH Malhotra, AK AF Hodgkinson, CA Goldman, D Jaeger, J Persaud, S Kane, JM Lipsky, RH Malhotra, AK TI Disrupted in Schizophrenia 1 (DISC1): Association with schizophrenia, schizoaffective disorder, and bipolar disorder SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GENOME SCAN METAANALYSIS; AMINO-ACID OXIDASE; SUSCEPTIBILITY LOCI; HAPLOTYPE RECONSTRUCTION; TRANSLOCATION; DISRUPTED-IN-SCHIZOPHRENIA-1; GENETICS; FAMILY; GENES; NUDEL AB Schizophrenia, schizoaffective disorder, and bipolar disorder are common psychiatric disorders with high heritabilities and variable phenotypes. The Disrupted in Schizophrenia 1 (DISC1) gene, on chromosome 1q42, was originally discovered and linked to schizophrenia in a Scottish kindred carrying a balanced translocation that disrupts DISC1 and DISC2. More recently, DISC1 was linked to schizophrenia, broadly defined, in the general Finnish population, through the undertransmission to affected women of a common haplotype from the region of intron 1/exon 2. We present data from a case-control study of a North American white population, confirming the underrepresentation of a common haplotype of the intron 1/exon 2 region in individuals with schizoaffective disorder. Multiple haplotypes contained within four haplotype blocks extending between exon 1 and exon 9 are associated with schizophrenia, schizoaffective disorder, and bipolar disorder. We also find overrepresentation of the exon 9 missense allele Phe607 in schizoaffective disorder. These data support the idea that these apparently distinct disorders have at least a partially convergent etiology and that variation at the DISC1 locus predisposes individuals to a variety of psychiatric disorders. C1 NIAAA, Sect Human Neurogenet, Rockville, MD USA. NIAAA, Neurogenet Lab, Rockville, MD USA. Zucker Hillside Hosp, Glen Oaks, NY USA. RP Hodgkinson, CA (reprint author), Pk 5 Bldg,Room 451,MSC8110,12420 Parklawn Dr, Rockville, MD 20852 USA. EM chodg@mail.nih.gov RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Lipsky, Robert/0000-0001-7753-1473 FU NIMH NIH HHS [K23 MH001760] NR 49 TC 289 Z9 297 U1 0 U2 8 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2004 VL 75 IS 5 BP 862 EP 872 DI 10.1086/425586 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 859YE UT WOS:000224303500011 PM 15386212 ER PT J AU Jiao, XD Ventruto, V Trese, MT Shastry, BS Hejtmancik, JF AF Jiao, XD Ventruto, V Trese, MT Shastry, BS Hejtmancik, JF TI Autosomal recessive familial exudative vitreoretinopathy is associated with mutations in LRP5 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID RECEPTOR-RELATED PROTEIN-5; CANDIDATE GENE ANALYSIS; MISSENSE MUTATIONS; LINKAGE ANALYSIS; BONE-DENSITY; LOCUS; HETEROGENEITY; D11S533; MICE; MAPS AB Familial exudative vitreoretinopathy (FEVR) is a hereditary eye disorder that affects both the retina and vitreous body. Autosomal recessive FEVR was diagnosed in multiple individuals from three consanguineous families of European descent. A candidate-locus-directed genome scan shows linkage to the region on chromosome 11q flanked by markers D11S905 and D11S1314. The maximum LOD score of 3.6 at theta = 0 is obtained with marker D11S987. Haplotype analysis confirms that the critical region is the 22-cM (311-Mb) interval flanked by markers D11S905 and D11S1314. This region contains LRP5 but not FZD4; mutations in both of these genes cause autosomal dominant FEVR. Sequencing of LRP5 shows, in all three families, homozygous mutations R570Q, R752G, and E1367K. This suggests that mutations in this gene can cause autosomal recessive as well as autosomal dominant FEVR. C1 NEI, NIH, Opthalm Genet & Visual Funct Branch, Bethesda, MD 20892 USA. CNR, Int Inst Genet & Biophys, I-80125 Naples, Italy. William Beaumont Hosp, Royal Oak, MI 48072 USA. Oakland Univ, Dept Biol Sci, Rochester, MI USA. RP Hejtmancik, JF (reprint author), NEI, NIH, Opthalm Genet & Visual Funct Branch, Bldg 10,Room 10B10,10 Ctr Dr MSC 1860, Bethesda, MD 20892 USA. EM f3h@helix.nih.gov NR 34 TC 86 Z9 94 U1 1 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2004 VL 75 IS 5 BP 878 EP 884 DI 10.1086/425080 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 859YE UT WOS:000224303500013 PM 15346351 ER PT J AU Malyarchuk, BA Rogozin, IB AF Malyarchuk, BA Rogozin, IB TI On the Etruscan mitochondrial DNA contribution to modern humans SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Letter ID CONTROL REGION; ANCIENT DNA; POPULATION; SEQUENCES C1 Russian Acad Sci, Inst Biol Problems N, Far E Branch, Magadan 685000, Russia. NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD USA. RP Malyarchuk, BA (reprint author), Russian Acad Sci, Inst Biol Problems N, Far E Branch, Portovaya St 18, Magadan 685000, Russia. EM malyar@ibpn.kolyma.ru NR 14 TC 7 Z9 7 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2004 VL 75 IS 5 BP 920 EP 923 DI 10.1086/425220 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 859YE UT WOS:000224303500020 PM 15457406 ER PT J AU Mitchell, CS Doyle, ML Moran, JB Lippy, B Hughes, JT Lum, M Agnew, J AF Mitchell, CS Doyle, ML Moran, JB Lippy, B Hughes, JT Lum, M Agnew, J TI Worker training for new threats: A proposed framework SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE training; hazardous materials; emergency response; bioterrorism; terrorism; weapons of mass destruction; occupational; HAZWOPER ID PREPAREDNESS; EMERGENCY; COMPETENCES; NURSES; CARE AB Background In an effort to identify health and safety training needs for various groups of workers related to weapons of mass destruction, including chemical, biological, radiological, and nuclear weapons and high yield explosives (CBRNE), a conference, "Worker Training in a New Era: Responding to New Threats," was held at the Johns Hopkins Bloomberg School of Public Health in October 2002. Methods Two questions were addressed: Which general skills and knowledge are common to all workers who might be exposed to terrorist threats from CBRNE weapons? What are the particular skills and knowledge relevant to these threats that are specific to workers in different sectors? Results Thirteen core components for pre- and post-event training were identified. Pre-event training applies to all workers. Post-event training applies to selected personnel including first responders, skilled support personnel, and other workers involved in these operations. Recommendations to improve worker safety training related to preparedness include: identify specific competencies for worker pre- and post-event training; coordinate Federal policy on worker training for CBRNE hazards; adopt federal guidelines or standards on worker training for new CBRNE threats, based on the competencies and coordinated Federal policy; conduct an inventory of training programs and other resources that could be used or adapted for use for new threats; and develop new training content and methods for pre- and post-event training to address specific competencies. Conclusions Given the possibility for the introduction of CBRNE threats into the work-place, all workers need some training in the potential hazards involved: the individual worker's specific role in an emergency; incident command; activation of the emergency notification system; use of personal protective equipment (PPE); and safe evacuation of the workplace. While some occupational sectors have developed effective training related to these new threats, there is a need to develop, implement, and evaluate training programs across many different sectors of the workforce. (C) 2004 Wiley-Liss, Inc. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. MDB Inc NW, Natl Clearinghouse Worker Safety & Hlth Training, Washington, DC USA. NIEHS, NIH, HHS, Worker Educ & Training Program, Res Triangle Pk, NC 27709 USA. NIOSH, CDC, Off Director, Washington, DC USA. Johns Hopkins Bloomberg Sch Publ Hlth, Johns Hopkins Educ & Res Ctr Occupat Hlth & Safet, Dept Environm Hlth Sci, Baltimore, MD USA. RP Mitchell, CS (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, 615 N Wolfe St,Rm 7041, Baltimore, MD 21205 USA. EM cmitchel@jhsph.edu RI Mitchell, Clifford/K-3936-2015 FU ODCDC CDC HHS [CCT310419-03] NR 15 TC 3 Z9 3 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD NOV PY 2004 VL 46 IS 5 BP 423 EP 431 DI 10.1002/ajim.20091 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 870RZ UT WOS:000225076900001 PM 15490470 ER PT J AU Kitiyakara, C Eggers, P Kopp, JB AF Kitiyakara, C Eggers, P Kopp, JB TI Twenty-one-year trend in ESRD due to focal segmental glomerulosclerosis in the United States SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE black; white; African American; Asian; Hispanic; race; glomerulonephritis; age; sex; renal failure; dialysis ID NEPHROTIC SYNDROME; RENAL-DISEASE; GLOMERULAR-DISEASES; RACIAL-DIFFERENCES; KIDNEY-DISEASE; ADULTS; GLOMERULONEPHRITIS; EPIDEMIOLOGY; BIOPSY; PREVALENCE AB Background Focal segmental glomerulosclerosis (FSGS) is a clinicopathologic syndrome with a substantial risk for progression to end-stage renal disease (ESRD). Recent studies of renal biopsy archives in the United States suggest that the incidence of FSGS has increased. FSGS has become the leading cause of idiopathic nephrotic syndrome in the United States, with the greatest incidence rates in the black population. In the absence of a population-based estimate of FSGS incidence, we wished to obtain a population-based estimate of incident ESRD cases caused by FSGS (FSGS ESRD) and characterize temporal changes in this group. Methods: We examined the incidence of FSGS ESRD during a 21-year period (1980 to 2000) using data from the United States Renal Data System. We excluded patients who were classified as having acquired immunodeficiency syndrome nephropathy. Results: The annual incidence of FSGS ESRD has increased considerably, whether expressed as an absolute number or a fraction of the total incident ESRD population. Thus, the proportion of ESRD attributed to FSGS has increased 11-fold, from 0.2% in 1980 to 2.3% in 2000. The recent increase in incident FSGS ESRD cases likely is multifactorial in origin, with contributions from changes in renal biopsy practices, changes in disease classification, and a real increase in the incidence of FSGS disease. Black individuals have a 4-fold greater risk of FSGS ESRD than white or Asian individuals. The peak decade for FSGS ESRD incidence is 40 to 49 years among black subjects and 70 to 79 years among white and Asian individuals. Males have 1.5- to 2-fold greater risk than females. Conclusion:The incidence of FSGS ESRD has increased considerably in the United States, with black individuals at greatest risk. Idiopathic FSGS now is the most common cause of ESRD caused by primary glomerular disease in the United States in both the black and white populations. C1 NIDDKD, NIH, Kidney Sect, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIDDKD, NIH, Epidemiol Res Program, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Kopp, JB (reprint author), NIDDKD, NIH, Kidney Sect, Dept Hlth & Human Serv, 10-3N116, Bethesda, MD 20892 USA. EM jbkopp@nih.gov OI Kopp, Jeffrey/0000-0001-9052-186X NR 32 TC 124 Z9 138 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD NOV PY 2004 VL 44 IS 5 BP 815 EP 825 DI 10.1053/j.ajkd.2004.07.008 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 870FX UT WOS:000225044100008 PM 15492947 ER PT J AU Tsilou, ET Chan, CC Sandrini, F Rubin, BI Shen, DF Carney, JA Kaiser-Kupfer, M Stratakis, CA AF Tsilou, ET Chan, CC Sandrini, F Rubin, BI Shen, DF Carney, JA Kaiser-Kupfer, M Stratakis, CA TI Eyelid myxoma in carney complex without PRKAR1A allelic loss SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE multiple endocrine neoplasia; loss of heterozygosity ID ALPHA REGULATORY SUBUNIT; I-ALPHA; ENDOCRINE OVERACTIVITY; ADRENOCORTICAL TUMORS; MUTATIONS; GENE; CANCER; PIGMENTATION; DISEASE AB Eyelid nodules were investigated in a patient with Carney complex who was heterozygous for the most commonly known PRKAR1A-inactivating mutation, c.578delTG. Immunohistochemical studies confirmed the diagnosis of myxoma. Loss of heterozygosity was not present, suggesting that haploinsufficiency alone was responsible for tumorigenesis of this eyelid lesion. Published 2004 Wiley-Liss, Inc.(dagger) C1 NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NICHD, Sect Endocrinol & Genet, Dev Endocrinol Branch, NIH, Bethesda, MD USA. Mayo Clin, Rochester, MN USA. RP Tsilou, ET (reprint author), NEI, Ophthalm Genet & Visual Funct Branch, NIH, 10 Ctr Dr,MSC-1860,Bldg 10,Room 10N226, Bethesda, MD 20892 USA. EM tsiloue@nei.nih.gov NR 15 TC 13 Z9 13 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-7299 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD NOV 1 PY 2004 VL 130A IS 4 BP 395 EP 397 DI 10.1002/ajmg.a.30279 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 866OE UT WOS:000224782000012 PM 15368482 ER PT J AU Castle, PE Schiffman, M Wheeler, CM AF Castle, PE Schiffman, M Wheeler, CM CA ALTS Grp TI Hybrid capture 2 viral load and the 2-year cumulative risk of cervical intraepithelial neoplasia grade 3 or cancer SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE human papillomavirus; viral load; cervical intraepithelial neoplasia grade 3; cervical cancer ID ATYPICAL SQUAMOUS-CELLS; HUMAN-PAPILLOMAVIRUS DNA; CARCINOMA IN-SITU; UNDETERMINED SIGNIFICANCE; RANDOMIZED-TRIAL; CYTOLOGY INTERPRETATIONS; LESION TRIAGE; MANAGEMENT; WOMEN; WORLDWIDE AB Objective: The purpose of this study was to determine the clinical value of a semiquantitative measure of human papillomavirus viral load by the hybrid capture 2 assay for stratification of the risk of histologic cervical intraepithelial neoplasia grade 3 or carcinoma. Study design: The Atypical Cells of Unknown Significance and Low-Grade Squamous Intraepithelial Lesions Triage Study was a randomized clinical trial of 5060 women with 2 years of follow-up to evaluate treatment strategies for women with equivocal or mildly abnormal cervical cytologic condition. The usefulness of the continuous hybrid capture 2 output relative light units/positive controls that were above the positive threshold (1.0 relative light units/positive controls), which was a surrogate for human papillomavirus viral load, for distinguishing between hybrid capture 2 positive women who were diagnosed with cervical intraepithelial neoplasia grade 3 or carcinoma during the study from those who were not diagnosed with cervical intraepithelial neoplasia grade 3 or carcinoma was examined with the use of receiver-operator characteristic analyses. Results: Relative light units/positive controls values did not further discriminate between hybrid capture 2 positive women with cervical intraepithelial neoplasia grade 3 or carcinoma from those with less than cervical intraepithelial neoplasia grade 3 or carcinoma. The use of a cervical intraepithelial neoplasia grade 2 or more severe or carcinoma case definition did not alter our findings. Conclusion: Among women with atypical cells of unknown significance or low-grade squamous intraepithelial lesion cervical cytologic findings, the hybrid capture 2 viral load measurement did not improve the detection of 2-year cumulative cases of cervical intraepithelial neoplasia grade 3 or carcinoma significantly. (C) 2004 Elsevier Inc. All rights reserved. C1 NCI, Dept Hlth & Human Serv, NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ New Mexico, Sch Med, Hlth Sci Ctr, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. Univ New Mexico, Sch Med, Hlth Sci Ctr, Dept Obstet & Gynecol, Albuquerque, NM 87131 USA. RP Castle, PE (reprint author), NCI, Dept Hlth & Human Serv, NIH, Div Canc Epidemiol & Genet, 6120 Eecut Blvd,Room 7074,EPS MSC 7234, Bethesda, MD 20892 USA. EM castlep@mail.nih.gov FU NCI NIH HHS [CN-55153, CN-55105, CN-55154, CN-55155, CN-55156, CN-55157, CN-55158, CN-55159] NR 24 TC 22 Z9 24 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD NOV PY 2004 VL 191 IS 5 BP 1590 EP 1597 DI 10.1016/j.ajog.2004.05.018 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 874FY UT WOS:000225337500013 PM 15547529 ER PT J AU Alvero, R Lund, K Armstrong, A Vontver, L Schlaff, W AF Alvero, R Lund, K Armstrong, A Vontver, L Schlaff, W TI The development of a computer-assisted curriculum in reproductive endocrinology and infertility for residents SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT CREOG/APGO 2004 Annual Meeting CY MAR 03-06, 2004 CL Lake Buena Vista, FL SP CREOG, APGO DE computer-based learning; problem-based learning; evidence-based medicine ID EVIDENCE-BASED MEDICINE; EDUCATION; INTERNET; PROGRAM; PROFESSIONS; INSTRUCTION; STUDENTS; OUTCOMES; PACKAGE AB Objective: This study was undertaken to determine the features of an effective computer-based residency curriculum in reproductive endocrinology and infertility. Study design: A review of the literature to determine those features that have been used by training programs in medicine. Reproductive endocrinology and infertility division directors, current obstetrics and gynecology residents, and obstetrics and gynecology practitioners in the community were surveyed to evaluate critical subjects for study. Results: Programs most successful in using computers in training health care providers use a case-based approach that prioritizes important subjects. Areas of greatest importance to the 3 groups surveyed include infertility, dysfunctional uterine bleeding, and management of the climacteric, and several other areas were also deemed critical. Conclusion: Benefits of computer-based learning include consistency, the ability to develop problem solving skills for life-long learning, and a self-paced approach, but its validity as a teaching tool will require rigorous appraisal. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Colorado, Hlth Sci Ctr, Dept Obstet & Gynecol, Aurora, CO 80010 USA. NICHHD, Bethesda, MD 20892 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. RP Alvero, R (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Obstet & Gynecol, 1635 N Ursula St,Mail Stop F701, Aurora, CO 80010 USA. EM ruben.alvero@uchsc.edu NR 29 TC 3 Z9 3 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD NOV PY 2004 VL 191 IS 5 BP 1777 EP 1781 DI 10.1016/j.ajog.2004.07.052 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 874FY UT WOS:000225337500047 PM 15547563 ER PT J AU Kim, YM Romero, R AF Kim, YM Romero, R TI Failure of physiologic transformation of the spiral arteries of the uteroplacental circulation in patients with preterm labor and intact membranes - Reply SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Letter C1 Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, Perinatol Res Branch,NICHHD, Detroit, MI 48201 USA. RP Romero, R (reprint author), Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, Perinatol Res Branch,NICHHD, Detroit, MI 48201 USA. EM awarfiel@med.wayne.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD NOV PY 2004 VL 191 IS 5 BP 1838 EP 1839 DI 10.1016/j.ajog.2004.05.092 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 874FY UT WOS:000225337500064 ER PT J AU Li, J Hu, XY Selvakumar, P Russell, RR Cushman, SW Holman, GD Young, LH AF Li, J Hu, XY Selvakumar, P Russell, RR Cushman, SW Holman, GD Young, LH TI Role of the nitric oxide pathway in AMPK-mediated glucose uptake and GLUT4 translocation in heart muscle SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE nitric oxide synthase; AMP-activated protein kinase; glucose transporter ID ACTIVATED PROTEIN-KINASE; ACETYL-COA CARBOXYLASE; HUMAN SKELETAL-MUSCLE; FATTY-ACID OXIDATION; INSULIN-RESISTANCE; ENDOTHELIAL-CELLS; NO SYNTHASE; TRANSPORT; METABOLISM; EXERCISE AB AMP-activated protein kinase (AMPK) is a serine-threonine kinase that regulates cellular metabolism and has an essential role in activating glucose transport during hypoxia and ischemia. The mechanisms responsible for AMPK stimulation of glucose transport are uncertain, but may involve interaction with other signaling pathways or direct effects on GLUT vesicular trafficking. One potential downstream mediator of AMPK signaling is the nitric oxide pathway. The aim of this study was to examine the extent to which AMPK mediates glucose transport through activation of the nitric oxide (NO)-signaling pathway in isolated heart muscles. Incubation with 1 mM 5-amino-4-imidazole-1-beta-carboxamide ribofuranoside (AICAR) activated AMPK (P<0.01) and stimulated glucose uptake (P<0.05) and translocation of the cardiomyocyte glucose transporter GLUT4 to the cell surface (P<0.05). AICAR treatment increased phosphorylation of endothelial NO synthase (eNOS) &SIM;1.8-fold (P<0.05). eNOS, but not neuronal NOS, coimmunoprecipitated with both the alpha(2) and alpha(1) AMPK catalytic subunits in heart muscle. NO donors also increased glucose uptake and GLUT4 translocation (P<0.05). Inhibition of NOS with N-ω-nitro-L-arginine and N-ω-methyl-L-arginine reduced AICAR-stimulated glucose uptake by 21&PLUSMN;3% (P<0.05) and 25+/-4% (P<0.05), respectively. Inhibition of guanylate cyclase with ODQ and LY-83583 reduced AICAR-stimulated glucose uptake by 31&PLUSMN;4% (P<.05) and 22+/-3% (P<.05), respectively, as well as GLUT4 translocation to the cell surface (P<.05). Taken together, these results indicate that activation of the NO-guanylate cyclase pathway contributes to, but is not the sole mediator of, AMPK stimulation of glucose uptake and GLUT4 translocation in heart muscle. C1 Yale Univ, Sch Med, Dept Internal Med, Sect Cardiovasc Med, New Haven, CT 06520 USA. NIH, Bethesda, MD 20892 USA. Univ Bath, Dept Biol & Biochem, Bath BA2 7AY, Avon, England. RP Young, LH (reprint author), Yale Univ, Sch Med, Dept Internal Med, Sect Cardiovasc Med, TAC S460, New Haven, CT 06520 USA. EM lawrence.young@yale.edu OI Holman, Geoffrey/0000-0001-7045-1358 FU NHLBI NIH HHS [R01-HL-68311] NR 48 TC 123 Z9 126 U1 1 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD NOV PY 2004 VL 287 IS 5 BP E834 EP E841 DI 10.1152/ajpendo.00234.2004 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 860YU UT WOS:000224382400007 PM 15265762 ER PT J AU Jaruga, B Hong, F Kim, WH Gao, B AF Jaruga, B Hong, F Kim, WH Gao, B TI IFN-gamma/STAT1 acts as a proinflammatory signal in T cell-mediated hepatitis via induction of multiple chemokines and adhesion molecules: a critical role of IRF-1 SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE concanavalin A; interferon-gamma; liver injury; Kupffer cells; sinusoid epithelial cells ID A-INDUCED HEPATITIS; C VIRUS-INFECTION; IFN-INDUCIBLE PROTEIN-10; REGULATORY FACTOR-I; CONCANAVALIN-A; INTERFERON-GAMMA; LIVER-INJURY; INTRAHEPATIC EXPRESSION; FULMINANT-HEPATITIS; CXC CHEMOKINES AB We have previously shown that IFN-gamma/STAT1 plays an essential role in concanavalin A (ConA)-induced T cell hepatitis via activation of apoptotic signaling pathways. Here we demonstrate that IFN-gamma/STAT1 also plays a crucial role in leukocyte infiltration into the liver in T cell hepatitis. After injection of ConA, leukocytes were significantly infiltrated into the liver, which was suppressed in IFN-gamma(-/-) and STAT1(-/-) mice. Disruption of the IFN regulatory factor-1 (IRF-1) gene, a downstream target of IFN-gamma/STAT1, abolished ConA-induced liver injury and suppressed leukocyte infiltration into the liver. Additionally, ConA injection induced expression of a wide variety of chemokines and adhesion molecules in the liver. Among them, expression of ICAM-1, VCAM-1, monokine induced by IFN-gamma (Mig), CC chemokine ligand-20, epithelial cell-derived neutrophil-activating peptide (ENA)-78, IFN-inducible T cell-alpha chemoattractant (I-TAC), and IFN-inducible protein-10 (IP-10) was markedly attenuated in IFN-gamma(-/-) STAT1(-/-), and IRF-1(-/-) mice. In primary mouse hepatocytes, Kupffer cells, and endothelial cells, in vitro treatment with IFN-gamma activated STAT1, STAT3, and IRF-1, and induced expression of VCAM-1, ICAM-1, Mig, ENA-78, I-TAC, and IP-10 mRNA. Induction of these chemokines and adhesion molecules was markedly diminished in STAT1(-/-) and IRF-1(-/-) hepatic cells compared with wild-type hepatic cells. These findings suggest that in addition to induction of apoptosis, previously well documented, IFN-gamma also stimulated hepatocytes, sinusoidal endothelial cells, and Kupffer cells partly via an STAT1/IRF-1-dependent mechanism to produce multiple chemokines and adhesive molecules responsible for promoting infiltration of leukocytes and, ultimately, resulting in hepatitis. C1 NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. RP Gao, B (reprint author), NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Pk Bldg Rm 120,12420 Parklawn Dr,MSC 8115, Bethesda, MD 20892 USA. EM bgao@mail.nih.gov NR 53 TC 78 Z9 78 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD NOV PY 2004 VL 287 IS 5 BP G1044 EP G1052 DI 10.1152/ajpgi.00184.2004 PG 9 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 860YV UT WOS:000224382600015 PM 15246962 ER PT J AU Pacher, P Mabley, JG Liaudet, L Evgenov, OV Marton, A Hasko, G Kollai, M Szabo, C AF Pacher, P Mabley, JG Liaudet, L Evgenov, OV Marton, A Hasko, G Kollai, M Szabo, C TI Left ventricular pressure-volume relationship in a rat model of advanced aging-associated heart failure SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE systolic dysfunction; diastolic dysfunction ID POLY(ADP-RIBOSE) POLYMERASE ACTIVATION; ENDOTHELIAL DYSFUNCTION; STRUCTURAL-PROPERTIES; AORTIC CONSTRICTION; FISCHER-344 RATS; AGE; MYOCARDIUM; COLLAGEN; CONTRACTILITY; RELAXATION AB Aging is associated with profound changes in the structure and function of the heart. A fundamental understanding of these processes, using relevant animal models, is required for effective prevention and treatment of cardiovascular disease in the elderly. Here, we studied cardiac performance in 4- to 5-mo-old ( young) and 24- to 26-mo-old ( old) Fischer 344 male rats using the Millar pressure-volume (P-V) conductance catheter system. We evaluated systolic and diastolic function in vivo at different preloads, including preload recruitable stroke work (PRSW), maximal slope of the systolic pressure increment (+dP/dt), and its relation to end-diastolic volume (+dP/dt-EDV) as well as the time constant of left ventricular pressure decay, as an index of relaxation. The slope of the end-diastolic P-V relation (EDPVR), an index of left ventricular stiffness, was also calculated. Aging was associated with decrease in left ventricular systolic pressure, +dP/dt, maximal slope of the diastolic pressure decrement, +dP/dt-EDV, PRSW, ejection fraction, stroke volume, cardiac and stroke work indexes, and efficiency. In contrast, total peripheral resistance, left ventricular end-diastolic volume, left ventricular end-diastolic pressure, and EDPVR were greater in aging than in young animals. Taken together, these data suggest that advanced aging is characterized by decreased systolic performance accompanied by delayed relaxation and increased diastolic stiffness of the heart in male Fischer 344 rats. P-V analysis is a sensitive method to determine cardiac function in rats. C1 Inotek Pharmaceut Corp, Beverly, MA 01915 USA. Semmelweis Univ, Dept Pharmacol & Pharmacotherapy, H-1082 Budapest, Hungary. Univ Hosp, Dept Internal Med, Crit Care Div, CH-1005 Lausanne, Switzerland. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA. Hungarian Acad Sci, Inst Expt Med, Dept Pharmacol, H-1083 Budapest, Hungary. Inst Human Physiol & Clin Expt Res, H-1082 Budapest, Hungary. RP Pacher, P (reprint author), NIAAA, Lab Physiol Studies, NIH, 12420 Parklawn Dr,MSC-8115, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov RI Mabley, Jon/D-2296-2010; Pacher, Pal/B-6378-2008; Liaudet, Lucas/E-1322-2017 OI Pacher, Pal/0000-0001-7036-8108; Liaudet, Lucas/0000-0003-2670-4930 FU Intramural NIH HHS [Z99 AA999999]; NIA NIH HHS [R01AG59266, 1R03-AG-21206-01] NR 40 TC 78 Z9 79 U1 2 U2 10 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD NOV PY 2004 VL 287 IS 5 BP H2132 EP H2137 DI 10.1152/ajpheart.00405.2004 PG 6 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 860TO UT WOS:000224366400037 PM 15231502 ER PT J AU Hostetter, TH Meyer, TW AF Hostetter, TH Meyer, TW TI The development of clearance methods for measurement of glomerular filtration and tubular reabsorption SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Editorial Material ID EXCRETION AB This essay looks at the historical significance of four APS classic papers that are freely available online: Jolliffe N, Shannon JA, and Smith HW. The excretion of urine in the dog. III. The use of non-metabolized sugars in the measurement of the glomerular filtrate. Am J Physiol 100: 301-312, 1932 (http://ajplegacy.physiology.org/cgi/reprint/100/2/301). Shannon JA. The excretion of inulin by the dog. Am J Physiol 112: 405-413, 1935 (http://ajplegacy.physiology.org/cgi/reprint/112/3/405). Shannon JA and Fisher S. The renal tubular reabsorption of glucose in the normal dog. Am J Physiol 122: 765-774, 1938 (http://ajplegacy.physiology.org/cgi/reprint/122/3/765). Shannon JA, Farber S, and Troast L. The measurement of glucose Tm in the normal dog. Am J Physiol 133: 752-761, 1941 (http://ajplegacy.physiology.org/cgi/reprint/133/3/752). C1 NIDDKD, NIH, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Dept Med,Div Nephrol, Palo Alto Vet Affairs Hlth Care Syst, Palo Alto, CA 94303 USA. RP Hostetter, TH (reprint author), NIDDKD, NIH, 6707 Democracy Blvd, Bethesda, MD 20892 USA. EM hostettert@extra.niddk.nih.gov; twmeyer@stanford.edu NR 11 TC 5 Z9 5 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD NOV PY 2004 VL 287 IS 5 BP F868 EP F870 DI 10.1152/classicessays.00009.2004 PG 3 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 860RO UT WOS:000224360900005 PM 15475540 ER PT J AU Praetorius, HA Praetorius, J Nielsen, S Frokiaer, J Spring, KR AF Praetorius, HA Praetorius, J Nielsen, S Frokiaer, J Spring, KR TI beta(1)-Integrins in the primary cilium of MDCK cells potentiate fibronectin-induced Ca(2+) signaling SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE intracellular calcium ion; antibody; Madin-Darby canine kidney cells; fibronectin; fluorescence imaging ID CANINE KIDNEY-CELLS; ENDOTHELIAL-CELLS; INTEGRIN; CALCIUM; ADHESION; PROTEIN; STRESS; FLOW; MECHANOTRANSDUCTION; TRANSDUCTION AB Because beta(1)-integrin is involved in sensing of fluid flow rate in endothelial cells, a function that in Madin-Darby canine kidney (MDCK) cells is confined to the primary cilium, we hypothesized beta(1)-integrin to be an important part of the primary ciliary mechanosensory apparatus in MDCK cells. We observed that beta(1)-integrin, alpha(3)-integrin, and perhaps alpha(5)-integrin were localized to the primary cilium of MDCK cells by combining lectin and immunofluorescence confocal microscopy. beta(1)-Integrin was also colocalized with tubulin to the primary cilia of the rat renal collecting ducts, as well as to the cilia of proximal tubules and thick ascending limbs. Immunogold-electron microscopy confirmed the presence of beta(1)-integrin on primary cilia of MDCK cells and rat collecting ducts. Intracellular Ca(2+) levels, monitored by fluorescence microscopy on fluo 4-loaded MDCK cells, significantly increased on addition of fibronectin, a beta(1)-integrin ligand, to mature MDCK cells with an IC(50) of 0.02 mg/l. In immature, nonciliated cells or in deciliated mature cells, the IC(50) was 0.40 mg/l. Blocking the fibronectin-binding sites of beta(1)-integrin with RGD peptide prevented the Ca(2+) signal. Crosslinking of beta(1)-integrins by Sambucus nigra agglutinin produced a Ca(2+) response similar to the addition of fibronectin. Furthermore, the fibronectin-induced response was not dependent on flow or a flow-induced Ca(2+) response. Finally, the flow-induced Ca(2+) response was not prevented by the fibronectin-induced signal. Although beta(1)-integrin on the primary cilium greatly potentiates the fibronectin-induced Ca(2+) signaling in MDCK cells, the flow-dependent Ca(2+) signal is not mediated through activation of beta(1)-integrin. C1 Univ Aarhus, Water & Salt Res Ctr, DK-8200 Aarhus, Denmark. Univ Aarhus, Inst Clin, DK-8200 Aarhus, Denmark. Univ Aarhus, Inst Anat, DK-8200 Aarhus, Denmark. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Praetorius, HA (reprint author), Univ Aarhus, Clin Inst, Water & Salt Res Ctr, Brendstrupgaardsvej, DK-8200 Aarhus N, Denmark. EM Helle.Praetorius@ki.au.dk NR 32 TC 52 Z9 53 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD NOV PY 2004 VL 287 IS 5 BP F969 EP F978 DI 10.1152/ajprenal.00096.2004 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 860RO UT WOS:000224360900018 PM 15226154 ER PT J AU London, SJ Promislow, JHE AF London, SJ Promislow, JHE TI Breastfeeding and asthma in adolescents SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Letter ID DURATION; BRAZIL C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP London, SJ (reprint author), NIEHS, Epidemiol Branch, Mail Drop A3-05,POB 12233, Res Triangle Pk, NC 27709 USA. EM london2@niehs.nih.gov NR 5 TC 0 Z9 0 U1 1 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD NOV PY 2004 VL 94 IS 11 BP 1843 EP 1843 DI 10.2105/AJPH.94.11.1843 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 866NS UT WOS:000224780800005 PM 15514216 ER PT J AU Brown, TM Fee, E AF Brown, TM Fee, E TI A role for public health history SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 Univ Rochester, Dept Hist, Rochester, NY 14627 USA. Univ Rochester, Dept Community & Prevent Med, Rochester, NY 14627 USA. Natl Lib Med, NIH, Hist Med Div, Bethesda, MD USA. RP Brown, TM (reprint author), Univ Rochester, Dept Hist, Rochester, NY 14627 USA. EM theodore_brown@urmc.rochester.edu NR 17 TC 2 Z9 2 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD NOV PY 2004 VL 94 IS 11 BP 1851 EP 1853 DI 10.2105/AJPH.94.11.1851 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 866NS UT WOS:000224780800012 PM 15514219 ER PT J AU McQuillan, GM Kruszon-Moran, D Kottiri, BJ Curtin, LR Lucas, JW Kington, RS AF McQuillan, GM Kruszon-Moran, D Kottiri, BJ Curtin, LR Lucas, JW Kington, RS TI Racial and ethnic differences in the seroprevalence of 6 infectious diseases in the United States: Data from NHANES III, 1988-1994 SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID SOCIOECONOMIC-STATUS; MORTALITY; PREVALENCE AB Objectives. We examined racial/ethnic differences in the seroprevalence of selected infectious agents in analyses stratified according to risk categories to identify patterns and to determine whether demographic, socioeconomic, and behavioral characteristics explain these differences. Methods. We analyzed data from the third National Health and Nutrition Examination Survey, comparing differences among groups in regard to the prevalence of infection with hepatitis A, B, and C viruses, Toxoplasma gondii, Helicobacter pylori, and herpes simplex virus type 2. Results. Racial/ethnic differences were greater among those in the low-risk category. In the case of most infectious agents, odds associated with race/ethnicity were almost 2 times greater in that category than in the high-risk category. Conclusions. Stratification and adjustment for socioeconomic factors reduced or eliminated racial/ethnic differences in the prevalence of infection in the high-risk but not the low-risk group, wherein race/ethnicity remained significant and might have been a surrogate for unmeasured risk factors. C1 Natl Ctr Hlth Stat, Div Hlth Examinat Surveys, Hyattsville, MD 20782 USA. Natl Ctr Hlth Stat, Div Hlth Interview Stat, Hyattsville, MD 20782 USA. NIH, Bethesda, MD 20892 USA. RP McQuillan, GM (reprint author), Natl Ctr Hlth Stat, Div Hlth Examinat Surveys, 3311 Toledo Rd,Room 4204, Hyattsville, MD 20782 USA. EM gmm2@cdc.gov NR 18 TC 67 Z9 68 U1 0 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD NOV PY 2004 VL 94 IS 11 BP 1952 EP 1958 DI 10.2105/AJPH.94.11.1952 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 866NS UT WOS:000224780800029 PM 15514236 ER PT J AU Kirk, AD AF Kirk, AD TI What's new - What's hot in basic science: American Transplant Congress 2004 SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material DE transplantation immunology; rejection ID ENDOTHELIAL GROWTH-FACTOR; RENAL-ALLOGRAFT REJECTION; REGULATORY T-CELLS; NONHUMAN-PRIMATES; JAK-STAT; TOLERANCE; IMMUNITY; PROLIFERATION; SUPPRESSORS; PROTEINS AB The field of transplantation biology has, in the past year, given rise to several improved models explaining the in vivo phenomena of allograft rejection and acceptance. Although T-cells remain central participants in allorecognition, innate immune cells are increasingly recognized as critical. There is also growing acceptance that T-cell responses can vary widely not only based on their repertoire, but also on their immune experience in general, and their participation in homeostatic proliferation. Additional signaling pathways and molecules, such as the Janus kinase pathway and vascular endothelial growth factor have been added to those recognized as important in pharmacologic immunosuppression, and the concepts of regulation, once polarized between CD8+ and CD4+ camps, have begun to converge upon a recognition that there are many phenotypes of regulatory cells. In addition to improved basic science, several translational fields have accelerated in the past 12 months. Promising and clinically applicable islet transplant regimens have been developed and look appropriate for near-term clinical trials. Significant progress in discordant xenotransplantation is also apparent. This manuscript will review the past year in transplantation science as reported at the 2004 American Transplant Congress. C1 NIDDKD, Transplantat Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Kirk, AD (reprint author), NIDDKD, Transplantat Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. EM allank@intra.niddk.nih.gov RI Kirk, Allan/B-6905-2012 NR 31 TC 2 Z9 3 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 NOV PY 2004 VL 4 IS 11 BP 1741 EP 1746 DI 10.1111/j.1600-6143.2004.00632.x PG 6 WC Surgery; Transplantation SC Surgery; Transplantation GA 861RD UT WOS:000224435000006 PM 15476470 ER PT J AU Ottesen, EA Weil, GJ Lammie, PJ Bradley, MH Kumaraswami, V Addiss, DG Mackenzie, C Malecela-Lazaro, M Twum-Danso, N Gyapong, JO Dadzie, KY Basanez, MG Richards, F Burkot, T Bockarie, M McFarland, DA Barrett, LC King, CL Kazura, JW Hoerauf, A Steel, C Williams, SA AF Ottesen, EA Weil, GJ Lammie, PJ Bradley, MH Kumaraswami, V Addiss, DG Mackenzie, C Malecela-Lazaro, M Twum-Danso, N Gyapong, JO Dadzie, KY Basanez, MG Richards, F Burkot, T Bockarie, M McFarland, DA Barrett, LC King, CL Kazura, JW Hoerauf, A Steel, C Williams, SA TI Towards a strategic plan for research to support the global program to eliminate lymphatic filariasis - Summary of immediate needs and opportunities for research on lymphatic filariasis identified by the Filariasis community of scientists in association with an "LF research forum", convened in Philadelphia, December 9-10, 2003 SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Review ID WUCHERERIA-BANCROFTI INFECTION; POLYMERASE-CHAIN-REACTION; LOA-LOA INFECTION; PAPUA-NEW-GUINEA; LARVAL ONCHOCERCA-VOLVULUS; VECTOR-CONTROL SYNERGIES; BRUGIA-MALAYI INFECTION; RAPID DIPSTICK TEST; ROLL BACK MALARIA; PROTECTIVE IMMUNITY AB The Global Program to Eliminate Lymphatic Filariasis (GPELF), now four years old and clearly providing enormous health benefits from its broad deworming effects in the poorest sectors of the developing world, represents a societal investment already measured in the tens of millions of dollars. Despite rapid progress in scaling up the program to more than 38 endemic countries (or perhaps even because of this rapid progress), there is one element essential for ultimate program success that is now being severely neglected-research, both operational and basic (upstream). The dramatic research successes in developing effective tools and strategies during the 1980s and 1990s provided the foundation for the GPELF. Generous public-private partnerships enabled its implementation, in concert with the 1997 formal resolution by the World Health Assembly calling for the elimination of LF as a public health problem worldwide. Implementation alone, however, does not guarantee success. An essential characteristic of all successful public health programs is the continuing involvement of an active research community ready to provide solutions for program problems as they arise and for anticipated problems or barriers that might appear during program activities. Indeed, such operational research must be especially vigorous and focused in programs (such as the GPELF) with a time-limited goal for disease elimination. For lessons to be learned, program strategies improved, and activities made more effective and cost-efficient, there must be a problem-solving research community actively engaged with the ongoing program initiatives and focused on their challenges. Furthermore, for diseases such as LF, the neglected 10/90 diseases of poverty, where research funds are particularly limited, it is especially critical that the most acute research needs of the program be accurately identified, effectively prioritized, and clearly laid out so that the research community and the organizations supporting it can recognize the most important opportunities available and focus their resources accordingly. It was toward this end that efforts were made during 2003-2004 to gather diverse and valued input from a very broad representation of the filariasis community, both program and research oriented. More than 90 research, clinical, and public health experts in LF came together in meetings (Annexes 1-3) and deliberations for the purpose of creating a comprehensive, collective assessment of today's LF research horizon and research needs. While there was broad agreement that the GPELF remains very much on target, in-depth assessments were made of ways to improve program support or increase understanding for each of the most important issues related to operational and basic, upstream research. For each of these domains, needs and opportunities were first defined and then prioritized. For program-oriented, operational research the greatest needs fall into four clusters: 1) to establish the tools and measures of program success by a) evaluating comparatively the diagnostics and sampling strategies available, both in humans and in vectors, b) testing the endpoints for declaring transmission interruption, c) creating/testing sets of indicators developed to monitor i) morbidity-control/disability-prevention efforts, ii) multi-disease integrated program activities, iii) the GPELF impact on national health systems, 2) to enhance current program effectiveness by a) identifying adjunctive measures that could reduce the number of mass drug administrations (MDAs) required to achieve success (e.g., vector control, modified regimens of available drugs), b) refining predictive models for decision-making, c) improving methods and tools to treat difficult populations (especially urban and Loa-endemic communities), d) integrating LF programs with others having cost-effective complementarities, e) optimizing social mobilization techniques, and f) developing creative advocacy and fundraising strategies, 3) to ensure good clinical/morbidity management by a) standardizing clinical terminology and technical approaches to patient assessment, b) establishing best practices for home-based care for lymphedema, surgical care for hydrocoele/tymphocoele, and treatment for individuals with LF infection, c) assessing reversibility of clinical/subclinical LF disease, 4) to protect effectiveness of drug-based PELFs by a) establishing a definition for decreasing drug sensitivity, b) developing parasite repositories and surveillance for genotypic signs of drug resistance, c) continuing new and alternative drug development. Particularly important for upstream research study are those issues defining the 1) effect of LF co-infections on clinical expression of other diseases and on responsiveness to routine vaccines, 2) mechanisms that determine the pathogenesis of lymphatic disease and its clinical expression, 3) susceptibility and resistance to LF and the effect of MDA on natural immunity to LF in treated populations, 4) genomics and proteomics of filarial parasites It is clear that public health programs require both implementers and problem solvers. When problems loom large, society invests greatly in problem solving (i.e., research). When solutions are found, investments appropriately shift towards implementation. It is essential to recognize, however, that the need for problem solving (even to develop increased program efficiencies or cost-effectiveness) remains, and if not supported, threatens the very success of the program, putting at risk not only society's initial investment but also the health and welfare of the underserved populations for whom the program was created. The LF Research Community and their programmatic colleagues have deliberated extensively to define how best to strengthen the GPELF to ensure its immediate success and to enhance its research base to ensure longterm availability of problem solving research to provide solutions for program needs that are sure to arise. The clearer understanding that has emerged now promises to create a much stronger, more effective partnership between the implementing and research communities of the GPELF and the public and private funding organizations whose support is so essential for program success. C1 Emory Univ, Atlanta, GA 30322 USA. Washington Univ, Sch Med, St Louis, MO USA. Ctr Dis Control & Prevent, Atlanta, GA USA. GlaxoSmithKline, Brentford, England. TB Res Ctr, Madras, Tamil Nadu, India. Michigan State Univ, E Lansing, MI 48824 USA. Task Force Child Survival & Dev, Decatur, GA USA. Minist Hlth, Accra, Ghana. Global Alliance Eliminate LF, Accra, Ghana. Univ London Imperial Coll Sci Technol & Med, London, England. Papua New Guinea Inst Med Res, Madang, Papua N Guinea. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Bonn, D-5300 Bonn, Germany. NIH, Bethesda, MD 20892 USA. Smith Coll, Northampton, MA 01063 USA. RP Emory Univ, Atlanta, GA 30322 USA. RI Burkot, Thomas/C-6838-2013 NR 197 TC 8 Z9 8 U1 0 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 NOV PY 2004 VL 71 IS 5 SU S BP 1 EP 46 PG 46 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 877SA UT WOS:000225589200001 ER PT J AU Yamaguchi, N Kitchener, AC Driscoll, CA Ward, JM Macdonald, DW AF Yamaguchi, N Kitchener, AC Driscoll, CA Ward, JM Macdonald, DW TI Craniological differentiation amongst wild-living cats in Britain and southern Africa: natural variation or the effects of hybridisation? SO ANIMAL CONSERVATION LA English DT Article ID FELIS-SILVESTRIS; DOMESTIC CATS; POPULATIONS; SCOTLAND; HYBRIDS AB The natural morphological variation in the wildcat, Felis silvestris, and morphological changes possibly caused by introgressive hybridisation with the domestic cat, F catus, were examined, based on up to 39 variables concerning cranial morphology. The samples of wild-living cats originated from Scotland and southern Africa and consisted of both classical wildcat and other pelage types. Principal component and cluster analyses suggested that introgressive hybridisation occurred in both areas, with the consequence that the characteristics of local wildcat populations had been altered in terms of the frequencies of occurrence of certain characters, especially those concerning cranial capacity. In both regions the clustering patterns of wild-living cats can be interpreted as containing four main groups. One of these consisted mainly of 'non-wildcats' and groups furthest from the 'non-wild' cluster consisted of the highest proportion of 'wildcats' (c. 80%). We propose that where a population is heavily introgressed, the only feasible way to define a wildcat is on the basis of inter-correlated features and conservationists must take a population-based approach to assess the extent of introgression. This approach may provide an operational standard for assessing the impact of hybridisation between wildcats and domestic cats throughout the species' range; it suggests that the Scottish wildcats may be critically endangered. C1 Wildlife Conservat Res Unit, Dept Zool, Oxford OX1 3PS, England. Natl Museums Scotland, Edinburgh EH1 1JF, Midlothian, Scotland. NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP Yamaguchi, N (reprint author), Wildlife Conservat Res Unit, Dept Zool, S Parks Rd, Oxford OX1 3PS, England. EM nobuyuki.yamaguchi@zoo.ox.ac.uk OI Driscoll, Carlos/0000-0003-2392-505X NR 32 TC 16 Z9 16 U1 1 U2 15 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1367-9430 J9 ANIM CONSERV JI Anim. Conserv. PD NOV PY 2004 VL 7 BP 339 EP 351 DI 10.1017/S1367943004001520 PN 4 PG 13 WC Biodiversity Conservation; Ecology SC Biodiversity & Conservation; Environmental Sciences & Ecology GA 878SJ UT WOS:000225666800002 ER PT J AU Norton, JA Jensen, RT AF Norton, JA Jensen, RT TI Resolved and unresolved controversies in the surgical management of patients with Zollinger-Ellison syndrome SO ANNALS OF SURGERY LA English DT Review ID MULTIPLE ENDOCRINE NEOPLASIA; SOMATOSTATIN-RECEPTOR SCINTIGRAPHY; ISLET-CELL TUMORS; COMPARATIVE GENOMIC HYBRIDIZATION; ENTEROCHROMAFFIN-LIKE CELLS; LAPAROSCOPIC RADIOFREQUENCY ABLATION; HEPATIC ARTERIAL CHEMOEMBOLIZATION; GASTRIC-ACID HYPERSECRETION; PRIMARY NODAL GASTRINOMAS; DUODENAL CARCINOID-TUMOR AB Objective: Highlight unresolved controversies in the management of Zollinger-Ellison syndrome (ZES). Summary Background Data: Recent studies have resolved some of the previous controversies including the surgical cure rate in patients with and without Multiple Endocrine Neoplasia-type1 (MEN1), the biological behavior of duodenal and pancreatic gastrinomas, role of imaging studies to localize tumor, and gastrectomy to manage acid output. Methods: Review of the literature based on computer searches in Index Medicus, Pubmed and Ovid. Results: Current controversies as identified in the literature include the role of endoscopic ultrasound (EUS), surgery in ZES patients with MEN1, pancreaticoduodenectomy (Whipple procedure), lymph node primary gastrinoma, parietal cell vagotomy, reoperation and surgery for metastatic tumor, and the use of minimally invasive surgical techniques to localize and remove gastrinoma. Conclusions: It is hoped that future studies will focus on these issues to improve the surgical management of ZES patients. C1 Stanford Univ, Med Ctr, Dept Surg, Stanford, CA 94305 USA. NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Norton, JA (reprint author), Stanford Univ, Med Ctr, Dept Surg, Rm H-3591,300 Pasteur Dr, Stanford, CA 94305 USA. EM janorton@stanford.edu NR 284 TC 116 Z9 125 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD NOV PY 2004 VL 240 IS 5 BP 757 EP 773 DI 10.1097/01.sla.0000143252.02142.3e PG 17 WC Surgery SC Surgery GA 865YD UT WOS:000224739200005 PM 15492556 ER PT J AU O'Shea, JJ AF O'Shea, JJ TI Targeting the Jak/STAT pathway for immunosuppression SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article; Proceedings Paper CT 6th International Symposium on Advances in Targeted Therapies CY APR 28-MAY 02, 2004 CL Venice, ITALY ID SEVERE COMBINED IMMUNODEFICIENCY; PROTEIN-TYROSINE KINASE; CYTOKINE SIGNAL-TRANSDUCTION; COMBINED IMMUNE-DEFICIENCY; NATURAL-KILLER-CELLS; JAK-3 JANUS KINASE; COMMON GAMMA-CHAIN; CD8 T-CELLS; IL-2 RECEPTOR; TRANSCRIPTION FACTORS C1 NIAMSD, NIH, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA. RP O'Shea, JJ (reprint author), NIAMSD, NIH, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA. EM osheajo@mail.nih.gov NR 68 TC 46 Z9 46 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD NOV PY 2004 VL 63 SU 2 BP 67 EP 71 DI 10.1136/ard.2004.028290 PG 5 WC Rheumatology SC Rheumatology GA 865VD UT WOS:000224731000014 ER PT J AU Hope, WW Tabernero, L Denning, DW Anderson, MJ AF Hope, WW Tabernero, L Denning, DW Anderson, MJ TI Molecular mechanisms of primary resistance to flucytosine in Candida albicans SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID GONDII URACIL PHOSPHORIBOSYLTRANSFERASE; SACCHAROMYCES-CEREVISIAE; GENE-PRODUCT; FUR1 GENE; 5-FLUOROCYTOSINE; PURIFICATION; EXPRESSION; SYSTEM; CLADE; UMP AB Primary resistance in Candida albicans to flucytosine (5-FC) was investigated in 25 strains by identifying and sequencing the genes FCA1, FUR1, FCY21, and FCY22, which code for cytosine deaminase, uracil phosphoribosyltransferase (UPRT), and two purine-cytosine permeases, respectively. These proteins are involved in pyrimidine salvage and 5-FC metabolism. An association between a polymorphic nucleotide and resistance to 5-FC was found within FUR1 where the substitution of cytidylate for thymidylate at nucleotide position 301 results in the replacement of arginine with cysteine at amino acid position 101 in UPRT. Isolates that are homozygous for this mutation display increased levels of resistance to 5-FC, whereas heterozygous isolates have reduced susceptibility. Three-dimensional protein modeling of UPRT suggests that the Arg101Cys mutation disturbs the quaternary structure of the enzyme, which is postulated to compromise optimal enzyme activity. A single resistant isolate, lacking the above polymorphism in FUR1, has a homozygous polymorphism in FCA1 that results in a glycine-to-aspartate substitution at position 28 in cytosine deaminase. C1 Univ Manchester, Sch Med, Manchester M13 9PT, Lancs, England. Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England. RP Hope, WW (reprint author), NCI, NIH, CRC, Immunocompromised Host Sect, Room 1-5700,10 Ctr Dr,MSC 1100, Bethesda, MD 20892 USA. EM hopew@mail.nih.gov OI Tabernero, Lydia/0000-0001-8867-455X; Denning, David/0000-0001-5626-2251; Hope, William/0000-0001-6187-878X NR 28 TC 51 Z9 64 U1 2 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD NOV PY 2004 VL 48 IS 11 BP 4377 EP 4386 DI 10.1128/AAC.48.11.4377-4386.2004 PG 10 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 869XM UT WOS:000225017900044 PM 15504867 ER PT J AU Borucki, MJ Spritzler, J Asmuth, DM Gnann, J Hirsch, MS Nokta, M Aweeka, F Nadler, PI Sattler, F Alston, B Nevin, TT Owens, S Waterman, K Hubbard, L Caliendo, A Pollard, RB AF Borucki, MJ Spritzler, J Asmuth, DM Gnann, J Hirsch, MS Nokta, M Aweeka, F Nadler, PI Sattler, F Alston, B Nevin, TT Owens, S Waterman, K Hubbard, L Caliendo, A Pollard, RB CA AACTG 266 Team TI A phase II, double-masked, randomized, placebo-controlled evaluation of a human monoclonal anti-Cytomegalovirus antibody (MSL-109) in combination with standard therapy versus standard therapy alone in the treatment of AIDS patients with Cytomegalovirus retinitis SO ANTIVIRAL RESEARCH LA English DT Article DE MSL-109; AIDS; cytomegalovirus retinitis; cytomegalovirus; monoclonal antibody ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; MARROW-TRANSPLANT RECIPIENTS; STEM-CELL TRANSPLANTATION; HUMORAL IMMUNE-RESPONSE; ACQUIRED-IMMUNODEFICIENCY; GANCICLOVIR THERAPY; INFECTION; DISEASE; TRIAL AB ACTG 266 was designed as a randomized study to evaluate two doses of the human monoclonal antibody directed against CMV gH (MSL-109) versus placebo, each in combination with standard antiviral therapy for the treatment of newly diagnosed Cytomegalovirus (CMV) retinitis in AIDS patients. A total of 82 subjects were enrolled and received either placebo (n = 28), or MSL-109 at 15 mg (n = 26) or 60 mg (n = 28) every 2 weeks until disease progression was diagnosed. The primary endpoint, disease progression, was determined by masked reading of retinal photographs taken every 4 weeks read by a single investigator. The median time to progression was 8.0, 8.3, and 12.1 weeks in the placebo, MSL-109 15 mg, and MSL-109 60 mg cohorts, respectively (P = 0.087, placebo versus 60 mg cohort). There were 22 deaths during the study period (9, 9, and 4 in the placebo. MSL-109 15 mg and MSL-109 60 mg cohorts, respectively (P = 0.0058, placebo versus 60 mg cohort)). MSL-109 was well tolerated with no significant adverse events attributable to study medication. The unexplained survival advantage in the higher dose cohort was discordant with the findings of the parallel Studies of ocular Complications of AIDS Research Group (SOCA)-Monoclonal Anti-CMV Retinitis Trial (MACRT), which was prematurely halted because of increased mortality in subjects treated with high-dose MSL-109, recognizing that A266 enrolled subjects with newly diagnosed, whereas the MACRT enrolled subjects with relapsed, CMV retinitis. (C) 2004 Elsevier B.V. All rights reserved. C1 Univ Calif Davis, Med Ctr, Div Infect Dis, Sacramento, CA 95817 USA. Univ Texas, Ctr Hlth, Tyler, TX USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Alabama, Birmingham, AL USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Prot Design Labs, Mountain View, CA USA. Univ So Calif, Keck Sch Med, Los Angeles, CA USA. NIH, Bethesda, MD 20892 USA. Social & Sci Syst Inc, Silver Spring, MD USA. Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Univ Wisconsin, Madison, WI USA. Emory Univ Hosp, Atlanta, GA 30322 USA. RP Asmuth, DM (reprint author), Univ Calif Davis, Med Ctr, Div Infect Dis, 4150 V St,PSSB Suite G500, Sacramento, CA 95817 USA. EM david.asmuth@ucdmc.ucdavis.edu FU NCRR NIH HHS [RR00044]; NEI NIH HHS [U01 EY08057]; NIAID NIH HHS [AI-27658, U01 AI 32783]; PHS HHS [U01A127673-14] NR 44 TC 14 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD NOV PY 2004 VL 64 IS 2 BP 103 EP 111 DI 10.1016/j.antivirial.2004.06.012 PG 9 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 868XR UT WOS:000224946900004 PM 15498605 ER PT J AU Pipe, ME Sutherland, R Webster, N Jones, C La Rooy, D AF Pipe, ME Sutherland, R Webster, N Jones, C La Rooy, D TI Do early interviews affect children's long-term event recall? SO APPLIED COGNITIVE PSYCHOLOGY LA English DT Article ID FUZZY-TRACE THEORY; EYEWITNESS TESTIMONY; PRESCHOOLERS MEMORIES; MEDICAL EMERGENCIES; QUESTION REPETITION; RETENTION INTERVAL; TIME; REINSTATEMENT; ADULTS; AGAIN AB The present study examined the effects of the timing of an initial interview on children's recall of an event over delays of I and 2 years. Fifty-five children who had originally participated in a novel event when they were between 5- and 6-years old and had been interviewed about it following either short (I week or less) or long (I or 6 month) delays were re-interviewed I and 2 years after the original experience. An additional 20 children not interviewed prior to the 1-year interview were included as a no-prior-interview control group. Long delays to the initial interview led to better open-ended recall at the I-year delay than short delays to initial interview or no prior interview. However, initial interviews that followed short delays had a greater impact on children's responses to specific questions. The results suggest that prior interview history is an important consideration when examining the effects of long delays on children's event reports, and that the effects of the timing of an initial interview depend on the nature of the information recalled. Copyright (C) 2004 John Wiley Sons, Ltd. C1 NICHHD, Sect Social & Emot Dev, Bethesda, MD 20892 USA. Victoria Univ Wellington, Wellington, New Zealand. Univ Otago, Dunedin, New Zealand. RP Pipe, ME (reprint author), NICHHD, Sect Social & Emot Dev, Rockledge 1 Ctr,Suite 8048,6705 Rockledge Dr, Bethesda, MD 20892 USA. EM pipem@mail.nih.gov RI la rooy, david/A-2104-2009 NR 65 TC 12 Z9 12 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0888-4080 J9 APPL COGNITIVE PSYCH JI Appl. Cogn. Psychol. PD NOV PY 2004 VL 18 IS 7 BP 823 EP 839 DI 10.1002/acp.1053 PG 17 WC Psychology, Experimental SC Psychology GA 870ED UT WOS:000225035900003 ER PT J AU Rao, MR Brenner, RA Schisterman, EF Vik, T Mills, JL AF Rao, MR Brenner, RA Schisterman, EF Vik, T Mills, JL TI Long term cognitive development in children with prolonged crying SO ARCHIVES OF DISEASE IN CHILDHOOD LA English DT Article ID FOR-GESTATIONAL-AGE; BREAST-FED INFANTS; SMOKING; PREGNANCY AB Background: Long term studies of cognitive development and colic have not differentiated between typical colic and prolonged crying. Objective: To evaluate whether colic and excessive crying that persists beyond 3 months is associated with adverse cognitive development. Design: Prospective cohort study. A sample of 561 women was enrolled in the second trimester of pregnancy. Colic and prolonged crying were based on crying behaviour assessed at 6 and 13 weeks. Children's intelligence, motor abilities, and behaviour were measured at 5 years (n=327). Known risk factors for cognitive impairment were ascertained prenatally, after birth, at 6 and 13 weeks, at 6, 9, and 13 months, and at 5 years of age. Results: Children with prolonged crying (but not those with colic only) had an adjusted mean IQ that was 9 points lower than the control group. Their performance and verbal IQ scores were 9.2 and 6.7 points lower than the control group, respectively. The prolonged crying group also had significantly poorer fine motor abilities compared with the control group. Colic had no effect on cognitive development. Conclusions: Excessive, uncontrolled crying that persists beyond 3 months of age in infants without other signs of neurological damage may be a marker for cognitive deficits during childhood. Such infants need to be examined and followed up more intensively. C1 NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. Norwegian Univ Sci & Technol, Dept Community Med & Gen Practice, N-7034 Trondheim, Norway. RP Rao, MR (reprint author), NIAID, Parasitol & Int Programs Branch, NIH, 6610 Rockledge Dr,Room 5095, Bethesda, MD 20892 USA. EM mr8u@nih.gov OI Schisterman, Enrique/0000-0003-3757-641X NR 31 TC 46 Z9 49 U1 2 U2 7 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-9888 J9 ARCH DIS CHILD JI Arch. Dis. Child. PD NOV PY 2004 VL 89 IS 11 BP 989 EP 992 DI 10.1136/adc.2003.039198 PG 4 WC Pediatrics SC Pediatrics GA 865IU UT WOS:000224696700002 PM 15499048 ER PT J AU Grant, BF Hasin, DS Chou, SP Stinson, FS Dawson, DA AF Grant, BF Hasin, DS Chou, SP Stinson, FS Dawson, DA TI Nicotine dependence and psychiatric disorders in the United States - Results from the National Epidemiologic Survey on Alcohol and Related Conditions SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID DSM-III-R; INTERVIEW SCHEDULE AUDADIS; GENERAL-POPULATION SAMPLE; ICD-10 ALCOHOL; DRUG MODULES; IV ALCOHOL; NOSOLOGICAL COMPARISONS; PERSONALITY-DISORDERS; MAJOR DEPRESSION; ABUSE DIAGNOSES AB Background: No information is available on the co-occurrence of DSM-IV nicotine dependence and Axis I and 11 psychiatric disorders in the US population. Objectives: To present national data on the co-occurrence of current DSM-IV nicotine dependence and other psychiatric disorders by sex and to estimate the burden of all US tobacco consumption carried by nicotine-dependent and psychiatrically ill individuals. Design: Face-to-face interviews. Setting: The United States. Participants: Household and group-quarters adults (N = 43 093). Main Outcome Measures: Prevalence and comorbidity of current nicotine dependence and Axis I and II disorders and the percentage of cigarettes consumed in the United States among psychiatrically vulnerable subgroups. Results: Among US adults, 12.8% (95% confidence interval, 12.0-13.6) were nicotine dependent. Associations between nicotine dependence and specific Axis I and II disorders were all strong and statistically significant (P<.05) in the total population and among men and women. Nicotine-dependent individuals made up only 12.8% (95% confidence interval, 12.0-13.6) of the population yet consumed 57.5% of all cigarettes smoked in the United States. Nicotine-dependent individuals with a comorbid psychiatric disorder made up 7.1% (95% confidence interval, 6.6-7.6) of the population yet consumed 34.2% of all cigarettes smoked in the United States. Conclusions: Nicotine-dependent and psychiatrically ill individuals consume about 70% of all cigarettes smoked in the United States. The results of this study highlight the importance of focusing smoking cessation efforts on individuals who are nicotine dependent, individuals who have psychiatric disorders, and individuals who have comorbid nicotine dependence and other psychiatric disorders. Further, awareness of industry segmentation strategies can improve smoking cessation efforts of clinicians and other health professionals among all smokers and especially among the most vulnerable. C1 NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Columbia Univ, Dept Epidemiol, New York, NY USA. Columbia Univ, Dept Psychiat, New York, NY USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Grant, BF (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH,Dept Hlth & Human Serv, Room 3077, Bethesda, MD 20892 USA. EM bgrant@willco.niaaa.nih.gov NR 53 TC 707 Z9 722 U1 2 U2 39 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD NOV PY 2004 VL 61 IS 11 BP 1107 EP 1115 DI 10.1001/archpsyc.61.11.1107 PG 9 WC Psychiatry SC Psychiatry GA 868FE UT WOS:000224898700004 PM 15520358 ER PT J AU Barr, CS Newman, TK Lindell, S Shannon, C Champoux, M Lesch, KP Suomi, SJ Goldman, D Higley, JD AF Barr, CS Newman, TK Lindell, S Shannon, C Champoux, M Lesch, KP Suomi, SJ Goldman, D Higley, JD TI Interaction between serotonin transporter gene variation and rearing condition in alcohol preference and consumption in female primates SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID PITUITARY-ADRENAL-AXIS; 5-HYDROXYINDOLEACETIC ACID CONCENTRATIONS; DIMINISHED SOCIAL COMPETENCE; LINKED POLYMORPHIC REGION; ANXIETY-RELATED TRAITS; PROMOTER POLYMORPHISM; EARLY EXPERIENCE; REGULATORY REGION; RHESUS-MONKEYS; LIFE STRESS AB Background: Serotonin neurotransmission and limbic-hypothalamic-pituitary-adrenal (LHPA) axis hormones are thought to be involved in the reinforcement of alcohol intake and contribute to the risk for alcoholism. In humans and macaques, a promoter polymorphisin that decreases transcription of the serotonin transporter gene is associated with anxiety and altered LHPA-axis responses to stress, and in female macaques, exposure to early-life stress alters LHPA-axis activation in response to alcohol. We wanted to determine whether serotonin transporter gene promoter variation (rh-5HTTLPR) and rearing condition would interact to influence alcohol preference in female rhesus macaques. Because of the involvement of stress and LHPA-axis activity in symptoms of withdrawal and relapse, we also wanted to determine whether serotonin transporter gene variation and rearing condition would influence changes in the patterns of alcohol consumption across a 6-week alcohol consumption paradigm. Methods: Female macaques were reared with their mothers in social groups (n = 18) or in peer-only groups (n = 14). As young adults, they were given access to an aspartame-sweetened 8.4% alcohol solution and vehicle for 1 hour per day, and volumes of consumption of alcoholic and nonalcoholic solutions were recorded. Serotonin transporter genotype (l/l and l/s) was determined using polymerase chain reaction followed by gel electrophoresis. Results: We found interactions between rearing condition and serotonin transporter genotype, such that l/s peer-reared females demonstrated higher levels of ethanol preference. We also found an effect of rearing condition on the percentage change in alcohol consumed during the 6 weeks as well as a phase by rearing interaction, such that peer-reared animals progressively increased their levels of consumption across the course of the study. This was especially evident for peer-reared females with the l/s rh5-HTTLPR genotype. Conclusion: These data suggest a potential interaction between serotonin transporter gene variation and early experience in vulnerability to alcoholism. C1 Natl Inst Hlth, Anim Ctr, Poolesville, MD 20837 USA. Natl Inst Child Hlth & Human Dev, Lab Comparat Ethol, Poolesville, MD 20837 USA. NIAAA, Clin Studies Lab, Poolesville, MD 20837 USA. Univ Wurzburg, Dept Psychiat Psychotherapy, Wurzburg, Germany. NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. RP Barr, CS (reprint author), Natl Inst Hlth, Anim Ctr, POB 529,Bldg 112, Poolesville, MD 20837 USA. EM cbarr@mail.nih.gov RI Goldman, David/F-9772-2010; Lesch, Klaus-Peter/J-4906-2013 OI Goldman, David/0000-0002-1724-5405; Lesch, Klaus-Peter/0000-0001-8348-153X NR 55 TC 185 Z9 188 U1 2 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD NOV PY 2004 VL 61 IS 11 BP 1146 EP 1152 DI 10.1001/archpsyc.61.11.1146 PG 7 WC Psychiatry SC Psychiatry GA 868FE UT WOS:000224898700009 PM 15520362 ER PT J AU Rapoport, SI Schapiro, MB May, C AF Rapoport, SI Schapiro, MB May, C TI Reduced brain delivery of homovanillic acid to cerebrospinal fluid during human aging SO ARCHIVES OF NEUROLOGY LA English DT Article ID SENSITIVE TRANSPORT-SYSTEM; MONOAMINE METABOLITES; PARKINSONS-DISEASE; DOPAMINE; AGE; DEMENTIA; MARKERS; PLEXUS; LUMBAR AB Background: Markers of human brain dopamine metabolism are reported to decline with age. However, the cerebrospinal fluid (CSF) concentration of homovanillic acid (HVA), a major dopamine metabolite, is reported to not change or to increase in elderly individuals. Objective: To estimate the rate of delivery of HVA from the brain to CSF, taking into account the HVA concentration gradient in the spinal subarachnoid space and CSF flow. Methods: Homovanillic acid concentrations were measured in 5 serial 6-mL aliquots of CSF removed from the L3-4 or L4-5 interspaces of 7 healthy young (mean +/- SD age, 28.7 +/- 4.6 years) subjects and 7 healthy elderly (mean +/- SD age, 77.1 +/- 6.3 years) subjects. Cisterna magna HVA concentrations were estimated from the slopes of the HVA concentrations along the spinal subarachnoid space. The products of cisternal HVA concentrations and published values for CSF flow were used to estimate lower limits for brain delivery of HVA to CSF, according to the Fick principle. Results: The mean +/- SD HVA concentration in the initial lumbar CSF sample in the young subjects, 116 +/- 66 pmol/mL, did not differ significantly from 140 +/- 86 pmol/mL in the elderly subjects. Estimated cisternal HVA concentrations equaled 704 and 640 pmol/mL, respectively, in the young and elderly subjects. Multiplying these concentrations by CSF flow rates of 591 and 294 mL/d, respectively, gave lower limits for rates of delivery of HVA from the brain to CSF. These rates equaled 416 and 175 nmol/d, respectively. Conclusion: A 50% decline in the lower limit for the rate of HVA delivery from the brain to CSF in elderly individuals is consistent with other evidence that brain dopaminergic neurotransmission declines with age. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. Univ Cincinnati, Cincinnati Childrens Hosp, Dept Pediat, Med Ctr, Cincinnati, OH USA. Univ Cincinnati, Cincinnati Childrens Hosp, Div Neurol, Med Ctr, Cincinnati, OH USA. VA Med Hlth Care Syst, Baltimore, MD USA. RP Rapoport, SI (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 10,Room 6N-202, Bethesda, MD 20892 USA. EM sir@helix.nih.gov NR 29 TC 8 Z9 8 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD NOV PY 2004 VL 61 IS 11 BP 1721 EP 1724 DI 10.1001/archneur.61.11.1721 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 869EJ UT WOS:000224965900011 PM 15534183 ER PT J AU Manolio, T Boerwinkle, E O'Donnell, C Wilson, AF AF Manolio, T Boerwinkle, E O'Donnell, C Wilson, AF TI Noninvasive phenotypes of atherosclerosis - Response SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Letter ID CAROTID ATHEROSCLEROSIS C1 NHLBI, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. NHLBI, Framingham, MA USA. NHGRI, Baltimore, MD USA. RP Manolio, T (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA. RI Wilson, Alexander/C-2320-2009 NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD NOV PY 2004 VL 24 IS 11 BP E188 EP E189 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 868FU UT WOS:000224900300043 ER PT J AU Yang, D Oppenheim, JJ AF Yang, D Oppenheim, JJ TI Antimicrobial proteins act as "Alarmins" in joint immune defense SO ARTHRITIS AND RHEUMATISM LA English DT Editorial Material ID INNATE IMMUNITY; HOST-DEFENSE; PEPTIDES; MICE C1 NCI, SAIC Frederick, NIH, Frederick, MD 21702 USA. NCI, Mol Immunoregulat Lab, NIH, Frederick, MD USA. RP Yang, D (reprint author), NCI, SAIC Frederick, NIH, Frederick, MD 21702 USA. EM dyang@mail.ncifcrf.gov NR 15 TC 36 Z9 38 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD NOV PY 2004 VL 50 IS 11 BP 3401 EP 3403 DI 10.1002/art.20604 PG 3 WC Rheumatology SC Rheumatology GA 870QB UT WOS:000225071700001 PM 15529365 ER PT J AU Carbone, LD Nevitt, MC Wildy, K Barrow, KD Harris, F Felson, D Peterfy, C Visser, M Harris, TB Wang, BWE Kritchevsky, SB AF Carbone, LD Nevitt, MC Wildy, K Barrow, KD Harris, F Felson, D Peterfy, C Visser, M Harris, TB Wang, BWE Kritchevsky, SB CA Hlth Aging Body Composition Study TI The relationship of antiresorptive drug use to structural findings and symptoms of knee osteoarthritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID ESTROGEN REPLACEMENT THERAPY; BONE-RESORPTION; RISK-FACTORS; RADIOGRAPHIC OSTEOARTHRITIS; ARTICULAR CHONDROCYTES; POSTMENOPAUSAL WOMEN; HEALTHY WOMEN; CARTILAGE; JOINT; ASSOCIATION AB Objective. To examine the cross-sectional association between use of medications that have a bone antiresorptive effect (estrogen, raloxifene, and alendronate) and both the structural features of knee osteoarthritis (OA), assessed by magnetic resonance imaging (MRI) and radiography, and the symptoms of knee OA in elderly women. Methods. Women in the Health, Aging and Body Composition Study underwent MRI and radiography of the knee if they reported symptoms of knee OA, and women without significant knee symptoms were selected as controls. MR images of the knee were assessed for multiple features of OA using the Whole-Organ MRI scoring method, and radiographs were read for Kellgren and Lawrence grade and individual features of OA. Concurrent medication use and knee symptoms were assessed by interview, and knee pain severity was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Results. There were 818 postmenopausal women from whom we obtained MR images of the knee and data on medication use. Among these women, 214 (26.2%) were receiving antiresorptive drugs. We found no significant association between overall use of antiresorptive drugs and the presence of knee pain and radiographic changes of OA of the knee. Use of alendronate, but not estrogen, was associated with less severity of knee pain as assessed by WOMAC scores. Both alendronate use and estrogen use were associated with significantly less subchondral bone attrition and bone marrow edema-like abnormalities in the knee as assessed by MRI, as compared with women who had not received these medications. Conclusion. Elderly women being treated with alendronate and estrogen had a significantly decreased prevalence of knee OA-related subchondral bone lesions compared with those reporting no use of these medications. Alendronate use was also associated with a reduction in knee pain according to the WOMAC scores. C1 Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. Univ Calif San Francisco, Prevent Sci Grp, San Francisco, CA 94143 USA. Univ Pittsburgh, Pittsburgh, PA USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Synarc Inc, San Francisco, CA USA. Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. NIA, Bethesda, MD 20892 USA. Wake Forest Univ Hlth Sci, Winston Salem, NC USA. RP Carbone, LD (reprint author), Univ Tennessee, Ctr Hlth Sci, 956 Court Ave,Room E336 Coleman Bldg, Memphis, TN 38163 USA. EM lcarbone@utmem.edu OI Felson, David/0000-0002-2668-2447; Kritchevsky, Stephen/0000-0003-3336-6781 NR 63 TC 136 Z9 144 U1 2 U2 12 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD NOV PY 2004 VL 50 IS 11 BP 3516 EP 3525 DI 10.1002/art.20627 PG 10 WC Rheumatology SC Rheumatology GA 870QB UT WOS:000225071700015 PM 15529367 ER PT J AU O'Hanlon, T Koneru, B Bayat, E Love, L Targoff, I Malley, J Malley, K Miller, F AF O'Hanlon, T Koneru, B Bayat, E Love, L Targoff, I Malley, J Malley, K Miller, F CA Environmental Myositis Study Grp TI Immunogenetic differences between caucasian women with and those without silicone implants in whom myositis develops SO ARTHRITIS AND RHEUMATISM LA English DT Article ID IDIOPATHIC INFLAMMATORY MYOPATHY; CONNECTIVE-TISSUE DISEASES; BREAST IMPLANTS; AUTOANTIBODIES AB Objective. To determine whether patients in whom myositis develops after they receive silicone breast implants have distinct clinical, serologic, and/or immunogenetic features compared with patients with myositis who do not have silicone implants. Methods. A preliminary case series study was followed by a larger, independent, matched case-control study to evaluate women in whom myositis developed after they received silicone implants (MASI patients) compared with healthy women with silicone implants and women with myositis but without silicone implants (idiopathic inflammatory myopathy; IIM patients). Results. In a preliminary study, 11 MASI patients differed from 76 IIM patients in having an increased frequency of HLA-DQA1*0102 (odds ratio [OR] 9.8, 95% confidence interval [95% CI] 1.77-96.79) and decreased frequencies of the myositis-associated risk factor DRB1*0301 (OR 0.1 [95% CI 0.002-0.63]) and its linked allele DQA1*0501 (OR 0.2 [95% CI 0.02-0.87]). A subsequent independent, matched case-control study revealed that although clinical features and autoantibodies did not differ significantly between the MASI and IIM groups, MASI patients again had decreased frequencies of DRB1*0301 (OR 0.2 [95% CI 0.07-0.72]) and DQA1*0501 (OR 0.2 [95% CI 0.08-0.84]) compared with IIM patients. Additional comparisons between MASI patients from both studies combined (n = 37) and a larger population of IIM patients (n = 453) suggested that HLA-DQA1*0102 may be uniquely associated with MASI (OR 2.6 [95% CI 1.25-5.46]). Conclusion. Women in whom inflammatory myopathy develops after they receive silicone implants constitute an immunogenetically distinct group of patients with myositis. These and other data suggest that autoimmune diseases as now defined may consist of multiple distinct entities, each of which is characterized by different genes and environmental exposures. C1 NIEHS, Environm Autoimmun Grp, NIH, Bethesda, MD 20892 USA. Univ Oklahoma, Med Sci Ctr, Oklahoma City, OK USA. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. Res Programming Inc, Rockville, MD USA. RP O'Hanlon, T (reprint author), NIEHS, Environm Autoimmun Grp, NIH, 9 Mem Dr,Room 1W101, Bethesda, MD 20892 USA. EM ohanlon@niehs.nih.gov OI Miller, Frederick/0000-0003-2831-9593; Malley, James/0000-0002-9895-7454 NR 15 TC 9 Z9 9 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD NOV PY 2004 VL 50 IS 11 BP 3646 EP 3650 DI 10.1002/art.20587 PG 5 WC Rheumatology SC Rheumatology GA 870QB UT WOS:000225071700031 PM 15529361 ER PT J AU Diaz, A Hu, CB Kastner, DL Schaner, P Reginato, AM Richards, N Gumucio, DL AF Diaz, A Hu, CB Kastner, DL Schaner, P Reginato, AM Richards, N Gumucio, DL TI Lipopolysaccharide-induced expression of multiple alternatively spliced MEFV transcripts in human synovial fibroblasts SO ARTHRITIS AND RHEUMATISM LA English DT Article ID FAMILIAL MEDITERRANEAN FEVER; ENCODING MEVALONATE KINASE; NECROSIS-FACTOR-ALPHA; EXPANDING FAMILY; PAPA SYNDROME; PYRIN DOMAIN; KAPPA-B; MUTATIONS; GENE; PROTEIN AB Objective. To investigate the expression of the familial Mediterranean fever (IMF) gene (MEFP) in human synovial fibroblasts. Methods. MEFV messenger RNA in synovial fibroblasts, chondrocytes, and peripheral blood leukocytes (PBLs) was analyzed by semiquantitative and real-time polymerase chain reaction and ribonuclease protection assay. The subcellular localization of pyrin, the MEFV product, was determined in transfected synovial fibroblasts and HeLa cells with plasmids encoding pyrin isoforms. Native pyrin was detected with an antipyrin antibody. Results. MEFV was expressed in synovial fibroblasts, but not in chondrocytes. Four alternatively spliced transcripts were identified: an extension of exon 8 (exon 8ext) resulting in a frameshift that predicts a truncated protein lacking exons 9 and 10, the addition of an exon (exon 4a) predicting a truncated protein at exon 5, the in-frame substitution of exon 2a for exon 2, and the previously described removal of exon 2 (exon 2Delta). Exon 8ext transcripts represented 27% of the total message population in synovial fibroblasts. All other alternatively spliced transcripts were rare. Consensus and alternatively spliced transcripts were induced by lipopolysaccharide in synovial fibroblasts and PBLs. In transfected cells, the proteins encoded by all highly expressed splice forms were cytoplasmic. In contrast, native pyrin was predominantly nuclear in synovial fibroblasts, neutrophils, and dendritic cells, but was cytoplasmic in monocytes. Conclusion. Several MEFV transcripts are expressed and inducible in synovial fibroblasts. A prominent isoform lacks the C-terminal domain that contains the majority of mutations found in patients with IMF. While recombinant forms of all major pyrin isoforms are cytoplasmic, native pyrin is nuclear in several cell types. Thus, mechanisms in addition to splicing patterns must control pyrin's subcellular distribution. C1 Univ Michigan, Sch Med, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Gumucio, DL (reprint author), Univ Michigan, Sch Med, Dept Cell & Dev Biol, 1301 Catherine St,5704 MS 2, Ann Arbor, MI 48109 USA. EM dgumucio@umich.edu FU NIAID NIH HHS [R01 AI 053262-01A1, K08 AI 50092-01A1] NR 37 TC 63 Z9 64 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD NOV PY 2004 VL 50 IS 11 BP 3679 EP 3689 DI 10.1002/art.20600 PG 11 WC Rheumatology SC Rheumatology GA 870QB UT WOS:000225071700036 PM 15529356 ER PT J AU Suwannarat, P Phornphutkul, C Bernardini, I Turner, M Gahl, WA AF Suwannarat, P Phornphutkul, C Bernardini, I Turner, M Gahl, WA TI Minocycline-induced hyperpigmentation masquerading as alkaptonuria in individuals with joint pain SO ARTHRITIS AND RHEUMATISM LA English DT Article ID RHEUMATOID-ARTHRITIS; PIGMENTATION AB Alkaptonuria, a rare autosomal-recessive disorder caused by mutations in the HGD gene and a deficiency of homogentisate 1,2-dioxygenase, is characterized by accumulation of homogentisic acid (HGA), ochronosis, and destruction of connective tissue resulting in joint disease. Certain medications have been reported to cause cutaneous hyperpigmentation resembling that of alkaptonuria. We present 5 such cases. Eighty-eight patients with a possible diagnosis of alkaptonuria were examined at the National Institutes of Health Clinical Center between June 2000 and March 2004. The diagnosis of alkaptonuria was confirmed or ruled out by measurement of HGA in the urine. Five patients with findings consistent with ochronosis, including pigmentary changes of the ear and mild degenerative disease of the spine and large joints, were diagnosed clinically as having alkaptonuria, but the diagnosis was withdrawn based on normal urine HGA levels. All 5 patients were women who had taken minocycline for dermatologic or rheumatologic disorders for extended periods. Minocycline-induced hyperpigmentation should be considered in the differential diagnosis of ochronosis. This could be of increased significance now that minocycline and other tetracyclines have been proposed as therapeutic options for rheumatoid arthritis, bringing a new population of patients with ochronosis and arthritis to medical attention with the potential, but incorrect, diagnosis of alkaptonuria. C1 NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Suwannarat, P (reprint author), NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bldg 10,Room 10C103,10 Ctr Dr,MSC 1851, Bethesda, MD 20892 USA. EM suwannar@nhgri.nih.gov NR 12 TC 11 Z9 12 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD NOV PY 2004 VL 50 IS 11 BP 3698 EP 3701 DI 10.1002/art.20606 PG 4 WC Rheumatology SC Rheumatology GA 870QB UT WOS:000225071700038 PM 15529343 ER PT J AU Kolobow, T AF Kolobow, T TI The artificial lung: The past. A personal retrospective SO ASAIO JOURNAL LA English DT Editorial Material ID MECHANICAL VENTILATION; OXYGENATOR; FAILURE; HEART; PUMP C1 NHLBI, Pulm & Crit Care Med Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Kolobow, T (reprint author), NHLBI, Pulm & Crit Care Med Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. NR 19 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1058-2916 J9 ASAIO J JI Asaio J. PD NOV-DEC PY 2004 VL 50 IS 6 BP XLIII EP XLVIII DI 10.1097/01.MAT.0000147960.14376.D5 PG 6 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 879KX UT WOS:000225717800010 PM 15672779 ER PT J AU Martinez, A Oh, HR Unsworth, EJ Bregonzio, C Saavedra, JM Stetler-Stevenson, WG Cuttitta, F AF Martinez, A Oh, HR Unsworth, EJ Bregonzio, C Saavedra, JM Stetler-Stevenson, WG Cuttitta, F TI Matrix metalloproteinase-2 cleavage of adrenomedullin produces a vasoconstrictor out of a vasodilator SO BIOCHEMICAL JOURNAL LA English DT Article DE adrenomedullin; blood pressure; complement factor H; matrix metalloproteinase-2 (MMP-2); peptide fragment; vasoconstrictor ID NEUTRAL ENDOPEPTIDASE INHIBITION; RECEPTOR-LIKE RECEPTOR; COMPLEMENT FACTOR-H; BINDING-PROTEIN; HEART-FAILURE; GELATINASE-A; PEPTIDE; IDENTIFICATION; HYPERTENSION; EXPRESSION AB MMPs (matrix metalloproteinases) play a major role in the pathogenesis of hypertension by altering the extracellular matrix during cardiovascular remodelling. In the present study we show that MMP-2, but not MMP-9, cleaves the vasodilator peptide AM (adrenomedullin). Addition of the AM-binding protein, complement factor H. prevents this cleavage, providing a hitherto unknown mechanism of action for this binding protein. We identified the signature cleavage fragments and found some of them in human urine, suggesting that MMP-2 processing of AM may occur in vivo. Synthetic AM fragments regulated blood pressure in rats. The larger peptides are vasodilators, as is intact AM, whereas intermediate fragments did not affect blood pressure. In contrast, AM(11-22) elicited vasoconstriction. Studies of AM receptor activation in Rat2 cells confirm that the larger AM cleavage peptides activated this receptor, whereas AM(11-22) did not. The present study defines a new mechanism through which MMP-2 may regulate blood pressure by simultaneously eliminating a vasodilator and generating a vasoconstrictor. C1 NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA. NCI, Vasc Biol Fac, NIH, Bethesda, MD 20892 USA. NIMH, Lab Neurotoxicol, NIH, Bethesda, MD 20892 USA. NIMH, Pharmacol Sect, NIH, Bethesda, MD 20892 USA. RP Martinez, A (reprint author), NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA. EM martinea@mail.nih.gov RI Stetler-Stevenson, William/H-6956-2012; Martinez, Alfredo/A-3077-2013; Cuttitta, Frank/B-4758-2016 OI Stetler-Stevenson, William/0000-0002-5500-5808; Martinez, Alfredo/0000-0003-4882-4044; NR 33 TC 86 Z9 92 U1 0 U2 3 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD NOV 1 PY 2004 VL 383 BP 413 EP 418 DI 10.1042/BJ20040920 PN 3 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 873KQ UT WOS:000225279300002 PM 15307819 ER PT J AU Attoor, S Dougherty, ER Chen, Y Bittner, ML Trent, JM AF Attoor, S Dougherty, ER Chen, Y Bittner, ML Trent, JM TI Which is better for cDNA-microarray-based classification: ratios or direct intensities SO BIOINFORMATICS LA English DT Article ID GENE-EXPRESSION; STATISTICAL DESIGN; NOISE; NORMALIZATION AB Motivation: There are two general methods for making gene-expression microarrays: one is to hybridize a single test set of labeled targets to the probe, and measure the background-subtracted intensity at each probe site; the other is to hybridize both a test and a reference set of differentially labeled targets to a single detector array, and measure the ratio of the background-subtracted intensities at each probe site. Which method is better depends on the variability in the cell system and the random factors resulting from the microarray technology. It also depends on the purpose for which the microarray is being used. Classification is a fundamental application and it is the one considered here. Results: This paper describes a model-based simulation paradigm that compares the classification accuracy provided by these methods over a variety of noise types and presents the results of a study modeled on noise typical of cDNA microarray data. The model consists of four parts: (1) the measurement equation for genes in the reference state; (2) the measurement equation for genes in the test state; (3) the ratio and normalization procedure for a dual-channel system; and (4) the intensity and normalization procedure for a single-channel system. In the reference state, the mean intensities are modeled as a shifted exponential distribution, and the intensity for a particular gene is modeled via a normal distribution, Normal(I, alphaI), about its mean intensity I, with alpha being the coefficient of variation of the cell system. In the test state, some genes have their intensities up-regulated by a random factor. The model includes a number of random factors affecting intensity measurement: deposition gain d, labeling gain, and post-image-processing residual noise. The key conclusion resulting from the study is that the coefficient of variation governing the randomness of the intensities and the deposition gain are the most important factors for determining whether a single-channel or dual-channel system provides superior classification, and the decision region in the alpha-d plane is approximately linear. C1 Texas A&M Univ, Dept Elect Engn, College Stn, TX 77843 USA. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Translat Genom Res Inst, Phoenix, AZ 85004 USA. RP Dougherty, ER (reprint author), Texas A&M Univ, Dept Elect Engn, College Stn, TX 77843 USA. EM e-dougherty@tamu.edu NR 15 TC 18 Z9 19 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD NOV 1 PY 2004 VL 20 IS 16 BP 2513 EP 2520 DI 10.1093/bioinformatics/bth272 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 873AD UT WOS:000225250100004 PM 15454406 ER PT J AU Liu, DL Weinberg, CR Peddada, SD AF Liu, DL Weinberg, CR Peddada, SD TI A geometric approach to determine association and coherence of the activation times of cell-cycling genes under differing experimental conditions SO BIOINFORMATICS LA English DT Article ID IDENTIFICATION; REGRESSION AB Differing arresting agents and protocols can be used to synchronize cells in cultures to specific phases of the cell when studying cell-cycle gene expressions. Often, data derived from individual experiments are analyzed separately, since no appropriate statistical methodology is available at the moment to analyze the data from all such experiments simultaneously. The focus of this paper is to determine the association and coherence of the relative activation times of cell-cycling genes under different experimental conditions. Using a circular-circular regression model, we define two parameters, a rotation parameter for the angular difference between cells' arresting times (phases) in two cell-cycle experiments, and an association parameter to describe the correspondence between the cycle times of maximal expression (phase angles) for a set of genes studied in two experiments. Further, we propose a procedure to assess coherence across multiple experiments, i.e. to what extent the circular ordering of the phase angles of genes is maintained across multiple experiments. Coherence of genes across experiments suggests that functionally these genes tend to respond in a stereotypically sequenced way under different experimental conditions. Our proposed methodology is illustrated by applying it to a HeLa cell-cycle gene-expression data. C1 NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. RP Peddada, SD (reprint author), NIEHS, Biostat Branch, NIH, MDA3-03,POB 12233, Res Triangle Pk, NC 27709 USA. EM peddada@niehs.nih.gov RI Peddada, Shyamal/D-1278-2012 NR 12 TC 8 Z9 8 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD NOV 1 PY 2004 VL 20 IS 16 BP 2521 EP 2528 DI 10.1093/bioinformatics/bth274 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 873AD UT WOS:000225250100005 PM 15087309 ER PT J AU Dodd, LE Korn, EL McShane, LM Chandramouli, GVR Chuang, EY AF Dodd, LE Korn, EL McShane, LM Chandramouli, GVR Chuang, EY TI Correcting log ratios for signal saturation in cDNA microarrays SO BIOINFORMATICS LA English DT Article ID GENE-EXPRESSION; ERRORS; VARIABLES AB Motivation: Pixel saturation occurs when the pixel intensity exceeds a threshold and the recorded pixel intensity is truncated. Microarray experiments are commonly afflicted with saturated pixels. As a result, estimators of gene expression are biased, with the amount of bias increasing as a function of the proportion of pixels saturated. Saturation is directly related to the photomultiplier tube (PMT) voltage settings and RNA abundance and is not necessarily associated with poor array or poor spot quality. When choosing PMT settings, higher PMT settings are desired because of improved signal-to-noise ratios of low-intensity spots. This improved signal is somewhat offset by saturation of high-intensity spots. In practice, spots with saturated pixels are discarded or the biased value is used. Neither of these approaches is appealing, particularly the former approach when a highly expressed gene is discarded because of saturation. Results: We present a method to correct for saturation using pixel-level data. The method is based on a censored regression model. Evaluations on several arrays indicate that the method performs well. Simulation studies suggest that the method is robust under certain model violations. C1 NCI, Biometr Res Branch, DCTD, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Gaithersburg, MD 20877 USA. NCI, Radiat Oncol Branch, CCR, Bethesda, MD 20892 USA. RP Dodd, LE (reprint author), NCI, Biometr Res Branch, DCTD, Bethesda, MD 20892 USA. EM doddl@mail.nih.gov NR 15 TC 19 Z9 20 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD NOV 1 PY 2004 VL 20 IS 16 BP 2685 EP 2693 DI 10.1093/bioinformatics/bth309 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 873AD UT WOS:000225250100023 PM 15145811 ER PT J AU Sunderland, T Mirza, N Putnam, KT Linker, G Bhupali, D Durham, R Soares, H Kimmel, L Friedman, D Bergeson, J Csako, G Levy, JA Bartko, JJ Cohen, RM AF Sunderland, T Mirza, N Putnam, KT Linker, G Bhupali, D Durham, R Soares, H Kimmel, L Friedman, D Bergeson, J Csako, G Levy, JA Bartko, JJ Cohen, RM TI Cerebrospinal fluid beta-amyloid(1-42) and tau in control subjects at risk for Alzheimer's disease: The effect of APOE epsilon 4 allele SO BIOLOGICAL PSYCHIATRY LA English DT Article DE cerebrospinal fluid; Alzheimer's disease; APOE; beta-amyloid; tau ID MILD COGNITIVE IMPAIRMENT; APOLIPOPROTEIN E4 PROMOTES; AMYLOID-BETA-PROTEIN; MOUSE MODEL; E GENOTYPE; CSF-TAU; DEMENTIA; BRAIN; A-BETA-42; DIAGNOSIS AB Background: Cerebrospinal fluid (CSF) measures of beta-amyloid(1-42) and tau are linked with the known neuropathology of Alzheimer's disease (AD). Numerous lines of evidence have also suggested that individuals with at least one APOE epsilon4 allele on chromosome 19 are at increased risk of developing AD. We tested these CSF markers in groups of subjects with AD and healthy older control subjects, using the absence or presence of the APOE epsilon4 allele as a predictive variable in the search for possible prognostic biomarkers of AD. Methods. We assessed the levels of beta-amyloid(1-42) and total tau in the CSF of 292 subjects (142 control subjects and 150 subjects with mild-to-moderate AD), who were research, participants at the National Institute of Mental Health. The group of control subject was enriched with a high percentage of subjects with a positive family history of AD. All subject underwent extensive global cognitive testing. Results. When divided according to the absence or presence of the APOE epsilon4 allele, the control subjects with at least one epsilon4 allele had significantly lower CSF beta-amyloid(1-42) but not tau levels than control subjects without an APOE 64 allele (p < .01). As expected, the AD patients bad lower levels of CSF beta-amyloid(1-42) and higher CSF tau levels than the normal control group (p <.01). Conclusions. The association of APOE epsilon4 allele and lower, more AD-like levels of CSF beta-amyloid(1-42) in older control subjects is consistent with previous studies showing possible neuroimaging and cognitive abnormalities with 64 carriers and suggests that CSF beta-amyloid(1-42) decreases-tight represent an early biomarker of AD. Longitudinal follow-up is of course required to verify whether this biomarker is indeed predictive of clinical conversion to AD. C1 NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. NIMH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. Pfizer Inc, Pfizer Cent Res, Pharmacogenom & Clin Biochem Measurements Div, Groton, CT 06340 USA. RP Sunderland, T (reprint author), NIMH, Geriatr Psychiat Branch, Bldg 10,Room 3N228,9000 Rockville Pike, Bethesda, MD 20892 USA. EM trey@mail.nih.gov FU NIMH NIH HHS [Z01 MH00330-14] NR 50 TC 124 Z9 127 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 NOV 1 PY 2004 VL 56 IS 9 BP 670 EP 676 DI 10.1016/j.biopsych.2004.07.021 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 869OW UT WOS:000224994900009 PM 15522251 ER PT J AU Weickert, TW Goldberg, TE Mishara, A Apud, JA Kolachana, LS Egan, MF Weinberger, DR AF Weickert, TW Goldberg, TE Mishara, A Apud, JA Kolachana, LS Egan, MF Weinberger, DR TI Catechol-O-methyltransferase Val(108/158)Met genotype predicts working memory response to antipsychotic medications SO BIOLOGICAL PSYCHIATRY LA English DT Article DE catechol-O-methyltransferase; working memory; antipsychotics; schizophrenia; prefrontal cortex; dopamine ID PREFRONTAL CORTEX; CORTICAL FUNCTION; RECEPTOR GENE; MET GENOTYPE; SCHIZOPHRENIA; POLYMORPHISM; ASSOCIATION; DOPAMINE; MODULATION; CLOZAPINE AB Background: The gene encoding catechol-O-methyltransferase (COMT), an enzyme that regulates prefrontal cortex dopamine, contains a common functional polymorphism (val(108/158)met) that influences prefrontal cortex function in an allelic dose-dependant manner. A recent study reported that the COMT val(108/158)met polymorphism influences cognitive- and physiologic-related prefrontal cortex response to antipsychotic treatment. The present study tested the effects of several COMT polymorphisms on the cognitive response to antipsychotic medication in patients with schizophrenia. Methods: Twenty inpatients with schizophrenia or schizoaffective disorder (5 with the val-val genotype, 11 with val-met, and 4 with met-met) were administered cognitive tests at two time points: once after 4 weeks of treatment with antipsychotic medication and once after 4 weeks of placebo administration, according to a counterbalanced, double-blind, within-subject study design. Results: Patients homozygous for the COMT met allele displayed significant improvement on the working memory task after treatment. Patients homozygous for the COMT val allele did not show working memory improvement with treatment. Other COMT polymorphisms were not associated with significant differences between treatment and placebo conditions. Conclusions: These results support other data suggesting that the COMT val(108/158)met polymorphism might be an important factor in the cognitive response to antipsychotic medication. C1 NIH, NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RP Weickert, TW (reprint author), NIH, NIMH, Clin Brain Disorders Branch, Bldg 10,Room 4C 101,MSC 1379, Bethesda, MD 20892 USA. EM weickert@intra.nimh.nih.gov NR 37 TC 95 Z9 96 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 NOV 1 PY 2004 VL 56 IS 9 BP 677 EP 682 DI 10.1016/j.bps.2004.08.012 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 869OW UT WOS:000224994900010 PM 15522252 ER PT J AU Bradley, MM AF Bradley, MM TI Emotion and natural selective attention SO BIOLOGICAL PSYCHOLOGY LA English DT Meeting Abstract CT 10th Annual Meeting of the International-Society-for-the-Advancement-of-Respiratory-Psychophysiolog y CY SEP 22-24, 2003 CL Leuven, BELGIUM SP Int Soc Adv Respiratory Psychophysiol C1 Univ Florida, NIMH, Ctr Study Emot & Attent, Gainesville, FL 32611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD NOV PY 2004 VL 67 IS 3 BP 402 EP 402 PG 1 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 848BF UT WOS:000223441300015 ER PT J AU Ohno, M Costanzi, S Kim, HS Kempeneers, V Vastmans, K Herdewijn, P Maddileti, S Gao, ZG Harden, TK Jacobson, KA AF Ohno, M Costanzi, S Kim, HS Kempeneers, V Vastmans, K Herdewijn, P Maddileti, S Gao, ZG Harden, TK Jacobson, KA TI Nucleotide analogues containing 2-oxa-bicyclo[2.2.1]heptane and L-alpha-threofuranosyl ring systems: interactions with P2Y receptors SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE nucleoside; purine; pyrimidine; G protein-coupled receptor; carbocyclic; phospholipase C; radioligand binding; molecular model ID LOCKED NUCLEIC-ACID; CONFORMATIONAL-ANALYSIS; BIOLOGICAL-ACTIVITY; PHOSPHOLIPASE-C; SUGAR RING; ADENOSINE; AGONISTS; NUCLEOSIDES; ANTAGONISTS; RECOGNITION AB The ribose moiety of adenine nucleotide 3',5'-bisphosphate antagonists of the P2Y(1) receptor has been successfully substituted with a rigid methanocarba ring system, leading to the conclusion that the North (N) ring conformation is preferred in receptor binding. Similarly, at P2Y(2) and P2Y(4) receptors, nucleotides constrained in the (N) conformation interact equipolently with the corresponding ribosides. We now have synthesized and examined as P2Y receptor ligands nucleotide analogues substituted with two novel ring systems: (1) a (N) locked-carbocyclic (cLNA) derivative containing the oxabicyclo[2-2.1]heptane ring system and (2) L-alpha-threofuranosyl derivatives. We have also compared potencies and preferred conformations of these nucleotides with the known anhydrohexitol-containing P2Y(1) receptor antagonist MRS2283. A cLNA bisphosphate derivative MRS2584 21 displayed a K-i value of 22.5 nM in binding to the human P2Y 1 receptor, and antagonized the stimulation of PLC by the potent P2Y, receptor agonist 2-methylthio-ADP (30 nM) with an IC50 of 650 nM. The parent cLNA nucleoside bound only weakly to an adenosine receptor (A(3)) Thus, this ring system afforded some P2Y receptor selectivity. A L-a-threofuranosyl bisphosphate derivative 9 displayed an IC50 of 15.3 muM for inhibition of 2-methylthio-ADP-stimulated PLC activity. L-alpha-Threofuranosyl-UTP 13 was a P2Y receptor agonist with a preference for P2Y(2) (EC50 = 9.9 muM) versus P2Y(4) receptors. The P2Y(1) receptor binding modes, including rotational angles, were estimated using molecular modeling and receptor docking. (C) 2004 Elsevier Ltd. All rights reserved. C1 NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. Wonkwang Univ, Coll Pharm, Iksan 570749, Chonbuk, South Korea. Katholieke Univ Leuven, Rega Inst Med Res, Lab Pharmaceut Chem, B-3000 Louvain, Belgium. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009; Costanzi, Stefano/G-8990-2013; OI Jacobson, Kenneth/0000-0001-8104-1493; Costanzi, Stefano/0000-0003-3183-7332 FU Intramural NIH HHS [Z01 DK031116-20, Z01 DK031117-20] NR 36 TC 28 Z9 28 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD NOV 1 PY 2004 VL 12 IS 21 BP 5619 EP 5630 DI 10.1016/j.bmc.2004.07.067 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 862WT UT WOS:000224522700015 PM 15465340 ER PT J AU Bertram, R Satin, L Zhang, M Smolen, P Sherman, A AF Bertram, R Satin, L Zhang, M Smolen, P Sherman, A TI Calcium and glycolysis mediate multiple bursting modes in pancreatic islets SO BIOPHYSICAL JOURNAL LA English DT Article ID PULSATILE INSULIN-SECRETION; GLUCOSE-INDUCED OSCILLATIONS; INDUCED ELECTRICAL-ACTIVITY; PURINE NUCLEOTIDE CYCLE; SENSITIVE K+ CHANNELS; CYTOPLASMIC FREE CA2+; SINGLE-MOUSE ISLETS; BETA-CELLS HIT; METABOLIC OSCILLATIONS; OXYGEN-CONSUMPTION AB Pancreatic islets of Langerhans produce bursts of electrical activity when exposed to stimulatory glucose levels. These bursts often have a regular repeating pattern, with a period of 10-60 s. In some cases, however, the bursts are episodic, clustered into bursts of bursts, which we call compound bursting. Consistent with this are recordings of free Ca2+ concentration, oxygen consumption, mitochondrial membrane potential, and intraislet glucose levels that exhibit very slow oscillations, with faster oscillations superimposed. We describe a new mathematical model of the pancreatic beta-cell that can account for these multimodal patterns. The model includes the feedback of cytosolic Ca2+ onto ion channels that can account for bursting, and a metabolic subsystem that is capable of producing slow oscillations driven by oscillations in glycolysis. This slow rhythm is responsible for the slow mode of compound bursting in the model. We also show that it is possible for glycolytic oscillations alone to drive a very slow form of bursting, which we call "glycolytic bursting.'' Finally, the model predicts that there is bistability between stationary and oscillatory glycolysis for a range of parameter values. We provide experimental support for this model prediction. Overall, the model can account for a diversity of islet behaviors described in the literature over the past 20 years. C1 Florida State Univ, Dept Math, Tallahassee, FL 32306 USA. Florida State Univ, Inst Mol Biophys, Tallahassee, FL 32306 USA. Virginia Commonwealth Univ, Med Ctr, Dept Pharmacol & Toxicol, Richmond, VA USA. Univ Texas, Sch Med, WM Keck Ctr Neurobiol Learning & Memory, Dept Neurobiol & Anat, Houston, TX USA. NIDDKD, NIH, Biol Modeling Lab, Bethesda, MD USA. RP Bertram, R (reprint author), Florida State Univ, Dept Math, Tallahassee, FL 32306 USA. EM bertram@math.fsu.edu FU NIDDK NIH HHS [R01 DK-46409, R01 DK046409]; NINDS NIH HHS [P01 NS038310, P01NS38310] NR 74 TC 84 Z9 84 U1 0 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 2004 VL 87 IS 5 BP 3074 EP 3087 DI 10.1529/biophysj.104.049262 PG 14 WC Biophysics SC Biophysics GA 865VO UT WOS:000224732500014 PM 15347584 ER PT J AU Bezrukov, SM Krasilnikov, OV Yuldasheva, LN Berezhkovskii, AM Rodrigues, CG AF Bezrukov, SM Krasilnikov, OV Yuldasheva, LN Berezhkovskii, AM Rodrigues, CG TI Field-dependent effect of crown ether (18-crown-6) on ionic conductance of alpha-hemolysin channels SO BIOPHYSICAL JOURNAL LA English DT Article ID HEPTAMERIC TRANSMEMBRANE PORE; MACROCYCLIC POLYETHERS; MOLECULAR ADAPTERS; FORMING PROTEIN; LIPID-BILAYERS; MEMBRANES; TOXIN; TRANSPORT; POLYMERS; DYNAMICS AB Closing linear poly(ethylene glycol) (PEG) into a circular "crown'' dramatically changes its dynamics in the alpha-hemolysin channel. In the electrically neutral crown ether (C(2)H(4)O)(6), six ethylene oxide monomers are linked into a circle that gives the molecule ion-complexing capacity and increases its rigidity. As with linear PEG, addition of the crown to the membrane-bathing solution decreases the ionic conductance of the channel and generates additional conductance noise. However, in contrast to linear PEG, both the conductance reduction (reporting on crown partitioning into the channel pore) and the noise (reporting on crown dynamics in the pore) now depend on voltage strongly and nonmonotonically. Within the whole frequency range accessible in channel reconstitution experiments, the noise power spectrum is "white'', showing that crown exchange between the channel and the bulk solution is fast. Analyzing these data in the framework of a Markovian two-state model, we are able to characterize the process quantitatively. We show that the lifetime of the crown in the channel reaches its maximum (a few microseconds) at about the same voltage (similar to100 mV, negative from the side of protein addition) where the crown's reduction of the channel conductance is most pronounced. Our interpretation is that, because of its rigidity, the crown feels an effective steric barrier in the narrowest part of the channel pore. This barrier together with crown-ion complexing and resultant interaction with the applied field leads to behavior usually associated with voltage-dependent binding in the channel pore. C1 Univ Fed Pernambuco, Ctr Ciencias Biol, Dept Biofis & Radiobiol, BR-50670901 Recife, PE, Brazil. NICHHD, NIH, Lab Phys & Struct Biol, Bethesda, MD 20892 USA. NIH, Ctr Informat Technol, Math & Stat Comp Lab, Bethesda, MD 20892 USA. RP Krasilnikov, OV (reprint author), Univ Fed Pernambuco, Ctr Ciencias Biol, Dept Biofis & Radiobiol, Av Prof Moraes Rego S-N,Cidade Univ, BR-50670901 Recife, PE, Brazil. EM kras@ufpe.br NR 53 TC 23 Z9 23 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 2004 VL 87 IS 5 BP 3162 EP 3171 DI 10.1529/biophysj.104.044453 PG 10 WC Biophysics SC Biophysics GA 865VO UT WOS:000224732500021 PM 15507690 ER PT J AU Choi, EJ Dimitriadis, EK AF Choi, EJ Dimitriadis, EK TI Cytochrome c adsorption to supported, anionic lipid bilayers studied via atomic force microscopy SO BIOPHYSICAL JOURNAL LA English DT Article ID PROTEIN INTERACTIONS; PERIPHERAL PROTEINS; MITOCHONDRIA; MEMBRANES; BINDING; RELEASE; BAX; PHOSPHOLIPIDS; CARDIOLIPIN; INSERTION AB The adsorption of membrane-associated protein cytochrome c to anionic lipid bilayers of dioleoyl phosphatidylglycerol was studied in low ionic strength physiological buffer using atomic force microscopy. The bilayers were supported on polylysinated mica. The formation of stable, single lipid bilayers was confirmed by imaging and force spectroscopy. Upon addition of low concentrations of cytochrome c, protein molecules were not topographically visible on the lipid bilayer-buffer interface. However, the forces required to punch through the bilayer by indentation using the atomic force microscopy probe were significantly lower after protein adsorption, which suggest that the protein inserts into the bilayer. Moreover, the apparent thickness of the bilayer remained unchanged after cytochrome c adsorption. Yet, mass spectroscopy and visible light absorption spectroscopy confirmed the presence of cytochrome c in the lipid bilayers. These results suggest that 1), cytochrome c inserts into the bilayer and resides in its hydrophobic core; 2), cytochrome c insertion changes the mechanical properties of the bilayer significantly; and 3), bilayer force spectroscopy may be a useful tool in investigating lipid-protein interactions. C1 NIH, Off Director, Off Res Serv, Div Bioengn & Phys Sci,Instrumentat Res & Dev Res, Bethesda, MD 20892 USA. RP Dimitriadis, EK (reprint author), NIH, Off Director, Off Res Serv, Div Bioengn & Phys Sci,Instrumentat Res & Dev Res, 13 S Dr,MSC 5766,Bldg 13-3N17, Bethesda, MD 20892 USA. EM dimitria@helix.nih.gov NR 29 TC 40 Z9 40 U1 1 U2 14 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 2004 VL 87 IS 5 BP 3234 EP 3241 DI 10.1529/biophysj.104.047738 PG 8 WC Biophysics SC Biophysics GA 865VO UT WOS:000224732500028 PM 15347587 ER PT J AU Hirai, T Subramaniam, S AF Hirai, T Subramaniam, S TI Structure and transport mechanism of the bacterial oxalate transporter OxlT SO BIOPHYSICAL JOURNAL LA English DT Article ID MAJOR FACILITATOR SUPERFAMILY; ESCHERICHIA-COLI; PROJECTION STRUCTURE; TRANSLOCATION; PROKARYOTES; OXALOBACTER; PROTEINS AB Membrane proteins that belong to the major facilitator superfamily (MFS) are found in organisms across the evolutionary spectrum and mediate the transport of a variety of substrates ranging from small metabolites to neurotransmitters. The oxalate transporter ( OxlT) is a representative MFS protein, and exchanges formate for oxalate across the cytoplasmic membrane of the organism Oxalobacter formigenes. Here, we present a structural model for the protein conformational changes that occur during oxalate transport by combining a three-dimensional map of the oxalate-bound, "closed'' state of OxlT at 6.5 Angstrom determined by cryo-electron microscopy with a model of the "open'' state of OxlT based on the atomic structures of the related transporters, glycerol-3-phosphate transporter (GlpT) and lactose permease (LacY). We demonstrate that the principal structural change associated with substrate transport is a concerted rocking movement of the two structurally similar halves of the protein relative to each other. Our structural model places two positively charged residues, Arg-272 and Lys-355 in the central cavity, suggesting that electrostatic interactions between these residues and the oxalate anion is a key step in generating the conformational change between the open and closed states of the transporter. C1 NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Subramaniam, S (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, 50 South Dr,Rm 4306, Bethesda, MD 20892 USA. EM ss1@nih.gov RI Hirai, Teruhisa/G-2105-2015 OI Hirai, Teruhisa/0000-0002-2114-8149 NR 22 TC 40 Z9 42 U1 0 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 2004 VL 87 IS 5 BP 3600 EP 3607 DI 10.1529/biophysj.104.049320 PG 8 WC Biophysics SC Biophysics GA 865VO UT WOS:000224732500060 PM 15339805 ER PT J AU Taitt, CR Pancrazio, JJ AF Taitt, CR Pancrazio, JJ TI Microarrays for biodefense and environmental applications - Preface SO BIOSENSORS & BIOELECTRONICS LA English DT Editorial Material C1 USN, Res Lab, Ctr Biomol Sci & Engn, Washington, DC 20375 USA. NINDS Rockville, NIH, Rockville, MD USA. RP Taitt, CR (reprint author), USN, Res Lab, Ctr Biomol Sci & Engn, 4555 Overlook Ave SW, Washington, DC 20375 USA. EM crtaitt@cbmse.nrl.navy.mil RI Pancrazio, Joseph/M-3206-2015 OI Pancrazio, Joseph/0000-0001-8276-3690 NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER ADVANCED TECHNOLOGY PI OXFORD PA OXFORD FULFILLMENT CENTRE THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-5663 J9 BIOSENS BIOELECTRON JI Biosens. Bioelectron. PD NOV 1 PY 2004 VL 20 IS 4 BP 665 EP 667 DI 10.1016/j.bios.2004.06.010 PG 3 WC Biophysics; Biotechnology & Applied Microbiology; Chemistry, Analytical; Electrochemistry; Nanoscience & Nanotechnology SC Biophysics; Biotechnology & Applied Microbiology; Chemistry; Electrochemistry; Science & Technology - Other Topics GA 875IB UT WOS:000225412600001 ER PT J AU Sergeev, N Distler, M Courtney, S Al-Khaldi, SF Volokhov, D Chizhikov, V Rasooly, A AF Sergeev, N Distler, M Courtney, S Al-Khaldi, SF Volokhov, D Chizhikov, V Rasooly, A TI Multipathogen oligonucleotide microarray for environmental and biodefense applications SO BIOSENSORS & BIOELECTRONICS LA English DT Article DE oligonucleotide microarray; microbial pathogens ID CAMPYLOBACTER-JEJUNI; STAPHYLOCOCCUS-AUREUS; CLOSTRIDIUM-PERFRINGENS; LISTERIA-MONOCYTOGENES; VIRULENCE FACTORS; C-LARI; IDENTIFICATION; UPSALIENSIS; PATHOGENS; ASSAY AB Food-borne pathogens are a major health problem. The large and diverse number of microbial pathogens and their virulence factors has fueled interest in technologies capable of detecting multiple pathogens and multiple virulence factors simultaneously. Some of these pathogens and their toxins have potential use as bioweapons. DNA microarray technology allows the simultaneous analysis of thousands of sequences of DNA in a relatively short time, making it appropriate for biodefense and for public health uses. This paper describes methods for using DNA microarrays to detect and analyze microbial pathogens. The FDA-1 microarray was developed for the simultaneous detection of several food-borne pathogens and their virulence factors including Listeria spp., Campylobacter spp., Staphylococcus aureus enterotoxin genes and Clostridium perfringens toxin genes. Three elements were incorporated to increase confidence in the microarray detection system: redundancy of genes, redundancy of oligonuelcotide probes (oligoprobes) for a specific gene, and quality control oligoprobes to monitor array spotting and target DNA hybridization. These elements enhance the reliability of detection and reduce the chance of erroneous results due to the genetic variability of microbes or technical problems with the microarray. The results presented demonstrate the potential of oligonucteotide microarrays for detection of environmental and biodefense relevant microbial pathogens. (C) 2004 Elsevier B.V. All rights reserved. C1 FDA Ctr Food Safety & Appl Nutr, College Pk, MD USA. Joint Inst Food Safety & Appl Nutr, College Pk, MD USA. FDA Ctr Biol Evaluat & Res, Rockville, MD USA. FDA Ctr Devices & Radiol Hlth, Silver Spring, MD USA. NIH Natl Canc Inst, Rockville, MD 20852 USA. RP Rasooly, A (reprint author), FDA Ctr Food Safety & Appl Nutr, College Pk, MD USA. EM rasoslya@mail.nih.gov NR 23 TC 90 Z9 99 U1 0 U2 8 PU ELSEVIER ADVANCED TECHNOLOGY PI OXFORD PA OXFORD FULFILLMENT CENTRE THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-5663 J9 BIOSENS BIOELECTRON JI Biosens. Bioelectron. PD NOV 1 PY 2004 VL 20 IS 4 BP 684 EP 698 DI 10.1016/j.bios.2004.04.030 PG 15 WC Biophysics; Biotechnology & Applied Microbiology; Chemistry, Analytical; Electrochemistry; Nanoscience & Nanotechnology SC Biophysics; Biotechnology & Applied Microbiology; Chemistry; Electrochemistry; Science & Technology - Other Topics GA 875IB UT WOS:000225412600003 PM 15522583 ER PT J AU Mills, JL Signore, C AF Mills, JL Signore, C TI Neural tube defect rates before and after food fortification with folic acid SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Editorial Material DE neural tube defects; folic acid; fortified food; folate; birth defects; enriched food ID RISK; PREVALENCE AB BACKGROUND: Since 1998, enriched cereal grains sold in the United States have been fortified with folic acid, to reduce the incidence of neural tube defects (NTDs). The Centers for Disease Control and Prevention (CDC) recently reported that NTD rates have decreased 26% since fortification, but that additional effort is needed to achieve the national goal of a 50% reduction. However, accurate determination of NTD rates requires counting antenatally detected cases; the CDC study noted that the number of prenatally diagnosed cases was likely underestimated. METHODS AND RESULTS: We examined studies from the United States and Canada that compared rates of NTDs before and after very similar fortification programs were instituted in each country. U.S. studies had incomplete ascertainment of prenatally diagnosed NTD cases, and as a result, underreported the number of NTDs prevented. Canadian studies, in which ascertainment was more complete, showed decreases in NTD rates up to 54%. CONCLUSIONS: There is a strong correlation between the completeness of ascertainment and the percentage decrease in NTD rates. Studies that identify cases best show that folic acid fortification is preventing around 50% of NTDs. The percentage of NTDs that are folate-preventable in the United States is uncertain, but is probably 50-60%. Thus, we may be quite close to achieving the optimum level of protection at current fortification levels. Published 2004 Wiley-Liss, Inc. C1 NICHD, Pediat Epidemiol Sect, DESPR, HHS,NIH, Bethesda, MD 20892 USA. RP Mills, JL (reprint author), NICHD, Pediat Epidemiol Sect, DESPR, HHS,NIH, 6100 Bldg,Room 7B03, Bethesda, MD 20892 USA. EM jamesmills@nih.gov NR 15 TC 74 Z9 80 U1 0 U2 9 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD NOV PY 2004 VL 70 IS 11 BP 844 EP 845 DI 10.1002/bdra.20075 PG 2 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 876UE UT WOS:000225522500004 PM 15468072 ER PT J AU Fry, TJ Sinha, M Milliron, M Chu, YW Kapoor, V Gress, RE Thomas, E Mackall, CL AF Fry, TJ Sinha, M Milliron, M Chu, YW Kapoor, V Gress, RE Thomas, E Mackall, CL TI Flt3 ligand enhances thymic-dependent and thymic-independent immune reconstitution SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; T-CELL REGENERATION; DENDRITIC CELLS; HOMEOSTATIC PROLIFERATION; HEMATOPOIETIC STEM; VIRAL DIVERSITY; TREATED MICE; IN-VIVO; INTERLEUKIN-7; RECEPTOR AB Despite recent progress in our understanding of the biology of T-cell homeostasis, clinically available therapies to substantially improve immune reconstitution in patients sustaining T-cell depletion are lacking. T cells are regenerated via a dynamic interplay between thymopoiesis and thymic-independent homeostatic peripheral expansion (HPE). Using athymic mice subjected to T-cell depletion, we observed that HPE is critically dependent on dendritic cells (DCs) for presentation of antigen, raising the possibility that the availability of DCs might be limiting in vivo for HPE to occur efficiently. Indeed, flt3 ligand (flt3L) treatment of athymic mice subjected to T-cell depletion (without DC depletion) substantially enhanced HPE and improved immune competence. Following bone marrow transplantation (BMT) in athymic hosts, both dendritic cells and T cells were profoundly depleted and fIt3L therapy restored DC numbers and enhanced HPE. In addition, thymus-bearing BMT recipients treated with flt3L regenerated increased numbers of thymic-dependent progeny with increased numbers of T-cell receptor excision circle (TREC)-positive T cells, indicating increased thymopoiesis. Therefore, flt3L is a potent immunorestorative agent that enhances both thymic-dependent and thymic-independent pathways of T-cell regeneration. (C) 2004 by The American Society of Hematology. C1 NCI, Ctr Canc Res, Pediat Oncol Branch, NIH, Bethesda, MD USA. NCI, Canc Res Ctr, Expt Immunol Branch, NIH, Bethesda, MD USA. Immunex Corp, Seattle, WA USA. RP Fry, TJ (reprint author), Bldg 10,Rm 13N240,MSC 1928,10 Ctr Dr, Bethesda, MD USA. EM tf60y@nih.gov FU NCI NIH HHS [N01-CO-56000] NR 54 TC 55 Z9 60 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2004 VL 104 IS 9 BP 2794 EP 2800 DI 10.1182/blood-2003-11-3789 PG 7 WC Hematology SC Hematology GA 866TI UT WOS:000224795700035 PM 15226184 ER PT J AU Smed-Sorensen, A Lore, K Walther-Jallow, L Andersson, J Spetz, AL AF Smed-Sorensen, A Lore, K Walther-Jallow, L Andersson, J Spetz, AL TI HIV-1-infected dendritic cells up-regulate cell surface markers but fail to produce IL-12 p70 in response to CD40 ligand stimulation SO BLOOD LA English DT Article ID NF-KAPPA-B; IMMUNODEFICIENCY-VIRUS-INFECTION; T-CELLS; HIV-1 INFECTION; IN-VITRO; INTERLEUKIN-12 PRODUCTION; MEASLES-VIRUS; SUPPRESSION; EXPRESSION; MATURATION AB Dendritic cells (DCs) are antigen-presenting cells with the capacity to prime naive T cells for efficient cellular responses against pathogens such as HIV-1. DCs are also susceptible to HIV-1 infection, which may impair their ability to induce immunity. Here, we examined the ability of HIV-1-infected, in vitro-derived DCs to respond to CD40 ligand (CD40L) stimulation with the aim to study events during early HIV-1 infection. HIV-1(BaL)-infected p24(+) DCs were detected after only 3 days of exposure to highly concentrated virus. We show that HIV-1-infected DCs upregulated costimulatory molecules, but were skewed in their production of effector cytokines in response to CD40L stimulation. CD40L stimulation induced significant secretion of tumor necrosis factor a (TNFalpha) and interleukin 12 (IL-12) p70 from both HIV-1-exposed and unexposed DCs. Intracellular stainings of HIV-1-exposed DCs revealed that TNFalpha could be detected in both the p24(-) and p24(+) DCs, but IL-12 p70 could be found only in the p24(-)DCs. Thus, although p24+ DCs showed a mature phenotype similar to p24- DCs after CD40L stimulation, they appeared to have an impaired cytokine profile. These observations suggest that HIV-1 infection disables DC function, a phenomenon that may be relevant for optimal induction of HIV-1-specific immune responses. (C) 2004 by The American Society of Hematology. C1 Karolinska Univ, Karolinska Inst, Huddinge Hosp, Ctr Infect Med,Dept Med, S-14186 Huddinge, Sweden. NIH, Vaccine Res Ctr, Bethesda, MD USA. RP Smed-Sorensen, A (reprint author), Karolinska Univ, Karolinska Inst, Huddinge Hosp, Ctr Infect Med,Dept Med, F59, S-14186 Huddinge, Sweden. EM anna.smed.sorensen@medhs.ki.se RI Spetz, Anna-Lena/C-3543-2016 OI Spetz, Anna-Lena/0000-0003-3964-9512 NR 43 TC 82 Z9 82 U1 2 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2004 VL 104 IS 9 BP 2810 EP 2817 DI 10.1182/blood-2003-07-2314 PG 8 WC Hematology SC Hematology GA 866TI UT WOS:000224795700037 PM 15231570 ER PT J AU Montaner, S Sodhi, A Servitja, JM Ramsdell, AK Barac, A Sawai, ET Gutkind, JS AF Montaner, S Sodhi, A Servitja, JM Ramsdell, AK Barac, A Sawai, ET Gutkind, JS TI The small GTPase Rac1 links the Kaposi sarcoma-associated herpesvirus vGPCR to cytokine secretion and paracrine neoplasia SO BLOOD LA English DT Article ID PROTEIN-COUPLED RECEPTOR; NF-KAPPA-B; HUMAN-IMMUNODEFICIENCY-VIRUS; HETEROTRIMERIC G-PROTEINS; GENE-EXPRESSION; NUCLEAR-FACTOR; EXCHANGE FACTOR; RHO GTPASES; INTERLEUKIN-6 EXPRESSION; CONSTITUTIVE ACTIVATION AB Kaposi sarcoma (KS) is a multifocal angioproliferative neoplasm strictly dependent on angiogenic growth factors and cytokines and invariably associated with infection by the Kaposi sarcoma-associated herpesvirus (KSHV or HHV8). A G protein-coupled receptor encoded by KSHV (vGPCR) is able to initiate KS-like tumors when targeted to the vascular endothelium of mice. Analogous to human KS, vGPCR sarcomagenesis involves the paracrine secretion of angiogenic growth factors and proinflammatory molecules from vGPCR-expressing cells. Here we demonstrate that vGPCR up-regulates expression and secretion of critical KS cytokines by stimulating key transcription factors, including nuclear factor-KB (NFkappaB), activator protein-1 (AP-1), and nuclear factor of activated T cells (NFAT), through the activation of the small G protein Rac1. Inhibition of Rac1 blocked vGPCR-induced transcription and secretion of KS cytokines, including interleukin-6 (IL-6), IL-8, and growth-regulated oncogene alpha (GROalpha), in vitro and reduced vGPCR tumorigenesis in vivo. Moreover, endothelial-specific infection with the constitutively active Rac1QL induced vascular lesions in mice that were remarkably similar to early vGPCR experimental lesions. These results identify Rac1 as a key mediator of vGPCR paracrine neoplasia, suggesting that this small G protein and its downstream effectors may represent suitable therapeutic targets for the treatment of KS. (C) 2004 by The American Society of Hematology. C1 Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Davis, Grad Grp, Dept Med Pathol & Comparat Pathol, Davis, CA USA. RP Gutkind, JS (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Bldg 30,Rm 212, Bethesda, MD 20892 USA. EM sg39v@nih.gov RI Gutkind, J. Silvio/A-1053-2009; OI SERVITJA DUQUE, JOAN-MARC/0000-0002-1241-8004; Barac, Ana/0000-0002-9935-8904 FU NIAID NIH HHS [R0-1 AI46145-01A2] NR 63 TC 69 Z9 72 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2004 VL 104 IS 9 BP 2903 EP 2911 DI 10.1182/blood-2003-12-4436 PG 9 WC Hematology SC Hematology GA 866TI UT WOS:000224795700049 PM 15231571 ER PT J AU Wang, GJ Chang, L Volkow, ND Telang, F Logan, J Ernst, T Fowler, JS AF Wang, GJ Chang, L Volkow, ND Telang, F Logan, J Ernst, T Fowler, JS TI Decreased brain dopaminergic transporters in HIV-associated dementia patients SO BRAIN LA English DT Article DE HIV; dopamine; dementia; PET; cocaine ID IMMUNODEFICIENCY-VIRUS-INFECTION; BASAL GANGLIA; PARKINSONS-DISEASE; AIDS; METHYLPHENIDATE; DEGENERATION; APOPTOSIS; SYMPTOMS; SYSTEM; VOLUME AB HIV has a propensity to invade subcortical regions of the brain, which may lead to a subcortical dementia termed HIV-cognitive motor complex. Therefore, we aimed to assess whether dopamine (DA) D2 receptors and transporters (DAT) are affected in the basal ganglia of subjects with HIV, and how these changes relate to dementia status. Fifteen HIV subjects (age 44.5 +/- 11 years; CD4 185 +/- 130/mm(3)) and 13 seronegative controls (42 +/- 12 years) were evaluated with PET to assess availability of DAT ([C-11]cocaine) and DA D2 receptor ([C-11]raclopride). HIV patients with associated dementia (HAD), but not those without dementia (ND) had significantly lower DAT availability in putamen (-19.3%, P = 0.009) and ventral striatum (-13.6%, P = 0.03) compared with seronegative controls. Higher plasma viral load in the HIV dementia patients correlated with lower DAT in the caudate (r = -0.7, P = 0.02) and putamen (r = -0.69, P = 0.03). DA D2 receptor availability, however, showed mild and non-significant decreases in HIV patients. These results provide the first evidence of DA terminal injury in HIV dementia patients, and suggest that decreased DAT may contribute to the pathogenesis of HIV dementia. The greater DAT decrease in the putamen than in the caudate parallels that observed in Parkinson's disease. The inverse relationship between viral burden and DAT availability further supports HIV-mediated neurotoxicity to dopaminergic terminals. C1 Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. Brookhaven Natl Lab, Dept Chem, Upton, NY 11973 USA. NIAAA, Bethesda, MD USA. NIDA, Bethesda, MD 20892 USA. RP Chang, L (reprint author), Univ Hawaii, John A Burns Sch Med, Dept Med, Queens Univ Tower,7th Floor,1356 Lusitana St, Honolulu, HI 96813 USA. EM lchang@hawaii.edu OI Logan, Jean/0000-0002-6993-9994 FU NIDA NIH HHS [DA K24-DA16170, K02-DA16991] NR 30 TC 126 Z9 130 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD NOV PY 2004 VL 127 BP 2452 EP 2458 DI 10.1093/brain/awh269 PN 11 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 865LD UT WOS:000224703700008 PM 15319273 ER PT J AU Morgen, K Kadom, N Tessitore, A Ohayon, J McFarland, H Frank, J Martin, R Cohen, LG AF Morgen, K Kadom, N Tessitore, A Ohayon, J McFarland, H Frank, J Martin, R Cohen, LG TI Training-dependent plasticity in patients with multiple sclerosis SO BRAIN LA English DT Article DE multiple sclerosis; funcional MRI; plasticity; training; dorsal premotor cortex ID POSITRON-EMISSION-TOMOGRAPHY; ADAPTIVE FUNCTIONAL-CHANGES; POSTERIOR PARIETAL CORTEX; PRIMARY MOTOR CORTEX; CEREBRAL-CORTEX; PREMOTOR CORTEX; CHRONIC STROKE; CORTICAL ACTIVATION; HAND MOVEMENT; D-AMPHETAMINE AB Cortical reorganization has been demonstrated in the motor network that mediates performance of a motor task in patients with multiple sclerosis. How this network responds to motor training is not known. This study examined functional MRI (fMRI) activation patterns associated with performance of a motor task, consisting of repetition of directionally specific voluntary thumb movements, before and after motor training in a group of multiple sclerosis patients with mild motor impairment of the right upper extremity. Patients and healthy subjects were scanned in one session before, during and after a 30 min training period. fMRI data obtained during rest, thumb flexion (trained movement) and thumb extension (untrained movement) were analysed using random effects analysis (SPM99). Motor kinematics of training motions and EMG from the resting hand were monitored with an accelerometer and surface EMG electrodes. Kinematics of thumb movements before, during and after training were comparable in the absence of mirror EMG activity in the resting hand. Before training, thumb movements elicited more prominent activation of the contralateral dorsal premotor cortex [PMd, Brodmann area (BA) 6] in multiple sclerosis patients than in controls. After training, unlike the control group, multiple sclerosis patients did not exhibit task-specific reductions in activation in the contralateral primary somatosensory (S1), motor (M1) and adjacent parietal association (BA 40) cortices. These results indicate that patients engage the contralateral PMd more than controls in order to perform directionally specific movements before training. The absence of training-dependent reductions in activation in S1, M1 and BA 40 is consistent with a decreased capacity to optimize recruitment of the motor network with practice. C1 NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NIH, Lab Radiol Res, Bethesda, MD 20892 USA. Univ Giessen, Dept Neurol, Giessen, Germany. Bender Inst Neuroimaging, Giessen, Germany. RP Cohen, LG (reprint author), NINDS, Human Cort Physiol Sect, NIH, Bldg 10,Room 5N226,10 Ctr Dr,MSC-1430, Bethesda, MD 20892 USA. EM martinr@ninds.nih.gov; cohenL@ninds.nih.gov OI Kadom, Nadja/0000-0002-7073-956X NR 82 TC 61 Z9 63 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD NOV PY 2004 VL 127 BP 2506 EP 2517 DI 10.1093/brain/awh266 PN 11 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 865LD UT WOS:000224703700014 PM 15456705 ER PT J AU Bennett, LM Montgomery, JL Steinberg, SM Kulp, KS AF Bennett, LM Montgomery, JL Steinberg, SM Kulp, KS TI Flor-Essence (R) herbal tonic does not inhibit mammary tumor development in Sprague Dawley rats SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE complementary and alternative medicine; DMBA tumors; herbal tonic; mammary tumors; Sprague-Dawley rat model ID BREAST-CANCER; GLAND CARCINOGENESIS; GREEN TEA; GENISTEIN; TUMORIGENESIS; EXPOSURE; MEDICINE AB Background: Women who are diagnosed with breast cancer often self-administer complementary and alternative medicines to augment their conventional treatments, improve health, or prevent recurrence. Flor-Essence(R) tonic is a complex mixture of herbal extracts used by cancer patients because of anecdotal evidence that it can treat or prevent disease. Methods: Female Sprague-Dawley rats were given water or exposed to 3 or 6% Flor-Essence(R) beginning at 1 day of age. Mammary tumors were induced with a single oral 40 mg/kg/bw dose of dimethylbenz[ a] anthracene at 50 days of age and sacrificed at 23 weeks. Rats were maintained on AIN-76A diet. Results: Control rats had palpable mammary tumor incidence of 51.0% at 19 weeks of age compared to 65.0 and 59.4% for the 3 and 6% Flor-Essence(R) groups respectively. Overall, no significant difference in time until first palpable tumor was detected among any of the groups. At necropsy, mammary tumor incidence was 82.5% for controls compared to 90.0 and 97.3% for rats consuming 3 and 6% Flor-Essence(R), respectively. Mean mammary tumor multiplicity (+/-SEM) for the controls was 2.8 (+/-0.5) and statistically different from the 3 or 6% Flor-Essence(R) groups with 5.2 (+/-0.7), and 4.8 (+/-0.6), respectively (p less than or equal to 0.01). As expected, the majority of isolated tumors were diagnosed as adenocarcinomas. Conclusions: Flor-Essence(R) can promote mammary tumor development in the Sprague-Dawley rat model. This observation is contrary to widely available anecdotal evidence as well as the desire of the consumer that this commercially available herbal tonic will suppress and/or inhibit tumor growth. C1 Natl Canc Inst, Ctr Canc Res, NIH, Rockville, MD 20852 USA. Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, Livermore, CA USA. NCI, Biostat & Data Management Sect, CCR, NIH, Bethesda, MD 20892 USA. RP Bennett, LM (reprint author), Natl Canc Inst, Ctr Canc Res, NIH, Bldg 31 Room 3A11,31 Ctr Dr, Rockville, MD 20852 USA. EM lmbennett@nih.gov NR 34 TC 4 Z9 5 U1 1 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD NOV PY 2004 VL 88 IS 1 BP 87 EP 93 PG 7 WC Oncology SC Oncology GA 869YX UT WOS:000225022300010 PM 15538049 ER PT J AU Anderson, WF Chu, KC Devesa, SS AF Anderson, WF Chu, KC Devesa, SS TI Distinct incidence patterns among in situ and invasive breast carcinomas, with possible etiologic implications SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE age-specific breast cancer incidence rates; breast carcinoma in situ; estrogen receptor expression ID PROGESTERONE-RECEPTOR STATUS; END RESULTS DATABASE; CANCER CHARACTERISTICS; RACIAL/ETHNIC GROUPS; ESTROGEN-RECEPTOR; UNITED-STATES; RISK-FACTORS; FEMALE; EPIDEMIOLOGY; DIAGNOSIS AB Background. Incidence patterns are well-established for invasive breast carcinoma (InvBC) overall and for InvBC defined by estrogen receptor (ER) expression, but are not as well-defined for breast carcinoma in situ (CIS). Methods. We, therefore, examined and compared the incidence patterns for CIS and InvBC in the SEER program to define these patterns and to generate etiologic hypotheses. Data were stratified by age < 50 and &GE;50 years to approximate menopause. Results. During the years 1973-2000, annual age-adjusted incidence rates rose 660% for CIS and 36% for InvBC, with the most rapid increases occurring in women age &GE;50 years. Age-specific incidence rate curves for CIS increased until age 50 years, and then flattened, irrespective of ER expression. On the other hand, rates for InvBC overall and for InvBC defined by ER-positive expression increased continuously with aging, whereas rates for InvBC defined by ER-negative expression flattened after 50 years. Age frequency distribution for CIS and for ER-negative InvBC demonstrated bimodal populations, with a predominant early onset peak incidence at age 50 years. Age frequency distribution for ER-positive InvBC showed bimodal populations with a predominant late-onset mode at age 71 years. Conclusion. Over the last three decades, age-adjusted incidence trends differed for CIS and InvBC in the United States, possibly due to screening mammography and/or etiologic diversity. Indeed, age-specific incidence patterns suggested that carcinogenic events operating early in reproductive life had greater impact upon CIS and InvBC defined by ER-negative expression than upon InvBC overall and InvBC defined by ER-positive expression. C1 NCI, US Dept HHS, NIH, Div Canc Prevent,EPN, Bethesda, MD 20892 USA. NCI, US Dept HHS, NIH, Ctr Reduce Canc Hlth Dispar, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Anderson, WF (reprint author), NCI, US Dept HHS, NIH, Div Canc Prevent,EPN, Suite 2141,6130 Execut Blvd, Bethesda, MD 20892 USA. EM wanders@mail.nih.gov NR 49 TC 20 Z9 21 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD NOV PY 2004 VL 88 IS 2 BP 149 EP 159 DI 10.1007/s10549-004-1483-9 PG 11 WC Oncology SC Oncology GA 882XP UT WOS:000225974000006 PM 15564798 ER PT J AU Yamaguchi, Y Yoshida, S Sumikawa, Y Kubo, T Hosokawa, K Ozawa, K Hearing, VJ Yoshikawa, K Itami, S AF Yamaguchi, Y Yoshida, S Sumikawa, Y Kubo, T Hosokawa, K Ozawa, K Hearing, VJ Yoshikawa, K Itami, S TI Rapid healing of intractable diabetic foot ulcers with exposed bones following a novel therapy of exposing bone marrow cells and then grafting epidermal sheets SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article DE bone marrow cells; diabetes mellitus; diabetic foot ulcer; epidermal grafting; occlusive dressing; wound healing ID EPITHELIAL-MESENCHYMAL INTERACTIONS; PALMOPLANTAR FIBROBLASTS; STROMAL CELLS; STEM-CELLS; SKIN; MANAGEMENT; DIFFERENTIATION; ENGRAFTMENT; INFECTIONS; AMPUTATION AB Background Diabetic foot ulcers with exposed bones commonly result in amputation. Objectives To determine whether exposure of bone marrow cells and subsequent grafting of epidermal sheets accelerates healing and reduces the need for amputation. Methods Thirty-eight patients with chronic wounds caused by diabetes mellitus were enrolled in this study. Epidermal sheets obtained from suction blisters of each patient were grafted on to diabetic foot ulcers without exposed bones (n = 10) and were compared with the standard treatment of local wound care, debridement with a scalpel when indicated, bed rest and parenteral antibiotics (n = 8). In another group of patients, diabetic wounds with exposed bones were treated either with the standard procedure (n = 9) or with a newly developed experimental procedure (n = 11). In that new procedure, the affected bone was initially exposed by debridement with a scalpel, followed by partial excision with a bone scraper until fresh bleeding was observed from the exposed bone. The lesions were then immediately covered with an occlusive dressing, and finally the wound was covered with an epidermal graft of skin harvested from suction blisters. Patients in each group were matched with their counterparts by age, sex, wound size, wound infection and wound duration, to compare the time needed for total skin repair and rates of amputation. Results Epidermal grafting significantly accelerated the healing of diabetic foot ulcers (P = 0.042) without exposed bones, with site-specific differentiation. The newly developed combination therapy resulted in the healing of all diabetic ulcers with exposed bones without the occurrence of osteomyelitis or the necessity for amputation (P < 0.0001). Conclusions Our study indicates that early aggressive debridement of diabetic foot ulcers with exposed bones down to a bleeding vascularized base and then grafting epidermal sheets significantly improves healing and reduces the rate of amputation. C1 Osaka Univ, Grad Sch Med, Dept Dermatol, Suita, Osaka 5650871, Japan. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Itami, S (reprint author), Osaka Univ, Grad Sch Med, Dept Dermatol, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan. EM itami@derma.med.osaka-u.ac.jp RI Yamaguchi, Yuji/B-9312-2008 NR 37 TC 36 Z9 36 U1 1 U2 6 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD NOV PY 2004 VL 151 IS 5 BP 1019 EP 1028 DI 10.1111/j.1365-2133.2004.06170.x PG 10 WC Dermatology SC Dermatology GA 870TH UT WOS:000225080600009 PM 15541080 ER PT J AU Buist, DSM Anderson, ML Taplin, SH LaCroix, AZ AF Buist, DSM Anderson, ML Taplin, SH LaCroix, AZ TI The relationship between breast density and bone mineral density in postmenopausal women SO CANCER LA English DT Article DE breast density; bone mineral density; estrogen exposure; body mass index; hormone therapy ID MAMMOGRAPHIC PARENCHYMAL PATTERN; CANCER RISK; UNITED-STATES; OSTEOPOROTIC FRACTURES; REPLACEMENT THERAPY; ENDOGENOUS HORMONES; TIME; MASS; DETERMINANTS; EPIDEMIOLOGY AB BACKGROUND. It is not well understood whether breast density is a marker of cumulative exposure to estrogen or a marker of recent exposure to estrogen. The authors examined the relationship between bone mineral density (BMD; a marker of lifetime estrogen exposure) and breast density. METHODS. The authors conducted a cross-sectional analysis among 1800 postmenopausal women greater than or equal to 54 years. BMD data were taken from two population-based studies conducted in 1992-1993 (n = 1055) and in 1998-1999 (n = 753). The authors linked BMD data with breast density information collected as part of a mammography screening program. They used linear regression to evaluate the density relationship, adjusted for age, hormone therapy use, body mass index (BMI), and reproductive covariates. RESULTS. There was a small but significant negative association between BMD and breast density. The negative correlation between density measures was not explained by hormone therapy or age, and BMI was the only covariate that notably influenced the relationship. Stratification by BMI only revealed the negative correlation between bone and breast densities in women with normal BMI. There was no relationship in overweight or obese women. The same relationship was seen for all women who had never used hormone therapy, but it was not significant once stratified by BMI. CONCLUSIONS. BMD and breast density were not positively associated although both are independently associated with estrogen exposure. It is likely that unique organ responses obscure the relationship between the two as indicators of cumulative estrogen exposure. (C) 2004 American Cancer Society. C1 Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. NCI, Appl Res Program, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. RP Buist, DSM (reprint author), Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, 1730 Minor Ave Suite 1600, Seattle, WA 98101 USA. EM buist.d@ghc.org FU NCI NIH HHS [U01CA63731] NR 33 TC 8 Z9 8 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 2004 VL 101 IS 9 BP 1968 EP 1976 DI 10.1002/cncr.20565 PG 9 WC Oncology SC Oncology GA 864IL UT WOS:000224627100006 PM 15386302 ER PT J AU Hoffman, RM Gilliland, FD Penson, DF Stone, SN Hunt, WC Potosky, AL AF Hoffman, RM Gilliland, FD Penson, DF Stone, SN Hunt, WC Potosky, AL TI Cross-sectional and longitudinal comparisons of health-related quality of life between patients with prostate carcinoma and matched controls SO CANCER LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med DE prostatic neoplasms; quality of life; aging; prostatectomy; radiotherapy ID EXTERNAL-BEAM RADIATION; RADICAL PROSTATECTOMY; CANCER OUTCOMES; SEXUAL FUNCTION; MEN; THERAPY; RADIOTHERAPY; BRACHYTHERAPY; VALIDATION; CAPSURE AB BACKGROUND. Prostate carcinoma and treatments affect health-related quality of life (HRQOL). The authors prospectively compared prostate and general HRQOL between prostate carcinoma cases and an age-matched and ethnicity-matched control group. METHODS. The case cohort consisted of 293 men with localized prostate carcinoma who were selected randomly from the population-based New Mexico Tumor Registry, and the control cohort consisted of 618 men who were selected randomly from administrative databases and matched for age and ethnicity. Subjects completed a baseline survey of demographics, socioeconomic status, comorbidity, and prostate and general HRQOL. Also, 210 cases (71.7%) and 421 controls (67.8%) completed a follow-up survey 5 years later. Multinomial logistic regression models compared baseline characteristics as well as 5-year general HRQOL outcomes measured by selected domains of the Medical Outcomes Study SF-36. The authors used a mixed-model repeated-measures analysis of variance and multinomial regression analyses to compare longitudinal changes in urinary, bowel, and sexual function between groups. RESULTS. At baseline, patients with prostate carcinoma had better urinary control and sexual function than controls. Over 5 years, sexual function declined significantly among controls, although urinary function remained stable. However, patients with cancer subsequently reported significant declines in both domains and were left with much worse function and more bother than controls. Bowel function and general HRQOL were similar for both groups at follow-up. CONCLUSIONS. Prostate carcinoma treatment led to significant 5-year declines in urinary and sexual function that far exceeded age-related changes in controls. Patients with cancer had significantly worse function and more bother than controls for these disease-specific domains of HRQOL. Bowel function and general HRQOL were not affected by cancer status. Published 2004 by the American Cancer Society.* C1 New Mexico Vet Affairs Hlth Care Syst, Med Serv, Albuquerque, NM 87108 USA. Univ New Mexico, Canc Res & Treatment Ctr, Epidemiol & Canc Prevent Program, Albuquerque, NM 87131 USA. Univ So Calif, Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. Univ So Calif, Sch Med, Dept Surg, Los Angeles, CA 90033 USA. NCI, Div Canc Prevent & Control, Bethesda, MD 20892 USA. RP Hoffman, RM (reprint author), New Mexico Vet Affairs Hlth Care Syst, Med Serv, 111 GIM,1501 San Pedro SE, Albuquerque, NM 87108 USA. EM rhoffman@unm.edu FU NCI NIH HHS [N01PC67006, N01PC67007, N01PC67000, N01PC67010, N01PC67005, N01CN67009] NR 38 TC 41 Z9 42 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 2004 VL 101 IS 9 BP 2011 EP 2019 DI 10.1002/cncr.20608 PG 9 WC Oncology SC Oncology GA 864IL UT WOS:000224627100012 PM 15452835 ER PT J AU Tohnya, TM Figg, WD AF Tohnya, TM Figg, WD TI Immunomodulation of multiple myeloma SO CANCER BIOLOGY & THERAPY LA English DT Article DE immunomodulation; angiogenesis; thalidomide; CC-4047; multiple myeloma ID FIBROBLAST-GROWTH-FACTOR; THALIDOMIDE ANALOG; CANCERS AB Multiple myeloma is a multi-process disease, and these different processes are responsible for the reduced sensitivity to chemotherapy and radiotherapy, hence the relapse and refractory nature of multiple myeloma. Emphasis is now placed on the hypothesis that myeloma cell growth, inhibition of apoptosis and drug resistance are dependent on immunomodulatory cytokines such as IL-6 and pro-angiogenic factors such as VEGF. In addition to its anti-angiogenic effects, the immunomodulatory properties of thalidomide make it a possible therapy for patients with advanced multiple myeloma. This has lead to the clinical development of a number of immunomodulatory thalidomide analogues (IMiDs) which are more potent and have less side effects than the parent drug, thalidomide. In the August 15th issue of Journal of Clinical Oncology, Schey SA et al. suggested that an IMiD (CC-4047) maybe efficacious due to T-cell co-stimulation, and safe in patients with relapsed or refractory multiple myeloma. This article demonstrates a supporting role for IMiDs as immunomodulatory adjuvant therapy. C1 NCI, Med Oncol Clin Res Unit, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Sch Pharm, Dept Pharmaceut, Richmond, VA USA. RP Figg, WD (reprint author), NCI, Med Oncol Clin Res Unit, Bldg 10,Room 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 14 TC 6 Z9 6 U1 0 U2 1 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD NOV PY 2004 VL 3 IS 11 BP 1060 EP 1061 PG 2 WC Oncology SC Oncology GA 913FA UT WOS:000228135800012 PM 15640623 ER PT J AU Zheng, YF Zhang, JR Rao, ZG AF Zheng, YF Zhang, JR Rao, ZG TI Ribozyme targeting HPV16 E6E7 transcripts in cervical cancer cells suppresses cell growth and sensitizes cells to chemotherapy and radiotherapy SO CANCER BIOLOGY & THERAPY LA English DT Article DE ribozyme; human papillomavirus; cervical cancer; gene therapy; chemotherapy; radiotherapy ID LINE; P53 AB Human Papillomavirus (HPV) is related to more than 90% of cervical cancer. The virus is shown to be essential for the induction and maintenance of the malignant phenotype in cervical cancer. In this report, we designed a hammerhead ribozyme Rz170 to specifically target the HPV16 E6E7 transcripts, and our results demonstrated that Rz170 can cleave HPV16 E61E7 transcripts effectively and with high specificity. When transfected into a HPV 16 positive cervical cancer cell, CaSKi, the ribozyme reduced the expression of HPV16 E6 and E7 mRNA, and inhibited cell growth both in vitro and in vivo. The percentage of apoptosis cells was also increased. We found that Rz170 reduced the expression of the viral E6 and E7 proteins, and cellular c-myc, bcl-2 proteins, but increased the expression of p53 and Rb proteins. It is likely that the ribozyme inhibited cervical cancer cell growth by reducing the expression of the HPV16 E6 and E7gene, which may alter the expression of p53, Rb, c-myc and bcl-2, and led to apoptosis in cancer cells. We also found that CaSKi cells transfected with Rz170 showed increased sensitivity to cisplatin and radiation. Our study demonstrated the potential of Rz170 for treating cervical cancer, and the possibility of using a combined therapeutic strategy involving ribozyme, chemotherapy or radiotherapy. C1 NIAID, NIH, Mol Microbiol Lab, Rockville, MD 20852 USA. First Mil Med Univ, Zhujiang Hosp, Dept Oncol, Guangzhou, Peoples R China. RP Zheng, YF (reprint author), NIAID, NIH, Mol Microbiol Lab, Twinbrook 2 Facil,Rm201 12441 Parklawn Dr, Rockville, MD 20852 USA. EM yazheng@niaid.nih.gov NR 18 TC 19 Z9 21 U1 0 U2 2 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD NOV PY 2004 VL 3 IS 11 BP 1129 EP 1134 PG 6 WC Oncology SC Oncology GA 913FA UT WOS:000228135800023 PM 15467442 ER PT J AU Lawson, KA Anderson, K Snyder, RM Simmons-Menchaca, M Atkinson, J Sun, LZ Bandyopadhyay, A Knight, V Gilbert, BE Sanders, BG Kline, K AF Lawson, KA Anderson, K Snyder, RM Simmons-Menchaca, M Atkinson, J Sun, LZ Bandyopadhyay, A Knight, V Gilbert, BE Sanders, BG Kline, K TI Novel vitamin E analogue and 9-nitro-camptothecin administered as liposome aerosols decrease syngeneic mouse mammary tumor burden and inhibit metastasis SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE vitamin E analogue alpha-TEA; 9-nitrocamptothecin; metastasis; antitumor; syngeneic mouse mammary cancer model ID ANTITUMOR-ACTIVITY; BREAST-CANCER; IN-VITRO; PHASE-II; 9-NITROCAMPTOTHECIN; CAMPTOTHECIN; CELLS; MICE; TOXICITY; MELANOMA AB Purpose: To test the anticancer properties of a nonhydrolyzable ether-linked acetic acid analogue of vitamin E, 2,5,7,8-tetramethyl-2R-(4R, 8R, 12-trimethyltridecyl) chroman-6-yloxyacetic acid (alpha-TEA), and a derivative of camptothecin, 9-nitrocamptothecin (9-NC) singly and in combination against mouse mammary tumor cells ( line 66 clone 4 stably transfected with green fluorescent protein; 66c1-4-GFP) cultured in vitro or transplanted subcutaneously into the inguinal region of female BALB/c mice to form established tumors. Methods: Following in vitro treatment of 66cl-4-GFP cells with alpha-TEA and suboptimal concentrations of 9-NC, singly or in combination, apoptosis was measured by morphological evaluation of nuclei stained with 4', 6-diamidino- 2-phenylindole ( DAPI), and DNA synthesis arrest was measured by tritiated thymidine uptake. For in vivo analyses alpha-TEA and 9-NC, both water-insoluble compounds, were formulated into liposomes using dilauroylphosphatidylcholine and administered by aerosol to deliver doses calculated to be 36 and 0.4 mug/mouse per day, respectively, ( singly or each separately for combined treatments) 7 days per week. Results: Treatment of 66cl-4-GFP cells in culture for 3 days with a combination of alpha-TEA ( 10 mug/ml; singly produces 38% apoptosis), and suboptimal concentrations of 9-NC (15.6, 31.3, 62.5, or 125 ng/ml; singly produce 2 - 7% apoptosis), produced 47%, 58%, 64%, and 69% apoptosis. Likewise, combinations of alpha-TEA + 9-NC inhibited DNA synthesis more than either agent administered singly. A significant reduction (P< 0.001) in growth of subcutaneous transplanted tumors was observed with liposome-formulated and aerosolized delivery of α-TEA+ 9-NC to BALB/c mice. The incidence of macroscopic lung metastasis was 83% in control vs 8% in α-TEA-, 9-NC-, or combination-treated mice. Fluorescence microscopic examination of lungs and axillary and brachial lymph nodes showed a statistically significant decrease in metastasis observed in α-TEA-, 9-NC-, and combination- vs control-treated animals. Analyses of primary tumor tissue for proliferation and apoptosis showed treatment groups to have lower Ki-67 and higher terminal deoxynucleotidyl transferase-mediated nick end labeling, respectively. Treatments showed no measurable effects on two angiogenesis parameters, namely intratumoral blood volume as assessed by hemoglobin content and intratumoral blood vessel density as assessed with CD31 staining. Conclusions: Combination treatments enhanced antiproliferative and proapoptotic activities in cell culture, and when formulated in liposomes and delivered via aerosolization to treat an aggressive and metastatic syngeneic murine mammary tumor, the combination treatment showed a significant reduction in tumor volume in comparison to either treatment alone. Mechanistically, it appears that neither enhanced apoptosis, reduced cell proliferation, nor reduced blood vessel density can fully account for the enhanced effects of the combination treatment. C1 Univ Texas, Div Nutr, Austin, TX 78712 USA. NIH, Canc Prevent Fellowship Programs, NCI, DHHS, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Texas, Sch Biol Sci, Austin, TX 78712 USA. Brock Univ, Dept Chem, St Catharines, ON L2S 3A1, Canada. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. Baylor Coll Med, Dept Mol Physiol & Biophys, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. RP Kline, K (reprint author), Univ Texas, Div Nutr, Austin, TX 78712 USA. EM k.kline@mail.utexas.edu OI Atkinson, Jeffrey/0000-0003-3710-4893 FU NCI NIH HHS [CA79683, CA59739]; NIEHS NIH HHS [ES 07784, T32 ES 07247] NR 22 TC 42 Z9 43 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD NOV PY 2004 VL 54 IS 5 BP 421 EP 431 DI 10.1007/s00280-004-0817-y PG 11 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 864FD UT WOS:000224618500007 PM 15197487 ER PT J AU Strasser, AA Pickworth, WB Patterson, F Lerman, C AF Strasser, AA Pickworth, WB Patterson, F Lerman, C TI Smoking topography predicts abstinence following treatment with nicotine replacement therapy SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CIGARETTE SMOKERS; LUNG-CANCER; DEPENDENCE; CESSATION; EXPOSURE; PATCH; BEHAVIOR; PATTERNS; PUFF AB Objective: Smoking topography refers to how a person smokes a cigarette and includes measures of the number of puffs and puff volume, duration, and velocity. This study examined the relationship between smoking topography and abstinence from cigarettes following nicotine replacement therapy. A secondary objective was to determine the relationship of smoking topography to carbon monoxide (CO) exposure. Method: Participants (n = 113) smoked one of their preferred brands of cigarette through a smoking topography device prior to participating in an open-label trial of transdermal nicotine versus nicotine nasal spray. A subset of participants (n = 50) provided breath CO samples prior to and following smoking the cigarette. Results: Mean V-max [odds ratio (OR), 1.12; 95% confidence interval (95% CI), 1.02-1.24; P = 0.02], mean puff volume (OR, 0.95; 95% CI, 0.91-0.98; P = 0.01), mean interpuff interval (OR, 1.06; 95% CI, 1.00-1.11; P = 0.03), and cigarette type (full flavor versus light/ultralight; OR, 0.35; 95% CI, 0.14-0.89; P = 0.03) were significant predictors of abstinence in a model controlling for treatment group and nicotine dependence. Controlling for time since last cigarette and initial CO level, mean puff velocity (beta = 0.171; P = 0.01) was the only significant predictor of CO boost. Conclusion: These results suggest that smoking topography may be useful to predict abstinence after using nicotine replacement therapy and to assess harm from smoking. C1 Univ Penn, Transdisciplinary Tobacco Use Res Ctr, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Natl Inst Drug Abuse, Intramural Res Program, Clin Pharmacol Branch, Baltimore, MD 21224 USA. RP Strasser, AA (reprint author), Univ Penn, Transdisciplinary Tobacco Use Res Ctr, Dept Psychiat, 3535 Market St,Suite 4100, Philadelphia, PA 19104 USA. EM strasse3@mail.med.upenn.edu FU NCI NIH HHS [CA/DA P5084718] NR 30 TC 33 Z9 33 U1 3 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1800 EP 1804 PN 1 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QM UT WOS:000225072900018 PM 15533910 ER PT J AU Joshi, N Johnson, LL Wei, W Abnet, C Dong, ZW Taylor, PR Limburg, J Dawsey, SM Qiao, YL Kirsch, IR AF Joshi, N Johnson, LL Wei, W Abnet, C Dong, ZW Taylor, PR Limburg, J Dawsey, SM Qiao, YL Kirsch, IR TI Gene expression differences in normal tissues from patients whose dysplastic esophageal lesions regressed or progressed following selenomethionine treatment. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Beijing 100037, Peoples R China. Mayo Clin, Coll Med, Rochester, MN USA. RI Qiao, You-Lin/B-4139-2012 OI Qiao, You-Lin/0000-0001-6380-0871 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1829S EP 1829S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100010 ER PT J AU Szabo, E Lam, S Kucuk, O Mao, J McWilliams, A leRiche, J MacAulay, C Pas, H Stevens, T Madan, S Lonardo, F Upfal, M Adams, B Fishbein, M Rao, JY Dubinett, S Vourlekis, JS AF Szabo, E Lam, S Kucuk, O Mao, J McWilliams, A leRiche, J MacAulay, C Pas, H Stevens, T Madan, S Lonardo, F Upfal, M Adams, B Fishbein, M Rao, JY Dubinett, S Vourlekis, JS TI Incidence of bronchial dysplasia in cohorts identified via different screening strategies. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Bethesda, MD 20892 USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1831S EP 1831S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100015 ER PT J AU Crean, C Kopelovich, L Nakshatri, H AF Crean, C Kopelovich, L Nakshatri, H TI Senescence-like growth arrest of mammary epithelial cells induced by estrogen receptor alpha is associated with elevated cell cycle check-point kinase 2 (Chk2), p53 and p21 levels. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 Indiana Canc Res Inst, Indianapolis, IN USA. NCI, CADRG, DCP, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1834S EP 1835S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100029 ER PT J AU Yang, YP Martin, BK Sharan, SK AF Yang, YP Martin, BK Sharan, SK TI In vivo functional analysis of missense mutations in BRCA1 using humanized mouse models. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1837S EP 1837S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100036 ER PT J AU Gary, MA Coudry, RA Cooper, HS Litwin, S Concha, AC Lubet, RA Clapper, ML AF Gary, MA Coudry, RA Cooper, HS Litwin, S Concha, AC Lubet, RA Clapper, ML TI 5-aminosalicylic acid inhibits colitis-associated dysplasia in the mouse model of AOM/DSS-induced colitis. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Bethesda, MD 20892 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1839S EP 1839S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100045 ER PT J AU Taylor, PR Qiao, YL Dawsey, SM Johnson, LL Dong, ZW Yu, BB Mark, SD AF Taylor, PR Qiao, YL Dawsey, SM Johnson, LL Dong, ZW Yu, BB Mark, SD TI Total and cancer mortality following supplementation with multivitamins and minerals: Post-intervention follow-up of the General Population Nutrition Intervention Trial in Linxian, China. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Inst Canc, Beijing 100021, Peoples R China. Informat Management Serv Inc, Silver Spring, MD USA. RI Qiao, You-Lin/B-4139-2012 OI Qiao, You-Lin/0000-0001-6380-0871 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1843S EP 1843S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100059 ER PT J AU Grubbs, CJ End, DE Eto, I Juliana, MM Steele, VE Lubet, RA AF Grubbs, CJ End, DE Eto, I Juliana, MM Steele, VE Lubet, RA TI Chemopreventive efficacy of hormonal agents (tamoxifen, vorozole) together with targretin, 9-cis-retinoic acid or celecoxib in the methylnitrosourea (MNU)-induced mammary cancer model. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 Univ Alabama, Birmingham, AL USA. Johnson & Johnson Pharmaceut, Springs House, PA USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1844S EP 1844S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100062 ER PT J AU Patel, AC Zhao, FH Graubard, BI Shen, YH Barrett, JC Qiao, YL Forman, MR AF Patel, AC Zhao, FH Graubard, BI Shen, YH Barrett, JC Qiao, YL Forman, MR TI Tuberculosis and gynecologic infections are independent risk factors for oncogenic HPV infections and cervical cancer in unscreened women from a high-risk area in rural China. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, NIH, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Inst Canc, Beijing 100021, Peoples R China. RI Qiao, You-Lin/B-4139-2012 OI Qiao, You-Lin/0000-0001-6380-0871 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1848S EP 1849S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100081 ER PT J AU Rastogi, T Kao, RL Mathews, A Chatterjee, N Chu, KC Sinha, R AF Rastogi, T Kao, RL Mathews, A Chatterjee, N Chu, KC Sinha, R TI Cancer in Asian Indians (AI): Ecologic and US comparisons of incidence rates and survival. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Bethesda, MD 20892 USA. Reg Canc Ctr, Trivandrum 695011, Kerala, India. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1848S EP 1848S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100080 ER PT J AU Abnet, CC Lai, B Qiao, YL Vogt, S Luo, XM Taylor, PR Dong, ZW Mark, SD Dawsey, SM AF Abnet, CC Lai, B Qiao, YL Vogt, S Luo, XM Taylor, PR Dong, ZW Mark, SD Dawsey, SM TI Zinc concentration in esophageal biopsies measured by X-ray fluorescence and cancer risk. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Bethesda, MD 20892 USA. Argonne Natl Lab, Argonne, IL 60439 USA. Chinese Acad Med Sci, Inst Canc, Beijing 100021, Peoples R China. RI Qiao, You-Lin/B-4139-2012 OI Qiao, You-Lin/0000-0001-6380-0871 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1852S EP 1852S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100094 ER PT J AU Yang, G Shu, XO Li, HL Chow, WH Li, Q Ji, BT Gao, YT Zheng, W AF Yang, G Shu, XO Li, HL Chow, WH Li, Q Ji, BT Gao, YT Zheng, W TI Green tea drinking reduces colorectal cancer risk in a prospective study. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 Vanderbilt Univ, Med Ctr, Nashville, TN USA. Shanghai Canc Inst, Shanghai, Peoples R China. NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1853S EP 1853S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100097 ER PT J AU Gunter, MJ Divi, RM Kulldorff, M Strickland, P Poirier, MC Rothman, N Sinha, R AF Gunter, MJ Divi, RM Kulldorff, M Strickland, P Poirier, MC Rothman, N Sinha, R TI Dietary Benzo[a]pyrene, leukocyte polycyclic aromatic hydrocarbon-DNA adducts and colorectal adenoma risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Rockville, MD USA. Harvard Univ, Sch Med, Boston, MA USA. Johns Hopkins Univ, Baltimore, MD USA. RI Kulldorff, Martin/H-4282-2011; Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1854S EP 1854S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100101 ER PT J AU Sansbury, L Millikan, R Schroeder, J Moorman, P North, K Sandler, R AF Sansbury, L Millikan, R Schroeder, J Moorman, P North, K Sandler, R TI Use of non-steroidal anti-inflammatory drugs, cyclooxygenase-2 Val511Ala polymorphism, and association with colon cancer in a population-based study of African Americans and whites SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Canc Prevent Fellowship Program, Div Canc Prevent, Bethesda, MD 20892 USA. Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. Duke Univ, Med Ctr, Canc Prevent Detect & Control Res Program, Durham, NC USA. Univ N Carolina, Div Gastroenterol & Hepatol, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1855S EP 1855S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100104 ER PT J AU Dawsey, S Perez-Perez, G Pietinen, P Newschaffer, CJ Helzlsouer, K Shugart, YY Abnet, CC Albanes, D Virtamo, J Taylor, PR AF Dawsey, S Perez-Perez, G Pietinen, P Newschaffer, CJ Helzlsouer, K Shugart, YY Abnet, CC Albanes, D Virtamo, J Taylor, PR TI Helicobacter pylori and risk of gastric cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Bethesda, MD 20892 USA. NYU, New York, NY USA. Finland Natl Publ Hlth Inst, Helsinki, Finland. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. RI Albanes, Demetrius/B-9749-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1856S EP 1856S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100108 ER PT J AU Wright, ME Sequoia, J Pietinen, P Taylor, PR Virtamo, J Albanes, D AF Wright, ME Sequoia, J Pietinen, P Taylor, PR Virtamo, J Albanes, D TI A prospective investigation of height and prostate cancer risk in male smokers SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. NCI, Ctr Canc Res, NIH, US Dept HHS, Bethesda, MD 20892 USA. RI Albanes, Demetrius/B-9749-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1856S EP 1856S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100109 ER PT J AU Randolph-Steele, W Moser, RP Hesse, BW Viswanath, K AF Randolph-Steele, W Moser, RP Hesse, BW Viswanath, K TI Differences in cancer knowledge by socioeconomic status: A partial explanation for cancer health disparities? SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Rockville, MD USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1857S EP 1857S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100112 ER PT J AU Cantwell, MM Lacey, JV Schairer, C Schatzkin, A Michaud, DS AF Cantwell, MM Lacey, JV Schairer, C Schatzkin, A Michaud, DS TI Reproductive factors, oral contraceptive, and hormone therapy use and bladder cancer risk in a prospective study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Nutr Epidemiol Branch, NIH, Bethesda, MD 20892 USA. NCI, Hormonal & Reprod Epidemiol Branch, NIH, Bethesda, MD 20892 USA. NCI, Biostat Branch, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RI Michaud, Dominique/I-5231-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1858S EP 1858S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100115 ER PT J AU Mccaskill-Stevens, W Clegg, LMX Lu, KR Hankey, BF AF Mccaskill-Stevens, W Clegg, LMX Lu, KR Hankey, BF TI Hormone receptor concordance and predictors of contralateral breast cancer in surveillance, epidemiology, and end results (SEER) population-based registries. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1858S EP 1859S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100116 ER PT J AU Lee, IP Ohta, T Bae, S Pereira, MA Steele, VE AF Lee, IP Ohta, T Bae, S Pereira, MA Steele, VE TI 1SY16 isolated from Agaricus blazei Murill K as a potent multipotential chemopreventive agent. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 Kanazawa Univ, Grad Fac Med, Kanazawa, Ishikawa 920, Japan. Kanazawa Univ, Fac Pharmaceut Sci, Kanazawa, Ishikawa 920, Japan. Catholic Univ, Coll Med, Inst Basic Med Sci, Seoul, South Korea. Med Coll Ohio, Dept Pathol, Toledo, OH 43699 USA. NCI, Div Canc Prevent, Chemoprevent Agent Dev Program, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1861S EP 1861S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100128 ER PT J AU Kramer, PM Alyaqoub, FS Tao, LH Wang, W Casto, BC Steele, VE Lubet, RA Pereira, MA AF Kramer, PM Alyaqoub, FS Tao, LH Wang, W Casto, BC Steele, VE Lubet, RA Pereira, MA TI Chemoprevention by bexarotene and rosiglitazone of mouse lung and rat colon cancer. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 Med Coll Ohio, Toledo, OH 43699 USA. Ohio State Univ, Columbus, OH 43210 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1863S EP 1863S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100134 ER PT J AU Ballard-Barbash, R Barlow, WE Buist, DS Carney, P Cutter, G Dignan, M Geller, B Kerlikowske, K Miglioretti, D Rosenberg, R Taplin, S Yabroff, R Yankaskas, B Weaver, D AF Ballard-Barbash, R Barlow, WE Buist, DS Carney, P Cutter, G Dignan, M Geller, B Kerlikowske, K Miglioretti, D Rosenberg, R Taplin, S Yabroff, R Yankaskas, B Weaver, D TI Overview of the breast cancer surveillance consortium. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Bethesda, MD 20892 USA. Grp Hlth Cooperat Puget Sound, Seattle, WA 98121 USA. Dartmouth Coll Sch Med, Lebanon, NH USA. Univ Alabama, Birmingham, AL USA. Univ Kentucky, Lexington, KY USA. Vermont Canc Ctr, Burlington, VT USA. UCSF, San Francisco, CA USA. Univ New Mexico, Albuquerque, NM 87131 USA. Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1866S EP 1867S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100145 ER PT J AU Roth, MJ Abnet, CC Hu, N Wang, QH Green, L D'Alelio, M Qiao, YL Dawsey, SM Taylor, PR Woodson, K AF Roth, MJ Abnet, CC Hu, N Wang, QH Green, L D'Alelio, M Qiao, YL Dawsey, SM Taylor, PR Woodson, K TI MGMT, RAR beta 2, DAPk and p16 gene methylation in esophageal squamous cell carcinoma: Potential as a primary screening test. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Bethesda, MD 20892 USA. Shanxi Canc Hosp, Shanxi, Peoples R China. Chinese Acad Med Sci, Inst Canc, Beijing 100021, Peoples R China. RI Qiao, You-Lin/B-4139-2012 OI Qiao, You-Lin/0000-0001-6380-0871 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1872S EP 1872S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100164 ER PT J AU Hong, HHL Sills, RC Flake, G Clayton, N Boorman, GA Dunnick, J Devereux, TR AF Hong, HHL Sills, RC Flake, G Clayton, N Boorman, GA Dunnick, J Devereux, TR TI Characterization of molecular pathogenesis in o-nitrotoluene-induced large intestinal tumors in mice. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1873S EP 1873S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100166 ER PT J AU Moraitis, D Du, BH De Lorenzo, MS Boyle, JO Weksler, BB Cohen, EG Carew, JF Altorki, NK Kopelovich, L Subbaramaiah, K Dannenberg, AJ AF Moraitis, D Du, BH De Lorenzo, MS Boyle, JO Weksler, BB Cohen, EG Carew, JF Altorki, NK Kopelovich, L Subbaramaiah, K Dannenberg, AJ TI Levels of COX-2 are increased in the oral mucosa of smokers. Evidence for the role of EGFR and its ligands. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 Mem Sloan Kettering Canc Ctr, Dept Surg, Head & Neck Serv, New York, NY 10021 USA. Cornell Univ, Weill Med Coll, Dept Med, New York, NY USA. Cornell Univ, Weill Med Coll, Dept Otorhinolaryngol, New York, NY USA. Cornell Univ, Weill Med Coll, Dept Cardiothorac Surg, New York, NY USA. NCI, DCP, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1874S EP 1874S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100171 ER PT J AU Lavigne, JA Hursting, SD Chandramouli, GV Perkins, SN Barrett, JC AF Lavigne, JA Hursting, SD Chandramouli, GV Perkins, SN Barrett, JC TI Hepatic gene expression changes by dose of calorie restriction in female C57BL/6 mice. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, CCR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1876S EP 1876S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100179 ER PT J AU Christov, KT Shilkaitis, AL Green, AD Steele, VE Grubbs, CJ Lubet, RA AF Christov, KT Shilkaitis, AL Green, AD Steele, VE Grubbs, CJ Lubet, RA TI Validation of the efficacy of chemopreventive agents on mammary carcinogenesis by intermediate endpoint biomarkers: Cell proliferation and apoptosis assays. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 Univ Illinois, Chicago, IL USA. NCI, Bethesda, MD 20892 USA. Univ Alabama, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1878S EP 1878S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100185 ER PT J AU Williams, JL Kashfi, K Ouyang, N Liu, XP Kopelovich, L Rigas, B AF Williams, JL Kashfi, K Ouyang, N Liu, XP Kopelovich, L Rigas, B TI NO-donating aspirin inhibits intestinal carcinogenesis in min (Apc(min/+)) mice. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 SUNY Stony Brook, Stony Brook, NY 11794 USA. CUNY, Sch Med, New York, NY 10031 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1883S EP 1883S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100201 ER PT J AU Chow, HHS Hakim, IA Vining, DR Crowell, JA Ranger-Moore, J Chew, WM Celaya, CA Rodney, SR Hara, Y Alberts, DS AF Chow, HHS Hakim, IA Vining, DR Crowell, JA Ranger-Moore, J Chew, WM Celaya, CA Rodney, SR Hara, Y Alberts, DS TI Effects of dosing condition on the oral bioavailability of green tea catechins after single-dose administration of polyphenon E in healthy individuals. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. NCI, Bethesda, MD 20892 USA. Mitsui Norin Co Ltd, Shizuoka, Japan. NR 0 TC 1 Z9 1 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1885S EP 1885S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100208 ER PT J AU Wanke, KL Daston, C Slonim, A Albert, P Schatzkin, A Lanza, E AF Wanke, KL Daston, C Slonim, A Albert, P Schatzkin, A Lanza, E TI Super compliers? Factors associated with dietary-goal adherence in the polyp prevention trial. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Bethesda, MD 20892 USA. WESTAT Corp, Rockville, MD 20850 USA. Michigan Publ Hlth Inst, Okemos, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1889S EP 1890S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100223 ER PT J AU Chan, JM Holick, CN Leitzmann, MF Rimm, EB Willett, WC Stampfer, MJ Giovannucci, EL AF Chan, JM Holick, CN Leitzmann, MF Rimm, EB Willett, WC Stampfer, MJ Giovannucci, EL TI Post-diagnostic diet and the risk of prostate cancer progression, recurrence, and death in the Health Professionals Follow Up Study. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 Univ Calif San Francisco, Sch Med, San Francisco, CA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1890S EP 1890S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100226 ER PT J AU Cross, AJ Peters, U Andriole, GL Reding, D Hayes, RB Sinha, R AF Cross, AJ Peters, U Andriole, GL Reding, D Hayes, RB Sinha, R TI Red meat intake and prostate cancer risk in the PLCO Cancer Screening Trial. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, DCEG, Rockville, MD USA. Washington Univ, Sch Med, Div Urol Surg, St Louis, MO USA. Marshfield Clin Res Fdn, Marshfield, WI USA. RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1890S EP 1890S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100224 ER PT J AU Hartman, TJ Yu, BB Albert, PS Brewer, B Burt, R Caan, B Iber, F Kikendall, W Lance, P Marshall, J Paskett, E Shike, M Slattery, ML Weissfeld, J Schatzkin, A Lanza, E AF Hartman, TJ Yu, BB Albert, PS Brewer, B Burt, R Caan, B Iber, F Kikendall, W Lance, P Marshall, J Paskett, E Shike, M Slattery, ML Weissfeld, J Schatzkin, A Lanza, E TI Effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas: Possible effect modification by non-steroidal anti-inflammatory drug use. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 Penn State Univ, University Pk, PA 16802 USA. Informat Management Serv Inc, Rockville, MD USA. NCI, Bethesda, MD 20892 USA. WESTAT Corp, Rockville, MD 20850 USA. Univ Utah, Salt Lake City, UT USA. Kaiser Fdn Res Inst, Oakland, CA USA. Edward Hines Jr Hosp, Vet Affairs Med Ctr, Hines, IL USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. Univ Arizona, Tucson, AZ USA. Roswell Pk Canc Ctr, Buffalo, NY USA. Ohio State Canc Ctr, Columbus, OH USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1892S EP 1893S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100234 ER PT J AU Colbert, LH Westerlind, KC Perkins, SN Haines, DC Berrigan, D Wimbrow, H Hursting, SD AF Colbert, LH Westerlind, KC Perkins, SN Haines, DC Berrigan, D Wimbrow, H Hursting, SD TI Effects of exercise on tumorigenesis, body composition, insulin-like growth factor-1, and oxidative markers in a transgenic mouse model of breast cancer. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 Univ Wisconsin, Madison, WI USA. AMC Canc Res Ctr, Denver, CO USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1893S EP 1893S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100236 ER PT J AU Daugherty, SE Hayes, R Yeager, M Andriole, G Chatterjee, N Huang, WY Isaacs, W Pratt, E AF Daugherty, SE Hayes, R Yeager, M Andriole, G Chatterjee, N Huang, WY Isaacs, W Pratt, E TI 462(GLN) Variant of RNASEL is associated with clinically important prostate cancer. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Bethesda, MD 20892 USA. Washington Univ, Sch Med, St Louis, MO USA. Johns Hopkins Sch Med, Baltimore, MD USA. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1894S EP 1894S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100238 ER PT J AU De Roos, AJ Rothman, N Brown, M Inskip, PD AF De Roos, AJ Rothman, N Brown, M Inskip, PD TI Common variants in selected metabolic genes and the risk of adult brain tumors. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Core Genotyping Facil, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1898S EP 1899S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100255 ER PT J AU Rutten, LJ Wanke, K Augustson, E AF Rutten, LJ Wanke, K Augustson, E TI Systems and individual factors associated with smoking status: Evidence from Health Information National Trends Survey (HINTS). SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1902S EP 1902S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100267 ER PT J AU Hance, KW Umar, A Schlom, J Greiner, JW AF Hance, KW Umar, A Schlom, J Greiner, JW TI Chemopreventive agents inhibit proliferation and modulate cell surface markers of immune recognition in pancreatic cancer cells. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1904S EP 1904S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100272 ER PT J AU Berrigan, DA Potischman, N Dodd, K Nicar, M Mcquillan, G Lavigne, J Hursting, SD Barrett, JC Ballard-Barbash, R AF Berrigan, DA Potischman, N Dodd, K Nicar, M Mcquillan, G Lavigne, J Hursting, SD Barrett, JC Ballard-Barbash, R TI Serum levels of insulin-like growth factor 1 (IGF-I) and IGIF-I binding protein-3 (IGFBP-3): Quality control issues for studies of stored serum. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, NIH, Bethesda, MD 20892 USA. Baylor Univ, Med Ctr, Dallas, TX USA. Ctr Dis Control, Natl Ctr Hlth Stat, Hyattsville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1908S EP 1908S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100287 ER PT J AU Lubet, RA Wang, Y Yao, RS Grubbs, CJ Muccio, DD You, M AF Lubet, RA Wang, Y Yao, RS Grubbs, CJ Muccio, DD You, M TI Gene expression changes following treatment of estrogen receptor positive (ER+) mammary cancers or normal mammary epithelium with the RXR receptor agonist targretin. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 Washington Univ, St Louis, MO USA. Univ Alabama, Birmingham, AL USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1910S EP 1910S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100294 ER PT J AU Fenton, JI Hord, NG Hursting, S Lavigne, J AF Fenton, JI Hord, NG Hursting, S Lavigne, J TI Leptin, IGF-1 and IGF-2 are mitogens in murine models of preneoplastic, but not normal, colon epithelial cells. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Canc Prevent Fellowship Program, Div Canc Prevent, Bethesda, MD 20892 USA. Michigan State Univ, Dept Food Sci & Human Nutr, E Lansing, MI 48824 USA. NCI, Lab Biosyst & Canc, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1913S EP 1913S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100305 ER PT J AU Marks, CL AF Marks, CL TI The NCI programs for integrated human and model system susceptibility and prevention research. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1914S EP 1914S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100310 ER PT J AU Woditschka, S Haag, JD Chen, KS Kendziorski, CM Lubet, RA Gould, MN AF Woditschka, S Haag, JD Chen, KS Kendziorski, CM Lubet, RA Gould, MN TI The RXR-specific agonist LG100268 is able to prevent ovarian hormone dependent and independent mammary carcinomas in the neu-induced rat model. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 Univ Wisconsin, Madison, WI USA. NCI, Chemoprevent Branch, Bethesda, MD 20892 USA. RI Gould, Michael/C-7414-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1915S EP 1916S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100315 ER PT J AU Ouyang, N Williams, JL Tsioulias, GJ Iatropoulos, MJ Kopelovich, L Kashfi, K Rigas, B AF Ouyang, N Williams, JL Tsioulias, GJ Iatropoulos, MJ Kopelovich, L Kashfi, K Rigas, B TI NO-donating aspirin prevents pancreatic cancer through effects on cell kinetics, NF-kappa B (P21WAF1/CIP1) and COX-2 SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 SUNY Stony Brook, Stony Brook, NY 11794 USA. New York Med Coll, Valhalla, NY 10595 USA. NCI, NIH, Bethesda, MD 20892 USA. CUNY, Sch Med, New York, NY 10031 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1918S EP 1918S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100326 ER PT J AU Chen, J Kopelovich, L Rigas, B AF Chen, J Kopelovich, L Rigas, B TI The chemopreventive NO donating-ASA induces COX-2 expression in cultured human cancer cells SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 SUNY Stony Brook, Stony Brook, NY 11794 USA. NCI, DCP, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1919S EP 1919S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100328 ER PT J AU Shen, Q Zhang, Y Hill, J Lu, CH Kim, HT Chodosh, LA Young, M Colburn, N Brown, PH AF Shen, Q Zhang, Y Hill, J Lu, CH Kim, HT Chodosh, LA Young, M Colburn, N Brown, PH TI Transcription factor blockade for mammary gland biology and prevention of breast cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 Baylor Coll Med, Houston, TX 77030 USA. Univ Penn, Philadelphia, PA 19104 USA. NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1920S EP 1920S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100332 ER PT J AU Elmore, E Jain, A Steele, VE Redpath, JL AF Elmore, E Jain, A Steele, VE Redpath, JL TI Time and concentration related changes in gene expression profiles induced by curcumin in the colon polyp cell line, VACO 235. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Bethesda, MD 20892 USA. Univ Calif Irvine, Irvine, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1921S EP 1921S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100336 ER PT J AU Kelemen, L Cerhan, J Lim, U Davis, S Cozen, W Schenk, M Hartge, P Ward, M AF Kelemen, L Cerhan, J Lim, U Davis, S Cozen, W Schenk, M Hartge, P Ward, M TI Association of vegetables, fruits and antioxidant vitamins with non-Hodgkin's lymphoma: A population-based case-control study. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 Mayo Clin, Coll Med, Rochester, MN USA. NCI, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ So Calif, Los Angeles, CA USA. Karmanos Canc Inst, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1923S EP 1923S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100342 ER PT J AU Gaudet, MM Lund, MJ Porter, PL Brinton, LA Flagg, EW Coates, RJ Gammon, MD Abrahamson, PE Potischman, N Eley, JW AF Gaudet, MM Lund, MJ Porter, PL Brinton, LA Flagg, EW Coates, RJ Gammon, MD Abrahamson, PE Potischman, N Eley, JW TI Protein intake and breast cancer survival among young women. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 UNC Sch Publ Hlth, Chapel Hill, NC USA. Emory Univ, Atlanta, GA 30322 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NCI, Rockville, MD USA. Ctr Dis Control & Prevent, Atlanta, GA USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1924S EP 1924S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100346 ER PT J AU Nouraie, M Pietinen, P Kamangar, F Dawsey, SM Abnet, CC Albanes, D Virtamo, J Taylor, PR AF Nouraie, M Pietinen, P Kamangar, F Dawsey, SM Abnet, CC Albanes, D Virtamo, J Taylor, PR TI Fruits, vegetables, and antioxidants, and risk of gastric cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Bethesda, MD 20892 USA. Finland Natl Publ Hlth Inst, Helsinki, Finland. RI Albanes, Demetrius/B-9749-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1924S EP 1924S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100345 ER PT J AU Millen, AE Subar, AF Graubard, BI Peters, U Hayes, RB Weissfeld, JL Yokochi, L Ziegler, RG AF Millen, AE Subar, AF Graubard, BI Peters, U Hayes, RB Weissfeld, JL Yokochi, L Ziegler, RG TI Fruit and vegetable intake and prevalent colorectal adenoma. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Div Canc Epidmeiol & Genet, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Pittsburgh, Pittsburgh, PA USA. Pacific Hlth Res Inst, Honolulu, HI USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1925S EP 1925S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100349 ER PT J AU Leitzmann, MF Chang, SC Subar, A Kipnis, V Midthune, D Thompson, F Ballard-Barbash, R Mouw, T Hurwitz, P Carroll, L Hollenbeck, A Schatzkin, A AF Leitzmann, MF Chang, SC Subar, A Kipnis, V Midthune, D Thompson, F Ballard-Barbash, R Mouw, T Hurwitz, P Carroll, L Hollenbeck, A Schatzkin, A TI Physical activity and the risk of postmenopausal breast cancer in the NCI-AARP diet and health study. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, NIH, Rockville, MD USA. WESTAT Corp, Rockville, MD 20850 USA. Informat Management Serv Inc, Silver Spring, MD USA. AARP, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1926S EP 1926S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100351 ER PT J AU Rogers, CJ Berrigan, D Patel, AC Perkins, SD Schlom, J Greiner, JW Hursting, SD AF Rogers, CJ Berrigan, D Patel, AC Perkins, SD Schlom, J Greiner, JW Hursting, SD TI Effects of exercise and calorie restriction on systemic and mucosal immune function in C57BL/6 mice. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1926S EP 1927S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100353 ER PT J AU Michaud, DS Daugherty, S Platz, EA Berndt, S Yeager, M Crawford, D Hsing, A Huang, WY Hayes, R AF Michaud, DS Daugherty, S Platz, EA Berndt, S Yeager, M Crawford, D Hsing, A Huang, WY Hayes, R TI Cytokine gene Polymorphisms and prostate cancer risk. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Colorado, Denver, CO 80202 USA. RI Michaud, Dominique/I-5231-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1930S EP 1930S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100366 ER PT J AU Huang, WY Olshan, AF Schwartz, SM Berndt, SI Chu, C Hayes, RB AF Huang, WY Olshan, AF Schwartz, SM Berndt, SI Chu, C Hayes, RB TI A pooled analysis of DNA repair polymorphisms and head and neck cancer risk. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 Univ N Carolina, Chapel Hill, NC USA. NCI, NIH, DCEG, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1931S EP 1931S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100369 ER PT J AU Struewing, JP Stredrick, DL Doody, MM Sigurdson, AJ AF Struewing, JP Stredrick, DL Doody, MM Sigurdson, AJ TI Rare ATM genetic variants and breast cancer risk in the US radiologic technologist study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA. NCI, Radiat Epidemiol Branch, NIH, Bethesda, MD 20892 USA. RI Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1931S EP 1931S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100368 ER PT J AU Choi, JY Ritchie, MD Motsinger, AA Lee, KM Noh, DY Yoo, KY Moore, JH Kang, DH AF Choi, JY Ritchie, MD Motsinger, AA Lee, KM Noh, DY Yoo, KY Moore, JH Kang, DH TI Gene-gene interaction of CCND1, ESR1 and CDK7 on the risk of breast cancer detected by multifactor dimensionality reduction (MDR) and logistic regression. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 Seoul Natl Univ, Seoul, South Korea. Vanderbilt Univ, Nashville, TN USA. NCI, Bethesda, MD 20892 USA. RI Noh, Dong-Young/G-5531-2011; Kang, Dae Hee/E-8631-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1932S EP 1932S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100372 ER PT J AU Buist, DS Anderson, ML White, E Porter, P Ballard-Barbash, R Malone, K Taplin, SH AF Buist, DS Anderson, ML White, E Porter, P Ballard-Barbash, R Malone, K Taplin, SH TI Body mass index and risk of breast cancer recurrence and breast cancer mortality in a mammographically screened population. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 Grp Hlth Cooperat Puget Sound, Seattle, WA 98121 USA. Univ Washington, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1933S EP 1933S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100374 ER PT J AU Mahabir, S AF Mahabir, S TI Relations between regional DEXA adiposity, BMI and sex hormones in postmenopausal women in a controlled feeding study. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1935S EP 1935S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100382 ER PT J AU Vadaparampil, ST Wideroff, L Freedman, AN Viswanath, KV Olson, L AF Vadaparampil, ST Wideroff, L Freedman, AN Viswanath, KV Olson, L TI Physician exposure to advertisements for genetic tests for inherited cancer susceptibility and clinical care implications SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 H Lee Moffit Canc Ctr & Res Inst, Tampa, FL USA. NCI, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. ABT Associates Inc, Chicago, IL USA. RI Hernandez, Jessica/G-6527-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1936S EP 1936S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100385 ER PT J AU Lou, JR Malik, W Malone, W Greenwald, P Mclarty, J Ali, IU AF Lou, JR Malik, W Malone, W Greenwald, P Mclarty, J Ali, IU TI Identification of specific peptides binding to autoantibodies in lung cancer plasma samples using a phage display random peptide library. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Frederick, MD 21701 USA. NCI, Bethesda, MD 20892 USA. Louisiana State Univ, Ctr Hlth, Shreveport, LA 71105 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1937S EP 1937S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100389 ER PT J AU Snyder, DC Clipp, EC Sloane, R Lipkus, IM McBride, CM Lobach, D Kraus, W Demark-Wahnefried, W AF Snyder, DC Clipp, EC Sloane, R Lipkus, IM McBride, CM Lobach, D Kraus, W Demark-Wahnefried, W TI Accrual into the FRESH START diet and exercise trial for cancer survivors: Comparison of self-referred versus cancer registry solicited samples with regard to health behavior and socio-demographic factors. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 Duke Univ, Med Ctr, Durham, NC USA. NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1937S EP 1937S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100388 ER PT J AU Upfal, M Harvey, P Lonardo, F Madan, S Stevens, T Moore, M Szabo, E Kucuk, O AF Upfal, M Harvey, P Lonardo, F Madan, S Stevens, T Moore, M Szabo, E Kucuk, O TI Strategies for accrual of subjects with bronchial dysplasia for a lung cancer prevention study. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 Prentis Comp Canc Ctr Metro Detroit, Detroit, MI USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1937S EP 1938S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100390 ER PT J AU Alyaqoub, FS Kramer, PM Tao, LH Steele, VE Lubet, RA Pereira, MA AF Alyaqoub, FS Kramer, PM Tao, LH Steele, VE Lubet, RA Pereira, MA TI Prevention of mouse lung tumors and DNA hypomethylation by combinations containing budesonide and R115777 (Zarnestra (TM)) SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 Ohio State Univ, Columbus, OH 43210 USA. Med Coll Ohio, Toledo, OH 43699 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1938S EP 1938S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100391 ER PT J AU Simoneau, AR Meyskens, FL Gerner, EW Ziogas, A Lieberman, R Nagle, RD AF Simoneau, AR Meyskens, FL Gerner, EW Ziogas, A Lieberman, R Nagle, RD TI Preliminary results of a randomized controlled phase IIb prostate cancer chemoprevention trial with DFMO. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 Univ Calif Irvine, Long Beach, CA USA. Univ Arizona, Tucson, AZ USA. NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1940S EP 1940S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100398 ER PT J AU Hawk, ET AF Hawk, ET TI The promise of surrogate end points in cancer prevention. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1948S EP 1948S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100420 ER PT J AU Brown, P Wu, K Mohsin, S Hilsenbeck, SG Lamph, W Johnson, K Elledge, R AF Brown, P Wu, K Mohsin, S Hilsenbeck, SG Lamph, W Johnson, K Elledge, R TI Prevention of breast cancer with rexinoids: Preclinical and early phase clinical studies. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 Baylor Coll Med, Houston, TX 77030 USA. Ligand Pharmaceut Inc, San Diego, CA USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1952S EP 1952S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100433 ER PT J AU Kramer, BS AF Kramer, BS TI Prostate cancer screening. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1952S EP 1952S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100431 ER PT J AU Greenwald, P AF Greenwald, P TI Clinical prevention of breast and prostate cancers. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1953S EP 1953S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100435 ER PT J AU Kelloff, GJ AF Kelloff, GJ TI Molecular intraepithelial neoplasia. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Fairfax, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1954S EP 1954S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100438 ER PT J AU Viner, JL AF Viner, JL TI Combinations for cancer chemoprevention: Strategies for drug development. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1957S EP 1957S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100446 ER PT J AU Lipkin, M Yang, K Fan, KH Lamprecht, S Newmark, H Kopelovich, L Augenlicht, L Edelmann, W Kucherlapati, R AF Lipkin, M Yang, K Fan, KH Lamprecht, S Newmark, H Kopelovich, L Augenlicht, L Edelmann, W Kucherlapati, R TI Preclinical mouse models for chemoprevention of colon cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 Strang Canc Prevent Ctr, New York, NY USA. Rutgers State Univ, New Brunswick, NJ 08903 USA. NCI, Bethesda, MD 20892 USA. Albert Einstein Canc Ctr, Bronx, NY USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1960S EP 1961S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100459 ER PT J AU Hankey, BF AF Hankey, BF TI State Cancer Profiles: A web site that provides cancer surveillance data in a format to assist with cancer control planning. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Div Canc Control & Populat Sci, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1965S EP 1965S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100472 ER PT J AU Hawk, ET Viner, JL AF Hawk, ET Viner, JL TI Chemoprevention of esophageal cancer. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1965S EP 1965S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100470 ER PT J AU Dennis, PA AF Dennis, PA TI Tobacco carcinogen-induced transformation of lung epithelial cells alters activation and expression erbB family members in vitro and in vivo. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1966S EP 1967S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100477 ER PT J AU Etzioni, R Feuer, EJ AF Etzioni, R Feuer, EJ TI Learning from population cancer trends: The Cancer Intervention and Surveillance Modeling Network (CISNET). SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 3rd Annual AACR International Conference CY OCT 16-20, 2004 CL Seattle, WA SP AACR C1 NCI, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2004 VL 13 IS 11 BP 1966S EP 1966S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 870QO UT WOS:000225073100474 ER PT J AU Waalkes, MP Liu, J Goyer, RA Diwan, BA AF Waalkes, MP Liu, J Goyer, RA Diwan, BA TI Metallothionein-I/II double knockout mice are hypersensitive to lead-induced kidney carcinogenesis: Role of inclusion body formation SO CANCER RESEARCH LA English DT Article ID AMINOLEVULINIC-ACID DEHYDRATASE; RENAL-CELL CARCINOMA; OCCUPATIONAL EXPOSURE; BINDING PROTEINS; TOXICITY; EXPRESSION; CADMIUM; CANCER; BODIES; METALS AB Lead is an environmental nephrotoxicant and probable human carcinogen. Elucidating factors predisposing populations to lead toxicity is an important public health issue. Recently, we found that metallothionein-I/-II double knockout (metallothionein-null) mice that are unable to produce the major forms of metallothionein do not produce lead inclusion bodies, which are thought to mitigate lead toxicity, and were sensitive to the subchronic toxic effects of lead exposure (10 weeks), showing modestly diminished renal function and nephromegaly compared with wild-type (WT) mice. It is unclear how this knockout might impact lead carcinogenesis. Thus, the effects of lead(II) acetate were tested in groups (n = 25) of male metallothionein-mill and WT mice receiving drinking water with 0, 1,000, 2,000, or 4,000 parts per million lead for up to 104 weeks. Renal proliferative lesions (adenoma and cystic tubular atypical hyperplasia) were much more common and more severe in lead-exposed metallothionein-mill mice than in WT mice. A metastatic renal cell carcinoma also occurred in a lead-treated metallothionein-mill mouse, whereas none occurred in WT mice. Lead-induced renal proliferative lesions showed marked overexpression of cyclin D1, a common feature of human renal tumors. Renal lead-containing nuclear inclusion bodies were frequently observed in WT mice but did not form in metallothionein-mill mice. Metallothionein was often found associated with the outer portion of these inclusion bodies. Thus, the metallothionein-null mice cannot form renal inclusion bodies, even after protracted lead exposure, and this increases the carcinogenic potential of lead. Poor production of metallothionein may predispose human populations to lead carcinogenicity. C1 NIEHS, Inorgan Carcinogenesis Sect, NCI, Comparat Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. Sci Applicat Int Corp, NCI, Basic Res Program, Frederick, MD USA. RP Waalkes, MP (reprint author), NIEHS, Inorgan Carcinogenesis Sect, NCI, Comparat Carcinogenesis Lab, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM waalkes@nichs.nih.gov FU NCI NIH HHS [N01-CO-12400] NR 45 TC 41 Z9 44 U1 1 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2004 VL 64 IS 21 BP 7766 EP 7772 DI 10.1158/0008-5472.CAN-04-2220 PG 7 WC Oncology SC Oncology GA 866RM UT WOS:000224790600020 PM 15520181 ER PT J AU Li, AG Lu, SL Zhang, MX Deng, C Wang, XJ AF Li, AG Lu, SL Zhang, MX Deng, C Wang, XJ TI Smad3 knockout mice exhibit a resistance to skin chemical carcinogenesis SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR-ALPHA; TUMOR NECROSIS FACTOR; TGF-BETA RECEPTOR; TRANSGENIC MICE; MOUSE EPIDERMIS; INDEPENDENT PATHWAYS; MESSENGER-RNA; PHORBOL ESTER; KAPPA-B; C-JUN AB It has been shown that Smad3 exerts both tumor-suppressive and -promoting roles. To evaluate the role of Smad3 in skin carcinogenesis in vivo, we applied a chemical skin carcinogenesis protocol to Smad3 knockout mice (Smad3(-/-) and Smad3(+/-)) and wild-type littermates (Smad3(+/+)). Smad3(-/-) mice exhibited reduced papilloma formation in comparison with Smad3(+/+) mice and did not develop any squamous cell carcinomas. Further analysis revealed that Smad3 knockout mice were resistant to 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced epidermal hyperproliferation. Concurrently, increased apoptosis was observed in TPA-treated Smad3(-/-) skin and papillomas when compared with those of wild-type mice. Expression levels of activator protein-1 family members (c-jun, junB, junD, and c-fos) and transforming growth factor (TGF)-alpha were significantly lower in TPA-treated Smad3(-/-) skin, cultured keratinocytes, and papillomas, as compared with Smad3(+/+) controls. Smad3(-/-) papillomas also exhibited reduced leukocyte infiltration, particularly a reduction of tumor-associated macrophage infiltration, in comparison with Smad3(+/+) papillomas. All of these molecular and cellular alterations also occurred to a lesser extent in Smad3(+/-) mice as compared with Smad3(+/+) mice, suggesting a Smad3 gene dosage effect. Given that TGF-beta1 is a well-documented TPA-responsive gene and also has a potent chemotactic effect on macrophages, our study suggests that Smad3 may be required for TPA-mediated tumor promotion through inducing TGF-beta1-responsive genes, which are required for tumor promotion, and through mediating TGF-beta1-induced macrophage infiltration. C1 Oregon Hlth & Sci Univ, Dept Otolaryngol, Portland, OR USA. Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR USA. Oregon Hlth & Sci Univ, Dept Cell & Dev Biol, Portland, OR USA. NIDDKD, Mammalian Genet Sect, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Wang, XJ (reprint author), 3710 SW US Vet Hosp Rd,Mail Code R&D46, Portland, OR 97239 USA. EM wangxiao@ohsu.edu RI deng, chuxia/N-6713-2016 FU NCI NIH HHS [CA79998, CA87849] NR 68 TC 53 Z9 55 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2004 VL 64 IS 21 BP 7836 EP 7845 DI 10.1158/0008-5472.CAN-04-1331 PG 10 WC Oncology SC Oncology GA 866RM UT WOS:000224790600028 PM 15520189 ER PT J AU Kim, HW Park, IK Cho, CS Lee, KH Beck, GR Colburn, NH Cho, MH AF Kim, HW Park, IK Cho, CS Lee, KH Beck, GR Colburn, NH Cho, MH TI Aerosol delivery of glucosylated polyethylenimine/phosphatase and tensin homologue deleted on chromosome 10 complex suppresses Akt downstream pathways in the lung of K-ras null mice SO CANCER RESEARCH LA English DT Article ID MEDIATED GENE-TRANSFER; PROTEIN-KINASE B; CYSTIC-FIBROSIS; PLASMID DNA; TUMOR-SUPPRESSOR; NASAL EPITHELIUM; MAMMALIAN-CELLS; CANCER CELLS; CFTR CDNA; ADENOVIRUS AB Difficulties in achieving long-term survival of lung cancer patients treated with conventional therapies suggest that novel approaches are required. Although several genes have been investigated for antitumor activities using gene delivery, problems surrounding the methods used such as efficiency, specificity, and toxicity hinder its application as an effective therapy. This has lead to the re-emergence of aerosol gene delivery as a noninvasive approach to lung cancer therapy. In this study, glucosylated conjugated polyethylenimine (glucosylated PEI) was used as carrier. After confirming the efficiency of glucosylated PEI carriers in lungs, the potential effects of the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) tumor suppressor gene on Akt downstream pathways were investigated. Aerosol containing glucosylated PEI and recombinant plasmid pcDNA3.0-PTEN complex was delivered into K-ras null lung cancer model mice through a nose-only inhalation system. Investigation of proteins in the phosphatidylinositol 3'-kinase/Akt signaling pathway in PTEN-delivered mouse lung revealed that the PTEN protein was highly expressed, whereas the protein levels of PDK1, total Akt1, phospho-(Thr-308)-Akt, phospho-(Ser-2448)-mTOR, p70S6K, and 4E-BP1 were decreased to varying degrees. Additionally, the kinase activities of both Akt and mTOR were suppressed. Finally, apoptosis was detected in PTEN-delivered mouse lung by terminal deoxynucleotidyl-transferase-mediated nick end labeling assay, suggesting that our aerosol PTEN delivery is capable of functionally altering cell phenotype ill vivo. In summary, Western blot analysis, kinase assays, immunohistochemistry, and terminal deoxynucleotidyltransferase-mediated nick end labeling assays suggest that our aerosol gene delivery technique is compatible with ill vivo gene delivery and can be applied as a noninvasive gene therapy. C1 Seoul Natl Univ, Coll Vet Med, Toxicol Lab, Seoul 151742, South Korea. Seoul Natl Univ, Sch Agr Biotechnol, Seoul 151742, South Korea. Korea Inst Radiol & Med Sci, Mol Oncol Lab, Seoul, South Korea. NCI, Lab Canc Prevent, Frederick, MD 21701 USA. RP Cho, MH (reprint author), Seoul Natl Univ, Coll Vet Med, Toxicol Lab, Seoul 151742, South Korea. EM mchotox@snu.ac.kr RI CHO, Myung-Haing/B-7362-2014 NR 38 TC 48 Z9 48 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2004 VL 64 IS 21 BP 7971 EP 7976 DI 10.1158/0008-5472.CAN-04-1231 PG 6 WC Oncology SC Oncology GA 866RM UT WOS:000224790600043 PM 15520204 ER PT J AU Garnett, CT Palena, C Chakarborty, M Tsang, KY Schlom, J Hodge, JW AF Garnett, CT Palena, C Chakarborty, M Tsang, KY Schlom, J Hodge, JW TI Sublethal irradiation of human tumor cells modulates phenotype resulting in enhanced killing by cytotoxic T lymphocytes SO CANCER RESEARCH LA English DT Article ID HUMAN CARCINOEMBRYONIC ANTIGEN; RECOMBINANT VACCINIA VIRUS; INTERCELLULAR-ADHESION MOLECULE-1; PROSTATE-CANCER CELLS; HUMAN LUNG-CANCER; CLASS-I ANTIGENS; CARCINOMA-CELLS; IONIZING-RADIATION; GAMMA-IRRADIATION; GENE-EXPRESSION AB Local radiation of tumor masses is an established modality for the therapy of a range of human tumors. It has recently been recognized that doses of radiation, lower than or equal to those that cause direct cytolysis, may alter the phenotype of target tissue by up-regulating gene products that may make tumor cells more susceptible to T-cell-mediated immune attack. Previously, we demonstrated that radiation increased Fas (CD95) gene expression in carcinoembryonic antigen (CEA)-expressing marine tumor cells, which consequently enhanced their susceptibility to CEA-specific CTL-mediated killing. The present study was designed to determine whether these phenomena also occur with human tumor cells. Here, 23 human carcinoma cell lines (12 colon, 7 lung, and 4 prostate) were examined for their response to nonlytic doses of radiation (10 or 20 Gy). Seventy-two hours postirradiation, changes in surface expression of Fas (CD95), as well as expression of other surface molecules involved in T-cell-mediated immune attack such as intercellular adhesion molecule 1, mucin-1, CEA, and MHC class 1, were examined. Twenty-one of the 23 (91%) cell lines up-regulated one or more of these surface molecules postirradiation. Furthermore, five of five irradiated CEA(+)/A2(+) colon tumor cells lines demonstrated significantly enhanced killing by CEA-specific HLA-A2-restricted CD8(+) CTLs compared with nonirradiated counterparts. We then used microarray analysis to broaden the scope of observed changes in gene expression after radiation and found that many additional genes had been modulated. These up-regulated gene products may additionally enhance the tumor cells' susceptibility to T-cell-mediated immune attack or serve as additional targets for immunotherapy. Overall, the results of this study suggest that nonlethal doses of radiation can be used to make human tumors more amenable to immune system recognition and attack and form the rational basis for the combinatorial use of cancer vaccines and local tumor irradiation. C1 NCI, Tumor Immunol & Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Canc Res Ctr, NIH, 10 Ctr Dr,Bldg 10,Room 8B09,MSC 1750, Bethesda, MD 20892 USA. EM js141c@nih.gov RI Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 NR 49 TC 197 Z9 199 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2004 VL 64 IS 21 BP 7985 EP 7994 DI 10.1158/0008-5472.CAN-04-1525 PG 10 WC Oncology SC Oncology GA 866RM UT WOS:000224790600045 PM 15520206 ER PT J AU Sakai, Y Morrison, BJ Burke, JD Park, JM Terabe, M Janik, JE Forni, G Berzofsky, JA Morris, JC AF Sakai, Y Morrison, BJ Burke, JD Park, JM Terabe, M Janik, JE Forni, G Berzofsky, JA Morris, JC TI Vaccination by genetically modified dendritic cells expressing a truncated neu oncogene prevents development of breast cancer in transgenic mice SO CANCER RESEARCH LA English DT Article ID PEPTIDE-BASED VACCINES; IMMUNE-RESPONSES; T-CELL; GENE-THERAPY; MAMMARY CARCINOGENESIS; METASTATIC MELANOMA; ANTITUMOR IMMUNITY; ADENOVIRAL VECTORS; BONE-MARROW; BALB/C MICE AB Dendritic cells (DCs) are powerful antigen-presenting cells that process antigens and present peptide epitopes in the context of the major histocompatibility complex molecules to generate immune responses. DCs are being studied as potential anticancer vaccines because of their ability to present antigens to naive T cells and to stimulate the expansion of antigen-specific T-cell populations. We investigated an antitumor vaccination using DCs modified by transfer of a nonsignaling neu oncogene, a homologue of human HER-2/neu, in a transgenic model of breast cancer. BALB-neuT mice develop breast cancers as a consequence of mammary gland-specific expression of an activated neu oncogene. We vaccinated BALB-neuT mice with bone marrow-derived DCs transduced with Ad.Neu, a recombinant adenovirus expressing a truncated neu oncoprotein. The vaccine stimulated the production of specific anti-neu antibodies, enhanced interferon-gamma expression by T cells, and prevented or delayed the onset of mammary carcinomas in the mice. Over 65% of vaccinated mice remained tumor free at 28 weeks of age, whereas all of the mice in the control groups developed tumors. When challenged with a nett-expressing breast cancer cell line, vaccinated tumor-free animals had delayed tumor growth compared with controls. The antitumor effect of the vaccine was specific for expression of neu. Studies showed that CD4+ T cells were required in order to generate antitumor immunity. Importantly, the effectiveness of the vaccine was not diminished by preexisting immunity to adenovirus, whereas the protection afforded by vaccination that used direct injection of Ad.Neu was markedly reduced in mice with anti-adenovirus antibody titers. DCs modified by recombinant adenoviruses expressing tumor-associated antigens may provide an effective antitumor vaccination strategy. C1 NCI, Metab Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, Canc Gene Therapy Sect, NIH, Bethesda, MD 20892 USA. NCI, Mol Immunogenet & Vaccine Res Sect, Vaccine Branch, NIH, Bethesda, MD 20892 USA. NCI, Clin Trials, NIH, Bethesda, MD 20892 USA. Univ Turin, Dept Clin & Biol Sci, I-10124 Turin, Italy. RP Morris, JC (reprint author), NCI, Metab Branch, Canc Res Ctr, NIH, Bldg 10,Room 4N115,10 Ctr Dr, Bethesda, MD 20892 USA. EM jmorris@mail.nih.gov NR 51 TC 57 Z9 63 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2004 VL 64 IS 21 BP 8022 EP 8028 DI 10.1158/0008-5472.CAN-03-3442 PG 7 WC Oncology SC Oncology GA 866RM UT WOS:000224790600050 PM 15520211 ER PT J AU Lan, Q Mumford, JL Shen, M DeMarini, DM Bonner, MR He, XZ Yeager, M Welch, R Chanock, S Tian, LW Chapman, RS Zheng, TZ Keohavong, P Caporaso, N Rothman, N AF Lan, Q Mumford, JL Shen, M DeMarini, DM Bonner, MR He, XZ Yeager, M Welch, R Chanock, S Tian, LW Chapman, RS Zheng, TZ Keohavong, P Caporaso, N Rothman, N TI Oxidative damage-related genes AKR1C3 and OGG1 modulate risks for lung cancer due to exposure to PAH-rich coal combustion emissions SO CARCINOGENESIS LA English DT Article ID HOGG1 SER326CYS POLYMORPHISM; HYDROCARBON O-QUINONES; XUAN-WEI; MOLECULAR EPIDEMIOLOGY; SUPEROXIDE-DISMUTASE; DNA; CHINA; REPAIR; 8-HYDROXYGUANINE; SUSCEPTIBILITY AB Lung cancer rates among men and particularly among women, almost all of whom are non-smokers, in Xuan Wei County, China are among the highest in China and have been causally associated with exposure to indoor smoky coal emissions that contain very high levels of polycyclic aromatic hydrocarbons (PAHs). As such, this population provides a unique opportunity to study the pathogenesis of PAH-induced lung cancer that is not substantially influenced by the large number of other carcinogenic constituents of tobacco smoke. Aldo-keto reductases (AKRs) activate PAH dihydrodiols to yield their corresponding reactive and redox-active o-quinones, which can then generate reactive oxygen species that cause oxidative DNA damage. We therefore examined the association between single nucleotide polymorphisms (SNPs) in four genes (AKR1C3-Gln5His, NQO1-Pro187Ser, MnSOD-Val16Ala and OGG1-Ser326Cys) that play a role in the generation, prevention or repair of oxidative damage and lung cancer risk in a population-based, case-control study of 119 cases and 113 controls in Xuan Wei, China. The AKR1C3-Gln/Gln genotype was associated with a 1.84-fold [95% confidence interval (CI) = 0.98-3.45] increased risk and the combined OGG1-Cys/Cys and Ser/Cys genotypes were associated with a 1.93-fold (95% CI = 1.12-3.34) increased risk of lung cancer. Subgroup analysis revealed that the effects were particularly elevated among women who had relatively high cumulative exposure to smoky coal. SNPs in MnSOD and NQO1 were not associated with lung cancer risk. These results suggest that SNPs in the oxidative stress related-genes AKR1C3 and OGG1 may play a role in the pathogenesis of lung cancer in this population, particularly among heavily exposed women. However, due to the small sample size, additional studies are needed to evaluate these associations within Xuan Wei and other populations with substantial exposure to PAHs. C1 NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. Chinese Acad Prevent Med, Beijing, Peoples R China. Univ Calif Berkeley, Berkeley, CA 94720 USA. Yale Univ, Yale Sch Publ Hlth, New Haven, CT 06520 USA. Univ Pittsburgh, Dept Environm & Occupat Hlth, Pittsburgh, PA 15260 USA. RP Lan, Q (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. EM qingl@mail.nih.gov RI Tian, Linwei/A-9736-2009 OI Tian, Linwei/0000-0002-4739-1534 NR 36 TC 104 Z9 111 U1 2 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 2004 VL 25 IS 11 BP 2177 EP 2181 DI 10.1093/carcin/bgh240 PG 5 WC Oncology SC Oncology GA 873AO UT WOS:000225251200019 PM 15284179 ER PT J AU Maciag, A Sithanandam, G Anderson, LM AF Maciag, A Sithanandam, G Anderson, LM TI Mutant K-ras(V12) increases COX-2, peroxides and DNA damage in lung cells SO CARCINOGENESIS LA English DT Article ID INTESTINAL EPITHELIAL-CELLS; K-RAS; CYCLOOXYGENASE-2 EXPRESSION; SUPEROXIDE PRODUCTION; TYPE-2 PNEUMOCYTE; ONCOGENIC RAS; MESSENGER-RNA; CANCER; ACTIVATION; PROTEIN AB K-ras is frequently mutated in lung adenocarcinomas. Recent discovery that wild-type K-ras is tumor suppressive in the lung raises a question: how is mutant K-ras aggressively oncogenic? We hypothesized that mutant K-ras might lead to generation of reactive oxygen species (ROS) and DNA damage, contributing to malignant transformation. We stably transfected human mutant K-ras(V12) into non-transformed peripheral mouse lung epithelial cells (E10 line). Constitutively active mutant K-ras(V12) in E10 cells led to a highly significant (P < 0.001) increased level of peroxides, and a corresponding increase in the amount of DNA strand-break damage, compared with the parental line E10 and the vector control. Levels of superoxide were not increased, suggesting a direct source of peroxides, such as cyclooxygenase-2 (COX-2). COX-2 protein and activity measured as prostaglandin E-2 level were up-regulated in cells expressing mutant K-ras(V12); COX-2 activity correlated with K-ras activity (K-ras p21-GTP). Both peroxide generation and DNA single strand breaks were significantly reduced by pre-treatment with COX-2-specific inhibitor SC 58125, confirming COX-2 as the source of the ROS. COX-2 has been repeatedly implicated in lung cancer, and is known to be regulated by ras and to release ROS. Our data suggest that up-regulation of COX-2, with a consequent increase in peroxides and DNA damage, contributes to the dominant oncogenicity of mutant K-ras. C1 NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. RP Maciag, A (reprint author), NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. EM amaciag@mail.ncifcrf.gov FU NCI NIH HHS [NC-CO-12400] NR 41 TC 26 Z9 27 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 2004 VL 25 IS 11 BP 2231 EP 2237 DI 10.1093/carcin/bgh245 PG 7 WC Oncology SC Oncology GA 873AO UT WOS:000225251200026 PM 15284181 ER PT J AU Port, JL Yamaguchi, K Du, BH De Lorenzo, M Chang, M Heerdt, PM Kopelovich, L Marcus, CB Altorki, NK Subbaramaiah, K Dannenberg, AJ AF Port, JL Yamaguchi, K Du, BH De Lorenzo, M Chang, M Heerdt, PM Kopelovich, L Marcus, CB Altorki, NK Subbaramaiah, K Dannenberg, AJ TI Tobacco smoke induces CYP1B1 in the aerodigestive tract SO CARCINOGENESIS LA English DT Article ID CYTOCHROME P4501B1 CYP1B1; CANCER CELL-LINES; LUNG-CANCER; DETERMINES SUSCEPTIBILITY; BREAST-CANCER; EXPRESSION; TISSUE; 1B1; P450CYP1B1; GENE AB Several members of the P450 family, including cytochrome P450 1B1 (CYP1B1), can convert tobacco smoke (TS) procarcinogens, including benzo[a]pyrene (B[a]P), to carcinogenic intermediates. In this study we investigated the effects of TS condensate and B[a]P on the expression of CYP1B1 in vitro and in vivo. CYP1B1 mRNA and protein were induced by both TS condensate and B[a]P in cell lines derived from the human aerodigestive tract. Treatment with TS condensate stimulated binding of the aryl hydrocarbon receptor (AhR) to an oligonucleotide containing a canonical xenobiotic response element (XRE) site and induced XRE-luciferase activity. These findings are consistent with prior evidence that polycyclic aromatic hydrocarbons, known ligands of the AhR, stimulate CYP1B1 transcription by an XRE-dependent mechanism. To determine whether these in vitro findings applied in vivo, both murine and human studies were carried out. Short-term exposure to TS induced CYP1B1 in the tongue, esophagus, lung and colon of experimental mice. In contrast, CYP1B1 was not induced by TS in the aorta of these mice. Levels of CYP1B1 mRNA were also elevated in the bronchial mucosa of human tobacco smokers versus never smokers (P < 0.05). Taken together, these results support a role for CYP1B1 in TS-induced carcinogenesis in the aerodigestive tract. C1 Cornell Univ, Weill Med Coll, Dept Med, New York, NY 10021 USA. Cornell Univ, Weill Med Coll, Dept Cardiothorac Surg, New York, NY 10021 USA. Cornell Univ, Weill Med Coll, Dept Anesthesiol, New York, NY 10021 USA. NCI, DCP, Bethesda, MD 20892 USA. Univ New Mexico, Coll Pharm, Hlth Sci Ctr, Albuquerque, NM 87131 USA. Strang Canc Prevent Ctr, New York, NY 10021 USA. RP Dannenberg, AJ (reprint author), Cornell Univ, Weill Med Coll, Dept Med, 525 E 68th St,Room F-206, New York, NY 10021 USA. EM ajdannen@med.cornell.edu FU NCI NIH HHS [N01-CN-35107]; NIEHS NIH HHS [P30 ES012072, R01 ES09878] NR 38 TC 54 Z9 60 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 2004 VL 25 IS 11 BP 2275 EP 2281 DI 10.1093/carcin/bgh243 PG 7 WC Oncology SC Oncology GA 873AO UT WOS:000225251200031 PM 15297370 ER PT J AU Lu, XB Nguyen, TA Appella, E Donehower, LA AF Lu, XB Nguyen, TA Appella, E Donehower, LA TI Homeostatic regulation of base excision repair by a p53-induced phosphatase - Linking stress response pathways with DNA repair proteins SO CELL CYCLE LA English DT Article DE PPM1D; Wip1; p53; uracil DNA glycolase; UNG2; base excision repair; DNA repair ID CELLULAR STRESS; P53 REGULATION; BREAST-CANCER; UV-RADIATION; PPM1D; PHOSPHORYLATION; WIP1; P38; AMPLIFICATION; ACTIVATION AB The p53 protein plays a central role in the integration of cellular stress responses. If the cell incurs DNA damage, p53-induced cell cycle arrest is accompanied by p53-facilitated DNA repair. In particular, p53 has been demonstrated to promote both nucleotide excision repair (NER) and base excision repair (BER). Once these repair processes are completed, p53 activity declines and the cell can reenter the cell cycle. A critical mediator of this p53 negative regulatory feedback loop is Mdm2, a p53 transcriptional target whose protein mediates p53 proteolytic degradation. Another such p53 transcriptional target that may function in a p53 negative regulation is the PPM1D phosphatase. PPM1D may inhibit p53 activity through inactivating dephosphorylation of the p38 MAP kinase. We have recently shown that PPM1D suppresses BER in part through dephosphorylation of a key BER effector, the nuclear isoform of uracil DNA glycosylase, or UNG2. This finding further links p53 signaling to DNA repair pathways and illustrates a mechanism by which activated DNA repair systems are returned to a deactivated, homeostatic state. C1 Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. Baylor Coll Med, Interdepartmental Grad Program Cell & Mol Biol, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. NCI, Cell Biol Lab, Bethesda, MD 20892 USA. RP Donehower, LA (reprint author), Baylor Coll Med, Dept Mol Virol & Microbiol, 1 Baylor Plaza, Houston, TX 77030 USA. EM larryd@bcm.tmc.edu NR 39 TC 16 Z9 16 U1 0 U2 3 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD NOV PY 2004 VL 3 IS 11 BP 1363 EP 1366 DI 10.4161/cc.3.11.1241 PG 4 WC Cell Biology SC Cell Biology GA 877SS UT WOS:000225591100006 PM 15539943 ER PT J AU Reilly, KM AF Reilly, KM TI The importance of genome architecture in cancer susceptibility - Location, location, location SO CELL CYCLE LA English DT Article DE astrocytoma; mouse models; imprinting; epigenetics; cancer susceptibility; p53; Nf1; ras signaling pathways; tumor suppressor ID MALIGNANT HUMAN GLIOMAS; TUMOR-SUPPRESSOR GENES; SEX-CHROMOSOME LOSS; GLIOBLASTOMA-MULTIFORME; BRAIN-TUMORS; HUMAN GRB10; CELL LINES; PTEN GENE; ASTROCYTOMAS; PROGRESSION AB Tumorigenesis requires the interaction between different gene disruptions to convert a normal cell into a cancer cell. These gene disruptions can involve loss of expression or misexpression of genes through genetic or epigenetic mutations. It is becoming clear that these disruptions are not isolated events in the genome, but are affected by genome architecture and the syntenic relationship of alleles on chromosomes. A better understanding of the genetic and epigenetic changes in cancer is important for the rational design of new therapies. We have recently shown that background-specific polymorphisms and loci under epigenetic regulation have a strong effect on cancer susceptibility in a mouse model of astrocytoma. Although these mice carry mutations in p53 and ras signaling pathways ( through mutation of the rasGAP protein, Nf1), the susceptibility to different tumor types depends strongly on epigenetic regulation and does not show simple Mendelian inheritance. Our results demonstrate the importance of genome architecture and how tumorigenesis can be accelerated by concomitant loss or gain of multiple genes in a single chromosome rearrangement. Because genome architecture is very different between mice and humans, comparing patterns of genomic rearrangement in human cancer and mouse models may help distinguish causal genomic changes from correlative changes. C1 NCI, Frederick, MD 21702 USA. RP Reilly, KM (reprint author), NCI, W 7th St & Ft Detrick,POB B,Bldg 560,Room 32-31B, Frederick, MD 21702 USA. EM kreilly@ncifcrf.gov NR 46 TC 3 Z9 3 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD NOV PY 2004 VL 3 IS 11 BP 1378 EP 1382 DI 10.4161/cc.3.11.1253 PG 5 WC Cell Biology SC Cell Biology GA 877SS UT WOS:000225591100010 PM 15492507 ER PT J AU Iyer, LM Koonin, EV Aravind, L AF Iyer, LM Koonin, EV Aravind, L TI Novel predicted peptidases with a potential role in the ubiquitin signaling pathway SO CELL CYCLE LA English DT Article ID SECONDARY STRUCTURE PREDICTION; MULTIPLE SEQUENCE ALIGNMENT; SACCHAROMYCES-CEREVISIAE; DEUBIQUITINATING ENZYMES; MEMBRANE-PROTEIN; MEDIATED PROTEOLYSIS; CHESTNUT BLIGHT; BINDING-PROTEIN; GENOME ANALYSIS; CAPSID PROTEIN AB A multi-pronged strategy including extensive sequence searches, structural modeling, and analysis of contextual information extracted from domain architectures, genetic screens, and large-scale protein-protein interaction analyses was employed to predict previously undetected components of the eukaryotic ubiquitin (Ub) signaling system. Two novel groups of proteins that are likely to function as de-ubiquitinating and de-SUMOylating peptidases (DUBs) were identified. The first group of putative DUBs, designated PPPDE superfamily ( after Permuted Papain fold Peptidases of DsRNA viruses and Eukaryotes), consists of predicted thiol peptidases with a circularly permuted papain-like fold. The inference of the likely DUB function of the PPPDE superfamily proteins is based on the fusions of the catalytic domain to Ub-binding PUG ( PUB)/UBA domains and a novel alpha-helical Ub-associated domain ( the PUL domain, after PLAP, Ufd3p and Lub1p). The presence of the PPPDE superfamily proteins in most eukaryotic lineages, including basal ones, such as Giardia, suggests a role in deubiquitination of highly conserved proteins involved in key cellular functions, such as cell cycle control. In addition to eukaryotic proteins, the PPPDE superfamily includes predicted proteases from several groups of double-stranded RNA viruses and one single-stranded DNA virus. The apparent recruitment of DUBs for viral polyprotein processing seems to represent a common theme in evolution of viruses. The second group of putative DUBs identified in this study is the WLM (Wss1p-like metalloproteases) family of the Zincin-like superfamily of Zn-dependent peptidases, which are linked to the Ub-system by virtue of fusions with the UB-binding PUG ( PUB), Ub-like, and Little Finger domains. More specifically, genetic evidence implicates the WLM family in de-SUMOylation. If validated experimentally, the WLM family proteins will represent the first case of a Zincin-like metalloprotease involvement in Ub-signaling. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Aravind, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM aravind@ncbi.nlm.nih.gov NR 73 TC 64 Z9 67 U1 0 U2 2 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD NOV PY 2004 VL 3 IS 11 BP 1440 EP 1450 DI 10.4161/cc.3.11.1206 PG 11 WC Cell Biology SC Cell Biology GA 877SS UT WOS:000225591100021 PM 15483401 ER PT J AU Chung, IY Dong, HF Zhang, X Hassanein, NMA Howard, OMZ Oppenheim, JJ Chen, X AF Chung, IY Dong, HF Zhang, X Hassanein, NMA Howard, OMZ Oppenheim, JJ Chen, X TI Effects of IL-7 and dexamethasone: Induction of CD25, the high affinity IL-2 receptor, on human CD4(+) cells SO CELLULAR IMMUNOLOGY LA English DT Article DE CD4(+) CD25(+) regulatory T lymphocytes; dexamethasone; interleukin-7; suppression/anergy ID T-CELLS; AUTOIMMUNE-DISEASES; REGULATORY CELLS; SELF-TOLERANCE; ALPHA GENE; IN-VITRO; GLUCOCORTICOIDS; CD4(+)CD25(+); PROLIFERATION; ACTIVATION AB Since we have previously shown that dexamethasone (Dex) enhances the proportion of murine Treg cells, we tested the effect of IL-7, a promoter of T cell survival, together with Dex oil human CD4(+)CD25(+) Treg cells in an in vitro setting. The results showed that IL-7 in concert with Dex markedly augmented the generation of CD4(+)CD25(+) T cells. To discern the origin of the induced CD4(+)CD25(+) T cells, MACS-purified CD4(+)CD25(-), and CD4(+)CD25(+) cells were cultured in the presence of Dex and/or IL-7 for 4 days. Although two thirds of CD4(+)CD25(-) T cells became CD4(+)CD25(+) T cells, they had no Suppressive activity. In contrast, the original CD4(+)CD25(+) T cells maintained Suppressive activity after Dex/IL-7 treatment, however, there was not a significant expansion ill their cell number. Dex and IL-7 did not induce additional Treg cells, but additively induced the expression of the activation marker CD25 by CD4(+)CD25(-) T cells. This combination may provide a novel means of priming CD4 T cells to respond to IL-2 and may prove useful in up-regulation of normal immune responses in immune deficient diseases. (c) 2005 Elsevier Inc. All rights reserved. C1 Ctr Canc Res, Mol Immunoregulat Lab, Ft Detrick, MD 21702 USA. SAIC Frederick Inc, Basic Res Program, Ft Detrick, MD 21702 USA. Natl Canc Inst, Expt Immunol Lab, Ft Detrick, MD 21702 USA. RP Howard, OMZ (reprint author), Ctr Canc Res, Mol Immunoregulat Lab, Ft Detrick, MD 21702 USA. EM howardz@ncifcrf.gov RI Zhang, Xia/B-8152-2008; Howard, O M Zack/B-6117-2012; Chen, Xin/I-6601-2015 OI Zhang, Xia/0000-0002-9040-1486; Howard, O M Zack/0000-0002-0505-7052; Chen, Xin/0000-0002-2628-4027 FU PHS HHS [N01-C0-12400] NR 22 TC 9 Z9 14 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD NOV-DEC PY 2004 VL 232 IS 1-2 BP 57 EP 63 DI 10.1016/j.cellimm.2005.01.011 PG 7 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 935FF UT WOS:000229764300007 PM 15922716 ER PT J AU Bolla, KI Eldreth, DA Matochik, JA Cadet, JL AF Bolla, KI Eldreth, DA Matochik, JA Cadet, JL TI Sex-related differences in a gambling task and its neurological correlates SO CEREBRAL CORTEX LA English DT Article DE decision-making; neuroimaging; orbitofrontal; prefrontal cortex; sex-related differences ID CEREBRAL-BLOOD-FLOW; ABSTINENT COCAINE ABUSERS; DECISION-MAKING TASK; ORBITOFRONTAL CORTEX; GENDER-DIFFERENCES; PREFRONTAL CORTEX; GLUCOSE-METABOLISM; PET; REPRESENTATIONS; ACTIVATION AB We investigated sex-related differences in task performance and brain activity in the orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex (DLPFC) during performance of a decision-making task (the Iowa Gambling Task). When men and women were examined separately, men activated extensive regions of the right lateral OFC and right DLPFC, as well as the left lateral OFC. In contrast, women activated the left medial OFC. Examining sex differences directly, men showed better task performance and greater lateralized brain activity to the right hemisphere than women. This was exemplified by greater activation in a large area of the right lateral OFC of men during their performance of the Iowa Gambling Task. In contrast, women had greater activation in the left DLPFC, left medial frontal gyrus and temporal lobe during this task. Thus, brain mechanisms engaged by men and women when solving the same decision-making task are different. These observations indicate that sex-related differences contribute to the heterogeneity observed in both normal and abnormal brain functioning. These results also provide further evidence of sexual dimorphism in neurocognitive performance and brain function. C1 Johns Hopkins Univ, Sch Med, Bayview Med Ctr, Dept Neurol, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Bayview Med Ctr, Dept Psychiat & Behav Sci, Baltimore, MD 21224 USA. NIDA, Neuroimaging Res Branch, DHHS, NIH,Intramural Res Program, Baltimore, MD 21224 USA. NIDA, Mol Neuropsychiat Branch, DHHS, NIH,Intramural Res Program, Baltimore, MD 21224 USA. RP Bolla, KI (reprint author), Johns Hopkins Univ, Sch Med, Bayview Med Ctr, Dept Neurol, 4940 Eastern Ave, Baltimore, MD 21224 USA. FU NCRR NIH HHS [M01 RR02719]; NIDA NIH HHS [DA 11426] NR 41 TC 168 Z9 176 U1 2 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD NOV PY 2004 VL 14 IS 11 BP 1226 EP 1232 DI 10.1093/cercor/bhh083 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 860RG UT WOS:000224360100006 PM 15142963 ER PT J AU Guo, Q Gao, GH Qian, SY Mason, RP AF Guo, Q Gao, GH Qian, SY Mason, RP TI Novel identification of a sulfur-centered, radical-derived 5,5-dimethyl-1-pyrroline N-oxide nitrone adduct formed from the oxidation of DTT by LC/ELISA, LC/electrospray ionization-MS, and LC/tandem MS SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID LINOLEIC-ACID HYDROPEROXIDE; POLYUNSATURATED FATTY-ACIDS; TERT-BUTYL HYDROPEROXIDE; ORGANIC HYDROPEROXIDES; SOYBEAN LIPOXYGENASE; HYDROGEN-PEROXIDE; IMMUNOCHEMICAL DETECTION; MASS-SPECTROMETRY; CYTOCHROME-C; ONE-ELECTRON AB The detection of highly reactive free radicals generated in biological systems by an ESR spin-trapping technique is always difficult and limited due to the short lifetimes of ESR active spin-trapping radical adducts and poor structural information provided by ESR spectra. In this investigation, we have for the first time employed anti-5,5-dimethyl-1-pyrroline N-oxide (DMPO) polyclonal antiserum that specifically recognizes stable, ESR silent end products of DMPO radical adducts and combined HPLC with ELISA, electrospray ionization mass spectrometry (ESI-MS), and tandem mass spectrometry (MS/MS) to separate and characterize DMPO nitrone adducts derived from free radical metabolites. When mireoperoxidase-11 (MP-11) reacted with DTT in the presence of DMPO with or without H2O2, we detected radical-derived DMPO nitrone adducts by ELISA. Similar results were obtained when MP-11 was replaced by hemin. To identify the DMPO nitrone adducts formed in both reaction systems, LC separation was carried out, and the fractions eluted from the LC column were collected and analyzed by ELISA. In both reaction mixtures, we found that only one peak with the same retention time showed a strong positive ELISA signal, suggesting that this peak was from radical-derived DMPO nitrone adducts and that both systems produced the same free radical metabolites. Using online LC/ESI-MS, LC/MS/MS, and H-1 NMR, we demonstrated that the DMPO nitrone adducts formed are from the DMPO adducts of the sulfur-centered radical of DTT. The successful application of LC/ELISA, LC/MS, and LC/MS/MS in this study makes it possible to separate and identify the stable DMPO nitrone adducts derived from free radical metabolites generated in biological systems. C1 Natl Inst Environm Hlth Sci, NIH, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. RP Guo, Q (reprint author), Natl Inst Environm Hlth Sci, NIH, Lab Pharmacol & Chem, POB 12233, Res Triangle Pk, NC 27709 USA. EM guo1@niehs.nih.gov NR 51 TC 16 Z9 16 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD NOV PY 2004 VL 17 IS 11 BP 1481 EP 1490 DI 10.1021/tx049837o PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 873ME UT WOS:000225283600010 PM 15540946 ER PT J AU Lunn, MR Root, DE Martino, AM Flaherty, SP Kelley, BP Coovert, DD Burghes, AH Man, NT Morris, GE Zhou, JH Androphy, EJ Sumner, CJ Stockwell, BR AF Lunn, MR Root, DE Martino, AM Flaherty, SP Kelley, BP Coovert, DD Burghes, AH Man, NT Morris, GE Zhou, JH Androphy, EJ Sumner, CJ Stockwell, BR TI Indoprofen upregulates the survival motor neuron protein through a cyclooxygenase-independent mechanism SO CHEMISTRY & BIOLOGY LA English DT Article ID SPINAL MUSCULAR-ATROPHY; VALPROIC ACID INCREASES; DISEASE GENE-PRODUCT; PRE-MESSENGER-RNA; SPLICING ENHANCER; CHEMICAL GENETICS; POTENTIAL THERAPY; SNRNP BIOGENESIS; SMN PROTEIN; EXON-7 AB Most patients with the pediatric neurodegenerative disease spinal muscular atrophy have a homozygous deletion of the survival motor neuron 1 (SMN1) gene, but retain one or more copies of the closely related SMN2 gene. The SMN2 gene encodes the same protein (SMN) but produces it at a low efficiency compared with the SMN1 gene. We performed a high-throughput screen of 47,000 compounds to identify those that increase production of an SMN2-luciferase reporter protein, but not an SMN1-luciferase reporter protein. Indoprofen, a nonsteroidal anti-inflammatory drug (NSAID) and cyclooxygenase (COX) inhibitor, selectively increased SMN2-luciferase reporter protein and endogenous SMN protein and caused a 5-fold increase in the number of nuclear gems in fibroblasts from SMA patients. No other NSAIDs or COX inhibitors tested exhibited this activity. C1 Columbia Univ, Dept Biol Sci, Fairchild Ctr, New York, NY 10027 USA. Columbia Univ, Dept Chem, Fairchild Ctr, New York, NY 10027 USA. Ohio State Univ, Dept Mol & Cellular Biochem, Columbus, OH 43210 USA. Ohio State Univ, Dept Neurol, Columbus, OH 43210 USA. Robert Jones & Agnes Hunt Orthopaed Hosp, Ctr Inherited Neuromuscular Dis, Oswestry SY10 7AG, Shrops, England. Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. RP Stockwell, BR (reprint author), Columbia Univ, Dept Biol Sci, Fairchild Ctr, MC 2406,1212 Amsterdam Ave, New York, NY 10027 USA. EM stockwell@biology.columbia.edu OI Lunn, Mitchell/0000-0002-0068-0814; Androphy, Elliot/0000-0002-8104-0703 FU NCI NIH HHS [R01 CA097061-04, R01 CA097061] NR 41 TC 87 Z9 88 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD NOV PY 2004 VL 11 IS 11 BP 1489 EP 1493 DI 10.1016/j.chembiol.2004.08.024 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 877ZD UT WOS:000225613800007 PM 15555999 ER PT J AU Dubowitz, H DePanfilis, D Boyce, CA Runyon, D AF Dubowitz, H DePanfilis, D Boyce, CA Runyon, D TI Special Issue: Child Neglect Research: Initial papers from the NIH and ACYF Neglect Projects - Issue I - Introduction SO CHILD MALTREATMENT LA English DT Editorial Material C1 Univ Maryland, College Pk, MD 20742 USA. NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ N Carolina, Chapel Hill, NC USA. RP Dubowitz, H (reprint author), Univ Maryland, College Pk, MD 20742 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-5595 J9 CHILD MALTREATMENT JI Child Maltreatment PD NOV PY 2004 VL 9 IS 4 BP 343 EP 343 DI 10.1177/1077559504271150 PG 1 WC Family Studies; Social Work SC Family Studies; Social Work GA 864JJ UT WOS:000224629500001 ER PT J AU Wang, F Li, HM Liu, WW Xu, P Hu, GX Cheng, YD Jia, LB Huang, Q AF Wang, F Li, HM Liu, WW Xu, P Hu, GX Cheng, YD Jia, LB Huang, Q TI Gene expression profiles of the developing human retina SO CHINESE SCIENCE BULLETIN LA English DT Article DE retina; development; expression/gene; regulation/gene; microarray; expression profile/gene ID MICROARRAY ANALYSIS; MOUSE RETINA; PATTERNS; DISEASE AB Retina is a multilayer and highly specialized tissue important in converting light into neural signals. In humans, the critical period for the formation of complex multiplayer structure takes place during embryogenesis between 12 and 28 weeks. The morphologic changes during retinal development in humans have been studied but little is known about the molecular events essential for the formation of the retina. To gain further insights into this process, cDNA microarrays containing 16361 human gene probes were used to measure the gene expression levels in retinas. Of the 16361 genes, 68.7%, 71.4% and 69.7% showed positive hybridization with cDNAs made from 12-16 week fetal, 22-26 week fetal and adult retinas. A total of 814 genes showed a minimum of 3-fold changes between the lowest and highest expression levels among three time points and among them, 106 genes had expression levels with the hybridization intensity above 100 at one or more time points. The clustering analysis suggested that the majority of differentially expressed genes were down-regulated during the retinal development. The differentially expressed genes were further classified according to functions of known genes, and were ranked in decreasing order according to frequency: development, differentiation, signal transduction, protein synthesis and translation, metabolism, DNA binding and transcription, DNA synthesis-repair-recombination, immuno-response, ion channel-transport, cell receptor, cytoskeleton, cell cycle, pro-oncogene, stress and apoptosis related genes. Among these 106 differentially expressed genes, 60 are already present in NEI retina cDNA or EST Databank but the remaining 46 genes are absent and thus identified as "function unknown". To validate gene expression data from the microarray, real-time RT-PCR was performed for 46 "function unknown" genes and 6 known retina specific expression genes, and beta-actin was used as internal control. Twenty-seven of these genes showed very similar expression profiles between the microarray and real-time RT-PCR data. In situ hybridization revealed both expression level and cellular distribution of NNAT in retina. Finally, the chromosomal locations of 106 differentially expressed genes were also searched and one of these genes is associated with autosomal dominant cone or cone-rod dystrophy. The data from present study provide insights into understanding genetic programs during human retinal development and help identify additional retinal disease genes. C1 Shanghai Jiao Tong Univ, Peoples Hosp 1, Cent Expt Lab, Shanghai 200080, Peoples R China. Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China. NHGRI, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Huang, Q (reprint author), Shanghai Jiao Tong Univ, Peoples Hosp 1, Cent Expt Lab, Shanghai 200080, Peoples R China. EM huangq@online.sh.cn NR 15 TC 4 Z9 4 U1 0 U2 1 PU SCIENCE CHINA PRESS PI BEIJING PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA SN 1001-6538 J9 CHINESE SCI BULL JI Chin. Sci. Bull. PD NOV PY 2004 VL 49 IS 21 BP 2277 EP 2284 DI 10.1360/04wc0271 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 887SO UT WOS:000226326000010 ER PT J AU Kondapaka, SB Zarnowski, MJ Yver, DR Sausville, EA Cushman, SW AF Kondapaka, SB Zarnowski, MJ Yver, DR Sausville, EA Cushman, SW TI 7-hydroxystaurosporine (UCN-01) inhibition of Akt Thr(308) but not Ser(473) phosphorylation: A basis for decreased insulin-stimulated glucose transport SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 63rd Annual Meeting of the American-Diabetes-Association CY JUN 13-17, 2003 CL NEW ORLEANS, LA SP Amer Diabet Assoc ID PROTEIN-KINASE-B; GLYCOGEN-SYNTHASE KINASE; INTEGRIN-LINKED KINASE; DNA-DAMAGE CHECKPOINT; PHOSPHATIDYLINOSITOL 3-KINASE; GLUT4 TRANSLOCATION; GLUT4-CONTAINING VESICLES; SELECTIVE INHIBITOR; SIGNALING PATHWAY; 3T3-L1 ADIPOCYTES AB 7-Hydroxystaurosporine (UCN-01) infused for 72 hours by continuous i.v. infusion induced insulin resistance during phase I clinical trials. To understand the mechanism for this observation, we examined the effect of UCN-01 on insulin-stimulated glucose transport activity with 3-O-methylglucose in isolated rat adipose cells. UCN-01 inhibits glucose transport activity in a dose-dependent manner at all insulin concentrations. At the clinically relevant concentration of 0.25 mumol/L UCN-01, glucose transport is inhibited 66, 29, and 26% at insulin concentrations of 10, 50, and 100,000 (100K) microunits/mL respectively, thus shifting the dose-response curve to the right. Increasing concentrations of UCN-01 up to 2.5 mumol/L progressively shift the insulin dose-response curve even further. As Akt is known to mediate in part action initiated at the insulin receptor, we also studied the effect of UCN-01 on Akt activation in whole-cell homogenates of these cells. Decreased glucose transport activity directly parallels decreased Akt Thr(308) phosphorylation in both an insulin and UCN-01 dose-dependent manner, whereas Akt Ser(473) phosphorylation is inhibited only at the lowest insulin concentration, and then, only modestly. UCN-01 also inhibits insulin-induced Thr(308) but not Ser(473) phosphorylation of Akt associated with the plasma membranes and low-density microsomes and inhibits translocation of GLUT4 from low-density microsomes to plasma membranes as expected from the glucose transport activity measurements. These data suggest that UCN-01 induces clinical insulin resistance by blocking Akt activation and subsequent GLUT4 translocation in response to insulin, and this effect appears to occur by inhibiting Thr(308) phosphorylation even in the face of almost completely unaffected Ser(473) phosphorylation. C1 NCI, Dev Therapeut Program, Frederick, MD 21702 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Kondapaka, SB (reprint author), NCI, Dev Therapeut Program, Bldg 322,Room 102, Frederick, MD 21702 USA. EM kodapakas@ncifcrf.gov NR 47 TC 42 Z9 46 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2004 VL 10 IS 21 BP 7192 EP 7198 DI 10.1158/1078-0432.CCR-04-0772 PG 7 WC Oncology SC Oncology GA 869HZ UT WOS:000224975300013 PM 15534092 ER PT J AU Davidson, B Konstantinovsky, S Nielsen, S Dong, HP Berner, A Vyberg, M Reich, R AF Davidson, B Konstantinovsky, S Nielsen, S Dong, HP Berner, A Vyberg, M Reich, R TI Altered expression of metastasis-associated and regulatory molecules in effusions from breast cancer patients: A novel model for tumor progression SO CLINICAL CANCER RESEARCH LA English DT Article ID MALIGNANT PLEURAL EFFUSION; ETS TRANSCRIPTION FACTORS; KDA LAMININ RECEPTOR; MATRIX METALLOPROTEINASES; OVARIAN-CARCINOMA; CELL-SURFACE; PROGNOSTIC VALUE; INTERSTITIAL COLLAGENASE; ALPHA-6 INTEGRIN; POOR SURVIVAL AB Purpose: The aim of this study was to characterize phenotypic alterations along the progression of breast carcinoma from primary tumor to pleural effusion through analysis of the expression of proteases, laminin receptors (LRs), and transcription factors involved in invasion and metastasis. Experimental Design: The material studied consisted of 60 malignant pleural effusions from breast cancer patients and 68 corresponding solid tumors (37 primary and 31 metastatic tumors). Expression of matrix metalloproteinases [MMPs (MMP-1, MMP-2, MMP-9, and MMP-14)], the MMP inhibitor tissue inhibitor of metalloproteinase-2, the MMP inducer EMMPRIN, the 67-kDa LR, the alpha(6) integrin subunit, and the transcription factors AP-2, Ets-1, and PEA3 was studied using immunohistochemistry, mRNA in situ hybridization, reverse transcription-polymerase chain reaction, zymography, and flow cytometry. Hormone receptor (estrogen receptor and progesterone receptor) status and c-erbB-2 status were also studied. Results: Significantly reduced estrogen receptor (P < 0.001) and progesterone receptor (P = 0.001) expression was seen in effusions compared with primary tumors, with opposite findings for c-erbB-2 (P = 0.003). Tumor cell MMP-2 protein expression in effusions was higher than that in primary tumors (P < 0.001) and lymph node metastases (P = 0.01). In situ hybridization demonstrated higher MMP-2 (P = 0.007), PEA3 (P = 0.038), and EMMPRIN (P = 0.026) mRNA expression in effusions. The time to progression from primary tumor to effusion was significantly shorter for patients whose primary tumors expressed MMP-1 (P = 0.016) and who expressed the 67-kDa LR protein in primary tumor (P = 0.007) and effusion (P = 0.015). Conclusions: Our data provide documented evidence of molecular events that occur during the progression of breast carcinoma from primary tumor to effusion. The coordinated up-regulation of MMP-2 and Ets transcription factors in carcinoma cells in effusions is in full agreement with our previous reports linking these factors to poor prognosis in ovarian cancer. The rapid progression to effusion in cases showing MMP-1 and 67-kDa LR expression in primary tumor cells links aggressive clinical behavior with expression of metastasis-associated molecules in this setting. C1 Univ Oslo, Dept Pathol, Norwegian Radium Hosp, Oslo, Norway. Hebrew Univ Jerusalem, Sch Pharm, Fac Med, Dept Pharmacol & Expt Therapeut, IL-91120 Jerusalem, Israel. Univ Aalborg, Dept Pathol, Aalborg, Denmark. Hebrew Univ Jerusalem, David R Bloom Ctr Pharm, Jerusalem, Israel. RP Davidson, B (reprint author), NIH, Pathol Lab, Bldg 10,Room 2A33,9000 Rockville Pike, Bethesda, MD 20892 USA. EM davidsob@mail.nih.gov RI Vyberg, Mogens/E-7576-2016 OI Vyberg, Mogens/0000-0002-6392-9517 NR 73 TC 52 Z9 55 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2004 VL 10 IS 21 BP 7335 EP 7346 DI 10.1158/1078-0432.CCR-04-0183 PG 12 WC Oncology SC Oncology GA 869HZ UT WOS:000224975300031 PM 15534110 ER PT J AU Saito, T Wtsadik, A Scheidweiler, KB Fortner, N Takeichi, S Huestis, MA AF Saito, T Wtsadik, A Scheidweiler, KB Fortner, N Takeichi, S Huestis, MA TI Validated gas chromatographic-negative ion chemical ionization mass spectrometric method for Delta(9)-tetrahydrocannabinol in sweat patches SO CLINICAL CHEMISTRY LA English DT Article ID WHOLE-BLOOD; ORAL FLUID; GC-MS; METABOLITES; URINE; CANNABINOIDS; COCAINE; SALIVA; PLASMA; ABUSE AB Background: A sensitive gas chromatography-negative ion chemical ionization mass spectrometry (GC/MS-NICI) method was developed and validated for the measurement of Delta(9)-tetrahydrocannabinol (THC) in human sweat patches. Methods: THC-d(0) and THC-d(3) were added to worn blank sweat patches (PharmChek(TM); PharmChem Incorporated) and extracted with 3 mL of methanol-0.2 mol/L sodium acetate buffer (pH 5.0, 3:1 by volume) on a reciprocating shaker at ambient temperature for 30 min. Extracted solution (2 mL) was diluted with 8 mL of 0.1 mol/L sodium acetate buffer (pH 4.5) and extracted by use of solid-phase extraction columns (CleanScreen(R); United Chemical Technologies). Dried extracts were derivatized with trifluoroacetic acid and analyzed with an Agilent 6890 gas chromatograph interfaced with an Agilent 5973 mass selective detector operated in NICI-selected ion-monitoring mode. Results: The lower limits of detection and quantification for THC in human sweat were 0.2 and 0.4 ng/patch, respectively. The calibration curve was linear from 0.4 to 10 ng/patch (R-2 > 0.995). Overall recovery of THC from blank worn patches to which 0.6, 4.0, and 8.0 ng of THC had been added was 44-46%. Assay imprecision, expressed as CV, was <10% for 0.6, 4.0, and 8.0 ng/patch quality-control samples. Twenty-one potential interfering compounds (50 ng/patch) added to low quality-control samples (0.6 ng/patch) did not influence THC quantification. Conclusions: This GC/MS-NICI assay for THC in human sweat provides adequate sensitivity and performance characteristics for analyzing THC in sweat patches and meets the requirements of the proposed Substance Abuse and Mental Health Administration's guidelines for sweat testing. (C) 2004 American Association for Clinical Chemistry. C1 Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Tokai Univ, Sch Med, Dept Forens Med, Isehara, Kanagawa 25911, Japan. PharmChem Inc, Haltom City, TX USA. RP Huestis, MA (reprint author), Natl Inst Drug Abuse, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov NR 26 TC 32 Z9 32 U1 1 U2 4 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD NOV PY 2004 VL 50 IS 11 BP 2083 EP 2090 DI 10.1373/clinchem.2004.034868 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 865QL UT WOS:000224717500021 PM 15271860 ER PT J AU Levy, C Seeff, LD Lindor, KD AF Levy, Cynthia Seeff, Leonard D. Lindor, Keith D. TI Use of Herbal Supplements for Chronic Liver Disease SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Review ID HEPATITIS-B-VIRUS; SHO-SAIKO-TO; RANDOMIZED CONTROLLED-TRIAL; BLOOD MONONUCLEAR-CELLS; PHYLLANTHUS-AMARUS; DOUBLE-BLIND; HEPATOCELLULAR-CARCINOMA; ALTERNATIVE MEDICINE; SURFACE-ANTIGEN; FLAVONOID ANTIOXIDANT AB Background & Aims: Complementary and alternative medicine (CAM) is becoming popular among patients with liver disease. Although there is a growing body of evidence regarding potential mechanisms of action of these and other herbs, caution must be used to interpret the results of the few clinical trials available. Our goal was to discuss the biologic rationale for the use of specific herbs (silymarin, glycyrrhizin, sho-saiko-to, Phyllanthus amarus, Picrorrhiza kurroa, Compound 861, CH-100, and LIV. 52) in the treatment of chronic liver diseases, as well as the evidence for their efficacy and adverse effects according to clinical trials. Methods: Because of the relative paucity of clinical studies using herbs, every trial published in English was reviewed. Results: Although many trials suggest that these herbs can decrease serum transaminase levels, the effects on hepatic histopathology and long-term survival are either poorly studied or conflicting. LIV. 52 has been withdrawn from the market because of deleterious effects in patients with liver disease. Conclusions: Based on current evidence, we cannot recommend the use of herbal supplements for the routine treatment of any chronic liver disease and further well-designed clinical trials are necessary. C1 [Levy, Cynthia; Lindor, Keith D.] Mayo Clin Rochester, Div Gastroenterol & Hepatol, Rochester, MN 55905 USA. [Seeff, Leonard D.] NIDDK, Div Digest Dis & Nutr, NIH, Bethesda, MD USA. RP Lindor, KD (reprint author), Mayo Clin Rochester, Div Gastroenterol & Hepatol, 200 1st St SW, Rochester, MN 55905 USA. EM lindor.keith@mayo.edu NR 83 TC 38 Z9 41 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD NOV PY 2004 VL 2 IS 11 BP 947 EP 956 DI 10.1053/S1542-3565(04)00455-0 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA V19KW UT WOS:000208072300002 PM 15551246 ER PT J AU Wattanasirichaigoon, D Limwongse, C Jariengprasert, C Yenchitsomanus, PT Tocharoenthanaphol, C Thongnoppakhun, W Thawil, C Charoenpipop, D Pho-iam, T Thongpradit, S Duggal, P AF Wattanasirichaigoon, D Limwongse, C Jariengprasert, C Yenchitsomanus, PT Tocharoenthanaphol, C Thongnoppakhun, W Thawil, C Charoenpipop, D Pho-iam, T Thongpradit, S Duggal, P TI High prevalence of V37I genetic variant in the connexin-26 (GJB2) gene among non-syndromic hearing-impaired and control Thai individuals SO CLINICAL GENETICS LA English DT Article DE connexin; genes; mutation; sensorineural hearing loss ID CHILDHOOD DEAFNESS; SENSORINEURAL DEAFNESS; MOLECULAR-BASIS; GAP-JUNCTIONS; MUTATIONS; CHILDREN; CHANNEL; POPULATION; JAPANESE; DFNB1 AB Hearing loss is highly prevalent with a worldwide incidence of 1-2 per 1000 newborns. Several previous studies have demonstrated that mutations of connexin 26 (Cx26 or GJB2) are responsible for most cases of the recessive non-syndromic sensorineural hearing loss (NSSHL). Certain mutations have been described frequently among various populations, which include 35delG, 167delT, and 235delC. Recently, a missense mutation, V37I, was reported as a pathogenic change in East Asian affected individuals. To identify genetic variants associated with NSSHL in Thai population, we performed mutation analysis of Cx26 in 166 unrelated probands with NSSHL and 205 controls. We identified seven novel genetic variants in Cx26. We also identified a high prevalence of the V37I mutation among both affected probands (11.1%) and control subjects (8.5%), which suggests that the pathologic role of V37I may be modified by other genes. Our data support previous studies that show heterogeneity in the frequencies and types of mutations in Cx26 within populations and among ethnicities and that before clinical significance and causality can be attributed to a genetic variant, functional characterization is necessary. C1 Mahidol Univ, Ramathibodi Hosp, Fac Med, Dept Pediat, Bangkok 10400, Thailand. Siriraj Hosp, Fac Med, Dept Med, Bangkok, Thailand. Siriraj Hosp, Fac Med, Dept Res & Dev, Bangkok, Thailand. Mahidol Univ, Ramathibodi Hosp, Fac Med, Dept Otolaryngol, Bangkok 10400, Thailand. Mahidol Univ, Ramathibodi Hosp, Fac Med, Res Ctr, Bangkok 10400, Thailand. NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD USA. RP Wattanasirichaigoon, D (reprint author), Mahidol Univ, Ramathibodi Hosp, Fac Med, Dept Pediat, 270 Rama 4 Rd, Bangkok 10400, Thailand. EM radwc@mahidol.ac.th NR 43 TC 45 Z9 53 U1 0 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD NOV PY 2004 VL 66 IS 5 BP 452 EP 460 DI 10.1111/j.1399-0004.2004.00325.x PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 861RA UT WOS:000224434700013 PM 15479191 ER PT J AU Beigel, J AF Beigel, J TI Interpreting diagnostic studies in SARS - Defining the reference SO CLINICAL IMMUNOLOGY LA English DT Editorial Material ID ACUTE-RESPIRATORY-SYNDROME; LYME-DISEASE; CORONAVIRUS INFECTION; SERODIAGNOSIS C1 NIH, Dept Crit Care Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Beigel, J (reprint author), NIH, Dept Crit Care Med, Warren G Magnuson Clin Ctr, Bldg 10 7D43,10 Ctr Dr,MSC 1662, Bethesda, MD 20892 USA. RI Beigel, John/A-7111-2009 NR 11 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD NOV PY 2004 VL 113 IS 2 BP 117 EP 118 DI 10.1016/j.clim.2004.07.007 PG 2 WC Immunology SC Immunology GA 860HP UT WOS:000224333400001 PM 15451465 ER PT J AU Zhuang, P Li, YJ Hallett, M AF Zhuang, P Li, YJ Hallett, M TI Neuronal activity in the basal ganglia and thalamus in patients with dystonia SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE basal ganglia; thalamus; neuronal activity; microrecording; stereotactic surgery; dystonia ID DEEP BRAIN-STIMULATION; GLOBUS-PALLIDUS INTERNUS; OFF-PERIOD DYSTONIA; GENERALIZED DYSTONIA; SUBTHALAMIC NUCLEUS; PARKINSONS-DISEASE; MOVEMENT-DISORDERS; CERVICAL DYSTONIA; NEURAL MECHANISMS; PRIMATE MODEL AB Objective: To explore the role of abnormal neuronal activity in the basal ganglia and thalamus in the generation of dystonia. Methods: Microelectrode recording was performed in the globus pallidus internus (GPi), ventral thalamic nuclear group ventral oral posterior/ventral intermediate, Vop/Vim) and subthalamic nucleus (STN) in patients with primary dystonia (n = 11) or secondary dystonia (n,= 9) during surgery. Electromyogram (EMG) was simultaneously recorded in selected muscle groups. Single unit analysis and cross-correlations were carried out. Results: Three hundred and sixty-seven neurons were obtained from 29 trajectories (GPi: 13; Vop/Vim: 12; STN: 4), 87% exhibited altered neuronal activity including grouped discharges in GPi (n = 79) and STN (n = 37), long-lasting neuronal activity (n = 70) and rapid neuronal discharge (n = 86) in Vop/Vim. There were neurons in Vop, GPi and STN firing at the same frequency as EMG during dystonia (mean: 0.39 Hz, range 0.12-0.84 Hz). Significant correlations between neuronal activity and EMG at the frequency of dystonia were obtained (GPi: r(2) = 0.7 (n = 31), Vop/Vim: r(2) = 0.64 (n = 18) and STN: r(2) = 0.86 (n = 17)). Conclusions: Consistent with previous findings of abnormalities observed in Vop/VIM and GPi in relation to dystonia, the present data further show that the altered activity in GPi, specifically in dorsal subregions of GPi, Vop/Vim and STN is likely to be directly involved in the production of dystonic movement. Dystonia-related neuronal activity observed in motor thalamus and basal ganglia nuclei of GPi and STN indicates a critical role of their interactions affecting both indirect and direct pathways in the development of either generalized or focal dystonia. Significance: These data support a central role of the basal ganglia in producing dystonic movements. (C) 2004 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 Capital Univ Med Sci, Xuanwu Hosp, Beijing Inst Funct Neurosurg, Beijing 100053, Peoples R China. NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Li, YJ (reprint author), Capital Univ Med Sci, Xuanwu Hosp, Beijing Inst Funct Neurosurg, Beijing 100053, Peoples R China. NR 55 TC 72 Z9 79 U1 0 U2 9 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD NOV PY 2004 VL 115 IS 11 BP 2542 EP 2557 DI 10.1016/j.clinph.2004.06.006 PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 865RK UT WOS:000224720200015 PM 15465444 ER PT J AU Schroeder, C Tank, J Goldstein, DS Stoeter, M Haertter, S Luft, FC Jordan, J AF Schroeder, C Tank, J Goldstein, DS Stoeter, M Haertter, S Luft, FC Jordan, J TI Influence of St John's wort on catecholamine turnover and cardiovascular regulation in humans SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID DOPAMINE-BETA-HYDROXYLASE; HYPERICUM PERFORATUM L; O-METHYLTRANSFERASE; MONOAMINE-OXIDASE; ORTHOSTATIC INTOLERANCE; BIOCHEMICAL ACTIVITIES; INHIBITION; NOREPINEPHRINE; PLASMA; EXTRACTS AB Background: St John's wort (Hypericum perforatum) is a popular over-the-counter antidepressant. Its antidepressive effect has been attributed in part to inhibition of monoamine transporters and monoamine oxidase, on the basis of in vitro studies. Methods. In a double-blind, randomized, placebo-controlled, crossover study, 16 healthy subjects (11 men and 5 women; mean age, 31 +/- 5 years) ingested either St John's wort (300 mg three times daily) or placebo for 7 days. Imipramine treatment (50 mg three times daily) in 7 subjects served as a positive control. After treatment, physiologic and biochemical tests included cardiovascular reflex testing, graded head-up tilt testing, and plasma catecholamine determinations. Results. St John's wort had no effect on blood pressure, heart rate, heart rate variability, or blood pressure variability, regardless of the test condition. St John's wort had no effect on plasma concentrations of norepinephrine and its main metabolite, dihydroxyphenylglycol, whereas plasma dihydroxyphenylacetic acid (DOPAC; the main metabolite of dopamine) concentrations increased in every subject (1661 +/- 924 pg/mL versus 1110 +/- 322 pg/mL with placebo, P = .04). In contrast, imipramine increased resting blood pressure (124 +/- 10 mm. Hg/71 +/- 5 mm Hg versus 110 +/- 8 mm Hg/61 +/- 6 mm Hg with placebo, P = .005 for systolic values and P = .003 for diastolic values) and heart rate (74 +/- 7 beats/min versus 62 +/- 6 beats/min with placebo, P = .005) and elicited a marked orthostatic tachycardia (increase in heart rate of 43 +/- 17 beats/min versus 26 +/- 8 beats/min with placebo, P = .006). Conclusions. Our findings challenge the concept that St John's wort elicits a major change in norepinephrine uptake or monoamine oxidase activity in vivo. The consistent increase in plasma DOPAC concentrations might suggest a novel mode of action or an inhibitory effect on dopamine beta-hydroxylase that should be followed up. We propose that a combination of physiologic and biochemical profiling may help better define the mode of action and potential side effects of herbal remedies. C1 Med Univ Charite, Franz Volhard Ctr Clin Res, D-13125 Berlin, Germany. Helios Klinikum, Berlin, Germany. NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD USA. Univ Mainz, Neurochem Lab, D-6500 Mainz, Germany. RP Jordan, J (reprint author), Med Univ Charite, Franz Volhard Ctr Clin Res, Wiltbergstr 50,Haus 129,Campus Buch, D-13125 Berlin, Germany. EM jordan@fvk.charite-buch.de OI Luft, Friedrich/0000-0002-8635-1199 NR 38 TC 11 Z9 11 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD NOV PY 2004 VL 76 IS 5 BP 480 EP 489 DI 10.1016/j.clpt.2004.08.005 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 870EK UT WOS:000225036600009 PM 15536462 ER PT J AU Deans, KJ Minneci, PC Eichacker, PQ Natanson, C AF Deans, KJ Minneci, PC Eichacker, PQ Natanson, C TI The efficacy of drotrecogin alfa depends on severity of illness SO CRITICAL CARE MEDICINE LA English DT Editorial Material ID ACTIVATED PROTEIN-C; SEVERE SEPSIS C1 NIH, Dept Crit Care Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Deans, KJ (reprint author), NIH, Dept Crit Care Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NR 10 TC 7 Z9 9 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD NOV PY 2004 VL 32 IS 11 BP 2347 EP 2347 DI 10.1097/01.CCM.0000146002.38054.70 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 872MN UT WOS:000225211400028 PM 15640655 ER PT J AU Nesterova, M Cho-Chung, YS AF Nesterova, M Cho-Chung, YS TI Killing the messenger: Antisense DNA and siRNA SO CURRENT DRUG TARGETS LA English DT Review DE gene therapy; gene silencing; oligonucleotides; antisense; RNA interference ID DOUBLE-STRANDED-RNA; PROTEIN-KINASE-A; SMALL INTERFERING RNA; RI-ALPHA SUBUNIT; MIXED-BACKBONE OLIGONUCLEOTIDES; NUCLEIC-ACID THERAPEUTICS; CULTURED-MAMMALIAN-CELLS; FIBROBLAST-GROWTH-FACTOR; GENE-EXPRESSION; PHASE-I AB Among the technologies available for gene knockdown RNase Xi-dependent antisense oligonucleotides and RNAi are very popular. Both offer specificity and efficient knockdown of the genes; both are useful tools to study gene functions. Antisense and RNAi methods share many practical problems such as site selection, toxicity at high concentration, and the difficulty of transfection in certain cell types. We will focus in this review on the most important issues in the development of both methods and their possible use in gene-silencing therapy. C1 NCI, Cellular Biochem Sect, BRL, CCR,NIH,Therapeut Oligo Int Grp, Bethesda, MD 20892 USA. RP Cho-Chung, YS (reprint author), NCI, Cellular Biochem Sect, BRL, CCR,NIH,Therapeut Oligo Int Grp, Bldg 10,Rm 5B05,9000 Rockville Pike, Bethesda, MD 20892 USA. EM yc12b@nih.gov NR 124 TC 22 Z9 29 U1 2 U2 5 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-4501 J9 CURR DRUG TARGETS JI Curr. Drug Targets PD NOV PY 2004 VL 5 IS 8 BP 683 EP 689 DI 10.2174/1389450043345137 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 874YE UT WOS:000225385800003 PM 15578949 ER PT J AU Dundr, M Misteli, T AF Dundr, M Misteli, T TI Transcriptional complexity from dynamic interaction networks in vivo SO CURRENT GENOMICS LA English DT Article DE chromatin; transcription; dynamics; diffusion; gene expression; networks; stochastic ID RNA-POLYMERASE-II; EUKARYOTIC GENE-EXPRESSION; ESTROGEN-RECEPTOR-ALPHA; LIVING CELLS; GLUCOCORTICOID-RECEPTOR; HIGH-MOBILITY; NUCLEAR-ORGANIZATION; MOLECULAR CHAPERONES; PROTEIN DYNAMICS; MAMMALIAN-CELLS AB The last decades have lead to the identification and characterization or most key steps in gene expression including chromatin remodeling, transcription, RNA processing, export and translation. Extensive biochemical, genetic and molecular approaches have not only revealed the key players involved in these processes, but have yielded detailed insights into the molecular behavior of many. Despite the wealth of molecular and structural information of distinct processes of gene expression and of single molecular components, fundamental aspects of the system behavior of the gene expression machinery have remained elusive. It is just now becoming clear that the single steps in the gene expression process are tightly interlinked and virtually nothing is known about how the various components of genome regulation and expression machineries are integrated into presumably complex networks of interactions and pathways. Even more elusive has been the elucidation of how gene expression processes occur in their natural setting of the cell nucleus in intact living cells. Recent advances in qualitative and quantitative imaging methods are beginning to provide tools to study the complexity of the gene expression process in living cells. We briefly review here some emerging in vivo imaging technologies and summarize the recent results and the conceptual impact these methods are making on understanding transcriptional complexity in vivo. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM mistelit@mail.nih.gov NR 56 TC 1 Z9 1 U1 0 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2029 J9 CURR GENOMICS JI Curr. Genomics PD NOV PY 2004 VL 5 IS 7 BP 559 EP 566 DI 10.2174/1389202043348823 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 874ZN UT WOS:000225389300004 ER PT J AU Mancardi, D Ridnour, LA Thomas, DD Katori, T Tocchetti, CG Espey, MG Miranda, KM Paolocci, N Wink, DA AF Mancardi, D Ridnour, LA Thomas, DD Katori, T Tocchetti, CG Espey, MG Miranda, KM Paolocci, N Wink, DA TI The chemical dynamics of NO and reactive nitrogen oxides: A practical guide SO CURRENT MOLECULAR MEDICINE LA English DT Review ID LOW-DENSITY-LIPOPROTEIN; NEURONAL NITRIC-OXIDE; HYDROXY-L-ARGININE; ACTIVATED MURINE MACROPHAGES; PROTEIN-TYROSINE NITRATION; OXIDIZED LIPID DERIVATIVES; SOLUBLE GUANYLATE-CYCLASE; WOODCHUCK HEPATITIS-VIRUS; CENTER-DOT-NO; SUPEROXIDE-DISMUTASE AB Nitric oxide has emerged as one of the most important and diverse players in physiology. This small diatomic radical stunned researchers because of its existence and unique biological properties in human physiology. Over the last two decades it was found that NO often has fickle behavior in pathophysiological mechanisms. Where benefiting the host in one case yet inducing and augmenting injury in another. This has lead to confusion in is NO good or bad? Much of the answers to this dichotomy lies in the chemistry of NO and its related nitrogen oxide species. To help understand the complex chemistry with perspective to biology, a discussion on the chemical biology of NO is useful. The chemical biology defines the relevant chemical reaction of NO and nitrogen monoxide in the context of the biological conditions. We discuss in this article the chemistry of nitrogen oxide with different types of biological motifs. Reaction of NO with metal complexes and radicals require low concentration, where formation of reactive nitrogen oxide species require considerably higher amounts and generally are isolated to specific microenvironments in vivo. Though many reactive nitrogen oxide species are formed from chemical reactions with NO, there are several which appear to not require NO to be present, HNO and NO2. These two species have unique physiological effects and represent additional complexity to this biological picture. From this discussion, a picture can be formed concerning the possible chemical dynamics, which can be plausible in different biological mechanisms. C1 Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA. NCI, Tumor Biol Sect, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Div Cardiol, Dept Med, Baltimore, MD 21287 USA. Univ Arizona, Dept Chem, Tucson, AZ 85721 USA. RP Wink, DA (reprint author), Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA. EM wink@mail.nih.gov RI Miranda, Katrina/B-7823-2009; OI tocchetti, carlo gabriele/0000-0001-5983-688X; MANCARDI, Daniele/0000-0003-3809-6047 NR 182 TC 28 Z9 28 U1 1 U2 9 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5240 J9 CURR MOL MED JI Curr. Mol. Med. PD NOV PY 2004 VL 4 IS 7 BP 723 EP 740 DI 10.2174/1566524043359854 PG 18 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 861YH UT WOS:000224454000001 PM 15579020 ER PT J AU Christopher-Stine, L Plotz, PH AF Christopher-Stine, L Plotz, PH TI Myositis: an update on pathogenesis SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE inflammatory myopathy; polymyositis; dermatomyositis; inclusion body myositis; pathogenesis ID INCLUSION-BODY MYOSITIS; IDIOPATHIC INFLAMMATORY MYOPATHIES; INTERSTITIAL LUNG-DISEASE; SENSITIVE AMINE OXIDASE; NECROSIS-FACTOR-ALPHA; WEST-NILE-VIRUS; CLASS-I; AMYOPATHIC DERMATOMYOSITIS; NECROTIZING MYOPATHY; MUSCULAR-DYSTROPHY AB Purpose of review The etiology and much about the pathogenesis of the inflammatory myopathies remain a mystery. In this review, we investigate recent research efforts to understand the pathogenesis of the diverse entities of polymyositis (PM), dermatomyositis (DM), and inclusion body myositis (IBM), diseases that result from interactions between environmental risk factors and genetic susceptibility. Recent findings Over the past year, there has been considerable progress toward better understanding of IBM, with relatively few developments toward understanding PM and DM. Although these diseases may share some common clinical phenotypic and serologic components, they differ on a molecular and cellular level. Summary The need for definitive, safer therapies in these diseases makes vital the search for defining detailed pathogenesis of inflammation and muscle fiber damage at the molecular level. C1 NIAMSD, Arthrit & Rheumat Branch, Clin Ctr 9N244, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Div Rheumatol, Baltimore, MD USA. RP Plotz, PH (reprint author), NIAMSD, Arthrit & Rheumat Branch, Clin Ctr 9N244, NIH, Bethesda, MD 20892 USA. EM plotzp@mail.nih.gov NR 50 TC 22 Z9 26 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI CURR. OPIN. RHEUMATOL. PD NOV PY 2004 VL 16 IS 6 BP 700 EP 706 DI 10.1097/01.bor.0000141925.21941.d8 PG 7 WC Rheumatology SC Rheumatology GA 865QQ UT WOS:000224718000007 PM 15577607 ER PT J AU Elshal, M Khan, S Solomon, M McCoy, JP AF Elshal, M Khan, S Solomon, M McCoy, JP TI Characterization of CD146 expression on peripheral blood lymphocytes. SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Meeting Abstract CT 19th Annual Meeting of the Clinical-Cytometry-Society CY OCT 17-19, 2004 CL Long Beach, CA SP Clin Cytometry Soc C1 NHLBI, Flow Cytometry Core, NIH, Bethesda, MD USA. NIH, Dept Crit Care Med, CC, Bethesda, MD USA. RI Elshal, Mohamed/H-7953-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-4763 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD NOV PY 2004 VL 62B IS 1 BP 62 EP 63 PG 2 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 869KW UT WOS:000224983000020 ER PT J AU Khan, S Smith, M Reda, D Suffredini, A McCoy, JP AF Khan, S Smith, M Reda, D Suffredini, A McCoy, JP TI Multiplex bead array assays for detection of soluble cytokines: Comparisons of kits from multiple manufacturers. SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Meeting Abstract CT 19th Annual Meeting of the Clinical-Cytometry-Society CY OCT 17-19, 2004 CL Long Beach, CA SP Clin Cytometry Soc C1 NHLBI, Flow Cytometry Core Facil, NIH, Bethesda, MD USA. NIH, Crit Care Med Dept, Warren G Magnuson Clin Ctr, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-4763 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD NOV PY 2004 VL 62B IS 1 BP 65 EP 65 PG 1 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 869KW UT WOS:000224983000026 ER PT J AU Stetler-Stevenson, M Jasper, G Morris, J Waldmann, T Wilson, W Schrager, J Janik, J AF Stetler-Stevenson, M Jasper, G Morris, J Waldmann, T Wilson, W Schrager, J Janik, J TI Quantitation of CD2 expression by normal and neoplastic T cells in peripheral blood and lymph node. SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Meeting Abstract CT 19th Annual Meeting of the Clinical-Cytometry-Society CY OCT 17-19, 2004 CL Long Beach, CA SP Clin Cytometry Soc C1 NCI, Pathol Lab, CCR, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, CCR, NIH, Bethesda, MD 20892 USA. NCI, Lymphoma Sect, ETIB, CCR,NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-4763 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD NOV PY 2004 VL 62B IS 1 BP 70 EP 71 PG 2 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 869KW UT WOS:000224983000040 ER PT J AU Broihier, HT Kuzin, A Zhu, Y Odenwald, W Skeath, JB AF Broihier, HT Kuzin, A Zhu, Y Odenwald, W Skeath, JB TI Drosophila homeodornain protein Nkx6 coordinates motoneuron subtype identity and axonogenesis SO DEVELOPMENT LA English DT Article DE Drosophila melanogaster; neuronal fate specification; motoneurons; interneurons; axon outgrowth; Nkx6; hb9 (exex); lim3; islet; eve; vnd ID CELL-TYPE SPECIFICATION; CENTRAL-NERVOUS-SYSTEM; VENTRAL NEURAL-TUBE; MOTOR-NEURON; GENE-EXPRESSION; HOMEOBOX GENES; FASCICLIN-III; SPINAL-CORD; MELANOGASTER; NEUROBLASTS AB The regulatory networks acting in. individual neurons to control their stereotyped differentiation, connectivity, and function are not well understood. Here, we demonstrate that homeodomain protein Nkx6 is a key member of the genetic network of transcription factors that specifies neuronal fates in Drosophila. Nkx6 collaborates with the homeodomain protein Hb9 to specify ventrally projecting motoneuron fate and to repress dorsally projecting motoneuron fate. While Nkr6 acts in parallel with hb9 to regulate motoneuron fate, we find that Nkr6 plays a distinct role to promote axonogenesis, as axon growth of Nkx6- positive motoneurons is severely compromised in Nkx6 mutant embryos. Furthermore, Nkx6 is necessary for the expression of the neural adhesion molecule Fasciclin III in Nkx6-positive motoneurons. Thus, this work demonstrates that Nkx6 acts in a specific neuronal population to link neuronal subtype identity to neuronal morphology and connectivity. C1 Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. NINDS, Neural Cell Fate Determinants Sect, NIH, Bethesda, MD 20892 USA. RP Broihier, HT (reprint author), Case Western Reserve Univ, Sch Med, Dept Neurosci, 10900 Euclid Ave, Cleveland, OH 44106 USA. EM heather.broihier@case.edu FU NINDS NIH HHS [R01-NS-36570] NR 45 TC 41 Z9 41 U1 0 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD NOV PY 2004 VL 131 IS 21 BP 5233 EP 5242 DI 10.1242/dev.01394 PG 10 WC Developmental Biology SC Developmental Biology GA 875LQ UT WOS:000225422200003 PM 15456721 ER PT J AU Wine-Lee, L Ahn, KJ Richardson, RD Mishina, Y Lyons, KM Crenshaw, EB AF Wine-Lee, L Ahn, KJ Richardson, RD Mishina, Y Lyons, KM Crenshaw, EB TI Signaling through BMP type 1 receptors is required for development of interneuron cell types in the dorsal spinal cord SO DEVELOPMENT LA English DT Article DE bone morphogenetic protein receptor type 1; cremediated conditional Bmpr1a knockout; Bmpr1b mutant; dorsal interneuron development; neural tube patterning; mouse ID BONE MORPHOGENETIC PROTEINS; APICAL ECTODERMAL RIDGE; NERVOUS-SYSTEM; VERTEBRATE DEVELOPMENT; ROOF PLATE; COMMISSURAL INTERNEURONS; NEURONAL SPECIFICATION; LACZ EXPRESSION; NEURAL-TUBE; DIFFERENTIATION AB During spinal cord development, distinct classes of interneurons arise at stereotypical locations along the dorsoventral axis. In this paper, we demonstrate that signaling through bone morphogenetic protein (BMP) type 1 receptors is required for the formation of two populations of commissural neurons, DI1 and DI2, that arise within the dorsal neural tube. We have generated a double knockout of both BMP type 1 receptors, Bmpr1a and Bmpr1b, in the neural tube. These double knockout mice demonstrate a complete loss of D1 progenitor cells, as evidenced by loss of Math1 expression, and the subsequent failure to form differentiated DI1 interneurons. Furthermore, the DI2 interneuron population is profoundly reduced. The loss of these populations of cells results in a dorsal shift of the dorsal cell populations, DI3 and DI4. Other dorsal interneuron populations, DI5 and DI6, and ventral neurons appear unaffected by the loss of BMP signaling. The Bmpr double knockout animals demonstrate a reduction in the expression of Wnt and Id family members, suggesting that BMP signaling regulates expression of these factors in spinal cord development. These results provide genetic evidence that BMP signaling is crucial for the development of dorsal neuronal cell types. C1 Childrens Hosp Philadelphia, Abramsom Res Ctr 712, Mammalian Neurogenet Grp, Ctr Childhood Commun, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Neurosci Grad Grp, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Otorhinolaryngol, Philadelphia, PA 19104 USA. NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Orthopaed Surg, Dept Mol Cellular & Dev Biol & Biol Chem, Los Angeles, CA 90095 USA. RP Crenshaw, EB (reprint author), Childrens Hosp Philadelphia, Abramsom Res Ctr 712, Mammalian Neurogenet Grp, Ctr Childhood Commun, 34th & Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM crenshaw@email.chop.edu RI Lyons, Karen/P-1843-2014 OI Lyons, Karen/0000-0001-9420-5813 FU NIAMS NIH HHS [R01 AR044528] NR 51 TC 92 Z9 99 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD NOV PY 2004 VL 131 IS 21 BP 5393 EP 5403 DI 10.1242/dev.01379 PG 11 WC Developmental Biology SC Developmental Biology GA 875LQ UT WOS:000225422200017 PM 15469980 ER PT J AU Crump, JG Maves, L Lawson, ND Weinstein, BM Kimmel, CB AF Crump, JG Maves, L Lawson, ND Weinstein, BM Kimmel, CB TI An essential role for Fgfs in endodermal pouch formation influences later craniofacial skeletal patterning SO DEVELOPMENT LA English DT Article DE pouch; pharyngeal endoderm; cartilage; neural crest; segmentation; Fgf8; Fgf3; acerebellar; GFP; zebrafish ID DROSOPHILA TRACHEAL SYSTEM; NEURAL CREST CELLS; BRANCHING MORPHOGENESIS; EMBRYONIC-DEVELOPMENT; SEGMENTAL IDENTITY; PHARYNGEAL REGION; FOREGUT ENDODERM; ZEBRAFISH EMBRYO; VERTEBRATE HEAD; JAW JOINT AB Fibroblast growth factor (Fgf) proteins are important regulators of pharyngeal arch development. Analyses of Fgf8 function in chick and mouse and Fgf3 function in zebrafish have demonstrated a role for Fgfs in the differentiation and survival of postmigratory neural crest cells (NCC) that give rise to the pharyngeal skeleton. Here we describe, in zebrafish, an earlier, essential function for Fgf8 and Fgf3 in regulating the segmentation of the pharyngeal endoderm into pouches. Using time-lapse microscopy, we show that pharyngeal pouches form by the directed lateral migration of discrete clusters of endodermal cells. In animals doubly reduced for Fgf8 and Fgf3, the migration of pharyngeal endodermal cells is disorganized and pouches fail to form. Transplantation and pharmacological experiments show that Fgf8 and Fgf3 are required in the neural keel and cranial mesoderm during early somite stages to promote first pouch formation. In addition, we show that animals doubly reduced for Fgf8 and Fgf3 have severe reductions in hyoid cartilages and the more posterior branchial cartilages. By examining early pouch and later cartilage phenotypes in individual animals hypomorphic for Fgf function, we find that alterations in pouch structure correlate with later cartilage defects. We present a model in which Fgf signaling in the mesoderm and segmented hindbrain organizes the segmentation of the pharyngeal endoderm into pouches. Moreover, we argue that the Fgf-dependent morphogenesis of the pharyngeal endoderm into pouches is critical for the later patterning of pharyngeal cartilages. C1 Univ Oregon, Inst Neurosci, Eugene, OR 97403 USA. Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA. NICHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Crump, JG (reprint author), Univ Oregon, Inst Neurosci, 1254, Eugene, OR 97403 USA. EM gage@uoneuro.uoregon.edu FU NICHD NIH HHS [HD22486]; NIDCR NIH HHS [DE13834] NR 53 TC 113 Z9 117 U1 3 U2 16 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD NOV PY 2004 VL 131 IS 22 BP 5703 EP 5716 DI 10.1242/dev.01444 PG 14 WC Developmental Biology SC Developmental Biology GA 878MQ UT WOS:000225651300018 PM 15509770 ER PT J AU Lorent, K Yeo, SY Oda, T Chandrasekharappa, S Chitnis, A Matthews, RR Pack, M AF Lorent, K Yeo, SY Oda, T Chandrasekharappa, S Chitnis, A Matthews, RR Pack, M TI Inhibition of Jagged-mediated Notch signaling disrupts zebrafish biliary development and generates multi-organ defects compatible with an Alagille syndrome phenocopy SO DEVELOPMENT LA English DT Article DE zebrafish; Notch; jagged; Alagille syndrome; bile duct.; biliary development ID CELL DIFFERENTIATION; EMBRYONIC LETHALITY; LIVER DEVELOPMENT; IN-VITRO; GENE; MOUSE; MUTATIONS; EXPRESSION; HEART; MORPHOGENESIS AB The Alagille Syndrome (AGS) is a heritable disorder affecting the liver and other organs. Causative dominant mutations in human Jagged 1 have been identified in most AGS patients. Related organ defects occur in mice that carry jagged 1 and notch 2 mutations. Multiple jagged and notch genes are expressed in the developing zebrafish liver. Compound jagged and notch gene knockdowns alter zebrafish biliary, kidney, pancreatic, cardiac and craniofacial development in a manner compatible with an AGS phenocopy. These data confirm an evolutionarily conserved role for Notch signaling in vertebrate liver development, and support the zebrafish as a model system for diseases of the human biliary system. C1 Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. NICHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. Childrens Hosp Philadelphia, Div Gastroenterol & Nutr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. RP Pack, M (reprint author), Univ Penn, Sch Med, Dept Med, 421 Curie Blvd, Philadelphia, PA 19104 USA. EM mpack@mail.med.upenn.edu FU NIDDK NIH HHS [DK60369] NR 54 TC 108 Z9 114 U1 0 U2 7 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 EI 1477-9129 J9 DEVELOPMENT JI Development PD NOV PY 2004 VL 131 IS 22 BP 5753 EP 5766 DI 10.1242/dev.01411 PG 14 WC Developmental Biology SC Developmental Biology GA 878MQ UT WOS:000225651300022 PM 15509774 ER PT J AU Sedy, J Szeder, V Walro, JM Ren, ZG Nanka, O Tessarollo, L Sieber-Blum, M Grim, M Kucera, J AF Sedy, J Szeder, V Walro, JM Ren, ZG Nanka, O Tessarollo, L Sieber-Blum, M Grim, M Kucera, J TI Pacinian corpuscle development involves multiple Trk signaling pathways SO DEVELOPMENTAL DYNAMICS LA English DT Article DE mechanoreceptors; Pacinian corpuscle; neurotrophins; Trk receptors; sensory neurons; mutant mice ID CUTANEOUS SENSORY CORPUSCLES; MICE LACKING NEUROTROPHIN-3; PERIPHERAL NERVOUS-SYSTEM; IMMUNOHISTOCHEMICAL LOCALIZATION; DIFFERENTIAL DEPENDENCY; NEURONAL DEVELOPMENT; SYMPATHETIC NEURONS; TARGETED MUTATION; RECEPTOR GENE; SPINAL-CORD AB The development of crural Pacinian corpuscles was explored in neonatal mutant mice lacking nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT3) or neurotrophin-4 (NT4), or their cognate Trk receptors. Deficits of the corpuscles and their afferents were greatest in NT3, less in BDNF, and least in NT4 null mice. Deletion of NGF or p75(NTR) genes had little or no impact. No Pacinian corpuscles were present in NT3;BDNF and NT3;NT4 double or NT3,BDNF;NT4 triple null mice. Deficits were larger in NT3 than TrkC mutants and were comparable to deficits observed in TrkB or TrkA mutants. Afferents of all corpuscles coexpressed TrkA and TrkB receptors, and some afferents coexpressed all three Trk receptors. Our results suggest that multiple neurotrophins, in particular NT3, regulate the density of crural Pacinian corpuscles, most likely by regulating the survival of sensory neurons. In addition, NT3/TrkB and/or NT3/TrkA signaling plays a greater role than NT3/TrkC signaling in afferents to developing Pacinian corpuscles. (C) 2004 Wiley-Liss, Inc. C1 Charles Univ, Inst Anat, Fac Med 1, Prague 12800, Czech Republic. Med Coll Wisconsin, Dept Cell Biol Neurobiol & Anat, Milwaukee, WI 53226 USA. NE Ohio Coll Med, Dept Anat, Rootstown, OH USA. NCI, Neural Dev Grp, Frederick, MD 21701 USA. Vet Adm Med Ctr, Boston, MA USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. RP Grim, M (reprint author), Charles Univ, Inst Anat, Fac Med 1, Nemocnice 3, Prague 12800, Czech Republic. EM milos.grim@lf1.cuni.cz RI Nanka, Ondrej/R-6334-2016 OI Nanka, Ondrej/0000-0002-6300-395X FU NINDS NIH HHS [NS 38500] NR 56 TC 24 Z9 26 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD NOV PY 2004 VL 231 IS 3 BP 551 EP 563 DI 10.1002/dvdy.20156 PG 13 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 864QH UT WOS:000224647500010 PM 15376326 ER PT J AU Hong, Z Yakar, S Gavrilova, O Sun, H Zhang, Y Kim, HS Setser, J Jou, W LeRoith, D AF Hong, Z Yakar, S Gavrilova, O Sun, H Zhang, Y Kim, HS Setser, J Jou, W LeRoith, D TI Phloridzin improves hyperglycemia but not hepatic insulin resistance in a transgenic mouse model of type 2 diabetes SO DIABETES LA English DT Article ID MUSCLE-SPECIFIC INACTIVATION; A-ZIP/F-1 FATLESS MICE; BETA-CELL DYSFUNCTION; SKELETAL-MUSCLE; IN-VIVO; GLUCOSE-HOMEOSTASIS; PHLORIZIN TREATMENT; ADIPOSE-TISSUE; PLASMA LEPTIN; IGF-I AB The chronic hyperglycemia that occurs in type 2 diabetes may cause deterioration of beta-cell function and insulin resistance in peripheral tissues. Mice that express a dominant-negative IGF-1 receptor, specifically in skeletal muscle (MKR mice), exhibit severe insulin resistance, hyperinsulinemia, dyslipidemia, and hyperglycemia. To determine the role of hyperglycemia in the worsening of the diabetes state in these animals, MKR mice were treated with phloridzin (PHZ), which inhibits intestinal glucose uptake and renal glucose reabsorption. Blood glucose levels were decreased and urine glucose levels were increased in response to PHZ treatment in MKR mice. PHZ treatment also increased food intake in MKR mice; however, the fat mass was decreased and lean body mass did not change. Serum insulin, fatty acid, and triglyceride levels were not affected by PHZ treatment in MKR mice. Hyperinsulinemic-euglycemic clamp analysis demonstrated that glucose uptake in white adipose tissue was significantly increased in response to PHZ treatment. Despite the reduction in blood glucose following PHZ treatment, there was no improvement in insulin-stimulated whole-body glucose uptake in MKR mice and neither was there suppression of endogenous glucose production by insulin. These results suggest that glucotoxicity plays little or no role in the worsening of insulin resistance that occurs in the MKR mouse model of type 2 diabetes. C1 NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Mouse Metab Core Facil, NIH, Bethesda, MD 20892 USA. RP LeRoith, D (reprint author), NIDDK, Diabet Branch, NIH, Room 8D12,Bldg 10, Bethesda, MD 20892 USA. EM derek@helix.nih.gov NR 40 TC 0 Z9 0 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD NOV PY 2004 VL 53 IS 11 BP 2901 EP 2909 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 867EV UT WOS:000224826000020 ER PT J AU Carnethon, MR Loria, CM Hill, JO Sidney, S Savage, PJ Liu, K AF Carnethon, MR Loria, CM Hill, JO Sidney, S Savage, PJ Liu, K TI Risk factors for the metabolic syndrome - The Coronary Artery Risk Development in Young Adults (CARDIA) study, 1985-2001 SO DIABETES CARE LA English DT Article ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; INSULIN-RESISTANCE ATHEROSCLEROSIS; NON-HISPANIC WHITES; TREATMENT PANEL-III; HEART-DISEASE; ALCOHOL-CONSUMPTION; CARDIORESPIRATORY FITNESS; AFRICAN-AMERICANS; LOW-CARBOHYDRATE AB OBJECTIVE- The aim of this study was to describe the association of the metabolic syndrome with demographic characteristics and to identify modifiable risk factors For development of the metabolic syndrome. RESEARCH DESIGN AND METHODS- Men and women (55%) aged 18-30 years from the Coronary Artery Risk Development in Young Adults (CARDIA) study without the metabolic syndrome at baseline (n = 4,192, 49% black) were followed-up from 1985 to 2001. Incident metabolic syndrome, defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria, was ascertained 7, 10, and 15 years after baseline. Risk factors were measured via clinical examination and standardized questionnaires. RESULTS- The age-adjusted rate of metabolic syndrome was 10 per 1,000 person-years (n = 575). Metabolic syndrome risk increased with age and was higher among black participants and those with less than a high school education. Higher baseline BMI, no alcohol intake (Versus one to three drinks per day), higher intake of dietary carbohydrates, and lower intake of crude fiber were each associated with an increased risk for the metabolic syndrome (relative risk [RR] ranging from 1.3 to 1.9), and physical activity was protective (RR 0.84 [95% CI 0.76-0.92]). In models adjusting simultaneously for all factors, black participants and women were less likely to develop metabolic syndrome. Risk for metabolic syndrome increased 23% (20-27%) per 4.5 kg (10 lb) of weight gained, whereas regular physical activity over time versus low activity was protective (RR 0.49 [0.34-0.70]). CONCLUSIONS- BMI and weight gain are important risk factors for the metabolic syndrome. Regular physical activity may counter this risk. C1 Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. Univ Colorado, Hlth Sci Ctr, Ctr Human Nutr, Denver, CO 80202 USA. Kaiser Permanente Med Care Program, Div Res, Oakland, CA 94611 USA. RP Carnethon, MR (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, 680 N Lake Shore Dr,Suite 1102, Chicago, IL 60611 USA. EM carnethon@northwestem.edu FU NHLBI NIH HHS [N01-HC-95095, 1 K01 HL73249-01, N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050] NR 47 TC 153 Z9 165 U1 1 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2004 VL 27 IS 11 BP 2707 EP 2715 DI 10.2337/diacare.27.11.2707 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 867ET UT WOS:000224825800022 PM 15505009 ER PT J AU Ahmed, FE James, SI Lysle, DT Dobbs, LJ Johnke, RM Flake, G Stockton, P Sinar, DR Naziri, W Evans, MJ Kovacs, CJ Allison, RR AF Ahmed, FE James, SI Lysle, DT Dobbs, LJ Johnke, RM Flake, G Stockton, P Sinar, DR Naziri, W Evans, MJ Kovacs, CJ Allison, RR TI Improved methods for extracting RNA from exfoliated human colonocytes in stool and RT-PCR analysis SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE colon cancer; DNA; diagnosis; genes; markers; RNA; screening ID LASER CAPTURE MICRODISSECTION; REAL-TIME PCR; GENE-EXPRESSION; MOLECULAR MARKERS; COLORECTAL-CANCER; COLON-CANCER; DNA; QUANTIFICATION; AMPLIFICATION; ASSAYS AB In order to diagnose colon cancer at an earlier, more localized stage, there is a need to develop diagnostic markers (genes) which can detect early patterns of gene expression in exfoliated colonocytes shed in the stool during routine screening for this disease. An RNA-based detection is more pertinent than either a DNA-based or a protein-based method as a screening procedure, but it has not been widely used as a cancer screen because of the difficulty of handling and stabilizing the RNA molecule. We describe a method that permits extraction of intact nondegraded total RNA from human colonocytes in stool and from normal and malignant colon tissues (which were employed for comparison with stool). Because it utilizes commercially available kits, this method is simpler than other published methods and does not require isolation of messenger (m)RNA, thereby reducing the chances of contaminating the preparations with degrading nucleases, and even a small amount of isolated total RNA can be adequately reverse transcribed, making high-quality copy (c) DNA. This is followed by PCR (either qualitative end point or semiquantitative real-time) using colon cancer-specific gene primers. By routinely and systematically being able to perform quantitative gene expression measurements on noninvasive samples, the goal of this pilot work is to lay the groundwork for conducting a large clinical study to identify groups of selected genes whose expression is consistently altered at an early stage in the neoplastic process. Such work will permit noninvasive monitoring of at-risk patients through the analysis of their stool samples. Correct diagnosis will allow for surgical and/or other interventions before the tumor is well established and, thus, should decrease mortality from this preventable disease. C1 E Carolina Univ, Brody Sch Med, Leo W Jenkins Canc Ctr, Dept Radiat Oncol, Greenville, NC 27834 USA. Univ N Carolina, Dept Psychol, Chapel Hill, NC USA. E Carolina Univ, Brody Sch Med, Dept Pathol & Lab Med, Greenville, NC 27834 USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. E Carolina Univ, Brody Sch Med, Dept Internal Med, Greenville, NC 27834 USA. Carolina Phys PA, Greenville, NC USA. RP Ahmed, FE (reprint author), E Carolina Univ, Brody Sch Med, Leo W Jenkins Canc Ctr, Dept Radiat Oncol, LSB 014, Greenville, NC 27834 USA. EM ahmedf@mail.ecu.edu NR 31 TC 13 Z9 15 U1 0 U2 3 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD NOV-DEC PY 2004 VL 49 IS 11-12 BP 1889 EP 1898 DI 10.1007/s10620-004-9589-9 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 882WL UT WOS:000225971000029 PM 15628722 ER PT J AU Resnik, DB Shamoo, AE AF Resnik, DB Shamoo, AE TI Bioterrorism and the responsible conduct of biomedical research SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE bioterrorism; openness; research; ethics ID PUBLIC-HEALTH; VIRUS; EXPRESSION; COMMUNITY; SECURITY; THREATS AB This article discusses the ethical responsibilities of biomedical researchers to prevent bioterrorism, including duties related to research, publication, editorial review, public education, expert opinion, advocacy, and reporting suspicious activity. Since actions taken to avert bioterrorism may also undermine important scientific norms, such as openness, freedom, and collegiality, and individual rights, such as privacy, biomedical scientists may encounter ethical dilemmas and problems when they consider taking steps against terrorism. This article proposes some policies and recommendations that attempt to strike a fair and reasonable balance between protecting scientific norms and individual rights and promoting national and international security. This article articulates policies and recommendations that will help ensure that the norms that govern biomedical research and individual rights are not casualties in the struggle against terrorism. (c) 2005 Wiley-Liss, Inc. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD USA. RP Resnik, DB (reprint author), NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM resnikd@mail.niehs.nih.gov; ashamoo@umaryland.edu NR 41 TC 4 Z9 4 U1 1 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD NOV PY 2004 VL 63 IS 3 BP 121 EP 133 DI 10.1002/ddr.10406 PG 13 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 912ZI UT WOS:000228118800005 ER PT J AU Karpova, TS Chen, TY Sprague, BL McNally, JG AF Karpova, TS Chen, TY Sprague, BL McNally, JG TI Dynamic interactions of a transcription factor with DNA are accelerated by a chromatin remodeller SO EMBO REPORTS LA English DT Article DE FRAP; transcription; chromatin remodelling; nuclear mobility; DNA binding ID METALLOTHIONEIN GENE-TRANSCRIPTION; GLUCOCORTICOID-RECEPTOR; LIVING CELLS; IN-VIVO; PROTEIN; COMPLEX; YEAST; BINDING; MOBILITY; RSC AB Most components in the nucleus are in a state of dynamic equilibrium maintained by the rapid mobility of nuclear proteins within and between compartments. Mobility is believed to reflect transient binding, but the identity of the binding sites and the function of the transient interactions are a matter of debate. Furthermore, we know little about how these processes may be regulated. Here, we investigate the nature and regulation of transcription factor binding and mobility in the nucleus of yeast cells. Using the Ace1p transcriptional activator, we show that nonspecific DNA binding interactions seem to have a role in retarding Ace1p nuclear mobility. Surprisingly, we find that this binding is a regulated process using a chromatin remodeller to speed up Ace1p interactions at nonspecific DNA sites. Our results suggest that transcription factor mobility represents a diffusion-driven, rapid sampling of nonspecific DNA sites, and that chromatin remodellers accelerate this genomic search process. C1 NCI, CCR Core Fluorescence Imaging Facil, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP McNally, JG (reprint author), NCI, CCR Core Fluorescence Imaging Facil, Lab Receptor Biol & Gene Express, NIH, 41 Lib Dr, Bethesda, MD 20892 USA. EM mcnallyj@exchange.nih.gov RI Sprague, Brian/A-8923-2009 NR 29 TC 34 Z9 35 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD NOV PY 2004 VL 5 IS 11 BP 1064 EP 1070 DI 10.1038/sj.embor.7400281 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 867BD UT WOS:000224816200010 PM 15514679 ER PT J AU Legembre, P Barnhart, BC Zheng, LX Vijayan, S Straus, SE Puck, J Dale, JK Lenardo, M Peter, ME AF Legembre, P Barnhart, BC Zheng, LX Vijayan, S Straus, SE Puck, J Dale, JK Lenardo, M Peter, ME TI Induction of apoptosis and activation of NF-kappa B by CD95 require different signalling thresholds SO EMBO REPORTS LA English DT Article DE autoimmune lymphoproliferative syndrome; Fas; lpr(cg); MAPK; NF-kappa B ID AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; FAS GENE-MUTATIONS; INHIBITION; COMPLEX; CELLS AB Mutations in the death domain of the death receptor CD95 (APO-1/Fas) cause lymphoproliferation and autoimmune disease in both lpr(cg) mice and in patients with autoimmune lymphoproliferative syndrome (ALPS) type Ia. By testing lymphocytes from ALPS type Ia patients, comparing heterozygous with homozygous lprcg mice and coexpressing wild-type and mutant CD95 receptors, we demonstrate that induction of apoptosis requires two wild-type alleles of CD95. By contrast, nuclear factor-kappaB (NF-kappaB) can be fully activated in cells expressing both a mutant and a wild-type CD95 allele, suggesting different thresholds to activate the two signalling pathways. This was confirmed by testing lymphocytes from heterozygous lpr mice, which showed reduced sensitivity to CD95-mediated apoptosis but normal activation of NF-kappaB when compared with wild-type mice. Mutations in CD95 may eliminate the tumour-suppressive function of CD95, at the same time allowing induction of survival or proliferative pathways, which could contribute to the increased risk for lymphoma seen in ALPS type Ia patients. C1 Univ Chicago, Ben May Inst Canc Res, Chicago, IL 60637 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Peter, ME (reprint author), Univ Chicago, Ben May Inst Canc Res, 924 E 57th St, Chicago, IL 60637 USA. EM mpeter@uchicago.edu OI legembre, patrick/0000-0001-6649-8049 NR 18 TC 59 Z9 60 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD NOV PY 2004 VL 5 IS 11 BP 1084 EP 1089 DI 10.1038/sj.embor.7400280 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 867BD UT WOS:000224816200013 PM 15514680 ER PT J AU McDonald, M Anker, M Deal, C Mawle, A O'Connor, S Slaughter, L AF McDonald, M Anker, M Deal, C Mawle, A O'Connor, S Slaughter, L TI International Conference on Women and Infectious Diseases SO EMERGING INFECTIOUS DISEASES LA English DT Editorial Material C1 Ctr Dis Control & Prevent, Atlanta, GA USA. WHO, CH-1211 Geneva, Switzerland. NIH, Bethesda, MD 20892 USA. RP McDonald, M (reprint author), CDC, Natl Ctr Infect Dis, 1600 Clifton Rd NE,MS D62, Atlanta, GA 30333 USA. EM zzm0@cdc.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD NOV PY 2004 VL 10 IS 11 BP 1963 EP 1964 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 869PY UT WOS:000224997700013 ER PT J AU Gardner, P Pabbatireddy, S AF Gardner, P Pabbatireddy, S TI Vaccines for women age 50 and older SO EMERGING INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT International Conference on Women and Infectious Diseases CY FEB 27-28, 2004 CL Atlanta, GA ID INVASIVE PNEUMOCOCCAL DISEASE; HEALTH-CARE WORKERS; LONG-TERM-CARE; INFLUENZA VACCINATION; POLYSACCHARIDE VACCINE; MORTALITY; ADULTS; RECOMMENDATIONS; PNEUMONIA; REDUCTION AB For older populations, most of whom are women, preventing illnesses and deaths through the use of vaccines is a leading public health challenge. Our understanding about how age and sex affect the immune system is limited, and basic and translational research aimed at improving vaccines and immune responses of older persons is needed. In the meantime, fully implementing current vaccine recommendations, particularly those for influenza and pneumococcal vaccines, can save thousands of lives and prevent illnesses in persons >50 years of age. C1 Fogarty Int Ctr, NIH, Bethesda, MD 20892 USA. SUNY Stony Brook, New York, NY USA. RP Gardner, P (reprint author), Fogarty Int Ctr, NIH, Bldg 31,Rm B2C02, Bethesda, MD 20892 USA. EM gardnerp@nih.gov NR 36 TC 9 Z9 9 U1 0 U2 0 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD NOV PY 2004 VL 10 IS 11 BP 1990 EP 1995 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 869PY UT WOS:000224997700019 PM 15550213 ER PT J AU McKenzie, FE AF McKenzie, FE TI Smallpox models as policy tools SO EMERGING INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 4th International Conference on Emerging Infectious Diseases CY FEB 29-MAR 03, 2004 CL Atlanta, GA SP Ctr Dis Control & Prevent, Amer Soc Microbiol, Assoc Public Hlth Labs, Council State & Territorial Epidemiologists, WHO AB Mathematical models can help prepare for and respond to bioterrorism attacks, provided that their strengths and weaknesses are clearly understood. A series of initiatives within the Department of Health and Human Services brought modelers together with biologists and epidemiologists who specialize in smallpox and experts in bioterrorism response and health policy and has led to the parallel development of models with different technical approaches but standardized scenarios, parameter ranges, and outcome measures. Cross-disciplinary interactions throughout the process supported the development of models focused on systematically comparing alternate intervention strategies, determining the most important issues in decision-making, and identifying gaps in current knowledge. C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP McKenzie, FE (reprint author), NIH, Fogarty Int Ctr, Room 306,Bldg 16, Bethesda, MD 20892 USA. EM mckenzel@mail.nih.gov FU Intramural NIH HHS [Z99 TW999999] NR 5 TC 7 Z9 7 U1 0 U2 0 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD NOV PY 2004 VL 10 IS 11 BP 2044 EP 2047 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 869PY UT WOS:000224997700037 PM 15550219 ER PT J AU Carroll, D Gardner, P Kay, BA Osterholm, M Ryan, ET AF Carroll, D Gardner, P Kay, BA Osterholm, M Ryan, ET TI Transformation of the developing world: Socioeconomic matrix SO EMERGING INFECTIOUS DISEASES LA English DT Meeting Abstract CT 4th International Conference on Emerging Infectious Diseases CY FEB 29-MAR 03, 2004 CL Atlanta, GA SP Ctr Dis Control & Prevent, Amer Soc Microbiol, Assoc Public Hlth Labs, Council State & Territorial Epidemiologists, WHO C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. US Agcy Int Dev, Washington, DC 20523 USA. NIH, Bethesda, MD 20892 USA. WHO, Lyon, France. Univ Minnesota, Minneapolis, MN USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. EM etryan@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD NOV PY 2004 VL 10 IS 11 BP 2049 EP 2049 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 869PY UT WOS:000224997700039 PM 16010742 ER PT J AU Fueger, PT Hess, HS Bracy, DP Pencek, RR Posey, KA Charron, MJ Wasserman, DH AF Fueger, PT Hess, HS Bracy, DP Pencek, RR Posey, KA Charron, MJ Wasserman, DH TI Regulation of insulin-stimulated muscle glucose uptake in the conscious mouse: Role of glucose transport is dependent on glucose phosphorylation capacity SO ENDOCRINOLOGY LA English DT Article ID RATE-LIMITING STEPS; SKELETAL-MUSCLE; TRANSGENIC MICE; HEXOKINASE-II; GLYCOGEN-CONTENT; GLUT4 GENE; EXERCISE; OVEREXPRESSION; RATS; RESISTANCE AB Previous work suggests that normal GLUT4 content is sufficient for increases in muscle glucose uptake (MGU) during hyperinsulinemia, because glucose phosphorylation is the more formidable barrier to insulin-stimulated MGU. It was hypothesized that a partial ablation of GLUT4 would not impair insulin-stimulated MGU when glucose phosphorylation capacity is normal but would do so when glucose phosphorylation capacity is increased. Thus, chow-fed C57BL/6J mice with a GLUT4 partial knockout (GLUT4(+/-)), hexokinase II overexpression (HKTg), or both (HKTg+GLUT4(+/-)) and wild-type littermates were studied. Carotid artery and jugular vein catheters were implanted for sampling and infusions at 4 months of age. After a 5-d recovery, 5-h fasted mice (n = 8-11/group) underwent a 120-min saline infusion or insulin clamp (4 mU/kg.min insulin with glucose maintained at 165 mg/dl) and received a 2-deoxy[H-3] glucose bolus to provide an index of MGU (R-g) for the soleus, gastrocnemius, and superficial vastus lateralis. Basal R-g from all muscles studied from saline-infused mice were not changed by any of the genetic modifications. HKTg mice had augmented insulin-stimulated R-g in all muscles studied compared with remaining genotypes. Insulin-stimulated Rg was not impaired in any of the muscles studied from GLUT4(+/-) mice. However, the enhanced insulin-stimulated Rg created by HK overexpression was ablated in HKTg + GLUT4(+/-) mice. Thus, a 50% reduction of normal GLUT4 content in the presence of normal HK activity does not impair insulin-stimulated MGU. However, when the glucose phosphorylation barrier is lowered by HK overexpression, GLUT4 availability becomes a limitation to insulin-stimulated MGU. C1 Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Mouse Metab Phenotyping Ctr, Nashville, TN 37232 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10461 USA. RP Fueger, PT (reprint author), Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, 4321 Med Pk Dr,Suite 200, Durham, NC 27704 USA. EM patrick.fueger@duke.edu FU NIDDK NIH HHS [R01 DK-47425, R01 DK-54902, U24 DK-59637] NR 29 TC 22 Z9 22 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 2004 VL 145 IS 11 BP 4912 EP 4916 DI 10.1210/en.2004-0465 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 862SB UT WOS:000224510100017 PM 15284204 ER PT J AU Yamanaka, T Toyoshiba, H Sone, H Parham, FM Portier, CJ AF Yamanaka, T Toyoshiba, H Sone, H Parham, FM Portier, CJ TI The TAO-Gen algorithm for identifying gene interaction networks with application to SOS repair in E-coli SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE gene networks; microarray; Bayesian model selection; SOS repair; toxicogenomics ID ARYL-HYDROCARBON RECEPTOR; REGULATORY NETWORKS; EXPRESSION DATA; TOXICOGENOMICS; TOXICOLOGY AB One major unresolved issue in the analysis of gene expression data is the identification and quantification of gene regulatory networks. Several methods have been proposed for identifying gene regulatory networks, but these methods predominantly focus on the use of multiple pairwise comparisons to identify the network structure. In this article, we describe a method for analyzing gene expression data to determine a regulatory structure consistent with an observed set of expression profiles. Unlike other methods this method goes beyond pairwise evaluations by using likelihood-based statistical methods to obtain the network that is most consistent with the complete data set. The proposed algorithm performs accurately for moderate-sized networks with most errors being minor additions of linkages. However, the analysis also indicates that sample sizes may need to be increased to uniquely identify even moderate-sized networks. The method is used to evaluate interactions between genes in the SOS signaling pathway in Escherichia coli using gene expression data where each gene in the network is over-expressed using plasmids inserts. C1 NIEHS, Lab Computat Biol & Risk Anal, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Portier, CJ (reprint author), NIEHS, Lab Computat Biol & Risk Anal, NIH, Dept Hlth & Human Serv, POB 12233,MD A3-06,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM portier@niehs.nih.gov RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 23 TC 14 Z9 16 U1 0 U2 5 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2004 VL 112 IS 16 BP 1614 EP 1621 DI 10.1289/txg.7105 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 878WT UT WOS:000225678800013 PM 15598612 ER PT J AU Vezina, CM Walker, NJ Olson, JR AF Vezina, CM Walker, NJ Olson, JR TI Subchronic exposure to TCDD, PeCDF, PCB126, and PCB153: Effect on hepatic gene expression SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE AhR; HAH; liver; microarray; PCB; TCDD ID ARYL-HYDROCARBON RECEPTOR; POLYCHLORINATED BIPHENYL CONGENERS; CYCLASE-ASSOCIATED PROTEIN; SPRAGUE-DAWLEY RATS; DIBENZO-P-DIOXINS; LIVER DEVELOPMENT; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TCDD; ADENYLYL-CYCLASE; CANCER-MORTALITY; OXIDATIVE STRESS AB We employed DNA microarray to identify unique hepatic gene expression patterns associated with subchronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other halogenated aromatic hydrocarbons (HAHs). Female Harlan Sprague-Dawley rats were exposed for 13 weeks to toxicologically equivalent doses of four different HAHs based on the toxic equivalency factor of each chemical: TCDD (100 ng/kg/day), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF; 200 ng/kg/day), 3,3',4,4',5-pentachlorobiphenyl (PCB126; 1,000 ng/kg/day), or 2,2',4,4',5,5'hexachlorobiphenyl (PCB153; 1,000 mug/kg/day). Global gene expression profiles for each exposure, which account for 8,799 gene probe sets contained on Affymetrix RGU34A GeneChips, were compared by principal components analysis. The aryl hydrocarbon receptor (AhR) ligands TCDD, PeCDF, and PCB126 produced very similar global gene expression profiles that were unique from the nonAhR ligand PCB153, underscoring the extensive impact of AhR activation and/or the resulting hepatic injury on global gene expression in female rat liver. Many genes were co-expressed during the 13-week TCDD, PeCDF, or PCB126 exposures, including classical AhR-regulated genes and some genes not previously characterized as being AhR regulated, such as carcinoembryonic-cell adhesion molecule 4 (C-CAM4) and adenylate cyclase-associated protein 2 (CAP2). Real-time reverse-transcriptase polymerase chain reaction confirmed the increased expression of these genes in TCDD-, PeCDF-, and PCB126-exposed rats as well as the up- or down-regulation of several other novel dioxin-responsive genes. In summary, DNA microarray successfully identified dioxin-responsive genes expressed after exposure to AhR ligands (TCDD, PeCDF, PCB126) but not after exposure to the non-AhR ligand PCB153. Together, these findings may help to elucidate some of the fundamental features of dioxin toxicity and may further clarify the biologic role of the AhR signaling pathway. C1 Univ Buffalo, Dept Pharmacol & Toxicol, Buffalo, NY 14214 USA. Univ Wisconsin, Sch Pharm, Madison, WI 53706 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Olson, JR (reprint author), Univ Buffalo, Dept Pharmacol & Toxicol, 102 Farber Hall,3435 Main St, Buffalo, NY 14214 USA. EM jolson@buffalo.edu RI Walker, Nigel/D-6583-2012; OI Walker, Nigel/0000-0002-9111-6855; Vezina, Chad/0000-0001-7058-5399 FU NIEHS NIH HHS [ES 09440] NR 62 TC 100 Z9 106 U1 1 U2 4 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2004 VL 112 IS 16 BP 1636 EP 1644 DI 10.1289/txg.7253 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 878WT UT WOS:000225678800016 PM 15598615 ER PT J AU Ghosh, K Tiwari, RC AF Ghosh, K Tiwari, RC TI Bayesian density estimation using ranked set samples SO ENVIRONMETRICS LA English DT Article DE order statistics; Dirichlet process prior; Gibbs sampler; mixture distribution; Kullback-Leibler distance; L-2 distance ID MODELS AB In this article, we present a Bayesian approach for estimating the underlying density using a ranked set sample. We assume that the observations are generated front a Dirichlet process mixture model. Density (as well as moments) of future values generated from the process are estimated through Markov chain Monte Carlo simulations. This approach extends earlier work on density estimation based on a Dirichlet process prior from a simple random sample to a ranked set sample. We carry Out a simulation study using a normal kernel to compare the effect of using a simple random sample versus a ranked set sample on the predictive density. We show that the Bayesian density estimate resulting from a ranked set sample has a smaller average mean squared error than that from a simple random sample. Additionally, the average Kullback-Leibler distance of the density estimate based on the ranked set sample is shown to be closer to zero than that based on the corresponding simple random sample. We illustrate our method by applying it to shrub data available in the literature. Copyright (C) 2004 John Wiley Sons. Ltd. C1 NCI, Stat Res & Applicat Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. George Washington Univ, Dept Stat, Washington, DC 20052 USA. RP Tiwari, RC (reprint author), NCI, Stat Res & Applicat Branch, Div Canc Control & Populat Sci, 6116 Execut Blvd,MSC 8317, Bethesda, MD 20892 USA. EM tiwarir@nih.gov NR 30 TC 1 Z9 1 U1 2 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1180-4009 J9 ENVIRONMETRICS JI Environmetrics PD NOV PY 2004 VL 15 IS 7 BP 711 EP 728 DI 10.1002/env.667 PG 18 WC Environmental Sciences; Mathematics, Interdisciplinary Applications; Statistics & Probability SC Environmental Sciences & Ecology; Mathematics GA 879IW UT WOS:000225711200006 ER PT J AU Sausville, EA Holbeck, SL AF Sausville, EA Holbeck, SL TI Transcription profiling of gene expression in drug discovery and development: the NO experience SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE microarray; technologies; transcript profiling; drug candidates; gene expression; targets ID TUMOR-CELL-LINES; ANTITUMOR AGENTS; CANCER; PATTERNS; INHIBITORS; IDENTIFICATION; SENSITIVITY; SURVIVAL; SCREEN; GROWTH AB Transcript profiling, using microarray or other analogous technologies, to query on a large-scale the expression of genes in tumours or their derivative cell lines has numerous potential uses in oncology drug discovery and development. Characterisation of genes expressed in turnours may allow turnours to be separated into subsets defining subtypes that have a distinctive pathway utilisation. The molecular entities comprising the pathways which distinguish one disease subset from another then become potential candidate drug targets. Alternatively, gene expression patterns may be correlated with the degree of antiproliferative effect of candidate drug leads. This can reveal aspects of the drug's action that could serve to provide a further basis for benchmarking the generation of analogues or provide important information about pathways potentially modulated by the drug in achieving cytotoxicity. New information is emerging that the expression of drug transport-related molecules is a major variable that can be usefully explored using gene expression data, and the features promoting successful drug handling by the tumour cell may be an additional variable which can be illuminated by gene expression studies. Published by Elsevier Ltd. C1 NCI, Dev Therapeut Program, Informat Technol Branch, Bethesda, MD 20892 USA. RP Holbeck, SL (reprint author), NCI, Dev Therapeut Program, Informat Technol Branch, 6130 Eecut Blvd,Room 8014, Bethesda, MD 20892 USA. EM holbecks@mail.nih.gov NR 26 TC 20 Z9 22 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2004 VL 40 IS 17 BP 2544 EP 2549 DI 10.1016/j.ejca.2004.08.006 PG 6 WC Oncology SC Oncology GA 881JB UT WOS:000225858900003 PM 15541957 ER PT J AU Rapkiewicz, AV Espina, V Petricoin, EF Liotta, LA AF Rapkiewicz, AV Espina, V Petricoin, EF Liotta, LA TI Biomarkers of ovarian tumours SO EUROPEAN JOURNAL OF CANCER LA English DT Review DE biomarker; cancer; microarray; ovarian; proteomics ID GENE-EXPRESSION PROFILES; ACUTE LYMPHOBLASTIC-LEUKEMIA; MULTIPLE SERUM MARKERS; BENIGN PELVIC MASSES; B-CELL LYMPHOMA; BREAST-CANCER; PROSTATE-CANCER; CDNA MICROARRAY; LYSOPHOSPHATIDIC ACID; PREDICT SURVIVAL AB Ovarian cancer is one of the most aggressive gynaecological malignancies and most often the high mortality is a direct result of delays in diagnosis. The development of an ovarian cancer-specific biomarker for the early detection of disease has the capacity to improve the dismal survival rate. Currently, there are multiple investigations that are utilising both genomic and proteomic technologies to identify genes, gene products and proteins that may potentially identify diagnostic ovarian cancer biomarkers. Here, we review the studies that are involved in biomarker development for the detection of ovarian cancer. (C) 2004 Elsevier Ltd. All rights reserved. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Rapkiewicz, AV (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2N206,10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. EM rapkiewa@mail.nih.gov OI Espina, Virginia/0000-0001-5080-5972 NR 105 TC 51 Z9 51 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2004 VL 40 IS 17 BP 2604 EP 2612 DI 10.1016/j.ejca.2004.05.021 PG 9 WC Oncology SC Oncology GA 881JB UT WOS:000225858900007 PM 15541961 ER PT J AU Wulfkuhle, J Espina, V Liotta, L Petricoin, E AF Wulfkuhle, J Espina, V Liotta, L Petricoin, E TI Genomic and proteomic technologies for individualisation and improvement of cancer treatment SO EUROPEAN JOURNAL OF CANCER LA English DT Review DE molecular profiling; individual targeted therapy; genomics; proteomics; microarrays; protein microarrays; cancer ID GENE-EXPRESSION PROFILES; HUMAN PROSTATE-CANCER; PROTEIN IDENTIFICATION TECHNOLOGY; LASER CAPTURE MICRODISSECTION; KINASE INHIBITOR ZD1839; BREAST-CANCER; MASS-SPECTROMETRY; TARGETED THERAPY; OVARIAN-CANCER; MOLECULAR CLASSIFICATION AB The development of microarray-based technologies for characterising tumours, both at the genomic and proteomic levels, has had a significant impact on the field of oncology. Gene expression profiling of various human tumour tissues has led to the identification of expression patterns related to disease outcome and drug resistance, as well as to the discovery of new therapeutic targets and insights into disease pathogenesis. Protein microarray technologies, such as reverse-phase protein arrays, provide the unique opportunity to profile tissues and assess the activity of signalling pathways within isolated cell populations. This technology can be used to identify patients likely to benefit from specific treatment modalities and also to monitor therapeutic response in samples obtained during and after treatment. Routine application of genomic and proteomic microarray technologies in clinical practice will require significant efforts to standardise the techniques, controls and reference standards, and analytical tools used. Extensive, independent validation using large, statistically-powered datasets will also be necessary. Inclusion of concomitant genomic and proteomic-based molecular profiling techniques into clinical trial protocols will bring us closer to the reality of patient-tailored therapy. Published by Elsevier Ltd. C1 NCI, FDA, Clin Proteom Program, Pathol Lab,Ctr Canc Res, Bethesda, MD 20892 USA. NCI, FDA, Clin Proteomics Program, OffCell & Gene Therapy,Ctr Biol Evaluat & Res,Foo, Bethesda, MD 20892 USA. RP Wulfkuhle, J (reprint author), NCI, FDA, Clin Proteom Program, Pathol Lab,Ctr Canc Res, Bldg 29A-2 B20,HFM 710,8800 Rockville Pike, Bethesda, MD 20892 USA. EM wulfkuhle@cber.fda.gov OI Espina, Virginia/0000-0001-5080-5972 NR 113 TC 62 Z9 65 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2004 VL 40 IS 17 BP 2623 EP 2632 DI 10.1016/j.ejca.2004.05.020 PG 10 WC Oncology SC Oncology GA 881JB UT WOS:000225858900009 PM 15541963 ER PT J AU Laufer, EM Hartman, TJ Baer, DJ Gunter, EW Dorgan, JF Campbell, WS Clevidence, BA Brown, ED Albanes, D Judd, JT Taylor, PR AF Laufer, EM Hartman, TJ Baer, DJ Gunter, EW Dorgan, JF Campbell, WS Clevidence, BA Brown, ED Albanes, D Judd, JT Taylor, PR TI Effects of moderate alcohol consumption on folate and vitamin B-12 status in postmenopausal women SO EUROPEAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE alcohol; folate; vitamin B-12; homocysteine; methylmalonic acid; postmenopausal women ID BREAST-CANCER RISK; METHYLMALONIC ACID; NUTRIENT INTAKE; BEVERAGE CONSUMPTION; NUTRITIONAL-STATUS; TOTAL HOMOCYSTEINE; COLORECTAL-CANCER; PLASMA; DEFICIENCY; SERUM AB Background: Although alcohol intake has been positively associated with breast cancer risk in epidemiologic studies, a causal relationship has not been established, and the mechanisms mediating this association are speculative. Alcohol may act through altered status of folate and vitamin B-12, two vitamins required for DNA methylation and nucleotide synthesis, and thus cell integrity. Although the effects of heavy alcohol intake on folate and vitamin B-12 status have been well-documented, few studies have addressed the effects of moderate alcohol intake in a controlled setting. Objective: The objective of this study was to determine the effects of moderate alcohol intake on folate and vitamin B-12 status in healthy, well-nourished, postmenopausal women. Design: The study design was a randomized, diet-controlled crossover intervention. Postmenopausal women (n=53) received three 8-week alcohol treatments in random order: 0, 15, and 30 g/day. Treatment periods were preceded by 2-5-week washout periods. Blood collected at baseline and week 8 of each treatment period was analyzed for serum folate, vitamin B-12, homocysteine (HCY), and methylmalonic acid (MMA) concentrations. Results: After adjusting for body mass index (BMI), a significant 5% decrease was observed in mean serum vitamin B-12 concentrations from 0 to 30 g of alcohol/day (461.45+/-30.26 vs 440.25+/-30.24 pg/ml; P=0.03). Mean serum HCY concentrations tended to increase by 3% from 0 to 30 g of alcohol/day (9.44+/-0.37 vs 9.73+/-0.37 mumol/l; P=0.05). Alcohol intake had no significant effects on serum folate or MMA concentrations. Conclusions: Among healthy, well-nourished, postmenopausal women, moderate alcohol intake may diminish vitamin B-12 status. Sponsorship: NCI, NIH and ARS, USDA. C1 Penn State Univ, University Pk, PA 16802 USA. USDA, Beltsville, MD 20705 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NCI, Bethesda, MD 20892 USA. RP Hartman, TJ (reprint author), 5 Henderson Bldg, University Pk, PA 16802 USA. EM tjh9@psu.edu RI Albanes, Demetrius/B-9749-2015 NR 61 TC 23 Z9 24 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0954-3007 J9 EUR J CLIN NUTR JI Eur. J. Clin. Nutr. PD NOV PY 2004 VL 58 IS 11 BP 1518 EP 1524 DI 10.1038/sj.ejcn.1602002 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 865HV UT WOS:000224694200010 PM 15138463 ER PT J AU Charmandari, E Brook, CGD Hindmarsh, PC AF Charmandari, E Brook, CGD Hindmarsh, PC TI Classic congenital adrenal hyperplasia and puberty SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID BETA-HYDROXYSTEROID DEHYDROGENASE; HUMAN ADRENOCORTICAL-CELLS; GROWTH-HORMONE REPLACEMENT; POLYCYSTIC-OVARY-SYNDROME; I IGF-I; 11-BETA-HYDROXYSTEROID DEHYDROGENASE; 21-HYDROXYLASE DEFICIENCY; CORTISOL METABOLISM; INSULIN SENSITIVITY; SEXUAL-DIMORPHISM AB Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders resulting from deficiency of one of the five enzymes required for synthesis of cortisol in the adrenal cortex. The most common form of the disease is classic 21-hydroxylase deficiency, which is characterized by decreased synthesis of glucocorticoids and often mineralocorticoids, adrenal hyperandrogenism and impaired development and function of the adrenal medulla. The clinical management of classic 21-hydroxylase deficiency is often suboptimal, and patients are at risk of developing in tandem iatrogenic hypercortisolism and/or hyperandogenism. Limitations of current medical therapy include the inability to control hyperandrogenism without employing supraphysiologic doses of glucocorticoid, hyperresponsiveness of the hypertrophied adrenal glands to adrenocorticotropic hormone (ACTH) and difficulty in suppressing ACTH secretion from the anterior pituitary. Puberty imposes increased difficulty in attaining adrenocortical suppression despite optimal substitution therapy and adherence to medical treatment. Alterations in the endocrine milieu at puberty may influence cortisol pharmacokinetics and, consequently, the handling of hydrocortisone used as replacement therapy. Recent studies have demonstrated a significant increase in cortisol clearance at puberty and a shorter half-life of free cortisol in pubertal females compared with males. Furthermore, children with classic CAH have elevated fasting serum insulin concentrations and insulin resistance. The latter may further enhance adrenal and/or ovarian androgen secretion, decrease the therapeutic efficacy of glucocorticoids and contribute to later development of the metabolic syndrome and its complications. C1 NICHHD, Pediat & Reproduct Endocrinol Branch, NIH, Bethesda, MD 20892 USA. UCL, London Ctr Paediat Endocrinol, London, England. RP Charmandari, E (reprint author), NICHHD, Pediat & Reproduct Endocrinol Branch, NIH, Bethesda, MD 20892 USA. EM charmane@mail.nih.gov RI Hindmarsh, Peter/C-4964-2008; Charmandari, Evangelia/B-6701-2011 NR 55 TC 20 Z9 21 U1 0 U2 0 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0804-4643 EI 1479-683X J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD NOV PY 2004 VL 151 SU 3 BP U77 EP U82 DI 10.1530/eje.0.151U077 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 879QI UT WOS:000225731900012 PM 15554890 ER PT J AU Viboud, C Pakdaman, K Boelle, PY Wilson, ML Myers, MF Valleron, AJ Pakdaman, K AF Viboud, C Pakdaman, K Boelle, PY Wilson, ML Myers, MF Valleron, AJ Pakdaman, K TI Association of influenza epidemics with global climate variability SO EUROPEAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE climate; disease outbreaks/statistics & numerical data; ecology; environment; influenza/epidemiology; influenza/morbidity; influenza/mortality ID NINO-SOUTHERN OSCILLATION; EL-NINO; INFECTIOUS-DISEASE; FEVER EPIDEMICS; BORNE DISEASE; MALARIA; FRANCE; IMPACT; MORTALITY; DYNAMICS AB The reasons for the seasonality and annual changes in the impact of influenza epidemics remain poorly understood. We investigated the covariations between a major component of climate, namely the El Nino Southern Oscillation (ENSO), and indicators of the impact of influenza, as measured by morbidity, excess mortality and viral subtypes collected in France during the period 1971-2002. We show that both the circulating subtype and the magnitude of ENSO are associated with the impact of influenza epidemics. Recognition of this association could lead to better understanding of the mechanisms of emergence of influenza epidemics. C1 Univ St Antoine, Inst Natl Sante & Rech Med, Unit 444, Ctr Hosp, F-75571 Paris 12, France. WHO Collaborating Ctr Elect Dis Surveillance, F-75571 Paris, France. Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. NASA, Goddard Space Flight Ctr, Human Hlth Initiat, Greenbelt, MD 20770 USA. RP Viboud, C (reprint author), NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, 16 Ctr Dr, Bethesda, MD 20892 USA. EM viboudc@mail.nih.gov NR 40 TC 49 Z9 55 U1 0 U2 6 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0393-2990 J9 EUR J EPIDEMIOL JI Eur. J. Epidemiol. PD NOV PY 2004 VL 19 IS 11 BP 1055 EP 1059 DI 10.1007/s10654-004-2450-9 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 881XH UT WOS:000225902300010 PM 15648600 ER PT J AU Marroni, F Aretini, P D'Andrea, E Caligo, MA Cortesi, L Viel, A Ricevuto, E Montagna, M Cipollini, G Federico, M Santarosa, M Marchetti, P Bailey-Wilson, JE Bevilacqua, G Parmigiani, G Presciuttini, S AF Marroni, F Aretini, P D'Andrea, E Caligo, MA Cortesi, L Viel, A Ricevuto, E Montagna, M Cipollini, G Federico, M Santarosa, M Marchetti, P Bailey-Wilson, JE Bevilacqua, G Parmigiani, G Presciuttini, S TI Penetrances of breast and ovarian cancer in a large series of families tested for BRCA1/2 mutations SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE BRCA1; BRCA2; penetrance; genetic testing; predictive models; BRCAPRO ID POPULATION-BASED SERIES; GERMLINE MUTATIONS; SUSCEPTIBILITY GENES; CUMULATIVE RISK; PREVALENCE; HISTORY; HETEROGENEITY; BRCAPRO AB Accurate estimates of breast and ovarian cancer penetrance in BRCA1/2 mutation carriers are crucial in genetic counseling. Estimation is difficult because of the low frequency of mutated alleles and the often-uncertain mechanisms of family ascertainment. We estimated the penetrances of breast and ovarian cancers in carriers of BRCA1/2 mutations by maximizing the retrospective likelihood of the genetic model, given the observed test results, in 568 Italian families screened for germline mutations. The software BRCAPRO was used as a probability calculation tool in a Markov Chain Monte Carlo approach. Breast cancer penetrances were 27% (95% CI 20-34%) at age 50 years and 39% (27-52%) at age 70 in BRCA1 carriers, and 26% (0.18-0.34%) at age 50 and 44% (29-58%) at age 70 in BRCA2 carriers, and ovarian cancer penetrances were 14% (7-22%) at age 50 and 43% (21-66%) at age 70 in BRCA1 carriers and 3% (0-7%) at age 50 and 15% (4-26%) at age 70 in BRCA2 carriers. The new model gave a better fit than the current default in BRCAPRO, the likelihood being 70 log units greater; in addition, the observed numbers of mutations in families stratified by gene and by cancer profile were not significantly different from those expected. Our new penetrance functions are appropriate for predicting breast cancer risk, and for determining the probability of carrying BRCA1/2 mutations, in people who are presently referred to genetic counseling in Italy. Our approach could lead to country-customized versions of the BRCAPRO software by providing appropriate population-specific estimates. C1 Univ Pisa, Ctr Stat Genet, Dept Expt Pathol, I-56127 Pisa, Italy. Univ Pisa, Dept Oncol Transplants & New Technol, Sect Pathol, Pisa, Italy. Univ Padua, Dept Oncol & Surg Sci, Sect Oncol, Sect Viral & Mol Oncol, Padua, Italy. Univ Modena & Reggio Emilia, Dept Hematol & Oncol, Modena, Italy. IRCCS, Oncol Referral Ctr, Aviano, Italy. Univ Aquila, Dept Expt Med, I-67100 Laquila, Italy. Univ Padua, IST, Sect Viral & Mol Oncol, Padua, Italy. Univ Modena & Reggio Emilia, Modenas Oncol Ctr, Modena, Italy. NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD USA. Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA. Johns Hopkins Univ, Dept Biostat, Baltimore, MD USA. RP Presciuttini, S (reprint author), Univ Pisa, Ctr Stat Genet, Dept Expt Pathol, SS Abetone & Brennero 2, I-56127 Pisa, Italy. EM sprex@biomed.unipi.it RI montagna, marco/E-2225-2012; Santarosa, Manuela/A-7300-2013; D'Andrea, Emma/B-4374-2013; Federico, Massimo/J-5984-2014; Federico, Massimo/A-6801-2012; Marchetti, Paolo/K-1469-2016; OI montagna, marco/0000-0002-4929-2150; Federico, Massimo/0000-0002-5074-3262; Federico, Massimo/0000-0002-9889-3796; Marroni, Fabio/0000-0002-1556-5907; RICEVUTO, Enrico/0000-0001-5641-3187; Bailey-Wilson, Joan/0000-0002-9153-2920; Santarosa, Manuela/0000-0001-7682-2578 NR 35 TC 42 Z9 43 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD NOV PY 2004 VL 12 IS 11 BP 899 EP 906 DI 10.1038/sj.ejhg.5201256 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 863JT UT WOS:000224558500005 PM 15340362 ER PT J AU Seminario, MC Precht, P Bunnell, SC Warren, SE Morris, CM Taub, D Wange, RL AF Seminario, MC Precht, P Bunnell, SC Warren, SE Morris, CM Taub, D Wange, RL TI PTEN permits acute increases in D3-phosphoinositicle levels following TCR stimulation but inhibits distal signaling events by reducing the basal activity of Akt SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE T lymphocytes; PTEN; T cell receptors; cellular activation; signal transduction ID GLYCOGEN-SYNTHASE KINASE-3; T-CELL-ACTIVATION; DNA-BINDING ACTIVITY; NF-KAPPA-B; NEGATIVE REGULATION; EXPRESSION; IL-2; JUN; PROLIFERATION; COSTIMULATION AB Phosphoinositicle 3-kinase (PI3K) is important in TCR signaling. PI3K generates phosphatidylinositol 3, 4, 5-trisphosphate (PI-3,4,5-P(3)), which regulates membrane localization and/or activity of multiple signaling proteins. PTEN (phosphatase and tensin homologue deleted on chromosome 10) opposes PI3K, reversing this reaction. Maintaining the balance between these two enzymes is important for normal Tcell function. Here we use the PTEN-null Jurkat T cell line to address the role of PTEN in modulating proximal and distal TCR-signaling events. PTEN expression at levels that restored low basal Akt phosphorylation (an indicator of PI-3,4,5-P(3) levels), but which were not themselves cytotoxic, had minimal effect on TCR-stimulated activation of phospholipase Cgamma1 and Ca(2+) flux, but reduced the duration of extracellular signal-regulated kinase (Erk) activation. Distal signaling events, including nuclear factor of activated T cells (NFAI) activation, CD69 expression and IL-2 production, were all inhibited by PTEN expression. Notably, PTEN did not block TCR-stimulated PI-3,4,5-P(3) accumulation. The effect of PTEN on distal TCR signaling events was strongly correlated with the loss of the constitutive Akt activation and glycogen synthase kinase-3 (GSK3) inhibition that is typical of Jurkat cells, and could be reversed by expression of activated Akt or pharmacologic inhibition of GSK3. These results suggest that PTEN acts in Tcells primarily to control basal PI-3,4,5-P(3) levels, rather than opposing PI3K acutely during TCR stimulation. C1 NIA, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. NIA, Flow Cytometry Lab, Baltimore, MD 21224 USA. NIA, Immunol Lab, Baltimore, MD 21224 USA. RP Wange, RL (reprint author), NIA, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. EM wanger@grc.nia.nih.gov NR 41 TC 14 Z9 15 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD NOV PY 2004 VL 34 IS 11 BP 3165 EP 3175 DI 10.1002/eji.200425206 PG 11 WC Immunology SC Immunology GA 871YF UT WOS:000225171800022 PM 15468057 ER PT J AU Eilers, H Trilk, SL Lee, SY Xue, Q Jong, BE Moff, I Levine, JD Schumacher, MA AF Eilers, H Trilk, SL Lee, SY Xue, Q Jong, BE Moff, I Levine, JD Schumacher, MA TI Isolation of an mRNA binding protein homologue that is expressed in nociceptors SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE capsaicin; dorsal root ganglion; mitochondria; nerve growth factor; rat ID NERVE GROWTH-FACTOR; C-OXIDASE DEFICIENCY; ADULT SENSORY NEURONS; ROOT GANGLION-CELLS; RECEPTOR SUBTYPE 1; RAT DORSAL-ROOT; SACCHAROMYCES-CEREVISIAE; PERIPHERAL NEUROPATHY; DIFFERENTIAL DISPLAY; INDUCED HYPERALGESIA AB The peripheral detection of painful stimuli requires the activation of small-diameter primary afferent neurons known as nociceptors. We have exploited two features of nociceptor biology, expression of the high affinity receptor for nerve growth factor (TrkA) and sensitivity to capsaicin, to isolate novel proteins using a differential display cloning scheme. A resulting similar to4.3-kb cDNA was isolated and sequence analysis inferred a similar to157-kDa protein containing a signal/mitochondrial targeting peptide sequence. Due to its molecular weight and significant amino acid identity with 'human leucine-rich protein 130' [leucine-rich pentatricopeptide motif containing (LRPPRC)], we termed the cDNA candidate leucine-rich protein 157 (rLRP157). Western blot analysis of HEK293 cells over-expressing the candidate cDNA showed a single protein product of similar size to that found in rat dorsal root ganglion as well as in other neuronal tissues and cell lines. Although expressed in a wide variety of tissues, in situ hybridization and immunohistochemistry in dorsal root ganglion revealed that rLRP157 expression was restricted to the small-diameter neurons. Sequence identity with previously characterized mRNA binding proteins and its subcellular localization in sensory neurons suggest that rLRP157 is associated with mitochondrial function. Moreover, the genetic basis of French-Canadian Leigh syndrome, which confers a loss of mitochondrial cytochrome c oxidase and is characterized by neurodegeneration, was recently mapped to a mutation in the LRPPRC gene. Taken together with its expression in small-diameter sensory neurons, we hypothesize that rLRP157, the rat orthologue of the human LRPPRC, may play a role in the modulation of peripheral pain transduction and serve as a novel marker for nociceptor subtypes. C1 Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, NIH Pain Ctr, San Francisco, CA USA. RP Schumacher, MA (reprint author), Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, Box 0427, San Francisco, CA 94143 USA. EM schumac@itsa.ucsf.edu FU NIDCR NIH HHS [DE08973] NR 50 TC 11 Z9 12 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD NOV PY 2004 VL 20 IS 9 BP 2283 EP 2293 DI 10.1111/j.1460-9568.2004.03703.x PG 11 WC Neurosciences SC Neurosciences & Neurology GA 865XJ UT WOS:000224737200005 PM 15525270 ER PT J AU Hardy, J AF Hardy, J TI Is amyloid plaque imaging the key to monitoring brain pathology of Alzheimer's disease in vivo? For SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Editorial Material ID HYPOTHESIS; BETA C1 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Hardy, J (reprint author), NIA, Neurogenet Lab, NIH, Bldg 35,35 Convent Dr,Room 1A1015 MSC 3707, Bethesda, MD 20892 USA. EM hardyj@mail.nih.gov RI Hardy, John/C-2451-2009 NR 9 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD NOV PY 2004 VL 31 IS 11 BP 1539 EP 1540 DI 10.1007/s00259-004-1676-9 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 874SR UT WOS:000225370600014 PM 15372211 ER PT J AU Maisto, SA Carey, MP Carey, KB Gordon, CM Schum, JL AF Maisto, SA Carey, MP Carey, KB Gordon, CM Schum, JL TI Effects of alcohol and expectancies on HIV-related risk perception and behavioral skills in heterosexual women SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID HUMAN-SEXUALITY; CONDOM USE; YOUNG MEN; SEX; CONSEQUENCES; METAANALYSIS; EVENT AB This experiment tested the effects of alcohol and expectancies on determinants of safer sex according to the information-motivation-behavioral skills model. Sixty heterosexual women attended 2 sessions. During Session 1, participants completed a set of descriptive measures; during Session 2 they were randomly assigned to 1 of 4 beverage conditions: control, alcohol-low (.35 gm alcohol/kg body weight), alcohol-moderate (.70 gm alcohol/kg body weight), or placebo. After beverage consumption, all participants completed measures of motivation to engage in risky sex and condom use negotiation skills. Results showed that the higher dose of alcohol and stronger alcohol expectancies were associated with greater motivation to engage in risky sexual behavior. However, perceived intoxication, rather than actual alcohol consumption or expectancies, was the best predictor of condom use negotiation skills. Integration of the findings with past research and their implication for the design of HIV-prevention programs are discussed. C1 Syracuse Univ, Dept Psychol, Syracuse, NY 13244 USA. Syracuse Univ, Ctr Hlth & Behav, Syracuse, NY 13244 USA. NIH, Bethesda, MD 20892 USA. RP Maisto, SA (reprint author), Syracuse Univ, Dept Psychol, 430 Huntington Hall, Syracuse, NY 13244 USA. EM samaisto@psych.syr.edu FU NIMH NIH HHS [MH 11613, K02 MH001582, K02 MH001582-04, K02 MH001582-05, K02-MH01582] NR 33 TC 57 Z9 57 U1 2 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1064-1297 J9 EXP CLIN PSYCHOPHARM JI Exp. Clin. Psychopharmacol. PD NOV PY 2004 VL 12 IS 4 BP 288 EP 297 DI 10.1037/1064-1297.12.4.288 PG 10 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA 871YI UT WOS:000225172100008 PM 15571446 ER PT J AU Davis, CD Uthus, EO AF Davis, CD Uthus, EO TI DNA methylation, cancer susceptibility, and nutrient interactions SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Review DE DNA methylation; cancer; folate; selenium; epigenetics ID MODERATE FOLATE-DEPLETION; ACID-DEFINED DIETS; COLON-CANCER; METHYLENETETRAHYDROFOLATE REDUCTASE; COLORECTAL-CANCER; RAT-LIVER; ALCOHOL-DEHYDROGENASE; NETHERLANDS COHORT; GENE-EXPRESSION; BREAST-CANCER AB DNA methylation is an important epigenetic mechanism of transcriptional control. DNA methylation plays an essential role in maintaining cellular function, and changes in methylation patterns may contribute to the development of cancer. Aberrant methylation of DNA (global hypomethylation accompanied by region-specific hypermethylation) is frequently found in tumor cells. Global hypomethylation can result in chromosome instability, and hypermethylation has been associated with the inaction of tumor suppressor genes. Preclinical and clinical studies suggest that part of the cancer-protective effects associated with several bioactive food components may relate to DNA methylation patterns. Dietary factors that are involved in one-carbon metabolism provide the most compelling data for the interaction of nutrients and DNA methylation because they influence the supply of methyl groups, and therefore the biochemical pathways of methylation processes. These nutrients include folate, vitamin B(12), vitamin B(6), methionine, and choline. However, looking at individual nutrients may be too simplistic. Dietary methyl (folate, choline, and methionine) deficiency in combination causes decreased tissue S-adenosylmethionine, global DNA hypomethylation, hepatic steatosis, cirrhosis, and ultimately hepatic tumorigenesis in rodents in the absence of carcinogen treatment. Other dietary components such as vitamin B(12), alcohol, and selenium may modify the response to inadequate dietary folate. C1 NCI, Nutrit Sci Res Grp, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. USDA ARS, Grand Forks Human Nutr Res Ctr, Grand Forks, ND 58202 USA. RP Davis, CD (reprint author), NCI, Nutrit Sci Res Grp, Div Canc Prevent, NIH, 6130 Exeuct Blvd,Suite 3159, Bethesda, MD 20892 USA. EM davisci@mail.nih.gov NR 75 TC 222 Z9 236 U1 1 U2 22 PU SOC EXPERIMENTAL BIOLOGY MEDICINE PI MAYWOOD PA 195 WEST SPRING VALLEY AVE, MAYWOOD, NJ 07607-1727 USA SN 1535-3702 J9 EXP BIOL MED JI Exp. Biol. Med. PD NOV PY 2004 VL 229 IS 10 BP 988 EP 995 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 866SJ UT WOS:000224793100002 PM 15522834 ER PT J AU Wolfe, JD Csaky, KG AF Wolfe, JD Csaky, KG TI Indocyanine green enhanced retinal vessel laser closure in rats: histologic and immunohistochemical observations SO EXPERIMENTAL EYE RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04-09, 2003 CL FT LAUDERDALE, FL SP Assoc Res Vis & Ophthalmol DE indocyanine green; laser photocoagulation; thrombus; retinal vessels; rodent ID SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION; FEEDER VESSELS; PHOTODYNAMIC THERAPY; PLASMINOGEN-ACTIVATOR; UROKINASE-TYPE; TISSUE FACTOR; PHOTOCOAGULATION; MEMBRANES; INJURY AB Purpose. Feeder vessel photocoagulation using both thermal and indocyanine green (ICG) enhanced applications as a treatment for choroidal neovascularization is under investigation. While closure of feeder vessels is achievable, reperfusion of these vessels occurs. The purpose of the following study was to compare, contrast anatomic, and immunohistochemical findings in rat retinal arterioles following attempts at vessel closure using either the diode (810 nm) laser alone or in conjunction with intravascular ICG. Methods. The retinal arterioles of adult Lewis or Brown Norway rats were treated with diode laser alone or immediately following intravenous injection with 75 mg ml(-1) ICG. Retinal vessel closure was determined by examination of retinal flatmounts following FITC-dextran or rhodamine-dextran perfusion. Anatomic changes were examined by electron microscopy and quantitative cellular changes were measured by perfusion with Hoechst 33342 nuclear staining. Recruited macrophages were detected by ED1 immunohistochemistry, Results. Treatment with diode laser alone resulted in partial retinal arteriolar closure seen only in pigmented animals. The use of adjuvant ICG achieved complete vessel closure in albino animals with reperfusion seen in all vessels by 7 days. Electron microscopy revealed an intraluminal clot only in ICG-enhanced diode laser treated animals, but with accompanying endothelial and perivascular cellular damage. Immunohistochemistry of the site of retinal arteriolar closure revealed a large increase in perivascular cellularity with an apparent influx of ED1 positive cells. Conclusion. ICG-enhanced diode laser photocoagulation appears to be superior to diode treatment alone in achieving vessel closure, but is limited by clot resolution due to both excessive vascular damage and an accompanying inflammatory response. These results suggest that more durable feeder vessel closure rates may be achievable with either the use of accompanying anti-inflammatory therapies or with a less vascular damaging photoactivating dye. Published by Elsevier Ltd. C1 NEI, NIH, Bethesda, MD 20892 USA. RP Csaky, KG (reprint author), NEI, NIH, Bldg 10-10B11,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kcsaky@helix.nih.gov NR 29 TC 13 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD NOV PY 2004 VL 79 IS 5 BP 631 EP 638 DI 10.1016/j.exer.2004.05.018 PG 8 WC Ophthalmology SC Ophthalmology GA 871IV UT WOS:000225125200004 PM 15500822 ER PT J AU Bettelheim, FA Zigler, JS AF Bettelheim, FA Zigler, JS TI Regional mapping of molecular components of human liquid vitreous by dynamic light scattering SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE dynamic light scattering; human vitreous; hyaluronan; hydrodynamic diameter; regional distribution ID BOVINE; LENS AB The distribution of particle sizes was studied in six regions of human liquid vitreous samples. Particle sizes were calculated from dynamic light scattering measurements as hydrodynamic diameter of molecules. In general, particle sizes increased progressively from anterior (near lens) to posterior (near retina). A much weaker trend of increase in particle size was found from nasal to temporal regions. Relative concentrations of particles of certain sizes were calculated from dynamic light scattering parameters. Viscosity coefficients of liquid vitreous samples were measured in a semi-micro viscometer. Hyaluronan concentrations increased from anterior to posterior and the reverse was true for viscosity, implying that the lower concentration of hyaluronan near the lens was offset by increased molecular size. A similar concentration gradient was found with the 6 nm diameter particles, and to a lesser degree with the 15 nm particles. The identities of these proteins must be resolved by techniques of proteomics. (C) 2004 Elsevier Ltd. All rights reserved. C1 NEI, Lab Mech Ocular Dis, NIH, Bethesda, MD 20892 USA. RP Zigler, JS (reprint author), NEI, Lab Mech Ocular Dis, NIH, 7 Mem Dr,MSC 0703, Bethesda, MD 20892 USA. EM ziglers@nei.nih.gov NR 13 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD NOV PY 2004 VL 79 IS 5 BP 713 EP 718 DI 10.1016/j.exer.2004.07.011 PG 6 WC Ophthalmology SC Ophthalmology GA 871IV UT WOS:000225125200011 PM 15500829 ER PT J AU Chen, JC AF Chen, JC TI Senescence and functional failure in hematopoietic stem cells SO EXPERIMENTAL HEMATOLOGY LA English DT Review ID ACQUIRED APLASTIC-ANEMIA; BONE-MARROW; TELOMERE LENGTH; IN-VIVO; SERIAL TRANSPLANTATION; LIFELONG HEMATOPOIESIS; REPOPULATING ABILITY; ALLOPHENIC MICE; IRRADIATED MICE; GENETIC-CONTROL AB Maintaining normal function of hematopoietic stem cells (HSCs) is critical to blood coagulation, oxygen transportation, and host defense against infection. A potential cause of HSC dysfunction is senescence, in which HSCs and progenitor cells suffer from proliferative arrest. Studies on humans and various animal models have indicated that HSCs can become senescent, showing a significant decline in functional ability with increasing age. There are genetic elements mapped to specific chromosomal sites that regulate HSC senescence. These elements may differ among species, strains, and even individuals. HSC senescence and related pathological effects may not be obvious during normal lifetime under most circumstances since individual primitive HSC clones can function long-term to produce progeny that sustain life-long mature blood cell production. Shortening of telomeres at the chromosomal ends could contribute to HSC senescence, especially when HSCs are stressed under certain pathological conditions. Future studies should define the molecular elements that are important in the regulation of HSC senescence. (C) 2004 International Society for Experimental Hematology. Published by Elsevier Inc. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Chen, JC (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Room 7C118,9000 Rockville Pike, Bethesda, MD 20892 USA. EM chenji@nhlbi.nih.gov NR 73 TC 30 Z9 35 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD NOV PY 2004 VL 32 IS 11 BP 1025 EP 1032 DI 10.1016/j.exphem.2004.08.001 PG 8 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 873HZ UT WOS:000225271800002 PM 15539079 ER PT J AU Perry, TA Weerasuriya, A Mouton, PR Holloway, HW Greig, NH AF Perry, TA Weerasuriya, A Mouton, PR Holloway, HW Greig, NH TI Pyridoxine-induced toxicity in rats: a stereological quantification of the sensory neuropathy SO EXPERIMENTAL NEUROLOGY LA English DT Article DE sensory neuropathy; DRG; sciatic nerve; H reflex; M wave; axonopathy ID DORSAL-ROOT GANGLION; CONDUCTION-VELOCITY; BEAGLE DOGS; NERVE; NEUROTOXICITY; DEGENERATION; MERCURY; NEURONS; FIBERS; AXONS AB Excess ingestion of pyridoxine (vitamin B6) causes a severe sensory neuropathy in humans. The mechanism of action has not been fully elucidated, and studies of pyridoxine neuropathy in experimental animals have yielded disparate results. Pyridoxine intoxication appears to produce a neuropathy characterized by necrosis of dorsal root ganglion (DRG) sensory neurons and degeneration of peripheral and central sensory projections, with large diameter neurons being particularly affected. The major determinants affecting the severity of the pyridoxine neuropathy appear to be duration and dose of pyridoxine administration, differential neuronal vulnerability, and species susceptibility. The present study used design-based stereological techniques in conjunction with electrophysiological measures to quantify the morphological and physiological changes that occur in the DRG and the distal myelinated axons of the sciatic nerve following pyridoxine intoxication. This combined stereological and electrophysiological method demonstrates a general approach that could be used for assessing the correlation between pathophysiological and functional parameters in animal models of toxic neuropathy. Published by Elsevier Inc. C1 NIA, Sect Drug Design & Dev, Neurosci Lab, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA. Mercer Univ, Sch Med, Div Basic Med Sci, Macon, GA 31207 USA. NIA, Lab Expt Gerontol, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Perry, TA (reprint author), NIA, Sect Drug Design & Dev, Neurosci Lab, Gerontol Res Ctr,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM tracyann.perry@amylin.com; greign@nia.nih.gov NR 36 TC 29 Z9 30 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD NOV PY 2004 VL 190 IS 1 BP 133 EP 144 DI 10.1016/j.expneurol.2004.07.013 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 867DJ UT WOS:000224822100012 PM 15473987 ER PT J AU Kollmar, R Henninger, N Bardutzky, J Schellinger, PD Schabitz, WR Schwab, S AF Kollmar, R Henninger, N Bardutzky, J Schellinger, PD Schabitz, WR Schwab, S TI Combination therapy of moderate hypothermia and thrombolysis in experimental thromboembolic stroke - An MRI study SO EXPERIMENTAL NEUROLOGY LA English DT Article DE cerebral ischemia; stroke; thrombolysis; hypothermia; MRI; combination therapy; Rt-PA ID FOCAL CEREBRAL-ISCHEMIA; TISSUE-PLASMINOGEN ACTIVATOR; EMBOLIC STROKE; MILD HYPOTHERMIA; INFARCT VOLUME; BLOOD-FLOW; RATS; MODEL; REPERFUSION; HALOTHANE AB Thrombolysis (T) is limited by reperfusion-associated injury and the short therapeutic window after stroke onset. The present study investigates whether hypothermia alone or in combination with thrombolysis has beneficial effects after experimental thromboembolic stroke. Wistar rats (n = 60) were subjected to thromboembolic occlusion (TE) of the middle cerebral artery (MCA). Thrombolysis (T) was performed with intravenous recombinant tissue-plasminogen activator (rt-PA) 1 h (early T) or 3 h (late T) after TE. Hypothermia (Hy) was applied for 4 h at 33degreesC started 1 h after TE. Experimental groups included control (C), early thrombolysis (ET), late thrombolysis (LT), hypothermia (Hy), early thrombolysis plus hypothermia (ET+Hy), and late thrombolysis plus hypothermia (LT+Hy). Animals were investigated by MRI and silver infarct staining (SIS) to assess the cerebral infarct size. All animals of group Hy survived, in contrast to 40% in group C (P < 0.05). ET+HY and LT+Hy showed a trend towards better survival as compared to ET and LT alone. PWI parameters were not significantly different between ET versus ET+HY and LT versus LT+Hy, but rt-PA administration led to improved cerebral, perfusion in MRI. Significant differences in infarct volumes (T2/SIS) were found after 24 h in all treatment groups versus the control group (P < 0.05). The lesion volume calculated from T2 was significantly smaller in ET (16% +/- 5%), ET+Hy (10 +/- 4%), and LT+Hy (20% +/- 9%) after 5.5 h (10.8% +/- 4.8%) versus C (42% +/- 15%), (P < 0.05). These data indicate that hypothermia improves survival and decreases infarct volume. However, there were no significant differences between the use of rt-PA alone or in combination with hypothermia. Further studies are needed to confirm these effects, also several days after stroke onset. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Heidelberg, Dept Neurol, D-69120 Heidelberg, Germany. NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. RP Kollmar, R (reprint author), Univ Heidelberg, Dept Neurol, Neuenheimer Feld 400, D-69120 Heidelberg, Germany. EM Rainer_Kollmar@med.uni-heidelberg.de OI Henninger, Nils/0000-0002-3883-5623 NR 29 TC 30 Z9 31 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD NOV PY 2004 VL 190 IS 1 BP 204 EP 212 DI 10.1016/j.expneurol.2004.07.006 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 867DJ UT WOS:000224822100018 PM 15473993 ER PT J AU Kleta, R Gahl, WA AF Kleta, R Gahl, WA TI Pharmacological treatment of nephropathic cystinosis with cysteamine SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Review DE CTNS; cystamine; cysteamine; cystinosin; lysosomal storage disorder; nephropathic cystinosis; renal Fanconi syndrome ID TOPICAL CYSTEAMINE; HUMAN-FIBROBLASTS; CORNEAL CRYSTALS; CTNS MUTATIONS; CLINICAL-TRIAL; GENE CTNS; THERAPY; CHILDREN; PROTEIN; DISEASE AB Cystinosis, clinically recognised since 1903, is an autosomal recessive lysosomal storage disease caused by mutations in CTNS. This gene codes for a lysosomal cystine transporter, whose absence leads to intracellular cystine crystals, widespread cellular destruction, renal Fanconi syndrome in infancy, renal glomerular failure in later childhood and other systemic complications. Before the availability of kidney transplantation, patients affected with cystinosis uniformly died during childhood. After solid organ transplantations became successful in the 1960s, cystinosis patients survived, but eventually developed life-threatening consequences of the disease (e.g., swallowing disorders). Since the introduction of cysteamine into the pharmacological management of cystinosis, well-treated adolescent and young adult patients have experienced normal growth and maintenance of renal glomerular function. Oral cysteamine therapy is given at doses of 60 - 90 mg/kg/day q.i.d. every 6 h, and generally achieves similar to 90% depletion of cellular cystine, as measured in circulating leucocytes. Cysteamine (and kidney transplantation) have commuted the death sentence of cystinosis into a nearly normal life with a chronic disease. Because treatment with oral cysteamine can prevent, or significantly delay, the complications of cystinosis, early and accurate diagnosis, as well as proper treatment, is critical. C1 NHGRI, Bethesda, MD 20892 USA. RP Kleta, R (reprint author), NHGRI, Bldg 10,Room 10C-107,MSC 1851,10 Ctr Dr, Bethesda, MD 20892 USA. EM kletar@mail.nih.gov NR 64 TC 45 Z9 46 U1 0 U2 3 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1465-6566 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD NOV PY 2004 VL 5 IS 11 BP 2255 EP 2262 DI 10.1517/14656566.5.11.2255 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 868WU UT WOS:000224944600006 PM 15500372 ER PT J AU Player, A Barrett, JC Kawasaki, ES AF Player, A Barrett, JC Kawasaki, ES TI Laser capture microdissection, microarrays and the precise definition of a cancer cell SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Review DE gene expression profining; laser capture microdissection; microarrays; single-cell analysis ID MESSENGER-RNA AMPLIFICATION; GENE-EXPRESSION PROFILES; POLYMERASE-CHAIN-REACTION; HUMAN PROSTATE-CANCER; BREAST-CANCER; STEM-CELLS; LINEAR AMPLIFICATION; PROTEOMIC ANALYSIS; CDNA MICROARRAY; SINGLE CELLS AB Most expression profiling studies of solid tumors have used biopsy samples containing large numbers of contaminating stromal and other cell types, thereby complicating any precise delineation of gene expression In nontumor versus tumor cell types. Combining laser capture microdissection, RNA amplification protocols, microarray technologies and our knowledge of the human genome sequence, it is possible to isolate pure populations of cells or even a single cell and interrogate the expression of thousands of sequences for the purpose of more precisely defining the biology of the tumor cell. Although many of the studies that currently allow for characterization of small sample preparations and single cells were performed utilizing noncancer cell types, and in some cases isolation protocols other than laser capture microdissection, a list of protocols are described that could be used for the expression analysis of individual tumor cells. Application of these experimental approaches to cancer studies may permit a more accurate definition of the biology of the cancer cell, so that ultimately; more specific targeted therapies can be developed. C1 NCI, Ctr Adv Technol, Microarray Facil, Gaithersburg, MD 20877 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Player, A (reprint author), NCI, Ctr Adv Technol, Microarray Facil, Gaithersburg, MD 20877 USA. EM playera@mail.nih.gov NR 97 TC 24 Z9 26 U1 0 U2 2 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD NOV PY 2004 VL 4 IS 6 BP 831 EP 840 DI 10.1586/14737159.4.6.831 PG 10 WC Pathology SC Pathology GA 942QI UT WOS:000230296500008 PM 15525225 ER PT J AU Myers, ER Silva, S Barnhart, K Groben, PA Richardson, MS Robboy, SJ Leppert, P Coutitaris, C AF Myers, ER Silva, S Barnhart, K Groben, PA Richardson, MS Robboy, SJ Leppert, P Coutitaris, C CA NICHD National Cooperative Reprodu TI Interobserver and intralobserver variability in the histological dating of the endometrium in fertile and infertile women SO FERTILITY AND STERILITY LA English DT Article DE luteal phase defect; infertility; observer variability; endometrial biopsy; histopathology ID DIAGNOSIS; IMPACT AB Objective: To assess effects of biopsy timing and fertility status on inter- and intraobserver variability in dating of the endometrium. Design: Endometrial biopsy slides randomly selected from a multicenter study testing the utility of biopsy in the diagnosis of infertility were distributed to three gynecologic pathologists, who estimated cycle day using standard criteria. Readers were blinded to the purpose of the study, patient age, fertility status, or timing of biopsy relative to LH surge or next menses. Setting: Multicenter academic research programs in reproductive medicine. Patient(s): Eighty-two women with proven fertility, 83 infertile patients. Intervention(s): Endometrial biopsy during midluteal (days 21-22) or late (days 26-27) luteal phase. Main Outcome Measure(s): Intraclass correlation coefficient (ICC), kappa. Result(s): Overall agreement was excellent (ICC 0.88); addition of readings by local pathologists decreased ICC only slightly. In subgroup analyses, ICCs were lowest for infertile women during the midluteal phase (0.65 vs. 0.71 for fertile women in the midluteal phase, and 0.88-0.90 for both groups in the late luteal phase). Intraobserver reliability was excellent (0.9-0.99). Agreement for diagnoses of "out-of-phase" was only moderate, with kappa values between 0.4 and 0.6. Conclusion(s): Observer variability in dating the endometrium was greatest in infertile women during the window of implantation. (C) 2004 by American Society for Reproductive Medicine. C1 Duke Univ, Med Ctr, Dept Obstet & Gynaecol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27710 USA. Univ Penn, Sch Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. Univ N Carolina, Sch Med, Dept Pathol, Chapel Hill, NC 27515 USA. Med Univ S Carolina, Dept Pathol, Charleston, SC 29425 USA. Duke Univ, Ctr Med, Dept Pathol, Durham, NC 27706 USA. NICHHD, Reprod Sci Branch, Bethesda, MD 20892 USA. RP Myers, ER (reprint author), Duke Univ, Med Ctr, Dept Obstet & Gynaecol, DUMC 3279, Durham, NC 27710 USA. EM myers008@mc.duke.edu FU NICHD NIH HHS [HD27049, U01 HD38997] NR 14 TC 33 Z9 36 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD NOV PY 2004 VL 82 IS 5 BP 1278 EP 1282 DI 10.1016/j.fertnstert.2004.04.058 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 871JT UT WOS:000225128300004 PM 15533342 ER PT J AU Hooth, MJ Sills, RC Burka, LT Haseman, JK Witt, KL Orzech, DP Fuciarelli, AF Graves, SW Johnson, JD Bucher, JR AF Hooth, MJ Sills, RC Burka, LT Haseman, JK Witt, KL Orzech, DP Fuciarelli, AF Graves, SW Johnson, JD Bucher, JR TI Toxicology and carcinogenesis studies of microencapsulated trans-cinnamaldehyde in rats and mice SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE trans-cinnamaldehyde; food additives; fragrance additives; GRAS list; microencapsulation; toxicity; rats; mice; hippuric acid; cinnamyl; anthranilate ID SALMONELLA MUTAGENICITY TESTS; HAMSTER OVARY CELLS; ZERO DOSE CONTROL; CHEMICALS; DROSOPHILA; TOXICITY; PROGRAM; MOUSE; FEED AB trans-Cinnamaldehyde is a widely used natural ingredient that is added to foods and cosmetics as a flavoring and fragrance agent. Mate and female F344/N rats and B6C3F(1) mice were exposed to microencapsulated trans-cinnamaldehyde in the feed for three months or two years. All studies included untreated and vehicle control groups. In the three-month studies, rats and mice were given diets containing 4100, 8200, 16,500, or 33,000 ppm trans-cinnamaldehyde. In rats, feed consumption was reduced in all exposed groups. In mice, feed consumption was reduced in the highest dose groups. Body weights of all treated males were less than controls. Body weights were reduced in female rats exposed to 16,500 or 33,000 ppm and female mice exposed to 8200 ppm or greater. All rats survived to the end of the study but some male mice in the highest dose groups died due to inanition from unpalatability of the dosed feed. The incidence of squamous epithelia] hyperplasia of the forestomach was significantly increased in rats exposed to 8200 ppm or greater and female mice exposed to 33,000 ppm. In mice, the incidence of olfactory epithelial degeneration of the nasal cavity was significantly increased in males and females exposed to 16,500 ppm and females exposed to 33,000 ppm. In the two-year studies, rats and mice were exposed to 1000, 2 100, or 4 100 ppm trans-cinnamaldehyde. Body weights were reduced in mice exposed to 2 100 ppm and in rats and mice exposed to 4100 ppm. In rats, hippuric acid excretion was dose proportional indicating that absorption, metabolism, and excretion were not saturated. No neoplasms were attributed to trans-cinnamaldehyde in rats or mice. Squamous cell papillomas and carcinomas of the forestomach were observed in male and female mice but the incidences were within the NTP historical control range and were not considered to be related to trans-cinnamaldehyde exposure. Published by Elsevier Ltd. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Battelle Toxicol NW, Richland, WA 99352 USA. Battelle Lab, Columbus, OH 43201 USA. RP Hooth, MJ (reprint author), NIEHS, Mail Drop EC-35,79 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM hooth@niehs.nih.gov NR 40 TC 8 Z9 10 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD NOV PY 2004 VL 42 IS 11 BP 1757 EP 1768 DI 10.1016/j.fct.2004.07.002 PG 12 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 859IX UT WOS:000224257700005 PM 15350673 ER PT J AU Davila, JA Morgan, RO Shaib, Y McGlynn, KA El-Serag, HB AF Davila, JA Morgan, RO Shaib, Y McGlynn, KA El-Serag, HB TI Hepatitis C infection and the increasing incidence of hepatocellular carcinoma: A population-based study SO GASTROENTEROLOGY LA English DT Article ID CHRONIC LIVER-DISEASE; UNITED-STATES; INTERFERON THERAPY; DIABETES-MELLITUS; VIRAL-HEPATITIS; VIRUS-INFECTION; RISK-FACTORS; CIRRHOSIS; CANCER AB Background & Aims: A significant increase in the incidence of hepatocellular carcinoma (HCC) has been reported in the United States. The risk factors underlying this increase remain unclear. Methods: By using Surveillance, Epidemiology, and End-Results program (SEER)-Medicare-linked data, we conducted a population-based study to examine temporal changes in risk factors for patients 65 years and older diagnosed with HCC between 1993 and 1999. Only patients with continuous Medicare enrollment for 2 years before and up to 2 years after HCC diagnosis were examined. Univariate and multiple logistic regression analyses were used to evaluate changes in risk factors over time (January 1993-June 1996 and July 1996-December 1999). Results: The age-adjusted incidence of HCC among persons 65 years of age and older significantly increased from 14.2 per 100,000 in 1993 to 18.1 per 100,000 in 1999. We identified 2584 patients with continuous Medicare enrollment 2 years before and up to 2 years after HCC diagnosis. The proportion of hepatitis C virus (HCV)-related HCC increased from 11% during January of 1993 to June of 1996 to 21% during July of 1996 to December of 1999, whereas hepatitis B virus (HBV)-related HCC increased from 6% to 11% (P < .0001). In multiple logistic regression analyses that adjusted for age, sex, race, and geographic region, the risk for HCV-related HCC and HBV-related HCC increased by 226% and 67%, respectively. Idiopathic HCC decreased from 43% to 39%. This decrease did not fully account for the significant increases observed for HCV and HBV. No significant changes over time were observed for alcohol-induced liver disease, nonspecific cirrhosis, or nonspecific hepatitis. Conclusions: There has been a significant recent increase in HCV- and HBV-related HCC. Increasing rates of HCV-related HCC can explain a substantial proportion of the reported increase in HCC incidence during recent years. C1 Houston Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP El-Serag, HB (reprint author), Houston Vet Affairs Med Ctr, Sect Hlth Serv Res, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu RI Morgan, Robert/A-8577-2009 NR 23 TC 284 Z9 296 U1 1 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2004 VL 127 IS 5 BP 1372 EP 1380 DI 10.1053/j.gastro.2004.07.020 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 870IC UT WOS:000225049800012 PM 15521006 ER PT J AU Sun, R Gao, B AF Sun, R Gao, B TI Negative regulation of liver regeneration by innate immunity (natural killer cells/interferon-gamma) SO GASTROENTEROLOGY LA English DT Article ID CHRONIC HEPATITIS-C; DOUBLE-STRANDED-RNA; CELL-CYCLE PROGRESSION; TOLL-LIKE RECEPTOR-3; HEPATOCYTE REGENERATION; PARTIAL-HEPATECTOMY; INTERFERON-GAMMA; NK CELLS; NONPARENCHYMAL CELLS; VIRUS-INFECTION AB Background & Aims: Hepatic lymphocytes are composed mainly of natural killer (NK) cells and NKT cells, which play key roles in innate immune responses against pathogens and tumors in the liver. This report analyzes the effects of activation of innate immunity by viral infection or the toll-like receptor 3 (TLR3) ligand on liver regeneration. Methods: The partial hepatectomy (PHx) method was used as a model of liver regeneration. Murine cytomegalovirus (MCMV) infection and the TLR3 ligand polyinosinic-polycytidylic acid [poly(I:C)] were used to activate innate immunity. Results: NK cells are activated after PHx, as evidenced by producing interferon (IFN)-gamma. Infection with MCMV or injection of poly(I:C) further activates NK cells to produce IFN-gamma and attenuates liver regeneration in the PHx model. Depletion of NK cells or disruption of either the IFN-gamma gene or the IFN-gamma receptor gene enhances liver regeneration and partially abolishes the negative effects of MCMV and polyl:C on liver regeneration, whereas NKT cells may only play a minor role in suppression of liver regeneration. Adoptive transfer of IFN-gamma(+/+) NK cells, but not IFN-gamma(-/-) NK cells, restores the ability of polyl:C to attenuate liver regeneration in NK-depleted mice. Finally, administration of polyl:C or IFN-gamma enhances expression of several antiproliferative proteins, including STAT1, IRF-1, and p21cip1/waf1 in the livers of partially hepatectomized mice. Conclusions: Our findings suggest that viral infection and the TLR3 ligand negatively regulate liver regeneration via activation of innate immunity (NK/ IFN-gamma), which may play an important role in the pathogenesis of viral hepatitis. C1 NIAAA, Sect Liver Biol, NIH, Lab Physiol Studies, Bethesda, MD 20892 USA. RP Gao, B (reprint author), NIAAA, Sect Liver Biol, NIH, Lab Physiol Studies, Pk Bldg,Room 120, Bethesda, MD 20892 USA. EM bgao@mail.nih.gov NR 70 TC 100 Z9 108 U1 0 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2004 VL 127 IS 5 BP 1525 EP 1539 DI 10.1053/j.gastro.2004.08.055 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 870IC UT WOS:000225049800026 PM 15521020 ER PT J AU Gharib, AM Thomasson, D Li, KCP AF Gharib, AM Thomasson, D Li, KCP TI Molecular imaging of hepatocellular carcinoma SO GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT Workshop on Hepatocellular Carcinoma CY APR 01-03, 2004 CL Bethesda, MD ID POSITRON-EMISSION-TOMOGRAPHY; RESISTANCE ASSOCIATED PROTEIN; TUMOR ANGIOGENESIS; ASIALOGLYCOPROTEIN RECEPTOR; COMPUTED-TOMOGRAPHY; GENE-EXPRESSION; P-GLYCOPROTEIN; IN-VIVO; SCINTIGRAPHY; FLUORINE-18-FLUORODEOXYGLUCOSE AB Molecular imaging may be defined as spatially localized and/or temporally resolved sensing of molecular and cellular processes in vivo. An imageable molecular event may be the result of the overexpression of a gene that produces a specific messenger RNA. The overexpressed protein could be an enzyme or could be incorporated into cell-surface transporters or receptors. Any step of this process is a potential target for molecular imaging. Current molecular imaging modalities include magnetic resonance imaging, nuclear imaging, ultrasound, and optical imaging. Nuclear medicine has been at the forefront of molecular imaging because of the relatively high sensitivity to detect nanomolar or picomolar quantities of the radiolabeled imaging probe. Imaging has had a central role in the diagnosis of hepatocellular carcinoma (HCC), which is considered the fifth most frequent malignancy worldwide. Nuclear imaging was one of the earlier modalities used for liver imaging. Traditional tracers included technetium 99m (Tc-99m) sulfur colloid, gallium 67, and Tc-99m iminodiacetate acid analogues. Other less traditional probes include 99mTc diethylenetriamine pentaacetic acid-galactosyl-human serum albumin for evaluation of functional liver volume and Tc-99m-labeled tetrofosmin and methoxisobutylisonitrile for detecting drug resistance. Fluorodeoxyglucose is the most widely used probe for positron emission tomography (PET) tumor imaging; however, carbon 11-labeled acetate appears to show improved sensitivity and specificity for HCC. Oxygen 15 PET imaging allows for the measurement of hepatic and tumor blood flow. Difficulties developing specific imaging methods for HCC are caused by the lack of obvious specific molecular targets, problems with drug delivery, and poor contrast-to-noise. No magic molecular imaging method exists today to accurately detect, characterize, and monitor HCC in vivo. C1 NIH, Warren G Magnuson Clin Ctr, Dept Radiol, Bethesda, MD 20892 USA. RP Li, KCP (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Radiol, Bldg 10,Room 1C626,10 Ctr Dr, Bethesda, MD 20892 USA. EM kingli@cc.nih.gov RI Gharib, Ahmed/O-2629-2016 OI Gharib, Ahmed/0000-0002-2476-481X NR 42 TC 13 Z9 13 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2004 VL 127 IS 5 SU 1 BP S153 EP S158 DI 10.1053/j.gastro.2004.09.029 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 871TJ UT WOS:000225156200020 PM 15508079 ER PT J AU Hoofnagle, JH AF Hoofnagle, JH TI Hepatocellular carcinoma: Summary and recommendations SO GASTROENTEROLOGY LA English DT Editorial Material ID PRIMARY LIVER-CANCER; CHRONIC HEPATITIS-C; UNITED-STATES; INTERFERON THERAPY; CIRRHOSIS; MORTALITY; STATISTICS; SURVIVAL; EUROPE; TRENDS C1 NIDDKD, Liver Dis Res Branch, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Hoofnagle, JH (reprint author), NIDDKD, Liver Dis Res Branch, Div Digest Dis & Nutr, NIH, Bldg 31,Room 9A27,31 Ctr Dr, Bethesda, MD 20892 USA. EM HoofnagleJ@extra.niddk.nih.gov NR 44 TC 31 Z9 32 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2004 VL 127 IS 5 SU 1 BP S319 EP S323 DI 10.1053/j.gastro.2004.09.047 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 871TJ UT WOS:000225156200039 PM 15508100 ER PT J AU Lee, JS Thorgeirsson, SS AF Lee, JS Thorgeirsson, SS TI Genome-scale profiling of gene expression in hepatocellular carcinoma: Classification, survival prediction, and identification of therapeutic targets SO GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT Workshop on Hepatocellular Carcinoma CY APR 01-03, 2004 CL Bethesda, MD ID B-CELL LYMPHOMA; NATURAL-HISTORY; MICROARRAY; RECURRENCE; PROGNOSIS; PROTEIN; CANCER AB The heterogeneous nature of human hepatocellular carcinoma (HCC) has hampered both treatment and prognostic predictions. Gene expression profiles of human HCC were analyzed to define the molecular characteristics of the tumors and to test the prognostic value of the expression profiles. By applying global gene expression analyses, including unsupervised and supervised methods, 2 distinctive subclasses of HCC that were highly homogeneous for both the underlying biology and the clinical outcome were discovered. Tumors from the low survival subclass had strong cell proliferation and antiapoptosis gene expression signatures. In addition, the low survival subclass displayed higher expression of genes involved in ubiquitination and sumoylation, suggesting an etiologic involvement of these processes in accelerating the progression of HCC. Genes most strongly associated with survival were identified by using the Cox proportional hazards survival analysis. This approach identified a limited number of genes that accurately predicted the length of survival and provided new molecular insights into the pathogenesis of HCC. Future studies will evaluate potential diagnostic markers and therapeutic targets identified during the global gene expression studies. Furthermore, cross-species similarity of gene expression patterns will also allow prioritization of a long list of genes obtained from human gene expression profiling studies and focus on genes whose expression is altered during tumorigenesis in both species. C1 NCI, Expt Carcinogenesis Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Canc Res Ctr, NIH, 37 Convent Dr,MSC 4262,Bldg 37,Room 4146A, Bethesda, MD 20892 USA. EM snorri_thorgeirsson@nih.gov NR 23 TC 96 Z9 102 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2004 VL 127 IS 5 SU 1 BP S51 EP S55 DI 10.1053/j.gastro.2004.09.015 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 871TJ UT WOS:000225156200006 PM 15508103 ER PT J AU Liang, TJ Heller, T AF Liang, TJ Heller, T TI Pathogenesis of hepatitis C-associated hepatocellular carcinoma SO GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT Workshop on Hepatocellular Carcinoma CY APR 01-03, 2004 CL Bethesda, MD ID VIRUS CORE PROTEIN; NONSTRUCTURAL 5A PROTEIN; TRANSGENIC MICE; INTERFERON THERAPY; OXIDATIVE STRESS; UNITED-STATES; MIXED CRYOGLOBULINEMIA; STRUCTURAL PROTEINS; LIPID-PEROXIDATION; ENVELOPE PROTEIN AB Epidemiologic, clinical, and virologic data have shown a close association between chronic infection with hepatitis C virus (HCV) and the development of hepatocellular carcinoma (HCC). In many countries of the developed world, HCV infection accounts for more than half of the cases of HCC. HCC usually arises after 2-4 decades of infection, typically in the context of an underlying cirrhosis. Treatment of hepatitis C with interferon-alfa can lead to sustained clearance of HCV, and small prospective studies as well as larger retrospective analyses suggest that interferon therapy leads to a decrease in the incidence of HCC. Without a reliable tissue culture system or a small animal model of HCV infection, analysis of the mechanisms by which HCV leads to cancer has been difficult. Nevertheless, both in vitro expression systems and in vivo transgenic mice studies suggest that HCV has an inherent carcinogenic potential. Understanding the pathogenesis of HCV-associated HCC Is important in developing effective means of prevention and treatment of this highly malignant form of cancer. C1 NIDDKD, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. RP Liang, TJ (reprint author), Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. EM Jakel@intra.niddk.nih.gov NR 104 TC 141 Z9 145 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2004 VL 127 IS 5 SU 1 BP S62 EP S71 DI 10.1053/j.gastro.2004.09.017 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 871TJ UT WOS:000225156200008 PM 15508105 ER PT J AU Seeff, LB AF Seeff, LB TI Introduction: The burden of hepatocellular carcinoma SO GASTROENTEROLOGY LA English DT Editorial Material ID C VIRUS-INFECTION; HEPATITIS-B VIRUS; UNITED-STATES; FOLLOW-UP; MORTALITY; CANCER; MORBIDITY; CIRRHOSIS; SURVIVAL; OBESITY C1 NIDDK, Liver Dis Res Branch, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Seeff, LB (reprint author), NIDDK, Liver Dis Res Branch, Div Digest Dis & Nutr, NIH, 31A Ctr Dr,Room 9A27, Bethesda, MD 20892 USA. EM seeffl@extra.niddk.nih.gov NR 17 TC 35 Z9 36 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2004 VL 127 IS 5 SU 1 BP S1 EP S4 DI 10.1016/j.gastro.2004.09.010 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 871TJ UT WOS:000225156200001 PM 15508071 ER PT J AU Nakaya, MA Habas, R Biris, K Dunty, WC Kato, Y He, X Yamaguchi, TP AF Nakaya, MA Habas, R Biris, K Dunty, WC Kato, Y He, X Yamaguchi, TP TI Identification and comparative expression analyses of Daam genes in mouse and Xenopus SO GENE EXPRESSION PATTERNS LA English DT Article DE Wnt; Formin; Dishevelled; Rho; planar cell polarity; convergent extension; gastrulation; embryogenesis; neural tube; mouse; Xenopus ID REGULATES CONVERGENT EXTENSION; IN-SITU HYBRIDIZATION; VERTEBRATE GASTRULATION; MOVEMENTS; RHO; ACTIVATION; GRADIENT; PATHWAY; EMBRYO; WNTS AB During vertebrate embryogenesis, secreted Writ molecules regulate cell fates by signaling through the canonical pathway mediated by beta-catenin, and regulate planar cell polarity (PCP) and convergent extension movements through alternative pathways. The phosphoprotein Dishevelled (Dsh/Dvl) is a Wnt signal transducer thought to function in all Wnt signaling pathways. A recently identified member of the Formin family, Daarn (Dishevelled-associated activator of morphogenesis), regulates the morphogenetic movements of vertebrate gastrulation in a Wnt-dependent manner through direct interactions with Dsh/Dvl and RhoA. We describe two mouse Daam cDNAs, mDaam1 and mDaam2, which encode proteins characterized by highly conserved formin homology domains and which are expressed in complementary patterns during mouse development. Cross-species comparisons indicate that the expression domains of Xenopus Daam1 (XDaam1) mirror mDaam1 expression. Our results demonstrate that Daams are expressed in tissues known to require Writs and are consistent with Daams being effectors of Wnt signaling during vertebrate development. (C) 2004 Elsevier B.V. All rights reserved. C1 NCI, Canc Res Ctr, Canc & Dev Biol Lab, NIH, Frederick, MD 21702 USA. Harvard Univ, Childrens Hosp, Sch Med, Div NeurosciDept Neurol, Boston, MA 02115 USA. NICHHD, Mol Genet Lab, Bethesda, MD 20892 USA. RP Yamaguchi, TP (reprint author), NCI, Canc Res Ctr, Canc & Dev Biol Lab, NIH, 1050 Boyles St,Bldg 539,Rm 218, Frederick, MD 21702 USA. EM tyamaguchi@ncifcrf.gov NR 21 TC 30 Z9 32 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-133X J9 GENE EXPR PATTERNS JI Gene Expr. Patterns PD NOV PY 2004 VL 5 IS 1 BP 97 EP 105 DI 10.1016/j.modgep.2004.06.001 PG 9 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 874RR UT WOS:000225368000013 PM 15533824 ER PT J AU Ma, CM AF Ma, CM TI Spatial and temporal expression patterns of Xenopus Nkx-2.3 gene in skin epidermis during metamorphosis SO GENE EXPRESSION PATTERNS LA English DT Article DE metamorphosis; Xenopus; XNkx-2.3; 63 kDa keratin; epidermis ID TINMAN-RELATED GENES; THYROID-HORMONE; HOMEOBOX GENES; HEART DEVELOPMENT; DIFFERENTIAL EXPRESSION; CARDIAC DIFFERENTIATION; LAEVIS; HOMOLOGS; XNKX2-5; NKX2-3 AB Using PCR cloning, the mRNA of XNkx-2.3 gene, a Xenopus tinman homologue, was identified in a cDNA library prepared from thyroid hormone (T-3)-treated tadpole skin. Quantitative RT-PCR and RNase Protection Assay confirmed the expression of XNkx-2.3 in adult frog skin and its amount was similar to the amount found in heart. In situ hybridization indicated that XNkx-2.3 was expressed in the frog epidermis. Further analysis of XNkx-2.3 expression patterns demonstrates that it shares great similarities with a 63 kDa keratin, a well-characterized marker for skin maturation, in the following aspects. First, XNkx-2.3 was expressed in tadpole skin during metamorphosis (stages 55-59), but not in pre-metamorphic (stage 54) skin. Secondly, XNkx-2.3 expression in skin responded to T-3 stimulation because it could be precociously induced by T-3 at pre-metamorphic stage, both in tadpoles and in cultures of skin explants. Finally, the T-3-induced appearance of XNkx-2.3 in head skin occurred earlier and at higher level than that in tail skin. These data suggest that XNkx-2.3 may be an important factor for skin maturation and may also serve as a good marker to indicate the maturation of Xenopus epidermis. (C) 2004 Elsevier B.V. All rights reserved. C1 NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. RP Ma, CM (reprint author), NICHHD, Lab Mammalian Genes & Dev, NIH, 2B211,Bldg 6B,9000 Rockville Pike, Bethesda, MD 20892 USA. EM mach@mail.nih.gov NR 31 TC 3 Z9 3 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-133X J9 GENE EXPR PATTERNS JI Gene Expr. Patterns PD NOV PY 2004 VL 5 IS 1 BP 129 EP 134 DI 10.1016/j.modgep.2004.05.003 PG 6 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 874RR UT WOS:000225368000017 PM 15533828 ER EF