FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Wilson, WH O'Connor, OA Czuczman, MS LaCasce, A Gerecitano, J Leonard, JP Tulpule, A Xiong, H Chiu, YL Busman, T Enschede, S Krivoshik, A Humerickhouse, R AF Wilson, Wyndham H. O'Connor, Owen A. Czuczman, Myron S. LaCasce, Ann Gerecitano, John Leonard, John P. Tulpule, Anil Xiong, Hao Chiu, Yi-Lin Busman, Todd Enschede, Sari Krivoshik, Andrew Humerickhouse, Rod TI Phase 1/2a Study of ABT-263 in Relapsed or Refractory Lymphoid Malignancies. SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Wilson, Wyndham H.] NCI, CCR, NIH, Bethesda, MD 20892 USA. [O'Connor, Owen A.] NYU, Langone Med Ctr, Inst Canc, New York, NY USA. [Czuczman, Myron S.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [LaCasce, Ann] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gerecitano, John] Mem Sloan Kettering Canc Ctr, Lymphoma Serv, New York, NY 10021 USA. [Leonard, John P.] Weill Cornell Med Coll, New York, NY USA. [Tulpule, Anil] USC, Sch Med, Norris Canc Ctr, Los Angeles, CA USA. [Xiong, Hao; Chiu, Yi-Lin; Busman, Todd; Enschede, Sari; Krivoshik, Andrew; Humerickhouse, Rod] Abbott Labs, Abbott Pk, IL 60064 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 20 PY 2009 VL 114 IS 22 BP 682 EP 682 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725802079 ER PT J AU Katzmann, J Clark, R Dispenzieri, A Kyle, R Landgren, O Bradwell, A Rajkumar, SV AF Katzmann, Jerry Clark, Raynell Dispenzieri, Angela Kyle, Robert Landgren, Ola Bradwell, Arthur Rajkumar, S. Vincent TI Isotype-Specific Heavy/Light Chain (HLC) Suppression as a Predictor of Myeloma Development in Monoclonal Gammopathy of Undetermined Significance (MGUS). SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Katzmann, Jerry; Clark, Raynell; Dispenzieri, Angela; Kyle, Robert; Rajkumar, S. Vincent] Mayo Clin, Rochester, MN USA. [Landgren, Ola] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Bradwell, Arthur] Univ Birmingham, Sch Med, Dept Immunol, Birmingham B15 2TT, W Midlands, England. NR 0 TC 1 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 20 PY 2009 VL 114 IS 22 BP 711 EP 711 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725802156 ER PT J AU Landgren, O Devesa, S Mink, P Anderson, WF Weiss, B Kristinsson, SY McGlynn, K AF Landgren, Ola Devesa, Susan Mink, Pamela Anderson, William F. Weiss, Brendan Kristinsson, Sigurdur Y. McGlynn, Katherine TI African-American Multiple Myeloma Patients Have a Better Survival Than Caucasian Patients: a Population-Based Study Including 28,636 Patients SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Landgren, Ola] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Devesa, Susan; Anderson, William F.; McGlynn, Katherine] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Mink, Pamela] Emory Univ, Atlanta, GA 30322 USA. [Weiss, Brendan] Walter Reed Army Med Ctr, Washington, DC 20307 USA. [Kristinsson, Sigurdur Y.] Karolinska Univ Hosp & Inst, Div Hematol, Dept Med, Stockholm, Sweden. RI Kristinsson, Sigurdur /M-2910-2015 OI Kristinsson, Sigurdur /0000-0002-4964-7476 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 20 PY 2009 VL 114 IS 22 BP 727 EP 727 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725802200 ER PT J AU Kristinsson, SY Pfeiffer, R Bjorkhohm, M Goldin, LR Schulman, S Blimark, C Mellqvist, UH Wahlin, A Turesson, I Landgren, O AF Kristinsson, Sigurdur Y. Pfeiffer, Ruth Bjorkhohm, Magnus Goldin, Lynn R. Schulman, Sam Blimark, Cecilie Mellqvist, Ulf-Henrik Wahlin, Anders Turesson, Ingemar Landgren, Ola TI Arterial and Venous Thrombosis in Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma: A Population-Based Study SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Kristinsson, Sigurdur Y.; Bjorkhohm, Magnus] Karolinska Univ Hosp, Dept Med, Div Hematol, Stockholm, Sweden. [Kristinsson, Sigurdur Y.; Bjorkhohm, Magnus] Karolinska Inst, Stockholm, Sweden. [Pfeiffer, Ruth] NCI, Biostat Branch, NIH, Bethesda, MD 20892 USA. [Goldin, Lynn R.] NCI, Genet Epidemiol Branch, NIH, Bethesda, MD 20892 USA. [Schulman, Sam] McMaster Univ, Dept Med, Hamilton, ON, Canada. [Blimark, Cecilie; Mellqvist, Ulf-Henrik] Sahlgrens Univ Hosp, Dept Med, Sect Hematol & Coagulat, S-41345 Gothenburg, Sweden. [Wahlin, Anders] Umea Univ Hosp, S-90185 Umea, Sweden. [Turesson, Ingemar] Malmo Univ Hosp, Dept Med, Malmo, Sweden. [Landgren, Ola] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. RI Pfeiffer, Ruth /F-4748-2011; Wahlin, Anders/F-6043-2013; Kristinsson, Sigurdur /M-2910-2015 OI Wahlin, Anders/0000-0001-6402-0463; Kristinsson, Sigurdur /0000-0002-4964-7476 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 20 PY 2009 VL 114 IS 22 BP 743 EP 743 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725802240 ER PT J AU Miasnikova, GY Niu, XM Nouraie, M Sergueeva, AI Okhotin, DJ Ammosova, T Nekhai, S Aliyu, Z Sable, C Dham, N Gordeuk, VR AF Miasnikova, Galina Y. Niu, Xiaomei Nouraie, Mehdi Sergueeva, Adelina I. Okhotin, Daniel J. Ammosova, Tatiana Nekhai, Sergei Aliyu, Zakari Sable, Craig Dham, Niti Gordeuk, Victor R. TI Effect of Phlebotomy Therapy On Hemoglobin Concentration and Tricuspid Regurgitation Velocity in Chuvash Polycythemia SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Miasnikova, Galina Y.] Chuvash Republ Clin Hosp 1, Chuvashia, Russia. [Nouraie, Mehdi; Ammosova, Tatiana] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20059 USA. [Sergueeva, Adelina I.] Cheboksary Childrens Hosp, Cheboksary, Russia. [Okhotin, Daniel J.] Russian Res Serv Corp, Vancouver, WA USA. [Aliyu, Zakari] NIH, Catonsville, MD USA. [Sable, Craig; Dham, Niti] Childrens Natl Med Ctr, Washington, DC 20010 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 20 PY 2009 VL 114 IS 22 BP 753 EP 753 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725802265 ER PT J AU Elliott, NE Cleveland, S Grann, V Janik, JE Dave, UP AF Elliott, Natalina E. Cleveland, Susan Grann, Victor Janik, John E. Dave, Utpal P. TI The Role of JAK3 mutations in Adult T-Cell Leukemia/Lymphoma SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Elliott, Natalina E.; Cleveland, Susan; Dave, Utpal P.] Vanderbilt Univ, Ctr Med, Nashville, TN 37232 USA. [Grann, Victor] Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY USA. [Janik, John E.] NCI, Metab Branch, Ctr Canc Res, 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 20 PY 2009 VL 114 IS 22 BP 769 EP 769 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725802308 ER PT J AU Bonzheim, I Irmler, M Anastasov, N Klier-Richter, M Schaefer, S Beckers, J Pittaluga, S Fend, F Raffeld, M Quintanilla-Martinez, L AF Bonzheim, Irina Irmler, Martin Anastasov, Natasa Klier-Richter, Margit Schaefer, Sabine Beckers, Johannes Pittaluga, Stefania Fend, Falko Raffeld, Mark Quintanilla-Martinez, Leticia TI Identification of Genes Which Play a Crucial Role in C/EBP beta Downstream Signalling in ALK(+) ALCL Cell Lines SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting and Exposition of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Bonzheim, Irina; Klier-Richter, Margit; Schaefer, Sabine; Fend, Falko; Quintanilla-Martinez, Leticia] Univ Tubingen, Univ Tubingen Hosp, Tubingen, Germany. [Irmler, Martin; Beckers, Johannes] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Expt Genet, Neuherberg, Germany. [Pittaluga, Stefania] NCI, NIH, Bethesda, MD 20892 USA. [Raffeld, Mark] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RI Irmler, Martin/B-3317-2013; Anastasov, Natasa/M-9848-2014 OI Irmler, Martin/0000-0003-3169-479X; Anastasov, Natasa/0000-0002-4088-1119 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 20 PY 2009 VL 114 IS 22 BP 770 EP 770 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725802311 ER PT J AU Cardesa-Salzmann, TM Colomo, L Climent, F Gonzalez-Barca, E Lopez-Guillermo, A Gutierrez, G Mercadal, S Gascoyne, RD Connors, JM Rimsza, LM Braziel, RM Cook, JR Tubbs, RR Rosenwald, A Ott, G Mate, JL Ribera, JM Arenillas, L Serrano, S Combalia, N Delabie, J Lenz, G Wright, G Jaffe, ES Staudt, LM Chan, WC Weissenburger, D Campo, E AF Cardesa-Salzmann, Teresa M. Colomo, Luis Climent, Fina Gonzalez-Barca, Eva Lopez-Guillermo, Armando Gutierrez, Gonzalo Mercadal, Santiago Gascoyne, Randy D. Connors, Joseph M. Rimsza, Lisa M. Braziel, Rita M. Cook, James R. Tubbs, Raymond R. Rosenwald, Andreas Ott, German Luis Mate, Jose Ribera, Josep-Maria Arenillas, Leonor Serrano, Sergi Combalia, Neus Delabie, Jan Lenz, Georg Wright, George Jaffe, Elaine S. Staudt, Louis M. Chan, Wing C. Weissenburger, Dennis Campo, Elias TI High Microvascular Density Correlates with Poor Outcome in Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Treated with Rituximab Plus Chemotherapy (R-CT). SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Cardesa-Salzmann, Teresa M.; Colomo, Luis; Lopez-Guillermo, Armando; Gutierrez, Gonzalo; Campo, Elias] Hosp Clin Barcelona, Barcelona, Spain. [Climent, Fina] Hosp Univ Bellvitge, Barcelona, Spain. [Gonzalez-Barca, Eva] Hosp Univ Bellvitge, Lhospitalet De Llobregat, Spain. [Mercadal, Santiago] Inst Catala Oncol, Lhospitalet De Llobregat, Spain. [Gascoyne, Randy D.] British Columbia Canc Agcy, Dept Pathol, CTAG Lab, Vancouver, BC V5Z 4E6, Canada. [Gascoyne, Randy D.] British Columbia Canc Agcy, Dept Lab Med, CTAG Lab, Vancouver, BC V5Z 4E6, Canada. [Rimsza, Lisa M.] Univ Arizona, Tucson, AZ USA. [Braziel, Rita M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Cook, James R.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Tubbs, Raymond R.] Cleveland Clin, Cleveland, OH 44106 USA. [Rosenwald, Andreas] Univ Wurzburg, Wurzburg, Germany. [Ott, German] LLMPP, Wurzburg, Germany. [Luis Mate, Jose] Hosp Badalona Germans Trias & Pujol, Badalona, Spain. [Ribera, Josep-Maria] Hosp Badalona Germans Trias & Pujol, ICO, Barcelona, Spain. [Arenillas, Leonor] Hosp del Mar, Pathol GRETNHE, IMIM, Barcelona, Spain. [Serrano, Sergi] Hosp del Mar, Dept Pathol, Barcelona, Spain. [Combalia, Neus] Hosp Parc Tauli, Sabadell, Spain. [Delabie, Jan] Norwegian Radium Hosp, Oslo, Norway. [Wright, George; Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Chan, Wing C.; Weissenburger, Dennis] Univ Nebraska Med Ctr, Omaha, NE USA. RI Colomo, Luis/A-2259-2016 OI Colomo, Luis/0000-0001-5236-5085 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 20 PY 2009 VL 114 IS 22 BP 772 EP 772 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725802316 ER PT J AU Greenberg, KE Li, L Huso, D Wolff, L Small, D AF Greenberg, Kathleen E. Li, Li Huso, David Wolff, Linda Small, Donald TI Retroviral Insertional Mutagenesis Reveals Genes That Cooperate with FLT3-ITD in Leukemogenesis SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Li, Li; Huso, David] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Wolff, Linda] NCI, 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 20 PY 2009 VL 114 IS 22 BP 776 EP 777 PG 2 WC Hematology SC Hematology GA 532DS UT WOS:000272725802328 ER PT J AU Odenike, O Curran, E Iyengar, N Popplewell, L Kirschbaum, M Erba, HP Green, M Poire, X Ihonor, P Diaz-Flores, E Shannon, K Atallah, E Wade, JL Perdekamp, M Nattam, S Thomas, SP Smith, SE Doyle, LA Rich, ES Larson, RA Stock, W AF Odenike, Olatoyosi Curran, Emily Iyengar, Neil Popplewell, Leslie Kirschbaum, Mark Erba, Harry P. Green, Margaret Poire, Xavier Ihonor, Pamela Diaz-Flores, Ernesto Shannon, Kevin Atallah, Ehab Wade, James L., III Perdekamp, Maria Nattam, Sreenivasa Thomas, Sachdev P. Smith, Scott E. Doyle, L. Austin Rich, Elizabeth Shima Larson, Richard A. Stock, Wendy TI Phase II Study of the Oral MEK Inhibitor AZD6244 in Advanced Acute Myeloid Leukemia (AML) SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Odenike, Olatoyosi; Curran, Emily; Iyengar, Neil; Green, Margaret; Poire, Xavier; Ihonor, Pamela; Rich, Elizabeth Shima; Larson, Richard A.; Stock, Wendy] Univ Chicago, Chicago, IL 60637 USA. [Popplewell, Leslie; Kirschbaum, Mark] City Hope Natl Med Ctr, Duarte, CA USA. [Erba, Harry P.] Univ Michigan, Ann Arbor, MI 48109 USA. [Atallah, Ehab] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Diaz-Flores, Ernesto; Shannon, Kevin] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Wade, James L., III; Perdekamp, Maria] Decatur Mem Hosp, Decatur, IL USA. [Nattam, Sreenivasa] Ft Wayne Med Oncol & Hematol Inc, Ft Wayne, IN USA. [Thomas, Sachdev P.] Oncol Hematol Associates, Peoria, IL USA. [Smith, Scott E.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Doyle, L. Austin] NCI, Canc Therapy Evaluat Program, 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 20 PY 2009 VL 114 IS 22 BP 821 EP 822 PG 2 WC Hematology SC Hematology GA 532DS UT WOS:000272725802449 ER PT J AU Pulanic, D Liewehr, D Steinberg, S Mitchell, SA Baird, K Cowen, EW Joe, G Williams, KM Avila, D Salit, RB Atlam, N Carpenter, A Hakim, F Bishop, M Gress, RE Pavletic, SZ AF Pulanic, Drazen Liewehr, David Steinberg, Seth Mitchell, Sandra A. Baird, Kristin Cowen, Edward W. Joe, Galen Williams, Kirsten M. Avila, Daniele Salit, Rachel B. Atlam, Niveen Carpenter, Ashley Hakim, Fran Bishop, Michael Gress, Ronald E. Pavletic, Steven Z. TI Determinants of Platelet Counts in Patients with Chronic Graft Versus Host Disease SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Pulanic, Drazen; Williams, Kirsten M.; Avila, Daniele; Salit, Rachel B.; Carpenter, Ashley; Hakim, Fran; Bishop, Michael; Gress, Ronald E.; Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. [Liewehr, David; Steinberg, Seth; Atlam, Niveen] NCI, Biostat & Data Management Sect, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. [Mitchell, Sandra A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Baird, Kristin] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Cowen, Edward W.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. [Joe, Galen] NIH, Ctr Clin, Dept Rehabil 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 20 PY 2009 VL 114 IS 22 BP 884 EP 884 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725802611 ER PT J AU Foglietta, M Neelapu, S Fowler, DH Steinberg, SM Kwak, LW Bishop, MR AF Foglietta, Myriam Neelapu, Sattva Fowler, Daniel H. Steinberg, Seth M. Kwak, Larry W. Bishop, Michael R. TI Analysis of Antigen-Specific T-Cell Responses and Regulatory T Cells Following Sibling Donor Immunization with Patient-Derived Idiotype Vaccine Prior to Non-Myeloablative Allogeneic Stem Cell Transplantation for Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Foglietta, Myriam] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Houston, TX 77030 USA. [Fowler, Daniel H.; Steinberg, Seth M.; Bishop, Michael R.] NCI, 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 20 PY 2009 VL 114 IS 22 BP 887 EP 887 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725802618 ER PT J AU Jacobsohn, D Chai, XY Kurland, B Arai, S Arora, M Cutler, C Jagasia, M Pavletic, SZ Vogelsang, G Lee, SJ Flowers, MED AF Jacobsohn, David Chai, Xiaoyu Kurland, Brenda Arai, Sally Arora, Mukta Cutler, Corey Jagasia, Madan Pavletic, Steven Z. Vogelsang, Georgia Lee, Stephanie J. Flowers, Mary E. D. TI Correlation of the NIH and Vienna Skin Scores with Provider and Patient-Reported Skin Changes in Chronic Graft-Versus-Host Disease (GVHD) SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Jacobsohn, David] Childrens Mem Hosp, Chicago, IL 60614 USA. [Chai, Xiaoyu; Kurland, Brenda; Lee, Stephanie J.; Flowers, Mary E. D.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Arai, Sally] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Arora, Mukta] Univ Minnesota, Minneapolis, MN USA. [Cutler, Corey] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Jagasia, Madan] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. [Vogelsang, Georgia] Johns Hopkins Univ, Baltimore, MD 21218 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 20 PY 2009 VL 114 IS 22 BP 889 EP 889 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725802624 ER PT J AU Stringaris, K Adams, S Uribe, M Eniafe, R Wu, C Savani, BN Barrett, AJ AF Stringaris, Kate Adams, Sharon Uribe, Marcela Eniafe, Rhoda Wu, Colin Savani, Bipin N. Barrett, A. John TI A Reduced Rate of Leukaemia Relapse After HLA-Identical Sibling Stem Cell Transplantation for Acute Myeloid Leukaemia but Not Other Haematological Malignancies Is Associated with Donor KIR Genes 2DL5A, 2DS1 and 3DS1 SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Stringaris, Kate; Eniafe, Rhoda; Wu, Colin] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Savani, Bipin N.] Vanderbilt Univ, Nashville, TN 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 20 PY 2009 VL 114 IS 22 BP 899 EP 900 PG 2 WC Hematology SC Hematology GA 532DS UT WOS:000272725802650 ER PT J AU Liu, WL Lee, HW Rodgers, GP AF Liu, Wenli Lee, Hyun W. Rodgers, Griffin P. TI Olfactomedin 4 Mediates All-Trans Retinoic Acid Induced Growth Inhibition, Differentiation and Apoptosis in Myeloid Leukemia Cells and Inhibits 4E-BP1 Phosphorylation SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Liu, Wenli; Lee, Hyun W.; Rodgers, Griffin P.] NHLBI, Mol & Clin 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 20 PY 2009 VL 114 IS 22 BP 946 EP 946 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725802763 ER PT J AU Visconte, V de Latour, RP Calado, RT Desierto, M Chen, JC Young, NS AF Visconte, Valeria de Latour, Regis Peffault Calado, Rodrigo T. Desierto, Marie Chen, Jichun Young, Neal S. TI Reduced Hematopoietic Stem Cell Function in a Mouse Model with Conditional Pig-a Gene Deletion. SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Visconte, Valeria; de Latour, Regis Peffault; Calado, Rodrigo T.; Desierto, Marie; Chen, Jichun; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. 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 20 PY 2009 VL 114 IS 22 BP 958 EP 959 PG 2 WC Hematology SC Hematology GA 532DS UT WOS:000272725802796 ER PT J AU Melenhorst, JJ Scheinberg, P Williams, A Keyvanfar, K Smith, M McCoy, JP Hensel, NF Barrett, AJ AF Melenhorst, J. Joseph Scheinberg, Phillip Williams, Ann Keyvanfar, Keyvan Smith, Melody McCoy, J. Philip, Jr. Hensel, Nancy F. Barrett, A. John TI Both Naive and Memory T-Cell Subsets Participate in Alloresponses to HLA-Mismatched Targets - Implications for Adoptive Transfer of Viral Antigen-Specific T Cells. SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Melenhorst, J. Joseph; Williams, Ann; Keyvanfar, Keyvan; Hensel, Nancy F.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RI Scheinberg, Phillip/H-5251-2012 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 20 PY 2009 VL 114 IS 22 BP 963 EP 963 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725802807 ER PT J AU Kato, K Cui, SAY Kuick, R Mineishi, S Hexner, E Ferrara, JLM Marquez, VE Emerson, SG Zhang, Y AF Kato, Koji Cui, Shuaiying Kuick, Rork Mineishi, Shin Hexner, Elizabeth Ferrara, James L. M. Marquez, Victor E. Emerson, Stephen G. Zhang, Yi TI Alloreactive CD8(+) Effector T Cells Proliferate and Persist Upon Chronic Exposure to Alloantigens through Reactivation of Stem Cell Transcriptional Programs. SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting and Exposition of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Kato, Koji; Cui, Shuaiying; Mineishi, Shin; Ferrara, James L. M.] Univ Michigan, Blood & Marrow Transplant Program, Ann Arbor, MI 48109 USA. [Kuick, Rork] Univ Michigan, Comprehens Canc Ctr Biostat Core, Ann Arbor, MI 48109 USA. [Hexner, Elizabeth] Univ Penn, Philadelphia, PA 19104 USA. [Marquez, Victor E.] NIH, Med Chem Lab, Frederick, MD USA. [Emerson, Stephen G.] Haverford Coll, Haverford, PA 19041 USA. [Zhang, Yi] Univ Michigan, Sch Med, Ann Arbor, MI 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 20 PY 2009 VL 114 IS 22 BP 964 EP 964 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725802812 ER PT J AU Amarnath, S Costanzo, CM Foley, J Mariotti, J Konecki, DM Gangopadhyay, A Eckhaus, M Wong, S Levine, B June, CH Fowler, DH AF Amarnath, Shoba Costanzo, Carliann M. Foley, Jason Mariotti, Jacopo Konecki, Daniel M. Gangopadhyay, Anu Eckhaus, Michael Wong, Susan Levine, Bruce June, Carl H. Fowler, Daniel H. TI Rapamycin-Induced Autophagy Generates Anti-Apoptotic Th1/Tc1 Cells That Mediate Increased Xenogeneic Gvhd. SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Amarnath, Shoba; Costanzo, Carliann M.; Konecki, Daniel M.; Gangopadhyay, Anu; Eckhaus, Michael] NCI, Expt Transplantat Immunol Branch, NIH, Bethesda, MD 20892 USA. [Foley, Jason] Jason Foley, Expt Transplantat & Immunol, Bethesda, MD USA. [Mariotti, Jacopo] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Wong, Susan] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. [Levine, Bruce; June, Carl H.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. RI Levine, Bruce/D-1688-2009 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 20 PY 2009 VL 114 IS 22 BP 969 EP 969 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725803012 ER PT J AU Ballas, SK Bauserman, RL McCarthy, WF Waclawiw, MA Barton, BA AF Ballas, Samir K. Bauserman, Robert L. McCarthy, William F. Waclawiw, Myron A. Barton, Bruce A. TI Impact of Hydroxyurea On Employment Among Patients with Sickle Cell Anemia SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Ballas, Samir K.] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. [Bauserman, Robert L.; McCarthy, William F.; Barton, Bruce A.] Maryland Med Res Inst, Baltimore, MD USA. [Waclawiw, Myron A.] 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 20 PY 2009 VL 114 IS 22 BP 980 EP 980 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725803041 ER PT J AU Hsieh, MM Duan, ZG Wright, EC Tisdale, JF Rodgers, GP AF Hsieh, Matthew M. Duan, Zhigang Wright, Elizabeth C. Tisdale, John F. Rodgers, Griffin P. TI There Is No Difference in the Prevalence of Neutropenia or Fever in Hospitalized African-Americans and Caucasians with Cancer in the SEER-Medicare Database SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Rodgers, Griffin P.] NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD USA. [Tisdale, John F.] NHLBI, MCHB, 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 20 PY 2009 VL 114 IS 22 BP 986 EP 986 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725803055 ER PT J AU Allen, RS Jin, P North, T Goessling, W Tian, Y Metzger, ME Bonifacino, AC Stroncek, D Zon, LI Donahue, RE AF Allen, Robyn S. Jin, Ping North, Trista Goessling, Wolfram Tian, Yu Metzger, Mark E. Bonifacino, Aylin C. Stroncek, David Zon, Leonard I. Donahue, Robert E. TI Global Gene Expression Signatures in CD34+Hematopoietic Cells Following Exposure to 16,16-Dimethylprostaglandin E2 SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Allen, Robyn S.; Tian, Yu; Metzger, Mark E.; Bonifacino, Aylin C.; Donahue, Robert E.] NHLBI, Hematol Branch, Rockville, MD USA. [Jin, Ping; Stroncek, David] NIH, Bethesda, MD 20892 USA. [North, Trista] Harvard Univ, Sch Med, Dept Pathol, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Goessling, Wolfram] Harvard Univ, Brigham & Womens Hosp, Div Genet, Sch Med, Boston, MA 02115 USA. [Goessling, Wolfram] Harvard Univ, Brigham & Womens Hosp, Div Gastroenterol, Sch Med, Boston, MA 02115 USA. [Goessling, Wolfram] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Zon, Leonard I.] Harvard Stem Cell Inst, Boston, MA 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 20 PY 2009 VL 114 IS 22 BP 994 EP 994 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725803079 ER PT J AU Meier, ER Byrnes, C Weissman, M Noel, P Luban, NLC Miller, JL AF Meier, Emily Riehm Byrnes, Colleen Weissman, Maxine Noel, Pierre Luban, Naomi L. C. Miller, Jeffery L. TI Combining Fetal Hemoglobin and Reticulocytosis to Index Clinical Severity of Sickle Cell Disease in Children. SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Meier, Emily Riehm] NIDDK, Div Hematol, Childrens Natl Med Ctr, NIH, Washington, DC USA. [Meier, Emily Riehm] NIDDK, Mol Med Branch, NIH, Washington, DC USA. [Byrnes, Colleen; Miller, Jeffery L.] NIDDK, Mol Med Branch, NIH, Bethesda, MD USA. [Weissman, Maxine; Noel, Pierre] NIH, Serv Hematol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Luban, Naomi L. C.] George Washington Univ, Childrens Natl Med Ctr, Div Hematol, Med Ctr, Washington, DC USA. [Luban, Naomi L. C.] George Washington Univ, Dept Pediat, Med Ctr, Washington, DC 20052 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 20 PY 2009 VL 114 IS 22 BP 1003 EP 1004 PG 2 WC Hematology SC Hematology GA 532DS UT WOS:000272725803112 ER PT J AU Klings, ES Dworkis, DA Sedgewick, A Hartley, SW Allison, AK Telen, MJ Kato, GJ Gladwin, M Sebastiani, P Baldwin, CT Steinberg, MH AF Klings, Elizabeth S. Dworkis, Daniel A. Sedgewick, Amanda Hartley, Stephen W. Allison, Ashley-Koch Telen, Marilyn J. Kato, Gregory J. Gladwin, Mark Sebastiani, Paola Baldwin, Clinton T. Steinberg, Martin H. TI Genetic Polymorphisms in NEDD4L Are Associated with Pulmonary Hypertension of Sickle Cell Anemia. SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Klings, Elizabeth S.] Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA. [Sedgewick, Amanda; Hartley, Stephen W.; Sebastiani, Paola] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Allison, Ashley-Koch] Duke Univ, Dept Med, Durham, NC USA. [Telen, Marilyn J.] Duke Univ, Med Ctr, Durham, NC USA. [Kato, Gregory J.] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA. [Gladwin, Mark] Univ Pittsburgh, Med Ctr, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA. [Dworkis, Daniel A.; Baldwin, Clinton T.] Boston Univ, Sch Med, Ctr Human Genet, Boston, MA 02118 USA. [Steinberg, Martin H.] Boston Univ, Sch Med, Dept Med, Div Hematol & Oncol, Boston, MA 02118 USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 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 20 PY 2009 VL 114 IS 22 BP 1006 EP 1006 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725803118 ER PT J AU Hsu, LL Noguchi, AC Noguchi, C Wood, KC Taylor, JG Kato, GJ Gladwin, M Diwan, B AF Hsu, Lewis L. Noguchi, Audrey C. Noguchi, Constance Wood, Katherine C. Taylor, James G. Kato, Gregory J. Gladwin, Mark Diwan, Bhalchandra TI Liver Hypoxia and Tissue Injury Are Specific to Sickle Cell Mice in An Experimental Model of Sickle Cell Vaso-Occlusion SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 Childrens Natl Med Ctr, Washington, DC 20010 USA. [Noguchi, Audrey C.] NHLBI, Vasc Med Branch, Bethesda, MD 20892 USA. [Noguchi, Constance] NIDDK, Mol Med Branch, NIH, Bethesda, MD USA. [Wood, Katherine C.; Taylor, James G.] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA. [Gladwin, Mark] Univ Pittsburgh, Med Ctr, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA. [Diwan, Bhalchandra] NCI, Basic Sci Program, SAIC Frederick, Frederick, MD 21701 USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 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 20 PY 2009 VL 114 IS 22 BP 1008 EP 1009 PG 2 WC Hematology SC Hematology GA 532DS UT WOS:000272725803125 ER PT J AU Castro, OL Nouraie, M Luchtman-Jones, L Niu, XM Minniti, C Campbell, AD Rana, SR Kato, GJ Gladwin, M Gordeuk, VR AF Castro, Oswaldo L. Nouraie, Mehdi Luchtman-Jones, Lori Niu, Xiaomei Minniti, Caterina Campbell, Andrew D. Rana, Sohail R. Kato, Gregory J. Gladwin, Mark Gordeuk, Victor R. TI Lower Ferritin Concentrations Are Associated with Decreased Hemolysis in Sickle Cell Disease Children without Iron Overload SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Castro, Oswaldo L.; Nouraie, Mehdi; Niu, Xiaomei; Gordeuk, Victor R.] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20059 USA. [Luchtman-Jones, Lori] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Minniti, Caterina] NHLBI, Vasc Med Branch, Bethesda, MD 20892 USA. [Campbell, Andrew D.] Univ Michigan, Med Ctr, Ann Arbor, MI USA. [Rana, Sohail R.] Howard Univ Hosp, Dept Pediat & Child Hlth, Washington, DC USA. [Kato, Gregory J.] NHLBI, Pulm & Vasc Med Branch, Bethesda, MD 20892 USA. [Gladwin, Mark] Univ Pittsburgh, Med Ctr, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 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 20 PY 2009 VL 114 IS 22 BP 1009 EP 1009 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725803127 ER PT J AU Ballas, SK McCarthy, WF Bauseman, RI Castro, OL Swerdlow, PS Smith, W Waclawiw, MA Barton, BA AF Ballas, Samir K. McCarthy, William F. Bauseman, Robert I. Castro, Oswaldo L. Swerdlow, Paul S. Smith, Wally Waclawiw, Myron A. Barton, Bruce A. TI Patterns of Analgesic Utilization in the Multicenter Study of Hydroxyurea (MSH) SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Ballas, Samir K.] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. [McCarthy, William F.; Bauseman, Robert I.; Barton, Bruce A.] Maryland Med Res Inst, Baltimore, MD USA. [Castro, Oswaldo L.] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20059 USA. [Swerdlow, Paul S.] Wayne State Univ, Barbara Ann Karmanos Canc Inst, Detroit, MI USA. [Smith, Wally] Virginia Commonwealth Univ, Richmond, VA USA. [Waclawiw, Myron A.] 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 20 PY 2009 VL 114 IS 22 BP 1011 EP 1012 PG 2 WC Hematology SC Hematology GA 532DS UT WOS:000272725803133 ER PT J AU Ballas, SK McCarthy, WF Bauserman, RL Castro, OL Waclawiw, MA Barton, BA AF Ballas, Samir K. McCarthy, William F. Bauserman, Robert L. Castro, Oswaldo L. Waclawiw, Myron A. Barton, Bruce A. TI Sickle Cell Genetic Markers: Geographic Distribution and Relation to Pain Outcomes in Multicenter Study of Hydroxyurea in Sickle Cell Anemia SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. [McCarthy, William F.; Bauserman, Robert L.; Barton, Bruce A.] Maryland Med Res Inst, Baltimore, MD USA. [Castro, Oswaldo L.] Howard Univ, Ctr Sickle Cell Dis, Washington, DC USA. [Waclawiw, Myron A.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 20 PY 2009 VL 114 IS 22 BP 1013 EP 1014 PG 2 WC Hematology SC Hematology GA 532DS UT WOS:000272725803138 ER PT J AU Minniti, CP Hildesheim, M Sachdev, V Allen, D Castro, O Taylor, JG Kato, GJ AF Minniti, Caterina P. Hildesheim, Mariana Sachdev, Vandana Allen, Darlene Castro, Oswaldo Taylor, James G. Kato, Gregory J. TI Sickle Cell Leg Ulcers Are Associated with Hyperuricemia, Hemolysis, Pulmonary Hypertension and Death SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Minniti, Caterina P.] NIH, Chevy Chase, MD USA. [Hildesheim, Mariana; Allen, Darlene; Taylor, James G.; Kato, Gregory J.] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA. [Sachdev, Vandana] NIH, Translat Med Branch, Bethesda, MD 20892 USA. [Castro, Oswaldo] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20059 USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 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 20 PY 2009 VL 114 IS 22 BP 1014 EP 1014 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725803139 ER PT J AU Betal, SG Kato, GJ Lawrence, MP Seamon, C Setty, Y Stuart, MJ Krishnan, S AF Betal, Suhita Gayen Kato, Gregory J. Lawrence, Marlene Peters Seamon, Catherine Setty, Yamaja Stuart, Marie J. Krishnan, Suba TI Thrombin Generation in Sickle Cell Disease: Insights From Computerized Automated Thrombography SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Betal, Suhita Gayen; Setty, Yamaja; Stuart, Marie J.; Krishnan, Suba] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Kato, Gregory J.; Lawrence, Marlene Peters] NHLBI, Vasc Med Branch, 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 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 20 PY 2009 VL 114 IS 22 BP 1015 EP 1016 PG 2 WC Hematology SC Hematology GA 532DS UT WOS:000272725803142 ER PT J AU Chen, CL Janik, JE Kaucic, K Roskos, L Jallal, B Robbie, GJ AF Chen, Chunlin Janik, John E. Kaucic, Karen Roskos, Lorin Jallal, Bahija Robbie, Gabriel J. TI Population Pharmacokinetics of Siplizumab (MEDI-507), a Humanized Anti-CD2 Monoclonal Antibody, in Cancer Patients. SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Chen, Chunlin] Medimmune Inc, Translat Sci, Gaithersburg, MD USA. [Janik, John E.] NCI, Canc Res Ctr, 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 20 PY 2009 VL 114 IS 22 BP 1046 EP 1046 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725803225 ER PT J AU Buckstein, R Kuruvilla, J Chua, N Lee, C Macdonald, DA Al-Tourah, AJ Foo, A Walsh, W Ivy, SP Crump, M Eisenhauer, E AF Buckstein, Rena Kuruvilla, John Chua, Neil Lee, Christina Macdonald, David A. Al-Tourah, Abdulwahab J. Foo, Alison Walsh, Wendy Ivy, S. Percy Crump, Michael Eisenhauer, Elizabeth TI Sunitinib in Relapsed or Refractory Diffuse Large B Cell Lymphoma: Results of a Phase II Multi-Center Study of the NCIC Clinical Trials Group. SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Buckstein, Rena; Lee, Christina] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Kuruvilla, John; Crump, Michael] Princess Margaret Hosp, Univ Hlth Network, Dept Med Oncol & Hematol, Toronto, ON M4X 1K9, Canada. [Chua, Neil] Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. [Macdonald, David A.] QEII Hlth Sci Ctr, Halifax, NS, Canada. [Al-Tourah, Abdulwahab J.] BC Canc Ctr Fraser Valley Ctr, Surrey, BC, Canada. [Foo, Alison; Walsh, Wendy; Eisenhauer, Elizabeth] NCIC, Clin Trials Grp, Kingston, ON, Canada. [Ivy, S. Percy] NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 20 PY 2009 VL 114 IS 22 BP 1068 EP 1068 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725803284 ER PT J AU Zoppoli, G Cea, M Fruscione, F Bruzzone, S Soncini, D Bedognetti, D Moran, E Balleari, E Bruzzone, A Garuti, A Cirmena, G Rocco, I Gobbi, M Ghio, R Pommier, Y Carella, AM Ballestrero, A Parodi, S Patrone, F Nencioni, A AF Zoppoli, Gabriele Cea, Michele Fruscione, Floriana Bruzzone, Santina Soncini, Debora Bedognetti, Davide Moran, Eva Balleari, Enrico Bruzzone, Andrea Garuti, Anna Cirmena, Gabriella Rocco, Ilaria Gobbi, Marco Ghio, Riccardo Pommier, Yves Carella, Angelo Michele Ballestrero, Alberto Parodi, Silvio Patrone, Franco Nencioni, Alessio TI Potent Synergistic Activity of the NAD plus Synthesis Inhibitor APO866 and of the Apoptosis Inducer TRAIL in in Vitro and Ex Vivo Cellular Models of Non Hodgkin's Lymphoma and Chronic Lymphocytic Leukemia. SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Zoppoli, Gabriele; Gobbi, Marco; Pommier, Yves] NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. [Zoppoli, Gabriele; Cea, Michele; Soncini, Debora; Moran, Eva; Balleari, Enrico; Bruzzone, Andrea; Garuti, Anna; Cirmena, Gabriella; Rocco, Ilaria; Gobbi, Marco; Ghio, Riccardo; Ballestrero, Alberto; Patrone, Franco; Nencioni, Alessio] Univ Genoa, Dept Internal Med, I-16126 Genoa, Italy. [Fruscione, Floriana; Bruzzone, Santina] Univ Genoa, Dipartimento Med Sperimentale, Biochem Sect, I-16126 Genoa, Italy. [Bedognetti, Davide] Univ Study Genova, Dept Transfus Med, Genoa, Italy. [Carella, Angelo Michele] Univ San Martino, Azienda Osped, Div Hematol, BMT Unit, Genoa, Italy. [Parodi, Silvio] Univ Genoa, Dept Oncol Biol & Genet DOBIG, Genoa, Italy. RI Bedognetti, Davide/A-9090-2012; Bruzzone, Santina/A-4264-2015; Balleari, Enrico/R-3119-2016 OI Bruzzone, Santina/0000-0003-2034-3716; Balleari, Enrico/0000-0003-2186-8012 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 20 PY 2009 VL 114 IS 22 BP 1069 EP 1069 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725803288 ER PT J AU Rau, RE McIntyre, E Kaufmann, SH Espinoza-Delgado, I Karp, J Brown, P AF Rau, Rachel E. McIntyre, Emily Kaufmann, Scott H. Espinoza-Delgado, Igor Karp, Judith Brown, Patrick TI Combinations of the Histone Deacetylase Inhibitor Entinostat (SNDX-275, MS-275) and Imatinib Have Divergent Effects in Imatinib-Sensitive Vs. Imatinib-Resistant p210-(BCR/ABL) Expressing Cell Lines. SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting and Exposition of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Rau, Rachel E.; McIntyre, Emily; Brown, Patrick] Johns Hopkins Univ, Baltimore, MD USA. [Kaufmann, Scott H.] Mayo Clin, Rochester, MN USA. [Espinoza-Delgado, Igor] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Karp, Judith] Johns Hopkins Univ SOM, Div Hematol, 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 20 PY 2009 VL 114 IS 22 BP 1072 EP 1073 PG 2 WC Hematology SC Hematology GA 532DS UT WOS:000272725803297 ER PT J AU Gough, SM Chung, YJ Aplan, PD AF Gough, Sheryl M. Chung, Yang Jo Aplan, Peter D. TI Rag1 Deficiency Does Not Affect Myelodysplasia but Leads to More Rapid Leukemic Transformation in a Mouse Model of MDS. SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Gough, Sheryl M.; Chung, Yang Jo; Aplan, Peter D.] NCI, Genet Branch, CCR, Bethesda, MD 20892 USA. 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 20 PY 2009 VL 114 IS 22 BP 1089 EP 1089 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725803339 ER PT J AU Weiss, B Minter, A Laquer, M Howard, R Abadie, J Ascencao, J Schechter, GP Kuehl, M Landgren, O AF Weiss, Brendan Minter, Alex Laquer, Matthew Howard, Robin Abadie, Jude Ascencao, Joao Schechter, Geraldine P. Kuehl, Michael Landgren, Ola TI Patterns of Monoclonal Immunoglobulins and Serum Free Light Chains Are Significantly Different in African-American Compared to Caucasian MGUS Patients SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Weiss, Brendan; Minter, Alex] Walter Reed Army Med Ctr, Hematol Oncol Serv, Washington, DC 20307 USA. [Abadie, Jude] Walter Reed Army Med Ctr, Pathol & Area Lab Serv, Washington, DC 20307 USA. [Ascencao, Joao] Washington DC Vet Affairs Med Ctr, Hematol Serv, Washington, DC USA. [Schechter, Geraldine P.] Washington VA Med Ctr, Washington, DC USA. [Schechter, Geraldine P.] George Washington Univ, Washington, DC USA. [Kuehl, Michael] NCI, Genet Branch, Canc Res Ctr, Bethesda, MD 20892 USA. [Landgren, Ola] NCI, Med Oncol 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 20 PY 2009 VL 114 IS 22 BP 1108 EP 1109 PG 2 WC Hematology SC Hematology GA 532DS UT WOS:000272725803393 ER PT J AU Deffenbacher, KE Iqbal, J Liu, ZF Perkins, SL Lim, MS Fu, K Shen, YL Staudt, LM Rimsza, LM Jaffe, ES Rosenwald, A Ott, G Delabie, J Campo, E Gascoyne, RD Weisenburger, DD Greiner, TC Gross, T Chan, WC AF Deffenbacher, Karen E. Iqbal, Javeed Liu, Zhongfeng Perkins, Sherrie L. Lim, Megan S. Fu, Kai Shen, Yulei Staudt, Louis M. Rimsza, Lisa M. Jaffe, Elaine S. Rosenwald, Andreas Ott, German Delabie, Jan Campo, Elias Gascoyne, Randy D. Weisenburger, Dennis D. Greiner, Timothy C. Gross, Thomas Chan, Wing C. TI Chromosomal Alterations in Gene Expression-Defined Pediatric Aggressive B-Cell Non-Hodgkin Lymphoma (B-NHL) SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Deffenbacher, Karen E.; Iqbal, Javeed; Liu, Zhongfeng; Fu, Kai; Shen, Yulei; Weisenburger, Dennis D.; Greiner, Timothy C.; Chan, Wing C.] Univ Nebraska Med Ctr, Omaha, NE USA. [Perkins, Sherrie L.] ARUP Labs, Hematopathol Off, Salt Lake City, UT USA. [Lim, Megan S.] Univ Michigan, Ann Arbor, MI 48109 USA. [Staudt, Louis M.] NCI, Metab Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. [Rimsza, Lisa M.] Univ Arizona, Tucson, AZ USA. [Rosenwald, Andreas; Ott, German] Univ Wurzburg, Wurzburg, Germany. [Campo, Elias] Hosp Clin Barcelona, Barcelona, Spain. [Delabie, Jan] Norwegian Radium Hosp, Oslo, Norway. [Gascoyne, Randy D.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Gross, Thomas] Ohio State Univ, Nationwide Childrens Hosp, Columbus, OH 43210 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 20 PY 2009 VL 114 IS 22 BP 1142 EP 1142 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725803477 ER PT J AU Rudelius, M Pittaluga, S Sebasigari, D Davies-Hill, T Klier, M Quintanilla-Martinez, L Fend, F Tabe, Y Raffeld, M AF Rudelius, Martina Pittaluga, Stefania Sebasigari, Denise Davies-Hill, Theresa Klier, Margit Quintanilla-Martinez, Leticia Fend, Falko Tabe, Yoko Raffeld, Mark TI PTEN Regulates SYK-Directed AKT Activation in MCL. SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Rudelius, Martina] Tech Univ Munich, Inst Pathol, Munich, Germany. [Pittaluga, Stefania; Sebasigari, Denise; Davies-Hill, Theresa; Tabe, Yoko; Raffeld, Mark] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Klier, Margit; Quintanilla-Martinez, Leticia; Fend, Falko] Univ Tubingen, Univ Tubingen Hosp, Tubingen, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 20 PY 2009 VL 114 IS 22 BP 1149 EP 1149 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725803496 ER PT J AU Metais, JY Winkler, T Calado, RT Dunbar, CE AF Metais, Jean-Yves Winkler, Thomas Calado, Rodrigo T. Dunbar, Cynthia E. TI BCL2A1 Is a Survival and Immortalization Factor for Primitive Hematopoietic Cells SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Metais, Jean-Yves; Winkler, Thomas; Calado, Rodrigo T.; Dunbar, Cynthia E.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. 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 20 PY 2009 VL 114 IS 22 BP 1155 EP 1155 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725803512 ER PT J AU Greenblatt, SM Li, L Slape, C Huso, D Aplan, PD Small, D AF Greenblatt, Sarah M. Li, Li Slape, Christopher Huso, David Aplan, Peter D. Small, Donald TI Knock-in of a FLT3 Internal Tandem Duplication Mutation Cooperates with a NUP98-HOXD13 Fusion to Generate Acute Leukemia in a Mouse Model. SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Li, Li; Huso, David] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Slape, Christopher] Royal Melbourne Hosp, Bone Marrow Res Lab, Parkville, MD USA. [Aplan, Peter D.] NCI, Genet Branch, NIH, CCR, 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 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 20 PY 2009 VL 114 IS 22 BP 1156 EP 1157 PG 2 WC Hematology SC Hematology GA 532DS UT WOS:000272725803516 ER PT J AU Visconte, V de Latour, RP Raghavachari, N Liu, DL Keyvanfar, K Nunez, O Young, NS AF Visconte, Valeria de Latour, Regis Peffault Raghavachari, Nalini Liu, Delong Keyvanfar, Keyvan Nunez, Olga Young, Neal S. TI Differential Gene Expression Profile in the T Cell Compartment Between Classic PNH and Aplastic Anemia/PNH Syndrome SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Visconte, Valeria; de Latour, Regis Peffault; Raghavachari, Nalini; Keyvanfar, Keyvan; Nunez, Olga; Young, Neal S.] NHLBI, Hematol Branch, NIH, Genom Core Facil, Bethesda, MD 20892 USA. [Liu, Delong] CIT, Math & Stat Comp Lab, DCB, 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 20 PY 2009 VL 114 IS 22 BP 1173 EP 1173 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725803566 ER PT J AU Zhang, H Levine, B Voong, N Wayne, AS June, CH Mackall, CL AF Zhang, Hua Levine, Bruce Voong, Nga Wayne, Alan S. June, Carl H. Mackall, Crystal L. TI Artificial Antigen Presenting Cells (aAPC) Expanded NK-Mediated Enhanced Lysis of Allogeneic Tumor Cells Regardless of HLA Class I/KIR Mismatch and Its Implication of Use in Eradicating Acute Lymphoblastic Leukemia (ALL) SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Zhang, Hua; Mackall, Crystal L.] NCI, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Levine, Bruce; June, Carl H.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Voong, Nga] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. [Wayne, Alan S.] NCI, NIH, Bethesda, MD 20892 USA. RI Levine, Bruce/D-1688-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 20 PY 2009 VL 114 IS 22 BP 1178 EP 1178 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725803578 ER PT J AU Dhall, G Jones, T Radvinsky, D Robison, N Butturini, A Rubin, JI Gaynon, PS Panosyan, EH Avramis, IA Avramis, VI Ettinger, LJ Seibel, NL AF Dhall, Girish Jones, Tamekia Radvinsky, David Robison, Nathan Butturini, Anna Rubin, Joan I. Gaynon, Paul S. Panosyan, Eduard H. Avramis, Ioannis A. Avramis, Vassilios I. Ettinger, Lawrence J. Seibel, Nita L. TI Adverse Reactions to PEG and Erwinia Asparaginase and Correlation with Anti-Asparaginase Antibody Data and Survival in Children with Acute Lymphoblastic Leukemia (ALL): A Report From the Children's Oncology Group Study CCG 1961 SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Dhall, Girish] Univ So Calif, Childrens Hosp Los Angeles, Los Angeles, CA USA. [Jones, Tamekia] Childrens Oncol Grp, Dept Epidemiol & Hlth Policy Res, Gainesville, FL USA. [Radvinsky, David; Robison, Nathan; Butturini, Anna; Gaynon, Paul S.; Panosyan, Eduard H.; Avramis, Ioannis A.; Avramis, Vassilios I.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Rubin, Joan I.] St Peters Univ Hosp, New Brunswick, NJ USA. [Ettinger, Lawrence J.] Univ S Florida, All Childrens Hosp, St Petersburg, FL 33701 USA. [Seibel, Nita L.] NCI, Canc Therapy Evaluat Program, 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 20 PY 2009 VL 114 IS 22 BP 1197 EP 1197 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725803632 ER PT J AU Olnes, MJ Leitman, S Biancotto, A McCoy, JP Miranda, S Tucker, Z Pfannes, L Furnari, M Young, NS Sloand, EM AF Olnes, Matthew J. Leitman, Susan Biancotto, Angelique McCoy, J. Philip, Jr. Miranda, Susan Tucker, Zachary Pfannes, Loretta Furnari, Megan Young, Neal S. Sloand, Elaine M. TI Effects of Granulocyte Colony Stimulating Factor (G-CSF) On Monosomy 7 Aneuploidy and T Cell Subsets in Healthy Donors SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Olnes, Matthew J.; Tucker, Zachary; Pfannes, Loretta; Furnari, Megan] NIH, Hematol Branch, Bethesda, MD 20892 USA. [Leitman, Susan] NIH, Blood Serv Sect, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. [McCoy, J. Philip, Jr.] NHLBI, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 20 PY 2009 VL 114 IS 22 BP 1222 EP 1222 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725803702 ER PT J AU Giri, N Maric, I Wesley, R Arthur, DC Noel, P Savage, SA Alter, BP AF Giri, Neelam Maric, Irina Wesley, Robert Arthur, Diane C. Noel, Pierre Savage, Sharon A. Alter, Blanche P. TI Bone Marrow Fibrosis in Patients with Inherited Bone Marrow Failure Syndromes SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Giri, Neelam; Alter, Blanche P.] NCI, Clin Genet Branch, Rockville, MD USA. [Maric, Irina] NIH, DLM, CC, Bethesda, MD 20892 USA. [Arthur, Diane C.] NCI, LP, NIH, Bethesda, MD 20892 USA. [Wesley, Robert] NIH, OD, CC, Bethesda, MD 20892 USA. [Noel, Pierre] NIH, Hematol Serv, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Savage, Sharon A.] NCI, Div Canc Epidemiol & Gene, Bethesda, MD 20892 USA. RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 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 20 PY 2009 VL 114 IS 22 BP 1236 EP 1237 PG 2 WC Hematology SC Hematology GA 532DS UT WOS:000272725803747 ER PT J AU Hutson, S Han, P Al-Rahawan, MM Anand, S Rife, S Alter, BP AF Hutson, Sadie Han, Paul Al-Rahawan, Mohamad M. Anand, Sheeba Rife, Sean Alter, Blanche P. TI Stem Cell Transplanation for Fanconi Anemia: A Survey of Decision-Making among Families in the US and Canada. SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Hutson, Sadie] E Tennessee State Univ, Div Grad Studies, Johnson City, TN 37614 USA. [Hutson, Sadie] E Tennessee State Univ, Coll Nursing, Johnson City, TN 37614 USA. [Han, Paul] Maine Med Ctr, Ctr Outcomes Res & Evaluat, Portland, ME 04102 USA. [Al-Rahawan, Mohamad M.] Univ Illinois, Coll Med, Peoria, IL 61656 USA. [Al-Rahawan, Mohamad M.] St Jude Midwest Affiliate, Peoria, IL USA. [Rife, Sean] Kent State Univ, Social Relationships & Hlth Lab, Kent, OH 44242 USA. [Alter, Blanche P.] NCI, Clin Genet Branch, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 20 PY 2009 VL 114 IS 22 BP 1242 EP 1243 PG 2 WC Hematology SC Hematology GA 532DS UT WOS:000272725803762 ER PT J AU Rosenberg, PS Zeidler, C Bolyard, AA Alter, BP Bonilla, MA Dror, Y Kinsey, SE Link, DC Shimamura, A Newburger, PE Boxer, LA Welte, K Dale, DC AF Rosenberg, Philip S. Zeidler, Cornelia Bolyard, Audrey Anna Alter, Blanche P. Bonilla, Mary Ann Dror, Yigal Kinsey, Sally E. Link, Daniel C. Shimamura, Akiko Newburger, Peter E. Boxer, Laurence A. Welte, Karl Dale, David C. TI Stable Long-Term Risk of Leukemia in Patients with Severe Congenital Neutropenia Maintained On G-CSF Therapy. SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Alter, Blanche P.] NCI, Clin Genet Branch, Rockville, MD USA. [Zeidler, Cornelia] Hannover Med Sch, SCNIR, D-3000 Hannover, Germany. [Bolyard, Audrey Anna] Univ Washington, Severe Chron Neutropenia Int Registry, Seattle, WA 98195 USA. [Bonilla, Mary Ann] St Josephs Childrens Hosp, Paterson, NJ USA. [Dror, Yigal] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Kinsey, Sally E.] St James Univ Hosp, Leeds LS9 7TF, W Yorkshire, England. [Link, Daniel C.] Washington Univ, Sch Med, St Louis, MO USA. [Shimamura, Akiko] Washington Univ, Fred Hutchinson Canc Res Ctr, Seattle Childrens Hosp, St Louis, MO USA. [Newburger, Peter E.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Boxer, Laurence A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Welte, Karl] Hannover Med Sch, Dept Pediat Hematol Oncol, D-3000 Hannover, Germany. [Dale, David C.] Univ Washington, Seattle, WA 98195 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 20 PY 2009 VL 114 IS 22 BP 1242 EP 1242 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725803761 ER PT J AU Calado, RT Cooper, JN Scheinberg, P Wu, C Zago, MA Padilla-Nash, H Ried, T Sloand, EM Young, NS AF Calado, Rodrigo T. Cooper, James N. Scheinberg, Phillip Wu, Colin Zago, Marco A. Padilla-Nash, Hesed Ried, Thomas Sloand, Elaine M. Young, Neal S. TI Telomere Shortening Promotes Chromosomal Instability and Predicts Malignant Clonal Evolution in Aplastic Anemia. SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Calado, Rodrigo T.; Cooper, James N.; Scheinberg, Phillip; Wu, Colin; Sloand, Elaine M.; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Zago, Marco A.] Univ Sao Paulo, Sch Med, Dept Internal Med, BR-14049 Ribeirao Preto, Brazil. [Padilla-Nash, Hesed; Ried, Thomas] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. RI Calado, Rodrigo/G-2619-2011; Scheinberg, Phillip/H-5251-2012 NR 0 TC 0 Z9 0 U1 0 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 20 PY 2009 VL 114 IS 22 BP 1243 EP 1243 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725803763 ER PT J AU Zhu, BM Wickre, M Na, R Klover, P Martin, C Kimura, A Hennighausen, L AF Zhu, Bing-Mei Wickre, Mark Na, Risu Klover, Peter Martin, Cyril Kimura, Akiko Hennighausen, Lothar TI Stat5 Is Essential for BCR-ABL-Transformed Chronic Myeloid Leukemia (CML) Associated with Increased CCN3 Gene Expression. SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Zhu, Bing-Mei; Wickre, Mark; Na, Risu; Klover, Peter; Martin, Cyril; Kimura, Akiko; Hennighausen, Lothar] NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 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 20 PY 2009 VL 114 IS 22 BP 1266 EP 1266 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725803826 ER PT J AU Klemm, L Duy, C Iacobucci, I von Levetzow, G Feldhahn, N Kim, YM Hofmann, WK Jumaa, H Groffen, J Heisterkamp, N Martinelli, G Lieber, MR Casellas, R Muschen, M AF Klemm, Lars Duy, Cihangir Iacobucci, Ilaria von Levetzow, Gregor Feldhahn, Niklas Kim, Yong-mi Hofmann, Wolf-Karsten Jumaa, Hassan Groffen, John Heisterkamp, Nora Martinelli, Giovanni Lieber, Michael R. Casellas, Rafael Mueschen, Markus TI The B Cell Mutator AID Promotes B Lymphoid Blast Crisis and Drug-Resistance in Chronic Myeloid Leukemia SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Klemm, Lars; Duy, Cihangir; von Levetzow, Gregor; Groffen, John; Heisterkamp, Nora; Mueschen, Markus] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Leukemia & Lymphoma Program, Los Angeles, CA 90033 USA. [Iacobucci, Ilaria] Univ Bologna, Seragnoli Inst, Dept Hematol & Oncol Sci, Bologna, Italy. [Feldhahn, Niklas] Rockefeller Univ, New York, NY 10021 USA. [Kim, Yong-mi] Childrens Hosp Los Angeles, Leukemia Res Program, Los Angeles, CA 90027 USA. [Hofmann, Wolf-Karsten] Univ Hosp Mannheim, Dept Hematol & Oncol, Mannheim, Germany. [Jumaa, Hassan] Max Planck Inst Immunobiol, D-7800 Freiburg, Germany. [Casellas, Rafael] NIAMS, Natl Inst Hlth Genom Integr & Immun, 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 20 PY 2009 VL 114 IS 22 BP 1267 EP 1268 PG 2 WC Hematology SC Hematology GA 532DS UT WOS:000272725803829 ER PT J AU Le, RQ Bevans, M Savani, BN Mitchell, S Stringaris, K Koklanaris, EK Barrett, AJ AF Le, Robert Quan Bevans, Margaret Savani, Bipin N. Mitchell, Sandra Stringaris, Kate Koklanaris, Eleftheria K. Barrett, A. John TI Favorable Outcome and Quality of Life in Patients Surviving 5 or More Years After Allogeneic Hematopoietic Stem Cell Transplantation for Hematologic Malignancies SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Le, Robert Quan; Stringaris, Kate; Koklanaris, Eleftheria K.; Barrett, A. John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Bevans, Margaret; Mitchell, Sandra] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Savani, Bipin N.] Vanderbilt Univ, Med Ctr, Hematol & Stem Cell Transplantat Sect, Div Hematol Oncol,Dept Med, Nashville, TN USA. [Savani, Bipin N.] Vet Affairs Med Ctr, 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 20 PY 2009 VL 114 IS 22 BP 1284 EP 1284 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725803867 ER PT J AU Pusic, I DiPersio, JF Goran, SL Romvari, EM Bauer, SL Comer, HS Abboud, CN Cashen, AF Gale, RP Pavletic, SZ AF Pusic, Iskra DiPersio, John F. Goran, Stefanie L. Romvari, Edie M. Bauer, Stephanie L. Comer, Holly S. Abboud, Camille N. Cashen, Amanda F. Gale, Robert Peter Pavletic, Steven Z. TI Phase-2 Study of Pomalidomide in Advanced Corticosteroid-Resistant Chronic Graft-Versus-Host Disease (cGVHD) SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Pusic, Iskra; DiPersio, John F.; Goran, Stefanie L.; Romvari, Edie M.; Bauer, Stephanie L.; Comer, Holly S.; Abboud, Camille N.; Cashen, Amanda F.] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO USA. [Gale, Robert Peter] Celgene Corp, Summit, NJ USA. [Pavletic, Steven Z.] 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 20 PY 2009 VL 114 IS 22 BP 1290 EP 1290 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725803881 ER PT J AU Aue, G Soto, S Valdez, J Arthur, DC Roschewski, M Wiestner, A AF Aue, Georg Soto, Susan Valdez, Janet Arthur, Diane C. Roschewski, Mark Wiestner, Adrian TI A Phase II Trial of Pulse Dosing Lenalidomide: 3 Weeks On 3 Weeks off in Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Aue, Georg; Soto, Susan; Valdez, Janet; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Arthur, Diane C.] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Roschewski, Mark] Walter Reed Army Med Ctr, Washington, DC 20307 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 20 PY 2009 VL 114 IS 22 BP 1331 EP 1331 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725804092 ER PT J AU Kreitman, RJ Wilson, WH Stetler-Stevenson, M Noel, P FitzGerald, DJ Pastan, I AF Kreitman, Robert J. Wilson, Wyndham H. Stetler-Stevenson, Maryalice Noel, Pierre FitzGerald, David J. Pastan, Ira TI Long Term Results of BL22 (CAT-3888) in Multiply Relapsed Hairy Cell Leukemia SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Kreitman, Robert J.; FitzGerald, David J.; Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Stetler-Stevenson, Maryalice] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Noel, Pierre] NIH, Hematol Serv, Warren Grant Magnuson Clin 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 20 PY 2009 VL 114 IS 22 BP 1337 EP 1337 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725804107 ER PT J AU Cooper, N Rao, VK Fleisher, T Bussel, JB AF Cooper, Nichola Rao, V. Koneti Fleisher, Thomas Bussel, James B. TI Lymphocyte Homeostasis FAS Pathway Is Altered in Some Patients with Immune Thrombocytopenia. SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Cooper, Nichola] Hammersmith Hosp, Imperial Hlth Care NHS Trust, London, England. [Rao, V. Koneti] NIAID, ALPS Unit, LCID, NIH, Bethesda, MD 20892 USA. [Bussel, James B.] Weill Cornell Med Coll, Div Pediat Hematol Oncol, Platelet Disorders Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 20 PY 2009 VL 114 IS 22 BP 1363 EP 1363 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725804179 ER PT J AU Larochelle, A Savona, M Wiggins, M Anderson, S Morrison, SJ Dunbar, CE AF Larochelle, Andre Savona, Michael Wiggins, Michael Anderson, Stephanie Morrison, Sean J. Dunbar, Cynthia E. TI Human and Rhesus Macaque Hematopoietic Stem Cells Are Not Enriched in the CD150+CD48-SLAM Population SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Larochelle, Andre; Dunbar, Cynthia E.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Savona, Michael; Wiggins, Michael; Anderson, Stephanie] San Antonio Mil Med Ctr, Dept Hematol Oncol, San Antonio, TX USA. [Morrison, Sean J.] Howard Hughes Med Inst, Dept Internal Med, Ann Arbor, MI USA. [Morrison, Sean J.] Howard Hughes Med Inst, Ctr Stem Cell Biol & Life Sci, Ann Arbor, MI USA. [Morrison, Sean J.] Univ Michigan, Ann Arbor, MI 48109 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 20 PY 2009 VL 114 IS 22 BP 1370 EP 1370 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725804196 ER PT J AU Fitzhugh, C Hsieh, MM Phang, O Madison, C Luznik, L Powell, J Tisdale, JF AF Fitzhugh, Courtney Hsieh, Matthew M. Phang, Oswald Madison, Camille Luznik, Leo Powell, Jonathan Tisdale, John F. TI Post-Transplant Cyclophosphamide and Sirolimus Are Synergistic in Preventing Rejection and Inducing Stable Mixed Chimerism Independently of Regulatory T Cells SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Fitzhugh, Courtney; Hsieh, Matthew M.; Phang, Oswald; Madison, Camille; Tisdale, John F.] NHLBI, NIH, Bethesda, MD 20892 USA. [Luznik, Leo; Powell, Jonathan] Johns Hopkins Univ, 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 20 PY 2009 VL 114 IS 22 BP 1373 EP 1374 PG 2 WC Hematology SC Hematology GA 532DS UT WOS:000272725804205 ER PT J AU Mariotti, J Ryan, K Massey, P Buxhoeveden, N Foley, J Fowler, D AF Mariotti, Jacopo Ryan, Kaitlyn Massey, Paul Buxhoeveden, Nicole Foley, Jason Fowler, Daniel TI Pentostatin Facilitates Fully MHC-Disparate Murine Mini-Transplantation SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Mariotti, Jacopo; Ryan, Kaitlyn; Massey, Paul; Buxhoeveden, Nicole] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Foley, Jason] Jason Foley, Expt Transplantat & Immunol, 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 20 PY 2009 VL 114 IS 22 BP 1373 EP 1373 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725804204 ER PT J AU Bartelmez, S Bhatwadekar, A Iversen, P Ruscetti, FW Grant, M AF Bartelmez, Stephen Bhatwadekar, Ashay Iversen, Patrick Ruscetti, Francis W. Grant, Maria TI Transient Inhibition of Transforming Growth Factor-beta 1 in Human Blood-Derived CD34+Cells Enhances Survival and Proliferation in Vitro and Vascular Reparative functions In Vivo SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Bartelmez, Stephen] BetaStem Therapeut, Stem Cells, San Francisco, CA USA. [Bhatwadekar, Ashay; Grant, Maria] Univ Florida, Gainesville, FL USA. [Iversen, Patrick] AVI BioPharma, Biol, Corvallis, OR USA. [Ruscetti, Francis W.] NCI, Expt Immunol Lab, NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 20 PY 2009 VL 114 IS 22 BP 1376 EP 1376 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725804211 ER PT J AU Harrow, FJ Cline, AP Seidel, NE Persons, D Gallagher, PG Bodine, DM AF Harrow, Faith J. Cline, Amanda P. Seidel, Nancy E. Persons, Derek Gallagher, Patrick G. Bodine, David M. TI A Modified ANK-1 Promoter Directs Uniform, Copy Number Dependent Gamma Globin Gene Expression at Therapeutic Levels of a in a Lentivirus Vector. SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Harrow, Faith J.; Cline, Amanda P.; Seidel, Nancy E.; Bodine, David M.] NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. [Persons, Derek] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Gallagher, Patrick G.] Yale Univ, Sch Med, 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 20 PY 2009 VL 114 IS 22 BP 1382 EP 1382 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725804230 ER PT J AU Uchida, N Washington, K Hsieh, MM Tisdale, JF AF Uchida, Naoya Washington, Kareem Hsieh, Matthew M. Tisdale, John F. TI Chicken HS4 Insulators Have Minimal Functions in Human Hematopoietic Cells That Were Transduced with An HIV1-Based Lentiviral Vector. SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Uchida, Naoya; Washington, Kareem; Tisdale, John F.] NHLBI, MCHB, NIH, Bethesda, MD 20892 USA. [Hsieh, Matthew M.] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 20 PY 2009 VL 114 IS 22 BP 1384 EP 1384 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725804235 ER PT J AU Staber, JM Burnight, E Sarvida, ME McCaffrey, A Kaminski, J McCray, P AF Staber, Janice M. Burnight, Erin Sarvida, Marie-Ellen McCaffrey, Anton Kaminski, Joseph McCray, Paul TI Gene Transfer Targeting Hepatocytes Using the PiggyBac Transposon System: An Approach towards Hemophilia A Correction and Long Term Expression of Factor VIII. SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Staber, Janice M.; Burnight, Erin; McCaffrey, Anton; McCray, Paul] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. [Sarvida, Marie-Ellen] Loyola Univ Hlth Syst, Maywood, IL USA. [Kaminski, Joseph] NIH, Med Coll Georgia, Bethesda, MD 20892 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 20 PY 2009 VL 114 IS 22 BP 1385 EP 1385 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725804240 ER PT J AU Amarnath, S Wang, JCM Massey, PR Riley, JL Levine, B June, CH Medin, JA Fowler, D AF Amarnath, Shoba Wang, James C. M. Massey, Paul R. Riley, James L. Levine, Bruce June, Carl H. Medin, Jeffrey A. Fowler, Daniel TI PD-L1 Immuno-Gene Therapy Under Cell Fate Control: Persistence of Cellular Delivery Vehicle and Transgene Expression SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Amarnath, Shoba] NCI, Expt Transplantat Immunol Branch, NIH, Bethesda, MD 20892 USA. [Medin, Jeffrey A.] Univ Hlth Network, Ontario Canc Inst, Toronto, ON, Canada. [Massey, Paul R.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Riley, James L.; Levine, Bruce; June, Carl H.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. RI Levine, Bruce/D-1688-2009 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 20 PY 2009 VL 114 IS 22 BP 1387 EP 1387 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725804245 ER PT J AU Dejesus, CE Egen, JG Alvarez, X Metzger, ME Combs, CA Malide, DA Yu, ZX Donahue, RE AF Dejesus, Catherine E. Egen, Jackson G. Alvarez, Xavier Metzger, Mark E. Combs, Christian A. Malide, Daniela A. Yu, Zu Xi Donahue, Robert E. TI The Transient Neutropenia Following G-CSF Administration Is Associated with An Accumulation of Neutrophils in the Pulmonary and Splenic Vasculature SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Dejesus, Catherine E.; Metzger, Mark E.; Donahue, Robert E.] NHLBI, Hematol Branch, Rockville, MD USA. [Egen, Jackson G.] NIAID, Lymphocyte Biol Sect, Bethesda, MD 20892 USA. [Alvarez, Xavier] Tulane Natl Primate Res Ctr, Div Comparat Pathol, Covington, LA USA. [Combs, Christian A.; Malide, Daniela A.] NHLBI, Light Microscopy Core Facil, Bethesda, MD 20892 USA. [Yu, Zu Xi] 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 20 PY 2009 VL 114 IS 22 BP 1389 EP 1389 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725804251 ER PT J AU Tuschong, L Dejesus, CE Adams, M Bonifacino, AC Hickstein, DD Donahue, RE AF Tuschong, Laura Dejesus, Catherine E. Adams, Meredith Bonifacino, Aylin C. Hickstein, Dennis D. Donahue, Robert E. TI Leukocyte Integrin CD18 Expression Mediates Transient Neutropenia Following G-CSF Administration SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Tuschong, Laura; Hickstein, Dennis D.] NCI, Expt Transplantat & Immunol Ctr Canc Res, Bethesda, MD 20892 USA. [Dejesus, Catherine E.; Adams, Meredith; Bonifacino, Aylin C.; Donahue, Robert E.] NHLBI, Hematol Branch, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 20 PY 2009 VL 114 IS 22 BP 1389 EP 1390 PG 2 WC Hematology SC Hematology GA 532DS UT WOS:000272725804252 ER PT J AU Aerbajinai, W Chin, K Zhu, JQ Hyun, L Kumkhaek, C Rodgers, GP AF Aerbajinai, Wulin Chin, Kyung Zhu, Jianqiong Hyun, Lee Kumkhaek, Chutima Rodgers, Griffin P. TI Glia Maturation Factor-Gamma Mediates Lipopolysaccharide-Induced Inflammation Via p38 MAPK and NF-Kappab SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Chin, Kyung; Hyun, Lee] NHLBI, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. [Rodgers, Griffin P.] NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD USA. [Kumkhaek, Chutima] NIDDK, 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 20 PY 2009 VL 114 IS 22 BP 1393 EP 1393 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725804263 ER PT J AU Whittaker, S Kim, EJ Prince, M Demierre, MF Giver, C Lonial, S Pickarz, R Kim, YH Nichols, J Nix, D Bates, S AF Whittaker, Sean Kim, Ellen J. Prince, Miles Demierre, Marie France Giver, Cynthia Lonial, Sagar Pickarz, Richard Kim, Youn H. Nichols, Jean Nix, Darrell Bates, Susan TI Characterization of Cyclic Hematologic Changes Observed in Patients with Cutaneous T-Cell Lymphoma (CTCL) Receiving Romidepsin, a Novel Histone Deacetylase (HDAC) Inhibitor SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Whittaker, Sean] St Thomas Hosp, St Johns Inst Dermatol, London, England. [Kim, Ellen J.] Univ Penn, Philadelphia, PA 19104 USA. [Prince, Miles] Peter MacCallum Canc Ctr, Melbourne, Australia. [Demierre, Marie France] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Giver, Cynthia; Lonial, Sagar] Emory Univ, Winship Canc Ctr, Atlanta, GA 30322 USA. [Pickarz, Richard; Bates, Susan] NCI, Bethesda, MD 20892 USA. [Kim, Youn H.] Stanford Univ, Stanford, CA 94305 USA. [Nix, Darrell] Gloucester Pharmaceut, Drug Dev, Cambridge, MA 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 20 PY 2009 VL 114 IS 22 BP 1425 EP 1425 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725804365 ER PT J AU Cabell, C Bates, S Piekarz, R Whittaker, S Kim, YH Currie, M Godfrey, CJ Schoonmaker, C Nichols, J Nix, D Burris, HA AF Cabell, Christopher Bates, Susan Piekarz, Richard Whittaker, Sean Kim, Youn H. Currie, Michelle Godfrey, C. J. Schoonmaker, Christopher Nichols, Jean Nix, Darrell Burris, Howard A. TI Systematic Assessment of Potential Cardiac Effects of the Novel Histone Deacetylase (HDAC) Inhibitor Romidepsin. SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Cabell, Christopher] Quintiles Transnat, Durham, NC USA. [Bates, Susan; Piekarz, Richard] NCI, Bethesda, MD 20892 USA. [Whittaker, Sean] St Thomas Hosp, St Johns Inst Dermatol, London, England. [Kim, Youn H.] Stanford Univ, Stanford, CA 94305 USA. [Currie, Michelle; Schoonmaker, Christopher] Veristat Inc, Holliston, MA USA. [Godfrey, C. J.] Anoixis Corp, Natick, MA USA. [Nix, Darrell] Gloucester Pharmaceut, Drug Dev, Cambridge, MA USA. [Burris, Howard A.] Sarah Cannon Res Inst, Nashville, TN USA. NR 0 TC 2 Z9 2 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 20 PY 2009 VL 114 IS 22 BP 1428 EP 1429 PG 2 WC Hematology SC Hematology GA 532DS UT WOS:000272725804373 ER PT J AU Younes, A Copeland, AR Romaguera, J Fayad, L Fanale, M Faria, SD Medeiros, LJ Ivy, SP AF Younes, Anas Copeland, Amanda R. Romaguera, Jorge Fayad, Luis Fanale, Michelle Faria, Silvana de Castro Medeiros, L. Jeffrey Ivy, S. Percy TI Clinical and Biologic Activity of the Heat Shock Protein-90 (HSP-90) Inhibitor 17-AAG in Patients with Relapsed Lymphoma SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Younes, Anas; Copeland, Amanda R.] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Houston, TX 77030 USA. [Ivy, S. Percy] NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 2 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 20 PY 2009 VL 114 IS 22 BP 1441 EP 1441 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725804408 ER PT J AU Klier-Richter, M Irmler, M Bonzheim, I Schaefer, S Beckers, J Fend, F Raffeld, M Quintanilla-Martinez, L AF Klier-Richter, Margit Irmler, Martin Bonzheim, Irina Schaefer, Sabine Beckers, Johannes Fend, Falko Raffeld, Mark Quintanilla-Martinez, Leticia TI Identification of Cyclin D1-Dependent Genes by Gene Expression Profiling in MCL Cell Lines and Primary Cases. SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Klier-Richter, Margit; Bonzheim, Irina; Schaefer, Sabine; Fend, Falko; Quintanilla-Martinez, Leticia] Univ Tubingen, Univ Tubingen Hosp, Tubingen, Germany. [Irmler, Martin; Beckers, Johannes] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Expt Genet, Neuherberg, Germany. [Raffeld, Mark] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RI Irmler, Martin/B-3317-2013 OI Irmler, Martin/0000-0003-3169-479X 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 20 PY 2009 VL 114 IS 22 BP 1513 EP 1513 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725804600 ER PT J AU Sasaki, D Imaizumi, Y Hasegawa, H Osaka, A Tsuruda, K Tsukasaki, K Iwanaga, M Miyazaki, Y Yanagihara, K Marquez, V Kamihira, S Yamada, Y AF Sasaki, Daisuke Imaizumi, Yoshitaka Hasegawa, Hiroo Osaka, Akemi Tsuruda, Kazuto Tsukasaki, Kunihiro Iwanaga, Masako Miyazaki, Yasushi Yanagihara, Katsunori Marquez, Victor Kamihira, Shimeru Yamada, Yasuaki TI The Overexpression of Enhancer of Zeste Homologue 2 Is Associated with Tumor Proliferation and Aggressive Behavior in Adult T-Cell Leukemia/Lymphoma SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Sasaki, Daisuke; Imaizumi, Yoshitaka; Hasegawa, Hiroo; Osaka, Akemi; Tsuruda, Kazuto; Tsukasaki, Kunihiro; Iwanaga, Masako; Miyazaki, Yasushi; Yanagihara, Katsunori; Kamihira, Shimeru; Yamada, Yasuaki] Nagasaki Univ, Grad Sch Biomed Sci, Nagasaki 852, Japan. [Marquez, Victor] NCI, Med Chem Lab, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 20 PY 2009 VL 114 IS 22 BP 1522 EP 1522 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725804623 ER PT J AU Bergerson, RJ Collier, LS Lugthart, S Allaei, R Nixon, MJ Silverstein, KAT Sarver, A Fan, DF Lamblin, AFJ Wolff, L Kersey, JH O'Sullivan, G Delwel, R Kogan, SC Adams, DJ Largaespada, D AF Bergerson, Rachel Joy Collier, Lara S. Lugthart, Sanne Allaei, Raha Nixon, Molly J. Silverstein, Kevin A. T. Sarver, Aaron Fan, Danhua Flora Lamblin, Anne-Francoise J. Wolff, Linda Kersey, John H. O'Sullivan, Gerard Delwel, Ruud Kogan, Scott C. Adams, David J. Largaespada, David TI An Insertional Mutagenesis Screen for Genes That Cooperate with Mll-AF9 in Leukemogenesis SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Bergerson, Rachel Joy; Allaei, Raha; Nixon, Molly J.; Silverstein, Kevin A. T.; Sarver, Aaron; Fan, Danhua Flora; O'Sullivan, Gerard; Largaespada, David] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN USA. [Collier, Lara S.] Univ Wisconsin, Sch Pharm, Div Pharmaceut Sci, Madison, WI 53706 USA. [Lugthart, Sanne; Delwel, Ruud] Erasmus Univ, Med Ctr, Rotterdam, Netherlands. [Lamblin, Anne-Francoise J.] Univ Minnesota, Off Vice President Res, St Paul, MN 55108 USA. [Wolff, Linda] NCI, NIH, Bethesda, MD 20892 USA. [Kersey, John H.] Univ Minnesota, Lab Med & Pathol, Minneapolis, MN USA. [Kogan, Scott C.] Univ Calif San Francisco, Lab Med, San Francisco, CA 94143 USA. [Adams, David J.] Wellcome Trust Sanger Inst, Hinxton, England. 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 20 PY 2009 VL 114 IS 22 BP 1523 EP 1524 PG 2 WC Hematology SC Hematology GA 532DS UT WOS:000272725804626 ER PT J AU Aue, G Du, Y Cleveland, S Smith, S Dave, UP Jenkins, N Copeland, NG Dunbar, C AF Aue, Georg Du, Yang Cleveland, Susan Smith, Stephen Dave, Utpal P. Jenkins, Nancy Copeland, Neal G. Dunbar, Cynthia TI Sox4 Downregulates Pu.1 Gene Expression by Binding to An Upper Regulatory Element of Pu.1, a Mechanism Contributing to Leukemogenesis SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Aue, Georg; Dunbar, Cynthia] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Du, Yang] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Cleveland, Susan; Dave, Utpal P.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Smith, Stephen] Vanderbilt Univ, Sch Med, Nashville, TN USA. [Jenkins, Nancy; Copeland, Neal G.] Inst Mol & Cellular Biol, Singapore, Singapore. 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 20 PY 2009 VL 114 IS 22 BP 1529 EP 1529 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725804643 ER PT J AU Luetkhoff, LK Albisetti, M Bernard, TJ Bonduel, M Brandao, LR Chabrier, S Chan, A Fiedler, B Fullerton, HJ Ganesan, V Goldenberg, NA Golomb, M Grabowski, EF Heller, C Holzhauer, S Iorio, A Journeycake, J Kenet, G Kirkham, FJ Kurnik, K Lynch, JK Male, C Manco-Johnson, MJ Mesters, R Monagle, P van Ommen, HC Raffini, L Simioni, P Straeter, R Young, G Nowak-Gottl, U AF Luetkhoff, Lisa K. Albisetti, Manuela Bernard, Timothy J. Bonduel, Mariana Brandao, Leonardo R. Chabrier, Stephanie Chan, Anthony Fiedler, Barbara Fullerton, Heather J. Ganesan, Vijeja Goldenberg, Neil A. Golomb, Meredith Grabowski, Eric F. Heller, Christine Holzhauer, Susanne Iorio, Alfonso Journeycake, Janna Kenet, Gili Kirkham, Fenella J. Kurnik, Karin Lynch, John K. Male, Christoph Manco-Johnson, Marilyn J. Mesters, Rolf Monagle, Paul van Ommen, Heleen C. Raffini, Leslie Simioni, Paolo Straeter, Ronald Young, Guy Nowak-Gottl, Ulrike TI Impact of Thrombophilia On Arterial Ischemic Stroke or Cerebral Venous Sinus Thromboses in Children: A Systematic Review & Meta-Analysis of Observational Studies SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Luetkhoff, Lisa K.; Fiedler, Barbara; Straeter, Ronald] Univ Childrens Hosp Munster, Munster, Germany. [Albisetti, Manuela] Univ Childrens Hosp Zurich, Zurich, Switzerland. [Bernard, Timothy J.] Univ Colorado, Dept Pediat, Sect Hem Onc BMT, Aurora, CO USA. [Bernard, Timothy J.] Univ Colorado, Mt States Reg Hemophilia & Thrombosis Ctr, Aurora, CO USA. [Bernard, Timothy J.; Goldenberg, Neil A.; Manco-Johnson, Marilyn J.] Childrens Hosp, Aurora, CO USA. [Bonduel, Mariana] Hosp Pediat Prof Dr JP Garrahan, Serv Hematol & Oncol, Buenos Aires, DF, Argentina. [Brandao, Leonardo R.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Chabrier, Stephanie] Ctr Hosp Univ, Unit Neonatol & Reanimat Pediat, St Etienne, France. [Chan, Anthony] McMaster Univ, Hamilton, ON, Canada. [Fullerton, Heather J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Fullerton, Heather J.] UCSF Childrens Hosp, San Francisco, CA USA. [Ganesan, Vijeja; Kirkham, Fenella J.] UCL, Neurosci Unit 11, Inst Child Hlth, London, England. [Goldenberg, Neil A.] Univ Colorado Denver, Pediat & Mt States Reg Hemophilia & Thrombosis Ct, Aurora, CO USA. [Golomb, Meredith] Indiana Univ, Sch Med, Indianapolis, IN USA. [Grabowski, Eric F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Grabowski, Eric F.] Harvard Univ, Sch Med, Boston, MA USA. [Heller, Christine] Univ Hosp Frankfurt, Frankfurt, Germany. [Holzhauer, Susanne] Charite, Berlin, Germany. [Iorio, Alfonso] Univ Perugia, I-06100 Perugia, Italy. [Journeycake, Janna] Childrens Med Ctr Dallas, Dept Pediat 17, Dallas, TX USA. [Kenet, Gili] Chaim Sheba Med Ctr, Thrombosis Unit, IL-52621 Tel Hashomer, Israel. [Kurnik, Karin] Dr V Hauners Childrens Univ Hosp, Pediat Hemophilia Ctr, Munich, Germany. [Lynch, John K.] Natl Inst Neurol Disorders & Stroke, Div Stroke Diagnost & Therapeut 21, Bethesda, MD USA. [Male, Christoph] Med Univ Vienna, Dept Pediat, Vienna, Austria. [Mesters, Rolf] Univ Munster, Dept Internal Med, D-4400 Munster, Germany. [Monagle, Paul] Univ Melbourne, Dept Paediat, Parkville, Vic 3052, Australia. [van Ommen, Heleen C.] Emma Childrens Hosp AMC, Dept Pediat Hematol 25, Amsterdam, Netherlands. [Raffini, Leslie] Childrens Hosp Philadelphia, Dept Pediat, Div Hematol 27, Philadelphia, PA 19104 USA. [Simioni, Paolo] Univ Padua, Sch Med, Padua, Italy. [Young, Guy] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Nowak-Gottl, Ulrike] Univ Childrens Hosp, Dept Pediat Hem Onc, Munster, Germany. RI Kirkham, Fenella/C-2442-2009; OI Kirkham, Fenella/0000-0002-2443-7958; Young, Guy/0000-0001-6013-1254 NR 0 TC 0 Z9 0 U1 0 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 20 PY 2009 VL 114 IS 22 BP 1534 EP 1535 PG 2 WC Hematology SC Hematology GA 532DS UT WOS:000272725804657 ER PT J AU Tanno, T Sripichai, O Noh, SJ Byrnes, C Meier, ER Lee, YT Miller, JL AF Tanno, Toshihiko Sripichai, Orapan Noh, Seung-Jae Byrnes, Colleen Meier, Emily Riehm Lee, Y. Terry Miller, Jeffery L. TI Ineffective Erythropoiesis Caused by Phenylhydrazine Activates the Expression of GDF15 in Maturing Erythroblasts SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Tanno, Toshihiko; Sripichai, Orapan; Noh, Seung-Jae; Byrnes, Colleen; Meier, Emily Riehm; Lee, Y. Terry; Miller, Jeffery L.] NIDDKD, Mol Med Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 20 PY 2009 VL 114 IS 22 BP 1547 EP 1547 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725804696 ER PT J AU Wynne, E Perkins, K Price, S Louie, A Rao, VK AF Wynne, Elisabeth Perkins, Katie Price, Susan Louie, Adeline Rao, V. Koneti TI CT Scan Enumeration of Altered Spleen Status and Pulmonary Artery Size in Patients with Autoimmune Lymphoproliferative Syndrome (ALPS) SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Wynne, Elisabeth] UVA Sch Med, Charlottesville, VA USA. [Perkins, Katie; Price, Susan; Rao, V. Koneti] NIAID, ALPS Unit, LCID, NIH, Bethesda, MD 20892 USA. [Louie, Adeline] NIH, Dept Radiol, Ctr Clin, Bethesda, MD 20892 USA. NR 4 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 20 PY 2009 VL 114 IS 22 BP 1548 EP 1548 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725804698 ER PT J AU Tanno, T Rabel, A Lee, YT Leitman, S Miller, JL AF Tanno, Toshihiko Rabel, Antoinett Lee, Y. Terry Leitman, Susan Miller, Jeffery L. TI A Comparison of Serum Hepcidin and GDF15 Expression in Cases of Iron Depletion Due to Blood Loss SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Tanno, Toshihiko; Rabel, Antoinett; Lee, Y. Terry; Miller, Jeffery L.] NIDDKD, Mol Med Branch, NIH, Bethesda, MD 20892 USA. [Leitman, Susan] NIH, Blood Serv Sect, Warren Grant Magnuson Clin Ctr, 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 20 PY 2009 VL 114 IS 22 BP 1550 EP 1551 PG 2 WC Hematology SC Hematology GA 532DS UT WOS:000272725804706 ER PT J AU Falkenburg, WJJ Melenhorst, JJ Kester, MGD Hombrink, P Heemskerk, MHM Gostick, E Price, DA Falkenburg, JHF Barrett, AJ Jedema, I AF Falkenburg, Willem J. J. Melenhorst, J. Joseph Kester, Michel G. D. Hombrink, Pleun Heemskerk, Mirjam H. M. Gostick, Emma Price, David A. Falkenburg, J. H. Frederik Barrett, A. John Jedema, Inge TI Allogeneic HLA-A2-Restricted WT1-Specific T Cells From Mismatched Donors Are Highly Reactive but Show Potentially Hazardous Promiscuity SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Falkenburg, Willem J. J.; Melenhorst, J. Joseph; Barrett, A. John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Kester, Michel G. D.; Hombrink, Pleun; Heemskerk, Mirjam H. M.; Falkenburg, J. H. Frederik; Jedema, Inge] Leiden Univ, Med Ctr, Dept Hematol, Leiden, Netherlands. [Gostick, Emma; Price, David A.] Cardiff Univ, Sch Med, Cardiff, S Glam, Wales. RI Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 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 20 PY 2009 VL 114 IS 22 BP 1565 EP 1565 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725804744 ER PT J AU Lundqvist, A Berg, M Smith, A Cook, L Goodwin, R Ramos, C Vasu, S Pantin, J Lopez, R Khuu, H Fellowes, V Stroncek, D Donohue, T Childs, R AF Lundqvist, Andreas Berg, M. Smith, A. Cook, L. Goodwin, R. Ramos, C. Vasu, S. Pantin, J. Lopez, R. Khuu, H. Fellowes, V. Stroncek, D. Donohue, T. Childs, R. TI Adoptive Infusion of Ex Vivo Expanded Autologous Natural Killer (NK) Cells in Cancer Patients Treated with Bortezomib to Sensitize to NK-TRAIL Cytotoxicity SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Lundqvist, Andreas; Berg, M.; Smith, A.; Cook, L.; Goodwin, R.; Ramos, C.; Vasu, S.; Pantin, J.; Lopez, R.; Donohue, T.; Childs, R.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Khuu, H.] NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 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 20 PY 2009 VL 114 IS 22 BP 1565 EP 1565 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725804743 ER PT J AU Rezvani, K Yong, ASM Mielke, S Jafarpour, B Savani, BN Le, Q Eniafe, R Boss, C Kurlander, RJ Barrett, AJ AF Rezvani, Katayoun Yong, Agnes S. M. Mielke, Stephan Jafarpour, Behnam Savani, Bipin N. Le, Quan Eniafe, Rhoda Boss, Carol Kurlander, Roger J. Barrett, A. John TI The Response to Repeated Vaccination with PR1 and WT1 Peptides Admixed in Montanide Adjuvant Is Transient and Fails to Induce Sustained Anti-Leukemia Responses in Patients with Myeloid Malignancies. SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Rezvani, Katayoun] Univ London Imperial Coll Sci Technol & Med, Dept Haematol, London, England. [Yong, Agnes S. M.; Jafarpour, Behnam; Le, Quan; Eniafe, Rhoda] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Mielke, Stephan] Univ Wurzburg, Wurzburg, Germany. [Savani, Bipin N.] Vanderbilt Univ, Nashville, TN USA. [Kurlander, Roger J.] NIH, Dept Lab Med, 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 20 PY 2009 VL 114 IS 22 BP 1571 EP 1571 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725804759 ER PT J AU Mattson, MP AF Mattson, Mark P. TI Mitochondria in Neuroplasticity, Neurologic Disease and Aging. SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Mattson, Mark P.] NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 0 TC 0 Z9 0 U1 0 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 20 PY 2009 VL 114 IS 22 BP 1575 EP 1575 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725804762 ER PT J AU Wiestner, A AF Wiestner, Adrian TI Biology and Treatment of Mantle Cell Lymphoma in the Genomic Era SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Wiestner, Adrian] 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 20 PY 2009 VL 114 IS 22 BP 1581 EP 1581 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725804788 ER PT J AU Stroncek, D AF Stroncek, David TI TRALI Pathophysiology SO BLOOD LA English DT Meeting Abstract CT 51st Annual Meeting of the American-Society-of-Hematology CY DEC 05-08, 2009 CL New Orleans, LA SP Amer Soc Hematol C1 [Stroncek, David] 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 20 PY 2009 VL 114 IS 22 BP 1586 EP 1586 PG 1 WC Hematology SC Hematology GA 532DS UT WOS:000272725804808 ER PT J AU Blume, A Torner, L Liu, Y Subburaju, S Aguilera, G Neumann, ID AF Blume, Annegret Torner, Luz Liu, Ying Subburaju, Sivan Aguilera, Greti Neumann, Inga D. TI Prolactin induces Egr-1 gene expression in cultured hypothalamic cells and in the rat hypothalamus SO BRAIN RESEARCH LA English DT Article DE Signaling; Neuroplasticity; Stress; Hypothalamo-pituitary-adrenal axis; Transcription factor; Lactation ID TRANSCRIPTION FACTOR ZIF268/EGR-1; CORTICOTROPIN-RELEASING HORMONE; IMMEDIATE-EARLY GENE; NERVOUS-SYSTEM; MESSENGER-RNA; HYPOTHALAMONEUROHYPOPHYSEAL SYSTEM; STIMULATED NEUROGENESIS; GROWTH-FACTOR; LONG FORM; RECEPTOR AB Prolactin (PRL), the major lactogenic hormone, acts also as neuromodulator and regulator of neuronal and glial plasticity in the brain. There is an increase in synthesis and release of PRL within the hypothalamus during peripartum and in response to stress. To identify mechanisms by which PRL induces neuroplasticity, we studied the ability of PRL to induce the transcription factor Egr-1 in the hypothalamic cell line, 4B, in vitro, and in specific neuronal cell types of the hypothalamus in vivo. PAL induced Egr-1 mRNA expression in 4B cells, an effect which was prevented by the MEK inhibitor, U0126. In vivo, intracerebroventricular PRL (1 mu g) increased Egr-1 mRNA levels in the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON) of female rats. The increase in mRNA paralleled elevated Egr-1 protein expression in the PVN and SON. Double staining immunohistochemistry revealed Egr-1 localization in oxytocin neurons of the PVN and SON, but not in vasopressin neurons in these regions. In the dorsomedial PVN, a population of non-oxytocin or vasopressin cells localized in a region corresponding to corticotropin-releasing hormone neurons also showed marked Egr-1 immunoreactivity. The data suggest that PRL modulates plasticity in oxytocinergic neurons, through MAP kinase-dependent induction of Egr-1. Published by Elsevier B.V. C1 [Liu, Ying; Subburaju, Sivan; Aguilera, Greti] NICHHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. [Blume, Annegret; Torner, Luz; Neumann, Inga D.] Univ Regensburg, Inst Zool, Dept Behav & Mol Neuroendocrinol, D-8400 Regensburg, Germany. [Torner, Luz] IMSS, Biochem Res Ctr Michoacan, Morelia, Michoacan, Mexico. RP Aguilera, G (reprint author), NICHHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. EM Greti_Aguilera@nih.gov FU Intramural Research program of the NIH/NICHD; Bayerische Forschungsstiftung; Deutsche Forschungsgemeinschaft; VolkswagenStiftung FX The authors thank Luxiola Gonzalez and Remco Bredewold for expert technical assistance. This work was partially supported by the Intramural Research program of the NIH/NICHD (GA), by the Bayerische Forschungsstiftung (AB+IDN), the Deutsche Forschungsgemeinschaft (IDN) and the VolkswagenStiftung (IDN). NR 48 TC 7 Z9 7 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 20 PY 2009 VL 1302 BP 34 EP 41 DI 10.1016/j.brainres.2009.09.047 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 523KH UT WOS:000272071600004 PM 19769948 ER PT J AU Luo, Y Sarabi, SA Backman, C Shan, LF Hoffer, B Federoff, H AF Luo, Yu Sarabi, Sara Arezou Backman, Cristina Shan, Lufei Hoffer, Barry Federoff, Howard TI Expression pattern of NuIP gene in adult mouse brain SO BRAIN RESEARCH LA English DT Article DE Nurr1; Protein interactor; G protein ID NUCLEAR RECEPTOR NURR1; NGFI-B; CELLS; NEURONS; MICE; IDENTIFICATION; PROTEIN; MEMORY; NUR77; RAS AB We previously reported the identification of the Nurr1 interacting protein (NuIP) that was demonstrated to modulate the transcriptional activity of Nurr1, the orphan nuclear receptor required for midbrain dopaminergic neuron differentiation. NuIP was also cloned by others and referred to as a small G protein signaling modulators. The open reading frame of NuIP predicts a protein with an N-terminal RUN domain (RPIP8, UNC-14, and NESCA) and a C-terminal TBC domain (Tre-2, Bub2, and Cdc16) both of which are found in proteins of the GTPase activating protein (GAP) family, involved in the GTPase signaling pathway. To characterize the NuIP gene product, we developed a polyclonal antibody. Since NuIP gene is expressed most abundantly in adult and the level of expression during development is below the detection limit of immunohistochemistry, we now report the expression pattern of NuIP in adult mouse brain compared with the expression pattern of Nurr1 protein. Many regions co-expressed Nurr1 and NuIP including cortex, hippocampus, substantia nigra, and the cerebellum. However, there are also regions that exclusively express NuIP such as striatum, septum, globus pallidus, and the reticular thalamic nucleus. We also find that NuIP protein expresses mainly in NeuN-positive (neuronal nuclei) neurons but can be detected in GFAP-positive (glial fibrillary acidic protein) glial cells in hippocampus. Interestingly, NuIP is expressed in high levels in midbrain dopaminergic neurons including ventral tegmental area (VTA) and substantia nigra (SN) dopaminergic neurons but is not expressed or expressed in low levels in other dopaminergic neurons such as olfactory bulb and hypothalamus. Overall, the expression pattern of NuIP in adult mouse brain suggests that it may be involved in motor activity control in basal ganglia as well as higher central nervous system (CNS) functions such as cognition and memory in cortex and hippocampus. Published by Elsevier B.V. C1 [Luo, Yu; Sarabi, Sara Arezou; Backman, Cristina; Shan, Lufei; Hoffer, Barry] NIDA, Intramural Res Program, Baltimore, MD 21224 USA. [Federoff, Howard] Georgetown Univ, Dept Neurol, Washington, DC 20057 USA. RP Hoffer, B (reprint author), NIDA, Intramural Res Program, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM bhoffer@mail.nih.gov RI luo, Yu (Agnes)/E-4446-2010; backman, cristina/C-1276-2013 NR 25 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 20 PY 2009 VL 1302 BP 42 EP 53 DI 10.1016/j.brainres.2009.09.026 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 523KH UT WOS:000272071600005 PM 19765553 ER PT J AU Ma, XF Takeda, K Singh, A Yu, ZX Zerfas, P Blount, A Liu, CY Towbin, JA Schneider, MD Adelstein, RS Wei, QZ AF Ma, Xuefei Takeda, Kazuyo Singh, Aman Yu, Zu-Xi Zerfas, Patricia Blount, Anthony Liu, Chengyu Towbin, Jeffrey A. Schneider, Michael D. Adelstein, Robert S. Wei, Qize TI Conditional Ablation of Nonmuscle Myosin II-B Delineates Heart Defects in Adult Mice SO CIRCULATION RESEARCH LA English DT Article DE nonmuscle myosin II-B; cardiomyopathy; intercalated discs ID INTERCALATED DISK PROTEIN; HEAVY-CHAIN; CARDIAC-HYPERTROPHY; CONDUCTION DEFECTS; CELL-ADHESION; MXIN-ALPHA; GENE; CARDIOMYOPATHY; MIGRATION; CADHERIN AB Rationale: Germline ablation of the cytoskeletal protein nonmuscle myosin II (NMII)-B results in embryonic lethality, with defects in both the brain and heart. Tissue-specific ablation of NMII-B by a Cre recombinase strategy should prevent embryonic lethality and permit study of the function of NMII-B in adult hearts. Objective: We sought to understand the function of NMII-B in adult mouse hearts and to see whether the brain defects found in germline-ablated mice influence cardiac development. Methods and Results: We used a loxP/Cre recombinase strategy to specifically ablate NMII-B in the brains or hearts of mice. Mice ablated for NMII-B in neural tissues die between postnatal day 12 and 22 without showing cardiac defects. Mice deficient in NMII-B only in cardiac myocytes (B(alpha MHC)/B(alpha MHC) mice) do not show brain defects. However, B(alpha MHC)/B(alpha MHC) mice display novel cardiac defects not seen in NMII-B germline-ablated mice. Most of the B(alpha MHC)/B(alpha MHC) mice are born with enlarged cardiac myocytes, some of which are multinucleated, reflecting a defect in cytokinesis. Between 6 to 10 months, they develop a cardiomyopathy that includes interstitial fibrosis and infiltration of the myocardium and pericardium with inflammatory cells. Four of 5 B(alpha MHC)/B(alpha MHC) hearts develop marked widening of intercalated discs. Conclusions: By avoiding the embryonic lethality found in germline-ablated mice, we were able to study the function of NMII-B in adult mice and show that absence of NMII-B in cardiac myocytes results in cardiomyopathy in the adult heart. We also define a role for NMII-B in maintaining the integrity of intercalated discs. (Circ Res. 2009; 105: 1102-1109.) C1 [Ma, Xuefei; Takeda, Kazuyo; Singh, Aman; Blount, Anthony; Adelstein, Robert S.; Wei, Qize] NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. [Yu, Zu-Xi] NHLBI, Pathol Core Facil, NIH, Bethesda, MD 20892 USA. [Liu, Chengyu] NHLBI, Transgen Mouse Core Facil, NIH, Bethesda, MD 20892 USA. [Zerfas, Patricia] NIH, Div Vet Resources, Bethesda, MD 20892 USA. [Towbin, Jeffrey A.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Schneider, Michael D.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. RP Adelstein, RS (reprint author), NHLBI, Mol Cardiol Lab, NIH, Bldg 10,Room 6C-103,10 Ctr Dr,MSC-1583, Bethesda, MD 20892 USA. EM adelster@mail.nih.gov OI Schneider, Michael/0000-0001-9645-1938; Adelstein, Robert/0000-0002-8683-2144 FU Division of Intramural Research; National Heart, Lung, and Blood Institute, NIH FX This work was supported by the Division of Intramural Research, National Heart, Lung, and Blood Institute, NIH. NR 26 TC 16 Z9 17 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD NOV 20 PY 2009 VL 105 IS 11 BP 1102 EP U128 DI 10.1161/CIRCRESAHA.109.200303 PG 15 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 521UC UT WOS:000271948900008 PM 19815823 ER PT J AU Oldenhove, G Bouladoux, N Wohlfert, EA Hall, JA Chou, D Dos Santos, L O'Brien, S Blank, R Lamb, E Natarajan, S Kastenmayer, R Hunter, C Grigg, ME Belkaid, Y AF Oldenhove, Guillaume Bouladoux, Nicolas Wohlfert, Elizabeth A. Hall, Jason A. Chou, David Dos Santos, Liliane O'Brien, Shaun Blank, Rebecca Lamb, Erika Natarajan, Sundar Kastenmayer, Robin Hunter, Christopher Grigg, Michael E. Belkaid, Yasmine TI Decrease of Foxp3(+) Treg Cell Number and Acquisition of Effector Cell Phenotype during Lethal Infection SO IMMUNITY LA English DT Article ID REGULATORY T-CELLS; TOXOPLASMA-GONDII; DENDRITIC CELLS; RETINOIC-ACID; IFN-GAMMA; TGF-BETA; IN-VIVO; INTESTINAL INFLAMMATION; PERORAL INFECTION; C57BL/6 MICE AB Using a model of lethal oral infection with Toxoplasma gondii, we examined the fate of both induced and natural regulatory T (Treg) cells in the face of strong inflammatory responses occurring in a tolerogenicprone environment. We found that during highly T helper 1 (Th1) cell-polarized mucosal immune responses, Treg cell numbers collapsed via multiple pathways, including blockade of Treg cell induction and disruption of endogenous Treg cell homeostasis. In particular, shutdown of interleukin 2 (IL-2) in the highly Th1 cell-polarized environment triggered by infection directly contributes to Treg cell incapacity to suppress effector responses and eventually leads to immunopathogenesis. Furthermore, we found that environmental cues provided by both local dendritic cells and effector T cells can induce the expression of T-bet transcription factor and IFN-gamma by Treg cells. These data reveal a mechanism for Th1 cell pathogenicity that extends beyond their proinflammatory program to limit Treg cell survival. C1 [Oldenhove, Guillaume; Bouladoux, Nicolas; Wohlfert, Elizabeth A.; Hall, Jason A.; Chou, David; Dos Santos, Liliane; Blank, Rebecca; Belkaid, Yasmine] NIAID, Mucosal Immunol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Kastenmayer, Robin] NIAID, Comparat Med Branch, Bill Young Ctr Biodefense & Emerging Infect Dis, NIH, Bethesda, MD 20892 USA. [Lamb, Erika; Natarajan, Sundar; Grigg, Michael E.] NIAID, Mol Parasitol Unit, NIH, Bethesda, MD 20892 USA. [Hunter, Christopher] Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA. [Hall, Jason A.; O'Brien, Shaun] Univ Penn, Immunol Grad Grp, Philadelphia, PA 19104 USA. RP Belkaid, Y (reprint author), NIAID, Mucosal Immunol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. EM ybelkaid@niaid.nih.gov RI dos Santos, Liliane/D-1551-2010; Hunter, Christopher/H-1970-2011 FU Division of Intramural Research; National Institute of Allergy and Infectious Diseases; National Institutes of Health FX This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. We would like to thank the students of the Biology of Parasitism Course (Woods hole MBL 2008-2009) for contributing to some of the experiments. We thank Dr. F. Torres for help with pathological evaluation of samples. We thank Dr. K. Holmes and the MAID sorting facility and K. Beacht for technical assistance. We thank A. O'Hara (University of Pennsylvania, Immunology Graduate Program) for help with the parasite and Dr. G. Yap for helpful suggestions. We thank Drs. F.A. Sher and D. Jankovic for critical reading of the manuscript. NR 58 TC 297 Z9 302 U1 1 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD NOV 20 PY 2009 VL 31 IS 5 BP 772 EP 786 DI 10.1016/j.immuni.2009.10.001 PG 15 WC Immunology SC Immunology GA 523TQ UT WOS:000272097900012 PM 19896394 ER PT J AU Martin-Orozco, N Muranski, P Chung, Y Yang, XXO Yamazaki, T Lu, SJ Hwu, P Restifo, NP Overwijk, WW Dong, C AF Martin-Orozco, Natalia Muranski, Pawel Chung, Yeonseok Yang, Xuexian O. Yamazaki, Tomohide Lu, Sijie Hwu, Patrick Restifo, Nicholas P. Overwijk, Willem W. Dong, Chen TI T Helper 17 Cells Promote Cytotoxic T Cell Activation in Tumor Immunity SO IMMUNITY LA English DT Article ID POTENT ANTITUMOR IMMUNITY; DENDRITIC CELLS; IN-VIVO; TH17 CELLS; CROSS-PRESENTATION; LYMPHOPENIC HOSTS; CUTTING EDGE; CANCER; INTERLEUKIN-17; MELANOMA AB Although T helper 17 (Th17) cells have been found in tumor tissues, their function in cancer immunity is unclear. We found that interleukin-17A (IL-17A)-deficient mice were more susceptible to developing lung melanoma. Conversely, adoptive T cell therapy with tumor-specific Th17 cells prevented tumor development. Importantly, the Th17 cells retained their cytokine signature and exhibited stronger therapeutic efficacy than Th1 cells. Unexpectedly, therapy using Th17 cells elicited a remarkable activation of tumor-specific CD8(+) T cells, which were necessary for the antitumor effect. Th17 cells promoted dendritic cell recruitment into the tumor tissues and in draining lymph nodes increased CD8 alpha(+) dendritic cells containing tumor material. Moreover, Th17 cells promoted CCL20 chemokine production by tumor tissues, and tumor-bearing CCR6-deficient mice did not respond to Th17 cell therapy. Thus, 17 cells elicited a protective inflammation that promotes the activation of tumor-specific CD8(+) T cells. These findings have important implications in antitumor immunotherapies. C1 [Martin-Orozco, Natalia; Chung, Yeonseok; Yang, Xuexian O.; Yamazaki, Tomohide; Dong, Chen] Univ Texas Houston, MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA. [Lu, Sijie] Univ Texas Houston, MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cell Therapy, Houston, TX 77030 USA. [Hwu, Patrick; Overwijk, Willem W.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA. [Muranski, Pawel; Restifo, Nicholas P.] NCI, NIH, Bethesda, MD 20892 USA. RP Dong, C (reprint author), Univ Texas Houston, MD Anderson Canc Ctr, Dept Immunol, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM cdong@mdanderson.org RI dong, chen /B-3181-2009; Restifo, Nicholas/A-5713-2008; Martin Orozco, Natalia/E-4794-2010; Muranski, Pawel/E-5572-2010; OI dong, chen /0000-0002-0084-9130; Restifo, Nicholas P./0000-0003-4229-4580; Chung, Yeonseok/0000-0001-5780-4841 FU National Institute of Health; Targeted Therapy of MID Anderson Cancer Center; Leukemia and Lymphoma Society Scholar award; MD Anderson Cancer Center FX We thank the entire Dong lab for their help and discussion. This work is supported in part by grants from the National Institute of Health (to W.W.O. and C.D.) and a grant from the Center for Targeted Therapy of MID Anderson Cancer Center (to C.D. and N.M.O.). C.D. received a Leukemia and Lymphoma Society Scholar award and a Trust Fellowship of the MD Anderson Cancer Center. NR 40 TC 334 Z9 353 U1 4 U2 27 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV 20 PY 2009 VL 31 IS 5 BP 787 EP 798 DI 10.1016/j.immuni.2009.09.014 PG 12 WC Immunology SC Immunology GA 523TQ UT WOS:000272097900013 PM 19879162 ER PT J AU Shim, MS Kim, JY Jung, HK Lee, KH Xu, XM Carlson, BA Kim, KW Kim, IY Hatfield, DL Lee, BJ AF Shim, Myoung Sup Kim, Jin Young Jung, Hee Kyoung Lee, Kwang Hee Xu, Xue-Ming Carlson, Bradley A. Kim, Ki Woo Kim, Ick Young Hatfield, Dolph L. Lee, Byeong Jae TI Elevation of Glutamine Level by Selenophosphate Synthetase 1 Knockdown Induces Megamitochondrial Formation in Drosophila Cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SELENOPROTEIN SYNTHESIS; INDUCED APOPTOSIS; ESCHERICHIA-COLI; TRANSFER-RNA; SELENIUM; SELENOCYSTEINE; PROTEIN; GENE; MELANOGASTER; METABOLISM AB Although selenophosphate synthetase 1 (SPS1/SelD) is an essential gene in Drosophila, its function has not been determined. To elucidate its intracellular role, we targeted the removal of SPS1/SelD mRNA in Drosophila SL2 cells using RNA interference technology that led to the formation of vacuole-like globular structures. Surprisingly, these structures were identified as megamitochondria, and only depolarized mitochondria developed into megamitochondria. The mRNA levels of l(2) 01810 and glutamine synthetase 1 (GS1) were increased by SPS1/SelD knockdown. Blocking the expression of GS1 and l(2) 01810 completely inhibited the formation of megamitochondria induced by loss of SPS1/SelD activity and decreased the intracellular levels of glutamine to those of control cells suggesting that the elevated level of glutamine is responsible for megamitochondrial formation. Overexpression of GS1 and l(2) 01810 had a synergistic effect on the induction of megamitochondrial formation and on the synthesis of glutamine suggesting that l(2) 01810 is involved in glutamine synthesis presumably by activating GS1. Our results indicate that, in Drosophila, SPS1/SelD regulates the intracellular glutamine by inhibiting GS1 and l(2) 01810 expression and that elevated levels of glutamine lead to a nutritional stress that provides a signal for megamitochondrial formation. C1 [Shim, Myoung Sup; Kim, Jin Young; Jung, Hee Kyoung; Lee, Kwang Hee; Lee, Byeong Jae] Seoul Natl Univ, Sch Biol Sci, Inst Mol Biol & Genet, Lab Mol Genet & Genom, Seoul 151742, South Korea. [Xu, Xue-Ming; Carlson, Bradley A.; Hatfield, Dolph L.] NCI, Lab Canc Prevent, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kim, Ki Woo] Seoul Natl Univ, Coll Agr & Life Sci, Natl Instrumentat Ctr Environm Management, Seoul 151742, South Korea. [Kim, Ick Young] Korea Univ, Sch Life Sci & Biotechnol, Lab Cellular & Mol Biochem, Seoul 136701, South Korea. RP Lee, BJ (reprint author), Seoul Natl Univ, Sch Biol Sci, Inst Mol Biol & Genet, Lab Mol Genet & Genom, Bldg 504,Rm 523, Seoul 151742, South Korea. EM imbglmg@snu.ac.kr FU Korean Government [KRF-2005-070-C00086, KRF-2008-005-J00201]; NCI, Center for Cancer Research FX This work was supported by Korea Research Foundation Grants KRF-2005-070-C00086 and KRF-2008-005-J00201 funded by the Korean Government (Ministry of Education, Science, and Technology) (to B. J. L.). This work was also supported in part by a National Institutes of Health Intramural Research Program grant from NCI, Center for Cancer Research. NR 57 TC 16 Z9 18 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 20 PY 2009 VL 284 IS 47 BP 32881 EP 32894 DI 10.1074/jbc.M109.026492 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 522VR UT WOS:000272028400072 PM 19755423 ER PT J AU Matulonis, UA Berlin, S Ivy, P Tyburski, K Krasner, C Zarwan, C Berkenblit, A Campos, S Horowitz, N Cannistra, SA Lee, H Lee, J Roche, M Hill, M Whalen, C Sullivan, L Tran, C Humphreys, BD Penson, RT AF Matulonis, Ursula A. Berlin, Suzanne Ivy, Percy Tyburski, Karin Krasner, Carolyn Zarwan, Corrine Berkenblit, Anna Campos, Susana Horowitz, Neil Cannistra, Stephen A. Lee, Hang Lee, Julie Roche, Maria Hill, Margaret Whalen, Christin Sullivan, Laura Tran, Chau Humphreys, Benjamin D. Penson, Richard T. TI Cediranib, an Oral Inhibitor of Vascular Endothelial Growth Factor Receptor Kinases, Is an Active Drug in Recurrent Epithelial Ovarian, Fallopian Tube, and Peritoneal Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GYNECOLOGIC-ONCOLOGY-GROUP; SOLID TUMORS; PHASE-I; COLORECTAL-CANCER; BEVACIZUMAB; PACLITAXEL; GUIDELINES; EVALUATE; AZD2171; LYMPHANGIOGENESIS AB Purpose Angiogenesis is important for epithelial ovarian cancer (EOC) growth, and blocking angiogenesis can lead to EOC regression. Cediranib is an oral tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, VEGFR-3, and c-kit. Patients and Methods We conducted a phase II study of cediranib for recurrent EOC or peritoneal or fallopian tube cancer; cediranib was administered as a daily oral dose, and the original dose was 45 mg daily. Because of toxicities observed in the first 11 patients, the dose was lowered to 30 mg. Eligibility included <= two lines of chemotherapy for recurrence. End points included response rate (via Response Evaluation Criteria in Solid Tumors [RECIST] or modified Gynecological Cancer Inter-group CA-125), toxicity, progression-free survival (PFS), and overall survival (OS). Results Forty-seven patients were enrolled; 46 were treated. Clinical benefit rate (defined as complete response [CR] or partial response [PR], stable disease [SD] > 16 weeks, or CA-125 nonprogression > 16 weeks), which was the primary end point, was 30%; eight patients (17%; 95% CI, 7.6% to 30.8%) had a PR, six patients (13%; 95% CI, 4.8% to 25.7%) had SD, and there were no CRs. Eleven patients (23%) were removed from study because of toxicities before two cycles. Grade 3 toxicities (> 20% of patients) included hypertension (46%), fatigue (24%), and diarrhea (13%). Grade 2 hypothyroidism occurred in 43% of patients. Grade 4 toxicities included CNS hemorrhage (n = 1), hypertriglyceridemia/hypercholesterolemia/elevated lipase (n = 1), and dehydration/elevated creatinine (n = 1). No bowel perforations or fistulas occurred. Median PFS was 5.2 months, and median OS has not been reached; median follow-up time is 10.7 months. Conclusion Cediranib has activity in recurrent EOC, tubal cancer, and peritoneal cancer with predictable toxicities observed with other TKIs. C1 [Matulonis, Ursula A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Hematol & Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Gynecol Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Hematol & Oncol, Boston, MA 02215 USA. Lahey Clin Fdn, Dept Hematol & Oncol, Burlington, MA USA. Wyeth Pharmaceut, Cambridge, MA USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Matulonis, UA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM Ursula_matulonis@dfci.harvard.edu FU Madeline Franchi Ovarian Cancer Fund; Ovations for the Cure FX Supported in part by donations made by the Madeline Franchi Ovarian Cancer Fund and Ovations for the Cure. NR 26 TC 150 Z9 155 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 20 PY 2009 VL 27 IS 33 BP 5601 EP 5606 DI 10.1200/JCO.2009.23.2777 PG 6 WC Oncology SC Oncology GA 521VS UT WOS:000271954200019 PM 19826113 ER PT J AU Philip, PA Mooney, M Jaffe, D Eckhardt, G Moore, M Meropol, N Emens, L O'Reilly, E Korc, M Ellis, L Benedetti, J Rothenberg, M Willett, C Tempero, M Lowy, A Abbruzzese, J Simeone, D Hingorani, S Berlin, J Tepper, J AF Philip, Philip A. Mooney, Margaret Jaffe, Deborah Eckhardt, Gail Moore, Malcolm Meropol, Neal Emens, Leisha O'Reilly, Eileen Korc, Murray Ellis, Lee Benedetti, Jacqueline Rothenberg, Mace Willett, Christopher Tempero, Margaret Lowy, Andrew Abbruzzese, James Simeone, Diane Hingorani, Sunil Berlin, Jordan Tepper, Joel TI Consensus Report of the National Cancer Institute Clinical Trials Planning Meeting on Pancreas Cancer Treatment SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FACTOR RECEPTOR INHIBITION; PHASE-II TRIALS; K-RAS; STEM-CELLS; DUCTAL ADENOCARCINOMA; MESENCHYMAL TRANSITION; CHRONIC INFLAMMATION; TUMOR-GROWTH; GEMCITABINE; FARNESYLTRANSFERASE AB Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer mortality, despite significant improvements in diagnostic imaging and operative mortality rates. The 5-year survival rate remains less than 5% because of microscopic or gross metastatic disease at time of diagnosis. The Clinical Trials Planning Meeting in pancreatic cancer was convened by the National Cancer Institute's Gastrointestinal Cancer Steering Committee to discuss the integration of basic and clinical knowledge in the design of clinical trials in PDAC. Major emphasis was placed on the enhancement of research to identify and validate the relevant targets and molecular pathways in PDAC, cancer stem cells, and the microenvironment. Emphasis was also placed on developing rational combinations of targeted agents and the development of predictive biomarkers to assist selection of patient subsets. The development of preclinical tumor models that are better predictive of human PDAC must be supported with wider availability to the research community. Phase III clinical trials should be implemented only if there is a meaningful clinical signal of efficacy and safety in the phase II setting. The emphasis must therefore be on performing well-designed phase II studies with uniform sets of basic entry and evaluation criteria with survival as a primary endpoint. Patients with either metastatic or locally advanced PDAC must be studied separately. C1 [Philip, Philip A.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48201 USA. NCI, NIH, Bethesda, MD 20892 USA. Univ Colorado, Denver, CO 80202 USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Norris Cotton Canc Ctr, Lebanon, NH USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. SW Oncol Grp, Ctr Stat, Seattle, WA USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Pfizer Oncol, New York, NY USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Calif San Francisco, Med Ctr, San Francisco, CA 94143 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ Michigan, Ann Arbor, MI 48109 USA. RP Philip, PA (reprint author), Wayne State Univ, Karmanos Canc Inst, 4 Hudson Weber Canc Res Ctr,4100 John R St, Detroit, MI 48201 USA. EM philipp@karmanos.org FU Pfizer; OSI Pharmaceuticals; Genentech; Response Genetics; OncoMed Pharmaceuticals Expert Testimony FX Philip A. Philip, sanofi-aventis, Bristol-Myers Squibb, Pfizer; Malcolm Moore, OSI Pharmaceuticals; Leisha Emens, Genentech; Lee Ellis, sanofi-aventis; Margaret Tempero, Response Genetics; Diane Simeone, OncoMed Pharmaceuticals Expert Testimony: None Other Remuneration: Jordan Berlin, Pfizer NR 61 TC 131 Z9 135 U1 1 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 20 PY 2009 VL 27 IS 33 BP 5660 EP 5669 DI 10.1200/JCO.2009.21.9022 PG 10 WC Oncology SC Oncology GA 521VS UT WOS:000271954200027 PM 19858397 ER PT J AU Patnaik, S Dietz, HC Zheng, W Austin, C Marugan, JJ AF Patnaik, Samarjit Dietz, Harry C. Zheng, Wei Austin, Christopher Marugan, Juan J. TI Multi-Gram Scale Synthesis of FR180204 SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID ERK; INHIBITORS; PATHWAY; RAS AB A concise synthesis of the ERK inhibitor FR180204 has been developed. The synthesis consists of six operationally simple steps and can be utilized to make multi-gram quantities of FR180204. C1 [Patnaik, Samarjit; Zheng, Wei; Austin, Christopher; Marugan, Juan J.] NIH, Chem Genom Ctr, Rockville, MD 20850 USA. [Dietz, Harry C.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. RP Patnaik, S (reprint author), NIH, Chem Genom Ctr, 9800 Med Ctr Dr, Rockville, MD 20850 USA. EM patnaiks@mail.nih.gov OI Zheng, Wei/0000-0003-1034-0757 FU Intramural NIH HHS [Z99 HG999999] NR 15 TC 8 Z9 8 U1 0 U2 5 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 20 PY 2009 VL 74 IS 22 BP 8870 EP 8873 DI 10.1021/jo901835m PG 4 WC Chemistry, Organic SC Chemistry GA 518AR UT WOS:000271662500055 PM 19852504 ER PT J AU Jaworski, CJ Aryankalayil-John, M Campos, MM Fariss, RN Rowsey, J Agarwalla, N Reid, TW Dushku, N Cox, CA Carper, D Wistow, G AF Jaworski, C. J. Aryankalayil-John, M. Campos, M. M. Fariss, R. N. Rowsey, J. Agarwalla, N. Reid, T. W. Dushku, N. Cox, C. A. Carper, D. Wistow, G. TI Expression analysis of human pterygium shows a predominance of conjunctival and limbal markers and genes associated with cell migration SO MOLECULAR VISION LA English DT Article ID BRONCHIAL EPITHELIAL-CELLS; INDUCED CORNEAL ASTIGMATISM; BETAIG-H3 GENE; MESENCHYMAL TRANSITION; POLYAMINE ANALOGS; DOWN-REGULATION; BREAST-CANCER; BASAL CELLS; STEM-CELLS; HUMAN-EYE AB Purpose: Pterygium is a vision-impairing fibrovascular lesion that grows across the corneal surface and is associated with sunlight exposure. To increase our understanding of the cells types involved in pterygium, we have used expressed sequence tag analysis to examine the transcriptional repertoire of isolated pterygium and to identify marker genes for tissue origin and cell migration. Methods: An unnormalized unamplified cDNA library was prepared from 15 pooled specimens of surgically removed pterygia as part of the NEIBank project. Gene expression patterns were compared with existing data for human cornea, limbus, and conjunctiva, and expression of selected genes was verified by immunofluorescence localization in normal eye ocular surface and in pterygium. Results: Sequence analysis of 2,976 randomly selected clones produced over 1,800 unique clusters, potentially representing single genes. The most abundant complementary DNAs from pterygium include clusterin, keratins 13 (Krt13) and 4 (Krt4), S100A9/calgranulin B, and spermidine/spermine N1-acetyltransferase (SAT1). Markers for both conjunctiva (such as keratin 13/4 and AQP3) and corneal epithelium (such as keratin 12/3 and AQP5) were present. Immunofluorescence of Krt12 and 13 in the normal ocular surface showed specificity of Krt12 in cornea and Krt13 in conjunctival and limbal epithelia, with a fairly sharp boundary at the limbal-corneal border. In the pterygium there was a patchy distribution of both Krt12 and 13 up to a normal corneal epithelial region specific for Krt12. Immunoglobulins were also among the prominently expressed transcripts. Several of the genes expressed most abundantly in excised pterygium, particularly S100A9 and SAT1, have roles in cell migration. SAT1 exerts its effects through control of polyamine levels. IPENSpm, a polyamine analogue, showed a significant ability to reduce migration in primary cultures of pterygium. A number of genes highly expressed in cornea were not found in pterygium (several small leucine-rich proteoglycan family members) or were expressed at considerably lower levels (ALDH3A1 and decorin). Conclusions: The expression pattern of keratins and other markers in pterygium most closely resemble those of conjunctival and limbal cells; some corneal markers are present, notably Krt12, but at lower levels than equivalent conjunctival markers. Our data are consistent with the model of pterygium developing from the migration of conjunctivaland limbal-like cells into corneal epithelium. Identification of genes with roles in cell migration suggests potential therapeutic targets. In particular, the ability of polyamine analogues to reduce migration in primary cultures of pterygium presents a possible approach to slowing pterygium growth. C1 [Jaworski, C. J.] NEI, Sect Mol Therapeut, LRCMB, NIH, Bethesda, MD 20892 USA. [Aryankalayil-John, M.] NCI, Bethesda, MD 20892 USA. [Dushku, N.] Kaiser Permanente Med Ctr, Sacramento, CA USA. [Reid, T. W.] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA. [Campos, M. M.; Fariss, R. N.] NEI, NEI Biol Imaging Core, NIH, Bethesda, MD 20892 USA. [Wistow, G.] NEI, Sect Mol Struct & Funct Genom, NIH, Bethesda, MD 20892 USA. [Cox, C. A.] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. RP Jaworski, CJ (reprint author), NEI, Sect Mol Therapeut, LRCMB, NIH, Bldg 7,Room 202, Bethesda, MD 20892 USA. EM Jaworski@helix.nih.gov NR 72 TC 20 Z9 21 U1 0 U2 2 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD NOV 20 PY 2009 VL 15 IS 256-59 BP 2421 EP 2434 PG 14 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 528VP UT WOS:000272475400003 PM 19956562 ER PT J AU Calado, RT Regal, JA Kleiner, DE Schrump, DS Peterson, NR Pons, V Chanock, SJ Lansdorp, PM Young, NS AF Calado, Rodrigo T. Regal, Joshua A. Kleiner, David E. Schrump, David S. Peterson, Nathan R. Pons, Veronica Chanock, Stephen J. Lansdorp, Peter M. Young, Neal S. TI A Spectrum of Severe Familial Liver Disorders Associate with Telomerase Mutations SO PLOS ONE LA English DT Article ID IDIOPATHIC PULMONARY-FIBROSIS; NODULAR REGENERATIVE HYPERPLASIA; DOMINANT DYSKERATOSIS-CONGENITA; APLASTIC-ANEMIA; REVERSE-TRANSCRIPTASE; CANCER; GENE; RNA; VARIANTS; 5P15.33 AB Background: Telomerase is an enzyme specialized in maintaining telomere lengths in highly proliferative cells. Loss-of-function mutations cause critical telomere shortening and are associated with the bone marrow failure syndromes dyskeratosis congenita and aplastic anemia and with idiopathic pulmonary fibrosis. Here, we sought to determine the spectrum of clinical manifestations associated with telomerase loss-of-function mutations. Methodology/Principal Findings: Sixty-nine individuals from five unrelated families with a variety of hematologic, hepatic, and autoimmune disorders were screened for telomerase complex gene mutations; leukocyte telomere length was measured by flow fluorescence in situ hybridization in mutation carriers and some non-carriers; the effects of the identified mutations on telomerase activity were determined; and genetic and clinical data were correlated. In six generations of a large family, a loss-of-function mutation in the telomerase enzyme gene TERT associated with severe telomere shortening and a range of hematologic manifestations, from macrocytosis to acute myeloid leukemia, with severe liver diseases marked by fibrosis and inflammation, and one case of idiopathic pulmonary fibrosis but not with autoimmune disorders. Additionally, we identified four unrelated families in which loss-of-function TERC or TERT gene mutations tracked with marrow failure, pulmonary fibrosis, and a spectrum of liver disorders. Conclusions/Significance: These results indicate that heterozygous telomerase loss-of-function mutations associate with but are not determinant of a large spectrum of hematologic and liver abnormalities, with the latter sometimes occurring in the absence of marrow failure. Our findings, along with the link between pulmonary fibrosis and telomerase mutations, also suggest a common pathogenic mechanism for fibrotic diseases in which defective telomere repair plays important role. RP Calado, RT (reprint author), NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. EM calador@nhlbi.nih.gov RI Calado, Rodrigo/G-2619-2011; OI Kleiner, David/0000-0003-3442-4453 FU Canadian Institutes of Health Research [GMH79042, MOP38075]; Intramural NIH HHS NR 36 TC 83 Z9 83 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 20 PY 2009 VL 4 IS 11 AR e7926 DI 10.1371/journal.pone.0007926 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 522NL UT WOS:000272004800008 PM 19936245 ER PT J AU Ma, WX Zhao, L Fontainhas, AM Fariss, RN Wong, WT AF Ma, Wenxin Zhao, Lian Fontainhas, Aurora M. Fariss, Robert N. Wong, Wai T. TI Microglia in the Mouse Retina Alter the Structure and Function of Retinal Pigmented Epithelial Cells: A Potential Cellular Interaction Relevant to AMD SO PLOS ONE LA English DT Article ID MACULAR DEGENERATION; CHOROIDAL NEOVASCULARIZATION; SUBRETINAL MICROGLIA; FRACTALKINE RECEPTOR; UNITED-STATES; IMMUNE-SYSTEM; NITRIC-OXIDE; IN-VITRO; DRUSEN; INFLAMMATION AB Background: Age-related macular degeneration (AMD) is a leading cause of legal blindness in the elderly in the industrialized word. While the immune system in the retina is likely to be important in AMD pathogenesis, the cell biology underlying the disease is incompletely understood. Clinical and basic science studies have implicated alterations in the retinal pigment epithelium (RPE) layer as a locus of early change. Also, retinal microglia, the resident immune cells of the retina, have been observed to translocate from their normal position in the inner retina to accumulate in the subretinal space close to the RPE layer in AMD eyes and in animal models of AMD. Methodology/Principal Findings: In this study, we examined the effects of retinal microglia on RPE cells using 1) an in vitro model where activated retinal microglia are co-cultured with primary RPE cells, and 2) an in vivo mouse model where retinal microglia are transplanted into the subretinal space. We found that retinal microglia induced in RPE cells 1) changes in RPE structure and distribution, 2) increased expression and secretion of pro-inflammatory, chemotactic, and pro-angiogenic molecules, and 3) increased extent of in vivo choroidal neovascularization in the subretinal space. Conclusions/Significance: These findings share similarities with important pathological features found in AMD and suggest the relevance of microglia-RPE interactions in AMD pathogenesis. We speculate that the migration of retinal microglia into the subretinal space in early stages of the disease induces significant changes in RPE cells that perpetuate further microglial accumulation, increase inflammation in the outer retina, and fosters an environment conducive for the formation of neovascular changes responsible for much of vision loss in advanced AMD. RP Ma, WX (reprint author), NEI, Unit Neuron Glia Interact Retinal Dis, NIH, Bethesda, MD 20892 USA. EM wongw@nei.nih.gov RI Wong, Wai/B-6118-2017 OI Wong, Wai/0000-0003-0681-4016 FU Intramural NIH HHS NR 61 TC 84 Z9 90 U1 1 U2 15 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 20 PY 2009 VL 4 IS 11 AR e7945 DI 10.1371/journal.pone.0007945 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 522NL UT WOS:000272004800021 PM 19936204 ER PT J AU Chen, L Kwon, YD Zhou, TQ Wu, XL O'Dell, S Cavacini, L Hessell, AJ Pancera, M Tang, M Xu, L Yang, ZY Zhang, MY Arthos, J Burton, DR Dimitrov, DS Nabel, GJ Posner, MR Sodroski, J Wyatt, R Mascola, JR Kwong, PD AF Chen, Lei Kwon, Young Do Zhou, Tongqing Wu, Xueling O'Dell, Sijy Cavacini, Lisa Hessell, Ann J. Pancera, Marie Tang, Min Xu, Ling Yang, Zhi-Yong Zhang, Mei-Yun Arthos, James Burton, Dennis R. Dimitrov, Dimiter S. Nabel, Gary J. Posner, Marshall R. Sodroski, Joseph Wyatt, Richard Mascola, John R. Kwong, Peter D. TI Structural Basis of Immune Evasion at the Site of CD4 Attachment on HIV-1 gp120 SO SCIENCE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODY; NEUTRALIZING ANTIBODIES; BINDING-SITE; EFFICIENT NEUTRALIZATION; ENVELOPE GLYCOPROTEINS; INFECTED INDIVIDUALS; PROTEIN; PANEL; CRYSTALLIZATION AB The site on HIV-1 gp120 that binds to the CD4 receptor is vulnerable to antibodies. However, most antibodies that interact with this site cannot neutralize HIV-1. To understand the basis of this resistance, we determined co-crystal structures for two poorly neutralizing, CD4-binding site (CD4BS) antibodies, F105 and b13, in complexes with gp120. Both antibodies exhibited approach angles to gp120 similar to those of CD4 and a rare, broadly neutralizing CD4BS antibody, b12. Slight differences in recognition, however, resulted in substantial differences in F105- and b13-bound conformations relative to b12-bound gp120. Modeling and binding experiments revealed these conformations to be poorly compatible with the viral spike. This incompatibility, the consequence of slight differences in CD4BS recognition, renders HIV-1 resistant to all but the most accurately targeted antibodies. C1 [Chen, Lei; Kwon, Young Do; Zhou, Tongqing; Wu, Xueling; O'Dell, Sijy; Pancera, Marie; Tang, Min; Xu, Ling; Yang, Zhi-Yong; Nabel, Gary J.; Wyatt, Richard; Mascola, John R.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Cavacini, Lisa; Posner, Marshall R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Head & Neck Oncol Program, Boston, MA 02115 USA. [Hessell, Ann J.; Burton, Dennis R.] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. [Hessell, Ann J.; Burton, Dennis R.] Scripps Res Inst, Dept Microbial Sci, La Jolla, CA 92037 USA. [Hessell, Ann J.; Burton, Dennis R.] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA. [Zhang, Mei-Yun; Dimitrov, Dimiter S.] NCI, Ctr Canc Res, Frederick, MD 21702 USA. [Arthos, James] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Burton, Dennis R.] Massachusetts Gen Hosp, MIT, Ragon Inst, Boston, MA 02114 USA. [Burton, Dennis R.] Harvard Univ, Boston, MA 02114 USA. [Sodroski, Joseph] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Kwong, PD (reprint author), NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. EM pdkwong@nih.gov; pdkwong@nih.gov RI Zhang, Mei-Yun/E-9908-2010; Kwon, Young Do/A-6957-2010; Zhou, Tongqing/A-6880-2010 OI Zhou, Tongqing/0000-0002-3935-4637 FU NIH; International AIDS Vaccine Initiative; Bill and Melinda Gates Foundation Grand Challenges in Global Heath Initiative FX L. Chen produced and assessed for crystallization CD4BS antibodies with unconstrained gp120, crystallized the F105-gp120 complex, assisted with F105-gp120 data collection and structure solution, and carried out mutagenesis and SPR binding experiments. Y. D. K. assisted with F105-gp120 crystallization, data collection, and structure solution and refined and analyzed the F105-gp120 structure. T. Z. purified, crystallized, solved, and analyzed the b13-gp120 complex. X. W., S. O.' D. and J. R. M. assessed neutralization potency and breadth of CD4, patient sera, and CD4BS antibodies. L. Chen and M. P. carried out cell-surface JR-FL binding experiments. M. T. and R. W. provided YU2 core gp120; L. X. and G. J. N. provided stabilized-core gp120; Z.-Y. Y. and G. J. N. converted b13 from Fab to IgG format and provided b13 IgG; L. Cavacini and M. R. P. provided F105; M.-Y. Z. and D. S. D. provided m6, m14, and m18; A. J. H. and D. R. B. provided b3, b6, b11, b12; and J. A. provided dodecameric CD4. J. A., D. R. B., D. S. D., G. J. N., M. R. P., J. S., R. W., and J. R. M. assisted with analysis and writing, and P. D. K. assisted with crystallography and experimental planning and wrote the first draft. Figures, tables, and supporting online material were produced by L. Chen, Y. D. K., M. P., T. Z. and X. W. We thank L. Shapiro and members of the Structural Biology Section, Vaccine Research Center (VRC), for discussions and comments on the manuscript, M. Connors for patient serum, M. Fung for antibodies G3-42 and G3-299, J. Robinson for antibodies 1.5e and F91, J. Stuckey for assistance with figures and tables, S. Subramaniam for EM tomograms, C. Winter and C. Huang for S2 production of core YU2 gp120, X. Yang for preparation of JR-FL gp120, and the Flow Cytometry Core, VRC, for assistance with antibody binding to cell-surface-expressed HIV-1 spikes. Support for this work was provided by the Intramural Research Program of NIH, the International AIDS Vaccine Initiative, a grant from the Bill and Melinda Gates Foundation Grand Challenges in Global Heath Initiative, and grants from NIH. The use of insertion device 22 (Southeast Region Collaborative Access Team) at the Advanced Photon Source was supported by the U. S. Department of Energy, Basic Energy Sciences, Office of Science, under contract number W-31-109-Eng-38. Coordinates and structure factors for the F105-gp120 complex (accession code 3HI1) and the b13-gp120 complexes (accession codes 3IDX and 3IDY for C222 and C2221 forms, respectively) have been deposited with the Protein Data Bank. NR 33 TC 187 Z9 192 U1 0 U2 21 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 20 PY 2009 VL 326 IS 5956 BP 1123 EP 1127 DI 10.1126/science.1175868 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 521UW UT WOS:000271951000048 PM 19965434 ER PT J AU Flem, ET Kasymbekova, KT Vainio, K Gentsch, J Abdikarimov, ST Glass, RI Bresee, JS AF Flem, Elmira T. Kasymbekova, Kaliya T. Vainio, Kirsti Gentsch, Jon Abdikarimov, Sabirjan T. Glass, Roger I. Bresee, Joseph S. TI Rotavirus infection in hospitalized children and estimates of disease burden in Kyrgyzstan, 2005-2007 SO VACCINE LA English DT Article DE Rotavirus; Gastroenteritis; Epidemiology ID POLYMERASE CHAIN-REACTION; VACCINE; POPULATION; EFFICACY; DEATHS; SAFETY AB To estimate the rotavirus-associated burden in Kyrgyzstan, we conducted hospital surveillance among children <5 years old with diarrhoea during 2005-2007. Of 3756 children hospitalized with diarrhoea, 26% had rotavirus detected in stool samples by an enzyme immunoassay. The virus genotype G1P[8] was identified in 60% of 190 characterized samples from 2005 to 2006. The estimated risk for rotavirus hospitalization by age 5 years was 1 in 28 children. One quarter of all gastroenteritis hospitalizations in children <5 years old in Kyrgyzstan may be attributable to rotavirus. Rotavirus vaccination could be an important health intervention to reduce the burden of rotavirus gastroenteritis. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Flem, Elmira T.; Vainio, Kirsti] Norwegian Inst Publ Hlth, Div Infect Dis Control, N-0403 Oslo, Norway. [Kasymbekova, Kaliya T.; Abdikarimov, Sabirjan T.] Minist Hlth, Dept State Sanit Epidemiol Surveillance, Bishkek, Kyrgyzstan. [Gentsch, Jon; Bresee, Joseph S.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Glass, Roger I.] NIH, Fogarty Int, Bethesda, MD 20892 USA. RP Flem, ET (reprint author), Norwegian Inst Publ Hlth, Div Infect Dis Control, POB 4404, N-0403 Oslo, Norway. EM elmira.flem@fhi.no FU Program for Appropriate Technology in Health (PATH); GAVI Alliance; Research Council of Norway; Norwegian Institute of Public Health; U.S. Centers for Disease Control and Prevention FX This work was performed under a collaborative agreement with the Program for Appropriate Technology in Health (PATH) and was funded in full or in part by the GAVI Alliance, the Research Council of Norway, the Norwegian Institute of Public Health and the U.S. Centers for Disease Control and Prevention. NR 28 TC 9 Z9 9 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD NOV 20 PY 2009 VL 27 BP F35 EP F39 DI 10.1016/j.vaccine.2009.08.087 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 541KQ UT WOS:000273415000008 PM 19931716 ER PT J AU Le, LT Nguyen, TV Nguyen, PM Huong, NT Huong, NT Huong, NTM Hanh, TB Ha, DN Anh, DD Gentsch, JR Wang, YH Esona, MD Glass, RI Steele, AD Kilgore, PE Man, NV Jiang, BM Hien, ND AF Le, Luan T. Nguyen, Trang V. Nguyen, Phuong M. Huong, Nguyen T. Huong, Ngo T. Huong, Nguyen T. M. Hanh, Tran B. Ha, Dang N. Anh, Dang D. Gentsch, Jon R. Wang, Yuhuan Esona, Mathew D. Glass, Roger I. Steele, A. Duncan Kilgore, Paul E. Man, Nguyen V. Jiang, Baoming Hien, Nguyen D. TI Development and characterization of candidate rotavirus vaccine strains derived from children with diarrhoea in Vietnam SO VACCINE LA English DT Article DE Rotavirus vaccine; Diarrhoea; Vietnam ID POLYMERASE-CHAIN-REACTION; SEQUENCE-ANALYSIS; IDENTIFICATION; VIRUSES; BURDEN AB In Vietnam, rotavirus infection accounts for more than one-half of all hospitalizations for diarrhoea among children less than 5 years of age. While new vaccines to prevent rotavirus diarrhoea have been developed and introduced into some countries by multinational manufacturers, the ability for developing countries such as Vietnam to introduce several new and important vaccines into the routine infant immunization schedule may be challenging. In order to be partially self-sufficient in vaccine production, Vietnam has pursued the development of several rotavirus strains as candidate vaccines using isolates obtained from Vietnamese children with diarrhoea. This paper describes the origin, isolation and characterization of 3 human rotavirus strains being considered for further vaccine development in Vietnam. The goal is to prepare a monovalent G1P [8] rotavirus vaccine using one of these strains obtained in Vietnam and naturally attenuated by multiple passages in cell culture. While this is an ambitious project that will require several years' work, we are using the lessons learned to improve the overall quality of vaccine production including the use of Vero cell techniques for the manufacture of other vaccines in Vietnam. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Le, Luan T.; Huong, Nguyen T.; Huong, Ngo T.; Huong, Nguyen T. M.; Hanh, Tran B.; Ha, Dang N.; Man, Nguyen V.; Hien, Nguyen D.] POLYVAC, Ctr Res & Prod Vaccines & Biol, Hanoi, Vietnam. [Nguyen, Trang V.; Nguyen, Phuong M.; Anh, Dang D.] Natl Inst Hyg & Epidemiol, Hanoi, Vietnam. [Gentsch, Jon R.; Wang, Yuhuan; Esona, Mathew D.; Jiang, Baoming] US Ctr Dis Control & Prevent, Div Viral Dis, Atlanta, GA 30333 USA. [Glass, Roger I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Steele, A. Duncan] PATH, Seattle, WA USA. [Kilgore, Paul E.] Int Vaccine Inst, Seoul, South Korea. RP Le, LT (reprint author), POLYVAC, Ctr Res & Prod Vaccines & Biol, 135 Loduc St, Hanoi, Vietnam. EM luanpolyvac@gmail.com; bxj4@cdc.gov RI Kilgore, Paul/L-1462-2013 OI Kilgore, Paul/0000-0003-3214-4482 FU Ministry of Health and the Ministry of Science and Technology, Vietnam; World Health Organisation FX Supported by grants form the Ministry of Health and the Ministry of Science and Technology, Vietnam, and the World Health Organisation. NR 14 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD NOV 20 PY 2009 VL 27 SU 5 BP F130 EP F138 DI 10.1016/j.vaccine.2009.08.086 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 541KQ UT WOS:000273415000026 ER PT J AU Wilopo, SA Soenarto, Y Bresee, JS Tholib, A Aminah, S Cahyono, A Gentsch, JR Kilgore, P Glass, RI AF Wilopo, Siswanto Agus Soenarto, Yati Bresee, Joseph S. Tholib, Abu Aminah, Sri Cahyono, Anton Gentsch, Jon R. Kilgore, Paul Glass, Roger I. TI Rotavirus surveillance to determine disease burden and epidemiology in Java, Indonesia, August 2001 through April 2004 SO VACCINE LA English DT Article DE Epidemiology; Gastroenteritis; Rotavirus; Burden of disease; Indonesia ID ACUTE DIARRHEA; HONG-KONG; CHILDREN; GASTROENTERITIS; INFECTION; MORTALITY; VACCINES; JAKARTA; NETWORK AB This study estimates rotavirus disease burden in children under age 3 years presenting with acute gastroenteritis to hospitals in Purworejo district and Yogyakarta city from August 2001 to April 2004. Among a total of 8929 hospitalized children, 1397 (16%) presented with acute gastroenteritis and of the 1321 stool samples tested, 705 (53%) were positive for rotavirus. Rotavirus infections were most common among children aged 7-23 months and rotavirus was more common during the dry season (June through August). Logistic regression analysis showed no differences in socioeconomic indicators between the rotavirus positive and negative admissions. Rotavirus vaccination may prevent a large proportion of all hospitalizations of young children under 3 years of age presenting with acute gastroenteritis. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Wilopo, Siswanto Agus] Gadjah Mada Univ, CHN RL, Yogyakarta, Indonesia. [Wilopo, Siswanto Agus] Gadjah Mada Univ, Dept Publ Hlth, Yogyakarta, Indonesia. [Soenarto, Yati] Dr Sardjito Hosp, Dept Pediat, Yogyakarta, Indonesia. [Bresee, Joseph S.; Gentsch, Jon R.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Tholib, Abu] Gadjah Mada Univ, Dept Microbiol, Fac Med, Bulaksumur 55281, Yogyakarta, Indonesia. [Aminah, Sri] RSUD Wirosaban Hosp, Dept Pediat, Yogyakarta, Indonesia. [Cahyono, Anton] RSUD Purworedjo Dist Hosp, Dept Pediat, Purworedjo, Indonesia. [Kilgore, Paul] Int Vaccine Inst, Seoul, South Korea. [Glass, Roger I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Wilopo, SA (reprint author), Gadjah Mada Univ, Ctr Reprod Hlth, Dept Publ Hlth, Fac Med, IKM Bldg 1st Floor,Farmako 1 St,Sekip Utara, Bulaksumur 55281, Yogyakarta, Indonesia. EM sawilopo@yahoo.com RI Kilgore, Paul/L-1462-2013 OI Kilgore, Paul/0000-0003-3214-4482 FU Rotavirus Vaccine Program, PATH [GAV.1142-01-07211-SPS] FX This work was performed under a collaborative arrangement with PATH and CDC and was funded in full or in part by the Rotavirus Vaccine Program, PATH (GAV.1142-01-07211-SPS). NR 28 TC 5 Z9 5 U1 1 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 20 PY 2009 VL 27 BP F61 EP F66 DI 10.1016/j.vaccine.2009.09.004 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 541KQ UT WOS:000273415000013 PM 19931722 ER PT J AU Yee, EL Fang, ZY Liu, N Hadler, SC Liang, XF Wang, HQ Zhu, X Jiang, BM Parashar, U Widdowson, MA Glass, RI AF Yee, Eileen L. Fang, Zhao-Yin Liu, Na Hadler, Stephen C. Liang, Xiaofeng Wang, Huaqing Zhu, Xu Jiang, Baoming Parashar, Umesh Widdowson, Marc-Alain Glass, Roger I. TI Importance and challenges of accurately counting rotavirus deaths in China, 2002 SO VACCINE LA English DT Article DE Rotavirus; Mortality; Vaccine ID CHILDREN; DIARRHEA; DISEASE; BURDEN AB Rotavirus mortality is an important component of the total burden of rotavirus disease for children under 5 years old, but accurate estimation is difficult for many developing countries. Here we applied a more direct method to improve estimates of rotavirus mortality in China using 2002 Chinese-specific data. Results indicate that in 2002, approximately 13,400 children under 5 years old in China died from rotavirus and 70% of these deaths occur in rural areas. Thus, a national rotavirus immunization program targeting rural areas with high mortality from diarrhoea could dramatically reduce these deaths and urban areas could reduce childhood hospitalizations attributed to rotavirus by 43%. Published by Elsevier Ltd. C1 [Yee, Eileen L.; Jiang, Baoming; Parashar, Umesh; Widdowson, Marc-Alain; Glass, Roger I.] Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Div Viral Dis, Epidemiol Branch, Atlanta, GA 30333 USA. [Fang, Zhao-Yin; Liu, Na] Chinese Ctr Dis Control & Prevent, Natl Inst Viral Dis Control & Prevent, Viral Gastroenteritis Div, Beijing, Peoples R China. [Hadler, Stephen C.] WHO, Expanded Programme Immunizat, Beijing, Peoples R China. [Liang, Xiaofeng; Wang, Huaqing] Chinese Ctr Dis Control & Prevent, Natl Immunizat Program, Beijing, Peoples R China. [Zhu, Xu] UNICEF China, Hlth Nutr & WES Sect, Beijing, Peoples R China. [Glass, Roger I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Yee, EL (reprint author), Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Div Viral Dis, Epidemiol Branch, 1600 Clifton Rd NE,MS E02, Atlanta, GA 30333 USA. EM bwd3@cdc.gov OI Widdowson, Marc-Alain/0000-0002-0682-6933 FU Centers for Disease Control and Prevention FX This Study was supported by the Centers for Disease Control and Prevention. NR 12 TC 11 Z9 12 U1 0 U2 0 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 20 PY 2009 VL 27 BP F46 EP F49 DI 10.1016/j.vaccine.2009.08.065 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 541KQ UT WOS:000273415000010 PM 19931719 ER PT J AU Novozhilov, AS Koonin, EV AF Novozhilov, Artem S. Koonin, Eugene V. TI Exceptional error minimization in putative primordial genetic codes SO BIOLOGY DIRECT LA English DT Article ID AMINO-ACID SYNTHESIS; COEVOLUTION THEORY; PRIMITIVE EARTH; TRIPLET-CODE; EVOLUTION; ORIGIN; OPTIMIZATION; ASSOCIATION; ATMOSPHERES; CHEMISTRY AB Background: The standard genetic code is redundant and has a highly non-random structure. Codons for the same amino acids typically differ only by the nucleotide in the third position, whereas similar amino acids are encoded, mostly, by codon series that differ by a single base substitution in the third or the first position. As a result, the code is highly albeit not optimally robust to errors of translation, a property that has been interpreted either as a product of selection directed at the minimization of errors or as a non-adaptive by-product of evolution of the code driven by other forces. Results: We investigated the error-minimization properties of putative primordial codes that consisted of 16 supercodons, with the third base being completely redundant, using a previously derived cost function and the error minimization percentage as the measure of a code's robustness to mistranslation. It is shown that, when the 16-supercodon table is populated with 10 putative primordial amino acids, inferred from the results of abiotic synthesis experiments and other evidence independent of the code's evolution, and with minimal assumptions used to assign the remaining supercodons, the resulting 2-letter codes are nearly optimal in terms of the error minimization level. Conclusion: The results of the computational experiments with putative primordial genetic codes that contained only two meaningful letters in all codons and encoded 10 to 16 amino acids indicate that such codes are likely to have been nearly optimal with respect to the minimization of translation errors. This near-optimality could be the outcome of extensive early selection during the co-evolution of the code with the primordial, error-prone translation system, or a result of a unique, accidental event. Under this hypothesis, the subsequent expansion of the code resulted in a decrease of the error minimization level that became sustainable owing to the evolution of a high-fidelity translation system. C1 [Novozhilov, Artem S.; Koonin, Eugene V.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM novozhil@ncbi.nlm.nih.gov; koonin@ncbi.nlm.nih.gov RI Novozhilov, Artem/D-7544-2012; Novozhilov, Artem/C-9248-2013 OI Novozhilov, Artem/0000-0001-5469-2557 FU DHHS (NIH, National Library of Medicine) FX The authors' research is supported by intramural funds of the DHHS (NIH, National Library of Medicine). NR 69 TC 13 Z9 13 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6150 J9 BIOL DIRECT JI Biol. Direct PD NOV 19 PY 2009 VL 4 AR 44 DI 10.1186/1745-6150-4-44 PG 15 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 526XZ UT WOS:000272330900001 PM 19925661 ER PT J AU Gordeuk, VR Campbell, A Rana, S Nouraie, M Niu, XM Minniti, CP Sable, C Darbari, D Dham, N Onyekwere, O Ammosova, T Nekhai, S Kato, GJ Gladwin, MT Castro, OL AF Gordeuk, Victor R. Campbell, Andrew Rana, Sohail Nouraie, Mehdi Niu, Xiaomei Minniti, Caterina P. Sable, Craig Darbari, Deepika Dham, Niti Onyekwere, Onyinye Ammosova, Tatiana Nekhai, Sergei Kato, Gregory J. Gladwin, Mark T. Castro, Oswaldo L. TI Relationship of erythropoietin, fetal hemoglobin, and hydroxyurea treatment to tricuspid regurgitation velocity in children with sickle cell disease SO BLOOD LA English DT Article ID ENDOTHELIAL PROGENITOR CELLS; PULMONARY-HYPERTENSION; ECHOCARDIOGRAPHIC ABNORMALITIES; JET VELOCITY; RISK-FACTORS; ANEMIA; DEATH; MORTALITY; HEMOLYSIS; ASSOCIATION AB Hydroxyurea and higher hemoglobin F improve the clinical course and survival in sickle cell disease, but their roles in protecting from pulmonary hypertension are not clear. We studied 399 children and adolescents with sickle cell disease at steady state; 38% were being treated with hydroxyurea. Patients on hydroxyurea had higher hemoglobin concentration and lower values for a hemolytic component derived from 4 markers of hemolysis (P <= .002) but no difference in tricuspid regurgitation velocity compared with those not receiving hydroxyurea; they also had higher hemoglobin F (P < .001) and erythropoietin (P <= .012) levels. Hemoglobin F correlated positively with erythropoietin even after adjustment for hemoglobin concentration (P < .001). Greater hemoglobin F and erythropoietin each independently predicted higher regurgitation velocity in addition to the hemolytic component (P <= .023). In conclusion, increase in hemoglobin F in sickle cell disease may be associated with relatively lower tissue oxygen delivery as reflected in higher erythropoietin concentration. Greater levels of erythropoietin or hemoglobin F were independently associated with higher tricuspid regurgitation velocity after adjustment for degree of hemolysis, suggesting an independent relationship of hypoxia with higher systolic pulmonary artery pressure. The hemolysis-lowering and hemoglobin F-augmenting effects of hydroxyurea may exert countervailing influences on pulmonary blood pressure in sickle cell disease. ( Blood. 2009; 114: 4639-4644) C1 [Gordeuk, Victor R.] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20060 USA. [Campbell, Andrew] Univ Michigan, Ann Arbor, MI 48109 USA. [Minniti, Caterina P.; Kato, Gregory J.] NHLBI, Pulm & Vasc Med Branch, Bethesda, MD 20892 USA. [Minniti, Caterina P.; Kato, Gregory J.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Sable, Craig; Darbari, Deepika; Dham, Niti] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Gladwin, Mark T.] Univ Pittsburgh, Med Ctr, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15260 USA. [Gladwin, Mark T.] Univ Pittsburgh, Hemostasis & Vasc Biol Res Inst, Pittsburgh, PA 15260 USA. RP Gordeuk, VR (reprint author), Howard Univ, Ctr Sickle Cell Dis, 2041 Georgia Ave NW, Washington, DC 20060 USA. EM vgordeuk@howard.edu RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 FU National Heart, Lung, and Blood Institute (NHLBI) [2 R25 HL003679-08, 1 R01 HL079912-02]; National Center for Research Resources (NCRR), National Institutes of Health (NIH) [2MOI RR10284-10] FX This study was supported in part by grant nos. 2 R25 HL003679-08 and 1 R01 HL079912-02 from the National Heart, Lung, and Blood Institute ( NHLBI); by Howard University General Clinical Research Center ( GCRC) grant no. 2MOI RR10284-10 from the National Center for Research Resources (NCRR), National Institutes of Health (NIH); and by the intramural research program of the NIH. NR 40 TC 26 Z9 27 U1 0 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 19 PY 2009 VL 114 IS 21 BP 4639 EP 4644 DI 10.1182/blood-2009-04-218040 PG 6 WC Hematology SC Hematology GA 521WQ UT WOS:000271957400007 PM 19724057 ER PT J AU Arons, E Suntum, T Stetler-Stevenson, M Kreitman, RJ AF Arons, Evgeny Suntum, Tara Stetler-Stevenson, Maryalice Kreitman, Robert J. TI VH4-34(+) hairy cell leukemia, a new variant with poor prognosis despite standard therapy SO BLOOD LA English DT Article ID ENCODED MONOCLONAL-ANTIBODIES; V-H GENE; SYSTEMIC-LUPUS-ERYTHEMATOSUS; CHRONIC LYMPHOCYTIC-LEUKEMIA; TERM-FOLLOW-UP; B-LYMPHOCYTES; ABDOMINAL LYMPHADENOPATHY; SOMATIC HYPERMUTATION; COLD AGGLUTININS; ANTI-I AB Hairy cell leukemia variant (HCLv) presents with high disease burden, lack of typical antigens like CD25, and poor response to standard treatments like cladribine. Occasionally, patients with classic HCL respond poorly. Clinical and molecular features of HCL and HCLv has not been compared. Rearrangements expressing immunoglobulin VH chain were sequenced, including 22 from 20 patients with HCLv and 63 from 62 patients with classic HCL. Most patients were seeking relapsed/refractory trials, representing a poor-prognosis population. VH4-34, a gene commonly used in autoimmune disorders, was observed in 8 (40%) HCLv and 6 (10%) classic (P = .004) HCL patients. Compared with 71 VH4-34(-) rearrangements, 14 VH4-34(+) rearrangements were more frequently (P < .001) unmutated, defined as greater than 98% homologous to germline sequence. VH-434(+) patients had greater white blood cell counts at diagnosis (P = .002), lower response rate ( P < .001) and progression-free survival ( P = .007) after initial cladribine, and shorter overall survival from diagnosis (P < .001). Response and survival were more closely related to VH4-34 status than to whether or not patients had HCLv. VH4-34(-) HCL is an important disorder that only partly overlaps with the previously described HCLv. Response to initial single-agent cladribine therapy is suboptimal; these patients should be considered for alternative approaches, including antibody-related therapy. ( Blood. 2009; 114:4687-4695) C1 [Arons, Evgeny; Suntum, Tara; Kreitman, Robert J.] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Stetler-Stevenson, Maryalice] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Kreitman, RJ (reprint author), NCI, Mol Biol Lab, NIH, 37-5124B,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. EM kreitmar@mail.nih.gov FU NCI; NIH FX This work was supported by the intramural program, NCI, NIH. NR 71 TC 60 Z9 61 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 19 PY 2009 VL 114 IS 21 BP 4687 EP 4695 DI 10.1182/blood-2009-01-201731 PG 9 WC Hematology SC Hematology GA 521WQ UT WOS:000271957400012 PM 19745070 ER PT J AU Kimura, A Rieger, MA Simone, JM Chen, WP Wickre, MC Zhu, BM Hoppe, PS O'Shea, JJ Schroeder, T Hennighausen, L AF Kimura, Akiko Rieger, Michael A. Simone, James M. Chen, Weiping Wickre, Mark C. Zhu, Bing-Mei Hoppe, Philipp S. O'Shea, John J. Schroeder, Timm Hennighausen, Lothar TI The transcription factors STAT5A/B regulate GM-CSF-mediated granulopoiesis SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; PHYSIOLOGICAL NEGATIVE REGULATOR; HEMATOPOIETIC STEM-CELLS; FACTOR-RECEPTOR; EMERGENCY GRANULOPOIESIS; LYMPHOID DEVELOPMENT; GENE-EXPRESSION; DEFICIENT MICE; GROWTH-FACTOR; GRANULOCYTE AB Neutrophils play a vital role in the immune defense, which is evident by the severity of neutropenia causing life-threatening infections. Granulocyte macrophage-colony stimulating factor (GM-CSF) controls homeostatic and emergency development of granulocytes. However, little is known about the contribution of the downstream mediating transcription factors signal transducer and activator of transcription 5A and 5B (STAT5A/B). To elucidate the function of this pathway, we generated mice with complete deletion of both Stat5a/b genes in hematopoietic cells. In homeostasis, peripheral neutrophils were markedly decreased in these animals. Moreover, during emergency situations, such as myelosuppression, Stat5a/b mutant mice failed to produce enhanced levels of neutrophils and were unable to respond to GM-CSF. Both the GM-CSF permitted survival of mature neutrophils and the generation of granulocytes from granulocyte-macrophage progenitors (GMPs) were markedly reduced in Stat5a/b mutants. GMPs showed impaired colony-formation ability with reduced number and size of colonies on GM-CSF stimulation. Moreover, continuous cell fate analyses by time-lapse microscopy and single cell tracking revealed that Stat5a/b-null GMPs showed both delayed cell-cycle progression and increased cell death. Finally, transcriptome analysis indicated that STAT5A/B directs GM-CSF signaling through the regulation of proliferation and survival genes. ( Blood. 2009; 114: 4721-4728) C1 [Kimura, Akiko; Wickre, Mark C.; Zhu, Bing-Mei; Hennighausen, Lothar] NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. [Rieger, Michael A.; Hoppe, Philipp S.; Schroeder, Timm] German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Muenchen, Inst Stem Cell Res, Neuherberg, Germany. [Simone, James M.] NIAMSD, Flow Cytometry Sect, Off Sci & Technol, NIH, Bethesda, MD 20892 USA. [Chen, Weiping] NIDDK, Microarray Core Facil, Genom Core Lab, NIH, Bethesda, MD 20892 USA. [O'Shea, John J.] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. RP Hennighausen, L (reprint author), NIDDK, Lab Genet & Physiol, NIH, Bldg 8,Rm 101, Bethesda, MD 20892 USA. EM lotharh@niddk.nih.gov RI Schroeder, Timm/F-8448-2010 OI Schroeder, Timm/0000-0001-9320-0252 FU German Research Council (DFG); NIDDK/NIH; Deutsche Forschungsgemeinschaft FX This work was supported by the German Research Council (DFG) to T. S. and the intramural program of the NIDDK/NIH and the Deutsche Forschungsgemeinschaft Mercator Visiting Professor program to L. H. NR 49 TC 33 Z9 35 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 19 PY 2009 VL 114 IS 21 BP 4721 EP 4728 DI 10.1182/blood-2009-04-216390 PG 8 WC Hematology SC Hematology GA 521WQ UT WOS:000271957400016 PM 19779039 ER PT J AU Lisco, A Vanpouille, C Margolis, L AF Lisco, Andrea Vanpouille, Christophe Margolis, Leonid TI War and Peace between Microbes: HIV-1 Interactions with Coinfecting Viruses SO CELL HOST & MICROBE LA English DT Review ID HEPATITIS-C VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; IMMUNE-SYSTEM; REVERSE-TRANSCRIPTASE; HUMAN-PAPILLOMAVIRUS; HUMAN HERPESVIRUS-6; CHEMOKINE RECEPTOR; NATURAL-HISTORY; LYMPHOID-TISSUE; DOWN-REGULATION C1 [Lisco, Andrea; Vanpouille, Christophe; Margolis, Leonid] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA. RP Margolis, L (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA. EM margolil@mail.nih.gov NR 58 TC 16 Z9 16 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 J9 CELL HOST MICROBE JI Cell Host Microbe PD NOV 19 PY 2009 VL 6 IS 5 BP 403 EP 408 DI 10.1016/j.chom.2009.10.010 PG 6 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 529TE UT WOS:000272539700005 PM 19917495 ER PT J AU Bauer, AK Fostel, J Degraff, LM Rondini, EA Walker, C Grissom, SF Foley, J Kleeberger, SR AF Bauer, Alison K. Fostel, Jennifer Degraff, Laura M. Rondini, Elizabeth A. Walker, Christopher Grissom, Sherry F. Foley, Julie Kleeberger, Steven R. TI Transcriptomic analysis of pathways regulated by toll-like receptor 4 in a murine model of chronic pulmonary inflammation and carcinogenesis SO MOLECULAR CANCER LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; CELL LUNG-CANCER; GENE-EXPRESSION; OCCUPATIONAL-EXPOSURE; SIGNALING PATHWAY; TRANSGENIC MICE; TUMOR PROMOTION; EGFR MUTATIONS; MOUSE; RISK AB Background: Therapeutic strategies exist for human pulmonary neoplasia, however due to the heterogeneity of the disease, most are not very effective. The innate immunity gene, toll-like receptor 4 (TLR4), protects against chronic pulmonary inflammation and tumorigenesis in mice, but the mechanism is unclear. This study was designed to identify TLR4-mediated gene expression pathways that may be used as prognostic indicators of susceptibility to lung tumorigenesis in mice and provide insight into the mechanism. Methods: Whole lung mRNA was isolated from C.C3H-Tlr4(Lps-d) (BALB(Lps-d); Tlr4 mutant) and BALB/c (Tlr4 normal) mice following butylated hydroxytoluene (BHT)-treatment (four weekly ip. injections; 150-200 mg/kg/each; "promotion"). mRNA from micro-dissected tumors (adenomas) and adjacent uninvolved tissue from both strains were also compared 27 wks after a single carcinogen injection (3-methylcholanthrene (MCA), 10 mu g/g; "control") or followed by BHT (6 weekly ip. injections; 125-200 mg/kg/each; "progression"). Bronchoalveolar lavage fluid was analyzed for inflammatory cell content and total protein determination, a marker of lung hyperpermeability; inflammation was also assessed using immunohistochemical staining for macrophages (F4/80) and lymphocytes (CD3) in mice bearing tumors (progression). Results: During promotion, the majority of genes identified in the BALB(Lps-d) compared to BALB/c mice (P < 0.05) were involved in epithelial growth factor receptor (EGFR) signaling (e. g. epiregulin (Ereg)), secreted phosphoprotein 1(Spp1)), which can lead to cell growth and eventual tumor development. Inflammation was significantly higher in BALB(Lps-d) compared to BALB/c mice during progression, similar to the observed response during tumor promotion in these strains. Increases in genes involved in signaling through the EGFR pathway (e. g. Ereg, Spp1) were also observed during progression in addition to continued inflammation, chemotactic, and immune response gene expression in the BALB(Lps-d) versus BALB/c mice (P < 0.05), which appears to provide more favorable conditions for cell growth and tumor development. In support of these findings, the BALB/c mice also had significantly reduced expression of many immune response and inflammatory genes in both the tumors and uninvolved tissue. Conclusion: This transcriptomic study determined the protective effect of TLR4 in lung carcinogenesis inhibition of multiple pathways including EGFR (e. g. Ereg), inflammatory response genes (e.g. Cxcl5), chemotaxis (e.g. Ccr1) and other cell proliferation genes (e. g. Arg1, Pthlh). Future studies will determine the utility of these pathways as indicators of immune system deficiencies and tumorigenesis. C1 [Bauer, Alison K.; Rondini, Elizabeth A.] Michigan State Univ, Dept Pathobiol & Diagnost Invest, E Lansing, MI 48824 USA. [Fostel, Jennifer; Degraff, Laura M.; Walker, Christopher; Kleeberger, Steven R.] Natl Inst Environm Hlth Sci, Lab Resp Biol, Res Triangle Pk, NC USA. [Grissom, Sherry F.] Natl Inst Environm Hlth Sci, Mol Toxicol Lab, Res Triangle Pk, NC USA. [Foley, Julie] Natl Inst Environm Hlth Sci, Lab Cellular & Mol Pathol, Res Triangle Pk, NC USA. RP Bauer, AK (reprint author), Michigan State Univ, Dept Pathobiol & Diagnost Invest, E Lansing, MI 48824 USA. EM akbauer@msu.edu; fostel@niehs.nih.gov; miller12@niehs.nih.gov; rondinie@msu.edu; christopher.walker2@duke.edu; sherryfgrissom@gmail.com; foley1@niehs.nih.gov; kleeber1@niehs.nih.gov FU Division of Intramural Research of the NIEHS [HHSN273200700046U]; National Institute of Environmental Health Science; Michigan State University FX The authors would like to thank Drs. Alex Merrick and Pierre Bushel for critically reviewing the manuscript. J Fostel was supported by the Division of Intramural Research of the NIEHS contract HHSN273200700046U. S. R. K., L. M. D., C. W., J. F. and S. F. G. were supported by the Division of Intramural Research of the National Institute of Environmental Health Science. A. K. B. and E. A. R. were supported by Michigan State University internal funds. NR 55 TC 15 Z9 17 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-4598 J9 MOL CANCER JI Mol. Cancer PD NOV 19 PY 2009 VL 8 AR 107 DI 10.1186/1476-4598-8-107 PG 17 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 526IY UT WOS:000272282800001 PM 19925653 ER PT J AU Glocker, EO Kotlarz, D Boztug, K Gertz, EM Schaffer, AA Noyan, F Perro, M Diestelhorst, J Allroth, A Murugan, D Hatscher, N Pfeifer, D Sykora, KW Sauer, M Kreipe, H Lacher, M Nustede, R Woellner, C Baumann, U Salzer, U Koletzko, S Shah, N Segal, AW Sauerbrey, A Buderus, S Snapper, SB Grimbacher, B Klein, C AF Glocker, Erik-Oliver Kotlarz, Daniel Boztug, Kaan Gertz, E. Michael Schaeffer, Alejandro A. Noyan, Fatih Perro, Mario Diestelhorst, Jana Allroth, Anna Murugan, Dhaarini Haetscher, Nadine Pfeifer, Dietmar Sykora, Karl-Walter Sauer, Martin Kreipe, Hans Lacher, Martin Nustede, Rainer Woellner, Cristina Baumann, Ulrich Salzer, Ulrich Koletzko, Sibylle Shah, Neil Segal, Anthony W. Sauerbrey, Axel Buderus, Stephan Snapper, Scott B. Grimbacher, Bodo Klein, Christoph TI Inflammatory Bowel Disease and Mutations Affecting the Interleukin-10 Receptor SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID AUTOSOMAL RECESSIVE ENTEROCOLITIS; GENOME-WIDE ASSOCIATION; CROHNS-DISEASE; INTESTINAL INFLAMMATION; CYTOKINE PRODUCTION; ULCERATIVE-COLITIS; SEQUENCE VARIANTS; CRYSTAL-STRUCTURE; LOCI CONTRIBUTE; IL-10 AB BACKGROUND The molecular cause of inflammatory bowel disease is largely unknown. METHODS We performed genetic-linkage analysis and candidate-gene sequencing on samples from two unrelated consanguineous families with children who were affected by early-onset inflammatory bowel disease. We screened six additional patients with early-onset colitis for mutations in two candidate genes and carried out functional assays in patients' peripheral-blood mononuclear cells. We performed an allogeneic hematopoietic stem-cell transplantation in one patient. RESULTS In four of nine patients with early-onset colitis, we identified three distinct homozygous mutations in genes IL10RA and IL10RB, encoding the IL10R1 and IL10R2 proteins, respectively, which form a heterotetramer to make up the interleukin-10 receptor. The mutations abrogate interleukin-10-induced signaling, as shown by deficient STAT3 (signal transducer and activator of transcription 3) phosphorylation on stimulation with interleukin-10. Consistent with this observation was the increased secretion of tumor necrosis factor alpha and other proinflammatory cytokines from peripheral-blood mononuclear cells from patients who were deficient in IL10R subunit proteins, suggesting that interleukin-10-dependent "negative feedback" regulation is disrupted in these cells. The allogeneic stem-cell transplantation performed in one patient was successful. CONCLUSIONS Mutations in genes encoding the IL10R subunit proteins were found in patients with early-onset enterocolitis, involving hyperinflammatory immune responses in the intestine. Allogeneic stem-cell transplantation resulted in disease remission in one patient. C1 [Kotlarz, Daniel; Boztug, Kaan; Noyan, Fatih; Diestelhorst, Jana; Allroth, Anna; Murugan, Dhaarini; Haetscher, Nadine; Sykora, Karl-Walter; Sauer, Martin; Klein, Christoph] Hannover Med Sch, Dept Pediat Hematol Oncol, D-30625 Hannover, Germany. [Kreipe, Hans] Hannover Med Sch, Dept Pathol, D-30625 Hannover, Germany. [Nustede, Rainer] Hannover Med Sch, Dept Pediat Surg, D-30625 Hannover, Germany. [Baumann, Ulrich] Hannover Med Sch, Dept Pediat Pulmonol, D-30625 Hannover, Germany. [Glocker, Erik-Oliver; Perro, Mario; Woellner, Cristina; Grimbacher, Bodo] Royal Free Hosp, Dept Immunol, London NW3 2QG, England. [Segal, Anthony W.] UCL, Dept Med, London, England. [Shah, Neil] UCL, Great Ormond St Hosp, Dept Paediat Gastroenterol, London, England. [Gertz, E. Michael; Schaeffer, Alejandro A.] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. [Pfeifer, Dietmar] Univ Freiburg, Med Ctr, Dept Hematol Oncol, Core Facil Genom 2, D-7800 Freiburg, Germany. [Salzer, Ulrich] Univ Hosp Freiburg, Dept Rheumatol & Clin Immunol, Freiburg, Germany. [Lacher, Martin; Koletzko, Sibylle] Univ Munich, Dr von Haunersches Kinderspital, Munich, Germany. [Sauerbrey, Axel] HELIOS Hosp Erfurt, Dept Pediat, Erfurt, Germany. [Buderus, Stephan] St Marien Hosp Bonn, Dept Pediat, Bonn, Germany. [Snapper, Scott B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Snapper, Scott B.] Harvard Univ, Sch Med, Boston, MA USA. RP Klein, C (reprint author), Hannover Med Sch, Dept Pediat Hematol Oncol, Carl Neuberg Str 1, D-30625 Hannover, Germany. EM b.grimbacher@ucl.ac.uk; klein.christoph@mh-hannover.de RI Schaffer, Alejandro/F-2902-2012; OI Segal, Anthony/0000-0001-7602-9043; Gertz, E. Michael/0000-0001-8390-4387 FU European Commission Marie Curie Excellence program [MEXT-CT-2006-042316]; Deutsche Forschungsgemeinschaft [SFB621]; German Federal Ministry of Education and Research (PID-NET); Intramural Research Program of the National Institutes of Health; Deutsche Jose Carreras Leukmie-Stiftung; Else-Krner-Fresenius-Stiftung FX Supported by grants from the European Commission Marie Curie Excellence program (MEXT-CT-2006-042316,to Dr. Grim- bacher), Deutsche Forschungsgemeinschaft (SFB621, to Dr. Klein), and the German Federal Ministry of Education and Research (PID-NET), to Drs. Klein and Grimbacher; by the Intramural Research Program of the National Institutes of Health; and by fellowships from Deutsche Jose Carreras Leukmie-Stiftung (to Dr. Kotlarz) and Else-Krner-Fresenius-Stiftung ( to Dr. Boztug). NR 45 TC 504 Z9 523 U1 7 U2 23 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 19 PY 2009 VL 361 IS 21 BP 2033 EP 2045 DI 10.1056/NEJMoa0907206 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 521DA UT WOS:000271898600008 PM 19890111 ER PT J AU Zhang, Q Davis, JC Lamborn, IT Freeman, AF Jing, H Favreau, AJ Matthews, HF Davis, J Turner, ML Uzel, G Holland, SM Su, HC AF Zhang, Qian Davis, Jeremiah C. Lamborn, Ian T. Freeman, Alexandra F. Jing, Huie Favreau, Amanda J. Matthews, Helen F. Davis, Joie Turner, Maria L. Uzel, Gulbu Holland, Steven M. Su, Helen C. TI Combined Immunodeficiency Associated with DOCK8 Mutations SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HYPER-IGE SYNDROME; T-CELL IMMUNODEFICIENCY; STAT3 MUTATIONS; DIFFERENTIATION; DEFICIENCIES; ACTIVATOR; DELETION; DISEASES; EGRESS; FAMILY AB BACKGROUND Recurrent sinopulmonary and cutaneous viral infections with elevated serum levels of IgE are features of some variants of combined immunodeficiency. The genetic causes of these variants are unknown. METHODS We collected longitudinal clinical data on 11 patients from eight families who had recurrent sinopulmonary and cutaneous viral infections. We performed comparative genomic hybridization arrays and targeted gene sequencing. Variants with predicted loss-of-expression mutations were confirmed by means of a quantitative reverse-transcriptase-polymerase-chain-reaction assay and immunoblotting. We evaluated the number and function of lymphocytes with the use of in vitro assays and flow cytometry. RESULTS Patients had recurrent otitis media, sinusitis, and pneumonias; recurrent Staphylococcus aureus skin infections with otitis externa; recurrent, severe herpes simplex virus or herpes zoster infections; extensive and persistent infections with molluscum contagiosum; and human papillomavirus infections. Most patients had severe atopy with anaphylaxis; several had squamous-cell carcinomas, and one had T-cell lymphoma-leukemia. Elevated serum IgE levels, hypereosinophilia, low numbers of T cells and B cells, low serum IgM levels, and variable IgG antibody responses were common. Expansion in vitro of activated CD8 T cells was impaired. Novel homozygous or compound heterozygous deletions and point mutations in the gene encoding the dedicator of cytokinesis 8 protein (DOCK8) led to the absence of DOCK8 protein in lymphocytes. CONCLUSIONS Autosomal recessive DOCK8 deficiency is associated with a novel variant of combined immunodeficiency. C1 [Su, Helen C.] NIAID, NIH, Host Def Lab, Bethesda, MD 20892 USA. [Freeman, Alexandra F.; Davis, Joie; Uzel, Gulbu; Holland, Steven M.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Favreau, Amanda J.] NIAID, Res Technol Branch, Bethesda, MD 20892 USA. [Matthews, Helen F.] NIAID, Immunol Lab, Bethesda, MD 20892 USA. [Davis, Jeremiah C.] Howard Hughes Med Inst, Bethesda, MD 20817 USA. [Turner, Maria L.] NCI, Dermatol Branch, Bethesda, MD 20892 USA. RP Su, HC (reprint author), NIAID, NIH, Host Def Lab, CRC 5W3940,MSC 1456, Bethesda, MD 20892 USA. EM hsu@niaid.nih.gov RI Su, Helen/H-9541-2015; OI Su, Helen/0000-0002-5582-9110; Zhang, Qian/0000-0002-9040-3289 FU National Institutes of Health; National Institute of Allergy and Infectious Diseases; National Cancer Institute; Howard Hughes Medical Institute-National Institutes of Health Research Scholar Program FX Supported by the Intramural Research Program of the National Institutes of Health, the National Institute of Allergy and Infectious Diseases, and the National Cancer Institute, and by a grant from the Howard Hughes Medical Institute-National Institutes of Health Research Scholar Program ( to Mr. Davis). Sequencing was performed by the Genomics Unit of the Rocky Mountain Laboratories Research Technologies Section of the National Institute of Allergy and Infectious Diseases. NR 39 TC 252 Z9 260 U1 2 U2 8 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 19 PY 2009 VL 361 IS 21 BP 2046 EP 2055 DI 10.1056/NEJMoa0905506 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 521DA UT WOS:000271898600009 PM 19776401 ER PT J AU Kelsall, B AF Kelsall, Brian TI Interleukin-10 in Inflammatory Bowel Disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID RECOMBINANT HUMAN INTERLEUKIN-10; ACTIVE CROHNS-DISEASE; SUSCEPTIBILITY; EFFICACY; MULTIPLE; SAFETY; LOCI C1 NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Kelsall, B (reprint author), NIAID, Lab Mol Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 13 TC 6 Z9 6 U1 1 U2 1 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 19 PY 2009 VL 361 IS 21 BP 2091 EP 2093 DI 10.1056/NEJMe0909225 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 521DA UT WOS:000271898600016 PM 19890110 ER PT J AU Ahmet, I Spangler, E Shukitt-Hale, B Joseph, JA Ingram, DK Talan, M AF Ahmet, Ismayil Spangler, Edward Shukitt-Hale, Barbara Joseph, James A. Ingram, Donald K. Talan, Mark TI Survival and Cardioprotective Benefits of Long-Term Blueberry Enriched Diet in Dilated Cardiomyopathy Following Myocardial Infarction in Rats SO PLOS ONE LA English DT Article ID MITOCHONDRIAL PERMEABILITY TRANSITION; CARDIAC MYOCYTE APOPTOSIS; QUALITY-OF-LIFE; HEART-FAILURE; BEHAVIORAL DEFICITS; DISEASE; DEATH; SUPPLEMENTATION; DAMAGE AB Background: Despite remarkable progress in treatment of chronic heart failure (CHF) over the last two decades, mortality, personal suffering and cost remain staggering, and effective interventions are still a challenge. Previously we reported that a blueberry-enriched diet (BD) attenuated necroapoptosis and inflammation in periinfarct area in a rat model of myocardial infarction (MI). Objectives: To test the hypothesis that BD will attenuate the course of CHF, including mortality and cardiac remodeling during the first year after induction of MI in rats. Method and Results: Two weeks after coronary artery ligation, rats were divided into two groups of similar average MI size, measured by echocardiography, and then 12-mo dietary regimens were initiated as follows: ad libitum regular diet (control, CD, n = 27) and isocaloric food with 2% blueberry supplement (BD, n = 27) also available ad libitum. These dietary groups were compared to each other and to sham group (SH). Mortality over the 12 mo was reduced by 22% in BD compared with CD (p<0.01). In the course of developing CHF, BD had no effect on the body weight, heart rate or blood pressure. Bimonthly Echo revealed significant attenuation of the LV chamber remodeling, LV posterior wall thinning, and MI expansion in BD compared with CD. In fact, BD arrested the MI expansion. Conclusion: This is the first experimental evidence that a blueberry-enriched diet has positive effects on the course of CHF and thus warrants consideration for clinical evaluation. RP Ahmet, I (reprint author), NIA, Lab Cardiovasc Sci, NIH, Baltimore, MD 21224 USA. EM talanm@grc.nia.nih.gov FU Intramural NIH HHS NR 25 TC 18 Z9 18 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 19 PY 2009 VL 4 IS 11 AR e7975 DI 10.1371/journal.pone.0007975 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 522NJ UT WOS:000272004600024 PM 19936253 ER PT J AU D'Armiento, JM Scharf, SM Roth, MD Connett, JE Ghio, A Sternberg, D Goldin, JG Louis, TA Mao, JT O'Connor, GT Ramsdell, JW Ries, AL Schluger, NW Sciurba, FC Skeans, MA Voelker, H Walter, RE Wendt, CH Weinmann, GG Wise, RA Foronjy, RF AF D'Armiento, Jeanine M. Scharf, Steven M. Roth, Michael D. Connett, John E. Ghio, Andrew Sternberg, David Goldin, Jonathan G. Louis, Thomas A. Mao, Jenny T. O'Connor, George T. Ramsdell, Joe W. Ries, Andrew L. Schluger, Neil W. Sciurba, Frank C. Skeans, Melissa A. Voelker, Helen Walter, Robert E. Wendt, Christine H. Weinmann, Gail G. Wise, Robert A. Foronjy, Robert F. TI Eosinophil and T cell markers predict functional decline in COPD patients SO RESPIRATORY RESEARCH LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; SYNCYTIAL VIRUS-INFECTION; CIGARETTE-SMOKE; AIRWAY INFLAMMATION; RESPIRATORY VIRUSES; CHRONIC-BRONCHITIS; EFFECTOR ACTIVITY; EXACERBATIONS; LYMPHOCYTES; EMPHYSEMA AB Background: The major marker utilized to monitor COPD patients is forced expiratory volume in one second (FEV1). However, asingle measurement of FEV1 cannot reliably predict subsequent decline. Recent studies indicate that T lymphocytes and eosinophils are important determinants of disease stability in COPD. We therefore measured cytokine levels in the lung lavage fluid and plasma of COPD patients in order to determine if the levels of T cell or eosinophil related cytokines were predictive of the future course of the disease. Methods: Baseline lung lavage and plasma samples were collected from COPD subjects with moderately severe airway obstruction and emphysematous changes on chest CT. The study participants were former smokers who had not had a disease exacerbation within the past six months or used steroids within the past two months. Those subjects who demonstrated stable disease over the following six months (Delta FEV1 % predicted = 4.7 +/- 7.2; N = 34) were retrospectively compared with study participants who experienced a rapid decline in lung function (Delta FEV1 % predicted = -16.0 +/- 6.0; N = 16) during the same time period and with normal controls (N = 11). Plasma and lung lavage cytokines were measured from clinical samples using the Luminex multiplex kit which enabled the simultaneous measurement of several T cell and eosinophil related cytokines. Results and Discussion: Stable COPD participants had significantly higher plasma IL-2 levels compared to participants with rapidly progressive COPD (p = 0.04). In contrast, plasma eotaxin-1 levels were significantly lower in stable COPD subjects compared to normal controls (p < 0.03). In addition, lung lavage eotaxin-1 levels were significantly higher in rapidly progressive COPD participants compared to both normal controls (p < 0.02) and stable COPD participants (p < 0.05). Conclusion: These findings indicate that IL-2 and eotaxin-1 levels may be important markers of disease stability in advanced emphysema patients. Prospective studies will need to confirm whether measuring IL-2 or eotaxin-1 can identify patients at risk for rapid disease progression. C1 [D'Armiento, Jeanine M.; Sternberg, David; Schluger, Neil W.; Foronjy, Robert F.] Columbia Univ, Dept Med, New York, NY 10027 USA. [D'Armiento, Jeanine M.; Sternberg, David; Schluger, Neil W.; Foronjy, Robert F.] Columbia Univ, Dept Surg, New York, NY USA. [Scharf, Steven M.] Univ Maryland, Dept Med, Baltimore, MD 21201 USA. [Roth, Michael D.; Goldin, Jonathan G.; Mao, Jenny T.; Skeans, Melissa A.; Voelker, Helen; Wendt, Christine H.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Roth, Michael D.; Goldin, Jonathan G.; Mao, Jenny T.; Skeans, Melissa A.; Voelker, Helen; Wendt, Christine H.] Univ Calif Los Angeles, Dept Biol, Los Angeles, CA 90024 USA. [Connett, John E.] Univ Minnesota, Dept Med, CCBR, Twin Cities, CA USA. [Connett, John E.] Univ Minnesota, Dept Biostat, CCBR, Twin Cities, CA USA. [Ghio, Andrew; Wise, Robert A.] US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. [Louis, Thomas A.; Walter, Robert E.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [O'Connor, George T.] Boston Univ, Dept Med, Boston, MA 02215 USA. [Ramsdell, Joe W.; Ries, Andrew L.] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Sciurba, Frank C.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Weinmann, Gail G.] NIH, Bethesda, MD 20892 USA. RP Foronjy, RF (reprint author), Columbia Univ, Dept Med, New York, NY 10027 USA. EM jmd12@columbia.edu; sscharf@medicine.umaryland.edu; MRoth@mednet.ucla.edu; john-c@ccbr.umn.edu; Ghio.Andy@epamail.epa.gov; das9018@nyp.org; JGoldin@mednet.ucla.edu; tlouis@jhsph.edu; JMao@mednet.ucla.edu; goconnor@bu.edu; jramsdell@ucsd.edu; aries@ucsd.edu; ns311@columbia.edu; sciurbafc@msx.upmc.edu; melissas@ccbr.umn.edu; voelk002@umn.edu; walterb@bu.edu; wendt005@tc.umn.edu; gweinmann@nih.gov; rwise@welch.jhu.edu; rff5@columbia.edu RI Wendt, Chris/C-6823-2012 FU NHLBI NIH HHS [L30 HL074905, N01-HR-96140, N01-HR-96141-001, N01-HR-96142, N01-HR-96143, N01-HR-96144, N01-HR-96145, R01 HL098528, R01HL086936-03] NR 45 TC 20 Z9 20 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-9921 J9 RESP RES JI Respir. Res. PD NOV 19 PY 2009 VL 10 AR 113 DI 10.1186/1465-9921-10-113 PG 13 WC Respiratory System SC Respiratory System GA 526MH UT WOS:000272293200001 PM 19925666 ER PT J AU Sul, B Iwasa, KH AF Sul, Bora Iwasa, Kuni H. TI Effectiveness of Hair Bundle Motility as the Cochlear Amplifier SO BIOPHYSICAL JOURNAL LA English DT Article ID MECHANOELECTRICAL-TRANSDUCTION CHANNELS; CHICK BASILAR PAPILLA; CELL STEREOCILIA; MECHANICAL RESPONSES; LIMITING FREQUENCY; TECTORIAL MEMBRANE; NEGATIVE STIFFNESS; ACTIN-FILAMENTS; FAST ADAPTATION; BIRD COCHLEA AB The effectiveness of hair bundle motility in mammalian and avian ears is studied by examining energy balance for a small sinusoidal displacement of the hair bundle. The condition that the energy generated by a hair bundle must be greater than energy loss due to the shear in the subtectorial gap per hair bundle leads to a limiting frequency that can be supported by hair-bundle motility. Limiting frequencies are obtained for two motile mechanisms for fast adaptation, the channel re-closure model and a model that assumes that fast adaptation is an interplay between gating of the channel and the myosin motor. The limiting frequency obtained for each of these models is an increasing function of a factor that is determined by the morphology of hair bundles and the cochlea. Primarily due to the higher density of hair cells in the avian inner ear, this factor is similar to 10-fold greater for the avian ear than the mammalian ear, which has much higher auditory frequency limit. This result is consistent with a much greater significance of hair bundle motility in the avian ear than that in the mammalian ear. C1 [Sul, Bora; Iwasa, Kuni H.] Natl Inst Deafness & Other Commun Disorders, Biophys Sect, Lab Cellular Biol, NIH, Rockville, MD USA. RP Iwasa, KH (reprint author), Natl Inst Deafness & Other Commun Disorders, Biophys Sect, Lab Cellular Biol, NIH, Rockville, MD USA. EM iwasa@nih.gov OI Iwasa, Kuni/0000-0002-9397-7704 FU National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD FX This work was supported by the intramural program of the National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD. NR 65 TC 11 Z9 11 U1 0 U2 7 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 18 PY 2009 VL 97 IS 10 BP 2653 EP 2663 DI 10.1016/j.bpj.2009.08.039 PG 11 WC Biophysics SC Biophysics GA 521JQ UT WOS:000271917700002 PM 19917218 ER PT J AU Snyder, JS Choe, JS Clifford, MA Jeurling, SI Hurley, P Brown, A Kamhi, JF Cameron, HA AF Snyder, Jason S. Choe, Jessica S. Clifford, Meredith A. Jeurling, Sara I. Hurley, Patrick Brown, Ashly Kamhi, J. Frances Cameron, Heather A. TI Adult-Born Hippocampal Neurons Are More Numerous, Faster Maturing, and More Involved in Behavior in Rats than in Mice SO JOURNAL OF NEUROSCIENCE LA English DT Article ID GENERATED GRANULE CELLS; ENHANCED SYNAPTIC PLASTICITY; MORRIS WATER-MAZE; LONG-TERM-MEMORY; DENTATE GYRUS; SPATIAL MEMORY; NEUROGENESIS; BRAIN; MOUSE; EXPRESSION AB Neurons are born throughout adulthood in the hippocampus and show enhanced plasticity compared with mature neurons. However, there are conflicting reports on whether or not young neurons contribute to performance in behavioral tasks, and there is no clear relationship between the timing of maturation of young neurons and the duration of neurogenesis reduction in studies showing behavioral deficits. We asked whether these discrepancies could reflect differences in the properties of young neurons in mice and rats. We report that young neurons in adult rats show a mature neuronal marker profile and activity-induced immediate early gene expression 1-2 weeks earlier than those in mice. They are also twice as likely to escape cell death, and are 10 times more likely to be recruited into learning circuits. This comparison holds true in two different strains of mice, both of which show high rates of neurogenesis relative to other background strains. Differences in adult neurogenesis are not limited to the hippocampus, as the density of new neocortical neurons was 5 times greater in rats than in mice. Finally, in a test of function, we find that the contribution of young neurons to fear memory is much greater in rats than in mice. These results reveal substantial differences in new neuron plasticity and function between these two commonly studied rodent species. C1 [Snyder, Jason S.; Choe, Jessica S.; Clifford, Meredith A.; Jeurling, Sara I.; Hurley, Patrick; Brown, Ashly; Kamhi, J. Frances; Cameron, Heather A.] NIMH, Unit Neuroplast, NIH, Bethesda, MD 20892 USA. RP Snyder, JS (reprint author), NIMH, Unit Neuroplast, NIH, Bldg 35-3C911,MSC3718, Bethesda, MD 20892 USA. EM snyderjason@mail.nih.gov RI Snyder, Jason/F-3435-2011; Cameron, Heather/E-6221-2011; OI Cameron, Heather/0000-0002-3245-5777; Kamhi, J. Frances/0000-0002-3806-0506; Snyder, Jason/0000-0002-5509-0272 FU National Institutes of Health; National Institute of Mental Health [Z01-MH002784] FX This research was supported by the Intramural Program of the National Institutes of Health, National Institute of Mental Health, Z01-MH002784 ( H. A. C.). We thank Sarah Kellner, Andrea Moderi, and Kaitlin Sanzone for assistance with histological analyses and Anastasia Sowers and James Mitchell for assistance with the irradiation procedures. NR 64 TC 184 Z9 188 U1 1 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 18 PY 2009 VL 29 IS 46 BP 14484 EP 14495 DI 10.1523/JNEUROSCI.1768-09.2009 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 521SO UT WOS:000271944500011 PM 19923282 ER PT J AU Scimemi, A Tian, H Diamond, JS AF Scimemi, Annalisa Tian, Hua Diamond, Jeffrey S. TI Neuronal Transporters Regulate Glutamate Clearance, NMDA Receptor Activation, and Synaptic Plasticity in the Hippocampus SO JOURNAL OF NEUROSCIENCE LA English DT Article ID LONG-TERM POTENTIATION; D-ASPARTATE RECEPTORS; RELEASED GLUTAMATE; PYRAMIDAL CELLS; RAT HIPPOCAMPUS; IN-VITRO; SYNAPSES; SUBUNIT; CURRENTS; EAAC1 AB In the mammalian brain, the specificity of excitatory synaptic transmission depends on rapid diffusion of glutamate away from active synapses and the powerful uptake capacity of glutamate transporters in astrocytes. The extent to which neuronal glutamate transporters influence the lifetime of glutamate in the extracellular space remains unclear. Here we show that EAAC1, the predominant neuronal glutamate transporter at excitatory synapses in hippocampal area CA1, buffers glutamate released during synaptic events and prolongs the time course of its clearance by astrocytes. EAAC1 does not significantly alter activation of receptors in the synaptic cleft. Instead, it reduces recruitment of perisynaptic/extrasynaptic NR2B-containing NMDARs, thereby facilitating induction of long-term potentiation by short bursts of high-frequency stimulation. We describe novel roles of EAAC1 in regulating glutamate diffusion and propose that NMDARs at different subsynaptic locations can make distinct contributions to the regulation of synaptic strength. C1 [Scimemi, Annalisa; Tian, Hua; Diamond, Jeffrey S.] Natl Inst Neurol Disorders & Stroke, Synapt Physiol Sect, NIH, Bethesda, MD 20892 USA. RP Scimemi, A (reprint author), Natl Inst Neurol Disorders & Stroke, Synapt Physiol Sect, NIH, 35 Convent Dr,Bldg 35,Room 3C1006-3C1000, Bethesda, MD 20892 USA. EM scimemia@ninds.nih.gov; diamondj@ninds.nih.gov RI Scimemi, Annalisa/O-5396-2014; Diamond, Jeffrey/C-1835-2015 OI Scimemi, Annalisa/0000-0003-4975-093X; Diamond, Jeffrey/0000-0002-1770-2629 FU National Institute of Neurological Disorders and Stroke (NINDS) Intramural Research Program and Human Frontier Science Program [RGP50/2006] FX This work was supported by the National Institute of Neurological Disorders and Stroke (NINDS) Intramural Research Program and Human Frontier Science Program (RGP50/2006). We thank N. C. Danbolt for the EAAC1 antibody, the NINDS EM facility for technical assistance, and D. M. Kullmann and C. J. McBain for comments on this manuscript. Thanks to M. Dittrich for help with the MCell software and M. Beato, K. Paradiso, and A. V. Tzingounis for valuable discussions. A. S. performed electrophysiological recordings, EM analysis, 2P-LSM imaging, diffusion measurements, and modeling. H. T. performed molecular biology experiments. A. S. and J. S. D. designed the research and wrote this manuscript. NR 51 TC 77 Z9 78 U1 1 U2 9 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 18 PY 2009 VL 29 IS 46 BP 14581 EP 14595 DI 10.1523/JNEUROSCI.4845-09.2009 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 521SO UT WOS:000271944500020 PM 19923291 ER PT J AU Shahzad-Ul-Hussan, S Cai, ML Bewley, CA AF Shahzad-ul-Hussan, Syed Cai, Mengli Bewley, Carole A. TI Unprecedented Glycosidase Activity at a Lectin Carbohydrate-Binding Site Exemplified by the Cyanobacterial Lectin MVL SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID ANTI-HIV PROTEIN; SPERM-EGG INTERACTION; STRUCTURAL BASIS; CYANOVIRIN-N; SUBSTRATE-BINDING; DIPOLAR COUPLINGS; COMPLEX; NMR; SPECIFICITY; POTENT AB Carbohydrate binding proteins, or lectins, are engendered with the ability to bind specific carbohydrate structures, thereby mediating cell-cell and cell-pathogen interactions. Lectins are distinct from carbohydrate modifying enzymes and antibodies, respectively, as they do not carry out glycosidase or glycosyl transferase reactions, and they are of nonimmune origin. Cyanobacterial and algal lectins have become prominent in recent years due to their unique biophysical traits, such as exhibiting novel protein folds and unusually high carbohydrate affinity, and ability to potently inhibit HIV-1 entry through high affinity carbohydrate-mediated interactions with the HIV envelope glycoprotein gp120. The antiviral cyanobacterial lectin Microcystis viridis lectin (MVL), which contains two high affinity oligomannose binding sites, is one such example. Here we used glycan microarray profiling, NMR spectroscopy, and mutagenesis to show that one of the two oligomannose binding sites of MVL can catalyze the cleavage of chitin fragments (such as chitotriose) to GlcNAc, to determine the mode of MVL binding to and cleavage of chitotriose, to identify Asp75 as the primary catalytic residue involved in this cleavage, and to solve the solution structure of an inactive mutant of MVL in complex with this unexpected substrate. These studies represent the first demonstration of dual catalytic activity and carbohydrate recognition for discrete oligosaccharides at the same carbohydrate-binding site in a lectin. Sequence comparisons between the N- and C-domains of MVL, together with the sequences of new MVL homologues identified through bioinformatics, provide insight into the evolving roles of carbohydrate recognition. C1 [Shahzad-ul-Hussan, Syed; Bewley, Carole A.] NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Cai, Mengli] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Bewley, CA (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM caroleb@mail.nih.gov FU NIDDK; NIH; NIAID; NIGMS [M62116] FX We thank Dr. Richard Alvarez for glycan microarray profiling, Mr. Ali Shah for assistance with protein expression and purification, and Drs. Maria-Teresa Gutierrez-Lugo, Marius Clore, Son Lain and Y. C. Lee for contributive discussions during the course of this work. This research was supported in part by the Intramural Research Program, NIDDK, NIH; the AIDS-Targeted Antiviral Program of the Office of the Director, NIH (C.A.B.); an instrument grant from the Division of AIDS Research, NIAID (C.A.B.); and NIGMS - The Consortium for Functional Glycomics, Core H (GM62116). NR 44 TC 6 Z9 7 U1 2 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD NOV 18 PY 2009 VL 131 IS 45 BP 16500 EP 16508 DI 10.1021/ja905929c PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA 518VK UT WOS:000271723000044 PM 19856962 ER PT J AU Baker, SG AF Baker, Stuart G. TI Putting Risk Prediction in Perspective: Relative Utility Curves SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID BREAST-CANCER RISK; MODELS; VALIDATION; TESTS AB Risk prediction models based on medical history or results of tests are increasingly common in the cancer literature. An important use of these models is to make treatment decisions on the basis of estimated risk. The relative utility curve is a simple method for evaluating risk prediction in a medical decision-making framework. Relative utility curves have three attractive features for the evaluation of risk prediction models. First, they put risk prediction into perspective because relative utility is the fraction of the expected utility of perfect prediction obtained by the risk prediction model at the optimal cut point. Second, they do not require precise specification of harms and benefits because relative utility is plotted against a summary measure of harms and benefits (ie, the risk threshold). Third, they are easy to compute from standard tables of data found in many articles on risk prediction. An important use of relative utility curves is to evaluate the addition of a risk factor to the risk prediction model. To illustrate an application of relative utility curves, an analysis was performed on previously published data involving the addition of breast density to a risk prediction model for invasive breast cancer. C1 NCI, Biometry Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. RP Baker, SG (reprint author), NCI, Biometry Res Grp, Canc Prevent Div, EPN 3131,6130 Execut Blvd,MSC 7354, Bethesda, MD 20892 USA. EM sb16i@nih.gov NR 15 TC 44 Z9 44 U1 1 U2 4 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 18 PY 2009 VL 101 IS 22 BP 1538 EP 1542 DI 10.1093/jnci/djp353 PG 5 WC Oncology SC Oncology GA 523PL UT WOS:000272086400007 PM 19843888 ER PT J AU Baris, D Karagas, MR Verrill, C Johnson, A Andrew, AS Marsit, CJ Schwenn, M Colt, JS Cherala, S Samanic, C Waddell, R Cantor, KP Schned, A Rothman, N Lubin, J Fraumeni, JF Hoover, RN Kelsey, KT Silverman, DT AF Baris, Dalsu Karagas, Margaret R. Verrill, Castine Johnson, Alison Andrew, Angeline S. Marsit, Carmen J. Schwenn, Molly Colt, Joanne S. Cherala, Sai Samanic, Claudine Waddell, Richard Cantor, Kenneth P. Schned, Alan Rothman, Nathaniel Lubin, Jay Fraumeni, Joseph F., Jr. Hoover, Robert N. Kelsey, Karl T. Silverman, Debra T. TI A Case-Control Study of Smoking and Bladder Cancer Risk: Emergent Patterns Over Time SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ENVIRONMENTAL TOBACCO-SMOKE; MODELING TOTAL EXPOSURE; CIGARETTE-SMOKING; LUNG-CANCER; AROMATIC-AMINES; CHANGING CIGARETTE; HISTOLOGIC TYPE; POOLED ANALYSIS; CELL CARCINOMA; INTENSITY AB Cigarette smoking is a well-established risk factor for bladder cancer. The effects of smoking duration, intensity (cigarettes per day), and total exposure (pack-years); smoking cessation; exposure to environmental tobacco smoke; and changes in the composition of tobacco and cigarette design over time on risk of bladder cancer are unclear. We examined bladder cancer risk in relation to smoking practices based on interview data from a large, population-based case-control study conducted in Maine, New Hampshire, and Vermont from 2001 to 2004 (N = 1170 urothelial carcinoma case patients and 1413 control subjects). We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression. To examine changes in smoking-induced bladder cancer risk over time, we compared odds ratios from New Hampshire residents in this study (305 case patients and 335 control subjects) with those from two case-control studies conducted in New Hampshire in 1994-1998 and in 1998-2001 (843 case patients and 1183 control subjects). Regular and current cigarette smokers had higher risks of bladder cancer than never-smokers (for regular smokers, OR = 3.0, 95% CI = 2.4 to 3.6; for current smokers, OR = 5.2, 95% CI = 4.0 to 6.6). In New Hampshire, there was a statistically significant increasing trend in smoking-related bladder cancer risk over three consecutive periods (1994-1998, 1998-2001, and 2002-2004) among former smokers (OR = 1.4, 95% CI = 1.0 to 2.0; OR = 2.0, 95% CI = 1.4 to 2.9; and OR = 2.6, 95% CI = 1.7 to 4.0, respectively) and current smokers (OR = 2.9, 95% CI = 2.0 to 4.2; OR = 4.2, 95% CI = 2.8 to 6.3; OR = 5.5, 95% CI = 3.5 to 8.9, respectively) (P for homogeneity of trends over time periods = .04). We also observed that within categories of intensity, odds ratios increased approximately linearly with increasing pack-years smoked, but the slope of the increasing trend declined with increasing intensity. Smoking-related risks of bladder cancer appear to have increased in New Hampshire since the mid-1990s. Based on our modeling of pack-years and intensity, smoking fewer cigarettes over a long time appears more harmful than smoking more cigarettes over a shorter time, for equal total pack-years of cigarettes smoked. C1 [Baris, Dalsu; Colt, Joanne S.; Samanic, Claudine; Cantor, Kenneth P.; Rothman, Nathaniel; Lubin, Jay; Fraumeni, Joseph F., Jr.; Hoover, Robert N.; Silverman, Debra T.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Karagas, Margaret R.; Andrew, Angeline S.; Schned, Alan] Dartmouth Med Sch, Dept Community & Family Med, Hannover, NH, Germany. [Marsit, Carmen J.; Kelsey, Karl T.] Brown Univ, Dept Community Hlth & Pathol & Lab Med, Providence, RI 02912 USA. [Verrill, Castine; Schwenn, Molly] Maine Canc Registry, Augusta, ME USA. [Cherala, Sai] New Hampshire Canc Registry, Concord, NH USA. [Johnson, Alison] Vermont Canc Registry, Burlington, VT USA. RP Baris, D (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd,EPS Rm 8008, Bethesda, MD 20852 USA. EM barisd@mail.nih.gov RI Kelsey, Karl/I-1252-2014; OI Marsit, Carmen/0000-0003-4566-150X FU Intramural NIH HHS; NCI NIH HHS [CA121147, R01 CA057494, R01 CA121147, R01 CA57494]; NIEHS NIH HHS [P42 ES007373] NR 48 TC 78 Z9 79 U1 0 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 18 PY 2009 VL 101 IS 22 BP 1553 EP 1561 DI 10.1093/jnci/djp361 PG 9 WC Oncology SC Oncology GA 523PL UT WOS:000272086400009 PM 19917915 ER PT J AU Hollingshead, MG AF Hollingshead, Melinda G. TI Response: Re: Antitumor Efficacy Testing in Rodents SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID ADP-RIBOSE POLYMERASE; 0 CLINICAL-TRIAL; DRUG DEVELOPMENT C1 [Hollingshead, Melinda G.] NCI, Biol Testing Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21701 USA. RP Hollingshead, MG (reprint author), NCI, Div Canc Treatment, Fairview Ctr, Ste 205,1003 W 7th St, Frederick, MD 21701 USA. EM hollingm@mail.nih.gov NR 5 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 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 18 PY 2009 VL 101 IS 22 BP 1593 EP 1594 DI 10.1093/jnci/djp360 PG 2 WC Oncology SC Oncology GA 523PL UT WOS:000272086400014 ER PT J AU Mandelblatt, JS Cronin, KA Bailey, S Berry, DA de Koning, HJ Draisma, G Huang, H Lee, SJ Munsell, M Plevritis, SK Ravdin, P Schechter, CB Sigal, B Stoto, MA Stout, NK van Ravesteyn, NT Venier, J Zelen, M Feuer, EJ AF Mandelblatt, Jeanne S. Cronin, Kathleen A. Bailey, Stephanie Berry, Donald A. de Koning, Harry J. Draisma, Gerrit Huang, Hui Lee, Sandra J. Munsell, Mark Plevritis, Sylvia K. Ravdin, Peter Schechter, Clyde B. Sigal, Bronislava Stoto, Michael A. Stout, Natasha K. van Ravesteyn, Nicolien T. Venier, John Zelen, Marvin Feuer, Eric J. CA Canc Intervention Surveillance Mod TI Effects of Mammography Screening Under Different Screening Schedules: Model Estimates of Potential Benefits and Harms SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CARCINOMA IN-SITU; COST-EFFECTIVENESS ANALYSIS; BREAST-CANCER MORTALITY; UPPER AGE LIMIT; RANDOMIZED-TRIALS; FOLLOW-UP; UNITED-STATES; OLDER WOMEN; OVERDIAGNOSIS; OVERTREATMENT AB Background: Despite trials of mammography and widespread use, optimal screening policy is controversial. Objective: To evaluate U. S. breast cancer screening strategies. Design: 6 models using common data elements. Data Sources: National data on age-specific incidence, competing mortality, mammography characteristics, and treatment effects. Target Population: A contemporary population cohort. Time Horizon: Lifetime. Perspective: Societal. Interventions: 20 screening strategies with varying initiation and cessation ages applied annually or biennially. Outcome Measures: Number of mammograms, reduction in deaths from breast cancer or life-years gained (vs. no screening), false-positive results, unnecessary biopsies, and overdiagnosis. Results of Base-Case Analysis: The 6 models produced consistent rankings of screening strategies. Screening biennially maintained an average of 81% (range across strategies and models, 67% to 99%) of the benefit of annual screening with almost half the number of false-positive results. Screening biennially from ages 50 to 69 years achieved a median 16.5% (range, 15% to 23%) reduction in breast cancer deaths versus no screening. Initiating biennial screening at age 40 years (vs. 50 years) reduced mortality by an additional 3% (range, 1% to 6%), consumed more resources, and yielded more false-positive results. Biennial screening after age 69 years yielded some additional mortality reduction in all models, but overdiagnosis increased most substantially at older ages. Results of Sensitivity Analysis: Varying test sensitivity or treatment patterns did not change conclusions. Limitation: Results do not include morbidity from false-positive results, patient knowledge of earlier diagnosis, or unnecessary treatment. Conclusion: Biennial screening achieves most of the benefit of annual screening with less harm. Decisions about the best strategy depend on program and individual objectives and the weight placed on benefits, harms, and resource considerations. C1 [Mandelblatt, Jeanne S.] Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. NIH, Bethesda, MD 20892 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Erasmus Univ, Med Ctr, Rotterdam, Netherlands. Harvard Univ, Sch Publ Hlth, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Pilgrim Hlth Care, Boston, MA USA. Stanford Univ, Palo Alto, CA 94304 USA. Albert Einstein Coll Med, New York, NY USA. RP Mandelblatt, JS (reprint author), Lombardi Comprehens Canc Ctr, 3300 Whitehaven St,NW,Suite 4100, Washington, DC 20007 USA. EM mandelbj@georgetown.edu FU NCI [2U01CA088270, 2U01CA088283, 2U01CA088248, F32 CA125984, HHSN261200800769P, HHSN261200800002C]; NCI-funded BCSC [U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731, U01CA70040]; U.S. state public health departments and cancer registries FX By NCI cooperative agreements (2U01CA088270, 2U01CA088283, 2U01CA088248, and F32 CA125984). Portions of this work were performed under contract HHSN261200800769P. Data collection in the BCSC was supported by NCI-funded BCSC cooperative agreements (U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731, and U01CA70040) and several U.S. state public health departments and cancer registries. CISNET data management and Web site support were provided by Cornerstone Systems Northwest (NCI contract HHSN261200800002C). NR 64 TC 320 Z9 327 U1 1 U2 25 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 17 PY 2009 VL 151 IS 10 BP 738 EP W247 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 524LP UT WOS:000272145100007 PM 19920274 ER PT J AU Levine, RJ Vatten, LJ Horowitz, GL Qian, C Romundstad, PR Yu, KF Hollenberg, AN Hellevik, AI Asvold, BO Karumanchi, SA AF Levine, Richard J. Vatten, Lars J. Horowitz, Gary L. Qian, Cong Romundstad, Pal R. Yu, Kai F. Hollenberg, Anthony N. Hellevik, Alf I. Asvold, Bjorn O. Karumanchi, S. Ananth TI Pre-eclampsia, soluble fms-like tyrosine kinase 1, and the risk of reduced thyroid function: nested case-control and population based study SO BRITISH MEDICAL JOURNAL LA English DT Article ID UNITED-STATES POPULATION; HYPOTHYROIDISM; PREGNANCY; DISEASE; SUNITINIB; WOMEN; TRIAL; DYSFUNCTION; MECHANISMS; ANTIBODIES AB Objective To determine if pre-eclampsia is associated with reduced thyroid function during and after pregnancy. Design Nested case-control study during pregnancy and population based follow-up study after pregnancy. Setting Calcium for Pre-eclampsia Prevention trial of healthy pregnant nulliparous women in the United States during 1992-5, and a Norwegian population based study (Nord-Trondelag Health Study or HUNT-2) during 1995-7 with linkage to the medical birth registry of Norway. Participants All 141 women (cases) in the Calcium for Preeclampsia Prevention trial with serum measurements before 21 weeks' gestation (baseline) and after onset of pre-eclampsia (before delivery), 141 normotensive controls with serum measurements at similar gestational ages, and 7121 women in the Nord-Trondelag Health Study whose first birth had occurred in 1967 or later and in whom serum levels of thyroid stimulating hormone had been subsequently measured. Main outcome measures Thyroid function tests and human chorionic gonadotrophin and soluble fms-like tyrosine kinase 1 concentrations in the Calcium for Preeclampsia Prevention cohort and odds ratios for levels of thyroid stimulating hormone above the reference range, according to pre-eclampsia status in singleton pregnancies before the Nord-Trondelag Health Study. Results In predelivery specimens of the Calcium for Preeclampsia Prevention cohort after the onset of preeclampsia, thyroid stimulating hormone levels increased 2.42 times above baseline compared with a 1.48 times increase in controls. The ratio of the predelivery to baseline ratio of cases to that of the controls was 1.64 (95% confidence interval 1.29 to 2.08). Free triiodothyronine decreased more in the women with preeclampsia than in the controls (case ratio to control ratio 0.96, 95% confidence interval 0.92 to 0.99). The predelivery specimens but not baseline samples from women with pre-eclampsia were significantly more likely than those from controls to have concentrations of thyroid stimulating hormone above the reference range (adjusted odds ratio 2.2, 95% confidence interval 1.1 to 4.4). Both in women who developed pre-eclampsia and in normotensive controls the increase in thyroid stimulating hormone concentration between baseline and predelivery specimens was strongly associated with increasing quarters of predelivery soluble fms-like tyrosine kinase 1 (P for trend 0.002 and <0.001, respectively). In the Nord-Trondelag Health Study, women with a history of pre-eclampsia in their first pregnancy were more likely than other women (adjusted odds ratio 1.7, 95% confidence interval 1.1 to 2.5) to have concentrations of thyroid stimulating hormone above the reference range (>3.5 mIU/l). In particular, they were more likely to have high concentrations of thyroid stimulating hormone without thyroid peroxidase antibodies (adjusted odds ratio 2.6, 95% confidence interval 1.3 to 5.0), suggesting hypothyroid function in the absence of an autoimmune process. This association was especially strong (5.8, 1.3 to 25.5) if pre-eclampsia had occurred in both the first and the second pregnancies. Conclusion Increased serum concentration of soluble fms-like tyrosine kinase 1 during pre-eclampsia is associated with subclinical hypothyroidism during pregnancy. Pre-eclampsia may also predispose to reduced thyroid function in later years. C1 [Levine, Richard J.; Yu, Kai F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, US Dept HHS, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. [Vatten, Lars J.; Romundstad, Pal R.; Hellevik, Alf I.] Norwegian Univ Sci & Technol, Fac Med, Dept Publ Hlth, N-7034 Trondheim, Norway. [Horowitz, Gary L.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Horowitz, Gary L.; Hollenberg, Anthony N.; Karumanchi, S. Ananth] Harvard Univ, Sch Med, Boston, MA USA. [Qian, Cong] Glotech, Rockville, MD USA. [Hollenberg, Anthony N.; Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Boston, MA 02215 USA. [Karumanchi, S. Ananth] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Levine, RJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, US Dept HHS, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. EM LevineRJ@mail.nih.gov; sananth@bidmc.harvard.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [N01-HD-5-3398]; National Institute of Child Health and Human Development [N01-HD-1-3121-3126, N01-HD-3154, N01-HD-5-3246]; National Heart, Lung, and Blood Institute; Norwegian University of Science and Technology; Central Norway Regional Health Authority FX This study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (contract N01-HD-5-3398) and by salary support from the intramural research programme of the National Institutes of Health. The Calcium for Preeclampsia Prevention trial was supported by the National Institute of Child Health and Human Development (contracts N01-HD-1-3121-3126, N01-HD-3154, and N01-HD-5-3246), with cofunding from the National Heart, Lung, and Blood Institute. SAK is supported by a clinical scientist award by the Burroughs Wellcome Fund and is an investigator of the Howard Hughes Medical Institute and an established investigator of the American Heart Association. The Nord-Trondelag Health Study is a collaborative effort of the Norwegian University of Science and Technology, the Norwegian Institute of Public Health, and the Nord-Trondelag County Council. This substudy of the Nord-Trondelag Health Study was supported by the Norwegian University of Science and Technology and by the Central Norway Regional Health Authority. NR 35 TC 35 Z9 38 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8146 J9 BRIT MED J JI Br. Med. J. PD NOV 17 PY 2009 VL 339 AR b4336 DI 10.1136/bmj.b4336 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 523SZ UT WOS:000272096100002 PM 19920004 ER PT J AU Franco, OH Massaro, JM Civil, J Cobain, MR O'Malley, B D'Agostino, RB AF Franco, Oscar H. Massaro, Joseph M. Civil, Jacky Cobain, Mark R. O'Malley, Brendan D'Agostino, Ralph B., Sr. TI Trajectories of Entering the Metabolic Syndrome The Framingham Heart Study SO CIRCULATION LA English DT Article DE cardiovascular diseases; Framingham study; metabolic syndrome; prevention; syndrome X ID C-REACTIVE PROTEIN; MIDDLE-AGED MEN; DIABETES-MELLITUS; DISEASE; ASSOCIATION; DEFINITION; FAMILIES; WOMEN AB Background-We evaluated the progression of the metabolic syndrome (MetS) and its components, the trajectories followed by individuals entering MetS, and the manner in which different trajectories predict cardiovascular disease and mortality. Methods and Results-Using data from 3078 participants from the Framingham Offspring Study (a cohort study) who attended examinations 4 (1987), 5 (1991), and 6 (1995), we evaluated the progression of MetS and its components. MetS was defined according to the Adult Treatment Panel III criteria. Using logistic regression, we evaluated the predictive ability of the presence of each component of the MetS on the subsequent development of MetS. Additionally, we examined the probability of developing cardiovascular disease or mortality (until 2007) by having specific combinations of 3 that diagnose MetS. The prevalence of MetS almost doubled in 10 years of follow-up. Hyperglycemia and central obesity experienced the highest increase. High blood pressure was most frequently present when a diagnosis of MetS occurred (77.3%), and the presence of central obesity conferred the highest risk of developing MetS (odds ratio, 4.75; 95% confidence interval, 3.78 to 5.98). Participants who entered the MetS having a combination of central obesity, high blood pressure, and hyperglycemia had a 2.36-fold (hazard ratio, 2.36; 95% confidence interval, 1.54 to 3.61) increase of incident cardiovascular events and a 3-fold (hazard ratio, 3.09, 95% confidence interval, 1.93 to 4.94) increased risk of mortality. Conclusions-Particular trajectories and combinations of factors on entering the MetS confer higher risks of incident cardiovascular disease and mortality in the general population and among those with MetS. Intense efforts are required to identify populations with these particular combinations and to provide them with adequate treatment at early stages of disease. (Circulation. 2009; 120: 1943-1950.) C1 [Franco, Oscar H.] Univ Warwick, Dept Publ Hlth, Hlth Sci Res Inst, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England. [Franco, Oscar H.; Civil, Jacky; Cobain, Mark R.; O'Malley, Brendan] Unilever Corp Res, Sharnbrook, Beds, England. [Massaro, Joseph M.] Boston Univ, Dept Math Stat & Biostat, Boston, MA 02215 USA. [D'Agostino, Ralph B., Sr.] NHLBI, Framingham Heart Study, Framingham, MA USA. RP Franco, OH (reprint author), Univ Warwick, Dept Publ Hlth, Hlth Sci Res Inst, Warwick Med Sch, B-160, Coventry CV4 7AL, W Midlands, England. EM O.H.Franco@warwick.ac.uk OI Massaro, Joseph/0000-0002-2682-4812; O'Malley, Brendan/0000-0003-0822-3455 FU Unilever plc. FX This study was funded by Unilever plc. The funding organization did not participate in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, and approval of the manuscript. NR 20 TC 68 Z9 70 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 17 PY 2009 VL 120 IS 20 BP 1943 EP 1950 DI 10.1161/CIRCULATIONAHA.109.855817 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520QJ UT WOS:000271860500003 PM 19884471 ER PT J AU Sauseng, P Klimesch, W Heise, KF Gruber, WR Holz, E Karim, AA Glennon, M Gerloff, C Birbaumer, N Hummel, FC AF Sauseng, Paul Klimesch, Wolfgang Heise, Kirstin F. Gruber, Walter R. Holz, Elisa Karim, Ahmed A. Glennon, Mark Gerloff, Christian Birbaumer, Niels Hummel, Friedhelm C. TI Brain Oscillatory Substrates of Visual Short-Term Memory Capacity SO CURRENT BIOLOGY LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; EEG ALPHA-ACTIVITY; WORKING-MEMORY; INDIVIDUAL-DIFFERENCES; PHASE SYNCHRONIZATION; THETA-OSCILLATIONS; NEURONAL OSCILLATIONS; SPATIAL ATTENTION; NEURAL MEASURES; CORTEX AB The amount of information that can be stored in visual short-term memory is strictly limited to about four items [1]. Therefore, memory capacity relies not only on the successful retention of relevant information but also on efficient suppression of distracting information, visual attention, and executive functions [2-5]. However, completely separable neural signatures for these memory capacity-limiting factors remain to be identified. Because of its functional diversity [6-9], oscillatory brain activity may off er a utile solution. In the present study, we show that capacity-determining mechanisms, namely retention of relevant information and suppression of distracting information, are based on neural substrates independent of each other: the successful maintenance of relevant material in short-term memory is associated with cross-frequency phase synchronization between theta (rhythmical neural activity around 5 Hz) and gamma (>50 Hz) oscillations at posterior parietal recording sites. On the other hand, electroencephalographic alpha activity (around 10 Hz) predicts memory capacity based on efficient suppression of irrelevant information in short-term memory. Moreover, repetitive transcranial magnetic stimulation at alpha frequency can modulate short-term memory capacity by influencing the ability to suppress distracting information. Taken together, the current study provides evidence for a double dissociation of brain oscillatory correlates of visual short-term memory capacity. C1 [Sauseng, Paul; Heise, Kirstin F.; Gerloff, Christian; Hummel, Friedhelm C.] Univ Hamburg, Univ Krankenhaus Hamburg Eppendorf, Dept Neurol, Brain Imaging & Neurostimulat Lab, D-20246 Hamburg, Germany. [Sauseng, Paul; Klimesch, Wolfgang; Gruber, Walter R.; Holz, Elisa] Salzburg Univ, Dept Psychol, A-5020 Salzburg, Austria. [Karim, Ahmed A.; Birbaumer, Niels] Univ Tubingen, Inst Med Psychol & Behav Neurobiol, D-72074 Tubingen, Germany. [Karim, Ahmed A.] Int Max Planck Res Sch Neural & Behav Sci, D-72074 Tubingen, Germany. [Glennon, Mark] Natl Univ Ireland, Sch Psychol, Galway, Ireland. [Birbaumer, Niels] Natl Inst Neurol Disorders & Stroke, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. RP Sauseng, P (reprint author), Univ Hamburg, Univ Krankenhaus Hamburg Eppendorf, Dept Neurol, Brain Imaging & Neurostimulat Lab, Martinistr 52, D-20246 Hamburg, Germany. EM p.sauseng@uke.uni-hamburg.de RI Cognitive Neuroscience, Centre for/C-7888-2011; Sauseng, Paul/A-5273-2009; OI Heise, Kirstin-Friederike/0000-0003-3666-8531 FU Austrian Academy of Sciences; Deutsche Forschungsgemeinschaft [B1 195/51-1] FX This research was supported by the Austrian Academy of Sciences (P.S. is the recipient of an APART fellowship of the Austrian Academy of Sciences) and the Deutsche Forschungsgemeinschaft (B1 195/51-1). We thank R. Freunberger for helpful comments and T. Schwaiger for assistance during data recording. NR 46 TC 226 Z9 234 U1 7 U2 36 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD NOV 17 PY 2009 VL 19 IS 21 BP 1846 EP 1852 DI 10.1016/j.cub.2009.08.062 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 522AS UT WOS:000271970200028 PM 19913428 ER PT J AU McCulloch, DR Nelson, CM Dixon, LJ Silver, DL Wylie, JD Lindner, V Sasaki, T Cooley, MA Argraves, WS Apte, SS AF McCulloch, Daniel R. Nelson, Courtney M. Dixon, Laura J. Silver, Debra L. Wylie, James D. Lindner, Volkhard Sasaki, Takako Cooley, Marion A. Argraves, W. Scott Apte, Suneel S. TI ADAMTS Metalloproteases Generate Active Versican Fragments that Regulate Interdigital Web Regression SO DEVELOPMENTAL CELL LA English DT Article ID PROGRAMMED CELL-DEATH; MOUSE LIMB; IN-VIVO; FIBULIN-1 GENE; C-ELEGANS; TGF-BETA; EMBRYO; MORPHOGENESIS; EXPRESSION; AGGRECAN AB We show that combinatorial mouse alleles for the secreted metalloproteases Adamts5, Adamts20 (bt), and Adamts9 result in fully penetrant soft-tissue syndactyly. Interdigital webs in Adamts5(-/-);bt/bt mice had reduced apoptosis and decreased cleavage of the proteoglycan versican; however, the BMP-FGF axis, which regulates interdigital apoptosis was unaffected. BMP4 induced apoptosis, but without concomitant versican proteolysis. Haploinsufficiency of either Vcan or Fbln1, a cofactor for versican processing by ADAMTS5, led to highly penetrant syndactyly in bt mice, suggesting that cleaved versican was essential for web regression. The local application of an aminoterminal versican fragment corresponding to ADAMTS-processed versican, induced cell death in Adamts5(-/-);bt/bt webs. Thus, ADAMTS proteases cooperatively maintain versican proteolysis above a required threshold to create a permissive environment for apoptosis. The data highlight the developmental significance of proteolytic action on the ECM, not only as a clearance mechanism, but also as a means to generate bioactive versican fragments. C1 [McCulloch, Daniel R.; Nelson, Courtney M.; Dixon, Laura J.; Wylie, James D.; Apte, Suneel S.] Cleveland Clin, Lerner Res Inst, Dept Biomed Engn, Cleveland, OH 44195 USA. [Silver, Debra L.] NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA. [Lindner, Volkhard] Maine Med Ctr, Res Inst, Scarborough, ME 04074 USA. [Sasaki, Takako] Oregon Hlth & Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97239 USA. [Cooley, Marion A.; Argraves, W. Scott] Med Univ S Carolina, Dept Anat & Cell Biol, Charleston, SC 29403 USA. RP Apte, SS (reprint author), Cleveland Clin, Lerner Res Inst, Dept Biomed Engn, ND20,9500 Euclid Ave, Cleveland, OH 44195 USA. EM aptes@ccf.org RI McCulloch, Daniel/N-9142-2013; OI McCulloch, Daniel/0000-0003-0269-5857; Wylie, James/0000-0003-2657-0311 FU National Institutes of Health [AR49930, AR53890, HL095067, AR050953]; Arthritis Foundation; American Heart Association [0755346U] FX We thank Roche Pharmaceuticals, Corey Mjaatvedt and Christine B. Kern for hdf mice, David Beier for bt mice, Vernique Lefebvre, Radhika Atit, and Richard Harland for cDNAs, Preston Alexander and John Sandy for ADAMTS5 antibodies, Amanda Allamong and Michael Braun for assistance with histology, and James Lang for photography. Dieter Zimmermann provided the versican expression plasmid. This work was supported by National Institutes of Health grants to S.S.A (AR49930 and AR53890) and W.S.A. (HL095067), the Arthritis Foundation (Northeast Ohio Chapter Award to S.S.A.) and the American Heart Association (Grant-in-Aid 0755346U to W.S.A.). Histology and mCT was done at the Cleveland Clinic Musculoskeletal Core Center (supported by NIH grant AR050953). NR 52 TC 92 Z9 92 U1 2 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD NOV 17 PY 2009 VL 17 IS 5 BP 687 EP 698 DI 10.1016/j.devcel.2009.09.008 PG 12 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 523US UT WOS:000272100700013 PM 19922873 ER PT J AU Byun, JS Wong, MM Cui, WW Idelman, G Li, Q De Siervi, A Bilke, S Haggerty, CM Player, A Wang, YH Thirman, MJ Kaberlein, JJ Petrovas, C Koup, RA Longo, D Ozato, K Gardner, K AF Byun, Jung S. Wong, Madeline M. Cui, Wenwu Idelman, Gila Li, Quentin De Siervi, Adriana Bilke, Sven Haggerty, Cynthia M. Player, Audrey Wang, Yong Hong Thirman, Michael J. Kaberlein, Joseph J. Petrovas, Constantinos Koup, Richard A. Longo, Dan Ozato, Keiko Gardner, Kevin TI Dynamic bookmarking of primary response genes by p300 and RNA polymerase II complexes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE gene regulation; histone acetylation; transcription; ELL; epigenetics ID BROMODOMAIN PROTEIN BRD4; IMMEDIATE-EARLY GENES; ELONGATION-FACTOR; T-CELLS; C-FOS; COACTIVATOR COMPLEXES; CHROMATIN-STRUCTURE; ACTIVE PROMOTERS; HUMAN GENOME; P-TEFB AB Profiling the dynamic interaction of p300 with proximal promoters of human T cells identified a class of genes that rapidly coassemble p300 and RNA polymerase II (pol II) following mitogen stimulation. Several of these p300 targets are immediate early genes, including FOS, implicating a prominent role for p300 in the control of primary genetic responses. The recruitment of p300 and pol II rapidly transitions to the assembly of several elongation factors, including the positive transcriptional elongation factor (P-TEFb), the bromo-domain-containing protein (BRD4), and the elongin-like eleven nineteen lysine-rich leukemia protein (ELL). However, transcription at many of these rapidly induced genes is transient, wherein swift departure of P-TEFb, BRD4, and ELL coincides with termination of transcriptional elongation. Unexpectedly, both p300 and pol II remain accumulated or "bookmarked'' at the proximal promoter long after transcription has terminated, demarking a clear mechanistic separation between the recruitment and elongation phases of transcription in vivo. The bookmarked pol II is depleted of both serine-2 and serine-5 phosphorylation of its C-terminal domain and remains proximally positioned at the promoter for hours. Surprisingly, these p300/pol II bookmarked genes can be readily reactivated, and elongation factors can be reassembled by subsequent addition of nonmitogenic agents that, alone, have minimal effects on transcription in the absence of prior preconditioning by mitogen stimulation. These findings suggest that p300 is likely to play an important role in biological processes in which transcriptional bookmarking or preconditioning influences cellular growth and development through the dynamic priming of genes for response to rechallenge by secondary stimuli. C1 [Byun, Jung S.; Wong, Madeline M.; Cui, Wenwu; Idelman, Gila; Li, Quentin; Haggerty, Cynthia M.; Gardner, Kevin] NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. [De Siervi, Adriana] Univ Buenos Aires, Dept Biochem, Buenos Aires, DF, Argentina. [Bilke, Sven; Player, Audrey; Wang, Yong Hong] NCI, Genet Branch, Bethesda, MD 20892 USA. [Thirman, Michael J.; Kaberlein, Joseph J.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Petrovas, Constantinos; Koup, Richard A.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Longo, Dan] NIA, Immunol Lab, Baltimore, MD 21224 USA. [Ozato, Keiko] NICHHD, Lab Mol Growth Regulat, Bethesda, MD 20892 USA. RP Gardner, K (reprint author), NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. EM gardnerk@mail.nih.gov FU NIH; National Cancer Institute; National Institute on Aging FX We thank R. Owens, E. Kawasaki, B. Lewis, C. Smith, and K. Adelman for helpful discussions and acknowledge Q. Wang and I. Collins for technical contributions. This research was supported by the Intramural Research Program of the NIH, the National Cancer Institute and the National Institute on Aging. NR 42 TC 40 Z9 41 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 17 PY 2009 VL 106 IS 46 BP 19292 EP 19297 DI 10.1073/pnas.0905469106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 521GC UT WOS:000271907400015 PM 19880750 ER PT J AU Weiss, JM Back, TC Scarzello, AJ Subleski, JJ Hall, VL Stauffer, JK Chen, X Micic, D Alderson, K Murphy, WJ Wiltrout, RH AF Weiss, Jonathan M. Back, Timothy C. Scarzello, Anthony J. Subleski, Jeff J. Hall, Veronica L. Stauffer, Jimmy K. Chen, Xin Micic, Dejan Alderson, Kory Murphy, William J. Wiltrout, Robert H. TI Successful immunotherapy with IL-2/anti-CD40 induces the chemokine-mediated mitigation of an immunosuppressive tumor microenvironment SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE chemokines; tumor immunotherapy; CD40 ID RENAL-CELL CARCINOMA; REGULATORY T-CELLS; MACROPHAGE INFILTRATION; ANTITUMOR RESPONSES; MALIGNANT-MELANOMA; SUPPRESSOR-CELLS; INTERFERON-GAMMA; IFN-GAMMA; TNF-ALPHA; EXPRESSION AB Treatment of mice bearing orthotopic, metastatic tumors with anti-CD40 antibody resulted in only partial, transient anti-tumor effects whereas combined treatment with IL-2/anti-CD40, induced tumor regression. The mechanisms for these divergent anti-tumor responses were examined by profiling tumor-infiltrating leukocyte subsets and chemokine expression within the tumor microenvironment after immunotherapy. IL-2/anti-CD40, but not anti-CD40 alone, induced significant infiltration of established tumors by NK and CD8(+) T cells. To further define the role of chemokines in leukocyte recruitment into tumors, we evaluated anti-tumor responses in mice lacking the chemokine receptor, CCR2. The antitumor effects and leukocyte recruitment mediated by anti-CD40 alone, were completely abolished in CCR2(-/-) mice. In contrast, IL-2/anti-CD40-mediated leukocyte recruitment and reductions in primary tumors and metastases were maintained in CCR2(-/-) mice. Treatment of mice with IL-2/anti-CD40, but not anti-CD40 alone, also caused an IFN-gamma-dependent increase in the expression of multiple Th1 chemokines within the tumor microenvironment. Interestingly, although IL-2/anti-CD40 treatment increased Tregs in the spleen, it also caused a coincident IFN-gamma-dependent reduction in CD4(+)/FoxP3(+) Tregs, myeloid-derived suppressor cells and Th2 chemokine expression specifically within the tumor microenvironment that was not observed after treatment with anti-CD40 alone. Similar effects were observed using IL-15 in combination with anti-CD40. Taken together, our data demonstrate that IL-2/antiCD40, but not anti-CD40 alone, can preferentially reduce the overall immunosuppressive milieu within the tumor microenvironment. These results suggest that the use of anti-CD40 in combination with IL-2 or IL-15 may hold substantially more promise for clinical cancer treatment than anti-CD40 alone. C1 [Weiss, Jonathan M.; Back, Timothy C.; Scarzello, Anthony J.; Subleski, Jeff J.; Hall, Veronica L.; Stauffer, Jimmy K.; Chen, Xin; Micic, Dejan; Wiltrout, Robert H.] NCI, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21702 USA. [Alderson, Kory; Murphy, William J.] Univ Calif Davis, Dept Dermatol, Davis, CA 95616 USA. RP Wiltrout, RH (reprint author), NCI, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21702 USA. EM wiltrour@mail.nih.gov RI Chen, Xin/I-6601-2015 OI Chen, Xin/0000-0002-2628-4027 FU National Institutes of Health National Cancer Institute; National Cancer Institute [N01-CO-12400, R01-CA-95572] FX We thank Drs. Giorgio Trinchieri and John Ortaldo for critically reviewing the manuscript. This work was supported by the Intramural Research Program of the National Institutes of Health National Cancer Institute and with federal funds from the National Cancer Institute under Contracts N01-CO-12400 and R01-CA-95572 (to W.J.M.). NR 35 TC 37 Z9 39 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 17 PY 2009 VL 106 IS 46 BP 19455 EP 19460 DI 10.1073/pnas.0909474106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 521GC UT WOS:000271907400043 PM 19892741 ER PT J AU Lee, SJ Trostel, A Le, P Harinarayanan, R FitzGerald, PC Adhya, S AF Lee, Sang Jun Trostel, Andrei Le, Phuoc Harinarayanan, Rajendran FitzGerald, Peter C. Adhya, Sankar TI Cellular stress created by intermediary metabolite imbalances SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE galactose metabolism; gene signals; intracellular stress; tiling arrays ID ESCHERICHIA-COLI; GALACTOSE METABOLISM; HEREDITARY DEFECTS; GENE-EXPRESSION; MUTANTS; REPRESSION; PROMOTERS; INDUCTION; PROTEIN AB Small molecules generally activate or inhibit gene transcription as externally added substrates or as internally accumulated end-products, respectively. Rarely has a connection been made that links an intracellular intermediary metabolite as a signal of gene expression. We report that a perturbation in the critical step of a metabolic pathway-the D-galactose amphibolic pathway changes the dynamics of the pathways leading to accumulation of the intermediary metabolite UDP-galactose. This accumulation causes cell stress and transduces signals that alter gene expression so as to cope with the stress by restoring balance in the metabolite pool. This underscores the importance of studying the global effects of alterations in the level of intermediary metabolites in causing stress and coping with it by transducing signals to genes to reach a stable state of equilibrium (homeostasis). Such studies are an essential component in the integration of metabolomics, proteomics, and transcriptomics. C1 [Lee, Sang Jun; Trostel, Andrei; Le, Phuoc; Adhya, Sankar] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Harinarayanan, Rajendran] NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. [FitzGerald, Peter C.] NICHHD, Genome Anal Unit, Bethesda, MD 20892 USA. RP Adhya, S (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. EM sadhya@helix.nih.gov FU National Institutes of Health; National Cancer Institute; Center for Cancer Research FX We thank R. Edgar, D. E. A. Lewis, M. Cashel for helpful discussions, and R. Edgar and R. A. Weisberg for critical reading of the manuscript and suggestions. We thank D.J. Jin and C.L. Turnbough, Jr. for the gift of bacterial strains. This work was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 30 TC 32 Z9 32 U1 1 U2 15 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 17 PY 2009 VL 106 IS 46 BP 19515 EP 19520 DI 10.1073/pnas.0910586106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 521GC UT WOS:000271907400053 PM 19887636 ER PT J AU Iwatani, Y Chan, DSB Liu, L Yoshii, H Shibata, J Yamamoto, N Levin, JG Gronenborn, AM Sugiura, W AF Iwatani, Yasumasa Chan, Denise S. B. Liu, Lin Yoshii, Hiroaki Shibata, Junko Yamamoto, Naoki Levin, Judith G. Gronenborn, Angela M. Sugiura, Wataru TI HIV-1 Vif-mediated ubiquitination/degradation of APOBEC3G involves four critical lysine residues in its C-terminal domain SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE structure model; deaminase; antiviral ID IMMUNODEFICIENCY-VIRUS TYPE-1; VIRION INFECTIVITY FACTOR; UBIQUITIN-LIGASE COMPLEX; FUNCTIONAL IMPLICATIONS; ANTIVIRAL ACTIVITY; CRYSTAL-STRUCTURE; CATALYTIC DOMAIN; ENZYME APOBEC3G; SOCS-BOX; DEGRADATION AB During coevolution with the host, HIV-1 developed the ability to hijack the cellular ubiquitin/proteasome degradation pathway to counteract the antiviral activity of APOBEC3G (A3G), a host cytidine deaminase that can block HIV-1 replication. Abrogation of A3G function involves the HIV-1 Vif protein, which binds A3G and serves as an adapter molecule to recruit A3G to a Cullin5-based E3 ubiquitin ligase complex. Structure-guided mutagenesis of A3G focused on the 14 most surface-exposed Lys residues allowed us to identify four Lys residues (Lys-297, 301, 303, and 334) that are required for Vif-mediated A3G ubiquitination and degradation. Substitution of Arg for these residues confers Vif resistance and restores A3G's antiviral activity in the presence of Vif. In our model, the critical four Lys residues cluster at the C terminus, opposite to the known N-terminal Vif-interaction region in the protein. Thus, spatial constraints imposed by the E3 ligase complex may be an important determinant in Vif-dependent A3G ubiquitination. C1 [Iwatani, Yasumasa; Yoshii, Hiroaki; Shibata, Junko; Sugiura, Wataru] Natl Hosp Org Nagoya Med Ctr, Clin Res Ctr, Naka Ku, Aichi 4600001, Japan. [Iwatani, Yasumasa; Sugiura, Wataru] Nagoya Univ, Grad Sch Med, Aichi 4668550, Japan. [Iwatani, Yasumasa; Yamamoto, Naoki; Sugiura, Wataru] Natl Inst Infect Dis, AIDS Res Ctr, Tokyo 1628640, Japan. [Chan, Denise S. B.; Liu, Lin; Gronenborn, Angela M.] Univ Pittsburgh, Sch Med, Dept Biol Struct, Pittsburgh, PA 15260 USA. [Chan, Denise S. B.] Univ Hong Kong, Dept Chem, Hong Kong, Hong Kong, Peoples R China. [Levin, Judith G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Iwatani, Y (reprint author), Natl Hosp Org Nagoya Med Ctr, Clin Res Ctr, Naka Ku, 4-1-1 San No Maru, Aichi 4600001, Japan. EM iwataniy@nnh.hosp.go.jp OI Gronenborn, Angela M/0000-0001-9072-3525 FU Ministry of Education, Culture, Sports, Science and Technology, Japan; National Institutes of Health [GM082251]; National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development; Ministry of Health, Labor, and Welfare, Japan FX This work was supported in part by a grant-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan (to Y.I.); National Institutes of Health Grant GM082251 (to A.M.G); the Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development (to J.G.L.); and a grant-in-aid for AIDS Research from the Ministry of Health, Labor, and Welfare, Japan (to W.S.). NR 48 TC 32 Z9 34 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 17 PY 2009 VL 106 IS 46 BP 19539 EP 19544 DI 10.1073/pnas.0906652106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 521GC UT WOS:000271907400057 PM 19887642 ER PT J AU Ji, YY Yang, F Papaleo, F Wang, HX Gao, WJ Weinberger, DR Lu, B AF Ji, Yuanyuan Yang, Feng Papaleo, Francesco Wang, Huai-Xing Gao, Wen-Jun Weinberger, Daniel R. Lu, Bai TI Role of dysbindin in dopamine receptor trafficking and cortical GABA function SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE dopamine D2 receptor; schizophrenia; prefrontal cortex ID LYSOSOME-RELATED ORGANELLES; PREFRONTAL CORTEX; MEMBRANE TRAFFICKING; SUSCEPTIBILITY GENE; D2 RECEPTORS; SCHIZOPHRENIA; INTERNEURONS; MECHANISMS; PROTEIN; BLOC-1 AB Dysbindin has been implicated in the pathogenesis of schizophrenia, but little is known about how dysbindin affects neuronal function in the circuitry underlying psychosis and related behaviors. Using a dysbindin knockout line (dys(-/-)) derived from the natural dysbindin mutant Sandy mice, we have explored the role of dysbindin in dopamine signaling and neuronal function in the prefrontal cortex (PFC). Combined cell imaging and biochemical experiments revealed a robust increase in the dopamine receptor D2, but not D1, on cell surface of neurons from dys(-/-) cortex. This was due to an enhanced recycling and insertion, rather than reduced endocytosis, of D2. Disruption of dysbindin gene resulted in a marked decrease in the excitability of fast-spiking (FS) GABA-ergic interneurons in both PFC and striatum. Dys(-/-) mice also exhibited a decreased inhibitory input to pyramidal neurons in layer V of PFC. The increased D2 signaling in dys(-/-) FS interneurons was associated with a more pronounced increase in neuronal firing in response to D2 agonist, compared to that in wild-type interneurons. Taken together, these results suggest that dysbindin regulates PFC function by facilitating D2-mediated modulation of GABAergic function. C1 [Ji, Yuanyuan; Yang, Feng; Lu, Bai] NICHHD, Sect Neural Dev & Plast, Bethesda, MD 20892 USA. [Papaleo, Francesco; Weinberger, Daniel R.; Lu, Bai] Natl Inst Mental Hlth, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA. [Wang, Huai-Xing; Gao, Wen-Jun] Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19129 USA. RP Lu, B (reprint author), NICHHD, Sect Neural Dev & Plast, Bethesda, MD 20892 USA. EM bailu@mail.nih.gov RI Yang, Feng/C-9530-2011; Lu, Bai/A-4018-2012; OI Papaleo, Francesco/0000-0002-6326-0657 FU National Institute of Child Health and Human Development; National Institute of Mental Health FX We thank Dr. David R. Sibley (National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda) for N-terminal FLAG-D2 human cDNA and Dr. Richard T. Swank (Roswell Park Cancer Institute, Buffalo, NY) for genotyping information of dys-/- mice. This work is supported by the Intramural Research Programs of the National Institute of Child Health and Human Development and the National Institute of Mental Health. NR 44 TC 77 Z9 81 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 17 PY 2009 VL 106 IS 46 BP 19593 EP 19598 DI 10.1073/pnas.0904289106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 521GC UT WOS:000271907400066 PM 19887632 ER PT J AU Bristow, GC Lane, TA Walker, M Chen, L Sei, Y Hyde, TM Kleinman, JE Harrison, PJ Eastwood, SL AF Bristow, Greg C. Lane, Tracy A. Walker, Mary Chen, Li Sei, Yoshi Hyde, Thomas M. Kleinman, Joel E. Harrison, Paul J. Eastwood, Sharon L. TI Expression of Kinase Interacting with Stathmin (KIS, UHMK1) in human brain and lymphoblasts: effects of schizophrenia and genotype SO BRAIN RESEARCH LA English DT Article DE Bipolar disorder; Gene expression; Psychosis; Schizophrenia; UHMK1 ID CYTOSOLIC ROUTING DETERMINANTS; PEPTIDE-PROCESSING ENZYME; MESSENGER-RNA; PROTEIN-KINASE; GENETIC ASSOCIATION; CHROMOSOME 1Q23.3; P27(KIP1); MIGRATION; CORTEX; DOMAINS AB Single nucleotide polymorphisms (SNPs) within the gene encoding the serine/threonine kinase KIS (Kinase interacting with Stathmin, also known as UHMK1) have recently been associated with schizophrenia. As none of the disease associated SNPs are coding, they may confer susceptibility by altering some facet of KIS expression. Here we have characterised the cellular distribution of KIS in human brain using in situ hybridisation and immunohistochemistry, and quantified KIS protein and mRNA in two large brain series to determine if KIS expression is altered in schizophrenia or bipolar disorder or in relation to a schizophrenia-associated SNP (rs7513662). Post-mortem tissue from the superior temporal gyrus of schizophrenia and control subjects, and also dorsolateral prefrontal cortex, anterior cingulate cortex, and cerebellum from schizophrenia, bipolar disorder, and control subjects were used. KIS expression was measured by quantitative PCR (mRNA) and immunoautoradiography (protein), and was also quantified by immunoblot in lymphoblast cell lines derived from schizophrenia and control subjects. Our results demonstrate that KIS is expressed in neurons, and its encoded protein is localised to the nucleus and cytoplasm. No difference in KIS expression was found between diagnostic groups, or in the lymphoblast cell lines, and no effect of rs7S13662 genotype on KIS expression was found. Hence, these data do not provide support for the hypothesis that altered expression is the mechanism by which genetic variation of KIS may increase susceptibility to schizophrenia, nor evidence that KIS expression is altered in the disease itself, at least in terms of the parameters studied here. (C) 2009 Elsevier B.V. All rights reserved. C1 [Bristow, Greg C.; Lane, Tracy A.; Walker, Mary; Chen, Li; Harrison, Paul J.; Eastwood, Sharon L.] Warneford Hosp, Univ Dept Psychiat, Oxford OX3 7JX, England. [Sei, Yoshi] NIMH, Blood Genom Lab, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. [Hyde, Thomas M.; Kleinman, Joel E.] NIMH, Sect Neuropathol, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program,IRP,NIH, Bethesda, MD 20892 USA. RP Eastwood, SL (reprint author), Warneford Hosp, Univ Dept Psychiat, Neurosci Bldg, Oxford OX3 7JX, England. EM sharon.eastwood@psych.ox.ac.uk OI Bristow, Greg/0000-0002-6395-6806 FU Intramural NIH HHS [Z01 MH002903-01]; Medical Research Council [, G0500180] NR 30 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 16 PY 2009 VL 1301 BP 197 EP 206 DI 10.1016/j.brainres.2009.08.090 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 523UN UT WOS:000272100200022 PM 19747464 ER PT J AU Schuck, S Prinz, WA Thorn, KS Voss, C Walter, P AF Schuck, Sebastian Prinz, William A. Thorn, Kurt S. Voss, Christiane Walter, Peter TI Membrane expansion alleviates endoplasmic reticulum stress independently of the unfolded protein response SO JOURNAL OF CELL BIOLOGY LA English DT Article ID TRANSCRIPTIONAL REGULATORY NETWORKS; PHOSPHOLIPID BIOSYNTHETIC GENES; PLASMA-CELL DIFFERENTIATION; SACCHAROMYCES-CEREVISIAE; TRANSMEMBRANE PROTEIN; INDUCIBLE MEMBRANES; LIPID BIOSYNTHESIS; PHOSPHATIDIC-ACID; FACTOR XBP-1; YEAST AB Cells constantly adjust the sizes and shapes of their organelles according to need. In this study, we examine endoplasmic reticulum (ER) membrane expansion during the unfolded protein response (UPR) in the yeast Saccharomyces cerevisiae. We find that membrane expansion occurs through the generation of ER sheets, requires UPR signaling, and is driven by lipid biosynthesis. Uncoupling ER size control and the UPR reveals that membrane expansion alleviates ER stress independently of an increase in ER chaperone levels. Converting the sheets of the expanded ER into tubules by reticulon overexpression does not affect the ability of cells to cope with ER stress, showing that ER size rather than shape is the key factor. Thus, increasing ER size through membrane synthesis is an integral yet distinct part of the cellular program to overcome ER stress. C1 [Schuck, Sebastian; Walter, Peter] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA. [Schuck, Sebastian; Thorn, Kurt S.; Walter, Peter] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA. [Prinz, William A.; Voss, Christiane] NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. RP Schuck, S (reprint author), Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA. EM sebastian.schuck@ucsf.edu RI di Ronza, Alberto/H-7674-2016; OI di Ronza, Alberto/0000-0002-9813-5143; Thorn, Kurt/0000-0001-9310-288X FU Intramural NIH HHS NR 61 TC 127 Z9 129 U1 1 U2 14 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD NOV 16 PY 2009 VL 187 IS 4 BP 525 EP 536 DI 10.1083/jcb.200907074 PG 12 WC Cell Biology SC Cell Biology GA 520HI UT WOS:000271833400010 PM 19948500 ER PT J AU Zhang, YW Hughes, KJ Zahm, SH Zhang, YQ Holford, TR Dai, L Bai, YN Han, XS Qin, Q Lan, Q Rothman, N Zhu, Y Leaderer, B Zheng, TZ AF Zhang, Yawei Hughes, Kathryn J. Zahm, Shelia Hoar Zhang, Yaqun Holford, Theodore R. Dai, Li Bai, Yana Han, Xuesong Qin, Qin Lan, Qing Rothman, Nathaniel Zhu, Yong Leaderer, Brian Zheng, Tongzhang TI Genetic Variations in Xenobiotic Metabolic Pathway Genes, Personal Hair Dye Use, and Risk of Non-Hodgkin Lymphoma SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE genetics; hair dyes; lymphoma; non-Hodgkin; xenobiotics ID GLUTATHIONE-S-TRANSFERASE; LUNG-CANCER; N-ACETYLTRANSFERASE-1 NAT1; BIOTRANSFORMATION ENZYMES; MOLECULAR-GENETICS; GSTT1 GENOTYPES; POLYMORPHISMS; ASSOCIATION; SMOKING; GSTM3 AB From 1996 to 2000, the authors conducted a population-based case-control study among Connecticut women to test the hypothesis that genetic variation in xenobiotic metabolic pathway genes modifies the relation between hair dye use and risk of non-Hodgkin lymphoma. No effect modifications were found for women who started using hair dyes in 1980 or afterward. For women who started using hair dye before 1980 as compared with never users, a statistically significantly increased risk of non-Hodgkin lymphoma was found for carriers of CYP2C9 Ex3-52C > T TT/CT genotypes (odds ratio (OR) = 2.9, 95% confidence interval (CI): 1.4, 6.1), CYP2E1 -332T > A AT/AA genotypes (OR = 2.0, 95% CI: 1.2, 3.4), a homozygous or heterozygous 3-base-pair deletion in intron 6 of GSTM3 (OR = 2.3, 95% CI: 1.3, 4.1), GSTP1 Ex5-24A > G AA genotypes (OR = 1.8, 95% CI: 1.1, 2.9), or NAT2 genotypes conferring intermediate/rapid acetylator status (OR = 1.6, 95% CI: 1.0, 2.7). The observed associations were mainly seen for follicular lymphoma. In contrast, no significantly increased risk was observed for starting hair dye use before 1980 (relative to never use) among women who were homozygous wild-type for the CYP2C9, CYP2E1, or GSTM3 polymorphisms, women carrying 1 or 2 copies of the variant GSTP1 allele, or women who were slow NAT2 acetylators. A possible role of genetic variation in xenobiotic metabolism in the carcinogenicity of hair dye use needs to be confirmed in larger studies. C1 [Zhang, Yawei; Hughes, Kathryn J.; Holford, Theodore R.; Dai, Li; Bai, Yana; Han, Xuesong; Zhu, Yong; Leaderer, Brian; Zheng, Tongzhang] Yale Univ, Sch Publ Hlth, New Haven, CT 06520 USA. [Zahm, Shelia Hoar; Lan, Qing; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Zhang, Yaqun] Gansu Prov Design & Res Inst Environm Sci, Lanzhou, Peoples R China. [Dai, Li] Sichuan Univ, W China Univ Hosp 2, Natl Ctr Birth Defect Monitoring, Chengdu 610064, Peoples R China. [Bai, Yana] Lanzhou Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Lanzhou 730000, Peoples R China. [Qin, Qin] Univ So Maine, Ctr Toxicol & Environm Hlth, Portland, ME 04103 USA. RP Zhang, YW (reprint author), Yale Univ, Sch Publ Hlth, 60 Coll St,LEPH 440,POB 208034, New Haven, CT 06520 USA. EM yawei.zhang@yale.edu RI Zahm, Shelia/B-5025-2015 FU National Cancer Institute [CA62006]; National Institutes of Health (NIH) [1D43TW007864-01]; National Center for Research Resources, NIH [UL1 RR024139] FX This study was supported by grant CA62006 from the National Cancer Institute; the Intramural Research Program of the National Cancer Institute, National Institutes of Health (NIH); and Fogarty training grant 1D43TW007864-01 from the NIH. Publication of this article was made possible by Clinical and Translational Science Award UL1 RR024139 from the National Center for Research Resources, NIH, and by the NIH Roadmap for Medical Research. NR 35 TC 6 Z9 6 U1 0 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 15 PY 2009 VL 170 IS 10 BP 1222 EP 1230 DI 10.1093/aje/kwp263 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 514FN UT WOS:000271379800004 PM 19822571 ER PT J AU Villanueva, CM Silverman, DT Kogevinas, M AF Villanueva, Cristina M. Silverman, Debra T. Kogevinas, Manolis TI Re: "Determinants of Quality of Interview and Impact on Risk Estimates in a Case-Control Study of Bladder Cancer" - Three Authors Reply SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter C1 [Villanueva, Cristina M.; Kogevinas, Manolis] Ctr Res Environm Epidemiol CREAL, Barcelona 08003, Spain. [Villanueva, Cristina M.; Kogevinas, Manolis] IMIM Hosp Mar, Municipal Inst Med Res, Barcelona 08003, Spain. [Villanueva, Cristina M.; Kogevinas, Manolis] CIBERESP, Barcelona 08003, Spain. [Silverman, Debra T.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Kogevinas, Manolis] Natl Sch Publ Hlth, Athens 11521, Greece. RP Villanueva, CM (reprint author), Ctr Res Environm Epidemiol CREAL, Barcelona 08003, Spain. EM cvillanueva@creal.cat RI Benavides, Fernando/A-5137-2008; Villanueva, Cristina/N-1942-2014; Kogevinas, Manolis/C-3918-2017 OI Benavides, Fernando/0000-0003-0747-2660; Villanueva, Cristina/0000-0002-0783-1259; NR 2 TC 0 Z9 0 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 15 PY 2009 VL 170 IS 10 BP 1319 EP 1320 DI 10.1093/aje/kwp286 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 514FN UT WOS:000271379800015 ER PT J AU Gunay-Aygun, M AF Gunay-Aygun, Meral TI Liver and Kidney Disease in Ciliopathies SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS LA English DT Review DE ductal plate malformation; congenital hepatic fibrosis; Caroli syndrome; polycystic liver disease; portal hypertension; polycystic kidney disease; nephronophthisis; cystic dysplastic kidneys; medullary sponge kidney; multicystic dysplastic kidneys; primary cilia; ciliopathy ID CONGENITAL HEPATIC-FIBROSIS; MOON-BIEDL SYNDROME; INTRAHEPATIC BILE-DUCTS; DIGITAL SYNDROME TYPE-1; AUTOSOMAL-DOMINANT; POLYCYSTIC LIVER; JOUBERT-SYNDROME; RENAL-DISEASE; PANCREATIC DYSPLASIA; JEUNE-SYNDROME AB Hepatorenal fibrocystic diseases (HRFCDs) are among the most common inherited human disorders. The discovery that proteins defective in the autosomal dominant and recessive polycystic kidney diseases (ADPKD and ARPKD) localize to the primary cilia and the recognition of the role these organelles play in the pathogenesis of HRFCDs led to the term "ciliopathies." While ADPKD and ARPKD are the most common ciliopathies associated with both liver and kidney disease, variable degrees of renal and/or hepatic involvement occur in many other ciliopathies, including Joubert, Bardet-Biedl, Meckel-Gruber, and oral-facial-digital syndromes. The ductal plate malformation (DPM), a developmental abnormality of the portobiliary system, is the basis of the liver disease in ciliopathies that manifest congenital hepatic fibrosis (CHF), Caroli syndrome (CS), and polycystic liver disease (PLD). Hepatocellular function remains relatively preserved in ciliopathy-associated liver diseases. The major morbidity associated with CHF is portal hypertension (PH), often leading to esophageal varices and hypersplenism. In addition, CD predisposes to recurrent cholangitis. PLD is not typically associated with PH, but may result in complications due to mass effects. The kidney pathology in ciliopathies ranges from non-functional cystic dysplastic kidneys to an isolated urinary concentration defect; the disorders contributing to this pathology, in addition to ADPKD and ARPKD, include nephronophithisis (NPHP), glomerulocystic kidney disease and medullary sponge kidneys. Decreased urinary concentration ability, resulting in polyuria and polydypsia, is the first and most common renal symptom in ciliopathies. While the majority of ADPKD, ARPKD, and NPHP patients require renal transplantation, the frequency and rate of progression to renal failure varies considerably in other ciliopathies. This review focuses on the kidney and liver disease found in the different ciliopathies. Published 2009 Wiley-Liss, Inc.(dagger) C1 [Gunay-Aygun, Meral] NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Gunay-Aygun, Meral] Johns Hopkins Univ, Sch Medicine, Baltimore, MD 21218 USA. RP Gunay-Aygun, M (reprint author), NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, 10 Ctr Dr,Bldg 10,Rm 10C103, Bethesda, MD 20892 USA. EM mgaygun@mail.nih.gov FU Intramural NIH HHS [Z99 HG999999] NR 109 TC 72 Z9 75 U1 4 U2 8 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4868 J9 AM J MED GENET C JI Am. J. Med. Genet. C PD NOV 15 PY 2009 VL 151C IS 4 BP 296 EP 306 DI 10.1002/ajmg.c.30225 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 516MT UT WOS:000271547300004 PM 19876928 ER PT J AU Parisi, MA AF Parisi, Melissa A. TI Clinical and Molecular Features of Joubert syndrome and Related Disorders SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS LA English DT Review DE Joubert syndrome; COACH syndrome; molar tooth sign; ciliary disorder; ciliopathy; cerebellar vermis hypoplasia ID MECKEL-GRUBER-SYNDROME; MOLAR TOOTH SIGN; BARDET-BIEDL-SYNDROME; OCULO-RENAL SYNDROMES; SENIOR-LOKEN-SYNDROME; AHI1 GENE-MUTATIONS; SYNDROME TYPE-B; CEREBELLAR VERMIS; JUVENILE NEPHRONOPHTHISIS; CENTROSOMAL PROTEIN AB Joubert syndrome (JBTS; OMIM 213300) is a rare, autosomal recessive disorder characterized by a specific congenital malformation of the hindbrain and a broad spectrum of other phenotypic findings that is now known to be caused by defects in the structure and/or function of the primary cilium. The complex hindbrain malformation that is characteristic of JBTS can be identified on axial magnetic resonance imaging and is known as the molar tooth sign (MTS); other diagnostic criteria include intellectual disability, hypotonia, and often, abnormal respiratory pattern and/or abnormal eye movements. In addition, a broad spectrum of other anomalies characterize Joubert syndrome and related disorders (JSRD), and may include retinal dystrophy, ocular coloboma, oral frenulae and tongue tumors, polydactyly, cystic renal disease (including cystic dysplasia or juvenile nephronophthisis), and congenital hepatic fibrosis. The clinical course can be variable, but most children with this condition survive infancy to reach adulthood. At least eight genes cause JSRD, with some genotype-phenotype correlations emerging, including the association between mutations in the MKS3 gene and hepatic fibrosis characteristic of the JSRD subtype known as COACH syndrome. Several of the causative genes for JSRD are implicated in other ciliary disorders, such as juvenile nephronophthisis and Meckel syndrome, illustrating the close association between these conditions and their overlapping clinical features that reflect a shared etiology involving the primary cilium. (C) 2009 Wiley-Liss, Inc. C1 [Parisi, Melissa A.] Seattle Childrens Hosp, Seattle, WA USA. [Parisi, Melissa A.] Univ Washington, Seattle, WA 98195 USA. RP Parisi, MA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intellectual & Dev Disabil Branch, NIH, Bethesda, MD 20892 USA. EM parisima@mail.nih.gov FU National Institutes of Health [K23NS45832, P30HD002274]; March of Dimes Endowment for Healthier Babies FX Grant sponsor: National Institutes of Health; Grant numbers: K23NS45832, P30HD002274; Grant sponsor: March of Dimes Endowment for Healthier Babies. NR 108 TC 68 Z9 73 U1 2 U2 8 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4868 J9 AM J MED GENET C JI Am. J. Med. Genet. C PD NOV 15 PY 2009 VL 151C IS 4 BP 326 EP 340 DI 10.1002/ajmg.c.30229 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 516MT UT WOS:000271547300007 PM 19876931 ER PT J AU Fessler, MB AF Fessler, Michael B. TI Simvastatin as a Potential Therapeutic for Acute Respiratory Distress Syndrome SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Letter ID PULMONARY INFLAMMATION; OXIDATIVE STRESS; REDUCTASE C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Fessler, MB (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 6 TC 1 Z9 1 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV 15 PY 2009 VL 180 IS 10 BP 1031 EP 1031 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 519VR UT WOS:000271797600022 PM 19897776 ER PT J AU Bezrukov, L Blank, PS Polozov, IV Zimmerberg, J AF Bezrukov, Ludmila Blank, Paul S. Polozov, Ivan V. Zimmerberg, Joshua TI An adhesion-based method for plasma membrane isolation: Evaluating cholesterol extraction from cells and their membranes SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE Fibroblast cells; Cholesterol/phospholipid ratio; Differential extraction; Methyl-beta-cyclodextrin; Polylysine ID COATED POLYACRYLAMIDE BEADS; HELA-CELLS; PHOSPHOLIPID-COMPOSITION; GLASS BEADS; POLYLYSINE; HEMAGGLUTININ; PURIFICATION; FIBROBLASTS; ASYMMETRY; SURFACE AB A method to isolate large quantities of directly accessible plasma membrane from attached cells is presented. The method is based on the adhesion of cells to an adsorbed layer of polylysine on glass plates, followed by hypotonic lysis with ice-cold distilled water and subsequent washing steps. Optimal conditions for coating glass plates and time for cell attachment were established. No additional chemical or mechanical treatments were used. Contamination of the isolated plasma membrane by cell organelles was less than 5%. The method uses inexpensive, commercially available polylysine and reusable glass plates. Plasma membrane preparations can be made in 15 min. Using this method, we determined that methyl-beta-cyclodextrin differentially extracts cholesterol from fibroblast cells and their plasma membranes and that these differences are temperature dependent. Determination of the cholesterol/phospholipid ratio from intact cells does not reflect methyl-beta-cyclodextrin plasma membrane extraction properties. Published by Elsevier Inc. C1 [Bezrukov, Ludmila; Blank, Paul S.; Polozov, Ivan V.; Zimmerberg, Joshua] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Zimmerberg, J (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, Natl Inst Hlth, Bethesda, MD 20892 USA. EM zimmerbj@mail.nih.gov FU National Institutes of Health; Eunice Kennedy Shriver National Institute of Health and Human Development FX The authors thank K. Melikov, E. Zaitseva, and J. Mazar for fruitful discussions and suggestions. This study was supported by the Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Health and Human Development. NR 27 TC 13 Z9 13 U1 2 U2 14 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 2009 VL 394 IS 2 BP 171 EP 176 DI 10.1016/j.ab.2009.07.027 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 534GI UT WOS:000272884000004 PM 19631189 ER PT J AU Cope, K Seifried, H Seifried, R Milner, J Kris-Etherton, P Harrison, EH AF Cope, Keary Seifried, Harold Seifried, Rebecca Milner, John Kris-Etherton, Penny Harrison, Earl H. TI A gas chromatography-mass spectrometry method for the quantitation of N-nitrosoproline and N-acetyl-S-allylcysteine in human urine: Application to a study of the effects of garlic consumption on nitrosation SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE Biomarkers; Allyl sulfur compounds; Nitrosation; Nutrition; Cancer ID ALLYL-L-CYSTEINE; DRINKING-WATER; ASCORBIC-ACID; ENDOGENOUS NITROSATION; EXCRETION; NITRATE; MECHANISMS; NITRITE; CANCER; NITROSODIMETHYLAMINE AB Biomarkers in urine can provide useful information about the bioactivation of chemical carcinogens and can be used to investigate the chemoprotective properties of dietary nutrients. N-Nitrosoproline (NPRO) excretion has been used as an index for endogenous nitrosation. In vitro and animal studies have reported that compounds in garlic may suppress nitrosation and inhibit carcinogenesis. We present a new method for extraction and sensitive detection of both NPRO and N-acetyl-S-allylcysteine from urine. The latter is a metabolite of S-allylcysteine, which is found in garlic. Urine was acidified and the organic acids were extracted by reversed-phase extraction (RP-SPE) and use of a polymeric weak anion exchange (WAX-SPE) resin. NPRO was quantified by isotope dilution gas chromatography-mass spectrometry (GC-MS) using [(13)C(5)]NPRO and N-nitrosopipecolinic acid (NPIC) as internal standards. This method was used to analyze urine samples from a study that was designed to test whether garlic supplementation inhibits NPRO synthesis. Using this method, 2.4 to 46.0 ng NPRO/ml urine was detected. The method is straightforward and reliable, and it can be performed with readily available GC-MS instruments. N-Acetyl-S-allylcysteine was quantified in the same fraction and detectable at levels of 4.1 to 176.4 ng/ml urine. The results suggest that 3 to 5 g of garlic supplements inhibited NPRO synthesis to an extent similar to a 0.5-g dose of ascorbic acid or a commercial supplement of aged garlic extract. Urinary NPRO concentration was inversely associated with the N-acetyl-S-allylcysteine concentration. It is possible that allyl sulfur compounds found in garlic may inhibit nitrosation in humans. (C) 2009 Elsevier Inc. All rights reserved. C1 [Harrison, Earl H.] Ohio State Univ, Dept Human Nutr, Columbus, OH 43210 USA. [Cope, Keary; Seifried, Rebecca; Harrison, Earl H.] USDA Human Nutr Res Ctr, Phytonutrients Lab, Beltsville, MD 20705 USA. [Seifried, Harold; Milner, John] NCI, Nutr Sci Res Grp, Canc Prevent Div, Rockville, MD 20892 USA. [Seifried, Rebecca; Milner, John; Kris-Etherton, Penny] Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA. RP Harrison, EH (reprint author), Ohio State Univ, Dept Human Nutr, Columbus, OH 43210 USA. EM harrison.304@osu.edu FU NHLBI NIH HHS [R01 HL049879, R01 HL049879-08]; NIDDK NIH HHS [R01 DK044498, R01 DK044498-09] NR 28 TC 2 Z9 2 U1 0 U2 11 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 2009 VL 394 IS 2 BP 243 EP 248 DI 10.1016/j.ab.2009.07.035 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 534GI UT WOS:000272884000014 PM 19643074 ER PT J AU Pan, BX Ito, W Morozov, A AF Pan, Bing-Xing Ito, Wataru Morozov, Alexei TI Divergence Between Thalamic and Cortical Inputs to Lateral Amygdala During Juvenile-Adult Transition in Mice SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Amygdala; development; fear; juvenile; LTP; synaptic transmission ID LONG-TERM POTENTIATION; SYNAPTIC PLASTICITY; SILENT SYNAPSES; TRANSMITTER RELEASE; GLUTAMATE UPTAKE; FEAR; PATHWAY; BRAIN; LTP; ADOLESCENCE AB Background: Adolescence is considered a critical time of life for emotional development in humans. During this period the amygdala, which regulates emotions, undergoes structural reorganization. Auditory fear conditioning, a form of amygdala-dependent emotional learning, occurs differently in juvenile and adult rodents. Because this learning is mediated by plastic changes in the thalamic and cortical inputs to lateral amygdala (LA), we investigated changes in synaptic properties of these inputs during juvenile-to-adult transition. Methods: Whole-cell patch clamp recording in amygdala slices from juvenile and young adult mice was conducted to investigate long-term potentiation and basal synaptic transmission in the thalamic and cortical inputs to LA. Results: We show that physiological differences develop between thalamic and cortical afferents to LA during the juvenile-to-adult transition. Although in juvenile mice the two pathways have similar properties, in young adult mice the thalamic pathway has reduced plasticity, increased number of quanta released by a single action potential, and decreased proportion of silent synapses. Conclusions: Changes in thalamic but not cortical inputs to amygdala take place during late development and might contribute to differences in auditory fear conditioning between juveniles and adults. C1 [Pan, Bing-Xing; Ito, Wataru; Morozov, Alexei] NIMH, Unit Behav Genet, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Morozov, A (reprint author), NIMH, Unit Behav Genet, Mol Pathophysiol Lab, NIH, 35 Convent Dr, Bethesda, MD 20892 USA. EM morozova@mail.nih.gov RI PAN, BINGXING/C-7870-2011 FU National Institute of Mental Health FX This research was supported by the National Institute of Mental Health Intramural Research Program. We thank, Chao Yang for editorial work. NR 48 TC 11 Z9 12 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 15 PY 2009 VL 66 IS 10 BP 964 EP 971 DI 10.1016/j.biopsych.2009.07.006 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 515UC UT WOS:000271497400010 PM 19699473 ER PT J AU Youssef, D Potter, E Jha, M De Clercq, E Balzarini, J Stables, JP Jha, A AF Youssef, Dani Potter, Elizabeth Jha, Mamta De Clercq, Erik Balzarini, Jan Stables, James P. Jha, Amitabh TI Design, synthesis and bioevaluation of novel maleamic amino acid ester conjugates of 3,5-bisarylmethylene-4-piperidones as cytostatic agents SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE 3,5-Bisarylmethylene-4-piperidones; Cytostatic activity; Anticancer; Topoisomerase inhibitions; QSAR ID DNA TOPOISOMERASE-II; CYTOTOXIC PROPERTIES; ANTICANCER AGENTS; ANALOGS; 3,5-BIS(ARYLIDENE)-4-PIPERIDONES; INHIBITION; MECHANISM; TOXICITY; KINASE; CELLS AB A novel series of maleamic amino acid ester conjugates of 3,5-bisarylmethylene-4-piperidones were prepared to investigate the efficacy of micronutrient conjugation in enhancing cytotoxic potency by improving selectivity and delivery. These compounds, prepared as anticancer agents, were expected to demonstrate enhanced selectivity towards malignant cells through the inhibition of topoisomerase II alpha via protein thiolation. The cytostatic effects of these compounds were evaluated against three cell lines, namely murine L1210 leukemia cells, human Molt 4/C8 and CEM T-lymphocyte cells. All compounds were found to have greater potency than the reference drug melphalan. Several compounds were found to potently inhibit topoisomerase IIa and displayed cytostatic activity in the nanomolar range. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Youssef, Dani; Potter, Elizabeth; Jha, Mamta; Jha, Amitabh] Acadia Univ, Dept Chem, Wolfvile, NS B4P 2R6, Canada. [Youssef, Dani] Univ St Anna, Dept Sci, Pointe De Leglise, NS B0W 1M0, Canada. [De Clercq, Erik; Balzarini, Jan] Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium. [Stables, James P.] NINDS, Rockville, MD 20852 USA. RP Jha, A (reprint author), Acadia Univ, Dept Chem, Wolfvile, NS B4P 2R6, Canada. EM ajha@acadiau.ca RI Jha, Amitabh/B-5452-2010; Youssef, Diaa/H-9813-2012 OI Jha, Amitabh/0000-0002-6305-0721; FU Nova Scotia Health Research Foundation; Concerted Research Actions [GOA 05/19] FX The authors thank the following agencies for financial support, the Nova Scotia Health Research Foundation (A. J., E. P.) and the Concerted Research Actions (GOA 05/19) (J. B.). Appreciation is extended to Mrs. Lisette van Berckelaer for conducting the Molt 4/C8, CEM, and L1210 assays, and the National Institute of Neurological Disorders and Stroke, USA, for undertaking the short term toxicity studies in mice. Dr. Sherri McFarland (Acadia University) is thanked for demonstrating the topoisomerase assay protocol. NR 31 TC 9 Z9 9 U1 0 U2 3 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 2009 VL 19 IS 22 BP 6364 EP 6367 DI 10.1016/j.bmcl.2009.09.069 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 509PH UT WOS:000271029600023 PM 19819135 ER PT J AU Fuller, CD Wang, SJ Choi, M Czito, BG Cornell, J Welzel, TM McGlynn, KA Luh, JY Thomas, CR AF Fuller, Clifton D. Wang, Samuel J. Choi, Mehee Czito, Brian G. Cornell, John Welzel, Tania M. McGlynn, Katherine A. Luh, Join Y. Thomas, Charles R., Jr. TI Multimodality Therapy for Locoregional Extrahepatic Cholangiocarcinoma A Population-Based Analysis SO CANCER LA English DT Article DE cholangiocarcinoma; bile duct cancer; radiotherapy; surgery; lognormal survival ID BILE-DUCT CARCINOMA; EXTERNAL-BEAM RADIOTHERAPY; RESECTED BILIARY MALIGNANCIES; SEER DATABASE ANALYSIS; ADJUVANT RADIOTHERAPY; HILAR CHOLANGIOCARCINOMA; RADICAL RESECTION; RADIATION-THERAPY; IMPROVED SURVIVAL; BREAST-CANCER AB BACKGROUND: Although surgical resection is the mainstay of treatment for extrahepatic cholangiocarcinoma, the majority of patients present with advanced disease. Due in part to numeric rarity, the optimum role of radiotherapy (RT) for extrahepatic cholangiocarcinoma, as well as its relative benefit, is an area of debate. The specific aim of this series was to estimate survival for extrahepatic cholangiocarcinoma patients receiving surgery and adjuvant RT using a robust population-based data set. METHODS: Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) limited-use data set for selected extrahepatic cholangiocarcinoma cases. Lognormal multivariate survival analysis was implemented to estimate survival for patients for treatment cohorts based on extent of surgical intervention and RT. RESULTS: Parametric estimated median survival for patients receiving total/radical resection+RT was 26 months; it was 25 months for total/radical resection alone, 25 months for subtotal/debulking resection+RT, 21 months for subtotal/debulking resection, 12 months for RT alone, and 9 months for those not receiving surgery or RT. Parametric multivariate analysis revealed age, American Joint Committee on Cancer Stage, grade, and surgical/radiation regimen as statistically significant covariates with survival. Surgery alone and adjuvant RT cohorts demonstrated evidence of improved survival compared with no treatment; comparatively, RT alone was associated with survival decrement. Early improvement in survival in adjuvant cohorts was not observed at later time points. CONCLUSIONS: Survival estimates using SEER data suggest an early survival advantage for adjuvant RT for patients with locoregional extrahepatic cholangiocarcinoma. Although future prospective series are needed to confirm these observations, SEER data represent the largest domestic population-based extrahepatic cholangiocarcinoma cohort, and may provide useful baseline survival estimates for future studies. Cancer 2009;115:5175-83. Published 2009 by the American Cancer Society*. C1 [Fuller, Clifton D.; Luh, Join Y.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiat Oncol, San Antonio, TX 78229 USA. [Fuller, Clifton D.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, Grad Div Radiol Sci, San Antonio, TX 78229 USA. [Fuller, Clifton D.; Wang, Samuel J.; Choi, Mehee; Thomas, Charles R., Jr.] Oregon Hlth & Sci Univ, Inst Canc, Dept Radiat Med, Portland, OR 97201 USA. [Czito, Brian G.] Duke Univ, Dept Radiat Oncol, Durham, NC USA. [Cornell, John] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Welzel, Tania M.; McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Luh, Join Y.] St Joseph Hosp, Eureka, CA USA. RP Fuller, CD (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Radiat Oncol, 7703 Floyd Curl Dr,MSC 7889, San Antonio, TX 78229 USA. EM fullercd@uthscsa.edu OI Fuller, Clifton/0000-0002-5264-3994 FU National Institutes of Health/National Institute of Biomedical Imaging and BioEngineering/UTHSCSA [5T32EB000817-04] FX Dr. Fuller received funding support from the National Institutes of Health/National Institute of Biomedical Imaging and BioEngineering/UTHSCSA Graduate Division of Radiological Sciences Multidisciplinary Training Grant in Human Imaging (5T32EB000817-04). NR 63 TC 26 Z9 26 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD NOV 15 PY 2009 VL 115 IS 22 BP 5175 EP 5183 DI 10.1002/cncr.24572 PG 9 WC Oncology SC Oncology GA 516SW UT WOS:000271564100010 PM 19637356 ER PT J AU Abdeen, A Chou, AJ Healey, JH Khanna, C Osborne, TS Hewitt, SM Kim, M Wang, D Moody, K Gorlick, R AF Abdeen, Ayesha Chou, Alexander J. Healey, John H. Khanna, Chand Osborne, Tanasa S. Hewitt, Stephen M. Kim, Mimi Wang, Dan Moody, Karen Gorlick, Richard TI Correlation Between Clinical Outcome and Growth Factor Pathway Expression in Osteogenic Sarcoma SO CANCER LA English DT Article DE osteosarcoma; immunohistochemistry; survival; signal transduction ID POOR-PROGNOSIS; OSTEOSARCOMA; CHEMOTHERAPY; METASTASIS; EXPERIENCE; VEGF AB BACKGROUND: Multiple cell-signaling ligands and receptors-including vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), endothelial growth factor (EGF), v-akt murine thymoma viral oncogene homolog (AKT), platelet-derived growth factor (PDGF), mitogen-activated protein kinase (MAPK), and 70-kilodalton (kD) protein S6 kinase (p70S6 kinase)-reportedly are variably expressed in osteogenic sarcoma. Expression of these proteins may have future implications for prognostication and targeted therapy. The objective of the current study was to determine the relation between clinical outcome and the expression of these proteins. METHODS: A paraffin-embedded microarray of 48 human osteogenic sarcoma tissue specimens was stained with the antibodies against VEGF, IGF, EGF, AKT, PDGF, MAPK, and p70S6 kinase. Staining for each protein included the total protein and, when applicable, the phosphorylated version of the protein. Immunohistochemical staining was then correlated with patient survival (overall survival [OS] and event-free survival [EFS]), histologic response to chemotherapy, and serum markers. RESULTS: There was a negative correlation between VEGF receptor 3 (VEGF-R3) and both OS and EFS. VEGF-B was correlated with a poor histologic response to chemotherapy. Serum markers were not correlated with any specific proteins. When using a P value of .05, multiple correlations were observed between proteins of various pathways. CONCLUSIONS: The current results suggested that the VEGF pathway is a critical signaling pathway in osteogenic sarcoma. These data have identified specific proteins within these pathways toward which future investigations should be directed to further clarify their prognostic potential. Cancer 2009;115:5243-50. Published 2009 by the American Cancer Society.* C1 [Abdeen, Ayesha; Healey, John H.] Cornell Univ, Weill Med Coll, Mem Sloan Kettering Canc Ctr, Dept Orthopaed Surg, New York, NY 10021 USA. [Chou, Alexander J.] Cornell Univ, Weill Med Coll, Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. [Khanna, Chand; Osborne, Tanasa S.] NCI, Tumor & Metastasis Biol Sect, Pediat Oncol Branch, LLR, Bethesda, MD 20892 USA. [Hewitt, Stephen M.] NCI, TARP, Pathol Lab, LLR, Bethesda, MD 20892 USA. [Kim, Mimi; Wang, Dan] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Moody, Karen; Gorlick, Richard] Yeshiva Univ, Albert Einstein Coll Med, Montefiore Med Ctr, Dept Pediat, Bronx, NY USA. RP Gorlick, R (reprint author), Childrens Hosp Montefiore, Div Pediat Hematol Oncol, 3415 Bainbridge Ave,Rosenthal Bldg,Room 300, Bronx, NY 10467 USA. EM rgorlick@montefiore.org OI Hewitt, Stephen/0000-0001-8283-1788; Chou, Alexander/0000-0002-7926-3326 NR 11 TC 41 Z9 44 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 15 PY 2009 VL 115 IS 22 BP 5243 EP 5250 DI 10.1002/cncr.24562 PG 8 WC Oncology SC Oncology GA 516SW UT WOS:000271564100018 PM 19670450 ER PT J AU Dignam, JJ Huang, L Ries, L Reichman, M Mariotto, A Feuer, E AF Dignam, James J. Huang, Lan Ries, Lynn Reichman, Marsha Mariotto, Angela Feuer, Eric TI Estimating Breast Cancer-Specific and Other-Cause Mortality in Clinical Trial and Population-Based Cancer Registry Cohorts SO CANCER LA English DT Article DE relative survival; cause-specific survival; breast cancer; life tables ID SURGICAL ADJUVANT BREAST; RELATIVE SURVIVAL RATES; INDIVIDUAL PATIENT DATA; RESULTS SEER PROGRAM; 18 RANDOMIZED-TRIALS; LOCOREGIONAL RECURRENCES; TUMOR RECURRENCE; COLON-CANCER; END-POINTS; EPIDEMIOLOGY AB BACKGROUND: To compute net cancer-specific survival rates using population data sources (eg, the National Cancer Institute's Surveillance, Epidemiology, and End Results [SEER] Program), 2 approaches primarily are used: relative survival (observed survival adjusted for life expectancy) and cause-specific survival based on death certificates. The authors of this report evaluated the performance of these estimates relative to a third approach based on detailed clinical follow-up history. METHODS: By using data from Cancer Cooperative Group clinical trials in breast cancer, the authors estimated 1) relative survival, 2) breast cancer-specific survival (BCSS) determined from death certificates, and 3) BCSS obtained by attributing cause according to clinical events after diagnosis, which, for this analysis was considered the benchmark "true" estimate. Noncancer life expectancy also was compared between trial participants, SEER registry patients, and the general population. RESULTS: Among trial patients, relative survival overestimated true BCSS in patients with lymph node-negative breast cancer; whereas, in patients with lymph node-positive breast cancer, the 2 estimates were similar. For higher risk patients (younger age, larger tumors), relative survival accurately estimated true BCSS. In lower risk patients, death certificate BCSS was more accurate than relative survival. Noncancer life expectancy was more favorable among trial participants than in the general population and among SEER patients. Tumor size at diagnosis, which is a potential surrogate for screening use, partially accounted for this difference. CONCLUSIONS: In the clinical trials, relative survival accurately estimated BCSS in patients who had higher risk disease despite more favorable other-cause mortality than the population at large. In patients with lower risk disease, the estimate using death certificate information was more accurate. For SEER data and other data sources where detailed postdiagnosis clinical history was unavailable, death certificate-based estimates of cause-specific survival may be a superior choice. Cancer 2009;115:5272-83. (C) 2009 American Cancer Society. C1 [Dignam, James J.] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Dignam, James J.] Univ Chicago, Canc Res Ctr, Chicago, IL 60637 USA. [Huang, Lan; Ries, Lynn; Reichman, Marsha; Mariotto, Angela; Feuer, Eric] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Dignam, JJ (reprint author), Univ Chicago, Dept Hlth Studies, 5841 S Maryland Ave,MC 2007, Chicago, IL 60637 USA. EM jdignam@health.bsd.uchicago.edu FU US. National Cancer Institute [263-MQ-611334, NCI-U10-CA-69, NCI-U10-CA-651, NCI-U10-CA-12, NCI-U10-CA-027]; Susan G. Komen for the Cure Foundation FX Supported by, contract 263-MQ-611334 to J.J.D. from the Division of Cancer Control and Population Sciences/Surveillance Research Program/Statistical Research and Applications Branch of the US. National Cancer Institute and by a research grant from the Susan G. Komen for the Cure Foundation. The clinical trials were Supported by Public Health Service grants NCI-U10-CA-69,651 and NCI-U10-CA-12,027 from the US. National Cancer Institute. NR 24 TC 20 Z9 20 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD NOV 15 PY 2009 VL 115 IS 22 BP 5272 EP 5283 DI 10.1002/cncr.24617 PG 12 WC Oncology SC Oncology GA 516SW UT WOS:000271564100021 PM 19670456 ER PT J AU Fujisawa, T Joshi, B Nakajima, A Puri, RK AF Fujisawa, Toshio Joshi, Bharat Nakajima, Atsushi Puri, Raj K. TI A Novel Role of Interleukin-13 Receptor alpha 2 in Pancreatic Cancer Invasion and Metastasis SO CANCER RESEARCH LA English DT Article ID PROTEIN-KINASE PATHWAYS; PSEUDOMONAS EXOTOXIN; MATRIX METALLOPROTEINASES; SIGNAL-TRANSDUCTION; IN-VIVO; CELLS; CHAIN; EXPRESSION; FIBROSIS; TARGET AB Whereas interleukin-13 receptor alpha 2 chain (IL-13R alpha 2) is over-expressed in a variety of human solid cancers including pancreatic cancer, we investigated its significance in cancer invasion and metastasis. We used two pancreatic cancer cell lines, IL-13R alpha 2-negative HPAF-H and IL-13R alpha 2-positive HS766T, and generated IL-13Ra2 stably transfected HPAF-II as well as IL-13Ra2 RNA interference knocked-down HS766T cells. Ability of invasion and signal transduction was compared between IL-13R alpha 2-negative and IL-13R alpha 2-positive cells and tumor metastasis was assessed in murine model for human pancreatic cancer with orthotopic implantation of tumors. IL-13 treatment enhanced cell invasion in IL13R alpha 2-positive cancer cell lines but not in IL-13R alpha 2-negative cell lines. Furthermore, gene transfer of IL-13R alpha 2 in negative cell lines enhanced invasion, whereas its silencing downmodulated invasion of pancreatic cell lines in a Matrigel invasion assay. In vivo study revealed that II-13R alpha 2-positive cancer metastasized to lymph nodes, liver, and peritoneum at. a significantly higher rate compared with IL-13R alpha 2-negative tumors. The expression of IL-13R alpha 2 in metastatic lesions was found to be increased compared with primary tumors, and mice with IL-13R alpha 2-positive cancer displayed cachexia and poor prognosis. Invasion and metastasis also correlated with increased matrix metalloproteinase protease activity in these cells. Mechanistically, IL-13 activated extracellular signal-regulated kinase 1/2 and activator protein-1 nuclear factors in IL-13R alpha 2-positive pancreatic cancer cell lines but not in IL-13R alpha 2-negative cell lines. Taken together, our results show for the first time that IL-13 can signal through IL-13R alpha 2 in pancreatic cancer cells and IL-13Ra2 may serve as a prognostic biomarker of invasion and metastasis in pancreatic cancer. [Cancer Res 2009;69(22):8678-85] C1 [Fujisawa, Toshio; Joshi, Bharat; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Nakajima, Atsushi] Yokohama City Univ, Sch Med, Div Gastroenterol, Yokohama, Kanagawa 232, Japan. RP Puri, RK (reprint author), US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, NIH Bldg 29B,Room 2NN20 HFM 735,29 Lincoln Dr, Bethesda, MD 20892 USA. EM raj.puri@fda.hhs.gov NR 35 TC 47 Z9 53 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2009 VL 69 IS 22 BP 8678 EP 8685 DI 10.1158/0008-5472.CAN-09-2100 PG 8 WC Oncology SC Oncology GA 520JC UT WOS:000271839200020 PM 19887609 ER PT J AU Vo, DD Prins, RM Begley, JL Donahue, TR Morris, LF Bruhn, KW de la Rocha, P Yang, MY Mok, S Garban, HJ Craft, N Economou, JS Marincola, FM Wang, E Ribas, A AF Vo, Dan D. Prins, Robert M. Begley, Jonathan L. Donahue, Timothy R. Morris, Lilah F. Bruhn, Kevin W. de la Rocha, Pilar Yang, Meng-Yin Mok, Stephen Garban, Hermes J. Craft, Noah Economou, James S. Marincola, Francesco M. Wang, Ena Ribas, Antoni TI Enhanced Antitumor Activity Induced by Adoptive T-Cell Transfer and Adjunctive Use of the Histone Deacetylase Inhibitor LAQ824 SO CANCER RESEARCH LA English DT Article ID MYELOID-LEUKEMIA CELLS; MHC CLASS-I; LISTERIA-MONOCYTOGENES VACCINE; SUBERIC BISHYDROXAMATE; DENDRITIC CELLS; MELANOMA-CELLS; EXPRESSION; MODULATION; NVP-LAQ824; APOPTOSIS AB Tumors grow in the presence of antigen-specific T cells, suggesting the existence of intrinsic cancer cell escape mechanisms. We hypothesized that a histone deacetylase (HDAC) inhibitor could sensitize tumor cells to immunotherapy because this class of agents has been reported to increase tumor antigen expression and shift gene expression to a proapoptotic milieu in cancer cells. To test this question, we treated 1116 murine melanoma with the combination of the HDAC inhibitor LAQ824 and the adoptive transfer of gp100 melanoma antigen-specific pmel-1 T cells. The combined therapy significantly improved antitumor activity through several mechanisms: (a) increase in MHC and tumor-associated antigen expression by tumor cells; (b) decrease in competing endogenous lymphocytes in recipient mice, resulting in a proliferative advantage for the adoptively transferred cells; and (c) improvement in the functional activity of the adoptively transferred lymphocytes. We confirmed the beneficial effects of this HDAC inhibitor as a sensitizer to immunotherapy in a different model of prophylactic prime-boost vaccination with the melanoma antigen tyrosinase-related protein 2, which also showed a significant improvement in antitumor activity against B16 melanoma. In conclusion, the HDAC inhibitor LAQ824 significantly enhances tumor immunotherapy through effects on target tumor cells as well as improving the antitumor activity of tumor antigen-specific lymphocytes. [Cancer Res 2009;69(22):8693-9] C1 [Ribas, Antoni] Univ Calif Los Angeles, Dept Med, Div Hematol Oncol, Med Ctr, Los Angeles, CA 90095 USA. [Vo, Dan D.; Donahue, Timothy R.; Morris, Lilah F.; de la Rocha, Pilar; Mok, Stephen; Garban, Hermes J.; Economou, James S.; Ribas, Antoni] Univ Calif Los Angeles, Dept Surg, Div Surg Oncol, Los Angeles, CA 90095 USA. [Prins, Robert M.; Yang, Meng-Yin] Univ Calif Los Angeles, Dept Neurosurg, Los Angeles, CA 90095 USA. [Prins, Robert M.; Economou, James S.; Ribas, Antoni] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Bruhn, Kevin W.; Craft, Noah] Harbor UCLA Med Ctr, Dept Med, Div Dermatol, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. [Marincola, Francesco M.; Wang, Ena] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Ribas, A (reprint author), Univ Calif Los Angeles, Dept Med, Div Hematol Oncol, Med Ctr, 11-934 Factor Bldg,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM aribas@mednet.ucla.edu RI Bruhn, Kevin/F-9772-2013; OI Garban, Hermes/0000-0001-7754-5357; Prins, Robert/0000-0002-6282-6583 FU Harry J. Hoyd Charitable Trust; Waxman Foundation; W.M. Keck Foundation; Monkarsh land; NIH [CAI6042]; [P50 CA086306] FX Harry J. Hoyd Charitable Trust, P50 CA086306, Waxman Foundation. W.M. Keck Foundation, and Monkarsh land. Flow cytometry was done at the University of California-Los Angeles Jonsson Comprehensive Cancer Center Core Facility, which is supported by the NIH award CAI6042. NR 38 TC 56 Z9 57 U1 0 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 2009 VL 69 IS 22 BP 8693 EP 8699 DI 10.1158/0008-5472.CAN-09-1456 PG 7 WC Oncology SC Oncology GA 520JC UT WOS:000271839200022 PM 19861533 ER PT J AU Espey, MG Chen, Q Levine, M AF Espey, Michael Graham Chen, Qi Levine, Mark TI Comment re: Vitamin C Antagonizes the Cytotoxic Effects of Chemotherapy SO CANCER RESEARCH LA English DT Letter ID DEHYDROASCORBIC ACID C1 [Espey, Michael Graham; Chen, Qi; Levine, Mark] NIDDK, Mol & Clin Nutr Sect, NIH, Bethesda, MD 20892 USA. RP Espey, MG (reprint author), NIDDK, Mol & Clin Nutr Sect, NIH, Bethesda, MD 20892 USA. RI Chen, Qi/D-8278-2015 OI Chen, Qi/0000-0002-7173-8411 NR 8 TC 5 Z9 5 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2009 VL 69 IS 22 BP 8830 EP 8830 DI 10.1158/0008-5472.CAN-08-3798 PG 1 WC Oncology SC Oncology GA 520JC UT WOS:000271839200039 PM 19843868 ER PT J AU Figueroa, A Fujita, Y Gorospe, M AF Figueroa, Angelica Fujita, Yasuyuki Gorospe, Myriam TI Hacking RNA Hakai promotes tumorigenesis by enhancing the RNA-binding function of PSF SO CELL CYCLE LA English DT Article DE E-cadherin; PSF; PTB-associated splicing factor; proliferation; tumor progression; RNA binding protein; oncogene ID RENAL-CELL CARCINOMA; E-CADHERIN; SPLICING FACTOR; MESSENGER-RNA; PROTEIN; IDENTIFICATION; P54(NRB)/NONO; TRANSCRIPTION; LOCALIZATION; ONCOPROTEIN AB Hakai, an E3 ubiquitin ligase for the E-cadherin complex, plays a crucial role in lowering cell-cell contacts in epithelial cells, a hallmark feature of tumor progression. Recently, Hakai was also found to interact with PSF (PTB-associated splicing factor). While PSF can function as a DNA-binding protein with a tumor suppressive function, its association with Hakai promotes PSF's RNA-binding ability and post-transcriptional influence on target mRNAs. Hakai overexpression enhanced the binding of PSF to mRNAs encoding cancer-related proteins, while knockdown of Hakai reduced the RNA-binding ability of PSF. Furthermore, the knockdown of PSF suppressed Hakai-induced cell proliferation. Thus, Hakai can affect the oncogenic phenotype both by altering E-cadherin-based intercellular adhesions and by increasing PSF's ability to bind RNAs that promote cancer-related gene expression. C1 [Figueroa, Angelica] Univ A Coruna, Inst Invest Biomed A Coruna, Complejo Hosp, La Coruna, Spain. [Fujita, Yasuyuki] UCL, MRC Lab Mol Cell Biol, London, England. [Fujita, Yasuyuki] UCL, Cell Biol Unit, London, England. [Fujita, Yasuyuki] UCL, Dept Cell & Dev Biol, London, England. [Gorospe, Myriam] NIA, LCMB, NIH, Baltimore, MD 21224 USA. RP Figueroa, A (reprint author), Univ A Coruna, Inst Invest Biomed A Coruna, Complejo Hosp, La Coruna, Spain. EM angelica.figueroa.conde-valvis@sergas.es RI Fujita, Yasuyuki/A-4324-2012 FU Secretaria Xeral I+D+I, Xunta de Galicia, Spain; NIA-IRP, NIH FX A. F. is supported by Parga Pondal Program, Secretaria Xeral I+D+I, Xunta de Galicia, Spain. Y. F. is supported by MRC funding to the Cell Biology Unit. M. G. is supported by the NIA-IRP, NIH. NR 31 TC 12 Z9 12 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD NOV 15 PY 2009 VL 8 IS 22 BP 3648 EP 3651 PG 4 WC Cell Biology SC Cell Biology GA 525MB UT WOS:000272219000017 PM 19855157 ER PT J AU Lopez-Otin, C Palavalli, LH Samuels, Y AF Lopez-Otin, Carlos Palavalli, Lavanya H. Samuels, Yardena TI Protective roles of matrix metalloproteinases From mouse models to human cancer SO CELL CYCLE LA English DT Article DE matrix metalloproteinases; MMP-8; tumor suppressor gene; mouse model; somatic mutation ID HUMAN BREAST; TUMOR; GENE; PROGRESSION; SUPPRESSOR; THERAPY; IDENTIFICATION; CHROMOSOME; ESOPHAGEAL; REVEALS AB Matrix metalloproteinases (MMPs) have long been linked to cancer progression owing to their ability to breakdown tissue barriers for metastatic spread. Accordingly, multiple studies have examined the potential value of these enzymes as targets for cancer therapy. Unfortunately, most clinical trials with MMP inhibitors have yielded negative results which has made necessary to re-evaluate the role of these proteases in cancer. Recent works mainly based on the use of mouse models deficient in specific MMPs have revealed that these enzymes play many roles in cancer distinct from matrix destruction, influencing early steps of tumor evolution, and expanding their pro-tumorigenic properties. However, these in vivo studies have also shown that, unexpectedly, some MMP family members like MMP8 may have paradoxical anti-tumor functions. Nevertheless, the final validation of these MMPs as bona fide tumor suppressors requested the identification of the putative genetic or epigenetic changes underlying their inactivation during cancer development. To this purpose, very recent large-scale genomic studies have explored the possibility that MMPs could be genetically altered in a panel of human malignant tumors from different sources. These studies have demonstrated that MMP8 is a frequently mutated gene in human melanoma. Functional analysis of the identified mutations has confirmed that all of them lead to the loss-of-function of MMP8 and enhance the progression of melanoma, thus providing definitive evidence that MMP8 is a tumor-suppressor gene. Parallel studies have extended these findings to other MMP-related metalloproteinases such as ADAMTS15, which has been found to be genetically inactivated in human colorectal cancer. This review describes the identification and validation of some MMPs and related enzymes as anti-tumor proteases and speculates about the molecular mechanisms underlying their protective roles in tumor development. Finally, the review explores the clinical applications derived from the identification of MMPs that favour the host instead of the tumor. C1 [Palavalli, Lavanya H.; Samuels, Yardena] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Lopez-Otin, Carlos] Univ Oviedo, Inst Univ Oncol, Dept Bioquim & Biol Mol, Fac Med, Oviedo, Spain. RP Samuels, Y (reprint author), NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. EM samuelsy@mail.nih.gov RI Lopez-Otin, Carlos/C-6657-2013 OI Lopez-Otin, Carlos/0000-0001-6964-1904 FU Ministerio de Ciencia e Innovacion-Spain, Fundacion; European Union FP7-MicroEnviMet; National Human Genome Research Institute; National Institutes of Health FX This work was supported by grants from Ministerio de Ciencia e Innovacion-Spain, Fundacion "M. Botin", the European Union FP7-MicroEnviMet (to C.L.-O.) and the Intramural Research Programs of the National Human Genome Research Institute, National Institutes of Health, USA (to Y. S.). NR 38 TC 51 Z9 51 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD NOV 15 PY 2009 VL 8 IS 22 BP 3657 EP 3662 PG 6 WC Cell Biology SC Cell Biology GA 525MB UT WOS:000272219000019 PM 19844170 ER PT J AU Jian, BX Nagineni, CN Meleth, S Grizzle, W Bland, K Chaudry, I Raju, R AF Jian, Bixi Nagineni, Chandrasekharam N. Meleth, Sreelatha Grizzle, William Bland, Kirby Chaudry, Irshad Raju, Raghavan TI Anosmin-1 involved in neuronal cell migration is hypoxia inducible and cancer regulated SO CELL CYCLE LA English DT Article DE HIF-1 alpha; anosmin; hypogonadism; colon cancer; apoptosis; tumor; metastasis; anosmia ID GROWTH-FACTOR-BETA; KALLMANN-SYNDROME; ENDOPLASMIC-RETICULUM; GENE-EXPRESSION; HYDROXYLATION; ACTIVATION; FIBROSIS; ADHESION; PATHWAY; TWIST AB Functional expression of KAL1 gene is critical in the migration of GnRH neurons from the olfactory placode to the hypothalamus in embryogenesis. This gene thus far has not been shown to play a functional role in any other physiological or pathological process either in the developed brain or in peripheral tissues. We show here that KAL1 gene expression is decreased in early stage and increased in later stages of cancers. Screening of colon, lung and ovarian cancer cDNA panels indicated significant decrease in KAL1 expression in comparison to corresponding uninvolved tissues. However, KAL1 expression increased with the progression of cancer from early (I and II) stages to later (III and IV) stages of the cancer. There was a direct correlation between the TGF beta and KAL1 expression in colon cancer cDNA. Using colon cancer cell lines, we showed that TGF beta induces KAL1 gene expression and secretion of anosmin-1 protein (KAL1 coded protein). We further report that hypoxia induces anosmin-1 expression; anosmin-1 protects cancer cells from apoptosis activated by hypoxia and increases cancer cell mobility. Using siRNA technique we found that KAL1 expression following hypoxia is hypoxia-inducible factor (HIF-1)alpha dependent. Our results suggest that KAL1 gene expression plays an important role in cancer metastasis and protection from apoptosis. C1 [Jian, Bixi; Bland, Kirby; Chaudry, Irshad; Raju, Raghavan] Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. [Meleth, Sreelatha] Univ Alabama, Comprehens Canc Ctr Biostat, Birmingham, AL 35294 USA. [Grizzle, William] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. [Chaudry, Irshad; Raju, Raghavan] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. [Nagineni, Chandrasekharam N.] NEI, NIH, Bethesda, MD 20892 USA. RP Raju, R (reprint author), Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. EM RRaju@uab.edu RI Raju, Raghavan/E-9219-2011 FU HSF-GEF Scholar Award FX This work was supported by the HSF-GEF Scholar Award. NR 30 TC 15 Z9 15 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD NOV 15 PY 2009 VL 8 IS 22 BP 3770 EP 3776 PG 7 WC Cell Biology SC Cell Biology GA 525MB UT WOS:000272219000034 PM 19844165 ER PT J AU Mai, W Kawakami, K Shakoori, A Kyo, S Miyashita, K Yokoi, K Jin, MJ Shimasaki, T Motoo, Y Minamoto, T AF Mai, Wei Kawakami, Kazuyuki Shakoori, Abbas Kyo, Satoru Miyashita, Katsuyoshi Yokoi, Kenji Jin, Mingji Shimasaki, Takeo Motoo, Yoshiharu Minamoto, Toshinari TI Deregulated GSK3 beta Sustains Gastrointestinal Cancer Cells Survival by Modulating Human Telomerase Reverse Transcriptase and Telomerase SO CLINICAL CANCER RESEARCH LA English DT Article ID GLYCOGEN-SYNTHASE KINASE-3-BETA; HUMAN COLON-CANCER; COLORECTAL-CANCER; CELLULAR SENESCENCE; GENE-TRANSCRIPTION; ONCOGENE ADDICTION; PANCREATIC-CANCER; GASTRIC-CANCER; BETA-CATENIN; KAPPA-B AB Purpose: Glycogen synthase kinase-3 beta (GSK3 beta) regulates multiple cell signaling pathways and has been implicated in glucose intolerance, neurodegenerative disorders, and inflammation. We investigated the expression, activity, and putative pathologic role of GSK3 beta in gastrointestinal, pancreatic, and liver cancers. Experimental Design: Colon, stomach, pancreatic, and liver cancer cell lines; nonneoplastic HEK293 cells; and matched pairs of normal and tumor tissues of stomach and colon cancer patients were examined for GSK3 beta expression and its phosphorylation at serine 9 (inactive form) and tyrosine 216 (active form) by Western immunoblotting and for GSK3 beta activity by in vitro kinase assay. The effects of small-molecule GSK3 beta inhibitors and of RNA interference on cell survival, proliferation, and apoptosis were examined in vitro and on human colon cancer cell xenografts in athymic mice. The effects of GSK3 beta inhibition on human telomerase reverse transcriptase (hTERT) expression and telomerase activity were compared between colon cancer and HEK293 cells. Results: Cancer cell lines and most cancer tissues showed increased GSK3 beta expression and increased tyrosine 216 phosphorylation and activity but decreased serine 9 phosphorylation compared with HEK293 cells and nonneoplastic tissues. Inhibition of GSK3 beta resulted in attenuated cell survival and proliferation and increased apoptosis in most cancer cell lines and in HT-29 xenografts in rodents but not in HEK293 cells. GSK3 beta inhibition in colon cancer cells was associated with decreased hTERT expression and telomerase activity. Conclusion: The results indicate that deregulated GSK3 beta sustains gastrointestinal cancer cells survival through modulation of hTERT and telomerase. (Clin Cancer Res 2009;15(22):6810-19) C1 [Minamoto, Toshinari] Kanazawa Univ, Canc Res Inst, Div Translat & Clin Oncol, Kanazawa, Ishikawa 9200934, Japan. [Kyo, Satoru] Kanazawa Univ, Dept Obstet & Gynecol, Grad Sch Med Sci, Kanazawa, Ishikawa 9200934, Japan. [Miyashita, Katsuyoshi] Kanazawa Univ, Dept Neurosurg, Grad Sch Med Sci, Kanazawa, Ishikawa 9200934, Japan. [Yokoi, Kenji] Kanazawa Univ, Dept Cardiothorac & Gen Surg, Grad Sch Med Sci, Kanazawa, Ishikawa 9200934, Japan. [Shakoori, Abbas] NCI, Sect Canc Genom, NIH, Bethesda, MD 20892 USA. [Shimasaki, Takeo; Motoo, Yoshiharu] Kanazawa Med Univ, Dept Med Oncol, Uchinada, Ishikawa 92002, Japan. [Yokoi, Kenji] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA. RP Minamoto, T (reprint author), Kanazawa Univ, Canc Res Inst, Div Translat & Clin Oncol, 13-1 Takara Machi, Kanazawa, Ishikawa 9200934, Japan. EM minamoto@staff.kanazawa-u.ac.jp RI Yokoi, Kenji/J-1216-2014 FU Japanese Ministry of Education, Science, Sports, Technology and Culture; Ministry of Health, Labour and Welfare; Japan Society for the Promotion of Science FX Supported in part by Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Science, Sports, Technology and Culture; from the Ministry of Health, Labour and Welfare; and from the Japan Society for the Promotion of Science. NR 51 TC 45 Z9 46 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 2009 VL 15 IS 22 BP 6810 EP 6819 DI 10.1158/1078-0432.CCR-09-0973 PG 10 WC Oncology SC Oncology GA 520EJ UT WOS:000271822600010 PM 19903789 ER PT J AU Hong, DS Sebti, SM Newman, RA Blaskovich, MA Ye, L Gagel, RF Moulder, S Wheler, JJ Naing, A Tannir, NM Ng, CS Sherman, SI El Naggar, AK Khan, R Trent, J Wright, JJ Kurzrock, R AF Hong, David S. Sebti, Said M. Newman, Robert A. Blaskovich, Michelle A. Ye, Lei Gagel, Robert F. Moulder, Stacy Wheler, Jennifer J. Naing, Aung Tannir, Nizar M. Ng, Chaan S. Sherman, Steven I. El Naggar, Adel K. Khan, Rabia Trent, Jon Wright, John J. Kurzrock, Razelle TI Phase I Trial of a Combination of the Multikinase Inhibitor Sorafenib and the Farnesyltransferase Inhibitor Tipifarnib in Advanced Malignancies SO CLINICAL CANCER RESEARCH LA English DT Article ID RENAL-CELL CARCINOMA; FARNESYL TRANSFERASE INHIBITORS; THYROID-CANCER; MYELODYSPLASTIC SYNDROME; KINASE INHIBITOR; SOLID TUMORS; R115777; THERAPY; TARGET AB Purpose: We evaluated the safety, maximum tolerated dose, pharmacokinetics, and biological effects of the combination of the Raf-1, RET, KIT, platelet-derived growth factor receptor, and vascular endothelial growth factor receptor 2 kinase inhibitor sorafenib and the farnesyltransferase inhibitor tipifarnib. Experimental Design: A standard 3 + 3 phase I dose-escalation design was used with a 28-day cycle (sorafenib daily and tipifarnib for 21 days, by mouth). Results: Fifty patients were treated; 43 reached restaging evaluation after cycle 2. The most common side effects were grade 1 to 2 rash, hyperglycemia, and diarrhea. Dose-limiting toxicity was rash, and the recommended phase 11 dose is sorafenib 400 mg p.o. qam/200 mg p.o. qpm and tipifarnib p.o. 100 mg bd. Despite the low doses of tipifarnib, one quarter of patients had >= 50% reduction in farnesyltransferase levels. Interestingly, six of eight patients with medullary thyroid cancer had durable stable disease (n = 3) or partial remissions (n = 3), lasting 12 to 26+ months. Five of the six responders had available tissue, and RET gene mutations were identified in them. Prolonged (>= 6 months) stable disease was also seen in nine patients as follows: papillary thyroid cancer (n = 4; 18+ to 27+ months), adrenocortical cancer (n = 2; 7 and 11 months), and one each of melanoma (platelet-derived growth factor receptor mutation positive; 14 months), renal (6 months), and pancreatic cancer (6 months). Conclusions: Our study shows that the combination of tipifarnib and sorafenib is well tolerated. Activity was seen, especially in patients with medullary thyroid cancer, a tumor characterized by RET mutations. (Clin Cancer Res 2009;15(22):7061-8) C1 [Hong, David S.; Wheler, Jennifer J.; Naing, Aung; Khan, Rabia; Kurzrock, Razelle] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Invest Canc Therapeut, Phase Clin Trials Program 1, Houston, TX 77030 USA. [Newman, Robert A.] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Expt Canc Therapeut, Houston, TX 77030 USA. [Ye, Lei; Gagel, Robert F.; Sherman, Steven I.] Univ Texas MD Anderson Canc Ctr, Div Internal Med, Dept Endocrine Neoplasia & Hormonal Disorders, Houston, TX 77030 USA. [Moulder, Stacy] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Breast Med Oncol, Houston, TX 77030 USA. [Tannir, Nizar M.] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept GU Med Oncol, Houston, TX 77030 USA. [Ng, Chaan S.] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Radiol, Houston, TX 77030 USA. [El Naggar, Adel K.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Trent, Jon] Univ Texas MD Anderson Canc Ctr, Dept Sarcoma, Houston, TX 77030 USA. [Sebti, Said M.; Blaskovich, Michelle A.] Univ S Florida, H Lee Moffitt Canc Ctr & Res Inst, Dept Drug Discovery Program, Tampa, FL USA. [Sebti, Said M.; Blaskovich, Michelle A.] Univ S Florida, Dept Oncol Sci, Tampa, FL USA. [Wright, John J.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Hong, DS (reprint author), Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Invest Therapeut, Phase Program 1, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM dshong@mdanderson.org OI Sherman, Steven/0000-0002-3079-5153 FU NIH [5 U01 CA062461]; Translational Initiative [25XS0688] FX Grant support: NIH grant 5 U01 CA062461 (R. Kurzrock) and Translational Initiative Grant 25XS0688 (D.S. Hong). NR 30 TC 53 Z9 54 U1 0 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 2009 VL 15 IS 22 BP 7061 EP 7068 DI 10.1158/1078-0432.CCR-09-1241 PG 8 WC Oncology SC Oncology GA 520EJ UT WOS:000271822600038 PM 19903778 ER PT J AU Deeks, SG Gange, SJ Kitahata, MM Saag, MS Justice, AC Hogg, RS Eron, JJ Brooks, JT Rourke, SB Gill, MJ Bosch, RJ Benson, CA Collier, AC Martin, JN Klein, MB Jacobson, LP Rodriguez, B Sterling, TR Kirk, GD Napravnik, S Rachlis, AR Calzavara, LM Horberg, MA Silverberg, MJ Gebo, KA Kushel, MB Goedert, JJ McKaig, RG Moore, RD AF Deeks, Steven G. Gange, Stephen J. Kitahata, Mari M. Saag, Michael S. Justice, Amy C. Hogg, Robert S. Eron, Joseph J. Brooks, John T. Rourke, Sean B. Gill, M. John Bosch, Ronald J. Benson, Constance A. Collier, Ann C. Martin, Jeffrey N. Klein, Marina B. Jacobson, Lisa P. Rodriguez, Benigno Sterling, Timothy R. Kirk, Gregory D. Napravnik, Sonia Rachlis, Anita R. Calzavara, Liviana M. Horberg, Michael A. Silverberg, Michael J. Gebo, Kelly A. Kushel, Margot B. Goedert, James J. McKaig, Rosemary G. Moore, Richard D. CA N Amer AIDS Cohort Collaboration R TI Trends in Multidrug Treatment Failure and Subsequent Mortality among Antiretroviral Therapy-Experienced Patients with HIV Infection in North America SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; VIROLOGICAL FAILURE; DRUG-RESISTANCE; HIV-1-INFECTED PATIENTS; RISK; COHORT; PROGRESSION; PREVALENCE; PREDICTORS; INHIBITORS AB Background. Although combination antiretroviral therapy continues to evolve, with potentially more effective options emerging each year, the ability of therapy to prevent multiple regimen failure and mortality in clinical practice remains poorly defined. Methods. Sixteen cohorts representing over 60 sites contributed data on all individuals who initiated combination antiretroviral therapy. We identified those individuals who experienced virologic failure (defined as a human immunodeficiency virus [HIV] RNA level 11000 copies/mL),received modified therapy, and subsequently had a second episode of virologic failure. Multivariate Cox regression was used to assess factors associated with time to second regimen failure and the time to death after the onset of second regimen failure. Results. Of the 42,790 individuals who received therapy, 7159 experienced a second virologic failure. The risk of second virologic failure decreased from 1996 (56 cases per 100 person-years) through 2005 (16 cases per 100 person-years; P < .001). The cumulative mortality after onset of second virologic failure was 26% at 5 years and decreased over time. A history of AIDS, a lower CD4(+) T cell count, and a higher plasma HIV RNA level were each independently associated with mortality. Similar trends were observed when analysis was limited to the subset of previously treatment-naive patients Conclusions. Although the rates of multiple regimen failure have decreased dramatically over the past decade, mortality rates for those who have experienced failure of at least 2 regimens have remained high. Plasma HIV RNA levels, CD4(+) T cell counts at time of treatment failure, and a history of AIDS remain independent risk factors for death, which emphasizes that these factors remain important targets for those in need of more-aggressive therapeutic interventions. C1 [Deeks, Steven G.; Martin, Jeffrey N.; Kushel, Margot B.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Benson, Constance A.] Univ Calif San Diego, San Diego, CA 92103 USA. [Horberg, Michael A.; Silverberg, Michael J.] Kaiser Permanente No Calif, Oakland, CA USA. [Gange, Stephen J.; Jacobson, Lisa P.; Kirk, Gregory D.; Gebo, Kelly A.; Moore, Richard D.] Johns Hopkins Univ, Baltimore, MD USA. [Goedert, James J.; McKaig, Rosemary G.] NIH, Bethesda, MD 20892 USA. [Kitahata, Mari M.; Collier, Ann C.] Univ Washington, Seattle, WA 98195 USA. [Saag, Michael S.] Univ Alabama, Birmingham, AL USA. [Justice, Amy C.] Yale Univ, New Haven, CT USA. [Eron, Joseph J.; Napravnik, Sonia] Univ N Carolina, Chapel Hill, NC USA. [Brooks, John T.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Bosch, Ronald J.] Harvard Univ, Boston, MA 02115 USA. [Rodriguez, Benigno] Case Western Reserve Univ, Cleveland, OH USA. [Sterling, Timothy R.] Vanderbilt Univ, Nashville, TN USA. [Hogg, Robert S.] Simon Fraser Univ, Vancouver, BC, Canada. [Rourke, Sean B.; Rachlis, Anita R.; Calzavara, Liviana M.] Univ Toronto, Toronto, ON, Canada. [Gill, M. John] Univ Calgary, Calgary, AB, Canada. [Klein, Marina B.] McGill Univ, Montreal, PQ, Canada. RP Deeks, SG (reprint author), San Francisco Gen Hosp, Ward 84,Bldg 80,995 Potrero Ave, San Francisco, CA 94110 USA. EM sdeeks@php.ucsf.edu RI Hogg, Robert/B-2783-2012; Rodriguez, Benigno/C-3365-2009; Gill, John/G-7083-2016; OI Rodriguez, Benigno/0000-0001-9736-7957; Gill, John/0000-0002-8546-8790; Gange, Stephen/0000-0001-7842-512X; Hogg, Robert/0000-0003-3463-5488 FU NCI NIH HHS [N02CP55504, Z01 CP010176]; NCRR NIH HHS [M01 RR000071, M01 RR000079, M01 RR000083, M01 RR000722, M01-RR00071, M01-RR00079, M01-RR00083]; NIAAA NIH HHS [R01 AA016893, R01-AA16893, U01 AA013566, U01-AA013566]; NIAID NIH HHS [AI-69432, K01 AI071754, K01-AI071754, K23-AI-61-0320, P30 AI027757, P30 AI027767, P30 AI050410, P30 AI054999, P30-AI27757, P30-AI27767, P30-AI50410, P30-AI54999, R24 AI067039, R24-AI067039, U01 AI031834, U01 AI034989, U01 AI034993, U01 AI034994, U01 AI035004, U01 AI035039, U01 AI035040, U01 AI035041, U01 AI035042, U01 AI035043, U01 AI037613, U01 AI037984, U01 AI038855, U01 AI038858, U01 AI042590, U01 AI068634, U01 AI068636, U01 AI069432, U01 AI069918, U01 AI069918-01, U01-AI069918, U01-AI31834, U01-AI34989, U01-AI34993, U01-AI34994, U01-AI35004, U01-AI35039, U01-AI35040, U01-AI35041, U01-AI35042, U01-AI35043, U01-AI37613, U01-AI37984, U01-AI38855, U01-AI38858, U01-AI42590, U01-AI68634, U01-AI68636, UM1 AI069432]; NICHD NIH HHS [U01 HD032632, U01-HD32632]; NIDA NIH HHS [R01-DA11602, R01 DA004334, R01 DA011602, R01 DA012568, R01-DA04334, R01-DA12568, R56 DA004334]; NIMH NIH HHS [R01 MH054907, R01-MH54907]; PHS HHS [AHQ290-01-0012, K24-00432] NR 28 TC 28 Z9 28 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV 15 PY 2009 VL 49 IS 10 BP 1582 EP 1590 DI 10.1086/644768 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 511EH UT WOS:000271146200021 PM 19845473 ER PT J AU Rajagopal, R Huang, J Dattilo, LK Kaartinen, V Mishina, Y Deng, CX Umans, L Zwijsen, A Roberts, AB Beebe, DC AF Rajagopal, Ramya Huang, Jie Dattilo, Lisa K. Kaartinen, Vesa Mishina, Yuji Deng, Chu-Xia Umans, Lieve Zwijsen, An Roberts, Anita B. Beebe, David C. TI The type I BMP receptors, Bmpr1a and Acvr1, activate multiple signaling pathways to regulate lens formation SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Lens formation; Bone morphogenetic proteins; Smads ID EARLY MOUSE EMBRYO; CONDITIONAL KNOCKOUT; PRESUMPTIVE LENS; CHICK-EMBRYO; DEFECTS; PROLIFERATION; INDUCTION; CELLS; MICE; EYE AB BMPs play multiple roles in development and BMP signaling is essential for lens formation. However, the mechanisms by which BMP receptors function in vertebrate development are incompletely understood. To determine the downstream effectors of BMP signaling and their functions in the ectoderm that will form the lens, we deleted the genes encoding the type 1 BMP receptors. Bmpr1a and Acvr1, and the canonical transducers of BMP signaling, Smad4, Smad1 and Smad5. Bmpr1a and Acvr1 regulated cell survival and proliferation, respectively. Absence of both receptors interfered with the expression of proteins involved in normal lens development and prevented lens formation, demonstrating that BMPs induce lens formation by acting directly on the prospective lens ectoderm. Remarkably, the canonical Smad signaling pathway was not needed for most of these processes. Lens formation, placode cell proliferation, the expression of FoxE3, a lens-specific transcription factor, and the lens protein, alpha A-crystallin were regulated by BMP receptors in a Smad-independent manner. Placode cell survival was promoted by R-Smad signaling, but in a manner that did not involve Smad4. Of the responses tested, only maintaining a high level of Sox2 protein, a transcription factor expressed early in placode formation, required the canonical Smad pathway. A key function of Smad-independent BMP receptor signaling may be reorganization of actin cytoskeleton to drive lens invagination. (C) 2009 Elsevier Inc. All rights reserved. C1 [Kaartinen, Vesa] Univ So Calif, Childrens Hosp Los Angeles, Keck Sch Med, Dev Biol Program,Dept Pathol & Surg, Los Angeles, CA 90027 USA. [Mishina, Yuji] Natl Inst Environm Hlth Sci, Lab Reprod & Dev Toxicol, Mol Dev Biol Grp, Res Triangle Pk, NC USA. [Deng, Chu-Xia] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD USA. [Umans, Lieve; Zwijsen, An] VIB, Dept Mol & Dev Genet, Lab Mol Biol Celgen, Louvain, Belgium. [Umans, Lieve; Zwijsen, An] Katholieke Univ Leuven, Ctr Human Genet, Lab Mol Biol Celgen, Louvain, Belgium. [Roberts, Anita B.] NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. [Rajagopal, Ramya; Huang, Jie; Dattilo, Lisa K.; Beebe, David C.] Washington Univ, Dept Ophthalmol, St Louis, MO 63110 USA. [Rajagopal, Ramya; Huang, Jie; Dattilo, Lisa K.; Beebe, David C.] Washington Univ, Dept Visual Sci, St Louis, MO 63110 USA. RP Beebe, DC (reprint author), Washington Univ, Dept Ophthalmol & Visual Sci, 660 S Euclid Ave,Campus Box 8096,Rm 101 McMillan, St Louis, MO 63110 USA. EM beebe@wustl.edu RI Huang, Jie/D-7728-2014; deng, chuxia/N-6713-2016; OI Kaartinen, Vesa/0000-0002-9432-510X FU Research to Prevent Blindness; NIH [EY02687, EY04853, 5R01HL074862, 5R01DE013085] FX We thank Drs. Ruth Ashery-Padan and Judy West-Mays for providing the Le-Cre mice and are grateful for the expert technical assistance of Chenghua Wu and Mary Feldmeier with genotyping and Belinda McMahan and Jean Jones with histology and immunohistochemistry. We are indebted to Drs. Jeffrey Miner and Peter Carlsson for the laminin and FoxE3 antibodies, respectively. This work was supported by an unrestricted grant from Research to Prevent Blindness and NIH Core Grant EY02687 to the Department of Ophthalmology and Visual Sciences, NIH grant EY04853 to DCB and 5R01HL074862 and 5R01DE013085 to VK. Drs. Lieve Umans and An Zwijsen are indebted to Dr. Danny Huylebroeck for his support of their work. NR 44 TC 49 Z9 51 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 2009 VL 335 IS 2 BP 305 EP 316 DI 10.1016/j.ydbio.2009.08.027 PG 12 WC Developmental Biology SC Developmental Biology GA 517GJ UT WOS:000271601000002 PM 19733164 ER PT J AU Xie, JC Sun, BG Wang, SB Ito, Y AF Xie, Jianchun Sun, Baoguo Wang, Shuaibin Ito, Yoichiro TI Isolation and purification of nootkatone from the essential oil of fruits of Alpinia oxyphylla Miquel by high-speed counter-current chromatography SO FOOD CHEMISTRY LA English DT Article DE Counter-current chromatography; Alpinia oxyphylla Miquel; Sesquiterpenoid; Nootkatone; Flavor; Bioactive component ID PREPARATIVE ISOLATION; SEPARATION AB HSCCC technique in a semi-preparative scale was successfully applied in isolation and purification of nootkatone from the essential oil of fruits of Alpinia oxyphylla Miquel. Twelve kinds of two-phase solvent systems. consisting of seven non-aqueous and five organic-aqueous solvent systems, were selected with not only suitable partition coefficients of nootkatone but also suitable separation factors between nootkatone and valencene, the dominant impurity in the essential oil. Further on HSCCC, n-hexane-chloroform-acetonitrile (10:1:10, v/v) amongst the non-aqueous solvent systems and n-hexane-methanol-water (5:4:1, v/v) amongst the organic-aqueous solvent systems were separately screened out. However, n-hexane-methanol-water (5:4:1, v/v) was thought optimal due to quite shorter elution time and better HSCCC peak form. By eluting the lower phase of this solvent system in head-tail mode, 3.1 mg of nootkatone was obtained at a purity of 92.30% by GC-MS from 80 mg of crude essential oil in one step operation in less than 4 h. The chemical structure of nootkatone fraction was confirmed by EI-MS and (1)H NMR. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Xie, Jianchun; Sun, Baoguo; Wang, Shuaibin] Beijing Technol & Business Univ, Sch Chem & Environm Engn, Beijing 100048, Peoples R China. [Ito, Yoichiro] NHLBI, Bioseparat Technol Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. RP Xie, JC (reprint author), Beijing Technol & Business Univ, Sch Chem & Environm Engn, Beijing 100048, Peoples R China. EM xjchun@th.btbu.edu.cn FU Beijing Municipal Talent Development Organization [20051D0500310]; National Natural Science Foundation of China [NSFC20676003] FX The present work was supported by Beijing Municipal Talent Development Organization (No. 20051D0500310) and National Natural Science Foundation of China (NSFC20676003). NR 16 TC 20 Z9 22 U1 2 U2 23 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0308-8146 J9 FOOD CHEM JI Food Chem. PD NOV 15 PY 2009 VL 117 IS 2 BP 375 EP 380 DI 10.1016/j.foodchem.2009.04.011 PG 6 WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics SC Chemistry; Food Science & Technology; Nutrition & Dietetics GA 465RP UT WOS:000267604800031 PM 20209043 ER PT J AU Qian, L Hu, XM Zhang, D Snyder, A Wu, HM Li, YC Wilson, B Lu, RB Hong, JS Flood, PM AF Qian, Li Hu, Xiaoming Zhang, Dan Snyder, Amanda Wu, Hung-Ming Li, Yachen Wilson, Belinda Lu, Ru-Band Hong, Jau-Shyong Flood, Patrick M. TI beta 2 Adrenergic Receptor Activation Induces Microglial NADPH Oxidase Activation and Dopaminergic Neurotoxicity Through an ERK-Dependent/Protein Kinase A-Independent Pathway SO GLIA LA English DT Article DE beta 2AR; oxidative stress; neuroinflammation ID LIPOPOLYSACCHARIDE-INDUCED NEUROTOXICITY; BETA-ADRENERGIC AGONISTS; TUMOR-NECROSIS-FACTOR; BETA(2)-ADRENERGIC RECEPTOR; PARKINSONS-DISEASE; PROTEIN-KINASE; RESPIRATORY BURST; TETRAZOLIUM SALT; RAT-BRAIN; CELLS AB Activation of the beta 2 adrenergic receptor (beta 2AR) on immune cells has been reported to possess anti-inflammatory properties, however, the pro-inflammatory properties of beta 2AR activation remain unclear. In this study, using rat primary mesencephalic neuron-glia cultures, we report that salmeterol, a long-acting beta 2AR agonist, selectively induces dopaminergic (DA) neurotoxicity through its ability to activate microglia. Salmeterol selectively increased the production of reactive oxygen species (ROS) by NADPH oxidase (PHOX), the major superoxide-producing enzyme in microglia. A key role of PHOX in mediating salmeterol-induced neurotoxicity was demonstrated by the inhibition of DA neurotoxicity in cultures pretreated with diphenylene-iodonium (DPI), an inhibitor of PHOX activity. Mechanistic studies revealed the activation of microglia by salmeterol results in the selective phosphorylation of ERK, a signaling pathway required for the translocation of the PHOX cytosolic subunit p47(phox) to the cell membrane. Furthermore, we found ERK inhibition, but not protein kinase A (PKA) inhibition, significantly abolished salmeterol-induced superoxide production, p47(phox) translocation, and its ability to mediate neurotoxicity. Together, these findings indicate that beta 2AR activation induces microglial PHOX activation and DA neurotoxicity through an ERK-dependent/PKA-independent pathway. (C) 2009 Wiley-Liss, Inc. C1 [Qian, Li; Snyder, Amanda; Flood, Patrick M.] Univ N Carolina, Comprehens Ctr Inflammatory Disorders, Chapel Hill, NC 27599 USA. [Qian, Li; Hu, Xiaoming; Zhang, Dan; Wu, Hung-Ming; Li, Yachen; Wilson, Belinda; Hong, Jau-Shyong] NIEHS, Neuropharmacol Sect, Pharmacol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Wu, Hung-Ming; Lu, Ru-Band] Natl Cheng Kung Univ, Coll Med, Inst Behav Med, Tainan 70101, Taiwan. [Wu, Hung-Ming; Lu, Ru-Band] Natl Cheng Kung Univ, Coll Med, Dept Psychiat, Tainan 70101, Taiwan. RP Flood, PM (reprint author), Univ N Carolina, Comprehens Ctr Inflammatory Disorders, Chapel Hill, NC 27599 USA. EM pat_flood@dentistry.unc.edu FU National Institute for Dental and Craniofacial Research [DE-13079]; NIH/NIEHS FX Grant sponsor: National Institute for Dental and Craniofacial Research; Grant number: DE-13079; Grant sponsor: NIH/NIEHS (Intramural Research Program). NR 46 TC 16 Z9 16 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-1491 J9 GLIA JI Glia PD NOV 15 PY 2009 VL 57 IS 15 BP 1600 EP 1609 DI 10.1002/glia.20873 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 508MG UT WOS:000270934900003 PM 19330844 ER PT J AU Antoniou, AC Sinilnikova, OM McGuffog, L Healey, S Nevanlinna, H Heikkinen, T Simard, J Spurdle, AB Beesley, J Chen, XQ Neuhausen, SL Ding, YC Couch, FJ Wang, XS Fredericksen, Z Peterlongo, P Peissel, B Bonanni, B Viel, A Bernard, L Radice, P Szabo, CI Foretova, L Zikan, M Claes, K Greene, MH Mai, PL Rennert, G Lejbkowicz, F Andrulis, IL Ozcelik, H Glendon, G Gerdes, AM Thomassen, M Sunde, L Caligo, MA Laitman, Y Kontorovich, T Cohen, S Kaufman, B Dagan, E Baruch, RG Friedman, E Harbst, K Barbany-Bustinza, G Rantala, J Ehrencrona, H Karlsson, P Domchek, SM Nathanson, KL Osorio, A Blanco, I Lasa, A Benitez, J Hamann, U Hogervorst, FBL Rookus, MA Collee, JM Devilee, P Ligtenberg, MJ van der Luijt, RB Aalfs, CM Waisfisz, Q Wijnen, J van Roozendaal, CEP Peock, S Cook, M Frost, D Oliver, C Platte, R Evans, DG Lalloo, F Eeles, R Izatt, L Davidson, R Chu, C Eccles, D Cole, T Hodgson, S Godwin, AK Stoppa-Lyonnet, D Buecher, B Leone, M Bressac-de Paillerets, B Remenieras, A Caron, O Lenoir, GM Sevenet, N Longy, M Ferrer, SF Prieur, F Goldgar, D Miron, A John, EM Buys, SS Daly, MB Hopper, JL Terry, MB Yassin, Y Singer, C Gschwantler-Kaulich, D Staudigl, C Hansen, TVO Barkardottir, RB Kirchhoff, T Pal, P Kosarin, K Offit, K Piedmonte, M Rodriguez, GC Wakeley, K Boggess, JF Basil, J Schwartz, PE Blank, SV Toland, AE Montagna, M Casella, C Imyanitov, EN Allavena, A Schmutzler, RK Versmold, B Engel, C Meindl, A Ditsch, N Arnold, N Niederacher, D Deissler, H Fiebig, B Suttner, C Schonbuchner, I Gadzicki, D Caldes, T de la Hoya, M Pooley, KA Easton, DF Chenevix-Trench, G AF Antoniou, Antonis C. Sinilnikova, Olga M. McGuffog, Lesley Healey, Sue Nevanlinna, Heli Heikkinen, Tuomas Simard, Jacques Spurdle, Amanda B. Beesley, Jonathan Chen, Xiaoqing Neuhausen, Susan L. Ding, Yuan C. Couch, Fergus J. Wang, Xianshu Fredericksen, Zachary Peterlongo, Paolo Peissel, Bernard Bonanni, Bernardo Viel, Alessandra Bernard, Loris Radice, Paolo Szabo, Csilla I. Foretova, Lenka Zikan, Michal Claes, Kathleen Greene, Mark H. Mai, Phuong L. Rennert, Gad Lejbkowicz, Flavio Andrulis, Irene L. Ozcelik, Hilmi Glendon, Gord Gerdes, Anne-Marie Thomassen, Mads Sunde, Lone Caligo, Maria A. Laitman, Yael Kontorovich, Tair Cohen, Shimrit Kaufman, Bella Dagan, Efrat Baruch, Ruth Gershoni Friedman, Eitan Harbst, Katja Barbany-Bustinza, Gisela Rantala, Johanna Ehrencrona, Hans Karlsson, Per Domchek, Susan M. Nathanson, Katherine L. Osorio, Ana Blanco, Ignacio Lasa, Adriana Benitez, Javier Hamann, Ute Hogervorst, Frans B. L. Rookus, Matti A. Collee, J. Margriet Devilee, Peter Ligtenberg, Marjolijn J. van der Luijt, Rob B. Aalfs, Cora M. Waisfisz, Quinten Wijnen, Juul van Roozendaal, Cornelis E. P. Peock, Susan Cook, Margaret Frost, Debra Oliver, Clare Platte, Radka Evans, D. Gareth Lalloo, Fiona Eeles, Rosalind Izatt, Louise Davidson, Rosemarie Chu, Carol Eccles, Diana Cole, Trevor Hodgson, Shirley Godwin, Andrew K. Stoppa-Lyonnet, Dominique Buecher, Bruno Leone, Melanie Bressac-de Paillerets, Brigitte Remenieras, Audrey Caron, Olivier Lenoir, Gilbert M. Sevenet, Nicolas Longy, Michel Ferrer, Sandra Fert Prieur, Fabienne Goldgar, David Miron, Alexander John, Esther M. Buys, Saundra S. Daly, Mary B. Hopper, John L. Terry, Mary Beth Yassin, Yosuf Singer, Christian Gschwantler-Kaulich, Daphne Staudigl, Christine Hansen, Thomas V. O. Barkardottir, Rosa Bjork Kirchhoff, Tomas Pal, Prodipto Kosarin, Kristi Offit, Kenneth Piedmonte, Marion Rodriguez, Gustavo C. Wakeley, Katie Boggess, John F. Basil, Jack Schwartz, Peter E. Blank, Stephanie V. Toland, Amanda E. Montagna, Marco Casella, Cinzia Imyanitov, Evgeny N. Allavena, Anna Schmutzler, Rita K. Versmold, Beatrix Engel, Christoph Meindl, Alfons Ditsch, Nina Arnold, Norbert Niederacher, Dieter Deissler, Helmut Fiebig, Britta Suttner, Christian Schoenbuchner, Ines Gadzicki, Dorothea Caldes, Trinidad de la Hoya, Miguel Pooley, Karen A. Easton, Douglas F. Chenevix-Trench, Georgia CA Kathleen Cuningham Fdn Consortium OCGN HEBON EMBRACE GEMO Breast Canc Family Registry CIMBA TI Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriers SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; ESTROGEN-RECEPTOR; OVARIAN-CANCER; SUSCEPTIBILITY; GENE; POPULATION; EXPRESSION; ALLELES AB Genome-wide association studies of breast cancer have identified multiple single nucleotide polymorphisms (SNPs) that are associated with increased breast cancer risks in the general population. In a previous study, we demonstrated that the minor alleles at three of these SNPs, in FGFR2, TNRC9 and MAP3K1, also confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. Three additional SNPs rs3817198 at LSP1, rs13387042 at 2q35 and rs13281615 at 8q24 have since been reported to be associated with breast cancer in the general population, and in this study we evaluated their association with breast cancer risk in 9442 BRCA1 and 5665 BRCA2 mutation carriers from 33 study centres. The minor allele of rs3817198 was associated with increased breast cancer risk only for BRCA2 mutation carriers [hazard ratio (HR) = 1.16, 95% CI: 1.07-1.25, P-trend = 2.8 x 10(-4)]. The best fit for the association of SNP rs13387042 at 2q35 with breast cancer risk was a dominant model for both BRCA1 and BRCA2 mutation carriers (BRCA1: HR = 1.14, 95% CI: 1.04-1.25, P = 0.0047; BRCA2: HR = 1.18 95% CI: 1.04-1.33, P = 0.0079). SNP rs13281615 at 8q24 was not associated with breast cancer for either BRCA1 or BRCA2 mutation carriers, but the estimated association for BRCA2 mutation carriers (per-allele HR = 1.06, 95% CI: 0.98-1.14) was consistent with odds ratio estimates derived from population-based case-control studies. The LSP1 and 2q35 SNPs appear to interact multiplicatively on breast cancer risk for BRCA2 mutation carriers. There was no evidence that the associations vary by mutation type depending on whether the mutated protein is predicted to be stable or not. C1 [Antoniou, Antonis C.; McGuffog, Lesley; Peock, Susan; Cook, Margaret; Frost, Debra; Oliver, Clare; Platte, Radka; Pooley, Karen A.; Easton, Douglas F.; EMBRACE] Univ Cambridge, Dept Publ Hlth & Primary Care, Canc Res UK Genet Epidemiol Unit, Cambridge, England. [Sinilnikova, Olga M.; Leone, Melanie] Univ Lyon, CNRS, Hosp Civils Lyon,Ctr Leon Berard,UMR5201, Unite Mixte Genet Constitut Canc Frequents, Lyon, France. [Healey, Sue; Spurdle, Amanda B.; Beesley, Jonathan; Chen, Xiaoqing; Chenevix-Trench, Georgia] Queensland Inst Med Res, Brisbane, Qld 4029, Australia. [Nevanlinna, Heli; Heikkinen, Tuomas] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland. [Simard, Jacques] Univ Laval, Quebec City, PQ, Canada. [Simard, Jacques] Univ Quebec, Ctr Hosp, Canada Res Chair Oncogenet, Canc Genom Lab, Quebec City, PQ, Canada. [Kathleen Cuningham Fdn Consortium] Peter MacCallum Canc Inst, Melbourne, Vic 3002, Australia. [Neuhausen, Susan L.; Ding, Yuan C.] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA. [Couch, Fergus J.; Wang, Xianshu; Fredericksen, Zachary] Mayo Clin, Rochester, MN USA. [Peterlongo, Paolo; Peissel, Bernard; Radice, Paolo] Fdn IRCCS Ist Nazl Tumori, Milan, Italy. [Peterlongo, Paolo; Radice, Paolo] Fdn Ist FIRC Oncol Molecolare, Milan, Italy. [Bonanni, Bernardo; Bernard, Loris] Ist Europeo Oncol, Milan, Italy. [Viel, Alessandra] IRCCS, Ctr Riferimento Oncol, Aviano, Italy. [Bernard, Loris] Cogentech, Consortium Genom Technol, Milan, Italy. [Szabo, Csilla I.] Mayo Clin, Coll Med, Dept Lab Med & Pathol, Rochester, MN USA. [Foretova, Lenka] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic. [Zikan, Michal] Charles Univ Prague, Dept Biochem & Expt Oncol, Fac Med 1, Prague, Czech Republic. [Claes, Kathleen] Ghent Univ Hosp, Ctr Med Genet, B-9000 Ghent, Belgium. [Greene, Mark H.; Mai, Phuong L.] US Natl Canc Inst, Clin Genet Branch, Rockville, MD USA. [Rennert, Gad; Lejbkowicz, Flavio] CHS Natl Canc Control Ctr, Haifa, Israel. [Rennert, Gad; Lejbkowicz, Flavio] Carmel Hosp, Dept Community Med & Epidemiol, Haifa, Israel. [Rennert, Gad; Lejbkowicz, Flavio] B Rappaport Fac Med, Haifa, Israel. [Andrulis, Irene L.; Glendon, Gord; OCGN] Canc Care Ontario, Ontario Canc Genet Network, Toronto, ON M5G 2L7, Canada. [Andrulis, Irene L.] Mt Sinai Hosp, Fred A Litwin Ctr Canc Genet, Samuel Lunenfeld Res Inst, Toronto, ON, Canada. [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Gerdes, Anne-Marie; Thomassen, Mads] Odense Univ Hosp, Dept Biochem Pharmacol & Genet, DK-5000 Odense, Denmark. [Sunde, Lone] Aarhus Univ Hosp, Dept Clin Genet, DK-8000 Aarhus, Denmark. [Caligo, Maria A.] Univ Pisa, Div Surg Mol & Ultrastructural Pathol, Dept Oncol, Pisa, Italy. [Caligo, Maria A.] Pisa Univ Hosp, Pisa, Italy. [Laitman, Yael; Kontorovich, Tair; Cohen, Shimrit; Friedman, Eitan] Chaim Sheba Med Ctr, Susanne Levy Gertner Oncogenet Unit, IL-52621 Tel Hashomer, Israel. [Kaufman, Bella] Chaim Sheba Med Ctr, Inst Oncol, IL-52621 Tel Hashomer, Israel. [Kaufman, Bella; Friedman, Eitan] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. [Dagan, Efrat; Baruch, Ruth Gershoni] Rambam Med Ctr, Genet Inst, Haifa, Israel. [Harbst, Katja] Lund Univ, Dept Oncol, S-22100 Lund, Sweden. [Barbany-Bustinza, Gisela; Rantala, Johanna] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden. [Ehrencrona, Hans] Uppsala Univ, Dept Genet & Pathol, Uppsala, Sweden. [Karlsson, Per] Sahlgrenska Univ, Dept Oncol, Gothenburg, Sweden. [Domchek, Susan M.; Nathanson, Katherine L.] Univ Penn, Philadelphia, PA 19104 USA. [Osorio, Ana; Benitez, Javier] Ctr Invest Biomed Red Enfermedades Raras CIBERERE, Inst Salud Carlos III, Madrid, Spain. [Osorio, Ana; Benitez, Javier] Spanish Natl Canc Ctr CNIO, Human Canc Genet Programme, Human Genet Grp, Madrid, Spain. [Blanco, Ignacio] Catalan Inst Oncol ICO, Canc Genet Counseling Program, Barcelona, Spain. [Lasa, Adriana] Hosp Santa Creu & Sant Pau, Genet Serv, Barcelona, Spain. [Hamann, Ute] Deutsch Krebsforschungszentrum, Neuenheimer Feld 580 69120, D-6900 Heidelberg, Germany. [Hogervorst, Frans B. L.] Netherlands Canc Inst, Dept Pathol, Family Canc Clin, NL-1066 CX Amsterdam, Netherlands. [Rookus, Matti A.] Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands. [Collee, J. Margriet] Erasmus Univ, Dept Clin Genet, Rotterdam Family Canc Clin, Med Ctr, NL-3000 DR Rotterdam, Netherlands. [Devilee, Peter] Dept Genet Epidemiol, Leiden, Netherlands. [Wijnen, Juul] Leiden Univ, Med Ctr, Ctr Human & Clin Genet, Leiden, Netherlands. [Ligtenberg, Marjolijn J.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. [van der Luijt, Rob B.] Univ Utrecht, Med Ctr, Dept Clin Mol Genet, NL-3508 TC Utrecht, Netherlands. [Aalfs, Cora M.] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands. [Waisfisz, Quinten] Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet, Amsterdam, Netherlands. [van Roozendaal, Cornelis E. P.] Univ Med Ctr, Dept Clin Genet, Maastricht, Netherlands. [Evans, D. Gareth; Lalloo, Fiona] Cent Manchester Univ Hosp, NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [Eeles, Rosalind] Inst Canc Res, Translat Canc Genet Team, London SW3 6JB, England. [Eeles, Rosalind] Royal Marsden NHS Fdn Trust, London, England. [Izatt, Louise] Guys Hosp, Clin Genet, London SE1 9RT, England. [Davidson, Rosemarie] Ferguson Smith Ctr Clin Genet, Glasgow, Lanark, Scotland. [Chu, Carol] Yorkshire Reg Genet Serv, Leeds, W Yorkshire, England. [Eccles, Diana] Princess Anne Hosp, Wessex Clin Genet Serv, Southampton, Hants, England. [Cole, Trevor] Birmingham Womens Hosp Healthcare, NHS Trust, W Midlands Reg Genet Serv, Birmingham, W Midlands, England. [Hodgson, Shirley] Univ London, Dept Canc Genet, St Georges Hosp, London, England. [Godwin, Andrew K.; Daly, Mary B.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Stoppa-Lyonnet, Dominique] Univ Paris 05, Paris, France. [Stoppa-Lyonnet, Dominique; GEMO] Inst Curie, INSERM U509, Serv Genet Oncol, Paris, France. [Buecher, Bruno] Inst Curie, Dept Genet, Paris, France. [Bressac-de Paillerets, Brigitte; Remenieras, Audrey; Lenoir, Gilbert M.] Inst Cancrol Gustave Roussy, Dept Genet, Villejuif, France. [Bressac-de Paillerets, Brigitte] Inst Cancerol Gustave Roussy, INSERM U946, Villejuif, France. [Caron, Olivier] Inst Cancerol Gustave Roussy, Dept Med, Villejuif, France. [Lenoir, Gilbert M.] Inst Cancerol Gustave Roussy, CNRS FRE2939, Villejuif, France. [Sevenet, Nicolas; Longy, Michel] Inst Bergonie, Lab Genet Constitutionnelle, Bordeaux, France. [Longy, Michel] Inst Bergonie, INSERM U916, Bordeaux, France. [Ferrer, Sandra Fert] Hop Hotel Dieu, Ctr Hosp, Lab Genet Chromosom, Chambery, France. [Prieur, Fabienne] CHU St Etienne, Serv Genet Clin Chromosom, St Etienne, France. [Goldgar, David] Univ Utah, Dept Dermatol, Salt Lake City, UT 84112 USA. [Miron, Alexander; Yassin, Yosuf] Dana Farber Canc Inst, Boston, MA 02115 USA. [John, Esther M.] No Calif Canc Ctr, Fremont, CA USA. [John, Esther M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Buys, Saundra S.] Univ Utah, Hlth Sci Ctr, Huntsman Canc Inst, Salt Lake City, UT USA. [Hopper, John L.] Univ Melbourne, Melbourne, Australia. [Terry, Mary Beth] Columbia Univ, New York, NY USA. [Singer, Christian; Gschwantler-Kaulich, Daphne; Staudigl, Christine] Med Univ Vienna, Div Special Gynecol, Dept OB GYN, Vienna, Austria. [Hansen, Thomas V. O.] Univ Copenhagen, Rigshosp, Dept Clin Biochem, DK-2100 Copenhagen, Denmark. [Barkardottir, Rosa Bjork] Landspitali Univ Hosp, Dept Pathol, Reykjavik, Iceland. [Kirchhoff, Tomas; Pal, Prodipto; Kosarin, Kristi; Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, New York, NY 10021 USA. [Piedmonte, Marion] Roswell Pk Canc Inst, GOG Stat & Data Ctr, Buffalo, NY 14263 USA. [Rodriguez, Gustavo C.] Evanston NW Healthcare, NorthShore Univ Hlth Syst, Evanston, IL 60201 USA. [Wakeley, Katie] Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. [Boggess, John F.] Univ N Carolina, Chapel Hill, NC 27599 USA. [Basil, Jack] St Elizabeth Hosp, Edgewood, KY 41017 USA. [Schwartz, Peter E.] Yale Univ, Sch Med, New Haven, CT 06510 USA. [Blank, Stephanie V.] NYU, Sch Med, New York, NY 10016 USA. [Toland, Amanda E.] Ohio State Univ, Dept Internal Med, Columbus, OH 43210 USA. [Toland, Amanda E.] Ohio State Univ, Div Human Canc Genet, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Montagna, Marco; Casella, Cinzia] IRCCS, Ist Oncologico Veneto, Immunol & Mol Oncol Unit, Padua, Italy. [Imyanitov, Evgeny N.] NN Petrov Inst Res Inst, St Petersburg, Russia. [Allavena, Anna] Univ Turin, Dept Genet Biol & Biochem, Turin, Italy. [Schmutzler, Rita K.; Versmold, Beatrix; Arnold, Norbert] Univ Cologne, Dept Obstet & Gynaecol, Div Mol Gynaeco Oncol, Cologne, Germany. [Engel, Christoph] Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany. [Meindl, Alfons] Tech Univ Munich, Dept Obstet & Gynaecol, Munich, Germany. [Ditsch, Nina] Univ Munich, Dept Obstet & Gynecol, Munich, Germany. Univ Schleswig Holstein, Dept Obstet & Gynaecol, Campus Kiel, Germany. [Niederacher, Dieter] Univ Duesseldorf, Dept Obstet & Gynaecol, Mol Genet Lab, Dusseldorf, Germany. [Deissler, Helmut] Univ Ulm, Dept Obstet & Gynaecol, Ulm, Germany. [Fiebig, Britta] Univ Regensburg, Inst Human Genet, Regensburg, Germany. [Suttner, Christian] Univ Heidelberg, Inst Human Genet, Heidelberg, Germany. [Schoenbuchner, Ines] Univ Wurzburg, Inst Human Genet, D-8700 Wurzburg, Germany. [Gadzicki, Dorothea] Med Univ, Inst Cellular & Mol Pathol, Hannover, Germany. [Caldes, Trinidad; de la Hoya, Miguel] Hosp Clinico San Carlos 28040, Madrid, Spain. RP Antoniou, AC (reprint author), Strangeways Res Lab, CR UK Genet Epidemiol, Cambridge CB1 8RN, England. EM antonis@srl.cam.ac.uk RI Spurdle, Amanda/A-4978-2011; Ehrencrona, Hans/M-5619-2014; Arnold, Norbert/E-3012-2010; Toland, Amanda/E-4202-2011; montagna, marco/E-2225-2012; Andrulis, Irene/E-7267-2013; Sunde, Lone/H-7402-2013; Hoogerbrugge, Nicoline/O-1016-2013; Radice, Paolo/O-3119-2013; Blanco, Ignacio/D-2565-2013; Ditsch, Nina/F-6267-2014; Osorio, Ana/I-4324-2014; Bernard, Loris/K-5953-2014; GLADIEFF, Laurence/O-5129-2014; Ligtenberg, Marjolijn/N-9666-2013; Peissel, Bernard/E-8187-2017; OI Spurdle, Amanda/0000-0003-1337-7897; Ehrencrona, Hans/0000-0002-5589-3622; Arnold, Norbert/0000-0003-4523-8808; montagna, marco/0000-0002-4929-2150; Blanco, Ignacio/0000-0002-7414-7481; Osorio, Ana/0000-0001-8124-3984; GLADIEFF, Laurence/0000-0002-6980-9719; Ligtenberg, Marjolijn/0000-0003-1290-1474; Peissel, Bernard/0000-0001-9233-3571; Nordling, Margareta/0000-0002-4047-4994; Nathanson, Katherine/0000-0002-6740-0901; Eeles, Rosalind/0000-0002-3698-6241; Sunde, Lone/0000-0002-8479-165X; Nevanlinna, Heli/0000-0002-0916-2976; Kirchhoff, Tomas/0000-0002-9055-2364; Evans, Gareth/0000-0002-8482-5784 FU Cancer Research UK; Associazione Italiana per la Ricerca sul Cancro FX The CIMBA genotyping, data management and statistical analysis are supported by Cancer Research UK. A.C.A. is a Cancer Research UK Senior Cancer Research Fellow. We thank Ellen Goode for organizing the distribution of the standard DNA plates. NR 26 TC 72 Z9 74 U1 4 U2 22 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 2009 VL 18 IS 22 BP 4442 EP 4456 DI 10.1093/hmg/ddp372 PG 15 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 510RB UT WOS:000271107300019 PM 19656774 ER PT J AU Periasamy, S Kolenbrander, PE AF Periasamy, Saravanan Kolenbrander, Paul E. TI Mutualistic Biofilm Communities Develop with Porphyromonas gingivalis and Initial, Early, and Late Colonizers of Enamel SO JOURNAL OF BACTERIOLOGY LA English DT Article ID FUSOBACTERIUM-NUCLEATUM; DENTAL PLAQUE; STREPTOCOCCUS-GORDONII; ORAL BACTERIA; COAGGREGATION; SALIVA; COMMUNICATION; COLONIZATION; LACTOSE; FLOW AB Porphyromonas gingivalis is present in dental plaque as early as 4 h after tooth cleaning, but it is also associated with periodontal disease, a late-developing event in the microbial successions that characterize daily plaque development. We report here that P. gingivalis ATCC 33277 is remarkable in its ability to interact with a variety of initial, early, middle, and late colonizers growing solely on saliva. Integration of P. gingivalis into multispecies communities was investigated by using two in vitro biofilm models. In flow cells, bacterial growth was quantified using fluorescently conjugated antibodies against each species, and static biofilm growth on saliva-submerged polystyrene pegs was analyzed by quantitative real-time PCR using species-specific primers. P. gingivalis could not grow as a single species or together with initial colonizer Streptococcus oralis but showed mutualistic growth when paired with two other initial colonizers, Streptococcus gordonii and Actinomyces oris, as well as with Veillonella sp. (early colonizer), Fusobacterium nucleatum (middle colonizer), and Aggregatibacter actinomycetemcomitans (late colonizer). In three-species flow cells, P. gingivalis grew with Veillonella sp. and A. actinomycetemcomitans but not with S. oralis and A. actinomycetemcomitans. Also, it grew with Veillonella sp. and F. nucleatum but not with S. oralis and F. nucleatum, indicating that P. gingivalis and S. oralis are not compatible. However, P. gingivalis grew in combination with S. gordonii and S. oralis, demonstrating its ability to overcome the incompatibility when cultured with a second initially colonizing species. Collectively, these data help explain the observed presence of P. gingivalis at all stages of dental plaque development. C1 [Periasamy, Saravanan; Kolenbrander, Paul E.] NIDCR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Kolenbrander, PE (reprint author), NIDCR, Oral Infect & Immun Branch, NIH, Bldg 30,Room 310,30 Convent Dr,MSC 4350, Bethesda, MD 20892 USA. EM pkolenbrander@dir.nidcr.nih.gov FU National Institute of Dental and Craniofacial Research; National Institutes of Health FX This research was supported in part by the Intramural Research Program of the National Institute of Dental and Craniofacial Research, National Institutes of Health and in part by the Colgate-Palmolive Co. CRADA. NR 23 TC 94 Z9 100 U1 4 U2 23 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD NOV 15 PY 2009 VL 191 IS 22 BP 6804 EP 6811 DI 10.1128/JB.01006-09 PG 8 WC Microbiology SC Microbiology GA 511UO UT WOS:000271195300006 PM 19749049 ER PT J AU Kang, YS Zhao, XH Lovaas, J Eisenberg, E Greene, LE AF Kang, Young-Shin Zhao, Xiaohong Lovaas, Jenna Eisenberg, Evan Greene, Lois E. TI Clathrin-independent internalization of normal cellular prion protein in neuroblastoma cells is associated with the Arf6 pathway SO JOURNAL OF CELL SCIENCE LA English DT Article DE Prion; Clathrin; Raft; Arf6 ID ENDOCYTIC PATHWAY; TRAFFICKING; DISEASE; INHIBITION; DOMAINS; TOXIN; CARGO AB To understand the role of clathrin-mediated endocytosis in the internalization of normal cellular prion protein (PrP(c)) in neuronal cells, N2a cells were depleted of clathrin by RNA interference. PrP(c) internalization via the constitutive endocytic pathway in the absence of Cu(2+) and the stimulated pathway in the presence of Cu(2+) were measured in both control and clathrin-depleted cells. Depletion of clathrin had almost no effect on the internalization of PrP(c) either in the presence or absence of Cu(2+), in contrast to the marked reduction observed in transferrin uptake. By contrast, the internalization of PrP(c) was inhibited by the raft-disrupting drugs filipin and nystatin, and by the dominant-negative dynamin-1 mutant dynamin-1 K44A, both in the presence and absence of Cu(2+). The internalized PrP(c) was found to colocalize with cargo that traffic in the Arf6 pathway and in large vacuoles in cells expressing the Arf6 dominant-active mutant. These results show that PrP(c) is internalized in a clathrin-independent pathway that is associated with Arf6. C1 [Kang, Young-Shin; Zhao, Xiaohong; Lovaas, Jenna; Eisenberg, Evan; Greene, Lois E.] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Greene, LE (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM greenel@helix.nih.gov NR 36 TC 15 Z9 16 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD NOV 15 PY 2009 VL 122 IS 22 BP 4062 EP 4069 DI 10.1242/jcs.046292 PG 8 WC Cell Biology SC Cell Biology GA 518HJ UT WOS:000271681300007 PM 19843586 ER PT J AU Zhou, ZG Wang, YL Bryant, SH AF Zhou, Zhigang Wang, Yanli Bryant, Stephen H. TI Computational Analysis of the Cathepsin B Inhibitors Activities Through LR-MMPBSA Binding Affinity Calculation Based on Docked Complex SO JOURNAL OF COMPUTATIONAL CHEMISTRY LA English DT Article DE cathepsin B protein; free energy of binding; virtual screening; modeling; drug design; regression; PubChem ID ATOM FORCE-FIELD; CYSTEINE PROTEASES; ENZYMATIC-REACTIONS; ALZHEIMERS-DISEASE; ACCURATE DOCKING; LIGAND-BINDING; DRUG DESIGN; HIV-1 RT; MM-PBSA; CANCER AB Cathepsin B. a ubiquitous lysosomal cysteine protease, is involved in many biological processes related to several human diseases. Inhibitors targeting the enzyme have been investigated as possible diseases treatments. A set of 37 compounds were recently found active in a high throughput screening assay to inhibit the catalytic activity of Cathepsin B, with chemical structures and biological test results available to the public in the PubChem BioAssay Database (AID 820). In this study, we compare these experimental activities to the results of theoretical predictions from binding affinity calculation with it LR-MM-PNSA approach based oil clocked complexes. Strong correlations (r(2) = 0.919 and q(2) = 0.887 for the best) are observed between the theoretical predictions and experimental biological activity. The models are cross-validated by four independent predictive experiments with randomly split compounds into training and test sets. Our results also show that the results based oil protein dimer show better correlations with experimental activity when compared to results based on monomer in the in silico calculations. (C) 2009 Wiley Periodicals, Inc.* J Comput Chem 30: 2165-2175, 2009 C1 [Zhou, Zhigang; Wang, Yanli; Bryant, Stephen H.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Bryant, SH (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM bryant@ncbi.nlm.nih.gov FU Intramural NIH HHS [Z01 LM100604-04, Z99 LM999999] NR 41 TC 7 Z9 7 U1 1 U2 17 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0192-8651 J9 J COMPUT CHEM JI J. Comput. Chem. PD NOV 15 PY 2009 VL 30 IS 14 BP 2165 EP 2175 DI 10.1002/jcc.21214 PG 11 WC Chemistry, Multidisciplinary SC Chemistry GA 496AL UT WOS:000269939600001 PM 19242965 ER PT J AU Choi, CW Chung, YJ Slape, C Aplan, PD AF Choi, Chul Won Chung, Yang Jo Slape, Christopher Aplan, Peter D. TI A NUP98-HOXD13 Fusion Gene Impairs Differentiation of B and T Lymphocytes and Leads to Expansion of Thymocytes with Partial TCRB Gene Rearrangement SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; IN-SITU HYBRIDIZATION; MYELODYSPLASTIC SYNDROMES; BONE-MARROW; TRANSGENIC MICE; CELL; PROGENITOR; LINEAGE; TRANSPLANTATION AB Expression of a NUP98-HOXD13 (NHD13) fusion gene leads to myelodysplastic syndrome in mice. In addition to ineffective hematopoiesis, we observed that NHD13 mice were lymphopenic; the lymphopenia was due to a decrease in both T and B lymphocytes. Although the pro-B cell (B220(+)/CD43(+)) populations from the NHD13 and wild-type mice were similar, the NHD13 mice showed decreased pre-B cells (B220(+)/CD43(-)), indicating impaired differentiation at the pro-B to pre-B stage. Thymi from NHD13 mice were smaller and overexpressed Hoxa cluster genes, including Hoxa7, Hoxa9, and Hoxa10. In addition, the NHD13 thymi contained fewer thymocytes, with an increased percentage of CD4(-)/CD8(-) (double-negative (DN)) cells and a decreased percentage of CD4(+)/CD8(+) (double-positive) cells; the DN1/DN2 population was increased and the DN3/DN4 population was decreased, suggesting a partial block at the DN2 to DN3 transition. To determine clonality of the thymocytes, we used degenerate RT-PCR to identify clonal Tcrb gene rearrangements. Five of six NHD13 thymi showed an unusual Tcrb gene rearrangement pattern with common, clonal DJ rearrangements, but distinct V-D junctions, suggesting a marked clonal expansion of thymocytes that had undergone a DJ rearrangement, but not completed a VDJ rearrangement. Taken together, these findings demonstrate that expression of the NHD13 transgene inhibits lymphoid as well as myeloid and erythroid differentiation, results in overexpression of Hoxa cluster genes, and leads to a precursor T cell lymphoblastic leukemia/lymphoma. The Journal of Immunology, 2009,183: 6227-6235. C1 [Choi, Chul Won; Chung, Yang Jo; Slape, Christopher; Aplan, Peter D.] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20889 USA. RP Aplan, PD (reprint author), Navy 8,Room 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM aplanp@mail.nih.gov RI Slape, Christopher/H-8586-2016; Aplan, Peter/K-9064-2016 OI Slape, Christopher/0000-0002-8407-3092; FU National Institutes of Health, National Cancer Institute FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. NR 30 TC 12 Z9 13 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 2009 VL 183 IS 10 BP 6227 EP 6235 DI 10.4049/jimmunol.0901121 PG 9 WC Immunology SC Immunology GA 519KQ UT WOS:000271765700024 PM 19841179 ER PT J AU Cohen, R Torres, A Ma, HT Holowka, D Baird, B AF Cohen, Roy Torres, Alexis Ma, Hong-Tao Holowka, David Baird, Barbara TI Ca2+ Waves Initiate Antigen-Stimulated Ca2+ Responses in Mast Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CAPACITATIVE CALCIUM-ENTRY; BASOPHILIC LEUKEMIA-CELL; ACCOMPANY NEUTROPHIL POLARIZATION; OPERATED CRAC CHANNELS; HIGH-SPEED MICROSCOPY; CURRENT I-CRAC; BONE-MARROW; FORMYLMETHIONYLLEUCYLPHENYLALANINE STIMULATION; 2-AMINOETHOXYDIPHENYL BORATE; INOSITOL TRISPHOSPHATE AB Ca2+ mobilization is central to many cellular processes, including stimulated exocytosis and cytokine production in mast cells. Using single cell stimulation by IgE-specific Ag and high-speed imaging of conventional or genetically encoded Ca2+ sensors in rat basophilic leukemia and bone marrow-derived rat mast cells, we observe Ca2+ waves that originate most frequently from the tips of extended cell protrusions, as well as Ca2+ oscillations throughout the cell that usually follow the initiating Ca2+ wave. In contrast, Ag conjugated to the tip of a micropipette stimulates local, repetitive Ca2+ puffs at the region of cell contact. Initiating Ca2+ waves are observed in most rat basophilic leukemia cells stimulated with soluble Ag and are sensitive to inhibitors of Ca2+ release from endoplasmic reticulum stores and to extracellular Ca2+, but they do not depend on store-operated Ca2+ entry. Knockdown of transient receptor potential channel (TRPC)1 and TRPC3 channel proteins by short hairpin RNA reduces the sensitivity of these cells to Ag and shifts the wave initiation site from protrusions to the cell body. Our results reveal spatially encoded Ca2+ signaling in response to immunoreceptor activation that utilizes TRPC channels to specify the initiation site of the Ca2+ response. The Journal of Immunology, 2009, 183: 6478-6488. C1 [Cohen, Roy; Torres, Alexis; Holowka, David; Baird, Barbara] Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY 14850 USA. [Ma, Hong-Tao] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Holowka, D (reprint author), Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY 14850 USA. EM dah24@cornell.edu FU National Institutes of Health [AI022449]; Nanobiotechnology Center at Cornell [NSF:ECS-9876771]; National Heart, Lung, and Blood Institute, National Institutes of Health FX This work was supported by National Institutes of Health Grant AI022449 and by the Nanobiotechnology Center at Cornell (NSF:ECS-9876771). H.-T.M. is supported by the International Program of the National Heart, Lung, and Blood Institute, National Institutes of Health. NR 77 TC 23 Z9 23 U1 1 U2 7 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 2009 VL 183 IS 10 BP 6478 EP 6488 DI 10.4049/jimmunol.0901615 PG 11 WC Immunology SC Immunology GA 519KQ UT WOS:000271765700051 PM 19864608 ER PT J AU Taha, TE Kumwenda, J Cole, SR Hoover, DR Kafulafula, G Fowler, MG Thigpen, MC Li, Q Kumwenda, NI Mofenson, L AF Taha, Taha E. Kumwenda, Johnstone Cole, Stephen R. Hoover, Donald R. Kafulafula, George Fowler, Mary Glenn Thigpen, Michael C. Li, Qing Kumwenda, Newton I. Mofenson, Lynne TI Postnatal HIV-1 Transmission after Cessation of Infant Extended Antiretroviral Prophylaxis and Effect of Maternal Highly Active Antiretroviral Therapy SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID BREAST-MILK; INTERRUPTION; OUTCOMES; MOTHER; WOMEN; CHILD AB Background. The association between postnatal human immunodeficiency virus type 1 (HIV-1) transmission and maternal highly active antiretroviral therapy (HAART) after infant extended antiretroviral prophylaxis was assessed. Methods. A follow-up study was conducted for the Post-Exposure Prophylaxis of Infants trial in Blantyre, Malawi (PEPI-Malawi). In PEPI-Malawi, breast-feeding infants of HIV-infected women were randomized at birth to receive a either control regimen (single-dose nevirapine plus 1 week of zidovudine); the control regimen plus nevirapine to age 14 weeks; or the control regimen plus nevirapine and zidovudine to age 14 weeks. Infant HIV infection, maternal CD4 cell count, and HAART use were determined. Maternal HAART use was categorized as HAART eligible but untreated (CD4 cell count of <250 cells/mu L, no HAART received), HAART eligible and treated (CD4 cell count of <250 cells/mu L, HAART received), and HAART ineligible (CD4 cell count of >= 250 cells/mu L). The incidence of HIV infection and the association between postnatal HIV transmission and maternal HAART were calculated among infants who were HIV negative at 14 weeks. Results. Of 2318 infants, 130 (5.6%) acquired HIV infection, and 310 mothers (13.4%) received HAART. The rates of HIV transmission (in cases per 100 person-years) were as follows: for the HAART-eligible/untreated category, 10.56 (95% confidence interval [CI], 7.91-13.82); for the HAART-eligible/treated category, 1.79 (95% CI, 0.58-4.18); and for the HAART-ineligible category, 3.66 (95% CI, 2.86-4.61). The HIV transmission rate ratio for the HAART-eligible/treated category versus the HAART-eligible/untreated category, adjusted for infant prophylaxis, was 0.18 (95% CI, 0.07-0.44). Conclusions. Postnatal HIV transmission continues after cessation of infant prophylaxis. HAART-eligible women should start treatment early for their own health and to reduce postnatal HIV transmission to their infants. C1 [Taha, Taha E.; Li, Qing; Kumwenda, Newton I.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Fowler, Mary Glenn] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Mofenson, Lynne] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Cole, Stephen R.] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. [Hoover, Donald R.] Rutgers State Univ, Piscataway, NJ USA. [Thigpen, Michael C.] Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Natl Ctr HIV AIDS Viral Hepatitis STD & TB Preven, Atlanta, GA USA. [Kumwenda, Johnstone; Kafulafula, George] Univ Malawi, Coll Med, Blantyre, Malawi. RP Taha, TE (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Rm E7138,615 N Wolfe St, Baltimore, MD 21205 USA. EM ttaha@jhsph.edu OI Mofenson, Lynne/0000-0002-2818-9808 NR 28 TC 45 Z9 47 U1 0 U2 0 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 2009 VL 200 IS 10 BP 1490 EP 1497 DI 10.1086/644598 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 511EQ UT WOS:000271147100002 PM 19832114 ER PT J AU Ripamonti, C Orenstein, A Kutty, G Huang, L Schuhegger, R Sing, A Fantoni, G Atzori, C Vinton, C Huber, C Conville, PS Kovacs, JA AF Ripamonti, Chiara Orenstein, Abigail Kutty, Geetha Huang, Laurence Schuhegger, Regina Sing, Andreas Fantoni, Giovanna Atzori, Chiara Vinton, Carol Huber, Charles Conville, Patricia S. Kovacs, Joseph A. TI Restriction Fragment Length Polymorphism Typing Demonstrates Substantial Diversity among Pneumocystis jirovecii Isolates SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID MAJOR SURFACE GLYCOPROTEIN; INTERNAL TRANSCRIBED SPACER; HIV-INFECTED PATIENTS; F SP. HOMINIS; EXPRESSION SITE; CARINII; GENES; PNEUMONIA; TRANSMISSION; REGIONS AB Better understanding of the epidemiology and transmission patterns of human Pneumocystis should lead to improved strategies for preventing Pneumocystis pneumonia (PCP). We have developed a typing method for Pneumocystis jirovecii that is based on restriction fragment length polymorphism (RFLP) analysis after polymerase chain reaction amplification of an similar to 1300 base-pair region of the msg gene family, which comprises an estimated 50-100 genes/genome. The RFLP pattern was reproducible in samples containing >1000 msg copies/reaction and was stable over time, based on analysis of serial samples from the same patient. In our initial analysis of 48 samples, we found that samples obtained from different individuals showed distinct banding patterns; only samples obtained from the same patient showed an identical RFLP pattern. Despite this substantial diversity, samples tended to cluster on the basis of country of origin. In an evaluation of samples obtained from an outbreak of PCP in kidney transplant recipients in Germany, RFLP analysis demonstrated identical patterns in samples that were from 12 patients previously linked to this outbreak, as well as from 2 additional patients. Our results highlight the presence of a remarkable diversity in human Pneumocystis strains. RFLP may be very useful for studying clusters of PCP in immunosuppressed patients, to determine whether there is a common source of infection. C1 [Ripamonti, Chiara; Orenstein, Abigail; Kutty, Geetha; Fantoni, Giovanna; Vinton, Carol; Kovacs, Joseph A.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Huber, Charles; Conville, Patricia S.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Huang, Laurence] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, San Francisco, CA USA. [Schuhegger, Regina; Sing, Andreas] Bavarian Hlth & Food Safety Author Bavarian LGL, Oberschleissheim, Germany. [Atzori, Chiara] Luigi Sacco Hosp, Dept Infect Dis, Milan, Italy. RP Kovacs, JA (reprint author), NIH, Dept Crit Care Med, Cin Ctr, 10 Rm 2C145,MSC 1662, Bethesda, MD 20892 USA. EM jkovacs@nih.gov FU National Institutes of Health (NIH) Clinical Center; NIH [K24 HL087713, R01 HL090335] FX Financial support: Intramural Research Program of the National Institutes of Health (NIH) Clinical Center and NIH (K24 HL087713 and R01 HL090335 to L. H.). NR 25 TC 10 Z9 12 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2009 VL 200 IS 10 BP 1616 EP 1622 DI 10.1086/644643 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 511EQ UT WOS:000271147100019 PM 19795979 ER PT J AU Ishibashi, T Lee, PR Baba, H Fields, RD AF Ishibashi, Tomoko Lee, Philip R. Baba, Hiroko Fields, R. Douglas TI Leukemia Inhibitory Factor Regulates the Timing of Oligodendrocyte Development and Myelination in the Postnatal Optic Nerve SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE myelin; LIF; oligodendrocyte; astrocyte; optic nerve; transcription; OPC; differentiation ID ACTION-POTENTIALS; PRECURSOR CELLS; SPINAL-CORD; TRANSCRIPTIONAL CONTROL; PROTEOLIPID PROTEIN; GROWTH-FACTOR; EXPRESSION; DIFFERENTIATION; DEMYELINATION; SURVIVAL AB Leukemia inhibitory factor (LIF) promotes the survival of oligodendrocytes both in vitro and in an animal model of multiple sclerosis, but the possible role of LIF signaling in myelination during normal development has not been investigated. We find that LIF(-/-) mice have a pronounced myelination defect in optic nerve at postnatal day 10. Myelin basic protein (MBP)- and proteolipid protein (PLP)-positive myelin was evident throughout the optic nerve in the wild-type mice, but staining was present only at the chiasmal region in LIF(-/-) mice of the same age. Further experiments suggest that the myelination defect was a consequence of a delay in maturation of oligodendrocyte precursor cell (OPC) population. The number of Olig2-positive cells was dramatically decreased in optic nerve of LIF(-/-) mice, and the distribution of Olig2-positive cells was restricted to the chiasmal region of the nerve in a steep gradient toward the retina. Gene expression profiling and cell culture experiments revealed that OPCs from P10 optic nerve of LIF(-/-) mice remained in a highly proliferative immature stage compared with littermate controls. Interestingly by postnatal day 14, MBP immunostaining in the LIF(-/-) optic nerve was comparable to that of LIF(+/+) mice. These results suggest that, during normal development of mouse optic nerve, there is a defined developmental time window when LIF is required for correct myelination. Myelination seems to recover by postnatal day 14, so LIF is not necessary for the completion of myelination during postnatal development. (C) 2009 Wiley-Liss, Inc. C1 [Ishibashi, Tomoko; Lee, Philip R.; Fields, R. Douglas] NIH, Nervous Syst Dev & Plast Sect, Bethesda, MD 20892 USA. [Ishibashi, Tomoko; Baba, Hiroko] Tokyo Univ Pharm & Life Sci, Tokyo, Japan. RP Fields, RD (reprint author), NIH, Nervous Syst Dev & Plast Sect, NICHD Bldg 35,Room 2A211,MSC 371335 Lincoln Dr, Bethesda, MD 20892 USA. EM fieldsd@mail.nih.gov FU NICHD; Japan Society for the Promotion of Science [19800043] FX Contract grant sponsor: NICHD; Contract grant sponsor: Japan Society for the Promotion of Science; Contract grant number: 19800043 (to T. I.). NR 46 TC 29 Z9 31 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD NOV 15 PY 2009 VL 87 IS 15 BP 3343 EP 3355 DI 10.1002/jnr.22173 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 507HR UT WOS:000270843400012 PM 19598242 ER PT J AU Hoshino, Y Katano, H Zou, P Hohman, P Marques, A Tyring, SK Follmann, D Cohen, JI AF Hoshino, Yo Katano, Harutaka Zou, Ping Hohman, Patricia Marques, Adriana Tyring, Stephen K. Follmann, Dean Cohen, Jeffrey I. TI Long-Term Administration of Valacyclovir Reduces the Number of Epstein-Barr Virus (EBV)-Infected B Cells but Not the Number of EBV DNA Copies per B Cell in Healthy Volunteers SO JOURNAL OF VIROLOGY LA English DT Article ID INFECTIOUS-MONONUCLEOSIS; CEREBROSPINAL-FLUID; IN-VIVO; ACYCLOVIR; REPLICATION; RECIPIENTS; LYMPHOMA; THERAPY AB Epstein-Barr virus (EBV) establishes a latent infection in B cells in the blood, and the latent EBV load in healthy individuals is generally stable over time, maintaining a "set point." It is unknown if the EBV load changes after long-term antiviral therapy in healthy individuals. We treated volunteers with either valacyclovir (valaciclovir) or no antiviral therapy for 1 year and measured the amount of EBV DNA in B cells every 3 months with a novel, highly sensitive assay. The number of EBV-infected B cells decreased in subjects receiving valacyclovir (half-life of 11 months; P = 0.02) but not in controls (half-life of 31 years; P = 0.86). The difference in the slopes of the lines for the number of EBV-infected B cells over time for the valacyclovir group versus the control group approached significance (P = 0.054). In contrast, the number of EBV DNA copies per B cell remained unchanged in both groups (P = 0.62 and P = 0.92 for the control and valacyclovir groups, respectively). Valacyclovir reduces the frequency of EBV-infected B cells when administered over a long period and, in theory, might allow eradication of EBV from the body if reinfection does not occur. C1 [Hoshino, Yo; Katano, Harutaka; Zou, Ping; Cohen, Jeffrey I.] NIAID, Med Virol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Hohman, Patricia; Marques, Adriana] NIAID, Clin Studies Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Tyring, Stephen K.] Univ Texas Hlth Sci Ctr, Dept Dermatol, Houston, TX USA. [Follmann, Dean] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. RP Cohen, JI (reprint author), NIAID, Med Virol Sect, Lab Clin Infect Dis, NIH, Bldg 10,Room 11N234,10 Ctr Dr,MSC 1888, Bethesda, MD 20892 USA. EM jcohen@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases FX This study was supported by the intramural research program of the National Institute of Allergy and Infectious Diseases. NR 24 TC 21 Z9 22 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV 15 PY 2009 VL 83 IS 22 BP 11857 EP 11861 DI 10.1128/JVI.01005-09 PG 5 WC Virology SC Virology GA 510JJ UT WOS:000271084100044 PM 19740997 ER PT J AU Migueles, SA Weeks, KA Nou, E Berkley, AM Rood, JE Osborne, CM Hallahan, CW Cogliano-Shutta, NA Metcalf, JA McLaughlin, M Kwan, R Mican, JM Davey, RT Connors, M AF Migueles, Stephen A. Weeks, Kristin A. Nou, Eric Berkley, Amy M. Rood, Julia E. Osborne, Christine M. Hallahan, Claire W. Cogliano-Shutta, Nancy A. Metcalf, Julia A. McLaughlin, Mary Kwan, Richard Mican, Joann M. Davey, Richard T., Jr. Connors, Mark TI Defective Human Immunodeficiency Virus-Specific CD8(+) T-Cell Polyfunctionality, Proliferation, and Cytotoxicity Are Not Restored by Antiretroviral Therapy SO JOURNAL OF VIROLOGY LA English DT Article ID LONG-TERM NONPROGRESSORS; VIRAL REPLICATION CAPACITY; ACUTE HIV-1 INFECTION; HIV-1-INFECTED SUBJECTS; ELITE SUPPRESSORS; TYPE-1 INFECTION; IMMUNE CONTROL; ANTIGEN LOAD; INTERLEUKIN-2; EXPRESSION AB Identifying the functions of human immunodeficiency virus (HIV)-specific CD8(+) T cells that are not merely modulated by the level of virus but clearly distinguish patients with immune control from those without such control is of paramount importance. Features of the HIV-specific CD8(+) T-cell response in antiretroviral-treated patients ( designated Rx < 50) and untreated patients (long-term nonprogressors [LTNP]) matched for very low HIV RNA levels were comprehensively examined. The proliferative capacity of HIV-specific CD8(+) T cells was not restored in Rx < 50 to the level observed in LTNP, even though HIV-specific CD4(+) T-cell proliferation in the two patient groups was comparable. This diminished HIV-specific CD8(+) T-cell proliferation in Rx < 50 was primarily due to a smaller fraction of antigen-specific cells recruited to divide and not to the numbers of divisions that proliferating cells had undergone. Exogenous interleukin-2 (IL-2) induced proliferating cells to divide further but did not rescue the majority of antigen-specific cells with defective proliferation. In addition, differences in HIV-specific CD8(+) T-cell proliferation could not be attributed to differences in cellular subsets bearing a memory phenotype, IL-2 production, or PD-1 expression. Although polyfunctionality of HIV-specific CD8(+) T cells in Rx < 50 was not restored to the levels observed in LTNP despite prolonged suppression of HIV RNA levels, per-cell cytotoxic capacity was the functional feature that most clearly distinguished the cells of LTNP from those of Rx < 50. Taken together, these data suggest that there are selective qualitative abnormalities within the HIV-specific CD8(+) T-cell compartment that persist under conditions of low levels of antigen. C1 [Migueles, Stephen A.; Weeks, Kristin A.; Nou, Eric; Berkley, Amy M.; Rood, Julia E.; Osborne, Christine M.; Cogliano-Shutta, Nancy A.; Metcalf, Julia A.; McLaughlin, Mary; Kwan, Richard; Mican, Joann M.; Davey, Richard T., Jr.; Connors, Mark] NIAID, LIR, NIH, Bethesda, MD 20892 USA. [Hallahan, Claire W.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. RP Connors, M (reprint author), NIAID, LIR, NIH, 10 Rm 11B-09,10 Ctr Dr,MSC 1876, Bethesda, MD 20892 USA. EM mconnors@niaid.nih.gov FU Intramural Research Program of the NIH; National Institute of Allergy and Infectious Diseases FX This research was supported in part by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases. NR 51 TC 88 Z9 89 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV 15 PY 2009 VL 83 IS 22 BP 11876 EP 11889 DI 10.1128/JVI.01153-09 PG 14 WC Virology SC Virology GA 510JJ UT WOS:000271084100046 PM 19726501 ER PT J AU Bok, K Abente, EJ Realpe-Quintero, M Mitra, T Sosnovtsev, SV Kapikian, AZ Green, KY AF Bok, Karin Abente, Eugenio J. Realpe-Quintero, Mauricio Mitra, Tanaji Sosnovtsev, Stanislav V. Kapikian, Albert Z. Green, Kim Y. TI Evolutionary Dynamics of GII.4 Noroviruses over a 34-Year Period SO JOURNAL OF VIROLOGY LA English DT Article ID NORWALK-LIKE VIRUSES; POSITIVE SELECTION PRESSURE; QUASI-SPECIES DYNAMICS; BLOOD GROUP ANTIGENS; VIRAL GASTROENTERITIS; HUMAN-POPULATIONS; GII-4 NOROVIRUS; CAPSID PROTEIN; P2 DOMAIN; EPIDEMIC AB Noroviruses are a major cause of epidemic gastroenteritis in children and adults, and GII.4 has been the predominant genotype since its first documented occurrence in 1987. This study examined the evolutionary dynamics of GII.4 noroviruses over more than three decades to investigate possible mechanisms by which these viruses have emerged to become predominant. Stool samples (n = 5,424) from children hospitalized at the Children's Hospital in Washington, DC, between 1974 and 1991 were screened for the presence of noroviruses by a custom multiplex real-time reverse transcription-PCR. The complete genome sequences of five GII.4 noroviruses ( three of which predate 1987 by more than a decade) in this archival collection were determined and compared to the sequences of contemporary strains. Evolutionary analysis determined that the GII.4 VP1 capsid gene evolved at a rate of 4.3 x 10(-3) nucleotide substitutions/site/year. Only six sites in the VP1 capsid protein were found to evolve under positive selection, most of them located in the shell domain. No unique mutations were observed in or around the two histoblood group antigen (HBGA) binding sites in the P region, indicating that this site has been conserved since the 1970s. The VP1 proteins from the 1974 to 1977 noroviruses contained a unique sequence of four consecutive amino acids in the P2 region, which formed an exposed protrusion on the modeled capsid structure. This protrusion and other observed sequence variations did not affect the HBGA binding profiles of recombinant virus-like particles derived from representative 1974 and 1977 noroviruses compared with more recent noroviruses. Our analysis of archival GII.4 norovirus strains suggests that this genotype has been circulating for more than three decades and provides new ancestral strain sequences for the analysis of GII.4 evolution. C1 [Bok, Karin] NIAID, Norovirus Gastroenteritis Unit, Infect Dis Lab, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Bok, K (reprint author), NIAID, Norovirus Gastroenteritis Unit, Infect Dis Lab, NIH,Dept Hlth & Human Serv, 50 South Dr,Bldg 50,Room 6316, Bethesda, MD 20892 USA. EM bokk@niaid.nih.gov OI Abente, Eugenio/0000-0002-3390-2786 FU NIH; NIAID FX This research was supported by the Intramural Research Program of the NIH, NIAID. NR 49 TC 135 Z9 141 U1 1 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV 15 PY 2009 VL 83 IS 22 BP 11890 EP 11901 DI 10.1128/JVI.00864-09 PG 12 WC Virology SC Virology GA 510JJ UT WOS:000271084100047 PM 19759138 ER PT J AU Beliakova-Bethell, N Terry, LJ Bilanchone, V DaSilva, R Nagashima, K Wente, SR Sandmeyer, S AF Beliakova-Bethell, Nadejda Terry, Laura J. Bilanchone, Virginia DaSilva, Rhonda Nagashima, Kunio Wente, Susan R. Sandmeyer, Suzanne TI Ty3 Nuclear Entry Is Initiated by Viruslike Particle Docking on GLFG Nucleoporins SO JOURNAL OF VIROLOGY LA English DT Article ID AVIAN-SARCOMA VIRUS; TRANSFER-RNA GENES; PORE COMPLEX; NUCLEOCYTOPLASMIC TRANSPORT; SACCHAROMYCES-CEREVISIAE; LOCALIZATION SIGNAL; RETROTRANSPOSON TF1; NONDIVIDING CELLS; EXPORT RECEPTOR; POLY(A)(+) RNA AB Yeast retrotransposons form intracellular particles within which replication occurs. Because fungal nuclear membranes do not break down during mitosis, similar to retroviruses infecting nondividing cells, the cDNA produced must be translocated through nuclear pore complexes. The Saccharomyces cerevisiae long terminal repeat retrotransposon Ty3 assembles its Gag3 and Gag3-Pol3 precursor polyproteins into viruslike particles in association with perinuclear P-body foci. These perinuclear clusters of Ty3 viruslike particles localized to sites of clustered nuclear pore complexes (NPCs) in a nup120 Delta mutant, indicating that Ty3 particles and NPCs interact physically. The NPC channels are lined with nucleoporins (Nups) with extended FG (Phe-Gly) motif repeat domains, further classified as FG, FxFG, or GLFG repeat types. These domains mediate partitioning of proteins between the cytoplasm and the nucleus. Here we have systematically examined the requirements for FG repeat domains in Ty3 nuclear transport. The GLFG domains interacted in vitro with virus-like particle Gag3, and this interaction was disrupted by mutations in the amino-terminal domain of Gag3, which is predicted to lie on the external surface of the particles. Accordingly, Ty3 transposition was decreased in strains with the GLFG repeats deleted. The spacer-nucleocapsid domain of Gag3, which is predicted to be internal to the particle, interacted with GLFG repeats and nucleocapsid localized to the nucleus. We conclude that Ty3 particle docking on nuclear pores is facilitated by interactions between Gag3 and GLFG Nups and that nuclear entry of the preintegration complex is further promoted by nuclear localization signals within the nucleocapsid and integrase. C1 [Beliakova-Bethell, Nadejda; Bilanchone, Virginia; Sandmeyer, Suzanne] Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92697 USA. [Terry, Laura J.; Wente, Susan R.] Vanderbilt Univ, Dept Cell & Dev Biol, Med Ctr, Nashville, TN 37232 USA. [DaSilva, Rhonda; Nagashima, Kunio] SAIC Frederick Inc, Elect Microscope Lab, NCI Frederick, Frederick, MD 21702 USA. RP Sandmeyer, S (reprint author), Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92697 USA. EM sbsandme@uci.edu FU National Institutes of Health [R01 GM33281, R01 GM051219, 5 T32 AI 07319, 5 T32 CA 009385]; National Cancer Institute [NO1-CO-12400] FX This research was supported in part by funds from National Institutes of Health grants R01 GM33281 to S. B. S. and R01 GM051219 to S. R. W. The research was also funded in part by National Cancer Institute contract NO1-CO-12400 to K. N. N. B.-B. and L. J. T. were supported by National Institutes of Health Training Grants 5 T32 AI 07319 and 5 T32 CA 009385, respectively. NR 64 TC 10 Z9 10 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD NOV 15 PY 2009 VL 83 IS 22 BP 11914 EP 11925 DI 10.1128/JVI.01192-09 PG 12 WC Virology SC Virology GA 510JJ UT WOS:000271084100049 PM 19759143 ER PT J AU Lanke, KHW van der Schaar, HM Belov, GA Feng, Q Duijsings, D Jackson, CL Ehrenfeld, E van Kuppeveld, FJM AF Lanke, Kjerstin H. W. van der Schaar, Hilde M. Belov, George A. Feng, Qian Duijsings, Daniel Jackson, Catherine L. Ehrenfeld, Ellie van Kuppeveld, Frank J. M. TI GBF1, a Guanine Nucleotide Exchange Factor for Arf, Is Crucial for Coxsackievirus B3 RNA Replication SO JOURNAL OF VIROLOGY LA English DT Article ID CELLULAR-PROTEIN SECRETION; ADP-RIBOSYLATION FACTOR; ENDOPLASMIC-RETICULUM; BREFELDIN-A; MEMBRANE ASSOCIATION; VIRAL-PROTEINS; POLIOVIRUS RNA; 3A PROTEINS; GOLGI; INHIBITION AB The replication of enteroviruses is sensitive to brefeldin A (BFA), an inhibitor of endoplasmic reticulum-to-Golgi network transport that blocks activation of guanine exchange factors (GEFs) of the Arf GTPases. Mammalian cells contain three BFA-sensitive Arf GEFs: GBF1, BIG1, and BIG2. Here, we show that coxsackievirus B3 (CVB3) RNA replication is insensitive to BFA in MDCK cells, which contain a BFA-resistant GBF1 due to mutation M832L. Further evidence for a critical role of GBF1 stems from the observations that viral RNA replication is inhibited upon knockdown of GBF1 by RNA interference and that replication in the presence of BFA is rescued upon overexpression of active, but not inactive, GBF1. Overexpression of Arf proteins or Rab1B, a GTPase that induces GBF1 recruitment to membranes, failed to rescue RNA replication in the presence of BFA. Additionally, the importance of the interaction between enterovirus protein 3A and GBF1 for viral RNA replication was investigated. For this, the rescue from BFA inhibition of wild-type (wt) replicons and that of mutant replicons of both CVB3 and poliovirus (PV) carrying a 3A protein that is impaired in binding GBF1 were compared. The BFA-resistant GBF1-M832L protein efficiently rescued RNA replication of both wt and mutant CVB3 and PV replicons in the presence of BFA. However, another BFA-resistant GBF1 protein, GBF1-A795E, also efficiently rescued RNA replication of the wt replicons, but not that of mutant replicons, in the presence of BFA. In conclusion, this study identifies a critical role for GBF1 in CVB3 RNA replication, but the importance of the 3A-GBF1 interaction requires further study. C1 [Lanke, Kjerstin H. W.; van der Schaar, Hilde M.; Duijsings, Daniel; van Kuppeveld, Frank J. M.] Radboud Univ Nijmegen, Med Ctr, Nijmegen Ctr Mol Life Sci, Dept Med Microbiol, NL-6500 HB Nijmegen, Netherlands. [Lanke, Kjerstin H. W.; van der Schaar, Hilde M.; Duijsings, Daniel; van Kuppeveld, Frank J. M.] Radboud Univ Nijmegen, Med Ctr, Nijmegen Inst Infect Inflammat & Immun, NL-6500 HB Nijmegen, Netherlands. [Belov, George A.; Feng, Qian; Ehrenfeld, Ellie] NIAID, NIH, Bethesda, MD 20892 USA. [Jackson, Catherine L.] CNRS, Lab Enzymol & Biochem Struct, Gif Sur Yvette, France. RP van Kuppeveld, FJM (reprint author), Radboud Univ Nijmegen, Med Ctr, Nijmegen Ctr Mol Life Sci, Dept Med Microbiol, POB 9101, NL-6500 HB Nijmegen, Netherlands. EM f.vankuppeveld@ncmls.ru.nl RI Belov, George/B-4625-2008; Jackson, Catherine/A-3421-2013 OI Belov, George/0000-0002-0892-1731; Jackson, Catherine/0000-0002-0843-145X FU Netherlands Organization for Scientific Research [NWO-VIDI-917.46.306, NWO-ECHO-700.57.001]; NIAID, NIH FX This work was partly supported by grants from The Netherlands Organization for Scientific Research (NWO-VIDI-917.46.306 and NWO-ECHO-700.57.001 to F. V. K.) and by the intramural research program of the NIAID, NIH. NR 35 TC 71 Z9 72 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV 15 PY 2009 VL 83 IS 22 BP 11940 EP 11949 DI 10.1128/JVI.01244-09 PG 10 WC Virology SC Virology GA 510JJ UT WOS:000271084100051 PM 19740986 ER PT J AU Wang, PF Lin, CQ Smith, ER Guo, H Sanderson, BW Wu, M Gogol, M Alexander, T Seidel, C Wiedemann, LM Ge, K Krumlauf, R Shilatifard, A AF Wang, Pengfei Lin, Chengqi Smith, Edwin R. Guo, Hong Sanderson, Brian W. Wu, Min Gogol, Madelaine Alexander, Tara Seidel, Christopher Wiedemann, Leanne M. Ge, Kai Krumlauf, Robb Shilatifard, Ali TI Global Analysis of H3K4 Methylation Defines MLL Family Member Targets and Points to a Role for MLL1-Mediated H3K4 Methylation in the Regulation of Transcriptional Initiation by RNA Polymerase II SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID LYSINE-4 METHYLTRANSFERASE COMPLEX; MIXED-LINEAGE LEUKEMIA; HISTONE-H3 LYSINE-4; GENE-EXPRESSION; H2B MONOUBIQUITINATION; HUMAN GENOME; CHROMATIN; COMPASS; TRITHORAX; PROTEIN AB A common landmark of activated genes is the presence of trimethylation on lysine 4 of histone H3 (H3K4) at promoter regions. Set1/COMPASS was the founding member and is the only H3K4 methylase in Saccharomyces cerevisiae; however, in mammals, at least six H3K4 methylases, Set1A and Set1B and MLL1 to MLL4, are found in COMPASS-like complexes capable of methylating H3K4. To gain further insight into the different roles and functional targets for the H3K4 methylases, we have undertaken a genome-wide analysis of H3K4 methylation patterns in wild-type Mll1(+/+) and Mll1(-/-) mouse embryonic fibroblasts (MEFs). We found that Mll1 is required for the H3K4 trimethylation of less than 5% of promoters carrying this modification. Many of these genes, which include developmental regulators such as Hox genes, show decreased levels of RNA polymerase II recruitment and expression concomitant with the loss of H3K4 methylation. Although Mll1 is only required for the methylation of a subset of Hox genes, menin, a component of the Mll1 and Mll2 complexes, is required for the overwhelming majority of H3K4 methylation at Hox loci. However, the loss of MLL3/MLL4 and/or the Set1 complexes has little to no effect on the H3K4 methylation of Hox loci or their expression levels in these MEFs. Together these data provide insight into the redundancy and specialization of COMPASS-like complexes in mammals and provide evidence for a possible role for Mll1-mediated H3K4 methylation in the regulation of transcriptional initiation. C1 [Wang, Pengfei; Lin, Chengqi; Smith, Edwin R.; Sanderson, Brian W.; Wu, Min; Gogol, Madelaine; Alexander, Tara; Seidel, Christopher; Wiedemann, Leanne M.; Krumlauf, Robb; Shilatifard, Ali] Stowers Inst Med Res, Kansas City, MO 64110 USA. [Guo, Hong; Ge, Kai] NIDDK, Nucl Receptor Biol Sect, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. [Wiedemann, Leanne M.] Univ Kansas, Sch Med, Dept Pathol & Lab Med, Kansas City, KS USA. [Krumlauf, Robb] Univ Kansas, Sch Med, Dept Anat & Cell Biol, Kansas City, KS USA. RP Shilatifard, A (reprint author), Stowers Inst Med Res, 1000 East 50th St, Kansas City, MO 64110 USA. EM ASH@Stowers.org OI Ge, Kai/0000-0002-7442-5138 FU NCI [5R01CA089455]; Stowers Institute for Medical Research FX This work was supported by grants from the NCI to A. S. (5R01CA089455) and by support of A. S. and R. K. by the Stowers Institute for Medical Research. NR 60 TC 163 Z9 167 U1 3 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV 15 PY 2009 VL 29 IS 22 BP 6074 EP 6085 DI 10.1128/MCB.00924-09 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 511ZB UT WOS:000271209600009 PM 19703992 ER PT J AU Zou, QH Wu, CW Stein, EA Zang, YF Yang, YH AF Zou, Qihong Wu, Changwei W. Stein, Elliot A. Zang, Yufeng Yang, Yihong TI Static and dynamic characteristics of cerebral blood flow during the resting state SO NEUROIMAGE LA English DT Article DE CBF; Static; Dynamic; Functional connectivity; ALFF; ReHo; Resting state ID INDEPENDENT COMPONENT ANALYSIS; BOLD SIGNAL FLUCTUATIONS; DEFAULT-MODE NETWORK; FUNCTIONAL CONNECTIVITY; HUMAN BRAIN; LOW-FREQUENCY; REGIONAL HOMOGENEITY; ALZHEIMERS-DISEASE; GLOBAL SIGNAL; SMALL-WORLD AB In this study, the static and dynamic characteristics of cerebral blood flow (CBF) in the resting state were investigated using an arterial spin labeling (ASL) perfusion imaging technique. Consistent with previous PET results, static CBF measured by ASL was significantly higher in the posterior cingulate cortex (PCC), thalamus, insula/superior temporal gyrus (STG) and medial prefrontal cortex (MPFC) than the average CBF of the brain. The dynamic measurement of CBF fluctuations showed high correlation ( functional connectivity) between components in the default mode network. These brain regions also had high local temporal synchrony and high fluctuation amplitude, as measured by regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) analyses. The spatial pattern of the static CBF correlated well with that of the dynamic indices. The high static and dynamic activities in the PCC, MPFC, insula/STG and thalamus suggest that these regions play a vital role in maintaining and facilitating fundamental brain functions. Published by Elsevier Inc. C1 [Zou, Qihong; Zang, Yufeng] Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China. [Zou, Qihong; Wu, Changwei W.; Stein, Elliot A.; Yang, Yihong] NIDA, Neuroimaging Res Branch, NIH, Baltimore, MD 21224 USA. [Wu, Changwei W.] Natl Taiwan Univ, Dept Elect Engn, Taipei 10764, Taiwan. RP Zang, YF (reprint author), Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, 19 Xinjiekouwai St, Beijing 100875, Peoples R China. EM zangyf@bnu.edu.cn; yihongyang@intra.nida.nih.gov RI ZANG, Yu-Feng/J-1558-2012 OI ZANG, Yu-Feng/0000-0003-1833-8010 FU Intramural Research Program of the National Institute on Drug Abuse (NIDA); National Institute of Health (NIH) FX This work was supported by the Intramural Research Program of the National Institute on Drug Abuse (NIDA), National Institute of Health (NIH). The authors thank Dr. Christian F. Beckmann for providing dual regression method for ICA denoising, Dr. Xinian Zuo for preparing the vessel mask and suggestions for removing noise using ICA, and Dr. Thomas J. Ross and Dr. Yong He for helpful discussions. NR 59 TC 94 Z9 96 U1 1 U2 19 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD NOV 15 PY 2009 VL 48 IS 3 BP 515 EP 524 DI 10.1016/j.neuroimage.2009.07.006 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 558EQ UT WOS:000274724000004 PM 19607928 ER PT J AU Hakk, H Diliberto, JJ Birnbaum, LS AF Hakk, Heldur Diliberto, Janet J. Birnbaum, Linda S. TI The effect of dose on 2,3,7,8-TCDD tissue distribution, metabolism and elimination in CYP1A2 (-/-) knockout and C57BL/6N parental strains of mice SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE 2,3,7,8-Tetrachlorodibenzo-p-dioxin TCDD; CYP1A2; Knockout mice; Metabolism; Mouse major urinary protein ID DIBENZO-P-DIOXINS; RESPONSE RELATIONSHIPS; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TCDD; METHYLSULFONYL METABOLITE; POLYCHLORINATED BIPHENYL; HEPATIC SEQUESTRATION; RAT; BINDING; EXCRETION; PROTEINS AB Numerous metabolism studies have demonstrated that the toxic contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is poorly metabolized. A hallmark feature of TCDD exposure is induction of hepatic CYP1A2 and subsequent sequestration leading to high liver-to-fat concentration ratios. This study was initiated to determine whether TCDD was inherently poorly metabolized or unavailable for metabolism because of sequestration to CYP1A2. [H-3]TCDD was administered as a single, oral dose (0.1 and 10 mu g/kg) to 12 male C57BL/6N mice or 12 CYP1A2 (-/-) mice. At 96 h, less than 5% of the dose was eliminated in the urine of all groups, and TCDD detected in urine was bound to mouse major urinary protein (mMUP). Feces were the major elimination pathway (24-31% of dose), and fecal extracts and non-extractables were quantitated by HPLC for metabolites. No great differences in urinary or fecal elimination (% dose) were observed between the high and low dose treatments. TCDD concentrations were the highest in adipose tissue for CYP1A2 knockout mice but in liver for C57BL/6N mice supporting the role of hepatic CYP1A2 in the sequestration of TCDD. Overall metabolism between parental and knockout strains showed no statistical differences at either the high or low doses. The data suggested that metabolism of TCDD is inherently slow, due principally to CYP1A7, and that hepatic CYP1A2 is not an active participant in the metabolism of TCDD in male mice. Rather, CYP1A2 governs the pharmacokinetics of TCDD by making it unavailable for hepatic CYP1A1 through sequestration and attenuating extrahepatic tissue disposition. Published by Elsevier Inc. C1 [Hakk, Heldur] ARS, USDA, Biosci Res Lab, Fargo, ND USA. [Diliberto, Janet J.] US EPA ORD, Natl Hlth Effects & Environm Res Lab, Expt Toxicol Div, Res Triangle Pk, NC USA. [Birnbaum, Linda S.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Hakk, H (reprint author), ARS, USDA, Biosci Res Lab, POB 5674, Fargo, ND USA. EM heldur.hakk@ars.usda.gov NR 42 TC 20 Z9 21 U1 1 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X EI 1096-0333 J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV 15 PY 2009 VL 241 IS 1 BP 119 EP 126 DI 10.1016/j.taap.2009.08.009 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 514QH UT WOS:000271409400011 PM 19695277 ER PT J AU Horkay, F Basser, PJ Londono, DJ Hecht, AM Geissler, E AF Horkay, Ferenc Basser, Peter J. Londono, David J. Hecht, Anne-Marie Geissler, Erik TI Ions in hyaluronic acid solutions SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID POLYELECTROLYTE SOLUTIONS; CARTILAGE AGGRECAN; LIGHT-SCATTERING; POLYSACCHARIDES; ORGANIZATION; VISCOSITY; SALT; DNA AB Hyaluronic acid (HA) is an anionic biopolymer that is almost ubiquitous in biological tissues. An attempt is made to determine the dominant features that account for both its abundance and its multifunctional role, and which set it apart from other types of biopolymers. A combination of osmotic and scattering techniques is employed to quantify its dynamic and static properties in near-physiological solution conditions, where it is exposed both to mono- and divalent counterions. An equation of state is derived for the osmotic pressure Pi in the semidilute concentration region, in terms of two variables, the polymer concentration c and the ionic strength J of the added salt, according to which Pi=1.4x10(3)c(9/4)/J(3/4) kPa, where c and J are expressed in mole. Over the physiological ion concentration range, the effect of the sodium chloride and calcium chloride on the osmotic properties of HA solutions is fully accounted for by their contributions to the ionic strength. The absence of precipitation, even at high CaCl(2) concentrations, distinguishes this molecule from other biopolymers such as DNA. Dynamic light scattering measurements reveal that the collective diffusion coefficient in HA solutions exceeds that in aqueous solutions of typical neutral polymers by a factor of approximately 5. This property ensures rapid adjustment to, and recovery from, stress applied to HA-containing tissue. Small angle x-ray scattering measurements confirm the absence of appreciable structural reorganization over the observed length scale range 10-1000 angstrom, as a result of calcium-sodium ion exchange. The scattered intensity in the transfer momentum range q>0.03 angstrom(-1) varies as 1/q, indicating that the HA chain segments in semidilute solutions are linear over an extended concentration range. The osmotic compression modulus c partial derivative Pi/partial derivative c, a high value of which is a prerequisite in structural biopolymers, is several times greater than in typical neutral polymer solutions. (C) 2009 American Institute of Physics. [doi: 10.1063/1.3262308] C1 [Horkay, Ferenc; Basser, Peter J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Tissue Biophys & Biomimet, Program Phys Biol, NIH, Bethesda, MD 20892 USA. [Londono, David J.] Dupont Nemours & Co, Dupont Cent Res, Expt Stn, Wilmington, DE 19880 USA. [Hecht, Anne-Marie; Geissler, Erik] Univ Grenoble 1, CNRS, Spectrometrie Phys Lab, UMR 5588, F-38402 St Martin Dheres, France. RP Horkay, F (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Tissue Biophys & Biomimet, Program Phys Biol, NIH, 13 South Dr, Bethesda, MD 20892 USA. EM horkay@helix.nih.gov RI Basser, Peter/H-5477-2011 FU NICHD, NIH; National Science Foundation [DMR-9423101] FX This research was supported by the Intramural Research Program of the NICHD, NIH. We express our gratitude to the Advanced Photon Source, Argonne National Laboratory, for access to the DND-CAT small angle instrument. This work is partially based upon activities supported by the National Science Foundation under Grant No. DMR-9423101. NR 35 TC 16 Z9 16 U1 1 U2 25 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 14 PY 2009 VL 131 IS 18 AR 184902 DI 10.1063/1.3262308 PG 8 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 528NY UT WOS:000272454500041 PM 19916626 ER PT J AU Bray, GA Chatellier, A Duncan, C Greenway, FL Levy, E Ryan, DH Polonsky, KS Tobian, J Ehrmann, D Matulik, MJ Clark, B Czech, K DeSandre, C Hilbrich, R McNabb, W Semenske, AR Goldstein, BJ Smith, KA Wildman, W Pepe, C Goldberg, RB Calles, J Ojito, J Castillo-Florez, S Florez, HJ Giannella, A Lara, O Veciana, B Haffner, SM Montez, MG Lorenzo, C Martinez, A Hamman, RF Testaverde, L Bouffard, A Dabelea, D Jenkins, T Lenz, D Perreault, L Price, DW Steinke, SC Horton, ES Poirier, CS Swift, K Caballero, E Jackson, SD Lambert, L Lawton, KE Ledbury, S Kahn, SE Montgomery, BK Fujimoto, W Knopp, RH Lipkin, EW Marr, M Murillo, A Trence, D Kitabchi, AE Murphy, ME Applegate, WB Bryer-Ash, M Dagogo-Jack, S Frieson, SL Lambeth, H Lichtermann, LC Otkaei, H Rutledge, LMK Sherman, AR Smith, CM Soberman, JE Williams-Cleaves, B Metzger, BE Molitch, ME Johnson, MK Giles, MM Larsen, D Niznik, C Pen, SC Schinleber, PA Nathan, DM McKitrick, C Turgeon, H Abbott, K Altshuler, D Anderson, E Bissett, L Cagliero, E D'Anna, K Delahanty, L Florez, JC Goldman, V Poulos, A Tseng, B Barrett-Connor, E Carrion-Petersen, ML Horne, J Leos, D Mudaliar, S Smith, J Vejvoda, K Pi-Sunyer, FX Lee, JE Foo, ST Hagamen, S Marrero, DG Kelly, SM Ackermann, RT Fineberg, ES Hadden, A Jackson, MA Kirkman, MS Mather, KJ Roach, PJ Wheeler, ML Ratner, RE Aroda, V Shapiro, S Bavido-Arrage, C Gibbs, P Uwaifo, G Wiggins, R Saad, MF Watson, K Botrous, M Jinagouda, S Budget, M Conzues, C Magpuri, P Ngo, K Xapthalamous, K White, NH Das, S Santiago, A Brown, AL Wernimont, C Saudek, CD Whittington, T Clark, JM Greene, A Jiggetts, D Mosley, H Reusing, J Rubin, RR Stephen, S Utsey, E Schade, DS Adams, KS Hemphill, C Hyde, P Butler, L Canady, JL Colleran, K Gonzales, Y Hernandez-McGinnis, DA Katz, P King, C Crandall, J Brown-Friday, JO Adorno, E Duffy, H Martinez, H Pompi, D Shamoon, H Walker, EA Wylie-Rosett, J Orchard, T Jeffries, S Kramer, MK Smith, M Kriska, A Pettigrew, J Semler, L Venditti, E Weinzierl, V Arakaki, RF Baker-Ladao, NK Isonaga, MK Bermudez, NE Mau, MK Knowler, WC Cooeyate, N Hoskin, MA Natewa, C Percy, CA Acton, KJ Andre, VL Begay, S Bucca, BC Cook, S Doughty, MS Glass, J Glass, M Hanson, RL Hassenpflug, D Ingraham, LE Kobus, KM Krakoff, J Manus, C McCabe, C Michaels, S Morgan, T Nelson, JA Roy, RJ Smart, M Tonemah, DP Wilson, C Fowler, S Brenneman, T Abebe, S Bamdad, J Callaghan, J Christophi, CA Edelstein, SL Gao, Y Gooding, R Gottlieb, A Grover, N Hoffman, H Jablonski, K Katz, R Kolinjivadi, P Lachin, JM Ma, Y Reamer, S Sapozhnikova, A Sherif, H Temprosa, M Venditti, EM Kriska, AM Semler, L Weinzierl, V Marcovina, S Strylewicz, G Albers, J Prineas, RJ Alexander, T Campbell, C Hall, S Hensley, S Li, Y Mills, M Soliman, E Zhang, Z Fradkin, J Garfield, S Mayer-Davis, E Moran, RR Ganiats, T Sarkin, AJ AF Bray, G. A. Chatellier, A. Duncan, C. Greenway, F. L. Levy, E. Ryan, D. H. Polonsky, K. S. Tobian, J. Ehrmann, D. Matulik, M. J. Clark, B. Czech, K. DeSandre, C. Hilbrich, R. McNabb, W. Semenske, A. R. Goldstein, B. J. Smith, K. A. Wildman, W. Pepe, C. Goldberg, R. B. Calles, J. Ojito, J. Castillo-Florez, S. Florez, H. J. Giannella, A. Lara, O. Veciana, B. Haffner, S. M. Montez, M. G. Lorenzo, C. Martinez, A. Hamman, R. F. Testaverde, L. Bouffard, A. Dabelea, D. Jenkins, T. Lenz, D. Perreault, L. Price, D. W. Steinke, S. C. Horton, E. S. Poirier, C. S. Swift, K. Caballero, E. Jackson, S. D. Lambert, L. Lawton, K. E. Ledbury, S. Kahn, S. E. Montgomery, B. K. Fujimoto, W. Knopp, R. H. Lipkin, E. W. Marr, M. Murillo, A. Trence, D. Kitabchi, A. E. Murphy, M. E. Applegate, W. B. Bryer-Ash, M. Dagogo-Jack, S. Frieson, S. L. Lambeth, H. Lichtermann, L. C. Otkaei, H. Rutledge, L. M. K. Sherman, A. R. Smith, C. M. Soberman, J. E. Williams-Cleaves, B. Metzger, B. E. Molitch, M. E. Johnson, M. K. Giles, M. M. Larsen, D. Niznik, C. Pen, S. C. Schinleber, P. A. Nathan, D. M. McKitrick, C. Turgeon, H. Abbott, K. Altshuler, D. Anderson, E. Bissett, L. Cagliero, E. D'Anna, K. Delahanty, L. Florez, J. C. Goldman, V. Poulos, A. Tseng, B. Barrett-Connor, E. Carrion-Petersen, M. L. Horne, J. Leos, D. Mudaliar, S. Smith, J. Vejvoda, K. Pi-Sunyer, F. X. Lee, J. E. Foo, S. T. Hagamen, S. Marrero, D. G. Kelly, S. M. Ackermann, R. T. Fineberg, E. S. Hadden, A. Jackson, M. A. Kirkman, M. S. Mather, K. J. Roach, P. J. Wheeler, M. L. Ratner, R. E. Aroda, V. Shapiro, S. Bavido-Arrage, C. Gibbs, P. Uwaifo, Gl Wiggins, R. Saad, M. F. Watson, K. Botrous, M. Jinagouda, S. Budget, M. Conzues, C. Magpuri, P. Ngo, K. Xapthalamous, K. White, N. H. Das, S. Santiago, A. Brown, A. L. Wernimont, C. Saudek, C. D. Whittington, T. Clark, J. M. Greene, A. Jiggetts, D. Mosley, H. Reusing, J. Rubin, R. R. Stephen, S. Utsey, E. Schade, D. S. Adams, K. S. Hemphill, C. Hyde, P. Butler, L. Canady, J. L. Colleran, K. Gonzales, Y. Hernandez-McGinnis, D. A. Katz, P. King, C. Crandall, J. Brown-Friday, J. O. Adorno, E. Duffy, H. Martinez, H. Pompi, D. Shamoon, H. Walker, E. A. Wylie-Rosett, J. Orchard, T. Jeffries, S. Kramer, M. K. Smith, M. Kriska, A. Pettigrew, J. Semler, L. Venditti, E. Weinzierl, V. Arakaki, R. F. Baker-Ladao, N. K. Isonaga, M. K. Bermudez, N. E. Mau, M. K. Knowler, W. C. Cooeyate, N. Hoskin, M. A. Natewa, C. Percy, C. A. Acton, K. J. Andre, V. L. Begay, S. Bucca, B. C. Cook, S. Doughty, M. S. Glass, J. Glass, M. Hanson, R. L. Hassenpflug, D. Ingraham, L. E. Kobus, K. M. Krakoff, J. Manus, C. McCabe, C. Michaels, S. Morgan, T. Nelson, J. A. Roy, R. J. Smart, M. Tonemah, D. P. Wilson, C. Fowler, S. Brenneman, T. Abebe, S. Bamdad, J. Callaghan, J. Christophi, C. A. Edelstein, S. L. Gao, Y. Gooding, R. Gottlieb, A. Grover, N. Hoffman, H. Jablonski, K. Katz, R. Kolinjivadi, P. Lachin, J. M. Ma, Y. Reamer, S. Sapozhnikova, A. Sherif, H. Temprosa, M. Venditti, E. M. Kriska, A. M. Semler, L. Weinzierl, V. Marcovina, S. Strylewicz, G. Albers, J. Prineas, R. J. Alexander, T. Campbell, C. Hall, S. Hensley, S. Li, Y. Mills, M. Soliman, E. Zhang, Z. Fradkin, J. Garfield, S. Mayer-Davis, E. Moran, R. R. Ganiats, T. Sarkin, A. J. CA Diabet Prevention Program Res Grp TI 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study SO LANCET LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; LIFE-STYLE INTERVENTION; COST-EFFECTIVENESS; RISK-FACTORS; METFORMIN; MELLITUS; PEOPLE; TRIAL; REDUCTION; DIAGNOSIS AB Background In the 2.8 years of the Diabetes Prevention Program (DPP) randomised clinical trial, diabetes incidence in high-risk adults was reduced by 58% with intensive lifestyle intervention and by 31% with metformin, compared with placebo. We investigated the persistence of these effects in the long term. Methods All active DPP participants were eligible for continued follow-up. 2766 of 3150 (88%) enrolled for a median additional follow-up of 5.7 years (IQR 5.5-5.8). 910 participants were from the lifestyle, 924 from the metformin, and 932 were from the original placebo groups. On the basis of the benefits from the intensive lifestyle intervention in the DPP, all three groups were offered group-implemented lifestyle intervention. Metformin treatment was continued in the original metformin group (850 mg twice daily as tolerated), with participants unmasked to assignment, and the original lifestyle intervention group was offered additional lifestyle support. The primary outcome was development of diabetes according to American Diabetes Association criteria. Analysis was by intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT00038727. Findings During the 10.0-year (IQR 9.0-10.5) follow-up since randomisation to DPP, the original lifestyle group lost, then partly regained weight. The modest weight loss with metformin was maintained. Diabetes incidence rates during the DPP were 4.8 cases per 100 person-years (95% CI 4.1-5.7) in the intensive lifestyle intervention group, 7.8 (6.8-8.8) in the metformin group, and 11.0 (9.8-12.3) in the placebo group. Diabetes incidence rates in this follow-up study were similar between treatment groups: 5.9 per 100 person-years (5.1-6.8) for lifestyle, 4.9 (4.2-5.7) for metformin, and 5.6 (4.8-6.5) for placebo. Diabetes incidence in the 10 years since DPP randomisation was reduced by 34% (24-42) in the lifestyle group and 18% (7-28) in the metformin group compared with placebo. Interpretation During follow-up after DPP, incidences in the former placebo and metformin groups fell to equal those in the former lifestyle group, but the cumulative incidence of diabetes remained lowest in the lifestyle group. Prevention or delay of diabetes with lifestyle intervention or metformin can persist for at least 10 years. C1 [Bray, G. A.; Fowler, S.; Brenneman, T.; Abebe, S.; Bamdad, J.; Callaghan, J.; Christophi, C. A.; Edelstein, S. L.; Gao, Y.; Gooding, R.; Gottlieb, A.; Grover, N.; Hoffman, H.; Jablonski, K.; Katz, R.; Kolinjivadi, P.; Lachin, J. M.; Ma, Y.; Reamer, S.; Sapozhnikova, A.; Sherif, H.; Temprosa, M.] George Washington Univ, Diabet Prevent Program Coordinating Ctr, Ctr Biostat, Rockville, MD 20852 USA. [Bray, G. A.; Chatellier, A.; Duncan, C.; Greenway, F. L.; Levy, E.; Ryan, D. H.] Pennington Biomed Res Ctr, Baton Rouge, LA USA. [Polonsky, K. S.; Tobian, J.; Ehrmann, D.; Matulik, M. J.; Clark, B.; Czech, K.; DeSandre, C.; Hilbrich, R.; McNabb, W.; Semenske, A. R.] Univ Chicago, Chicago, IL 60637 USA. [Goldstein, B. J.; Smith, K. A.; Wildman, W.; Pepe, C.] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. [Goldberg, R. B.; Calles, J.; Ojito, J.; Castillo-Florez, S.; Florez, H. J.; Giannella, A.; Lara, O.; Veciana, B.] Univ Miami, Miami, FL USA. [Haffner, S. M.; Montez, M. G.; Lorenzo, C.; Martinez, A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Hamman, R. F.; Testaverde, L.; Bouffard, A.; Dabelea, D.; Jenkins, T.; Lenz, D.; Perreault, L.; Price, D. W.; Steinke, S. C.] Univ Colorado, Denver, CO 80202 USA. [Horton, E. S.; Poirier, C. S.; Swift, K.; Caballero, E.; Jackson, S. D.; Lambert, L.; Lawton, K. E.; Ledbury, S.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Kahn, S. E.; Montgomery, B. K.; Fujimoto, W.; Knopp, R. H.; Lipkin, E. W.; Marr, M.; Murillo, A.; Trence, D.] Univ Washington, Seattle, WA 98195 USA. [Kitabchi, A. E.; Murphy, M. E.; Applegate, W. B.; Bryer-Ash, M.; Dagogo-Jack, S.; Frieson, S. L.; Lambeth, H.; Lichtermann, L. C.; Otkaei, H.; Rutledge, L. M. K.; Sherman, A. R.; Smith, C. M.; Soberman, J. E.; Williams-Cleaves, B.] Univ Tennessee, Memphis, TN USA. [Metzger, B. E.; Molitch, M. E.; Johnson, M. K.; Giles, M. M.; Larsen, D.; Niznik, C.; Pen, S. C.; Schinleber, P. A.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Nathan, D. M.; McKitrick, C.; Turgeon, H.; Abbott, K.; Altshuler, D.; Anderson, E.; Bissett, L.; Cagliero, E.; D'Anna, K.; Delahanty, L.; Florez, J. C.; Goldman, V.; Poulos, A.; Tseng, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Barrett-Connor, E.; Carrion-Petersen, M. L.; Horne, J.; Leos, D.; Mudaliar, S.; Smith, J.; Vejvoda, K.] Univ Calif San Diego, San Diego, CA 92103 USA. [Pi-Sunyer, F. X.; Lee, J. E.; Foo, S. T.; Hagamen, S.] St Lukes Roosevelt Hosp, New York, NY 10025 USA. [Marrero, D. G.; Kelly, S. M.; Ackermann, R. T.; Fineberg, E. S.; Hadden, A.; Jackson, M. A.; Kirkman, M. S.; Mather, K. J.; Roach, P. J.; Wheeler, M. L.] Indiana Univ, Indianapolis, IN 46204 USA. [Ratner, R. E.; Aroda, V.; Shapiro, S.; Bavido-Arrage, C.; Gibbs, P.; Uwaifo, Gl; Wiggins, R.] Medstar Res Inst, Washington, DC USA. [Saad, M. F.; Watson, K.; Botrous, M.; Jinagouda, S.; Budget, M.; Conzues, C.; Magpuri, P.; Ngo, K.; Xapthalamous, K.] Univ Calif Los Angeles, Univ So Calif, Res Ctr, Alhambra, CA USA. [White, N. H.; Das, S.; Santiago, A.; Brown, A. L.; Wernimont, C.] Washington Univ, St Louis, MO USA. [Saudek, C. D.; Whittington, T.; Clark, J. M.; Greene, A.; Jiggetts, D.; Mosley, H.; Reusing, J.; Rubin, R. R.; Stephen, S.; Utsey, E.] Johns Hopkins Sch Med, Baltimore, MD USA. [Schade, D. S.; Adams, K. S.; Hemphill, C.; Hyde, P.; Butler, L.; Canady, J. L.; Colleran, K.; Gonzales, Y.; Hernandez-McGinnis, D. A.; Katz, P.; King, C.] Univ New Mexico, Albuquerque, NM 87131 USA. [Crandall, J.; Brown-Friday, J. O.; Adorno, E.; Duffy, H.; Martinez, H.; Pompi, D.; Shamoon, H.; Walker, E. A.; Wylie-Rosett, J.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Orchard, T.; Jeffries, S.; Kramer, M. K.; Smith, M.; Kriska, A.; Pettigrew, J.; Semler, L.; Venditti, E.; Weinzierl, V.] Univ Pittsburgh, Pittsburgh, PA USA. [Arakaki, R. F.; Baker-Ladao, N. K.; Isonaga, M. K.; Bermudez, N. E.; Mau, M. K.] Univ Hawaii, Honolulu, HI 96822 USA. [Knowler, W. C.; Cooeyate, N.; Hoskin, M. A.; Natewa, C.; Percy, C. A.; Acton, K. J.; Andre, V. L.; Begay, S.; Bucca, B. C.; Cook, S.; Doughty, M. S.; Glass, J.; Glass, M.; Hanson, R. L.; Hassenpflug, D.; Ingraham, L. E.; Kobus, K. M.; Krakoff, J.; Manus, C.; McCabe, C.; Michaels, S.; Morgan, T.; Nelson, J. A.; Roy, R. J.; Smart, M.; Tonemah, D. P.; Wilson, C.] SW Amer Indian Ctr, Phoenix, AZ USA. [Knowler, W. C.; Cooeyate, N.; Hoskin, M. A.; Natewa, C.; Percy, C. A.; Acton, K. J.; Andre, V. L.; Begay, S.; Bucca, B. C.; Cook, S.; Doughty, M. S.; Glass, J.; Glass, M.; Hanson, R. L.; Hassenpflug, D.; Ingraham, L. E.; Kobus, K. M.; Krakoff, J.; Manus, C.; McCabe, C.; Michaels, S.; Morgan, T.; Nelson, J. A.; Roy, R. J.; Smart, M.; Tonemah, D. P.; Wilson, C.] SW Amer Indian Ctr, Shiprock, NM USA. [Knowler, W. C.; Cooeyate, N.; Hoskin, M. A.; Natewa, C.; Percy, C. A.; Acton, K. J.; Andre, V. L.; Begay, S.; Bucca, B. C.; Cook, S.; Doughty, M. S.; Glass, J.; Glass, M.; Hanson, R. L.; Hassenpflug, D.; Ingraham, L. E.; Kobus, K. M.; Krakoff, J.; Manus, C.; McCabe, C.; Michaels, S.; Morgan, T.; Nelson, J. A.; Roy, R. J.; Smart, M.; Tonemah, D. P.; Wilson, C.] SW Amer Indian Ctr, Zuni, NM USA. [Marcovina, S.; Strylewicz, G.; Albers, J.] Cent Biochem Lab, Seattle, WA USA. [Prineas, R. J.; Alexander, T.; Campbell, C.; Hall, S.; Hensley, S.; Li, Y.; Mills, M.; Soliman, E.; Zhang, Z.] Epidemiol Cardiol Res Ctr Epicare, Winston Salem, NC USA. [Fradkin, J.; Garfield, S.] NIDDK, NIH, Bethesda, MD USA. [Mayer-Davis, E.; Moran, R. R.] Nutr Coding Ctr, Columbia, SC USA. [Ganiats, T.; Sarkin, A. J.] Qual Well Being Ctr, La Jolla, CA USA. RP Bray, GA (reprint author), George Washington Univ, Diabet Prevent Program Coordinating Ctr, Ctr Biostat, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA. EM dppmail@biostat.bsc.gwu.edu RI Altshuler, David/A-4476-2009; Uwaifo, Gabriel/M-2361-2016 OI Altshuler, David/0000-0002-7250-4107; Uwaifo, Gabriel/0000-0002-6962-9304 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health FX This study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) as a cooperative agreement. We thank the participants of the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study for their commitment and dedication; the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health for funding to the clinical and coordinating centres that designed and undertook the study, and collected, managed, analysed and interpreted the data; and the General Clinical Research Center Program and the National Center for Research Resources for support of data collection at many of the clinical centres. The Southwestern American Indian Centers were supported directly by the NIDDK, including its Intramural Research Program, and by the Indian Health Service. Funding was also provided by the National Institute of Child Health and Human Development, the National Institute on Aging, the National Eye Institute, the National Heart Lung and Blood Institute, the Office of Women's Health, the National Center for Minority Health and Human Disease, the Centers for Disease Control and Prevention, and the American Diabetes Association. Lipha (Merck-Sante) provided medicines, and LifeScan donated materials. The opinions expressed are those of the investigators and do not necessarily reflect the views of the funding agencies. NR 28 TC 800 Z9 806 U1 12 U2 82 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD NOV 14 PY 2009 VL 374 IS 9702 BP 1677 EP 1686 DI 10.1016/S0140-6736(09)61457-4 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 522LP UT WOS:000271999700023 ER PT J AU Landi, MT Chatterjee, N Yu, K Goldin, LR Goldstein, AM Rotunno, M Mirabello, L Jacobs, K Wheeler, W Yeager, M Bergen, AW Li, QZ Consonni, D Pesatori, AC Wacholder, S Thun, M Diver, R Oken, M Virtamo, J Albanes, D Wang, ZM Burdette, L Doheny, KF Pugh, EW Laurie, C Brennan, P Hung, R Gaborieau, V McKay, JD Lathrop, M McLaughlin, J Wang, Y Tsao, MS Spitz, MR Wang, YF Krokan, H Vatten, L Skorpen, F Arnesen, E Benhamou, S Bouchard, C Metsapalu, A Vooder, T Nelis, M Valk, K Field, JK Chen, C Goodman, G Sulem, P Thorleifsson, G Rafnar, T Eisen, T Sauter, W Rosenberger, A Bickeboller, H Risch, A Chang-Claude, J Wichmann, HE Stefansson, K Houlston, R Amos, CI Fraumeni, JF Savage, SA Bertazzi, PA Tucker, MA Chanock, S Caporaso, NE AF Landi, Maria Teresa Chatterjee, Nilanjan Yu, Kai Goldin, Lynn R. Goldstein, Alisa M. Rotunno, Melissa Mirabello, Lisa Jacobs, Kevin Wheeler, William Yeager, Meredith Bergen, Andrew W. Li, Qizhai Consonni, Dario Pesatori, Angela C. Wacholder, Sholom Thun, Michael Diver, Ryan Oken, Martin Virtamo, Jarmo Albanes, Demetrius Wang, Zhaoming Burdette, Laurie Doheny, Kimberly F. Pugh, Elizabeth W. Laurie, Cathy Brennan, Paul Hung, Rayjean Gaborieau, Valerie McKay, James D. Lathrop, Mark McLaughlin, John Wang, Ying Tsao, Ming-Sound Spitz, Margaret R. Wang, Yufei Krokan, Hans Vatten, Lars Skorpen, Frank Arnesen, Egil Benhamou, Simone Bouchard, Christine Metsapalu, Andres Vooder, Tonu Nelis, Mari Vaelk, Kristian Field, John K. Chen, Chu Goodman, Gary Sulem, Patrick Thorleifsson, Gudmar Rafnar, Thorunn Eisen, Timothy Sauter, Wiebke Rosenberger, Albert Bickeboeller, Heike Risch, Angela Chang-Claude, Jenny Wichmann, H. Erich Stefansson, Kari Houlston, Richard Amos, Christopher I. Fraumeni, Joseph F., Jr. Savage, Sharon A. Bertazzi, Pier Alberto Tucker, Margaret A. Chanock, Stephen Caporaso, Neil E. TI A Genome-wide Association Study of Lung Cancer Identifies a Region of Chromosome 5p15 Associated with Risk for Adenocarcinoma SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID TELOMERASE REVERSE-TRANSCRIPTASE; IDIOPATHIC PULMONARY-FIBROSIS; SUSCEPTIBILITY LOCUS; FAMILY-HISTORY; MUTATIONS; VARIANTS; POPULATION; EXPRESSION; TERT; METAANALYSIS AB Three genetic loci for lung cancer risk have been identified by genome-wide association studies (GWAS), but inherited susceptibility to specific histologic types of king cancer is not well established. We conducted a GWAS of lung cancer and its major histologic types, genotyping 515,922 single-nucleotide polymorphisms (SNPs) in 5739 lung cancer cases and 5848 controls from one population-based case-control study and three cohort studies. Results were combined with summary data from ten additional studies, for a total of 13,300 cases and 19,666 controls of European descent. Four Studies also provided histology data for replication, resulting in 3333 adenocarcinomas (AD), 2589 squamous cell carcinomas (SQ), and 1418 small cell carcinomas (SQ. In analyses by histology, rs2736100 (TERT), on chromosome 5p15.33, was associated with risk of adenocarcinoma (odds ratio [OR] = 1.23, 95% confidence interval [CI] = 1.13-1.33, p = 3.02 x 10(-7)), but not with other histologic types (OR = 1.01, p = 0.84 and OR = 1.00, p = 0.93 for SQ and SC, respectively). This finding was confirmed in each replication study and overall meta-analysis (OR = 1.24, 95% CI = 1.17-1.31, p = 3.74 x 10(-14) for AD; OR = 0.99, p = 0.69 and OR = 0.97, p = 0.48 for SQ and SC, respectively). Other previously reported association signals on 15q25 and 6p21 were also refined, but no additional loci reached genome-wide significance. In conclusion, a lung cancer GWAS identified a distinct hereditary contribution to adenocarcinoma. C1 [Landi, Maria Teresa; Chatterjee, Nilanjan; Yu, Kai; Goldin, Lynn R.; Goldstein, Alisa M.; Rotunno, Melissa; Mirabello, Lisa; Jacobs, Kevin; Yeager, Meredith; Li, Qizhai; Wacholder, Sholom; Albanes, Demetrius; Wang, Zhaoming; Burdette, Laurie; Fraumeni, Joseph F., Jr.; Savage, Sharon A.; Tucker, Margaret A.; Chanock, Stephen; Caporaso, Neil E.] NCI, Div Canc Epidemiol, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Wheeler, William] Informat Management Serv Inc, Rockville, MD 20852 USA. [Bergen, Andrew W.] SRI Int, Ctr Hlth Sci, Mol Genet program, Menlo Pk, CA 94025 USA. [Li, Qizhai] Chinese Acad Sci, Acad Math & Syst Sci, Key Lab Syst & Control, Beijing 100190, Peoples R China. [Consonni, Dario; Pesatori, Angela C.; Bertazzi, Pier Alberto] Osped Maggiore Policlin Mangiagalli & Regina Elen, Fdn Ist Ricevero & Cura Carattere Sci, Epidemiol Unit, I-20122 Milan, Italy. [Consonni, Dario; Pesatori, Angela C.; Bertazzi, Pier Alberto] Univ Milan, Dept Occupat & Environm Hlth, I-20122 Milan, Italy. [Thun, Michael; Diver, Ryan] Amer Canc Soc Epidemiol & Surveillance Res, Atlanta, GA 30301 USA. [Oken, Martin] Univ Minnesota, Hubert H Humphrey Canc Ctr, Minneapolis, MN 55455 USA. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki 00280, Finland. [Doheny, Kimberly F.; Pugh, Elizabeth W.] Johns Hopkins Univ, Sch Med, Inst Med Genet, Ctr Inherited Dis Res, Baltimore, MD 21224 USA. [Laurie, Cathy] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Brennan, Paul; Gaborieau, Valerie; McKay, James D.] Int Agcy Res Canc, F-69372 Lyon, France. [Hung, Rayjean; McLaughlin, John; Wang, Ying] Univ Toronto, Dalla Lana Sch Publ Hlth, Div Epidemiol, Samuel Lunenfeld Res Inst, Toronto, ON M5T 3L9, Canada. [Lathrop, Mark; Benhamou, Simone] Fdn Jean Dausset, Ctr Etud Polymorphisme Humain, F-75010 Paris, France. [Tsao, Ming-Sound] Princess Margaret Hosp, Univ Hlth Network, Dept Pathol, Toronto, ON M5T 3L9, Canada. [Spitz, Margaret R.; Amos, Christopher I.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Wang, Yufei; Houlston, Richard] Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England. [Krokan, Hans; Vatten, Lars; Skorpen, Frank] Norwegian Univ Sci & Technol, Fac Med, N-7489 Trondheim, Norway. [Arnesen, Egil] Univ Tromso, Dept Community Med, N-9037 Tromso, Norway. [Benhamou, Simone] INSERM, F-75010 Paris, France. [Bouchard, Christine] Geneva Canc Registry, CH-1205 Geneva, Switzerland. [Metsapalu, Andres; Vooder, Tonu; Nelis, Mari; Vaelk, Kristian] Univ Tartu, Inst Mol & Cell Biol, Estonian Bioctr, EE-51010 Tartu, Estonia. [Metsapalu, Andres; Vooder, Tonu; Nelis, Mari; Vaelk, Kristian] Univ Tartu, Estonian Genome Project, Estonian Bioctr, EE-51010 Tartu, Estonia. [Field, John K.] Univ Liverpool, Canc Res Ctr, Roy Castle Lung Canc Res Program, Liverpool L3 97A, Merseyside, England. [Chen, Chu; Goodman, Gary] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98109 USA. [Sulem, Patrick; Thorleifsson, Gudmar; Rafnar, Thorunn; Stefansson, Kari] DeCODE Genet, IS-101 Reykjavik, Iceland. [Eisen, Timothy] Univ Cambridge, Dept Oncol, Cambridge CB2 2RE, England. [Sauter, Wiebke; Wichmann, H. Erich] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Epidemiol, D-85764 Neuherberg, Germany. [Wichmann, H. Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Chair Epidemiol, D-81377 Munich, Germany. [Wichmann, H. Erich] Univ Munich, Klinikum Grosshadern, D-81377 Munich, Germany. [Rosenberger, Albert; Bickeboeller, Heike] Univ Gottingen, Dept Genet Epidemiol, Sch Med, D-37073 Gottingen, Germany. [Risch, Angela; Chang-Claude, Jenny] German Canc Res Ctr, Div Epigenom & Canc Risk Factors, D-69120 Heidelberg, Germany. RP Landi, MT (reprint author), NCI, Div Canc Epidemiol, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM landim@mail.nih.gov RI Hung, Rayjean/A-7439-2013; McLaughlin, John/E-4577-2013; Tucker, Margaret/B-4297-2015; Albanes, Demetrius/B-9749-2015; Savage, Sharon/B-9747-2015; Benhamou, Simone/K-6554-2015; Risch, Angela/H-2669-2013; bertazzi, pietro alberto/D-5039-2017; OI Houlston, Richard/0000-0002-5268-0242; Savage, Sharon/0000-0001-6006-0740; Risch, Angela/0000-0002-8026-5505; bertazzi, pietro alberto/0000-0003-3475-2449; pesatori, angela/0000-0002-0261-3252; Field, John/0000-0003-3951-6365 FU Medical Research Council [G9900432]; NCI NIH HHS [R01 CA127219, R01 CA127219-02, R01 CA127219-04] NR 54 TC 295 Z9 299 U1 2 U2 22 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV 13 PY 2009 VL 85 IS 5 BP 679 EP 691 DI 10.1016/j.ajhg.2009.09.012 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 521JH UT WOS:000271916500014 PM 19836008 ER PT J AU Bhatti, P Kampa, D Alexander, BH McClure, C Ringer, D Doody, MM Sigurdson, AJ AF Bhatti, Parveen Kampa, Diane Alexander, Bruce H. McClure, Christopher Ringer, Danny Doody, Michele M. Sigurdson, Alice J. TI Blood spots as an alternative to whole blood collection and the effect of a small monetary incentive to increase participation in genetic association studies SO BMC MEDICAL RESEARCH METHODOLOGY LA English DT Article ID US RADIOLOGIC TECHNOLOGISTS; DNA BANKING; CANCER AB Background: Collection of buccal cells from saliva for DNA extraction offers a less invasive and convenient alternative to venipuncture blood collection that may increase participation in genetic epidemiologic studies. However, dried blood spot collection, which is also a convenient method, offers a means of collecting peripheral blood samples from which analytes in addition to DNA can be obtained. Methods: To determine if offering blood spot collection would increase participation in genetic epidemiologic studies, we conducted a study of collecting dried blood spot cards by mail from a sample of female cancer cases (n = 134) and controls (n = 256) who were previously selected for a breast cancer genetics study and declined to provide a venipuncture blood sample. Participants were also randomized to receive either a $2.00 bill or no incentive with the blood spot collection kits. Results: The average time between the venipuncture sample refusal and recruitment for the blood spot collection was 4.4 years. Thirty-seven percent of cases and 28% of controls provided a dried blood spot card. While the incentive was not associated with participation among controls (29% for $2.00 incentive vs. 26% for no incentive, p = 0.6), it was significantly associated with participation among the breast cancer cases (48% vs. 27%, respectively, p = 0.01). There did not appear to be any bias in response since no differences between cases and controls and incentive groups were observed when examining several demographic, work history and radiation exposure variables. Conclusion: This study demonstrates that collection of dried blood spot cards in addition to venipuncture blood samples may be a feasible method to increase participation in genetic case-control studies. C1 [Bhatti, Parveen] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98104 USA. [Bhatti, Parveen; Doody, Michele M.; Sigurdson, Alice J.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. [Kampa, Diane; Alexander, Bruce H.] Univ Minnesota, Sch Publ Hlth, Div Environm Hlth Sci, Minneapolis, MN USA. [McClure, Christopher; Ringer, Danny] Res Triangle Inst, Rockville, MD USA. RP Bhatti, P (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, 1124 Columbia St, Seattle, WA 98104 USA. EM pbhatti@fhcrc.org; dkampa@umn.edu; balex@umn.edu; cmcclure@rti.org; dringer@rti.org; doodym@mail.nih.gov; sigurdsa@mail.nih.giv FU Intramural Research Program of the Division of Cancer Epidemiology and Genetics [NO1-CP-31018, NO2-CP-31013, NO2-CP-31003]; National Cancer Institute; National Institutes of Health; Department of Health and Human Services FX We are grateful to the radiologic technologists who participated in the USRT Study; Jerry Reid of the American Registry of Radiologic Technologists for continued support of this study; Allison Iwan of the University of Minnesota for coordinating the blood spot collection and Kim Doeden of Research Triangle International for preparing the blood spot collection pictogram. This study was supported in part by contracts NO1-CP-31018, NO2-CP-31013, and NO2-CP-31003 from the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services. NR 13 TC 11 Z9 12 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2288 J9 BMC MED RES METHODOL JI BMC Med. Res. Methodol. PD NOV 13 PY 2009 VL 9 AR 76 DI 10.1186/1471-2288-9-76 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 527ZH UT WOS:000272409300001 PM 19912630 ER PT J AU Beard, WA Shock, DD Batra, VK Pedersen, LC Wilson, SH AF Beard, William A. Shock, David D. Batra, Vinod K. Pedersen, Lars C. Wilson, Samuel H. TI DNA Polymerase beta Substrate Specificity SIDE CHAIN MODULATION OF THE "A-RULE" SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INDUCED-FIT MECHANISM; ABASIC SITE; STRUCTURAL BASIS; NUCLEOTIDE INCORPORATION; CRYSTAL-STRUCTURES; BASE SUBSTITUTION; TERNARY COMPLEXES; TEMPLATE-PRIMER; MINOR-GROOVE; T-OPPOSITE AB Apurinic/apyrimidinic (AP) sites are continuously generated in genomic DNA. Left unrepaired, AP sites represent noninstructional premutagenic lesions that are impediments to DNA synthesis. When DNA polymerases encounter an AP site, they generally insert dAMP. This preferential insertion is referred to as the A-rule. Crystallographic structures of DNA polymerase (pol) beta, a family X polymerase, with active site mismatched nascent base pairs indicate that the templating (i.e. coding) base is repositioned outside of the template binding pocket thereby diminishing interactions with the incorrect incoming nucleotide. This effectively produces an abasic site because the template pocket is devoid of an instructional base. However, the template pocket is not empty; an arginine residue (Arg-283) occupies the space vacated by the templating nucleotide. In this study, we analyze the kinetics of pol beta insertion opposite an AP site and show that the preferential incorporation of dAMP is lost with the R283A mutant. The crystallographic structures of pol beta bound to gapped DNA with an AP site analog (tertrahydrofuran) in the gap (binary complex) and with an incoming nonhydrolyzable dATP analog (ternary complex) were solved. These structures reveal that binding of the dATP analog induces a closed polymerase conformation, an unstable primer terminus, and an upstream shift of the templating residue even in the absence of a template base. Thus, dATP insertion opposite an abasic site and dATP misinsertions have common features. C1 [Beard, William A.; Shock, David D.; Batra, Vinod K.; Pedersen, Lars C.; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, 111 TW Alexander Dr,POB 12233,MD F3-01, Res Triangle Pk, NC 27709 USA. EM wilson5@niehs.nih.gov FU National Institutes of Health, NIEHS [Z01-ES0500158, Z01-ES050161]; National Institutes of Health [1U19CA105010] FX This work was supported, in whole or in part, by Research Projects Z01-ES0500158 and Z01-ES050161 (to S. H. W.) in the Intramural Research Program, National Institutes of Health, NIEHS, and was in association with National Institutes of Health Grant 1U19CA105010. NR 62 TC 32 Z9 32 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 13 PY 2009 VL 284 IS 46 BP 31680 EP 31689 DI 10.1074/jbc.M109.029843 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 516VZ UT WOS:000271572700023 PM 19759017 ER PT J AU Pletnev, S Gurskaya, NG Pletneva, NV Lukyanov, KA Chudakov, DM Martynov, VI Popov, VO Kovalchuk, MV Wlodawer, A Dauter, Z Pletnev, V AF Pletnev, Sergei Gurskaya, Nadya G. Pletneva, Nadya V. Lukyanov, Konstantin A. Chudakov, Dmitri M. Martynov, Vladimir I. Popov, Vladimir O. Kovalchuk, Mikhail V. Wlodawer, Alexander Dauter, Zbigniew Pletnev, Vladimir TI Structural Basis for Phototoxicity of the Genetically Encoded Photosensitizer KillerRed SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RED FLUORESCENT PROTEIN; INTERNAL WATER CHAIN; IN-VIVO; CRYSTAL-STRUCTURE; ELECTRON-TRANSFER; CHROMOPHORE FORMATION; MONOMERIC RED; CYTOCHROME F; CANCER-CELLS; WHOLE-BODY AB KillerRed is the only known fluorescent protein that demonstrates notable phototoxicity, exceeding that of the other green and red fluorescent proteins by at least 1,000-fold. KillerRed could serve as an instrument to inactivate target proteins or to kill cell populations in photodynamic therapy. However, the nature of KillerRed phototoxicity has remained unclear, impeding the development of more phototoxic variants. Here we present the results of a high resolution crystallographic study of KillerRed in the active fluorescent and in the photobleached non-fluorescent states. A unique and striking feature of the structure is a water-filled channel reaching the chromophore area from the end cap of the beta-barrel that is probably one of the key structural features responsible for phototoxicity. A study of the structure-function relationship of KillerRed, supported by structure-based, site-directed mutagenesis, has also revealed the key residues most likely responsible for the phototoxic effect. In particular, Glu(68) and Ser(119), located adjacent to the chromophore, have been assigned as the primary trigger of the reaction chain. C1 [Dauter, Zbigniew] NCI, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, SAIC Frederick Inc, Argonne, IL 60439 USA. [Gurskaya, Nadya G.; Pletneva, Nadya V.; Lukyanov, Konstantin A.; Chudakov, Dmitri M.; Martynov, Vladimir I.; Pletnev, Vladimir] Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow 117997, Russia. [Popov, Vladimir O.] Russian Acad Sci, AN Bach Inst Biochem, Moscow 117234, Russia. [Kovalchuk, Mikhail V.] Russian Acad Sci, Inst Crystallog, Moscow 119333, Russia. [Wlodawer, Alexander] NCI, Prot Struct Sect, Macromol Crystallog Lab, NIH, Frederick, MD 21702 USA. RP Pletnev, S (reprint author), SAIC Frederick Inc, Basic Res Program, Argonne, IL 60439 USA. EM svp@ncifcrf.gov RI Chudakov, Dmitriy/G-7741-2014; Pletneva, Nadya/F-7839-2014; Pletnev, Vladimir/Q-6151-2016; Martynov, Vladimir/S-3483-2016 OI Chudakov, Dmitriy/0000-0003-0430-790X; Martynov, Vladimir/0000-0003-4923-6842 FU National Institutes of Health Intramural Research Program, NCI, Center for Cancer Research; National Institutes of Health, NCI [HHSN2612008000001E]; Russian Foundation for Basic Research [07-04-00054, 08-04-01702-a]; Russian Federal Agency for Science and Innovations [02.513.12.3013]; Molecular and Cell Biology Program RAS; President of the Russian Federation [MD-2780.2009.4]; United States Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38] FX This work was supported, in whole or in part, by the National Institutes of Health Intramural Research Program, NCI, Center for Cancer Research and by National Institutes of Health, NCI, Contract HHSN2612008000001E. This project was also supported in part by Russian Foundation for Basic Research Grants 07-04-00054 and 08-04-01702-a; by Russian Federal Agency for Science and Innovations Grant 02.513.12.3013; by the Molecular and Cell Biology Program RAS; and by grants from the President of the Russian Federation (MD-2780.2009.4). Use of the Advanced Photon Source was supported by the United States Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract W-31-109-Eng-38. NR 58 TC 61 Z9 63 U1 0 U2 14 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 13 PY 2009 VL 284 IS 46 BP 32028 EP 32039 DI 10.1074/jbc.M109.054973 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 516VZ UT WOS:000271572700058 PM 19737938 ER PT J AU Wang, H Hu, LP Dalen, K Dorward, H Marcinkiewicz, A Russell, D Gong, DW Londos, C Yamaguchi, T Holm, C Rizzo, MA Brasaemle, D Sztalryd, C AF Wang, Hong Hu, Liping Dalen, Knut Dorward, Heidi Marcinkiewicz, Amy Russell, Deanna Gong, Dawei Londos, Constantine Yamaguchi, Tomohiro Holm, Cecilia Rizzo, Mark A. Brasaemle, Dawn Sztalryd, Carole TI Activation of Hormone-sensitive Lipase Requires Two Steps, Protein Phosphorylation and Binding to the PAT-1 Domain of Lipid Droplet Coat Proteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADIPOSE TRIGLYCERIDE LIPASE; FLUORESCENCE POLARIZATION MICROSCOPY; A-MEDIATED LIPOLYSIS; PERILIPIN-A; ENDOPLASMIC-RETICULUM; STIMULATED LIPOLYSIS; ADIPOCYTE LIPOLYSIS; 3T3-L1 ADIPOCYTES; STORAGE DROPLET; ALPHA-SYNUCLEIN AB Lipolysis is an important metabolic pathway controlling energy homeostasis through degradation of triglycerides stored in lipid droplets and release of fatty acids. Lipid droplets of mammalian cells are coated with one or more members of the PAT protein family, which serve important functions in regulating lipolysis. In this study, we investigate the mechanisms by which PAT family members, perilipin A, adipose differentiation-related protein (ADFP), and LSDP5, control lipolysis catalyzed by hormone-sensitive lipase (HSL), a major lipase in adipocytes and several non-adipose cells. We applied fluorescence microscopic tools to analyze proteins in situ in cultured Chinese hamster ovary cells using fluorescence recovery after photo-bleaching and anisotropy Forster resonance energy transfer. Fluorescence recovery after photobleaching data show that ADFP and LSDP5 exchange between lipid droplet and cytoplasmic pools, whereas perilipin A does not. Differences in protein mobility do not correlate with PAT protein-mediated control of lipolysis catalyzed by HSL or endogenous lipases. Forster resonance energy transfer and co-immunoprecipitation experiments reveal that each of the three PAT proteins bind HSL through interaction of the lipase with amino acids within the highly conserved amino-terminal PAT-1 domain. ADFP and LSDP5 bind HSL under basal conditions, whereas phosphorylation of serine residues within three amino-terminal protein kinase A consensus sequences of perilipin A is required for HSL binding and maximal lipolysis. Finally, protein kinase A-mediated phosphorylation of HSL increases lipolysis in cells expressing ADFP or LSDP5; in contrast, phosphorylation of perilipin A exerts the major control over HSL-mediated lipolysis when perilipin is the main lipid droplet protein. C1 [Wang, Hong; Hu, Liping; Gong, Dawei; Sztalryd, Carole] Univ Maryland, Sch Med, Dept Med, Div Endocrinol, Baltimore, MD 21201 USA. [Wang, Hong; Hu, Liping; Sztalryd, Carole] Univ Maryland, Sch Med, Baltimore Vet Affairs Hlth Care Ctr, Geriatr Res Educ & Clin Ctr, Baltimore, MD 21201 USA. [Dalen, Knut; Dorward, Heidi; Londos, Constantine; Rizzo, Mark A.] NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. [Marcinkiewicz, Amy; Russell, Deanna; Brasaemle, Dawn] Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ 08901 USA. [Holm, Cecilia] Lund Univ, Dept Expt Med Sci, SE-22184 Lund, Sweden. [Rizzo, Mark A.] Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. [Yamaguchi, Tomohiro] Hyogo Med Univ, Grad Sch Life Sci, Kamigori, Hyogo 6781297, Japan. RP Sztalryd, C (reprint author), Univ Maryland, Sch Med, Dept Med, Div Endocrinol, Rm 445,Howard Hall,660 W Redwood St, Baltimore, MD 21201 USA. EM csztalry@grecc.umaryland.edu RI Dalen, Knut Tomas/C-4719-2016; OI Dalen, Knut Tomas/0000-0002-0270-5982; Brasaemle, Dawn/0000-0002-8553-8285 FU National Institutes of Health [RO1 DK075017, RO1 DK054797]; NIDDK Intramural Research Programs; American Diabetes Association [1-05-CD-17]; Geriatric Research, Education, and Clinical Center, Baltimore Veterans Affairs Health Care Center; Clinical Nutrition Research Unit of Maryland [DK072488] FX This work was supported, in whole or in part, by National Institutes of Health Grants RO1 DK075017 (to C. S.) and RO1 DK054797 (to D. L. B.) and NIDDK Intramural Research Programs. This work was also supported by Career Development Award 1-05-CD-17 from the American Diabetes Association (to C. S.), the Geriatric Research, Education, and Clinical Center, Baltimore Veterans Affairs Health Care Center, and the Clinical Nutrition Research Unit of Maryland Grant DK072488. NR 44 TC 77 Z9 80 U1 0 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 13 PY 2009 VL 284 IS 46 BP 32116 EP 32125 DI 10.1074/jbc.M109.006726 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 516VZ UT WOS:000271572700066 PM 19717842 ER PT J AU McElwee, MK Song, MO Freedman, JH AF McElwee, Matthew K. Song, Min Ok Freedman, Jonathan H. TI Copper Activation of NF-kB Signaling in HepG2 Cells SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE copper; NF-kappa B; HepG2 cells; gene expression; microarray ID KAPPA-B ACTIVATION; HEPATITIS-C VIRUS; TOXIC MILK MOUSE; GENE-EXPRESSION; HEPATOCELLULAR-CARCINOMA; WILSONS-DISEASE; METAL-IONS; IN-VIVO; LIVER; PHOSPHORYLATION AB Copper is a persistent environmental contaminant, and exposure to elevated levels of this transition metal can result in a variety of pathologies. Copper affects the transcription of multiple defense and repair genes to protect against metal-induced pathologies. HepG2 cells were treated with copper under multiple conditions and microarray analyses were previously performed to better understand the mechanisms by which copper affects the transcription of stress-responsive genes. Analysis of the microarray data indicated that copper modulates multiple signal transduction pathways, including those mediated by NF-kappa B. Luciferase assays, quantitative reverse transcription real-time PCR, and chemical inhibition in HepG2 cells validated the microarray results and confirmed that NF-kappa B was activated by stress-inducible concentrations of copper. In addition, two novel NF-kappa B-regulated genes, SRXN1 (sulfiredoxin 1 homolog) and ZFAND2A (zinc-finger, AN1-type domain 2A), were identified. Our results indicate that the activation of NF-kappa B may be important for survival under elevated concentrations of copper. Published by Elsevier Ltd. C1 [McElwee, Matthew K.; Song, Min Ok; Freedman, Jonathan H.] NIEHS, Mol Toxicol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [McElwee, Matthew K.] Duke Univ, Nicholas Sch Environm, Durham, NC 27708 USA. RP Freedman, JH (reprint author), NIEHS, Mol Toxicol Lab, NIH, DHHS, Box 12233,MD E1-05,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM freedma1@niehs.nih.gov FU National Institutes of Health [U19ES011375, P42 ES10356]; National Institutes of Health; National Institute of Environmental Health Sciences [Z01ES102045] FX This work was supported (in part) by National Institutes of Health Grants U19ES011375 and P42 ES10356 and by the Intramural Research Program of the National Institutes of Health and National Institute of Environmental Health Sciences (Z01ES102045). NR 47 TC 24 Z9 24 U1 1 U2 6 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 13 PY 2009 VL 393 IS 5 BP 1013 EP 1021 DI 10.1016/j.jmb.2009.08.077 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 517ER UT WOS:000271596500002 PM 19747488 ER PT J AU Wolf, RC Vasic, N Sambataro, F Hose, A Frasch, K Schmid, M Walter, H AF Wolf, Robert Christian Vasic, Nenad Sambataro, Fabio Hoese, Annett Frasch, Karel Schmid, Markus Walter, Henrik TI Temporally anticorrelated brain networks during working memory performance reveal aberrant prefrontal and hippocampal connectivity in patients with schizophrenia SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE Functional connectivity; Functional magnetic resonance imaging; Hippocampus; Independent component analysis; Prefrontal cortex; Schizophrenia ID ALTERED EFFECTIVE CONNECTIVITY; POSITRON-EMISSION-TOMOGRAPHY; TASK-INDUCED DEACTIVATION; BOLD SIGNAL FLUCTUATIONS; DEFAULT MODE NETWORK; FUNCTIONAL CONNECTIVITY; CORTICAL DYSFUNCTION; CORTEX DYSFUNCTION; FMRI ACTIVATION; DEPRESSION AB Functional neuroimaging studies on cognitive dysfunction in schizophrenia have suggested regional brain activation changes in the dorsolateral prefrontal cortex and the medial temporal lobe. However, less is known about the functional coupling of these areas during cognitive performance. In this study, we used functional magnetic resonance imaging, a verbal working memory (WM) task and multivariate statistical techniques to investigate the functional coupling of temporally anticorrelated neural networks during cognitive processing in patients with schizophrenia (n=16) compared to healthy controls (n=16). Independent component analysis identified 18 independent components (ICs) among which two ICs were selected for further analyses. These ICs included temporally anticorrelated networks which were most highly associated with the delay period of the task in both healthy controls and patients with schizophrenia. Functional network abnormalities in patients with schizophrenia were detected within a "task-positive" lateral frontoparietal network, where increased functional connectivity was found in bilateral dorsolateral prefrontal regions. In addition, aberrant functional coupling of the hippocampal cortex in patients with schizophrenia was detected within a "task-negative" medial frontotemporal network. In patients with schizophrenia, functional connectivity indices in the left dorsolateral prefrontal cortex and the right hippocampal cortex were positively correlated with accuracy during the WM task, while the connectivity strength in the right dorsolateral prefrontal cortex was negatively correlated with measures of symptom severity. These data suggest that within two temporally anticorrelated network states, patients with schizophrenia exhibit increased and persistent dorsolateral prefrontal and hippocampal connectivity during WM performance. (C) 2009 Elsevier Inc. All rights reserved. C1 [Wolf, Robert Christian; Vasic, Nenad; Schmid, Markus] Univ Ulm, Dept Psychiat & Psychotherapy 3, D-89075 Ulm, Germany. [Sambataro, Fabio] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. [Hoese, Annett; Frasch, Karel] Univ Ulm, Dept Psychiat & Psychotherapy 2, Gunzburg, Germany. [Walter, Henrik] Univ Bonn, Div Med Psychol, Dept Psychiat, Bonn, Germany. RP Wolf, RC (reprint author), Univ Ulm, Dept Psychiat & Psychotherapy 3, Leimgrubenweg 12-14, D-89075 Ulm, Germany. EM christian.wolf@uni-ulm.de RI Sambataro, Fabio/E-3426-2010; Walter, Henrik/O-2612-2013; OI Sambataro, Fabio/0000-0003-2102-416X; Frasch, Karel/0000-0003-3308-4258 NR 82 TC 47 Z9 47 U1 3 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD NOV 13 PY 2009 VL 33 IS 8 BP 1464 EP 1473 DI 10.1016/j.pnpbp.2009.07.032 PG 10 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 532RL UT WOS:000272767100023 PM 19666074 ER PT J AU Baskar, S Suschak, JM Samija, I Srinivasan, R Childs, RW Pavletic, SZ Bishop, MR Rader, C AF Baskar, Sivasubramanian Suschak, Jessica M. Samija, Ivan Srinivasan, Ramaprasad Childs, Richard W. Pavletic, Steven Z. Bishop, Michael R. Rader, Christoph TI A human monoclonal antibody drug and target discovery platform for B-cell chronic lymphocytic leukemia based on allogeneic hematopoietic stem cell transplantation and phage display SO BLOOD LA English DT Article ID GRAFT-VERSUS-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; MINOR HISTOCOMPATIBILITY ANTIGEN; BONE-MARROW-TRANSPLANTATION; AFFINITY MATURATION; COMPLETE RESPONSE; MULTIPLE-MYELOMA; IMMUNE-RESPONSES; POTENTIAL TARGET; EXPRESSION AB Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only potentially curative treatment available for patients with B-cell chronic lymphocytic leukemia (B-CLL). Here, we show that post-alloHSCT antibody repertoires can be mined for the discovery of fully human monoclonal antibodies to B-CLL cellsurface antigens. Sera collected from B-CLL patients at defined times after alloHSCT showed selective binding to primary B-CLL cells. Pre-alloHSCT sera, donor sera, and control sera were negative. To identify post-alloHSCT serum antibodies and subsequently B-CLL cell-surface antigens they recognize, we generated a human antibody-binding fragment (Fab) library from post-alloHSCT peripheral blood mononuclear cells and selected it on primary B-CLL cells by phage display. A panel of Fab with B-CLL cell-surface reactivity was strongly enriched. Selection was dominated by highly homologous Fab predicted to bind the same antigen. One Fab was converted to immunoglobulin G1 and analyzed for reactivity with peripheral blood mononuclear cells from B-CLL patients and healthy volunteers. Cell-surface antigen expression was restricted to primary B cells and up-regulated in primary B-CLL cells. Mining post-alloHSCT antibody repertoires offers a novel route to discover fully human monoclonal antibodies and identify antigens of potential therapeutic relevance to B-CLL and possibly other cancers. Trials described herein were registered at www.clinicaltrials.gov as nos. NCT00055744 and NCT00003838. (Blood. 2009;114:4494-4502) C1 [Rader, Christoph] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Srinivasan, Ramaprasad; Childs, Richard W.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Rader, C (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 10 CRC,Rm 3-3150, Bethesda, MD 20892 USA. EM raderc@mail.nih.gov OI Samija, Ivan/0000-0002-5633-5745 FU Intramural Research Program of the Center for Cancer Research; National Cancer Institute, NIH; National Foundation for Science, Higher Education and Technological Development of the Republic of Croatia FX This work was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH (C.R.) and through a stipend from the National Foundation for Science, Higher Education and Technological Development of the Republic of Croatia (I.S.). NR 50 TC 8 Z9 8 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 12 PY 2009 VL 114 IS 20 BP 4494 EP 4502 DI 10.1182/blood-2009-05-222786 PG 9 WC Hematology SC Hematology GA 518WW UT WOS:000271727500022 PM 19667400 ER PT J AU Chang, CC Zhou, XB Taylor, JJ Huang, WT Ren, XW Monzon, F Feng, YD Rao, PH Lu, XY Fabio, F Hilsenbeck, S Creighton, CJ Jaffe, ES Lau, CC AF Chang, Chung-Che Zhou, Xiaobo Taylor, Jesalyn J. Huang, Wan-Ting Ren, Xianwen Monzon, Federico Feng, Yongdong Rao, Pulivarthi H. Lu, Xin-Yan Fabio, Facchetti Hilsenbeck, Susan Creighton, Chad J. Jaffe, Elaine S. Lau, Ching-Ching TI Genomic profiling of plasmablastic lymphoma using array comparative genomic hybridization (aCGH): revealing significant overlapping genomic lesions with diffuse large B-cell lymphoma SO JOURNAL OF HEMATOLOGY & ONCOLOGY LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; ORAL-CAVITY; MICROARRAY; GENES; IDENTIFICATION; EXPRESSION; ERA AB Background: Plasmablastic lymphoma (PL) is a subtype of diffuse large B-cell lymphoma (DLBCL). Studies have suggested that tumors with PL morphology represent a group of neoplasms with clinopathologic characteristics corresponding to different entities including extramedullary plasmablastic tumors associated with plasma cell myeloma (PCM). The goal of the current study was to evaluate the genetic similarities and differences among PL, DLBCL (AIDS-related and non AIDS-related) and PCM using array-based comparative genomic hybridization. Results: Examination of genomic data in PL revealed that the most frequent segmental gain (>40%) include: 1p36.11-1p36.33, 1p34.1-1p36.13, 1q21.1-1q23.1, 7q11.2-7q11.23, 11q12-11q13.2 and 22q12.2-22q13.3. This correlated with segmental gains occurring in high frequency in DLBCL (AIDS-related and non AIDS-related) cases. There were some segmental gains and some segmental loss that occurred in PL but not in the other types of lymphoma suggesting that these foci may contain genes responsible for the differentiation of this lymphoma. Additionally, some segmental gains and some segmental loss occurred only in PL and AIDS associated DLBCL suggesting that these foci may be associated with HIV infection. Furthermore, some segmental gains and some segmental loss occurred only in PL and PCM suggesting that these lesions may be related to plasmacytic differentiation. Conclusion: To the best of our knowledge, the current study represents the first genomic exploration of PL. The genomic aberration pattern of PL appears to be more similar to that of DLBCL (AIDS-related or non AIDS-related) than to PCM. Our findings suggest that PL may remain best classified as a subtype of DLBCL at least at the genome level. C1 [Chang, Chung-Che; Taylor, Jesalyn J.; Monzon, Federico; Feng, Yongdong] Methodist Hosp, Dept Pathol, Houston, TX 77030 USA. [Chang, Chung-Che; Taylor, Jesalyn J.; Monzon, Federico; Feng, Yongdong] Methodist Hosp, Res Inst, Houston, TX 77030 USA. [Chang, Chung-Che; Monzon, Federico] Weill Cornell Med Coll, Dept Pathol, New York, NY USA. [Zhou, Xiaobo; Ren, Xianwen] Methodist Hosp, Dept Bioinformat Core, Houston, TX 77030 USA. [Rao, Pulivarthi H.; Lu, Xin-Yan; Lau, Ching-Ching] Baylor Coll Med, Texas Childrens Canc Ctr, Dept Pediat, Houston, TX 77030 USA. [Fabio, Facchetti] Univ Brescia, Dept Pathol 1, Spedali Civili, Brescia, Italy. [Hilsenbeck, Susan] Dept Med, Houston, TX USA. [Hilsenbeck, Susan; Creighton, Chad J.] Dan L Duncan Canc Ctr, Houston, TX USA. [Creighton, Chad J.] Div Biostat, Houston, TX USA. [Jaffe, Elaine S.] NCI, Dept Hematol, NIH, Bethesda, MD 20892 USA. RP Chang, CC (reprint author), Methodist Hosp, Dept Pathol, Houston, TX 77030 USA. EM jeffchang@tmhs.org; XZhou@tmhs.org; jesalynt@hotmail.com; huang_minnie@hotmail.com; renxwise@gmail.com; FAMonzon@tmhs.org; YFeng@tmhs.org; prao@bcm.edu; xxlu@txccc.org; facchett@med.unibs.it; sgh@bcm.edu; creighto@bcm.edu; ejaffe@mail.nih.gov; clau@txccc.org FU National Institute of Dental and Craniofacial Research, National Institute of Health [DE017086] FX The authors would like to express appreciation to AIDS and Cancer Specimen Resource, National Cancer Institute for providing some specimens for this study. This study was supported by a grant from National Institute of Dental and Craniofacial Research, National Institute of Health (DE017086) (C-C. C.). NR 20 TC 24 Z9 27 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-8722 J9 J HEMATOL ONCOL JI J. Hematol. Oncol. PD NOV 12 PY 2009 VL 2 AR 47 DI 10.1186/1756-8722-2-47 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 528ZE UT WOS:000272484700002 PM 19909553 ER PT J AU Park, KD Morieux, P Salome, C Cotten, SW Reamtong, O Eyers, C Gaskell, SJ Stables, JP Liu, RH Kohn, H AF Park, Ki Duk Morieux, Pierre Salome, Christophe Cotten, Steven W. Reamtong, Onrapak Eyers, Claire Gaskell, Simon J. Stables, James P. Liu, Rihe Kohn, Harold TI Lacosamide Isothiocyanate-Based Agents: Novel Agents To Target and Identify Lacosamide Receptors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID N-BENZYLACETAMIDE DERIVATIVES; GATED SODIUM-CHANNELS; ANTIEPILEPTIC DRUGS; ANTICONVULSANT ACTIVITIES; MEDIATED PHENOMENA; OPIOID RECEPTORS; IRREVERSIBLE LIGANDS; AFFINITY LIGANDS; AMINO-ACIDS; BENZODIAZEPINE-RECEPTORS AB (R)-Lacosamide ((R)-2, (R)-N-benzyl 2-acetamido-3-methoxypropionamide) has recently gained regulatory approval for the treatment of partial-onset seizures in adults. Whole animal pharmacological studies have documented that (R)-2 function is unique: A robust strategy is advanced for the discovery of interacting proteins associated with function and toxicity of (R)-2 through the use of (R)-2 analogues, 3, which contain "affinity bait (AB)" and "chemical reporter (CR)" functional groups. In 3, covalent modification of the interacting proteins proceeds at the AB moiety, and detection or isolation of the selectively captured protein occurs through the bioorthogonal CR group upon reaction with all appropriate probe. We report the synthesis, pharmacological evaluation, and interrogation of the mouse soluble brain proteome using 3 where the AB group is an isothiocyanate moiety. One compound, (R)-N-(4-isothiocyanato)benzyl 2-acetamido-3-(prop-2-ynyloxy)propionamide ((R)-9), exhibited excellent Seizure protection in mice, and like (R)-2, anticonvulsant activity principally resided in the (R)-stereoisomer. Several proteins were preferentially labeled by (R)-9 compared with (S)-9, including collapsin response mediator protein 2. C1 [Park, Ki Duk; Morieux, Pierre; Salome, Christophe; Cotten, Steven W.; Liu, Rihe; Kohn, Harold] Univ N Carolina, Div Med Chem & Nat Prod, Eshelman Sch Pharm, Chapel Hill, NC 27599 USA. [Reamtong, Onrapak; Eyers, Claire; Gaskell, Simon J.] Univ Manchester, Manchester Interdisciplinary Bioctr, Michael Barber Ctr Mass Spectrometry, Manchester M1 7DN, Lancs, England. [Stables, James P.] NINDS, Anticonvulsant Screening Program, NIH, Rockville, MD 20892 USA. [Liu, Rihe] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA. [Kohn, Harold] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. RP Liu, RH (reprint author), Univ N Carolina, Div Med Chem & Nat Prod, Eshelman Sch Pharm, Chapel Hill, NC 27599 USA. EM rliu@email.unc.edu; hkohn@email.unc.edu RI Eyers, Claire/C-6291-2013 OI Eyers, Claire/0000-0002-3223-5926 FU NINDS and the Anticonvulsant Screening Program (ASP) at the National Institutes of Health; National Institute of Netll-ological Disorders and Stroke [R01NS054112, F31NS060358]; Korean Government (MOEHRD) [KRF-2006-352-C00042] FX The authors thank the NINDS and the Anticonvulsant Screening Program (ASP) at the National Institutes of Health for kindly performing the pharmacological studies via the ASP's contract site at the University of Utah with Drs. H. Wolfe, H. S. White, and K. Wilcox. Funds for this study was generously provided by Grants R01NS054112 (H.K., R.L.) and F31NS060358 (P.M.) from the National Institute of Netll-ological Disorders and Stroke and by the Korean Research Foundation Grant funded by the Korean Government (MOEHRD) Grant KRF-2006-352-C00042 (K.D.P.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Neurological Disorders and Stroke of- the National Institutes of Health. Harold Kohn has a royalty-stake position in (R)-2. NR 85 TC 29 Z9 30 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD NOV 12 PY 2009 VL 52 IS 21 BP 6897 EP 6911 DI 10.1021/jm9012054 PG 15 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 514WW UT WOS:000271427900041 PM 19795888 ER PT J AU Scott, I AF Scott, Iain TI No special cases in efforts to stop immigration fraud SO NATURE LA English DT Letter C1 NHLBI, Bethesda, MD 20892 USA. RP Scott, I (reprint author), NHLBI, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM scotti@nhlbi.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 12 PY 2009 VL 462 IS 7270 BP 159 EP 159 DI 10.1038/462159a PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 517YM UT WOS:000271655100019 PM 19907474 ER PT J AU Keiser, MJ Setola, V Irwin, JJ Laggner, C Abbas, AI Hufeisen, SJ Jensen, NH Kuijer, MB Matos, RC Tran, TB Whaley, R Glennon, RA Hert, J Thomas, KLH Edwards, DD Shoichet, BK Roth, BL AF Keiser, Michael J. Setola, Vincent Irwin, John J. Laggner, Christian Abbas, Atheir I. Hufeisen, Sandra J. Jensen, Niels H. Kuijer, Michael B. Matos, Roberto C. Tran, Thuy B. Whaley, Ryan Glennon, Richard A. Hert, Jerome Thomas, Kelan L. H. Edwards, Douglas D. Shoichet, Brian K. Roth, Bryan L. TI Predicting new molecular targets for known drugs SO NATURE LA English DT Article ID SEROTONIN RECEPTORS; REUPTAKE INHIBITOR; CHEMICAL BIOLOGY; DOUBLE-BLIND; AGONIST; N,N-DIMETHYLTRYPTAMINE; HALLUCINOGEN; PHARMACOLOGY; PROMISCUITY; MECHANISM AB Although drugs are intended to be selective, at least some bind to several physiological targets, explaining side effects and efficacy. Because many drug-target combinations exist, it would be useful to explore possible interactions computationally. Here we compared 3,665 US Food and Drug Administration (FDA)-approved and investigational drugs against hundreds of targets, defining each target by its ligands. Chemical similarities between drugs and ligand sets predicted thousands of unanticipated associations. Thirty were tested experimentally, including the antagonism of the beta(1) receptor by the transporter inhibitor Prozac, the inhibition of the 5-hydroxytryptamine (5-HT) transporter by the ion channel drug Vadilex, and antagonism of the histamine H(4) receptor by the enzyme inhibitor Rescriptor. Overall, 23 new drug-target associations were confirmed, five of which were potent (<100 nM). The physiological relevance of one, the drug N,N-dimethyltryptamine (DMT) on serotonergic receptors, was confirmed in a knockout mouse. The chemical similarity approach is systematic and comprehensive, and may suggest side-effects and new indications for many drugs. C1 [Keiser, Michael J.; Irwin, John J.; Laggner, Christian; Hert, Jerome; Thomas, Kelan L. H.; Edwards, Douglas D.; Shoichet, Brian K.] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. [Keiser, Michael J.] Univ Calif San Francisco, Grad Grp Bioinformat, San Francisco, CA 94143 USA. [Setola, Vincent; Kuijer, Michael B.; Matos, Roberto C.; Tran, Thuy B.; Whaley, Ryan; Roth, Bryan L.] Case Western Reserve Univ, Sch Med, Dept Pharmacol, NIMH Psychoact Drug Screening Program, Cleveland, OH 44106 USA. [Abbas, Atheir I.] Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA. [Hufeisen, Sandra J.; Jensen, Niels H.; Roth, Bryan L.] Univ N Carolina, Chapel Hill Sch Med, Div Med Chem & Nat Prod, Chapel Hill, NC 27759 USA. [Hufeisen, Sandra J.; Jensen, Niels H.; Roth, Bryan L.] Univ N Carolina, Chapel Hill Sch Med, Dept Pharmacol, Chapel Hill, NC 27759 USA. [Glennon, Richard A.] Virginia Commonwealth Univ, Dept Med Chem, Sch Pharm, Med Coll Virginia Campus, Richmond, VA 23298 USA. [Thomas, Kelan L. H.] Univ Michigan Hlth Syst, Ann Arbor, MI 48109 USA. RP Shoichet, BK (reprint author), Univ Calif San Francisco, Dept Pharmaceut Chem, 1700 4th St, San Francisco, CA 94143 USA. EM shoichet@cgl.ucsf.edu; bryan_roth@med.unc.edu RI Hert, Jerome/A-8158-2008; Roth, Bryan/F-3928-2010; Keiser, Michael/F-2825-2016; OI Keiser, Michael/0000-0002-1240-2192; Irwin, John/0000-0002-1195-6417; Thomas, Kelan/0000-0003-2818-270X; Hert/0000-0003-3062-8029 FU National Institutes of Health (NIH); National Science Foundation; European Commission; Max Kade Foundation; NARSAD; Michael Hooker Chair FX Supported by grants from the National Institutes of Health (NIH) supporting chemoinformatics (to B. K. S. and J. J. I.) and NIH grants and contracts supporting drug discovery and receptor pharmacology (to B. L. R). M. J. K., J. H. and C. L. were supported by fellowships from the National Science Foundation, the 6th FP of the European Commission, and the Max Kade Foundation, respectively. B. L. R. was also supported by a Distinguished Investigator Award from the NARSAD and the Michael Hooker Chair. We thank T. Oprea of Sunset Molecular for WOMBAT, Elsevier MDL for the MDDR, Scitegic for PipelinePilot, J. Overington of the European Bioinformatics Institute (EMBL-EBI) for StARlite, Daylight Chemical Information Systems Inc. for the Daylight toolkit, and J. Gingrich for 5-HT2A knockout mice. NR 53 TC 685 Z9 703 U1 14 U2 116 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 12 PY 2009 VL 462 IS 7270 BP 175 EP U48 DI 10.1038/nature08506 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 517YM UT WOS:000271655100034 PM 19881490 ER PT J AU Soeda, A Park, M Lee, D Mintz, A Androutsellis-Theotokis, A McKay, RD Engh, J Iwama, T Kunisada, T Kassam, AB Pollack, IF Park, DM AF Soeda, A. Park, M. Lee, D. Mintz, A. Androutsellis-Theotokis, A. McKay, R. D. Engh, J. Iwama, T. Kunisada, T. Kassam, A. B. Pollack, I. F. Park, D. M. TI Hypoxia promotes expansion of the CD133-positive glioma stem cells through activation of HIF-1 alpha SO ONCOGENE LA English DT Article DE glioma; cancer stem cell; HIF-1 alpha; hypoxia; CD133 ID INDUCIBLE FACTOR 1-ALPHA; CENTRAL-NERVOUS-SYSTEM; ENDOTHELIAL GROWTH-FACTOR; TUMOR ANGIOGENESIS; TRANSCRIPTIONAL ACTIVITY; HUMAN GLIOBLASTOMA; CANCER CELLS; FACTOR-I; EXPRESSION; PROLIFERATION AB Hypoxia contributes to the progression of a variety of cancers by activating adaptive transcriptional programs that promote cell survival, motility and tumor angiogenesis. Although the importance of hypoxia and subsequent hypoxia-inducible factor-1 alpha (HIF-1 alpha) activation in tumor angiogenesis is well known, their role in the regulation of glioma-derived stem cells is unclear. In this study, we show that hypoxia (1% oxygen) promotes the self-renewal capacity of CD133-positive human glioma-derived cancer stem cells (CSCs). Propagation of the glioma-derived CSCs in a hypoxic environment also led to the expansion of cells bearing CXCR4 (CD184), CD44(low) and A2B5 surface markers. The enhanced self-renewal activity of the CD133-positive CSCs in hypoxia was preceded by upregulation of HIF-1 alpha. Knockdown of HIF-1 alpha abrogated the hypoxia-mediated CD133-positive CSC expansion. Inhibition of the phosphatidylinositol 3-kinase (PI3K)-Akt or ERK1/2 pathway reduced the hypoxia-driven CD133 expansion, suggesting that these signaling cascades may modulate the hypoxic response. Finally, CSCs propagated at hypoxia robustly retained the undifferentiated phenotype, whereas CSCs cultured at normoxia did not. These results suggest that response to hypoxia by CSCs involves the activation of HIF-1a to enhance the self-renewal activity of CD133-positive cells and to inhibit the induction of CSC differentiation. This study illustrates the importance of the tumor microenvironment in determining cellular behavior. Oncogene (2009) 28, 3949-3959; doi:10.1038/onc.2009.252; published online 31 August 2009 C1 [Park, D. M.] Univ Pittsburgh, Inst Canc, UPMC Canc Pavil, Brain Tumor Program, Pittsburgh, PA 15232 USA. [Mintz, A.; Engh, J.; Kassam, A. B.; Pollack, I. F.; Park, D. M.] Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15232 USA. [Androutsellis-Theotokis, A.; McKay, R. D.] NIH, Mol Biol Lab, Bethesda, MD 20892 USA. [Iwama, T.] Gifu Univ, Sch Med, Dept Neurosurg, Gifu 500, Japan. [Kunisada, T.] Gifu Univ, Sch Med, Dept Tissue & Organ Dev Regenerat & Adv Med Sci, Gifu 500, Japan. [Park, D. M.] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15232 USA. RP Park, DM (reprint author), Univ Pittsburgh, Inst Canc, UPMC Canc Pavil, Brain Tumor Program, 5th Floor,5150 Ctr Ave, Pittsburgh, PA 15232 USA. EM parkdm@upmc.edu RI Park, Deric/C-5675-2013; OI Kunisada, Takahiro/0000-0003-1651-2716 FU Uehara Memorial Foundation FX Akio Soeda is in part supported by the Uehara Memorial Foundation. NR 51 TC 287 Z9 303 U1 4 U2 35 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 12 PY 2009 VL 28 IS 45 BP 3949 EP 3959 DI 10.1038/onc.2009.252 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 530AC UT WOS:000272560300001 PM 19718046 ER PT J AU Cadet, JL Mccoy, MT Cai, NS Krasnova, IN Ladenheim, B Beauvais, G Wilson, N Wood, W Becker, KG Hodges, AB AF Cadet, Jean Lud Mccoy, Michael T. Cai, Ning Sheng Krasnova, Irina N. Ladenheim, Bruce Beauvais, Genevieve Wilson, Natascha Wood, William, III Becker, Kevin G. Hodges, Amber B. TI Methamphetamine Preconditioning Alters Midbrain Transcriptional Responses to Methamphetamine-Induced Injury in the Rat Striatum SO PLOS ONE LA English DT Article ID THYROTROPIN-RELEASING-HORMONE; PROTEIN-TYROSINE PHOSPHATASES; DISMUTASE TRANSGENIC MICE; MESSENGER-RNA EXPRESSION; NEUROTROPHIC FACTOR; DOPAMINERGIC-NEURONS; GENE-EXPRESSION; CEREBRAL-ISCHEMIA; HEME OXYGENASE-1; FREE-RADICALS AB Methamphetamine (METH) is an illicit drug which is neurotoxic to the mammalian brain. Numerous studies have revealed significant decreases in dopamine and serotonin levels in the brains of animals exposed to moderate-to-large METH doses given within short intervals of time. In contrast, repeated injections of small nontoxic doses of the drug followed by a challenge with toxic METH doses afford significant protection against monoamine depletion. The present study was undertaken to test the possibility that repeated injections of the drug might be accompanied by transcriptional changes involved in rendering the nigrostriatal dopaminergic system refractory to METH toxicity. Our results confirm that METH preconditioning can provide significant protection against METH-induced striatal dopamine depletion. In addition, the presence and absence of METH preconditioning were associated with substantial differences in the identity of the genes whose expression was affected by a toxic METH challenge. Quantitative PCR confirmed METH-induced changes in genes of interest and identified additional genes that were differentially impacted by the toxic METH challenge in the presence of METH preconditioning. These genes include small heat shock 27 kD 27 protein 2 (HspB2), thyrotropin-releasing hormone (TRH), brain derived neurotrophic factor (BDNF), c-fos, and some encoding antioxidant proteins including CuZn superoxide dismutase (CuZnSOD), glutathione peroxidase (GPx)-1, and heme oxygenase-1 (Hmox-1). These observations are consistent, in part, with the transcriptional alterations reported in models of lethal ischemic injuries which are preceded by ischemic or pharmacological preconditioning. Our findings suggest that multiple molecular pathways might work in tandem to protect the nigrostriatal dopaminergic pathway against the deleterious effects of the toxic psychostimulant. Further analysis of the molecular and cellular pathways regulated by these genes should help to provide some insight into the neuroadaptive potentials of the brain when repeatedly exposed to drugs of abuse. RP Cadet, JL (reprint author), NIDA, Mol Neuropsychiat Res Branch, DHHS, NIH,Intramural Res Program, Baltimore, MD USA. EM jcadet@intra.nida.nih.gov OI Becker, Kevin/0000-0002-6794-6656 NR 128 TC 28 Z9 28 U1 4 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 12 PY 2009 VL 4 IS 11 AR e7812 DI 10.1371/journal.pone.0007812 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 518UW UT WOS:000271721400011 PM 19915665 ER PT J AU Koonin, EV Wolf, YI AF Koonin, Eugene V. Wolf, Yuri I. TI Is evolution Darwinian or/and Lamarckian? SO BIOLOGY DIRECT LA English DT Review ID HORIZONTAL GENE-TRANSFER; PROVIDES ACQUIRED-RESISTANCE; STRESS-INDUCED MUTAGENESIS; GENOME-WIDE HYPERMUTATION; STATIONARY-PHASE; TUMOR MICROENVIRONMENT; ANTIBIOTIC-RESISTANCE; METABOLIC NETWORKS; TRANSFERRED GENES; DIRECTED MUTATION AB Background: The year 2009 is the 200th anniversary of the publication of Jean-Bapteste Lamarck's Philosophie Zoologique and the 150th anniversary of Charles Darwin's On the Origin of Species. Lamarck believed that evolution is driven primarily by non-randomly acquired, beneficial phenotypic changes, in particular, those directly affected by the use of organs, which Lamarck believed to be inheritable. In contrast, Darwin assigned a greater importance to random, undirected change that provided material for natural selection. The concept: The classic Lamarckian scheme appears untenable owing to the non-existence of mechanisms for direct reverse engineering of adaptive phenotypic characters acquired by an individual during its life span into the genome. However, various evolutionary phenomena that came to fore in the last few years, seem to fit a more broadly interpreted (quasi) Lamarckian paradigm. The prokaryotic CRISPR-Cas system of defense against mobile elements seems to function via a bona fide Lamarckian mechanism, namely, by integrating small segments of viral or plasmid DNA into specific loci in the host prokaryote genome and then utilizing the respective transcripts to destroy the cognate mobile element DNA (or RNA). A similar principle seems to be employed in the piRNA branch of RNA interference which is involved in defense against transposable elements in the animal germ line. Horizontal gene transfer (HGT), a dominant evolutionary process, at least, in prokaryotes, appears to be a form of (quasi) Lamarckian inheritance. The rate of HGT and the nature of acquired genes depend on the environment of the recipient organism and, in some cases, the transferred genes confer a selective advantage for growth in that environment, meeting the Lamarckian criteria. Various forms of stress-induced mutagenesis are tightly regulated and comprise a universal adaptive response to environmental stress in cellular life forms. Stress-induced mutagenesis can be construed as a quasi-Lamarckian phenomenon because the induced genomic changes, although random, are triggered by environmental factors and are beneficial to the organism. Conclusion: Both Darwinian and Lamarckian modalities of evolution appear to be important, and reflect different aspects of the interaction between populations and the environment. C1 [Koonin, Eugene V.; Wolf, Yuri I.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov; wolf@ncbi.nlm.nih.gov FU Intramural NIH HHS NR 104 TC 101 Z9 106 U1 8 U2 93 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6150 J9 BIOL DIRECT JI Biol. Direct PD NOV 11 PY 2009 VL 4 AR 42 DI 10.1186/1745-6150-4-42 PG 14 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 526XV UT WOS:000272330400001 PM 19906303 ER PT J AU Hansen, DF Feng, HQ Zhou, Z Bai, YW Kay, LE AF Hansen, D. Flemming Feng, Haniqiao Zhou, Zheng Bai, Yawen Kay, Lewis E. TI Selective Characterization of Microsecond Motions in Proteins by NMR Relaxation SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID CHEMICAL-SHIFT ANISOTROPY; MAGNETIC-RESONANCE RELAXATION; LIQUID-CRYSTALLINE PHASE; MODEL-FREE APPROACH; CONFORMATIONAL DYNAMICS; BACKBONE DYNAMICS; CHAPERONE CHZ1; SPECTROSCOPY; EXCHANGE; DOMAIN AB The three-dimensional structures of macromolecules fluctuate over a wide range of time-scales. Separating the individual dynamic processes according to frequency is of importance in relating protein motions to biological function and stability. We present here a general NMR method for the specific characterization of microsecond motions at backbone positions in proteins even in the presence of other dynamics such as large-amplitude nanosecond motions and millisecond chemical exchange processes. The method is based on measurement of relaxation rates of four bilinear coherences and relies on the ability of strong continuous radio frequency fields to quench millisecond chemical exchange. The utility of the methodology is demonstrated and validated through two specific examples focusing on the thermostable proteins, ubiquitin and protein L, where it is found that small-amplitude microsecond dynamics are more pervasive than previously thought. Specifically, these motions are localized to a helices, loop regions, and regions along the rim of beta sheets in both of the proteins examined. A third example focuses on a 28 kDa ternary complex of the chaperone Chz1 and the histones H2A.Z/H2B, where it is established that pervasive microsecond motions are localized to a region of the chaperone that is important for stabilizing the complex. It is further shown that these motions can be well separated from extensive millisecond dynamics that are also present and that derive from exchange of Chz1 between bound and free states. The methodology is straightforward to implement, and data recorded at only a single static magnetic field are required. C1 [Hansen, D. Flemming; Kay, Lewis E.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada. [Hansen, D. Flemming; Kay, Lewis E.] Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada. [Hansen, D. Flemming; Kay, Lewis E.] Univ Toronto, Dept Chem, Toronto, ON M5S 1A8, Canada. [Feng, Haniqiao; Zhou, Zheng; Bai, Yawen] NCI, Biochem & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Hansen, DF (reprint author), Univ Toronto, Dept Mol Genet, 100 Coll St, Toronto, ON M5S 1A8, Canada. EM flemming@pound.med.utoronto.ca; kay@pound.med.utoronto.ca FU Canadian Institutes of Health Research (CIHR); Canada Research Chair in Biochemistry FX We would like to thank Professors Silke Wiesner (Max Planck Institute for Developmental Biology, Tubingen, Germany) and Voula Kanelis (University of Toronto, Canada) for preparing the human ubiquitin and protein L samples, respectively. This work was supported by a grant from the Canadian Institutes of Health Research (CIHR). D.F.H. acknowledges a postdoctoral fellowship from CIHR. L.E.K. is the recipient of a Canada Research Chair in Biochemistry. NR 62 TC 29 Z9 29 U1 1 U2 20 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD NOV 11 PY 2009 VL 131 IS 44 BP 16257 EP 16265 DI 10.1021/ja906842s PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA 516AJ UT WOS:000271513700061 PM 19842628 ER PT J AU Ju, JH Maeng, JS Lee, DY Piszczek, G Gelmann, EP Gruschus, JM AF Ju, Jeong Ho Maeng, Jin-Soo Lee, Duck-Yeon Piszczek, Grzegory Gelmann, Edward P. Gruschus, James M. TI Interactions of The Acidic Domain and SRF Interacting Motifs with the NKX3.1 Homeodomain SO BIOCHEMISTRY LA English DT Article ID PROSTATE-CANCER; DNA-BINDING; VND/NK-2 HOMEODOMAIN; PROTEIN; GENE; HOMEOPROTEIN; EXPRESSION; MUTATIONS; DELETION; RESIDUE AB NKX3.1 is a prostate tumor Suppressor belonging to the NK-2 family of homeodomain (HD) transcription factors NK-2family members often possess as( retch of 10-15 residues enriched in acidic amino acids, the acidic domain (AD), in the flexible, disordered region N-terminal to the HD. Interactions between the N-terminal region of NKX3 1 and its homeodomain affect protein stability and DNA binding. CD spectroscopy measuring the thermal unfolding of NKX3 I Constructs showed a 2 degrees C intramolecular stabilization of the H 1) by the N-terminal region containing the acidic domain (residues 85-96) CD of mixtures of various N-terminal peptides With it construct containing just the HD showed that the acidic domain and the following legion, the SRF interacting (SI) motif (residues 99-105), was necessary For this stabilization. Phosphorylation of the acidic domain is known to slow proteasomal degradation of NKX3.1 in prostate cells, and MAR spectroscopy Was Used 10 measure and map the Interaction of the HD with phosphorylated and nonphosphorylated forms of the AD peptide The interaction with the phosphorylated AD peptide was considerably stronger (K-d = 0 5 +/- 0 2 mM). resulting in large chemical shift perturbations For residues Ser 150 and Arg 175 in the HD, as well as a 2 degrees C increase ill the HD thermal stability compared to that of the nonphosphorylated form. NKX3 1 constructs with AD phosphorylation site threonine residues (89 and 93) mutated to glutamate were 4 degrees C more stable than HD alone Using polymer theory, effective concentrations for interactions between domains connected by flexible linkers are predicted to be ill the millimolar range, and thus. the weak intramolecular interactions observed here could conceivably modulate or compete With stronger, intermolecular interactions with the NKX3.1 HD C1 [Lee, Duck-Yeon; Piszczek, Grzegory; Gruschus, James M.] NHLBI, NIH, Bethesda, MD 20892 USA. [Ju, Jeong Ho; Gelmann, Edward P.] Columbia Univ, Herbert Irving Comprehens Canc Ctr, Div Hematol Oncol, New York, NY 10032 USA. [Maeng, Jin-Soo] Sch Biol Sci & Technol, Kwangju 500757, South Korea. RP Gruschus, JM (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. FU National Heart. Lung and Blood Institute; Natinal Institute of Environmental Health Sciences [ES09888] FX This work was supported to part by the Intramural Research Program of the National Heart. Lung and Blood Institute and by Natinal Institute of Environmental Health Sciences Grant ES09888 to EPG NR 29 TC 4 Z9 5 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 10 PY 2009 VL 48 IS 44 BP 10601 EP 10607 DI 10.1021/bi9013374 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 512IU UT WOS:000271242200015 PM 19780584 ER PT J AU Lubet, RA Yao, RS Grubbs, CJ You, M Wang, Y AF Lubet, Ronald A. Yao, Ruisheng Grubbs, Clinton J. You, Ming Wang, Yian TI Induced expression of drug metabolizing enzymes by preventive agents: Role of the antioxidant response element SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article DE Chemopreventive agents; Phase I/II inducers; Antioxidant response element ID MAMMARY CARCINOGENESIS; PHENOLIC ANTIOXIDANTS; BETA-NAPHTHOFLAVONE; CIGARETTE-SMOKE; DNA-ADDUCTS; CANCER; INHIBITION; RATS; CHEMOPREVENTION; INDOLE-3-CARBINOL AB Identifying agents that block tumor initiation is a goal of cancer prevention. The ability of a chemically varied group of agents to induce various drug metabolizing genes in livers of rats was examined. Sprague-Dawley rats were treated for 7 days with various agents in the diet or by gavage. The agents examined, which might be expected to respond via specific nuclear receptors (CAR. AhR) as well as antioxidant response elements (AREs), included Phase I/II inducers [5,6-benzoflavone (BF, 5000 mg/kg diet), diallyl sulfide (DAS, 500 mg/kg BW/clay). ethoxyqum (EXC, 300 mg/kg BW/day) and phenobarbital (PB, 500 mg/kg diet)] or pure Phase II inducers [1,2-dithiol-3-thione (DTT, 500 mg/kg diet), and cyclopentadithiolthione (CPDTT, 175 mg/kg BW/day)]. Liver RNA expression was analyzed employing oligonucleotide microarrays. The agents yielded unique expression profiles. In genes with known AREs, the induction ratios (Levels Treated/Levels Controls) were: quinone oxidoreductase (BF, 8.1; DTT. 3.2:1; CPDTT, 3:1; DAS, 1.81; Exo, 1.7;1), glutatione transferase Pi (DTT, 36:1; CPDTT, 34:1: EXO, 8:1; DAS, 5:1; BF, 2.5:1;), and alclehyde keto reductase 7A3 (AFAR) (DTT and CPDTT 14:1: DAS, 6:1; EXC, 4:1; PB, 1.5:1).When the search included a wider variety of Phase II drug metabolizing enzymes, no clear pattern was observed. Agent induced gene expression and preventive activity in published carcinogen induced tumor models showed limited correlation: questioning whether measuring the induction of one or two genes (e.g., quinone reductase) is a surrogate for overall Phase 11 inducing (antioxidant) and potential anti-tumor activity. Published by Elsevier Ireland Ltd. C1 [Lubet, Ronald A.] NCI, Canc Prevent Div, Rockville, MD 20852 USA. [Yao, Ruisheng; You, Ming; Wang, Yian] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Yao, Ruisheng; You, Ming; Wang, Yian] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA. [Grubbs, Clinton J.] Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. RP Lubet, RA (reprint author), NCI, Canc Prevent Div, Execut Plaza N,Suite 2110,6130 Execut Blvd, Rockville, MD 20852 USA. EM lubetr@mail.nih.gov FU NCI [HHSN261200433001C] FX The authors would like to thank Ms. Mary Jo Cagle and Jeanne Hale for their editorial assistance in the preparation of this manuscript. The funding for the studies was provided in part by NCI Contract Number HHSN261200433001C. NR 36 TC 11 Z9 11 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD NOV 10 PY 2009 VL 182 IS 1 BP 22 EP 28 DI 10.1016/j.cbi.2009.08.011 PG 7 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 510XK UT WOS:000271127100004 PM 19695238 ER PT J AU Anderson, WF Jatoi, I Sherman, ME AF Anderson, William F. Jatoi, Ismail Sherman, Mark E. TI Qualitative Age Interactions in Breast Cancer Studies: Mind the Gap SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID RISK-FACTORS; GENE-EXPRESSION; UNITED-STATES; SEER PROGRAM; YOUNG AGE; WOMEN; EPIDEMIOLOGY; PROGNOSIS; PATTERNS; RECEPTOR C1 [Anderson, William F.; Sherman, Mark E.] NCI, Dept Hlth & Human Serv, NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Jatoi, Ismail] Natl Naval Med Ctr, Breast Care Ctr, Bethesda, MD USA. RP Anderson, WF (reprint author), NCI, Dept Hlth & Human Serv, NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 CP010183-06] NR 44 TC 20 Z9 21 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 10 PY 2009 VL 27 IS 32 BP 5308 EP 5311 DI 10.1200/JCO.2009.22.9450 PG 4 WC Oncology SC Oncology GA 516GT UT WOS:000271530900004 PM 19826117 ER PT J AU Piekarz, RL Frye, R Turner, M Wright, JJ Allen, SL Kirschbaum, MH Zain, J Prince, HM Leonard, JP Geskin, LJ Reeder, C Joske, D Figg, WD Gardner, ER Steinberg, SM Jaffe, ES Stetler-Stevenson, M Lade, S Fojo, AT Bates, SE AF Piekarz, Richard L. Frye, Robin Turner, Maria Wright, John J. Allen, Steven L. Kirschbaum, Mark H. Zain, Jasmine Prince, H. Miles Leonard, John P. Geskin, Larisa J. Reeder, Craig Joske, David Figg, William D. Gardner, Erin R. Steinberg, Seth M. Jaffe, Elaine S. Stetler-Stevenson, Maryalice Lade, Stephen Fojo, A. Tito Bates, Susan E. TI Phase II Multi-Institutional Trial of the Histone Deacetylase Inhibitor Romidepsin As Monotherapy for Patients With Cutaneous T-Cell Lymphoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SEZARY-SYNDROME; MYCOSIS-FUNGOIDES; DEPSIPEPTIDE FR901228; CLINICAL-TRIALS; CANCER-THERAPY; FK228; DIFFERENTIATION; IDENTIFICATION; POPULATION; INDUCERS AB Purpose Romidepsin (depsipeptide or FK228) is a member of a new class of antineoplastic agents active in T-cell lymphoma, the histone deacetylase inhibitors. On the basis of observed responses in a phase I trial, a phase II trial of romidepsin in patients with T-cell lymphoma was initiated. Patients and Methods The initial cohort was limited to patients with cutaneous T-cell lymphoma (CTCL), or subtypes mycosis fungoides or Sezary syndrome, who had received no more than two prior cytotoxic regimens. There were no limits on other types of therapy. Subsequently, the protocol was expanded to enroll patients who had received more than two prior cytotoxic regimens. Results Twenty-seven patients were enrolled onto the first cohort, and a total of 71 patients are included in this analysis. These patients had undergone a median of four prior treatments, and 62 patients (87%) had advanced-stage disease ( stage IIB, n = 15; stage III, n = 6; or stage IV, n = 41). Toxicities included nausea, vomiting, fatigue, and transient thrombocytopenia and granulocytopenia. Pharmacokinetics were evaluated with the first administration of romidepsin. Complete responses were observed in four patients, and partial responses were observed in 20 patients for an overall response rate of 34% (95% CI, 23% to 46%). The median duration of response was 13.7 months. Conclusion The histone deacetylase inhibitor romidepsin has single-agent clinical activity with significant and durable responses in patients with CTCL. C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Canc Therapy Evaluat Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. SAIC Frederick, Clin Pharmacol Program, Frederick, MD USA. N Shore Univ Hosp, Manhasset, NY USA. New York Presbyterian Hosp, New York, NY USA. City Hope Natl Canc Ctr, Duarte, CA USA. Univ Pittsburgh, Pittsburgh, PA USA. Mayo Clin Scottsdale, Scottsdale, AZ USA. Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. Univ Melbourne, Melbourne, Vic, Australia. Sir Charles Gairdner Hosp, Nedlands, WA 6009, Australia. RP Piekarz, RL (reprint author), 10 Ctr Dr,MSC 1903,Bldg 10,Rm 12N226, Bethesda, MD 20892 USA. EM rpiekarz@nih.gov RI Figg Sr, William/M-2411-2016; OI Allen, Steven/0000-0002-3482-3182 FU National Institutes of Health (NIH) [N01-CO-12400]; National Cancer Institute; Center for Cancer Research; Gloucester Pharmaceuticals, Cambridge, MA FX Supported in part by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research and by a Cooperative Research and Development Agreement with Gloucester Pharmaceuticals, Cambridge, MA; also supported in part by federal funds from the National Cancer Institute, NIH, under Grant No. N01-CO-12400 (E.R.G.). NR 36 TC 335 Z9 348 U1 2 U2 14 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 10 PY 2009 VL 27 IS 32 BP 5410 EP 5417 DI 10.1200/JCO.2008.21.6150 PG 8 WC Oncology SC Oncology GA 516GT UT WOS:000271530900020 PM 19826128 ER PT J AU Sa, JM Twu, O Hayton, K Reyes, S Fay, MP Ringwald, P Wellems, TE AF Sa, Juliana Martha Twu, Olivia Hayton, Karen Reyes, Sahily Fay, Michael P. Ringwald, Pascal Wellems, Thomas E. TI Geographic patterns of Plasmodium falciparum drug resistance distinguished by differential responses to amodiaquine and chloroquine SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE malaria; pfcrt; pfmdr1 ID PAPUA-NEW-GUINEA; GENE HAPLOTYPE SVMNT; TRANSPORTER PFCRT; SULFADOXINE-PYRIMETHAMINE; QUININE RESISTANCE; PFMDR1 MUTATIONS; EAST-AFRICA; WILD-TYPE; MALARIA; SENSITIVITY AB Chloroquine (CQ) resistance (CQR) in Plasmodium falciparum originated from at least six foci in South America, Asia, and Oceania. Malaria parasites from these locations exhibit contrasting resistance phenotypes that are distinguished by point mutations and microsatellite polymorphisms in and near the CQR transporter gene, pfcrt, and the multidrug resistance transporter gene, pfmdr1. Amodiaquine (AQ), a 4-aminoquinoline related to CQ, is recommended and often used successfully against CQ-resistant P. falciparum in Africa, but it is largely ineffective across large regions of South America. The relationship of different pfcrt and pfmdr1 combinations to these drug-resistant phenotypes has been unclear. In two P. falciparum genetic crosses, particular pfcrt and pfmdr1 alleles from South America interact to yield greater levels of resistance to monodesethylamodiaquine (MDAQ; the active metabolite of AQ) than to CQ, whereas a pfcrt allele from Southeast Asia and Africa is linked to greater CQ than MDAQ resistance with all partner pfmdr1 alleles. These results, together with (i) available haplotype data from other parasites; (ii) evidence for an emerging focus of AQ resistance in Tanzania; and (iii) the persistence of 4-aminoquinoline-resistant parasites in South America, where CQ and AQ use is largely discontinued, suggest that different histories of drug use on the two continents have driven the selection of distinct suites of pfcrt and pfmdr1 mutations. Increasing use of AQ in Africa poses the threat of a selective sweep of highly AQ-resistant, CQ-resistant parasites with pfcrt and pfmdr1 mutations that are as advantaged and persistent as in South America. C1 [Sa, Juliana Martha; Twu, Olivia; Hayton, Karen; Reyes, Sahily; Wellems, Thomas E.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Fay, Michael P.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. [Ringwald, Pascal] WHO, Global Malaria Program, CH-1211 Geneva 27, Switzerland. RP Wellems, TE (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM twellems@niaid.nih.gov OI Twu, Olivia/0000-0002-5175-3016; Fay, Michael P./0000-0002-8643-9625 FU The Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases FX We thank Jianbing Mu for assistance in genotyping the P. falciparum clones; Hongying Jiang, Xinzhuan Su, Jeff Skinner, Vivek Gopalan, Jason Barnett, Yentram Huyen, and William Knight for assistance with in vitro drug assays and automated analysis of IC50s and IC90s; and Erika Phelps, Sarnia Laurent, Michael Krause, and Rick Fairhurst for assistance with QTL mapping, DNA sequencing, and discussions. The Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases, supported this research. NR 71 TC 111 Z9 113 U1 1 U2 7 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 10 PY 2009 VL 106 IS 45 BP 18883 EP 18889 DI 10.1073/pnas.0911317106 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 517SJ UT WOS:000271637500005 PM 19884511 ER PT J AU Das, R Andre, I Shen, Y Wu, YB Lemak, A Bansal, S Arrowsmith, CH Szyperski, T Baker, D AF Das, Rhiju Andre, Ingemar Shen, Yang Wu, Yibing Lemak, Alexander Bansal, Sonal Arrowsmith, Cheryl H. Szyperski, Thomas Baker, David TI Simultaneous prediction of protein folding and docking at high resolution SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE homo-oligomers; molecular replacement; NMR structure inference; protein structure prediction; symmetry ID RESIDUAL DIPOLAR COUPLINGS; NMR CHEMICAL-SHIFTS; X-RAY-STRUCTURE; COILED-COIL; ROSETTA; COMPLEXES; ASSEMBLIES; SEQUENCES; SYMMETRY; TARGETS AB Interleaved dimers and higher order symmetric oligomers are ubiquitous in biology but present a challenge to de novo structure prediction methodology: The structure adopted by a monomer can be stabilized largely by interactions with other monomers and hence not the lowest energy state of a single chain. Building on the Rosetta framework, we present a general method to simultaneously model the folding and docking of multiple-chain interleaved homo-oligomers. For more than a third of the cases in a benchmark set of interleaved homo-oligomers, the method generates near-native models of large alpha-helical bundles, interlocking beta sandwiches, and interleaved alpha/beta motifs with an accuracy high enough for molecular replacement based phasing. With the incorporation of NMR chemical shift information, accurate models can be obtained consistently for symmetric complexes with as many as 192 total amino acids; a blind prediction was within 1 angstrom rmsd of the traditionally determined NMR structure, and fit independently collected RDC data equally well. Together, these results show that the Rosetta "fold-and-dock'' protocol can produce models of homo-oligomeric complexes with nearatomic-level accuracy and should be useful for crystallographic phasing and the rapid determination of the structures of multimers with limited NMR information. C1 [Das, Rhiju; Andre, Ingemar; Baker, David] Univ Washington, Dept Biochem, Seattle, WA 98195 USA. [Shen, Yang] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Wu, Yibing; Szyperski, Thomas] SUNY Buffalo, Dept Chem, Buffalo, NY 14260 USA. [Wu, Yibing; Szyperski, Thomas] SUNY Buffalo, Dept Biol Struct, Buffalo, NY 14260 USA. [Wu, Yibing; Szyperski, Thomas] SUNY Buffalo, NE Struct Genom Consortium, Buffalo, NY 14260 USA. [Lemak, Alexander; Arrowsmith, Cheryl H.] Univ Toronto, Dept Med Biophys, Ontario Canc Inst, Toronto, ON M5G IL5, Canada. [Lemak, Alexander; Arrowsmith, Cheryl H.] Univ Toronto, NE Struct Genom Consortium, Toronto, ON M5G IL5, Canada. [Bansal, Sonal] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63108 USA. RP Baker, D (reprint author), Univ Washington, Dept Biochem, Seattle, WA 98195 USA. EM dabaker@u.washington.edu RI Shen, Yang/C-3064-2008; Andre, Ingemar/O-4777-2014; Baker, David/K-8941-2012 OI Shen, Yang/0000-0003-1408-8034; Andre, Ingemar/0000-0002-4753-8233; Baker, David/0000-0001-7896-6217 FU Howard Hughes Medical Institute; Knut and Alice Wallenberg Foundation; Jane Coffin Childs Foundation and a Burroughs-Wellcome Career Award; Intramural Research Program of the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health Protein Structure Initiative [U54-GM074958]; Canada Research Chair in Structural Proteomics FX We thank Keith Laidig and Darwin Alonso for flawless administration of computational resources; the users of Rosetta@ home for donating their computer time; developers in the Rosetta community for contributions to our shared codebase; and Suzanne Pfeffer for informing us about the GCC185 coiled-coil sequence before the release of its crystal structure. This work was supported by the Howard Hughes Medical Institute ( to D. B.), the Knut and Alice Wallenberg Foundation ( to I. A.), the Jane Coffin Childs Foundation and a Burroughs-Wellcome Career Award at the Scientific Interface ( to R. D.), the Intramural Research Program of the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases ( to Y. S.), and the National Institutes of Health Protein Structure Initiative Grant U54-GM074958 ( to T. S. and C. H. A.). C. H. A. holds a Canada Research Chair in Structural Proteomics. NR 39 TC 88 Z9 88 U1 2 U2 21 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 10 PY 2009 VL 106 IS 45 BP 18978 EP 18983 DI 10.1073/pnas.0904407106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 517SJ UT WOS:000271637500021 PM 19864631 ER PT J AU Ieva, R Bernstein, HD AF Ieva, Raffaele Bernstein, Harris D. TI Interaction of an autotransporter passenger domain with BamA during its translocation across the bacterial outer membrane SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE autotransporter; Bam complex; outer membrane; protein secretion; virulence factors ID ESCHERICHIA-COLI; PROTEIN; SECRETION; BIOGENESIS; MECHANISM; COMPONENT; CLEAVAGE; COMPLEX; YAET; GENE AB Autotransporters are a superfamily of virulence factors produced by Gram-negative bacteria consisting of a large N-terminal extracellular domain ("passenger domain'') and a C-terminal beta barrel domain ("beta domain''). The mechanism by which the passenger domain is translocated across the outer membrane (OM) is unknown. Here we show that the insertion of a small linker into the passenger domain of the Escherichia coli O157:H7 autotransporter EspP effectively creates a translocation intermediate by transiently stalling translocation near the site of the insertion. Using a site-specific photocrosslinking approach, we found that residues adjacent to the stall point interact with BamA, a component of a heterooligomeric complex (Bam complex) that catalyzes OM protein assembly, and that residues closer to the EspP N terminus interact with the periplasmic chaperones SurA and Skp. The EspP-BamA interaction was short-lived and could be detected only when passenger domain translocation was stalled. These results support a model in which molecular chaperones prevent misfolding of the passenger domain before its secretion and the Bam complex catalyzes both the integration of the beta domain into the OM and the translocation of the passenger domain across the OM in a C-to N-terminal direction. C1 [Ieva, Raffaele; Bernstein, Harris D.] NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Bernstein, HD (reprint author), NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. EM harris_bernstein@nih.gov RI Ieva, Raffaele/J-9207-2014 OI Ieva, Raffaele/0000-0002-3405-0650 FU National Institute of Diabetes and Digestive and Kidney Diseases FX We thank Natacha Ruiz and Tom Silhavy for providing the BamA antisera used in preliminary experiments and Janine Peterson for providing technical assistance. We also thank Nathalie Dautin and Susan Buchanan for their critical reading of the manuscript. This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases Intramural Research Program. NR 28 TC 103 Z9 104 U1 0 U2 11 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 10 PY 2009 VL 106 IS 45 BP 19120 EP 19125 DI 10.1073/pnas.0907912106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 517SJ UT WOS:000271637500045 PM 19850876 ER PT J AU Joksimovic, M Anderegg, A Roy, A Campochiaro, L Yun, B Kittappa, R McKay, R Awatramani, R AF Joksimovic, Milan Anderegg, Angela Roy, Anil Campochiaro, Laura Yun, Beth Kittappa, Raja McKay, Ronald Awatramani, Rajeshwar TI Spatiotemporally separable Shh domains in the midbrain define distinct dopaminergic progenitor pools SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE dopamine; Sonic hedgehog; lineage; substantia nigra ID EMBRYONIC STEM-CELLS; FLOOR PLATE CELLS; PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; GENETIC LINEAGES; SONIC-HEDGEHOG; MUTANT MICE; NEURONS; FATE; IDENTIFICATION AB Midbrain dopamine neurons (mDA) are important regulators of diverse physiological functions, including movement, attention, and reward behaviors. Accordingly, aberrant function of dopamine neurons underlies a wide spectrum of disorders, such as Parkinson's disease (PD), dystonia, and schizophrenia. The distinct functions of the dopamine system are carried out by neuroanatomically discrete subgroups of dopamine neurons, which differ in gene expression, axonal projections, and susceptibility in PD. The developmental underpinnings of this heterogeneity are undefined. We have recently shown that in the embryonic CNS, mDA originate from the midbrain floor plate, a ventral midline structure that is operationally defined by the expression of the molecule Shh. Here, we develop these findings to reveal that in the embryonic midbrain, the spatiotemporally dynamic Shh domain defines multiple progenitor pools. We deduce 3 distinct progenitor pools, medial, intermediate, and lateral, which contribute to different mDA clusters. The earliest progenitors to express Shh, here referred to as the medial pool, contributes neurons to the rostral linear nucleus and mDA of the ventral tegmental area/interfascicular regions, but remarkably, little to the substantia nigra pars compacta. The intermediate Shh+ progenitors give rise to neurons of all dopaminergic nuclei, including the SNpc. The last and lateral pool of Shh+ progenitors generates a cohort that populates the red nucleus, Edinger Westphal nucleus, and supraoculomotor nucleus and cap. Subsequently, these lateral Shh+ progenitors produce mDA. This refined ontogenetic definition will expand understanding of dopamine neuron biology and selective susceptibility, and will impact stem cell-derived therapies and models for PD. C1 [Joksimovic, Milan; Anderegg, Angela; Roy, Anil; Campochiaro, Laura; Yun, Beth; Awatramani, Rajeshwar] Northwestern Univ, Feinberg Sch Med, Dept Neurol, Chicago, IL 60611 USA. [Joksimovic, Milan; Anderegg, Angela; Roy, Anil; Campochiaro, Laura; Yun, Beth; Awatramani, Rajeshwar] Ctr Genet Med, Chicago, IL 60611 USA. [Kittappa, Raja; McKay, Ronald] NINDS, Mol Biol Lab, Bethesda, MD 20892 USA. RP Awatramani, R (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Neurol, 7-113 Lurie Bldg,303 E Super St, Chicago, IL 60611 USA. EM r-awatramani@northwestern.edu RI Joksimovic, Milan/A-4952-2016 OI Joksimovic, Milan/0000-0002-3936-4632 FU Whitehall Foundation; Brain Research Foundation; American Parkinson's Disease Association; Parkinson's Disease Foundation FX We thank Dr. Cliff Tabin for Shh: CreGFP and Shh: CreERT2 mice and Shh cDNA; Dr. Michael German for anti-Lmx1a; Drs. Thomas Muller and Carmen Birchmeier for anti-Lmx1b; and Dr. Eric Turner for antiBrn3a antibodies. We thank Dr. Doug Kim for useful comments and Dr. Abdelhak Belmadani and Bor-Shuen Wang for imaging and technical assistance. R. A. was supported by the Whitehall Foundation, Brain Research Foundation, and the American Parkinson's Disease Association. M. J. was supported by the Parkinson's Disease Foundation. NR 40 TC 62 Z9 63 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 10 PY 2009 VL 106 IS 45 BP 19185 EP 19190 DI 10.1073/pnas.0904285106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 517SJ UT WOS:000271637500056 PM 19850875 ER PT J AU Guettier, JM Gautam, D Scarselli, M de Azua, IR Li, JH Rosemond, E Ma, XC Gonzalez, FJ Armbruster, BN Lu, HY Roth, BL Wess, J AF Guettier, Jean-Marc Gautam, Dinesh Scarselli, Marco de Azua, Inigo Ruiz Li, Jian Hua Rosemond, Erica Ma, Xiaochao Gonzalez, Frank J. Armbruster, Blaine N. Lu, Huiyan Roth, Bryan L. Wess, Juergen TI A chemical-genetic approach to study G protein regulation of beta cell function in vivo SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE beta cells; G protein-coupled receptors; transgenic mice; type 2 diabetes ID MUSCARINIC ACETYLCHOLINE-RECEPTOR; PHASIC INSULIN RELEASE; COUPLED RECEPTORS; GLUCOSE; MECHANISMS; EXPRESSION; SECRETION AB Impaired functioning of pancreatic beta cells is a key hallmark of type 2 diabetes. beta cell function is modulated by the actions of different classes of heterotrimeric G proteins. The functional consequences of activating specific beta cell G protein signaling pathways in vivo are not well understood at present, primarily due to the fact that beta cell G protein-coupled receptors (GPCRs) are also expressed by many other tissues. To circumvent these difficulties, we developed a chemical-genetic approach that allows for the conditional and selective activation of specific beta cell G proteins in intact animals. Specifically, we created two lines of transgenic mice each of which expressed a specific designer GPCR in beta cells only. Importantly, the two designer receptors differed in their G protein-coupling properties (G(q/11) versus G(s)). They were unable to bind endogenous ligand(s), but could be efficiently activated by an otherwise pharmacologically inert compound (clozapine-N-oxide), leading to the conditional activation of either beta cell G(q/11) or G(s) G proteins. Here we report the findings that conditional and selective activation of beta cell G(q/11) signaling in vivo leads to striking increases in both first-and second-phase insulin release, greatly improved glucose tolerance in obese, insulin-resistant mice, and elevated beta cell mass, associated with pathway-specific alterations in islet gene expression levels. Selective stimulation of beta cell G(s) triggered qualitatively similar in vivo metabolic effects. Thus, this developed chemical-genetic strategy represents a powerful approach to study G protein regulation of beta cell function in vivo. C1 [Guettier, Jean-Marc; Gautam, Dinesh; Scarselli, Marco; de Azua, Inigo Ruiz; Li, Jian Hua; Rosemond, Erica; Wess, Juergen] NIDDKD, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Ma, Xiaochao; Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. [Lu, Huiyan] NIDDKD, Mouse Transgen Core Facil, NIH, Bethesda, MD 20892 USA. [Armbruster, Blaine N.; Roth, Bryan L.] Univ N Carolina, Dept Pharmacol, Chapel Hill Med Sch, Chapel Hill, NC 27514 USA. [Armbruster, Blaine N.; Roth, Bryan L.] Univ N Carolina, Div Med Chem & Nat Prod, Chapel Hill Med Sch, Chapel Hill, NC 27514 USA. RP Guettier, JM (reprint author), NIDDKD, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM guettierj@mail.nih.gov; jwess@helix.nih.gov RI Roth, Bryan/F-3928-2010; Li, Jianhua/B-7671-2011; OI Li, Jianhua/0000-0002-5744-3182; Scarselli, Marco/0000-0001-5087-3182 FU Intramural Research Program; National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health; U. S. Department of Health and Human Services; National Institutes of Health [U19MH82441, NO1MH80004, RO1MH61887] FX We thank Ms. Xiaohong Zhang and Ms. Yinghong Cui for excellent technical assistance; Dr. Elliot Ross (UT Southwestern Medical Center, Dallas, TX) for providing the turkey beta1-adrenergic receptor expression vector; The National Institutes of Health Inter-institute Endocrine Training Program, particularly Drs. M. C. Skarulis, L. K. Nieman, D. LeRoith, and P. Gorden for support of this work. This work was supported by the Intramural Research Program, the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; U. S. Department of Health and Human Services; and National Institutes of Health Grants U19MH82441, NO1MH80004, and RO1MH61887. NR 24 TC 96 Z9 96 U1 0 U2 7 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 10 PY 2009 VL 106 IS 45 BP 19197 EP 19202 DI 10.1073/pnas.0906593106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 517SJ UT WOS:000271637500058 PM 19858481 ER PT J AU Ramot, Y Nyska, A Lieuallen, W Maly, A Flake, G Kissling, GE Brix, A Malarkey, DE Hooth, MJ AF Ramot, Yuval Nyska, Abraham Lieuallen, Warren Maly, Alex Flake, Gordon Kissling, Grace E. Brix, Amy Malarkey, David E. Hooth, Michelle J. TI Inflammatory and chloracne-like skin lesions in B6C3F1 mice exposed to 3,3 ',4,4 '-tetrachloroazobenzene for 2 years SO TOXICOLOGY LA English DT Article DE TCAB; Dioxin; Chloracne; Mice; Inflammation ID SPRAGUE-DAWLEY-RATS; DIOXIN-LIKE COMPOUNDS; POLYCYCLIC AROMATIC-HYDROCARBONS; POLYCHLORINATED-BIPHENYLS; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TCDD; CHRONIC TOXICITY; HUMAN KERATINOCYTES; HAIRLESS MOUSE; ORAL TREATMENT; CARCINOGENICITY AB Exposure to dioxin and dioxin-like compounds (DLCs) has been connected to the induction of chloracne in humans and animals. 3,3',4,4'-Tetrachloroazobenzene (TCAB) is an environmental contaminant that induces chloracne in humans. TCAB has been studied only to a limited extent in laboratory animals. While performing a 2-year gavage study in B6C3F1 mice to evaluate the toxic and carcinogenic effects of TCAB, we also explored potential chloracnegenic properties. Groups of 50 male and 50 female B6C3F1 mice were exposed by gavage to TCAB at dose levels of 0, 3, 10 and 30 mg/kg for 5 days a week for 2 years. The animals developed treatment-related gross inflammatory skin lesions, which were characterized histologically by inflammation, fibrosis, hyperplasia, and ulcers. Additionally, many of the animals developed follicular dilatation and sebaceous gland atrophy, consistent with chloracne-like lesions. This current 2-year study supports recently published papers showing susceptibility to chloracne in mouse strains other than hairless mice. The chloracne-like lesions were not clinically evident; therefore, our study highlights the need for careful examination of the skin in order to identify subtle lesions consistent with chloracne-like changes in rodents exposed to dioxin and DLCs. Since previous short-term studies did not demonstrate any skin lesions, we suggest that reliable assessment of all safety issues involving dioxin and DLCs requires evaluation following chronic exposure. Such studies in animal models will help to elucidate the mechanisms of dioxin-related health hazards. Published by Elsevier Ireland Ltd. C1 [Flake, Gordon; Kissling, Grace E.; Malarkey, David E.; Hooth, Michelle J.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. [Ramot, Yuval] Hadassah Hebrew Univ, Med Ctr, IL-91200 Jerusalem, Israel. [Nyska, Abraham] Tel Aviv Univ, IL-36576 Tel Aviv, Israel. [Lieuallen, Warren] Charles River Labs Pathol Associates, Durham, NC 27703 USA. [Brix, Amy] Expt Pathol Labs, Res Triangle Pk, NC 27709 USA. RP Hooth, MJ (reprint author), NIEHS, Natl Toxicol Program, POB 12233,Mail Drop K2-13,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM hooth@niehs.nih.gov FU NIH, National Institute of Environmental Health Sciences [1 Z01 ES045004-11 BB] FX The authors gratefully acknowledge Ms. JoAnne Johnson, Dr. Robert Sills, and Dr. Nigel Walker from the NTP/NIEHS for their critical review of the manuscript. This research was supported [in part] by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences under Research Project Number 1 Z01 ES045004-11 BB. NR 87 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD NOV 9 PY 2009 VL 265 IS 1-2 BP 1 EP 9 DI 10.1016/j.tox.2009.08.017 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 518SM UT WOS:000271713500001 PM 19737593 ER PT J AU Nakamura, T Ito, Y Yanagiba, Y Ramdhan, DH Kono, Y Naito, H Hayashi, Y Li, YF Aoyama, T Gonzalez, FJ Nakajima, T AF Nakamura, Toshiki Ito, Yuki Yanagiba, Yukie Ramdhan, Doni Hikmat Kono, Yasuhide Naito, Hisao Hayashi, Yumi Li, Yufei Aoyama, Toshifumi Gonzalez, Frank J. Nakajima, Tamie TI Microgram-order ammonium perfluorooctanoate may activate mouse peroxisome proliferator-activated receptor alpha, but not human PPAR alpha SO TOXICOLOGY LA English DT Article DE Ammonium perflurooctanate; Peroxisome proliferator-activated receptor (PPAR) alpha; Humanized PPAR alpha mouse; Ppar alpha-null mouse; Lipid metabolism ID FLUOROCHEMICAL PRODUCTION WORKERS; RAT-LIVER; PFOA CONCENTRATIONS; NULL MICE; WILD-TYPE; ACID; EXPRESSION; INDUCTION; TRICHLOROETHYLENE; PURIFICATION AB Perfluorooctanoic acid (PFOA) is a ligand for peroxisome proliferator-activated receptor (PPAR)alpha, which exhibits marked species differences in expression and function, especially between rodents and humans. We investigated the functional difference in PFOA response between mice and humans, using a humanized PPAR alpha transgenic mouse line. Three genotyped mice, 129/5v wild-type (mPPAR alpha), Ppar alpha-null mice and humanized PPAR alpha (hPPAR alpha) mice (8-week-old males) were divided into three groups: the first was treated with water daily for 2 weeks by gavage (control group), and the remaining two groups were treated with 0.1 and 0.3 mg/kg ammonium perflurooctanate (APFO), respectively, for 2 weeks by gavage. The APFO dosages used did not influence the plasma triglyceride or total cholesterol levels in any mouse line, but the high dose increased both hepatic lipid levels only in mPPAR alpha mice. APFO increased mRNA and/or protein levels of PPAR alpha target genes cytochrome P450 Cyp4a10, peroxisomal thiolase and bifunctional protein only in the liver of mPPAR alpha mice, but not in Ppar alpha-null or hPPAR alpha mice. This chemical also increased expression of mitochondrial very long chain acyl-CoA dehydrogenase only in the liver of mPPAR alpha mice. Taken together, human PPAR alpha may be less responsive to PFOA than that of mice when a relatively low dose is applied. This information may be very valuable in considering whether PFOA influences the lipid metabolism in humans. (c) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Nakamura, Toshiki; Ito, Yuki; Yanagiba, Yukie; Ramdhan, Doni Hikmat; Kono, Yasuhide; Naito, Hisao; Hayashi, Yumi; Li, Yufei; Nakajima, Tamie] Nagoya Univ, Dept Occupat & Environm Hlth, Grad Sch Med, Showa Ku, Aichi 4668550, Japan. [Aoyama, Toshifumi] Shinshu Univ, Dept Metab Regulat, Grad Sch Med, Nagano 3908621, Japan. [Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Nakajima, T (reprint author), Nagoya Univ, Dept Occupat & Environm Hlth, Grad Sch Med, Showa Ku, 65 Tsurumai Cho, Aichi 4668550, Japan. EM tnasu23@med.nagoya-u.ac.jp RI Ito, Yuki/C-3698-2008 FU Japan Society for the Promotion of Science [B. 14370121, B. 17390169] FX We wish to thank Mr. Nakagawa, Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine for his valuable assistance. This study was supported in part by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (B. 14370121 and B. 17390169). NR 43 TC 20 Z9 23 U1 1 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD NOV 9 PY 2009 VL 265 IS 1-2 BP 27 EP 33 DI 10.1016/j.tox.2009.09.004 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 518SM UT WOS:000271713500004 PM 19751795 ER PT J AU Maguire, AM High, KA Auricchio, A Wright, JF Pierce, EA Testa, F Mingozzi, F Bennicelli, JL Ying, GS Rossi, S Fulton, A Marshall, KA Banfi, S Chung, DC Morgan, JIW Hauck, B Zelenaia, O Zhu, XS Raffini, L Coppieters, F De Baere, E Shindler, KS Volpe, NJ Surace, EM Acerra, C Lyubarsky, A Redmond, TM Stone, E Sun, JW McDonnell, JW Leroy, BP Simonelli, F Bennett, J AF Maguire, Albert M. High, Katherine A. Auricchio, Alberta Wright, J. Fraser Pierce, Eric A. Testa, Francesco Mingozzi, Federico Bennicelli, Jeannette L. Ying, Gui-shuang Rossi, Settimio Fulton, Ann Marshall, Kathleen A. Banfi, Sandra Chung, Daniel C. Morgan, Jessica I. W. Hauck, Bernd Zelenaia, Olga Zhu, Xiaosong Raffini, Leslie Coppieters, Frauke De Baere, Elfride Shindler, Kenneth S. Volpe, Nicholas J. Surace, Enrico M. Acerra, Carmela Lyubarsky, Arkady Redmond, T. Michael Stone, Edwin Sun, Junwei McDonnell, Jennifer Wellman Leroy, Bart P. Simonelli, Francesca Bennett, Jean TI Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial SO LANCET LA English DT Article ID VISUAL CYCLE; RETINITIS-PIGMENTOSA; VISION; MUTATIONS; BLINDNESS; ROD; ISOMEROHYDROLASE; ISOMERASE; KINETICS; SAFETY AB Background Gene therapy has the potential to reverse disease or prevent further deterioration of vision in patients with incurable inherited retinal degeneration. We therefore did a phase 1 trial to assess the effect of gene therapy on retinal and visual function in children and adults with Leber's congenital amaurosis. Methods We assessed the retinal and visual function in 12 patients (aged 8-44 years) with RPE65-associated Leber's congenital amaurosis given one subretinal injection of adeno-associated virus (AAV) containing a gene encoding a protein needed for the isomerohydrolase activity of the retinal pigment epithelium (AAV2-hRPE65v2) in the worst eye at low (1.5x10(10) vector genomes), medium (4.8x10(10) vector genomes), or high dose (1.5x10(11) vector genomes) for up to 2 years. Findings AAV2-hRPE65v2 was well tolerated and all patients showed sustained improvement in subjective and objective measurements of vision (ie, dark adaptometry, pupillometry, electroretinography, nystagmus, and ambulatory behaviour). Patients had at least a 2 log unit increase in pupillary light responses, and an 8-year-old child had nearly the same level of light sensitivity as that in age-matched normal-sighted individuals. The greatest improvement was noted in children, all of whom gained ambulatory vision. The study is registered with ClinicalTrials.gov, number NCT00516477. Interpretation The safety, extent, and stability of improvement in vision in all patients support the use of AAV mediated gene therapy for treatment of inherited retinal diseases, with early intervention resulting in the best potential gain. C1 [Bennett, Jean] Univ Penn, Stellar Chance Labs 309C, Scheie Eye Inst, FM Kirby Ctr Mol Ophthalmol, Philadelphia, PA 19104 USA. [Maguire, Albert M.; High, Katherine A.; Wright, J. Fraser; Mingozzi, Federico; Marshall, Kathleen A.; Hauck, Bernd; Zelenaia, Olga; Sun, Junwei; McDonnell, Jennifer Wellman; Bennett, Jean] Childrens Hosp Philadelphia, Ctr Cellular & Mol Therapeut, Abramson Pediat Res Ctr, Philadelphia, PA 19104 USA. [Maguire, Albert M.; Pierce, Eric A.; Zhu, Xiaosong] Childrens Hosp Philadelphia, Dept Ophthalmol, Philadelphia, PA 19104 USA. [High, Katherine A.; Raffini, Leslie] Univ Penn, Childrens Hosp Philadelphia, Dept Hematol, Dept Pediat, Philadelphia, PA 19104 USA. [High, Katherine A.; Stone, Edwin] Univ Penn, Howard Hughes Med Inst, Philadelphia, PA 19104 USA. [High, Katherine A.; Stone, Edwin] Univ Iowa, Howard Hughes Med Inst, Iowa City, IA 52242 USA. [Auricchio, Alberta; Banfi, Sandra; Surace, Enrico M.] TIGEM, Naples, Italy. [Auricchio, Alberta] Univ Naples Federico 2, Dept Pediat, Naples, Italy. [Testa, Francesco; Rossi, Settimio; Acerra, Carmela; Simonelli, Francesca] Univ Naples 2, Dept Ophthalmol, Naples, Italy. [Ying, Gui-shuang; Volpe, Nicholas J.] Univ Penn, Scheie Eye Inst, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, Philadelphia, PA 19104 USA. [Fulton, Ann] Childrens Hosp Boston, Dept Ophthalmol, Boston, MA USA. [Coppieters, Frauke; De Baere, Elfride; Leroy, Bart P.] Univ Ghent, Ctr Med Genet, B-9000 Ghent, Belgium. Univ Penn, Scheie Eye Inst, Neuroophthalmol Serv, Dept Ophthalmol, Philadelphia, PA 19104 USA. [Redmond, T. Michael] NEI, Lab Retinal Cell & Mol Biol, NIH, Bethesda, MD 20892 USA. [Stone, Edwin] Univ Iowa, Coll Med, Dept Ophthalmol, Carver Ctr, Iowa City, IA 52242 USA. [Wright, J. Fraser] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Leroy, Bart P.] Univ Ghent, Dept Ophthalmol, B-9000 Ghent, Belgium. [Leroy, Bart P.] Ghent Univ Hosp, B-9000 Ghent, Belgium. RP Bennett, J (reprint author), Univ Penn, Stellar Chance Labs 309C, Scheie Eye Inst, FM Kirby Ctr Mol Ophthalmol, 422 Curie Blvd, Philadelphia, PA 19104 USA. EM jebennet@mail.med.upenn.edu RI Shindler, Kenneth/D-2095-2009; Testa, Francesco/J-3185-2012; Rossi, Settimio/J-4922-2012; OI Testa, Francesco/0000-0002-1482-1577; Simonelli, Francesca/0000-0001-8520-6769; AURICCHIO, Alberto/0000-0002-0832-2472; Redmond, T. Michael/0000-0002-1813-5291; Surace, Enrico Maria/0000-0002-2975-942X; BANFI, Sandro/0000-0002-6541-8833; Pierce, Eric/0000-0002-2354-4102 FU Funding Center for Cellular and Molecular Therapeutics at the Children's Hospital of Philadelphia; Foundation Fighting Blindness; Telethon; Research to Prevent Blindness; F M Kirby Foundation; Mackall Foundation Trust; Regione Campania Convenzione; European Union; Associazione Italiana Amaurosi Congenita di Leber; Fund for Scientific Research; Fund for Research in Ophthalmology; National Center for Research Resources FX Funding Center for Cellular and Molecular Therapeutics at the Children's Hospital of Philadelphia, Foundation Fighting Blindness, Telethon, Research to Prevent Blindness, F M Kirby Foundation, Mackall Foundation Trust, Regione Campania Convenzione, European Union, Associazione Italiana Amaurosi Congenita di Leber, Fund for Scientific Research, Fund for Research in Ophthalmology, and National Center for Research Resources. NR 26 TC 373 Z9 386 U1 3 U2 35 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD NOV 7 PY 2009 VL 374 IS 9701 BP 1597 EP 1605 DI 10.1016/S0140-6736(09)61836-5 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 518EZ UT WOS:000271674600033 PM 19854499 ER PT J AU Chen, E Finkel, T AF Chen, Edmund Finkel, Toren TI The Tortoise, the Hare, and the FoxO SO CELL STEM CELL LA English DT Editorial Material ID OXIDATIVE STRESS; CELLS; MAINTENANCE; HOMEOSTASIS AB Maintaining stem cell quiescence is intimately connected to preserving long-term self-renewal potential. In this issue of Cell Stem Cell, Paik et al. (2009) and Renault et al. (2009) demonstrate a role for FoxO transcription factors in regulating neural stem cell proliferation and in maintaining stem and progenitor cell homeostasis. C1 [Chen, Edmund; Finkel, Toren] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. RP Finkel, T (reprint author), NHLBI, Translat Med Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM finkelt@nih.gov NR 11 TC 6 Z9 6 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD NOV 6 PY 2009 VL 5 IS 5 BP 451 EP 452 DI 10.1016/j.stem.2009.10.011 PG 2 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 522SR UT WOS:000272019500001 PM 19896431 ER PT J AU Seth, M Zhang, ZS Mao, L Graham, V Burch, J Stiber, J Tsiokas, L Winn, M Abramowitz, J Rockman, HA Birnbaumer, L Rosenberg, P AF Seth, Malini Zhang, Zhu-Shan Mao, Lan Graham, Victoria Burch, Jarrett Stiber, Jonathan Tsiokas, Leonidas Winn, Michelle Abramowitz, Joel Rockman, Howard A. Birnbaumer, Lutz Rosenberg, Paul TI TRPC1 Channels Are Critical for Hypertrophic Signaling in the Heart SO CIRCULATION RESEARCH LA English DT Article DE transient receptor potential channels; G protein receptor signaling; cardiac hypertrophy ID METABOTROPIC GLUTAMATE RECEPTORS; SMOOTH-MUSCLE-CELLS; CARDIAC-HYPERTROPHY; CATION CHANNEL; GROWTH CONES; ACTIVATION; GENE; MYOCYTES; HOMER; MICE AB Rationale: Cardiac muscle adapts to increase workload by altering cardiomyocyte size and function resulting in cardiac hypertrophy. G protein-coupled receptor signaling is known to govern the hypertrophic response through the regulation of ion channel activity and downstream signaling in failing cardiomyocytes. Objective: Transient receptor potential canonical (TRPC) channels are G protein-coupled receptor operated channels previously implicated in cardiac hypertrophy. Our objective of this study is to better understand how TRPC channels influence cardiomyocyte calcium signaling. Methods and Results: Here, we used whole cell patch clamp of adult cardiomyocytes to show upregulation of a nonselective cation current reminiscent of TRPC channels subjected to pressure overload. This TRPC current corresponds to the increased TRPC channel expression noted in hearts of mice subjected to pressure overload. Importantly, we show that mice lacking TRPC1 channels are missing this putative TRPC current. Moreover, Trpc1(-/-) mice fail to manifest evidence of maladaptive cardiac hypertrophy and maintain preserved cardiac function when subjected to hemodynamic stress and neurohormonal excess. In addition, we provide a mechanistic basis for the protection conferred to Trpc1(-/-) mice as mechanosensitive signaling through calcineurin/NFAT, mTOR and Akt is altered in Trpc1(-/-) mice. Conclusions: From these studies, we suggest that TRPC1 channels are critical for the adaptation to biomechanical stress and TRPC dysregulation leads to maladaptive cardiac hypertrophy and failure. (Circ Res. 2009;105:1023-1030.) C1 [Seth, Malini; Zhang, Zhu-Shan; Mao, Lan; Graham, Victoria; Burch, Jarrett; Stiber, Jonathan; Winn, Michelle; Rockman, Howard A.; Rosenberg, Paul] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA. [Tsiokas, Leonidas] Univ Oklahoma, Hlth Sci Ctr, Dept Cell Biol, Oklahoma City, OK USA. [Abramowitz, Joel; Birnbaumer, Lutz] NIEHS, Neurobiol Lab, Res Triangle Pk, NC 27709 USA. RP Rosenberg, P (reprint author), Suite 200,4321 Med Pk Dr, Durham, NC 27704 USA. EM rosen029@mc.duke.edu RI Abramowitz, Joel/A-2620-2015; OI Rosenberg, Paul/0000-0002-5659-160X FU NIH [R01-HL093470]; Muscular Dystrophy Association; NIH; National Institute of Environmental Health Sciences FX This work was supported by NIH grant R01-HL093470 (to P. R.), the Mandel Center at Duke (P.R.), and a Muscular Dystrophy Association research award (P.R.) and, in part, by the Intramural Program of the NIH, National Institute of Environmental Health Sciences ( to J.A. and L.B.). NR 45 TC 99 Z9 108 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD NOV 6 PY 2009 VL 105 IS 10 BP 1023 EP U190 DI 10.1161/CIRCRESAHA.109.206581 PG 17 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 515XE UT WOS:000271505400011 PM 19797170 ER PT J AU Kim, KK Adelstein, RS Kawamoto, S AF Kim, Kee K. Adelstein, Robert S. Kawamoto, Sachiyo TI Identification of Neuronal Nuclei (NeuN) as Fox-3, a New Member of the Fox-1 Gene Family of Splicing Factors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NEURAL STEM-CELLS; HEAVY CHAIN-B; DIAGNOSTIC HISTOPATHOLOGY; HUMAN TISSUES; MARKER NEUN; SPINAL-CORD; ADULT MICE; IN-VIVO; PROTEIN; EXPRESSION AB NeuN (neuronal nuclei) is a neuron-specific nuclear protein which is identified by immunoreactivity with a monoclonal antibody, anti-NeuN. Anti-NeuN has been used widely as a reliable tool to detect most postmitotic neuronal cell types in neuroscience, developmental biology, and stem cell research fields as well as diagnostic histopathology. To date, however, the identity of its antigen, NeuN itself, has been unknown. Here, we identify NeuN as the Fox-3 gene product by providing the following evidence: 1) Mass spectrometry analysis of anti-NeuN immunoreactive protein yields the Fox-3 amino acid sequence. 2) Recombinant Fox-3 is recognized by anti-NeuN. 3) Short hairpin RNAs targeting Fox-3 mRNA down-regulate NeuN expression. 4) Fox-3 expression is restricted to neural tissues. 5) Anti-Fox-3 immunostaining and anti-NeuN immunostaining overlap completely in neuronal nuclei. We also show that a protein cross-reactive with anti-NeuN is the synaptic vesicle protein, synapsin I. Anti-NeuN recognizes synapsin I in immunoblots with one order of magnitude lower affinity than Fox-3, and does not recognize synapsin I using immunohistology. Fox-3 (also called hexaribonucleotide-binding protein 3 and D11Bwg0517e) contains an RNA recognition motif and is classified as a member of the Fox-1 gene family that binds specifically to an RNA element, UGCAUG. We demonstrate that Fox-3 functions as a splicing regulator using neural cell-specific alternative splicing of the non-muscle myosin heavy chain II-B pre-mRNA as a model. Identification of NeuN as Fox-3 clarifies an important element of neurobiology research. C1 [Kim, Kee K.; Adelstein, Robert S.; Kawamoto, Sachiyo] NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Kawamoto, S (reprint author), NHLBI, Mol Cardiol Lab, NIH, Bldg 10,Rm 6C209,10 Ctr Dr MSC 1762, Bethesda, MD 20892 USA. EM kawamots@mail.nih.gov RI Kim, Kee/F-8784-2011; OI Adelstein, Robert/0000-0002-8683-2144 FU Division of Intramural Research; NHLBI; National Institutes of Health FX This work was supported, in whole or in part, by the Division of Intramural Research, NHLBI, National Institutes of Health. NR 40 TC 156 Z9 161 U1 0 U2 10 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 6 PY 2009 VL 284 IS 45 BP 31052 EP 31061 DI 10.1074/jbc.M109.052969 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 514EZ UT WOS:000271378400034 PM 19713214 ER PT J AU Ghosh, A Rossi, ML Aulds, J Croteau, D Bohr, VA AF Ghosh, Avik Rossi, Marie L. Aulds, Jason Croteau, Deborah Bohr, Vilhelm A. TI Telomeric D-loops Containing 8-Oxo-2 '-deoxyguanosine Are Preferred Substrates for Werner and Bloom Syndrome Helicases and Are Bound by POT1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SINGLE-STRANDED-DNA; RECQ HELICASES; MAMMALIAN TELOMERES; OXIDATIVE STRESS; SYNDROME PROTEIN; SYNDROME GENE; WRN PROTEIN; IN-VITRO; BINDING; SITE AB 8-Oxo-2'-deoxyguanosine (8-oxodG) is one of the most important oxidative DNA lesions, and G-rich telomeric DNA is especially susceptible to oxidative DNA damage. RecQ helicases WRN and BLM and telomere- binding protein POT1 are thought to play roles in telomere maintenance. This study examines the ability of WRN, BLM, and RecQ5 to unwind and POT1 to bind telomeric D-loops containing 8-oxodG. The results demonstrate that WRN and BLM preferentially unwind telomeric D-loops containing 8-oxodG and that POT1 binds with higher affinity to telomeric D-loops with 8-oxodG but shows no preference for telomeric single-stranded DNA with 8-oxodG. We speculate that telomeric D-loops with 8-oxodG may have a greater tendency to form G-quadruplex DNA structures than telomeric DNA lacking 8-oxodG. C1 [Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM BohrV@.nih.gov FU National Institute on Aging FX This work was supported, in whole or in part, by the National Institutes of Health Intramural Program of the National Institute on Aging. NR 51 TC 35 Z9 35 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 6 PY 2009 VL 284 IS 45 BP 31074 EP 31084 DI 10.1074/jbc.M109.027532 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 514EZ UT WOS:000271378400036 PM 19734539 ER PT J AU Prokunina-Olsson, L Hall, JL AF Prokunina-Olsson, Ludmila Hall, Jennifer L. TI No effect of cancer-associated SNP rs6983267 in the 8q24 region on co-expression of MYC and TCF7L2 in normal colon tissue SO MOLECULAR CANCER LA English DT Article ID GENOME-WIDE ASSOCIATION; COLORECTAL-CANCER; PROSTATE-CANCER; CHROMOSOME 8Q24; C-MYC; SMALL-INTESTINE; RISK; GENE; EXPRESSION; TARGET AB A single nucleotide polymorphism (SNP) rs6983267, located within the 8q24 region, is strongly associated with risk of colorectal and prostate cancer. It has been suggested that the mechanism of this association is related to differential interaction of TCF7L2 protein (previously known as TCF-4) with alleles of rs6983267, influencing the expression of a well-known oncogene, MYC, located 335 Kb telomeric. Here, we tested the correlation between mRNA expression of MYC and several alternatively spliced forms of TCF7L2 in 117 non-cancer colon samples. We observed a strong correlation (r = 0.60, p < 10(-6)) between expression of MYC and a unique splicing form of TCF7L2. The level of MYC expression in these samples was associated with expression of some TCF7L2 splicing forms but not with genotypes of rs6983267, or interaction of rs6983267 with TCF7L2 expression. These findings suggest that some splicing forms of TCF7L2 may be functionally important for regulation of MYC expression in colon tissue but this regulation is not directly dependent on rs6983267. C1 [Prokunina-Olsson, Ludmila] NCI, Lab Translat Gen, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Hall, Jennifer L.] Univ Minnesota, Dept Med, Lillehei Heart Inst, Minneapolis, MN 55455 USA. RP Prokunina-Olsson, L (reprint author), NCI, Lab Translat Gen, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. EM prokuninal@mail.nih.gov; jlhall@umn.edu OI Prokunina-Olsson, Ludmila/0000-0002-9622-2091 FU NCI/NIH (LPO); R21 award [1R21DK078029-01] FX We thank Yi-Ping Fu for help with statistical analysis. The study was supported by the intramural research program of NCI/NIH (LPO) and by an R21 award to JLH (1R21DK078029-01). We would like to thank Cullan Welch, Nikki Usher, and Marj Carlson for their technical assistance with the tissue processing. NR 33 TC 15 Z9 16 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-4598 J9 MOL CANCER JI Mol. Cancer PD NOV 6 PY 2009 VL 8 AR 96 DI 10.1186/1476-4598-8-96 PG 5 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 526IL UT WOS:000272281400001 PM 19895682 ER PT J AU Ren, D Labandeira, CC Santiago-Blay, JA Rasnitsyn, A Shih, C Bashkuev, A Logan, MAV Hotton, CL Dilcher, D AF Ren, Dong Labandeira, Conrad C. Santiago-Blay, Jorge A. Rasnitsyn, Alexandr Shih, ChungKun Bashkuev, Alexei Logan, M. Amelia V. Hotton, Carol L. Dilcher, David TI A Probable Pollination Mode Before Angiosperms: Eurasian, Long-Proboscid Scorpionflies SO SCIENCE LA English DT Article ID REPRODUCTIVE STRUCTURES; INSECT POLLINATION; POLLEN MORPHOLOGY; FOSSIL EVIDENCE; DIVERSITY; DIPTERA; DIVERSIFICATION; COEVOLUTION; BRACHYCERA; MOUTHPARTS AB The head and mouthpart structures of 11 species of Eurasian scorpionflies represent three extinct and closely related families during a 62-million-year interval from the late Middle Jurassic to the late Early Cretaceous. These taxa had elongate, siphonate ( tubular) proboscides and fed on ovular secretions of extinct gymnosperms. Five potential ovulate host-plant taxa co-occur with these insects: a seed fern, conifer, ginkgoopsid, pentoxylalean, and gnetalean. The presence of scorpionfly taxa suggests that siphonate proboscides fed on gymnosperm pollination drops and likely engaged in pollination mutualisms with gymnosperms during the mid-Mesozoic, long before the similar and independent coevolution of nectar-feeding flies, moths, and beetles on angiosperms. All three scorpionfly families became extinct during the later Early Cretaceous, coincident with global gymnosperm-to-angiosperm turnover. C1 [Ren, Dong; Shih, ChungKun] Capital Normal Univ, Coll Life Sci, Beijing 100048, Peoples R China. [Labandeira, Conrad C.; Santiago-Blay, Jorge A.; Hotton, Carol L.; Dilcher, David] Smithsonian Inst, Natl Museum Nat Hist, Dept Paleobiol, Washington, DC 20013 USA. [Labandeira, Conrad C.] Univ Maryland, Dept Entomol, College Pk, MD 20742 USA. [Santiago-Blay, Jorge A.] Gallaudet Univ, Dept Biol, Washington, DC 20003 USA. [Rasnitsyn, Alexandr] Russian Acad Sci, Inst Paleontol, Moscow 117997, Russia. [Rasnitsyn, Alexandr] Nat Hist Museum, Dept Palaeontol, London SW7 5BD, England. [Logan, M. Amelia V.] Smithsonian Inst, Natl Museum Nat Hist, Dept Mineral Sci, Washington, DC 20013 USA. [Hotton, Carol L.] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. [Dilcher, David] Univ Florida, Florida Museum Nat Hist, Gainesville, FL 32611 USA. RP Labandeira, CC (reprint author), Capital Normal Univ, Coll Life Sci, Beijing 100048, Peoples R China. EM labandec@si.edu FU National Science Foundation of China [30430100, 40872022]; Natural Science Foundation of Beijing [5082002]; Key and PHR Program of the Beijing Municipal Commission of Education; Origin and Evolution of the Biosphere program of the Presidium of the Russian Academy of Sciences; Intramural Research Program of the National Library of Medicine FX This is contribution 152 of the Evolution of Terrestrial Ecosystems consortium at the National Museum of Natural History and contribution 614 of the Florida Museum of Natural History. Supported by the National Science Foundation of China ( grants 30430100 and 40872022), the Natural Science Foundation of Beijing ( grant 5082002), and the Key and PHR Program of the Beijing Municipal Commission of Education ( D. R.); the Origin and Evolution of the Biosphere program of the Presidium of the Russian Academy of Sciences ( A. B.); and the Intramural Research Program of the National Library of Medicine. We thank F. Marsh for drafting the figures, T. Lott for a presubmission review, P. Crane for comments, T. Rose for assistance on the geochemical analyses, J. Corman for collection of data, B. Wagner and R. Johnson for translations, P. Peltier for proofreading, and W. Wu for general assistance. X. Wang provided data and images for Problematospermum ovale, and D. Grimaldi of the American Museum of Natural History ( New York) made an important specimen available for study. NR 54 TC 113 Z9 128 U1 2 U2 49 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD NOV 6 PY 2009 VL 326 IS 5954 BP 840 EP 847 DI 10.1126/science.1178338 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 515KG UT WOS:000271468000041 PM 19892981 ER PT J AU Coutellier, L Wurbel, H AF Coutellier, Laurence Wuerbel, Hanno TI Early environmental cues affect object recognition memory in adult female but not male C57BL/6 mice SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Maternal environment; Object recognition memory; Predator cues; Offspring ID POSTNATAL MATERNAL ENVIRONMENT; COGNITIVE FUNCTION; STRESS REACTIVITY; CARE; RESPONSES; RATS; BEHAVIOR; EXPRESSION; ENRICHMENT; FEAR AB We studied the effects of variations in maternal environment on maternal behaviour and offspring memory in mice by exposing lactating C57BL/6J dams to predator cues and/or environmental enrichment. At 10 weeks of age, object recognition memory in the offspring was assessed. The presence of enrichment in the maternal environment had no effect on offspring memory. In contrast, female offspring of dams that were not exposed to predator cues displayed a significant preference for the novel object (p = 0.05) and a significantly higher preference score (PS) than female offspring of dams that were exposed to predator cues (F= 4.23, p = 0.05) indicating an impairment in object recognition memory in the latter. Conversely, there was no evidence of object recognition memory in male offspring, except for males of dams exposed to predator cues without shelter (p = 0.03). These effects can be explained by an interaction between variations in maternal care and the stressfulness of the rearing conditions since a regression analysis revealed an inverse relationship between the level of licking-grooming and the PS, but only in female offspring reared by dams exposed to the predator cues (beta = -0.96, p = 0.001). The present findings thus provide some evidence that early rearing conditions may affect cognitive abilities of mice. The data also suggest that these effects may be sex-specific, and that females may be more sensitive to early environmental variations than males. (C) 2009 Elsevier B.V. All rights reserved. C1 [Coutellier, Laurence] NIMH, Sect Fundamental Neurosci, NIH, Bethesda, MD 20892 USA. [Wuerbel, Hanno] Univ Giessen, Div Anim Welf & Ethol, D-35392 Giessen, Germany. RP Coutellier, L (reprint author), NIMH, Sect Fundamental Neurosci, NIH, 35 Convent Dr, Bethesda, MD 20892 USA. EM coutellierl@mail.nih.gov RI Wurbel, Hanno/D-6281-2012 OI Wurbel, Hanno/0000-0002-2934-3010 NR 24 TC 13 Z9 13 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD NOV 5 PY 2009 VL 203 IS 2 BP 312 EP 315 DI 10.1016/j.bbr.2009.05.001 PG 4 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 475MP UT WOS:000268364100021 PM 19427334 ER PT J AU Flegel, WA AF Flegel, Willy Albert TI Immunogenicity reloaded SO BLOOD LA English DT Editorial Material C1 Natl Inst Hlth, Bethesda, MD 20892 USA. RP Flegel, WA (reprint author), Natl Inst Hlth, Bethesda, MD 20892 USA. NR 5 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 5 PY 2009 VL 114 IS 19 BP 3979 EP 3980 DI 10.1182/blood-2009-09-241448 PG 4 WC Hematology SC Hematology GA 515TJ UT WOS:000271495500005 PM 19892725 ER PT J AU Li, ZY Wang, HS Xue, LQ Shin, DM Roopenian, D Xu, W Qi, CF Sangster, MY Orihuela, CJ Tuomanen, E Rehg, JE Cui, XL Zhang, QG Morse, HC Morris, SW AF Li, Zhaoyang Wang, Hongsheng Xue, Liquan Shin, Dong-Mi Roopenian, Derry Xu, Wu Qi, Chen-Feng Sangster, Mark Y. Orihuela, Carlos J. Tuomanen, Elaine Rehg, Jerold E. Cui, Xiaoli Zhang, Quangeng Morse, Herbert C., III Morris, Stephan W. TI E mu-BCL10 mice exhibit constitutive activation of both canonical and noncanonical NF-kappa B pathways generating marginal zone (MZ) B-cell expansion as a precursor to splenic MZ lymphoma SO BLOOD LA English DT Article ID POSITIVE SELECTION; MALT LYMPHOMA; NUCLEAR EXPRESSION; PLASMA-CELL; B1B CELLS; T-CELL; BCL10; LYMPHOCYTES; BAFF; APRIL AB BCL10, required for nuclear factor kappa B (NF-kappa B) activation during antigen-driven lymphocyte responses, is aberrantly expressed in mucosa-associated lymphoid tissue-type marginal zone (MZ) lymphomas because of chromosomal translocations. E mu-driven human BCL10 transgenic (Tg) mice, which we created and characterize here, had expanded populations of MZ B cells and reduced follicular and B1a cells. Splenic B cells from Tg mice exhibited constitutive activation of both canonical and noncanonical NF-kappa B signaling pathways is associated with increased expression of NF-kappa B target genes. These genes included Tnfsf13b, which encodes the B-cell activating factor (BAFF). In addition, levels of BAFF were significantly increased in sera from Tg mice. MZ B cells of Tg mice exhibited reduced turnover in vivo and enhanced survival in vitro, indicative of lymphoaccumulation rather than lymphoproliferation as the cause of MZ expansion. In vivo antibody responses to both T-independent, and especially T-dependent, antigens were significantly reduced in Tg mice. Mortality was accelerated in Tg animals, and some mice older than 8 months had histologic and molecular findings indicative of clonal splenic MZ lymphoma. These results suggest that, in addition to constitutive activation of BCL10 in MZ B cells, other genetic factors or environmental influences are required for short latency oncogenic transformation. (Blood. 2009; 114:4158-4168) C1 [Zhang, Quangeng] Capital Med Univ, Dept Immunol, Beijing 100069, Peoples R China. [Li, Zhaoyang; Wang, Hongsheng; Shin, Dong-Mi; Qi, Chen-Feng; Morse, Herbert C., III] NIAID, Immunopathol Lab, NIH, Rockville, MD 20852 USA. [Xue, Liquan; Rehg, Jerold E.; Cui, Xiaoli; Morris, Stephan W.] St Jude Childrens Hosp, Dept Pathol, Memphis, TN 38105 USA. [Xue, Liquan; Rehg, Jerold E.; Cui, Xiaoli; Morris, Stephan W.] St Jude Childrens Hosp, Dept Oncol, Memphis, TN 38105 USA. [Roopenian, Derry] Jackson Lab, Bar Harbor, ME 04609 USA. [Xu, Wu] Univ Louisiana, Dept Chem, Lafayette, LA USA. [Sangster, Mark Y.] Univ Tennessee, Dept Microbiol, Knoxville, TN 37996 USA. [Orihuela, Carlos J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, San Antonio, TX 78229 USA. [Tuomanen, Elaine] St Jude Childrens Hosp, Dept Infect Dis, Memphis, TN 38105 USA. RP Zhang, QG (reprint author), Capital Med Univ, Dept Immunol, Rm 1121,2nd Teaching Bldg,10 Xi Tou Tiao, Beijing 100069, Peoples R China. EM zhangqg@ccmu.edu.cn; hmorse@niaid.nih.gov; steve.morris@stjude.org RI Li, Chaoyang/A-7980-2012; OI Morse, Herbert/0000-0002-9331-3705 FU Intramural Research Program of the National Institutes of Health; National Institute of Allergy and Infectious Diseases; National Cancer Institute [R01 CA87064]; Cancer Center [CA21765]; American Lebanese Syrian Associated Charities (ALSAC); St Jude Children's Research Hospital FX This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases and by National Cancer Institute (NCI; grant R01 CA87064, S.W.M.), Cancer Center (CORE; grant CA21765), and the American Lebanese Syrian Associated Charities (ALSAC), St Jude Children's Research Hospital. NR 50 TC 31 Z9 33 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 5 PY 2009 VL 114 IS 19 BP 4158 EP 4168 DI 10.1182/blood-2008-12-192583 PG 11 WC Hematology SC Hematology GA 515TJ UT WOS:000271495500029 PM 19696203 ER PT J AU Drazen, JM Van Der Weyden, MB Sahni, P Rosenberg, J Marusic, A Laine, C Kotzin, S Horton, R Hebert, PC Haug, C Godlee, F Frizelle, FA de Leeuw, PW DeAngelis, CD AF Drazen, Jeffrey M. Van Der Weyden, Martin B. Sahni, Peush Rosenberg, Jacob Marusic, Ana Laine, Christine Kotzin, Sheldon Horton, Richard Hebert, Paul C. Haug, Charlotte Godlee, Fiona Frizelle, Frank A. de Leeuw, Peter W. DeAngelis, Catherine D. TI Uniform Format for Disclosure of Competing Interests in ICMJE Journals. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Kotzin, Sheldon] Natl Lib Med, Bethesda, MD 20894 USA. RI Marusic, Ana/E-7683-2013; OI Marusic, Ana/0000-0001-6272-0917; Sahni, Peush/0000-0002-6910-062X NR 0 TC 48 Z9 53 U1 0 U2 1 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 5 PY 2009 VL 361 IS 19 BP 1896 EP 1897 DI 10.1056/NEJMe0909052 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 514OZ UT WOS:000271405800017 PM 19825973 ER PT J AU Tsaneva-Atanasova, K Sherman, A AF Tsaneva-Atanasova, Krasimira Sherman, Arthur TI Accounting for Near-Normal Glucose Sensitivity in K(ir)6.2[AAA] Transgenic Mice SO BIOPHYSICAL JOURNAL LA English DT Article ID PANCREATIC-BETA-CELLS; K-ATP CHANNELS; SINGLE POTASSIUM CHANNELS; INSULIN-SECRETION; B-CELLS; ELECTRICAL-ACTIVITY; CA2+ CONCENTRATION; INTRACELLULAR ATP; MINIMAL MODEL; MEMBRANE AB K(ir)6.2[AAA] transgenic mouse islets exhibit mosaicism such that similar to 70% of the beta-cells have nonfunctional ATP-sensitive potassium (K-ATP) channels, whereas the remainder have normal KATP function. Despite this drastic reduction, the glucose dose-response curve is only shifted by similar to 2 mM. We use a previously published mathematical model, in which K-ATP conductance is increased by rises in cytosolic calcium through indirect effects on metabolism, to investigate how cells could compensate for the loss of K-ATP conductance. Compensation is favored by the assumption that only a small fraction of K-ATP channels are open during oscillations, which renders it easy to upregulate the open fraction via a modest elevation of calcium. We show further that strong gap-junctional coupling of both membrane potential and calcium is needed to overcome the stark heterogeneity of cell properties in these mosaic islets. C1 [Tsaneva-Atanasova, Krasimira; Sherman, Arthur] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD USA. RP Sherman, A (reprint author), NIDDK, Lab Biol Modeling, NIH, Bethesda, MD USA. EM asherman@nih.gov RI Tsaneva-Atanasova, Krasimira/A-7153-2011; OI Tsaneva-Atanasova, Krasimira/0000-0002-6294-7051 FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD FX A.S. Was Supported by the intramural research program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD. NR 57 TC 7 Z9 7 U1 0 U2 0 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 4 PY 2009 VL 97 IS 9 BP 2409 EP 2418 DI 10.1016/j.bpj.2009.07.060 PG 10 WC Biophysics SC Biophysics GA 515FU UT WOS:000271454000006 PM 19883583 ER PT J AU Zhu, FQ Hummer, G AF Zhu, Fangqiang Hummer, Gerhard TI Gating Transition of Pentameric Ligand-Gated Ion Channels SO BIOPHYSICAL JOURNAL LA English DT Article ID NICOTINIC ACETYLCHOLINE-RECEPTOR; KCSA POTASSIUM CHANNEL; NORMAL-MODE ANALYSIS; MOLECULAR-DYNAMICS SIMULATIONS; ELASTIC NETWORK MODEL; X-RAY-STRUCTURE; MECHANOSENSITIVE CHANNEL; CONFORMATIONAL-CHANGE; ENERGY LANDSCAPES; OPEN-STATE AB Pentameric ligand-gated ion channels are an important family of membrane proteins and play key roles in physiological processes, including signal transduction at chemical synapses. Here, we study the conformational changes associated with the opening and closing of the channel pore. Based on recent crystal structures of two prokaryotic members of the family in open and closed states, respectively, mixed elastic network models are constructed for the transmembrane domain. To explore the conformational changes in the gating transition, a coarse-grained transition path is computed that smoothly connects the closed and open conformations of the channel. We find that the conformational transition involves no major rotations of the transmembrane helices, and is instead characterized by a concerted tilting of helices M2 and M3. In addition, helix M2 changes its bending state, which results in an early closure of the pore during the open-to-closed transition. C1 [Zhu, Fangqiang; Hummer, Gerhard] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Hummer, G (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM hummer@helix.nih.gov RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. NR 49 TC 30 Z9 30 U1 0 U2 6 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 4 PY 2009 VL 97 IS 9 BP 2456 EP 2463 DI 10.1016/j.bpj.2009.08.020 PG 8 WC Biophysics SC Biophysics GA 515FU UT WOS:000271454000011 PM 19883588 ER PT J AU Costanzo-Garvey, DL Pfluger, PT Dougherty, MK Stock, JL Boehm, M Chaika, O Fernandez, MR Fisher, K Kortum, RL Hong, EG Jun, JY Ko, HJ Schreiner, A Volle, DJ Treece, T Swift, AL Winer, M Chen, D Wu, M Leon, LR Shaw, AS McNeish, J Kim, JK Morrison, DK Tschop, MH Lewis, RE AF Costanzo-Garvey, Diane L. Pfluger, Paul T. Dougherty, Michele K. Stock, Jeffery L. Boehm, Matthew Chaika, Oleg Fernandez, Mario R. Fisher, Kurt Kortum, Robert L. Hong, Eun-Gyoung Jun, John Y. Ko, Hwi Jin Schreiner, Aimee Volle, Deanna J. Treece, Tina Swift, Amy L. Winer, Mike Chen, Denise Wu, Min Leon, Lisa R. Shaw, Andrey S. McNeish, John Kim, Jason K. Morrison, Deborah K. Tschoep, Matthias H. Lewis, Robert E. TI KSR2 Is an Essential Regulator of AMP Kinase, Energy Expenditure, and Insulin Sensitivity SO CELL METABOLISM LA English DT Article ID ACTIVATED PROTEIN-KINASE; GLUCOSE-TRANSPORT; CELLULAR-ENERGY; SKELETAL-MUSCLE; IN-VIVO; SCAFFOLD; PHOSPHORYLATION; OBESITY; IDENTIFICATION; SUPPRESSOR AB Kinase suppressors of Ras 1 and 2 (KSR1 and KSR2) function as molecular scaffolds to potently regulate the MAP kinases ERK1/2 and affect multiple cell fates. Here we show that KSR2 interacts with and modulates the activity of AMPK. KSR2 regulates AMPK-dependent glucose uptake and fatty acid oxidation in mouse embryonic fibroblasts and glycolysis in a neuronal cell line. Disruption of KSR2 in vivo impairs AMPK-regulated processes affecting fatty acid oxidation and thermogenesis to cause obesity. Despite their increased adiposity, ksr2(-/-) mice are hypophagic and hyperactive but expend less energy than wild-type mice. In addition, hyperinsulinemic-euglycemic clamp studies reveal that ksr2(-/-) mice are profoundly insulin resistant. The expression of genes mediating oxidative phosphorylation is also downregulated in the adipose tissue of ksr2(-/-) mice. These data demonstrate that ksr2(-/-) mice are highly efficient in conserving energy, revealing a novel role for KSR2 in AMPK-mediated regulation of energy metabolism. C1 [Costanzo-Garvey, Diane L.; Boehm, Matthew; Chaika, Oleg; Fernandez, Mario R.; Fisher, Kurt; Kortum, Robert L.; Schreiner, Aimee; Volle, Deanna J.; Treece, Tina; Lewis, Robert E.] Univ Nebraska Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA. [Pfluger, Paul T.; Tschoep, Matthias H.] Univ Cincinnati, Dept Med, Obes Res Ctr, Cincinnati, OH 45237 USA. [Dougherty, Michele K.; Morrison, Deborah K.] NCI, Lab Cell & Dev Signaling, Ctr Canc Res, NIH, Frederick, MD 21702 USA. [Stock, Jeffery L.; McNeish, John] Pfizer Global Res & Dev, Genet Technol, Groton, CT 06340 USA. [Hong, Eun-Gyoung; Jun, John Y.; Ko, Hwi Jin; Kim, Jason K.] Penn State Coll Med, Penn State Mouse Metab Phenotyping Ctr, Dept Cellular & Mol Physiol, Hershey, PA 17033 USA. [Swift, Amy L.; Winer, Mike; Chen, Denise; Wu, Min] Seahorse Biosci, N Billerica, MA 01862 USA. [Leon, Lisa R.] USA, Thermal Mt Med Div, Environm Med Res Inst, Natick, MA 01760 USA. [Shaw, Andrey S.] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA. [Shaw, Andrey S.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. RP Lewis, RE (reprint author), Univ Nebraska Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA. EM rlewis@unmc.edu RI Pfluger, Paul/B-4889-2010; Tschoep, Matthias/I-5443-2014; OI Tschoep, Matthias/0000-0002-4744-371X FU National Institutes of Health (NIH) [DK52809, DK69987, DK59630, DK56863, P20 RR016469]; Nebraska Research Initiative; Skala Fellowship; University of Nebraska Medical Center (UNMC); American Diabetes Association FX We thank the members of the Lewis laboratory for comments and criticism. M. Birnbaum (University of Pennsylvania) is thanked for his gift of the constitutively active AMPK construct. This work was supported by National Institutes of Health (NIH) grants to R.E.L. (DK52809) and M.H.T. (DK69987, DK59630, and DK56863) and by support from the Nebraska Research Initiative (to R.E.L.). M.R.F was supported by the Skala Fellowship, and M.B. was supported by the Bukey Fellowship from the University of Nebraska Medical Center (UNMC). K.F. was supported by a Physician/Scientist Training Award from the American Diabetes Association. The UNMC Microarray Core Facility receives partial support from NIH grant P20 RR016469. For those studies conducted at United States Army Research Institute Environmental Medicine (USARIEM), the opinions or assertions contained herein are the private views of the author(s) and are not to be construed as official or reflecting the views of the Army or the Department of Defense. Any citations of commercial organizations and trade names in this report do not constitute an official Department of the Army endorsement of approval of the products or services of these organizations. NR 43 TC 60 Z9 60 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD NOV 4 PY 2009 VL 10 IS 5 BP 366 EP 378 DI 10.1016/j.cmet.2009.09.010 PG 13 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 515UP UT WOS:000271498700006 PM 19883615 ER PT J AU Kemper, JK Xiao, Z Ponugoti, B Miao, J Fang, S Kanamaluru, D Tsang, S Wu, SY Chiang, CM Veenstra, TD AF Kemper, Jongsook Kim Xiao, Zhen Ponugoti, Bhaskar Miao, Ji Fang, Sungsoon Kanamaluru, Deepthi Tsang, Stephanie Wu, Shwu-Yuan Chiang, Cheng-Ming Veenstra, Timothy D. TI FXR Acetylation Is Normally Dynamically Regulated by p300 and SIRT1 but Constitutively Elevated in Metabolic Disease States SO CELL METABOLISM LA English DT Article ID BILE-ACID BIOSYNTHESIS; FARNESOID-X-RECEPTOR; NUCLEAR RECEPTOR; GLUCOSE-HOMEOSTASIS; PGC-1-ALPHA; SHP; ACTIVATION; COMPLEX; TRANSCRIPTION; CHOLESTEROL AB The nuclear bile acid receptor FXR is critical for regulation of lipid and glucose metabolism. Here, we report that FXR is a target of SIRT1, a deacetylase that mediates nutritional and hormonal modulation of hepatic metabolism. Lysine 217 of FXR is the major acetylation site targeted by p300 and SIRT1. Acetylation of FXR increases its stability but inhibits heterodimerization with RXR alpha, DNA binding, and transactivation activity. Downregulation of hepatic SIRT1 increased FXR acetylation with deleterious metabolic outcomes. Surprisingly, in mouse models of metabolic disease, FXR interaction with SIRT1 and p300 was dramatically altered, FXR acetylation levels were elevated, and overexpression of SIRT1 or resveratrol treatment reduced acetylated FXR levels. Our data demonstrate that FXR acetylation is normally dynamically regulated by p300 and SIRT1 but is constitutively elevated in metabolic disease states. Small molecules that inhibit FXR acetylation by targeting SIRT1 or p300 may be promising therapeutic agents for metabolic disorders. C1 [Kemper, Jongsook Kim; Ponugoti, Bhaskar; Miao, Ji; Fang, Sungsoon; Kanamaluru, Deepthi; Tsang, Stephanie] Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL 61801 USA. [Xiao, Zhen; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [Wu, Shwu-Yuan; Chiang, Cheng-Ming] Univ Texas SW Med Ctr Dallas, Dept Biochem, Simmons Comprehens Canc Ctr, Dallas, TX 75390 USA. [Wu, Shwu-Yuan; Chiang, Cheng-Ming] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA. RP Kemper, JK (reprint author), Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL 61801 USA. EM jongsook@uiuc.edu RI PONUGOTI, BHASKAR/H-2230-2011 FU NIH [CA103867, CA124760, DK062777, DK80032]; National Cancer Institute, National Institutes of Health [N01-CO-12400] FX We are grateful to P. Puigserver for Ad-siSIRT1 and Ad-flag-SIRT1, P. Edwards for FXR deletion constructs, M. Leid for GST-SIRT1 constructs, R. Sato for plasmids CMV-3 flag-FXR and G4DBD-FXR, W. Gu and T. Finkel for plasmids for SIRT1 WT and mutant, M. Ananthanarayanan for (FXRE)3-tkluc, Yoon K. Lee for the Shp-luc reporter plasmid, and T. Imamura for the HA-Ub plasmid. Special thanks to Dr. T.M. Willson for providing GW4064. We also thank B. Kemper for helpful discussions. This study was supported by NIH grants CA103867 and CA124760 to C.-M.C. and NIH DK062777, NIH DK80032, and ADA basic research award to J.K.K. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health under Contract N01-CO-12400 to T.D.V. NR 39 TC 137 Z9 143 U1 2 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD NOV 4 PY 2009 VL 10 IS 5 BP 392 EP 404 DI 10.1016/j.cmet.2009.09.009 PG 13 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 515UP UT WOS:000271498700008 PM 19883617 ER PT J AU Merikangas, KR Lehner, T Risch, NJ AF Merikangas, Kathleen Ries Lehner, Thomas Risch, Neil J. TI Gene-Environment Interactions and Depression Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID POLYMORPHISM C1 [Merikangas, Kathleen Ries; Lehner, Thomas] NIMH, Genet Epidemiol Res Branch, Bethesda, MD 20892 USA. [Risch, Neil J.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. RP Merikangas, KR (reprint author), NIMH, Genet Epidemiol Res Branch, Bethesda, MD 20892 USA. EM kathleen.merikangas@nih.gov NR 2 TC 3 Z9 3 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 4 PY 2009 VL 302 IS 17 BP 1861 EP 1862 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 514DU UT WOS:000271375300011 ER PT J AU Dorgan, JF Stanczyk, FZ Egleston, BL Kahle, LL Shaw, CM Spittle, CS Godwin, AK Brinton, LA AF Dorgan, Joanne F. Stanczyk, Frank Z. Egleston, Brian L. Kahle, Lisa L. Shaw, Christiana M. Spittle, Cynthia S. Godwin, Andrew K. Brinton, Louise A. TI Prospective Case-Control Study of Serum Mullerian Inhibiting Substance and Breast Cancer Risk SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID POLYCYSTIC-OVARY-SYNDROME; POSTMENOPAUSAL WOMEN; MENSTRUAL-CYCLE; HORMONE-LEVELS; FREE TESTOSTERONE; GROWTH; AGE; SECRETION; AROMATASE; DECLINE AB Mullerian inhibiting substance (MIS) is a member of the transforming growth factor beta family of growth and differentiation factors that inhibits elongation and branching of mammary ducts and has been shown to inhibit mammary tumor growth in vitro and in animal models. The objective of this study was to determine whether serum MIS levels are associated with breast cancer risk. We conducted a prospective case-control study of 309 participants who were registered in the Columbia, Missouri Serum Bank. Each of 105 in situ or invasive breast cancer case patients with prediagnostic serum collected before menopause was matched to two control subjects by age, date, menstrual cycle day, and time of day of blood collection. MIS was measured in serum by using an enzyme-linked immunosorbent assay, and estradiol and testosterone concentrations were quantified by using specific radioimmunoassays. Data were analyzed using conditional logistic regression. All tests of statistical significance were two-sided. The relative odds ratio of breast cancer for women in increasing MIS quartiles were 1, 2.8 (95% confidence interval [CI] = 1.0 to 7.4), 5.9 (95% CI = 2.4 to 14.6), and 9.8 (95% CI = 3.3 to 28.9, P-trend < .001). The association of MIS with breast cancer was weaker in women who were not taking oral contraceptives at the time of blood collection, but adjustment for estradiol and testosterone levels did not materially alter results for these women. The association of MIS with breast cancer did not vary by age at blood collection but was stronger among women who were diagnosed with breast cancer at an older age than among those who were diagnosed at a younger age. MIS may be a novel biomarker of increased breast cancer risk. Additional research including confirmatory epidemiological studies and mechanistic studies is needed. C1 [Dorgan, Joanne F.; Egleston, Brian L.; Shaw, Christiana M.; Spittle, Cynthia S.; Godwin, Andrew K.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Stanczyk, Frank Z.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Stanczyk, Frank Z.] Univ So Calif, Keck Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90033 USA. [Kahle, Lisa L.] Informat Management Serv Inc, Rockville, MD USA. [Brinton, Louise A.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Dorgan, JF (reprint author), Fox Chase Canc Ctr, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM joanne.dorgan@fccc.edu RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 FU Department of Defense [BC062367]; National Institutes of Health [P30CA006927]; National Institutes of Health intramural research program FX Department of Defense (BC062367 to J.F.D.), National Institutes of Health (P30CA006927), and National Institutes of Health intramural research program. NR 31 TC 8 Z9 9 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD NOV 4 PY 2009 VL 101 IS 21 BP 1501 EP 1509 DI 10.1093/jnci/djp331 PG 9 WC Oncology SC Oncology GA 516WX UT WOS:000271575100010 PM 19820206 ER PT J AU Parisiadou, L Xie, CS Cho, HJ Lin, X Gu, XL Long, CX Lobbestael, E Baekelandt, V Taymans, JM Sun, LX Cai, HB AF Parisiadou, Loukia Xie, Chengsong Cho, Hyun Jin Lin, Xian Gu, Xing-Long Long, Cai-Xia Lobbestael, Evy Baekelandt, Veerle Taymans, Jean-Marc Sun, Lixin Cai, Huaibin TI Phosphorylation of Ezrin/Radixin/Moesin Proteins by LRRK2 Promotes the Rearrangement of Actin Cytoskeleton in Neuronal Morphogenesis SO JOURNAL OF NEUROSCIENCE LA English DT Article ID PARKINSONS-DISEASE; KINASE-ACTIVITY; ERM PROTEINS; HIPPOCAMPAL-NEURONS; AXON FORMATION; GROWTH CONES; IN-VIVO; MUTATIONS; MORPHOLOGY; MOTILITY AB Leucine-rich repeat kinase 2 (LRRK2) functions as a putative protein kinase of ezrin, radixin, and moesin (ERM) family proteins. A Parkinson's disease-related G2019S substitution in the kinase domain of LRRK2 further enhances the phosphorylation of ERM proteins. The phosphorylated ERM (pERM) proteins are restricted to the filopodia of growing neurites in which they tether filamentous actin (F-actin) to the cytoplasmic membrane and regulate the dynamics of filopodia protrusion. Here, we show that, in cultured neurons derived from LRRK2 G2019S transgenic mice, the number of pERM-positive and F-actin-enriched filopodia was significantly increased, and this correlates with the retardation of neurite outgrowth. Conversely, deletion of LRRK2, which lowered the pERM and F-actin contents in filopodia, promoted neurite outgrowth. Furthermore, inhibition of ERM phosphorylation or actin polymerization rescued the G2019S-dependent neuronal growth defects. These data support a model in which the G2019S mutation of LRRK2 causes a gain-of-function effect that perturbs the homeostasis of pERM and F-actin in sprouting neurites critical for neuronal morphogenesis. C1 [Parisiadou, Loukia; Xie, Chengsong; Cho, Hyun Jin; Lin, Xian; Gu, Xing-Long; Long, Cai-Xia; Sun, Lixin; Cai, Huaibin] NIA, Unit Transgenesis, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Lobbestael, Evy; Baekelandt, Veerle; Taymans, Jean-Marc] Katholieke Univ Leuven, Lab Neurobiol & Gene Therapy, Div Mol Med, Dept Mol & Cellular Med,Fac Med, B-3000 Leuven, Belgium. RP Cai, HB (reprint author), NIA, Unit Transgenesis, Neurogenet Lab, NIH, Bldg 35,Room 1A116,MSC 3707,35 Convent Dr, Bethesda, MD 20892 USA. EM caih@mail.nih.gov RI gu, xinglong/A-3054-2011; Cai, Huaibin/H-3359-2013; OI gu, xinglong/0000-0002-0437-5606; Cai, Huaibin/0000-0002-8596-6108; Taymans, Jean-Marc/0000-0001-5503-5524 FU National Institutes of Health (NIH) [AG000944-01]; Fonds Wetenschappelijk Onderzoek (FWO) [G.0666.09]; Science and Technology in Flanders [IWT SBO/80020]; Katholieke Universiteit Leuven [IOF-KP/07/001, OT/08/052A] FX This work was supported in part by National Institutes of Health (NIH)-National Institute on Aging Intramural Research Program Grant AG000944-01 and by Fonds Wetenschappelijk Onderzoek (FWO) Vlaanderen Grant G.0666.09, Institute for the Promotion of Innovation by Science and Technology in Flanders Grant IWT SBO/80020, and Katholieke Universiteit Leuven Grants IOF-KP/07/001 and OT/08/052A. E. L. is a research assistant and J.-M. T. is a postdoctoral researcher of the Flemish Fund for Scientific Research (FWO Vlaanderen). We thank Dr. Zu- Hang Sheng for his helpful suggestions, Chris Van Den Haute and Anke Vander Perren for technical support, and the NIH Fellows Editorial Board for editing this manuscript. NR 39 TC 170 Z9 171 U1 2 U2 9 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 4 PY 2009 VL 29 IS 44 BP 13971 EP 13980 DI 10.1523/JNEUROSCI.3799-09.2009 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 515LG UT WOS:000271471400023 PM 19890007 ER PT J AU Simon, RM Paik, S Hayes, DF AF Simon, Richard M. Paik, Soonmyung Hayes, Daniel F. TI Use of Archived Specimens in Evaluation of Prognostic and Predictive Biomarkers SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID CLINICAL-TRIAL DESIGN; BREAST-CANCER; TUMOR-MARKERS; COLORECTAL-CANCER; AMERICAN SOCIETY; RECOMMENDATIONS; ONCOLOGY; VALIDATION; PACLITAXEL; MUTATIONS AB The development of tumor biomarkers ready for clinical use is complex. We propose a refined system for biomarker study design, conduct, analysis, and evaluation that incorporates a hierarchal level of evidence scale for tumor marker studies, including those using archived specimens. Although fully prospective randomized clinical trials to evaluate the medical utility of a prognostic or predictive biomarker are the gold standard, such trials are costly, so we discuss more efficient indirect "prospective-retrospective" designs using archived specimens. In particular, we propose new guidelines that stipulate that 1) adequate amounts of archived tissue must be available from enough patients from a prospective trial (which for predictive factors should generally be a randomized design) for analyses to have adequate statistical power and for the patients included in the evaluation to be clearly representative of the patients in the trial; 2) the test should be analytically and preanalytically validated for use with archived tissue; 3) the plan for biomarker evaluation should be completely specified in writing before the performance of biomarker assays on archived tissue and should be focused on evaluation of a single completely defined classifier; and 4) the results from archived specimens should be validated using specimens from one or more similar, but separate, studies. C1 [Simon, Richard M.] NCI, Biometr Res Branch, Bethesda, MD 20892 USA. [Paik, Soonmyung] Univ Pittsburgh, Div Pathol, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. [Hayes, Daniel F.] Univ Michigan, Ctr Comprehens Canc, Breast Oncol Program, Ann Arbor, MI 48109 USA. RP Simon, RM (reprint author), NCI, Biometr Res Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM rsimon@nih.gov NR 28 TC 447 Z9 451 U1 0 U2 15 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 4 PY 2009 VL 101 IS 21 BP 1446 EP 1452 DI 10.1093/jnci/djp335 PG 7 WC Oncology SC Oncology GA 516WX UT WOS:000271575100006 PM 19815849 ER PT J AU Taube, SE Clark, GM Dancey, JE McShane, LM Sigman, CC Gutman, SI AF Taube, Sheila E. Clark, Gary M. Dancey, Janet E. McShane, Lisa M. Sigman, Caroline C. Gutman, Steven I. TI A Perspective on Challenges and Issues in Biomarker Development and Drug and Biomarker Codevelopment SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID GROWTH-FACTOR RECEPTOR; CELL LUNG-CANCER; HER2-POSITIVE BREAST-CANCER; METASTATIC COLORECTAL-CANCER; CLINICAL-TRIAL DESIGN; ADJUVANT CHEMOTHERAPY; PREDICTIVE MARKER; KRAS MUTATIONS; GENE-MUTATIONS; OVARIAN-CANCER AB A workshop sponsored by the National Cancer Institute and the US Food and Drug Administration addressed past lessons learned and ongoing challenges faced in biomarker development and drug and biomarker codevelopment. Participants agreed that critical decision points in the product life cycle depend on the level of understanding of the biology of the target and its interaction with the drug, the preanalytical and analytical factors affecting biomarker assay performance, and the clinical disease process. The more known about the biology and the greater the strength of association between an analytical signal and clinical result, the more efficient and less risky the development process will be. Rapid entry into clinical practice will only be achieved by using a rigorous scientific approach, including careful specimen collection and standardized and quality-controlled data collection. Early interaction with appropriate regulatory bodies will ensure studies are appropriately designed and biomarker test performance is well characterized. C1 [Taube, Sheila E.] ST Consulting, Glen Echo, MD 20812 USA. [Clark, Gary M.] ArrayBiopharma Inc, Biostat & Data Management, Boulder, CO USA. [Dancey, Janet E.] Ontario Inst Canc Res, Toronto, ON, Canada. [McShane, Lisa M.] NCI, Biometr Res Branch, Bethesda, MD 20892 USA. [Sigman, Caroline C.] CCS Associates, Mountain View, CA USA. [Gutman, Steven I.] Univ Cent Florida, Coll Med, Tampa, FL USA. RP Taube, SE (reprint author), ST Consulting, POB 260, Glen Echo, MD 20812 USA. EM taubese63@alumni.brandeis.edu FU National Cancer Institute FX National Cancer Institute. C. S. also received National Cancer Institute support for scientific and editorial assistance. NR 60 TC 61 Z9 62 U1 0 U2 8 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 4 PY 2009 VL 101 IS 21 BP 1453 EP 1463 DI 10.1093/jnci/djp334 PG 11 WC Oncology SC Oncology GA 516WX UT WOS:000271575100007 PM 19855077 ER PT J AU Shao, W Kearney, M Maldarelli, F Mellors, JW Stephens, RM Lifson, JD KewalRamani, VN Ambrose, Z Coffin, JM Palmer, SE AF Shao, Wei Kearney, Mary Maldarelli, Frank Mellors, John W. Stephens, Robert M. Lifson, Jeffrey D. KewalRamani, Vineet N. Ambrose, Zandrea Coffin, John M. Palmer, Sarah E. TI RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy SO RETROVIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; TO-CHILD TRANSMISSION; DRUG-RESISTANCE MUTATIONS; REVERSE-TRANSCRIPTASE; WITHIN-HOST; ANTIRETROVIRAL THERAPY; MINORITY POPULATIONS; PROTEASE INHIBITORS; RANDOMIZED-TRIAL; RHESUS MACAQUES AB Background: To study the dynamics of wild-type and drug-resistant HIV-1 RT variants, we developed a methodology that follows the fates of individual genomes over time within the viral quasispecies. Single genome sequences were obtained from 3 pigtail macaques infected with a recombinant simian immunodeficiency virus containing the RT coding region from HIV-1 (RT-SHIV) and treated with short-course efavirenz monotherapy 13 weeks post-infection followed by daily combination antiretroviral therapy (ART) beginning at week 17. Bioinformatics tools were constructed to trace individual genomes from the beginning of infection to the end of the treatment. Results: A well characterized challenge RT-SHIV inoculum was used to infect three monkeys. The RT-SHIV inoculum had 9 variant subpopulations and the dominant subpopulation accounted for 80% of the total genomes. In two of the three monkeys, the inoculated wild-type virus was rapidly replaced by new wild type variants. By week 13, the original dominant subpopulation in the inoculum was replaced by new dominant subpopulations, followed by emergence of variants carrying known NNRTI resistance mutations. However, during ART, virus subpopulations containing resistance mutations did not outgrow the wide-type subpopulations until a minor subpopulation carrying linked drug resistance mutations (K103N/M184I) emerged. We observed that persistent viremia during ART is primarily made up of wild type subpopulations. We also found that subpopulations carrying the V75L mutation, not known to be associated with NNRTI resistance, emerged initially in week 13 in two macaques. Eventually, all subpopulations from these two macaques carried the V75L mutation. Conclusion: This study quantitatively describes virus evolution and population dynamics patterns in an animal model. The fact that wild type subpopulations remained as dominant subpopulations during ART treatment suggests that the presence or absence of at least some known drug resistant mutations may not greatly affect virus replication capacity in vivo. Additionally, the emergence and prevalence of V75L indicates that this mutation may provide the virus a selective advantage, perhaps escaping the host immure system surveillance. Our new method to quantitatively analyze viral population dynamics enabled us to observe the relative competitiveness and adaption of different viral variants and provided a valuable tool for studying HIV subpopulation emergence, persistence, and decline during ART. C1 [Shao, Wei; Stephens, Robert M.] NCI, Adv Biomed Comp Ctr, SAIC Frederick Inc, Frederick, MD USA. [Kearney, Mary; Maldarelli, Frank; KewalRamani, Vineet N.; Palmer, Sarah E.] NCI, HIV Drug Resistance Program, Frederick, MD USA. [Mellors, John W.; Ambrose, Zandrea] Univ Pittsburgh, Sch Med, Div Infect Dis, Pittsburgh, PA USA. [Lifson, Jeffrey D.] NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD USA. [Coffin, John M.] Tufts Univ, Boston, MA 02111 USA. [Palmer, Sarah E.] Swedish Inst Infect Dis Control, Dept Virol, Stockholm, Sweden. [Palmer, Sarah E.] Karolinska Inst, Stockholm, Sweden. RP Shao, W (reprint author), NCI, Adv Biomed Comp Ctr, SAIC Frederick Inc, Frederick, MD USA. EM shaow@mail.nih.gov; kearneym@mail.nih.gov; fmalli@mail.nih.gov; Mellors@dom.pitt.edu; stephensr@mail.nih.gov; Jeffrey.Lifson@nih.gov; vineet@ncifcrf.gov; zaa4@pitt.edu; coffinj@mail.nih.gov; sarah.palmer@smi.se FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; George Kirby Foundation; American Foundation for AIDS Research (amfAR) [106404-33-RFMC, 107149-44-RGRL]; Swedish Research Council FX The authors thank Dr. Shiu-Lok Hu for directing the animal study and Dr. Michael Piatak, Jr. and Kelli Oswald for assistance with plasma viral load determinations. Funding for this research was provided by the National Cancer Institute's intramural Center for Cancer Research and in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. JMC was a research professor of the American Cancer Society, with support from the George Kirby Foundation. ZA was funded, in part, by grants 106404-33-RFMC and 107149-44-RGRL from the American Foundation for AIDS Research (amfAR). Sarah Palmer was funded, in part, by the Swedish Research Council. NR 34 TC 12 Z9 12 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD NOV 4 PY 2009 VL 6 AR 101 DI 10.1186/1742-4690-6-101 PG 13 WC Virology SC Virology GA 518FI UT WOS:000271675600001 PM 19889213 ER PT J AU Alkhalil, A Strand, S Mucker, E Huggins, JW Jahrling, PB Ibrahim, SM AF Alkhalil, Abdulnaser Strand, Sarah Mucker, Eric Huggins, John W. Jahrling, Peter B. Ibrahim, Sofi M. TI Inhibition of Monkeypox virus replication by RNA interference SO VIROLOGY JOURNAL LA English DT Article ID DOUBLE-STRANDED-RNA; POXVIRUS INFECTIONS; CIDOFOVIR; GENE; DELIVERY; CELLS; SIRNAS; TRANSCRIPTION; POLYMERASE; DISEASE AB The Orthopoxvirus genus of Poxviridae family is comprised of several human pathogens, including cowpox (CPXV), Vaccinia (VACV), monkeypox (MPV) and Variola (VARV) viruses. Species of this virus genus cause human diseases with various severities and outcome ranging from mild conditions to death in fulminating cases. Currently, vaccination is the only protective measure against infection with these viruses and no licensed antiviral drug therapy is available. In this study, we investigated the potential of RNA interference pathway (RNAi) as a therapeutic approach for orthopox virus infections using MPV as a model. Based on genome-wide expression studies and bioinformatic analysis, we selected 12 viral genes and targeted them by small interference RNA (siRNA). Forty-eight siRNA constructs were developed and evaluated in vitro for their ability to inhibit viral replication. Two genes, each targeted with four different siRNA constructs in one pool, were limiting to viral replication. Seven siRNA constructs from these two pools, targeting either an essential gene for viral replication (A6R) or an important gene in viral entry (E8L), inhibited viral replication in cell culture by 65-95% with no apparent cytotoxicity. Further analysis with wild-type and recombinant MPV expressing green fluorescence protein demonstrated that one of these constructs, siA6-a, was the most potent and inhibited viral replication for up to 7 days at a concentration of 10 nM. These results emphasis the essential role of A6R gene in viral replication, and demonstrate the potential of RNAi as a therapeutic approach for developing oligonucleotide-based drug therapy for MPV and other orthopox viruses. C1 [Alkhalil, Abdulnaser; Strand, Sarah; Mucker, Eric; Huggins, John W.; Ibrahim, Sofi M.] USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. [Jahrling, Peter B.] NIAID, Emerging Viral Pathogens Sect, NIH, Bethesda, MD 20892 USA. RP Alkhalil, A (reprint author), USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. EM naser.alkhalil@amedd.army.mil; sarah.strand@amedd.army.mil; muckerEM@amedd.army.mil; hugginsJW@amedd.army.mil; peter.jahrling@amedd.army.mil; sofi.ibrahim@amedd.army.mil FU Defense Threat Reduction Agency [4.10022_07_RD_B] FX We thank Mohamed Ait Ichou, Jason Farlow, Lorraine Farinick, and Catherine Kenyon for thoughtful discussions, critical review, and assistance during manuscript preparation. The research described herein was supported by a grant from the Defense Threat Reduction Agency, Project number 4.10022_07_RD_B. NR 46 TC 13 Z9 13 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-422X J9 VIROL J JI Virol. J. PD NOV 4 PY 2009 VL 6 AR 188 DI 10.1186/1743-422X-6-188 PG 10 WC Virology SC Virology GA 526OB UT WOS:000272299300003 PM 19889227 ER PT J AU Yabroff, KR Saraiya, M Meissner, HI Haggstrom, DA Wideroff, L Yuan, G Berkowitz, Z Davis, WW Benard, VB Coughlin, SS AF Yabroff, K. Robin Saraiya, Mona Meissner, Helen I. Haggstrom, David A. Wideroff, Louise Yuan, Gigi Berkowitz, Zahava Davis, William W. Benard, Vicki B. Coughlin, Steven S. TI Specialty Differences in Primary Care Physician Reports of Papanicolaou Test Screening Practices: A National Survey, 2006 to 2007 SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CERVICAL-CANCER PREVENTION; UNITED-STATES; OLDER WOMEN; HUMAN-PAPILLOMAVIRUS; ABNORMAL MAMMOGRAMS; COST-EFFECTIVENESS; HEALTH; BREAST; NEOPLASIA; SERVICES AB Background: Cervical cancer screening guidelines were substantially revised in 2002 and 2003. Little information is available about primary care physicians' current Papanicolaou (Pap) test screening practices, including initiation, frequency, and stopping. Objective: To assess current Pap test screening practices in the United States. Design: Cross-sectional survey. Setting: Nationally representative sample of physicians during 2006 to 2007. Participants: 1212 primary care physicians. Measurements: The survey included questions about physician and practice characteristics and recommendations for Pap screening presented as clinical vignettes describing women by age and by sexual and screening histories. A composite measure-guideline-consistent recommendations-was created by using responses to vignettes in which major guidelines were uniform. Results: Most physicians reported providing Pap tests to their eligible patients (91.0% [95% CI, 89.0% to 92.6%]). Among Pap test providers (n = 1114), screening practices, including number of tests ordered or performed, use of patient reminder systems, and cytology method used, varied by physician specialty (P < 0.001). Although most Pap test providers reported that screening guidelines were very influential in their clinical practice, few had guideline-consistent recommendations for starting and stopping Pap screening across multiple vignettes (22.3% [CI, 19.9% to 25.0%]). Guideline-consistent recommendations varied by specialty (obstetrics/gynecology, 16.4%; internal medicine, 27.5%; and family or general practice, 21.1%). Compared with obstetricians/gynecologists, internal medicine specialists and family or general practice specialists were more likely to have guideline-consistent screening recommendations (odds ratio, 1.98 [CI, 1.22 to 3.23] and 1.45 [CI, 0.99 to 2.13], respectively) in multivariate analysis. Limitation: Physician self-report may reflect idealized rather than actual practice. Conclusion: Primary care physicians' recommendations for Pap test screening are not consistent with screening guidelines, reflecting overuse of screening. Implementation of effective interventions that focus on potentially modifiable physician and practice factors is needed to improve screening practice. Primary Funding Source: National Cancer Institute, Centers for Disease Control and Prevention, and Agency for Healthcare Research and Quality. C1 [Yabroff, K. Robin] NCI, Hlth Serv, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. Informat Management Serv Inc, Silver Spring, MD USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Regenstrief Inst Hlth Care, Vet Affairs Med Ctr, Indianapolis, IN USA. Indiana Univ, Sch Med, Indianapolis, IN USA. Dept Vet Affairs, Washington, DC USA. RP Yabroff, KR (reprint author), NCI, Hlth Serv, Execut Plaza N,Room 4005,6130 Execut Blvd, Bethesda, MD 20892 USA. EM yabroffr@mail.nih.gov RI Hernandez, Jessica/G-6527-2011; OI Yabroff, K. Robin/0000-0003-0644-5572 FU National Cancer Institute [N02-PC51308]; Centers for Disease Control and Prevention [Y3-PC-6017-01]; Agency for Healthcare Research and Quality [Y3-PC-5019-01, Y3-PC-5019-02] FX By the National Cancer Institute (contract N02-PC51308), Centers for Disease Control and Prevention (interagency agreement Y3-PC-6017-01), and Agency for Healthcare Research and Quality ( interagency agreements Y3-PC-5019-01 and Y3-PC-5019-02). NR 49 TC 65 Z9 67 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD NOV 3 PY 2009 VL 151 IS 9 BP 602 EP W197 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 514IM UT WOS:000271387700002 PM 19884621 ER PT J AU Arora, G Gona, P Salton, CJ Chuang, ML Jhaveri, RR Velagaleti, RS Yeon, SB O'Donnell, CJ Manning, WJ AF Arora, Garima Gona, Philmon Salton, Carol J. Chuang, Michael L. Jhaveri, Rahul R. Velagaleti, Raghava S. Yeon, Susan B. O'Donnell, Christopher J. Manning, Warren J. TI Normal Right Ventricle Anatomy and Function in a Longitudinally Followed Cohort Free of Hypertension and Cardiovascular Disease: A Cardiovascular Magnetic Resonance Study of the Framingham Heart Study Offspring Cohort SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Arora, Garima; Salton, Carol J.; Chuang, Michael L.; Jhaveri, Rahul R.; Yeon, Susan B.; O'Donnell, Christopher J.; Manning, Warren J.] Beth Israel Deaconess Med Cntr, Boston, MA USA. [Gona, Philmon] Boston Univ, Framingham, MA USA. [Gona, Philmon; Velagaleti, Raghava S.] NHLBI, Framingham Heart Study, Framingham, MA USA. RI Arora, Garima/F-3481-2011 NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S546 EP S546 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501197 ER PT J AU Arora, G Gona, P Salton, CJ Chuang, ML Jhaveri, RR O'Donnell, CJ Manning, WJ AF Arora, Garima Gona, Philmon Salton, Carol J. Chuang, Michael L. Jhaveri, Rahul R. O'Donnell, Christopher J. Manning, Warren J. TI Impact of Aging on the Normal Right Ventricle: A Cardiovascular Magnetic Resonance Study SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Arora, Garima; Salton, Carol J.; Chuang, Michael L.; Jhaveri, Rahul R.; Manning, Warren J.] Beth Israel Deaconess Med Cntr, Boston, MA USA. [Gona, Philmon] Boston Univ, Framingham, MA USA. [Gona, Philmon; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. RI Arora, Garima/F-3481-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S338 EP S338 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500159 ER PT J AU Becker, LC Herrera, JE Yanek, LR Yang, XP Johnson, AD Chen, MH O'Donnell, CJ Becker, DM Faraday, N AF Becker, Lewis C. Herrera, J. E. Yanek, Lisa R. Yang, Xiao P. Johnson, Andrew D. Chen, Ming-Huei O'Donnell, Christopher J. Becker, Diane M. Faraday, Nauder TI A Variant in Intron 1 of the Platelet Endothelial Aggregation Receptor-1 (PEAR1) Gene is Strongly Associated With Increased Platelet Aggregability SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Becker, Lewis C.; Herrera, J. E.; Yanek, Lisa R.; Yang, Xiao P.; Becker, Diane M.; Faraday, Nauder] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Johnson, Andrew D.; O'Donnell, Christopher J.] NIH, Framingham, MA USA. [Chen, Ming-Huei] Boston Univ, Boston, MA 02215 USA. RI Johnson, Andrew/G-6520-2013 NR 0 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S599 EP S599 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501414 ER PT J AU Berkowitz, SJ Yan, R Fernandez, VR Wu, C Rosen, B Redheuil, A Bluemke, DA Lima, JA AF Berkowitz, Seth J. Yan, Raymond Fernandez, Veronica R. Wu, Colin Rosen, Boza Redheuil, Alban Bluemke, David A. Lima, Joao A. TI The Relationship Between Left Ventricular Hypertrophy and Temporal Decline in Myocardial Function: Longitudinal Analysis of Myocardial Tagging in the Multi-Ethnic Study of Atherosclerosis (MESA) SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Berkowitz, Seth J.; Yan, Raymond; Fernandez, Veronica R.; Redheuil, Alban; Lima, Joao A.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Wu, Colin; Bluemke, David A.] NIH, Bethesda, MD 20892 USA. [Rosen, Boza] Univ Utah, Hlth Sci Cntr, Salt Lake City, UT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S304 EP S304 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500025 ER PT J AU Cao, JJ Gudnason, V Sigurdson, S Eiriksdottir, G Launer, L Harris, T Arai, AE AF Cao, Jie J. Gudnason, Vilmundur Sigurdson, Sigurdur Eiriksdottir, Gudny Launer, Lenore Harris, Tamara Arai, Andrew E. TI Association of Left Ventricular Concentric Hypertrophy and Thoracic Aortic Calcification With Cardiac Morbidity and Mortality in Elderly Subjects in the ICELAND-MI Substudy of AGES-Reykjavik SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Cao, Jie J.] St Francis Hosp, Roslyn, NY USA. [Gudnason, Vilmundur; Sigurdson, Sigurdur; Eiriksdottir, Gudny] Iceland Heart Assoc, Reykjavik, Iceland. [Launer, Lenore; Harris, Tamara; Arai, Andrew E.] NIH, Bethesda, MD 20892 USA. RI Gudnason, Vilmundur/K-6885-2015 OI Gudnason, Vilmundur/0000-0001-5696-0084 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S304 EP S304 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500024 ER PT J AU Chavakis, E Hain, A Orlandi, A Carmona, G Quertermous, T Chavakis, T Dimmeler, S AF Chavakis, Emmanouil Hain, Andreas Orlandi, Alessia Carmona, Guillaume Quertermous, Thomas Chavakis, Triantafyllos Dimmeler, Stefanie TI Del-1, a New Beta2-integrin Ligand, Which Inhibits Mobilization, Adhesion and Homing of Progenitor Cells SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Chavakis, Emmanouil; Hain, Andreas; Orlandi, Alessia; Carmona, Guillaume; Dimmeler, Stefanie] Goethe Univ Frankfurt, Frankfurt, Germany. [Quertermous, Thomas] Stanford Univ, Stanford, CA 94305 USA. [Chavakis, Triantafyllos] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1029 EP S1029 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831503526 ER PT J AU Eijgelsheim, M Newton-Cheh, C Sotoodehnia, N de Bakker, PI Muller, M Morrison, AC Smith, AV Isaacs, A Sanna, S Dorr, M Navarro, P Fuchsberger, C Wilson, JF Pramstaller, PP van Duijn, CM Lakatta, EG Felix, SB Gudnason, V Pfeufer, A Heckbert, SR Stricker, BH Boerwinkle, E O'Donnell, CJ AF Eijgelsheim, Mark Newton-Cheh, Christpher Sotoodehnia, Nona de Bakker, Paul I. Mueller, Martina Morrison, Alanna C. Smith, Albert V. Isaacs, Aaron Sanna, Serena Doerr, Marcus Navarro, Pau Fuchsberger, Christian Wilson, James F. Pramstaller, Peter P. van Duijn, Cornelia M. Lakatta, Edward G. Felix, Stephan B. Gudnason, Vilmundur Pfeufer, Arne Heckbert, Susan R. Stricker, Bruno H. Boerwinkle, Eric O'Donnell, Christopher J. TI Genome-wide Association Analysis of 25,330 Individuals Identifies Multiple Loci Associated With Resting Heart Rate SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Eijgelsheim, Mark; Isaacs, Aaron; van Duijn, Cornelia M.; Stricker, Bruno H.] Erasmus MC, Rotterdam, Netherlands. [Newton-Cheh, Christpher] Massachusetts Gen Hosp, Ctr Human Genet Res, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Sotoodehnia, Nona; Heckbert, Susan R.] Univ Washington, Seattle, WA 98195 USA. [de Bakker, Paul I.] Broad Inst Harvard & MIT, Program Med Populat Genet, Boston, MA USA. [Mueller, Martina] Helmholtz Ctr Munich, Munich, Germany. [Morrison, Alanna C.; Boerwinkle, Eric] Univ Texas Houston, Houston, TX USA. [Smith, Albert V.; Gudnason, Vilmundur] Iceland Heart Assoc Res Inst, Kopavagur, Iceland. [Sanna, Serena] Ist Neurogenet & Neurofarmacol, Monserrato, Italy. [Doerr, Marcus] Ernst Moritz Arndt Univ Greifswald, Greifswald, Germany. [Navarro, Pau] Western Gen Hosp, Edinburgh EH4 2XU, Midlothian, Scotland. [Fuchsberger, Christian; Pramstaller, Peter P.] European Acad Bozen, Bolzano, Italy. [Wilson, James F.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Lakatta, Edward G.] NIA, Baltimore, MD 21224 USA. [O'Donnell, Christopher J.] NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA USA. RI Fuchsberger, Christian/C-9646-2010; Pfeufer, Arne/B-6634-2013; Pramstaller, Peter/C-2357-2008; de Bakker, Paul/B-8730-2009; Gudnason, Vilmundur/K-6885-2015 OI de Bakker, Paul/0000-0001-7735-7858; Gudnason, Vilmundur/0000-0001-5696-0084 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S579 EP S579 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501330 ER PT J AU Einstein, AJ Elliston, CD Arai, AE Chen, MY Mather, R Pearson, GD DeLapaz, RL Nickoloff, EL Dutta, A Brenner, DJ AF Einstein, Andrew J. Elliston, Carl D. Arai, Andrew E. Chen, Marcus Y. Mather, Richard Pearson, Gregory D. DeLapaz, Robert L. Nickoloff, Edward L. Dutta, Ajoy Brenner, David J. TI Radiation Dose From Single Heartbeat Coronary CT Angiography Performed Using a 320 Detector-Row Volume Scanner SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Einstein, Andrew J.; Elliston, Carl D.; Pearson, Gregory D.; DeLapaz, Robert L.; Nickoloff, Edward L.; Dutta, Ajoy; Brenner, David J.] Columbia Univ, Med Cntr, New York, NY USA. [Arai, Andrew E.; Chen, Marcus Y.] NHLBI, Bethesda, MD 20892 USA. [Mather, Richard] Toshiba Amer Med Syst, Tustin, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S311 EP S311 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500053 ER PT J AU Fleg, JL Leifer, E Kitzman, DW Whellan, DJ Kokkinos, P Wolfel, G Gardin, JM AF Fleg, Jerome L. Leifer, Eric Kitzman, Dalane W. Whellan, David J. Kokkinos, Peter Wolfel, Gene Gardin, Julius M. TI Clinical and Doppler Echocardiographic Correlates of VE/VCO2 Slope in Systolic Heart Failure: The HF-ACTION Trial SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Fleg, Jerome L.; Leifer, Eric] NHLBI, NIH, Bethesda, MD 20892 USA. [Kitzman, Dalane W.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Whellan, David J.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Kokkinos, Peter] Washington VA Med Ctr, Washington, DC USA. [Wolfel, Gene] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Gardin, Julius M.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S365 EP S365 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500263 ER PT J AU Forman, DE Clare, R Kitzman, DW Ellis, SJ Chiara, T Fletcher, G Fleg, JL Kraus, WE AF Forman, Daniel E. Clare, Robert Kitzman, Dalane W. Ellis, Stephen J. Chiara, Toni Fletcher, Gerald Fleg, Jerome L. Kraus, William E. TI Impact of Age on Aerobic Capacity in Patients With Systolic Heart Failure: The HF-ACTION Study SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Forman, Daniel E.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Clare, Robert; Ellis, Stephen J.] Duke Clin Res Inst, Durham, NC USA. [Kitzman, Dalane W.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [Chiara, Toni] Univ Florida, Gainesville, FL USA. [Fletcher, Gerald] Mayo Clin, Jacksonville, FL 32224 USA. [Fleg, Jerome L.] NHLBI, Bethesda, MD 20892 USA. [Kraus, William E.] Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S550 EP S550 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501211 ER PT J AU Gaskins, RB Lagasse, L Hai, L Shankaran, S Lester, BM Bada, H Bauer, CR Das, A Higgins, R AF Gaskins, Ronnesia B. Lagasse, Linda Hai, Lin Shankaran, Seetha Lester, Barry M. Bada, Henrietta Bauer, Charles R. Das, Abik Higgins, Rosemary TI Externalizing Behavioral Problems, Stress Reactivity and Obesity Adolescents Within Utero Cocaine Exposure SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Gaskins, Ronnesia B.; Lagasse, Linda; Hai, Lin; Lester, Barry M.] Brown Univ, Warren Alpert Med Sch, Women & Infants Hosp Rhode Isl, Providence, RI 02912 USA. [Shankaran, Seetha] Wayne State Univ, Detroit, MI USA. [Bada, Henrietta] Univ Kentucky, Lexington, KY USA. [Bauer, Charles R.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Das, Abik] Res Triangle Inst, Res Triangle Pk, NC 27709 USA. [Higgins, Rosemary] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S492 EP S492 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500769 ER PT J AU Georgiopoulou, VV Kalogeropoulos, AP Psaty, BM Rodondi, N Bauer, DC Butler, AB Koster, A Smith, AL Harris, TB Newman, AB Kritchevsky, SB Butler, J AF Georgiopoulou, Vasiliki V. Kalogeropoulos, Andreas P. Psaty, Bruce M. Rodondi, Nicolas Bauer, Douglas C. Butler, Abida B. Koster, Annemarie Smith, Andrew L. Harris, Tamara B. Newman, Anne B. Kritchevsky, Stephen B. Butler, Javed TI Abnormal Lung Function and Risk for Heart Failure in the Elderly: The Health, Aging, and Body Composition Study SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Georgiopoulou, Vasiliki V.; Kalogeropoulos, Andreas P.; Smith, Andrew L.; Butler, Javed] Emory Univ, Atlanta, GA 30322 USA. [Psaty, Bruce M.] Univ Washington, Seattle, WA 98195 USA. [Rodondi, Nicolas] Univ Lausanne, Lausanne, Switzerland. [Bauer, Douglas C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Butler, Abida B.] Louisiana State Univ, Bogalusa Med Cntr, Bogalusa, LA USA. [Koster, Annemarie; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Newman, Anne B.] Univ Pittsburgh, Pittsburgh, PA USA. [Kritchevsky, Stephen B.] Wake Forest Univ, Winston Salem, NC 27109 USA. RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S505 EP S505 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501035 ER PT J AU Goto, K Iso, T Suga, T Matsui, H Arai, M Gonzalez, FJ Kurabayashi, M AF Goto, Kosaku Iso, Tatsuya Suga, Toshihiro Matsui, Hiroki Arai, Masashi Gonzalez, Frank J. Kurabayashi, Masahiko TI Notch-peroxisome Proliferator Activated Receptor Gamma 2 Pathway Regulates Transendothelial Fatty Acid Transport via Induction of Fatty Acid Binding Protein 4 and Fatty Acid Translocase in Capillary Endothelial Cells in Heart SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Goto, Kosaku; Iso, Tatsuya; Suga, Toshihiro; Matsui, Hiroki; Arai, Masashi; Kurabayashi, Masahiko] Gunma Univ, Grad Sch Med, Gunma, Japan. [Gonzalez, Frank J.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1115 EP S1115 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831504090 ER PT J AU He, M Cornelis, MC Franks, PW Zhang, CL Hu, FB Qi, L AF He, Meian Cornelis, Marilyn C. Franks, Paul W. Zhang, Cuilin Hu, Frank B. Qi, Lu TI Obesity Genotype Score and Cardiovascular Risk in Women With Type 2 Diabetes SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [He, Meian; Cornelis, Marilyn C.; Hu, Frank B.; Qi, Lu] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Franks, Paul W.] Umea Univ Hosp, S-90185 Umea, Sweden. [Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S467 EP S467 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500669 ER PT J AU Horwich, T Leifer, ES Brawner, CA Fitz-Gerald, MB Fonarow, GC AF Horwich, Tamara Leifer, Eric S. Brawner, Clinton A. Fitz-Gerald, Meredith B. Fonarow, Gregg C. TI The Relationship Between Body Mass Index and Cardiopulmonary Exercise Testing in Chronic Systolic Heart Failure SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Horwich, Tamara; Fonarow, Gregg C.] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. [Leifer, Eric S.] Natl Heart Lung Blood Inst, Bethesda, MD USA. [Brawner, Clinton A.] Henry Ford Hosp, Detroit, MI 48202 USA. [Fitz-Gerald, Meredith B.] Univ Alabama, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S757 EP S757 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831502239 ER PT J AU Hsu, DT Zak, V Mahony, L Sleeper, LA Atz, AM Levine, JC Barker, PC Ravishankar, C McCrindle, BW Williams, RV Altmann, K Ghanayem, NS Margossian, R Chung, WK Border, WL Pearson, GD Stylianou, MP Mital, S AF Hsu, Daphne T. Zak, Victor Mahony, Lynn Sleeper, Lynn A. Atz, Andrew M. Levine, Jami C. Barker, Piers C. Ravishankar, Chitra McCrindle, Brian W. Williams, Richard V. Altmann, Karen Ghanayem, Nancy S. Margossian, Renee Chung, Wendy K. Border, William L. Pearson, Gail D. Stylianou, Mario P. Mital, Seema TI Enalapril Does Not Improve Growth or Ventricular Function in Infants With Single Ventricle: A Multicenter Clinical Trial SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Hsu, Daphne T.] Childrens Hosp Montefiore, Bronx, NY USA. [Zak, Victor; Sleeper, Lynn A.] New England Res Inst, Watertown, MA 02172 USA. [Mahony, Lynn] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Atz, Andrew M.] Med Univ S Carolina, Charleston, SC 29425 USA. [Levine, Jami C.; Margossian, Renee] Childrens Hosp, Boston, MA 02115 USA. [Barker, Piers C.] Duke Univ, Med Ctr, Durham, NC USA. [Ravishankar, Chitra] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [McCrindle, Brian W.; Mital, Seema] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Williams, Richard V.] Primary Childrens Med Ctr, Salt Lake City, UT 84103 USA. [Altmann, Karen; Chung, Wendy K.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Ghanayem, Nancy S.] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA. [Border, William L.] Cincinnati Childrens Hosp, Cincinnati, OH USA. [Pearson, Gail D.; Stylianou, Mario P.] NHLBI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S560 EP S561 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501254 ER PT J AU Hsu, LY Groves, DW Kellman, P Aletras, AH Aral, AE AF Hsu, Li-Yueh Groves, Daniel W. Kellman, Peter Aletras, Anthony H. Aral, Andrew E. TI Quantification of Absolute Myocardial Blood Flow With Contrast Enhanced MRI Approaching a Pixel Resolution: Validation vs. Microspheres SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Hsu, Li-Yueh; Groves, Daniel W.; Kellman, Peter; Aletras, Anthony H.; Aral, Andrew E.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S299 EP S299 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500004 ER PT J AU Huang, CM Wang, KL Cheng, HM Vhuang, SY Ting, CT Lakatta, EG Yin, F Chou, P Chen, CH AF Huang, Chi-Ming Wang, Kang-Ling Cheng, Hao-Min Vhuang, Shao-Yuan Ting, Chih-Tai Lakatta, Edward G. Yin, Frank Chou, Pesus Chen, Chen-Huan TI Central or Ambulatory Peripheral Blood Pressure: Which Best Relates to Target-organs and Future Mortality? SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Huang, Chi-Ming; Wang, Kang-Ling; Cheng, Hao-Min; Chen, Chen-Huan] Taipei Vet Gen Hosp, Taipei, Taiwan. [Vhuang, Shao-Yuan] Acad Sinica, Taipei 115, Taiwan. [Ting, Chih-Tai] Taichung Vet Gen Hosp, Taichung, Taiwan. [Lakatta, Edward G.] NIA, Baltimore, MD 21224 USA. [Yin, Frank] Washington Univ, St Louis, MO USA. [Chou, Pesus] Natl Yang Ming Univ, Taipei 112, Taiwan. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1060 EP S1060 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831503655 ER PT J AU Isenberg, JS Bauer, E Qin, Y Miller, T Bandle, R Csanyi, G Pagano, PJ Bauer, PM Schnermann, JB Roberts, DD AF Isenberg, Jeffrey S. Bauer, Eileen Qin, Yan Miller, Thomas Bandle, Russell Csanyi, Gabor Pagano, Patrick J. Bauer, Phillip M. Schnermann, Jurgen B. Roberts, David D. TI Thrombospondin-1, via CD47, Blocks Endothelial-Dependent Arterial Relaxation by Limiting Endothelial Nitric Oxide Synthase Activation SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Isenberg, Jeffrey S.; Bauer, Eileen; Csanyi, Gabor; Pagano, Patrick J.; Bauer, Phillip M.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Qin, Yan; Miller, Thomas; Bandle, Russell; Schnermann, Jurgen B.; Roberts, David D.] NIH, Bethesda, MD 20892 USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1132 EP S1132 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831504168 ER PT J AU Jain, A McClelland, RL Polak, JF Shea, SJ Burke, GL Bild, DE Watson, KE Budoff, MJ Liu, K Post, W Folsom, AR Lima, JA Bluemke, DA AF Jain, Aditya McClelland, Robyn L. Polak, Joseph F. Shea, Steven J. Burke, Gregory L. Bild, Diane E. Watson, Karol E. Budoff, Matthew J. Liu, Kiang Post, Wendy Folsom, Aaron R. Lima, Joao A. Bluemke, David A. TI Imaging Measures for Prediction of Cardiovascular Events in Men and Women: The Multi-Ethnic Study of Atherosclerosis (MESA) SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Jain, Aditya; Post, Wendy; Lima, Joao A.] Johns Hopkins Univ, Baltimore, MD USA. [McClelland, Robyn L.] Univ Washington, Seattle, WA 98195 USA. [Polak, Joseph F.] Tufts Univ, Boston, MA 02111 USA. [Shea, Steven J.] Columbia Univ, New York, NY USA. [Burke, Gregory L.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Bild, Diane E.] NHLBI, Bethesda, MD 20892 USA. [Watson, Karol E.] Univ Calif Los Angeles, Los Angeles, CA USA. [Budoff, Matthew J.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. [Liu, Kiang] Northwestern Univ, Chicago, IL 60611 USA. [Folsom, Aaron R.] Univ Minnesota, Minneapolis, MN USA. [Bluemke, David A.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S463 EP S463 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500650 ER PT J AU Johnson, AD Ehret, GB Rice, K Verwoert, GC Launer, LJ Gudnason, V Larson, MG Chakravarti, A Psaty, BM van Duijn, CM Levy, D AF Johnson, Andrew D. Ehret, Georg B. Rice, Kenneth Verwoert, Germaine C. Launer, Lenore J. Gudnason, Vilmundur Larson, Martin G. Chakravarti, Aravinda Psaty, Bruce M. van Duijn, Cornelia M. Levy, Daniel CA CHARGE Consortium TI Association of Hypertension Drug Target Genes With Blood Pressure and Hypertension: Results From a Genome-wide Association Study in 29,136 Individuals SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Johnson, Andrew D.; Levy, Daniel] NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Ehret, Georg B.; Chakravarti, Aravinda] Johns Hopkins Univ, Baltimore, MD USA. [Rice, Kenneth; Psaty, Bruce M.] Univ Washington, Seattle, WA 98195 USA. [Verwoert, Germaine C.; van Duijn, Cornelia M.] Erasmus Univ, Med Ctr, Rotterdam, Netherlands. [Launer, Lenore J.] NIA, Bethesda, MD 20892 USA. [Gudnason, Vilmundur] Iceland Heart Assoc, Reykjavik, Iceland. [Larson, Martin G.] Boston Univ, Framingham, MA USA. RI Rice, Kenneth/A-4150-2013; Johnson, Andrew/G-6520-2013; Gudnason, Vilmundur/K-6885-2015 OI Rice, Kenneth/0000-0001-5779-4495; Gudnason, Vilmundur/0000-0001-5696-0084 NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S588 EP S588 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501368 ER PT J AU Johnson, AD Yanek, LR Chen, MH Kraja, AT Larson, MG Lin, R Tofler, GH Becker, DM Yang, Q Province, MA O'Donnell, CJ Becker, LC AF Johnson, Andrew D. Yanek, Lisa R. Chen, Ming-Huei Kraja, Aldi T. Larson, Martin G. Lin, Rosa Tofler, Geoffrey H. Becker, Diane M. Yang, Qiong Province, Michael A. O'Donnell, Christopher J. Becker, Lewis C. TI Multiple Platelet Aggregation Genes Are Identified by Genome-wide Association Meta-analyses SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Johnson, Andrew D.; Tofler, Geoffrey H.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Yanek, Lisa R.; Becker, Diane M.; Becker, Lewis C.] Johns Hopkins Univ, Baltimore, MD USA. [Chen, Ming-Huei; Yang, Qiong] Boston Univ, Boston, MA 02215 USA. [Kraja, Aldi T.; Lin, Rosa; Province, Michael A.] Washington Univ, St Louis, MO USA. [Larson, Martin G.] Boston Univ, Framingham, MA USA. RI Johnson, Andrew/G-6520-2013; Yang, Qiong/G-5438-2014 NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S588 EP S588 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501366 ER PT J AU Johnson, AD Bhimavarapu, A Benjamin, EJ Fox, C Levy, D Jarvik, GP O'Donnell, CJ AF Johnson, Andrew D. Bhimavarapu, Anupama Benjamin, Emelia J. Fox, Caroline Levy, Daniel Jarvik, Gail P. O'Donnell, Christopher J. TI Notifiable Genetic Variants on Commercially Available SNP Arrays: Implications for Research Participants in Genome-wide Association Studies for Cardiovascular Disease SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Johnson, Andrew D.; Fox, Caroline; Levy, Daniel; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Bhimavarapu, Anupama] Harvard Univ, Sch Med, Cambridge, MA USA. [Benjamin, Emelia J.] Boston Univ, Boston, MA 02215 USA. [Jarvik, Gail P.] Univ Washington, Seattle, WA 98195 USA. RI Johnson, Andrew/G-6520-2013; Jarvik, Gail/N-6476-2014 OI Jarvik, Gail/0000-0002-6710-8708 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S559 EP S559 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501247 ER PT J AU Johnson, BD Eteiba, W Sharaf, B Pepine, CJ Reis, SA Rogers, W Kelsey, SF Vido, D Bittner, V Sopko, G Shaw, LJ Merz, NB AF Johnson, B. Delia Eteiba, Wafia Sharaf, Barry Pepine, Carl J. Reis, Steven A. Rogers, William Kelsey, Sheryl F. Vido, Diane Bittner, Vera Sopko, George Shaw, Leslee J. Merz, Noel Bairey TI Sudden Cardiac Death and Severity of Obstructive Coronary Artery Disease: A Report From the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE) Study SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Johnson, B. Delia; Eteiba, Wafia; Kelsey, Sheryl F.] Univ Pittsburgh GSPH, Pittsburgh, PA USA. [Sharaf, Barry] Rhode Isl Hosp, Providence, RI USA. [Pepine, Carl J.] Univ Florida, Gainesville, FL USA. [Reis, Steven A.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Rogers, William; Bittner, Vera] Univ Alabama, Birmingham, AL USA. [Vido, Diane] Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. [Sopko, George] NIH, Bethesda, MD 20892 USA. [Shaw, Leslee J.] Emory Univ, Atlanta, GA 30322 USA. [Merz, Noel Bairey] Cedars Sinai Med Ctr, Los Angeles, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S394 EP S394 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500374 ER PT J AU Kadakia, MB Fox, CS Scirica, BM Murphy, SA Bonaca, MP Morrow, DA AF Kadakia, Mitul B. Fox, Caroline S. Scirica, Benjamin M. Murphy, Sabina A. Bonaca, Marc P. Morrow, David A. TI Central Obesity and Cardiovascular Outcomes in Patients With Acute Coronary Syndromes: Observations From the MERLIN-TIMI 36 Trial SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Kadakia, Mitul B.; Scirica, Benjamin M.; Murphy, Sabina A.; Bonaca, Marc P.; Morrow, David A.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Kadakia, Mitul B.; Scirica, Benjamin M.; Murphy, Sabina A.; Bonaca, Marc P.; Morrow, David A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S510 EP S510 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501052 ER PT J AU Kalogeropoulos, AP Georgiopoulou, VV Psaty, BM Rodondi, N Smith, AL Harrison, DG Liu, YM Hoffmann, U Bauer, DC Newman, AB Kritchevsky, SB Harris, TB Butler, J AF Kalogeropoulos, Andreas P. Georgiopoulou, Vasiliki V. Psaty, Bruce M. Rodondi, Nicolas Smith, Andreas L. Harrison, David G. Liu, Yongmei Hoffmann, Udo Bauer, Douglas C. Newman, Anne B. Kritchevsky, Stephen B. Harris, Tamara B. Butler, Javed TI Inflammatory Markers and Incident Heart Failure Risk in Older Adults: The Health, Aging, and Body Composition Study SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Kalogeropoulos, Andreas P.; Georgiopoulou, Vasiliki V.; Smith, Andreas L.; Harrison, David G.; Butler, Javed] Emory Univ, Atlanta, GA 30322 USA. [Psaty, Bruce M.] Univ Washington, Seattle, WA 98195 USA. [Rodondi, Nicolas] Univ Lausanne, Lausanne, Switzerland. [Liu, Yongmei; Kritchevsky, Stephen B.] Wake Forest Univ, Winston Salem, SC USA. [Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Bauer, Douglas C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Newman, Anne B.] Univ Pittsburgh, Pittsburgh, PA USA. [Harris, Tamara B.] NIA, Intramural Rsch Program, Bethesda, MD 20892 USA. RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S505 EP S505 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501036 ER PT J AU Kalogeropoulos, AP Georgiopoulou, VV Agha, SA Giamouzis, G Smith, AL Kritchevsky, SB Najjar, S Bibbins-Domingo, K Sutton-Tyrrell, K Harris, TB Butler, J AF Kalogeropoulos, Andreas P. Georgiopoulou, Vasiliki V. Agha, Syed A. Giamouzis, Grigorios Smith, Andrew L. Kritchevsky, Stephen B. Najjar, Samir Bibbins-Domingo, Kristen Sutton-Tyrrell, Kim Harris, Tamara B. Butler, Javed TI Systolic Blood Pressure and Heart Failure Risk in the Elderly: The Health, Aging, and Body Composition Study SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Kalogeropoulos, Andreas P.; Georgiopoulou, Vasiliki V.; Agha, Syed A.; Giamouzis, Grigorios; Smith, Andrew L.; Butler, Javed] Emory Univ, Atlanta, GA 30322 USA. [Kritchevsky, Stephen B.] Wake Forest Univ, Winston Salem, SC USA. [Najjar, Samir; Harris, Tamara B.] NIA, Intramural Rsch Program, Bethesda, MD 20892 USA. [Bibbins-Domingo, Kristen] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Sutton-Tyrrell, Kim] Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S505 EP S506 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501037 ER PT J AU Kaludercic, N Takimoto, E Nagayama, T Lai, E Bedja, D Chen, K Gabrielson, K Shih, JC Pacak, K Kass, DA Di Lisa, F Paolocci, N AF Kaludercic, Nina Takimoto, Eiki Nagayama, Takahiro Lai, Edwin Bedja, Djahida Chen, Kevin Gabrielson, Kathleen Shih, Jean C. Pacak, Karel Kass, David A. Di Lisa, Fabio Paolocci, Nazareno TI Pharmacological and Genetic Inhibition of Monoamine Oxidase A Prevents Enhanced Norepinephrine Catabolism and Heart Failure After Pressure Overload SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Kaludercic, Nina; Takimoto, Eiki; Nagayama, Takahiro; Bedja, Djahida; Gabrielson, Kathleen; Kass, David A.; Paolocci, Nazareno] Johns Hopkins Univ, Baltimore, MD USA. [Lai, Edwin; Pacak, Karel] NICHD, NIH, Bethesda, MD USA. [Chen, Kevin; Shih, Jean C.] Univ So Calif, Los Angeles, CA USA. [Di Lisa, Fabio] Univ Padua, Padua, Italy. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S720 EP S720 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831502085 ER PT J AU Kim, HC Greenland, P Rossouw, J Manson, J Cochrane, B Lasser, N Limacher, M Lloyd-Jones, D Margolis, K Robinson, J AF Kim, Hyeon Chang Greenland, Philip Rossouw, Jacques Manson, JoAnn Cochrane, Barbara Lasser, Norman Limacher, Marian Lloyd-Jones, Donald Margolis, Karen Robinson, Jennifer TI Multi-marker Prediction of Coronary Heart Disease Risk: The Women's Health Initiative SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Kim, Hyeon Chang; Greenland, Philip; Lloyd-Jones, Donald] Northwestern Univ, Chicago, IL 60611 USA. [Rossouw, Jacques] NHLBI, Bethesda, MD 20892 USA. [Manson, JoAnn] Brigham & Womens Hosp, Boston, MA 02115 USA. [Cochrane, Barbara] Univ Washington, Seattle, WA 98195 USA. [Lasser, Norman] Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. [Limacher, Marian] Univ Florida, Gainesville, FL USA. [Margolis, Karen] HealthPartners Rsch Fdn & Med Grp, Minneapolis, MN USA. [Robinson, Jennifer] Univ Iowa, Iowa City, IA USA. RI Lloyd-Jones, Donald/C-5899-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S424 EP S424 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500497 ER PT J AU Kovacic, JC Gupta, R Lee, AC Ma, MC Fang, F Tolbert, CN Walls, AD Beltran, LE San, H Chen, GB Boehm, M AF Kovacic, Jason C. Gupta, Rohit Lee, Angela C. Ma, Mingchao Fang, Fang Tolbert, Claire N. Walls, Avram D. Beltran, Leilani E. San, Hong Chen, Guibin Boehm, Manfred TI STAT3-dependent Acute RANTES Production in Vascular Smooth Muscle Cells Modulates Inflammation Following Arterial Injury SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Kovacic, Jason C.; Gupta, Rohit; Lee, Angela C.; Ma, Mingchao; Fang, Fang; Tolbert, Claire N.; Walls, Avram D.; Beltran, Leilani E.; Chen, Guibin; Boehm, Manfred] NHLBI, NIH, Bethesda, MD 20892 USA. [San, Hong] NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1078 EP S1078 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831503735 ER PT J AU Lipshultz, SE Williams, P Shearer, WT Rich, K Leister, E Hazra, R Kaltman, J Jacobson, D Dooley, L Wilkinson, JD Scott, G Colan, SD AF Lipshultz, Steven E. Williams, Paige Shearer, William T. Rich, Kenneth Leister, Erin Hazra, Rohan Kaltman, Jonathan Jacobson, Denise Dooley, Laurie Wilkinson, James D. Scott, Gwendolyn Colan, Steven D. CA PHACS Study Team TI Increased Left Ventricular and Aortic Dimensions in Long-Term Muttiagent Antiretroviral Therapy (ART)-Treated HIV-Infected Children: The NIH Multicenter Pediatric HIV/AIDS Cohort Study (PHACS) SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Lipshultz, Steven E.; Wilkinson, James D.; Scott, Gwendolyn] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Williams, Paige; Leister, Erin; Jacobson, Denise] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Shearer, William T.] Baylor Coll Med, Houston, TX 77030 USA. [Shearer, William T.] Texas Childrens Hosp, Houston, TX 77030 USA. [Rich, Kenneth] Univ Illinois, Chicago, IL USA. [Hazra, Rohan] NICHHD, Bethesda, MD 20892 USA. [Kaltman, Jonathan] NHLBI, Bethesda, MD 20892 USA. [Dooley, Laurie] Frontier Sci Technol & Rsch Fdn, Amherst, NY USA. [Colan, Steven D.] Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S909 EP S909 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831503053 ER PT J AU Liu, JK Taylor, HA Fox, CS Sung, JH Hickson, D Sarpong, D Ekunwe, L May, WD AF Liu, Jiankang Taylor, Herman A. Fox, Caroline S. Sung, Jung Hye Hickson, DeMarc Sarpong, Daniel Ekunwe, Lynette May, Warren D. TI Pericardial Fat and Cardiovascular Disease Risk Factors: The Jackson Heart Study SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Liu, Jiankang; Taylor, Herman A.; May, Warren D.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Fox, Caroline S.] NHLBI, Framingham Heart Dis Epidemiol Study, Boston, MA USA. [Sung, Jung Hye; Hickson, DeMarc; Sarpong, Daniel; Ekunwe, Lynette] Jackson State Univ, Jackson, MS USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S402 EP S403 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500412 ER PT J AU Liu, LJ Eisen, HJ Sullivan, DH Kanaya, A Rodondi, N Satterfield, S Sutton-Tyrrell, K Harris, TB AF Liu, Longjian Eisen, Howard J. Sullivan, Dennis H. Kanaya, Alka Rodondi, Nicolas Satterfield, Suzanne Sutton-Tyrrell, Kim Harris, Tamara B. CA Hlth ABC Study TI Serum Leptin Concentration, Body Mass Index and Incident Heart Failure: The Health, Aging, and Body Composition Study SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Liu, Longjian] Drexel Univ, Sch Publ Hlth, Philadelphia, PA 19104 USA. [Eisen, Howard J.] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. [Sullivan, Dennis H.] Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. [Sullivan, Dennis H.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Kanaya, Alka] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Rodondi, Nicolas] Univ Lausanne, Lausanne, Switzerland. [Satterfield, Suzanne] Univ Tennessee, Memphis, TN USA. [Sutton-Tyrrell, Kim] Univ Pittsburgh, Pittsburgh, PA USA. [Harris, Tamara B.] NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S399 EP S399 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500397 ER PT J AU Marine, JE Shetty, V Chow, GV Wright, J Gerstenblith, G Najjar, SS Fleg, JL AF Marine, Joseph E. Shetty, Veena Chow, Grant V. Wright, Jeanette Gerstenblith, Gary Najjar, Samer S. Fleg, Jerome L. TI Prognostic Significance of Exercise-induced Non-sustained Ventricular Tachycardia in Asymptomatic Volunteers: The Baltimore Longitudinal Study of Aging SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Marine, Joseph E.; Chow, Grant V.; Gerstenblith, Gary] Johns Hopkins Univ, Sch Med, Baltimore, MD 20892 USA. [Shetty, Veena] MedStar Res Inst, Hyattsville, MD USA. [Wright, Jeanette; Najjar, Samer S.] NIA, Baltimore, MD USA. [Fleg, Jerome L.] NHLBI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S661 EP S661 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501672 ER PT J AU Massing, MW Chambless, LE Jiang, NT Ni, HY AF Massing, Mark W. Chambless, Lloyd E. Jiang, Niantao Ni, Hanyu TI Heart Failure Diagnostic Codes: Concordance of Medical Records and Medicare Administrative Claims. The ARIC Study SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Massing, Mark W.; Chambless, Lloyd E.; Jiang, Niantao] Univ N Carolina, Chapel Hill, NC USA. [Ni, Hanyu] NHLBI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S399 EP S399 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500396 ER PT J AU McDermott, MM Liu, K Ferrucci, L Tian, L Green, D Guralnik, J Tao, HM Ridker, P Criqui, M AF McDermott, Mary M. Liu, Kiang Ferrucci, Luigi Tian, Lu Green, David Guralnik, Jack Tao, Huimin Ridker, Paul Criqui, Michael TI High Levels of Homocysteine and D-dimer Are Associated With Faster Functional Decline Among Men and Women With Lower Extremity Peripheral Arterial Disease SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [McDermott, Mary M.; Liu, Kiang; Tian, Lu; Green, David; Tao, Huimin] Northwestern Univ, Chicago, IL 60611 USA. [Ferrucci, Luigi; Guralnik, Jack] NIH, Bethesda, MD 20892 USA. [Ridker, Paul] Harvard Univ, Boston, MA 02115 USA. [Criqui, Michael] Univ Calif San Diego, San Diego, CA 92103 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1148 EP S1149 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831504237 ER PT J AU Mewton, N Viallon, M Kellman, P Stemmer, A Rappachi, S Bi, XM Zuehlsdorff, S Revel, D Croisille, P AF Mewton, Nathan Viallon, Magalie Kellman, Peter Stemmer, Alto Rappachi, Stanislas Bi, Xiaoming Zuehlsdorff, Sven Revel, Didier Croisille, Pierre TI Observer Performance With State-of-the-Art T2 Weighted Sequences-T2p-singleshot SSFP, TSESSFP( ACUTE), IR-TSE (TIRM) and BLADE- for the Detection of Acute Myocardial Injury SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Rappachi, Stanislas; Revel, Didier; Croisille, Pierre] Hop Cardiovasc L Pradel, CREATIS, Bron, France. [Viallon, Magalie] Hop Cantonal Univ Geneva, Geneva, Switzerland. [Kellman, Peter] NHLBI, NIH, Bethesda, MD 20892 USA. [Stemmer, Alto] Siemens Med Solut, Healthcare Sector, Erlangen, Germany. [Bi, Xiaoming; Zuehlsdorff, Sven] Siemens Med Solut, Healthcare Sector, Chicago, IL USA. RI Croisille, Pierre/H-4928-2014; Magalie, Viallon/H-4471-2014; Revel, Didier/M-4553-2014; Clarysse, Patrick/G-6371-2014 OI Croisille, Pierre/0000-0003-4019-3460; Magalie, Viallon/0000-0001-9118-0438; Clarysse, Patrick/0000-0002-5495-7655 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S322 EP S322 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500094 ER PT J AU Miao, CL Chen, SG Macedo, R Carr, JJ Brown, E Lai, SH Liu, K Li, DB Vogel-Clausen, J Lima, JA Ding, JZ Bluemke, D AF Miao, Cuilian Chen, Shaoguang Macedo, Robson Carr, J. Jeffrey Brown, Elizabeth Lai, Shenghan Liu, Kiang Li, Debiao Vogel-Clausen, Jens Lima, Joao A. Ding, Jingzhong Bluemke, David TI The Association of Pericardial Fat With Coronary Artery Plaque by MRI: The Multi-ethnic Study of Atherosclerosis (MESA) SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Miao, Cuilian; Chen, Shaoguang; Macedo, Robson; Lai, Shenghan; Vogel-Clausen, Jens; Lima, Joao A.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Carr, J. Jeffrey; Ding, Jingzhong] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [Brown, Elizabeth] Univ Washington, Seattle, WA 98195 USA. [Liu, Kiang] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Li, Debiao] Northwestern Univ, Sch Med, Chicago, IL 60611 USA. [Bluemke, David] NIH, Bethesda, MD 20892 USA. RI Li, Debiao/B-7622-2009; Carr, John/A-1938-2012 OI Carr, John/0000-0002-4398-8237 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S464 EP S464 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500655 ER PT J AU Morawietz, H Catar, RA Goettsch, C Taye, A Muller, G Lehmann, S Ziegler, CG Bornstein, SR Krug, AW Walther, T AF Morawietz, Henning Catar, Rusan A. Goettsch, Claudia Taye, Ashraf Muller, Gregor Lehmann, Susann Ziegler, Christian G. Bornstein, Stefan R. Krug, Alexander W. Walther, Thomas TI Novel Cross-Talk Between Oxidized LDL, Angiotensin II and Oxidative Stress After AT1 Blockade and AT1a/AT1b Double Knockout SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Morawietz, Henning; Goettsch, Claudia; Taye, Ashraf; Muller, Gregor; Lehmann, Susann; Ziegler, Christian G.; Bornstein, Stefan R.] Tech Univ Dresden, D-8027 Dresden, Germany. [Catar, Rusan A.] Charite, Berlin, Germany. [Krug, Alexander W.] NIH Baltimore, Baltimore, MD USA. [Walther, Thomas] Univ Hull, Kingston Upon Hull HU6 7RX, N Humberside, England. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1133 EP S1133 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831504171 ER PT J AU Murray, CI Gao, WD Zhong, X Stanley, BA Foster, DB King, SB Wink, DA Van Eyk, JE Paolocci, N AF Murray, Christopher I. Gao, Wei Dong Zhong, Xin Stanley, Brian A. Foster, D. Brain King, S. Bruce Wink, David A. Van Eyk, Jennifer E. Paolocci, Nazareno TI HNO Induces a Disulfide Bond Between Cysteine Residues on Actin (Cys 257) and Tropomyosin (Cys 190) Increasing Cardiac Force Development A Novel, Redox-based Mechanism for Contractile Regulation SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Murray, Christopher I.; Gao, Wei Dong; Zhong, Xin; Stanley, Brian A.; Foster, D. Brain; Van Eyk, Jennifer E.; Paolocci, Nazareno] Johns Hopkins Univ, Baltimore, MD USA. [King, S. Bruce] Wake Forest, Winston Salem, NC USA. [Wink, David A.] NCI, Bethesda, MD 20892 USA. RI Foster, D. Brian/C-6350-2009 OI Foster, D. Brian/0000-0002-9290-9590 NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S871 EP S871 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831502710 ER PT J AU Ohye, RG Tabbutt, S Sleeper, LA Pearson, GD Mahony, L Newburger, JW Lu, MM Laussen, PC Goldberg, CS Ghanayem, NS Frommelt, PC Atz, AM Colan, S Jacobs, JP Jaggers, J Kanter, KR Krawczeski, CD Lewis, AB McCrindle, BW Minick, LL Mital, S Pizarro, C Ravishankar, C Williams, IA Gaynor, JW AF Ohye, Richard G. Tabbutt, Sarah Sleeper, Lynn A. Pearson, Gail D. Mahony, Lynn Newburger, Jane W. Lu, Minmin Laussen, Peter C. Goldberg, Caren S. Ghanayem, Nancy S. Frommelt, Peter C. Atz, Andrew M. Colan, Steven Jacobs, Jeffrey P. Jaggers, James Kanter, Kirk R. Krawczeski, Catherine D. Lewis, Alan B. McCrindle, Brian W. Minick, L. L. Mital, Seema Pizarro, Christian Ravishankar, Chitra Williams, Ismee A. Gaynor, J. W. TI Outcomes of the Norwood Operation in Infants Randomized to a Modified Blalock-Taussig versus Right Ventricle-to-Pulmonary Artery Shunt: The Pediatric Heart Network Single Ventricle Reconstruction Trial SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Ohye, Richard G.; Goldberg, Caren S.] Univ Michigan, Congenital Heart Cntr, Ann Arbor, MI 48109 USA. [Tabbutt, Sarah] Childrens Hosp Philadelphia, Watertown, MA USA. [Sleeper, Lynn A.; Lu, Minmin] New England Res Inst, Boston, MA USA. [Pearson, Gail D.] NHLBI, Bethesda, MD 20892 USA. [Mahony, Lynn] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Newburger, Jane W.; Laussen, Peter C.; Colan, Steven] Childrens Hosp, Boston, MA 02115 USA. [Ghanayem, Nancy S.; Frommelt, Peter C.] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA. [Atz, Andrew M.] Med Univ S Carolina, Ann Arbor, MI USA. [Jacobs, Jeffrey P.] Childrens Heart Inst Florida, St Petersburg, FL USA. [Jaggers, James] Duke Univ, Med Ctr, Durham, NC USA. [Kanter, Kirk R.] Emory Univ, Atlanta, GA 30322 USA. [Krawczeski, Catherine D.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Lewis, Alan B.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [McCrindle, Brian W.; Mital, Seema] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Minick, L. L.] Univ Utah, Salt Lake City, UT USA. [Pizarro, Christian] Alfred I DuPont Hosp Children, Wilmington, DE USA. [Ravishankar, Chitra; Gaynor, J. W.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Williams, Ismee A.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S560 EP S560 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501252 ER PT J AU Owens, DS Plehn, JF Sigurdsson, S Probstfield, JL Launer, LJ Eiriksdottir, G Gudnason, V Harris, TB O'Brien, KD AF Owens, David S. Plehn, Jonathan F. Sigurdsson, Sigurdur Probstfield, Jeffrey L. Launer, Lenore J. Eiriksdottir, Guony Gudnason, Vilmundur Harris, Tamara B. O'Brien, Kevin D. TI Aortic Valve Calcium Scores Are Strong Predictors of Aortic Stenosis in a Population-Based Setting: The AGES-Reykjavik Study SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Owens, David S.; Probstfield, Jeffrey L.; O'Brien, Kevin D.] Univ Washington, Seattle, WA 98195 USA. [Plehn, Jonathan F.] Covance Inc, Princeton, NJ USA. [Sigurdsson, Sigurdur; Eiriksdottir, Guony; Gudnason, Vilmundur] Iceland Heart Assoc, Reykjavik, Iceland. [Launer, Lenore J.; Harris, Tamara B.] NIA, NIH, Bethesda, MD 20892 USA. RI Gudnason, Vilmundur/K-6885-2015 OI Gudnason, Vilmundur/0000-0001-5696-0084 NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S313 EP S314 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500061 ER PT J AU Payne, AR Berry, C Kellman, P Anderson, R Chen, MY Watkins, S McPhaden, AR Schenke, W Wright, V Lederman, RJ Aletras, AH Arai, AE AF Payne, Alexander R. Berry, Colin Kellman, Peter Anderson, Rachel Chen, Marcus Y. Watkins, Stuart McPhaden, Alan R. Schenke, William Wright, Victor Lederman, Robert J. Aletras, Anthony H. Arai, Andrew E. TI T2-weighted MRI Has High Diagnostic Accuracy for Myocardial Hemorrhage in Myocardial Infarction: A Preclinical Validation Study in Swine SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Payne, Alexander R.; Berry, Colin; Kellman, Peter; Anderson, Rachel; Chen, Marcus Y.; Schenke, William; Wright, Victor; Lederman, Robert J.; Aletras, Anthony H.; Arai, Andrew E.] NIH, Bethesda, MD 20892 USA. [Watkins, Stuart] Golden Jubilee Natl Hosp, Glasgow, Lanark, Scotland. [McPhaden, Alan R.] Glasgow Royal Infirm, Glasgow G4 0SF, Lanark, Scotland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S321 EP S321 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500089 ER PT J AU Pencina, M D'Agostino, RB Fox, CS Vasan, RS Kannel, WB AF Pencina, Michael D'Agostino, Ralph B. Fox, Caroline S. Vasan, Ramachandran S. Kannel, William B. TI Obesity is Independently Associated With Long-term Risk of Cardiovascular Mortality and Underweight With Risk of Non-cardiovascular Mortality in Framingham Offspring Cohort SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Pencina, Michael; D'Agostino, Ralph B.] Boston Univ, Boston, MA 02215 USA. [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Vasan, Ramachandran S.] Boston Univ, Framingham Heart Study, Framingham, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S508 EP S508 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501045 ER PT J AU Polak, JF Pencina, MJ O'Donnell, CJ Wolf, PA D'Agostino, R AF Polak, Joseph F. Pencina, Michael J. O'Donnell, Christopher J. Wolf, Philip A. D'Agostino, Ralph, Sr. TI Added Value of the Common and Internal Carotid Intima-media Thickness (IMT) for the Prediction of Cardiovascular Events: The Framingham Offspring Study SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Polak, Joseph F.] Tufts Univ, Sch Med, Tufts Med Cntr, Boston, MA 02111 USA. [Wolf, Philip A.] Boston Univ, Sch Med, Boston, MA 02215 USA. [O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Polak, Joseph F.] Tufts Univ, Sch Med, Tufts Med Ctr, Boston, MA 02111 USA. [Pencina, Michael J.; Wolf, Philip A.; D'Agostino, Ralph, Sr.] Boston Univ, Sch Med, Boston, MA 02215 USA. [O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S425 EP S425 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500501 ER PT J AU Polak, JF Wong, Q Johnson, WC Bluemke, DA Harrington, A O'Leary, DH Yanez, ND AF Polak, Joseph F. Wong, Quenna Johnson, W. C. Bluemke, David A. Harrington, Anita O'Leary, Daniel H. Yanez, N. D. TI Associations Between Inter-adventitial Diameters of the Common Carotid Artery, Cardiovascular Risk Factors, Carotid Intima-media Thickness and Left Ventricular Mass: The Multi-Ethnic Study of Atherosclerosis (MESA) SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Polak, Joseph F.] Tufts Univ, Sch Med, Tufts Med Cntr, Boston, MA 02111 USA. [Wong, Quenna; Johnson, W. C.; Yanez, N. D.] Univ Washington, Seattle, WA 98195 USA. [Bluemke, David A.] Natl Inst Hlth, Bethesda, MD USA. [O'Leary, Daniel H.] Tufts Univ, Sch Med, Carney Hosp, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S400 EP S400 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500401 ER PT J AU Pop-Busui, R Waberski, BH Cleary, PA Herman, WH Low, PA Martin, CL Lima, JA Bluemke, D AF Pop-Busui, Rodica Waberski, Barbara H. Cleary, Patricia A. Herman, William H. Low, Phillip A. Martin, Catherine L. Lima, Joao A. Bluemke, David TI Cardiac Autonomic Neuropathy and Left Ventricular Function in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Intervention and Complications Study (DCCT/EDIC) SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Pop-Busui, Rodica; Herman, William H.; Martin, Catherine L.] Univ Michigan, Ann Arbor, MI 48109 USA. [Waberski, Barbara H.; Cleary, Patricia A.] George Washington Univ, Rockville, MD USA. [Low, Phillip A.] Mayo Clin, Rochester, MN USA. [Lima, Joao A.] Johns Hopkins Univ, Baltimore, MD USA. [Bluemke, David] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S546 EP S547 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501198 ER PT J AU Rajesh, M Mukhopadhyay, P Patel, V Batkai, S Ungvari, Z Hasko, G Pacher, P AF Rajesh, Mohanraj Mukhopadhyay, Partha Patel, Vivek Batkai, Sandor Ungvari, Zoltan Hasko, Gyorgy Pacher, Pal TI Cannabidiol Attenuates Myocardial Dysfunction, Fibrosis, Inflammation, Cell Death and Interrelated Signaling Pathways Associated With Diabetic Cardiomyopathy SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Rajesh, Mohanraj; Mukhopadhyay, Partha; Patel, Vivek; Batkai, Sandor; Pacher, Pal] NIH, Rockville, MD USA. [Ungvari, Zoltan] New York Med Coll, Valhalla, NY 10595 USA. [Hasko, Gyorgy] Univ Med & Dent New Jersey, Newark, NJ 07103 USA. RI Batkai, Sandor/G-3889-2010; Batkai, Sandor/H-7983-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S868 EP S868 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831502696 ER PT J AU Schnabel, RB Baumert, J Barbalic, M Dupuis, J Ellinor, PT Durda, P Dehghan, A Bis, JC Witteman, JC Hoogeveen, RC Benjamin, EJ Koenig, W Tracy, RP AF Schnabel, Renate B. Baumert, Jens Barbalic, Maja Dupuis, Josee Ellinor, Patrick T. Durda, Peter Dehghan, Abbas Bis, Joshua C. Witteman, Jacqueline C. Hoogeveen, Ron C. Benjamin, Emelia J. Koenig, Wolfgang Tracy, Russell P. CA CHARGE Consortium TI Duffy Antigen Receptor for Chemokines (Darc) Polymorphism Regulates Circulating Concentrations of Monocyte Chemoattractant Protein-1 and Other Circulating Inflammatory Mediators SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Schnabel, Renate B.] Johannes Gutenberg Univ Mainz, Mainz, 02114, Germany. [Baumert, Jens] German Rsch Cntr Environm Hlth, Helmholtz Zentrum Munchen, Neuherberg, 05405, Germany. [Barbalic, Maja; Hoogeveen, Ron C.] Univ Texas Hlth Sci Ctr, Human Genet Cntr, Houston, TX USA. [Barbalic, Maja; Hoogeveen, Ron C.] Univ Texas Hlth Sci Ctr, Inst Mol Med, Houston, TX 98195 USA. [Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Rsch Cntr, Boston, MA USA. [Durda, Peter] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT USA. [Dehghan, Abbas] Erasmus Med Cntr, Dept Epidemiol, D-7900 Rotterdam, Netherlands. [Bis, Joshua C.] Univ Washington, Seattle, WA 05405 USA. [Witteman, Jacqueline C.] Erasmus Med Cntr, Rotterdam, Netherlands. [Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Koenig, Wolfgang] Univ Ulm, Dept Internal Med 2, Med Cntr, Ulm, Germany. [Tracy, Russell P.] Univ Vermont, Coll Med, Dept Biochem, Burlington, VT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S559 EP S559 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501249 ER PT J AU Schoenhoff, FS Griswold, BF Matt, P Sloper, LJ Yamazaki, M Carlson, OD Dietz, HC Van Eyk, JE McDonnell, NB AF Schoenhoff, Florian S. Griswold, Benjamin F. Matt, Peter Sloper, Leslie J. Yamazaki, Michiyo Carlson, Olga D. Dietz, Harry C. Van Eyk, Jennifer E. McDonnell, Nazli B. TI The Role of Circulating Transforming Growth Factor-beta in Vascular Ehlers-Danlos Syndrome: Implications for Drug Therapy SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Schoenhoff, Florian S.; Matt, Peter; Yamazaki, Michiyo; Dietz, Harry C.; Van Eyk, Jennifer E.] Johns Hopkins Univ, Baltimore, MD USA. [Griswold, Benjamin F.; Sloper, Leslie J.; Carlson, Olga D.; McDonnell, Nazli B.] NIA, Baltimore, MD 21224 USA. NR 0 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1048 EP S1048 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831503606 ER PT J AU Sibley, CT Gottlieb, I Cox, C Godoy, G Spooner, AE Bluemke, DA Lima, JA AF Sibley, Christopher T. Gottlieb, Ilan Cox, Christopher Godoy, Gustavo Spooner, Amy E. Bluemke, David A. Lima, Joao A. TI Comparative Effect of Statins vs Niacin on MRI Measured Regression of Carotid Atherosclerosis in a Randomized Clinical Trial: The NIA Plaque Study SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Sibley, Christopher T.; Godoy, Gustavo; Lima, Joao A.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Gottlieb, Ilan] Univ Fed Rio de Janeiro, Rio De Janeiro, Brazil. [Cox, Christopher] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Spooner, Amy E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bluemke, David A.] NIH, Bethesda, MD 20892 USA. RI Sibley, Christopher/C-9900-2013 NR 0 TC 9 Z9 9 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S376 EP S376 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500305 ER PT J AU Thanassoulis, G Massaro, JM Hoffman, U Mahabadi, AA Vasan, RS O'Donnell, CJ Fox, CS AF Thanassoulis, George Massaro, Joseph M. Hoffman, Udo Mahabadi, Amir A. Vasan, Ramachandran S. O'Donnell, Christopher J. Fox, Caroline S. TI Prevalence and Distribution of High Pericardial and Intra-thoracic Fat Depots in the Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Thanassoulis, George; Mahabadi, Amir A.; Vasan, Ramachandran S.; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, NIH, Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S539 EP S540 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501172 ER PT J AU Thanassoulis, G Massaro, JM O'Donnell, CJ Levy, D Hoffman, U Ellinor, PT Wang, TJ Vasan, RS Fox, CS Benjamin, EJ AF Thanassoulis, George Massaro, Joseph M. O'Donnell, Christopher J. Levy, Daniel Hoffman, Udo Ellinor, Patrick T. Wang, Thomas J. Vasan, Ramachandran S. Fox, Caroline S. Benjamin, Emelia J. TI Pericardial Fat is Associated With Prevalent AF - The Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Thanassoulis, George; O'Donnell, Christopher J.; Vasan, Ramachandran S.; Fox, Caroline S.; Benjamin, Emelia J.] NHLBI, NIH, Framingham Heart Study, Framingham, MA USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Hoffman, Udo; Ellinor, Patrick T.; Wang, Thomas J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S519 EP S519 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501091 ER PT J AU Tofler, GH Massaro, J O'Donnell, CJ Wilson, PW Vasan, RS Sutherland, PA Lipinska, I Meigs, JB Levy, D D'Agostino, RB AF Tofler, Geoffrey H. Massaro, Joseph O'Donnell, Christopher J. Wilson, Peter W. Vasan, Ramachandran S. Sutherland, Patrice A. Lipinska, Izabela Meigs, James B. Levy, Daniel D'Agostino, Ralph B. TI Plasminogen Activator Inhibitor (PAI-1) and Risk of Cardiovascular Disease: The Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Tofler, Geoffrey H.] Royal N Shore Hosp, Sydney, NSW 02215, Australia. [Massaro, Joseph; Vasan, Ramachandran S.; Lipinska, Izabela; D'Agostino, Ralph B.] Boston Univ, Boston, MA USA. [O'Donnell, Christopher J.; Levy, Daniel] NHLBI, Framingham, MA USA. [O'Donnell, Christopher J.; Sutherland, Patrice A.; Levy, Daniel] Framingham Heart Dis Epidemiol Study, Framingham, MA 30322 USA. [Wilson, Peter W.] Emory Univ, Atlanta, GA 02114 USA. [Meigs, James B.] Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S454 EP S454 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500614 ER PT J AU Vazquez, E Sethi, AA Sampson, M Remaley, AT Chaudhry, H Cannon, RO AF Vazquez, Edward Sethi, Amar A. Sampson, Maureen Remaley, Alan T. Chaudhry, Hira Cannon, Richard O., III TI "Dysfunctional" High-density Lipoprotein Despite Normal Cholesterol Content in Sedentary Obese Women SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Vazquez, Edward; Sethi, Amar A.; Sampson, Maureen; Remaley, Alan T.; Chaudhry, Hira; Cannon, Richard O., III] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S470 EP S470 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500681 ER PT J AU Velagaleti, RS Pencina, MJ Aragam, J Wang, TJ Levy, D D'Agostino, RB Kannel, WB Benjamin, EJ Vasan, RS AF Velagaleti, Raghava S. Pencina, Michael J. Aragam, Jayashri Wang, Thomas J. Levy, Daniel D'Agostino, Ralph B. Kannel, William B. Benjamin, Emelia J. Vasan, Ramachandran S. TI Left Ventricular Hypertrophy Patterns and the Incidence of Heart Failure: The Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Velagaleti, Raghava S.; Pencina, Michael J.; Wang, Thomas J.; Levy, Daniel; D'Agostino, Ralph B.; Kannel, William B.; Benjamin, Emelia J.; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Aragam, Jayashri] Vet Adm Hosp, W Roxbury, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S415 EP S415 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500462 ER PT J AU Velagaleti, RS Gona, P Chuang, ML Yeon, SB Salton, CJ Fox, CS Massaro, J Hoffmann, U Manning, WJ O'Donnell, CJ AF Velagaleti, Raghava S. Gona, Philimon Chuang, Michael L. Yeon, Susan B. Salton, Carol J. Fox, Caroline S. Massaro, Joseph Hoffmann, Udo Manning, Warren J. O'Donnell, Christopher J. TI Aortic Atherosclerosis and Left Ventricular Structure in the Community SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Velagaleti, Raghava S.; Gona, Philimon; Fox, Caroline S.; Massaro, Joseph; O'Donnell, Christopher J.] NHLBI, Framingham, MA USA. [Chuang, Michael L.; Yeon, Susan B.; Salton, Carol J.; Manning, Warren J.] Beth Israel Deaconess Med Cntr, Boston, MA USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S380 EP S380 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500321 ER PT J AU Vickers, KC Aponte, AM Remaley, AT AF Vickers, Kasey C. Aponte, Angel M. Remaley, Alan T. TI A Novel Pathway for the Regulation of Hepatic Cholesterol Synthesis by microRNA's SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Vickers, Kasey C.; Aponte, Angel M.; Remaley, Alan T.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S476 EP S476 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500705 ER PT J AU Vogel-Claussen, J Tomas, MS Newatia, A Boyce, D Pinheiro, A Abraham, R Abraham, T Bluemke, DA AF Vogel-Claussen, Jens Tomas, Miguel Santaularia Newatia, Amit Boyce, Danielle Pinheiro, Aurelio Abraham, Roselle Abraham, Theodore Bluemke, David A. TI Left Ventricular Outflow Tract (LVOT) Diameter/Aortic Valve Diameter Ratio is an Accurate Non-invasive Cardiac MRI Marker for Estimation of LVOT Obstruction in Patients With Hypertrophic Cardiomyopathy SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Vogel-Claussen, Jens; Tomas, Miguel Santaularia; Newatia, Amit; Boyce, Danielle; Pinheiro, Aurelio; Abraham, Roselle; Abraham, Theodore] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Bluemke, David A.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S379 EP S379 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500318 ER PT J AU Wang, KL Cheng, HM Chuang, SY Spurgeon, H Ting, CT Najjar, S Lakatta, E Yin, F Chou, P Chen, CH AF Wang, Kang-Ling Cheng, Hao-Min Chuang, Shao-Yuan Spurgeon, Harold Ting, Chih-Tai Najjar, Samer Lakatta, Edward Yin, Frank Chou, Pesus Chen, Chen-Huan TI Waveform Reflections and Arterial Stiffness in the Prediction of 15.1-Year All-Cause and Cardiovascular Mortalities: A Community-Based Study SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Wang, Kang-Ling; Cheng, Hao-Min; Chen, Chen-Huan] Taipei Vet Gen Hosp, Taipei, Taiwan. [Chuang, Shao-Yuan] Acad Sinica, Taipei 115, Taiwan. [Spurgeon, Harold; Najjar, Samer; Lakatta, Edward] NIA, Baltimore, MD 21224 USA. [Ting, Chih-Tai] Taichung Vet Gen Hosp, Taichung, Taiwan. [Yin, Frank] Washington Univ, St Louis, MO USA. [Chou, Pesus] Yang Ming Univ, Taipei, Taiwan. RI Chuang, Shao-Yuan/B-3478-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1061 EP S1062 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831503661 ER PT J AU Williams, RV Travison, T Kaltman, JR Cecchin, F Colan, S Idriss, SF Lu, M Margossian, R Reed, JH Silver, EE Stephenson, EA Vetter, VL AF Williams, Richard V. Travison, Thomas Kaltman, Jonathan R. Cecchin, Frank Colan, Steven Idriss, Salim F. Lu, Minmin Margossian, Renee Reed, John H. Silver, Eric E. Stephenson, Elizabeth A. Vetter, Victoria L. CA Pediat Heart Network Investigators TI Decreased Functional Status and Ventricular Function in Fontan Patients With Pacemakers SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Williams, Richard V.] Univ Utah, Salt Lake City, UT USA. [Travison, Thomas; Lu, Minmin] New England Res Inst, Watertown, MA 02172 USA. [Kaltman, Jonathan R.] NHLBI, Bethesda, MD 20892 USA. [Cecchin, Frank; Colan, Steven; Margossian, Renee] Childrens Hosp, Boston, MA 02115 USA. [Idriss, Salim F.] Duke Univ, Durham, NC USA. [Reed, John H.] Med Univ S Carolina, Charleston, SC 29425 USA. [Silver, Eric E.] Columbia Univ, New York, NY USA. [Stephenson, Elizabeth A.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Vetter, Victoria L.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S600 EP S601 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501419 ER PT J AU Wu, Q Chambliss, KL Oltmann, SC Umetani, M Yuhanna, IS Korach, KS Thomas, GD Mineo, C Kim, SH Madak-Erdogan, Z Maggi, A Dineen, SP Roland, CL Brekken, RA Katzenellenbogen, JA Katzenellenbogen, BS Shaul, PW AF Wu, Qian Chambliss, Ken L. Oltmann, Sarah C. Umetani, Michihisa Yuhanna, Ivan S. Korach, Kenneth S. Thomas, Gail D. Mineo, Chieko Kim, Sung Hoon Madak-Erdogan, Zeynep Maggi, Adriana Dineen, Sean P. Roland, Christina L. Brekken, Rolf A. Katzenellenbogen, John A. Katzenellenbogen, Benita S. Shaul, Philip W. TI Extranuclear Estrogen Receptor a Signaling Promotes Endothelial Monolayer Integrity but Not Breast Cancer or Uterine Growth in Mice SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Wu, Qian; Chambliss, Ken L.; Oltmann, Sarah C.; Umetani, Michihisa; Yuhanna, Ivan S.; Thomas, Gail D.; Mineo, Chieko; Dineen, Sean P.; Roland, Christina L.; Brekken, Rolf A.; Shaul, Philip W.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Korach, Kenneth S.] NIEHS, Res Triangle Pk, NC 27709 USA. [Kim, Sung Hoon; Madak-Erdogan, Zeynep; Katzenellenbogen, John A.; Katzenellenbogen, Benita S.] Univ Illinois, Urbana, IL 61801 USA. [Maggi, Adriana] Univ Milan, Milan, Italy. RI Dineen, Sean/B-6222-2013; Oltmann, Sarah/L-3245-2014; Dineen, Sean/M-3741-2013; Dineen, Sean/K-1471-2015 OI Oltmann, Sarah/0000-0002-7180-4167; Dineen, Sean/0000-0002-2012-2238 NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S1161 EP S1161 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831504293 ER PT J AU Yeon, SB Salton, CJ Gona, P Chuang, ML Tsao, CW Danias, PG Levy, D O'Donnell, CJ Manning, WJ AF Yeon, Susan B. Salton, Carol J. Gona, Philimon Chuang, Michael L. Tsao, Connie W. Danias, Peter G. Levy, Daniel O'Donnell, Christopher J. Manning, Warren J. TI Gender Differences in Left Ventricular Parameters in a Normotensive Population: Impact of Indexation for Fat Free Mass SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Yeon, Susan B.; Salton, Carol J.; Tsao, Connie W.; Manning, Warren J.] Beth Israel Deaconess Med Cntr, Boston, MA USA. [Gona, Philimon; Levy, Daniel; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Gona, Philimon] NHLBI, Framingham Heart Study, Boston, MA USA. [Gona, Philimon] Boston Univ, Framingham, MA USA. [Gona, Philimon] Boston Univ, Boston, MA 02215 USA. [Danias, Peter G.] Tufts Univ, Sch Med, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S545 EP S545 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831501193 ER PT J AU Zhao, Q Gu, DF Chen, J Bazzano, LA Rao, DC Hixson, J Jaquish, CE Cao, J Chen, JC Li, JX Rice, T He, J AF Zhao, Qi Gu, Dongfeng Chen, Jing Bazzano, Lydia A. Rao, D. C. Hixson, James Jaquish, Cashell E. Cao, Jie Chen, Jichun Li, Jianxin Rice, Treva He, Jiang TI Correlation Between Blood Pressure Responses to Dietary Sodium and Potassium Intervention in a Chinese Population SO CIRCULATION LA English DT Meeting Abstract CT 82nd Scientific Session of the American-Heart-Association CY NOV 14-18, 2009 CL Orlando, FL SP Amer Heart Assoc C1 [Zhao, Qi; Bazzano, Lydia A.; He, Jiang] Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA 70118 USA. [Gu, Dongfeng; Cao, Jie; Chen, Jichun; Li, Jianxin] Chinese Acad Med Sci, Fuwai Hosp & Cardiovasc Inst, Beijing 100037, Peoples R China. [Gu, Dongfeng; Cao, Jie; Chen, Jichun; Li, Jianxin] Peking Univ, Coll Med, Beijing 100871, Peoples R China. [Gu, Dongfeng; Cao, Jie; Chen, Jichun; Li, Jianxin] Chinese Natl Ctr Cardiovasc Dis Control & Res, Beijing, Peoples R China. [Rao, D. C.; Rice, Treva] Washington Univ, Sch Med, St Louis, MO USA. [Hixson, James] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. [Jaquish, Cashell E.] NIH, Bethesda, MD 20892 USA. [He, Jiang] Tulane Univ, Sch Med, New Orleans, LA 70118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 3 PY 2009 VL 120 IS 18 SU 2 BP S447 EP S447 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 520GV UT WOS:000271831500587 ER PT J AU Bird, GS Hwang, SY Smyth, JT Fukushima, M Boyles, RR Putney, JW AF Bird, Gary S. Hwang, Sung-Yong Smyth, Jeremy T. Fukushima, Miwako Boyles, Rebecca R. Putney, James W., Jr. TI STIM1 Is a Calcium Sensor Specialized for Digital Signaling SO CURRENT BIOLOGY LA English DT Article ID EMBRYONIC KIDNEY-CELLS; LOCAL CA2+ INFLUX; MAST-CELLS; CRAC CHANNEL; ENTRY; ACTIVATION; OSCILLATIONS; RELEASE; ORAI1 AB When cells are activated by calcium-mobilizing agonists at low, physiological concentrations, the resulting calcium signals generally take the form of repetitive regenerative discharges of stored calcium, termed calcium oscillations [1]. These intracellular calcium oscillations have long fascinated biologists as a mode of digitized intracellular signaling. Recent work has highlighted the role of calcium influx as an essential component of calcium oscillations [2]. This influx occurs through a process known as store-operated calcium entry, which is initiated by calcium sensor proteins, STIM1 and STIM2, in the endoplasmic reticulum [3]. STIM2 is activated by changes in endoplasmic reticulum calcium near the resting level, whereas a threshold of calcium depletion is required for STIM1 activation [4]. Here we show that, surprisingly, it is STIM1 and not STIM2 that is exclusively involved in calcium entry during calcium oscillations. The implication is that each oscillation produces a transient drop in endoplasmic reticulum calcium and that this drop is sufficient to transiently activate STIM1. This transient activation of STIM1 can be observed in some cells by total internal reflection fluorescence microscopy. This arrangement nicely provides a clearly defined and unambiguous signaling system, translating a digital calcium release signal into calcium influx that can signal to downstream effectors. C1 [Bird, Gary S.; Hwang, Sung-Yong; Smyth, Jeremy T.; Fukushima, Miwako; Boyles, Rebecca R.; Putney, James W., Jr.] Natl Inst Environm Hlth Sci, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Putney, JW (reprint author), Natl Inst Environm Hlth Sci, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. EM putney@niehs.nih.gov OI Boyles, Rebecca/0000-0003-0073-6854 FU National Institute of Environmental Health Sciences; National Institutes of Health FX We thank Drs. Jerrel Yakel, Steve Shears, and Wayne DeHaven, who read the manuscript and provided helpful comments. This work was supported by funds from the Intramural Program of the National Institute of Environmental Health Sciences and the National Institutes of Health. NR 23 TC 64 Z9 65 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD NOV 3 PY 2009 VL 19 IS 20 BP 1724 EP 1729 DI 10.1016/j.cub.2009.08.022 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 515UM UT WOS:000271498400028 PM 19765994 ER PT J AU Ferrari, PF Paukner, A Ionica, C Suomi, SJ AF Ferrari, Pier Francesco Paukner, Annika Ionica, Consuel Suomi, Stephen J. TI Reciprocal Face-to-Face Communication between Rhesus Macaque Mothers and Their Newborn Infants SO CURRENT BIOLOGY LA English DT Article ID CHIMPANZEES PAN-TROGLODYTES; IMITATION AB Human mothers interact emotionally with their newborns through exaggerated facial expressions, speech, mutual gaze, and body contact, a capacity that has long been considered uniquely human [1-4]. Current developmental psychological theories propose that this pattern of mother-infant exchange promotes the regulation of infant emotions [4-6] and serves as a precursor of more complex forms of social exchange including perspective taking and empathy. Here we report that in rhesus macaques, mother-infant pairs also communicate intersubjectively via complex forms of emotional exchanges including exaggerated lipsmacking, sustained mutual gaze, mouth-mouth contacts, and neonatal imitation. Infant macaques solicit their mother's affiliative responses and actively communicate to her. However, this form of communication disappears within the infant's first month of life. Our data challenge the view that the mother-infant communicative system functions in order to sustain proximity and that infants are simply passive recipients in such interaction. Thus, emotional communication between mother and infant is not uniquely human. Instead, we can trace back to macaques the evolutionary foundation of those behaviors that are crucial for the establishment of a functional capacity to socially exchange with others. C1 [Ferrari, Pier Francesco] Univ Parma, Dipartimento Biol Evolut & Funz, I-43100 Parma, Italy. [Ferrari, Pier Francesco] Univ Parma, Dipartimento Neurosci, I-43100 Parma, Italy. [Ferrari, Pier Francesco; Paukner, Annika; Ionica, Consuel; Suomi, Stephen J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, NIH, Bethesda, MD 20892 USA. RP Ferrari, PF (reprint author), Univ Parma, Dipartimento Biol Evolut & Funz, Via Usberti 11A, I-43100 Parma, Italy. EM pierfrancesco.ferrari@unipr.it RI Ionica, Consuel/A-5186-2009 FU NICHD; National Institutes of Health; MIUR-COFIN; NeuroCom FX This study was supported by the Division of Intramural Research of the NICHD, the National Institutes of Health, MIUR-COFIN 2007, and NeuroCom. We thank D. Stern and E. Palagi for valuable comments on an early draft of the manuscript. NR 23 TC 60 Z9 61 U1 3 U2 17 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD NOV 3 PY 2009 VL 19 IS 20 BP 1768 EP 1772 DI 10.1016/j.cub.2009.08.055 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 515UM UT WOS:000271498400036 PM 19818617 ER PT J AU Rohrer, JD Guerreiro, R Vandrovcova, J Uphill, J Reiman, D Beck, J Isaacs, AM Authier, A Ferrari, R Fox, NC Mackenzie, IRA Warren, JD de Silva, R Holton, J Revesz, T Hardy, J Hardy, J Mead, S Rossor, MN AF Rohrer, J. D. Guerreiro, R. Vandrovcova, J. Uphill, J. Reiman, D. Beck, J. Isaacs, A. M. Authier, A. Ferrari, R. Fox, N. C. Mackenzie, I. R. A. Warren, J. D. de Silva, R. Holton, J. Revesz, T. Hardy, J. Hardy, J. Mead, S. Rossor, M. N. TI The heritability and genetics of frontotemporal lobar degeneration SO NEUROLOGY LA English DT Article ID PRIMARY-PROGRESSIVE-APHASIA; AMYOTROPHIC-LATERAL-SCLEROSIS; CORTICOBASAL DEGENERATION; SUPRANUCLEAR PALSY; TAU-MUTATIONS; DEMENTIA; PROGRANULIN; FREQUENCY; CONSENSUS; CRITERIA AB Background: Frontotemporal lobar degeneration (FTLD) is a genetically and pathologically heterogeneous neurodegenerative disorder. Methods: We collected blood samples from a cohort of 225 patients with a diagnosis within the FTLD spectrum and examined the heritability of FTLD by giving each patient a family history score, from 1 (a clear autosomal dominant history of FTLD) through to 4 (no family history of dementia). We also looked for mutations in each of the 5 disease-causing genes (MAPT, GRN, VCP, CHMP2B, and TARDP) and the FUS gene, known to cause motor neuron disease. Results: A total of 41.8% of patients had some family history (score of 1, 2, 3, or 3.5), although only 10.2% had a clear autosomal dominant history (score of 1). Heritability varied across the different clinical subtypes of FTLD with the behavioral variant being the most heritable and frontotemporal dementia-motor neuron disease and the language syndromes (particularly semantic dementia) the least heritable. Mutations were found in MAPT (8.9% of the cohort) and GRN (8.4%) but not in any of the other genes. Of the remaining patients without mutations but with a strong family history, 7 had pathologic confirmation, falling into 2 groups: type 3 FTLD-TDP without GRN mutations (6) and FTLD-UPS (1). Conclusion: These findings show that frontotemporal lobar degeneration (FTLD) is a highly heritable disorder but heritability varies between the different syndromes. Furthermore, while MAPT and GRN mutations account for a substantial proportion of familial cases, there are other genes yet to be discovered, particularly in patients with type 3 FTLD-TDP without a GRN mutation. Neurology (R) 2009; 73:1451-1456 C1 [Rohrer, J. D.; Fox, N. C.; Warren, J. D.; Rossor, M. N.] UCL, Inst Neurol, Dept Mol Neurosci, Dementia Res Ctr, London WC1N 3BG, England. [Uphill, J.; Reiman, D.; Beck, J.; Isaacs, A. M.; Authier, A.; Mead, S.] UCL, Inst Neurol, Dept Mol Neurosci, MRC Prion Unit, London WC1N 3BG, England. [Ferrari, R.; Holton, J.] UCL, Inst Neurol, Dept Neurodegenerat Dis, Reta Lila Weston Inst,Dept Mol Neurosci, London WC1N 3BG, England. [Vandrovcova, J.; de Silva, R.; Holton, J.; Revesz, T.] UCL, Inst Neurol, Dept Mol Neurosci, Queen Sq Brain Bank, London WC1N 3BG, England. [Ferrari, R.] Texas Tech Univ, Hlth Sci Ctr, Dept Internal Med, Lubbock, TX 79430 USA. [Guerreiro, R.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Guerreiro, R.] Univ Coimbra, Ctr Neurosci & Cell Biol, Coimbra, Portugal. [Mackenzie, I. R. A.] Univ British Columbia, Dept Pathol & Lab Med, Vancouver Gen Hosp, Vancouver, BC V5Z 1M9, Canada. RP Rossor, MN (reprint author), UCL, Inst Neurol, Dept Mol Neurosci, Dementia Res Ctr, Queen Sq, London WC1N 3BG, England. EM mrossor@dementia.ion.ucl.ac.uk RI Revesz, Tamas/A-8732-2010; Mead, Simon/E-9414-2011; Holton, Janice/F-6831-2011; Hardy, John/C-2451-2009; Guerreiro, Rita/A-1327-2011; de Silva, Rohan/C-1734-2008; Fox, Nick/B-1319-2009 OI Revesz, Tamas/0000-0003-2501-0259; Mead, Simon/0000-0002-4326-1468; Holton, Janice/0000-0002-3882-5249; de Silva, Rohan/0000-0002-5052-5775; Fox, Nick/0000-0002-6660-657X FU Department of Health's NIHR Biomedical Research Centres; Wellcome Trust; Medical Research Council Prion Unit; Alzheimer's Research Trust; UCL Hospitals Clinical Research and Development Committee; Elan Corporation; Wyeth; Lundbeck Inc.; Sanofi-Aventis; IXICO Ltd.; Pfizer Inc.; Neurochem Inc.; MRC [G0801306, G0601846]; NIH [U01 AG024904 (Co-I)]; Alzheimer Research Trust [ART/RF/2007/1]; Canadian Institutes of Health Research; Pacific Alzheimer Research Foundation; Michael Smith Foundation for Health Research; The Sarah Matheson Trust; Action Medical Research; BrainNet Europe; Myositis Support Group; Orion Pharma; European Commission; BrainNet Europe II; Network of Excellence; Sarah Matheson Trust; Parkinson's Disease Society, UK; Department of Health FX Dr. Rohrer has received research support from the Wellcome Trust (Clinical Research Fellowship) and Brain (Exit Scholarship). R. Guerreiro, Dr. Vandrovcova, J. Uphill, D. Reiman, and J. Beck report no disclosures. Dr. Isaacs receives research support from the Medical Research Council Prion Unit, Alzheimer's Research Trust, and UCL Hospitals Clinical Research and Development Committee. A. Authier and R. Ferrari report no disclosures. Dr. Fox has served on scientific advisory boards for the Alzheimer's Research Forum and GE Healthcare; may accrue revenue on Patent PCT/GB2008/001537 (issued: 04/05/2007): QA Box; has received honoraria from GE Healthcare and Lancet Neurology (reviewer fee); has served as a consultant to Eli Lilly and Company, Abbott, and Lundbeck Inc.; has received research support (to the Dementia Research Centre) from Elan Corporation, Wyeth, Lundbeck Inc., Sanofi-Aventis, IXICO Ltd., Pfizer Inc., and Neurochem Inc.; and receives research support from the MRC [G0801306 (PI) and G0601846 (PI)], the NIH [U01 AG024904 (Co-I)], and the Alzheimer Research Trust [ART/RF/2007/1 (PI)]. Dr. Mackenzie serves on the advisory board of the 2009 International Conference on Alzheimer's Disease; has received funding for travel and speaker honoraria for non-industry-sponsored activities; serves on editorial boards for the Journal of Neuropathology & Experimental Neurology, the Journal of Neuroinflammation, and Clinical Neuropathology; and receives research support from Canadian Institutes of Health Research, Pacific Alzheimer Research Foundation, and Michael Smith Foundation for Health Research. Dr. Warren and Dr. De Silva report no disclosures. Dr. Holton serves on the editorial board of Neuropathology & Applied Neurobiology and has received research support from the Alzheimer's Research Trust, The Sarah Matheson Trust, Action Medical Research, BrainNet Europe, and the Myositis Support Group. Dr. Revesz serves on editorial boards for Acta Neuropathological, Clinical Neuropathology, and Neuropathology & Applied Neurobiology; has received speaker honoraria from Boehringer Ingelheim; and receives research support from Orion Pharma, the Alzheimer's Research Trust, the European Commission, BrainNet Europe II, Network of Excellence, the Sarah Matheson Trust, and the Parkinson's Disease Society, UK. Dr. Hardy serves as a consultant to Eisai Inc. Dr. Mead receives research support from the Medical Research Council Prion Unit and Wellcome Trust. Dr. Rossor serves on a scientific advisory board for Elan Corporation and Wyeth; serves as Editor-in-Chief of the Journal of Neurology, Neurosurgery and Psychiatry, and on the editorial boards of Practical Neurology, Dementia and Geriatric Cognitive Disorders, Neurodegenerative Diseases, and the British Medical Journal; receives royalties from publishing Brain's Diseases of the Nervous System (11th edition), Oxford University Press, 2001, and Brain's Diseases of the Nervous System (12th edition), Oxford University Press, 2009; and receives research support from the Department of Health and the Alzheimer's Research Trust. NR 39 TC 110 Z9 113 U1 0 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV 3 PY 2009 VL 73 IS 18 BP 1451 EP 1456 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 514XN UT WOS:000271429900005 PM 19884572 ER PT J AU Han, T Manoharan, AP Harkins, TT Bouffard, P Fitzpatrick, C Chu, DS Thierry-Mieg, D Thierry-Mieg, J Kim, JK AF Han, Ting Manoharan, Arun Prasad Harkins, Tim T. Bouffard, Pascal Fitzpatrick, Colin Chu, Diana S. Thierry-Mieg, Danielle Thierry-Mieg, Jean Kim, John K. TI 26G endo-siRNAs regulate spermatogenic and zygotic gene expression in Caenorhabditis elegans SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE endogenous siRNA; germline; RNA interference ID DIRECTED RNA-POLYMERASE; GERM-LINE DEVELOPMENT; C-ELEGANS; ENDOGENOUS SIRNAS; INTERFERING RNAS; MESSENGER-RNAS; SOMATIC-CELLS; MOUSE OOCYTES; PIRNA COMPLEX; DROSOPHILA AB Endogenous small interfering RNAs (endo-siRNAs) regulate diverse gene expression programs in eukaryotes by either binding and cleaving mRNA targets or mediating heterochromatin formation; however, the mechanisms of endo-siRNA biogenesis, sorting, and target regulation remain poorly understood. Here we report the identification and function of a specific class of germline-generated endo-siRNAs in Caenorhabditis elegans that are 26 nt in length and contain a guanine at the first nucleotide position (i.e., 26G RNAs). 26G RNAs regulate gene expression during spermatogenesis and zygotic development, and their biogenesis requires the ERI-1 exonuclease and the RRF-3 RNA-dependent RNA polymerase (RdRP). Remarkably, we identified two nonoverlapping subclasses of 26G RNAs that sort into specific RNA-induced silencing complexes (RISCs) and differentially regulate distinct mRNA targets. Class I 26G RNAs target genes are expressed during spermatogenesis, whereas class II 26G RNAs are maternally inherited and silence gene expression during zygotic development. These findings implicate a class of endo-siRNAs in the global regulation of transcriptional programs required for fertility and development. C1 [Han, Ting; Manoharan, Arun Prasad; Kim, John K.] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA. [Harkins, Tim T.] Roche Appl Sci, Indianapolis, IN 46250 USA. [Bouffard, Pascal] Roche Co, Life Sci 454, Branford, CT 06405 USA. [Fitzpatrick, Colin; Chu, Diana S.] San Francisco State Univ, Dept Biol, San Francisco, CA 94132 USA. [Thierry-Mieg, Danielle; Thierry-Mieg, Jean] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20895 USA. [Kim, John K.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. RP Kim, JK (reprint author), Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA. EM jnkim@umich.edu RI THIERRY-MIEG, Jean/F-1975-2017 OI THIERRY-MIEG, Jean/0000-0002-0396-6789 FU National Science Foundation; National Institutes of Health [S06 GM52588, HG004276-01]; National Library of Medicine FX We thank John Moran, Harrison Gabel, Chi Zhang, Tammy Wu, Kris Gunsalus, Scott Kennedy, Patrick Hu, and Allison Billi for helpful comments; Sylvia Fischer (Massachusetts General Hospital) for dcr-1( ok247) total RNA, the Caenorhabditis Genetics Center and Shohei Mitani (Tokyo Women's Medical University) for strains, Marco Marra and Martin Hirst of the British Columbia Cancer Centre for Solexa deep sequencing, and David Miller of Applied Biosystems for Taqman probes. This work was supported by a National Science Foundation CAREER Award, National Institutes of Health Grant S06 GM52588 (to D.S.C.), the Intramural Research Program of the National Institutes of Health and the National Library of Medicine (to D.T.-M. and J.T.-M.), and National Institutes of Health Grant HG004276-01 grant (to J.K.K.). NR 45 TC 69 Z9 84 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 3 PY 2009 VL 106 IS 44 BP 18674 EP 18679 DI 10.1073/pnas.0906378106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 514XM UT WOS:000271429800048 PM 19846761 ER PT J AU Hasumi, Y Baba, M Ajima, R Hasumi, H Valera, VA Klein, ME Haines, DC Merino, MJ Hong, SB Yamaguchi, TP Schmidt, LS Linehan, WM AF Hasumi, Yukiko Baba, Masaya Ajima, Rieko Hasumi, Hisashi Valera, Vladimir A. Klein, Mara E. Haines, Diana C. Merino, Maria J. Hong, Seung-Beom Yamaguchi, Terry P. Schmidt, Laura S. Linehan, W. Marston TI Homozygous loss of BHD causes early embryonic lethality and kidney tumor development with activation of mTORC1 and mTORC2 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Birt-Hogg-Dube syndrome; kidney cancer; mouse model; mTOR; tumor suppressor ID HOGG-DUBE-SYNDROME; POLYCYSTIC KIDNEYS; RENAL TUMORS; COMPLEX 2; GENE; PROTEIN; CANCER; INACTIVATION; MUTATIONS; NEOPLASIA AB Germline mutations in the BHD/FLCN tumor suppressor gene predispose patients to develop renal tumors in the hamartoma syndrome, Birt-Hogg-Dube (BHD). BHD encodes folliculin, a protein with unknown function that may interact with the energy-and nutrient-sensing AMPK-mTOR signaling pathways. To clarify BHD function in the mouse, we generated a BHD knockout mouse model. BHD homozygous null (BHD(d/d)) mice displayed early embryonic lethality at E5.5-E6.5, showing defects in the visceral endoderm. BHD heterozygous knockout (BHD(d/+)) mice appeared normal at birth but developed kidney cysts and solid tumors as they aged (median kidney-lesion-free survival = 23 months, median tumor-free survival = 25 months). As observed in human BHD kidney tumors, three different histologic types of kidney tumors developed in BHD(d/+) mice including oncocytic hybrid, oncocytoma, and clear cell with concomitant loss of heterozygosity (LOH), supporting a tumor suppressor function for BHD in the mouse. The PI3K-AKT pathway was activated in both human BHD renal tumors and kidney tumors in BHD(d/+) mice. Interestingly, total AKT protein was elevated in kidney tumors compared to normal kidney tissue, but without increased levels of AKT mRNA, suggesting that AKT may be regulated by folliculin through post translational or post-transcriptional modification. Finally, BHD inactivation led to both mTORC1 and mTORC2 activation in kidney tumors from BHD(d/+) mice and human BHD patients. These data support a role for PI3K-AKT pathway activation in kidney tumor formation caused by loss of BHD and suggest that inhibitors of both mTORC1 and mTORC2 may be effective as potential therapeutic agents for BHD-associated kidney cancer. C1 [Hasumi, Yukiko; Baba, Masaya; Hasumi, Hisashi; Valera, Vladimir A.; Klein, Mara E.; Hong, Seung-Beom; Schmidt, Laura S.; Linehan, W. Marston] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Merino, Maria J.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Ajima, Rieko; Yamaguchi, Terry P.] NCI, Cell Signaling Vertebrate Dev Sect, Canc & Dev Biol Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. [Schmidt, Laura S.] NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Haines, Diana C.] NCI, Pathol Histotechnol Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM wml@nih.gov RI Baba, Masaya/L-7490-2013 OI Baba, Masaya/0000-0002-5308-6683 FU National Institutes of Health (NIH); National Cancer Institute (NCI); Center for Cancer Research; NCI, NIH [HHSN261200800001E] FX We thank Louise Cromwell for excellent technical support with the mouse studies, Serguei Kozlov for helpful discussions, Yelena Golubeva for her technical support regarding laser microdissection (LCM), Jaime Rodriguez-Canales and Jeffrey Hanson for their technical expertise regarding LCM procedures, and Kristin K. Biris for her technical support regarding in situ hybridization. This research was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute (NCI), Center for Cancer Research; federal funds from the NCI, NIH, under Contract HHSN261200800001E. NR 26 TC 107 Z9 107 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 3 PY 2009 VL 106 IS 44 BP 18722 EP 18727 DI 10.1073/pnas.0908853106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 514XM UT WOS:000271429800056 PM 19850877 ER PT J AU Khan, MA Goila-Gaur, R Kao, S Miyagi, E Walker, RC Strebel, K AF Khan, Mohammad A. Goila-Gaur, Ritu Kao, Sandra Miyagi, Eri Walker, Robert C., Jr. Strebel, Klaus TI Encapsidation of APOBEC3G into HIV-1 virions involves lipid raft association and does not correlate with APOBEC3G oligomerization SO RETROVIROLOGY LA English DT Article ID VIRUS TYPE-1 VIF; ANTIVIRAL ACTIVITY; 7SL RNA; INFECTIVITY FACTOR; PLASMA-MEMBRANE; VIRAL-RNA; PROTEIN; PARTICLES; GAG; DETERMINANTS AB Background: The cellular cytidine deaminase APOBEC3G (A3G), when incorporated into the human immunodeficiency virus type 1 (HIV-1), renders viral particles non-infectious. We previously observed that mutation of a single cysteine residue of A3G (C100S) inhibited A3G packaging. In addition, several recent studies showed that mutation of tryptophan 127 (W127) and tyrosine 124 (Y124) inhibited A3G encapsidation suggesting that the N-terminal CDA constitutes a viral packaging signal in A3G. It was also reported that W127 and Y124 affect A3G oligomerization. Results: Here we studied the mechanistic basis of the packaging defect of A3G W127A and Y124A mutants. Interestingly, cell fractionation studies revealed a strong correlation between encapsidation, lipid raft association, and genomic RNA binding of A3G. Surprisingly, the presence of a C-terminal epitope tag affected lipid raft association and encapsidation of the A3G W127A mutant but had no effect on wt A3G encapsidation, lipid raft association, and interaction with viral genomic RNA. Mutation of Y124 abolished A3G encapsidation irrespective of the presence or absence of an epitope tag. Contrasting a recent report, our co-immunoprecipitation studies failed to reveal a correlation between A3G oligomerization and A3G encapsidation. In fact, our W127A and Y124A mutants both retained the ability to oligomerize. Conclusion: Our results confirm that W127 and Y124 residues in A3G are important for encapsidation into HIV-1 virions and our data establish a novel correlation between genomic RNA binding, lipid raft association, and viral packaging of A3G. In contrast, we were unable to confirm a role of W127 and Y124 in A3G oligomerization and we thus failed to confirm a correlation between A3G oligomerization and virus encapsidation. C1 [Khan, Mohammad A.; Goila-Gaur, Ritu; Kao, Sandra; Miyagi, Eri; Walker, Robert C., Jr.; Strebel, Klaus] NIAID, Mol Microbiol Lab, Viral Biochem Sect, NIH, Bethesda, MD 20892 USA. RP Strebel, K (reprint author), NIAID, Mol Microbiol Lab, Viral Biochem Sect, NIH, Bldg 4,Room 310,4 Ctr Dr,MSC 0460, Bethesda, MD 20892 USA. EM mkhan@niaid.nih.gov; rgaur@niaid.nih.gov; skao@niaid.nih.gov; emiyagi@niaid.nih.gov; walkerrobert@niaid.nih.gov; kstrebel@niaid.nih.gov FU NIH Intramural AIDS Targeted Antiviral Program; Intramural Research Program of the NIH, NIAID FX We thank Amy Andrew for critical comments on the manuscript and Melissa Gilden and Sandrine Opi for plasmid construction and help with reagents. We are grateful to Michael Malim for providing pA3G, pA3G W127A, pA3G-HA, and pA3G-HA W127A vectors. This work was supported by a Grant from the NIH Intramural AIDS Targeted Antiviral Program to K. S. and by the Intramural Research Program of the NIH, NIAID. NR 43 TC 14 Z9 15 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD NOV 3 PY 2009 VL 6 AR 99 DI 10.1186/1742-4690-6-99 PG 12 WC Virology SC Virology GA 518FH UT WOS:000271675500001 PM 19886996 ER PT J AU Lerbret, A Mason, PE Venable, RM Cesaro, A Saboungi, ML Pastor, RW Brady, JW AF Lerbret, A. Mason, P. E. Venable, R. M. Cesaro, A. Saboungi, M. -L Pastor, R. W. Brady, J. W. TI Molecular dynamics studies of the conformation of sorbitol SO CARBOHYDRATE RESEARCH LA English DT Article DE Molecular dynamics simulation; Sorbitol; Conformation; Hydrogen bonding; Glucose ID X-RAY-DIFFRACTION; D-GLUCITOL; ANOMERIC EQUILIBRIUM; LIQUID WATER; FORCE-FIELD; FREE-ENERGY; C-13 NMR; SIMULATIONS; DEPENDENCE; MALTITOL AB Molecular dynamics simulations of a 3 molal aqueous solution Of D-Sorbitol (also called D-glucitol) have been performed at 300 K, as well as at two elevated temperatures to promote conformational transitions. In principle, sorbitol is more flexible than glucose since it does not contain a constraining ring. However, a conformational analysis revealed that the sorbitol chain remains extended in solution, in contrast to the bent conformation found experimentally in the crystalline form. While there are 243 staggered conformations of the backbone possible for this open-chain polyol, only a very limited number were found to be stable in the simulations. Although many conformers were briefly sampled, only eight were significantly populated in the simulation. The carbon backbones of all but two of these eight conformers were completely extended, unlike the bent crystal conformation. These extended conformers were stabilized by a quite persistent intramolecular hydrogen bond between the hydroxyl groups of carbon C-2 and C-4. The conformational populations were found to be in good agreement with the limited available NMR data except for the C-2-C-3 torsion (spanned by the O2-O-4 hydrogen bond), where the NMR data support a more bent structure. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Lerbret, A.; Mason, P. E.; Brady, J. W.] Cornell Univ, Dept Food Sci, Ithaca, NY 14853 USA. [Venable, R. M.; Pastor, R. W.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. [Saboungi, M. -L] Ctr Rech Mat Divisee, F-45071 Orleans, France. [Cesaro, A.] Univ Trieste, Dip Sci Vita, Trieste, Italy. RP Brady, JW (reprint author), Cornell Univ, Dept Food Sci, Stocking Hall, Ithaca, NY 14853 USA. EM jwb7@cornell.edu RI Saboungi, Marie-Louise/C-5920-2013 OI Saboungi, Marie-Louise/0000-0002-0607-4815 FU National Institutes of Health [GM63018, GM70855] FX This project was supported by grants GM63018 and GM70855 from the National Institutes of Health. The authors thank Alexander D. MacKerell and Gerald Lelong for helpful discussions. NR 34 TC 18 Z9 18 U1 2 U2 16 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD NOV 2 PY 2009 VL 344 IS 16 BP 2229 EP 2235 DI 10.1016/j.carres.2009.08.003 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 512MY UT WOS:000271254800016 PM 19744646 ER PT J AU Carrozza, MJ Stefanick, DF Horton, JK Kedar, PS Wilson, SH AF Carrozza, Michael J. Stefanick, Donna F. Horton, Julie K. Kedar, Padmini S. Wilson, Samuel H. TI PARP inhibition during alkylation-induced genotoxic stress signals a cell cycle checkpoint response mediated by ATM SO DNA REPAIR LA English DT Article DE PARP-1; PARP inhibitor; Methyl methanesulfonate; ATM; Chk2; Cell cycle ID DNA-POLYMERASE-BETA; DOUBLE-STRAND BREAKS; BASE-EXCISION-REPAIR; POLY(ADP-RIBOSE) POLYMERASE; IONIZING-RADIATION; KINASE INHIBITORS; DAMAGING AGENTS; NUCLEAR ANTIGEN; CANCER-THERAPY; ACTIVATES ATM AB By limiting cell cycle progression following detection of DNA damage, checkpoints are critical for cell survival and genome stability. Methylated DNA damage, when combined with inhibition of PARP activity, results in an ATR-dependent S phase delay of the cell cycle. Here, we demonstrate that another checkpoint kinase, ATM, also is involved in the DNA damage response following treatment with a sub-lethal concentration of MMS combined with the PARP inhibitor 4-AN. Both ATM and PARP activities are important for moderating cellular sensitivity to MMS. Loss of ATM activity, or that of its downstream effector Chk2, limited the duration of the S phase delay. The combination of MMS and 4-AN resulted in ATM and Chk2 phosphorylation and the time course of phosphorylation for both kinases correlated with the S phase delay. Chk2 phosphorylation was reduced in the absence of ATM activity. The Chk2 phosphorylation that remained in the absence of ATM appeared to be dependent on ATR and DNA-PK. The results demonstrate that, following initiation of base excision repair and inhibition of PARP activity, ATM activation is critical for preventing the cell from progressing through S phase, and for protection against MMS-induced cytotoxicity. Published by Elsevier B.V. C1 [Carrozza, Michael J.; Stefanick, Donna F.; Horton, Julie K.; Kedar, Padmini S.; Wilson, Samuel H.] NIEHS, Struct Biol Lab, Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, Natl Inst Hlth, 111 TW Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. EM wilson5@niehs.nih.gov FU NIH [ES050159]; National Institute of Environmental Health Sciences; NIH/NIEHS; Constella/SRA, LLC [HHSN273200700046U] FX We thank Rebecca Childress and Jennifer Zeng for technical assistance. This research was Supported by Research Project Number ES050159 in the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. Dr. Kedar's contribution was funded in whole with federal funds from NIH/NIEHS, under delivery order HHSN273200700046U to Constella/SRA, LLC. NR 51 TC 12 Z9 12 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD NOV 2 PY 2009 VL 8 IS 11 BP 1264 EP 1272 DI 10.1016/j.dnarep.2009.07.010 PG 9 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 518HY UT WOS:000271683000002 PM 19717351 ER PT J AU Masaoka, A Horton, JK Beard, WA Wilson, SH AF Masaoka, Aya Horton, Julie K. Beard, William A. Wilson, Samuel H. TI DNA polymerase beta and PARP activities in base excision repair in living cells SO DNA REPAIR LA English DT Article DE Base excision repair; DNA polymerase beta; Poly(ADP-ribose) polymerase; Luciferase; Plasmid-based assay ID STRAND BREAK REPAIR; POLY(ADP-RIBOSE) POLYMERASE-1; COCKAYNE-SYNDROME; MAMMALIAN-CELLS; RNA-POLYMERASE; TRANSCRIPTION ELONGATION; DIFFERENT EFFICIENCIES; INDUCED CYTOTOXICITY; MOUSE FIBROBLASTS; OXIDATIVE STRESS AB To examine base excision repair (BER) capacity in the context of living cells, we developed and applied a plasmid-based reporter assay. Non-replicating plasmids containing unique DNA base lesions were designed to express luciferase only after lesion repair had occurred, and luciferase expression in transfected cells was measured continuously during a repair period of 14 h. Two types of DNA lesions were examined: uracil opposite T reflecting repair primarily by the single-nucleotide BER sub-pathway, and the abasic site analogue tetrahydrofuran (THF) opposite C reflecting repair by long-patch BER. We found that the repair capacity for uracil-DNA in wild type mouse fibroblasts was very strong, whereas the repair capacity for THF-DNA, although strong, was slightly weaker. Repair capacity in DNA polymerase beta (Pol beta) null cells for uracil-DNA and THF-DNA was reduced by approximately 15% and 20%, respectively, compared to that in wild type cells. In both cases, the repair deficiency was fully complemented in Pol beta null cells expressing recombinant Pol beta. The effect of inhibition of poly(ADP-ribose) polymerase (PARP) activity on repair capacity was examined by treatment of cells with the inhibitor 4-amino-1,8-naphthalimide (4-AN). PARP inhibition decreased the repair capacity for both lesions in wild type cells, and this reduction was to the same level as that seen in Pol beta null cells. In contrast, 4-AN had no effect on repair in Pol 0 null cells. The results highlight that Pol beta and PARP function in the same repair pathway, but also suggest that there is repair independent of both Pol beta and PARP activities. Thus, before the BER capacity of a cell can be predicted or modulated, a better understanding of Pol beta and PARP activity-independent BER pathways is required. Published by Elsevier B.V. C1 [Masaoka, Aya; Horton, Julie K.; Beard, William A.; Wilson, Samuel H.] NIEHS, Struct Biol Lab, Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. EM wilson5@niehs.nih.gov FU National Institutes of Health [Z01-ES050158, Z01-ES050159]; National Institute of Environmental Health Sciences FX We thank Kenjiro Asagoshi, Michael Carrozza, Graciela Spivak and Philip Hanawalt for discussions and critical reading of the manuscript and Ms. Bonnie Mesmer for editorial assistance. This research was supported by Research Project Numbers Z01-ES050158 and Z01-ES050159 in the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. NR 68 TC 25 Z9 26 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD NOV 2 PY 2009 VL 8 IS 11 BP 1290 EP 1299 DI 10.1016/j.dnarep.2009.08.004 PG 10 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 518HY UT WOS:000271683000005 PM 19748837 ER PT J AU Watanabe, K Nagaoka, T Lee, JM Bianco, C Gonzales, M Castro, NP Rangel, MC Sakamoto, K Sun, YP Callahan, R Salomon, DS AF Watanabe, Kazuhide Nagaoka, Tadahiro Lee, Joseph M. Bianco, Caterina Gonzales, Monica Castro, Nadia P. Rangel, Maria Cristina Sakamoto, Kei Sun, Youping Callahan, Robert Salomon, David S. TI Enhancement of Notch receptor maturation and signaling sensitivity by Cripto-1 SO JOURNAL OF CELL BIOLOGY LA English DT Article ID GLYCOSYLPHOSPHATIDYLINOSITOL-ANCHOR; STEM-CELLS; ROLES; FURIN; PATHWAY; CANCER; GENE AB Nodal and Notch signaling pathways play essential roles in vertebrate development. Through a yeast two-hybrid screening, we identified Notch3 as a candidate binding partner of the Nodal coreceptor Cripto-1. Coimmunoprecipitation analysis confirmed the binding of Cripto-1 with all four mammalian Notch receptors. Deletion analyses revealed that the binding of Cripto-1 and Notch1 is mediated by the Cripto-1/FRL-1/Cryptic domain of Cripto-1 and the C-terminal region of epidermal growth factor-like repeats of Notch1. Binding of Cripto-1 to Notch1 occurred mainly in the endoplasmic reticulum-Golgi network. Cripto-1 expression resulted in the recruitment of Notch1 protein into lipid raft microdomains and enhancement of the furin-like protein convertase-mediated proteolytic maturation of Notch1 (S1 cleavage). Enhanced S1 cleavage resulted in the sensitization to ligand-induced activation of Notch signaling. In addition, knockdown of Cripto-1 expression in human and mouse embryonal carcinoma cells desensitized the ligand-induced Notch signaling activation. These results suggest a novel role of Cripto-1 in facilitating the post-translational maturation of Notch receptors. C1 [Watanabe, Kazuhide; Nagaoka, Tadahiro; Lee, Joseph M.; Bianco, Caterina; Gonzales, Monica; Castro, Nadia P.; Rangel, Maria Cristina; Callahan, Robert; Salomon, David S.] NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Sakamoto, Kei] Tokyo Med & Dent Univ, Grad Sch, Bunkyo Ku, Tokyo 1138549, Japan. [Sun, Youping] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Watanabe, K (reprint author), NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM kazuhidew@yahoo.com; salomond@mail.nih.gov RI Rangel, Maria Cristina/P-7216-2014; OI Rangel, Maria Cristina/0000-0002-8002-9617; Nagaoka, Tadahiro/0000-0002-9391-0243 FU National Institutes of Health FX This work was supported by National Institutes of Health intramural funding. NR 21 TC 25 Z9 25 U1 1 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD NOV 2 PY 2009 VL 187 IS 3 BP 343 EP 353 DI 10.1083/jcb.200905105 PG 11 WC Cell Biology SC Cell Biology GA 514DJ UT WOS:000271374200006 PM 19948478 ER PT J AU Ye, XY Johann, DJ Hakami, RM Xiao, Z Meng, ZJ Ulrich, RG Issaq, HJ Veenstra, TD Blonder, J AF Ye, Xiaoying Johann, Donald J. Hakami, Ramin M. Xiao, Zhen Meng, Zhaojing Ulrich, Robert G. Issaq, Haleem J. Veenstra, Timothy D. Blonder, Josip TI Optimization of protein solubilization for the analysis of the CD14 human monocyte membrane proteome using LC-MS/MS SO JOURNAL OF PROTEOMICS LA English DT Article DE CD14 monocyte; Membrane proteins; Solubilization; Methanol; Detergents; LC-MS/MS ID SPECTROMETRY-COMPATIBLE SURFACTANTS; TANDEM MASS-SPECTROMETRY; ENZYMATIC DIGESTION; CLEAVABLE DETERGENTS; RAT-LIVER; BACTERIORHODOPSIN; IDENTIFICATION; CELLS; EXPRESSION; METHANOL AB Proteomic profiling of membrane proteins is of vital importance in the search for disease biomarkers and drug development. However, the slow pace in this field has resulted mainly from the difficulty to analyze membrane proteins by mass spectrometry (MS). The objective of this investigation was to explore and optimize solubilization. of membrane proteins for shotgun membrane proteomics of the CD14 human monocytes by examining different systems that rely on: i) an organic solvent (methanol) ii) an acid-labile detergent 3-[3-(1,1-bisalkyloxyethyl)pyridin-1-yl) propane-1-sulfonate (PPS), iii) a combination of both agents (methanol+PPS). Solubilization efficiency of different buffers was first compared using bacteriorhodopsin as a model membrane protein. Selected approaches were then applied on a membrane subproteome isolated from a highly enriched human monocyte population that was similar to 98% positive for CD14 expression as determined by FACS analysis. A methanol-based buffer yielded 194 proteins of which 93 (48%) were mapped as integral membrane proteins. The combination of methanol and acid-cleavable detergent gave similar results; 203 identified proteins of which 93 (46%) were mapped integral membrane proteins. However, employing PPS 216 proteins were identified of which 75 (35%) were mapped as integral membrane proteins. These results indicate that methanol alone or in combination with PPS yielded significantly higher membrane protein identification/enrichment than the PPS alone. (C) 2009 Elsevier B.V. All rights reserved. C1 [Ye, Xiaoying; Xiao, Zhen; Meng, Zhaojing; Issaq, Haleem J.; Veenstra, Timothy D.; Blonder, Josip] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Johann, Donald J.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Hakami, Ramin M.] Oak Ridge Associated Univ, Fac Res Program, Belcamp, MD 21017 USA. [Ulrich, Robert G.] USA, Med Res Inst Infect Dis, Frederick, MD 21702 USA. RP Blonder, J (reprint author), NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. EM blonder@ncifcrf.gov FU National Cancer Institute; National Institutes of Health [N01-CO-12400] FX This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organization imply endorsement by the United States Government. NR 62 TC 16 Z9 18 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1874-3919 J9 J PROTEOMICS JI J. Proteomics PD NOV 2 PY 2009 VL 73 IS 1 BP 112 EP 122 DI 10.1016/j.jprot.2009.08.008 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 522GL UT WOS:000271985800010 PM 19709643 ER PT J AU Simonelli, V D'Errico, M Palli, D Prasad, R Wilson, SH Dogliotti, E AF Simonelli, Valeria D'Errico, Mariarosaria Palli, Domenico Prasad, Rajendra Wilson, Samuel H. Dogliotti, Eugenia TI Characterization of DNA polymerase beta splicing variants in gastric cancer: The most frequent exon 2-deleted isoform is a non-coding RNA SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE DNA polymerase beta; Splicing variants; Gastric cancer; DNA repair; ncRNA ID BASE-EXCISION-REPAIR; MESSENGER-RNA; MICROSATELLITE INSTABILITY; CELLULAR-TRANSFORMATION; COLORECTAL-CANCER; OXIDATIVE STRESS; BLADDER-CANCER; OVEREXPRESSION; MUTATIONS; CELLS AB DNA repair polymerase beta (Pol beta) gene variants are frequently associated with tumor tissues. In this study a search for Pol beta mutants and splice variants was conducted in matched normal and tumor gastric tissues and blood samples from healthy donors. No tumor associated mutations were found while a variety of alternative Pol beta splicing variants were detected with high frequency in all the specimens analysed. Quantitative PCR of the Pol beta variant lacking exon 2 (Ex2 Delta) and the isoforms with exon 11 skipping allowed to clarify that these variants are not tumor-neither tissue-specific and their levels vary greatly among different individuals. The most frequent Ex2 Delta variant was further characterized. We clearly demonstrated that this variant does not encode protein, as detected by both western blotting and immunofluorescence analysis of human AGS cells expressing HA-tagged Ex2 Delta. The lack of translation was confirmed by comparing the DNA gap-filling capacity and alkylation sensitivity of wild type and Pol beta null murine fibroblasts expressing the human Ex2 Delta variant. We showed that the Ex2 Delta transcript is polyadenylated and its half-life is significantly longer than that of the wild type mRNA as inferred by treating AGS cells with actinomycin D. Moreover, we found that it localizes to polyribosomes suggesting a role as post-transcriptional regulator. This study identifies a new type of DNA repair variants that do not give rise to functional proteins but to non-coding RNAs that could either modulate target mRNAs or represent unproductive splicing events. (C) 2009 Elsevier B.V. All rights reserved. C1 [Simonelli, Valeria; D'Errico, Mariarosaria; Dogliotti, Eugenia] Ist Super Sanita, Dept Environm & Primary Prevent, I-00161 Rome, Italy. [Palli, Domenico] Canc Res & Prevent Inst ISPO, Mol & Nutr Epidemiol Unit, Florence, Italy. [Prasad, Rajendra; Wilson, Samuel H.] Natl Inst Hlth Environm Sci, NIH, Chapel Hill, NC USA. RP Dogliotti, E (reprint author), Ist Super Sanita, Dept Environm & Primary Prevent, Viale Regina Elena 299, I-00161 Rome, Italy. EM eugenia.dogliotti@iss.it OI Simonelli, Valeria/0000-0002-3726-518X FU Progetto Integrato Oncologia; Regione Toscana-Ministero della Salute; Associazione Italiana per la Ricerca Sul Cancro (AIRC); MIUR/FIRB [RBNE01RNN]; ISS/NIH; National Institutes of Health, NIEHS FX We would like to thank Ettore Meccia for helpful suggestions. Grant support: Progetto Integrato Oncologia, Regione Toscana-Ministero della Salute, Associazione Italiana per la Ricerca Sul Cancro (AIRC), MIUR/FIRB (RBNE01RNN7), Collaborative Project ISS/NIH. This research was supported in part by the Intramural Research Program of the National Institutes of Health, NIEHS. NR 46 TC 4 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD NOV 2 PY 2009 VL 670 IS 1-2 BP 79 EP 87 DI 10.1016/j.mrfmmm.2009.07.007 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 522RE UT WOS:000272015200011 PM 19635489 ER PT J AU Lea, IA Jackson, MA Dunnick, JK AF Lea, Isabel A. Jackson, Marcus A. Dunnick, June K. TI Genetic pathways to colorectal cancer SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE Colorectal cancer; Gene mutation; Loss of heterozygosity ID HUMAN BREAST; TUMORIGENESIS; METHYLATION; HYPOMETHYLATION; MUTATIONS AB The colorectal cancer paradigm explains how genetic and histological changes lead normal epithelial cell to transform into pre-malignant adenomas then progress to malignant carcinomas. Using the Genetic Alterations in Cancer Knowledge System intragenic allele loss and gene mutation data from approximately 9000 colorectal tumors were compared to the model of colorectal tumor development. The distribution of mutations along the TP53 codons as a function of tumorigenesis also was analyzed. Alterations of APC, KRAS and TP53 were observed in a higher percentage of adenocarcinomas compared to adenomas (P < 0.05) indicating that the alterations accumulated with malignancy. Alterations in BRAF, CTNNB, HRAS and NRAS were infrequent regardless of morphology. Differences were observed in the distribution of TP53 mutations with tumorigenesis. Mutations (single base substitutions) occurred most frequently at codons 175 and 273 in both tumor types; however, in adenocarcinomas the mutation incidence at codon 248 was approximately three times that reported in adenomas. It is proposed that the higher incidence of mutation at codon 248 is a later event in colorectal tumorigenesis that occurs as the tumors become malignant. (C) 2009 Elsevier B.V. All rights reserved. C1 [Lea, Isabel A.; Jackson, Marcus A.] Integrated Lab Syst Inc, Res Triangle Pk, NC 27709 USA. [Dunnick, June K.] NIEHS, Res Triangle Pk, NC 27709 USA. RP Lea, IA (reprint author), Integrated Lab Syst Inc, POB 13501, Res Triangle Pk, NC 27709 USA. EM ilea@ils-inc.com FU National Institutes of Health, National Institute of Environmental Health Sciences [N43-ES-15477] FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences [contract number N43-ES-15477]. NR 18 TC 11 Z9 12 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD NOV 2 PY 2009 VL 670 IS 1-2 BP 96 EP 98 DI 10.1016/j.mrfmmm.2009.06.011 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 522RE UT WOS:000272015200013 PM 19576232 ER PT J AU D'Onofrio, G Goldstein, AB Denisco, RA Hingson, R Heffelfinger, JD Post, LA AF D'Onofrio, Gail Goldstein, Amy B. Denisco, Richard A. Hingson, Ralph Heffelfinger, James D. Post, Lori A. TI Emergency Medicine Public Health Research Funded by Federal Agencies: Progress and Priorities SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE federal funding; public health; emergency medicine; emergency departments ID ALCOHOL INTERVENTIONS; CARE; ACCESS; RISK; DEPARTMENTS; RESISTANT; LIFE AB The emergency department (ED) visit provides an opportunity to impact the health of the public throughout the entire spectrum of care, from prevention to treatment. As the federal government has a vested interest in funding research and providing programmatic opportunities that promote the health of the public, emergency medicine (EM) is prime to develop a research agenda to advance the field. EM researchers need to be aware of federal funding opportunities, which entails an understanding of the organizational structure of the federal agencies that fund medical research, and the rules and regulations governing applications for grants. Additionally, there are numerous funding streams outside of the National Institutes of Health (NIH; the primary federal health research agency). EM researchers should seek funding from agencies according to each agency's mission and aims. Finally, while funds from the Department of Health and Human Services (HHS) are an important source of support for EM research, we need to look beyond traditional sources and appeal to other agencies with a vested interest in promoting public health in EDs. EM requires a broad skill set from a multitude of medical disciplines, and conducting research in the field will require looking for funding opportunities in a variety of traditional and not so traditional places within and without the federal government. The following is the discussion of a moderated session at the 2009 Academic Emergency Medicine consensus conference that included panel discussants from the National Institutes of Mental Health, Drug Abuse, and Alcoholism and Alcohol Abuse and the Centers for Disease Control and Prevention (CDC). Further information is also provided to discuss those agencies and centers not represented. C1 [D'Onofrio, Gail; Post, Lori A.] Yale Univ, Sch Med, Dept Emergency Med, New Haven, CT 06520 USA. [Goldstein, Amy B.] NIMH, Bethesda, MD 20892 USA. [Denisco, Richard A.] NIDA, Bethesda, MD 20892 USA. [Hingson, Ralph] NIAAA, Bethesda, MD USA. [Heffelfinger, James D.] Ctr Dis Control & Prevent, Atlanta, GA USA. RP D'Onofrio, G (reprint author), Yale Univ, Sch Med, Dept Emergency Med, New Haven, CT 06520 USA. EM gail.donofrio@yale.edu OI D'Onofrio, Gail/0000-0002-3833-1871 FU Agency for Healthcare Research and Quality; National Institute of Mental Health; National Institute of Drug Abuse; National Institute of Alcoholism and Alcohol Abuse; Substance Abuse and Mental Health Administration Services FX The authors thank the Society for Academic Emergency Medicine for providing the forum for this presentation. In addition, we thank the many agencies, institutes, and centers for funding this conference, specifically the Agency for Healthcare Research and Quality, the National Institute of Mental Health, the National Institute of Drug Abuse, the National Institute of Alcoholism and Alcohol Abuse, and the Substance Abuse and Mental Health Administration Services. Finally, the authors thank Brian Biroscak for his help in the preparation of the manuscript. The views expressed in this article are the opinions of the authors and do not necessarily represent the views of the Department of Health and Human Services or the United States government. NR 43 TC 4 Z9 4 U1 1 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD NOV PY 2009 VL 16 IS 11 BP 1065 EP 1071 DI 10.1111/j.1553-2712.2009.00555.x PG 7 WC Emergency Medicine SC Emergency Medicine GA 515JC UT WOS:000271465000007 PM 20053224 ER PT J AU Tang, WK Li, DY Esser, L Xia, D AF Tang, Wai-Kwan Li, Dongyang Esser, Lothar Xia, Di TI Purification, crystallization and preliminary X-ray diffraction analysis of disease-related mutants of p97 SO ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION COMMUNICATIONS LA English DT Article ID BLUE NATIVE PAGE; FRONTOTEMPORAL DEMENTIA; AAA ATPASE; PROTEIN; P97/VCP; BONE; MYOPATHY; FAMILY AB The human type II Lambda Lambda Lambda+ protein p97 participates in various cellular activities, presumably through its involvement in the ubiquitin-proteasome degradation pathway. Mutations in p97 have been implicated in patients with inclusion-body myopathy associated with Paget's disease of the bone and frontotemporal dementia (IBMPFD). In this work, three mutant p97 N-D1 fragments, R86A, R95G and R155H, were crystallized in the presence of ATP gamma S with PEG 3350 as a main precipitant, yielding two different crystal forms. The R155H mutant crystal belonged to space group R3, with unit-cell parameters in the hexagonal setting of a = b = 134.2, c = 182.9 angstrom, and was merohedrally twinned, with an estimated twin fraction of 0.34. The crystals of the R86A and R95G mutants belonged to space group P1, with similar unit-cell parameters of a = 90.89, b = 102.6, c = 107.2 angstrom, alpha = 97.5, beta = 90.6, gamma = 91.5 degrees and a = 92.76, b = 103.7, c = 107.7 angstrom, alpha = 97.7, beta = 91.9, gamma = 89.7 degrees, respectively. C1 [Tang, Wai-Kwan; Li, Dongyang; Esser, Lothar; Xia, Di] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Xia, D (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM dixia@helix.nih.gov RI Tang, Wai Kwan/A-6158-2012 FU NIH; National Cancer Institute; Center for Cancer Research FX The authors wish to thank the staff members of the SER-CAT beamline (ID-22) at Advanced Photon Source, Argonne National Laboratory for their assistance in data collection. We also thank George Leiman for editorial assistance. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 26 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1744-3091 J9 ACTA CRYSTALLOGR F JI Acta Crystallogr. F-Struct. Biol. Cryst. Commun. PD NOV PY 2009 VL 65 BP 1166 EP 1170 DI 10.1107/S174430910904055X PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 514US UT WOS:000271421800022 PM 19923742 ER PT J AU Jegalian, AG Facchetti, F Jaffe, ES AF Jegalian, Armin G. Facchetti, Fabio Jaffe, Elaine S. TI Plasmacytoid Dendritic Cells Physiologic Roles and Pathologic States SO ADVANCES IN ANATOMIC PATHOLOGY LA English DT Review DE plasmacytoid dendritic cell; interferon-alpha; blastic plasmacytoid dendritic cell neoplasm; CD4(+)/CD56(+) hematodermic neoplasm ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; INTERFERON-PRODUCING CELLS; CD4(+)/CD56(+) HEMATODERMIC NEOPLASM; CHRONIC MYELOMONOCYTIC LEUKEMIA; LINEAGE-NEGATIVE MALIGNANCIES; DRAINING LYMPH-NODES; TOLL-LIKE RECEPTORS; MURINE BONE-MARROW; T-CELLS; I INTERFERON AB Plasmacytoid dendritic cells (PDCs) have perplexed pathologists for decades, undergoing multiple adjustments in nomenclature as their lineage and functions have been characterized. Although PDCs account for less than 0.1% of peripheral blood mononuclear cells, they serve as a principal source of interferon-a and are also known as interferon-I producing cells (IPCs). Upon activation in vitro, they can differentiate into dendritic cells, and recent studies have substantiated a potential role in antigen presentation. Thus, PDCs may act as a link between innate and adaptive immunity. Normally found in small quantities in primary and secondary lymphoid organs, PDCs accumulate in a variety of inflammatory conditions, including Kikuchi-Fujimoto lymphadenopathy, hyaline-vascular Castleman disease, and autoimmune diseases, and in certain malignancies such as classical Hodgkin lymphoma and carcinomas. Demonstrating potential for neoplastic transformation reflective of varying stages of maturation, clonal proliferations range from PDC nodules most commonly associated with chronic myelomonocytic leukemia to the rare but highly aggressive malignancy now known as blastic plasmacytoid dendritic cell neoplasm (BPDCN). Formerly called blastic natural killer cell lymphoma or CD4(+)/CD56(+) hematodermic neoplasm, BPDCN, unlike natural killer cell lymphomas, is not associated with Epstein-Barr virus infection and is generally not curable with treatment regimens for non-Hodgkin lymphomas. In fact, this entity is no longer considered to be a lymphoma and instead represents a unique precursor hematopoietic neoplasm. Acute leukemia therapy regimens may lead to sustained clinical remission of BPDCN, with bone marrow transplantation in first complete remission potentially curative in adult patients. C1 [Jegalian, Armin G.; Jaffe, Elaine S.] NCI, Pathol Lab, Hematopathol Sect, Bethesda, MD 20892 USA. [Facchetti, Fabio] Univ Brescia, Dept Pathol, Brescia, Italy. RP Jaffe, ES (reprint author), 10 Ctr Dr,MSC 1500,Bldg 10,Room 2B42, Bethesda, MD 20892 USA. EM elainejaffe@nih.gov RI Facchetti, Fabio/E-7190-2010 OI Facchetti, Fabio/0000-0003-4975-2388 NR 151 TC 52 Z9 66 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-4109 J9 ADV ANAT PATHOL JI Adv. Anat. Pathol. PD NOV PY 2009 VL 16 IS 6 BP 392 EP 404 PG 13 WC Pathology SC Pathology GA 515OU UT WOS:000271482500003 PM 19851130 ER PT J AU Liu, CL Yang, Y Gange, SJ Weber, K Sharp, GB Wilson, TE Levine, A Robison, E Goparaju, L Ganhdi, M Merenstein, D AF Liu, Chenglong Yang, Yang Gange, Stephen J. Weber, Kathleen Sharp, Gerald B. Wilson, Tracey E. Levine, Alexandra Robison, Esther Goparaju, Lakshmi Ganhdi, Monica Merenstein, Dan TI Disclosure of Complementary and Alternative Medicine Use to Health Care Providers among HIV-Infected Women SO AIDS PATIENT CARE AND STDS LA English DT Article ID ST JOHNS WORT; ANTIRETROVIRAL THERAPY; ADHERENCE; SATISFACTION; ADULTS; AIDS; MEN AB To determine prevalence and predictors of complementary and alternative medicine (CAM) use disclosure to health care providers and whether CAM use disclosure is associated with highly active antiretroviral therapy (HAART) adherence among HIV-infected women, we analyzed longitudinal data collected between October 1994 and March 2002 from HIV-infected CAM-using women enrolled in the Women's Interagency HIV Study. Repeated measures Poisson regression models were constructed to evaluate associations of selected predictors with CAM use disclosure and association between CAM use disclosure and HAART adherence. A total of 1377 HIV-infected women reported CAM use during study follow-up and contributed a total of 4689 CAM-using person visits. The overall prevalence of CAM use disclosure to health care providers was 36% across study visits. Women over 45 years old, with a college education, or with health insurance coverage were more likely to disclose their CAM use to health care providers, whereas women identified as non-Hispanic Black or other ethnicities were less likely to communicate their CAM usage. More health care provider visits, more CAM domains used, and higher health care satisfaction scores had significant relationships with increased levels of CAM use disclosure. Restricting analysis to use of herbal or nonherbal medications only, similar results were obtained. Compared to other CAM domains, mind-body practice had the lowest prevalence of CAM use disclosure. Additionally, CAM use disclosure was significantly associated with higher HAART adherence. From this study, we showed that a high percentage of HIV-infected women did not discuss their CAM use with health care providers. Interventions targeted towards both physicians and patients may enhance communication of CAM use, avoid potential adverse events and drug interactions, and enhance HAART adherence. C1 [Liu, Chenglong; Goparaju, Lakshmi] Georgetown Univ, Dept Med, Washington, DC 20007 USA. [Yang, Yang] Georgetown Univ, Dept Biostat Bioinformat & Biomath, Washington, DC 20007 USA. [Gange, Stephen J.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Weber, Kathleen] John H Stroger Hosp Cook Cty, Chicago, IL USA. [Sharp, Gerald B.] NIAID, Epidemiol Branch, Basic Sci Program, NIH, Bethesda, MD 20892 USA. [Wilson, Tracey E.] SUNY Hlth Sci Ctr, Dept Prevent Med & Community Hlth, Brooklyn, NY 11203 USA. [Levine, Alexandra] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Robison, Esther] Montefiore Med Ctr, Bronx, NY 10467 USA. [Ganhdi, Monica] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Merenstein, Dan] Georgetown Univ, Dept Family Med, Med Ctr, Washington, DC 20007 USA. RP Liu, CL (reprint author), Georgetown Univ, Dept Med, 2233 Wisconsin Ave NW,Suite 214, Washington, DC 20007 USA. EM cl278@georgetown.edu OI Gange, Stephen/0000-0001-7842-512X FU National Cancer Institute; National Institute on Drug Abuse [UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]; National Institute of Child Health and Human Development [UO1-HD-32632]; National Center for Research Resources [MO1-RR-00071, MO1-RR-00079, MO1-RR-00083] FX Data in this manuscript were collected by the Women's Interagency HIV Study (WIHS) Collaborative Study Group with centers (Principal Investigators) at New York City/Bronx Consortium (Kathryn Anastos); Brooklyn, New York (Howard Minkoff); Washington, D.C. Metropolitan Consortium (Mary Young); The Connie Wofsy Study Consortium of Northern California (Ruth Greenblatt); Los Angeles County/Southern California Consortium (Alexandra Levine); Chicago Consortium (Mardge Cohen); Data Coordinating Center (Stephen Gange). WIHS is funded by the National Institute of Allergy and Infectious Diseases with supplemental funding from the National Cancer Institute and the National Institute on Drug Abuse (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590). Funding is also provided by the National Institute of Child Health and Human Development (UO1-HD-32632) and the National Center for Research Resources (MO1-RR-00071, MO1-RR-00079, MO1-RR-00083). NR 33 TC 19 Z9 21 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD NOV PY 2009 VL 23 IS 11 BP 965 EP 971 DI 10.1089/apc.2009.0134 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 522KD UT WOS:000271995700008 PM 19821723 ER PT J AU Ruscetti, EF Petrow-Sadowski, C Janik, J Huang, Y Bertolette, D Morris, J Waldmann, T Jones, K AF Ruscetti, E. F. Petrow-Sadowski, C. Janik, J. Huang, Y. Bertolette, D. Morris, J. Waldmann, T. Jones, K. TI In Vivo and in Vitro HTLV-1-Infection of Plasmacytoid Dendritic Cells: Pathogenic Considerations SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 14th International Conference on Human Retrovirology HTLV and Related Retroviruses CY JUL 01-04, 2009 CL Salvador, BRAZIL C1 [Ruscetti, E. F.; Huang, Y.; Bertolette, D.] NCI, Canc & Inflammat Program, Frederick, MD 21701 USA. [Petrow-Sadowski, C.; Jones, K.] SAIC Frederick, Basic Sci Program, Frederick, MD USA. [Janik, J.; Morris, J.; Waldmann, T.] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 2009 VL 25 IS 11 BP 1202 EP 1202 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 524ZF UT WOS:000272182200028 ER PT J AU Akahata, Y Matsuura, E Jacobson, S Oh, U AF Akahata, Y. Matsuura, E. Jacobson, S. Oh, U. TI High Expression of CD244 and SAP Regulated CD8+T Cell Responses of Patients with HTLV-I Associated Neurologic Disease SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 14th International Conference on Human Retrovirology HTLV and Related Retroviruses CY JUL 01-04, 2009 CL Salvador, BRAZIL C1 [Akahata, Y.; Matsuura, E.; Jacobson, S.; Oh, U.] NINDS, NIH, Bethesda, MD 20892 USA. RI MATSUURA, EIJI/E-1231-2013 OI MATSUURA, EIJI/0000-0001-8215-8853 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 2009 VL 25 IS 11 BP 1203 EP 1204 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 524ZF UT WOS:000272182200032 ER PT J AU Gordon, S Weissman, A Cecchinato, V Zaffiri, L Andresen, V Jones, K Ferrari, MG Chung, HK Ruscetti, F Franchini, G AF Gordon, S. Weissman, A. Cecchinato, V Zaffiri, L. Andresen, V Jones, K. Ferrari, M. G. Chung, H. K. Ruscetti, F. Franchini, G. TI HTLV-II Establishes a Persistent Infection in Rhesus Macaques and Does Not Exacerbate SIV Infection SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 14th International Conference on Human Retrovirology HTLV and Related Retroviruses CY JUL 01-04, 2009 CL Salvador, BRAZIL C1 NCI, Anim Models & Retroviral Vaccines Sect, NIH, Bethesda, MD 20892 USA. NCI, Basic Res Program, Saic Frederick Inc, NIH, Frederick, MD 21701 USA. Adv Biosci Labs Inc, Kensington, MD 20895 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 2009 VL 25 IS 11 BP 1212 EP 1212 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 524ZF UT WOS:000272182200054 ER PT J AU Akahata, Y Matsuura, E Jacobson, S Oh, U AF Akahata, Y. Matsuura, E. Jacobson, S. Oh, U. TI Minocycline Modulates Antigen-Specific CTL Activity through Inactivation of Mononuclear Phagocytes in Patients with HAM/TSP SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 14th International Conference on Human Retrovirology HTLV and Related Retroviruses CY JUL 01-04, 2009 CL Salvador, BRAZIL C1 [Akahata, Y.; Matsuura, E.; Jacobson, S.; Oh, U.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. RI MATSUURA, EIJI/E-1231-2013 OI MATSUURA, EIJI/0000-0001-8215-8853 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 2009 VL 25 IS 11 BP 1214 EP 1215 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 524ZF UT WOS:000272182200060 ER PT J AU Oh, U Akahata, Y Turner, R Graham, J Waldmann, T Jacobson, S AF Oh, U. Akahata, Y. Turner, R. Graham, J. Waldmann, T. Jacobson, S. TI The Use of Humanized-MiK-????1, a Monoclonal Antibody Against CD122, In HTLV-I-Associated Myelopathy Tropical Spastic Paraparesis (HAM/TSP) SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 14th International Conference on Human Retrovirology HTLV and Related Retroviruses CY JUL 01-04, 2009 CL Salvador, BRAZIL C1 [Oh, U.; Akahata, Y.; Turner, R.; Graham, J.; Jacobson, S.] NINDS, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. [Waldmann, T.] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 2009 VL 25 IS 11 BP 1216 EP 1216 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 524ZF UT WOS:000272182200063 ER PT J AU Matsuura, E Yao, K Jacobson, S Oh, U Akahata, Y Tanaka, Y AF Matsuura, E. Yao, K. Jacobson, S. Oh, U. Akahata, Y. Tanaka, Y. TI Interaction of Cytotoxic T Lymphocytes and Monocytes: Role in HTLV-I Associated Neurologic Disease SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 14th International Conference on Human Retrovirology HTLV and Related Retroviruses CY JUL 01-04, 2009 CL Salvador, BRAZIL C1 [Matsuura, E.; Yao, K.; Jacobson, S.; Oh, U.; Akahata, Y.; Tanaka, Y.] NINDS, NIH, Bethesda, MD USA. RI MATSUURA, EIJI/E-1231-2013 OI MATSUURA, EIJI/0000-0001-8215-8853 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 2009 VL 25 IS 11 BP 1218 EP 1218 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 524ZF UT WOS:000272182200068 ER PT J AU Lambert, S Bouttier, M Vassy, R Seigneuret, M Petrow-Sadowski, C Janvier, S Heveker, N Ruscetti, FW Perret, G Jones, KS Pique, C AF Lambert, S. Bouttier, M. Vassy, R. Seigneuret, M. Petrow-Sadowski, C. Janvier, S. Heveker, N. Ruscetti, F. W. Perret, G. Jones, K. S. Pique, C. TI Molecular Mimicry between the HTLV-1 SU and VEGF(165) Governs HTLV-1 Entry through Heparan Sulfate Proteoglycans and Neuropilin 1 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 14th International Conference on Human Retrovirology HTLV and Related Retroviruses CY JUL 01-04, 2009 CL Salvador, BRAZIL C1 [Lambert, S.; Bouttier, M.; Seigneuret, M.; Pique, C.] Univ Paris 05, CNRS, INSERM, UMR 8104,U567, F-75014 Paris, France. [Vassy, R.; Perret, G.] Univ Paris 13, UMR 7033, Bobigny, France. [Petrow-Sadowski, C.; Jones, K. S.] NCI, Basic Sci Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [Janvier, S.; Heveker, N.] Univ Montreal, Dept Biochim, Quebec City, PQ, Canada. [Janvier, S.; Heveker, N.] Hop St Justine, Ctr Rech 6737, Quebec City, PQ, Canada. [Ruscetti, F. W.] NCI, Lab Expt Immunol, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA. RI PERRET, gerard/A-7379-2008; Heveker, Nikolaus/G-5306-2012 OI PERRET, gerard/0000-0003-0645-3337; NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 2009 VL 25 IS 11 BP 1224 EP 1225 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 524ZF UT WOS:000272182200084 ER PT J AU Fukumoto, R Andresen, V Bialuk, I Cecchinato, V Walser, JC Valeri, VW Nauroth, JM Gessain, A Nicot, C Franchini, G AF Fukumoto, R. Andresen, V Bialuk, I Cecchinato, V Walser, J. -C Valeri, V. W. Nauroth, J. M. Gessain, A. Nicot, C. Franchini, G. TI In Vivo Genetic Mutations Define Predominant Functions of the Human T-Cell Leukemia/Lymphoma Virus P12I Protein SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 14th International Conference on Human Retrovirology HTLV and Related Retroviruses CY JUL 01-04, 2009 CL Salvador, BRAZIL C1 [Fukumoto, R.; Andresen, V; Bialuk, I; Cecchinato, V; Valeri, V. W.; Nauroth, J. M.; Franchini, G.] Natl Canc Inst, Anim Models & Retroviral Vaccines Sect, Bethesda, MD USA. [Walser, J. -C] NIDDK, Lab Mol & Cellular Biol, Bethesda, MD USA. [Gessain, A.] Inst Pasteur, Unite DepideMol & Physiopathol Virus OncogeNes, Dept Virol, Paris, France. [Nicot, C.] Univ Kansas, Med Ctr, Dept Microbiol Mol Genet & Immunol, Kansas City, KS 66103 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 2009 VL 25 IS 11 BP 1226 EP 1226 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 524ZF UT WOS:000272182200088 ER PT J AU Andresen, V Nicot, C Franchini, G Fukumoto, R Parks, RW Datta, US Cecchinato, V AF Andresen, V Nicot, C. Franchini, G. Fukumoto, R. Parks, R. W. Datta, U. S. Cecchinato, V TI The HTLV-1 P13 II Protein Interacts with Tax, Inhibits Tax Dependent Transcription and Decreases Viral Replication SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 14th International Conference on Human Retrovirology HTLV and Related Retroviruses CY JUL 01-04, 2009 CL Salvador, BRAZIL C1 [Andresen, V; Nicot, C.; Franchini, G.; Fukumoto, R.; Parks, R. W.; Datta, U. S.; Cecchinato, V] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 2009 VL 25 IS 11 BP 1227 EP 1227 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 524ZF UT WOS:000272182200090 ER PT J AU Tosi, G Badarou, L Andresen, V Franchini, G Accolla, RS AF Tosi, G. Badarou, L. Andresen, V Franchini, G. Accolla, R. S. TI CIITA, the Master Regulator of MHC Class II Gene Transcription, Targets the Viral Transactivator Tax-1 to Inhibit HTLV-I Viral Replication and NFKB Activation SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 14th International Conference on Human Retrovirology HTLV and Related Retroviruses CY JUL 01-04, 2009 CL Salvador, BRAZIL C1 [Tosi, G.; Badarou, L.; Accolla, R. S.] Univ Insubria, Dept Clin & Biol Sci, Varese, Italy. [Andresen, V; Franchini, G.] NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 2009 VL 25 IS 11 BP 1245 EP 1245 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 524ZF UT WOS:000272182200131 ER PT J AU Prooyen, NV Franchini, G Gold, H Bialuk, I Fukumoto, R Andresen, V AF Prooyen, N., V Franchini, G. Gold, H. Bialuk, I Fukumoto, R. Andresen, V TI Effect of HTLV-1 ORF I Protein Products on the Immunological Synapse and Actin Remodeling SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 14th International Conference on Human Retrovirology HTLV and Related Retroviruses CY JUL 01-04, 2009 CL Salvador, BRAZIL C1 [Prooyen, N., V; Franchini, G.; Gold, H.; Bialuk, I; Fukumoto, R.; Andresen, V] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 2009 VL 25 IS 11 BP 1246 EP 1247 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 524ZF UT WOS:000272182200135 ER PT J AU Janik, JE O'mahony, D Wharfe, G Morris, JC Urquhart, N Seam, P Fioravanti, S Waldmann, TA AF Janik, J. E. O'mahony, D. Wharfe, G. Morris, J. C. Urquhart, N. Seam, P. Fioravanti, S. Waldmann, T. A. TI Phase II Trial of Denileukin Diftitox in Adult T-Cell Leukemia/Lymphoma SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 14th International Conference on Human Retrovirology HTLV and Related Retroviruses CY JUL 01-04, 2009 CL Salvador, BRAZIL C1 [Janik, J. E.; O'mahony, D.; Wharfe, G.; Morris, J. C.; Urquhart, N.; Seam, P.; Fioravanti, S.; Waldmann, T. A.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 2009 VL 25 IS 11 BP 1252 EP 1253 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 524ZF UT WOS:000272182200150 ER PT J AU Evangelou, I McFarland, H Jacobson, S Oh, U AF Evangelou, I McFarland, H. Jacobson, S. Oh, U. TI Detection and Quantification of Cervical and Thoracic Spinal Cord Atrophy of HAM/TSP Patients Using a 3D Semi-Automatic Technique SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 14th International Conference on Human Retrovirology HTLV and Related Retroviruses CY JUL 01-04, 2009 CL Salvador, BRAZIL C1 [Evangelou, I; McFarland, H.; Jacobson, S.; Oh, U.] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 2009 VL 25 IS 11 BP 1270 EP 1270 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 524ZF UT WOS:000272182200191 ER PT J AU Jones, KS Andresen, V Valeri, VW Petrow-Sadowski, C Bertolette, D Franchini, G Ruscetti, F AF Jones, K. S. Andresen, V. Valeri, V. W. Petrow-Sadowski, C. Bertolette, D. Franchini, G. Ruscetti, F. TI P30II is Required for the Persistent Infection of Dendritic Cells by HTLV-1 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 14th International Conference on Human Retrovirology HTLV and Related Retroviruses CY JUL 01-04, 2009 CL Salvador, BRAZIL C1 [Jones, K. S.; Petrow-Sadowski, C.] SAIC Frederick, Basic Sci Program, Frederick, MD USA. [Andresen, V.; Valeri, V. W.; Franchini, G.] NCI, Anim Models & Retroviral Vacc Sect, NIH, Bethesda, MD 20892 USA. [Bertolette, D.; Ruscetti, F.] NCI, Canc & Inflammat Program, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 2009 VL 25 IS 11 BP 1286 EP 1286 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 524ZF UT WOS:000272182200229 ER PT J AU Bialuk, I Gessain, A Castro, BG Franchini, G Walser, JC Graham, J Alcantara, LC Fukumoto, R Jacobson, S Andresen, V AF Bialuk, I. Gessain, A. Castro, B. G. Franchini, G. Walser, J. C. Graham, J. Alcantara, L. C. Fukumoto, R. Jacobson, S. Andresen, V. TI The 8 kDa Form Encoded by the HTLV-I ORF-I is Associated with Low Provirus Levels in a Subset of HTLV-I Infected Individuals SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 14th International Conference on Human Retrovirology HTLV and Related Retroviruses CY JUL 01-04, 2009 CL Salvador, BRAZIL C1 NCI, NIH, Bethesda, MD 20892 USA. Med Univ Bialystok, Bialystok, Poland. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 2009 VL 25 IS 11 BP 1297 EP 1297 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 524ZF UT WOS:000272182200258 ER PT J AU Graham, J Jacobson, S Oh, U Akahata, Y AF Graham, J. Jacobson, S. Oh, U. Akahata, Y. TI The Effect of the Histone Deacetylase Inhibitor Valproic Acid on Tax Expression, Spontaneous Degranulation and Cell Survival in HTLV-I Infected Peripheral Blood Mononuclear Cells SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 14th International Conference on Human Retrovirology HTLV and Related Retroviruses CY JUL 01-04, 2009 CL Salvador, BRAZIL C1 [Graham, J.; Jacobson, S.; Oh, U.; Akahata, Y.] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 2009 VL 25 IS 11 BP 1297 EP 1298 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 524ZF UT WOS:000272182200259 ER PT J AU Rende, F Cavallari, I Silic-Benussi, M Corradin, A Toulza, F Valeri, VW Chieco-Bianchi, L D'Agostino, DM Jacobson, S Franchini, G Bangham, CRM Ciminale, V AF Rende, F. Cavallari, I. Silic-Benussi, M. Corradin, A. Toulza, F. Valeri, V. W. Chieco-Bianchi, L. D'Agostino, D. M. Jacobson, S. Franchini, G. Bangham, C. R. M. Ciminale, V. TI Temporal Regulation of HTLV-1 Gene Expression SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 14th International Conference on Human Retrovirology HTLV and Related Retroviruses CY JUL 01-04, 2009 CL Salvador, BRAZIL C1 [Rende, F.; Cavallari, I.; Silic-Benussi, M.; Chieco-Bianchi, L.; D'Agostino, D. M.; Ciminale, V.] Univ Padua, Dept Oncol & Surg Sci, I-35100 Padua, Italy. [Corradin, A.] Univ Padua, Dept Informat Engn, I-35100 Padua, Italy. [Toulza, F.; Bangham, C. R. M.] Univ London Imperial Coll Sci Technol & Med, Dept Immunol, London, England. [Jacobson, S.] NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. [Franchini, G.] NCI, Anim Models & Retroviral Vaccines Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 2009 VL 25 IS 11 BP 1297 EP 1297 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 524ZF UT WOS:000272182200257 ER PT J AU Mahieux, R Gessain, A Sadowski, CP Bertolette, D Ruscetti, F Jones, K Afonso, P Chevalier, S Huang, Y AF Mahieux, R. Gessain, A. Sadowski, C. P. Bertolette, D. Ruscetti, F. Jones, K. Afonso, P. Chevalier, S. Huang, Y. TI The Receptor Complex Associated with HTLV-3 ENV-Mediated Binding and Entry is Distinct from, but Overlaps with, the Receptor Complexes of HTLV-1 and HTLV-2 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 14th International Conference on Human Retrovirology HTLV and Related Retroviruses CY JUL 01-04, 2009 CL Salvador, BRAZIL C1 Saic Frederick Inc, Natick, MA USA. NCI Frederick, Frederick, MD USA. Inst Pasteur, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 2009 VL 25 IS 11 BP 1298 EP 1298 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 524ZF UT WOS:000272182200260 ER PT J AU Ciccocioppo, R Gehlert, DR Ryabinin, A Kaur, S Cippitelli, A Thorsell, A Le, AD Hipskind, PA Hamdouchi, C Lu, JL Hembre, EJ Cramer, J Song, M McKinzie, D Morin, M Economidou, D Stopponi, S Cannella, N Braconi, S Kallupi, M de Guglielmo, G Massi, M George, DT Gilman, J Hersh, J Tauscher, JT Hunt, SP Hommer, D Heilig, M AF Ciccocioppo, Roberto Gehlert, Donald R. Ryabinin, Andrey Kaur, Simranjit Cippitelli, Andrea Thorsell, Annika Le, Anh D. Hipskind, Philip A. Hamdouchi, Chafiq Lu, Jianliang Hembre, Erik J. Cramer, Jeffrey Song, Min McKinzie, David Morin, Michelle Economidou, Daina Stopponi, Serena Cannella, Nazzareno Braconi, Simone Kallupi, Marsida de Guglielmo, Giordano Massi, Maurizio George, David T. Gilman, Jody Hersh, Jacqueline Tauscher, Johannes T. Hunt, Stephen P. Hommer, Daniel Heilig, Markus TI Stress-related neuropeptides and alcoholism: CRH, NPY, and beyond SO ALCOHOL LA English DT Article; Proceedings Paper CT Conference on Alcoholism and Stress - A Framework for Future Treatment Strategies CY MAY 06-08, 2008 CL Volterra, ITALY DE CRH; Nociceptin/orphanin FQ; Neurokinins; Substance P; Neuropeptide Y; Urocortin ID CORTICOTROPIN-RELEASING-FACTOR; EDINGER-WESTPHAL NUCLEUS; PITUITARY-ADRENAL AXIS; NOCICEPTIN/ORPHANIN FQ; SEEKING BEHAVIOR; LATERAL SEPTUM; UROCORTIN EXPRESSION; ETHANOL-CONSUMPTION; INDUCED HYPOTHERMIA; RECEPTORS MEDIATE AB This article summarizes the proceedings of a symposium held at the conference on "Alcoholism and Stress: A Framework for Future Treatment Strategies" in Volterra, Italy, May 6-9, 2008. Chaired by Markus Heilig and Roberto Ciccocioppo, this symposium offered a forum for the presentation of recent data linking neuropetidergic neurotransmission to the regulation of different alcohol-related behaviors in animals and in humans. Dr. Donald Gehlert described the development of a new corticotrophin-releasing factor receptor I antagonist and showed its efficacy in reducing alcohol consumption and stress-induced relapse in different animal models of alcohol abuse. Dr. Andrey Ryabinin reviewed recent findings in his laboratory, indicating a role of the urocortin I receptor system in the regulation of alcohol intake. Dr. Annika Thorsell showed data supporting the significance of the neuropeptide Y receptor system in the modulation of behaviors associated with a history of ethanol intoxication. Dr. Roberto Ciccocioppo focused his presentation on the nociceptin/orphanin FQ (N/OFQ) receptors as treatment targets for alcoholism. Finally, Dr. Markus Heilig showed recent preclinical and clinical evidence suggesting that neurokinin I antagonism may represent a promising new treatment for alcoholism. Collectively, these investigators highlighted the significance of neuropeptidergic neurotransmission in the regulation of neurobiological mechanisms of alcohol addiction. Data also revealed the importance of these systems as treatment targets for the development of new medication for alcoholism. (C) 2009 Elsevier Inc. All rights reserved. C1 [Ciccocioppo, Roberto; Cippitelli, Andrea; Economidou, Daina; Stopponi, Serena; Cannella, Nazzareno; Braconi, Simone; Kallupi, Marsida; de Guglielmo, Giordano; Massi, Maurizio] Univ Camerino, Dept Expt Med & Publ Hlth, I-62032 Camerino, Macerata, Italy. [Gehlert, Donald R.; Hipskind, Philip A.; Hamdouchi, Chafiq; Lu, Jianliang; Hembre, Erik J.; Cramer, Jeffrey; Song, Min; McKinzie, David; Morin, Michelle; Tauscher, Johannes T.] Lilly Res Labs, Indianapolis, IN 46285 USA. [Ryabinin, Andrey; Kaur, Simranjit] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. [Cippitelli, Andrea; Thorsell, Annika; George, David T.; Gilman, Jody; Hersh, Jacqueline; Hommer, Daniel; Heilig, Markus] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. [Le, Anh D.] Univ Toronto, Ctr Addict & Mental Hlth, Toronto, ON M5S 2S1, Canada. [Hunt, Stephen P.] UCL, Dept Anat & Dev Biol, London WC1E 6BT, England. RP Ciccocioppo, R (reprint author), Univ Camerino, Dept Expt Med & Publ Hlth, Via Madonna Carceri, I-62032 Camerino, Macerata, Italy. EM roberto.ciccocioppo@unicam.it RI Tauscher, Johannes/M-5976-2016; OI Heilig, Markus/0000-0003-2706-2482; Kallupi, Marsida/0000-0002-8688-709X; Cannella, Nazzareno/0000-0002-2891-8679; Thorsell, Annika/0000-0003-3535-3845 FU NIAAA NIH HHS [AA016647, AA013738, AA01435, R01 AA013108, R01 AA013738, R01 AA013738-05, R01 AA014351, R01 AA014351-05, U01 AA016647, U01 AA016647-04] NR 73 TC 32 Z9 32 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-8329 J9 ALCOHOL JI Alcohol PD NOV PY 2009 VL 43 IS 7 BP 491 EP 498 DI 10.1016/j.alcohol.2009.08.003 PG 8 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 526SU UT WOS:000272314700002 PM 19913192 ER PT J AU Witkiewitz, K Holmes, A Ray, LA Murphy, JG Richardson, HN Chen, YC McDevitt-Murphy, ME Cruz, MT Roberto, M AF Witkiewitz, Katie Holmes, Andrew Ray, Lara A. Murphy, James G. Richardson, Heather N. Chen, Yi-Chyan McDevitt-Murphy, Meghan E. Cruz, Maureen T. Roberto, Marisa TI Young Investigator Award Symposium SO ALCOHOL LA English DT Article; Proceedings Paper CT Conference on Alcoholism and Stress - A Framework for Future Treatment Strategies CY MAY 06-08, 2008 CL Volterra, ITALY DE Alcohol; Stress; Human; Mouse; Rat; Glutamate; Naltrexone; HPA axis ID CORTICOTROPIN-RELEASING-FACTOR; PITUITARY-ADRENAL AXIS; ETHANOL-DEPENDENT RATS; POSTTRAUMATIC-STRESS-DISORDER; ANXIETY-LIKE BEHAVIOR; CHRONIC SWIM STRESS; NMDA RECEPTOR NR2A; ALCOHOL DEPENDENCE; ADRENOCORTICAL AXIS; NORMAL VOLUNTEERS AB This article highlights the research presented at the inaugural meeting of Alcoholism and Stress: A Framework for future Treatment Strategies. This meeting was held on May 6-8, 2008 in Volterra, Italy. It is an international meeting dedicated to developing preventive strategies and pharmacotherapeutic remedies for stress- and alcohol-related disorders. For the first time, the National Institute on Alcohol Abuse and Alcoholism (NIAAA) conferred a Young Investigator Award to promote the work of young researchers and highlight their outstanding achievements in the fields of addiction medicine and stress disorders. The awardees were Dr. Katie Witkiewitz (University of Washington), Dr. Andrew Holmes (NIAAA), Dr. Lara A. Ray (Brown University), Dr. James Murphy (University of Memphis), and Dr. Heather Richardson (The Scripps Research Institute). The symposium was chaired by Drs. Fulton Crews and Antonio Noronha. (C) 2009 Published by Elsevier Inc. C1 [Richardson, Heather N.; Cruz, Maureen T.; Roberto, Marisa] Scripps Res Inst, Comm Neurobiol Addict Disorders, La Jolla, CA 92037 USA. [Witkiewitz, Katie] Univ Washington, Inst Alcohol & Drug Abuse, Seattle, WA 98105 USA. [Holmes, Andrew] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. [Ray, Lara A.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Murphy, James G.; McDevitt-Murphy, Meghan E.] Univ Memphis, Dept Psychol, Memphis, TN 38152 USA. [Richardson, Heather N.] Univ Massachusetts, Dept Psychol Neurosci, Amherst, MA 01003 USA. [Chen, Yi-Chyan] Triserv Gen Hosp, Natl Def Med Ctr, Dept Psychiat, Taipei, Taiwan. RP Roberto, M (reprint author), Scripps Res Inst, Comm Neurobiol Addict Disorders, La Jolla, CA 92037 USA. OI Richardson, Heather/0000-0001-7659-1212 FU NIAAA NIH HHS [P60 AA006420] NR 99 TC 0 Z9 0 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-8329 J9 ALCOHOL JI Alcohol PD NOV PY 2009 VL 43 IS 7 BP 499 EP 508 DI 10.1016/j.alcohol.2009.06.004 PG 10 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 526SU UT WOS:000272314700003 PM 19913193 ER PT J AU Mason, BJ Shaham, Y Weiss, F Le, AD AF Mason, Barbara J. Shaham, Yavin Weiss, Friedbert Le, A. D. TI Stress, alcohol craving, and relapse risk: mechanisms and viable treatment targets SO ALCOHOL LA English DT Article; Proceedings Paper CT Conference on Alcoholism and Stress - A Framework for Future Treatment Strategies CY MAY 06-08, 2008 CL Volterra, ITALY ID CORTICOTROPIN-RELEASING-FACTOR; YOHIMBINE-INDUCED INCREASES; SEEKING; RATS; RECEPTORS; AGONIST; REINSTATEMENT; ABSTINENCE; GLUTAMATE; LY379268 C1 [Mason, Barbara J.; Weiss, Friedbert] Scripps Res Inst, La Jolla, CA 92037 USA. [Shaham, Yavin] NIDA, Baltimore, MD USA. [Le, A. D.] Univ Toronto, Toronto, ON, Canada. RP Mason, BJ (reprint author), Scripps Res Inst, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM mason@scripps.edu RI shaham, yavin/G-1306-2014; Mason, Barbara/P-6604-2016 FU NIAAA NIH HHS [R01 AA010531-13, R01 AA010531, R01 AA012602, R01 AA012602-09, R01 AA013108, R01AA012602, R37 AA014028, R37 AA014028-06, R37AA014028]; NIDA NIH HHS [R37 DA007348, R37 DA007348-14] NR 17 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-8329 J9 ALCOHOL JI Alcohol PD NOV PY 2009 VL 43 IS 7 SI SI BP 541 EP 543 DI 10.1016/j.alcohol.2009.09.024 PG 3 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 526SU UT WOS:000272314700007 PM 19913197 ER PT J AU Levine, M Eck, P AF Levine, Mark Eck, Peter TI Vitamin C: working on the x-axis SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Editorial Material ID ASCORBIC-ACID C1 [Levine, Mark] NIDDK, Mol & Clin Nutr Sect, Digest Dis Branch, Intramural Res Program,NIH, Bethesda, MD 20892 USA. [Eck, Peter] Univ Manitoba, Dept Human Nutr Sci, Richardson Ctr Funct Foods & Nutraceut, Winnipeg, MB, Canada. RP Levine, M (reprint author), NIDDK, Mol & Clin Nutr Sect, Digest Dis Branch, Intramural Res Program,NIH, Bldg 10,Room 4D52,MSC 1372,10 Ctr Dr, Bethesda, MD 20892 USA. EM mark.levine@nih.gov OI Eck, Peter/0000-0003-2371-9774 NR 10 TC 10 Z9 10 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 1 PY 2009 VL 90 IS 5 BP 1121 EP 1123 DI 10.3945/ajcn.2009.28687 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 508TO UT WOS:000270959500002 PM 19812178 ER PT J AU Savastano, DM Gorbach, AM Eden, HS Brady, SM Reynolds, JC Yanovski, JA AF Savastano, David M. Gorbach, Alexander M. Eden, Henry S. Brady, Sheila M. Reynolds, James C. Yanovski, Jack A. TI Adiposity and human regional body temperature SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID RESTING ENERGY-EXPENDITURE; ARTERIOVENOUS ANASTOMOSES; SUBCUTANEOUS FAT; METABOLIC-RATE; BLOOD-FLOW; SKIN; TISSUE; OBESE; VESSELS; SYSTEM AB Background: Human obesity is associated with increased heat production; however, subcutaneous adipose tissue provides an insulating layer that impedes heat loss. To maintain normothermia, therefore, obese individuals must increase their heat dissipation. Objective: The objective was to test the hypothesis that temperature in a heat-dissipating region of the hand is elevated in obese adults. Design: Obese [body mass index (in kg/m(2)) >= 30] and normal-weight (NW; body mass index = 18-25) adults were studied under thermoneutral conditions at rest. Core body temperature was measured by using ingested telemetric capsules. The temperatures of the third fingernail bed of the right hand and of abdominal skin from an area 1.5 cm inferior to the umbilicus were determined by using infrared thermography. Abdominal skin temperatures were also measured via adhesive thermistors that were placed over a prominent skin-surface blood vessel and over an adjacent nonvessel location. The groups were compared by analysis of covariance with age, sex, race, and room temperature as covariates. Results: Core temperature did not differ significantly between the 23 obese and 13 NW participants (P = 0.74). However, infrared thermography-measured fingernail-bed temperature was significantly higher in obese subjects than in NW subjects (33.9 6 +/- 0.7 degrees C compared with 28.6 +/- 0.9 degrees C; P < 0.001). Conversely, infrared thermography-measured abdominal skin temperature was significantly lower in obese subjects than in NW subjects (31.8 +/- 0.2 degrees C compared with 32.8 +/- 0.3 degrees C; P = 0.02). Nonvessel abdominal skin temperatures measured by thermistors were also lower in obese subjects (P = 0.04). Conclusions: Greater subcutaneous abdominal adipose tissue in obese adults may provide a significant insulating layer that blunts abdominal heat transfer. Augmented heat release from the hands may offset heat retention in areas of the body with greater adiposity, thereby helping to maintain normothermia in obesity. This trial was registered at clinicaltrials.gov as NCT00266500. Am J Clin Nutr 2009; 90: 1124-31. C1 [Savastano, David M.; Brady, Sheila M.; Yanovski, Jack A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Growth & Obes, Program Dev Endocrinol & Genet, Bethesda, MD 20892 USA. [Gorbach, Alexander M.; Eden, Henry S.] Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, Bethesda, MD USA. [Reynolds, James C.] NIH, Dept Diagnost Radiol, Hatfield Clin Res Ctr, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Yanovski, JA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth, Unit Growth & Obes, Program Dev Endocrinol & Genet, NIH,Hatfield Clin Res Ctr, 10 Ctr Dr,Room 1-3330,MSC 1103, Bethesda, MD 20892 USA. EM jy15i@nih.gov OI Yanovski, Jack/0000-0001-8542-1637 FU Intramural NIH HHS [Z01 EB000032-01] NR 41 TC 54 Z9 58 U1 0 U2 20 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD NOV 1 PY 2009 VL 90 IS 5 BP 1124 EP 1131 DI 10.3945/ajcn.2009.27567 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 508TO UT WOS:000270959500003 PM 19740972 ER PT J AU Manini, TM Everhart, JE Anton, SD Schoeller, DA Cummings, SR Mackey, DC Delmonico, MJ Bauer, DC Simonsick, EM Colbert, LH Visser, M Tylavsky, F Newman, AB Harris, TB AF Manini, Todd M. Everhart, James E. Anton, Stephen D. Schoeller, Dale A. Cummings, Steve R. Mackey, Dawn C. Delmonico, Matthew J. Bauer, Douglas C. Simonsick, Eleanor M. Colbert, Lisa H. Visser, Marjolein Tylavsky, Frances Newman, Anne B. Harris, Tamara B. CA Hlth Aging & Body Composition Stud TI Activity energy expenditure and change in body composition in late life SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID DOUBLY-LABELED WATER; PHYSICAL-ACTIVITY; RESPIRATORY CHAMBER; RESISTANCE-EXERCISE; SKELETAL-MUSCLE; WEIGHT CHANGE; OLDER MEN; HUMANS; PEOPLE; WOMEN AB Background: Change in body composition, specifically loss of fat-free mass and gain in fat mass, in older adults is a major pathway leading to the onset of functional decline and physical disability. Objective: The objective was to determine the association of activity-related energy expenditure with change in body mass and composition among older men and women. Design: Total energy expenditure ( TEE) was assessed over 2 wk by using the doubly labeled water method in 302 community-dwelling older adults aged 70-82 y. Resting metabolic rate (RMR) was measured by using indirect calorimetry, and the thermic effect of meals was estimated at 10% of TEE. Activity energy expenditure (AEE) was calculated as [TEE(0.9) - RMR]. Total body mass, fat-free mass (FFM), and fat mass ( FM) were assessed by dual-energy X-ray absorptiometry annually over a mean (+/- SD) of 4.9 +/- 1.3 y. Results: In multivariate models adjusted for baseline age, smoking status, and race, men and women had a decline ( in kg/y) in body mass ( men: -0.34, 95% CI: -0.71, 0.02; women: -0.45, 95% CI: -0.71, -0.19) and FFM ( men: -0.48, 95% CI: -0.67, -0.29; women: -0.14, 95% CI: -0.026, -0.03). No changes (in kg/y) were observed in FM ( men: 0.14, 95% CI: -0.10, 0.38; women: -0.28, 95% CI: -0.49, -0.07). In men and women, higher AEE at baseline was associated with greater FFM. The average change in these outcomes (ie, slope), however, was similar across tertiles of AEE. Conclusions: These data suggest that accumulated energy expenditure from all physical activities is associated with greater FFM, but the effect does not alter the trajectory of FFM change in late life. Am J Clin Nutr 2009; 90: 1336-42. C1 [Manini, Todd M.; Anton, Stephen D.] Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL 32611 USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Everhart, James E.] NIDDKD, Bethesda, MD 20892 USA. [Schoeller, Dale A.] Univ Wisconsin, Dept Nutr Sci, Madison, WI 53706 USA. [Colbert, Lisa H.] Univ Wisconsin, Dept Kinesiol, Madison, WI 53706 USA. [Delmonico, Matthew J.] Univ Rhode Isl, Dept Kinesiol, Kingston, RI 02881 USA. [Visser, Marjolein] Vrije Univ Amsterdam, Fac Earth & Life Sci, Inst Hlth Sci, Amsterdam, Netherlands. [Visser, Marjolein] Vrije Univ Amsterdam, Med Ctr, EMGO, Amsterdam, Netherlands. [Tylavsky, Frances] Univ Tennessee, Dept Biostat & Epidemiol, Memphis, TN USA. [Cummings, Steve R.; Mackey, Dawn C.] Calif Pacific Med Ctr, San Francisco Coordinating Ctr, San Francisco, CA USA. [Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Simonsick, Eleanor M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Bauer, Douglas C.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Bauer, Douglas C.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. RP Manini, TM (reprint author), Univ Florida, Dept Aging & Geriatr Res, POB 112610, Gainesville, FL 32611 USA. EM tmanini@aging.ufl.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NIA Claude D. Pepper Center [P30AG028740]; Institute on Aging at the University of Florida; NIH, National Institute on Aging [N01AG-6-2106, N01-AG-6-2101, N01-AG-6-2103]; National Institute of Diabetes and Digestive and Kidney Diseases FX Supported by the NIA Claude D. Pepper Center (P30AG028740) and a grant from the Institute on Aging at the University of Florida. The Health, Aging and Body Composition Study was supported by the Intramural Research Program of the NIH, National Institute on Aging (contracts N01AG-6-2106, N01-AG-6-2101, and N01-AG-6-2103) with additional support from the National Institute of Diabetes and Digestive and Kidney Diseases. NR 31 TC 18 Z9 19 U1 1 U2 4 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 1 PY 2009 VL 90 IS 5 BP 1336 EP 1342 DI 10.3945/ajcn.2009.27659 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 508TO UT WOS:000270959500030 PM 19740971 ER PT J AU Yong, LC Petersen, MR Sigurdson, AJ Sampson, LA Ward, EM AF Yong, Lee C. Petersen, Martin R. Sigurdson, Alice J. Sampson, Laura A. Ward, Elizabeth M. TI High dietary antioxidant intakes are associated with decreased chromosome translocation frequency in airline pilots SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID IONIZING-RADIATION; FREE-RADICALS; VITAMINS C; CANCER; VEGETABLES; DAMAGE; REPRODUCIBILITY; QUESTIONNAIRE; CAROTENOIDS; VALIDITY AB Background: Dietary antioxidants may protect against DNA damage induced by endogenous and exogenous sources, including ionizing radiation (IR), but data from IR-exposed human populations are limited. Objective: The objective was to examine the association between the frequency of chromosome translocations, as a biomarker of cumulative DNA damage, and intakes of vitamins C and E and carotenoids in 82 male airline pilots. Design: Dietary intakes were estimated by using a self-administered semiquantitative food-frequency questionnaire. Translocations were scored by using fluorescence in situ hybridization with whole chromosome paints. Negative binomial regression was used to estimate rate ratios and 95% CIs, adjusted for potential confounders. Results: Significant and inverse associations were observed between translocation frequency and intakes of vitamin C, beta-carotene, beta-cryptoxanthin, and lutein-zeaxanthin from food (P < 0.05). Translocation frequency was not associated with the intake of vitamin E, alpha-carotene, or lycopene from food; total vitamin C or E from food and supplements; or vitamin C or E or multivitamin supplements. The adjusted rate ratios ( 95% CI) for >= median compared with, = median compared with, median combined intakes of vitamins C and E, beta- carotene, beta-cryptoxanthin, and lutein-zeaxanthin from food: 0.27 (0.14, 0.55). Conclusion: High combined intakes of vitamins C and E, beta- carotene, beta-cryptoxanthin, and lutein-zeaxanthin from food, or a diet high in their food sources, may protect against cumulative DNA damage in IR-exposed persons. Am J Clin Nutr 2009;90:1402-10. C1 [Yong, Lee C.] NIOSH, Ctr Dis Control & Prevent, Industrywide Studies Branch, Div Surveillance Hazard Evaluat & Field Studies, Cincinnati, OH 45226 USA. [Sigurdson, Alice J.] NCI, NIH, Bethesda, MD 20892 USA. [Sampson, Laura A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Ward, Elizabeth M.] Amer Canc Soc, Atlanta, GA 30329 USA. RP Yong, LC (reprint author), NIOSH, Ctr Dis Control & Prevent, Industrywide Studies Branch, Div Surveillance Hazard Evaluat & Field Studies, 4676 Columbia Pkwy,R-15, Cincinnati, OH 45226 USA. EM lay7@cdc.gov FU National Institute for Occupational Safety and Health and the National Cancer Institute [Y1CP802904]; Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute FX Supported in part by an interagency agreement between the National Institute for Occupational Safety and Health and the National Cancer Institute ( contract Y1CP802904) and by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute. NR 40 TC 11 Z9 11 U1 0 U2 2 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD NOV 1 PY 2009 VL 90 IS 5 BP 1402 EP 1410 DI 10.3945/ajcn.2009.28207 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 508TO UT WOS:000270959500038 PM 19793852 ER PT J AU Sinha, R Park, Y Graubard, BI Leitzmann, MF Hollenbeck, A Schatzkin, A Cross, AJ AF Sinha, Rashmi Park, Yikyung Graubard, Barry I. Leitzmann, Michael F. Hollenbeck, Albert Schatzkin, Arthur Cross, Amanda J. TI Meat and Meat-related Compounds and Risk of Prostate Cancer in a Large Prospective Cohort Study in the United States SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE amines; benzo(a)pyrene; heme; meat; nitrates; nitrites; polycyclic hydrocarbons, aromatic; prostatic neoplasms ID HETEROCYCLIC AMINE CONTENT; FOOD-FREQUENCY QUESTIONNAIRE; HEALTH-AMERICAN-ASSOCIATION; RETIRED-PERSONS DIET; COLORECTAL-CANCER; ANIMAL PRODUCTS; N-NITROSATION; RED MEAT; NATIONAL-INSTITUTES; NETHERLANDS COHORT AB The authors examined associations between meat consumption (type, cooking method, and related mutagens), heme iron, nitrite/nitrate, and prostate cancer in a cohort of 175,343 US men aged 50-71 years. During 9 years of follow-up (1995-2003), they ascertained 10,313 prostate cancer cases (1,102 advanced) and 419 fatal cases. Hazard ratios comparing the fifth intake quintile with the first revealed elevated risks associated with red and processed meat for total (red meat: hazard ratio (HR) = 1.12, 95% confidence interval (CI): 1.04, 1.21; processed meat: HR = 1.07, 95% CI: 1.00, 1.14) and advanced (red meat: HR = 1.31, 95% CI: 1.05, 1.65; processed meat: HR = 1.32, 95% CI: 1.08, 1.61) prostate cancer. Heme iron, barbecued/grilled meat, and benzo[a]pyrene were all positively associated with total (HR = 1.09 (95% CI: 1.02, 1.17), HR = 1.11 (95% CI: 1.03, 1.19), and HR = 1.09 (95% CI: 1.00, 1.18), respectively) and advanced (HR = 1.28 (95% CI: 11.03, 1.58), HR = 1.36 (95% CI: 1.10, 1.69), and HR = 1.28 (95% CI: 1.00, 1.65), respectively) disease. Nitrite (HR = 1.24, 95% CI: 1.02, 1.51) and nitrate (HR = 1.31, 95% CI: 1.07, 1.61) intakes were associated with advanced prostate cancer. There were no clear associations for fatal prostate cancer. Red and processed meat may be positively associated with prostate cancer via mechanisms involving heme iron, nitrite/nitrate, grilling/barbecuing, and benzo[a]pyrene. C1 [Sinha, Rashmi; Park, Yikyung; Graubard, Barry I.; Schatzkin, Arthur; Cross, Amanda J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Leitzmann, Michael F.] Univ Regensburg, Inst Epidemiol & Prevent Med, Regensburg, Germany. [Hollenbeck, Albert] AARP, Washington, DC USA. RP Sinha, R (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Rockville, MD 20892 USA. EM sinhar@nih.gov RI Sinha, Rashmi/G-7446-2015; OI Sinha, Rashmi/0000-0002-2466-7462; Park, Yikyung/0000-0002-6281-489X NR 62 TC 63 Z9 63 U1 3 U2 19 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 2009 VL 170 IS 9 BP 1165 EP 1177 DI 10.1093/aje/kwp280 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 511KR UT WOS:000271163700013 PM 19808637 ER PT J AU Singer, ST Kim, HY Olivieri, NF Kwiatkowski, JL Coates, TD Carson, S Neufeld, E Cunningham, MJ Giardina, PJ Mueller, BU Quinn, CT Fung, E Vichinsky, E AF Singer, Sylvia Titi Kim, Hae-Young Olivieri, Nancy F. Kwiatkowski, Janet L. Coates, Thomas D. Carson, Susan Neufeld, Ellis Cunningham, Melody J. Giardina, Patricia J. Mueller, Brigitta U. Quinn, Charles T. Fung, Ellen Vichinsky, Elliott CA Thalassemia Clinical Res Network TI Hemoglobin H-constant spring in North America: An alpha Thalassemia with frequent complications SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Letter ID INTERMEDIA PATIENTS; CHINESE PATIENTS; MARROW ACTIVITY; IRON OVERLOAD; DISEASE; CALIFORNIA; GENOTYPES; FEATURES; ANEMIA AB Hemoglobin H-constant spring (Hb H-CS), the most common nondeletional alpha thalassemia in Asia is increasingly recognized in North America due to shifts in immigration patterns. In California, alpha (alpha)-thalassemia syndromes are the second most frequent finding among newborns screened for hemoglobinopathies with a two-fold increase compared to a decade earlier [1,2]. Though known to have a more severe anemia than Hb H disease, the other clinical findings of Hb H-CS are not well described. Moreover, beneficial therapies that have become available in the last decade are often not applied to their care. This analysis of 46 patients enrolled in the Thalassemia Clinical Research Network (TCRN) age 13+/- 10 years old, with Hb H-CS revealed moderate anemia (mean 8.7 +/- 1.5 g/dl), regular transfusion therapy in 24% of patients, and spienomegaly or prior splenectomy in one-third of them. Serum transferin receptor (sTfr), was elevated; (44.4 +/- 18 mcg/ml normal range 2.9-8.3 mcg/ml), reflecting ineffective erythropoiesis, which in turn leads to high iron absorption and increased ferritin levels in younger (median = 187 ng/ml) and older (median = 465 ng/ml) nontransfused patients. These findings along with moderate growth delay and low bone mass were more prevalent in Hlb H-CS patients compared to deletional Hlb H disease. Our results highlight the required monitoring of the extent of anemia, growth, splenomegaly, iron overload, gallstones, bone density and assessment of need for transfusions and specific treatments for disease complications. C1 [Singer, Sylvia Titi] Childrens Hosp, NHLBI, Oakland, CA 94609 USA. [Singer, Sylvia Titi; Fung, Ellen; Vichinsky, Elliott; Thalassemia Clinical Res Network] Res Ctr Oakland, Oakland, CA 94609 USA. [Kim, Hae-Young] New England Res Inst, Watertown, MA 02172 USA. [Olivieri, Nancy F.] Toronto Gen Hosp, Univ Hlth Network, Toronto, ON, Canada. [Kwiatkowski, Janet L.] Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA 19104 USA. [Coates, Thomas D.; Carson, Susan] Childrens Hosp Los Angeles, Childrens Ctr Canc & Blood Dis, Los Angeles, CA 90027 USA. [Neufeld, Ellis; Cunningham, Melody J.] Childrens Hosp, Boston, MA 02115 USA. [Giardina, Patricia J.] Weill Cornell Med Coll, New York, NY USA. [Mueller, Brigitta U.] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. [Quinn, Charles T.] Univ Texas SW Med Ctr Dallas, Div Pediat Hematol Oncol, Dallas, TX 75390 USA. RP Singer, ST (reprint author), Childrens Hosp, NHLBI, 747 52nd St, Oakland, CA 94609 USA. EM tsinger@mail.cho.org RI Vichinsky, Elliott/F-8541-2011; Quinn, Charles/J-6842-2012; OI Vichinsky, Elliott/0000-0002-0500-9579; Quinn, Charles/0000-0002-2372-2175; Coates, Thomas/0000-0001-9878-6029 FU NCRR NIH HHS [M01 RR001271]; NHLBI NIH HHS [U01 HL065232, U01 HL065233, U01 HL065238, U01 HL065239, U01 HL065244, U01 HL065260] NR 21 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 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD NOV PY 2009 VL 84 IS 11 BP 759 EP 761 DI 10.1002/ajh.21523 PG 3 WC Hematology SC Hematology GA 516KC UT WOS:000271539900013 PM 19787795 ER PT J AU Lampl, M Kusanovic, JP Erez, O Gotsch, F Espinoza, J Goncalves, L Lee, W Gomez, R Nien, JK Frongillo, EA Romero, R AF Lampl, Michelle Kusanovic, Juan Pedro Erez, Offer Gotsch, Francesca Espinoza, Jimmy Goncalves, Luis Lee, Wesley Gomez, Ricardo Kae Nien, Jyh Frongillo, Edward A. Romero, Roberto TI Growth Perturbations in a Phenotype with Rapid Fetal Growth Preceding Preterm Labor and Term Birth SO AMERICAN JOURNAL OF HUMAN BIOLOGY LA English DT Article ID FOR-GESTATIONAL-AGE; INTRAUTERINE GROWTH; IMPRINTED GENES; IN-UTERO; RESTRICTED FETUSES; AMNIOTIC-FLUID; FATTY LIVER; WEIGHT; PREGNANCY; HORMONE AB The variability in fetal growth rates and gestation duration in humans is not well understood. Of interest are women presenting with an episode of preterm labor and subsequently delivering a term neonate, who is small relative to peers of similar gestational age. To further understand these relationships, fetal growth patterns predating an episode of preterm labor were investigated. Retrospective analysis of fetal biometry assessed by serial ultrasound in a prospectively studied sample of pregnancies in Santiago, Chile, tested the hypothesis that fetal growth patterns among uncomplicated pregnancies (n = 3,706) and those with an episode of preterm labor followed by term delivery (n = 184) were identical across the time intervals 16-22 weeks, 22-28 weeks, and 28-34 weeks in a multilevel mixed-effects regression. The hypothesis was not supported. Fetal weight growth rate was faster from 16 weeks among pregnancies with an episode of preterm labor (P < 0.05), declined across midgestation (22-28 weeks, P < 0.05), and rebounded between 28 and 34 weeks (P = 0.06). This was associated with perturbations in abdominal circumference growth and proportionately larger biparietal diameter from 22 gestational weeks (P = 0.03), greater femur (P = 0.01), biparietal diameter (P = 0.001) and head circumference (P = 0.02) dimensions relative to abdominal circumference across midgestation (22-28 weeks), followed by proportionately smaller femur diaphyseal length (P = 0.02) and biparietal diameter (P = 0.03) subsequently. A distinctive rapid growth phenotype characterized fetal growth preceding an episode of preterm labor among this sample of term-delivered neonates. Perturbations in abdominal circumference growth and patterns of proportionality suggest an altered growth strategy pre-dating the preterm labor episode. Am. J. Hum. Biol. 21:782-792, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Lampl, Michelle] Emory Univ, Dept Anthropol, Atlanta, GA 30322 USA. [Lampl, Michelle; Kusanovic, Juan Pedro; Erez, Offer; Gotsch, Francesca; Espinoza, Jimmy; Goncalves, Luis; Lee, Wesley; Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Lampl, Michelle] Emory Univ, Predict Hlth Ctr Hlth Discovery, Atlanta, GA 30322 USA. [Kusanovic, Juan Pedro; Erez, Offer] Wayne State Univ, Dept Obstet & Gynecol, Hutzel Womens Hosp, Detroit, MI USA. [Gomez, Ricardo; Kae Nien, Jyh] Pontificia Univ Catolica Chile, Sotero Rio Hosp, Ctr Perinatal Diag & Res CEDIP, Puente Alto, Chile. [Frongillo, Edward A.] Univ S Carolina, Dept Hlth Promot Educ & Behav, Columbia, SC 29208 USA. [Romero, Roberto] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI USA. RP Lampl, M (reprint author), Emory Univ, Dept Anthropol, Atlanta, GA 30322 USA. EM mlampl@emory.edu RI Lampl, Michelle/B-1619-2013 FU Intramural Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX Contract grant sponsor: Intramural Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS NR 74 TC 7 Z9 7 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1042-0533 J9 AM J HUM BIOL JI Am. J. Hum. Biol. PD NOV-DEC PY 2009 VL 21 IS 6 BP 782 EP 792 DI 10.1002/ajhb.20880 PG 11 WC Anthropology; Biology SC Anthropology; Life Sciences & Biomedicine - Other Topics GA 517BZ UT WOS:000271589100010 PM 19298010 ER PT J AU Masi, CM Hawkley, LC Xu, X Veenstra, TD Cacioppo, JT AF Masi, Christopher M. Hawkley, Louise C. Xu, Xia Veenstra, Timothy D. Cacioppo, John T. TI Serum Estrogen Metabolites and Systolic Blood Pressure Among Middle-Aged and Older Women and Men SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article ID ESTRADIOL METABOLITES; HYPERTENSION; PREVALENCE; AWARENESS; RECEPTOR; TRENDS; CELLS AB BACKGROUND Hypertension is more common among men at younger ages and among women after age 60, suggesting a possible link between endogenous estrogens and systolic blood pressure (SBP) We tested whether serum 17 beta-estradiol (E(2)) or any of its metabolites were associated with SBP among middle-aged and older adults. METHODS Using a cross-sectional study design, we examined data from a population-based sample of 98 adults living in Cook County, Illinois. Age ranged between 55 and 69 years and body mass index (BMI) ranged between 19.8 and 50.6 kg/m(2). Serum was analyzed for 17 beta-E(2) and 14 estrogen metabolites (EMS) using mass spectrometry. SBP was measured using a tonometric device that records a pulse wave at the radial artery. Demographic and health history information were obtained via questionnaires. RESULTS Univariate analysis revealed an inverse relationship between SBP and both natural log (in) 16 alpha-hydroxyestrone (OHE(1)) (r = -0.360, P < 0.05) and In 16-ketoestradiol (ketoE(2)) (r = -0.360, P < 0.05) among women but not men. No significant correlations were found between SBP and 17 beta-E(2) in either sex. In multivariate analysis which adjusted for age, race, ethnicity, BMI, and use of cardiovascular medications, In 16 alpha-hydroxyestrone (16 alpha-OHE(1)) (B = -5.3, s.e. = 2.1, P < 0.05) and In 16-ketoE(2) (B = -4.7, s.e. = 1.9, P < 0.05) continued to be negatively associated with SBP among postmenopausal women. CONCLUSIONS These data suggest that serum 16 alpha-OHE(1) or 16-ketoE(2) may be important for vascular health among postmenopausal women but not among similarly aged men. Am J Hypertens 2009; 22:1148-1153 (C) 2009 American Journal of Hypertension, Ltd. C1 [Masi, Christopher M.] Univ Chicago, Gen Internal Med Sect, Chicago, IL 60637 USA. [Masi, Christopher M.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Hawkley, Louise C.; Cacioppo, John T.] Univ Chicago, Ctr Cognit & Social Neurosci, Chicago, IL 60637 USA. [Hawkley, Louise C.; Cacioppo, John T.] Univ Chicago, Dept Psychol, Chicago, IL 60637 USA. [Xu, Xia; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, SAIC Frederick Inc, Adv Technol Program, Frederick, MD 21701 USA. RP Masi, CM (reprint author), Univ Chicago, Gen Internal Med Sect, Chicago, IL 60637 USA. EM cmasi@medicine.bsd.uchicago.edu FU National Institute on Aging Career Development Award [5K08AG027200-02]; National Institute on Aging [R01 AG034052-01]; National Cancer Institute, National Institutes of Health [N01-CO-12400]; Department of Health and Human Services FX This work was supported by a National Institute on Aging Career Development Award 5K08AG027200-02 (principal investigator: C.M. Masi) and a National Institute on Aging R01 AG034052-01 (principal investigator: J.T. Cacioppo). This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 17 TC 10 Z9 10 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD NOV PY 2009 VL 22 IS 11 BP 1148 EP 1153 DI 10.1038/ajh.2009.155 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 516IB UT WOS:000271534400006 PM 19713943 ER PT J AU Solomon, BD Pineda-Alvarez, DE Balog, JZ Hadley, D Gropman, AL Nandagopal, R Han, JC Hahn, JS Blain, D Brooks, B Muenke, M AF Solomon, Benjamin D. Pineda-Alvarez, Daniel E. Balog, Joan Z. Hadley, Donald Gropman, Andrea L. Nandagopal, Radha Han, Joan C. Hahn, Jin S. Blain, Delphine Brooks, Brian Muenke, Maximilian TI Compound Heterozygosity for Mutations in PAX6 in a Patient With Complex Brain Anomaly, Neonatal Diabetes Mellitus, and Microophthalmia SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE PAX6; microophthalmia; aniridia; neonatal diabetes mellitus ID CRYSTAL-STRUCTURE; ANIRIDIA; GENE; HOMEODOMAIN; DNA AB We report on a patient with trisomy 21, microophthalmia, neonatal diabetes mellitus, hypopituitarism, and a complex structural brain anomaly who was a member of a large bilineal family with eye anomalies. The patient inherited a different mutation in PAX6 from each parent and is the only known living and second reported patient with compound heterozygosity for mutations in PAX6. PAX6 is a transcription factor involved in eye and brain development and has roles in pancreatic and pituitary development. Clinical evaluation of the propositus and his parents demonstrated the effects of mutations of differing severity in multiple individuals. Published 2009 Wiley-Liss, Inc.(dagger) C1 [Solomon, Benjamin D.; Pineda-Alvarez, Daniel E.; Balog, Joan Z.; Hadley, Donald; Gropman, Andrea L.; Muenke, Maximilian] NHGRI, NIH, Bethesda, MD 20892 USA. [Gropman, Andrea L.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Nandagopal, Radha; Han, Joan C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Hahn, Jin S.] Stanford Univ, Palo Alto, CA 94304 USA. [Blain, Delphine; Brooks, Brian] NEI, NIH, Bethesda, MD 20892 USA. [Blain, Delphine] MedStar Res Inst, Hyattsville, MD USA. RP Muenke, M (reprint author), NHGRI, NIH, Bldg 35,Room 1B-203,MSC 3717, Bethesda, MD 20892 USA. EM mamuenke@mail.nih.gov FU National Human Genome Research Institute; National Institutes of Health FX Grant sponsor: National Human Genome Research Institute, National Institutes of Health. NR 18 TC 28 Z9 29 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD NOV PY 2009 VL 149A IS 11 BP 2543 EP 2546 DI 10.1002/ajmg.a.33081 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 517BL UT WOS:000271587600031 PM 19876904 ER PT J AU Conde-Agudelo, A Romero, R AF Conde-Agudelo, Agustin Romero, Roberto TI Amniotic fluid embolism: an evidence-based review SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Review DE amniotic fluid embolism; cardiovascular collapse; DIC; disseminated intravascular coagulation; maternal death; maternal morbidity; maternal mortality; perinatal mortality; pregnancy ID DISSEMINATED INTRAVASCULAR COAGULATION; OF-THE-LITERATURE; MATERNAL PULMONARY CIRCULATION; MONOCLONAL-ANTIBODY TKH-2; BLUNT ABDOMINAL-TRAUMA; UNITED-STATES; HEMODYNAMIC-ALTERATIONS; ATYPICAL PRESENTATION; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; HISTOLOGICAL DIAGNOSIS AB We reviewed the best evidence on amniotic fluid embolism (AFE). The estimated incidence of AFE is 1: 15,200 and 1: 53,800 deliveries in North America and Europe, respectively. The case fatality rate and perinatal mortality associated with AFE are 13-30% and 9-44%, respectively. Risk factors associated with increased risk of AFE include advanced maternal age, placental abnormalities, operative deliveries, eclampsia, polyhydramnios, cervical laceration, and uterine rupture. Hemodynamic response to AFE is biphasic, with initial pulmonary hypertension and right ventricular failure, followed by left ventricular failure. Promising therapies include selective pulmonary vasodilators and recombinant activated factor VIIa. Important topics for future research are presented. C1 [Conde-Agudelo, Agustin; Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Conde-Agudelo, Agustin; Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. RP Conde-Agudelo, A (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health; Department of Health and Human Services FX This study was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services. NR 151 TC 29 Z9 37 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD NOV PY 2009 VL 201 IS 5 AR 445.e1 DI 10.1016/j.ajog.2009.04.052 PG 13 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 514FO UT WOS:000271379900012 PM 19879393 ER PT J AU Willinger, M Ko, CW Reddy, UM AF Willinger, Marian Ko, Chia-Wen Reddy, Uma M. TI Racial disparities in stillbirth risk across gestation in the United States SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE racial disparity; stillbirth ID FETAL-DEATH; PERINATAL-MORTALITY; ETHNIC-DIFFERENCES; AFRICAN-AMERICANS; INFANT-MORTALITY; BIRTH-WEIGHT; PREGNANCY; RATES; AGE; CERTIFICATES AB OBJECTIVE: We sought to determine factors associated with racial disparities in stillbirth risk. STUDY DESIGN: Stillbirth hazard was analyzed using 5,138,122 singleton gestations from the National Center of Health Statistics perinatal mortality and birth files, 2001-2002. RESULTS: Black women have a 2.2-fold increased risk of stillbirth compared with white women. The black/white disparity in stillbirth hazard at 20-23 weeks is 2.75, decreasing to 1.57 at 39-40 weeks. Higher education reduced the hazard for whites more than for blacks and Hispanics. Medical, pregnancy, and labor complications accounted for 30% of the hazard in blacks and 20% in whites and Hispanics. Congenital anomalies and small for gestational age contributed more to preterm stillbirth risk among whites than blacks. Pregnancy and labor conditions contributed more to preterm stillbirth risk among blacks than whites. CONCLUSION: The excess stillbirth risk for blacks was greatest at preterm gestations, and factors contributing to stillbirth risk vary by race and gestational age. C1 [Willinger, Marian; Reddy, Uma M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, Ctr Dev Biol & Perinatal Med, NIH, Bethesda, MD USA. [Ko, Chia-Wen] Natl Inst Deafness & Other Commun Disorders, Epidemiol & Biostat Program, NIH, Bethesda, MD USA. RP Willinger, M (reprint author), NICHHD, Pregnancy & Perinatol Branch, Ctr Dev Biol & Perinatal Med, 6100 Execut Blvd,Room 4B03H, Rockville, MD 20852 USA. EM willingm@mail.nih.gov FU Intramural NIH HHS [Z99 HD999999] NR 30 TC 14 Z9 14 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD NOV PY 2009 VL 201 IS 5 AR 469.e1 DI 10.1016/j.ajog.2009.06.057 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 514FO UT WOS:000271379900018 PM 19762004 ER PT J AU Sen, HN Nussenblatt, RB AF Sen, H. Nida Nussenblatt, Robert B. TI Sympathetic Ophthalmia: What Have We Learned? SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Editorial Material ID TRENDS C1 [Sen, H. Nida; Nussenblatt, Robert B.] NEI, NIH, Bethesda, MD 20892 USA. RP Sen, HN (reprint author), NEI, NIH, 10 Ctr Dr,Bldg 10,Room 10N112, Bethesda, MD 20892 USA. EM senh@nei.nih.gov FU Intramural NIH HHS [Z99 EY999999] NR 17 TC 10 Z9 10 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD NOV PY 2009 VL 148 IS 5 BP 632 EP 633 DI 10.1016/j.ajo.2009.07.024 PG 2 WC Ophthalmology SC Ophthalmology GA 518DA UT WOS:000271669300002 PM 19878754 ER PT J AU Sen, HN Levy-Clarke, G Faia, LJ Li, ZQ Yeh, S Barron, KS Ryan, JG Hammel, K Nussenblatt, RB AF Sen, H. Nida Levy-Clarke, Grace Faia, Lisa J. Li, Zhuqing Yeh, Steven Barron, Karyl S. Ryan, John G. Hammel, Keri Nussenblatt, Robert B. TI High-dose Daclizumab for the Treatment of Juvenile Idiopathic Arthritis-Associated Active Anterior Uveitis SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID REFRACTORY CHILDHOOD UVEITIS; RHEUMATOID-ARTHRITIS; RENAL-TRANSPLANTATION; NONINFECTIOUS UVEITIS; OCULAR COMPLICATIONS; VISUAL OUTCOMES; ACUTE REJECTION; CLINICAL-TRIAL; RISK-FACTORS; THERAPY AB PURPOSE: To provide preliminary data regarding the safety and efficacy of high-dose intravenous daclizumab (Zenapax; Roche Inc, Nutley, New Jersey, USA) thereapy for the treatment of juvenile idiopathic arthritis (JIA)-associated active anterior uveitis. DESIGN: Interventional case series; open,label prospective, phase 11 pilot study. METHODS: Six patients were recruited into the study and received daclizumab therapy at doses of 8 mg/kg at baseline, 4 mg/kg at week 2, and 2 mg/kg every 4 weeks thereafter, for a total of 52 weeks. The study was done at the National Eye Institute between June 29, 2005 and July 9, 2008. The primary outcome was a two-step decrease in inflammation grade assessed at week 12. Primary safety outcome was assessed at weeks 2 and 4. The ocular inflammation was assessed according to the Standardization of Uveitis Nomenclature criteria. RESULTS: Four of the 6 participants achieved two,step reduction in anterior chamber cells according to Standardization of Uveitis Nomenclature Working Group grading scheme for anterior chamber cells 12 weeks into the study and met the primary efficacy endpoint. One additional patient responded to reinduction whereas 1 patient failed reinduction and was considered an ocular treatment failure. Visual acuity improved from a mean of 68 Early Treatment Diabetic Retinopathy Study letters in the worse eye to a mean of 79.6 letters (2 Snellen lines). Three participants were terminated before 52 weeks: First, because of a rash possibly induced by daclizumab; Second, because of ocular treatment failure; and Last, because of uncontrolled systemic manifestations of JIA. CONCLUSION: High,dose intravenous daclizumab can help reduce active inflammation in active JIA-associated anterior uveitis; however, patients need to be monitored for potential side effects. Larger randomized trials are needed to better assess treatment effect and safety. (Am J Ophthalmol 2009;148:696-703. Published by Elsevier Inc.) C1 [Sen, H. Nida; Levy-Clarke, Grace; Faia, Lisa J.; Li, Zhuqing; Yeh, Steven; Nussenblatt, Robert B.] NEI, NIH, Bethesda, MD 20892 USA. [Barron, Karyl S.] NIAID, NIH, Bethesda, MD 20892 USA. [Ryan, John G.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Hammel, Keri] EMMES Corp, Rockville, MD USA. RP Sen, HN (reprint author), NEI, NIH, 10 Ctr Dr,Bldg 10,Rm 10N112, Bethesda, MD 20892 USA. EM senh@nei.nih.gov FU NATIONAL EYE INSTITUTE INTRAMURAL PROGRAM; NATIONAL INSTITUTE OF HEALTH, Bethesda, Maryland FX THIS STUDY WAS SUPPORTED BY THE NATIONAL EYE INSTITUTE INTRAMURAL PROGRAM, NATIONAL INSTITUTE OF HEALTH, Bethesda, Maryland. The authors indicate no financial conflict of interest. Involved in design and conduct of study (G.L.C., R.B.N., K.B., J.R., L.J.F., S.Y., K.H.); collection of data (H.N.S., L.J.F., S.Y.); management (R.B.N.), analysis (H.N.S.), and interpretation of data (H.N.S., R.B.N., Z.L.); and preparation (H.N.S., L.J.F.), review, or approval of the manuscript (H.N.S., L.J.F., R.B.N.). The study was conducted at the National Eye Institute, National Institutes of Health underan Investigational New Drug (IND) application. The study protocol was reviewed and approved by the Institutional Review Board of the National Eye Institute and all procedures conformed to the tenets of the Declaration of Helsinki. Clinical Trials registration: NCT00130637 (NEI protocol no.: 05-EI-0208). NR 35 TC 31 Z9 31 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD NOV PY 2009 VL 148 IS 5 BP 696 EP 703 DI 10.1016/j.ajo.2009.06.003 PG 8 WC Ophthalmology SC Ophthalmology GA 518DA UT WOS:000271669300010 PM 19664754 ER PT J AU Andersson, S Sowjanya, P Wangsa, D Hjerpe, A Johansson, B Auer, G Gravitt, PE Larsson, C Wallin, KL Ried, T Heselmeyer-Haddad, K AF Andersson, Sonia Sowjanya, Pavani Wangsa, Darawalee Hjerpe, Anders Johansson, Bo Auer, Gert Gravitt, Patti E. Larsson, Catharina Wallin, Keng-Ling Ried, Thomas Heselmeyer-Haddad, Kerstin TI Detection of Genomic Amplification of the Human Telomerase Gene TERC, a Potential Marker for Triage of Women with HPV-Positive, Abnormal Pap Smears SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; CERVICAL-CANCER PROGRESSION; HUMAN-PAPILLOMAVIRUS TYPES; HIGH-RISK; EPITHELIAL-CELLS; UTERINE CERVIX; VIRAL LOAD; CHROMOSOMAL-ABERRATIONS; RECURRENT PATTERN; IN-SITU AB The vast majority of invasive cervical carcinomas harbor additional copies of the chromosome arm 3q, resulting in genomic amplification of the human telomerase gene TERC. Here, we evaluated TERC amplification in routinely collected liquid based cytology (LBC) samples with histologically confirmed diagnoses. A set of 78 LBC samples from a Swedish patient cohort were analyzed with a four-color fluorescence in situ hybridization probe panel that included TERC. Clinical follow-up included additional histological evaluation and Pap smears. Human papillomavirus status was available for all cases. The correlation of cytology, TERC amplification, human papillomavirus typing, and histological diagnosis showed that infection with high-risk human papillomavirus was detected in 64% of the LBC samples with normal histopathology, in 65% of the cervical intraepithelial neoplasia (CIN)1, 95% of the CIN2, 96% of the CIN3 lesions, and all carcinomas. Seven percent of the lesions with normal histopathology were positive for TERC amplification, 24% of the CIN1, 64% of the CIN2, 91% of the CIN3 lesions, and 100% of invasive carcinomas. This demonstrates that detection of genomic amplification of TERC in LBC samples can identify patients with histopathologically confirmed CIN3 or cancer. indeed, the proportion of TERC-positive cases increases with the severity of dysplasia. Among the markers tested, detection of TERC amplification in cytological samples has the highest combined sensitivity and specificity for discernment of low-grade from high-grade dysplasia and cancer. (Am J Pathol 2009, 175:1831-1847; DOI. 10.2353/ajpath.2009.090122) C1 [Sowjanya, Pavani; Wangsa, Darawalee; Ried, Thomas; Heselmeyer-Haddad, Kerstin] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Andersson, Sonia] Karolinska Univ Hosp Huddinge, Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden. [Hjerpe, Anders] Karolinska Univ Hosp Huddinge, Karolinska Inst, Div Obstet & Gynecol, Dept Lab Med, Stockholm, Sweden. [Johansson, Bo] Karolinska Univ Hosp Huddinge, Karolinska Inst, Div Clin Virol, Dept Lab Med, Stockholm, Sweden. [Wangsa, Darawalee] Karolinska Univ Hosp Solna, Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden. [Gravitt, Patti E.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Ried, T (reprint author), NCI, Genet Branch, Ctr Canc Res, NIH, 50 S Dr,Bldg 50,Rm 1306, Bethesda, MD 20892 USA. EM riedt@mail.nih.gov FU Swedish Cancer Foundation [CAN 2007/1044]; Swedish Research Council; Medical Research Council; Cancer Society in Stockholm; Goran Gustafsson Foundation; Stockholm County Council; Swedish Labor Market Insurance; NIH, National Cancer Institute; NIH SPORE [P50 CA98252] FX Supported by The Swedish Cancer Foundation (CAN 2007/1044), the Swedish Research Council, the Medical Research Council, the Cancer Society in Stockholm, the Goran Gustafsson Foundation, the Stockholm County Council, and the Swedish Labor Market Insurance and the Intramural Research Program of the NIH, National Cancer Institute. P. Gravitt and P. Sowjanya were funded via the NIH SPORE P50 CA98252. NR 41 TC 36 Z9 45 U1 0 U2 5 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 2009 VL 175 IS 5 BP 1831 EP 1847 DI 10.2353/ajpath.2009.090122 PG 17 WC Pathology SC Pathology GA 515BH UT WOS:000271440800007 PM 19880826 ER PT J AU Yuasa, T Kondo, N Yasuhara, R Shimono, K Mackeem, S Pacifici, M Iwamoto, M Enomoto-Iwamoto, M AF Yuasa, Takahito Kondo, Naoki Yasuhara, Rika Shimono, Kengo Mackeem, Susan Pacifici, Maurizio Iwamoto, Masahiro Enomoto-Iwamoto, Motomi TI Transient Activation of Wnt/beta-Catenin Signaling Induces Abnormal Growth Plate Closure and Articular Cartilage Thickening in Postnatal Mice SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID CHONDROCYTE DIFFERENTIATION; STEM/PROGENITOR CELLS; LIMB SKELETOGENESIS; PROGENITOR CELLS; GENE-EXPRESSION; NOTCH RECEPTORS; SYNOVIAL JOINT; SELF-RENEWAL; APOPTOSIS; TRANSCRIPTION AB Wnt/beta-catenin signaling is required for skeletal development and organization and for function of the growth plate and articular cartilage. To further clarify these roles and their possible pathophysiological importance, we created a new transgenic mouse model in which Wnt/beta-catenin signaling can be activated in cartilage for specific periods of time. These transgenic mice expressed a constitutive active form of beta-catenin fused to a modified estrogen receptor ligand-binding domain under the control of cartilage-specific collagen 11 alpha 2 promoter/enhancer. Transient Wnt/beta-catenin signaling activation in young adult mice by tamoxifen injections induced growth retardation and severe deformities in knee joints. Tibial and femoral growth plates displayed an excessive number of apoptotic cells and eventually underwent abnormal regression. Articular cartilage exhibited an initial acute loss of proteoglycan matrix that was followed by increases in thickness, cell density, and cell proliferation. In reciprocal studies, we found that conditional ablation of beta-catenin in postnatal mice using a Col2-CreER strategy led to hypocellularity in articular cartilage, growth plate disorganization, and a severe reduction in bone volume. Together, these data provide evidence that Wnt/beta-catenin signaling has important and distinct roles in growth plate and articular cartilage and that postnatal dysregulation of this signaling pathway causes diverse structural and functional changes in the two cartilaginous structures. (Am J Pathol 2009, 175:1993-2003; DOI: 10.2353/ajpath.2009.081173) C1 [Yuasa, Takahito; Kondo, Naoki; Yasuhara, Rika; Shimono, Kengo; Pacifici, Maurizio; Iwamoto, Masahiro; Enomoto-Iwamoto, Motomi] Thomas Jefferson Univ, Dept Orthoped Surg, Coll Med, Philadelphia, PA 19107 USA. [Mackeem, Susan] NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Enomoto-Iwamoto, M (reprint author), Thomas Jefferson Univ, Dept Orthoped Surg, Coll Med, 1015 Walnut St,501 Curtis Bldg, Philadelphia, PA 19107 USA. EM motomi.iwamoto@jefferson.edu FU National Institute of Arthritis & Musculoskeletal Skin Diseases [AR050507, AR046000]; National Institute on Aging [AG025868] FX Supported by the National Institute of Arthritis & Musculoskeletal & Skin Diseases (grants AR050507 and AR046000) and the National Institute on Aging (grant AG025868). NR 38 TC 36 Z9 36 U1 1 U2 6 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 2009 VL 175 IS 5 BP 1993 EP 2003 DI 10.2353/ajpath.2009.081173 PG 11 WC Pathology SC Pathology GA 515BH UT WOS:000271440800021 PM 19815716 ER PT J AU Bianco, C Cotten, C Lonardo, E Strizzi, L Baraty, C Mancino, M Gonzales, M Watanabe, K Nagaoka, T Berry, C Arai, AE Minchiotti, G Salomon, DS AF Bianco, Caterina Cotten, Catherine Lonardo, Enza Strizzi, Luigi Baraty, Christina Mancino, Mario Gonzales, Monica Watanabe, Kazuhide Nagaoka, Tadahiro Berry, Colin Arai, Andrew E. Minchiotti, Gabriella Salomon, David S. TI Cripto-1 Is Required for Hypoxia to Induce Cardiac Differentiation of Mouse Embryonic Stem Cells SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID GROWTH-FACTOR; FACTOR 1-ALPHA; MAMMARY-GLAND; TUMOR-GROWTH; COLON-CANCER; FACTOR-I; EXPRESSION; GENE; MORPHOGENESIS; ANGIOGENESIS AB Cripto-1 is a membrane-bound protein that is highly expressed in embryonic stem cells and in human tumors. in the present study, we investigated the effect of low levels of oxygen, which occurs naturally in rapidly growing tissues, on Cripto-1 expression in mouse embryonic stem (mES) cells and in human embryonal carcinoma cells. During hypoxia, Cripto-1 expression levels were significantly elevated in mES cells and in Ntera-2 or NCCIT human embryonal carcinoma cells, as compared with cells growing with normal oxygen levels. The transcription factor hypoxia-inducible factor-1 alpha directly regulated Cripto-1 expression by binding to hypoxia-responsive elements within the promoter of mouse and human Cripto-1 genes in mES and NCCIT cells, respectively. Furthermore, hypoxia modulated differentiation of mES cells by enhancing formation of beating cardiomyocytes as compared with mES cells that were differentiated under normoxia. However, hypoxia failed to induce differentiation of mES cells into cardiomyocytes in the absence of Cripto-1 expression, demonstrating that Cripto-1 is required for hypoxia to fully differentiate mES cells into cardiomyocytes. Finally, cardiac tissue samples derived from patients who had suffered ischemic heart disease showed a dramatic increase in Cripto-1 expression as compared with nonischemic heart tissue samples, suggesting that hypoxia may also regulate Cripto-1 in vivo. (Ani J Pathol 2009, 175:2146-2158, DOI: 10.2353/ajpath.2009.090218) C1 [Bianco, Caterina; Cotten, Catherine; Strizzi, Luigi; Baraty, Christina; Mancino, Mario; Gonzales, Monica; Watanabe, Kazuhide; Nagaoka, Tadahiro; Salomon, David S.] NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Arai, Andrew E.] NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. [Lonardo, Enza; Berry, Colin; Minchiotti, Gabriella] CNR, Inst Genet & Biophys A Buzzati Traverso, Stem Cell Fate Lab, Naples, Italy. RP Salomon, DS (reprint author), NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, 37 Convent Dr,Bldg 37,Room 1118, Bethesda, MD 20892 USA. EM Salomond@mail.nih.gov RI Lonardo, Enza/A-8786-2011; OI Nagaoka, Tadahiro/0000-0002-9391-0243 FU Intramural Research program of the National Institutes of Health; National Cancer Institute; Center for Cancer Research; Associazione Italiana per la Ricerca sul Cancro; Faculty of Medicine, University of Glaskow FX Supported by Intramural Research program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research, by a grant from the Associazione Italiana per la Ricerca sul Cancro (to G.M.), and by a grant of the Faculty of Medicine, University of Glaskow (to C.B.). NR 47 TC 33 Z9 33 U1 0 U2 3 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 2009 VL 175 IS 5 BP 2146 EP 2158 DI 10.2353/ajpath.2009.090218 PG 13 WC Pathology SC Pathology GA 515BH UT WOS:000271440800035 PM 19834060 ER PT J AU Grobman, WA Lai, YL Landon, MB Spong, CY Leveno, KJ Rouse, DJ Varner, MW Moawad, AH Simhan, HN Harper, M Wapner, RJ Sorokin, Y Miodovnik, M Carpenter, M O'Sullivan, MJ Sibai, BM Langer, O Thorp, JM Ramin, SM Mercer, BM AF Grobman, William A. Lai, Yinglei Landon, Mark B. Spong, Catherine Y. Leveno, Kenneth J. Rouse, Dwight J. Varner, Michael W. Moawad, Atef H. Simhan, Hyagriv N. Harper, Margaret Wapner, Ronald J. Sorokin, Yoram Miodovnik, Menachem Carpenter, Marshall O'Sullivan, Mary J. Sibai, Baha M. Langer, Oded Thorp, John M. Ramin, Susan M. Mercer, Brian M. TI Does Information Available at Admission for Delivery Improve Prediction of Vaginal Birth after Cesarean? SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Article DE Trial of labor; vaginal birth after cesarean; prediction ID LABOR AB We sought to construct a predictive model for vaginal birth after cesarean (VBAC) that combines factors that can be ascertained only as the pregnancy progresses with those known at initiation of prenatal care. Using multivariable modeling, we constructed a predictive model for VBAC that included patient factors known at the initial prenatal visit as well as those that only become evident as the pregnancy progresses to the admission for delivery. We analyzed 9616 women. The regression equation for VBAC success included multiple factors that could not be known at the first prenatal visit. The area under the curve for this model was significantly greater (p<0.001) than that of a model that included only factors available at the first prenatal visit. A prediction model for VBAC success, which incorporates factors that can be ascertained only as the pregnancy progresses, adds to the predictive accuracy of a model that uses only factors available at a first prenatal visit. C1 [Grobman, William A.] Northwestern Univ, Dept Obstet, Chicago, IL 60611 USA. [Grobman, William A.] Northwestern Univ, Dept Gynecol, Chicago, IL 60611 USA. [Lai, Yinglei] George Washington Univ, Ctr Biostat, Washington, DC USA. [Landon, Mark B.] Ohio State Univ, Columbus, OH 43210 USA. [Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Leveno, Kenneth J.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Rouse, Dwight J.] Univ Alabama, Birmingham, AL USA. [Varner, Michael W.] Univ Chicago, Chicago, IL 60637 USA. [Moawad, Atef H.] Univ Utah, Salt Lake City, UT USA. [Simhan, Hyagriv N.] Univ Pittsburgh, Pittsburgh, PA USA. [Harper, Margaret] Wake Forest Univ, Winston Salem, NC 27109 USA. [Wapner, Ronald J.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Sorokin, Yoram] Wayne State Univ, Detroit, MI USA. [Miodovnik, Menachem] Columbia Univ, New York, NY USA. [Miodovnik, Menachem] Univ Cincinnati, Cincinnati, OH USA. [Carpenter, Marshall] Brown Univ, Providence, RI 02912 USA. [O'Sullivan, Mary J.] Univ Miami, Miami, FL USA. [Sibai, Baha M.] Univ Tennessee, Memphis, TN USA. [Langer, Oded] Univ Texas San Antonio, San Antonio, TX USA. [Thorp, John M.] Univ N Carolina, Chapel Hill, NC USA. [Ramin, Susan M.] Univ Texas Houston, Houston, TX USA. [Mercer, Brian M.] Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Grobman, WA (reprint author), 250 E Super St,Suite 05-2175, Chicago, IL 60611 USA. EM w-grobman@northwestern.edu RI Varner, Michael/K-9890-2013 OI Varner, Michael/0000-0001-9455-3973 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [HD21410, HD21414, HD27860, HD27861, HD27869, HD27905, HD27915, HD27917, HD34116, HD34122, HD34136, HD34208, HD34210, HD40500, HD40485, HD40544, HD40545, HD40560, HD40512, HD36801] FX Supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD21410, HD21414, HD27860, HD27861, HD27869, HD27905, HD27915, HD27917, HD34116, HD34122, HD34136, HD34208, HD34210, HD40500, HD40485, HD40544, HD40545, HD40560, HD40512, and HD36801). NR 7 TC 29 Z9 30 U1 0 U2 3 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0735-1631 J9 AM J PERINAT JI Am. J. Perinatol. PD NOV PY 2009 VL 26 IS 10 BP 693 EP 701 DI 10.1055/s-0029-1239494 PG 9 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 507VN UT WOS:000270883400002 PM 19813165 ER PT J AU Muniyappa, R Chen, H Muzumdar, RH Einstein, FH Yan, X Yue, LQ Barzilai, N Quon, MJ AF Muniyappa, Ranganath Chen, Hui Muzumdar, Radhika H. Einstein, Francine H. Yan, Xu Yue, Lilly Q. Barzilai, Nir Quon, Michael J. TI Comparison between surrogate indexes of insulin sensitivity/resistance and hyperinsulinemic euglycemic clamp estimates in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE glucose clamp; calibration model; quantitative insulin-sensitivity check index ID HOMEOSTASIS MODEL ASSESSMENT; TYPE-2 DIABETIC-PATIENTS; FASTING PLASMA-GLUCOSE; BETA-CELL FUNCTION; CHECK INDEX; CARDIOVASCULAR-DISEASE; RECIPROCAL INDEX; VISCERAL FAT; RESISTANCE; MICE AB Muniyappa R, Chen H, Muzumdar RH, Einstein FH, Yan X, Yue LQ, Barzilai N, Quon MJ. Comparison between surrogate indexes of insulin sensitivity/resistance and hyperinsulinemic euglycemic clamp estimates in rats. Am J Physiol Endocrinol Metab 297: E1023-E1029, 2009. First published August 25, 2009; doi: 10.1152/ajpendo.00397.2009.-Assessing insulin resistance in rodent models gives insight into mechanisms that cause type 2 diabetes and the metabolic syndrome. The hyperinsulinemic euglycemic glucose clamp, the reference standard for measuring insulin sensitivity in humans and animals, is labor intensive and technically demanding. A number of simple surrogate indexes of insulin sensitivity/resistance have been developed and validated primarily for use in large human studies. These same surrogates are also frequently used in rodent studies. However, in general, these indexes have not been rigorously evaluated in animals. In a recent validation study in mice, we demonstrated that surrogates have a weaker correlation with glucose clamp estimates of insulin sensitivity/resistance than in humans. This may be due to increased technical difficulties in mice and/or intrinsic differences between human and rodent physiology. To help distinguish among these possibilities, in the present study, using data from rats substantially larger than mice, we compared the clamp glucose infusion rate (GIR) with surrogate indexes, including QUICKI, HOMA, 1/HOMA, log (HOMA), and 1/fasting insulin. All surrogates were modestly correlated with GIR (r = 0.34-0.40). Calibration analyses of surrogates adjusted for body weight demonstrated similar predictive accuracy for GIR among all surrogates. We conclude that linear correlations of surrogate indexes with clamp estimates and predictive accuracy of surrogate indexes in rats are similar to those in mice (but not as substantial as in humans). This additional rat study (taken with the previous mouse study) suggests that application of surrogate insulin sensitivity indexes developed for humans may not be appropriate for determining primary outcomes in rodent studies due to intrinsic differences in metabolic physiology. However, use of surrogates may be appropriate in rodents, where feasibility of clamps is an obstacle and measurement of insulin sensitivity is a secondary outcome. C1 [Muniyappa, Ranganath; Chen, Hui; Quon, Michael J.] NIH, Diabet Unit, NCCAM, Bethesda, MD 20892 USA. [Yan, Xu; Yue, Lilly Q.] US FDA, Div Biostat, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. [Muzumdar, Radhika H.; Einstein, Francine H.; Barzilai, Nir] Albert Einstein Coll Med, Inst Aging Res, Bronx, NY 10467 USA. [Muzumdar, Radhika H.; Einstein, Francine H.; Barzilai, Nir] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. RP Quon, MJ (reprint author), NIH, Diabet Unit, NCCAM, 9 Mem Dr,Bldg 9,Rm 1N-105 MSC 0920, Bethesda, MD 20892 USA. EM quonm@nih.gov RI Muzumdar, Radhika/D-9860-2014; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 FU Intramural Research Program; National Center for Complementary and Alternative Medicine; National Institutes of Health [K08-AG-027462, P60-DK-20541, R01-AG-18381, T32-AG-23475, P01-AG-021654]; Albert Einstein Diabetes Research and Training Center [P60-DK-20541] FX This work was supported by the Intramural Research Program, the National Center for Complementary and Alternative Medicine, and grants from the National Institutes of Health (K08-AG-027462 and P60-DK-20541 to R. H. Muzumdar; R01-AG-18381, T32-AG-23475, and P01-AG-021654 to N. Barzilai) and the Core Laboratories of the Albert Einstein Diabetes Research and Training Center (P60-DK-20541). NR 30 TC 25 Z9 26 U1 0 U2 2 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 2009 VL 297 IS 5 BP E1023 EP E1029 DI 10.1152/ajpendo.00397.2009 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 509CL UT WOS:000270990500007 PM 19706785 ER PT J AU Deschamps, AM Murphy, E AF Deschamps, Anne M. Murphy, Elizabeth TI Activation of a novel estrogen receptor, GPER, is cardioprotective in male and female rats SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE Langendorff; ischemia-reperfusion; G-1; G protein-coupled receptor 30; G protein-coupled estrogen receptor ID PROTEIN-COUPLED RECEPTOR; GROWTH-FACTOR RECEPTOR; ISCHEMIA-REPERFUSION INJURY; CORONARY-HEART-DISEASE; CARDIOVASCULAR-SYSTEM; POSTMENOPAUSAL WOMEN; SELECTIVE AGONIST; SIGNAL STRENGTH; CANCER-CELLS; KINASE AB Deschamps AM, Murphy E. Activation of a novel estrogen receptor, GPER, is cardioprotective in male and female rats. Am J Physiol Heart Circ Physiol 297: H1806-H1813, 2009. First published August 28, 2009; doi:10.1152/ajpheart.00283.2009.-Premenopausal females have a lower incidence of cardiovascular disease than their male counterparts, but the mechanism is unclear. Estrogen has been thought to signal through two nuclear receptors: estrogen receptor-alpha or estrogen receptor-beta; however, a third, membrane-bound receptor G protein-coupled estrogen receptor (GPER), has been identified and shown to bind estrogen with high affinity. To date, there is little information on GPER in the heart and no study has looked at the effect of GPER activation during myocardial ischemia-reperfusion (I/R). Therefore, the goal of this study was to determine whether activation of GPER is cardioprotective in rats. A highly specific GPER agonist, G-1, was administered to Sprague-Dawley (200-350 g) rat hearts 10 min before 20 min of ischemic followed by 120 min of reperfusion using a Langendorff model. Similar levels of GPER were found in both male and female rat hearts. With administration of 110 nM of G-1, postischemic contractile dysfunction was significantly reduced compared with untreated controls (43.8 +/- 4.3% vs. 26.9 +/- 2.1% of preischemic rate pressure product; P < 0.05). Additionally, infarct size was reduced in the G-1-treated animals when compared with control (18.8 +/- 2.7% vs. 32.4 +/- 2.1%; P < 0.05). These observations were demonstrated in both male and intact female rat hearts. Through Western blot analysis, it was demonstrated that G-1 induces the activation of both Akt and ERK1/2. Furthermore, the protection afforded by G-1 was blocked by coadministration of a phosphatidylinositol 3-kinase (PI3K) inhibitor (wortmannin, 100 nM). Taken together, the data show that G-1 activation of GPER improves functional recovery and reduces infarct size in isolated rat hearts following I/R through a PI3K-dependent, gender-independent mechanism. C1 [Deschamps, Anne M.; Murphy, Elizabeth] NHLBI, NIH, Translat Med Branch, Lab Cardiac Physiol, Bethesda, MD 20892 USA. RP Murphy, E (reprint author), NHLBI, NIH, Translat Med Branch, Lab Cardiac Physiol, Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. EM murphy1@mail.nih.gov OI Deschamps, Anne/0000-0001-7415-1408 FU National Heart, Lung, and Blood Institute FX These studies were supported by the National Heart, Lung, and Blood Institute intramural program. NR 37 TC 94 Z9 98 U1 0 U2 7 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 2009 VL 297 IS 5 BP H1806 EP H1813 DI 10.1152/ajpheart.00283.2009 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 511DF UT WOS:000271143400032 PM 19717735 ER PT J AU Nomura-Kitabayashi, A Phoon, CKL Kishigami, S Rosenthal, J Yamauchi, Y Abe, K Yamamura, K Samtani, R Lo, CW Mishina, Y AF Nomura-Kitabayashi, Aya Phoon, Colin K. L. Kishigami, Satoshi Rosenthal, Julie Yamauchi, Yasutaka Abe, Kuniya Yamamura, Ken-ichi Samtani, Rajeev Lo, Cecilia W. Mishina, Yuji TI Outflow tract cushions perform a critical valve-like function in the early embryonic heart requiring BMPRIA-mediated signaling in cardiac neural crest SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE bone morphogenetic proteins; endocardial cushions; heart defects congenital; heart development; ultrasound biomicroscopy ID MORPHOGENETIC PROTEIN-RECEPTOR; ULTRASOUND BIOMICROSCOPY-DOPPLER; ENDOCARDIAL CUSHION; MOUSE EMBRYOGENESIS; TRANSCRIPTION FACTOR; CONDUCTION SYSTEM; GENE-EXPRESSION; NF-ATC; SEPTATION; MICE AB Nomura-Kitabayashi A, Phoon CK, Kishigami S, Rosenthal J, Yamauchi Y, Abe K, Yamamura K, Samtani R, Lo CW, Mishina Y. Outflow tract cushions perform a critical valve-like function in the early embryonic heart requiring BMPRIA-mediated signaling in cardiac neural crest. Am J Physiol Heart Circ Physiol 297: H1617-H1628, 2009. First published August 28, 2009; doi:10.1152/ajpheart.00304.2009.-Neural crest-specific ablation of BMP type IA receptor (BMPRIA) causes embryonic lethality by embryonic day (E) 12.5, and this was previously postulated to arise from a myocardial defect related to signaling by a small population of cardiac neural crest cells (cNCC) in the epicardium. However, as BMP signaling via cNCC is also required for proper development of the outflow tract cushions, precursors to the semilunar valves, a plausible alternate or additional hypothesis is that heart failure may result from an outflow tract cushion defect. To investigate whether the outflow tract cushions may serve as dynamic valves in regulating hemodynamic function in the early embryo, in this study we used noninvasive ultrasound biomicroscopy-Doppler imaging to quantitatively assess hemodynamic function in mouse embryos with P0-Cre transgene mediated neural crest ablation of Bmpr1a (P0 mutants). Similar to previous studies, the neural crest-deleted Bmpr1a P0 mutants died at similar to E12.5, exhibiting persistent truncus arteriosus, thinned myocardium, and congestive heart failure. Surprisingly, our ultrasound analyses showed normal contractile indices, heart rate, and atrioventricular conduction in the P0 mutants. However, reversed diastolic arterial blood flow was detected as early as E11.5, with cardiovascular insufficiency and death rapidly ensuing by E12.5. Quantitative computed tomography showed thinning of the outflow cushions, and this was associated with a marked reduction in cell proliferation. These results suggest BMP signaling to cNCC is required for growth of the outflow tract cushions. This study provides definitive evidence that the outflow cushions perform a valve-like function critical for survival of the early mouse embryo. C1 [Phoon, Colin K. L.] NYU, Pediat Cardiol Program, Sch Med, New York, NY 10016 USA. [Nomura-Kitabayashi, Aya; Kishigami, Satoshi] Natl Inst Environm Hlth Sci, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC USA. [Rosenthal, Julie; Samtani, Rajeev; Lo, Cecilia W.] NHLBI, Dev Biol Lab, NIH, Bethesda, MD 20892 USA. [Yamauchi, Yasutaka; Abe, Kuniya; Yamamura, Ken-ichi] Kumamoto Univ, Dept Dev Genet, Inst Mol Embryol & Genet, Kumamoto, Japan. [Mishina, Yuji] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA. RP Phoon, CKL (reprint author), NYU, Pediat Cardiol Program, Sch Med, 160 E 32nd St,2nd Floor, New York, NY 10016 USA. EM colin.phoon@med.nyu.edu FU National Heart, Lung, and Blood Institute [K08-HL-04414]; American Heart Association (Heritage Affiliate) [655907T, Z01-HL-005701]; National Institute of Environmental Health Sciences [ES071003-10]; Japanese Science Promotion Society; Ministry of Education, Culture, Sports, Science, and Technology (Monkasho, Japan) FX This work was supported by National Heart, Lung, and Blood Institute Grants K08-HL-04414 and American Heart Association (Heritage Affiliate) Grant-in-Aid No. 655907T (to C. K. L. Phoon) and Grant Z01-HL-005701 (to C. W. Lo), the Intramural Research Program of the National Institute of Environmental Health Sciences Grant ES071003-10, and a conditional gift from RIKEN-Brain Science Institute to Y. Mishina. S. Kishigami was supported in part by the Japanese Science Promotion Society. K. Yamamura was supported in part by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology (Monkasho, Japan). NR 55 TC 21 Z9 21 U1 0 U2 2 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 2009 VL 297 IS 5 BP H1617 EP H1628 DI 10.1152/ajpheart.00304.2009 PG 12 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 511DF UT WOS:000271143400011 PM 19717734 ER PT J AU Ungvari, Z Labinskyy, N Mukhopadhyay, P Pinto, JT Bagi, Z Ballabh, P Zhang, CH Pacher, P Csiszar, A AF Ungvari, Zoltan Labinskyy, Nazar Mukhopadhyay, Partha Pinto, John T. Bagi, Zsolt Ballabh, Praveen Zhang, Cuihua Pacher, Pal Csiszar, Anna TI Resveratrol attenuates mitochondrial oxidative stress in coronary arterial endothelial cells SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE vasoprotection; histone deacetylase; sirtuin 1 ID SMALL-MOLECULE ACTIVATORS; LIFE-SPAN; SUPEROXIDE-PRODUCTION; CALORIC RESTRICTION; HYDROGEN-PEROXIDE; ENERGY-METABOLISM; SKELETAL-MUSCLE; LIVE CELLS; IN-VIVO; SIRT1 AB Ungvari Z, Labinskyy N, Mukhopadhyay P, Pinto JT, Bagi Z, Ballabh P, Zhang C, Pacher P, Csiszar A. Resveratrol attenuates mitochondrial oxidative stress in coronary arterial endothelial cells. Am J Physiol Heart Circ Physiol 297: H1876-H1881, 2009. First published September 11, 2009; doi:10.1152/ajpheart.00375.2009. The production of hyperglycemia-induced mitochondrial reactive oxygen species (mtROS) is a key event in the development of diabetic complications. Because resveratrol, a naturally occurring polyphenol, has been reported to confer vasoprotection, improving endothelial function and preventing complications of diabetes, we investigated the effect of resveratrol on mtROS production in cultured human coronary arterial endothelial cells (CAECs). The measurement of MitoSox fluorescence showed that resveratrol attenuates both steady-state and high glucose (30 mM)-induced mtROS production in CAECs, an effect that was prevented by the knockdown of the protein deacetylase silent information regulator 2/sirtuin 1 (SIRT1), an intracellular target of resveratrol. An overexpression of SIRT1 mimicked the effects of resveratrol, attenuating mtROS production. Similar results were obtained in CAECs transfected with mitochondria-targeted H(2)O(2)-sensitive HyPer-Mito fluorescent sensor. Amplex red assay showed that resveratrol and SIRT1 overexpression significantly reduced cellular H(2)O(2) levels as well. Resveratrol upregulated MnSOD expression and increased cellular GSH content in a concentration-dependent manner (measured by HPLC coulometric analysis). These effects were attenuated by SIRT1 knockdown and mimicked by SIRT1 overexpression. We propose that resveratrol, via a pathway that involves the activation of SIRT1 and the upregulation of antioxidant defense mechanisms, attenuates mtROS production, suggesting the potential for new treatment approaches targeting endothelial mitochondria in metabolic diseases. C1 [Ungvari, Zoltan; Labinskyy, Nazar; Bagi, Zsolt; Csiszar, Anna] New York Med Coll, Dept Physiol, Valhalla, NY 10595 USA. [Pinto, John T.] New York Med Coll, Dept Biochem, Valhalla, NY 10595 USA. [Ballabh, Praveen] New York Med Coll, Dept Anat & Cell Biol & Pediat, Valhalla, NY 10595 USA. [Ungvari, Zoltan; Csiszar, Anna] Univ Oklahoma, Hlth Sci Ctr, Dept Geriatr Med, Reynolds Oklahoma Ctr Aging, Oklahoma City, OK USA. [Mukhopadhyay, Partha; Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD USA. [Zhang, Cuihua] Univ Missouri, Dept Internal Med Med Pharmacol & Physiol & Nutr, Columbia, MO USA. RP Csiszar, A (reprint author), New York Med Coll, Dept Physiol, Valhalla, NY 10595 USA. EM zoltan-ungvari@ouhsc.edu; anna_csiszar@nymc.edu RI MUKHOPADHYAY, PARTHA/G-3890-2010; Pacher, Pal/B-6378-2008 OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Pacher, Pal/0000-0001-7036-8108 FU American Federation for Aging Research; American Diabetes Association; American Heart Association [110350047A]; National Institutes of Health (NIH) [HL-077256, HL-43023, CA-111842, RO1-HL-077566, RO1-HL-085119] FX This work was supported by grants from the American Federation for Aging Research (to A. Csiszar) and the American Diabetes Association (to Z. Ungvari); by American Heart Association Grant 110350047A (to C. Zhang) and National Institutes of Health (NIH) Grants HL-077256 and HL-43023 (to Z. Ungvari and A. Csiszar), CA-111842 (to J. PT. Pinto), and RO1-HL-077566 and RO1-HL-085119 (to C. Zhang); and by the Intramural Research Program of the NIH (to P. Pacher). NR 50 TC 162 Z9 165 U1 2 U2 17 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 2009 VL 297 IS 5 BP H1876 EP H1881 DI 10.1152/ajpheart.00375.2009 PG 6 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 511DF UT WOS:000271143400041 PM 19749157 ER PT J AU Meir, T Levi, R Lieben, L Libutti, S Carmeliet, G Bouillon, R Silver, J Naveh-Many, T AF Meir, Tomer Levi, Ronen Lieben, Liesbet Libutti, Steven Carmeliet, Geert Bouillon, Roger Silver, Justin Naveh-Many, Tally TI Deletion of the vitamin D receptor specifically in the parathyroid demonstrates a limited role for the receptor in parathyroid physiology SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE serum calcium; calcium homeostasis; secondary hyperparathyroidism; calcium receptor; parathyroid hormone ID CALCIUM-SENSING RECEPTOR; EXTRACELLULAR CA2+-SENSING RECEPTOR; MINERAL ION HOMEOSTASIS; VDR-KNOCKOUT MICE; SKELETAL PHENOTYPE; NUCLEAR RECEPTOR; D METABOLITES; ABLATED MICE; HORMONE; GENE AB Meir T, Levi R, Lieben L, Libutti S, Carmeliet G, Bouillon R, Silver J, Naveh-Many T. Deletion of the vitamin D receptor specifically in the parathyroid demonstrates a limited role for the receptor in parathyroid physiology. Am J Physiol Renal Physiol 297: F1192-F1198, 2009. First published August 19, 2009; doi: 10.1152/ajprenal.00360.2009.-1,25(OH)(2)D(3) decreases parathyroid hormone (PTH) gene transcription through the vitamin D receptor (VDR). Total body VDR(-/-) mice have high PTH levels, hypocalcemia, hypophosphatemia, and bone malformations. To investigate PTH regulation by the VDR specifically in the parathyroid, we generated parathyroid-specific VDR knockout mice (PT-VDR(-/-)). In both strains, there was a decrease in parathyroid calcium receptor (CaR) levels. The number of proliferating parathyroid cells was increased in the VDR(-/-) mice but not in the PT-VDR(-/-) mice. Serum PTH levels were moderately but significantly increased in the PT-VDR(-/-) mice with normal serum calcium levels. The sensitivity of the parathyroid glands of the PT-VDR(-/-) mice to calcium was intact as measured by serum PTH levels after changes in serum calcium. This indicates that the reduced CaR in the PT-VDR(-/-) mice enables a physiologic response to serum calcium. Serum C-terminal collagen crosslinks, a marker of bone resorption, were increased in the PT-VDR(-/-) mice with no change in the bone formation marker, serum osteocalcin, consistent with a resorptive effect due to the increased serum PTH levels in the PT-VDR(-/-) mice. Therefore, deletion of the VDR specifically in the parathyroid decreases parathyroid CaR expression and only moderately increases basal PTH levels, suggesting that the VDR has a limited role in parathyroid physiology. C1 [Meir, Tomer; Levi, Ronen; Silver, Justin; Naveh-Many, Tally] Hadassah Hebrew Univ Hosp, Minerva Ctr Calcium & Bone Metab, Serv Nephrol, IL-91120 Jerusalem, Israel. [Lieben, Liesbet; Carmeliet, Geert; Bouillon, Roger] NCI, Bethesda, MD 20892 USA. [Libutti, Steven] Katholieke Univ Leuven, Lab Expt Med & Endocrinol, Louvain, Belgium. RP Silver, J (reprint author), Hadassah Hebrew Univ Hosp, Minerva Ctr Calcium & Bone Metab, Serv Nephrol, POB 12000, IL-91120 Jerusalem, Israel. EM silver@huji.ac.il; tally@cc.huji.ac.il OI Lieben, Liesbet/0000-0002-3076-4947 FU Israel Academy of Sciences; D-Cure; Amgen FX The work was supported in part by grants from the Israel Academy of Sciences, D-Cure, and Amgen. NR 37 TC 34 Z9 35 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD NOV PY 2009 VL 297 IS 5 BP F1192 EP F1198 DI 10.1152/ajprenal.00360.2009 PG 7 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 514DO UT WOS:000271374700007 PM 19692484 ER PT J AU Oppermann, M Qin, Y Lai, EY Eisner, C Li, LL Huang, YN Mizel, D Fryc, J Wilcox, CS Briggs, J Schnermann, J Castrop, H AF Oppermann, Mona Qin, Yan Lai, En Yin Eisner, Christoph Li, Lingli Huang, Yuning Mizel, Diane Fryc, Justyna Wilcox, Christopher S. Briggs, Josephine Schnermann, Jurgen Castrop, Hayo TI Enhanced tubuloglomerular feedback in mice with vascular overexpression of A(1) adenosine receptors SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE single nephron glomerular filtration rate; smooth muscle; juxtaglomerular apparatus ID GLOMERULAR-FILTRATION RATE; RAT-KIDNEY; GENE-EXPRESSION; DEPENDENT INHIBITION; AFFERENT ARTERIOLES; RENIN SECRETION; A(2A) RECEPTORS; DEFICIENT MICE; MESSENGER-RNA; MOUSE STRAIN AB Oppermann M, Qin Y, Lai EY, Eisner C, Li L, Huang Y, Mizel D, Fryc J, Wilcox CS, Briggs J, Schnermann J, Castrop H. Enhanced tubuloglomerular feedback in mice with vascular overexpression of A(1) adenosine receptors. Am J Physiol Renal Physiol 297: F1256-F1264, 2009. First published September 9, 2009; doi: 10.1152/ajprenal.00264.2009.-Adenosine 1 receptors (A1AR) in the kidney are expressed in the vasculature and the tubular system. Pharmacological inhibition or global genetic deletion of A1AR causes marked reductions or abolishment of tubuloglomerular feedback (TGF) responses. To assess the function of vascular A1AR in TGF, we generated transgenic mouse lines in which A1AR expression in smooth muscle was augmented by placing A1AR under the control of a 5.38-kb fragment of the rat smooth muscle alpha-actin promoter and first intron (12). Two founder lines with highest expression in the kidney [353 +/- 42 and 575 +/- 43% compared with the wild type (WT)] were used in the experiments. Enhanced expression of A1AR at the expected site in these lines was confirmed by augmented constrictor responses of isolated afferent arterioles to administration of the A1AR agonist N-6-cyclohexyladenosine. Maximum TGF responses (0-30 nl/min flow step) were increased from 8.4 +/- 0.9 mmHg in WT (n = 21) to 14.2 +/- 0.7 mmHg in A1AR-transgene (tg) 4 (n = 22; P < 0.0001), and to 12.6 +/- 1.2 mmHg in A1AR-tg7 (n = 12; P < 0.02). Stepwise changes in perfusion flow caused greater numerical TGF responses in A1AR-tg than WT in all flow ranges with differences reaching levels of significance in the intermediate flow ranges of 7.5-10 and 10-15 nl/min. Proximal-distal single-nephron glomerular filtration rate (SNGFR) differences (free-flow micropuncture) were also increased in A1AR-tg, averaging 6.25 +/- 1.5 nl/min compared with 2.6 +/- 0.51 nl/min in WT (P = 0.034). Basal plasma renin concentrations as well as the suppression of renin secretion after volume expansion were similar in A1AR-tg and WT mice, suggesting lack of transgene expression in juxtaglomerular cells. These data indicate that A1AR expression in vascular smooth muscle cells is a critical component for TGF signaling and that changes in renal vascular A1AR expression may determine the magnitude of TGF responses. C1 [Castrop, Hayo] Univ Regensburg, Inst Physiol, D-93040 Regensburg, Germany. [Oppermann, Mona; Qin, Yan; Eisner, Christoph; Li, Lingli; Huang, Yuning; Mizel, Diane; Fryc, Justyna; Schnermann, Jurgen] NIDDKD, Bethesda, MD 20892 USA. [Briggs, Josephine] NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. [Oppermann, Mona] Childrens Hosp, Univ Med Ctr, Regensburg, Germany. [Lai, En Yin; Wilcox, Christopher S.] Georgetown Univ, Div Nephrol & Hypertens, Washington, DC USA. [Lai, En Yin; Wilcox, Christopher S.] Georgetown Univ, Cardiovasc Kidney Hypertens Inst, Washington, DC USA. RP Castrop, H (reprint author), Univ Regensburg, Inst Physiol, Univ Str 31, D-93040 Regensburg, Germany. EM hayo@castrop.com RI Briggs, Josephine/B-9394-2009 OI Briggs, Josephine/0000-0003-0798-1190 FU NIDDK; Deutsche Forschungsgemeinschaft [SFB 699/A4]; NIH [DK-36079, DK-49870, HL-68686-01] FX This work was supported by the intramural research program of the NIDDK and by a grant from the Deutsche Forschungsgemeinschaft (SFB 699/A4). C. S. Wilcox was supported by NIH Grants DK-36079, DK-49870, and HL-68686-01. NR 35 TC 10 Z9 11 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD NOV PY 2009 VL 297 IS 5 BP F1256 EP F1264 DI 10.1152/ajprenal.00264.2009 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 514DO UT WOS:000271374700014 PM 19741017 ER PT J AU Wangemann, P Kim, HM Billings, S Nakaya, K Li, XM Singh, R Sharlin, DS Forrest, D Marcus, DC Fong, PY AF Wangemann, Philine Kim, Hyoung-Mi Billings, Sara Nakaya, Kazuhiro Li, Xiangming Singh, Ruchira Sharlin, David S. Forrest, Douglas Marcus, Daniel C. Fong, Peying TI Developmental delays consistent with cochlear hypothyroidism contribute to failure to develop hearing in mice lacking Slc26a4/pendrin expression SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE DFNB4; Pendred syndrome; thyroid; Tectb; bicarbonate ID TYPE-2 IODOTHYRONINE DEIODINASE; ENLARGED VESTIBULAR AQUEDUCT; THYROID EPITHELIAL-CELLS; PENDRED-SYNDROME GENE; APICAL IODIDE EFFLUX; SYNDROME MOUSE MODEL; POSTNATAL-DEVELOPMENT; TECTORIAL MEMBRANE; CHLORIDE CHANNEL; PDS MUTATIONS AB Wangemann P, Kim HM, Billings S, Nakaya K, Li X, Singh R, Sharlin DS, Forrest D, Marcus DC, Fong P. Developmental delays consistent with cochlear hypothyroidism contribute to failure to develop hearing in mice lacking Slc26a4/pendrin expression. Am J Physiol Renal Physiol 297: F1435-F1447, 2009. First published August 19, 2009; doi:10.1152/ajprenal. 00011.2009.-Mutations of SLC26A4 cause an enlarged vestibular aqueduct, nonsyndromic deafness, and deafness as part of Pendred syndrome. SLC26A4 encodes pendrin, an anion exchanger located in the cochlea, thyroid, and kidney. The goal of the present study was to determine whether developmental delays, possibly mediated by systemic or local hypothyroidism, contribute to the failure to develop hearing in mice lacking Slc26a4 (Slc26a4(-/-)). We evaluated thyroid function by voltage and pH measurements, by array-assisted gene expression analysis, and by determination of plasma thyroxine levels. Cochlear development was evaluated for signs of hypothyroidism by microscopy, in situ hybridization, and quantitative RT-PCR. No differences in plasma thyroxine levels were found in Slc26a4(-/-) and sexmatched Slc26a4(+/-) littermates between postnatal day 5 (P5) and P90. In adult Slc26a4(-/-) mice, the transepithelial potential and the pH of thyroid follicles were reduced. No differences in the expression of genes that participate in thyroid hormone synthesis or ion transport were observed at P15, when plasma thyroxine levels peaked. Scala media of the cochlea was 10-fold enlarged, bulging into and thereby displacing fibrocytes, which express Dio2 to generate a cochlear thyroid hormone peak at P7. Cochlear development, including tunnel opening, arrival of efferent innervation at outer hair cells, endochondral and intramembraneous ossification, and developmental changes in the expression of Dio2, Dio3, and Tectb were delayed by 1-4 days. These data suggest that pendrin functions as a HCO(3)(-) transporter in the thyroid, that Slc26a4(-/-) mice are systemically euthyroid, and that delays in cochlear development, possibly due to local hypothyroidism, lead to the failure to develop hearing. C1 [Wangemann, Philine; Kim, Hyoung-Mi; Billings, Sara; Nakaya, Kazuhiro; Li, Xiangming; Singh, Ruchira; Marcus, Daniel C.; Fong, Peying] Kansas State Univ, Dept Anat & Physiol, Manhattan, KS 66506 USA. [Nakaya, Kazuhiro] Tohoku Univ, Dept Otolaryngol, Sendai, Miyagi 980, Japan. [Sharlin, David S.; Forrest, Douglas] NIDDK, Bethesda, MD USA. RP Wangemann, P (reprint author), Kansas State Univ, Dept Anat & Physiol, 205 Coles Hall, Manhattan, KS 66506 USA. EM wange@vet.ksu.edu RI Wangemann, Philine/N-2826-2013 FU National Institutes of Health (NIH) [NIH-R01-DC01098, NIH-R01-DC00212, NIH-P20-RR017686]; College of Veterinary Medicine at Kansas State University SFYI; National Institute of Diabetes and Digestive and Kidney Diseases FX We gratefully acknowledge the support by grants from the National Institute on Deafness and Other Communication Disorders National Institutes of Health (NIH)-R01-DC01098 to P. Wangemann and NIH-R01-DC00212 to D. C. Marcus, grants from the National Institute for Research Resources NIH-P20-RR017686-Project 2 to P. Fong, NIH-P20-RR017686-Core B to D. C. Marcus, and NIH-P20-RR017686-Core C to D. C. Marcus, and grants from College of Veterinary Medicine at Kansas State University SFYI to P. Fong and SMILE to P. Wangemann. Furthermore, the support of the intermural program at National Institute of Diabetes and Digestive and Kidney Diseases at the NIH to D. Forrest is gratefully acknowledged. NR 66 TC 37 Z9 37 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 2009 VL 297 IS 5 BP F1435 EP F1447 DI 10.1152/ajprenal.00011.2009 PG 13 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 514DO UT WOS:000271374700033 PM 19692489 ER PT J AU Rashid, JR Spengler, RF Wagner, RM Melanson, C Skillen, EL Mays, RA Heurtin-Roberts, S Long, JA AF Rashid, Jamila R. Spengler, Robert F. Wagner, Robin M. Melanson, Cindi Skillen, Elizabeth L. Mays, Robert A., Jr. Heurtin-Roberts, Suzanne Long, Judith A. TI Eliminating Health Disparities Through Transdisciplinary Research, Cross-Agency Collaboration, and Public Participation SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID UNITED-STATES; TRENDS; SCIENCE; DISEASE AB Despite efforts to the contrary, disparities in health and health care persist in the United States. To solve this problem, federal agencies representing different disciplines and perspectives are collaborating on a variety of transdisciplinary research initiatives. The most recent of these initiatives was launched in 2006 when the Centers for Disease Control and Prevention's Office of Public Health Research and the Department of Health and Human Services' Office of Minority Health brought together federal partners representing a variety of disciplines to form the Federal Collaboration on Health Disparities Research (FCHDR). FCHDR collaborates with a wide variety of federal and nonfederal partners to support and disseminate research that aims to reduce or eliminate disparities in health and health care. Given the complexity involved in eliminating health disparities, there is a need for more transdisciplinary, collaborative research, and facilitating that research is FCHDR's mission. (Am J Public Health. 2009;99:1955-1961. doi:10.2105/AJPH.2009.167932) C1 [Rashid, Jamila R.; Spengler, Robert F.; Wagner, Robin M.; Melanson, Cindi; Skillen, Elizabeth L.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Heurtin-Roberts, Suzanne] Off Minor Hlth, Dept Hlth & Human Serv, Rockville, MD USA. [Mays, Robert A., Jr.] NIH, Bethesda, MD 20892 USA. [Long, Judith A.] Philadelphia VA Ctr Hlth Equ Res & Promot, Dept Vet Affairs, Philadelphia, PA USA. RP Rashid, JR (reprint author), HHS, Off Minor Hlth, 1101 Wootton Pkwy,Suite 600, Rockville, MD 20852 USA. EM jamila.rashid@hhs.gov RI Heurtin-Roberts, Suzanne/D-7274-2013 NR 31 TC 16 Z9 16 U1 0 U2 9 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD NOV PY 2009 VL 99 IS 11 BP 1955 EP 1961 DI 10.2105/AJPH.2009.167932 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 511ZD UT WOS:000271209900012 PM 19762652 ER PT J AU Safran, MA Mays, RA Huang, LN McCuan, R Pham, PK Fisher, SK McDuffie, KY Trachtenberg, A AF Safran, Marc A. Mays, Robert A., Jr. Huang, Larke Nahme McCuan, Ron Pham, Phuong Kim Fisher, Sylvia Kay McDuffie, Kathleen Y. Trachtenberg, Alan TI Mental Health Disparities SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID INTERNATIONAL DIAGNOSTIC INTERVIEW; DSM-IV; LIMITATIONS; PARADIGM; VALIDITY; ILLNESS AB Mental health disparities have received increased attention in the literature in recent years. After considering 165 different health disparity conditions, the Federal Collaborative for Health Disparities Research chose mental health disparity as one of four topics warranting its immediate national research attention. In this essay, we describe the challenges and opportunities encountered in developing a research agenda to address mental health disparities in the United States. Varying definitions of mental health disparity, the heterogeneity of populations facing such disparity, and the power, complexity, and intertwined nature of contributing factors are among the many challenges. We convey an evolving interagency approach to mental health disparities research and guidance for further work in the field. (Am J Public Health. 2009;99:1962-1966. doi:10.2105/AJPH.2009.167346) C1 [Safran, Marc A.; McDuffie, Kathleen Y.] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. [Mays, Robert A., Jr.; Pham, Phuong Kim] NIMH, NIH, Bethesda, MD 20892 USA. [Huang, Larke Nahme; Fisher, Sylvia Kay] Subst Abuse & Mental Hlth Serv Adm, Rockville, MD USA. [McCuan, Ron] Natl Inst Correct, Washington, DC USA. [Trachtenberg, Alan] Indian Hlth Serv, Rockville, MD USA. RP Safran, MA (reprint author), Ctr Dis Control & Prevent, 1600 Clifton Rd,Mail Stop E-44, Atlanta, GA 30333 USA. EM MSafran@cdc.gov NR 40 TC 26 Z9 26 U1 5 U2 9 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD NOV PY 2009 VL 99 IS 11 BP 1962 EP 1966 DI 10.2105/AJPH.2009.167346 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 511ZD UT WOS:000271209900013 PM 19820213 ER PT J AU Reddy, NM Suryanaraya, V Yates, MS Kleeberger, SR Hassoun, PM Yamamoto, M Liby, KT Sporn, MB Kensler, TW Reddy, SP AF Reddy, Narsa M. Suryanaraya, Vegiraju Yates, Melinda S. Kleeberger, Steven R. Hassoun, Paul M. Yamamoto, Masayuki Liby, Karen T. Sporn, Michael B. Kensler, Thomas W. Reddy, Sekhar P. TI The Triterpenoid CDDO-Imidazolide Confers Potent Protection against Hyperoxic Acute Lung Injury in Mice SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE Nrf2; Keap1; antioxidants; stress response ID RESPIRATORY-DISTRESS-SYNDROME; PERMEABLE RADICAL SCAVENGER; OXIDATIVE STRESS; ORGAN INJURY; NRF2; INFLAMMATION; MECHANISMS; INDUCTION; RESPONSES; OXIDANTS AB Rationale: Oxygen supplementation (e.g., hyperoxia) is used to support critically ill patients with noninfectious and infectious acute lung injury (ALI); however, hyperoxia exposure can potentially further contribute to and/or perpetuate preexisting ALI. Thus, developing novel therapeutic agents to minimize the side effects of hyperoxia is essential to improve the health of patients with severe ALI and respiratory dysfunction. We have previously shown that mice with a genetic disruption of the Nrf2 transcription factor, which squelches cellular stress by up-regulating the induction of several antioxidant enzymes and proteins, have greater susceptibility to hyperoxic lung injury. Moreover, we have recently demonstrated that Nrf2-deficiency impairs the resolution of lung injury and inflammation after nonlethal hyperoxia exposure. Objectives: To test the hypothesis that amplification of endogenous Nrf2 activity would prevent or dampen ALI induced by hyperoxia. Methods: Here, we tested our hypothesis using a synthetic triterpenoid compound CDDO-imidazole (CDDO-Im) (1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl] imidazole) in Nrf2-sufficient and Nrf2-deficient mice subjected to hyperoxia-induced ALI. Measurements and Main Results: We demonstrate that oral administration of CDDO-Im at a dose of 30 mu mol/kg body weight during the hyperoxic exposure is sufficient to markedly attenuate hyperoxia-induced ALI in Nrf2-sufficient but not Nrf2-deficient mice. This protection by the CDDO-Im against hyperoxic insult was accompanied by increased levels of Nrf2-regulated cytoprotective gene expression and reduced levels of DNA damage in the lung. Conclusions: These results suggest that up-regulation of Nrf2 signaling by CDDO-Im or its analogs may provide a novel therapeutic strategy to minimize the adverse effects of hyperoxia. C1 [Reddy, Narsa M.; Suryanaraya, Vegiraju; Yates, Melinda S.; Kensler, Thomas W.; Reddy, Sekhar P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. [Kleeberger, Steven R.] Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC USA. [Hassoun, Paul M.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Yamamoto, Masayuki] Tohoku Univ, Dept Med Biochem, Sendai, Miyagi 980, Japan. [Liby, Karen T.; Sporn, Michael B.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Pharmacol & Toxicol, Hanover, NH 03756 USA. RP Reddy, SP (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Room E7610,615 N Wolfe St, Baltimore, MD 21205 USA. EM sreddy@jhsph.edu RI Yamamoto, Masayuki/A-4873-2010; Kensler, Thomas/D-8686-2014 OI Kensler, Thomas/0000-0002-6676-261X FU National Institute of Health [HL66109, Est 1863, HL049441, SCCOR P50 HL073994, CA94076, P30 ES03819]; National Institutes of Health; National Institute of Environmental Health Sciences FX Supported by National Institute of Health grants HL66109 and Est 1863 (S.P.R.), HL049441 (P.M.H), SCCOR P50 HL073994 (S.P.R. and P.M.H.), CA94076 (T.W.K.), P30 ES03819, and in part by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (S. R. K.). NR 42 TC 30 Z9 30 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV 1 PY 2009 VL 180 IS 9 BP 867 EP 874 DI 10.1164/rccm.200905-0670OC PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 512AX UT WOS:000271215500011 PM 19679692 ER PT J AU Summers, RM Swift, JA Dwyer, AJ Choi, JR Pickhardt, PJ AF Summers, Ronald M. Swift, Jeffrey A. Dwyer, Andrew J. Choi, J. Richard Pickhardt, Perry J. TI Normalized Distance Along the Colon Centerline: A Method for Correlating Polyp Location on CT Colonography and Optical Colonoscopy SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article; Proceedings Paper CT Digestive Disease Week/110th Annual Meeting of the American-Gastroenterological-Association CY MAY 30-JUN 04, 2009 CL Chicago, IL SP Amer Gastroenterol Assoc DE colorectal cancer screening; colon polyp; CT colonography; optical colonoscopy ID CURVED CROSS-SECTIONS; FEASIBILITY; SYSTEM AB OBJECTIVE. The ability to accurately locate a polyp found on CT colonography (CTC) at subsequent optical colonoscopy (OC) is an important part of the successful implementation of CTC for colorectal cancer screening. The purpose of this study was to determine whether a polyp's normalized distance along the colon centerline derived from CTC data can accurately predict its location on OC. MATERIALS AND METHODS. The polyp population consisted of 152 polyps in 121 patients. CTC polyp findings were verified by same-day segmentally-unblinded OC. Each polyp's normalized distance along the colon centerline was computed by dividing its distance from the anorectal junction measured along the colon centerline by the length of the colon at CTC. The predicted polyp location at OC was computed by multiplying the normalized distance along the colon centerline by the colon length at OC (i.e., the distance to the cecum as determined at full colonoscope insertion). The differences between the true and predicted polyp locations at OC were compared using paired Student's t tests, linear regression, prediction interval assessment, and Bland-Altman analyses. RESULTS. The differences between the true and predicted polyp locations at OC using the supine and prone CTC-normalized distances along the colon centerline were 2.2 +/- 10.5 cm (mean +/- SD; n = 136) and 1.5 +/- 10.5 cm (n = 135), respectively. The predicted location was within 10 cm of its true location for 71.3% (97/136) to 74.8% (101/135) of polyps and within 20 cm of its true location for 93.3% (126/135) to 93.4% (127/136) of polyps. CONCLUSION. By computing the normalized distance along the colon centerline of a polyp found at CTC, the location of a polyp at OC can be predicted to within 10 cm (i.e., 1 colonoscope mark) for the majority of polyps. C1 [Summers, Ronald M.; Swift, Jeffrey A.; Dwyer, Andrew J.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Choi, J. Richard] Walter Reed Army Med Ctr, Washington, DC 20307 USA. [Pickhardt, Perry J.] Univ Wisconsin, Dept Radiol, Sch Med, Madison, WI 53706 USA. RP Summers, RM (reprint author), NIH, Ctr Clin, Bldg 10,Rm 1C368X,MSC 1182, Bethesda, MD 20892 USA. EM rms@nih.gov FU Intramural NIH HHS [Z01 CL040003-05, Z01 CL040003-06, ZIA CL040003-07, ZIA CL040003-08, ZIA CL040003-09] NR 15 TC 17 Z9 18 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD NOV PY 2009 VL 193 IS 5 BP 1296 EP 1304 DI 10.2214/AJR.09.2611 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 508ST UT WOS:000270956700015 PM 19843745 ER PT J AU Summers, RM Liu, JM Yao, JH Brown, L Choi, JR Pickhardt, PJ AF Summers, Ronald M. Liu, Jiamin Yao, Jianhua Brown, Linda Choi, J. Richard Pickhardt, Perry J. TI Automated Measurement of Colorectal Polyp Height at CT Colonography: Hyperplastic Polyps Are Flatter Than Adenomatous Polyps SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article; Proceedings Paper CT 94th Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY NOV 30-DEC 05, 2008 CL Chicago, IL SP Radiol Soc N Amer DE automated size measurement; colonoscopy; colorectal cancer screening; CT colonography; optical colonoscopy ID VIRTUAL COLONOSCOPY; ASYMPTOMATIC ADULTS; MISS RATE; IN-VITRO; COLON; LESIONS; PREVALENCE; MANAGEMENT; MODEL; RATES AB OBJECTIVE. Hyperplastic polyps are more difficult to detect than adenomatous polyps at CT colonography (CTC), and it has been theorized that this difference in detectability is because hyperplastic polyps are flatter. Using automated software that computes polyp height, we determined whether hyperplastic colonic polyps on CTC are indeed flatter than adenomatous polyps of comparable width. MATERIALS AND METHODS. At three medical centers, 1,186 patients underwent oral contrast-enhanced CTC and same-day optical colonoscopy (OC) with segment unblinding for colorectal cancer screening. One hundred eighty-five of the patients had at least one hyperplastic or adenomatous polyp 6-10 mm visible at both OC and CTC, where size was determined by a calibrated guidewire at OC. To assess flatness, the heights of the polyps at CTC were measured using a validated automated software program. The heights and height-to-width ratios of the hyperplastic polyps were compared with those of the adenomatous polyps using a Student's t test (two-tailed, unpaired, unequal variance). RESULTS. There were 176 adenomatous and 83 hyperplastic polyps visible at segment-unblinded OC. The fraction of these polyps that were measurable at CTC using the automated software was not significantly different for adenomatous versus hyperplastic polyps (158/176 [89.8%] vs 73/87 [83.9%], respectively; p = 0.2). The average height-to-width ratios using automated width measurements were 15% less for hyperplastic polyps: 0.39 +/- 0.20 (n = 158) and 0.33 +/- 0.19 (n = 73) for adenomatous and hyperplastic polyps, respectively (p = 0.03). When polyps of comparable OC size or CTC width were considered, the heights of hyperplastic polyps were up to 27% less than those of adenomatous polyps. CONCLUSION. For 6-10 mm polyps of a given size as determined by OC or a given width at CTC, hyperplastic polyps tend to be flatter (i.e., have lower height) compared with adenomatous polyps. C1 [Summers, Ronald M.; Liu, Jiamin; Yao, Jianhua; Brown, Linda] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Choi, J. Richard] Walter Reed Army Med Ctr, Washington, DC 20307 USA. [Pickhardt, Perry J.] Univ Wisconsin, Dept Radiol, Sch Med, Madison, WI 53706 USA. RP Summers, RM (reprint author), NIH, Ctr Clin, Bldg 10,Rm 1C368X,MSC 1182, Bethesda, MD 20892 USA. EM rms@nih.gov FU Intramural NIH HHS [Z01 CL040003-05, Z01 CL040003-06, ZIA CL040003-07, ZIA CL040003-08, ZIA CL040003-09] NR 32 TC 11 Z9 11 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD NOV PY 2009 VL 193 IS 5 BP 1305 EP 1310 DI 10.2214/AJR.09.2442 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 508ST UT WOS:000270956700016 PM 19843746 ER PT J AU Anderson, JM Lopez, J Sogoba, N Schrumpf, ME Raffel, SJ Schwan, TG AF Anderson, Jennifer M. Lopez, Job Sogoba, Nafomon Schrumpf, Merry E. Raffel, Sandra J. Schwan, Tom G. TI TICK BORNE RELAPSING FEVER IN MALI SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Anderson, Jennifer M.] NIH, Rockville, MD USA. [Lopez, Job; Schrumpf, Merry E.; Raffel, Sandra J.; Schwan, Tom G.] NIH, Hamilton, MT USA. [Sogoba, Nafomon] Malaria Res & Training Ctr, Bamako, Mali. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 11 BP 4 EP 4 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956700012 ER PT J AU Keesen, TS Antonelli, LR Guimaraes, LH Carvalho, EM Dutra, WO Gollob, KJ AF Keesen, Tatjana S. Antonelli, Lis R. Guimaraes, Luiz H. Carvalho, Edgar M. Dutra, Walderez O. Gollob, Kenneth J. TI CD4+T CELLS SUBSETS IN HUMAN CUTANEOUS LEISHMANIASIS HAVE A DISTINCT RECEPTOR REPERTOIRES AND CYTOKINE EXPRESSION SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Keesen, Tatjana S.; Dutra, Walderez O.; Gollob, Kenneth J.] Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil. [Antonelli, Lis R.] NIH, Bethesda, MD 20892 USA. [Guimaraes, Luiz H.; Carvalho, Edgar M.] Univ Fed Bahia, Salvador, BA, Brazil. RI Antonelli, Lis/G-2907-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 37 BP 11 EP 11 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956700038 ER PT J AU Shrestha, B Brien, JD Sukupolvi-Petty, S O'Brien, K Nelson, S Pierson, TC Diamond, MS AF Shrestha, Bimmi Brien, James D. Sukupolvi-Petty, Soila O'Brien, Kathryn Nelson, Steevenson Pierson, Theodore C. Diamond, Michael S. TI NEUTRALIZING ANTIBODIES AGAINST DENGUE VIRUS TYPE-1 MAP TO DOMAIN III OF THE E PROTEIN AND PROTECT MICE FROM LETHAL CHALLENGE SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Shrestha, Bimmi; Brien, James D.; Sukupolvi-Petty, Soila; O'Brien, Kathryn; Diamond, Michael S.] Washington Univ, Sch Med, St Louis, MO USA. [Nelson, Steevenson; Pierson, Theodore C.] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 95 BP 27 EP 27 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956700096 ER PT J AU Morens, DM AF Morens, David M. TI JOSEPH JAMES KINYOUN: FOUNDING FATHER OF AMERICAN MICROBIOLOGY SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Morens, David M.] NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 109 BP 31 EP 32 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956700110 ER PT J AU Addo, R Pillai, AD Desai, SA AF Addo, Rachel Pillai, Ajay D. Desai, Sanjay A. TI PLASMODIUM FALCIPARUM CULTIVATION IN A SODIUM-FREE MEDIUM SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Addo, Rachel; Pillai, Ajay D.; Desai, Sanjay A.] NIAID, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 147 BP 42 EP 42 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956700147 ER PT J AU Onyamboko, MA Atibu, J Lokomba, V Meshnick, S Douoguih, M Hemingway-Foday, J Koch, M Wesche, D Capparelli, E Fleckenstein, L Ryder, R Bose, C Wright, L Tshefu, A AF Onyamboko, Marie A. Atibu, Jef Lokomba, Vicky Meshnick, Steven Douoguih, Macaya Hemingway-Foday, Jennifer Koch, Matthew Wesche, David Capparelli, Edmund Fleckenstein, Larry Ryder, Robert Bose, Carl Wright, Linda Tshefu, Antoinette TI PHARMACOKINETICS (PK) AND PHARMACODYNAMICS (PD) AND SAFETY OF ARTESUNATE (AS) AND DIHYDROARTEMISININ (DHA) FOLLOWING A SINGLE ORAL DOSE OF ARTESUNATE DURING THE 2(ND) AND 3(RD) TRIMESTER OF PREGNANCY SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Onyamboko, Marie A.; Atibu, Jef; Lokomba, Vicky; Tshefu, Antoinette] Kinshasa Sch Publ Hlth, Kinshasa, Zaire. [Meshnick, Steven; Bose, Carl] Univ N Carolina, Chapel Hill, NC USA. [Douoguih, Macaya] Aeras Global TB Vaccine Fdn, Rockville, MD USA. [Hemingway-Foday, Jennifer; Koch, Matthew] RTI Int, Res Triangle Pk, NC USA. [Wesche, David] Lundbeck Inc, Deerfield, IL USA. [Capparelli, Edmund; Ryder, Robert] Univ Calif San Diego, San Diego, CA 92103 USA. [Fleckenstein, Larry] Univ Iowa, Iowa City, IA USA. [Wright, Linda] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 224 BP 63 EP 63 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956700224 ER PT J AU Molina-Cruz, A Ortega, C Winikor, J Rodrigues, J Barillas-Mury, C AF Molina-Cruz, Alvaro Ortega, Corrie Winikor, Jared Rodrigues, Janneth Barillas-Mury, Carolina TI HOW DOES PLASMODIUM FALCIPARUM EVADE OF THE MOSQUITO IMMUNE SYSTEM SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Molina-Cruz, Alvaro; Ortega, Corrie; Winikor, Jared; Rodrigues, Janneth; Barillas-Mury, Carolina] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 237 BP 67 EP 67 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956700237 ER PT J AU Nkhoma, ET Mu, JB Krause, MA Diakite, SA Kalilani, L Rogerson, SJ Fairhurst, RM Meshnick, SR AF Nkhoma, Ella T. Mu, Jianbing Krause, Michael A. Diakite, Seidina A. Kalilani, Linda Rogerson, Stephen J. Fairhurst, Rick M. Meshnick, Steven R. TI EFFECT OF THE A-FORM OF G6PD DEFICIENCY ON MATERNAL PLASMODIUM FALCIPARUM PARASITEMIA AND PREGNANCY OUTCOMES SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Nkhoma, Ella T.; Meshnick, Steven R.] Univ N Carolina, Chapel Hill, NC USA. [Mu, Jianbing; Krause, Michael A.; Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Diakite, Seidina A.] Univ Bamako, Dept Immunogenet, Bamako, Mali. [Kalilani, Linda] Univ Malawi, Coll Med, Blantyre, Malawi. [Rogerson, Stephen J.] Univ Melbourne, Dept Med, Parkville, Vic 3052, Australia. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 303 BP 86 EP 86 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956700303 ER PT J AU Mahanty, S Berns, AL Scott, E Lizak, M Nash, T AF Mahanty, Siddhartha Berns, Abby L. Scott, Erick Lizak, Martin Nash, Theodore TI A RAT MODEL OF INTRACEREBRAL INFECTION WITH TAENIA CRASSICEPS FOR THE STUDY OF INFLAMMATION ASSOCIATED WITH ANTHELMINTIC THERAPY IN NEUROCYSTICERCOSIS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Mahanty, Siddhartha; Berns, Abby L.; Scott, Erick; Lizak, Martin; Nash, Theodore] NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 309 BP 88 EP 88 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956700309 ER PT J AU Krolewiecki, AJ Ramanathan, R Fink, V Won, K Cajal, S Juarez, M Acosta, N Lee, R Lammie, P Abraham, D Nutman, T AF Krolewiecki, Alejandro J. Ramanathan, Roshan Fink, Valeria Won, Kimberly Cajal, Silvana Juarez, Marisa Acosta, Norma Lee, Rogan Lammie, Patrick Abraham, David Nutman, Thomas TI EVALUATION OF NEW SEROLOGIC TECHNIQUES FOR THE DIAGNOSIS OF STRONGYLOIDES STERCORALIS INFECTIONS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Krolewiecki, Alejandro J.; Cajal, Silvana; Juarez, Marisa; Acosta, Norma] Inst Invest Enfermedades Trop, Oran, Argentina. [Ramanathan, Roshan; Nutman, Thomas] NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. [Fink, Valeria] Fdn Huesped, Buenos Aires, DF, Argentina. [Won, Kimberly; Lammie, Patrick] Ctr Dis Control & Prevent, Div Parasit Dis, Atlanta, GA USA. [Lee, Rogan] Westmead Hosp, Inst Clin Pathol & Med Res, Westmead, NSW 2145, Australia. [Abraham, David] Thomas Jefferson Univ, Dept Microbiol & Immunol, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 312 BP 89 EP 89 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956700312 ER PT J AU Eksi, S Haile, Y Morahan, BJ Furuya, T Suri, A Jiang, HY Su, XZ Williamson, KC AF Eksi, Saliha Haile, Yoseph Morahan, Belinda J. Furuya, Tetsuya Suri, Amreena Jiang, Hongying Su, Xinzhuan Williamson, Kim C. TI PERINUCLEAR PROTEIN, P. FALCIPARUM GAMETOCYTOGENESIS INDUCER 1, PFGYI1, PLAYS AN IMPORTANT ROLE IN GAMETOCYTOGENESIS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Eksi, Saliha; Haile, Yoseph; Morahan, Belinda J.; Suri, Amreena; Williamson, Kim C.] Loyola Univ, Chicago, IL 60611 USA. [Furuya, Tetsuya; Jiang, Hongying; Su, Xinzhuan] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 316 BP 90 EP 90 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956700316 ER PT J AU Ssekitoleko, R Moore, CC Jacob, ST Pinkerton, R Banura, P Meya, D Reynolds, SJ Kenya-Mugisha, N Mayanja-Kizza, H Scheld, WM AF Ssekitoleko, Richard Moore, Christopher C. Jacob, Shevin T. Pinkerton, Relana Banura, Patrick Meya, David Reynolds, Steven J. Kenya-Mugisha, Nathan Mayanja-Kizza, Harriet Scheld, W. Michael TI HYPOGLYCEMIA IS ASSOCIATED WITH MORTALITY IN UGANDAN PATIENTS WITH SEVERE SEPSIS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Ssekitoleko, Richard] Mbarara Univ, Mbarara, Uganda. [Moore, Christopher C.; Pinkerton, Relana; Scheld, W. Michael] Univ Virginia, Charlottesville, VA USA. [Jacob, Shevin T.] Univ Washington, Seattle, WA 98195 USA. [Banura, Patrick] Masaka Reg Referral Hosp, Masaka, Uganda. [Meya, David; Mayanja-Kizza, Harriet] Makerere Univ, Kampala, Uganda. [Reynolds, Steven J.] NIH, Bethesda, MD 20892 USA. [Kenya-Mugisha, Nathan] Minist Hlth, Kampala, Uganda. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 322 BP 92 EP 92 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956700322 ER PT J AU Bharti, N Broutin, H Grais, R Djibo, A Grenfell, B AF Bharti, Nita Broutin, Helene Grais, Rebecca Djibo, Ali Grenfell, Bryan TI SPATIAL PATTERNS OF MENINGITIS IN NIGER SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Bharti, Nita; Grenfell, Bryan] Penn State Univ, University Pk, PA 16802 USA. [Broutin, Helene] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Grais, Rebecca] Epicentre, Paris, France. [Djibo, Ali] Minist Sante, Direct Gen Sante Publ, Niamey, Niger. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 325 BP 93 EP 93 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956700325 ER PT J AU Cantey, PT Richard, S Richard, S Dorkenoo, A Sodahlon, Y Mathieu, E AF Cantey, Paul T. Richard, Stephanie Richard, Stephanie Dorkenoo, Ameyo Sodahlon, Yao Mathieu, Els TI PATIENT TREATMENT COSTS FOR MANAGEMENT OF LYMPHEDEMA AND ACUTE ATTACKS IN TOGO SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Cantey, Paul T.; Mathieu, Els] Ctr Dis Control & Prevent, Div Parasit Dis, NCZVED, Atlanta, GA USA. [Richard, Stephanie] Fogarty Int Ctr, Bethesda, MD USA. [Richard, Stephanie] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Dorkenoo, Ameyo] Togo Natl Program Eliminat Lymphat Filariasis, Lome, Togo. [Sodahlon, Yao] Mectizan Donat Program, Decatur, GA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 329 BP 94 EP 94 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956700329 ER PT J AU Coulibaly, YI Dembele, B Konate, S Dolo, H Coulibaly, SY Sanogo, D Soumaoro, L Coulibaly, ME Doumbia, SS Diallo, AA Traore, SF Keita, AD Nutman, TB Klion, AD AF Coulibaly, Yaya I. Dembele, Benoit Konate, Siaka Dolo, Housseini Coulibaly, Siaka Y. Sanogo, Dramane Soumaoro, Lamine Coulibaly, Michel E. Doumbia, Salif S. Diallo, Abdallah A. Traore, Sekou F. Keita, Adama D. Nutman, Thomas B. Klion, Amy D. TI HIGH DOSE BIANNUAL ALBENDAZOLE AND IVERMECTIN SUPPRESS WUCHERERIA BANCROFTI MICROFILARIAL LEVELS MORE EFFECTIVELY THAN STANDARD DOSE ANNUAL TREATMENT SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Coulibaly, Yaya I.; Dembele, Benoit; Konate, Siaka; Dolo, Housseini; Coulibaly, Siaka Y.; Sanogo, Dramane; Soumaoro, Lamine; Coulibaly, Michel E.; Doumbia, Salif S.; Diallo, Abdallah A.; Traore, Sekou F.] Univ Bamako, Bamako, Mali. [Keita, Adama D.] Hosp Point G, Bamako, Mali. [Nutman, Thomas B.; Klion, Amy D.] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 332 BP 95 EP 95 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956700332 ER PT J AU Ho, M Beaudry, SD White, A Lee, K Arie, T Deitsch, K Fairhurst, RM AF Ho, May Beaudry, Steven D. White, Aaron Lee, Kristine Arie, Takayuki Deitsch, Kirk Fairhurst, Rick M. TI EXPRESSION OF PLASMODIUM FALCIPARUM ERYTHROCYTE MEMBRANE PROTEIN 1 (PFEMP1) IS IRON-DEPENDENT SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 Univ Calgary, Dept Microbiol & Infect Dis, Calgary, AB, Canada. NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 334 BP 95 EP 95 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956700334 ER PT J AU Pillai, AD Desai, SA AF Pillai, Ajay D. Desai, Sanjay A. TI GENETIC VALIDATION OF THE PLASMODIAL SURFACE ANION CHANNEL AS AN ANTIMALARIAL DRUG TARGET SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Pillai, Ajay D.; Desai, Sanjay A.] NIAID, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 337 BP 96 EP 96 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956700337 ER PT J AU Bokhari, AA Desai, SA AF Bokhari, Abdullah A. Desai, Sanjay A. TI GENETIC MAPPING IN TWO PLASMODIUM FALCIPARUM CROSSES IDENTIFIES A LOCUS ENCODING THE PLASMODIAL SURFACE ANION CHANNEL SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Bokhari, Abdullah A.; Desai, Sanjay A.] NIAID, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 340 BP 97 EP 97 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956700340 ER PT J AU McQueen, PG McKenzie, FE AF McQueen, Philip G. McKenzie, F. Ellis TI IMMUNE CONSTRAINTS ON PARASITEMIA AND GAMETOCYTEMIA IN MALARIA: INSIGHT FROM NUMERICAL STUDIES SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [McQueen, Philip G.; McKenzie, F. Ellis] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 342 BP 97 EP 98 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956700342 ER PT J AU Singh, K Gitti, RK Gittis, AG Nguyen, PG Mohan, MJ Gowda, DC Gowda, DC Tullo, G Zhou, H Fairhurst, R Long, C Garboczi, DN AF Singh, Kavita Gitti, Rossitza K. Gittis, Apostolos G. Nguyen, Phuc G. Mohan, Michael J. Gowda, D. Channe Gowda, D. Channe Tullo, Gregory Zhou, Hong Fairhurst, Rick Long, Carole Garboczi, David N. TI STRUCTURAL AND BIOCHEMICAL CHARACTERIZATION OF THE BINDING REGION OF PLASMODIUM FALCIPARUM VAR2CSA DBL3X WITH CHONDROITIN SULFATE A SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Singh, Kavita; Gittis, Apostolos G.; Nguyen, Phuc G.; Mohan, Michael J.; Gowda, D. Channe; Tullo, Gregory; Zhou, Hong; Fairhurst, Rick; Long, Carole; Garboczi, David N.] NIAID, NIH, Rockville, MD USA. [Gitti, Rossitza K.] ECB Forens Analyt Branch, Aberdeen, MD USA. [Gowda, D. Channe] Penn State Univ, Coll Med, Hershey, PA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 344 BP 98 EP 98 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956700344 ER PT J AU Durbin, AP Whitehead, SS Elwood, D Kagucia, W Thumar, B Wanionek, KA Pierro, D Murphy, BR Schmidt, AC AF Durbin, Anna P. Whitehead, Stephen S. Elwood, Daniel Kagucia, Wangeci Thumar, Bhavin Wanionek, Kimberli A. Pierro, Dennis Murphy, Brian R. Schmidt, Alexander C. TI SAFETY AND IMMUNOGENICITY OF A 2-DOSE REGIMEN OF RDEN1 Delta 30 DENGUE SEROTYPE 1 VACCINE WITH BOOSTING AT FOUR VERSUS SIX MONTHS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Durbin, Anna P.; Elwood, Daniel; Kagucia, Wangeci; Thumar, Bhavin; Wanionek, Kimberli A.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Whitehead, Stephen S.; Pierro, Dennis; Murphy, Brian R.; Schmidt, Alexander C.] NIAID, NIH, Bethesda, MD 20892 USA. RI Mavoa, Suzanne/B-5372-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 397 BP 114 EP 114 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956700397 ER PT J AU Whitehead, SS Schmidt, AC McArthur, JH Marron, JA Elwood, D Thumar, B Wanionek, KA Pierro, D Blaney, JE Murphy, BR Durbin, AF AF Whitehead, Stephen S. Schmidt, Alexander C. McArthur, Julie H. Marron, Jennifer A. Elwood, Daniel Thumar, Bhavin Wanionek, Kimberli A. Pierro, Dennis Blaney, Joseph E. Murphy, Brian R. Durbin, Anna F. TI CLINICAL EVALUATION OF LIVE ATTENUATED DEN3 VACCINE CANDIDATES SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Whitehead, Stephen S.; Schmidt, Alexander C.; Pierro, Dennis; Blaney, Joseph E.; Murphy, Brian R.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [McArthur, Julie H.; Marron, Jennifer A.; Elwood, Daniel; Thumar, Bhavin; Wanionek, Kimberli A.; Durbin, Anna F.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. RI Mavoa, Suzanne/B-5372-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 396 BP 114 EP 114 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956700396 ER PT J AU Bosio, CF Jarrett, CO Hinnebusch, BJ AF Bosio, Christopher F. Jarrett, Clayton O. Hinnebusch, B. Joseph TI EFFECTS OF FLEA FEEDING ON EARLY INNATE IMMUNE EVENTS IN THE SKIN AND TRANSMISSION OF YERSINIA PESTIS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Bosio, Christopher F.; Jarrett, Clayton O.; Hinnebusch, B. Joseph] NIAID, Rocky Mt Labs, Hamilton, MT 59840 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 418 BP 120 EP 120 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956700418 ER PT J AU Doumbia, S Faye, O Oliveira, F Anderson, JM Traore, P Diarra, S Tall, K Sissoko, IM Diallo, D Samake, S Coulibaly, CA Traore, B Teixeira, C Gomez, R Soucko, C Lawyer, P Keita, S Fairhurst, R Kamhawi, S Valenzuela, JL AF Doumbia, Seydou Faye, Ousmane Oliveira, Fabiano Anderson, Jennifer M. Traore, Pierre Diarra, Souleymane Tall, Koureissi Sissoko, Ibrahim M. Diallo, Daouda Samake, Sibiry Coulibaly, Cheick Amadou Traore, Bourama Teixeira, Clarissa Gomez, Regis Soucko, Constance Lawyer, Phil Keita, Somita Fairhurst, Rick Kamhawi, Shaden Valenzuela, Jesus L. TI A COHORT-BASED STUDY OF LEISHMANIA MAJOR INFECTION AND CUTANEOUS LEISHMANIASIS IN MALI SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Doumbia, Seydou; Diarra, Souleymane; Sissoko, Ibrahim M.; Diallo, Daouda; Samake, Sibiry; Coulibaly, Cheick Amadou; Traore, Bourama; Soucko, Constance] Univ Bamako, Fac Med Pharm & Odontostomatol, Malaria Res & Training Ctr, Bamako, Mali. [Faye, Ousmane; Traore, Pierre; Tall, Koureissi; Keita, Somita] Ctr Natl Appui Lutte Malad, Bamako, Mali. [Oliveira, Fabiano; Anderson, Jennifer M.; Teixeira, Clarissa; Gomez, Regis; Lawyer, Phil; Fairhurst, Rick; Kamhawi, Shaden; Valenzuela, Jesus L.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. RI Oliveira, Fabiano/B-4251-2009 OI Oliveira, Fabiano/0000-0002-7924-8038 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 481 BP 137 EP 137 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956700480 ER PT J AU Delgado, S Neyra, RC Machaca, VRQ Juarez, JA Verastegui, M Bocangel, CD Comrie, A Naquira, C del Carpio, JGC Gilman, RH Bern, C Levy, MZ AF Delgado, Stephen Castillo Neyra, Ricardo Quispe Machaca, Victor R. Ancca Juarez, Jenny Verastegui, Manuela Bocangel, Cesar D. Comrie, Andrew Naquira, Cesar Cornejo del Carpio, Juan G. Gilman, Robert H. Bern, Caryn Levy, Michael Z. TI SPATIO-TEMPORAL PERSPECTIVES ON PREVALENCE OF TRYPANOSOMA CRUZI INFECTION IN PERI-URBAN AREQUIPA, PERU SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Delgado, Stephen; Comrie, Andrew] Univ Arizona, Tucson, AZ USA. [Castillo Neyra, Ricardo; Quispe Machaca, Victor R.; Ancca Juarez, Jenny; Verastegui, Manuela; Bocangel, Cesar D.; Naquira, Cesar] Univ Peruana Cayetano Heredia, Lima, Peru. [Cornejo del Carpio, Juan G.] Minist Salud, Direcc Reg, Arequipa, Peru. [Gilman, Robert H.] Johns Hopkins Univ, Baltimore, MD USA. [Bern, Caryn] Ctr Dis Control & Prevent, Atlanta, GA USA. [Levy, Michael Z.] Fogarty Int Ctr, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 484 BP 138 EP 138 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956700483 ER PT J AU Hernandez, Y Kiphart, C Joshi, MB Dwyer, DM AF Hernandez, Yunuen Kiphart, Courtney Joshi, Manju B. Dwyer, Dennis M. TI CHARACTERIZATION AND EXPRESSION OF A NOVEL SECRETORY NUCLEASE, LMEXNUCS, IN THE HUMAN PATHOGEN LEISHMANIA MEXICANA SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Hernandez, Yunuen; Kiphart, Courtney; Joshi, Manju B.; Dwyer, Dennis M.] NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 499 BP 142 EP 142 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956700497 ER PT J AU Sissoko, MS Assadou, MH Kone, M Karnate, B Guindo, O Diallo, A Sagara, I Guindo, MA Saye, R Fay, MP Imeru, A Pierce, MA Dicko, A Guindo, A Diallo, DA Doumbo, O Miller, LH Ellis, RD AF Sissoko, Mahamadou S. Assadou, Mahamadoun H. Kone, Mamady Karnate, Beh Guindo, Ousmane Diallo, Abdoulbaki Sagara, Issaka Guindo, Merapen A. Saye, Renion Fay, Michael P. Imeru, Alemush Pierce, Mark A. Dicko, Alassane Guindo, Aldiouma Diallo, Dapa A. Doumbo, Ogobara Miller, Louis H. Ellis, Ruth D. TI MALARIA INCIDENCE IN INFANTS IN BANCOUMANA, MALI SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Sissoko, Mahamadou S.; Assadou, Mahamadoun H.; Kone, Mamady; Karnate, Beh; Guindo, Ousmane; Diallo, Abdoulbaki; Sagara, Issaka; Guindo, Merapen A.; Saye, Renion; Dicko, Alassane; Guindo, Aldiouma; Diallo, Dapa A.; Doumbo, Ogobara] Univ Bamako, Malaria Res & Training Ctr, Fac Med Pharm & Odontostomatol, Bamako, Mali. [Fay, Michael P.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. [Imeru, Alemush; Pierce, Mark A.; Miller, Louis H.; Ellis, Ruth D.] NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 541 BP 154 EP 154 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956700539 ER PT J AU Ellis, RD Sissoko, M Assadou, MH Guindo, MA Saye, R Kone, M Kante, O Kamate, B Guindo, O Sagara, I Dicko, A Imeru, A Fay, MP Pierce, M Miller, L Miura, K Diallo, D Doumbo, O AF Ellis, Ruth D. Sissoko, Mahamadou Assadou, Mahamadoun H. Guindo, Merapen A. Saye, Renion Kone, Mamady Kante, Ousmane Kamate, Beh Guindo, Ousmane Sagara, Issaka Dicko, Alassane Imeru, Alemush Fay, Michael P. Pierce, Mark Miller, Louis Miura, Kazutoyo Diallo, Dapa Doumbo, Ogobara TI ANTIBODY LEVELS TO AMA1 AND MSP142 IN MALIAN INFANTS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Ellis, Ruth D.; Imeru, Alemush; Pierce, Mark; Miller, Louis; Miura, Kazutoyo] NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD USA. [Sissoko, Mahamadou; Assadou, Mahamadoun H.; Guindo, Merapen A.; Saye, Renion; Kone, Mamady; Kante, Ousmane; Kamate, Beh; Guindo, Ousmane; Sagara, Issaka; Dicko, Alassane; Diallo, Dapa; Doumbo, Ogobara] Univ Bamako, Fac Med Pharm & Dent, Malaria Res & Training Ctr, Bamako, Mali. [Fay, Michael P.] NIAID, Biostat Res Branch, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 552 BP 157 EP 157 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956700550 ER PT J AU Tachibana, M Iriko, H Muratova, O Song, GH Wu, YM Sattabongkot, J Takeo, S Otsuki, H Torii, M Tsuboi, T AF Tachibana, Mayumi Iriko, Hideyuki Muratova, Olga Song, Guanhong Wu, Yimin Sattabongkot, Jetsumon Takeo, Satoru Otsuki, Hitoshi Torii, Motomi Tsuboi, Takafumi TI IMMUNIZATION WITH N-TERMINAL REGION OF A GAMETOCYTE PROTEIN PFS230 SUCCESSFULLY INDUCE TRANSMISSION-BLOCKING ANTIBODIES AGAINST PLASMODIUM FALCIPARUM SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Tachibana, Mayumi; Otsuki, Hitoshi; Torii, Motomi] Ehime Univ, Toon, Japan. [Iriko, Hideyuki] Tottori Univ, Yonago, Tottori, Japan. [Muratova, Olga; Song, Guanhong; Wu, Yimin] NIAID, Rockville, MD USA. [Sattabongkot, Jetsumon] AF Res Inst Med Sci, Bangkok, Thailand. [Takeo, Satoru; Tsuboi, Takafumi] Ehime Univ, Matsuyama, Ehime, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 562 BP 160 EP 160 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956700560 ER PT J AU Miura, K Perera, S Brockley, S Zhou, H Aebig, JA Moretz, SE Miller, L Sagara, I Dicko, A Ellis, RD Long, C AF Miura, Kazutoyo Perera, Suwani Brockley, Sarah Zhou, Hong Aebig, Joan A. Moretz, Samuel E. Miller, Louis Sagara, Issaka Dicko, Alassane Ellis, Ruth D. Long, Carole TI PURIFIED IGGS WHICH ARE OBTAINED FROM MALIAN CHILDREN AND WHICH DO NOT BIND TO APICAL MEMBRANE ANTIGEN 1(AMA1) INTERFERE WITH THE BIOLOGICAL ACTIVITY OF AMA1-SPECIFIC IGGS AS JUDGED BY THE IN VITRO GROWTH INHIBITION ASSAY SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Miura, Kazutoyo; Perera, Suwani; Brockley, Sarah; Aebig, Joan A.; Miller, Louis; Ellis, Ruth D.] NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD USA. [Zhou, Hong; Moretz, Samuel E.; Long, Carole] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. [Sagara, Issaka; Dicko, Alassane] Univ Bamako, Fac Med Pharm & Dent, Malaria Res & Training Ctr, Bamako, Mali. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 565 BP 161 EP 161 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956700563 ER PT J AU Lehmann, T Alpha, A Diallo, M Yaro, AS Kassogue, Y Dao, A AF Lehmann, Tovi Alpha, Adamou Diallo, Moussa Yaro, Alpha S. Kassogue, Yaya Dao, Adama TI LONGEVITY OF ANOPHELES GAMBIAE SL UNDER NATURAL CONDITIONS USING A MODIFIED MARK RELEASE RECAPTURE APPROACH SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Lehmann, Tovi] NIAID, NIH, Rockville, MD USA. [Alpha, Adamou; Diallo, Moussa; Yaro, Alpha S.; Kassogue, Yaya; Dao, Adama] Univ Mali, Malaria Res & Training Ctr, Bamako, Mali. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 588 BP 167 EP 168 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701004 ER PT J AU Rodrigues, J Dixit, R Ortega, C Molina-Cruz, A Mury, CB AF Rodrigues, Janneth Dixit, Rajnikant Ortega, Corrie Molina-Cruz, Alvaro Mury, Carolina Barillas TI IMMUNOLOGICAL PRIMING IN ANOPHELES GAMBIAE: CAN MOSQUITOES 'LEARN' FROM A CHALLENGE WITH PLASMODIUM? SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Rodrigues, Janneth; Dixit, Rajnikant; Ortega, Corrie; Molina-Cruz, Alvaro; Mury, Carolina Barillas] NIAID, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 595 BP 169 EP 170 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701011 ER PT J AU Sogoba, N Keita, M Diakite, M Diallo, M Baber, I Manoukis, NC Traore, SF Doumbia, S Ribeiro, JM AF Sogoba, Nafomon Keita, Moussa Diakite, Mahamadou Diallo, M'Bouye Baber, Ibrahima Manoukis, Nicholas C. Traore, Sekou F. Doumbia, Seydou Ribeiro, Jose M. TI MALARIA TRANSMISSION ALONG THE NIGER RIVER IN A SUDAN SAVANNA AREA OF MALI SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Sogoba, Nafomon; Keita, Moussa; Diakite, Mahamadou; Diallo, M'Bouye; Baber, Ibrahima; Traore, Sekou F.; Doumbia, Seydou; Ribeiro, Jose M.] Univ Bamako, Malaria Res & Training Ctr, Fac Med Pharm & Odontostomatol, Bamako, Mali. [Manoukis, Nicholas C.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 598 BP 170 EP 170 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701014 ER PT J AU Fink, DL Klion, A Nutman, TB AF Fink, Doran L. Klion, Amy Nutman, Thomas B. TI THE TRANSCRIPTOME OF LOA LOA L3 INFECTIVE LARVAE IN COMPARISON TO THE L3 TRANSCRIPTOMES OF THE OTHER MAJOR HUMAN PATHOGENIC FILARIAE SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Fink, Doran L.; Klion, Amy; Nutman, Thomas B.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S BP 192 EP 193 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701087 ER PT J AU Bennuru, S Nutman, TB AF Bennuru, Sasisekhar Nutman, Thomas B. TI DECODING THE INVASION AND MOLTING PROCESSES OF BRUGIA MALAYI L3 LARVAE SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Bennuru, Sasisekhar; Nutman, Thomas B.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S BP 193 EP 193 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701088 ER PT J AU Conrad, PA VanWormer, E Shapiro, K Miller, M Kreuder-Johnson, C Tinker, T Grigg, M Largier, J Carpenter, T Mazet, JK AF Conrad, Patricia A. VanWormer, Elizabeth Shapiro, Karen Miller, Melissa Kreuder-Johnson, Chris Tinker, Tim Grigg, Michael Largier, John Carpenter, Tim Mazet, Jonna K. TI TRACKING TOXOPLASMA GONDII FROM LAND TO SEA SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Conrad, Patricia A.; VanWormer, Elizabeth; Shapiro, Karen; Kreuder-Johnson, Chris; Largier, John; Carpenter, Tim; Mazet, Jonna K.] Univ Calif Davis, Davis, CA 95616 USA. [Miller, Melissa] Calif Dept Fish & Game, Santa Cruz, CA USA. [Tinker, Tim] USGS, WERC, Santa Cruz, CA USA. [Grigg, Michael] NIAID, Bethesda, MD 20892 USA. RI Tinker, Martin/F-1277-2011; Mazet, Jonna/B-4811-2012 NR 0 TC 0 Z9 0 U1 0 U2 11 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 690 BP 198 EP 198 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701106 ER PT J AU Chretien, JP Buczak, AL Anyamba, A Small, J Philip, TL Jessup, C Nuckols, J Leyk, S Miller, M Lewis, SH AF Chretien, Jean-Paul Buczak, Anna L. Anyamba, Assaf Small, Jennifer Philip, Trudy L. Jessup, Christine Nuckols, John Leyk, Stefan Miller, Mark Lewis, Sheri H. TI FORECASTING CHOLERA EPIDEMICS IN AFRICA SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Chretien, Jean-Paul] Walter Reed Army Inst Res, Silver Spring, MD 20771 USA. [Buczak, Anna L.; Philip, Trudy L.; Lewis, Sheri H.] Johns Hopkins Univ, Appl Phys Lab, Laurel, MD 20892 USA. [Anyamba, Assaf; Small, Jennifer] NASA, Goddard Space Flight Ctr, Greenbelt, MD 80309 USA. [Jessup, Christine; Nuckols, John; Leyk, Stefan; Miller, Mark] NIH, Fogarty Int Ctr, Bethesda, MD USA. [Leyk, Stefan] Univ Colorado, Dept Geography, Boulder, CO 80309 USA. NR 0 TC 0 Z9 0 U1 1 U2 6 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 717 BP 206 EP 206 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701133 ER PT J AU Brayner-Santos, FA Araujo, HR Alves, LC Pimenta, PF AF Brayner-Santos, Fabio A. Araujo, Helena R. Alves, Luiz C. Pimenta, Paulo F. TI ULTRASTRUCTURAL STUDY OF AEDES ALBOPICTUS SKUSE, 1895 (DIPTERA: CULICIDAE) HEMOCYTES SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Brayner-Santos, Fabio A.; Alves, Luiz C.] NIH, Rockville, MD USA. [Araujo, Helena R.; Pimenta, Paulo F.] IRR, Belo Horizonte, MG, Brazil. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 755 BP 218 EP 219 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701171 ER PT J AU Alves, LC Araujo, HR Baryner-Santos, FA Pimenta, PF AF Alves, Luiz C. Araujo, Helena R. Baryner-Santos, Fabio A. Pimenta, Paulo F. TI CHARACTERIZATION OF HEMOCYTES FROM AEDES AEGYPTI AND AEDES ALBOPICTUS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Alves, Luiz C.; Baryner-Santos, Fabio A.] NIH, Rockville, MD USA. [Araujo, Helena R.; Pimenta, Paulo F.] Inst Rene Rachou, Belo Horizonte, MG, Brazil. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 758 BP 219 EP 219 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701174 ER PT J AU Santiago, HC Bennuru, S Nutman, T AF Santiago, Helton C. Bennuru, Sasisekhar Nutman, Thomas TI STRUCTURAL AND IMMUNOLOGIC CROSS REACTIVITY AMONG ALLERGENS AND HOMOLOGOUS HELMINTH ANTIGENS: LESSONS LEARNED FROM TROPOMYOSIN AND THEIR IMPLICATION FOR THE HYGIENE HYPOTHESIS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Santiago, Helton C.; Bennuru, Sasisekhar; Nutman, Thomas] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 820 BP 236 EP 237 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701236 ER PT J AU Crivat, G Sa, JM Hwang, J Tokumasu, F Wellems, TE AF Crivat, Georgeta Sa, Juliana Martha Hwang, Jeeseong Tokumasu, Fuyuki Wellems, Thomas E. TI FLUORESCENCE MULTIPLEXING IMAGING FOR STUDYING PROTEIN TRAFFICKING IN PLASMODIUM FALCIPARUM INFECTED HUMAN ERYTHROCYTES USING TETRACYSTEINE-TAGGED KNOB-ASSOCIATED PROTEINS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Crivat, Georgeta; Hwang, Jeeseong] NIST, NIH, Rockville, MD USA. [Sa, Juliana Martha; Tokumasu, Fuyuki; Wellems, Thomas E.] NIAID, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 840 BP 242 EP 242 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701255 ER PT J AU Diakite, SAS Doumbia, S Lopera-Mesa, TM Traore, K Konate, D Doumbia, M Krause, MA Diouf, A Huaman, MC Anderson, JM Doumbia, S Long, CA Diakite, M Fairhurst, RM AF Diakite, Seidina A. S. Doumbia, Saibou Lopera-Mesa, Tatiana M. Traore, Karim Konate, Drissa Doumbia, Mory Krause, Michael A. Diouf, Ababacar Huaman, Maria Cecilia Anderson, Jennifer M. Doumbia, Seydou Long, Carole A. Diakite, Mahamadou Fairhurst, Rick M. TI RELATIONSHIPS BETWEEN HEMOGLOBIN/RED BLOOD CELL POLYMORPHISMS AND HEMOGLOBIN LEVELS IN MALI SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Diakite, Seidina A. S.; Doumbia, Saibou; Traore, Karim; Konate, Drissa; Doumbia, Mory; Doumbia, Seydou; Diakite, Mahamadou] Malaria Res & Training Ctr, Bamako, Mali. [Lopera-Mesa, Tatiana M.; Krause, Michael A.; Diouf, Ababacar; Huaman, Maria Cecilia; Anderson, Jennifer M.; Long, Carole A.; Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 845 BP 243 EP 243 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701260 ER PT J AU Ostera, GR Lukat-Rodgers, G Tokumasu, F Kumar, S Rodgers, K AF Ostera, Graciela R. Lukat-Rodgers, Gudrun Tokumasu, Fuyuki Kumar, Sanjai Rodgers, Kenton TI ASSOCIATION OF NITRIC OXIDE WITH HEME IN PLASMODIUM FALCIPARUM FOOD VACUOLES SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Ostera, Graciela R.; Tokumasu, Fuyuki] NIH, Rockville, MD USA. [Lukat-Rodgers, Gudrun; Rodgers, Kenton] N Dakota State Univ, Fargo, ND 58105 USA. [Kumar, Sanjai] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 844 BP 243 EP 243 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701259 ER PT J AU Mzayek, F Deng, HY Hadi, MA Mave, V Mather, FJ Goodenough, C Mushatt, DM Lertora, JJ Krogstad, D AF Mzayek, Fawaz Deng, Haiyan Hadi, M. Azam Mave, Vidya Mather, Frances J. Goodenough, Christopher Mushatt, David M. Lertora, Juan J. Krogstad, Donald TI RANDOMIZED CLINICAL TRIAL (RCT) WITH A CROSSOVER STUDY DESIGN TO EXAMINE THE SAFETY AND PHARMACOKINETICS OF A 2100 MG DOSE OF AQ-13 AND THE EFFECTS OF A STANDARD FATTY MEAL ON ITS BIOAVAILABILITY SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Mzayek, Fawaz] Univ Memphis, Memphis, TN 38152 USA. [Deng, Haiyan; Hadi, M. Azam; Mave, Vidya; Mather, Frances J.; Goodenough, Christopher; Mushatt, David M.; Krogstad, Donald] Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70118 USA. [Lertora, Juan J.] NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S BP 252 EP 252 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701290 ER PT J AU Yuan, J Johnson, R Huang, RL Wichterman, J Jiang, HY Hayton, K Fidock, D Wellems, T Inglese, J Austin, C Su, XZA AF Yuan, Jing Johnson, Ronald Huang, Ruiling Wichterman, Jennifer Jiang, Hongying Hayton, Karen Fidock, David Wellems, Thomas Inglese, James Austin, Christopher Su, Xinzhuan TI SCREENING AND GENETIC MAPPING TARGETS OF DIFFERENTIAL CHEMICAL-RESPONSE PHENOTYPES IN PLASMODIUM FALCIPARUM SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Yuan, Jing; Jiang, Hongying; Hayton, Karen; Wellems, Thomas; Su, Xinzhuan] NIAID, LMVR, NIH, Rockville, MD USA. [Johnson, Ronald; Huang, Ruiling; Wichterman, Jennifer; Inglese, James; Austin, Christopher] NHGRI, NCGC, NIH, Rockville, MD USA. [Fidock, David] Columbia Univ, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 888 BP 255 EP 256 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701303 ER PT J AU Richards, JS Stanisic, DI Michon, P Dabod, E Chitnis, CE Narum, DE Thompson, JK Cowman, AF Mueller, I Beeson, JG AF Richards, Jack S. Stanisic, Danielle I. Michon, Pascal Dabod, Elijah Chitnis, Chetan E. Narum, David E. Thompson, Jennifer K. Cowman, Alan F. Mueller, Ivo Beeson, James G. TI ANTIBODIES AGAINST THE ERYTHROCYTE BINDING ANTIGENS OF PLASMODIUM FALCIPARUM ARE STRONGLY ASSOCIATED WITH PROTECTION AGAINST CLINICAL MALARIA AND HIGH PARASITEMIA SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Richards, Jack S.; Thompson, Jennifer K.; Cowman, Alan F.; Beeson, James G.] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia. [Stanisic, Danielle I.; Michon, Pascal; Dabod, Elijah; Mueller, Ivo] Papua New Guinea Inst Med Res, Madang, Papua N Guinea. [Chitnis, Chetan E.] Int Ctr Genet Engn & Biotechnol, New Delhi, India. [Narum, David E.] NIH, Rockville, MD USA. RI Mueller, Ivo/C-7251-2013; Cowman, Alan/C-7642-2013 OI Mueller, Ivo/0000-0001-6554-6889; Cowman, Alan/0000-0001-5145-9004 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 911 BP 262 EP 262 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701325 ER PT J AU Alvarenga, PH Calvo, E Francischetti, IM Sa-Nunes, A Ribeiro, JM Andersen, JF AF Alvarenga, Patricia H. Calvo, Eric Francischetti, Ivo M. Sa-Nunes, Anderson Ribeiro, Jose Marcos Andersen, John F. TI ANOPHELES STEPHENSI D7 L: A SALIVARY GLAND PROTEIN WITH BOTH ANTI-INFLAMMATORY AND ANTIHEMOSTATIC EFFECT SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Alvarenga, Patricia H.; Calvo, Eric; Francischetti, Ivo M.; Sa-Nunes, Anderson; Ribeiro, Jose Marcos; Andersen, John F.] NIAID, NIH, Rockville, MD USA. RI Sa-Nunes, Anderson/D-8667-2012 OI Sa-Nunes, Anderson/0000-0002-1859-4973 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 945 BP 272 EP 273 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701359 ER PT J AU Takeo, S Sakamoto, H Kaneko, T Tachibana, M Miura, K Varma, S Sattabongkot, J Torii, M Tsuboi, T AF Takeo, Satoru Sakamoto, Hirokazu Kaneko, Takamasa Tachibana, Mayumi Miura, Kazutoyo Varma, Sudhir Sattabongkot, Jetsumon Torii, Motomi Tsuboi, Takafumi TI IDENTIFICATION OF NOVEL BLOOD-STAGE VACCINE CANDIDATES AGAINST PLASMODIUM FALCIPARUM BY HIGH-THROUGHPUT IMMUNOSCREENING SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Takeo, Satoru; Sakamoto, Hirokazu; Kaneko, Takamasa; Tachibana, Mayumi; Torii, Motomi; Tsuboi, Takafumi] Ehime Univ, Matsuyama, Ehime 790, Japan. [Miura, Kazutoyo] NIAID, MVDB, NIH, Rockville, MD USA. [Varma, Sudhir] NIAID, BCBB, NIH, Bethesda, MD 20892 USA. [Sattabongkot, Jetsumon] Armed Forces Res Inst Med Sci, Bangkok 10400, Thailand. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 944 BP 272 EP 272 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701358 ER PT J AU Coulibaly, MB Diallo, B Guindo, A Traore, MM Traore, SA Konate, M Anderson, JM Lobo, NF Besansky, NJ Ribeiro, JM Traore, SF AF Coulibaly, Mamadou B. Diallo, Brehima Guindo, Amadou Traore, Mohamed M. Traore, Sekou A. Konate, Mamadou Anderson, Jennifer M. Lobo, Neil F. Besansky, Nora J. Ribeiro, Jose M. Traore, Sekou F. TI GENE EXPRESSION PROFILE ASSOCIATED WITH BLOOD FEEDING AND PLASMODIUM FALCIPARUM INFECTION IN THE MALARIA VECTOR ANOPHELES FUNESTUS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Coulibaly, Mamadou B.; Diallo, Brehima; Guindo, Amadou; Traore, Mohamed M.; Traore, Sekou A.; Konate, Mamadou; Traore, Sekou F.] Malaria Res & Training Ctr, Bamako, Mali. [Anderson, Jennifer M.; Ribeiro, Jose M.] NIH, Bethesda, MD 20892 USA. [Lobo, Neil F.; Besansky, Nora J.] Univ Notre Dame, Notre Dame, IN 46556 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 961 BP 277 EP 277 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701375 ER PT J AU Manoukis, NC Sogoba, N Diallo, M Ribeiro, JM AF Manoukis, Nicholas C. Sogoba, Nafomon Diallo, Moussa Ribeiro, Jose M. TI EVIDENCE OF PASSIVE DISPERSAL OF ANOPHELES GAMBIAE IN THE EARLY ADULT PHASE SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Manoukis, Nicholas C.; Ribeiro, Jose M.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Sogoba, Nafomon; Diallo, Moussa] Fac Med, Malaria Res & Training Ctr, Bamako, Mali. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 972 BP 280 EP 280 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701386 ER PT J AU Kelly-Hope, LA McKenzie, FE AF Kelly-Hope, Louise A. McKenzie, F. Ellis TI ENVIRONMENTAL FACTORS ASSOCIATED WITH THE MALARIA VECTORS ANOPHELES GAMBIAE S.L AND ANOPHELES FUNESTUS IN KENYA SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Kelly-Hope, Louise A.] Univ Liverpool, Liverpool Sch Trop Med, Liverpool L3 5QA, Merseyside, England. [McKenzie, F. Ellis] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 979 BP 282 EP 282 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701393 ER PT J AU Crompton, PD Kayala, MA Traore, B Kayentao, K Ongoiba, A Weiss, GE Molina, DM Burk, CR Waisberg, M Jasinskas, A Doumbo, S Doumtabe, D Kone, Y Narum, DL Liang, XW Doumbo, OK Miller, LH Doolan, DL Baldi, P Felgner, PL Pierce, SK AF Crompton, Peter D. Kayala, Matthew A. Traore, Boubacar Kayentao, Kassoum Ongoiba, Aissata Weiss, Greta E. Molina, Douglas M. Burk, Chad R. Waisberg, Michael Jasinskas, Algis Doumbo, Safiatou Doumtabe, Didier Kone, Younoussou Narum, David L. Liang, Xiaowu Doumbo, Ogobara K. Miller, Louis H. Doolan, Denise L. Baldi, Pierre Felgner, Philip L. Pierce, Susan K. TI PROFILING ANTIBODY RESPONSES TO P. FALCIPARUM INFECTION BY PROTEIN MICROARRAY. A STRATEGY FOR IDENTIFYING NOVEL MALARIA VACCINE TARGETS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Crompton, Peter D.; Weiss, Greta E.; Waisberg, Michael; Pierce, Susan K.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Kayala, Matthew A.; Baldi, Pierre] Univ Calif Irvine, Sch Informat & Comp Sci, Inst Genom & Bioinformat, Irvine, CA USA. [Traore, Boubacar; Kayentao, Kassoum; Ongoiba, Aissata; Doumbo, Safiatou; Doumtabe, Didier; Kone, Younoussou; Doumbo, Ogobara K.] Univ Bamako, Malaria Res & Training Ctr, Fac Med Pharm & Dent, Bamako, Mali. [Molina, Douglas M.; Liang, Xiaowu] Antigen Discovery Inc, Irvine, CA USA. [Burk, Chad R.; Jasinskas, Algis; Felgner, Philip L.] Univ Calif Irvine, Dept Med, Div Infect Dis, Irvine, CA 92717 USA. [Narum, David L.; Miller, Louis H.] NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD 20852 USA. [Doolan, Denise L.] Queensland Inst Med Res, Mol Vaccinol Lab, Brisbane, Qld 4006, Australia. RI Doolan, Denise/F-1969-2015; Crompton, Peter/N-1130-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 1007 BP 290 EP 290 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701421 ER PT J AU Diakite, SAS Krause, MA Traore, K Lopera-Mesa, TM Doumbia, S Konate, D Huaman, MC Doumbia, M Diouf, A Anderson, JM Doumbia, S Long, CA Fairhurst, RM Diakite, M AF Diakite, Seidina A. S. Krause, Michael A. Traore, Karim Lopera-Mesa, Tatiana M. Doumbia, Saibou Konate, Drissa Huaman, Maria Cecilia Doumbia, Mory Diouf, Ababacar Anderson, Jennifer M. Doumbia, Seydou Long, Carole A. Fairhurst, Rick M. Diakite, Mahamadou TI HEMOGLOBIN AND RED BLOOD CELL POLYMORPHISMS THAT CONFER PROTECTION AGAINST SEVERE PLASMODIUM FALCIPARUM MALARIA ARE EXCEEDINGLY COMMON IN MALI SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Diakite, Seidina A. S.; Traore, Karim; Doumbia, Saibou; Konate, Drissa; Doumbia, Mory; Doumbia, Seydou; Diakite, Mahamadou] Malaria Res & Training Ctr, Bamako, Mali. [Krause, Michael A.; Lopera-Mesa, Tatiana M.; Huaman, Maria Cecilia; Diouf, Ababacar; Anderson, Jennifer M.; Long, Carole A.; Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 1039 BP 299 EP 299 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701453 ER PT J AU Yusibov, V Chichester, JA Farrance, CE Mett, V Musiychuk, K Shamloul, M Sharma, S Streatfield, S Ugulava, N Sauerwein, RW Roeffen, W Wu, YM Muratova, O Miller, LH Holtzman, DA AF Yusibov, Vidadi Chichester, Jessica A. Farrance, Christine E. Mett, Vadim Musiychuk, Konstantin Shamloul, Moneim Sharma, Satish Streatfield, Stephen Ugulava, Natalia Sauerwein, Robert W. Roeffen, Will Wu, Yimin Muratova, Olga Miller, Louis H. Holtzman, Douglas A. TI ANTIBODIES TO PLANT-PRODUCED PLASMODIUM FALCIPARUM SEXUAL STAGE PROTEIN PFS25 EXHIBIT TRANSMISSION BLOCKING ACTIVITY SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Yusibov, Vidadi; Chichester, Jessica A.; Farrance, Christine E.; Mett, Vadim; Musiychuk, Konstantin; Shamloul, Moneim; Sharma, Satish; Streatfield, Stephen; Ugulava, Natalia] Fraunhofer USA, Ctr Mol Biotechnol, Newark, DE USA. [Sauerwein, Robert W.; Roeffen, Will] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Wu, Yimin; Muratova, Olga; Miller, Louis H.] NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD USA. [Holtzman, Douglas A.] Bill & Melinda Gates Fdn, Seattle, WA USA. RI Sauerwein, Robert/C-8519-2013; Roeffen, W.F.G./L-4607-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 1038 BP 299 EP 299 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701452 ER PT J AU Tozan, Y Panicker, R Darley, SR Laxminarayan, R Breman, JG AF Tozan, Yesim Panicker, Rajashree Darley, Sarah R. Laxminarayan, Ramanan Breman, Joel G. TI PRE-REFERRAL RECTAL ARTESUNATE IS COST-EFFECTIVE FOR TREATING SEVERE CHILDHOOD MALARIA SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Tozan, Yesim] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Panicker, Rajashree; Darley, Sarah R.; Laxminarayan, Ramanan] Resources Future Inc, Washington, DC USA. [Breman, Joel G.] NIH, Fogarty Int Ctr, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 1057 BP 305 EP 305 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701471 ER PT J AU Moretz, SE Diouf, A Zhou, H Tullo, G El Sahli, H Keitel, W Long, CA AF Moretz, Samuel E. Diouf, Ababacar Zhou, Hong Tullo, Gregory El Sahli, Hanaa Keitel, Wendy Long, Carole A. TI ANALYSIS OF THE BIOLOGICAL FUNCTION OF ANTIBODIES ELICITED FOLLOWING IMMUNIZATION OF MALARIA-NAIVE SUBJECTS WITH A PLASMODIUM FALCIPARUM ERYTHROCYTE-BINDING ANTIGEN 175 (EBA175) VACCINE SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Moretz, Samuel E.; Diouf, Ababacar; Zhou, Hong; Tullo, Gregory; Long, Carole A.] NIAID, Lab Malaria & Vector Res, Rockville, MD USA. [El Sahli, Hanaa; Keitel, Wendy] Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 1067 BP 308 EP 308 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701481 ER PT J AU McCarthy, JS Marjason, J Elliott, S Fahey, P Malkin, E Tierney, E Cross, N Richards, JS Boyle, M Bang, G Long, C Druilhe, P Beeson, J Anders, RF AF McCarthy, James S. Marjason, Joanne Elliott, Suzanne Fahey, Paul Malkin, Elissa Tierney, Eveline Cross, Nadia Richards, Jack S. Boyle, Michelle Bang, Gilles Long, Carole Druilhe, Pierre Beeson, James Anders, Robin F. TI A PHASE 1 TRIAL OF A BIVALENT MSP2 BLOOD-STAGE MALARIA VACCINE FORMULATED WITH MONTANIDE ISA 720 SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [McCarthy, James S.] Univ Queensland, Queensland Inst Med Res, Brisbane, Qld 20892, Australia. [Marjason, Joanne; Elliott, Suzanne] Q Pharm Pty Ltd, Brisbane, Qld, Australia. [Fahey, Paul; Malkin, Elissa; Tierney, Eveline] PATH Malaria Vaccine Initiat, Bethesda, MD USA. [Cross, Nadia; Richards, Jack S.; Boyle, Michelle; Beeson, James] Walter & Eliza Hall Inst Med Res, Melbourne, Vic, Australia. [Long, Carole] NIAID, NIH, Bethesda, MD USA. [Bang, Gilles; Druilhe, Pierre] Inst Pasteur, Paris, France. [Anders, Robin F.] La Trobe Univ, Dept Biochem, Melbourne, Vic, Australia. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 1076 BP 310 EP 311 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701490 ER PT J AU Miura, K Zhou, H Diouf, A Tullo, G Aebig, JA Miller, LH Saul, A Doumbo, OK Sagara, I Dicko, A Long, CA Ellis, RD AF Miura, Kazutoyo Zhou, Hong Diouf, Ababacar Tullo, Gregory Aebig, Joan A. Miller, Louis H. Saul, Allan Doumbo, Ogobara K. Sagara, Issaka Dicko, Alassane Long, Carole A. Ellis, Ruth D. TI IMPACT OF PLASMODIUM FALCIPARUM APICAL MEMBRANE ANTIGEN 1-COMBINATION 1/ALHYDROGEL VACCINE ON GROWTH-INHIBITORY ACTIVITY OF ANTIBODIES IN CHILDREN IN MALI SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Miura, Kazutoyo; Aebig, Joan A.; Miller, Louis H.; Saul, Allan; Ellis, Ruth D.] NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD USA. [Zhou, Hong; Diouf, Ababacar; Tullo, Gregory; Long, Carole A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. [Doumbo, Ogobara K.; Sagara, Issaka; Dicko, Alassane] Univ Bamako, Malaria Res & Training Ctr, Fac Med Pharm & Dent, Bamako, Mali. RI Saul, Allan/I-6968-2013 OI Saul, Allan/0000-0003-0665-4091 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 1075 BP 310 EP 310 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701489 ER PT J AU Mahapatra, L Dembele, B Metenou, S Konate, S Dolo, H Coulibaly, ME Soumaoro, L Panka, R Chaussabel, D Coulibaly, SY Sanogo, D Doumbia, SS Diallo, AA Nutman, TB Mahanty, S Semnani, RT AF Mahapatra, Lily Dembele, Benoit Metenou, Simon Konate, Siaka Dolo, Housseini Coulibaly, Michel E. Soumaoro, Lamine Panka, Rungnapa Chaussabel, Damien Coulibaly, Siaka Y. Sanogo, Dramane Doumbia, Salif Seriba Diallo, Abdallah A. Nutman, Thomas B. Mahanty, Siddhartha Semnani, Roshanak Tolouei TI INCREASED POPULATIONS OF CIRCULATING MYELOID AND PLASMACYTOID DENDRITIC CELLS IN PATENT FILARIAL INFECTIONS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Mahapatra, Lily; Metenou, Simon; Nutman, Thomas B.; Mahanty, Siddhartha; Semnani, Roshanak Tolouei] NIAID, NIH, Bethesda, MD 20892 USA. [Dembele, Benoit; Konate, Siaka; Dolo, Housseini; Coulibaly, Michel E.; Soumaoro, Lamine; Coulibaly, Siaka Y.; Sanogo, Dramane; Doumbia, Salif Seriba; Diallo, Abdallah A.] Univ Bamako, FMPOS, Filariasis Unit, Bamako, Mali. [Panka, Rungnapa; Chaussabel, Damien] Baylor Univ, Baylor Inst Immunol Res, Dallas, TX USA. RI Metenou, Simon/C-1101-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 1081 BP 312 EP 312 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701495 ER PT J AU Babu, S Bhat, SQ Kumar, P Anuradha, R Kumaran, P Gopi, PG Kolappan, C Kumaraswami, V Nutman, TB AF Babu, Subash Bhat, Sajid Q. Kumar, Pavan Anuradha, R. Kumaran, Paul Gopi, P. G. Kolappan, C. Kumaraswami, V. Nutman, Thomas B. TI ATTENUATION OF TLR EXPRESSION AND FUNCTION IN LATENT TUBERCULOSIS BY COEXISTENT FILARIAL INFECTION WITH RESTORATION FOLLOWING ANTIFILARIAL CHEMOTHERAPY SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Babu, Subash; Bhat, Sajid Q.; Kumar, Pavan; Anuradha, R.] NIH TRC ICER, Madras, Tamil Nadu, India. [Kumaran, Paul; Gopi, P. G.; Kolappan, C.; Kumaraswami, V.] TB Res Ctr, Madras, Tamil Nadu, India. [Nutman, Thomas B.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 1085 BP 313 EP 314 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701499 ER PT J AU Dembele, B Metenou, S Dolo, H Konate, S Coulibaly, SY Sanogo, D Mahanty, S Coulibaly, ME Soumaoro, L Doumbia, SS Diallo, AA Guindo, MA Diallo, DA Traore, SF Coulibaly, YI Nutman, TB Klion, AD AF Dembele, Benoit Metenou, Simon Dolo, Housseini Konate, Siaka Coulibaly, Siaka Y. Sanogo, Dramane Mahanty, Siddhartha Coulibaly, Michel E. Soumaoro, Lamine Doumbia, Salif S. Diallo, Abdallah A. Guindo, Merepin A. Diallo, Dapa A. Traore, Sekou F. Coulibaly, Yaya I. Nutman, Thomas B. Klion, Amy D. TI PRE-EXISTING FILARIAL INFECTION INFLUENCES CYTOKINE PRODUCTION DURING ACUTE MALARIA IN CHILDREN AND YOUNG ADULTS IN A COENDEMIC REGION OF MALI SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Dembele, Benoit; Dolo, Housseini; Konate, Siaka; Coulibaly, Siaka Y.; Sanogo, Dramane; Coulibaly, Michel E.; Soumaoro, Lamine; Doumbia, Salif S.; Diallo, Abdallah A.; Guindo, Merepin A.; Diallo, Dapa A.; Traore, Sekou F.; Coulibaly, Yaya I.] Univ Bamako, Bamako, Mali. [Metenou, Simon; Mahanty, Siddhartha; Nutman, Thomas B.; Klion, Amy D.] NIAID, NIH, Bethesda, MD 20892 USA. RI Metenou, Simon/C-1101-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 1083 BP 313 EP 313 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701497 ER PT J AU Metenou, S Dembele, B Konate, S Dolo, H Soumaoro, L Diallo, AA Coulibaly, ME Coulibaly, SY Sanogo, D Coulibaly, YI Traore, SF Mahanty, S Klion, AD Nutman, TB AF Metenou, Simon Dembele, Benoit Konate, Siaka Dolo, Housseini Soumaoro, Lamine Diallo, Abdallah A. Coulibaly, Michel E. Coulibaly, Siaka Y. Sanogo, Dramane Coulibaly, Yaya I. Traore, Sekou F. Mahanty, Siddhartha Klion, Amy D. Nutman, Thomas B. TI PATENT FILARIAL INFECTION MODULATES THE QUALITY OF T CELL RESPONSES TO MALARIAL ANTIGENS IN MALARIA/FILARIAL CO-ENDEMIC VILLAGE OF MALI SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Metenou, Simon; Mahanty, Siddhartha; Klion, Amy D.; Nutman, Thomas B.] NIH, Bethesda, MD 20892 USA. [Dembele, Benoit; Konate, Siaka; Dolo, Housseini; Soumaoro, Lamine; Diallo, Abdallah A.; Coulibaly, Michel E.; Coulibaly, Siaka Y.; Sanogo, Dramane; Coulibaly, Yaya I.; Traore, Sekou F.] Univ Bamako, Filaria Unit, FMPOS, Bamako, Mali. RI Metenou, Simon/C-1101-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 1084 BP 313 EP 313 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701498 ER PT J AU Lisk, G Desai, SA AF Lisk, Godfrey Desai, Sanjay A. TI A GENE LINKED TO A NEW ANTIMALARIAL DRUG RESISTANCE MECHANISM: REDUCED UPTAKE BY INFECTED ERYTHROCYTES SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Lisk, Godfrey; Desai, Sanjay A.] NIAID, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 1108 BP 320 EP 320 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701522 ER PT J AU Ellis, RD Sagara, I Durbin, A Dicko, A Shaffer, D Pierce, M Miller, L Assadou, MH Kone, M Kamate, B Guindo, O Fay, MP Diallo, D Doumbo, OK Emmanuel, E Millum, J AF Ellis, Ruth D. Sagara, Issaka Durbin, Anna Dicko, Alassane Shaffer, Donna Pierce, Mark Miller, Louis Assadou, Mahamadoun H. Kone, Mamady Kamate, Beh Guindo, Ousmane Fay, Michael P. Diallo, Dapa Doumbo, Ogobara K. Emmanuel, Ezekiel Millum, Joseph TI COMPARING THE QUALITY OF INFORMED CONSENT IN THE UNITED STATES AND MALI SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 18-22, 2009 CL Washington, DC SP Amer Soc Trop Med & Hyg C1 [Ellis, Ruth D.; Pierce, Mark; Miller, Louis] NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD USA. [Sagara, Issaka; Dicko, Alassane; Assadou, Mahamadoun H.; Kone, Mamady; Kamate, Beh; Guindo, Ousmane; Diallo, Dapa; Doumbo, Ogobara K.] Univ Bamako, Malaria Res & Training Ctr, Fac Med Pharm & Dent, Bamako, Mali. [Durbin, Anna; Shaffer, Donna] Johns Hopkins Ctr Immunizat Res, Washington, DC USA. [Fay, Michael P.] NIAID, Biostat Res Branch, NIH, Rockville, MD USA. [Emmanuel, Ezekiel] NIH, Clin Ctr Dept Bioeth, Bethesda, MD 20892 USA. [Millum, Joseph] NIH, Clin Ctr Dept Bioeth, Fogarty Int Ctr, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 SU S MA 1137 BP 328 EP 328 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WK UT WOS:000271956701551 ER PT J AU Wright, PF Durbin, AP Whitehead, SS Ikizler, MR Henderson, S Blaney, JE Thumar, B Ankrah, S Rock, MT McKinney, BA Murphy, BR Schmidt, AC AF Wright, Peter F. Durbin, Anna P. Whitehead, Stephen S. Ikizler, Mine R. Henderson, Susan Blaney, Joseph E. Thumar, Bhavin Ankrah, Sharon Rock, Michael T. McKinney, Brett A. Murphy, Brian R. Schmidt, Alexander C. TI Phase 1 Trial of the Dengue Virus Type 4 Vaccine Candidate rDEN4 Delta 30-4995 in Healthy Adult Volunteers SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID 3' UNTRANSLATED REGION; HUMAN LIVER-CELLS; YELLOW-FEVER; HEMORRHAGIC-FEVER; SHOCK SYNDROME; IMMUNOGENICITY; SAFETY; ATTENUATION; FORMULATIONS; ANTIBODY AB rDEN4 Delta 30-4995 is a live attenuated dengue virus type 4 (DENV4) vaccine candidate specifically designed as a further attenuated derivative of the rDEN4 Delta 30 parent virus. In a previous study, 5 of 20 vaccinees who received 10(5) plaque-forming units (PFU) of rDEN4 Delta 30 developed a transient elevation of the serum alanine aminotransferase (ALT) level and an asymptomatic maculopapular rash developed in 10 of 20. In the current study, 28 healthy adult volunteers were randomized to receive 10(5) PFU of rDEN4 Delta 30-4995 (20) or placebo (8) as a single subcutaneous injection. The vaccine was safe, well-tolerated, and immunogenic.An asymptomatic generalized maculopapular rash and elevations in ALT levels were observed in 10% of the rDEN4 Delta 30-4995 vaccinees. None of the rDEN4 Delta 30-4995 vaccinees became viremic, yet 95% developed a four-fold or greater increase in neutralizing antibody titers. Thus, rDEN4 Delta 30-4995 was demonstrated to be safe, highly attenuated, and immunogenic. However, an asymptomatic localized erythematous rash at the injection site was seen in 17/20 rDEN4 Delta 30-4995 vaccinees. Therefore, alternative DENV4 vaccine strains were selected for further clinical development. C1 [Whitehead, Stephen S.; Blaney, Joseph E.; Murphy, Brian R.; Schmidt, Alexander C.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Dartmouth Med Sch, Dept Pediat, Lebanon, NH 03756 USA. Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA. [Durbin, Anna P.; Thumar, Bhavin] Johns Hopkins Sch Pulb Hlth, Ctr Immunizat Res, Baltimore, MD 21205 USA. Johns Hopkins Bloomberg Sch Pulb Hlth, Ctr Immunizat Res, Dept Int Hlth, Baltimore, MD USA. [Henderson, Susan; Ankrah, Sharon; Rock, Michael T.] Vanderbilt Univ, Div Pediat Infect Dis, Nashville, TN 37232 USA. [McKinney, Brett A.] Univ Alabama, Sch Med, Dept Genet, Birmingham, AL 35294 USA. RP Schmidt, AC (reprint author), NIAID, Infect Dis Lab, NIH, 50 South Dr,Room 6511, Bethesda, MD 20892 USA. EM peter.f.wright@dartmouth.edu; adurbin@jhsph.edu; swhitehead@niaid.nih.gov; mine.ikizler@vanderbilt.edu; shende8@emory.edu; jblaney@niaid.nih.gov; bthumar@jhsph.edu; sharon.n.ankrah@vanderbilt.edu; michael.rock@vanderbilt.edu; brett.mckinney@gmail.com; bmurphy@niaid.nih.gov; as337y@nih.gov FU National Institutes of Allergy and Infectious Diseases; National Institutes of Health; Johns Hopkins Bloomberg School of Public Health; Vanderbilt University Medical Center FX This study was supported by the Intramural Research Program of the National Institutes of Allergy and Infectious Diseases, National Institutes of Health, in part through a contract with the Johns Hopkins Bloomberg School of Public Health and a subcontract with Vanderbilt University Medical Center. NR 45 TC 29 Z9 30 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2009 VL 81 IS 5 BP 834 EP 841 DI 10.4269/ajtmh.2009.09-0131 PG 8 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 521WI UT WOS:000271956500019 PM 19861619 ER PT J AU Titus, SA Beacham, D Shahane, SA Southall, N Xia, MH Huang, RL Hooten, E Zhao, Y Shou, L Austin, CP Zheng, W AF Titus, Steven A. Beacham, Daniel Shahane, Sampada A. Southall, Noel Xia, Menghang Huang, Ruili Hooten, Elizabeth Zhao, Yong Shou, Louie Austin, Christopher P. Zheng, Wei TI A new homogeneous high-throughput screening assay for profiling compound activity on the human ether-a-go-go-related gene channel SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE Human ether-a-go-go-related gene (hERG); Quantitative high-throughput screening (qHTS); FluxOR; Thallium flux; Baculovirus; BacMam ID HERG POTASSIUM CHANNEL; FLUORESCENCE QUENCHING TECHNIQUE; DRUG DISCOVERY; CARDIAC-ARRHYTHMIA; QT PROLONGATION; K+ CHANNELS; DE-POINTES; DROSOPHILA; MUTATIONS; CELLS AB Long QT syndrome, either inherited or acquired from drug treatments, can result in ventricular arrhythmia (torsade de pointes) and sudden death. Human ether-a-go-go-related gene (hERG) channel inhibition by drugs is now recognized as a common reason for the acquired form of long QT syndrome. It has been reported that more than 100 known drugs inhibit the activity of the hERG channel. Since 1997, several drugs have been withdrawn from the market due to the long QT syndrome caused by hERG inhibition. Food and Drug Administration regulations now require safety data on hERG channels for investigative new drug (IND) applications. The assessment of compound activity on the hERG channel has now become an important part of the safety evaluation in the process of drug discovery. During the past decade, several in vitro assay methods have been developed and significant resources have been used to characterize hERG channel activities. However, evaluation of compound activities on hERG have not been performed for large compound collections due to technical difficulty, lack of throughput, and/or lack of biological relevance to function. Here we report a modified form of the FluxOR thallium flux assay, capable of measuring hERG activity in a homogeneous 1536-well plate format. To validate the assay, we screened a 7-point dilution series of the LOPAC 1280 library collection and reported rank order potencies of ten common hERG inhibitors. A correlation was also observed for the hERG channel activities of 10 known hERG inhibitors determined in this thallium flux assay and in the patch clamp experiment. Our findings indicate that this thallium flux assay can be used as an alternative method to pro. le large-volume compound libraries for compound activity on the hERG channel. Published by Elsevier Inc. C1 [Titus, Steven A.; Shahane, Sampada A.; Southall, Noel; Xia, Menghang; Huang, Ruili; Shou, Louie; Austin, Christopher P.; Zheng, Wei] NHGRI, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA. [Beacham, Daniel] Life Technol, Cellular Syst Div, Eugene, OR 97403 USA. [Hooten, Elizabeth; Zhao, Yong] Cerep, Redmond, WA 98052 USA. RP Zheng, W (reprint author), NHGRI, NIH, Chem Genom Ctr, 9800 Med Ctr Dr, Bethesda, MD 20892 USA. EM wzheng@mail.nih.gov RI Southall, Noel/H-8991-2012; Zheng, Wei/J-8889-2014 OI Southall, Noel/0000-0003-4500-880X; Zheng, Wei/0000-0003-1034-0757 FU NIH; National Human Genome Research Institute FX This research was supported by the Molecular Libraries Initiative of the NIH Roadmap for Medical Research and the Intramural Research Programs of the National Human Genome Research Institute. The authors thank Paul Shinn for assistance with compound management. The authors also thank Shouming Du of Hamamatsu for technical support with the FDSS 7000 kinetic plate reader; Michael O'Grady, Matt Robers, and George Hanson of Invitrogen/Life Technologies and Blake Anson of Cellular Dynamics for technical assistance; and Darryl Leja for help with artwork. NR 44 TC 30 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 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD NOV 1 PY 2009 VL 394 IS 1 BP 30 EP 38 DI 10.1016/j.ab.2009.07.003 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 534GH UT WOS:000272883900005 PM 19583963 ER PT J AU Chikkaveeraiah, BV Bhirde, A Malhotra, R Patel, V Gutkind, JS Rusling, JF AF Chikkaveeraiah, Bhaskara V. Bhirde, Ashwin Malhotra, Ruchika Patel, Vyomesh Gutkind, J. Silvio Rusling, James F. TI Single-Wall Carbon Nanotube Forest Arrays for Immunoelectrochemical Measurement of Four Protein Biomarkers for Prostate Cancer SO ANALYTICAL CHEMISTRY LA English DT Article ID ELECTROCHEMICAL DETECTION; ANALYTICAL PERFORMANCE; SENSOR ARRAYS; ANTIGEN; IMMUNOSENSORS; PROTEOMICS; MARKERS; AMPLIFICATION; IMMUNOASSAY; CHALLENGES AB Protein arrays that measure multiple protein cancer biomarkers in clinical samples hold great promise for reliable early cancer detection. Herein, we report a prototype 4-unit electrochemical immunoarray based on single-wall carbon nanotube forests for the simultaneous detection of multiple protein biomarkers for prostate cancer. Immunoarray procedures were designed to measure prostate specific antigen (PSA), prostate specific membrane antigen (PSMA), platelet factor-4 (PF-4), and interleukin-6 (IL-6) simultaneously in a single serum sample. All of these proteins are elevated in serum of patients with prostate cancer, but they have widely different relative levels of serum concentration. Horseradish peroxidase (HRP) was used as label on detection (secondary) antibodies in a sandwich immunoassay scheme. Biotinylated secondary antibodies (Ab(2)) that bind specifically to streptavidin-HRP conjugates provided 14-16 labels per antibody and gave the necessary higher sensitivity required for PF-4 and IL-6 detection at physiological levels. Conventional singly labeled Ab(2)-HRP conjugates were sufficient for PSA and PSMA detection. Immunoarrays were used to measure four biomarkers in clinical human serum samples of prostate cancer patients and controls with excellent correlation to referee enzyme-linked immunosorbent (ELISA) assays. C1 [Chikkaveeraiah, Bhaskara V.; Bhirde, Ashwin; Malhotra, Ruchika; Rusling, James F.] Univ Connecticut, Dept Chem, Storrs, CT 06269 USA. [Chikkaveeraiah, Bhaskara V.; Bhirde, Ashwin; Malhotra, Ruchika; Rusling, James F.] Univ Connecticut, Inst Mat Sci, Storrs, CT 06269 USA. [Rusling, James F.] Univ Connecticut, Ctr Hlth, Dept Cell Biol, Farmington, CT 06032 USA. [Rusling, James F.] Natl Univ Ireland, Sch Chem, Galway, Ireland. [Patel, Vyomesh; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Phatyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Rusling, JF (reprint author), Univ Connecticut, Dept Chem, 55 N Eagleville Rd, Storrs, CT 06269 USA. EM james.rusling@uconn.edu RI Gutkind, J. Silvio/A-1053-2009 FU NIEHS/NIH [ES013557]; Intramural Research Program; NIDCR; NIH FX This work was supported by PHS Grant ES013557 from NIEHS/NIH and partially by the Intramural Research Program, NIDCR, NIH. We thank Debra Rood and Lawrence K. Silbart for assistance with ELISA measurements. NR 39 TC 92 Z9 94 U1 3 U2 40 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 1 PY 2009 VL 81 IS 21 BP 9129 EP 9134 DI 10.1021/ac9018022 PG 6 WC Chemistry, Analytical SC Chemistry GA 577AL UT WOS:000276191900066 PM 19775154 ER PT J AU Moyo, VM Mvundura, E Khumalo, H Gangaidzo, IT Saungweme, T Nouraie, M Rouault, TA Gomo, ZAR Gordeuk, VR AF Moyo, Victor M. Mvundura, Elisha Khumalo, Hlosukwazi Gangaidzo, Innocent T. Saungweme, Thokozile Nouraie, Mehdi Rouault, Tracey A. Gomo, Zvenyika A. R. Gordeuk, Victor R. TI Serum ferritin concentrations in Africans with low dietary iron SO ANNALS OF HEMATOLOGY LA English DT Article DE African iron overload; Iron status; Ferritin; Dietary iron ID ERYTHROCYTE SEDIMENTATION-RATE; HEREDITARY HEMOCHROMATOSIS; OVERLOAD; POPULATION; GENE; FORTIFICATION; DEFICIENCY; NUTRITION; AMERICAN; BEER AB In the setting of high dietary, several studies have provided evidence for a strong effect of both high dietary iron and an unidentified genetic locus on iron stores in Africans. To investigate whether these effects are discernible in the setting of low dietary iron, serum ferritin concentrations were measured in 194 Zimbabwean men > 30 years of age and 299 postmenopausal women who consumed a non-iron-fortified diet and who did not drink iron-rich traditional beer or other alcoholic beverages. Comparisons were made with non-alcohol drinking African-Americans studied in the third National Health and Nutritional Examination Survey (NHANES III) who consume an iron-fortified diet. As stratified by age and sex, serum ferritin concentrations were significantly lower in the 493 Zimbabweans studied than in 1,380 comparable African-Americans (P < 0.0005). Nevertheless, nine Zimbabwean subjects (1.8% of all cases) had modestly elevated serum ferritin concentrations not associated with evidence of inflammation or hepatic dysfunction. These data suggest that mild serum ferritin concentration elevations may occur among Zimbabweans not exposed to high dietary iron and that iron fortification of the diet may have substantial effects on serum ferritin concentration. C1 [Nouraie, Mehdi; Gordeuk, Victor R.] Howard Univ, Dept Med, Washington, DC 20060 USA. [Nouraie, Mehdi; Gordeuk, Victor R.] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20060 USA. [Moyo, Victor M.] Ortho Biotech LLC, Clin Affairs, Oncol Hematol, Bridgewater, NJ USA. [Mvundura, Elisha] Georgetown Hosp, Dept Obstet & Gynecol, Washington, DC USA. [Khumalo, Hlosukwazi] Univ Witwatersrand, Fac Hlth Sci, Johannesburg, South Africa. [Gangaidzo, Innocent T.; Saungweme, Thokozile] Univ Zimbabwe, Sch Med, Dept Med, Harare, Zimbabwe. [Rouault, Tracey A.] NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. RP Gordeuk, VR (reprint author), Howard Univ, Dept Med, 2041 Georgia Ave NW, Washington, DC 20060 USA. EM vgordeuk@howard.edu FU NIH [UH1-HL03679-07]; Office of Research on Minority Health; Howard University General Clinical Research Center [MO1-RR10284]; National Institute of Child Health and Human Development [1-HD-3-3196]; J.F. Kapnek Charitable Trust (Philadelphia, PA); University of Zimbabwe (Harare, Zimbabwe) FX This study was supported in part by the NIH research grant no. UH1-HL03679-07 from the National Heart, Lung and Blood Institute and the Office of Research on Minority Health and by Howard University General Clinical Research Center grant no. MO1-RR10284, by National Institute of Child Health and Human Development contract no. 1-HD-3-3196, by a grant from the J.F. Kapnek Charitable Trust (Philadelphia, PA), and by a grant allocation from the Research Board of the University of Zimbabwe (Harare, Zimbabwe). NR 34 TC 5 Z9 5 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0939-5555 J9 ANN HEMATOL JI Ann. Hematol. PD NOV PY 2009 VL 88 IS 11 BP 1131 EP 1136 DI 10.1007/s00277-009-0718-6 PG 6 WC Hematology SC Hematology GA 495SX UT WOS:000269916400010 PM 19259672 ER PT J AU Marenne, G Chanock, S Rothman, N Rodriguez-Santiago, B Rico, D Pita, G Perez-Jurado, L Valencia, A Jacobs, K Pisano, DG Diaz-Uriarte, R Earl, J Garcia-Closas, M Silverman, D Kogevinas, M Genin, E Real, FX Malats, N AF Marenne, Gaelle Chanock, Stephen Rothman, Nathaniel Rodriguez-Santiago, Benjamin Rico, Daniel Pita, Guillermo Perez-Jurado, Luis Valencia, Alfonso Jacobs, Kevin Pisano, David G. Diaz-Uriarte, Ramon Earl, Julie Garcia-Closas, Montserrat Silverman, Debra Kogevinas, Manolis Genin, Emmanuelle Real, Francisco X. Malats, Nuria TI CNV assessment using the Illumina Infinium 1M platform: Agreement according to algorithm and source of DNA SO ANNALS OF HUMAN GENETICS LA English DT Meeting Abstract CT European Mathematical Genetics Meeting CY MAY 14-15, 2009 CL Munich, GERMANY C1 [Marenne, Gaelle; Rico, Daniel; Pita, Guillermo; Valencia, Alfonso; Pisano, David G.; Diaz-Uriarte, Ramon; Earl, Julie; Real, Francisco X.; Malats, Nuria] Spanish Natl Canc Res Ctr CNIO, Madrid, Spain. [Chanock, Stephen; Rothman, Nathaniel; Jacobs, Kevin; Garcia-Closas, Montserrat; Silverman, Debra] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Rodriguez-Santiago, Benjamin; Perez-Jurado, Luis] Univ Pompeu Fabra, Fac Ciencies Salut, Barcelona, Spain. [Kogevinas, Manolis] CREAL IMIM, Hosp Mar, Barcelona, Spain. [Marenne, Gaelle; Genin, Emmanuelle] INSERM, UMR S946, Fdn Jean Dausset CEPH, Paris, France. [Genin, Emmanuelle] Univ Paris Diderot, Paris, France. RI Genin, Emmanuelle/C-4974-2013; Valencia, Alfonso/I-3127-2015; Perez Jurado, Luis Alberto/M-7706-2015; Kogevinas, Manolis/C-3918-2017; Pisano, David/N-5817-2014 OI Genin, Emmanuelle/0000-0003-4117-2813; Valencia, Alfonso/0000-0002-8937-6789; Pisano, David/0000-0002-4895-4124 NR 0 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD NOV PY 2009 VL 73 BP 660 EP 660 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 505VL UT WOS:000270726900017 ER PT J AU Minig, L Biffi, R Zanagnolo, V Attanasio, A Beltrami, C Bocciolone, L Botteri, E Colombo, N Iodice, S Landoni, F Peiretti, M Roviglione, G Maggioni, A AF Minig, Lucas Biffi, Roberto Zanagnolo, Vanna Attanasio, Anna Beltrami, Carmen Bocciolone, Luca Botteri, Edoardo Colombo, Nicoletta Iodice, Simona Landoni, Fabio Peiretti, Michele Roviglione, Giovanni Maggioni, Angelo TI Reduction of Postoperative Complication Rate with the Use of Early Oral Feeding in Gynecologic Oncologic Patients Undergoing a Major Surgery: A Randomized Controlled Trial SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID QUALITY-OF-LIFE; NORTHERN EUROPEAN COUNTRIES; ENTERAL NUTRITION; OVARIAN-CANCER; MATERNAL SATISFACTION; QUESTIONNAIRE MODULE; SURGICAL PATIENTS; CESAREAN-SECTION; CLINICAL IMPACT; FOOD-INTAKE AB A randomized controlled trial was performed to assess the outcome of early oral postoperative feeding (EOF) compared with traditional oral feeding (TOF) in gynecologic oncology patients undergoing a complex laparotomy, including upper abdominal surgery. Patients aged 18-75 years, undergoing an elective laparotomy and with a preoperative suspicion of gynecologic malignancy, were eligible. Exclusion criteria included infectious conditions, intestinal obstruction, severe malnutrition, American Society of Anesthesiologists score a parts per thousand yen4, intestinal resection, and postoperative stay in the intensive care unit lasting > 24 h. Patients allocated to EOF received liquid diet in the first postoperative day and then regular diet. Patients received traditional feeding scheme until resolution of postoperative ileus to start liquid diet. The primary end-point of the trial was length of hospital stay. Between January 1, 2007, and November 17, 2007, a total of 143 patients were randomized to receive either EOF or TOF. Hospital stay for patients who received EOF (n = 71) was 4.7 vs. 5.8 days for the TOF group (n = 72) (P = 0.006). The mean level of postoperative satisfaction was significantly higher in the EOF group (82.8 vs. 71.7 mm, P a parts per thousand currency sign 0.001). Patients who received the TOF scheme had significantly higher overall postoperative complications (39 vs. 17% in EOF group, P = 0.003) and infective complications (14% in TOF group vs. 3% in EOF group, P = 0.017). Variables such as nausea and vomiting, analgesic and antiemetic requirement as well as level of pain and quality of life were not different between groups. On the basis of these findings, the policy of EOF should be used after a complex gynecologic oncologic laparotomy. C1 [Minig, Lucas; Zanagnolo, Vanna; Bocciolone, Luca; Colombo, Nicoletta; Landoni, Fabio; Peiretti, Michele; Roviglione, Giovanni; Maggioni, Angelo] European Inst Oncol, Dept Gynecol, Milan, Italy. [Biffi, Roberto] European Inst Oncol, Abdominopelv Surg Dept, Milan, Italy. [Attanasio, Anna] European Inst Oncol, Dept Anesthesiol, Milan, Italy. [Beltrami, Carmen] European Inst Oncol, Gynecol Nurses Dept, Milan, Italy. [Botteri, Edoardo; Iodice, Simona] European Inst Oncol, Div Epidemiol & Biostat, Milan, Italy. [Minig, Lucas] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. RP Minig, L (reprint author), European Inst Oncol, Dept Gynecol, Milan, Italy. EM lucasminig@yahoo.com NR 47 TC 20 Z9 21 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD NOV PY 2009 VL 16 IS 11 BP 3101 EP 3110 DI 10.1245/s10434-009-0681-4 PG 10 WC Oncology; Surgery SC Oncology; Surgery GA 510LE UT WOS:000271089200018 PM 19760046 ER PT J AU Jonsson, H Helgadottir, GP Aspelund, T Eiriksdottir, G Sigurdsson, S Ingvarsson, T Harris, TB Launer, L Gudnason, V AF Jonsson, H. Helgadottir, G. P. Aspelund, T. Eiriksdottir, G. Sigurdsson, S. Ingvarsson, T. Harris, T. B. Launer, L. Gudnason, V. TI Hand osteoarthritis in older women is associated with carotid and coronary atherosclerosis: the AGES Reykjavik study SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID BONE-MARROW EDEMA; MYOCARDIAL-INFARCTION; RISK-FACTORS; KLOTHO GENE; DISEASE; POPULATION; PREVALENCE; ROTTERDAM; MORTALITY; ADULTS AB Objective: There is evidence that atherosclerosis may contribute to the initiation or progression of osteoarthritis. To test this hypothesis, the presence and severity of hand osteoarthritis (HOA) was compared with markers of atherosclerotic vascular disease in an elderly population. Patients and Methods: The AGES Reykjavik Study is a population-based multidisciplinary study of ageing in the elderly population of Reykjavik. In a study of 2264 men ( mean age 76 years; SD 6) and 3078 women ( mean age 76 years; SD 6) the severity of HOA, scored from photographs, was compared with measures of atherosclerosis. These included carotid intimal thickness and plaque severity, coronary calcifications (CAC) and aortic calcifications and reported cardiac and cerebrovascular events. Results: After adjustment for confounders, both carotid plaque severity and CAC were significantly associated with HOA in women, with an odds ratio of 1.42 (95% CI 1.14 to 1.76, p=0.002) for having CAC and 1.25 ( 95% CI 1.04 to 1.49, p=0.016) for having moderate or severe carotid plaques. Both carotid plaques and CAC also exhibited significant linear trends in relation to HOA severity in women in the whole AGES Reykjavik cohort (p<0.001 and p=0.027, respectively, for trend). No significant associations were seen in men. Despite this evidence of increased atherosclerosis, women with HOA did not report proportionally more previous cardiovascular or cerebrovascular events. Conclusions: The results indicate a linear association between the severity of HOA and atherosclerosis in older women. The pathological process of HOA seems to have some components in common with atherosclerosis. Prospective studies may help elucidate the possible mechanisms of this relationship. C1 [Jonsson, H.] Landspitalinn Univ Hosp, Dept Rheumatol, IS-108 Reykjavik, Iceland. [Aspelund, T.] Univ Iceland, Iceland Heart Assoc, Reykjavik, Iceland. [Ingvarsson, T.] Akureyri Cent Hosp, Akureyri, Iceland. [Harris, T. B.; Launer, L.] NIA, Bethesda, MD 20892 USA. RP Jonsson, H (reprint author), Landspitalinn Univ Hosp, Dept Rheumatol, IS-108 Reykjavik, Iceland. EM helgijon@landspitali.is RI Aspelund, Thor/F-4826-2011; Aspelund, Thor/C-5983-2008; Gudnason, Vilmundur/K-6885-2015 OI Aspelund, Thor/0000-0002-7998-5433; Gudnason, Vilmundur/0000-0001-5696-0084 FU National Institutes of Health [N01AG-12100]; NIA Intramural Research Program, Hjartavernd ( the Icelandic Heart Association); Althingi ( the Icelandic Parliament); Icelandic Osteoarthritis Fund; University of Iceland Science Fund FX This study has been funded by National Institutes of Health contract N01AG-12100, the NIA Intramural Research Program, Hjartavernd ( the Icelandic Heart Association) and the Althingi ( the Icelandic Parliament). The study was also supported by the Icelandic Osteoarthritis Fund and the University of Iceland Science Fund. NR 29 TC 45 Z9 47 U1 1 U2 5 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 2009 VL 68 IS 11 BP 1696 EP 1700 DI 10.1136/ard.2008.096289 PG 5 WC Rheumatology SC Rheumatology GA 505NP UT WOS:000270700900008 PM 19033292 ER PT J AU Cook, MB Greenwood, DC Hardie, LJ Forman, D Wild, CP AF Cook, Michael B. Greenwood, Darren C. Hardie, Laura J. Forman, David Wild, Christopher P. TI On the Association Between Body Mass Index and Barrett's Esophagus SO ANNALS OF THORACIC SURGERY LA English DT Letter ID METAANALYSIS C1 [Cook, Michael B.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Greenwood, Darren C.] Univ Leeds, Div Biostat, Ctr Biostat & Epidemiol, Leeds Inst Genet Hlth & Therapeut, Leeds LS2 9JT, W Yorkshire, England. [Wild, Christopher P.] Int Agcy Res Canc, F-69372 Lyon, France. [Forman, David] Leeds Inst Genet Hlth & Therapeut, Ctr Biostat & Epidemiol, Canc Epidemiol Grp, Leeds, W Yorkshire, England. [Hardie, Laura J.] Leeds Inst Genet Hlth & Therapeut, Ctr Biostat & Epidemiol, Mol Epidemiol Unit, Leeds, W Yorkshire, England. RP Cook, MB (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 5012, Rockville, MD 20852 USA. EM cookmich@mail.nih.gov; d.c.greenwood@leeds.ac.uk; laura.j.hardie@leeds.ac.uk; d.forman@leeds.ac.uk; director@iarc.fr RI Greenwood, Darren/C-3220-2008; Cook, Michael/A-5641-2009 OI Greenwood, Darren/0000-0001-7035-3096; Cook, Michael/0000-0002-0533-7302 FU Intramural NIH HHS [NIH0013132602]; PHS HHS [NIH0013132602] NR 2 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD NOV PY 2009 VL 88 IS 5 BP 1728 EP 1728 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 512AZ UT WOS:000271215700077 PM 19853166 ER PT J AU Tulloch-Reid, M Skarulis, MC Sherman, SI Sarlis, NJ Santarpia, L AF Tulloch-Reid, Marshall Skarulis, Monica C. Sherman, Steven I. Sarlis, Nicholas J. Santarpia, Libero TI Long-term Eradication of Locally Recurrent Invasive Follicular Thyroid Carcinoma after Taxane-based Concomitant Chemoradiotherapy SO ANTICANCER RESEARCH LA English DT Article DE Aerodigestive tract; external beam; radioiodine; radiosensitizer; radiotherapy; paclitaxel; taxane; carboplatin ID SQUAMOUS-CELL CARCINOMA; CONCURRENT WEEKLY DOCETAXEL; BEAM RADIATION-THERAPY; PHASE-II TRIAL; HYPERFRACTIONATED RADIOTHERAPY; SURGICAL-MANAGEMENT; BOOST RADIATION; NECK-CANCER; HEAD; DEATH AB A 46-year-old woman with history of radioiodine-refractory follicular thyroid carcinoma (FTC) presented with locally recurrent, high-risk, invasive disease. She was treated with paclitaxel/carboplatin concomitant chemoradiotherapy (CRT), which was well tolerated, resulting in complete remission and freedom from residual or recurrent FTC for longer than 5 years until her last follow-up at age 52. This case highlights the possibility of combining taxane-based chemotherapy with definitive radiotherapy (as CRT) for the management of locally aggressive recurrences in poorly differentiated thyroid carcinoma, thereby resulting in rapid and persistent disease eradication. Even in the light of recent data on the potential benefit of novel targeted therapy agents in poorly differentiated thyroid carcinoma, this approach in similar clinical settings deserves future investigation. C1 [Sherman, Steven I.; Sarlis, Nicholas J.; Santarpia, Libero] Univ Texas MD Anderson Canc Ctr, Dept Endocrine Neoplasia & Hormonal Disorders, Houston, TX 77030 USA. [Tulloch-Reid, Marshall; Skarulis, Monica C.] NIDDKD, NIH, Bethesda, MD 20892 USA. [Santarpia, Libero] Hosp Prato, Translat Res Unit, Florence, Italy. [Santarpia, Libero] Ist Toscana Tumori, Florence, Italy. RP Santarpia, L (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Endocrine Neoplasia & Hormonal Disorders, Houston, TX 77030 USA. EM lsantarp@mdanderson.org RI Tulloch-Reid, Marshall/E-4383-2012; OI Santarpia, Libero/0000-0001-6777-1449; Sherman, Steven/0000-0002-3079-5153 FU Intramural NIH HHS [ZIA DK047053-04] NR 50 TC 2 Z9 2 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD NOV PY 2009 VL 29 IS 11 BP 4665 EP 4671 PG 7 WC Oncology SC Oncology GA 538SC UT WOS:000273203300046 PM 20032418 ER PT J AU Christen-Zaech, S Imoto, K Khan, SG Oh, KS Tamura, D DiGiovanna, JJ Boyle, J Patronas, NJ Schiffmann, R Kraemer, KH Paller, AS AF Christen-Zaech, Stephanie Imoto, Kyoko Khan, Sikandar G. Oh, Kyu-Seon Tamura, Deborah DiGiovanna, John J. Boyle, Jennifer Patronas, Nickolas J. Schiffmann, Raphael Kraemer, Kenneth H. Paller, Amy S. TI Unexpected Occurrence of Xeroderma Pigmentosum in an Uncle and Nephew SO ARCHIVES OF DERMATOLOGY LA English DT Article ID GROUP-A PATIENTS; DNA-REPAIR GENE; COCKAYNE-SYNDROME; XPAC GENE; MUTATIONS; DAMAGE; TRICHOTHIODYSTROPHY; DISORDERS; NEURODEGENERATION; POPULATION AB Background: Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by a decreased ability to repair DNA damaged by UV radiation and the early development of cutaneous and ocular malignant neoplasms. Approximately 20% of patients with XP also develop progressive neurologic degeneration. Observations: We describe a boy who was found to have XP after a severe burn following minimal sun exposure. His maternal uncle, now age 20 years, had been diagnosed with XP after a similar sunburn in infancy. The uncle has the typical skin pigmentary findings of XP along with severe progressive neurologic involvement. Although the infant's parents were not known to be blood relatives, the infant and his affected uncle proved to be compound heterozygotes for the same 2 frameshift mutations in the XPA DNA repair gene (c.288delT and c.349_353del). After the diagnosis of XP in the infant, genealogic investigation identified a common Dutch ancestor for both of his grandfathers 5 generations back. Conclusions: Counseling families at risk for a rare inherited disease is not always straightforward. The sociocultural and demographic backgrounds of the families must be considered for evaluation of risk assessment. C1 [Christen-Zaech, Stephanie; Paller, Amy S.] Northwestern Univ, Feinberg Sch Med, Dept Dermatol, Chicago, IL 60611 USA. [Christen-Zaech, Stephanie; Paller, Amy S.] Northwestern Univ, Feinberg Sch Med, Dept Pediat, Chicago, IL 60611 USA. [Imoto, Kyoko; Khan, Sikandar G.; Oh, Kyu-Seon; Tamura, Deborah; DiGiovanna, John J.; Boyle, Jennifer; Kraemer, Kenneth H.] NCI, DNA Repair Sect, Basic Res Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [DiGiovanna, John J.] Brown Univ, Warren Alpert Med Sch, Dept Dermatol, Div Dermatopharmacol, Providence, RI 02912 USA. [Patronas, Nickolas J.] NIH, Dept Radiol, Ctr Clin, Bethesda, MD 20892 USA. [Schiffmann, Raphael] NINDS, NIH, Bethesda, MD 20892 USA. RP Paller, AS (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Dermatol, 676 N St Clair St,Ste 1600, Chicago, IL 60611 USA. EM apaller@northwestern.edu FU Intramural Research Program of the NIH; Center for Cancer Research, NCI FX Funding/Support: This research was supported in part by the Intramural Research Program of the NIH, Center for Cancer Research, NCI. NR 32 TC 3 Z9 3 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD NOV PY 2009 VL 145 IS 11 BP 1285 EP 1291 PG 7 WC Dermatology SC Dermatology GA 520ZS UT WOS:000271889100010 PM 19917958 ER PT J AU Chodick, G Kleinerman, RA Stovall, M Abramson, DH Seddon, JM Smith, SA Tucker, MA AF Chodick, Gabriel Kleinerman, Ruth A. Stovall, Marilyn Abramson, David H. Seddon, Johanna M. Smith, Susan A. Tucker, Margaret A. TI Risk of Cataract Extraction Among Adult Retinoblastoma Survivors SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID RADIATION-THERAPY; RADIOTHERAPY; SURGERY; IRRADIATION; GENE AB Objective: To investigate the risk of cataract extraction among adult retinoblastoma survivors. Design: A retrospective cohort study was performed on retinoblastoma survivors who received the diagnosis from 1914 to 1984 and were interviewed in 2000. Lens doses were estimated from radiotherapy records. The cumulative time interval to cataract extraction between dose groups was compared using the log-rank test and Cox regression. Results: Seven hundred fifty-three subjects (828 eyes) were available for analysis for an average of 32 years of follow-up. During this period, 51 cataract extractions were reported. One extraction was reported in an eye with no radiotherapy compared with 36 extractions in 306 eyes with 1 course of radiotherapy and 14 among 38 eyes with 2 or 3 treatments. The average time interval to cataract extraction in irradiated eyes was 51 years (95% confidence interval [ CI], 48-54) following 1 treatment and 32 years (95% CI, 27-37) after 2 or 3 treatments. Eyes exposed to a therapeutic radiation dose of 5 Gy or more had a 6-fold increased risk (95% CI, 1.3-27.2) of cataract extraction compared with eyes exposed to 2.5 Gy or less. Conclusions: The results emphasize the importance of ophthalmologic examination of retinoblastoma survivors who have undergone radiotherapy. The risk of cataract extraction in untreated eyes with retinoblastoma is comparable with the risk of the general population. C1 [Chodick, Gabriel; Kleinerman, Ruth A.; Tucker, Margaret A.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA. [Stovall, Marilyn; Smith, Susan A.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. [Abramson, David H.] Mem Sloan Kettering Canc Ctr, Ophthalm Oncol Serv, New York, NY 10021 USA. [Seddon, Johanna M.] Tufts Med Ctr, Ophthalm Epidemiol & Genet Serv, New England Eye Ctr, Boston, MA USA. RP Chodick, G (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM hodik_g@mac.org.il OI Kleinerman, Ruth/0000-0001-7415-2478 FU National Institutes of Health; National Cancer Institute; Division of Cancer Epidemiology and Genetics FX This research was supported by the Intramural Research Program of the National Institutes of Health, the National Cancer Institute, Division of Cancer Epidemiology and Genetics. NR 36 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD NOV PY 2009 VL 127 IS 11 BP 1500 EP 1504 PG 5 WC Ophthalmology SC Ophthalmology GA 516ZY UT WOS:000271583700012 PM 19901216 ER PT J AU Sikdar, S Shah, JP Gebreab, T Yen, RH Gilliams, E Danoff, J Gerber, LH AF Sikdar, Siddhartha Shah, Jay P. Gebreab, Tadesse Yen, Ru-Huey Gilliams, Elizabeth Danoff, Jerome Gerber, Lynn H. TI Novel Applications of Ultrasound Technology to Visualize and Characterize Myofascial Trigger Points and Surrounding Soft Tissue SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Myofascial pain syndromes; Rehabilitation; Sonoelastography; Trigger points, myofascial; Ultrasonography ID MAGNETIC-RESONANCE ELASTOGRAPHY; HUMAN SKELETAL-MUSCLE; TAUT BANDS; PAIN; PREVALENCE; TENSION AB Objective: To apply ultrasound (US) imaging techniques to better describe the characteristics of myofascial trigger points (MTrPs) and the immediately adjacent soft tissue. Design: Four sites in each patient were labeled based on physical examination as active myofascial trigger points (A-MTrPs; spontaneously painful), latent myofascial trigger points (L-MTrPs; nonpainful), or normal myofascial tissue. US examination was performed on each subject by a team blinded to the physical findings. A 12 similar to 5MHz US transducer was used. Vibration sonoelastography (VSE) was performed by color Doppler variance imaging while simultaneously inducing vibrations (similar to 92Hz) with a handheld massage vibrator. Each site was assigned a tissue imaging score as follows: 0, uniform. echogenicity and stiffness; 1, focal hypoechoic region with stiff nodule; 2, multiple hypoechoic regions with stiff nodules. Blood flow in the neighborhood of MTrPs was assessed using Doppler imaging. Each site was assigned a blood flow waveform score as follows: 0, normal arterial flow in muscle; 1, elevated diastolic flow; 2, high-resistance flow waveform with retrograde diastolic flow. Setting: Biomedical research center. Participants: Subjects (N=9) meeting Travell and Simons' criteria for MTrPs in a taut band in the upper trapezius. Interventions: Not applicable. Main Outcome Measures: MTrPs were evaluated by (1) physical examination, (2) pressure algometry, and (3) three types of US imaging including gray-scale (2-dimensional [2D] US), VSE, and Doppler. Results: MTrPs appeared as focal, hypoechoic regions on 2D US, indicating local changes in tissue echogenicity, and as focal regions of reduced vibration amplitude on VSE, indicating a localized, stiff nodule. MTrPs were elliptical, with a size of.16 +/- 11cm(2). There were no significant differences in size between A-MTrPs and L-MTrPs. Sites containing MTrPs were more likely to have a higher tissue imaging score compared with normal myofascial tissue (P<002). Small arteries (or enlarged arterioles) near A-MTrPs showed retrograde flow in diastole, indicating a highly resistive vascular bed. A-MTrP sites were more likely to have a higher blood flow score compared with L-MTrPs (P<.021). Conclusions: Preliminary findings show that, under the conditions of this investigation, US imaging techniques can be used to distinguish myofascial tissue containing MTrPs from normal myofascial tissue (lacking trigger points). US enables visualization and some characterization of MTrPs and adjacent soft tissue. C1 [Sikdar, Siddhartha] George Mason Univ, Dept Elect & Comp Engn, Fairfax, VA 22030 USA. [Gerber, Lynn H.] George Mason Univ, Ctr Study Chron Illness & Disabil, Fairfax, VA 22030 USA. [Shah, Jay P.; Gebreab, Tadesse; Yen, Ru-Huey; Gilliams, Elizabeth; Danoff, Jerome; Gerber, Lynn H.] NIH, Dept Rehabil Med, Bethesda, MD 20892 USA. RP Sikdar, S (reprint author), George Mason Univ, Dept Elect & Comp Engn, 4400 Univ Dr,MS 1G5, Fairfax, VA 22030 USA. EM ssikdar@gmu.edu OI Sikdar, Siddhartha/0000-0002-6426-2320 FU National Institutes of Health (NIH) FX Supported by the Intramural Research Program, National Institutes of Health (NIH), and the Clinical Center and Office of the Director, NIH. NR 34 TC 102 Z9 106 U1 2 U2 19 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD NOV PY 2009 VL 90 IS 11 BP 1829 EP 1838 DI 10.1016/j.apmr.2009.04.015 PG 10 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 520XC UT WOS:000271881900003 PM 19887205 ER PT J AU Rider, LG Lachenbruch, PA Monroe, JB Ravelli, A Cabalar, I Feldman, BM Villalba, ML Myones, BL Pachman, LM Rennebohm, RM Reed, AM Miller, FW AF Rider, Lisa G. Lachenbruch, Peter A. Monroe, Jason B. Ravelli, Angelo Cabalar, Imelda Feldman, Brian M. Villalba, Maria L. Myones, Barry L. Pachman, Lauren M. Rennebohm, Robert M. Reed, Ann M. Miller, Frederick W. CA IMACS Grp TI Damage Extent and Predictors in Adult and Juvenile Dermatomyositis and Polymyositis as Determined With the Myrositis Damage Index SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; IDIOPATHIC INFLAMMATORY MYOPATHIES; COLLABORATING-CLINICS/AMERICAN-COLLEGE; 3 ETHNIC-GROUPS; MULTICENTER COHORT; INITIAL VALIDATION; DISEASE-ACTIVITY; CHILDHOOD-ONSET; RISK-FACTORS; ASSOCIATION AB Objective. We undertook this study to validate the Myositis Damage Index (MDI) in juvenile and adult myositis, to describe the degree and types of damage and to develop predictors of damage. Methods. Retrospective MDI evaluations and prospective assessment of disease activity and illness features were conducted. Patients with juvenile-onset disease (n = 143) were evaluated a median of 18 months after diagnosis; 135 patients were assessed 7-9 months later, and 121 were last assessed a median of 82 months after diagnosis. Ninety-six patients with adult-onset dermatomyositis or polymyositis had a baseline assessment a median of 30 months after diagnosis; 77 patients had a 6-month followup evaluation, and 55 had a final assessment a median of 60 months after diagnosis. Results. Damage was present in 79% of juvenile patients and in 97% of adult patients. In juveniles, scarring, contractures, persistent weakness, muscle dysfunction, and calcinosis were most frequent (23-30%) at the last evaluation. In adults, muscle atrophy, muscle dysfunction, and muscle weakness were most frequent (74-84%). MDI severity correlated with physician-assessed global damage, serum creatinine, and muscle atrophy on magnetic resonance imaging, and in juveniles also with functional disability and weakness. MDI damage scores and frequency were highest in patients with a chronic illness course and in adult patients who died. Predictors of damage included functional disability, duration of active disease, disease severity at diagnosis, physician-assessed global disease activity, and illness features, including ulcerations in children and pericarditis in adults. Conclusion. Damage is common in myositis after a median duration of 5 years in patients with adult-onset disease and 6.8 years in patients with juvenile-onset disease. The MDI has good content, construct, and predictive validity in juvenile and adult myositis. C1 [Rider, Lisa G.] Natl Inst Environm Hlth Sci, Environm Autoimmun Grp, NIH, Bethesda, MD 20892 USA. [Lachenbruch, Peter A.] Oregon State Univ, Corvallis, OR 97331 USA. [Ravelli, Angelo] Univ Genoa, Genoa, Italy. [Ravelli, Angelo] IRCCS G Gaslini, Genoa, Italy. [Cabalar, Imelda] NIAMS, NIH, Bethesda, MD USA. [Feldman, Brian M.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Feldman, Brian M.] Univ Toronto, Toronto, ON, Canada. [Villalba, Maria L.] FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Myones, Barry L.] Texas Childrens Hosp, Houston, TX 77030 USA. [Myones, Barry L.] Baylor Coll Med, Houston, TX 77030 USA. [Pachman, Lauren M.] Childrens Mem Hosp, Chicago, IL 60614 USA. [Pachman, Lauren M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Rennebohm, Robert M.] Columbus Childrens Hosp, Columbus, OH 43205 USA. [Rennebohm, Robert M.] Ohio State Univ, Columbus, OH USA. [Reed, Ann M.] Mayo Clin, Rochester, MN USA. RP Rider, LG (reprint author), Natl Inst Environm Hlth Sci, Environm Autoimmun Grp, NIH, CRC 4-2332,MSC 1301,10 Ctr Dr, Bethesda, MD 20892 USA. EM riderl@mail.nih.gov RI Feldman, Brian/A-8586-2011; Harris-Love, Michael/J-1359-2014; RAVELLI, ANGELO/J-8161-2016; OI Harris-Love, Michael/0000-0002-1842-3269; RAVELLI, ANGELO/0000-0001-9658-0385; Rider, Lisa/0000-0002-6912-2458 FU National Institute of Environmental Health Sciences; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH [1R-21-AR-048349-01]; Cure JM Foundation; Arthritis Foundation FX Supported in part by the intramural research programs of the National Institute of Environmental Health Sciences and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH. Dr. Lachenbruch's work was supported in part by a grant from the Cure JM Foundation. Dr. Pachman's work was supported in part by a grant from the Arthritis Foundation. The work of Dr. Reed and that of contributors from the International Myositis Assessment and Clinical Studies Group who are not employed by the US government was supported by the NIH (NIAMS grant 1R-21-AR-048349-01). NR 35 TC 40 Z9 44 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD NOV PY 2009 VL 60 IS 11 BP 3425 EP 3435 DI 10.1002/art.24904 PG 11 WC Rheumatology SC Rheumatology GA 519QF UT WOS:000271781400032 PM 19877055 ER PT J AU Benjamin, D Chabris, C Glaeser, E Gudnason, V Harris, T Laibson, D Launer, L Purcell, S Smith, A AF Benjamin, Daniel Chabris, Christopher Glaeser, Edward Gudnason, Vilmundur Harris, Tamara Laibson, David Launer, Lenore Purcell, Shaun Smith, Albert TI Genetic influences on economic behavior SO BEHAVIOR GENETICS LA English DT Meeting Abstract CT 39th Annual Meeting of the Behavior-Genetics-Association CY JUN 17-20, 2009 CL Mineapolis, MN SP Behav Genet Assoc C1 [Benjamin, Daniel] Cornell Univ, Ithaca, NY 14853 USA. [Chabris, Christopher] Union Coll, Schenectady, NY USA. [Glaeser, Edward; Laibson, David] Harvard Univ, Cambridge, MA 02138 USA. [Harris, Tamara; Launer, Lenore] NIA, Bethesda, MD 20892 USA. RI Gudnason, Vilmundur/K-6885-2015 OI Gudnason, Vilmundur/0000-0001-5696-0084 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD NOV PY 2009 VL 39 IS 6 BP 636 EP 636 PG 1 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 522VL UT WOS:000272027300016 ER PT J AU Chester, C Horwitz, B Spotts, EL Ganiban, J Lichtenstein, P Reiss, D Neiderhiser, JM AF Chester, Charlene Horwitz, Brianna Spotts, Erica L. Ganiban, Jody Lichtenstein, Paul Reiss, David Neiderhiser, Jenae M. TI Quality of sibling relationships in middle adulthood: Genetic and environmental Influences SO BEHAVIOR GENETICS LA English DT Meeting Abstract CT 39th Annual Meeting of the Behavior-Genetics-Association CY JUN 17-20, 2009 CL Mineapolis, MN SP Behav Genet Assoc C1 [Chester, Charlene; Horwitz, Brianna; Neiderhiser, Jenae M.] Penn State Univ, University Pk, PA 16802 USA. [Spotts, Erica L.] NIA, Bethesda, MD 20892 USA. [Ganiban, Jody] George Washington Univ, Washington, DC 20052 USA. [Lichtenstein, Paul] Karolinska Inst, S-10401 Stockholm, Sweden. [Reiss, David] Yale Univ, New Haven, CT 06520 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD NOV PY 2009 VL 39 IS 6 BP 641 EP 642 PG 2 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 522VL UT WOS:000272027300034 ER PT J AU de Moor, MHM Boomsma, DI de Geus, EJC Willemsen, G Hottenga, JJ Distel, MA Abecasis, GR Terracciano, A McCrae, RR Costa, PT Hartman, CA Spinhoven, P Penninx, BW Esko, T Allik, J Realo, A Metspalu, A Hansell, NK Medland, SE Wray, NR Wright, MJ Martin, NG Amin, N Aulchenko, YS Janssens, AC Oostra, BA van Duijn, CM AF de Moor, Marleen H. M. Boomsma, Dorret, I de Geus, Eco J. C. Willemsen, Gonneke Hottenga, Jouke-Jan Distel, Marijn A. Abecasis, Goncalo R. Terracciano, Antonio McCrae, Robert R. Costa, Paul T. Hartman, Catharina A. Spinhoven, Philip Penninx, Brenda W. Esko, Tonu Allik, Jueri Realo, Anu Metspalu, Andres Hansell, Narelle K. Medland, Sarah E. Wray, Naomi R. Wright, Margie J. Martin, Nicholas G. Amin, Najaf Aulchenko, Yurii S. Janssens, A. Cecile Oostra, Ben A. van Duijn, Cornelia M. TI Meta-analysis of genome-wide association results in > 10.000 individuals for the big five personality traits SO BEHAVIOR GENETICS LA English DT Meeting Abstract CT 39th Annual Meeting of the Behavior-Genetics-Association CY JUN 17-20, 2009 CL Mineapolis, MN SP Behav Genet Assoc C1 [de Moor, Marleen H. M.; Boomsma, Dorret, I; de Geus, Eco J. C.; Willemsen, Gonneke; Hottenga, Jouke-Jan; Distel, Marijn A.] Vrije Univ Amsterdam, Dept Biol Psychol, NL-1081 BT Amsterdam, Netherlands. [Abecasis, Goncalo R.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Terracciano, Antonio; McCrae, Robert R.; Costa, Paul T.] NIA, NIH, Baltimore, MD 21224 USA. [Hartman, Catharina A.] Univ Groningen, Dept Psychiat, Groningen, Netherlands. [Spinhoven, Philip] Leiden Univ, Dept Psychiat & Psychol, Leiden, Netherlands. [Penninx, Brenda W.] VU Univ Med Ctr Amsterdam, Inst Neurosci, EMGO Inst, Dept Psychiat, Amsterdam, Netherlands. [Esko, Tonu] Univ Tartu, Inst Mol & Cell Biol, Estonian Bioctr, EE-50410 Tartu, Estonia. [Allik, Jueri; Realo, Anu] Univ Tartu, Inst Psychol, EE-50410 Tartu, Estonia. [Metspalu, Andres] Univ Tartu, Estonian Bioctr, Inst Mol & Cell Biol, EE-50410 Tartu, Estonia. [Hansell, Narelle K.; Medland, Sarah E.; Wray, Naomi R.; Wright, Margie J.; Martin, Nicholas G.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Amin, Najaf; Aulchenko, Yurii S.; Janssens, A. Cecile; van Duijn, Cornelia M.] Erasmus Univ, Med Ctr, Dept Epidemiol & Biostat, NL-3000 CA Rotterdam, Netherlands. [Oostra, Ben A.] Erasmus Univ, Med Ctr, Dept Clin Genet, NL-3000 CA Rotterdam, Netherlands. RI Allik, Juri/D-5609-2009; terracciano, antonio/B-1884-2008; Aulchenko, Yurii/M-8270-2013; Realo, Anu/M-9524-2016; Hansell, Narelle/A-4553-2016; OI Allik, Juri/0000-0002-8358-4747; Aulchenko, Yurii/0000-0002-7899-1575; Hansell, Narelle/0000-0002-8229-9741; de Geus, Eco/0000-0001-6022-2666 NR 0 TC 3 Z9 3 U1 1 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD NOV PY 2009 VL 39 IS 6 BP 643 EP 643 PG 1 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 522VL UT WOS:000272027300038 ER PT J AU Evrony, HK Ganiban, JM Haddad, SK Lichtenstein, P Spotts, E Reiss, D Neiderhiser, JM AF Evrony, Hilah K. Ganiban, Jody M. Haddad, Suzanne K. Lichtenstein, Paul Spotts, Erica Reiss, David Neiderhiser, Jenae M. TI Personality accounting for genetic and environmental associations between recalled parenting and marital satisfaction SO BEHAVIOR GENETICS LA English DT Meeting Abstract CT 39th Annual Meeting of the Behavior-Genetics-Association CY JUN 17-20, 2009 CL Mineapolis, MN SP Behav Genet Assoc C1 [Evrony, Hilah K.; Ganiban, Jody M.; Haddad, Suzanne K.] George Washington Univ, Washington, DC USA. [Lichtenstein, Paul] Karolinska Inst, Stockholm, Sweden. [Spotts, Erica] NIA, Bethesda, MD 20892 USA. [Reiss, David] Yale Univ, New Haven, CT USA. [Neiderhiser, Jenae M.] Penn State Univ, University Pk, PA 16802 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD NOV PY 2009 VL 39 IS 6 BP 649 EP 649 PG 1 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 522VL UT WOS:000272027300054 ER PT J AU Horwitz, B Ganiban, J Spotts, E Reiss, D Lichtenstein, P Neiderhiser, J AF Horwitz, Briana Ganiban, Jody Spotts, Erica Reiss, David Lichtenstein, Paul Neiderhiser, Jenae TI The role of parent's personality and family relationships in explaining global family conflict SO BEHAVIOR GENETICS LA English DT Meeting Abstract CT 39th Annual Meeting of the Behavior-Genetics-Association CY JUN 17-20, 2009 CL Mineapolis, MN SP Behav Genet Assoc C1 [Horwitz, Briana; Neiderhiser, Jenae] Penn State Univ, University Pk, PA 16802 USA. [Ganiban, Jody] George Washington Univ, Washington, DC 20052 USA. [Spotts, Erica] NIA, Bethesda, MD 20892 USA. [Reiss, David] Yale Univ, New Haven, CT 06520 USA. [Lichtenstein, Paul] Karolinska Inst, S-10401 Stockholm, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD NOV PY 2009 VL 39 IS 6 BP 657 EP 657 PG 1 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 522VL UT WOS:000272027300075 ER PT J AU Narusyte, J Andershed, AK Neiderhiser, J D'Onofrio, B Reiss, D Spotts, E Ganiban, J Lichtenstein, P AF Narusyte, Jurgita Andershed, Anna-Karin Neiderhiser, Jenae D'Onofrio, Brian Reiss, David Spotts, Erica Ganiban, Jody Lichtenstein, Paul TI Parental criticism and externalizing behavior problems in adolescents: The role of environment and genotype-environment correlation SO BEHAVIOR GENETICS LA English DT Meeting Abstract CT 39th Annual Meeting of the Behavior-Genetics-Association CY JUN 17-20, 2009 CL Mineapolis, MN SP Behav Genet Assoc C1 [Narusyte, Jurgita; Lichtenstein, Paul] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Andershed, Anna-Karin] Univ Orebro, Dept Behav Social & Legal Sci, Orebro, Sweden. [Neiderhiser, Jenae] Penn State Univ, Dept Psychol, University Pk, PA 16802 USA. [D'Onofrio, Brian] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN USA. [Reiss, David] Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT USA. [Spotts, Erica] NIA, NIH, Bethesda, MD 20892 USA. [Ganiban, Jody] George Washington Univ, Dept Psychol, Washington, DC 20052 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD NOV PY 2009 VL 39 IS 6 BP 672 EP 672 PG 1 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 522VL UT WOS:000272027300120 ER PT J AU Walum, H Westberg, L Henningsson, S Neiderhiser, JM Reiss, D Igl, W Ganiban, JM Spotts, EL Pedersen, NL Eriksson, E Lichtenstein, P AF Walum, Hasse Westberg, Lars Henningsson, Susanne Neiderhiser, Jenae M. Reiss, David Igl, Wilmar Ganiban, Jody M. Spotts, Erica L. Pedersen, Nancy L. Eriksson, Elias Lichtenstein, Paul TI Genetic variation in the vasopressin receptor 1a gene (AVPR1A) is associated with pair-bonding behavior in humans SO BEHAVIOR GENETICS LA English DT Meeting Abstract CT 39th Annual Meeting of the Behavior-Genetics-Association CY JUN 17-20, 2009 CL Mineapolis, MN SP Behav Genet Assoc C1 [Walum, Hasse; Igl, Wilmar; Pedersen, Nancy L.; Lichtenstein, Paul] Karolinska Inst, Dept Med Epidemiol & Biostat, S-10401 Stockholm, Sweden. [Westberg, Lars; Henningsson, Susanne; Eriksson, Elias] Univ Gothenburg, Inst Neurosci & Physiol, Dept Pharmacol, Gothenburg, Sweden. [Neiderhiser, Jenae M.] Penn State Univ, Dept Psychol, University Pk, PA 16802 USA. [Reiss, David] Yale Univ, Yale Child Study Ctr, New Haven, CT 06520 USA. [Ganiban, Jody M.] George Washington Univ, Dept Psychol, Washington, DC 20052 USA. [Spotts, Erica L.] NIA, Behav & Social Res Program, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 2 U2 20 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD NOV PY 2009 VL 39 IS 6 BP 689 EP 689 PG 1 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 522VL UT WOS:000272027300168 ER PT J AU Lebedeva, NA Rechkunova, NI Agama, K Pommier, Y Lavrik, OI AF Lebedeva, N. A. Rechkunova, N. I. Agama, K. Pommier, Y. Lavrik, O. I. TI Interaction of DNA topoisomerase 1 with DNA intermediates and proteins of base excision repair SO BIOCHEMISTRY-MOSCOW LA English DT Article DE DNA topoisomerase 1; DNA repair; base excision repair factors ID POSTTRANSLATIONAL MODIFICATION; CLEAVABLE COMPLEXES; ABASIC SITES; DAMAGE; CAMPTOTHECIN; REPLICATION; INHIBITORS; ENZYMES; KU AB The interaction of human recombinant DNA topoisomerase 1 (Top1) with linear and circular DNA structures containing a nick or short gap but lacking a specific Top1 recognition site was studied. The effect of key excision repair proteins on formation of the Top1 covalent adduct with the DNA repair intermediates was shown. Partial inhibition of the Top1-DNA-adduct formation upon addition of poly(ADP-ribose) polymerase 1 in the absence of NAD(+) was shown, whereas in the presence of NAD(+) formation of a high molecular weight product, most likely corresponding to poly(ADP)-ribosylated Top1-DNA adduct, was observed. The data show that the key base excision repair proteins can influence formation of suicide Top1-DNA adducts. Top1 was identified by immunoprecipitation in the bovine testis nuclear extract as the protein forming the main modification product with nick-containing DNA. C1 [Lebedeva, N. A.; Rechkunova, N. I.; Lavrik, O. I.] Inst Chem Biol & Fundamental Med, Novosibirsk 630090, Russia. [Lebedeva, N. A.] Novosibirsk State Univ, Novosibirsk 630090, Russia. [Agama, K.; Pommier, Y.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Lavrik, OI (reprint author), Inst Chem Biol & Fundamental Med, Pr Akad Lavrentieva 8, Novosibirsk 630090, Russia. EM lavrik@niboch.nsc.ru RI Lebedeva, Natalya /G-4758-2013; Rechkunova, Nadezda /G-5093-2013; Lavrik, Olga /G-4641-2013 FU Russian Foundation for Basic Research [07-04-00389, 09-04-91320]; HRJRG-102; Russian Academy of Sciences program; "Leading Research Schools" [652.2008]; FTsPK [2009-1.1-201-018-002]; CRDF-BRHE [RNP.2.2.2.3.10031] FX This work was supported by the Russian Foundation for Basic Research (grants 07-04-00389 and 09-04-91320), HRJRG-102, the Russian Academy of Sciences program "Molecular and Cell Biology", program "Leading Research Schools" (652.2008), FTsPK (State contract 2009-1.1-201-018-002), and CRDF-BRHE (RNP.2.2.2.3.10031). NR 29 TC 3 Z9 3 U1 1 U2 7 PU MAIK NAUKA/INTERPERIODICA/SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0006-2979 EI 0320-9725 J9 BIOCHEMISTRY-MOSCOW+ JI Biochem.-Moscow PD NOV PY 2009 VL 74 IS 11 BP 1278 EP 1284 DI 10.1134/S0006297909110157 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 522DQ UT WOS:000271978400015 PM 19916945 ER PT J AU Balaban, RS AF Balaban, Robert S. TI The role of Ca2+ signaling in the coordination of mitochondrial ATP production with cardiac work SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS LA English DT Review DE Dehydrogenase; F1-FO-ATPase; Membrane potential; Oxidative phosphorylation; NADH; Oxygen consumption; Sarcoplasmic reticulum; Starling effect; Energy homeostasis; Aralar; Citrin ID CYTOCHROME-C-OXIDASE; PERFUSED RAT-HEART; 2-OXOGLUTARATE DEHYDROGENASE COMPLEX; CALCIUM-BINDING PROTEIN; P-31 NMR-SPECTROSCOPY; INTRACELLULAR CALCIUM; OXIDATIVE-PHOSPHORYLATION; PYRUVATE-DEHYDROGENASE; OXYGEN-CONSUMPTION; IN-VIVO AB The heart is capable of balancing the rate of mitochondrial ATP production with utilization continuously over a wide range of activity. This results in a constant phosphorylation potential despite a large change in metabolite turnover. The molecular mechanisms responsible for generating this energy homeostasis are poorly understood. The best candidate for a cytosolic signaling molecule reflecting ATP hydrolysis is Ca2+. Since Ca2+ initiates and powers muscle contraction as well as serves as the primary substrate for SERCA, Ca2+ is an ideal feed-forward signal for priming ATP production. With the sarcoplasmic reticulum to cytosolic Ca2+ gradient near equilibrium with the free energy of ATP, cytosolic Ca2+ release is exquisitely sensitive to the cellular energy state providing a feedback signal. Thus, Ca2+ can serve as a feed-forward and feedback regulator of ATP production. Consistent with this notion is the correlation of cytosolic and mitochondrial Ca2+ with work in numerous preparations as well as the localization of mitochondria near Ca2+ release sites. How cytosolic Ca2+ signaling might regulate oxidative phosphorylation is a focus of this review. The relevant Ca2+ sensitive sites include several dehydrogenases and substrate transporters together with a post-translational modification of F1-FO-ATPase and cytochrome oxidase. Thus, Ca2+ apparently activates both the generation of the mitochondrial membrane potential as well as utilization to produce ATP. This balanced activation extends the energy homeostasis observed in the cytosol into the mitochondria matrix in the never resting heart. Published by Elsevier B.V. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Balaban, RS (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. EM rsb@nih.gov FU Intramural NIH HHS [Z01 HL004601-20] NR 145 TC 97 Z9 101 U1 1 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2728 EI 0006-3002 J9 BBA-BIOENERGETICS JI Biochim. Biophys. Acta-Bioenerg. PD NOV PY 2009 VL 1787 IS 11 SI SI BP 1334 EP 1341 DI 10.1016/j.bbabio.2009.05.011 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 492KI UT WOS:000269654000006 PM 19481532 ER PT J AU Lobanov, AV Hatfield, DL Gladyshev, VN AF Lobanov, Alexey V. Hatfield, Dolph L. Gladyshev, Vadim N. TI Eukaryotic selenoproteins and selenoproteomes SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Review DE Selenocysteine; Selenoprotein; Selenoproteome; SECIS element ID SELENOCYSTEINE INSERTION SYSTEM; SECIS ELEMENTS; THIOREDOXIN REDUCTASE; ONE CODON; IDENTIFICATION; PROTEIN; EVOLUTION; FAMILY; SELENIUM; ELEGANS AB Selenium is an essential trace element for which both beneficial and toxic effects in human health have been described. It is now clear that the importance of having adequate amounts of this micronutrient in the diet is primarily due to the fact that selenium is required for biosynthesis of selenocysteine, the twenty first naturally occurring amino acid in protein. In this review, we provide an overview of eukaryotic selenoproteins and selenoproteomes, which are sets of selenoproteins in these organisms. In eukaryotes, selenoproteins show a mosaic occurrence, with some organisms, such as vertebrates and algae, having dozens of these proteins, while other organisms, such as higher plants and fungi, having lost all selenoproteins during evolution. We also discuss selenoprotein functions and evolutionary trends in the use of these proteins in eukaryotes. Functional analysis of selenoproteins is critical for better understanding of the role of selenium in human health and disease. (C) 2009 Elsevier B.V. All rights reserved. C1 [Lobanov, Alexey V.; Gladyshev, Vadim N.] Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. [Lobanov, Alexey V.; Gladyshev, Vadim N.] Univ Nebraska, Redox Biol Ctr, Lincoln, NE 68588 USA. [Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Gladyshev, VN (reprint author), Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. EM vgladyshev1@unl.edu RI Gladyshev, Vadim/A-9894-2013 FU Intramural NIH HHS [ZIA BC010767-04]; NIGMS NIH HHS [R01 GM061603] NR 33 TC 116 Z9 123 U1 4 U2 36 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD NOV PY 2009 VL 1790 IS 11 BP 1424 EP 1428 DI 10.1016/j.bbagen.2009.05.014 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 515GA UT WOS:000271454600005 PM 19477234 ER PT J AU Hatfield, DL Yoo, MH Carlson, BA Gladyshev, VN AF Hatfield, Dolph L. Yoo, Min-Hyuk Carlson, Bradley A. Gladyshev, Vadim N. TI Selenoproteins that function in cancer prevention and promotion SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Review DE Selenoprotein; 15 kDa selenoprotein; Tumorigenesis; Thioredoxin reductase 1 ID THIOREDOXIN REDUCTASE; ENDOPLASMIC-RETICULUM; 15-KDA SELENOPROTEIN; SELENIUM-COMPOUNDS; TRANSGENIC MICE; SELENOCYSTEINE; GENE; CHEMOPREVENTION; DEFICIENCY; EXPRESSION AB Of the many health benefits attributed to selenium, the one that has received the most attention is its role in cancer prevention. Selenium-containing proteins (selenoproteins) have been shown in recent years to have roles in cancer prevention. However, selenoproteins have diverse functions and their view as antioxidants is oversimplified. Some selenoproteins appear to have a split personality in having roles both in preventing and promoting cancer. The contrasting roles of one selenoprotein, thioredoxin reductase 1, in cancer are discussed in detail, but as also noted, at least one other selenoprotein may also have such a dual function. In addition, we discuss examples of inhibition of cancer development by selenoprotein deficiency in mouse models. These studies highlight the complex nature of selenium in relation to cancer. Published by Elsevier B.V. C1 [Hatfield, Dolph L.; Yoo, Min-Hyuk; Carlson, Bradley A.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Gladyshev, Vadim N.] Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. [Gladyshev, Vadim N.] Univ Nebraska, Redox Biol Ctr, Lincoln, NE 68588 USA. RP Hatfield, DL (reprint author), NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bldg 37,Room 6032A, Bethesda, MD 20892 USA. EM hatfield@mail.nih.gov RI Gladyshev, Vadim/A-9894-2013 FU Intramural Research Program of the National Institutes of Health; National Cancer Institute; Center for Cancer Research FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research and NIH grants awarded to VNG. NR 53 TC 59 Z9 61 U1 0 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD NOV PY 2009 VL 1790 IS 11 BP 1541 EP 1545 DI 10.1016/j.bbagen.2009.03.001 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 515GA UT WOS:000271454600018 PM 19272412 ER PT J AU Ogawa, M Regino, CAS Seidel, J Green, MV Xi, WZ Williams, M Kosaka, N Choyke, PL Kobayashi, H AF Ogawa, Mikako Regino, Celeste A. S. Seidel, Jurgen Green, Michael V. Xi, Wenze Williams, Mark Kosaka, Nobuyuki Choyke, Peter L. Kobayashi, Hisataka TI Dual-Modality Molecular Imaging Using Antibodies Labeled with Activatable Fluorescence and a Radionuclide for Specific and Quantitative Targeted Cancer Detection SO BIOCONJUGATE CHEMISTRY LA English DT Article ID MONOCLONAL-ANTIBODIES; INDOCYANINE GREEN; OVARIAN-CANCER; PROBE; AGENT; EXPRESSION; METASTASES; CONJUGATE; VISION; LIGHT AB Multimodality molecular imaging should have potential for compensating the disadvantages and enhancing the advantages of each modality. Nuclear imaging is superior to optical imaging in whole body imaging and in quantification due to good tissue penetration of gamma rays. However, target specificity can be compromised by high background signal due to the always signal ON feature of nuclear probes. In contrast, optical imaging can be superior in target-specific imaging by employing target-specific signal activation systems, although it is not quantitative because of signal attenuation. In this study, to take advantage of the mutual cooperation of each modality, multimodality imaging was performed by a combination of quantitative radiolabeled probe and an activatable optical probe. The monoclonal antibodies, panitumumab (anti-HER1) and trastuzumab (anti-HER2), were labeled with In-111 and ICG and tested. in both HER1 and HER2 tumor bearing mice by the cocktail injection of radiolabeled and optical probes and by the single injection of a dual-labeled probe. The optical and nuclear images were obtained over 6 days after the conjugates injection. The fluorescence activation properties of ICG labeled antibodies were also investigated by in vitro microscopy. In vitro microscopy demonstrated that there was no fluorescence signal with either panitumumab-ICG or trastuzumab-ICG, when the probes were bound to cell surface antigens but were not yet internalized. After the conjugates were internalized into the cells, both conjugates showed bright fluorescence signal only in the target cells. These results show that both conjugates work as activatable probes. In in vivo multimodality imaging by injection of a cocktail of radio-optical probes, only the target specific tumor was visualized by optical imaging. Meanwhile, the biodistribution profile of the injected antibody was provided by nuclear imaging. Similar results were obtained with radio and optical dual-labeled probes, and it is confirmed that pharmacokinetic properties did not affect the results above. Here, we could characterize the molecular targets by activatable optical probes and visualize the delivery of targeting molecules quantitatively by radioactive probes. Multimodality molecular imaging combining activatable optical and radioactive probes has great potential for simultaneous visualization, characterization, and measurement of biological processes. C1 [Ogawa, Mikako; Regino, Celeste A. S.; Seidel, Jurgen; Green, Michael V.; Xi, Wenze; Williams, Mark; Kosaka, Nobuyuki; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,Room 1B40,MSC1088, Bethesda, MD 20892 USA. EM kobayash@mail.nih.gov FU Intramural Research Program of the NIH; National Cancer Institute; Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 43 TC 59 Z9 62 U1 1 U2 28 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD NOV PY 2009 VL 20 IS 11 BP 2177 EP 2184 DI 10.1021/bc900362k PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 520FP UT WOS:000271826600020 PM 19919110 ER PT J AU Blasi, G Hariri, AR Alce, G Taurisano, P Sambataro, F Das, S Bertolino, A Weinberger, DR Mattay, VS AF Blasi, Giuseppe Hariri, Ahmad R. Alce, Guilna Taurisano, Paolo Sambataro, Fabio Das, Saumitra Bertolino, Alessandro Weinberger, Daniel R. Mattay, Venkata S. TI Preferential Amygdala Reactivity to the Negative Assessment of Neutral Faces SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Amygdala; cingulate; facial expressions; fMRI; prefrontal cortex; social decision making ID PREFRONTAL CORTEX; EMOTIONAL STIMULI; COGNITIVE CONTROL; LATERAL AMYGDALA; FEAR; UNCERTAINTY; BRAIN; FMRI; CONNECTIVITY; NEUROBIOLOGY AB Background: Prior studies suggest that the amygdala shapes complex behavioral responses to socially ambiguous cues. We explored human amygdala function during explicit behavioral decision making about discrete emotional facial expressions that can represent socially unambiguous and ambiguous cues. Methods: During functional magnetic resonance imaging, 43 healthy adults were required to make complex social decisions (i.e., approach or avoid) about either relatively unambiguous (i.e., angry, fearful, happy) or ambiguous (i.e., neutral) facial expressions. Amygdala activation during this task was compared with that elicited by simple, perceptual decisions (sex discrimination) about the identical facial stimuli. Results: Angry and fearful expressions were more frequently judged as avoidable and happy expressions most often as approachable. Neutral expressions were equally judged as avoidable and approachable. Reaction times to neutral expressions were longer than those to angry, fearful, and happy expressions during social judgment only. Imaging data on stimuli judged to be avoided revealed a significant task by emotion interaction in the amygdala. Here, only neutral facial expressions elicited greater activity during social judgment than during sex discrimination. Furthermore, during social judgment only, neutral faces judged to be avoided were associated with greater amygdala activity relative to neutral faces that were judged as approachable. Moreover, functional coupling between the amygdala and both dorsolateral prefrontal (social judgment > sex discrimination) and cingulate (sex discrimination > social judgment) cortices was differentially modulated by task during processing of neutral faces. Conclusions: Our results suggest that increased amygdala reactivity and differential functional coupling with prefrontal circuitries may shape complex decisions and behavioral responses to socially ambiguous cues. C1 [Mattay, Venkata S.] NIMH, Clin Brain Disorders Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Blasi, Giuseppe; Taurisano, Paolo; Bertolino, Alessandro] Univ Bari, Dept Neurol & Psychiat Sci, Psychiat Neurosci Grp, Bari, Italy. [Hariri, Ahmad R.] Duke Univ, Dept Psychol & Neurosci, Durham, NC USA. [Hariri, Ahmad R.] Duke Univ, Inst Genome Sci & Policy, Durham, NC USA. RP Mattay, VS (reprint author), NIMH, Clin Brain Disorders Branch, NIH, Dept Hlth & Human Serv, Bldg 10,Ctr Dr,Room 3C-108, Bethesda, MD 20892 USA. EM vsm@mail.nih.gov RI Sambataro, Fabio/E-3426-2010; Hariri, Ahmad/D-5761-2011; Bertolino, Alessandro/O-6352-2016 OI Sambataro, Fabio/0000-0003-2102-416X; Bertolino, Alessandro/0000-0002-1251-1380 FU Intramural NIH HHS [Z01 MH002905-01] NR 39 TC 34 Z9 34 U1 4 U2 15 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 2009 VL 66 IS 9 BP 847 EP 853 DI 10.1016/j.biopsych.2009.06.017 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 512BH UT WOS:000271216800006 PM 19709644 ER PT J AU Dichter, GS Felder, JN Petty, C Bizzell, J Ernst, M Smoski, MJ AF Dichter, Gabriel S. Felder, Jennifer N. Petty, Christopher Bizzell, Joshua Ernst, Monique Smoski, Moria J. TI The Effects of Psychotherapy on Neural Responses to Rewards in Major Depression SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Cingulate gyrus; depression; fMRI; orbital frontal cortex; reward; striatum ID PRIMATE CAUDATE-NUCLEUS; BRAIN METABOLIC-CHANGES; COGNITIVE-BEHAVIOR THERAPY; MEDIAL PREFRONTAL CORTEX; SLEEP-DEPRIVATION; DECISION-MAKING; ANTIDEPRESSANT TREATMENT; ESCAPE PERFORMANCE; ANTERIOR CINGULATE; GLUCOSE-METABOLISM AB Background: Unipolar major depressive disorder (MDD) is characterized by anomalous neurobiological responses to pleasant stimuli, a pattern that may be linked to symptoms of anhedonia. However, the potential for psychotherapy to normalize neurobiological responses to pleasant stimuli has not been evaluated. Methods: Twelve adults with and 15 adults without MDD participated in two identical functional magnetic resonance imaging scans that used a Wheel of Fortune task. Between scans, MDD outpatients received Behavioral Activation Therapy for Depression, a psychotherapy modality designed to increase engagement with rewarding stimuli and reduce avoidance behaviors. Results: Seventy-five percent of adults with MDD were treatment responders, achieving post-treatment Hamilton Rating Scale for Depression score of six or below. Relative to changes in brain function in the matched nondepressed group, psychotherapy resulted in functional changes in structures that mediate responses to rewards, including the paracingulate gyrus during reward selection, the right caudate nucleus (i.e., the dorsal striatum), during reward anticipation, and the paracingulate and orbital frontal gyri during reward feedback. There was no effect of diagnostic status or psychotherapy on in-scanner task-related behavioral responses. Conclusions: Behavioral Activation Therapy for Depression, a psychotherapy modality designed to increase engagement with rewarding stimuli and reduce avoidance behaviors, results in improved functioning of unique reward structures during different temporal phases of responses to pleasurable stimuli, including the dorsal striatum during reward anticipation. C1 [Dichter, Gabriel S.; Bizzell, Joshua] Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC 27599 USA. [Dichter, Gabriel S.; Felder, Jennifer N.; Bizzell, Joshua] Univ N Carolina, Sch Med, Neurodev Disorders Res Ctr, Chapel Hill, NC 27599 USA. [Dichter, Gabriel S.; Bizzell, Joshua] Duke Univ, Med Ctr, Duke UNC Brain Imaging & Anal Ctr, Durham, NC USA. [Dichter, Gabriel S.; Smoski, Moria J.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. [Petty, Christopher] Durham VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Durham, NC USA. [Ernst, Monique] NIMH, Mood & Anxiety Disorders Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Dichter, GS (reprint author), Univ N Carolina, Sch Med, Dept Psychiat, CB 3366,101 Manning Dr, Chapel Hill, NC 27599 USA. EM dichter@med.unc.edu RI Dichter, Gabriel/K-6726-2015; OI Dichter, Gabriel/0000-0003-3407-5417; Felder, Jennifer/0000-0002-4598-7836 FU University of North Carolina neurodevelopmental Disorders Research Center; National Institute of Mental Health (NIMH) [T32-MH070448, K23 MH087754, K23 MH081285]; National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator award; Duke University Medical Center; National Institute of Child Health & Development (NICHD) [K12 HD043446, T32-HD40127]; University of North Carolina-Chapel Hill; National Institutes of Health National Center for Research Resources [K12 RR023248]; [MH078145] FX We would like to thank Todd Harshharger and Syam Gadde for assistance with image analysis; Prue Cuper Shian-Ling Keng, and Justin Woodlief for assistance with data collection; and magnetic resonance imaging technologists Susan Music, Natalie Gautkin, and Talagnair Venkatraman for assistance with data acquisition. This research was supported by MH078145 to GSD. Assistance for this study was provided by the Neuroimaging Core of the University of North Carolina neurodevelopmental Disorders Research Center. The author MJS was supported by National Institute of Mental Health (NIMH) T32-MH070448, a National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator award, a carrier development award from Duke University Medical Center, National Institute of Child Health & Development (NICHD), K12 HD043446, and NIMH K23 MH087754. The author GSD was supported by Postdoctoral Research in Neurodevelopmental Disorders, NICHD T32-HD40127, NARSAD Young Investigator awards, a career development award from University of North Carolina-Chapel Hill, National Institutes of Health National Center for Research Resources K12 RR023248 and NIMH K23 MH081285. The authors reported no biomedical financial interests or Potential conflicts of interest. NR 96 TC 92 Z9 96 U1 7 U2 20 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 2009 VL 66 IS 9 BP 886 EP 897 DI 10.1016/j.biopsych.2009.06.021 PG 12 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 512BH UT WOS:000271216800011 PM 19726030 ER PT J AU Netzel-Arnett, S Bugge, TH Hess, RA Carnes, K Stringer, BW Scarman, AL Hooper, JD Tonks, ID Kay, GF Antalis, TM AF Netzel-Arnett, Sarah Bugge, Thomas H. Hess, Rex A. Carnes, Kay Stringer, Brett W. Scarman, Anthony L. Hooper, John D. Tonks, Ian D. Kay, Graham F. Antalis, Toni M. TI The Glycosylphosphatidylinositol-Anchored Serine Protease PRSS21 (Testisin) Imparts Murine Epididymal Sperm Cell Maturation and Fertilizing Ability SO BIOLOGY OF REPRODUCTION LA English DT Article DE decapitated sperm; easily decapitated sperm; epididymis; fertilizing ability; male reproductive tract; PRSS21; serine protease; sperm; sperm maturation; testisin ID EPITHELIAL SODIUM-CHANNELS; TYROSINE PHOSPHORYLATION; MOUSE SPERMATOZOA; VOLUME REGULATION; ZONA-PELLUCIDA; MAMMALIAN SPERMATOZOA; IN-VIVO; MICE; CAPACITATION; GENE AB An estimated 25%-40% of infertile men have idiopathic infertility associated with deficient sperm numbers and quality. Here, we identify the membrane-anchored serine protease PRSS21, also known as testisin, to he a novel proteolytic factor that directs epididymal sperm cell maturation and sperm-fertilizing ability. PRSS21-deficient spermatozoa show decreased motility, angulated and curled tails, fragile necks, and dramatically increased susceptibility to decapitation. These defects reflect aberrant maturation during passage through the epididymis, because histological and electron microscopic structural analyses showed an increased tendency for curled and detached tails as spermatozoa transit from the corpus to the cauda epididymis. Cauda epididymal spermatozoa deficient in PRSS21 fail to mount a swelling response when exposed to hypotonic conditions, suggesting an impaired ability to respond to osmotic challenges facing maturing spermatozoa in the female reproductive tract. These data suggest that aberrant regulation of PRSS21 may underlie certain secondary male infertility syndromes, such as "easily decapitated" spermatozoa in humans. C1 [Netzel-Arnett, Sarah; Antalis, Toni M.] Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, Baltimore, MD 21201 USA. [Netzel-Arnett, Sarah; Antalis, Toni M.] Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. [Bugge, Thomas H.] Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Unit, NIH, Bethesda, MD USA. [Hess, Rex A.; Carnes, Kay] Univ Illinois, Dept Vet Biosci, Urbana, IL 61801 USA. [Stringer, Brett W.; Tonks, Ian D.; Kay, Graham F.] Queensland Inst Med Res, Herston, Qld 4006, Australia. [Scarman, Anthony L.; Hooper, John D.] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Kelvin Grove, Qld, Australia. RP Antalis, TM (reprint author), Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, 800 W Baltimore St, Baltimore, MD 21201 USA. EM tantalis@som.umaryland.edu RI Kay, Graham/A-4130-2011; Hooper, John/B-4153-2011; Hooper, John/C-1481-2016 OI Hooper, John/0000-0003-1054-8486 FU Lance Armstrong Foundation; National Institutes of Health (NIH) [CA098369, HL084387, HL07698]; NIH Intramural program; Department of Defense [DAMD-17-02-1-0693]; National Health and Medical Research Council; Consortium for Industrial Collaboration in Contraceptive Research (CICCR); program of Contraceptive Research and Development (CONRAD); Eastern Virginia Medical School; Nationa Institute of Child Health and Human Development (NICHD) Brain Nationa Institute of Child Health and Human Development (NICHD) Brain and Tissue Bank for Developmental Disorders at the University of Maryland School of Medicine; NICHD [N01-HD-4-3368, N01-HD-4-3383] FX Supported by the Lance Armstrong Foundation (T.M.A.); National Institutes of Health (NIH) grants CA098369 and HL084387 to T.M.A. and HL07698 to S.N.-A., the NIH Intramural program (T.H.B.); Department of Defense grant DAMD-17-02-1-0693 to T.H.B.; and the National Health and Medical Research Council (T.M.A. and G.F.K.) Partial support was provided by Consortium for Industrial Collaboration in Contraceptive Research (CICCR), a program of Contraceptive Research and Development (CONRAD), Eastern Virginia Medical School, to R.A.H. The views expressed by the authors do not necessarily reflect the views of CONRAD or CICCR. The Nationa Institute of Child Health and Human Development (NICHD) Brain and Tissue Bank for Developmental Disorders at the University of Maryland School of Medicine and NICHD contracts N01-HD-4-3368 and N01-HD-4-3383 are acknowledged for deidentified human tissues. NR 77 TC 29 Z9 32 U1 0 U2 3 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD NOV PY 2009 VL 81 IS 5 BP 921 EP 932 DI 10.1095/biolreprod.109.076273 PG 12 WC Reproductive Biology SC Reproductive Biology GA 509PP UT WOS:000271030700013 PM 19571264 ER PT J AU Donohue, SR Varnas, K Jia, ZS Gulyas, B Pike, VW Halldin, C AF Donohue, Sean R. Varnas, Katarina Jia, Zhisheng Gulyas, Balazs Pike, Victor W. Halldin, Christer TI Synthesis and in vitro autoradiographic evaluation of a novel high-affinity radioiodinated ligand for imaging brain cannabinoid subtype-1 receptors SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE SPECT; PET; CB(1) receptors; Radioiodination; Radioligand ID CB1 RECEPTORS; RAT-BRAIN; CANDIDATE RADIOLIGANDS; VIVO; SCHIZOPHRENIA; LOCALIZATION; BINDING; ANTAGONIST; DISCOVERY; DENSITY AB There is strong interest to study the involvement of brain cannabinoid subtype-1 (CB(1)) receptors in neuropsychiatric disorders with single photon emission computed tomography ( SPECT) and a suitable radioligand. Here we report the synthesis of a novel high-affinity radioiodinated CB(1) receptor ligand ([(125)I]8, [(125)I]1-(2-iodophenyl)-4-cyano-5-(4-methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxylate, [(125)I] SD7015). By autoradiography in vitro, [(125)I]8 showed selective binding to CB(1) receptors on human brain postmortem cryosections and now merits labeling with iodine-123 for further evaluation as a SPECT radioligand in non-human primate. (c) 2009 Elsevier Ltd. All rights reserved. C1 [Donohue, Sean R.; Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. [Donohue, Sean R.; Varnas, Katarina; Jia, Zhisheng; Gulyas, Balazs; Halldin, Christer] Karolinska Hosp, Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, S-17176 Stockholm, Sweden. RP Donohue, SR (reprint author), Johns Hopkins PET Ctr, Div Nucl Med, Nelson B1-122,600 N Wolfe St, Baltimore, MD 21287 USA. EM Sean_Donohue@tracer.nm.jhu.edu RI Gulyas, Balazs/F-9508-2015 FU National Institutes of Health; National Institute of Mental Health (NIMH) [ZO1MH002793]; University of Carolina at Chapel Hill [NO1MH32004] FX S. R. D. and V. W. P. were supported by the Intramural Research Program of the National Institutes of Health, specifically the National Institute of Mental Health (NIMH), project number ZO1MH002793. We thank the NIMH Psychoactive Drug Screening Program (PDSP) for performing binding assays and Siv Eriksson for the excellent technical assistance with autoradiographic experiments. The PDSP is directed by Bryan L. Roth, PhD, with project officer Jamie Driscoll ( NIMH) at the University of Carolina at Chapel Hill ( contract NO1MH32004). NR 26 TC 13 Z9 13 U1 0 U2 6 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 1 PY 2009 VL 19 IS 21 BP 6209 EP 6212 DI 10.1016/j.bmcl.2009.08.092 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 503SX UT WOS:000270561300048 PM 19767206 ER PT J AU Topol, I Collins, J Polyakov, I Grigorenko, B Nemukhin, A AF Topol, Igor Collins, Jack Polyakov, Igor Grigorenko, Bella Nemukhin, Alexander TI On photoabsorption of the neutral form of the green fluorescent protein chromophore SO BIOPHYSICAL CHEMISTRY LA English DT Article DE Green fluorescent protein; Photoabsorption spectra; Quantum calculations; Protein matrix influence ID ELECTRONIC EXCITATIONS; GAS-PHASE; ABSORPTION-SPECTRUM; PROTONATION STATES; GFP; ISOMERIZATION; CONSISTENT; VARIANTS; DYNAMICS; COLOR AB We present results of theoretical studies of the photoabsorption band corresponding to the vertical electronic transition S(0)-S(1) between first two singlet states of the model chromophore from the green fluorescent protein (GFP) in its neutral form. Predictions of quantum chemical approaches including ab initio and semi-empirical approximations are compared for the model systems which mimic the GFP chromophore in different environments. We provide evidences that the protein matrix in GFP accounts for a fairly large shift of about 40 nm in the S(0)-S(1) absorption band as compared to the gas phase. (C) 2009 Elsevier B.V. All rights reserved. C1 [Topol, Igor; Collins, Jack] SAIC Fredenick Inc, Adv Biomed Comp Ctr, Informat Syst Program, NCI Frederick, Frederick, MD 21702 USA. [Polyakov, Igor; Grigorenko, Bella; Nemukhin, Alexander] Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119991, Russia. [Nemukhin, Alexander] Russian Acad Sci, NM Emanuel Inst Biochem Phys, Moscow 119334, Russia. RP Topol, I (reprint author), SAIC Fredenick Inc, Adv Biomed Comp Ctr, Informat Syst Program, NCI Frederick, Frederick, MD 21702 USA. EM topol@ncifcrf.gov RI Nemukhin, Alexander/P-9662-2015 FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; Russian Foundation [07-03-00059] FX We thank the staff and administration of the Advanced Biomedical Computing Center for their support of this project. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organization imply endorsement by the U.S. Government. This work is partly supported by the Russian Foundation for Basic Research (project # 07-03-00059). NR 35 TC 19 Z9 19 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 J9 BIOPHYS CHEM JI Biophys. Chem. PD NOV PY 2009 VL 145 IS 1 BP 1 EP 6 DI 10.1016/j.bpc.2009.08.002 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA 512AA UT WOS:000271212800001 PM 19720446 ER PT J AU Hall, D Edskes, H AF Hall, Damien Edskes, Herman TI A model of amyloid's role in disease based on fibril fracture SO BIOPHYSICAL CHEMISTRY LA English DT Article DE Amyloid kinetics; Amyloid toxicity; Fibril fracture; Toxic oligomer hypothesis; Solid mass hypothesis ID ALZHEIMERS-DISEASE; MISFOLDING DISEASES; STRUCTURAL BASIS; POTENTIAL ROLES; IN-VITRO; PROTEIN; BETA; MECHANISM; TOXICITY; NEURODEGENERATION AB Although the correlative evidence relating the presence of amyloid fibrils and certain disease states (e.g. Alzheimer's disease and Type 2 Diabetes) is overwhelming, a direct causative role for amyloid has proved harder to establish. Current thinking links a narrow region of the aggregate protein size distribution, the so called 'early aggregate' domain to cellular toxicity. A troubling feature of this theory however is that the nucleated reaction mechanism by which amyloid formation is believed to occur results in a very low number concentration of early aggregates which are rapidly extended to form amyloid fibrils. Ibis situation means that the concentration of early aggregates is very low at the time when they are supposedly at their most toxic. Here we adopt a novel explicit simulation strategy to examine a kinetic regime involving nucleated growth combined with fibril fragmentation under which this situation can be reversed so as to produce a high number concentration of small on-pathway toxic aggregates. Dependent upon the rate of fragmentation, the time scale for generation of toxic early aggregates may be coupled. uncoupled or disassociated from the time scale for the appearance of amyloid fibrils. Furthermore the model presents itself as a biochemical 'switch' transitioning between modes of amyloid induced cell death dependent upon either specific amyloid toxicity or non-specific solid mass induced tissue damage. (C) 2009 Elsevier B.V. All rights reserved. C1 [Hall, Damien] Univ Tsukuba, Inst Basic Med Sci, Lab 225 B, Tsukuba, Ibaraki 3058577, Japan. [Edskes, Herman] Natl Inst Diabet Digest & Kidney Dis, Lab Biochem & Genet, NIH, Lab 226, Bethesda, MD 20892 USA. RP Hall, D (reprint author), Univ Tsukuba, Inst Basic Med Sci, Lab 225 B, Bldg D,1-1-1 Tennodai, Tsukuba, Ibaraki 3058577, Japan. EM damienhall@md.tsukuba.ac.jp; edskes@helix.nih.gov RI Hall, Damien/D-9927-2012 OI Hall, Damien/0000-0003-1538-7618 FU Intramural NIH HHS [Z99 DK999999] NR 51 TC 11 Z9 11 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 J9 BIOPHYS CHEM JI Biophys. Chem. PD NOV PY 2009 VL 145 IS 1 BP 17 EP 28 DI 10.1016/j.bpc.2009.08.004 PG 12 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA 512AA UT WOS:000271212800003 PM 19735971 ER PT J AU Aviner, S Garty, BZ Rachmel, A Baris, HN Sidransky, E Shuffer, A Attias, J Yaniv, Y Cohen, IJ AF Aviner, Shraga Garty, Ben-Zion Rachmel, Avinoam Baris, Hagit N. Sidransky, Ellen Shuffer, Avinoam Attias, Joseph Yaniv, Yisaac Cohen, Ian J. TI Type 2 Gaucher disease occurs in Ashkenazi Jews but is surprisingly rare SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article DE Type 2 Gaucher disease; Ashkenazi Jews; Glucocerebrosidase; Lysosomal storage disorder ID GLUCOCEREBROSIDASE GENE; PHENOTYPE; MUTATIONS AB Patients with Gaucher disease (GD) are divided into three types based on the presence and rate of progression of the neurologic manifestations. While type 1 GD has a strong predilection in the Jewish Ashkenazi population, both other types lack such a propensity. We report the occurrence of type 2 GD (GD2) in four pregnancies in two Jewish families in Israel (in one case the mother was not Ashkenazi but was from a Sfaradi Jewish family) and also review seven additional cases of GD2 in Ashkenazi Jewish families reported in the literature. Phenotypically, GD2 in Ashkenazi Jews does not differ significantly from this form in other ethnic groups. Genotypic analysis of probands from the two Israeli families demonstrates that each carried two heterozygous glucocerebrosidase mutations. We could find no explanation why GD2 is so rare in the Jewish Ashkenazi population but we could hypothesize that homozygosity for certain Ashkenazi alleles might be lethal, leading to a lower than expected frequency of GD2 and noted that no cases of homozygous L444P has ever been described in Ashkenazi Jews (C) 2009 Elsevier Inc. All rights reserved. C1 [Aviner, Shraga] Barzilai Govt Hosp, Dept Pediat, IL-78278 Ashqelon, Israel. [Aviner, Shraga] Ben Gurion Univ Negev, Fac Hlth Sci, Beer Sheva, Israel. [Garty, Ben-Zion] Schneider Childrens Med Ctr, Dept Pediat B, Petah Tiqwa, Israel. [Garty, Ben-Zion; Rachmel, Avinoam; Baris, Hagit N.; Shuffer, Avinoam; Attias, Joseph; Yaniv, Yisaac; Cohen, Ian J.] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Rachmel, Avinoam] Schneider Childrens Med Ctr, Dept Pediat A, Petah Tiqwa, Israel. [Baris, Hagit N.] Beilinson Med Ctr, Rabin Med Ctr, Raphael Recanati Genet Inst, Petah Tiqwa, Israel. [Sidransky, Ellen] NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Shuffer, Avinoam] Schneider Childrens Med Ctr, Dept Neurol, Petah Tiqwa, Israel. [Attias, Joseph] Schneider Childrens Med Ctr, Inst Clin Neurophysiol, Petah Tiqwa, Israel. [Yaniv, Yisaac; Cohen, Ian J.] Schneider Childrens Med Ctr, Dept Pediat Hematol & Oncol, Petah Tiqwa, Israel. RP Aviner, S (reprint author), Barzilai Govt Hosp, Dept Pediat, 2 Hahistadrut St, IL-78278 Ashqelon, Israel. EM aviners@barzi.health.gov.il RI Cohen, Ian/H-3358-2013 FU National Human Genome Research Institute, National Institutes of Health FX Ellen Sidransky's contribution to this work was funded by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. NR 21 TC 4 Z9 4 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 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD NOV-DEC PY 2009 VL 43 IS 3 BP 294 EP 297 DI 10.1016/j.bcmd.2009.08.004 PG 4 WC Hematology SC Hematology GA 515PO UT WOS:000271484600012 PM 19734074 ER PT J AU Williams-Gray, CH Evans, JR Goris, A Foltynie, T Ban, M Robbins, TW Brayne, C Kolachana, BS Weinberger, DR Sawcer, SJ Barker, RA AF Williams-Gray, Caroline H. Evans, Jonathan R. Goris, An Foltynie, Thomas Ban, Maria Robbins, Trevor W. Brayne, Carol Kolachana, Bhaskar S. Weinberger, Daniel R. Sawcer, Stephen J. Barker, Roger A. TI The distinct cognitive syndromes of Parkinson's disease: 5 year follow-up of the CamPaIGN cohort SO BRAIN LA English DT Article DE Parkinson's disease; dementia; cognitive deficits; microtubule-associated protein tau; catechol-O-methyltransferase ID PROGRESSIVE SUPRANUCLEAR PALSY; POSITRON-EMISSION-TOMOGRAPHY; ALZHEIMERS-DISEASE; ALPHA-SYNUCLEIN; MAPT LOCUS; LEWY BODY; TAU-GENE; DOPAMINE TRANSPORTER; VAL(158)MET GENOTYPE; PREFRONTAL CORTEX AB Cognitive abnormalities are common in Parkinson's disease, with important social and economic implications. Factors influencing their evolution remain unclear but are crucial to the development of targeted therapeutic strategies. We have investigated the development of cognitive impairment and dementia in Parkinson's disease using a longitudinal approach in a population-representative incident cohort (CamPaIGN study, n = 126) and here present the 5-year follow-up data from this study. Our previous work has implicated two genetic factors in the development of cognitive dysfunction in Parkinson's disease, namely the genes for catechol-O-methyltransferase (COMT Val(158)Met) and microtubule-associated protein tau (MAPT) H1/H2. Here, we have explored the influence of these genes in our incident cohort and an additional cross-sectional prevalent cohort (n = 386), and investigated the effect of MAPT H1/H2 haplotypes on tau transcription in post-mortem brain samples from patients with Lewy body disease and controls. Seventeen percent of incident patients developed dementia over 5 years [incidence 38.7 (23.9-59.3) per 1000 person-years]. We have demonstrated that three baseline measures, namely, age >= 72 years, semantic fluency less than 20 words in 90 s and inability to copy an intersecting pentagons figure, are significant predictors of dementia risk, thus validating our previous findings. In combination, these factors had an odds ratio of 88 for dementia within the first 5 years from diagnosis and may reflect the syndrome of mild cognitive impairment of Parkinson's disease. Phonemic fluency and other frontally based tasks were not associated with dementia risk. MAPT H1/H1 genotype was an independent predictor of dementia risk (odds ratio = 12.1) and the H1 versus H2 haplotype was associated with a 20% increase in transcription of 4-repeat tau in Lewy body disease brains. In contrast, COMT genotype had no effect on dementia, but a significant impact on Tower of London performance, a frontostriatally based executive task, which was dynamic, such that the ability to solve this task changed with disease progression. Hence, we have identified three highly informative predictors of dementia in Parkinson's disease, which can be easily translated into the clinic, and established that MAPT H1/H1 genotype is an important risk factor with functional effects on tau transcription. Our work suggests that the dementing process in Parkinson's disease is predictable and related to tau while frontal-executive dysfunction evolves independently with a more dopaminergic basis and better prognosis. C1 [Williams-Gray, Caroline H.; Evans, Jonathan R.; Barker, Roger A.] Univ Cambridge, Ctr Brain Repair, Dept Clin Neurosci, Cambridge CB2 0PY, England. [Goris, An; Ban, Maria; Sawcer, Stephen J.] Univ Cambridge, Neurol Unit, Dept Clin Neurosci, Cambridge CB2 0PY, England. [Goris, An] Katholieke Univ Leuven, Lab Neuroimmunol, Sect Expt Neurol, Leuven, Belgium. [Foltynie, Thomas] UCL, Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, London WC1E 6BT, England. [Robbins, Trevor W.] Univ Cambridge, Dept Expt Psychol, Cambridge CB2 0PY, England. [Brayne, Carol] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB2 0PY, England. [Kolachana, Bhaskar S.; Weinberger, Daniel R.] NIMH, Genes Cognit & Psychosis Program, Intramural Res Program, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Williams-Gray, CH (reprint author), Univ Cambridge, Cambridge Ctr Brain Repair, Dept Clin Neurosci, Forvie Site,Robinson Way, Cambridge CB2 0PY, England. EM chm27@cam.ac.uk RI Goris, An/F-2943-2010 OI Goris, An/0000-0002-1276-6682 FU Medical Research Council [RG38582]; Parkinson's Disease Society [RG39 906]; National Institutes of Health; Patrick Berthoud Clinical Research Fellowship; Foundation-Flanders (FWO-Vlaanderen) FX This work was supported by grants from Medical Research Council (RG38582, RAB) and the Parkinson's Disease Society (RG39 906, RAB), and the National Institutes of Health Research Biomedical Research Centre Award to the University of Cambridge. C. H. W. G. was supported by a Patrick Berthoud Clinical Research Fellowship, and held a Raymond and Beverly Sackler Studentship. A. G. is a Postdoctoral Fellow of the Research Foundation-Flanders (FWO-Vlaanderen). The sponsors had no role in study design, or collection, analysis and interpretation of data. NR 72 TC 306 Z9 313 U1 3 U2 30 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD NOV PY 2009 VL 132 BP 2958 EP 2969 DI 10.1093/brain/awp245 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 514JB UT WOS:000271389300007 PM 19812213 ER PT J AU Rowland, JH Meyerowitz, BE Crespi, CM Leedham, B Desmond, K Belin, TR Ganz, PA AF Rowland, Julia H. Meyerowitz, Beth E. Crespi, Catherine M. Leedham, Beth Desmond, Katherine Belin, Thomas R. Ganz, Patricia A. TI Addressing intimacy and partner communication after breast cancer: a randomized controlled group intervention SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Body image; Breast cancer; Partner communication; Sexuality; Survivor ID QUALITY-OF-LIFE; BODY CHANGE STRESS; LONG-TERM; PSYCHOLOGICAL ADJUSTMENT; ADJUVANT CHEMOTHERAPY; PSYCHOSOCIAL CONCERNS; DYADIC ADJUSTMENT; COMMUNITY SAMPLE; SEXUAL PROBLEMS; YOUNGER WOMEN AB While quality of life for most breast cancer survivors (BCS) returns to normal by 1 year post-treatment, problems in sexual function and intimacy often persist. The present study tested the efficacy of a 6-week psycho-educational group intervention in improving BCS's sexual well-being. We conducted a mailed survey of BCS 1-5 years post-diagnosis to identify a sample of women who reported moderately severe problems in body image, sexual function or partner communication, and were deemed eligible for the randomized intervention trial. Using a pre-randomized design, 70% (n = 284) were assigned to a 6-week psycho-educational group intervention and 30% (n = 127) were assigned to a control condition (print material only); however, only 83 BCS agreed to participate in the intervention. Four months post-intervention, the intervention and control groups were not significantly different on the primary outcome of emotional functioning; however, BCS randomized to the intervention group were more likely to report improvements in relationship adjustment and communication as well as increased satisfaction with sex compared to controls. Members of the intervention group who were the least satisfied with their sexual relationship appeared to improve the most. Although modest in its effects, this intervention can be delivered in standard clinical settings. Having an identified treatment may help reduce physician reluctance to ask BCS about problems in intimacy and as appropriate, refer them for timely help. C1 [Crespi, Catherine M.; Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA 90095 USA. [Rowland, Julia H.] NCI, Off Canc Survivorship, Bethesda, MD 20892 USA. [Rowland, Julia H.] NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Meyerowitz, Beth E.] Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA. [Crespi, Catherine M.; Belin, Thomas R.] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90095 USA. [Desmond, Katherine] Univ Calif Los Angeles, Ctr Community Hlth, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. RP Ganz, PA (reprint author), Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, 650 Charles Young Dr S,A2-125 CHS, Los Angeles, CA 90095 USA. EM rowlandj@mail.nih.gov; meyerow@rcf.usc.edu; ccrespi@ucla.edu; tbelin@mednet.ucla.edu; pganz@mednet.ucla.edu OI Crespi, Catherine/0000-0002-6150-2181 FU National Cancer Institute, National Institutes of Health, Department of Health and Human Services [R01CA63028]; National Institutes of Health [CA016042] FX This study was supported by Public Health Service grant R01CA63028 to Dr. Ganz from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services and National Institutes of Health grant CA016042 which supported part of Dr. Crespi's salary. The authors wish to thank Barbara Bass, Pamela W. Black, Bonnie A. Cesak, Romaine Clifton, Karin M. Johnson, Shirley Otis-Greene, Dominica T. Roth and Deborah S. Kulp for their work as leaders of the intervention groups. NR 54 TC 31 Z9 33 U1 1 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD NOV PY 2009 VL 118 IS 1 BP 99 EP 111 DI 10.1007/s10549-009-0398-x PG 13 WC Oncology SC Oncology GA 505YI UT WOS:000270737800011 PM 19390963 ER PT J AU Sigurdson, AJ Bhatti, P Chang, SC Rajaraman, P Doody, MM Bowen, L Simon, SL Weinstock, RM Linet, MS Rosenstein, M Stovall, M Alexander, BH Preston, DL Struewing, JP AF Sigurdson, Alice J. Bhatti, Parveen Chang, Shih-chen Rajaraman, Preetha Doody, Michele M. Bowen, Laura Simon, Steven L. Weinstock, Robert M. Linet, Martha S. Rosenstein, Marvin Stovall, Marilyn Alexander, Bruce H. Preston, Dale L. Struewing, Jeffery P. TI Polymorphisms in estrogen biosynthesis and metabolism-related genes, ionizing radiation exposure, and risk of breast cancer among US radiologic technologists SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Estrogen biosynthesis; Polymorphisms; Ionizing radiation; Interaction; Risk factors; Casecontrol; Radiologic technologists ID THERAPY AB Ionizing radiation-associated breast cancer risk appears to be modified by timing of reproductive events such as age at radiation exposure, parity, age at first live birth, and age at menopause. However, potential breast cancer risk modification of low to moderate radiation dose by polymorphic estrogen metabolism-related gene variants has not been routinely investigated. We assessed breast cancer risk of 12 candidate variants in 12 genes involved in steroid metabolism, catabolism, binding, or receptor functions in a study of 859 cases and 1,083 controls within the US radiologic technologists (USRT) cohort. Using cumulative breast dose estimates from a detailed assessment of occupational and personal diagnostic ionizing radiation exposure, we investigated the joint effects of genotype on the risk of breast cancer. In multivariate analyses, we observed a significantly decreased risk of breast cancer associated with the CYP3A4 M445T minor allele (rs4986910, OR = 0.3; 95% CI 0.1-0.9). We found a borderline increased breast cancer risk with having both minor alleles of CYP1B1 V432L (rs1056836, CC vs. GG, OR = 1.2; 95% CI 0.9-1.6). Assuming a recessive model, the minor allele of CYP1B1 V432L significantly increased the dose-response relationship between personal diagnostic X-ray exposure and breast cancer risk, adjusted for cumulative occupational radiation dose (p(interaction) = 0.03) and had a similar joint effect for cumulative occupational radiation dose adjusted for personal diagnostic X-ray exposure (pinteraction = 0.06). We found suggestive evidence that common variants in selected estrogen metabolizing genes may modify the association between ionizing radiation exposure and breast cancer risk. C1 [Sigurdson, Alice J.; Bhatti, Parveen; Rajaraman, Preetha; Doody, Michele M.; Simon, Steven L.; Linet, Martha S.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. [Chang, Shih-chen] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. [Chang, Shih-chen] AstraZeneca, Wilmington, DE USA. [Bowen, Laura] Informat Management Syst, Silver Spring, MD USA. [Weinstock, Robert M.] Res Triangle Inst, Bethesda, MD USA. [Stovall, Marilyn] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. [Alexander, Bruce H.] Univ Minnesota, Div Environm Hlth Sci, Minneapolis, MN USA. [Preston, Dale L.] HiroSoft Int Corp, Seattle, WA USA. [Struewing, Jeffery P.] NCI, Lab Populat Genet, Ctr Canc Res, NIH,DHHS, Bethesda, MD 20892 USA. RP Sigurdson, AJ (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,EPS 7060,MSC 7238, Bethesda, MD 20892 USA. EM sigurdsa@mail.nih.gov RI Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 FU National Institutes of Health FX We are grateful to the radiologic technologists who participated in the USRT study; Jerry Reid of the American Registry of Radiologic Technologists for continued support of this study; and Diane Kampa and Allison Iwan of the University of Minnesota for data collection and study coordination. This study was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health. NR 21 TC 7 Z9 8 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD NOV PY 2009 VL 118 IS 1 BP 177 EP 184 DI 10.1007/s10549-009-0307-3 PG 8 WC Oncology SC Oncology GA 505YI UT WOS:000270737800019 PM 19214745 ER PT J AU Campbell, A Minniti, CP Nouraie, M Arteta, M Rana, S Onyekwere, O Sable, C Ensing, G Dham, N Luchtman-Jones, L Kato, GJ Gladwin, MT Castro, OL Gordeuk, VR AF Campbell, Andrew Minniti, Caterina P. Nouraie, Mehdi Arteta, Manuel Rana, Sohail Onyekwere, Onyinye Sable, Craig Ensing, Gregory Dham, Niti Luchtman-Jones, Lori Kato, Gregory J. Gladwin, Mark T. Castro, Oswaldo L. Gordeuk, Victor R. TI Prospective evaluation of haemoglobin oxygen saturation at rest and after exercise in paediatric sickle cell disease patients SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE sickle cell disease; paediatric; oxygen saturation; six-minute walk; pulmonary hypertension ID REGURGITANT JET VELOCITY; PULSE OXIMETRY; PULMONARY-HYPERTENSION; CHEST SYNDROME; LUNG-FUNCTION; CHILDREN; ANEMIA; DESATURATION; STANDARDIZATION; HYPOXEMIA AB P>Low steady state haemoglobin oxygen saturation in patients with sickle cell anaemia has been associated with the degree of anaemia and haemolysis. How much pulmonary dysfunction contributes to low saturation is not clear. In a prospective study of children and adolescents with sickle cell disease aged 3-20 years at steady state and matched controls, 52% of 391 patients versus 24% of 63 controls had steady state oxygen saturation < 99% (P < 0 center dot 0001), 9% of patients versus no controls had saturation < 95% (P = 0 center dot 008) and 8% of patients versus no controls had exercise-induced reduction in saturation >= 3%. Decreasing haemoglobin concentration (P < 0 center dot 001) and increasing haemolysis (P < 0 center dot 003) but not pulmonary function tests were independent predictors of both lower steady-state saturation and exercise-induced reduction in saturation. Neither history of stroke nor history of acute chest syndrome was significantly associated with lower steady-state oxygen saturation or exercise-induced reduction in saturation. Tricuspid regurgitation velocity was higher in patients with lower steady state haemoglobin oxygen saturation (P = 0 center dot 003) and with greater decline in oxygen saturation during the six-minute walk (P = 0 center dot 022). In conclusion, lower haemoglobin oxygen saturation is independently associated with increasing degrees of anaemia and haemolysis but not pulmonary function abnormalities among children and adolescents with sickle cell disease. C1 [Gordeuk, Victor R.] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20001 USA. [Campbell, Andrew; Arteta, Manuel; Ensing, Gregory] Univ Michigan, Ann Arbor, MI 48109 USA. [Minniti, Caterina P.; Kato, Gregory J.] NHLBI, Bethesda, MD 20892 USA. [Minniti, Caterina P.; Kato, Gregory J.] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. [Sable, Craig; Dham, Niti; Luchtman-Jones, Lori] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Gladwin, Mark T.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. RP Gordeuk, VR (reprint author), Howard Univ, Ctr Sickle Cell Dis, 1840th St,Room 201, Washington, DC 20001 USA. EM vgordeuk@howard.edu RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 FU Intramural NIH HHS [Z01 CL008098-02, Z01 CL008098-01, ZIA HL006016-01, ZIA HL006016-02]; NCRR NIH HHS [2MOI RR10284-10, M01 RR010284]; NHLBI NIH HHS [1 R01 HL079912-02, 2 R25 HL003679-08, R01 HL079912, R25 HL003679] NR 32 TC 27 Z9 28 U1 0 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD NOV PY 2009 VL 147 IS 3 BP 352 EP 359 DI 10.1111/j.1365-2141.2009.07854.x PG 8 WC Hematology SC Hematology GA 505VT UT WOS:000270727900009 PM 19694721 ER PT J AU Anderson, LA Landgren, O Engels, EA AF Anderson, Lesley A. Landgren, Ola Engels, Eric A. TI Common community acquired infections and subsequent risk of chronic lymphocytic leukaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE chronic lymphocytic leukaemia; infection; risk factors; epidemiology ID RECEPTORS; ZOSTER AB Emerging evidence supports a role for immune-related factors in the causation of chronic lymphocytic leukaemia (CLL). Using the population-based U. S. Surveillance Epidemiology and End Results-Medicare database, 10 171 elderly CLL patients and 122 531 frequency-matched controls were identified in order to evaluate several community acquired infections associated with subsequent CLL risk. Odds ratios (ORs) were adjusted for gender, age, race, calendar year and number of physician claims. CLL risk was increased following Medicare claims for sinusitis (OR = 1.11; 95% CI = 1.05-1.17), pharyngitis (OR = 1.15; 1.08-1.22), bronchitis (OR = 1.14; 1.08-1.19), pneumonia(OR = 1.17; 1.11-1.24), influenza (OR = 1.10; 1.01-1.19), cellulitis (OR = 1.08; 1.02-1.14) and herpes zoster (OR = 1.26; 1.15-1.37). Associations with pneumonia and cellulitis remained significant when the 5-year period before diagnosis/control selection was excluded. CLL risk increased with increasing severity/frequency of pneumonia (P = 0.005), cellulitis (P < 0.001) and herpes zoster (P < 0.001). Our findings suggest that common infections may play a role in CLL aetiology. Alternatively, the associations might reflect an underlying immune disturbance present several years prior to CLL diagnosis. C1 [Anderson, Lesley A.] Queens Univ Belfast, Canc Epidemiol & Prevent Res Grp, Ctr Publ Hlth, Belfast BT12 6BJ, Antrim, North Ireland. [Landgren, Ola; Engels, Eric A.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Landgren, Ola] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Anderson, LA (reprint author), Queens Univ Belfast, Canc Epidemiol & Prevent Res Grp, Ctr Publ Hlth, Mulhouse Bldg,Grosvenor Rd, Belfast BT12 6BJ, Antrim, North Ireland. EM l.anderson@qub.ac.uk OI Anderson, Lesley/0000-0002-1000-3649 FU Intramural Research Programme of the National Cancer Institute; Research and Development Office, Northern Ireland; Cancer Prevention Fellowship Programme; Office of Preventive Oncology; National Cancer Institute; Surveillance, Epidemiology and End Results (SEER)-Medicare database FX This study was supported by the Intramural Research Programme of the National Cancer Institute. The Research and Development Office, Northern Ireland, funded Dr. Lesley Anderson to participate in the Cancer Prevention Fellowship Programme, Office of Preventive Oncology, National Cancer Institute. This study used the linked Surveillance, Epidemiology and End Results (SEER)-Medicare database. The interpretation and reporting of these data are the sole responsibility of the authors. The authors acknowledge the efforts of the Applied Research Programme, NCI; the Office of Research, Development and Information, Centres for Medicare and Medicaid Services; Information Management Services, Inc.; and the SEER Programme tumour registries in the creation of the SEER-Medicare database. The authors thank Winnie Ricker and Ruth Parsons, Information Management Services, Rockville, MD for constructing the dataset, and our colleagues on the SMAHRT Study, who provided advice and assistance with the SEER-Medicare dataset. NR 20 TC 30 Z9 31 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD NOV PY 2009 VL 147 IS 4 BP 444 EP 449 DI 10.1111/j.1365-2141.2009.07849.x PG 6 WC Hematology SC Hematology GA 512IN UT WOS:000271240900003 PM 19725826 ER PT J AU Bottos, J Miller, RH Belfort, RN Macedo, AC Belfort, R Grigg, ME AF Bottos, J. Miller, R. H. Belfort, R. N. Macedo, A. C. Belfort, R., Jr. Grigg, M. E. CA UNIFESP Toxoplasmosis Grp TI Bilateral retinochoroiditis caused by an atypical strain of Toxoplasma gondii SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID OCULAR TOXOPLASMOSIS; GLOBAL REASSESSMENT; MEMORIAL-LECTURE; SOUTHERN BRAZIL; GENOTYPE; DISEASE; INFECTION; HUMANS; GENE AB Background: A 53-year-old man presented with an acute bilateral posterior uveitis with extensive necrotising retinochoroiditis but without chorioretinal scarring. A thorough workup did not reveal any underlying disease. The possibilities of atypical ocular toxoplasmosis as well as herpetic retinal necrosis were considered and specific therapy instituted, with little improvement. The patient died within 2 months as result of an undifferentiated squamous cell carcinoma. Methods: Histopathological examination, immunohistochemistry and multilocus polymerase chain reaction confirmed Toxoplasma gondii infection of the retina Results: Macroscopic examination of enucleated globe showed extensive retinal necrosis and vitreous detachment. Histological examination of retinal tissue identified numerous round-to-elliptical toxoplasmic cysts within the retina, with retinal necrosis and minimal choroidal inflammation. Immunohistochemical analyses confirmed that the cysts were due to T gondii. DNA extracted from formalin-fixed, paraffin-embedded tissue sections was subjected to multilocus polymerase chain reaction (PCR) analysis at the following typing loci: SAG1, SAG2, SAG3, SAG4, B1, NTS2, GRA6 and GRA7. DNA sequencing of positive PCR products at the NTS2, SAG1 and GRA7 loci confirmed the presence of a non-archetypal strain of T gondii infecting the eye of the patient experiencing a severe, atypical ocular toxoplasmosis Conclusion: A highly divergent, non-archetypal strain of T gondii was responsible for causing a severe, atypical bilateral retinochoroiditis in a patient from Brazil. C1 [Bottos, J.; Belfort, R. N.; Macedo, A. C.; Belfort, R., Jr.] Univ Fed Sao Paulo, Vis Inst, Dept Ophthalmol, BR-04044010 Sao Paulo, Brazil. [Miller, R. H.; Grigg, M. E.] NIAID, Parasit Dis Lab, Mol Parasitol Unit, NIH, Bethesda, MD 20892 USA. [Belfort, R. N.] McGill Univ, Dept Ophthalmol, Henry C Witelson Ocular Pathol Lab, Montreal, PQ H3A 2T5, Canada. RP Bottos, J (reprint author), Univ Fed Sao Paulo, Vis Inst, Dept Ophthalmol, Rua Mirassol 236 Ap 22, BR-04044010 Sao Paulo, Brazil. EM jubottos@gmail.com RI Belfort Jr, Rubens/E-2252-2012 OI Belfort Jr, Rubens/0000-0002-8422-3898 FU FADA-UNIFESP; CNPq; NIH; NIAID FX This work was supported by the Intramural Research Program of the NIH and NIAID. MEG is a scholar of the Canadian Institute for Advanced Research (CIFAR) Program for Integrated Microbial Biodiversity. NR 19 TC 15 Z9 15 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD NOV PY 2009 VL 93 IS 11 BP 1546 EP 1550 DI 10.1136/bjo.2009.162412 PG 5 WC Ophthalmology SC Ophthalmology GA 510MF UT WOS:000271091900028 PM 19666926 ER PT J AU Boknik, P Grote-Wessels, S Barteska, G Jiang, M Muller, FU Schmitz, W Neumann, J Birnbaumer, L AF Boknik, P. Grote-Wessels, S. Barteska, G. Jiang, M. Mueller, F. U. Schmitz, W. Neumann, J. Birnbaumer, L. TI Genetic disruption of G proteins, G(i2)alpha or G(o)alpha, does not abolish inotropic and chronotropic effects of stimulating muscarinic cholinoceptors in atrium SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE acetylcholine; carbachol; muscarinic cholinoceptors; G proteins; parasympathomimetics; vagal stimulation ID OVEREXPRESSING A(1)-ADENOSINE RECEPTORS; SINOATRIAL NODE CELLS; NITRIC-OXIDE SYNTHASE; VENTRICULAR MYOCYTES; ADENOSINE RECEPTOR; PERTUSSIS-TOXIN; CYCLIC-AMP; ACETYLCHOLINE-RECEPTORS; MEDIATED INHIBITION; SIGNAL-TRANSDUCTION AB Background and purpose: Classically, stimulation of muscarinic cholinoceptors exerts negative inotropic and chronotropic effects in the atrium of mammalian hearts. These effects are crucial to the vagal regulation of the heart beat. This effect is assumed to be mediated via GTP binding (G) proteins, because they can be abolished by Pertussis toxin. However, it is unknown which G proteins are involved. Experimental approach: We studied contractility in isolated left or right atrium from genetically manipulated mice with deletion of one of two G proteins, either of the alpha subunit of G(i2) protein (G(i2)alpha) or of the alpha subunit of G(o) protein (G(o)alpha). Preparations were stimulated with carbachol alone or after pretreatment with the beta-adrenoceptor agonist isoprenaline. For comparison, the effects of carbachol on L-type Ca2+-channels in isolated ventricular cardiomyocytes were studied. Key results: The negative inotropic and chronotropic effects of carbachol alone or in the presence of isoprenaline were identical in atria from knockout or wild-type mice. However, the effect of carbachol on isoprenaline-activated L-type Ca2+-channel in isolated ventricular cardiomyocytes was greatly attenuated in both types of knockout mice studied. Conclusions and implications: These data imply that there is either redundancy of G proteins for signal transduction or that Pertussis toxin-sensitive proteins other than G(i2)alpha and G(o)alpha mediate the vagal stimulation in the atrium. Moreover, different G proteins mediate the effect of carbachol in ventricle compared with atrium. C1 [Boknik, P.; Grote-Wessels, S.; Barteska, G.; Mueller, F. U.; Schmitz, W.] Univ Munster, Inst Pharmakol & Toxikol, Univ Klinikum Munster, D-48149 Munster, Germany. [Jiang, M.] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA USA. [Neumann, J.] Univ Halle Wittenberg, Inst Pharmakol & Toxikol, Halle, Germany. [Birnbaumer, L.] NIEHS, NIH, Dept Human & Hlth Serv, Res Triangle Pk, NC 27709 USA. RP Boknik, P (reprint author), Univ Munster, Inst Pharmakol & Toxikol, Univ Klinikum Munster, Domagkstr 12, D-48149 Munster, Germany. EM boknik@uni-muenster.de FU NIH [Z01-ES-101643, DK069771] FX This work was supported in part by the Intramural Research Program of the NIH to LB (Z01-ES-101643) and by the NIH grant to MJ (DK069771). NR 55 TC 9 Z9 9 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD NOV PY 2009 VL 158 IS 6 BP 1557 EP 1564 DI 10.1111/j.1476-5381.2009.00441.x PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 512QC UT WOS:000271263900015 PM 19906118 ER PT J AU Adams, PC Barton, JC McLaren, GD Acton, RT Speechley, M McLaren, CE Reboussin, DM Leiendecker-Foster, C Harris, EL Snively, BM Vogt, T Sholinsky, P Thomson, E Dawkins, FW Gordeuk, VR Eckfeldt, JH AF Adams, Paul C. Barton, James C. McLaren, Gordon D. Acton, Ronald T. Speechley, Mark McLaren, Christine E. Reboussin, David M. Leiendecker-Foster, Catherine Harris, Emily L. Snively, Beverly M. Vogt, Thomas Sholinsky, Phyliss Thomson, Elizabeth Dawkins, Fitzroy W. Gordeuk, Victor R. Eckfeldt, John H. TI Screening for iron overload: Lessons from the HEmochromatosis and IRon Overload Screening (HEIRS) Study SO CANADIAN JOURNAL OF GASTROENTEROLOGY LA English DT Review DE Haemochromatosis; Hemochromatosis; HFE; Iron overload ID HFE C282Y HOMOZYGOTES; HEREDITARY HEMOCHROMATOSIS; COST-EFFECTIVENESS; FAMILY-HISTORY; SERUM FERRITIN; PRIMARY-CARE; POPULATION; PREVALENCE AB BACKGROUND: The HEmochromatosis and IRon Overload Screening (HEIRS) Study provided data on a racially, ethnically and geographically diverse cohort of participants in North America screened from primary care populations. METHODS: A total of 101,168 participants were screened by testing for HFE C282Y and H63D Mutations, and measuring serum ferritin concentration and transferrin saturation. In the present review, lessons from the HEIRS Study are highlighted in the context of the principles of screening for a medical disease as previously outlined by the World Health Organization. RESULTS: Genetic testing is well accepted, with minimal risk of discrimination. Transferrin saturation has high biological variability and relatively low sensitivity to detect HFE C282Y homozygotes, which limits its role as a screening rest. Symptoms attributable to HFE C282Y homozygosity are no more common in individuals identified by Population screening than in control subjects. CONCLUSIONS: Generalized Population screening in a primary care population as performed in the HEIRS Study is not recommended. There may be a role for focused screening ill Caucasian men, with some debate regarding genotyping followed by phenotyping, or phenotyping followed by genotyping. C1 [Adams, Paul C.] London Hlth Sci Ctr, Dept Med, London, ON, Canada. [Barton, James C.] So Iron Disorders Ctr, Birmingham, AL USA. [McLaren, Gordon D.] VA Long Beach Healthcare Syst, Long Beach, CA USA. [McLaren, Christine E.] Univ Calif Irvine, Dept Epidemiol, Irvine, CA 92717 USA. [Acton, Ronald T.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. [Reboussin, David M.; Snively, Beverly M.] Wake Forest Univ, Bowman Gray Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA. [Leiendecker-Foster, Catherine; Eckfeldt, John H.] Univ Minnesota, Dept Lab Med, Minneapolis, MN 55455 USA. [Leiendecker-Foster, Catherine; Eckfeldt, John H.] Univ Minnesota, Dept Pathol, Minneapolis, MN 55455 USA. [Harris, Emily L.] Natl Inst Dent & Craniofacial Res, Translat Genom Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Vogt, Thomas; Gordeuk, Victor R.] Kaiser Permanente Ctr Hlth Res, Honolulu, HI USA. [Sholinsky, Phyliss] NHLBI, Dept Epidemiol & Biostat, Epidemiol Branch, Bethesda, MD 20892 USA. [Thomson, Elizabeth] NHGRI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Dawkins, Fitzroy W.] Howard Univ, Dept Med, Washington, DC 20059 USA. RP Adams, PC (reprint author), Univ Western Ontario, Univ Hosp, Dept Med, 339 Windermere Rd, London, ON N6A 5A5, Canada. EM padams@uwo.ca FU National Heart, Lung, and Blood Institute; University of Minnesota, Minneapolis, Minnesota [N01-HC05185]; Howard University, Washington DC [N01-HC05186, N01-CM-07003-74]; University of Alabama, Birmingham, Alabama [N01-HC05188]; Kaiser Permanente Center for Health Research [N01-C05189]; University of California, Irvine, California [N01-HC05190]; London Health Sciences Centre, London, Ontario [N01-HC05191]; Wake Forest University, Winston-Salem, North Carolina [N01-C05192]; University of Alabama at Birmingham General Clinical Research Center (GCRC) [M01-RR00032]; Howard University GCRC [M01-RR10284]; University of California, Irvine UCSD/UCI Satellite GCRC [M01-RR00827]; National Center for Research Resources, National Institutes of Health (Bethesda, Maryland); National Heart, Lung, and Blood Institute, and the Office of Research on Minority Health (VRG) [UH1-HL03679-05]; Southern Iron Disorders Center (Birmingham, Alabama) FX The HEIRS Study was initiated and funded by the National Heart, Lung, and Blood Institute, in conjunction with the National Human Genome Research Institute (Bethesda, Maryland). The study is supported by contracts N01-HC05185 (University of Minnesota, Minneapolis, Minnesota); N01-HC05186, N01-CM-07003-74, and Minority CCOP (Howard University, Washington DC); N01-HC05188 (University of Alabama, Birmingham, Alabama); N01-C05189 (Kaiser Permanente Center for Health Research); N01-HC05190 (University of California, Irvine, California); N01-HC05191 (London Health Sciences Centre, London, Ontario); and N01-C05192 (Wake Forest University, Winston-Salem, North Carolina). Additional support was provided by the University of Alabama at Birmingham General Clinical Research Center (GCRC) grant M01-RR00032, Howard University GCRC grant M01-RR10284, and the University of California, Irvine UCSD/UCI Satellite GCRC grant M01-RR00827, sponsored by the National Center for Research Resources, National Institutes of Health (Bethesda, Maryland); Howard University Research Scientist Award UH1-HL03679-05 from the National Heart, Lung, and Blood Institute, and the Office of Research on Minority Health (VRG); and Southern Iron Disorders Center (Birmingham, Alabama) (JCB, RTA). NR 24 TC 8 Z9 8 U1 0 U2 3 PU PULSUS GROUP INC PI OAKVILLE PA 2902 S SHERIDAN WAY, OAKVILLE, ONTARIO L6J 7L6, CANADA SN 0835-7900 J9 CAN J GASTROENTEROL JI Can. J. Gastroenterol. PD NOV PY 2009 VL 23 IS 11 BP 769 EP 772 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 522JL UT WOS:000271993700006 PM 19893773 ER PT J AU Doria-Rose, VP Marcus, PM Szabo, E Tockman, MS Melamed, MR Prorok, PC AF Doria-Rose, V. Paul Marcus, Pamela M. Szabo, Eva Tockman, Melvyn S. Melamed, Myron R. Prorok, Philip C. TI Randomized Controlled Trials of the Efficacy of Lung Cancer Screening by Sputum Cytology Revisited A Combined Mortality Analysis From the Johns Hopkins Lung Project and the Memorial Sloan-Kettering Lung Study SO CANCER LA English DT Article DE lung cancer; screening; sputum cytology; chest X-ray ID DETECTION PROGRAM; NEW-YORK; CARCINOMA; SMOKERS; ATYPIA; COHORT AB BACKGROUND: Two randomized controlled trials of lung cancer screening initiated in the 1970s, the Johns Hopkins Lung Project and the Memorial Sloan Kettering Lung Study, compared 1 arm that received annual chest x-ray and 4-monthly sputum cytology (dual-screen) to a second arm that received annual chest x-ray only. Previous publications from these trials reported similar lung cancer mortality between the 2 groups. However, these findings were based on incomplete follow-up, and each trial on its own was under-powered to detect a modest mortality benefit. METHODS: The authors estimated the efficacy of lung cancer screening with sputum cytology in an intention to screen analysis of lung cancer mortality, using combined data from these trials (n = 20,426). RESULTS: Over 1/2 of squamous cell lung cancers diagnosed in the dual screen group were identified by cytology these cancers tended to be more localized than squamous cancers diagnosed in the X-ray only arm. After 9 years of follow-up, lung cancer mortality was slightly lower in the dual-screen in the X-ray only arm (rate ratio [RR], 0.88; 95% CI, 0.54-1.14) and in the heaviest smokers (RR, 0.81, 95% CI, 0.67-1.00). There were also fewer deaths from large cell carcinoma in the dual-screen group although the reason for this is unclear. CONCLUSIONS: These data are suggestive of a model benefit of sputum cytology screening although we cannot rule out chance as an explanation for these findings. Cancer 2009;115:5007-17. (C) 2009 American Cancer Society. C1 [Doria-Rose, V. Paul; Marcus, Pamela M.; Prorok, Philip C.] NCI, Biometry Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [Doria-Rose, V. Paul] NCI, Canc Prevent Fellowship Program, Ctr Canc Training, NIH, Bethesda, MD 20892 USA. [Szabo, Eva] NCI, Lung & Upper Aerodigest Canc Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [Tockman, Melvyn S.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Risk Assessment Detect & Intervent Program,Dept C, Tampa, FL 33612 USA. [Melamed, Myron R.] New York Med Coll, Dept Pathol, Valhalla, NY 10595 USA. RP Doria-Rose, VP (reprint author), NCI, Biometry Res Grp, Canc Prevent Div, NIH, 6130 Execut Blvd,Suite 3131, Bethesda, MD 20892 USA. EM doriarop@mail.nih.gov OI Doria-Rose, Vincent/0000-0002-8802-5143 FU National Cancer Institute [NO1-CN-45007, N01-CB-92172, N01-CN-45037, M01-RR-00035-21, RR00722] FX The trials were supported by the following grants and contracts from the National Cancer Institute: NO1-CN-45007 (Memorial Sloan-Kettering Lung Study) and N01-CB-92172, N01-CN-45037, M01-RR-00035-21, and RR00722 (Johns Hopkins Lung Project). NR 28 TC 23 Z9 24 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD NOV 1 PY 2009 VL 115 IS 21 BP 5007 EP 5017 DI 10.1002/cncr.24545 PG 11 WC Oncology SC Oncology GA 511LY UT WOS:000271167900017 PM 19637354 ER PT J AU Moore, SC Peters, TM Ahn, J Park, Y Schatzkin, A Albanes, D Hollenbeck, A Leitzmann, MF AF Moore, Steven C. Peters, Tricia M. Ahn, Jiyoung Park, Yikyung Schatzkin, Arthur Albanes, Demetrius Hollenbeck, Albert Leitzmann, Michael F. TI Age-Specific Physical Activity and Prostate Cancer Risk Among White Men and Black Men SO CANCER LA English DT Article DE physical activity; prostate; cancer; epidemiology ID UNITED-STATES; SEX-HORMONES; LARGE COHORT; AMERICAN; HEALTH; DIET AB BACKGROUND: The relation of physical activity across the lifespan to risk of prostate cancer has not been thoroughly investigated, particularly among black men. The authors investigated physical activity, including activity during different age periods and of various intensities, in relation to prostate cancer incidence among white men and black men. METHODS: In total, 160,006 white men and 3671 black men ages 51 years to 72 years who were enrolled in the National Institutes of Health-AARP Diet and Health Study reported their time spent per week engaging in physical activity during ages 15 to 18 years, 19 years to 29 years, 35 years to 39 years, and during the past 10 years. Cox regression models were used to examine physical activity, categorized by intensity (moderate or vigorous, light, and total), in relation to prostate cancer risk. RESULTS: During 7 years of follow-up, 9624 white men and 371 black men developed prostate cancer. Among white men, physical activity had no association with prostate cancer regardless of age period or activity intensity. Among black men, engaging in >= 4 hours of moderate/vigorous intensity physical activity versus infrequent activity during ages 19 years to 29 years was related to a 35% lower risk of prostate cancer (relative risk, 0.65; 95% confidence interval [95% CI], 0.43-0.99 [P(trend) = .01]). Frequent moderate/vigorous physical activity at ages 35 years to 39 years also potentially was related to reduced prostate cancer risk (relative risk, 0.59; 95% Cl, 0.36-0.96 [P(trend) = .15]). CONCLUSIONS: Regular physical activity may reduce prostate cancer risk among black men, and activity during young adulthood may yield the greatest benefit. This novel finding needs confirmation in additional studies. Cancer 2009;115:5060-70. Published 2009 by the American Cancer Society.* C1 [Moore, Steven C.; Peters, Tricia M.; Ahn, Jiyoung; Park, Yikyung; Schatzkin, Arthur; Albanes, Demetrius; Leitzmann, Michael F.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Hollenbeck, Albert] AARP, Washington, DC USA. RP Moore, SC (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM moorest@mail.nih.gov RI Albanes, Demetrius/B-9749-2015; Moore, Steven/D-8760-2016; OI Moore, Steven/0000-0002-8169-1661; Park, Yikyung/0000-0002-6281-489X FU National Institutes of Health, National Cancer Institute [TU2CA105666] FX Supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, and by grant TU2CA105666 (to S.C.M.). NR 25 TC 14 Z9 14 U1 0 U2 1 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 2009 VL 115 IS 21 BP 5060 EP 5070 DI 10.1002/cncr.24538 PG 11 WC Oncology SC Oncology GA 511LY UT WOS:000271167900022 PM 19645029 ER PT J AU Mohla, S Stearns, V Sathyamoorthy, N Rosenfeld, MG Nelson, P AF Mohla, Suresh Stearns, Vered Sathyamoorthy, Neeraja Rosenfeld, Michael G. Nelson, Peter TI The biology of hormone refractory breast and prostate cancer An NCI workshop report SO CANCER BIOLOGY & THERAPY LA English DT Editorial Material DE hormone refractory cancer; steroid receptors; breast cancer; prostate cancer ID ANDROGEN-RECEPTOR; GENE-EXPRESSION; THERAPEUTIC IMPLICATIONS; TAMOXIFEN RESISTANCE; CELLS; GROWTH; MECHANISMS; TESTOSTERONE; NUCLEAR; PATHWAY AB The molecular regulation of growth and progression of hormone refractory breast and prostate cancers remains challenging. The Division of Cancer Biology, NCI organized a small "think tank" style workshop and invited scientists in relevant areas to assess the state of science on the biology of hormone refractory tumors and to identify potential research opportunities to enhance a better understanding of the molecular regulation of these tumors. The meeting, held on May 27-29, 2008 in Bethesda, MD, was co-chaired by Drs. Michael Geoffrey Rosenfeld and Michael Press. While expression of estrogen or progesterone receptors (ER/PR) is required for benefit from endocrine manipulations, many women with breast cancer will not respond to primary endocrine manipulations despite ER/PR expression, and others acquire resistance while on treatment. Understanding the mechanisms that lead to Hormone Refractory Breast Cancer (HRBC) and defining interventions that may modulate the resistance to endocrine therapy are currently lacking. In contrast to breast cancers, the vast majority of both early and advanced prostate carcinomas exhibit androgen-pathway activity at diagnosis and the vast majority respond to treatments designed to inhibit AR-signaling. However, after initial benefit, advanced prostate cancers regularly progress to a clinical state termed Castration Resistant Prostate Cancer (CRPC) that reflects a diverse array of molecular events maintaining AR signaling. The workshop focused on both common and unique features of hormone refractory breast and prostate cancer with an orientation toward defining major research questions, delineating opportunities and recommending strategies for overcoming barriers to progress in understanding these important clinical disease states. C1 [Mohla, Suresh; Sathyamoorthy, Neeraja] NCI, Div Canc Biol, Bethesda, MD 20892 USA. [Stearns, Vered] Johns Hopkins Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Rosenfeld, Michael G.] Univ Calif San Diego, Howard Hughes Med Inst, San Diego, CA 92103 USA. [Nelson, Peter] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Mohla, S (reprint author), NCI, Div Canc Biol, Bethesda, MD 20892 USA. EM mohlas@mail.nih.gov NR 36 TC 13 Z9 13 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD NOV 1 PY 2009 VL 8 IS 21 BP 1975 EP 1985 DI 10.4161/cbt.8.21.9918 PG 11 WC Oncology SC Oncology GA 533BF UT WOS:000272796200003 PM 19783900 ER PT J AU Jonsson, JG Sissung, TM Figg, WD AF Jonsson, Johann G. Sissung, Tristan M. Figg, William D. TI A genomic strategy for predicting androgen receptor activity in prostate tumors SO CANCER BIOLOGY & THERAPY LA English DT Editorial Material DE genomic strategy; androgen receptor; activity; AR signature; prostate tumors; ADT; CRPC ID CANCER; CASTRATION; THERAPY AB Mendiratta et al. have developed an AR signature for prostate cancer that is based on the expression of 300 genes. The AR signature is decreased with androgen deprivation therapy, and in the development of androgen independent prostate cancer, however significant inter-individual variation in AR activity was noted. Decreased AR activity was also related to the expression of SRC kinase, and sensitivity to dasatinib. The work by Mendiratta et al. may be useful to determine the AR status of tumors in order to inform therapy and individualize treatment. C1 [Sissung, Tristan M.; Figg, William D.] NCI, Clin Pharmacol Program, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Jonsson, Johann G.] Univ Iceland, Fac Pharmaceut Sci, Reykjavik, Iceland. RP Figg, WD (reprint author), NCI, Clin Pharmacol Program, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 10 TC 1 Z9 1 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD NOV 1 PY 2009 VL 8 IS 21 BP 2002 EP 2003 DI 10.4161/cbt.8.21.10180 PG 2 WC Oncology SC Oncology GA 533BF UT WOS:000272796200006 PM 19838047 ER PT J AU Yang, SX Kummar, S Steinberg, SM Murgo, AJ Gutierrez, M Rubinstein, L Nguyen, D Kaur, G Chen, AP Giranda, VL Tomaszewski, JE Doroshow, JH AF Yang, Sherry X. Kummar, Shivaani Steinberg, Seth M. Murgo, Anthony J. Gutierrez, Martin Rubinstein, Larry Nguyen, Dat Kaur, Gurmeet Chen, Alice P. Giranda, Vincent L. Tomaszewski, Joseph E. Doroshow, James H. CA Natl Canc Inst Phase 0 Working Grp TI Immunohistochemical detection of poly(ADP-ribose) polymerase inhibition by ABT-888 in patients with refractory solid tumors and lymphomas SO CANCER BIOLOGY & THERAPY LA English DT Article DE ABT-888; immunohistochemistry; PARP; solid tumors and lymphomas; Phase 0 clinical trial ID ADP-RIBOSE POLYMERASE; METASTATIC BREAST-CANCER; 0 CLINICAL-TRIAL; ERLOTINIB TREATMENT; DNA-REPAIR; EXPRESSION; GLYCOHYDROLASE; DEATH; CELLS AB Purpose: Targeting the poly (ADP-ribose) polymerase (PAPARP) pathway for cancer treatment has been an active area of pre-clinical and clinical research. We aimed to determine whether the PAPARP inhibitor ABT-888 hits its therapeutic target in tumors by immunohistochemistry during a Phase 0 trial conducted at the National Cancer Institute. Experimental design: The expression of poly (ADP-ribose) (PAR) and full size PAPARP-1 were quantitatively examined by immunohistochemistry in paraffin-embedded tumor biopsies at baseline and 3-24 h after a single oral dose (25 or 50 mg) of ABT-888. Results: Baseline PAR levels were moderate to high in three patients with non-Hodgkin lymphomas, and one each with small cell lung cancer, squamous cell carcinoma of the tongue and melanoma; low in two patients with cutaneous T-cell lymphoma and one with adenocarcinoma of external ear canal. A significant decrease in PAR (median decrease 30.2, range -13.1 to -69.8) was achieved after drug administration (n = 6 pairs; p = 0.03), whereas an increase in PAPARP-1 expression was observed in five of the six tumors. This resulted in a decrease in the ratio of PAR to PARP-1 in tumor biopsies (median -6.76, range -0.41 to -22.59; p = 0.03). Conclusions: ABT-888 hits its therapeutic target by significantly reducing PAR levels and the ratio of PAR to PARP-1 in human tumor cells detected by immunohistochemistry. Baseline tumor PAPAR levels vary considerably among patients who entered this Phase 0 study. This underscores a need to investigate baseline PAPAR levels in association with response in future preclinical and clinical studies. C1 [Yang, Sherry X.; Rubinstein, Larry; Nguyen, Dat; Kaur, Gurmeet; Chen, Alice P.; Tomaszewski, Joseph E.; Doroshow, James H.] NCI, Div Canc Treatment & Diag, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kummar, Shivaani; Murgo, Anthony J.; Gutierrez, Martin] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Doroshow, James H.] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Giranda, Vincent L.] Abbott Labs, Chicago, IL USA. RP Yang, SX (reprint author), NCI, Div Canc Treatment & Diag, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM yangxia@mail.nih.gov; doroshoj@mail.nih.gov FU Division of Cancer Treatment and Diagnosis, National Cancer Institute (NCI) [N01-CO-12400] FX Funded in part by the Division of Cancer Treatment and Diagnosis, National Cancer Institute (NCI) and the NCI Contract N01-CO-12400. NR 28 TC 16 Z9 16 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD NOV 1 PY 2009 VL 8 IS 21 BP 2004 EP 2009 DI 10.4161/cbt.8.21.9917 PG 6 WC Oncology SC Oncology GA 533BF UT WOS:000272796200007 PM 19823047 ER PT J AU Tsilidis, KK Helzlsouer, KJ Smith, MW Grinberg, V Hoffman-Bolton, J Clipp, SL Visvanathan, K Platz, EA AF Tsilidis, Konstantinos K. Helzlsouer, Kathy J. Smith, Michael W. Grinberg, Victoriya Hoffman-Bolton, Judith Clipp, Sandra L. Visvanathan, Kala Platz, Elizabeth A. TI Association of common polymorphisms in IL10, and in other genes related to inflammatory response and obesity with colorectal cancer SO CANCER CAUSES & CONTROL LA English DT Article DE Inflammation; Obesity; Colorectal cancer; Genetic epidemiology; Prospective study ID C-REACTIVE PROTEIN; SINGLE-NUCLEOTIDE POLYMORPHISMS; COLON-CANCER; CRP LEVELS; INTERLEUKIN-10-DEFICIENT MICE; CARDIOVASCULAR EVENTS; INSULIN SENSITIVITY; PLASMA ADIPONECTIN; SEQUENCE VARIANTS; PROMOTER REGION AB Objective and methods The association of 17 candidate single nucleotide polymorphisms (SNPs) in IL10 and other immune response genes (CRP, TLR4, IL6, IL1B, IL8, TNF, RNASEL) and genes related to obesity (PPARG, TCF7L2, ADIPOQ, LEP) with colorectal cancer was investigated. Haplotype tagging SNPs were chosen for IL10, CRP, and TLR4. Incident colorectal cancer cases (n = 208) and matched controls (n = 381) were identified between baseline in 1989 and 2003 among participants in the CLUE II cohort. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using conditional logistic regression. Results Compared with the AA genotype at the candidate IL10-1082 locus (rs1800896), carrying one (OR, 0.79; 95% CI, 0.53-1.18) or two (OR, 0.58; 95% CI, 0.35-0.95) G alleles, a known higher producer of the anti-inflammatory cytokine IL-10, was associated with lower risk of colorectal cancer (p(trend) = 0.03). Statistically significant associations with colorectal cancer were observed for three tagSNPs in IL10 (rs1800890, rs3024496, rs3024498) and one common haplotype, but these associations were due to high linkage disequilibrium with IL10-1082. Two CRP haplotypes (global p = 0.04) and TLR4 tagSNPs (rs7873784, rs11536891), but not TLR4 haplotypes, were associated with colorectal cancer. Conclusions Our study suggests that polymorphisms in IL10, and also possibly in CRP and other genes related to immune response or obesity may be associated with colorectal cancer. C1 [Tsilidis, Konstantinos K.; Helzlsouer, Kathy J.; Hoffman-Bolton, Judith; Clipp, Sandra L.; Visvanathan, Kala; Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Helzlsouer, Kathy J.] St Johns Mercy Med Ctr, Weinberg Ctr Womens Hlth & Med, Prevent & Res Ctr, Baltimore, MD USA. [Helzlsouer, Kathy J.; Hoffman-Bolton, Judith; Clipp, Sandra L.] Johns Hopkins Bloomberg Sch Publ Hlth, George W Comstock Ctr Publ Hlth Res & Prevent, Hagerstown, MD USA. [Helzlsouer, Kathy J.; Visvanathan, Kala; Platz, Elizabeth A.] Johns Hopkins Med Inst, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA. [Grinberg, Victoriya] NCI Frederick, SAIC Frederick Inc, Adv Technol Program, Lab Mol Technol, Frederick, MD USA. RP Platz, EA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St,Rm E6132, Baltimore, MD 21205 USA. EM eplatz@jhsph.edu RI Smith, Michael/B-5341-2012 FU NCI NIH HHS [K07 CA111948, K07 CA111948-01A1] NR 68 TC 81 Z9 81 U1 0 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD NOV PY 2009 VL 20 IS 9 BP 1739 EP 1751 DI 10.1007/s10552-009-9427-7 PG 13 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 511VF UT WOS:000271198400022 PM 19760027 ER PT J AU Rixe, O Franco, SX Yardley, DA Johnston, SR Martin, M Arun, BK Letrent, SP Rugo, HS AF Rixe, Olivier Franco, Sandra X. Yardley, Denise A. Johnston, Stephen R. Martin, Miguel Arun, Banu K. Letrent, Stephen P. Rugo, Hope S. TI A randomized, phase II, dose-finding study of the pan-ErbB receptor tyrosine-kinase inhibitor CI-1033 in patients with pretreated metastatic breast cancer SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE CI-1033; Pan-ErbB receptor tyrosine-kinase inhibitor; Metastatic breast cancer; Efficacy; Safety ID PLUS CAPECITABINE; ORAL CL-1033; MULTICENTER; TRIAL; EFFICACY; FAMILY; SAFETY AB To evaluate the efficacy and safety of the pan-ErbB receptor tyrosine-kinase inhibitor CI-1033 in metastatic breast cancer (MBC). Patients with measurable, progressive, or recurrent MBC whose primary tumor expressed a parts per thousand yen1 ErbB receptor were randomized to the following CI-1033 regimens: 50 mg (arm A) or 150 mg (arm B) daily without rest period, or 450 mg/day x 14 days every 21 days (arm C). The primary endpoint was 1-year progression-free survival (PFS). Overall, 194 patients were treated. One-year PFS estimates were 3.8, 2.0, and 4.6%; median PFS was 61, 56, and 58 days; and investigator-assessed overall response rates were 1.5, 1.5, and 7.3%, in arms A, B, and C, respectively. Response duration was 110-419 days. In arm C, response (18.8 vs. 2.6%) and 1-year overall survival rates (86.7 vs. 47.5%) were greater in patients with HER2-positive versus HER2-negative tumors. The incidence of grade 3/4 adverse events (AEs) was dose-dependent, affecting 10.3, 48.6, and 80.4% of patients in arms A, B and C, respectively. The most common grade 3/4, treatment-related AEs were diarrhea, asthenia, and stomatitis. Arm C enrollment was prematurely discontinued due to a high frequency of grade 3/4 AEs. Single-agent CI-1033 did not show clinically meaningful activity in heavily pretreated patients with MBC expressing a parts per thousand yen1 ErbB receptor. Antitumor activity was observed in arm C patients with HER2-positive tumors. However, only the 50 mg dose was well tolerated, and the highest dose reached unacceptable levels of toxicity. C1 [Rixe, Olivier] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Rixe, Olivier] Hop La Pitie Salpetriere, APHP, Paris, France. [Franco, Sandra X.] Mem Canc Inst, Hollywood, FL USA. [Yardley, Denise A.] Sarah Cannon Res Inst, Nashville, TN USA. [Johnston, Stephen R.] Royal Marsden Hosp, London SW3 6JJ, England. [Martin, Miguel] Hosp Clin San Carlos, Madrid, Spain. [Arun, Banu K.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Letrent, Stephen P.] Pfizer Global Res & Dev, San Diego, CA USA. [Rugo, Hope S.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. RP Rixe, O (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, Bldg 10,Room 13N240 10 Ctr Dr, Bethesda, MD 20892 USA. EM rixeo@mail.nih.gov OI MARTIN, MIGUEL/0000-0001-9237-3231 FU ACUMED(R) (Tytherington, UK); Pfizer Inc. [MI 48105] FX The authors thank the study center staff, participating patients, and the clinical trial team for expert collaboration. We also thank Dr Patrice Herait for expert manuscript preparation assistance and acknowledge editorial support from ACUMED (R) (Tytherington, UK) with funding from Pfizer Inc. This study was supported by Pfizer, Inc., Clinical Research Department, 2800 Plymouth Road, Ann Arbor, MI 48105, USA. NR 25 TC 29 Z9 29 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 EI 1432-0843 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD NOV PY 2009 VL 64 IS 6 BP 1139 EP 1148 DI 10.1007/s00280-009-0975-z PG 10 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 485HU UT WOS:000269112600010 PM 19294387 ER PT J AU Shibata, SI Doroshow, JH Frankel, P Synold, TW Yen, Y Gandara, DR Lenz, HJ Chow, WA Leong, LA Lim, D Margolin, KA Morgan, RJ Somlo, G Newman, EM AF Shibata, Stephen I. Doroshow, James H. Frankel, Paul Synold, Timothy W. Yen, Yun Gandara, David R. Lenz, Heinz-Josef Chow, Warren A. Leong, Lucille A. Lim, Dean Margolin, Kim A. Morgan, Robert J. Somlo, George Newman, Edward M. TI Phase I trial of GTI-2040, oxaliplatin, and capecitabine in the treatment of advanced metastatic solid tumors: a California Cancer Consortium Study SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE GTI-2040; Oxaliplatin; Capecitabine; Ribonucleotide reductase; Pharmacokinetics ID MAMMALIAN RIBONUCLEOTIDE REDUCTASE; KINASE-C-ALPHA; M2 MESSENGER-RNA; ORNITHINE DECARBOXYLASE; COMPLEMENT ACTIVATION; COLORECTAL-CANCER; GENE-EXPRESSION; ANTISENSE; PROTEIN; SUBUNIT AB GTI-2040 is a 20-mer antisense oligonucleotide targeting the mRNA of ribonucleotide reductase M2. It was combined with oxaliplatin and capecitabine in a phase I trial in patients with advance solid tumors based on previous studies demonstrating potentiation of chemotherapy with ribonucleotide reductase inhibitors. Patients at least 18 years of age with advanced incurable solid tumors and normal organ function as well as a Karnofsky performance status of a parts per thousand yen60% were eligible. One prior chemotherapy regimen for advanced disease or relapse within 12 months of adjuvant chemotherapy was required. Patients could have received prior fluoropyrimidines, including capecitabine, but not oxaliplatin. Treatment cycles were 21 days. In each cycle, GTI-2040 was given as a continuous intravenous infusion over 14 days, oxaliplatin as a 2-h intravenous infusion on day 1, and capecitabine orally twice a day for 14 days. In cycle 1 only, oxaliplatin and capecitabine were started on day 2 to allow ribonucleotide reductase mRNA levels to be measured with and without oxaliplatin and capecitabine. Doses were escalated in cohorts of three patients using a standard 3 + 3 design until the maximum tolerated dose was established, defined as no more than one first-cycle dose-limiting toxicity among six patients treated at a given dose level. The maximum tolerated dose was estimated to be the combination of GTI-2040 3 mg/kg per day for 14 days, capecitabine 600 mg/m(2) twice daily for 14 days, and oxaliplatin 100 mg/m(2) every 21 days. Dose-limiting toxicities were hematologic. GTI-2040 pharmacokinetics, obtained at steady-state on days 7 and 14, showed the high inter-patient variability previously reported. Two of six patients had stable disease at the maximum tolerated dose and one patient, with heavily pre-treated non-small cell lung cancer, had a partial response at a higher dose level. In samples from a limited number of patients, there was no clear decrease in ribonucleotide reductase expression in peripheral blood mononuclear cells during treatment. A combination of GTI-2040, capecitabine and oxaliplatin is feasible in patients with advanced solid tumors. C1 [Shibata, Stephen I.; Doroshow, James H.; Frankel, Paul; Synold, Timothy W.; Yen, Yun; Chow, Warren A.; Leong, Lucille A.; Lim, Dean; Margolin, Kim A.; Morgan, Robert J.; Somlo, George; Newman, Edward M.] City Hope Comprehens Canc Ctr, Dept Med Oncol, Duarte, CA 91010 USA. [Gandara, David R.] Univ Calif Davis, Ctr Canc, Sacramento, CA 95817 USA. [Lenz, Heinz-Josef] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Doroshow, James H.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Shibata, SI (reprint author), City Hope Comprehens Canc Ctr, Dept Med Oncol, 1500 E Duarte Rd, Duarte, CA 91010 USA. EM sshibata@coh.org FU NCI NIH HHS [U01 CA062505, U01 CA062505-17, P30 CA033572] NR 32 TC 6 Z9 6 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD NOV PY 2009 VL 64 IS 6 BP 1149 EP 1155 DI 10.1007/s00280-009-0977-x PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 485HU UT WOS:000269112600011 PM 19322566 ER PT J AU Laiyemo, AO Kamangar, F Marcus, PM Taylor, PR Virtamo, J Albanes, D Stolzenberg-Solomon, RZ AF Laiyemo, Adeyinka O. Kamangar, Farin Marcus, Pamela M. Taylor, Philip R. Virtamo, Jarmo Albanes, Demetrius Stolzenberg-Solomon, Rachael Z. TI Serum pepsinogen level, atrophic gastritis and the risk of incident pancreatic cancer-A prospective cohort study SO CANCER EPIDEMIOLOGY LA English DT Article DE Serum pepsinogen; Atrophic gastritis; Pancreatic cancer ID HELICOBACTER-PYLORI INFECTION; ULCER AB Background: Pancreatic cancer is a highly fatal disease without screening tests. Studies have suggested possible etiologic similarities between gastric and pancreatic cancers. Atrophic gastritis, a pre-malignant condition for gastric cancer, is characterized by low serum pepsinogen I (SPGI) level. We hypothesized that low SPGI level may be associated with an increased risk of pancreatic cancer and be a useful biomarker for the disease. Methods: Our analytic cohort included 20,962 participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC) who had SPGI level measured. Of these, 1663 (7.9%) subjects had low SPGI levels (<25 mu g/l) and were invited for gastroscopy which was completed in 1059 (63.7%) participants. Atrophic gastritis was histologically confirmed in 1006 (95.0%) subjects. We used Cox proportional hazards regression to calculate the hazard ratios (HR) and 95% confidence intervals (CI) for pancreatic cancer. Results: During follow-up of up to 16.3 years (mean = 10.8 years; 226,325 person-years), 227 incident pancreatic cancers were diagnosed. The incidence rates were 9.9, 11.3, and 12.7 per 10,000 person-years of follow-up for participants with normal pepsinogen level (>= 25 mu g/l, low pepsinogen level and histologically confirmed atrophic gastritis, respectively. Compared to subjects with normal pepsinogen levels, there was no statistically significant increased risk of pancreatic cancer among subjects with low pepsinogen level (adjusted HR = 1.01; 95% CI: 0.63-1.62) or those with histologically confirmed atrophic gastritis (adjusted HR = 1.13; 95% CI: 0.66-1.95). Conclusions: Atrophic gastritis, serological or histological, is not associated with increased risk of pancreatic cancer. These findings do not provide any evidence for potential usefulness of SPGI for pancreatic cancer screening. Published by Elsevier Ltd. C1 [Laiyemo, Adeyinka O.] NCI, Canc Prevent Fellowship Program, Biometry Res Grp, Canc Prevent Div,Off Prevent Oncol,NIH, Bethesda, MD 20892 USA. [Kamangar, Farin; Albanes, Demetrius; Stolzenberg-Solomon, Rachael Z.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Kamangar, Farin] Morgan State Univ, Dept Publ Hlth Anal, Sch Community Hlth & Policy, Baltimore, MD 21239 USA. [Taylor, Philip R.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. RP Laiyemo, AO (reprint author), NCI, Canc Prevent Fellowship Program, Biometry Res Grp, Canc Prevent Div,Off Prevent Oncol,NIH, 6130 Executive Blvd,Suite 3131, Bethesda, MD 20892 USA. EM laiyemoa@mail.nih.gov RI Albanes, Demetrius/B-9749-2015 FU National Institutes of Health, Division of Cancer Epidemiology and Genetics, National Cancer Institute; Division of Cancer Prevention, National Institutes of Health, Department of Health and Human Services FX This study was supported by the Intramural Research Program of the National Institutes of Health, Division of Cancer Epidemiology and Genetics, National Cancer Institute, and the Division of Cancer Prevention, National Institutes of Health, Department of Health and Human Services. The funding agency had a role in the design and reporting of the study and in the decision to submit the manuscript for publication and approved the final version of the manuscript. NR 26 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1877-7821 J9 CANCER EPIDEMIOL JI Cancer Epidemiol. PD NOV PY 2009 VL 33 IS 5 BP 368 EP 373 DI 10.1016/j.canep.2009.09.001 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 538EY UT WOS:000273168300009 PM 19800305 ER PT J AU Platz, EA Till, C Goodman, PJ Parnes, HL Figg, WD Albanes, D Neuhouser, ML Klein, EA Thompson, IM Kristal, AR AF Platz, Elizabeth A. Till, Cathee Goodman, Phyllis J. Parnes, Howard L. Figg, William D. Albanes, Demetrius Neuhouser, Marian L. Klein, Eric A. Thompson, Ian M., Jr. Kristal, Alan R. TI Men with Low Serum Cholesterol Have a Lower Risk of High-Grade Prostate Cancer in the Placebo Arm of the Prostate Cancer Prevention Trial SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FOLLOW-UP; STATIN USE; PLASMA-CHOLESTEROL; NATIONAL-HEALTH; FINASTERIDE; COHORT; DRUGS; ASSOCIATION; POPULATION; SENSITIVITY AB Background: Several prospective studies suggest that use of cholesterol owe ring statin drugs is inversely associated with advanced stage and possibly high-grade prostate cancer. One study reported that men with low cholesterol had a lower risk of high-grade prostate cancer. Given these findings, we investigated the association between low serum cholesterol and prostate cancer risk in the Prostate Cancer Prevention Trial. Methods: We conducted a cohort study of 5,586 men ages >= 55 years who were randomized to the placebo arm of the Prostate Cancer Prevention Trial between 1993 and 1996. Serum cholesterol was measured enzy-matically at entry. By the end of follow-up, 1,251 prostate cancer cases were confirmed. We used logistic regression to calculate the multivariable odds ratio (OR) of total, and Gleason 2 to 6 (n = 993), 7 (n = 199), and 8 to 10 (n = 59) prostate cancer comparing low serum (normal, <200 mg/dL) to high-serum (borderline and elevated cholesterol, >= 200 mg/dL) cholesterol. Results: Men with low cholesterol had a lower risk of Gleason 8 to 10 prostate cancer [OR, 0.41; 95% confidence interval (CI), 0.22-0.77] than men with high cholesterol. No association was present for prostate cancer overall (OR, 0.97; 95% CI, 0.85-1.11), Gleason 2 to 6 disease (OR, 1.03; 95% CI, 0.89-1.18), or Gleason 7 disease (OR, 0.93; 95% CI, 0.69-1.24). Conclusion: These prospective results support that men with low cholesterol have a reduced risk of high-grade prostate cancer. These and other contemporary data that suggest that cholesterol metabolism should be investigated further in the etiology of prostate cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(11):2807-13) C1 [Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA. [Platz, Elizabeth A.] Johns Hopkins Med Inst, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA. [Till, Cathee; Goodman, Phyllis J.] Fred Hutchinson Canc Res Ctr, SW Oncol Grp, Ctr Stat, Seattle, WA 98104 USA. [Parnes, Howard L.] NCI, Canc Prevent Div, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Figg, William D.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Albanes, Demetrius] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Neuhouser, Marian L.; Kristal, Alan R.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Canc Prevent Program, Seattle, WA 98104 USA. [Klein, Eric A.] Cleveland Clin, Lerner Coll Med, Ctr Clin & Translational Res, Cleveland, OH 44106 USA. [Thompson, Ian M., Jr.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. RP Platz, EA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, James Buchanan Brady Urol Inst, Room E6132,615 N Wolfe St, Baltimore, MD 21205 USA. EM eplatz@jhsph.edu RI Albanes, Demetrius/B-9749-2015; Figg Sr, William/M-2411-2016; OI Kristal, Alan/0000-0002-7329-1617 FU NIH [P01 CA108964, U10 CA37429, P50 CA58236] FX Grant support: National Cancer Institute, NIH, (P01 CA108964, U10 CA37429, and P50 CA58236). NR 30 TC 79 Z9 80 U1 0 U2 7 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 2009 VL 18 IS 11 BP 2807 EP 2813 DI 10.1158/1055-9965.EPI-09-0472 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 516SJ UT WOS:000271562600002 PM 19887582 ER PT J AU Ahn, J Lim, U Weinstein, SJ Schatzkin, A Hayes, RB Virtamo, J Albanes, D AF Ahn, Jiyoung Lim, Unhee Weinstein, Stephanie J. Schatzkin, Arthur Hayes, Richard B. Virtamo, Jarmo Albanes, Demetrius TI Prediagnostic Total and High-Density Lipoprotein Cholesterol and Risk of Cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SERUM-CHOLESTEROL; LUNG-CANCER; HDL-CHOLESTEROL; BLOOD-CHOLESTEROL; PLASMA-LIPIDS; LIVER-CANCER; MORTALITY; METABOLISM; CELL; ASSOCIATION AB Background: Circulating total cholesterol has been inversely associated with cancer risk; however, the role of reverse causation and the associations for high-density lipoprotein (HDL) cholesterol have not been fully characterized. We examined the relationship between serum total and HDL cholesterol and risk of overall and site-specific cancers among 29,093 men in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study cohort. Methods: Fasting serum total and HDL cholesterol were assayed at baseline, and 7,545 incident cancers were identified during up to 18 years of follow-up. Multivariable proportional hazards models were conducted to estimate relative risks (RR). Results: Higher serum total cholesterol concentration was associated with decreased risk of cancer overall (RR for comparing high versus low quintile, 0.85; 95% confidence interval, 0.79-0.91; P trend <0.001; >276.7 versus <203.9 mg/dL), and the inverse association was particularly evident for cancers of the lung and liver. These associations were no longer significant, however, when cases diagnosed during the first 9 years of follow-up were excluded. Greater HDL cholesterol was also associated with decreased risk of cancer (RR for high versus low quintile, 0.89; 95% confidence interval, 0.83-0.97; P trend = 0.01; >55.3 versus <36.2 mg/dL). The inverse association of HDL cholesterol was evident for cancers of lung, prostate, liver, and the hematopoietic system, and the associations of HDL cholesterol with liver and lung cancers remained after excluding cases diagnosed within 12 years of study entry. Conclusion: Our findings suggest that prior observations regarding serum total cholesterol and cancer are largely explained by reverse causation. Although chance and reverse causation may explain some of the inverse HDL associations, we cannot rule out some etiologic role for this lipid fraction. (Cancer Epidemiol Biomarkers Prev 2009;18(11):2814-21) C1 [Albanes, Demetrius] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. RP Albanes, D (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, EPS 3044, Bethesda, MD 20892 USA. EM daa@nih.gov RI Albanes, Demetrius/B-9749-2015; OI Hayes, Richard/0000-0002-0918-661X FU NIH; Division of Cancer Epidemiology and Genetics; National Cancer Institute; Department of Health and Human Services and Public Health Service [N01-CN-45165, N01-RC45035, N01-RC-37004] FX Intramural Research Program of the NIH, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services and Public Health Service contracts N01-CN-45165, N01-RC45035, and N01-RC-37004. NR 38 TC 68 Z9 71 U1 1 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2009 VL 18 IS 11 BP 2814 EP 2821 DI 10.1158/1055-9965.EPI-08-1248 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 516SJ UT WOS:000271562600003 PM 19887581 ER PT J AU Sue, LY Schairer, C Ma, XM Williams, C Chang, SC Millers, AB McCarty, CA Willcox, BJ Ziegler, RG AF Sue, Laura Y. Schairer, Catherine Ma, Xiaomei Williams, Craig Chang, Shih-Chen Millers, Anthony B. McCarty, Catherine A. Willcox, Bradley J. Ziegler, Regina G. TI Energy Intake and Risk of Postmenopausal Breast Cancer: An Expanded Analysis in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) Cohort SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRES; DIETARY-FAT; CALORIC RESTRICTION; BALANCE; WOMEN; ADOLESCENCE; ASSOCIATION; VALIDATION; MECHANISMS; PREVENTION AB Although animal experiments have consistently shown a positive relationship between breast cancer and energy intake, evidence from human studies remains inconclusive. In the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial cohort, 29,170 women, ages 55 to 75 years, who successfully completed a food frequency questionnaire (FFQ) at entry (1993-2001), were followed through 2007, and 1,319 incident breast cancers were ascertained (median time from FFQ completion to diagnosis, 4.4 years). Women in the highest quartile of energy intake, relative to the lowest, had modestly, but significantly, increased breast cancer risk [multivariate relative risk (RR), 1.21; 95% confidence interval (95% CI), 1.03-1.42; P(trend) = 0.03]. The inclusion of body mass index and physical activity in the model reduced risk slightly (RR, 1.18; 95% CI, 1.00-1.39; P(trend) = 0.07). However, in similar analyses using energy intake from a FFQ administered approximately five years after entry (27,428 women; 806 incident breast cancers; median time from FFQ completion to diagnosis, 2.7 years), women in the highest and lowest quartiles of energy intake had similar risk. When follow-up time after the first FFQ was divided into three 4-year periods, the multivariate RRs for high versus low energy intake increased from 1.21 to 1.37 to 1.55 with increasing time since dietary assessment. Although the divergent results for the two FFQs could be due to subtle questionnaire differences, our findings suggest a modest positive association between energy intake and postmenopausal breast cancer that strengthens with time since dietary assessment. (Cancer Epidemiol Biomarkers Prev 2009;18(11):2842-50) C1 [Sue, Laura Y.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Ma, Xiaomei] Yale Univ, Sch Publ Hlth, Dept Epidemiol & Publ Hlth, New Haven, CT USA. [Williams, Craig] Informat Management Serv Inc, Rockville, MD USA. [Chang, Shih-Chen] AstraZeneca, Wilmington, DE USA. [Millers, Anthony B.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [McCarty, Catherine A.] Marshfield Clin Fdn Med Res & Educ, Ctr Human Genet, Marshfield, WI 54449 USA. [Willcox, Bradley J.] Pacific Hlth Res Inst, Honolulu, HI USA. RP Sue, LY (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd,EPS 6113, Bethesda, MD 20892 USA. EM suel@mail.nih.gov FU Intramural NIH HHS [Z01 CP010169-06] NR 36 TC 8 Z9 8 U1 3 U2 6 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 2009 VL 18 IS 11 BP 2842 EP 2850 DI 10.1158/1055-9965.EPI-09-0087 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 516SJ UT WOS:000271562600007 PM 19843674 ER PT J AU Eliassen, AH Ziegler, RG Rosner, B Veenstra, TD Roman, JM Xu, X Hankinson, SE AF Eliassen, A. Heather Ziegler, Regina G. Rosner, Bernard Veenstra, Timothy D. Roman, John M. Xu, Xia Hankinson, Susan E. TI Reproducibility of Fifteen Urinary Estrogens and Estrogen Metabolites over a 2-to 3-Year Period in Premenopausal Women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BREAST-CANCER-CELLS; CHROMATOGRAPHY-MASS SPECTROMETRY; STEROID-HORMONE CONCENTRATIONS; POSTMENOPAUSAL WOMEN; ENDOGENOUS ESTROGEN; MCF-7 CELLS; RISK; ESTRADIOL; RECEPTOR; SERUM AB Endogenous estrogens play an integral role in the etiology of breast, endometrial, and, possibly, ovarian cancers. Estrogen metabolism yields products that are potentially both estrogenic and genotoxic, yet individual metabolic patterns are just beginning to be explored in epidemiologic studies. Within the Nurses' Health Study 11, we examined reproducibility of 15 urinary estrogens and estrogen metabolites (EM) among 110 premenopausal women with three luteal-phase urine samples collected over 3 years. EM were measured by a recently developed high-performance liquid chromatography-tandem mass spectrometry (LC-MS2) method with high sensitivity, specificity, and precision. We assessed Spearman correlations and intraclass correlation coefficients (ICC) across the three samples. Correlations between urinary estrone or estradiol and EM were only modest (r = 0.1-0.5). The 2- and 4-hydroxylation pathways were highly correlated (r = 0.9) but weakly inversely correlated with the 16-hydroxylation pathway (r = -0.2). Within-woman reproducibility over time was fairly high for the three pathways, with ICCs ranging from 0.52 (16-hydroxylation pathway) to 0.72 (2-hydroxylation pathway). ICCs were similarly high for 2-catechols and the individual catechols (ICCs = 0.58-0.72). Individual and grouped methylated 2-catechols had fairly high ICCs (0.51-0.62), but methylated 4-catechols had low ICCs (0.14-0.27). These data indicate that, in general, urinary EM levels vary substantially among individuals compared with intraindiviual variability. Within-person reproducibility over time for most EM measures is comparable to or better than that for well-vetted biomarkers such as plasma cholesterol and, in postmenopausal women, estradiol. (Cancer Epidemiol Biomarkers Prev 2009;18(11):2860-8) C1 [Eliassen, A. Heather; Rosner, Bernard; Hankinson, Susan E.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Eliassen, A. Heather; Rosner, Bernard; Hankinson, Susan E.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Rosner, Bernard] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Hankinson, Susan E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Ziegler, Regina G.] NCI, Div Canc Epidemiol & Genet, Epidemiol & Biostat Program, Bethesda, MD 20892 USA. [Veenstra, Timothy D.; Roman, John M.; Xu, Xia] NCI, Sci Applicat Int Corp Frederick Inc, Adv Technol Program, Lab Prote & Analyt Technol, Frederick, MD 21701 USA. RP Eliassen, AH (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM heather.eliassen@channing.harvard.edu FU National Cancer Institute [CA67262, CA50385, HHSN261200800001E]; Harvard Medical School FX National Cancer Institute research grants CA67262 and CA50385, the Harvard Medical School Eleanor and Miles Shore Fellowship for Scholars in Medicine, the National Cancer Institute Intramural Funding Program of the Division of Cancer Epidemiology and Genetics, and federal funds from the National Cancer Institute awarded under contract HHSN261200800001E to Science Applications international Corporation-Frederick. The content of this publication does not necessarily reflect the views or policies of the U.S. Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 61 TC 33 Z9 33 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 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2009 VL 18 IS 11 BP 2860 EP 2868 DI 10.1158/1055-9965.EPI-09-0591 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 516SJ UT WOS:000271562600009 PM 19843676 ER PT J AU Boukheris, H Curtis, RE Land, CE Dores, GM AF Boukheris, Houda Curtis, Rochelle E. Land, Charles E. Dores, Graca M. TI Incidence of Carcinoma of the Major Salivary Glands According to the WHO Classification, 1992 to 2006: A Population-Based Study in the United States SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SQUAMOUS-CELL CARCINOMA; PAROTID-GLAND; RISK-FACTORS; CANCER INCIDENCE; TUMORS; EPIDEMIOLOGY; SURVIVAL; REGION; TRENDS; RATES AB Background: Carcinomas of the major salivary glands (M-SGC) comprise a morphologically diverse group of rare tumors of largely unknown cause. To gain insight into etiology, we evaluated incidence of M-SGC using the WHO classification schema (WHO-2005). Methods: We calculated age-adjusted incidence rates (IR) and IR ratios (IRR) for M-SGC diagnosed between 1992 and 2006 in the Surveillance, Epidemiology and End Results Program. Results: Overall, 6,391 M-SGC (IR, 11.95/1,000,000 person-years) were diagnosed during 1992 to 2006. Nearly 85% of cases (n = 5,370; IR, 10.00) were encompassed within WHO-2005, and among these, males had higher IRs than females [IRR, 1.51; 95% confidence interval (95% CI), 1.43-1.60]. Squamous cell (IR, 3.44) and mucoepidermoid (IR, 3.23) carcinomas occurred most frequently among males, whereas mucoepidermoid (IR, 2.67), acinic cell (IR, 1.57), and adenoid cystic (IR, 1.40) carcinomas were most common among females. Mucoepidermoid, acinic cell, and adenoid cystic carcinomas predominated in females through age similar to 50 years; thereafter, IRs of acinic cell and adenoid cystic carcinomas were nearly equal among females and males, whereas IRs of mucclepidermoid carcinoma among males exceeded IRs among females (IRR, 1.57; 95% CI, 1.38-1.78). Except for mucoepidermoid and adenoid cystic carcinomas, which occurred equally among all races, other subtypes had significantly lower incidence among Blacks and Asians/Pacific Islanders than among Whites. Adenoid cystic carcinoma occurred equally in the submandibular and parotid glands, and other M-SGC histologic subtypes evaluated had 77% to 98% lower IRS in the submandibular gland. Overall M-SGC IRs remained stable during 1992 to 2006. Conclusion: Distinct incidence patterns according to histologic subtype suggest that M-SGC are a diverse group of neoplasms characterized by etiologic and/or biological heterogeneity with varying susceptibility by gender and race. (Cancer Epidemiol Biomarkers Prev 2009;18(11):2899-906) C1 [Dores, Graca M.] Dept Vet Affairs Med Ctr, Med Serv, Oklahoma City, OK USA. [Boukheris, Houda; Curtis, Rochelle E.; Land, Charles E.; Dores, Graca M.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD USA. RP Dores, GM (reprint author), Dept Vet Affairs Med Ctr, Med Serv 111, 921 NE 13th St, Oklahoma City, OK 73104 USA. EM doresg@mail.nih.gov FU National Cancer Institute/NIH; Department of Health and Human Services; Department of Veterans Affairs FX Intramural Research Program of the National Cancer Institute/NIH, Department of Health and Human Services, and Department of Veterans Affairs. NR 40 TC 51 Z9 54 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 2009 VL 18 IS 11 BP 2899 EP 2906 DI 10.1158/1055-9965.EPI-09-0638 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 516SJ UT WOS:000271562600015 PM 19861510 ER PT J AU Fedirko, V Bostick, RM Flanders, WD Long, Q Sidelnikov, E Shaukat, A Daniel, CR Rutherford, RE Woodard, JJ AF Fedirko, Veronika Bostick, Roberd M. Flanders, W. Dana Long, Qi Sidelnikov, Eduard Shaukat, Aasma Daniel, Carrie R. Rutherford, Robin E. Woodard, Jill Joelle TI Effects of Vitamin D and Calcium on Proliferation and Differentiation In Normal Colon Mucosa: a Randomized Clinical Trial SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID EPITHELIAL-CELL PROLIFERATION; FAT DAIRY FOODS; COLORECTAL ADENOMAS; DIETARY CALCIUM; P21(WAF1/CIP1) EXPRESSION; SUPPLEMENTAL CALCIUM; RECTAL MUCOSA; CANCER; CARCINOGENESIS; NEOPLASIA AB To investigate the potential efficacy of calcium and vitamin D in reducing risk for colorectal neoplasms and to develop "treatable" phenotypic biomarkers of risk for colorectal neoplasms, we conducted a pilot, randomized, double-blind, placebo-controlled, 2 x 2 factorial clinical trial to test the effects of these agents on cell cycle markers in the normal colorectal mucosa. Ninety-two men and women with at least one pathology-confirmed colorectal adenoma were treated with 2 g/day calcium and/or 800 IU/day vitamin D(3) versus placebo over 6 months. Overall expression and distributions of p21(waf1/cip1) (marker of differentiation), MIB-1 (marker of short-term proliferation), and hTERT (marker of long-term proliferation) in colorectal crypts in the normal-appearing rectal mucosa were detected by automated immunohistochemistry and quantified by image analysis. In the calcium, vitamin D, and calcium plus vitamin D groups relative to the placebo, p21 expression increased by 201% (P = 0.03), 242% (P = 0.005), and 25% (P = 0.47), respectively, along the full lengths of colorectal crypts after 6 months of treatment. There were no statistically significant changes in the expression of either MIB-1 or hTERT in the crypts overall; however, the proportion of hTERT, but not MIB-1, expression that extended into the upper 40% of the crypts was reduced by 15% (P = 0.02) in the vitamin D plus calcium group relative to the placebo. These results indicate that calcium and vitamin D promote colorectal epithelial cell differentiation and may "normalize" the colorectal crypt proliferative zone in sporadic adenoma patients, and support further investigation of calcium and vitamin D as chemopreventive agents against colorectal neoplasms. (Cancer Epidemiol Biomarkers Prev 2009;18(11):2933-41) C1 [Fedirko, Veronika; Bostick, Roberd M.; Flanders, W. Dana; Sidelnikov, Eduard; Woodard, Jill Joelle] Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Fedirko, Veronika; Bostick, Roberd M.; Flanders, W. Dana; Long, Qi; Sidelnikov, Eduard; Woodard, Jill Joelle] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Flanders, W. Dana; Long, Qi] Emory Univ, Rollins Sch Publ Hlth, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA. [Rutherford, Robin E.] Emory Univ, Sch Med, Div Digest Dis, Atlanta, GA 30322 USA. [Shaukat, Aasma] Univ Minnesota, GI Div, Dept Med, Minneapolis, MN USA. [Daniel, Carrie R.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Bostick, RM (reprint author), Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, 1518 Clifton Rd NE, Atlanta, GA 30322 USA. EM rmbosti@sph.emory.edu FU National Cancer Institute; NIH [R01 CA104637]; Georgia Cancer Coalition Distinguished Scholar; Franklin Foundation; Georgia Cancer Coalition FX National Cancer Institute, NIH grant R01 CA104637 (R.M. Bostick), Georgia Cancer Coalition Distinguished Scholar award (R.M. Bostick), and the Franklin Foundation. The National Cancer Institute, the Georgia Cancer Coalition, and the Franklin Foundation had no influence on the design of the study; the collection, analysis, and interpretation of the data; the decision to submit the manuscript for publication; or the writing of the manuscript. NR 51 TC 49 Z9 49 U1 1 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 2009 VL 18 IS 11 BP 2933 EP 2941 DI 10.1158/1055-9965.EPI-09-0239 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 516SJ UT WOS:000271562600020 PM 19861511 ER PT J AU Gaudet, MM Campan, M Figueroa, JD Yang, XHR Lissowska, J Peplonska, B Brinton, LA Rimm, DL Laird, PW Garcia-Closas, M Sherman, ME AF Gaudet, Mia M. Campan, Mihaela Figueroa, Jonine D. Yang, Xiaohong R. Lissowska, Jolanta Peplonska, Beata Brinton, Louise A. Rimm, David L. Laird, Peter W. Garcia-Closas, Montserrat Sherman, Mark E. TI DNA Hypermethylation of ESR1 and PGR in Breast Cancer: Pathologic and Epidemiologic Associations SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ESTROGEN-RECEPTOR-ALPHA; GENE-EXPRESSION; HORMONE-RECEPTOR; METHYLATION ANALYSIS; PROTEIN EXPRESSION; MESSENGER-RNA; CPG ISLANDS; PROGESTERONE; CELLS; PROMOTERS AB Improved understanding of the etiology of estrogen receptor-alpha (ER alpha)-negative and progesterone receptor (PR)-negative breast cancers may permit improved risk prediction. In vitro studies implicate DNA hypermethylation of the ER alpha and PR promoters in the pathogenesis of ER alpha-negative and PR-negative tumors, but results are not definitive. We evaluated 200 invasive breast cancers selected from a population-based case-control study. DNA extracted from fixed tumor tissue cores was tested using MethyLight to assess DNA methylation at four CpG islands: ESR1 promoters A and B; PGR promoters A and B; and a CpG shore, ESR1 promoter C. DNA methylation results were compared with levels of ER alpha and PR, tumor characteristics, and breast cancer risk factors. We observed mild to moderate DNA methylation levels in most tumors for ESR1 promoters A and B and PGR promoter B, and a few tumors showed mild methylation in PGR promoter A. In contrast, ESR1 promoter C showed a wide range of methylation and was weakly correlated with lower expression levels of ER alpha (beta = -0.26; P < 0.0001) and PR (beta = -0.25; P < 0.0001). The percentage of tumors with methylated PGR promoters A and B was significantly higher for tumors with low ER alpha (A, Fisher's test P = 0.0001; B, P = 0.033) and PR levels (A, P = 0.0006; B, P = 0.001). Our data suggest that the relationships between DNA methylation of ESR1 and PGR promoters and protein expression are weak and unlikely to represent a predominant mechanism of receptor silencing. In contrast to CpG islands, ESR1 promoter C showed a wider range of methylation levels and inverse associations with ER alpha and PR expression. (Cancer Epidemiol Biomarkers Prev 2009;18(11):3036-43) C1 [Gaudet, Mia M.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. [Campan, Mihaela; Laird, Peter W.] Univ So Calif, Keck Sch Med, Dept Surg, Los Angeles, CA 90033 USA. [Laird, Peter W.] Univ So Calif, Keck Sch Med, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USA. [Laird, Peter W.] Univ So Calif, Keck Sch Med, Epigenome Ctr, Los Angeles, CA 90033 USA. [Laird, Peter W.] Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Figueroa, Jonine D.; Yang, Xiaohong R.; Lissowska, Jolanta; Brinton, Louise A.; Garcia-Closas, Montserrat; Sherman, Mark E.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Lissowska, Jolanta] M Sklodowska Curie Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Lissowska, Jolanta] Inst Oncol, Warsaw, Poland. [Peplonska, Beata] Nofer Inst Occupat Med, Dept Occupat & Environm Epidemiol, Lodz, Poland. [Rimm, David L.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. RP Gaudet, MM (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Belfer Bldg,Room 1303E,1300 Morris Pk Ave, Bronx, NY 10461 USA. EM mia.gaudet@einstein.yu.edu RI Peplonska, Beata/F-6004-2010; Laird, Peter/G-8683-2012; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Lissowska, Jolanta/0000-0003-2695-5799 FU National Cancer Institute, NIH FX Grant support: The intramural program of the National Cancer Institute, NIH. NR 49 TC 33 Z9 34 U1 0 U2 5 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 2009 VL 18 IS 11 BP 3036 EP 3043 DI 10.1158/1055-9965.EPI-09-0678 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 516SJ UT WOS:000271562600034 PM 19861523 ER PT J AU Dong, LM Shu, XO Gao, YT Milne, G Ji, BT Yang, G Li, HL Rothman, N Zheng, W Chow, WH Abnet, CC AF Dong, Linda M. Shu, Xiao-Ou Gao, Yu-Tang Milne, Ginger Ji, Bu-Tian Yang, Gong Li, Hong-Lan Rothman, Nathaniel Zheng, Wei Chow, Wong-Ho Abnet, Christian C. TI Urinary Prostaglandin E-2 Metabolite and Gastric Cancer Risk in the Shanghai Women's Health Study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; EXPRESSION; ESOPHAGEAL; METAANALYSIS; INHIBITION; CARCINOMA; ASPIRIN; CYCLOOXYGENASE-2; ADENOCARCINOMAS; COLON AB Chronic inflammation has been implicated in the etiology of gastric cancer. Prostaglandin E-2 (PGE(2)) is one of the major end-products of the cyclooxygenase-2 pathway, an enzyme that is an important mediator of inflammation. Using a novel method of quantifying the primary urinary metabolite of PGE(2) (PGE-M; 11 alpha-hydroxy-9,15-dioxo-2,3,4,5-tetranorprostane-1,20-dioic acid), we evaluated urinary PGE-M concentrations in association with subsequent risk of development of gastric cancer in the Shanghai Women's Health Study, a large population-based prospective cohort, using a nested case-control study design. Controls were matched (1:1) to 153 gastric cancer cases by menopausal status; age, time, and date of sample collection; time interval since last meal; and availability of urine sample. Odds ratios (95% confidence intervals) were calculated using conditional logistic regression adjusted for potential confounders. Baseline urinary PGE-M levels were slightly higher among gastric cancer cases with a median of 6.4 ng/mg creatinine (interquartile range, 3.4-11.2) compared with 5.4 ng/mg creatinine among controls (interquartile range, 2.8-9.0), but this difference was not statistically significant (P = 0.34, Wilcoxon). With increasing quartiles of urinary PGE-M levels, the odds ratios (95% confidence intervals) for risk of gastric cancer increased in quartiles 2 to 4: 1.00 (0.48-2.08), 1.40 (0.67-2.91), and 1.98 (0.95-4.13), with a statistically significant test for trend (P = 0.04). The association persisted after additional adjustment for Helicobacter pylori status and was slightly strengthened among non-nonsteroidal anti-inflammatory drug users, subjects with positive H. pylori status, and for cases diagnosed within 46 months after study enrollment. Our findings suggest that higher levels of urinary PGE-M, a marker of inflammation, may be associated with gastric cancer risk. (Cancer Epidemiol Biomarkers Prev 2009;18(11):3075-8) C1 [Dong, Linda M.; Ji, Bu-Tian; Rothman, Nathaniel; Chow, Wong-Ho; Abnet, Christian C.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Shu, Xiao-Ou; Milne, Ginger; Yang, Gong; Zheng, Wei] Vanderbilt Univ, Sch Med, Dept Med & Pharmacol, Nashville, TN 37212 USA. [Gao, Yu-Tang; Li, Hong-Lan] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. RP Dong, LM (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,MSC 7240, Bethesda, MD 20892 USA. EM donglm@mail.nih.gov RI Liao, Linda/B-3960-2011; Milne, Ginger/D-7648-2014; Abnet, Christian/C-4111-2015 OI Milne, Ginger/0000-0003-3890-151X; Abnet, Christian/0000-0002-3008-7843 FU NIH [R01 CA70867]; Intramural Research Program [N02 CP1101066] FX Grant support: NIH research grant R01 CA70867 and Intramural Research Program contract N02 CP1101066. NR 26 TC 24 Z9 25 U1 0 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 2009 VL 18 IS 11 BP 3075 EP 3078 DI 10.1158/1055-9965.EPI-09-0680 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 516SJ UT WOS:000271562600040 PM 19861525 ER PT J AU Prentice, RL Huang, Y Hinds, DA Peters, U Pettinger, M Cox, DR Beilharz, E Chlebowski, RT Rossouw, JE Caan, B Ballinger, DG AF Prentice, Ross L. Huang, Ying Hinds, David A. Peters, Ulrike Pettinger, Mary Cox, David R. Beilharz, Erica Chlebowski, Rowan T. Rossouw, Jacques E. Caan, Bette Ballinger, Dennis G. TI Variation in the FGFR2 Gene and the Effects of Postmenopausal Hormone Therapy on Invasive Breast Cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENOME-WIDE ASSOCIATION; ESTROGEN PLUS PROGESTIN; CONJUGATED EQUINE ESTROGENS; RANDOMIZED CONTROLLED-TRIAL; INITIATIVE CLINICAL-TRIAL; SUSCEPTIBILITY LOCI; AFRICAN-AMERICAN; WOMEN; RISK; DESIGN AB Background: Breast cancer concern is a major reason for the recent marked reduction in use of postmenopausal hormone therapy, although equally effective means of controlling menopausal symptoms are lacking. Single nucleotide polymorphisms (SNP) in the fibroblast growth factor receptor 2 (FGFR2) gene are substantially associated with postmenopausal breast cancer risk and could influence hormone therapy effects. Participants and Methods: We interrogated eight SNPs in intron 2 of the FGFR2 gene for 2,166 invasive breast cancer cases from the Women's Health Initiative clinical trial and one-to-one matched controls to confirm an association with breast cancer risk. We used case-only analyses to examine the dependence of estrogen plus progestin and estrogen-alone odds ratios on SNP genotype. Results: Seven FGFR2 SNPs, including six in a single linkage disequilibrium region, were found to associate strongly (p < 10(-7)) with breast cancer risk. SNP rs3750817 (minor allele T with frequency 0.39) had an estimated per-minor-allele odds ratio of 0.78, and was not in such strong linkage disequilibrium with the other SNPs. The genotype of this SNP related significantly (P < 0.05) to hormone therapy odds ratios. For estrogen plus progestin, the odds ratios (95% confidence intervals) at 0, 1, and 2 minor SNP alleles were 1.52 (1.14-2.02), 1.33 (1.01-1.75), and 0.69 (0.41-1.17), whereas the corresponding values for estrogen alone were 0.74 (0.51-1.09), 0.99 (0.68-1.44), and 0.34 (0.15-0.76). Conclusions: Postmenopausal women having T-F genotype for SNP rs3750817 have a reduced breast cancer risk and seem to experience comparatively favorable effects of postmenopausal hormone therapy. (Cancer Epidemiol Biomarkers Prev 2009;18(11):3079-85) C1 [Prentice, Ross L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Hinds, David A.; Cox, David R.; Beilharz, Erica; Ballinger, Dennis G.] Perlegen Sci Inc, Mountain View, CA USA. [Chlebowski, Rowan T.] Harbor UCLA Res & Educ Inst, Torrance, CA USA. [Rossouw, Jacques E.] NIH, Bethesda, MD 20892 USA. [Caan, Bette] Kaiser Permanente, Div Res, Oakland, CA USA. RP Prentice, RL (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,M3-A410,POB 19024, Seattle, WA 98109 USA. EM rprentic@fhcrc.org FU National Heart, Lung, and Blood Institute; NIH, U.S. Department of Health and Human Services [HHSN268200764314C, N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-19, 32122, 42107-26, 42129-32, 44221]; National Cancer Institute [CA53996] FX Grant support: National Heart, Lung, and Blood Institute; NIH, U.S. Department of Health and Human Services (contracts HHSN268200764314C, N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-19, 32122, 42107-26, 42129-32, and 44221). Clinical Trials Registration: ClinicalTrials.gov identifier: NCT00000611. National Cancer Institute grant CA53996 (R.L Prentice and Y Huang). NR 37 TC 44 Z9 44 U1 0 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 2009 VL 18 IS 11 BP 3079 EP 3085 DI 10.1158/1055-9965.EPI-09-0611 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 516SJ UT WOS:000271562600041 PM 19861516 ER PT J AU Hou, LF Savage, SA Blaser, MJ Perez-Perez, G Hoxha, M Dioni, L Pegoraro, V Dong, LM Zatonski, W Lissowska, J Chow, WH Baccarelli, A AF Hou, Lifang Savage, Sharon A. Blaser, Martin J. Perez-Perez, Guillermo Hoxha, Mirjam Dioni, Laura Pegoraro, Valeria Dong, Linda M. Zatonski, Witold Lissowska, Jolanta Chow, Wong-Ho Baccarelli, Andrea TI Telomere Length in Peripheral Leukocyte DNA and Gastric Cancer Risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HELICOBACTER-PYLORI; OXIDATIVE STRESS; STOMACH-CANCER; CHROMOSOME INSTABILITY; GENETIC POLYMORPHISMS; PREDISPOSITION FACTOR; CELLULAR SENESCENCE; CIGARETTE-SMOKING; BLADDER-CANCER; BLOOD CELLS AB Telomere length reflects lifetime cumulative oxidative stress from environmental exposures, such as cigarette smoking and chronic inflammation. Shortened telomere length is thought to cause genomic instability and has been associated with several cancers. We examined the association of telomere length in peripheral leukocyte DNA with gastric cancer risk as well as potential confounding factors and risk modifiers for telomere length-related risk. In a population-based study of gastric cancer conducted in a high-risk population in Warsaw, Poland, between 1994 and 1996, we measured relative telomere length in 300 cases and 416 age- and gender-matched controls using quantitative real-time PCR. Among controls, telomeres were significantly shorter in association with aging (P < 0.001), increasing pack-years of cigarette smoking (P = 0.02), decreasing fruit intake (P = 0.04), and Helicobacter pylori positivity (P = 0.03). Gastric cancer cases had significantly shorter telomere length (mean +/- SD relative telomere length, 1.25 +/- 0.34) than controls (1.34 +/- 0.35; P = 0.0008). Gastric cancer risk doubled [odds ratio (OR), 2.04; 95% confidence interval (95% Cl), 1.33-3.13] among subjects in the shortest compared with the highest quartile of telomere length (P(trend) < 0.001). Telomere length-associated risks were higher among individuals with the lowest risk profile, those H. pylori-negative (OR, 5.45; 95% CI, 2.10-14.1), nonsmokers (OR, 3.07; 95% Cl, 1.71-5.51), and individuals with high intake of fruits (OR, 2.43; 95% Cl, 1.46-4.05) or vegetables (OR, 2.39; 95% Cl, 1.51-3.81). Our results suggest that telomere length in peripheral leukocyte DNA was associated with H. pylori positivity, cigarette smoking, and dietary fruit intake. Shortened telomeres increased gastric cancer risk in this high-risk Polish population. (Cancer Epidemiol Biomarkers Prev 2009;18(11):3103-9) C1 [Hou, Lifang] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Hou, Lifang] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Savage, Sharon A.; Dong, Linda M.; Chow, Wong-Ho] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA. [Blaser, Martin J.; Perez-Perez, Guillermo] NYU, Dept Med & Microbiol, New York, NY USA. [Hoxha, Mirjam; Dioni, Laura; Pegoraro, Valeria; Baccarelli, Andrea] Univ Milan, Dept Environm & Occupat Hlth, Ctr Mol & Genet Epidemiol, Maggiore Policlin Hosp,Mangiagalli & Regina Elena, Milan, Italy. [Zatonski, Witold; Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Zatonski, Witold; Lissowska, Jolanta] Inst Oncol, Warsaw, Poland. RP Hou, LF (reprint author), Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, 680 N Lake Shore Dr,Suite 1102, Chicago, IL 60611 USA. EM l-hou@northwestern.edu RI Liao, Linda/B-3960-2011; Savage, Sharon/B-9747-2015; OI Savage, Sharon/0000-0001-6006-0740; Baccarelli, Andrea/0000-0002-3436-0640; Lissowska, Jolanta/0000-0003-2695-5799; Perez Perez, Guillermo /0000-0002-0131-5798 FU Division of Cancer Epidemiology and Genetics, National Cancer Institute/NIH; Diane Better Program for Human Microbial Diversity; NIH [R01GM63270] FX Grant support: Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute/NIH; Diane Better Program for Human Microbial Diversity; and NIH grant R01GM63270. NR 59 TC 59 Z9 59 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 2009 VL 18 IS 11 BP 3103 EP 3109 DI 10.1158/1055-9965.EPI-09-0347 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 516SJ UT WOS:000271562600044 PM 19861514 ER PT J AU Kiviniemi, MT Hay, JL James, AS Lipkus, IM Meissner, HI Stefanek, M Studts, JL Bridges, JFP Close, DR Erwin, DO Jones, RM Kaiser, K Kash, KM Kelly, KM Lee, SJC Purnell, JQ Siminoff, LA Vadaparampil, ST Wang, C AF Kiviniemi, Marc T. Hay, Jennifer L. James, Aimee S. Lipkus, Isaac M. Meissner, Helen I. Stefanek, Michael Studts, Jamie L. Bridges, John F. P. Close, David R. Erwin, Deborah O. Jones, Resa M. Kaiser, Karen Kash, Kathryn M. Kelly, Kimberly M. Lee, Simon J. Craddock Purnell, Jason Q. Siminoff, Laura A. Vadaparampil, Susan T. Wang, Catharine TI Decision Making about Cancer Screening: An Assessment of the State of the Science and a Suggested Research Agenda from the ASPO Behavioral Oncology and Cancer Communication Special Interest Group SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review ID NONPOLYPOSIS COLORECTAL-CANCER; BREAST-CANCER; CONJOINT-ANALYSIS; HEALTH LITERACY; INFORMED CHOICE; OVARIAN-CANCER; UNITED-STATES; RISK; WOMEN; WORRY C1 [Kiviniemi, Marc T.] SUNY Coll Buffalo, Dept Hlth Behav, Buffalo, NY 14222 USA. [Hay, Jennifer L.] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10021 USA. [James, Aimee S.] Washington Univ, Dept Surg, St Louis, MO USA. [Lipkus, Isaac M.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. [Meissner, Helen I.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. [Stefanek, Michael] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Studts, Jamie L.] Univ Kentucky, Coll Med, Dept Behav Sci, Lexington, KY 40536 USA. [Bridges, John F. P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. [Close, David R.] Joe A Arrington Canc Res & Treatment Ctr, Lubbock, TX USA. [Erwin, Deborah O.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Jones, Resa M.] Virginia Commonwealth Univ, Dept Epidemiol & Community Hlth, Sch Med, Richmond, VA USA. [Jones, Resa M.] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA USA. [Kaiser, Karen] Univ Illinois, Inst Hlth Res & Policy, Chicago, IL USA. [Kash, Kathryn M.] Thomas Jefferson Univ, Jefferson Sch Populat Hlth, Philadelphia, PA 19107 USA. [Kelly, Kimberly M.] Ohio State Univ, Dept Mol Virol, Columbus, OH 43210 USA. [Lee, Simon J. Craddock] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. [Lee, Simon J. Craddock] Univ Texas SW Med Ctr Dallas, Simmons Canc Ctr, Dallas, TX 75390 USA. [Purnell, Jason Q.] Washington Univ, Hlth Commun Res Lab, St Louis, MO USA. [Siminoff, Laura A.] Virginia Commonwealth Univ, Dept Social & Behav Hlth, Sch Med, Richmond, VA USA. [Vadaparampil, Susan T.] Univ S Florida, Dept Interdisciplinary Oncol, Tampa, FL USA. [Vadaparampil, Susan T.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Wang, Catharine] Boston Univ, Sch Publ Hlth, Dept Community Hlth Sci, Boston, MA USA. RP Kiviniemi, MT (reprint author), SUNY Coll Buffalo, Dept Hlth Behav, 314 Kimball Tower,3435 Main St, Buffalo, NY 14222 USA. EM mtk8@buffalo.edu RI Lee, Simon/B-2443-2008; Siminoff, Laura /H-6277-2012; Kiviniemi, Marc/B-8513-2013; OI Kiviniemi, Marc/0000-0002-1299-8416; James, Aimee/0000-0002-1411-9307; Wang, Catharine/0000-0001-8584-2781; Lee, Simon J. Craddock/0000-0001-6345-1237 FU NCI NIH HHS [K07 CA106225, K07 CA106225-04, K07 CA131103, K07 CA131103-02, K07CA106225, R25 CA057699, R25 CA057699-14]; PHS HHS [R25TCA57699-14] NR 72 TC 8 Z9 8 U1 4 U2 14 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2009 VL 18 IS 11 BP 3133 EP 3137 DI 10.1158/1055-9965.EPI-18-11-ASPO PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 516SJ UT WOS:000271562600049 PM 19900944 ER PT J AU Lee, TY Kim, YH Yoon, SW Choi, JC Yang, JM Kim, CJ Schiller, JT Sung, MH Poo, H AF Lee, Tae-Young Kim, Yang-Hyun Yoon, Sun-Woo Choi, Jai-Chul Yang, Jai-Myung Kim, Chul-Joong Schiller, John T. Sung, Moon-Hee Poo, Haryoung TI Oral administration of poly-gamma-glutamate induces TLR4-and dendritic cell-dependent antitumor effect SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE Poly-gamma-glutamate; MyD88; TLR4; Anti-tumor effect; Dendritic cell ID TOLL-LIKE RECEPTOR-4; SIGNALING PATHWAYS; GENE-EXPRESSION; IMMUNITY; INNATE; ACTIVATION; FAMILY; MYD88; MICE; LIPOPOLYSACCHARIDE AB Previously, we reported that the oral administration of high molecular mass poly-gamma-glutamate (gamma-PGA) induced antitumor immunity but the mechanism underlying this antitumor activity was not understood. In the present study, we found that application of high molecular mass gamma-PGA induced secretion of tumor necrosis factor (TNF)-alpha from the bone-marrow-derived macrophages of wild type (C57BL/6 and C3H/HeN) and Toll-like receptor 2 knockout (TLR2(-/-)) mice, but not those of myeloid differentiation factor 88 knockout (MyD88(-/-)) and TLR4-defective mice (C3H/HeJ). Production of interferon (IFN)-gamma-inducible protein 10 (IP-10) in response to treatment with gamma-PGA was almost abolished in C3H/HeJ mice. In contrast to LPS, gamma-PGA induced productions of TNF-alpha and IP-10 could not be blocked by polymyxin B. Furthermore, gamma-PGA-induced interleukin-12 production was also impaired in immature dendritic cells (iDCs) from MyD88(-/-) and C3H/HeJ mice. Downregulation of MyD88 and TLR4 expression using small interfering RNA (siRNA) significantly inhibited gamma-PGA-induced TNF-alpha secretion from the RAW264.7 cells. gamma-PGA-mediated intracellular signaling was markedly inhibited in C3H/HeJ cells. The antitumor effect of gamma-PGA was completely abrogated in C3H/HeJ mice compared with control mice (C3H/HeN) but significant antitumor effect was generated by the intratumoral administration of C3H/HeN mice-derived iDCs followed by 2,000 kDa gamma-PGA in C3H/HeJ. These findings strongly suggest that the antitumor activity of gamma-PGA is mediated by TLR4. C1 [Lee, Tae-Young; Kim, Yang-Hyun; Yoon, Sun-Woo; Poo, Haryoung] Korea Res Inst Biosci & Biotechnol, BioNanotechnol Res Ctr, Mucosal Immunol Lab, Taejon 305806, South Korea. [Choi, Jai-Chul; Sung, Moon-Hee] BioLeaders Corp, Taejon, South Korea. [Kim, Yang-Hyun; Yang, Jai-Myung] Sogang Univ, Dept Life Sci, Seoul, South Korea. [Kim, Chul-Joong] Chungnam Natl Univ, Coll Vet Med, Taejon, South Korea. [Schiller, John T.] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. [Sung, Moon-Hee] Kookmin Univ, Dept Bio & Nanochem, Seoul, South Korea. RP Poo, H (reprint author), Korea Res Inst Biosci & Biotechnol, BioNanotechnol Res Ctr, Mucosal Immunol Lab, Taejon 305806, South Korea. EM haryoung@kribb.re.kr FU Korea Health 21 RD Project [A050562]; National R&D Program for Cancer Control [0720510]; Ministry of Health & Welfare, Republic of Korea; KRIBB Initiative program FX We thank Dr S. Akira and Dr S. Uemastu for MyD88-/- and TLR2-/- mice, Dr J. Y. Lee and Dr Kate Fitzgerald for IRF3 luciferase plasmid, and Dr H. Kuroda for helpful advices. This work was supported by grants of the Korea Health 21 R&D Project ( A050562) and National R&D Program for Cancer Control ( 0720510), Ministry of Health & Welfare, Republic of Korea and a grant from KRIBB Initiative program to H. Poo. NR 39 TC 30 Z9 31 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 EI 1432-0851 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD NOV PY 2009 VL 58 IS 11 BP 1783 EP 1796 DI 10.1007/s00262-009-0689-4 PG 14 WC Oncology; Immunology SC Oncology; Immunology GA 485HW UT WOS:000269112900006 PM 19294383 ER PT J AU di Bari, MG Lutsiak, MEC Takai, S Mostbock, S Farsaci, B Semnani, RT Wakefield, LM Schlom, J Sabzevari, H AF di Bari, Maria Giovanna Lutsiak, M. E. Christine Takai, Shinji Mostbock, Sven Farsaci, Benedetto Semnani, Roshanak Tolouei Wakefield, Lalage M. Schlom, Jeffrey Sabzevari, Helen TI TGF-beta modulates the functionality of tumor-infiltrating CD8(+) T cells through effects on TCR signaling and Spred1 expression SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE T cells; Tolerance/suppression/anergy; Tumor immunity; Signal transduction ID ANTITUMOR IMMUNITY; GROWTH; ACTIVATION; TRANSDUCTION; SUPPRESSION; INDUCTION; CD4(+); PHOSPHORYLATION; MECHANISMS; GENERATION AB This study demonstrates that CD8(+) T cells in the tumor microenvironment display reduced functionality and hyporesponsiveness. TGF-beta contributed markedly to the tumor-infiltrating CD8(+) T cells' (TILs) reduced functionality, which could be reversed using a small molecule TGF-beta inhibitor. Upon T-cell receptor (TCR) activation, the activation of ITK and ERK kinases were reduced in CD8(+) TILs, as compared to splenic CD8(+) T cells: TGF-beta inhibitor could reverse this phenomenon. This study demonstrates for the first time the association of the Spred-1 gene, an inhibitor of the Ras/MAPK pathway, with CD8(+) TILs and TGF-beta activity. Spred-1 was upregulated in CD8(+) TILs and TGF-beta enhanced the expression of Spred-1 in effector/memory CD8(+) T cells and not in rested/memory CD8(+) T cells. Based on these findings, this study supports the hypothesis that TGF-beta mediates an inhibitory mechanism on CD8(+) TILs involving TCR-signaling blockade and the upregulation of Spred-1, thus implicating Spred-1 as a potential new target for future anti-tumor immune studies. C1 [di Bari, Maria Giovanna; Lutsiak, M. E. Christine; Takai, Shinji; Mostbock, Sven; Farsaci, Benedetto; Schlom, Jeffrey; Sabzevari, Helen] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Semnani, Roshanak Tolouei] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Wakefield, Lalage M.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B09,MSC 1750, Bethesda, MD 20892 USA. EM js141c@nih.gov RI Farsaci, Benedetto/L-9837-2014 OI Farsaci, Benedetto/0000-0001-8275-2561 FU National Institutes of Health Intramural Program; Center for Cancer Research; National Cancer Institute FX We thank Judith DiPietro for technical assistance, Lajuan Chase for mouse work and Debra Weingarten for editorial assistance in the preparation of this manuscript. This work was supported by the National Institutes of Health Intramural Program, Center for Cancer Research, National Cancer Institute. NR 41 TC 13 Z9 13 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 EI 1432-0851 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD NOV PY 2009 VL 58 IS 11 BP 1811 EP 1820 DI 10.1007/s00262-009-0692-9 PG 10 WC Oncology; Immunology SC Oncology; Immunology GA 485HW UT WOS:000269112900009 PM 19319531 ER PT J AU Kristinsson, SY Landgren, O Rajkumar, VS AF Kristinsson, Sigurdur Yngvi Landgren, Ola Rajkumar, Vincent S. TI Novel Therapies in Multiple Myeloma for Newly Diagnosed Nontransplant Candidates SO CANCER JOURNAL LA English DT Review DE multiple myeloma; therapy; prognosis ID STEM-CELL TRANSPLANTATION; LENALIDOMIDE PLUS DEXAMETHASONE; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; ELDERLY-PATIENTS; AUTOLOGOUS TRANSPLANTATION; COMBINATION CHEMOTHERAPY; 1ST-DEGREE RELATIVES; THALIDOMIDE ANALOGS; RANDOMIZED-TRIAL AB In the twenty-first century, melphalan-prednisone can no longer be regarded as the standard treatment of multiple myeloma patients not eligible for high-dose melphalan followed by autologous stern cell transplantation. The introduction of thalidomide, lenalidomide, and bortezomib has improved the arsenal of therapeutic options in multiple myeloma. Indeed, randomized studies have shown that melphalan-prednisone-thalidomide and melphalan-prednisone-bortezomib are superior to melphalan-prednisone alone. III addition, other combinations, including lenalidomide, are under study. III this review, we discuss the role of novel therapies in multiple myeloma in elderly multiple myeloma patients. Important aspects, such as toxicity and the role of prognostic factors, are also addressed. C1 [Rajkumar, Vincent S.] Mayo Clin, Div Hematol, Rochester, MN 55905 USA. [Kristinsson, Sigurdur Yngvi] Karolinska Univ, Hosp Solna, Dept Med, Div Hematol, Stockholm, Sweden. [Kristinsson, Sigurdur Yngvi] Karolinska Inst, Stockholm, Sweden. [Landgren, Ola] NCI, Div Med Oncol, Med Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Rajkumar, VS (reprint author), Mayo Clin, Div Hematol, Rochester, MN 55905 USA. EM rajkumar.vincent@mayo.edu RI Kristinsson, Sigurdur /M-2910-2015; OI Kristinsson, Sigurdur /0000-0002-4964-7476; Rajkumar, S. Vincent/0000-0002-5862-1833 FU National Cancer Institute, Bethesda, MD [CA62242, CA107476] FX Supported in part by National Cancer Institute, Bethesda, MD, grants CA62242 and CA107476. NR 63 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD NOV-DEC PY 2009 VL 15 IS 6 BP 473 EP 478 PG 6 WC Oncology SC Oncology GA 535EW UT WOS:000272951000005 PM 20010166 ER PT J AU Anastasiadou, E Vaeth, S Cuomo, L Boccellato, F Vincenti, S Cirone, M Presutti, C Junker, S Winberg, G Frati, L Wade, PA Faggioni, A Trivedi, P AF Anastasiadou, Eleni Vaeth, Signe Cuomo, Laura Boccellato, Francesco Vincenti, Sara Cirone, Mara Presutti, Carlo Junker, Steffen Winberg, Gosta Frati, Luigi Wade, Paul A. Faggioni, Alberto Trivedi, Pankaj TI Epstein-Barr virus infection leads to partial phenotypic reversion of terminally differentiated malignant B cells SO CANCER LETTERS LA English DT Article DE EBV; Latency; Myeloma; Differentiation ID LATENT GENE-EXPRESSION; EFFUSION LYMPHOMA-CELLS; NON-HODGKINS-LYMPHOMA; BURKITTS-LYMPHOMA; MULTIPLE-MYELOMA; TCL1 EXPRESSION; PLASMA-CELLS; EBV LATENCY; IN-VIVO; DISRUPTION AB The B cell lymphomas associated with Epstein-Barr virus (EBV) are not limited to any specific stage of B cell differentiation but covers widely different B cell phenotypes. In vitro infection of the virus negative tumors with a recombinant EBV strain has provided important insights into virus-tumor interaction. Here, we investigated the interaction between EBV and terminally differentiated tumor derived B cells, namely multiple myeloma (MM). The in vitro EBV infected MM expressed restricted viral latency. Acquisition of the virus was accompanied by a partial reprogramming to a mature B cell phenotype. Thus. the plasma cell markers syndecan-1 (CD138), Blimp1 and MUM1 were downregulated, while expression of HLADR, CIITA and TCL1, which are normally not expressed in plasmacytoid cells, was upregulated. The silenced transcription factor gene encoding Pax5 and its target BLNK were activated. Significantly. the free lambda light chains secreted in the medium were reduced in EBV infected MM clones. Collectively, these results suggest that the restricted EBV latency can cause at least partial phenotypic reversion of terminally differentiated B tumor cells. We suggest that the restricted EBV latent gene expression may not only be the consequence but the cause of the mature B cell phenotype, actively participating in the virus persistence. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Anastasiadou, Eleni; Boccellato, Francesco; Cirone, Mara; Frati, Luigi; Faggioni, Alberto; Trivedi, Pankaj] Univ Roma La Sapienza, Ist Pasteur Fdn Cenci Bolognetti, Dept Expt Med & Pathol, I-00161 Rome, Italy. [Vaeth, Signe; Junker, Steffen] Aarhus Univ, Dept Human Genet, Aarhus, Denmark. [Cuomo, Laura] San Filippo Neri Hosp, Dept Clin Pathol, I-00135 Rome, Italy. [Vincenti, Sara; Presutti, Carlo] Univ Roma La Sapienza, Dept Genet & Mol Biol, I-00185 Rome, Italy. [Winberg, Gosta] Karolinska Inst, MTC, Stockholm, Sweden. [Wade, Paul A.] NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Trivedi, P (reprint author), Univ Roma La Sapienza, Ist Pasteur Fdn Cenci Bolognetti, Dept Expt Med & Pathol, Viale Regina Elena 324, I-00161 Rome, Italy. EM alberto.faggioni@uniroma1.it; Pankaj.Trivedi@uniroma1.it RI Winberg, Gosta/I-5686-2013; OI Winberg, Gosta/0000-0002-3371-4056 FU MIUR; Associazione Italiana per la ricerca sul Cancro (AIRC); Fondazione Italiana per la sclerosi multipla (FISM); Ministero della Sanita, progetto AIDS; National Institute of Environmental Health Science, NIH; Danish Cancer Society; NOVO Foundation; Danish Medical Research Council; Eva and Henry Fraenkel Memorial Foundation FX This work was partially supported by Grants from MIUR and Associazione Italiana per la ricerca sul Cancro (AIRC), Fondazione Italiana per la sclerosi multipla (FISM) and from Ministero della Sanita, progetto AIDS. PW was supported by the Intramural Research Program of the National Institute of Environmental Health Science, NIH. S.J is supported by Danish Cancer Society, the NOVO Foundation, Danish Medical Research Council, and the Eva and Henry Fraenkel Memorial Foundation. We thank Dr. J. Epstein, Little Rock University, Arkansas, USA for CAG MM cell line 173 and Dr. Kenzo Takada for the recombinant EBV. Sandro Valia and Paola Ottaviani are acknowledged for technical help and photographic work. NR 27 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD NOV 1 PY 2009 VL 284 IS 2 BP 165 EP 174 DI 10.1016/j.canlet.2009.04.025 PG 10 WC Oncology SC Oncology GA 503JQ UT WOS:000270530700007 PM 19481340 ER PT J AU Steele, VE Rao, CV Zhang, YT Patlolla, J Boring, D Kopelovich, L Juliana, MM Grubbs, CJ Lubet, RA AF Steele, Vernon E. Rao, Chinthalapally V. Zhang, Yuting Patlolla, Jagan Boring, Daniel Kopelovich, Levy Juliana, M. Margaret Grubbs, Clinton J. Lubet, Ronald A. TI Chemopreventive Efficacy of Naproxen and Nitric Oxide-naproxen in Rodent Models of Colon, Urinary Bladder, and Mammary Cancers SO CANCER PREVENTION RESEARCH LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ABERRANT CRYPT FOCI; CYCLO-OXYGENASE-2 INHIBITORS; CYCLOOXYGENASE-2 INHIBITOR; PRENEOPLASTIC LESIONS; RANDOMIZED-TRIALS; CELECOXIB; CARCINOGENESIS; PREVENTION; AGENTS AB Nonsteroidal anti-inflammatory drugs (NSAID) have been highly effective in preventing colon, urinary bladder, and skin cancer preclinically, and also in clinical trials of colon adenoma formation. However, certain NSAIDs cause gastrointestinal ulceration and may increase cardiovascular events. Naproxen seems to cause the lowest cardiovascular events of the common NSAIDs other than aspirin. Nitric oxide (NO)-naproxen was tested based on the finding that adding a NO group to NSAIDs may help alleviate GI toxicity. In the azoxymethane-induced rat colon aberrant crypt foci (ACF) model, naproxen administered at 200 and 400 ppm in the diet reduced mean ACFs in the colon by about 45% to 60%, respectively. NO-naproxen was likewise administered in the diet at roughly equimolar doses (300 and 600 ppm) and reduced total ACF by 20% to 40%, respectively. In the hydroxybutyl (butyl) nitrosamine rat urinary bladder cancer model, NO-naproxen was given at 183 or 550 ppm in the diet, and naproxen at 128 ppm. The NO-naproxen groups had 77% and 73% decreases, respectively, in the development of large urinary bladder tumors, whereas the 128 ppm naproxen group also showed a strong decrease (69%). If treatments were started 3 months after hydroxybutyl (butyl) nitrosamine, NO-naproxen (550 ppm) and naproxen (400 ppm) were also highly effective (86-94% decreases). In the methylnitrosourea-induced mammary cancer model in rats, NO-naproxen and naproxen showed nonsignificant inhibitions (12% and 24%) at 550 and 400 ppm, respectively. These data show that both naproxen and NO-naproxen are effective agents against urinary bladder and colon, but not mammary, carcinogenesis. C1 [Steele, Vernon E.; Boring, Daniel; Kopelovich, Levy; Lubet, Ronald A.] NIH, Chemoprevent Agent Dev Res Grp, Canc Prevent Div, Bethesda, MD USA. [Rao, Chinthalapally V.; Zhang, Yuting; Patlolla, Jagan] Univ Oklahoma, Inst Canc, OUHSC, Oklahoma City, OK USA. [Juliana, M. Margaret; Grubbs, Clinton J.] Univ Alabama, Birmingham, AL USA. RP Steele, VE (reprint author), NCI, Execut Plaza N,Room 2118,6130 Execut Blvd, Rockville, MD 20852 USA. EM Steelev@mail.nih.gov FU National Cancer Institute [NCI-CN53300, NCI-CN43301] FX Grant support: National Cancer Institute Contracts NCI-CN53300 and NCI-CN43301. NR 33 TC 25 Z9 26 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD NOV PY 2009 VL 2 IS 11 BP 951 EP 956 DI 10.1158/1940-6207.CAPR-09-0080 PG 6 WC Oncology SC Oncology GA 515HG UT WOS:000271458400006 PM 19892664 ER PT J AU Turk, D Hall, MD Chu, BF Ludwig, JA Fales, HM Gottesman, MM Szakacs, G AF Tuerk, Dora Hall, Matthew D. Chu, Benjamin F. Ludwig, Joseph A. Fales, Henry M. Gottesman, Michael M. Szakacs, Gergely TI Identification of Compounds Selectively Killing Multidrug-Resistant Cancer Cells SO CANCER RESEARCH LA English DT Article ID TUMOR-SCREENING DATABASE; ANTICANCER DRUG SCREEN; P-GLYCOPROTEIN; LEUKEMIA-CELLS; RIBONUCLEOTIDE REDUCTASE; IRON CHELATORS; KB CELLS; INHIBITORS; LINES; AGENTS AB There is a great need for the development of novel chemotherapeutic agents that overcome the emergence of multidrug resistance (MDR) in cancer. We catalogued the National Cancer Institute's DTP drug repository in search of compounds showing increased toxicity in MDR cells. By comparing the sensitivity of parental cell lines with MDR derivatives, we identified 22 compounds possessing MDR-selective activity. Analysis of structural congeners led to the identification of 15 additional drugs showing increased toxicity in Pgp-expressing cells. Analysis of MDR-selective compounds led to the formulation of structure activity relationships and pharmacophore models. This data mining coupled with experimental data points to a possible mechanism of action linked to metal chelation. Taken together, the discovery of the MDR-selective compound set shows the robustness of the developing field of MDR-targeting therapy as a new strategy for resolving Pgp-mediated MDR. [Cancer Res 2009;69(21):8293-301] C1 [Tuerk, Dora; Szakacs, Gergely] Hungarian Acad Sci, Inst Enzymol, H-1113 Budapest, Hungary. [Hall, Matthew D.; Chu, Benjamin F.; Gottesman, Michael M.] NCI, Cell Biol Lab, Bethesda, MD 20892 USA. [Fales, Henry M.] NHLBI, Biophys Chem Lab, Bethesda, MD 20892 USA. [Ludwig, Joseph A.] Univ Texas MD Anderson Canc Ctr, Dept Sarcoma Med Oncol, Houston, TX 77030 USA. RP Szakacs, G (reprint author), Hungarian Acad Sci, Inst Enzymol, Karolina Ut 29, H-1113 Budapest, Hungary. EM szakacs@biomembrane.hu RI Szakacs, Gergely/A-2580-2009; Hall, Matthew/B-2132-2010 OI Szakacs, Gergely/0000-0002-9311-7827; FU OTKA [PF60435]; EMBO-SDIG; Marie Curie [046560, 041547]; NIH; Janos Bolyai Scholarship; Leukemia and Lymphoma Society FX Grant support: OTKA (PF60435), EMBO-SDIG, and Marie Curie grants (046560, 041547) as well as the Intramural Research Program of the NIH. G. Szakacs is the recipient of a Janos Bolyai Scholarship and a Special Fellow Award from the Leukemia and Lymphoma Society.; The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.; We thank the NCI DTP for generation of the database used in this study and Zsuzsanna Sebestyen for the technical help. NR 46 TC 51 Z9 51 U1 2 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2009 VL 69 IS 21 BP 8293 EP 8301 DI 10.1158/0008-5472.CAN-09-2422 PG 9 WC Oncology SC Oncology GA 514OA UT WOS:000271403000011 PM 19843850 ER PT J AU Moore, SC Rajaraman, P Dubrow, R Darefsky, AS Koebnick, C Hollenbeck, A Schatzkin, A Leitzmann, MF AF Moore, Steven C. Rajaraman, Preetha Dubrow, Robert Darefsky, Amy S. Koebnick, Corinna Hollenbeck, Albert Schatzkin, Arthur Leitzmann, Michael F. TI Height, Body Mass Index, and Physical Activity in Relation to Glioma Risk SO CANCER RESEARCH LA English DT Article ID BRAIN-TUMORS; CANCER STATISTICS; GROWTH-FACTORS; INSULIN; COHORT; ADULTS; VALIDITY; WEIGHT; SYSTEM; HEALTH AB Whether energy balance during early life and/or adulthood is related to glioma risk is unknown. We therefore investigated height, body mass index (BMI), and physical activity in relation to glioma risk in the prospective NIH-AARP Diet and Health Study. Participants completed a baseline questionnaire (sent in 1995-1996) inquiring about height, weight, and potential confounders. A second questionnaire (sent in 1996) inquired about physical activity during ages 15 to 18, 19 to 29, and 35 to 39 years and the past 10 years and body weight at ages 18, 35, and 50 years. During follow-up from 1995/1996 to 2003, we documented 480 cases of glioma among 499,437 respondents to the baseline questionnaire and 257 cases among 305,681 respondents to the second questionnaire. Glioma risk among tall persons (>= 1.90 m) was twice that of short persons [<1.60 m; multivariate relative risk (RR), 2.12; 95% confidence interval (95% CI), 1.18-3.81; P-trend = 0.006]. Risk among participants who were obese (BMI 30.0-34.9 kg/m(2)) at age 18 years was nearly four times that of persons of normal weight (BMI 18.5-24.9 kg/m(2)) at age 18 years (RR, 3.74; 95% CI, 2.03-6.90; P-trend = 0.003); 11 cases were obese at age 18 years. Risk among participants who were active during ages 15 to IS years was 36% lower than that of persons who were inactive during ages 15 to 18 years (RR, 0.64; 95% CI, 0.44-0.93; P-trend = 0.02). BMI and physical activity after age 18 years were unrelated to glioma risk. Adult height, BMI during adolescence, and physical activity during adolescence were each associated with glioma risk, supporting a role for early-life energy balance in glioma carcinogenesis. [Cancer Res 2009;69(21):8349-55] C1 [Moore, Steven C.; Schatzkin, Arthur] NCI, Nutr Epidemiol Branch, NIH, Dept Hlth & Human Serv, Rockville, MD USA. [Rajaraman, Preetha] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD USA. [Dubrow, Robert; Darefsky, Amy S.] Yale Univ, Sch Med, Yale Sch Publ Hlth, New Haven, CT USA. [Koebnick, Corinna] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA USA. [Hollenbeck, Albert] AARP, Washington, DC USA. [Leitzmann, Michael F.] Univ Regensburg, Med Ctr, Dept Epidemiol & Prevent Med, Regensburg, Germany. RP Moore, SC (reprint author), 6120 Execut Blvd, Bethesda, MD 20892 USA. EM moorest@mail.nih.gov RI Koebnick, Corinna/P-4767-2016; Moore, Steven/D-8760-2016 OI Koebnick, Corinna/0000-0001-8274-0309; Moore, Steven/0000-0002-8169-1661 FU NIH/National Cancer Institute FX Grant support: Intramural Research Program of the NIH/National Cancer Institute.; The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.; We thank the participants in the NIH-AARP Diet and Health Study for outstanding cooperation.; S.C. Moore had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.; Cancer incidence data from the Atlanta metropolitan area were collected by the Georgia Center for Cancer Statistics, Department of Epidemiology, Rollins School of Public Health, Emory University. Cancer incidence data from California were collected by the California Department of Health Services, Cancer Surveillance Section. Cancer incidence data from the Detroit metropolitan area were collected by the Michigan Cancer Surveillance Program, Community Health Administration, State of Michigan. The Florida cancer incidence data used in this report were collected by the Florida Cancer Data System under contract to the Department of Health. The views expressed herein are solely those of the authors and do not necessarily reflect those of the contractor or Department of Health. Cancer incidence data from Louisiana were collected by the Louisiana Tumor Registry, Louisiana State University Medical Center in New Orleans. Cancer incidence data from New Jersey were collected by the New Jersey State Cancer Registry, Cancer Epidemiology Services, New Jersey State Department of Health and Senior Services. Cancer incidence data from North Carolina were collected by the North Carolina Central Cancer Registry. Cancer incidence data from Pennsylvania were supplied by the Division of Health Statistics and Research, Pennsylvania Department of Health, Harrisburg, Pennsylvania. The Pennsylvania Department of Health specifically disclaims responsibility for any analyses, interpretations or conclusions. NR 29 TC 40 Z9 40 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2009 VL 69 IS 21 BP 8349 EP 8355 DI 10.1158/0008-5472.CAN-09-1669 PG 7 WC Oncology SC Oncology GA 514OA UT WOS:000271403000018 PM 19808953 ER PT J AU Collier, LS Adams, DJ Hackett, CS Bendzick, LE Akagi, K Davies, MN Diers, MD Rodriguez, FJ Bender, AM Tieu, C Matise, I Dupuy, AJ Copeland, NG Jenkins, NA Hodgson, JG Weiss, WA Jenkins, RB Largaespada, DA AF Collier, Lara S. Adams, David J. Hackett, Christopher S. Bendzick, Laura E. Akagi, Keiko Davies, Michael N. Diers, Miechaleen D. Rodriguez, Fausto J. Bender, Aaron M. Tieu, Christina Matise, Ilze Dupuy, Adam J. Copeland, Neal G. Jenkins, Nancy A. Hodgson, J. Graeme Weiss, William A. Jenkins, Robert B. Largaespada, David A. TI Whole-Body Sleeping Beauty Mutagenesis Can Cause Penetrant Leukemia/Lymphoma and Rare High-Grade Glioma without Associated Embryonic Lethality SO CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR; INSERTIONAL MUTAGENESIS; SOMATIC MUTAGENESIS; SITE PREFERENCES; GENE DISCOVERY; TRANSPOSON; CANCER; MOUSE; CELLS; MICE AB The Sleeping Beauty (SB) transposon system has been used as a somatic mutagen to identify candidate cancer genes. In previous studies, efficient leukemia/lymphoma formation on an otherwise wild-type genetic background occurred in mice undergoing whole-body mobilization of transposons, but was accompanied by high levels of embryonic lethality. To explore the utility of SB for large-scale cancer gene discovery projects, we have generated mice that carry combinations of different transposon and transposase transgenes. We have identified a transposon/transposase combination that promotes highly penetrant leukemia/lymphoma formation on an otherwise wild-type genetic background, yet does not cause embryonic lethality. Infiltrating gliomas also occurred at lower penetrance in these mice. SB-induced or accelerated tumors do not harbor large numbers of chromosomal amplifications or deletions, indicating that transposon mobilization likely promotes tumor formation by insertional mutagenesis of cancer genes, and not by promoting wide-scale genomic instability. Cloning of transposon insertions from lymphomas/leukemias identified common insertion sites at known and candidate novel cancer genes. These data indicate that a high mutagenesis rate can be achieved using SB without high levels of embryonic lethality or genomic instability. Furthermore, the SB system could be used to identify new genes involved in lymphomagenesis/leukemogenesis. [Cancer Res 2009;69(21):8429-37] C1 [Collier, Lara S.; Bendzick, Laura E.; Davies, Michael N.; Diers, Miechaleen D.; Largaespada, David A.] Univ Minnesota, Dept Genet Cell Biol & Dev, Mason Canc Ctr, Minneapolis, MN USA. [Matise, Ilze] Univ Minnesota, Mason Canc Ctr Histopathol Core, Minneapolis, MN USA. [Adams, David J.] Wellcome Trust Sanger Inst, Cambridge, England. [Hackett, Christopher S.; Hodgson, J. Graeme; Weiss, William A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Akagi, Keiko] NCI, Mouse Canc Genet Program, Frederick, MD 21701 USA. [Rodriguez, Fausto J.; Bender, Aaron M.; Tieu, Christina; Jenkins, Robert B.] Mayo Clin, Div Expt Pathol, Rochester, MN USA. [Dupuy, Adam J.] Univ Iowa, Dept Cell Biol & Anat, Iowa City, IA USA. [Copeland, Neal G.; Jenkins, Nancy A.] Natl Univ Singapore, Inst Mol & Cell Biol, Singapore 117548, Singapore. RP Collier, LS (reprint author), Univ Wisconsin, 4117 Rennebohm Hall, Madison, WI 53705 USA. EM lcollier@wisc.edu; larga002@umn.edu RI ASTAR, IMCB/E-2320-2012; Largaespada, David/C-9832-2014; OI Weiss, William/0000-0003-2230-9132 FU American Cancer Society predoctoral fellowship; Minnesota Department of Employment and Economic Development [SPAP-05-0013-P-FY06, R01CA113636-01A1, R01NS055750]; Cancer Research-UK; Wellcome Trust; [K01CA122183] FX Grant support: K01CA122183 and an American Cancer Society predoctoral fellowship (L.S. Collier), Minnesota Department of Employment and Economic Development SPAP-05-0013-P-FY06 (D.A. Largaespada and R.B. Jenkins), R01CA113636-01A1 (D.A. Largaespada), R01NS055750 (IA A. Weiss), Cancer Research-UK, and the Wellcome Trust (DJ. Adams). NR 34 TC 44 Z9 45 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2009 VL 69 IS 21 BP 8429 EP 8437 DI 10.1158/0008-5472.CAN-09-1760 PG 9 WC Oncology SC Oncology GA 514OA UT WOS:000271403000027 PM 19843846 ER PT J AU Ryan, BM O'Donovan, N Duffy, MJ AF Ryan, Brid M. O'Donovan, Norma Duffy, Michael J. TI Survivin: A new target for anti-cancer therapy SO CANCER TREATMENT REVIEWS LA English DT Review DE Survivin; BIRC5; IAP; Cancer; Treatment ID SQUAMOUS-CELL CARCINOMA; PROSTATE-CANCER CELLS; HUMAN-MELANOMA CELLS; CHEMOPREVENTIVE AGENT RESVERATROL; CHROMOSOMAL PASSENGER COMPLEX; RIBOZYME-MEDIATED INHIBITION; TRAIL-INDUCED APOPTOSIS; TUMOR-ANTIGEN SURVIVIN; NEGATIVE BREAST-CANCER; DRUG-INDUCED APOPTOSIS AB Survivin is one of the most cancer-specific proteins identified to date, being upregulated in almost all human tumors. Biologically, survivin has been shown to inhibit apoptosis, enhance proliferation and promote angiogenesis. Because of its upregulation in malignancy and its key role in apoptosis, proliferation and angiogenesis, survivin is currently attracting considerable attention as a new target for anti-cancer therapies. In several animal model systems, downregulation of survivin or inactivation of its function has been shown to inhibit tumor growth. Strategies under investigation to target survivin include antisense oligonucleotides, siRNA, ribozymes, immunotherapy and small molecular weight molecules. The translation of these findings to the clinic is currently ongoing with a number of phase I/II clinical trials targeting survivin in progress. These include use of the antisense oligonucleotide LY2181308, the low molecular weight molecule inhibitor YM155 and survivin-directed autologous cytotoxic T lymphocytes. The optimum use of survivin antagonists in the treatment of cancer is likely to be in combination with conventional cancer therapies. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Ryan, Brid M.] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, NIH, Bethesda, MD 20892 USA. [Ryan, Brid M.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [O'Donovan, Norma] Dublin City Univ, Natl Inst Cellular Biotechnol, Dublin 9, Ireland. [Duffy, Michael J.] St Vincents Univ Hosp, Dept Pathol & Lab Med, Dublin 4, Ireland. [Duffy, Michael J.] Univ Coll Dublin, Conway Inst, Sch Med & Med Sci, Dublin 4, Ireland. RP Ryan, BM (reprint author), NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, NIH, Bethesda, MD 20892 USA. EM ryanb@mail.nih.gov; norma.odonovan@dcu.ie; michael.j.duffy@ucd.ie RI O'Donovan, Norma/B-6710-2013; OI O'Donovan, Norma/0000-0003-1113-3872; Ryan, Brid/0000-0003-0038-131X FU Irish Cancer Society; Health Research Board of Ireland [PRP/2005/35] FX The authors' work on survivin was supported by the Irish Cancer Society and the Health Research Board of Ireland (Project No. PRP/2005/35). The authors declare no conflicts of interest. NR 174 TC 234 Z9 275 U1 6 U2 58 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0305-7372 J9 CANCER TREAT REV JI Cancer Treat. Rev. PD NOV PY 2009 VL 35 IS 7 BP 553 EP 562 DI 10.1016/j.ctrv.2009.05.003 PG 10 WC Oncology SC Oncology GA 523TV UT WOS:000272098400004 PM 19559538 ER PT J AU Itano, O Yang, K Fan, KH Kurihara, N Shinozaki, H Abe, S Jin, B Gravaghi, C Edelmann, W Augenlicht, L Kopelovich, L Kucherlapati, R Lamprecht, S Lipkin, M AF Itano, Osamu Yang, Kan Fan, Kunhua Kurihara, Naoto Shinozaki, Hiroharu Abe, Sadanori Jin, Bo Gravaghi, Claudia Edelmann, Winfried Augenlicht, Leonard Kopelovich, Levy Kucherlapati, Raju Lamprecht, Sergio Lipkin, Martin TI Sulindac effects on inflammation and tumorigenesis in the intestine of mice with Apc and Mlh1 mutations SO CARCINOGENESIS LA English DT Article ID FAMILIAL ADENOMATOUS POLYPOSIS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; LONG-TERM TREATMENT; P38 MAP-KINASES; OXIDATIVE STRESS; RECTAL-CANCER; COLORECTAL ADENOMAS; BOWEL-DISEASE; MOUSE; CELLS AB We have previously reported that sulindac, a non-steroidal anti-inflammatory drug, inhibited tumor formation in the small intestine but increased tumors in the colon of Apc(Min/+) mice, a model of human familial adenomatous polyposis. To further explore intestinal regional responses, we studied effects of sulindac on additional gene-targeted mouse models of human intestinal tumorigenesis; these were (i) Apc(1638N/+) mouse (chain termination mutation in exon 15 of the Apc gene); (ii) Mlh1(+/-) mouse (DNA mismatch repair deficiency, a mouse model of human hereditary non-polyposis colorectal cancer) and (iii) double-heterozygous Mlh1(+/-)Apc(1638N/+) mutant mouse. Mice were fed AIN-76A control diet with or without 0.02% sulindac for 6 months. Intestinal regional tumor incidence, multiplicity, volume and degree of inflammation were used as end points. The results showed the following: (i) sulindac inhibited tumor development in the small intestine of Apc(1638N/+) mice; (ii) in contrast, sulindac increased tumors in the small intestine of Mlh1 mutant mice, a neoplastic effect which persisted in heterozygous compound Mlh1(+/-)Apc(1638N/+) mutant mice; (iii) sulindac increased tumors in the cecum of all mice regardless of genetic background; (iv) sulindac decreased inflammation in the small intestine of Apc(1638N/+) mice, but it increased inflammation in the small intestine of Mlh1(+/-) mice and Mlh1(+/-)Apc(1638N/+) mice and (v) sulindac enhanced inflammation in the cecum of all mutant mice. Findings indicate that the effects of sulindac in the intestine of these mutant mouse models are probably related to genetic background and appear to be associated with its inflammatory-inducing response. C1 [Itano, Osamu; Yang, Kan; Fan, Kunhua; Kurihara, Naoto; Shinozaki, Hiroharu; Abe, Sadanori; Gravaghi, Claudia; Lamprecht, Sergio; Lipkin, Martin] Cornell Univ, Weill Med Coll, Dept Med, Strang Canc Res Lab,Div Gastroenterol & Hepatol, New York, NY 10021 USA. [Jin, Bo; Edelmann, Winfried] Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10467 USA. [Augenlicht, Leonard] Montefiore Med Ctr, Dept Oncol, Bronx, NY 10467 USA. [Kucherlapati, Raju] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Kopelovich, Levy] NCI, Canc Prevent Div, Bethesda, MD 20852 USA. RP Lipkin, M (reprint author), Cornell Univ, Weill Med Coll, Dept Med, Strang Canc Res Lab,Div Gastroenterol & Hepatol, New York, NY 10021 USA. EM mal2019@med.cornell.edu FU National Cancer Institute; National Institutes of Health [NO1-CN-15116, NO1-CN-43308, RO1 CA 87559] FX National Cancer Institute; National Institutes of Health (NO1-CN-15116, NO1-CN-43308, RO1 CA 87559). NR 44 TC 7 Z9 7 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 2009 VL 30 IS 11 BP 1923 EP 1926 DI 10.1093/carcin/bgp200 PG 4 WC Oncology SC Oncology GA 524YB UT WOS:000272179200014 PM 19755659 ER PT J AU Shi, SL Yoon, DY Hodge-Bell, KC Bebenek, IG Whitekus, MJ Zhang, RX Cochran, AJ Huerta-Yepez, S Yim, SH Gonzalez, FJ Jaiswal, AK Hankinson, O AF Shi, Shengli Yoon, Diana Y. Hodge-Bell, Kimberly C. Bebenek, Ilona G. Whitekus, Michael J. Zhang, Ruixue Cochran, Alistair J. Huerta-Yepez, Sara Yim, Sun-Hee Gonzalez, Frank J. Jaiswal, Anil K. Hankinson, Oliver TI The aryl hydrocarbon receptor nuclear translocator (Arnt) is required for tumor initiation by benzo[a]pyrene SO CARCINOGENESIS LA English DT Article ID MOUSE SKIN; AH RECEPTOR; INCREASES SUSCEPTIBILITY; DEFICIENT MICE; CARCINOGENESIS; HYDROXYLASE; DISRUPTION; INDUCTION; PROTEIN; GENE AB Benzo[a]pyrene (B[a]P) is a ligand for the aryl hydrocarbon receptor (Ahr). After binding ligand, Ahr dimerizes with the aryl hydrocarbon receptor nuclear translocator (Arnt) protein, and the dimer upregulates the transcription of Cyp1a1, Cyp1b1 and other enzymes involved in the metabolic activation of B[a]P. Arnt null mice die in utero. Mice in which Arnt deletion occurs constitutively in the epidermis die perinatally. In the current study, mice were developed in which the Arnt gene could be deleted specifically in adult skin epidermis. This deletion had no overt pathological effect. Homozygosity for a null reduced nicotinamide adenine dinucleotide (phosphate): quinone oxidoreductase allele was introduced into the above mouse strain to render it more susceptible to tumor initiation by B[a]P. Deletion of Arnt in the epidermis of this strain completely prevented the induction of skin tumors in a tumor initiation-promotion protocol in which a single topical application of B[a]P acted as the tumor-initiating event, and tumor promotion was provided by repeated topical applications of 12-O-tetradecanoyl phorbol-13-acetate (TPA). In contrast, deletion of Arnt did not prevent the induction of skin tumors in a protocol also using TPA as the promoter but using as the initiator N-methyl-N'-nitro-N-nitrosoguanidine, whose activity is unlikely to be affected by the activity of Ahr, Arnt or their target genes. These observations demonstrate that Arnt is required for tumor initiation by B[a]P in this system. C1 [Shi, Shengli; Yoon, Diana Y.; Hodge-Bell, Kimberly C.; Bebenek, Ilona G.; Whitekus, Michael J.; Zhang, Ruixue; Cochran, Alistair J.; Hankinson, Oliver] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Shi, Shengli; Yoon, Diana Y.; Hodge-Bell, Kimberly C.; Bebenek, Ilona G.; Whitekus, Michael J.; Zhang, Ruixue; Cochran, Alistair J.; Hankinson, Oliver] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Bebenek, Ilona G.; Hankinson, Oliver] Univ Calif Los Angeles, Mol Toxicol Program, Los Angeles, CA 90095 USA. [Huerta-Yepez, Sara] Hosp Infantil Mexico Dr Federico Gomez, Colonia Doctores 06720, DF, Mexico. [Yim, Sun-Hee; Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA. [Jaiswal, Anil K.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RP Hankinson, O (reprint author), Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. EM ohank@mednet.ucla.edu FU NIH [RO1 CA93471, RO1 CA28868]; National Cancer Institute FX NIH (RO1 CA93471); an underrepresented minority supplement (RO1 CA93471 to K. H. B.); NIH (RO1 CA28868); National Cancer Institute Intramural Research Program to F.J.G. and S.H.-Y. NR 29 TC 14 Z9 15 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 2009 VL 30 IS 11 BP 1957 EP 1961 DI 10.1093/carcin/bgp201 PG 5 WC Oncology SC Oncology GA 524YB UT WOS:000272179200019 PM 19755658 ER PT J AU Perry, TE Song, MJ Despres, DJ Kim, SM San, H Yu, ZX Raghavachari, N Schnermann, J Cannon, RO Orlic, D AF Perry, Tashera E. Song, Minjung Despres, Daryl J. Kim, Soo Mi San, Hong Yu, Zu-Xi Raghavachari, Nalini Schnermann, Jurgen Cannon, Richard O., III Orlic, Donald TI Bone marrow-derived cells do not repair endothelium in a mouse model of chronic endothelial cell dysfunction SO CARDIOVASCULAR RESEARCH LA English DT Article DE Stem cells; Bone marrow transplantation; Endothelial NOS deficiency; Hypertension ID NITRIC-OXIDE SYNTHASE; PROGENITOR CELLS; POSTNATAL VASCULOGENESIS; STEM-CELLS; BLOOD; NEOVASCULARIZATION; MOBILIZATION; CONTRIBUTE; ISCHEMIA; ANGIOGENESIS AB Aims Bone marrow (BM)-derived endothelial progenitor cells (EPCs) in the circulation replace damaged vascular endothelium. We assessed the hypothesis that a BM transplant from healthy animals would restore normal arterial endothelium and prevent hypertension in young endothelial nitric oxide synthase-deficient (eNOS(-/-)) mice. Methods and results Radiation or busulfan-induced BM ablation in eNOS(-/-) mice on day 6, day 14, or day 28 was followed by a BM transplant consisting of enhanced green fluorescent protein positive (EGFP(+)) cells from C57BL/6J mice. Peripheral blood cell chimerism was always greater than 85% at 4 months after BM transplant. Molecular assays of heart, kidney, and liver revealed low-level chimerism in all treatment groups, consistent with residual circulating EGFP+ blood cells. When aorta, coronary, renal, hepatic, and splenic arteries in BM-transplanted eNOS(-/-) mice were examined by confocal microscopy, there were no EGFP- or eNOS-positive endothelial cells detected in these vessels in any of the treatment groups. Likewise, telemetry did not detect any reduction in blood pressure. Thus, no differences were observed in our measurements using several different treatment protocols. Conclusion We found no evidence for BM-derived EPIC renewal of endothelium in this eNOS-deficient mouse model of a chronic vascular disease or in wild-type mice during postnatal growth. Hence, renewal of chronic dysfunctional endothelium and endothelial homeostasis may be dependent on resident vascular progenitor cells. C1 [Perry, Tashera E.; Song, Minjung; Cannon, Richard O., III; Orlic, Donald] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. [Despres, Daryl J.] Natl Inst Neurol Disorders & Stroke, Mouse Imaging Facil, NIH, Bethesda, MD USA. [Kim, Soo Mi; Schnermann, Jurgen] NIDDK, Kidney Dis Branch, NIH, Bethesda, MD USA. [San, Hong] NHGRI, NIH, Bethesda, MD 20892 USA. RP Orlic, D (reprint author), NHLBI, Translat Med Branch, NIH, 9000 Rockville Pike,Bldg 10-CRC,Room 6-3130, Bethesda, MD 20892 USA. EM dorlic@nhlbi.nih.gov FU NHLBI, National Institutes of Health, Bethesda, MD, USA FX This work was supported by the intramural research program of the NHLBI, National Institutes of Health, Bethesda, MD, USA. Funding to pay the Open Access charges was provided by the NHLBI, National Institutes of Health. NR 28 TC 37 Z9 38 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD NOV 1 PY 2009 VL 84 IS 2 BP 317 EP 325 DI 10.1093/cvr/cvp215 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 514VD UT WOS:000271422900020 PM 19578071 ER PT J AU Lederman, RJ AF Lederman, Robert J. TI Legs bend: Why Dynamic Angiography Is Important SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material ID ARTERY; DISEASE C1 NHLBI, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Lederman, RJ (reprint author), NHLBI, Div Intramural Res, NIH, Bldg 10, Bethesda, MD 20892 USA. EM lederman@nih.gov OI lederman, robert/0000-0003-1202-6673 FU Intramural NIH HHS [ZIA HL005062-07, ZID HL006061-03] NR 7 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 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD NOV 1 PY 2009 VL 74 IS 5 BP 799 EP 799 DI 10.1002/22268 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 515UD UT WOS:000271497500019 PM 19856463 ER PT J AU Khatami, M AF Khatami, Mahin TI Inflammation, Aging, and Cancer: Tumoricidal Versus Tumorigenesis of Immunity SO CELL BIOCHEMISTRY AND BIOPHYSICS LA English DT Review DE Unresolved inflammation; Aging; Cancer; Innate and adaptive immunity; Autoimmune and neurodegenerative diseases; Stem cells; Hormonal change ID COLONY-STIMULATING FACTOR; NF-KAPPA-B; TUMOR-ASSOCIATED MACROPHAGES; CENTRAL-NERVOUS-SYSTEM; ALTERNATIVELY ACTIVATED MACROPHAGES; PIGMENT EPITHELIAL-CELLS; C-REACTIVE PROTEIN; DENDRITIC CELLS; MAST-CELLS; STEM-CELLS AB Acute inflammation is a highly regulated defense mechanism of immune system possessing two well-balanced and biologically opposing arms termed apoptosis ('Yin') and wound healing ('Yang') processes. Unresolved or chronic inflammation (oxidative stress) is perhaps the loss of balance between 'Yin' and 'Yang' that would induce co-expression of exaggerated or 'mismatched' apoptotic and wound healing factors in the microenvironment of tissues ('immune meltdown'). Unresolved inflammation could initiate the genesis of many age-associated chronic illnesses such as autoimmune and neurodegenerative diseases or tumors/cancers. In this perspective 'birds' eye' view of major interrelated co-morbidity risk factors that participate in biological shifts of growth-arresting ('tumoricidal') or growth-promoting ('tumorigenic') properties of immune cells and the genesis of chronic inflammatory diseases and cancer will be discussed. Persistent inflammation is perhaps a common denominator in the genesis of nearly all age-associated health problems or cancer. Future challenging opportunities for diagnosis, prevention, and/or therapy of chronic illnesses will require an integrated understanding and identification of developmental phases of inflammation-induced immune dysfunction and age-associated hormonal and physiological readjustments of organ systems. Designing suitable cohort studies to establish the oxido-redox status of adults may prove to be an effective strategy in assessing individual's health toward developing personal medicine for healthy aging. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Khatami, M (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM mkgoodness@aol.com NR 237 TC 33 Z9 34 U1 0 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1085-9195 J9 CELL BIOCHEM BIOPHYS JI Cell Biochem. Biophys. PD NOV PY 2009 VL 55 IS 2 BP 55 EP 79 DI 10.1007/s12013-009-9059-2 PG 25 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 495WO UT WOS:000269926100001 PM 19672563 ER PT J AU Chavakis, T Orlova, VV Langer, HF AF Chavakis, Triantafyllos Orlova, Valeria V. Langer, Harald F. TI A possible crosstalk between DNA repair pathways and angiogenesis SO CELL CYCLE LA English DT Editorial Material ID DAMAGE RESPONSE; HISTONE H2AX; C-MYC; HYPOXIA; OXYGEN; ATM; PHOSPHORYLATION; REOXYGENATION; RECOGNITION; INSTABILITY C1 [Chavakis, Triantafyllos; Orlova, Valeria V.; Langer, Harald F.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Chavakis, T (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM chavakist@mail.nih.gov RI Orlova, Valeria/C-6065-2014 OI Orlova, Valeria/0000-0002-1169-2802 FU Intramural NIH HHS [NIH0012066627, Z01 BC010664-03] NR 24 TC 3 Z9 3 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD NOV 1 PY 2009 VL 8 IS 21 BP 3438 EP 3439 DI 10.4161/cc.8.21.9750 PG 2 WC Cell Biology SC Cell Biology GA 525LX UT WOS:000272218600003 PM 19838053 ER PT J AU Kino, T Su, YA Chrousos, GP AF Kino, Tomoshige Su, Yan A. Chrousos, George P. TI Human glucocorticoid receptor isoform beta: recent understanding of its potential implications in physiology and pathophysiology SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE Cytoplasmic to nuclear translocation; Glucocorticoid receptor; Ligand-binding pocket; Microarray; Splicing isoform; Zebrafish ID DOMINANT-NEGATIVE ACTIVITY; LIGAND-BINDING DOMAIN; TRANSCRIPTIONAL ACTIVITY; MESSENGER-RNA; RESISTANCE/HYPERSENSITIVITY SYNDROMES; COACTIVATOR PROTEINS; ACTIVATION DOMAIN; SPLICE VARIANT; GENE VARIANT; DNA-BINDING AB The human glucocorticoid receptor (GR) gene expresses two splicing isoforms alpha and beta through alternative use of specific exons 9 alpha and 9 beta. In contrast to the classic receptor GR alpha, which mediates most of the known actions of glucocorticoids, the functions of GR beta have been largely unexplored. Owing to newly developed methods, for example microarrays and the jellyfish fluorescence proteins, we and others have recently revealed novel functions of GR beta. Indeed, this enigmatic GR isoform influences positively and negatively the transcriptional activity of large subsets of genes, most of which are not responsive to glucocorticoids, in addition to its well-known dominant negative effect against GR alpha-mediated transcriptional activity. A recent report suggested that the "ligand-binding domain" of GR beta is active, forming a functional ligand-binding pocket associated with the synthetic compound RU 486. In this review, we discuss the functions of GR beta, its mechanisms of action, and its pathologic implications. C1 [Kino, Tomoshige] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Clin Res Ctr, Bethesda, MD 20892 USA. [Su, Yan A.] GenProMarkers Inc, Rockville, MD 20850 USA. [Chrousos, George P.] Univ Athens, Dept Pediat 1, Athens 11527, Greece. RP Kino, T (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Clin Res Ctr, Bldg 10,Rm 1E-3140,10 Ctr Dr MSC 1109, Bethesda, MD 20892 USA. EM kinot@mail.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD FX Literary work of this article was funded partly by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD. NR 75 TC 65 Z9 67 U1 1 U2 10 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD NOV PY 2009 VL 66 IS 21 BP 3435 EP 3448 DI 10.1007/s00018-009-0098-z PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 504QQ UT WOS:000270632600004 PM 19633971 ER PT J AU Kang, XZ Chao, DM Gu, QB Ding, GH Wang, YW Balboni, G Lazarus, LH Xia, Y AF Kang, Xuezhi Chao, Dongman Gu, Quanbao Ding, Guanghong Wang, Yingwei Balboni, Gianfranco Lazarus, Lawrence H. Xia, Ying TI delta-Opioid receptors protect from anoxic disruption of Na+ homeostasis via Na+ channel regulation SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Article; Proceedings Paper CT Beijing Joint Conference of Physiological Science CY 2008 CL Beijing, PEOPLES R CHINA DE delta-Opioid receptor; Na+ channels; Na+ influx; Hypoxia; Cortex ID RAT HIPPOCAMPAL SLICES; SENSITIVE SODIUM-CHANNELS; APOPTOTIC NEURONAL DEATH; NULL MUTANT MOUSE; FOREBRAIN ISCHEMIA; IN-VITRO; GLUCOSE DEPRIVATION; K+ HOMEOSTASIS; BRAIN; MODEL AB Hypoxic/ischemic disruption of ionic homeostasis is a critical trigger of neuronal injury/death in the brain. There is, however, no promising strategy against such pathophysiologic change to protect the brain from hypoxic/ischemic injury. Here, we present a novel finding that activation of delta-opioid receptors (DOR) reduced anoxic Na+ influx in the mouse cortex, which was completely blocked by DOR antagonism with naltrindole. Furthermore, we co-expressed DOR and Na+ channels in Xenopus oocytes and showed that DOR expression and activation indeed play an inhibitory role in Na+ channel regulation by decreasing the amplitude of sodium currents and increasing activation threshold of Na+ channels. Our results suggest that DOR protects from anoxic disruption of Na+ homeostasis via Na+ channel regulation. These data may potentially have significant impacts on understanding the intrinsic mechanism of neuronal responses to stress and provide clues for better solutions of hypoxic/ischemic encephalopathy, and for the exploration of acupuncture mechanism since acupuncture activates opioid system. C1 [Chao, Dongman; Xia, Ying] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Kang, Xuezhi; Gu, Quanbao; Ding, Guanghong] Shanghai Res Ctr Acupuncture & Meridians, Shanghai, Peoples R China. [Wang, Yingwei] Shanghai Jiao Tong Univ, Coll Med, Shanghai 200030, Peoples R China. [Balboni, Gianfranco] Univ Cagliari, Cagliari, Italy. [Lazarus, Lawrence H.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Xia, Y (reprint author), Yale Univ, Sch Med, 333 Cedar St,LMP 3107, New Haven, CT 06520 USA. EM ying.xia@yale.edu RI Kang, Xuezhi/L-6719-2016 OI Kang, Xuezhi/0000-0002-0582-2244 FU Intramural NIH HHS [Z01 ES090053-21, Z01 ES100472-06]; NCCIH NIH HHS [AT004422]; NICHD NIH HHS [HD34852, R01 HD034852] NR 50 TC 17 Z9 18 U1 0 U2 5 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD NOV PY 2009 VL 66 IS 21 BP 3505 EP 3516 DI 10.1007/s00018-009-0136-x PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 504QQ UT WOS:000270632600008 PM 19756387 ER PT J AU Ibarra, JA Steele-Mortimer, O AF Ibarra, J. Antonio Steele-Mortimer, Olivia TI Salmonella- the ultimate insider. Salmonella virulence factors that modulate intracellular survival SO CELLULAR MICROBIOLOGY LA English DT Review ID ENTERICA SEROVAR TYPHIMURIUM; III SECRETION SYSTEM; PHOSPHOTHREONINE LYASE ACTIVITY; EPITHELIAL-CELLS; SEROTYPE TYPHIMURIUM; INTESTINAL COLONIZATION; PATHOGENICITY ISLAND-1; COORDINATED REGULATION; BACTERIAL FLAGELLIN; VACUOLAR MEMBRANE AB P>Salmonella enterica serovar Typhimurium is a common facultative intracellular pathogen that causes food-borne gastroenteritis in millions of people worldwide. Intracellular survival and replication are important virulence determinants and the bacteria can be found in a variety of phagocytic and non-phagocytic cells in vivo. Invasion of host cells and intracellular survival are dependent on two type III secretion systems, T3SS1 and T3SS2, each of which translocates a distinct set of effector proteins. However, other virulence factors including ion transporters, superoxide dismutase, flagella and fimbriae are also involved in accessing and utilizing the intracellular niche. C1 [Ibarra, J. Antonio; Steele-Mortimer, Olivia] NIAID, Intracellular Parasites Lab, NIH, Rocky Mt Labs, Hamilton, MT USA. RP Steele-Mortimer, O (reprint author), NIAID, Intracellular Parasites Lab, NIH, Rocky Mt Labs, Hamilton, MT USA. EM omortimer@niaid.nih.gov FU Intramural Research Program (DIR) of the NIH, NIAID FX We apologize to all those whose work is not cited, or has not been adequately acknowledged, due to space limitations. Research in O.S.-M.'s laboratory is supported by the Intramural Research Program (DIR) of the NIH, NIAID. NR 84 TC 121 Z9 125 U1 3 U2 29 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD NOV PY 2009 VL 11 IS 11 BP 1579 EP 1586 DI 10.1111/j.1462-5822.2009.01368.x PG 8 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 504UE UT WOS:000270642400004 PM 19775254 ER PT J AU Knodler, LA Winfree, S Drecktrah, D Ireland, R Steele-Mortimer, O AF Knodler, Leigh A. Winfree, Seth Drecktrah, Dan Ireland, Robin Steele-Mortimer, Olivia TI Ubiquitination of the bacterial inositol phosphatase, SopB, regulates its biological activity at the plasma membrane SO CELLULAR MICROBIOLOGY LA English DT Article ID IV SECRETION SYSTEMS; HOST-CELL MEMBRANES; SALMONELLA-ENTERICA; EPITHELIAL-CELLS; CONTAINING VACUOLES; EFFECTOR PROTEINS; MASS-SPECTROMETRY; ESCHERICHIA-COLI; MAMMALIAN-CELLS; GENE-EXPRESSION AB P>The Salmonella type III effector, SopB, is an inositol polyphosphate phosphatase that modulates host cell phospholipids at the plasma membrane and the nascent Salmonella-containing vacuole (SCV). Translocated SopB persists for many hours after infection and is ubiquitinated but the significance of this covalent modification has not been investigated. Here we identify by mass spectrometry six lysine residues of SopB that are mono-ubiquitinated. Substitution of these six lysine residues with arginine, SopB-K6R, almost completely eliminated SopB ubiquitination. We found that ubiquitination does not affect SopB stability or membrane association, or SopB-dependent events in SCV biogenesis. However, two spatially and temporally distinct events are dependent on ubiquitination, downregulation of SopB activity at the plasma membrane and prolonged retention of SopB on the SCV. Activation of the mammalian pro-survival kinase Akt/PKB, a downstream target of SopB, was intensified and prolonged after infection with the SopB-K6R mutant. At later times, fewer SCV were decorated with SopB-K6R compared with SopB. Instead SopB-K6R was present as discrete vesicles spread diffusely throughout the cell. Altogether, our data show that ubiquitination of SopB is not related to its intracellular stability but rather regulates its enzymatic activity at the plasma membrane and intracellular localization. C1 [Knodler, Leigh A.; Winfree, Seth; Drecktrah, Dan; Ireland, Robin; Steele-Mortimer, Olivia] NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Knodler, LA (reprint author), NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM lknodler@niaid.nih.gov FU Taplin Mass Spectrometry Facility, Harvard Medical School for LC/MS-MS; Intramural Research Program (DIR) of NIH, NIAID FX We are grateful to Jean Celli for his helpful comments, Ross Tomaino at the Taplin Mass Spectrometry Facility, Harvard Medical School for LC/MS-MS analysis, Mark Jepson and Julian Downward for providing plasmids, Sandra Marcus for providing recombinant SopB, Anita Mora and Gary Hettrick for graphics assistance and the Genomics Core Facility at Rocky Mountain Laboratories for DNA sequence analysis. This research is supported by the Intramural Research Program (DIR) of NIH, NIAID. NR 69 TC 40 Z9 40 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD NOV PY 2009 VL 11 IS 11 BP 1652 EP 1670 DI 10.1111/j.1462-5822.2009.01356.x PG 19 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 504UE UT WOS:000270642400010 PM 19614667 ER PT J AU Cooper, G Gilbert, K Greidinger, E James, J Pfau, J Reinlib, L Richardson, B Rose, N AF Cooper, Glinda Gilbert, Kathleen Greidinger, Eric James, Judith Pfau, Jean Reinlib, Leslie Richardson, Bruce Rose, Noel TI Recent advances and opportunities in research on lupus: environmental influences and mechanisms of disease SO CIENCIA & SAUDE COLETIVA LA English DT Review DE Apoptosis; Epstein-Barr virus; Silica; Systemic lupus erythematosus; Trichloroethylene ID EPSTEIN-BARR-VIRUS; ZEALAND MIXED MICE; T-CELL-ACTIVATION; KINASE-C-DELTA; SYSTEMIC AUTOIMMUNE-DISEASE; TUMOR-NECROSIS-FACTOR; RESISTANT B10.A MICE; APOPTOTIC CELLS; ALVEOLAR MACROPHAGES; MURINE MODEL AB We summarize research on mechanisms through which environmental agents may affect the pathogenesis of lupus, discuss three exposures that have been the focus of research in this area, and propose recommendations for new research initiatives. We examined studies pertaining to key mechanistic events and specific exposures. Apoptosis leading to increased production or decreased clearance of immunogenic intracellular self-antigens and defective apoptosis of autoreactive immune cells both have been implicated in the loss of self-tolerance. The adjuvant or bystander effect is also needed to produce a sustained autoimmune response. Activation of toll-like receptors is one mechanism through which these effects may occur. Abnormal DNA methylation may contribute to the pathogenesis of lupus. Each of the specific exposures has been shown, in humans or in mice, to act upon one or more of these pathogenic steps. Specific recommendations for the continued advancement of our understanding of environmental influences on lupus and other autoimmune diseases include the development and use of mouse models with varying degrees of penetrance and manifestations of disease, identification of molecular or physiologic targets of specific exposures, development and use of improved exposure assessment methodologies, and multisite collaborations designed to examine understudied environmental exposures in humans. C1 [Cooper, Glinda] US EPA, Natl Ctr Environm Assessment, Washington, DC 20460 USA. [Gilbert, Kathleen] Univ Arkansas Med Sci, Dept Microbiol & Immunol, Little Rock, AR 72205 USA. [Greidinger, Eric] Univ Miami, Miller Sch Med, Div Rheumatol, Coral Gables, FL 33124 USA. [James, Judith] Oklahoma Med Res Fdn, Arthrit & Immunol Program, Oklahoma City, OK USA. [Pfau, Jean] Univ Montana, Dept Biomed & Pharmaceut Sci, Ctr Environm Hlth Sci, Missoula, MT 59812 USA. [Reinlib, Leslie] NIEHS, Div Extramural Res & Training, NIH, Bethesda, MD USA. [Richardson, Bruce] Univ Michigan, Ann Arbor, MI 48109 USA. [Rose, Noel] Johns Hopkins Univ, Johns Hopkins Ctr Autoimmune Dis, Dept Pathol, Baltimore, MD 21218 USA. RP Cooper, G (reprint author), US EPA, Natl Ctr Environm Assessment, 1200 Penn Ave NW, Washington, DC 20460 USA. EM cooper.glinda@epa.gov NR 107 TC 6 Z9 6 U1 0 U2 3 PU ABRASCO PI RIO DE JANEIRO PA RUA HESPERIA, 16-PARTE MANGUINHOS, RIO DE JANEIRO, 21050-040, BRAZIL SN 1413-8123 J9 CIENC SAUDE COLETIVA JI Cienc. Saude Coletiva PD NOV-DEC PY 2009 VL 14 IS 5 BP 1865 EP 1876 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 511KH UT WOS:000271162500028 PM 19851599 ER PT J AU Marques, A Brown, MR Fleisher, TA AF Marques, Adriana Brown, Margaret R. Fleisher, Thomas A. TI Natural Killer Cells in Chronic Lyme Disease Reply SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Letter ID EXPRESSION; PATTERNS; GENDER; TRIAL C1 [Marques, Adriana] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Brown, Margaret R.; Fleisher, Thomas A.] NIH, Serv Immunol, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. RP Marques, A (reprint author), NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM amarques@niaid.nih.gov NR 12 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD NOV PY 2009 VL 16 IS 11 BP 1704 EP 1706 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 514DE UT WOS:000271373700026 ER PT J AU Terabe, M Ambrosino, E Takaku, S O'Konek, JJ Venzon, D Lonnin, S McPherson, JM Berzofsky, JA AF Terabe, Masaki Ambrosino, Elena Takaku, Shun O'Konek, Jessica J. Venzon, David Lonnin, Scott McPherson, John M. Berzofsky, Jay A. TI Synergistic Enhancement of CD8(+) T Cell-Mediated Tumor Vaccine Efficacy by an Anti-Transforming Growth Factor-beta Monoclonal Antibody SO CLINICAL CANCER RESEARCH LA English DT Article ID HIGH-AVIDITY CTL; TGF-BETA; IMMUNE-RESPONSE; DOWN-REGULATION; MYELOID CELLS; NK CELLS; IN-VITRO; ABROGATION; DISEASE; MOUSE AB Purpose: Transforming growth factor-beta (TGF-beta) is an immunosuppressive cytokine, having direct suppressive activity against conventional CD4(+) and CD8(+)T cells and natural killer cells, thereby inhibiting tumor immunosurveillance. Here, we investigated possible synergy between anti-TGF-beta (1D11) and a peptide vaccine on induction of antitumor immunity, and the mechanisms accounting for synergistic efficacy. Experimental Design: The effect of combination treatment with a peptide vaccine and anti-TGF-beta was examined in a subcutaneous TC1 tumor model, as well as the mechanisms of protection induced by this treatment. Results: Anti-TGF-beta significantly and synergistically improved vaccine efficacy as measured by reduction in primary tumor growth, although anti-TGF-beta alone had no impact. The number of tumor antigen-specific CTL with high functional avidity as measured by IFN-gamma production and lytic activity was significantly increased in vaccinated mice by TGF-beta neutralization. Although TGF-beta is known to play a critical role in CD4(+)Foxp3(+) Treg cells, Treg depletion/suppression by an anti-CD25 monoclonal antibody (PC61) before tumor challenge did not enhance vaccine efficacy, and adding anti-TGF-beta did not affect Treg numbers in lymph nodes or tumors or their function. Also, TGF-beta neutralization had no effect on interleukin-17-producing T cells, which are induced by TGF-beta and interleukin-6. Absence of type II NKT cells, which induce myeloid cells to produce TGF-beta, was not sufficient to eliminate all sources of suppressive TGF-beta. Finally, the synergistic protection induced by anti-TGF-beta vaccine augmentation was mediated by CD8(+) T cells since anti-CD8 treatment completely abrogated the effect. Conclusions: These results suggest that TGF-beta blockade may be useful for enhancing cancer vaccine efficacy. (Clin Cancer Res 2009;15(21):6560-9) C1 [Terabe, Masaki; Ambrosino, Elena; Takaku, Shun; O'Konek, Jessica J.; Berzofsky, Jay A.] NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA. [Venzon, David] NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. [Lonnin, Scott; McPherson, John M.] Genzyme Corp, Framingham, MA 01701 USA. RP Terabe, M (reprint author), NCI, Vaccine Branch, NIH, Bldg 10,Room 61312,9000 Rockville Pike, Bethesda, MD 20892 USA. EM terabe@mail.nih.gov FU NIH; National Cancer Institute; Center for Cancer Research FX Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. National Cancer Institute has a Cooperative Research and Development Agreement with Genzyme Cooperation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. NR 44 TC 69 Z9 70 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2009 VL 15 IS 21 BP 6560 EP 6569 DI 10.1158/1078-0432.CCR-09-1066 PG 10 WC Oncology SC Oncology GA 513CP UT WOS:000271300200013 PM 19861451 ER EF